Article

Nasopharyngeal carcinoma treated by radical radiotherapy alone: Ten-year experience of a single institution

June 2006
International Journal of Radiation Oncology*Biology*Physics 65(1):161-8

June 2006
65(1):161-8

DOI:10.1016/j.ijrobp.2005.12.003

Source
PubMed

Authors:

Jun-Lin Yi

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

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To report on our experience in the treatment of nasopharyngeal carcinoma (NPC) by radical radiotherapy alone in our institution during the last decade. From January 1990 to May 1999, 905 NPC patients were treated and were studied retrospectively. Radical radiotherapy was given to this cohort by conventional technique in a routine dose of 70-72 Gy to the primary tumor and metastatic lymph nodes. In case of residual primary lesion, a boost dose of 8-24 Gy was delivered by either 192Ir afterloading brachytherapy, fractionated stereotactic radiotherapy, conformal radiotherapy, or small external-beam fields. The 5-year and 10-year local-regional control, overall survival, and disease-free survival rates were 81.7% and 76.7%, 76.1% and 66.5%, 58.4% and 52.1%, respectively. In case of residual primary lesions after a dose of 70-72 Gy of conventional external-beam radiotherapy (EBRT), an additional boost was able to achieve a local control of 80.8%, similar to that obtained with primary lesions that completely disappeared at 70-72 Gy (82.6%, p = 0.892). The treatment results of radical EBRT followed by a boost dose to the residual primary tumor for nasopharyngeal carcinoma in our institution are promising.

Failure Patterns of Recurrence and Metastasis After Intensity-Modulated Radiotherapy in Patients With Nasopharyngeal Carcinoma: Results of a Multicentric Clinical Study

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Feb 2022

Purpose This study aimed to explore factors associated with recurrence and metastasis after intensity-modulated radiotherapy (IMRT) in patients with nasopharyngeal carcinoma (NPC) and provide evidence for NPC treatment. Methods We retrospectively analysed the treatment dose and survival outcomes of 645 patients with nasopharyngeal carcinoma without distant metastases treated with IMRT for the first time at three treatment centres in the Guangxi Zhuang Autonomous Region, China, between January 2009 and December 2012. Results There were 9.3% of patients (60/645) had recurrence and 17.5% (113/645) had distant metastasis 5 years after treatment. The 1-year, 3-year and 5-year local recurrence rates were 0.9%, 6.5% and 9.0% respectively. And the 1-year, 3-year and 5-year distant metastasis rates were 3.4%, 10% and 17.2%, respectively. In the 60 patients with recurrence, the in-field, marginal-field, and out-field recurrence rates were 93.3% (56/60), 5.0% (3/60) and 1.7% (1/60), respectively. Recurrence failures occurring within the first three years after treatment accounted for 81.7% (49/60). In the 113 patients with metastasis, the size of the cervical lymph node, the presence of lower cervical lymph node metastasis, the residual cervical lymph node size and the time of residual cervical lymph node complete response (CR) were independent prognostic factors for DMFS (P <0.05). Conclusion Most recurrences occured in the first three years after IMRT. In-field recurrence was the most common pattern for loco-regional failure of NPC treatment. The risk of distant metastasis was positively correlated with higher N stage, lower neck nodal metastasis, larger size of cervical lymph nodes, and longer time to response for residual NPC in cervical adenopathy.

A prediction model for xerostomia in locoregionally advanced nasopharyngeal carcinoma patients receiving radical radiotherapy

Article

Full-text available

Jun 2022
BMC Oral Health

Background This study was to evaluate the predictors of xerostomia and Grade 3 xerostomia in locoregionally advanced nasopharyngeal carcinoma (NPC) patients receiving radical radiotherapy and establish prediction models for xerostomia and Grade 3 xerostomia based on the predictors. Methods Totally, 365 patients with locoregionally advanced NPC who underwent radical radiotherapy were randomly divided into the training set (n = 255) and the testing set (n = 110) at a ratio of 7:3. All variables were included in the least absolute shrinkage and selection operator regression to screen out the potential predictors for xerostomia as well as the Grade 3 xerostomia in locoregionally advanced NPC patients receiving radical radiotherapy. The random forest (RF), a decision tree classifier (DTC), and extreme-gradient boosting (XGB) models were constructed. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), area under the curve (AUC) and accuracy were analyzed to evaluate the predictive performance of the models. Results In the RF model for predicting xerostomia, the sensitivity was 1.000 (95%CI 1.000–1.000), the PPV was 0.990 (95%CI 0.975–1.000), the NPV was 1.000 (95%CI 1.000–1.000), the AUC was 0.999 (95%CI 0.997–1.000) and the accuracy was 0.992 (95%CI 0.981–1.000) in the training set. The sensitivity was 0.933 (95%CI 0.880–0.985), the PPV was 0.933 (95%CI 0.880–0.985), and the AUC was 0.915 (95%CI 0.860–0.970) in the testing set. Hypertension, age, total radiotherapy dose, dose at 50% of the left parotid volume, mean dose to right parotid gland, mean dose to oral cavity, and course of induction chemotherapy were important variables associated with the risk of xerostomia in locoregionally advanced NPC patients receiving radical radiotherapy. The AUC of DTC model for predicting xerostomia was 0.769 (95%CI 0.666–0.872) in the testing set. The AUC of the XGB model for predicting xerostomia was 0.834 (0.753–0.916) in the testing set. The RF model showed the good predictive ability with the AUC of 0.986 (95%CI 0.972–1.000) in the training set, and 0.766 (95%CI 0.626–0.905) in the testing set for identifying patients who at high risk of Grade 3 xerostomia in those with high risk of xerostomia. Conclusions An RF model for predicting xerostomia in locoregionally advanced NPC patients receiving radical radiotherapy and an RF model for predicting Grade 3 xerostomia in those with high risk of xerostomia showed good predictive ability.

Patterns of failure in patients with nasopharyngeal cancer of Northeastern region of India: a retrospective observational study

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Full-text available

Apr 2024
Eur Arch Oto Rhino Laryngol

Purpose We aimed to analyze patterns of failure and disease volume-treatment outcomes in patients with Nasopharyngeal carcinoma (NPC) treated with definitive radiation with or without concurrent chemotherapy at a tertiary cancer centre in northeast India. Methods From February 2018 to February 2022, 99 histopathologically proved non-metastatic NPC patients treated with curative-intent RT with or without chemotherapy were retrospectively analyzed. Locally advanced patients received neoadjuvant or adjuvant chemotherapy. The Cox proportional hazards model was used to investigate the impact of various prognostic factors on locoregional free survival (LRFS), distant metastasis free survival (DMFS), progression free survival (PFS) and overall survival (OS). The log-rank test and Kaplan–Meir curves compared outcome variables based on ROC analysis-classified tumor volume. Results During a median follow up of 25.4 months (17.3–39.2), 35(35.4%) patients developed recurrence. Twenty-three patients developed locoregional failures, of which 11 were in-field; 12 patient showed an out-field failure. The 3-year LRFS, DMFS, PFS and OS was 71.10%, 70.90%, 64.10% and 74.10% respectively. There was statistically significant difference in LRFS according to T staging (p < 0.0001). Gross tumor volume (GTVp) and gross nodal volume (GTVn) were an independent prognostic factor for OS, PFS, LRFS and DMFS. The cut-off volumes for GTVp and GTVn for distant metastases and locoregional failure, respectively, were found to be 13 and 22.7 mL and 3.7 and 39.2 mL, respectively, by ROC curve analysis. Based on this, 99 patients were divided into three subgroups. OS demonstrated significant differences among patients in different volume subgroups for GTVp (p = 0.03) and GTVn (p = 0.00024). Conclusions For NPC patients who undergo curative IMRT, primary tumour and nodal volumes are independent prognostic indicators. GTVp and GTVn are highly predictive of local control, distant metastases, disease-free survival, and overall survival. This justifies their use as quantitative prognostic indicator for NPC.

Nutritional status and its correlation to prognosis of nasopharyngeal carcinoma patients in different ages in China: a multicenter cohort study

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Oct 2023
SUPPORT CARE CANCER

Nasopharyngeal carcinoma (NPC) patients usually presented malnutrition under chemoradiotherapy (CRT)/radiotherapy (RT). Few studies stratified by age to investigate the association of nutritional status with overall survival (OS) in NPC patients. This study aimed to explore the nutritional parameters related prognosis of NPC patients in different age. The total 1365 NPC patients were classified into young (18~45), middle-aged (46~60), and old groups (> 60). PG-SGA scores, NRS-2002 scores, Karnofsky performance status scores, anthropometric, and blood indicators (albumin, prealbumin, transferrin, C-reactive protein, hemoglobin, and total lymphocyte) were assessed. Cox regression analysis was performed to evaluate the association between risk factors of nutritional status and the overall survival in different age group of NPC patients. Kaplan-Meier (KM) survival analysis was used to estimate the effect of nutritional indexes on prognosis. The abnormal rate of albumin, prealbumin, hemoglobin, hand grip strength, and calf circumference increased with age. The malnutrition occurred in all age group and low calf circumference (HR, 4.427, 1.167–16.791) was an independent death risk in young adults. Distant metastasis (HR, 4.754, 2.737–8.260), low albumin (HR, 3.530, 1.708–7.296), hand grip strength (HR, 1.901, 1.160–3.115), and the nutritional intervention requirement (NRS-2002 ≥ 3) (HR, 2.802, 1.211–6.483) was significantly correlated with poor OS in NPC patients with middled age adults. Distant metastasis (HR, 2.546, 1.497–4.330), low albumin (HR, 1.824, 0.949–3.507), low hemoglobin (HR, 1.757, 1.015–3.044), low hand grip strength (HR, 1.771, 1.112–2.818), and low calf circumference (HR, 1.951, 1.074–3.545) were associated with increased risk of death in the elderly. KM analysis indicated that over 60 years, distant metastasis, low albumin, low hand grip strength, low calf circumference, and malnutritional risk (NRS-2002 ≥ 3) were correlated to prognosis of NPC patients. Low calf circumference could be a prognosis not only in elderly but also in young adults of NPC patients, whereas low albumin and distant metastasis were the prognostic factors in middle-aged and elderly patients. Patients aged over 60 years exhibited poorer OS compared with young and middle-aged adults.

Application of FGD-BCEL loss function in segmenting temporal lobes on localized CT images for radiotherapy

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Oct 2023

Objectives The aim of this study was to find a new loss function to automatically segment temporal lobes on localized CT images for radiotherapy with more accuracy and a solution to dealing with the classification of class-imbalanced samples in temporal lobe segmentation. Methods Localized CT images for radiotherapy of 70 patients with nasopharyngeal carcinoma were selected. Radiation oncologists sketched mask maps. The dataset was randomly divided into the training set ( n = 49), the validation set ( n = 7), and the test set ( n = 14). The training set was expanded by rotation, flipping, zooming, and shearing, and the models were evaluated using Dice similarity coefficient (DSC), Jaccard similarity coefficient (JSC), positive predictive value (PPV), sensitivity (SE), and Hausdorff distance (HD). This study presented an improved loss function, focal generalized Dice-binary cross-entropy loss (FGD-BCEL), and compared it with four other loss functions, Dice loss (DL), generalized Dice loss (GDL), Tversky loss (TL), and focal Tversky loss (FTL), using the U-Net model framework. Results With the U-Net model based on FGD-BCEL, the DSC, JSC, PPV, SE, and HD were 0.87 ± 0.11, 0.78 ± 0.11, 0.90 ± 0.10, 0.87 ± 0.13, and 4.11 ± 0.75, respectively. Except for the SE, all the other evaluation metric values of the temporal lobes segmented by the FGD-BCEL-based U-Net model were improved compared to the DL, GDL, TL, and FTL loss function-based U-Net models. Moreover, the FGD-BCEL-based U-Net model was morphologically more similar to the mask maps. The over- and under-segmentation was lessened, and it effectively segmented the tiny structures in the upper and lower poles of the temporal lobe with a limited number of samples. Conclusions For the segmentation of the temporal lobe on localized CT images for radiotherapy, the U-Net model based on the FGD-BCEL can meet the basic clinical requirements and effectively reduce the over- and under-segmentation compared with the U-Net models based on the other four loss functions. However, there still exists some over- and under-segmentation in the results, and further improvement is needed.

Advance in integrating platinum-based chemotherapy with radiotherapy for locally advanced nasopharyngeal carcinoma

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Sep 2023

Nasopharyngeal carcinoma (NPC) is a malignant tumor characterized by the malignant transformation of nasopharyngeal epithelial cells. It is highly sensitive to radiation therapy, making radiotherapy the primary treatment modality. However, 60-80% of patients are initially diagnosed with locally advanced NPC (LA-NPC), where radiotherapy alone often fails to achieve desirable outcomes. Therefore, combining radiotherapy with chemotherapy has emerged as an effective strategy to optimize treatment for LA-NPC patients. Among the various chemotherapy regimens, concurrent chemoradiotherapy (CCRT) using platinum-based drugs has been established as the most commonly utilized approach for LA-NPC patients. The extensive utilization of platinum drugs in clinical settings underscores their therapeutic potential and emphasizes ongoing efforts in the development of novel platinum-based complexes for anticancer therapy. The aim of this review is to elucidate the remarkable advances made in the field of platinum-based therapies for nasopharyngeal carcinoma, emphasizing their transformative impact on patient prognosis.

Research trends of radiation induced temporal lobe injury in patients with nasopharyngeal carcinoma from 2000 to 2022: a bibliometric analysis

Article

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Sep 2023
Radiat Oncol

Background In patients with nasopharyngeal cancer (NPC), radiation-induced temporal lobe injury (TLI) is the most dreaded late-stage complication following radiation therapy (RT). We currently lack a definitive algorithmic administration for this entity. In the meantime, the pathogenesis of TLI and the mechanism-based interventions to prevent or treat this adverse effect remain unknown. To better answer the aforementioned questions, it is necessary to comprehend the intellectual foundations and prospective trends of this field through bibliometric analysis. Methods Articles were gathered from the Web of Science Core Collection (WoSCC) database between 2000 and 2022. CiteSpace was utilized to create a country/institutional co-authorship network, perform dual-map analysis, and find keywords with citation bursts. VOSviewer was used to build networks based on author co-authorship, journal citation, co-citation analysis of authors, references, and journals, and keyword co-occurrence. Results A total of 140 articles and reviews were included in the final analysis. The number of publications has steadily increased with some fluctuations over the years. The country and institution contributing most to this field are the China and Sun Yat-Sen University. Han Fei was the most prolific author, while Lee Awm was the most frequently cited. The analysis of co-occurrence revealed three clusters, including: “radiation-induced injury or necrosis in NPC,” “clinical studies on chemotherapy/radiotherapy complications and survival in recurrent NPC,” and “IMRT/chemotherapy outcomes and toxicities in head and neck cancer”). Most recent keyword bursts were “volume,” “temporal lobe injury,” “toxicities,” “model,” “survival,” “intensity modulated radiotherapy,” “induced brain injury,” “head and neck cancer,” and “temporal lobe.” Conclusion This study provides some insights of the major areas of interest in the field of radiation-induced TLI in patients with NPC by bibliometric analyses. This study assists scholars in locating collaborators and significant literature in this field, provides guidance for publishing journals, and identifies research hotspots. This analysis acknowledges significant contributions to the discipline and encourages the scientific community to conduct additional research.

Negative Prognostic Impact of Smoking on Long-term Survival in Patients With Nasopharyngeal Carcinoma Treated With Curative (Chemo)radiotherapy

Article

Jun 2023

Background/aim: To evaluate the effectiveness of curative (chemo)radiotherapy in patients with nasopharyngeal carcinoma and to identify prognostic factors influencing treatment outcomes. Patients and methods: We conducted a retrospective study of 73 consecutive patients, treated with definitive (chemo)radiotherapy from 2002 to 2019 (median stage III/IV 78%). The median total dose of radiotherapy achieved was 70 Gy. Concomitant chemotherapy was given to 82% of patients. Results: The five- and ten-year locoregional controls were 73% and 72%, respectively; the five- and ten-year distant controls were 93% and 93%, respectively. The five- and ten-year overall survival rates were 46% and 34%, respectively. A multivariate analysis identified age, smoking, and the initial response to treatment as the strongest prognostic factors in predicting survival. Conclusion: Smoking ≤5 years before starting curative (chemo)radiotherapy for nasopharyngeal carcinoma was shown to be an independent negative prognostic factor for overall survival with a four-fold higher risk of death compared to non-smokers.

Application of Artificial Intelligence to the Diagnosis and Therapy of Nasopharyngeal Carcinoma

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Full-text available

Apr 2023

Artificial intelligence (AI) is an interdisciplinary field that encompasses a wide range of computer science disciplines, including image recognition, machine learning, human−computer interaction, robotics and so on. Recently, AI, especially deep learning algorithms, has shown excellent performance in the field of image recognition, being able to automatically perform quantitative evaluation of complex medical image features to improve diagnostic accuracy and efficiency. AI has a wider and deeper application in the medical field of diagnosis, treatment and prognosis. Nasopharyngeal carcinoma (NPC) occurs frequently in southern China and Southeast Asian countries and is the most common head and neck cancer in the region. Detecting and treating NPC early is crucial for a good prognosis. This paper describes the basic concepts of AI, including traditional machine learning and deep learning algorithms, and their clinical applications of detecting and assessing NPC lesions, facilitating treatment and predicting prognosis. The main limitations of current AI technologies are briefly described, including interpretability issues, privacy and security and the need for large amounts of annotated data. Finally, we discuss the remaining challenges and the promising future of using AI to diagnose and treat NPC.

Assessment of Response to Different Induction Chemotherapy Regimens in Locally Advanced Nasopharyngeal Carcinoma

Article

Full-text available

Feb 2023

Purpose To compare the short-term treatment response and survival of the three induction chemotherapy (IC) regimens, including gemcitabine and cisplatin (GP), docetaxel and cisplatin (TP), and docetaxel, cisplatin, and fluoropyrimidines (TPF) in locally advanced nasopharyngeal carcinoma (LANPC). Methods We included stage III–IVA NPC patients who received ≥3 cycles of IC in this study. The chi-square test, multivariate logistic regression analysis, and Kaplan–Meier method were used for statistical analysis. Results A total of 227 patients were included. The overall response rate (ORR) of the primary nasopharyngeal tumors after IC with GP, TP, and TPF was 91.9%, 83.8%, and 91.7%, respectively (P=0.729), and the ORR of the cervical lymph nodes was 94.6%, 72.3%, and 85.0%, respectively (P<0.001). For the primary nasopharyngeal tumor, there was no significant difference in the ORR among the three IC regimens. For cervical lymph nodes, patients treated with GP had significantly higher ORR compared to those treated with the TP regimen (P=0.014), and comparable ORR was found between TPF and GP regimens (P=0.161). Similar progression-free survival (PFS) (P=0.501) and overall survival (OS) (P=0.504) were found among three IC regimens. There were comparable PFS (P=0.123) and OS (P=0.478) among those with complete response (CR), partial response (PR), and stable disease (SD)/progressive disease (PD) in the primary nasopharyngeal tumors. However, patients who had CR in the primary nasopharyngeal tumor (P=0.014) and the cervical lymph nodes (P=0.022) had better PFS compared to those who had PR or SD/PD. Conclusion GP and TPF regimens are equivalent to the TP regimen in the response to primary nasopharyngeal tumors after IC, but with better ORR in the cervical lymph nodes than the TP regimen. The response to IC may be a powerful indicator for predicting prognosis and developing individualized follow-up and treatment strategies for LANPC patients.

Identifying optimal candidates for postoperative adjuvant therapy among regional persistent/recurrent nasopharyngeal carcinoma patients after neck dissection

Article

Full-text available

Nov 2022
BMC CANCER

Purpose To analyze the clinical outcomes of patients with regional persistent/recurrent nasopharyngeal carcinoma (NPC) who received neck dissection, and to evaluate the clinical benefit of postoperative adjuvant therapy (PAT) based on patients’ positive lymph node counts (PLNs), extracapsular spread (ECS) and preoperative plasma EBV DNA levels. Methods From 2003 to 2017, 342 patients with regional persistent/recurrent NPC were included in this study. All patients were treated with neck dissection and 76 patients received PAT. Progression-free survival (PFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRFS) were compared between groups using propensity score matching (PSM). Results 152 patients without PAT treatment and 76 patients with PAT treatment were selected by the PSM. There was no significant difference in 2-year PFS (52.4% vs. 61.3%, P = 0.371), 2-year OS (91.9% vs. 90.5%, P = 0.097) or 2-year LRFS (66.3% vs. 67.9%, P = 0.872) between the two groups. However, the application of PAT brought survival benefits to patients in terms of 2-year DMFS (76.5% vs. 84.7%, P = 0.020). PLN, ECS and preoperative EBV DNA level remained independent risk factors for poorer PFS. Accordingly, patients were divided into low-risk and high-risk groups using receiver operating characteristic (ROC) curve; the 2-year PFS rates for two risk groups were 73.4% and 59.1% (P < 0.0001) respectively. The results showed that low-risk patients didn’t benefit from the addition of PAT. However, the 2-year DMFS rate was significantly improved in high-risk PAT-treated patients than those treated by neck dissection alone (83.7% vs. 71.7%, P = 0.023). Conclusions PLNs, ECS and preoperative EBV DNA level are associated with the prognosis of patients with regional persistent/recurrent NPC. High-risk patients identified by PLNs, ECS and preoperative EBV DNA level may benefit from the addition of PAT after neck dissection.

Undifferentiated carcinoma of nasopharyngeal type (UCNT): a Swiss single-institutional experience during 1990-2005

Article

Full-text available

May 2010
SWISS MED WKLY

A Nomogram to Identify the Optimal Candidates for Induction Chemotherapy in Advanced N-Stage Nasopharyngeal Carcinoma

Article

Full-text available

Jan 2022

Purpose We aimed to select optimal candidates benefiting from the addition of induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) in advanced N-stage nasopharyngeal carcinoma (NPC). Patients and Methods A total of 624 NPC patients with N2-3 stage received CCRT with or without IC were retrospectively reviewed. We constructed a nomogram for predicting overall survival (OS) based on the result of the multivariate analysis in the training cohort (n = 468) and then tested it on the validation cohort (n = 156). Harrell’s concordance indices (C-index) and time-independent receiver operating characteristic (tdROC) analysis were applied to evaluate the discriminatory ability of the nomogram and compare it with TNM staging. IC plus CCRT was compared with CCRT in the whole cohort and two risk groups based on the nomogram with balanced baseline characteristics. In addition, acute toxicities were compared between different treatment groups. Results The nomogram showed good prognostic accuracy with a C-index of 0.716 (95% CI 0.669–0.763) in the validation cohort. The 5-year OS of low and high-risk groups stratified by the nomogram were significantly different. IC+CCRT was significantly associated with superior OS as compared with CCRT (75.4 vs 52.6%, p = 0.009) in the high-risk group. However, no significant difference between IC plus CCRT and CCRT was observed (p = 0.843) in the low-risk group. IC plus CCRT was associated with more grade 1–4 acute toxicities. Conclusion Our study can help clinicians select NPC patients with advanced N stage who benefit from IC.

Nimotuzumab plus induction chemotherapy followed by radiotherapy/concurrent chemoradiotherapy plus nimotuzumab for locally advanced nasopharyngeal carcinoma: protocol of a multicentre, open-label, single-arm, prospective phase II trial

Article

Full-text available

Aug 2022

Epidermal growth factor receptor (EGFR) is a therapeutic target in nasopharyngeal carcinoma (NPC). The optimal combined modality of optimal combined modality of anti-EGFR monoclonal antibodies, induction chemotherapy (ICT), concurrent chemotherapy and radiotherapy for NPC remains poorly defined. None of previous studies have developed subsequent treatment strategies on the basis of stratification according to the efficacy following ICT plus anti-EGFR mAbs. This study aims to increase treatment intensity for patients with poor efficacy of ICT and reduce treatment toxicity for patients with favourable efficacy of ICT by assessing whether the efficacy of this treatment regimen is non-inferior to ICT plus concurrent chemoradiotherapy (historic controls). Introduction Methods and analysis Pathology-confirmed WHO type II/III NPC patients at clinical stage III–IVA (eighth American Joint Committee on Cancer/Union for International Cancer Control staging system) will be included in the study. They will receive ICT plus nimotuzumab (NTZ), followed by radiotherapy plus NTZ or concurrent chemoradiotherapy plus NTZ (stratified based on the efficacy of ICT plus NTZ). The primary endpoint is 3-year failure-free survival rate; while the secondary endpoints are 3-year overall survival rate, distant metastasis-free survival rate and locoregional recurrence-free survival rate, and short-term remission rate of tumour and treatment toxicity. Ethics and dissemination The study protocol has been approved by the Ethics Committee of the Second Affiliated Hospital of Nanchang University. Our findings will be disseminated in a peer-reviewed journal. Implementation strategies are in place to ensure privacy and confidentiality of participants. Trial registration number ChiCTR2000041139.

Efficacy of local therapy to metastatic foci in nasopharyngeal carcinoma: large-cohort strictly-matched retrospective study

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Full-text available

Jul 2022

Background Studies of local therapy (LT) to metastatic foci from nasopharyngeal carcinoma (NPC) are inconsistent and controversial. Here, we aimed to explore the survival benefit of LT directed at metastatic foci from NPC. Methods A retrospective analysis was conducted in NPC patients with liver, lung, and/or bone metastases. The postmetastatic overall survival (OS) rate was analyzed using the Kaplan–Meier method and compared by the log-rank test. Multivariate analysis was performed using the Cox hazard model. Subgroup analyses evaluating the effect of LT were performed for prespecified covariates. Propensity score matching was applied to homogenize the compared arms. Results Overall, 2041 of 2962 patients were eligible for analysis. At a median follow-up of 43.4 months, the 5-year OS improved by an absolute difference of 14.6%, from 46.2% in the LT group versus 31.6% in the non-LT group, which led to a hazard ratio of 0.634 for death ( p < 0.001). Matched-pair analyses confirmed that LT was associated with improved OS ( p = 0.003), and the survival benefits of LT remained consistent in the subcohorts of liver and lung metastasis ( p = 0.009 and p = 0.007, respectively) but not of bone metastasis (BoM; p = 0.614). Radiotherapy was predominantly used for BoM and biological effective dose (BED) >60 Gy was found to yield more survival benefit than that of BED ⩽ 60 Gy. Conclusions The addition of LT directed at metastasis has demonstrated an improvement to OS compared with non-LT group in the present matched-pair study, especially for patients with liver and/or lung metastases.

Nasopharyngeal Carcinoma Radiomic Evaluation with Serial PET/CT: Exploring Features Predictive of Survival in Patients with Long-Term Follow-Up

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Full-text available

Jun 2022

Purpose: We aim determine the value of PET and CT radiomic parameters on survival with serial follow-up PET/CT in patients with nasopharyngeal carcinoma (NPC) for which curative intent therapy is undertaken. Methods: Patients with NPC and available pre-treatment as well as follow up PET/CT were included from 2005 to 2006 and were followed to 2021. Baseline demographic, radiological and outcome data were collected. Univariable Cox proportional hazard models were used to evaluate features from baseline and follow-up time points, and landmark analyses were performed for each time point. Results: Sixty patients were enrolled, and two-hundred and seventy-eight (278) PET/CT were at baseline and during follow-up. Thirty-eight percent (38%) were female, and sixty-two patients were male. All patients underwent curative radiation or chemoradiation therapy. The median follow-up was 11.72 years (1.26-14.86). Five-year and ten-year overall survivals (OSs) were 80.0% and 66.2%, and progression-free survival (PFS) was 90.0% and 74.4%. Time-dependent modelling suggested that, among others, PET gray-level zone length matrix (GLZLM) gray-level non-uniformity (GLNU) (HR 2.74 95% CI 1.06, 7.05) was significantly associated with OS. Landmark analyses suggested that CT parameters were most predictive at 15 month, whereas PET parameters were most predictive at time points 3, 6, 9 and 15 month. Conclusions: This study with long-term follow up data on NPC suggests that mainly PET-derived radiomic features are predictive for OS but not PFS in a time-dependent evaluation. Furthermore, CT radiomic measures may predict OS and PFS best at initial and long-term follow-up time points and PET measures may be more predictive in the interval. These modalities are commonly used in NPC surveillance, and prospective validation should be considered.

In-vivo skin dose measurement using gafchromic EBT3 film dosimetry in the radiation therapy of Head and Neck cancers: 2DRT versus IMRT

Article

Full-text available

Jun 2022

Background and Purpose Head and neck cancers involve very high curative doses of about 70 Gy which is usually associated with acute toxicities most importantly of the skin as it receives the radiation first. Intensity-modulated radiotherapy (IMRT) has the potential to decrease the skin dose thereby reducing the side effects, as well as the unplanned treatment interruptions that could otherwise result in less outcome of treatment. The purpose of this study was to compare and evaluate the skin dose during head and neck radiation therapy between 2-dimensional radiotherapy (2DRT) with cobalt −60 beam and Intensity Modulated Radiotherapy (IMRT) with high energy linear accelerator. Materials and methods Nasopharynx carcinoma patients receiving adjuvant radiation therapy of 60 Gy were selected for the study. Study patients were divided into two groups Group I received 60 Gy by 2-dimensional radiotherapy (2DRT) and Group II received 60 Gy by seven field Intensity Modulated Radiotherapy (7F-IMRT). The surface dose was measured using multiple 2 cm² Gafchromic® EBT³ films placed underneath the thermoplastic cast along the treatment isocenter as well as other sites within the irradiated field. The paired t-test was used to analyze the difference in the skin doses between the two techniques. Results Sixty-three cases of head and neck irradiation from Group I and Group II both were analyzed for in-vivo skin dose for a prescribed dose of 2Gy per fraction to the target using Gafchromic® EBT³ films. The means were compared using a paired t-test. There was a significant difference in the dose to skin per fraction in 7F-IMRT (Mean = 1.62Gy, SD = 0.23) compared to 2D-RT(Mean = 2.21Gy, SD = 0.33), at the conditions of paired t-test with 62 degrees of freedom-t(62) = -10.015, p = 0.00 (Table 1). The skin dose was more in 2DRT by 26.7% than in 7F- IMRT. Also, measured dose was compared to the treatment planning calculated dose and a difference of less than 1.6% was observed. Conclusion Radiotherapy of Head and Neck Cancers is better managed with Intensity Modulated Radiotherapy not only in terms of the possible dose escalation but also in terms of better skin-sparing and thereby fewer skin toxicities.

An Investigation of the Mechanisms of Radiation-Induced Muscle Injury in a Tree Shrew ( Tupaia belangeri ) Model

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Full-text available

Mar 2022

Background Animal models suitable for investigating mechanisms behind radiation-induced muscle injury are lacking. We developed a tree shrew model of such injury and investigated pathological changes and mechanisms. Methods Animals were divided into control (n = 5), radiation-induced acute injury (n = 5), and radiation-induced chronic injury (n = 5) groups. Tensor veli palatini (TVP) muscles of acute injury and chronic injury groups were dissected under a microscope at 1 and 24 weeks after radiation therapy, respectively. TVP muscles were stained with HE and Masson to visualize pathological changes. ELISA was performed to measure oxidative injury. RT-qPCR and immunohistochemical staining was performed to measure expression levels of miR-206 and histone deacetylase 4 (HDAC4). Results Compared to the control group, acute injury group showed a significant decrease in miR-206 expression (.061 ± .38, P < .05) and a significant increase in HDAC4 expression (37.05 ± 20.68, P < .05). Chronic injury group showed a significant decrease in miR-206 expression (.23 ± .19, P < .05) and a significant increase in HDAC4 expression (9.66 ± 6.12, P < .05). Discussion A tree shrew model of radiation-induced muscle injury was established by exposing TVP muscle region to radiation of 20-Gy. Experimental results indicated that injury caused by radiation persisted despite gradual healing of the TVP muscle and miR-206 regulatory pathway plays a key role in regulating radiation-induced muscle injury.

Tumor Prognostic Prediction of Nasopharyngeal Carcinoma Using CT-Based Radiomics in Non-Chinese Patients

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Full-text available

Jan 2022

Purpose We aimed to construct predictive models for the overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) for nasopharyngeal carcinoma (NPC) patients by using CT-based radiomics. Materials and Methods We collected data from 197 NPC patients. For each patient, radiomic features were extracted from the CT image acquired at pretreatment via PyRadiomics. Feature selection was performed in two steps. First, features with high inter-observer variability based on multiple tumor delineations were excluded. Then, stratified bootstrappings were performed to identify feature combinations that most frequently achieved the highest (i) area under the receiver operating characteristic curve (AUC) for predicting 3-year OS, PFS, and DMFS or (ii) Harrell’s C-index for predicting time to event. Finally, regularized logistic regression and Cox proportional hazard models with the most frequently selected feature combinations as input were tuned using cross-validation. Additionally, we examined the robustness of the constructed model to variation in tumor delineation by simulating 100 realizations of radiomic feature values to mimic features extracted from different tumor boundaries. Results The combined model that used both radiomics and clinical features yielded significantly higher AUC and Harrell’s C-index than models using either feature set alone for all outcomes (p < 0.05). The AUCs and Harrell’s C-indices of the clinical-only and radiomics-only models ranged from 0.758 ± 0.091 to 0.789 ± 0.082 and from 0.747 ± 0.062 to 0.767 ± 0.074, respectively. In comparison, the combined models achieved AUC of 0.801 ± 0.075 to 0.813 ± 0.078 and Harrell’s C-indices of 0.779 ± 0.066 to 0.796 ± 0.069. The results showed that our models were robust to variation in tumor delineation with the coefficient of variation ranging from 4.8% to 6.4% and from 6.7% to 9.3% for AUC and Harrell’s C-index, respectively. Conclusion Our results demonstrated that using CT-based radiomic features together with clinical features provided superior NPC prognostic prediction than using either clinical or radiomic features alone.

Nasopharyngeal Carcinoma: Clinical Achievements and Considerations Among Treatment Options

Article

Full-text available

Nov 2021

Nasopharyngeal carcinoma (NPC) is a severe malignancy arising from the nasopharyngeal epithelium and is southern China’s third most common cancer. With the advancement of treatment methods, early-stage NPC patients usually have a better prognosis and more prolonged survival period than those with other malignant tumors. Most treatment failures are due to distant metastasis or a locally advanced stage of NPC in the initial diagnosis. In addition, approximately 10% of patients develop local recurrence, and 10%–20% of patients experience distant metastasis after treatment. These patients have a poor prognosis, with a median survival of only approximately 10–15 months. In the rapid development of treatment options, the efficacy and safety of some treatments have been validated and approved for first-line treatment, while those of other treatments remain unclear. The present study aims to provide a comprehensive overview of recent advances in NPC treatment and explain the various therapeutic possibilities in treating locally advanced, recurrent, and metastatic NPC patients.

Deep Learning for nasopharyngeal Carcinoma Identification Using Both White Light and Narrow‐Band Imaging Endoscopy

Article

Full-text available

Oct 2021

Objectives/hypothesis: To develop a deep-learning-based automatic diagnosis system for identifying nasopharyngeal carcinoma (NPC) from noncancer (inflammation and hyperplasia), using both white light imaging (WLI) and narrow-band imaging (NBI) nasopharyngoscopy images. Study design: Retrospective study. Methods: A total of 4,783 nasopharyngoscopy images (2,898 WLI and 1,885 NBI) of 671 patients were collected and a novel deep convolutional neural network (DCNN) framework was developed named Siamese deep convolutional neural network (S-DCNN), which can simultaneously utilize WLI and NBI images to improve the classification performance. To verify the effectiveness of combining the above-mentioned two modal images for prediction, we compared the proposed S-DCNN with two baseline models, namely DCNN-1 (only considering WLI images) and DCNN-2 (only considering NBI images). Results: In the threefold cross-validation, an overall accuracy and area under the curve of the three DCNNs achieved 94.9% (95% confidence interval [CI] 93.3%-96.5%) and 0.986 (95% CI 0.982-0.992), 87.0% (95% CI 84.2%-89.7%) and 0.930 (95% CI 0.906-0.961), and 92.8% (95% CI 90.4%-95.3%) and 0.971 (95% CI 0.953-0.992), respectively. The accuracy of S-DCNN is significantly improved compared with DCNN-1 (P-value <.001) and DCNN-2 (P-value = .008). Conclusion: Using the deep-learning technology to automatically diagnose NPC under nasopharyngoscopy can provide valuable reference for NPC screening. Superior performance can be obtained by simultaneously utilizing the multimodal features of NBI image and WLI image of the same patient. Level of evidence: 3 Laryngoscope, 2021.

Are People With Blood Group O More Susceptible to Nasopharyngeal Carcinoma and Have Worse Survival Rates? A Systematic Review and Meta-Analysis

Article

Full-text available

Aug 2021

Objective Nasopharyngeal carcinoma (NPC) is a common malignant tumour in Southeast Asia, especially in southern China. ABO blood groups have been proven to play an important role in many cancers. However, it is still controversial whether the ABO blood group has a definite relationship to susceptibility to NPC and the prognosis of NPC patients. This meta-analysis was performed to elucidate the correlation between ABO blood group and NPC to provide more data for clinical practice. Methods A systematic search was performed of the Chinese National Knowledge Infrastructure (CNKI), Wanfang, Web of Science, EMBASE, and PubMed databases up to December 31, 2020. Stata 11.0 statistical software was used for this meta-analysis. Results According to the inclusion and exclusion criteria, a total of 6 studies including 6938 patients with NPC were selected. Blood group O was relevant to Chinese NPC patients, and patients with blood group O had a significantly lower incidence of NPC, while blood group A had no correlation with susceptibility to NPC. There was no difference in the 3-year overall survival (OS), locoregional relapse-free survival (LRRFS) or distant metastasis-free survival (DMFS) rates between patients with blood group O and those with non-O blood groups; worse 5-year OS, LRRFS and DMFS rates were found in patients with blood group O, whereas blood group A was not related to prognosis. Conclusion Blood group O in Chinese patients with NPC seems to be a protective factor for morbidity. However, once patients with blood group O are diagnosed with NPC, this blood group often indicates unfavourable OS, LRRFS and DMFS rates. It is recommended that more attention should be paid to the influence of blood group factor on patients in the treatment of NPC.

Molecular landscape and subtype-specific therapeutic response of nasopharyngeal carcinoma revealed by integrative pharmacogenomics

Article

Full-text available

May 2021

Nasopharyngeal carcinoma (NPC) is a malignant head and neck cancer type with high morbidity in Southeast Asia, however the pathogenic mechanism of this disease is poorly understood. Using integrative pharmacogenomics, we find that NPC subtypes maintain distinct molecular features, drug responsiveness, and graded radiation sensitivity. The epithelial carcinoma (EC) subtype is characterized by activations of microtubule polymerization and defective mitotic spindle checkpoint related genes, whereas sarcomatoid carcinoma (SC) and mixed sarcomatoid-epithelial carcinoma (MSEC) subtypes exhibit enriched epithelial-mesenchymal transition (EMT) and invasion promoting genes, which are well correlated with their morphological features. Furthermore, patient-derived organoid (PDO)-based drug test identifies potential subtype-specific treatment regimens, in that SC and MSEC subtypes are sensitive to microtubule inhibitors, whereas EC subtype is more responsive to EGFR inhibitors, which is synergistically enhanced by combining with radiotherapy. Through combinational chemoradiotherapy (CRT) screening, effective CRT regimens are also suggested for patients showing less sensitivity to radiation. Altogether, our study provides an example of applying integrative pharmacogenomics to establish a personalized precision oncology for NPC subtype-guided therapies. Nasopharyngeal carcinoma (NPC) is a malignant cancer type with high morbidity in Asia, and its current molecular classification is insufficient to predict therapy outcomes. Here the authors explore NPC subtype-specific response to therapy with a pharmacogenomics strategy integrating genomics and drug response of patient-derived organoids.

Prognostic Value of Serum Epstein-Barr Virus Antibodies and Their Correlation with TNM Classiﬁcation in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma

Article

Full-text available

Jan 2021

Purpose: This study assessed the correlation between EBV biomarkers and the 8th American Joint Committee on Cancer staging system and the prognostic values of IgG antibodies against replication and transcription activator (Rta-IgG), and IgA antibodies against Epstein-Barr nuclear antigen1 (EBNA1-IgA) and BamH1 Z transactivator (Zta-IgA) in locoregionally advanced NPC patients. Materials and methods: Serum EBV antibody levels were measured by ELISA in 435 newly diagnosed stage III-IVA NPC patients administered intensity-modulated radiation therapy±chemotherapy. The primary endpoint was progression-free survival (PFS). Results: Rta-IgG and Zta-IgA levels were positively correlated with the N stage and clinical stage. Patients with high Rta-IgG levels (>29.07 U/mL) showed a significantly inferior prognosis as indicated by progression-free survival (PFS) (77% vs. 89.8%, p=0.004), distant metastasis-free survival (DMFS) (88.3% vs. 95.8%, P=0.021), and local recurrence-free survival (LRFS) (91.2% vs. 98.3%, p=0.009). High Rta-IgG levels were also significantly associated with inferior PFS and LRFS in multivariable analyses. In the low-level EBV DNA group (≤1500 copies/ml), patients with high Rta-IgG levels had significantly inferior PFS and DMFS (both p<0.05). However, in the high-level EBV DNA group, Rta-IgG levels were not significantly associated with PFS, DMFS, and LRFS. In the advanced T stage (T3-4) subgroup, high Rta-IgG levels were also significantly associated with inferior PFS, DMFS and LRFS (both p<0.05). Conclusion: Rta-IgG and Zta-IgA levels were strongly correlated with the TNM classification. Rta-IgG level was a negative prognostic factor in locoregionally advanced NPC patients, especially those with advanced T stage or low EBV DNA level.

Relationship between cyclooxygenase-2 (COX-2) content and prognosis in nasopharyngeal carcinoma before and after radiochemotherapy

Article

Full-text available

Sep 2020

Purpose: To identify new effective prognostic indicators for patients with nasopharyngeal carcinoma (NPC). Methods: The immunohistochemical staining method was used to detect cyclooxygenase-2 (COX-2) protein in tumor tissues of 100 patients before and after chemoradiation. All the patients had stage III poorly differentiated NPC. Results: The positive expression of COX-2 was decreased before and after chemotherapy. The expression levels of COX-2 in patients before treatment was associated with T stage (p<0.05). The changes in the positive expression of COX-2 following treatment was also associated with T stage (p<0.05). The clinical response rate (CR+PR) exhibited significant differences (p<0.05) in patients with negative, weakly positive, partially positive, and strongly positive COX-2 expression before treatment. The clinical response rate (CR+PR) exhibited significant differences (p<0.05) compared with the patients who were negative or weakly positive. The COX-2 positive expression level of patients with NPC before treatment was closely associated with the survival time and survival rate of the patients (p<0.05). The changes of COX-2 positive expression were associated with the survival time and survival rate (p<0.05) in patients with NPC following treatment. T stage, COX-2 expression before treatment and changes in COX-2 expression after treatment were independent factors affecting NPC prognosis (p<0.05). Conclusion: Changes in COX-2 expression levels before and after treatment may be a useful indicator for assessing the prognosis of NPC after chemoradiotherapy.

Significance of boost dose for T4 nasopharyngeal carcinoma with residual primary lesion after intensity-modulated radiotherapy

Article

Full-text available

Jul 2021
J CANCER RES CLIN

Background Previous studies showed poorer survival in T4 disease with residual lesion. To evaluate the efficacy and toxicity of a boost dose for T4 nasopharyngeal carcinoma (NPC), patients with a residual primary lesion after intensity-modulated radiotherapy (IMRT). Methods 398 T4 NPC patients with residual primary lesions after radical IMRT were retrospectively reviewed. An IMRT boost dose of 4–6.75 Gy was delivered to the residual lesions in 2–3 fractions. Propensity score matching (PSM) was applied to balance potential confounders between groups (ratio, 1:2). The presence of Epstein–Barr virus (EBV) DNA in plasma after IMRT was used for risk stratification. Results Patients who received boost radiation had significantly improved overall survival (OS) and local recurrence-free survival (LRFS) compared with those who did not (all P < 0.05). In the matched cohort, 3-year OS was 86.6% in the boost radiation group and 72.7% in the non-boost group (P = 0.022). Three-year LRFS was 93.4% in the boost radiation group and 83.5% in the non-boost group (P = 0.022). In the subgroup analysis, boost dose was shown to significantly improve 3-year OS (88.0% vs. 74.1%, P = 0.021) in the low-risk group (with undetectable plasma EBV DNA after IMRT). The administration of a boost dose also improved 3-year OS in the high-risk group (with detectable plasma EBV DNA after IMRT) (66.7% vs. 60.0%, P = 0.375). Multivariate analysis demonstrated that boost dose was the only protective prognostic factor. Conclusion The addition of a boost dose for T4 NPC patients with residual primary lesion after radical IMRT provides satisfactory tumor control and clinical benefit. Additional timely and effective strengthening treatments are recommended for patients with detectable levels of plasma EBV DNA after radiotherapy.

Clinical characteristics and prognosis of elderly nasopharyngeal carcinoma patients receiving intensity-modulated radiotherapy

Article

Full-text available

Jul 2021
Eur Arch Oto Rhino Laryngol

Purpose: To evaluate the clinical characteristics and prognosis of elderly nasopharyngeal carcinoma (NPC) patients receiving intensity-modulated radiotherapy (IMRT). Methods: From June 2008 to October 2014, 148 newly diagnosed non-metastatic elderly NPC patients (aged ≥ 70 years) receiving IMRT were recruited. Comorbid condition was evaluated using the age-adjusted Charlson Comorbidity Index (ACCI). Kaplan-Meier method was used to estimate survival rates and the differences were compared using log-rank test. Hazard ratio (HR) and the associated 95% confidence interval (CI) were calculated using Cox proportional hazard model by means of multivariate analysis. Results: The median follow-up time was 66.35 months. Estimated OS rate at 5 years for the entire group was 61.8% (95% confidence interval [CI] 0.542-0.703). The 5-year OS rate of RT alone group was 58.4% (95% [CI] 0.490-0.696) compared with 65.2% (95% [CI] 0.534-0.796) in CRT group (p = 0.45). In patients receiving IMRT only, ACCI score equal to 3 was correlated with superior 5-year OS rate in comparison with higher ACCI score 62.1% (95% [CI] 0.510-0.766) to 48.5% (95% [CI] 0.341-0.689), respectively; p = 0.024). A 5-year OS rate of 63.1% (95% [CI] 0.537-0.741) was observed in patients younger than 75 years old compared with 57.5% (95% [CI] 0.457-0.723) in patients older (p = 0.026). Patients with early-stage disease (I-II) showed better prognosis than patients with advanced-stage (III-IV) disease (5-year OS, 72.3-55.4%, respectively; p = 0.0073). The Cox proportional hazards model suggested that age independently predicted poorer OS (HR, 1.07; 95%CI 1.00-1.15, p = 0.04). Conclusion: The survival outcome of patients aged ≥ 70 years receiving IMRT only was similar to chemoradiotherapy with significantly less acute toxicities. Among the population, age is significantly prognostic for survival outcomes.

Development and Validation of a Prognostic Nomogram Based on Residual Tumor in Patients With Nondisseminated Nasopharyngeal Carcinoma

Article

Full-text available

Sep 2020
TECHNOL CANCER RES T

Objectives: To investigate the prognostic value of residual tumor based on Magnetic resonance imaging(MRI) and establish an effective prognostic nomogram model referring to clinical,pathological and other related factors for predicting prognosis in nasopharyngeal carcinoma. Methods: Overall, 538 patients with non-metastatic, histologically-confirmed nasopharyngeal carcinoma were retrospectively examined. Data from 397 patients were used for the construction and validation of a nomogram based on the presence of residual tumor. A concordance index (C-index) was employed to assess the predictive accuracy and discriminative ability of the nomogram. Results: The 3-year survival rates in the non-residual and residual tumor cohorts were as follows: progression-free survival, 73.4% vs. 61.0%, P = 0.009; locoregional recurrence-free survival, 81.9% vs. 72.0%, P = 0.02; and distant metastasis-free survival, 80.7% vs. 73.5%, P = 0.11. Nine significant factors were included in the nomogram model. The calibration curve for the probability of progression-free survival showed that the nomogram-based predictive values had good concordance with the actual observations. Conclusion: The results showed that the patients in the residual tumor cohorts had a worse prognosis.The proposed nomogram may predict the prognosis and guide clinical decision-making concerning local residual tumors in nasopharyngeal carcinoma patients. Patients with a high risk of progression require more timely and aggressive treatment.

Prognostic and Treatment Guiding Significance of MRI-Based Tumor Burden Features and Nodal Necrosis in Nasopharyngeal Carcinoma

Article

Full-text available

Sep 2020

We aimed to develop a nomogram integrating MRI-based tumor burden features (MTBF), nodal necrosis, and some clinical factors to forecast the distant metastasis-free survival (DMFS) of patients suffering from non-metastatic nasopharyngeal carcinoma (NPC). A total of 1640 patients treated at Sun Yat-sen University Cancer Center (Guangzhou, China) from 2011 to 2016 were enrolled, among which 1148 and 492 patients were randomized to a training cohort and an internal validation cohort, respectively. Additionally, 200 and 257 patients were enrolled in the Foshan and Dongguan validation cohorts, respectively, which served as independent external validation cohorts. The MTBF were developed from the stepwise regression of six multidimensional tumor burden variables, based on which we developed a nomogram also integrating nodal necrosis and clinical features. This model divided the patients into high- and low-risk groups by an optimal cutoff. Compared with those of patients in the low-risk group, the DMFS [hazard ratio (HR): 4.76, 95% confidence interval (CI): 3.39–6.69; p < 0.0001], and progression-free survival (PFS; HR: 4.11, 95% CI: 3.13–5.39; p < 0.0001) of patients in the high-risk group were relatively poor. Furthermore, in the training cohort, the 3-year DMFS of high-risk patients who received induction chemotherapy (ICT) combined with concurrent chemoradiotherapy (CCRT) was better than that of those who were treated with CCRT alone (p = 0.0340), whereas low-risk patients who received ICT + CCRT had a similar DMFS to those who only received CCRT. The outcomes we obtained were all verified in the three validation cohorts. The survival model can be used as a reliable prognostic tool for NPC patients and is helpful to determine patients who will benefit from ICT.

Lymph node-to-primary tumor standardized uptake value ratio on PET predicts distant metastasis in nasopharyngeal carcinoma

Article

Full-text available

Nov 2020
ORAL ONCOL

Objectives To investigate the prognostic value of the relative maximum standardized uptake value (SUV) ratio between neck lymph node and primary tumor (NTR) measured by pretreatment ¹⁸F-FDG PET in patients with nasopharyngeal carcinoma (NPC). Materials and methods We retrospectively reviewed patients with non-disseminated NPC who underwent PET scans before radical intensity-modulated radiotherapy (IMRT). Receiver operating characteristic analysis was performed to identify the optimal cut-off value for NTR. The prognostic value of NTR for distant metastasis-free survival (DMFS) was evaluated using Kaplan-Meier method for survival analyses and Cox regression for multivariable analysis. Results Among the 437 eligible patients, the median follow-up time was 62.9 (range, 2.1–113.0) months. Patients with high NTR (NTR > 0.9181) experienced significantly worse DMFS (5-year 80.5% vs. 91.6%, P < 0.001). In the subgroup analysis, we found that patients with high NTR had significantly lower DMFS in T1-2 category (5-year 86.1% vs. 98.1%, P = 0.002), T3-4 category (5-year 71.5% vs. 86.2%, P = 0.010), N2-3 category (5-year 75.3% vs. 86.2%, P = 0.048), and stage IVA-B (5-year 69.8% vs. 85.4%, P = 0.012). Multivariable analysis showed that NTR was an independent prognostic factor for DMFS (HR 2.20, 95% CI 1.20–4.03, P = 0.011). Conclusion Pretreatment NTR is an easily accessible but potential prognosticator for DMFS in NPC patients treated by IMRT, which may help in providing more personalized treatment or designing future clinical trials.

FACTORS THAT HAVE PROGNOSTIC VALUES IN THE MANAGEMENT OF NASOPHARYNGEAL CARCINOMA PATIENTS

Article

Mar 2020

Introduction: The survival rate of Nasopharyngeal carcinoma (NPC) patients is influenced by several prognostic factors, Such aspatient factors, tumor factors and therapeutic interventions carried out as well as the quality of care. Tumor factors in the form of spread of local invasion, regional lymphatic involvementand metastasis that is reflected in the TNM stage (Tumor, Nodule and Metastatic) are the most important prognostic factors of NPC. Objective: To determine the Prognostic factors that effectedsurvival rate of nasopharyngeal carcinoma patients. Material and methods: Analytic observational studywith particular design of survival analysis. Data was taken from medical records and then performed survival analysis on the studiedfactors. Sample of this studywas all patients who were first diagnosed NPC From January 2013 until December 2013 and meetinclusion and exclusion criteria is52 patients. Results:From 52 patients in the fifth year, 50% died and 50% survive. Survival was worse in the 30-39 year age group (30.8%), male sex (47.2%), Stage IV (44.4%), T4 size (40%), N1 size (23,1%), Distant metastases (40%), WHO type III (48.5%), chemoradiation (48.9%). In multivariate analysis, it was found that the variables that most influenced the survival of NPC patients based on p <0.05 and based on hazard ratio strength were T-size, N-size categories and Metastasis with 95% CI. Conclusion: Prognostic factors that affect the survival of NPC patients in RSUP. Dr. Mohammad Hoesin Palembang is a category of size T, N, and Metastasis.

MiR-375 Inhibits the Proliferation and Invasion of Nasopharyngeal Carcinoma Cells by Suppressing PDK1

Article

Full-text available

Mar 2020
BMRI

Purpose: In patients with nasopharyngeal carcinoma (NPC), the expression of PDK1 is remarkably improved in NPC tissue and correlated with the clinicopathological severity of NPC. We expressed miR-375 in NPC cells to study the effects on PDK1 gene expression. We also investigated the mechanism by which miR-375 affects the biological behavior of NPC cells through effects on PDK1. Methods: qRT-PCR was carried out to analyze miR-375 and PDK1 levels in NPC cells. NPC cells were transfected with miR-375 inhibitor or miR-375 mimic. CCK-8 testing, colony formation testing, transwell testing, and flow cytometry analysis were carried out to quantify the cells' biological behavior. Rescue experiments demonstrated that the recovery of PDK1 expression was able to reverse the influence of miR-375 inhibition on NPC diffusion and intrusion. The interaction between miR-375 and PDK1 was verified by dual-luciferase reporter gene testing. Results: The results revealed that miR-375 has a negative regulatory effect on PDK1 expression in NPC cells. Furthermore, PDK1 is a target gene for miR-375. The empirical results obtained demonstrated a negative correlation between tumor development and the level of miR-375 expression in NPC tissues. The excessive expression of miR-375 and the downregulation of PDK1 facilitated the diffusion and invasion of NPC cells. Conclusion: The diffusion and incursion of NPC cells may be inhibited by direct targeting of PDK1 and decreasing the expression of miR-375. Our study highlights efforts to target PDK1 and miR-375 as potential therapeutic strategies for use in the treatment of NPC.

Induction versus adjuvant chemotherapy combined with concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: A propensity score-matched analysis

Article

Full-text available

Jun 2020
ORAL ONCOL

Objectives To explore the role of induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) and CCRT plus adjuvant chemotherapy (AC) in locoregionally advanced nasopharyngeal carcinoma (LANPC). Materials and methods The propensity score-matched (PSM) method was adopted to balance variables. We identified independent prognostic factors using Cox regression analysis and compared outcomes between two chemotherapy treatment combinations for patients in different subgroups. Results A total of 550 patients were selected by one-to-two PSM. Survival outcomes for the matched data set indicated that the IC + CCRT group achieved higher 5-year overall survival (OS; 89.3% vs 85.3%, P = 0.119), failure-free survival (FFS; 80.2% vs 79.0%, P = 0.722) and distant metastasis-free survival (DMFS; 87.4% vs 84.4%, P = 0.322) compared with CCRT + AC, although this was statistically non-significant. Subgroup analysis revealed that IC + CCRT was associated with significantly improved OS (Hazard ratio [HR] = 2.68, 95% Confidence interval [CI] = 1.16–6.22, P = 0.017), FFS (HR = 1.94, 95% CI = 1.06–3.57, P = 0.029) and locoregional relapse-free survival (LRRFS; HR = 2.63, 95% CI = 1.04–6.68, P = 0.034) in T3 disease. Moreover, this combination of treatment could significantly prolong OS (HR = 3.72, 95% CI = 1.41–9.80, P = 0.004) in N2 disease. However, the superiority of CCRT + AC was only observed in LRRFS (HR = 0.18, 95% CI 0.04–0.79, P = 0.010) for the T4 subgroup. Conclusion IC + CCRT should be strongly considered by patients with LANPC, especially those with T3 or N2 disease.

TRIM21–SERPINB5 aids GMPS repression to protect nasopharyngeal carcinoma cells from radiation-induced apoptosis

Article

Full-text available

Dec 2020
J BIOMED SCI

Background: The main strategy against nasopharyngeal carcinoma (NPC) is radiotherapy. However, radioresistance mediated recurrence is a leading clinical bottleneck in NPC. Revealing the mechanism of NPC radioresistance will help improve the therapeutic effect. Methods: In this study, the role of TRIM21 (tripartite motif-containing 21) in NPC receiving ionizing radiation was firstly examined both in vivo and in vitro. Mass spectrometry analysis was performed to identify the downstream targets of TRIM21. NPC cells with TRIM21 or SERPINB5 (serpin family B member 5) overexpression or knockout were used to determine the epistatic relationship among SERPINB5, GMPS (guanine monophosphate synthase) and TRIM21. Flow cytometry, co-immunoprecipitation, western blot and immunofluorescence were employed to strengthen the results. Finally, immunohistochemistry using 4 radiosensitive and 8 radioresistent NPC patient samples was perform to examine the association between SERPINB5 or GMPS expression and patient radio-sensitivity. Results: As an E3 ligase, TRIM21 was highly expressed in NPC. After ionizing radiation, TRIM21 repressed TP53 expression by mediating GMPS ubiquitination and degradation. Overexpression of TRIM21 protected NPC cells from radiation mediated cell apoptosis in vitro and in vivo. Further analysis revealed that TRIM21 mediated GMPS repression was dependent on SERPINB5, and SERPINB5 served as an adaptor which prevented GMPS from entering into the nucleus and introduced TRIM21 for GMPS ubiquitination. Moreover, the in vitro and in vivo results validated the finding that SERPINB5 promoted NPC cell radioresistance, and the radioresistant patients had higher SERPINB5 expression. Conclusions: Overall, our data showed that TRIM21-SERPINB5-mediated GMPS degradation facilitated TP53 repression, which promoted the radioresistance of NPC cells. This novel working model related to TP53 suppression provided new insight into NPC radioresistence clinically.

Enhancing Nasopharyngeal Carcinoma Survival Prediction: Integrating Pre- and Post-Treatment MRI Radiomics with Clinical Data

Article

Apr 2024

Recurrences are frequent in nasopharyngeal carcinoma (NPC) despite high remission rates with treatment, leading to considerable morbidity. This study aimed to develop a prediction model for NPC survival by harnessing both pre- and post-treatment magnetic resonance imaging (MRI) radiomics in conjunction with clinical data, focusing on 3-year progression-free survival (PFS) as the primary outcome. Our comprehensive approach involved retrospective clinical and MRI data collection of 276 eligible NPC patients from three independent hospitals (180 in the training cohort, 46 in the validation cohort, and 50 in the external cohort) who underwent MRI scans twice, once within 2 months prior to treatment and once within 10 months after treatment. From the contrast-enhanced T1-weighted images before and after treatment, 3404 radiomics features were extracted. These features were not only derived from the primary lesion but also from the adjacent lymph nodes surrounding the tumor. We conducted appropriate feature selection pipelines, followed by Cox proportional hazards models for survival analysis. Model evaluation was performed using receiver operating characteristic (ROC) analysis, the Kaplan–Meier method, and nomogram construction. Our study unveiled several crucial predictors of NPC survival, notably highlighting the synergistic combination of pre- and post-treatment data in both clinical and radiomics assessments. Our prediction model demonstrated robust performance, with an accuracy of AUCs of 0.66 (95% CI: 0.536–0.779) in the training cohort, 0.717 (95% CI: 0.536–0.883) in the testing cohort, and 0.827 (95% CI: 0.684–0.948) in validation cohort in prognosticating patient outcomes. Our study presented a novel and effective prediction model for NPC survival, leveraging both pre- and post-treatment clinical data in conjunction with MRI features. Its constructed nomogram provides potentially significant implications for NPC research, offering clinicians a valuable tool for individualized treatment planning and patient counseling.

A prospective, single-arm trial of PD-1 inhibitors plus chemoradiotherapy for solitary metachronous metastasis nasopharyngeal carcinoma

Article

Jan 2024

Significance of chemotherapy for older patients with nasopharyngeal carcinoma in the intensity-modulated radiotherapy era: A propensity score matching analysis

Article

Nov 2023

Promoting the dissolution of delta ferrites by cyclic heat treatment in martensitic heat-resistant steel

Article

Nov 2022

Quickly eliminating delta ferrites in martensitic heat-resistant stainless steel is a recurring problem. We found that cyclic heat treatment can significantly promote the dissolution of delta ferrites in martensitic heat-resistant stainless steel. Therefore, in this paper, the promoting mechanism of cyclic heat treatment on the dissolution of delta ferrites was examined. The results showed that shape and distribution position have important effects on the dissolution rate of delta ferrites. Under a single heating process, delta ferrites transferred from the boundaries to the interior of austenite grains, with the specific surface area significantly decreasing with heating time, which led to a decrease in the dissolution rate of delta ferrites. Cyclic heat treatment can keep the delta ferrites on the boundaries of austenite grains while maintaining a large specific surface area, which is the reason for the high dissolution rate of delta ferrites under the cyclic heat treatment process.

Neck level Ib-sparing versus level Ib-irradiation in intensity-modulated radiotherapy for the treatment of nasopharyngeal carcinoma with high-risk factors: A propensity score-matched cohort study

Article

Nov 2022
RADIOTHER ONCOL

Aim Level Ib lymph nodes metastasis is rare in nasopharyngeal carcinoma (NPC). We aimed to evaluate the feasibility of sparing level Ib-irradiation in NPC patients with high-risk factors. Materials and methods Four hundred forty-three NPC patients with radiologic extranodal extension (rENE) or level II lymph node maximal axial diameter (MAD) ≥20 mm treated by intensity-modulated radiotherapy (IMRT) between 2009 and 2012 were included in this study. Propensity score matching (PSM) was applied to balance potential prognostic factors (including age, sex, T and N stage, pretreatment EBV DNA level, and level II rENE and MAD) between patients who received and omitted level Ib irradiation. Kaplan–Meier analysis and the log-rank test were used to compare regional survival outcomes. Results PSM resulted in 169 matched pairs of eligible patients. The median follow-up period was 119 months in the matched cohort. The number of level Ib failure in the level Ib-sparing and level-Ib irradiation groups were 3/169 (1.8%) vs 2/169 (1.2%), P>0.999. And the 5-year regional relapse-free survival (RRFS) rates of the two groups were 88.4% vs 92.6%, respectively. After PSM, RRFS (hazard ratio [HR]: 1.508, 95% confidence interval [CI]: 0.762-2.986, P=0.239), OS (HR: 1.219, 95% CI: 0.754-1.972, P=0.418), distant metastasis-free survival (DMFS) (HR: 1.605, 95% CI: 0.900-2.863, P=0.109), and local relapse-free (LRFS) (HR: 0.956, 95% CI: 0.436-2.095, P=0.910) were similar in the two arms. The incidence of grade ≥1 dry mouth after 5 years was higher in the level Ib-irradiation group (27.5% vs. 16.5%, P=0.029). However, the incidences of grade 3-4 late toxicities were similar between the two groups. Conclusion Neck level Ib-sparing appears to be safe and feasible in NPC patients with rENE or level II MAD ≥20 mm and negative level Ib lymph nodes. Compared with cervical level Ib-irradiation, omission of irradiation to level Ib provides less dry mouth symptom.

Real World Presentation and Treatment Outcomes with a Predominant Induction Chemotherapy Based Approach in Nasopharyngeal Carcinoma: A Sixteen Year Report from a Teaching Hospital in India

Article

Oct 2022
CANCER INVEST

Introduction: Nasopharyngeal carcinoma (NPC) is a rare malignancy in India except in north- eastern states. We present our institutional experience of 16 years highlighting management, outcomes, responses and toxicities . Materials and methods: Nasopharyngeal carcinoma patients registered at our center during the period of 2000-2015. The primary objective of the study was to assess the overall survival (OS). Secondary outcome included determinations of response rates, progression free survival (PFS) and to assess treatment-related toxicity (CTCAE v4.0). Institute ethics committee approval was obtained prior to initiation of this study. Results: Data was retrieved from complete records of 222 patients out of 390 registered during study period. There were 163 males (73.4%) and 59 females (26.6%) with a male to female ratio of 2.8:1.The median age was 35 years (range 6-73). Only 5.6% (n = 12) presented in early stage disease (stage I and II) while 89.6% (n = 199) were advanced stage (stage III, IVA, IVB). Five patients (2.2%) presented as metastatic disease. Majority of patients were treated with induction chemotherapy followed by CCRT (concurrent chemoradiation) {76.1%, n = 169}. Relapses were documented in 10.4% patients. 5% patients had loco-regional relapse while distant metastases was seen in 4% patients. The 3-year PFS (progression free survival) and OS (overall survival) rates are 60.9% and 68.4% respectively. Achieving a CR predicted superior OS on multivariate analysis. Conclusions: Nasopharyngeal carcinoma is a rare malignancy and majority presented with advanced stages. This data outlines our experience and outcomes with a predominantly induction chemotherapy followed by definitive CCRT based approach .

Nedaplatin-based chemotherapy or cisplatin-based chemotherapy combined with intensity-modulated radiotherapy achieve similar efficacy for stage II-IVa nasopharyngeal carcinoma patients

Article

Full-text available

Jul 2022

This retrospective study compared the efficacy and safety of nedaplatin-based chemoradiotherapy and cisplatin-based chemoradiotherapy in stage II-IVa nasopharyngeal carcinoma (NPC) patients. Patients treated with cisplatin-based or nedaplatin-based chemoradiotherapy between January 2012 and December 2015 were evaluated. Survival was estimated by the Kaplan‒Meier method and compared by the log-rank test. Multivariate analysis was performed using the Cox proportional hazards model. A cohort of 538 NPC patients was enrolled. There were no significant differences in the 5-year overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRRFS), or distant metastasis-free survival (DMFS) between the cisplatin and nedaplatin groups. During the whole treatment course, patients in the cisplatin group had higher incidences of grade 3‒4 vomiting and anorexia, while patients in the nedaplatin group had higher incidences of grade 3‒4 leucopenia and mucositis. In terms of late toxicities, patients in the cisplatin group had a higher incidence of xerostomia. In multivariate analysis, T stage, N stage, and clinical stage were prognostic factors for OS, PFS, and DMFS. In subgroup analyses, nedaplatin-based chemotherapy achieved comparable treatment outcomes in specific populations stratified by age, sex, ECOG PS score and clinical stage. Cisplatin and nedaplatin are effective choices for stage II-IVa NPC patients, with a different spectrum of side effects.

A Novel Fully Automated MRI-Based Deep-Learning Method for Segmentation of Nasopharyngeal Carcinoma Lymph Nodes

Article

Jul 2022

PurposeNasopharyngeal carcinoma (NPC) is epidemic in south China, especially in Guangdong province. Radiotherapy is the main treatment, with the non-keratinizing type accounting for more than 95% of cases. Metastatic lymph nodes, which should be included in the radiotherapy target volume, are detected among approximately 70–80% of cases when the disease is first diagnosed. Accurate spatial modelling of metastatic lymph nodes is important for successful treatment.Methods We propose a coarse-to-fine deep supervision convolutional neural network (CF-Net) to perform metastatic lymph node segmentation using a 3D residual V-Net. Contrast-enhanced axial T1-weighted (T1C) magnetic resonance images of more than 6000 patients with NPC were enrolled in this study. We used the probability map predicted at a coarse scale as the weight map for training at a fine scale. This method draws attention to a fine scale within an area already detected at a coarse scale.ResultsCF-Net achieves a median Dice score of 81.0% in the segmentation of metastatic lymph nodes with a sensitivity and specificity of 79.1% and 99.2%, respectively.Conclusion The results show that our method can accurately identify, locate and segment NPC lymph nodes. We compared CF-Net with popular methods: V-Net, DeepLab-v3, HR-Net, and DenseNet. Our proposed method, across all variants, consistently and statistically outperformed the other models.

Cost-Effectiveness analysis of combining plasma Epstein-Barr virus DNA testing and different surveillance imaging modalities for nasopharyngeal carcinoma patients in first remission

Article

May 2022
ORAL ONCOL

Background To evaluate the cost-effectiveness of stage-based post-radiotherapy (PRT) nasopharyngeal carcinoma (NPC) surveillance strategies. Methods Four post-radiotherapy surveillance strategies were established by a Markov model based on data from 1664 patients: 1) clinical follow-up (CFP) with biannual Epstein-Barr virus (EBV) DNA (EBV DNA strategy); 2) CFP with biannual EBV DNA, annual head and neck magnetic resonance imaging (HNMRI), chest X-ray, abdominal ultrasonography, bone scan (only for the first two years) for five years (MCWU strategy); 3) CFP with biannual EBV DNA, annual HNMRI, chest, abdomen, pelvic computerized tomography (CT) and bone scan for the first two years, followed by annual MCWU strategy (without bone scans) for the last three years (CT strategy); 4) CFP with biannual EBV DNA, annual whole-body positron emission/computerized tomography (PET/CT) for the first two years and biannual EBV DNA for the last three years (PET/CT strategy). Results Compared with the EBV DNA strategy, the MCWU, CT, and PET/CT strategies gained 0.017, 0.047, and 0.082 quality-adjusted life years (QALY) for stage I–II patients. For stage III and IVa patients, the PET/CT strategy had a favorable incremental effectiveness (ICERs) of 0.277 and 0.385 QALY, respectively. The ICERs for the MCWU, CT, and PET/CT strategies were $74,037, $34,882, and $34,696 for stage III and $62,364, $27,981, and $28,340 for stage IVa, respectively. Conclusion EBV DNA strategy was cost-effective for the long-term surveillance of stage I–II NPC patients with CR. PET/CT strategy was recommeded for patients having IVa NPC. As for stage III NPC, PET/CT strategy was still acceptable with the development of economy in China.

Nomogram-aided individual induction chemotherapy regimen selection in advanced nasopharyngeal carcinoma

Article

Nov 2021
ORAL ONCOL

Objective We undertook this study to clarify how TPF, TP and PF induction chemotherapy (IC) regimens benefit for nasopharyngeal carcinoma (NPC) patients with different risk of disease progression. Materials and Methods Patients with newly diagnosed, stage III-IVA NPC were included. A quantitative nomogram was built using the independent prognostic factors identified for disease-free survival (DFS). Patients were stratified into low-risk and high-risk groups by the nomogram. Survival outcomes and toxicities between different IC regimens were compared. Results In total, 1647 (41.0%), 1123 (28.0%) and 1242 (31.0%) patients received TPF, PF and TP regimen, respectively. Consequently, 2253 (56.2%) patients were clarified as low-risk group and the other 1759 (43.8%) as high-risk group. Survival outcomes did not significantly differ between TPF, PF and TP regimens within the low-risk group. However, TPF was associated with significantly improved 3-year DFS (76.2% vs. 67.5% vs. 68.3%), overall survival (88.3% vs. 84.1% vs. 83.9%), distant metastasis-free survival (81.9% vs. 75.0% vs. 77.4%) and locoregional relapse-free survival (92.0% vs. 87.5% vs. 86.9%; all P < 0.05) compared with PF and TP within high-risk group. Multivariate analysis also confirmed these findings. Toxicity analysis showed that TP regimen has the highest percentage of grade 3–5 hematologic toxicities while PF regimen achieved the lowest percentages of overall grade 3–5 adverse events. Conclusions Patients with high risk should receive TPF for better efficacy and PF may be a better choice for low-risk patients with regard to less grade 3–5 toxicities.

Long-Term Results of Intensity-Modulated Radiotherapy for T4 Nasopharyngeal Carcinoma: New Insight into the Value of Concurrent Chemotherapy

Article

Jun 2021

The aim of the study was to report long-term results of intensity-modulated radiotherapy for patients with T4 classification nasopharyngeal carcinoma(NPC). From September 2007 to January 2013, 155 patients were retrospectively analyzed. The estimated 10-year local recurrent–free survival(LRFS), regional recurrent–free survival(RRFS), distant metastasis–free survival(DMFS), and overall survival(OS) rates were 79.4%, 93.2%, 69.0%, and 54.2%, respectively. Cycle number of chemotherapy was significant predictor of LRFS, OS and PFS. There was no significant difference on survival rates between patients treated with induction chemotherapy(IC) plus concurrent chemoradiotherapy(CCRT) and patients with IC plus IMRT and adjuvant chemotherapy(AC).

Clinical Outcomes and Prognostic Factors of Locally Advanced Nasopharyngeal Cancer Treated with Intensity Modulated Radiotherapy: First Experience Report from Northeast India

Article

May 2021
Indian J Otolaryngol

The aim is to retrospectively evaluate the clinical outcomes and prognostic factors in patients of locally advanced nasopharyngeal cancer (NPC) treated with intensity-modulated radiotherapy (IMRT). The northeastern states report relatively more NPC cases in comparison to other states of India. This study is an attempt to assess the treatment outcomes and prognostic factors of locally advanced NPC who had been treated with definitive radiotherapy with or without chemotherapy in our institute from 2012 to 2016 using IMRT. This is a single institutional retrospective study. Thirty-one consecutive patients of locally advanced NPC treated with definitive chemoradiation using the IMRT technique between 2012 to 2016 were evaluated. The survival was analyzed using Kaplan–Meir method and their relations with various clinicopathologic parameters were compared. After a median follow-up time of 36 months, the 5-year overall survival (OS) and disease-free survival (DFS) was 47.3% and 26.1% respectively. The younger patients of < 50 years had improved OS (p = 0.05). Patients of stage IVA had inferior 5-year OS (p = 0.1) and 5-years DFS (0.02) than those of stage III. The patients who received neoadjuvant chemotherapy showed improved DFS at 5 years (p = 0.09). The treatment-related toxicities were within acceptable limit. This retrospective analysis has reported outcomes of locally advanced NPC patients treated with IMRT with concurrent chemotherapy when IMRT was first introduced in our institute. This is the first of its kind from the Northeastern region of India.

Clinical Characteristics and Prognostic Factors of Early and Late Recurrence After Definitive Radiotherapy for Nasopharyngeal Carcinoma

Article

Full-text available

Aug 2020

We investigated the clinical characteristics, prognostic factors, and post-recurrence prognostic factors of early- and late-recurrence patients for nasopharyngeal carcinoma (NPC) after definitive intensity-modulated radiation therapy (IMRT). This was a single-center retrospective analysis of patients in China from January 2010 to December 2015. The prognostic factors for overall survival (OS) and post-recurrence OS of early- and late-recurrence patients were identified using univariate and multivariate Cox regression analyses. Of the 9,468 patients included, 409 (4.3%), 325 (3.4%), and 182(1.9%) developed purely local recurrence, purely regional recurrence, and locoregional recurrence during follow-up, respectively. In the purely local recurrence group, 192 patients (46.9%) developed early local recurrence (ETR), and 217 patients (53.1%) developed late local recurrence (LTR). Of the 192 ETR patients, multivariate Cox regression analysis revealed that age and gender were independent risk factors of OS, and post-recurrence best supportive treatment (PRBST) was associated with poorer post-recurrence OS. Of the 217 LTR patients, the results revealed that baseline value of EBV-DNA was an independent risk factor for OS, while PRBST was associated with poorer post-recurrence OS. In the purely regional recurrence group, 183 patients (56.3%) developed early regional recurrence (ENR), and 142 patients (43.7%) developed late regional recurrence (LNR). Of the 183 ENR patients, multivariate Cox regression analysis revealed that alcohol abuse and TNM stage were independent risk factors of OS, while alcohol drinkers and PRBST were associated with poorer post-recurrence OS. Of the 142 LNR patients, PRBST was associated with poorer post-recurrence OS. In the locoregional recurrence group, 87 patients (47.8%) developed early locoregional recurrence (ELR), and 95 patients (52.2%) developed late locoregional recurrence (LLR). Of the 87 ELR patients, multivariate Cox regression analysis revealed that N stage and TNM stage were independent risk factors of OS, and N2/3 stage and PRBST were associated with poorer post-recurrence OS. Of the 95 LLR patients, the results revealed that T stage was an independent risk factor for OS, while T3/4 stage and PRBST were associated with poorer post-recurrence OS. Patients with LTR/LNR/LLR demonstrate significantly better OS compared with patients with ETR/ENR/ELR, Nevertheless, post-recurrence OS between patients with ETR/ENR/ELR and LTR/LNR/LLR was not significantly different.

An optimal posttreatment surveillance strategy for cancer survivors based on an individualized risk-based approach

Article

Full-text available

Aug 2020

The optimal post-treatment surveillance strategy that can detect early recurrence of a cancer within limited visits remains unexplored. Here we adopt nasopharyngeal carcinoma as the study model to establish an approach to surveillance that balances the effectiveness of disease detection versus costs. A total of 7,043 newly-diagnosed patients are grouped according to a clinic-molecular risk grouping system. We use a random survival forest model to simulate the monthly probability of disease recurrence, and thereby establish risk-based surveillance arrangements that can maximize the efficacy of recurrence detection per visit. Markov decision-analytic models further validate that the risk-based surveillance outperforms the control strategies and is the most cost-effective. These results are confirmed in an external validation cohort. Finally, we recommend the risk-based surveillance arrangement which requires 10, 11, 13 and 14 visits for group I to IV. Our surveillance strategies might pave the way for individualized and economic surveillance for cancer survivors. Monitoring patients for the recurrence of cancer can be costly and it is important to devise the optimum strategy for a given cancer and population. Here, the authors use nasopharyngeal cancer as a model and show using patient data an optimal follow-up schedule to detect recurrence of the cancer.

Prognostic factors in metastatic nasopharyngeal carcinoma

Article

Full-text available

Jul 2020
Braz J Otorhinolaryngol

Introduction Nasopharyngeal carcinoma has the highest metastatic potential of all head and neck cancers. The survival time of patients with nasopharyngeal carcinoma has improved significantly in the last decades due to the use of combination of chemotherapy and radiotherapy, as well as advances in radiotherapy techniques. However, appropriately 30% of patients with nasopharyngeal carcinoma suffer a poor prognosis, mainly due to distant metastasis. Objective The study aimed to identify the survival and prognostic factors in metastatic nasopharyngeal carcinoma. Methods A retrospective analysis was conducted in patients treated for synchronous metastatic nasopharyngeal carcinoma or metachronous metastatic nasopharyngeal carcinoma for 14 years (2003–2016). Overall survival was analyzed using the Kaplan-Meier method and compared using the log-rank test for the whole population and both groups of patients. Multivariate analysis was performed using the Cox model; p-values < 0.05 were considered to indicate statistical significance. Results One hundred and twelve patients with metastatic nasopharyngeal carcinoma were included (51 patients with metastatic nasopharyngeal carcinoma, and 61 patients with metachronous metastatic nasopharyngeal carcinoma). In the whole population, the median overall survival was 10 months (1–156 months). In the multivariate analysis, female gender, poor performance status (WHO > 1) and metachronous metastasis were independent prognostic factors. In the metastatic nasopharyngeal carcinoma patients, the median overall survival was 13 months (1–156 months). In multivariate analysis, independent prognostic factors were non-oligometastatic disease, severe (G3‒G4) chemotherapy toxicity and the lack of nasopharyngeal and metastatic site irradiation. In the metachronous metastatic nasopharyngeal carcinoma patients, the median overall survival was 7 months (1–41 months). In multivariate analysis, the poor performance status (WHO > 1) was an independent metastatic nasopharyngeal carcinoma prognostic factor. Conclusion Oligometastatic patients with synchronous metastatic nasopharyngeal carcinoma had better survival. The locoregional treatment of primitive nasopharyngeal carcinoma improved survival in patients with metastatic nasopharyngeal carcinoma who responded to induction chemotherapy. Local irradiation of metastatic sites improved survival of metastatic nasopharyngeal carcinoma patients. Grade 3 or 4 chemotherapy toxicity altered survival among patients with synchronous metastatic nasopharyngeal carcinoma.

An exceptional case of a duodenal metastasis from a nasopharyngeal carcinoma

Article

Full-text available

Mar 2020

Nasopharyngeal carcinoma (NPC) is a common head and neck cancer. The involvement of the digestive tract is exceptional. Herein we report the case of a 32-year-old man who initially presented with a T3N3M0 NPC according to the 7th edition of American Joint Committee on Cancer (AJCC) tumor/node/metastasis (TNM) classifications. The patient had a complete response after a treatment based on radiotherapy and concomitant chemotherapy. Fifteen months later, he presented with digestive symptoms. After explorations, radiological and histological findings concluded to a duodenal relapse of his NPC To our knowledge, this is the first case of a duodenal metastasis of a NPC reported in the literature.

Randomized clinical trial on 7-day-continuous accelerated irradiation (CAIR) of head and neck cancer - Report on 3-year tumour control and normal tissue toxicity

Article

Full-text available

May 2000
RADIOTHER ONCOL

To evaluate tumour and normal tissues 3-year response to 7-day-a-week continuous accelerated irradiation (CAIR) compared to a conventional treatment (5 days per week) in a randomized trial. One hundred patients with squamous cell carcinoma of the head and neck in stage T(2-4)N(0-1)M(0) were entered into the trial between December 1, 1993 and June 30, 1996. Dose per fraction of 2.0 Gy (to the end of 1994), and 1.8 Gy (since January 1, 1995) was the same in both arms and delivered once a day at regular 24-h intervals to total dose in the range of 66-72 Gy (depending on tumour stage). The only difference was overall treatment time being 5 weeks in the CAIR and 7 weeks in control arm. Actuarial 3-year local tumour control was 82% in the CAIR and 37% in the control group (P<0.0001) with reduction in local recurrence rate of 83%. Actuarial 3-year overall survival was 78 and 32% (P<0.0001), respectively. Confluent mucositis was significantly more severe and lasted longer in the CAIR than in control arm. After 2.0 Gy fractions five of 23 patients (22%) in the CAIR developed early necroses over a period of 2-4 months of follow-up which can be considered as a consequential to severe protracted acute mucosal reactions (CLE). For this reason dose per fraction was lowered to 1. 8 Gy and the CLE was not observed again until now. Thus the overall rate of CLE decreased to 10%. The gain in tumour control is likely the effect of shortening of overall treatment time by 14 days and regular continuous dose delivery during the whole course of radiation therapy including weekends. A 7-day schedule produces more severe acute mucosal reactions lasting longer than in conventional fractionation, however tolerable by patients. Relatively high rate (22%) of CLE in the 7-day arm observed during the first year of the study was eliminated by decreasing dose per fraction from 2.0 Gy to 1.8 Gy.

Concurrent Chemotherapy and Radiotherapy for Organ Preservation in Advanced Laryngeal Cancer

Article

Full-text available

Nov 2003
NEW ENGL J MED

Induction chemotherapy with cisplatin plus fluorouracil followed by radiotherapy is the standard alternative to total laryngectomy for patients with locally advanced laryngeal cancer. The value of adding chemotherapy to radiotherapy and the optimal timing of chemotherapy are unknown. We randomly assigned patients with locally advanced cancer of the larynx to one of three treatments: induction cisplatin plus fluorouracil followed by radiotherapy, radiotherapy with concurrent administration of cisplatin, or radiotherapy alone. The primary end point was preservation of the larynx. A total of 547 patients were randomly assigned to one of the three study groups. The median follow-up period was 3.8 years. At two years, the proportion of patients who had an intact larynx after radiotherapy with concurrent cisplatin (88 percent) differed significantly from the proportions in the groups given induction chemotherapy followed by radiotherapy (75 percent, P=0.005) or radiotherapy alone (70 percent, P<0.001). The rate of locoregional control was also significantly better with radiotherapy and concurrent cisplatin (78 percent, vs. 61 percent with induction cisplatin plus fluorouracil followed by radiotherapy and 56 percent with radiotherapy alone). Both of the chemotherapy-based regimens suppressed distant metastases and resulted in better disease-free survival than radiotherapy alone. However, overall survival rates were similar in all three groups. The rate of high-grade toxic effects was greater with the chemotherapy-based regimens (81 percent with induction cisplatin plus fluorouracil followed by radiotherapy and 82 percent with radiotherapy with concurrent cisplatin, vs. 61 percent with radiotherapy alone). The mucosal toxicity of concurrent radiotherapy and cisplatin was nearly twice as frequent as the mucosal toxicity of the other two treatments during radiotherapy. In patients with laryngeal cancer, radiotherapy with concurrent administration of cisplatin is superior to induction chemotherapy followed by radiotherapy or radiotherapy alone for laryngeal preservation and locoregional control.

Final Results of the 94–01 French Head and Neck Oncology and Radiotherapy Group Randomized Trial Comparing Radiotherapy Alone With Concomitant Radiochemotherapy in Advanced-Stage Oropharynx Carcinoma

Article

Full-text available

Feb 2004

We report the 5-year survival and late toxicity results of a randomized clinical trial, which showed a 3-year improvement in overall survival and locoregional control of stage III or IV oropharynx carcinoma, using concomitant radiochemotherapy (arm B), compared with standard radiotherapy (arm A). A total of 226 patients were entered onto a phase III multicenter randomized trial comparing radiotherapy alone (70 Gy in 35 fractions; arm A) with concomitant radiochemotherapy (70 Gy in 35 fractions with three cycles of a 4-day regimen comprising carboplatin and fluorouracil; arm B). Prognostic factors were evaluated by univariate and multivariate analysis. Five-year late toxicity was evaluated using National Cancer Institute Common Toxicity Criteria for neurological toxicity, hearing, taste, mandibula, and teeth damage, and Radiation Therapy Oncology Group toxicity criteria for skin, salivary gland, and mucosa. Five-year overall survival, specific disease-free survival, and locoregional control rates were 22% and 16% (log-rank P =.05), 27% and 15% (P =.01), and 48% and 25% (P =.002), in arm B and arm A, respectively. Stage IV, hemoglobin level lower than 125 g/L, and standard treatment were independent prognostic factors of short survival and locoregional failure by univariate and multivariate analysis. One or more grade 3 to 4 complications occurred in 56% of the patients in arm B, compared with 30% in arm A (P was not significant). Concomitant radiochemotherapy improved overall survival and locoregional control rates and does not statistically increase severe late morbidity. Anemia was the most important prognostic factor for survival in both arms.

Erythropoietin to treat head and neck cancer patients with anaemia undergoing radiotherapy: randomised, double-blind, placebo-controlled trial

Article

Jan 2003

Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer (vol 349, pg 2091, 2003)

Article

Mar 2004

Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data

Article

Mar 2000

Jean-Pierre Pignon

A Radiation Therapy Oncology Group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinomas: First report of RTOG 9003

Article

Aug 2000
INT J RADIAT ONCOL

Purpose: The optimal fractionation schedule for radiotherapy of head and neck cancer has been controversial. The objective of this randomized trial was to test the efficacy of hyperfractionation and two types of accelerated fractionation individually against standard fractionation. Methods and Materials: Patients with locally advanced head and neck cancer were randomly assigned to receive radiotherapy delivered with: 1) standard fractionation at 2 Gy/fraction/day, 5 days/week, to 70 Gy/35 fractions/7 weeks; 2) hyperfractionation at 1.2 Gy/fraction, twice daily, 5 days/week to 81.6 Gy/68 fractions/7 weeks; 3) accelerated fractionation with split at 1.6 Gy/fraction, twice daily, 5 days/week, to 67.2 Gy/42 fractions/6 weeks including a 2-week rest after 38.4 Gy; or 4) accelerated fractionation with concomitant boost at 1.8 Gy/fraction/day, 5 days/week and 1.5 Gy/fraction/day to a boost field as a second daily treatment for the last 12 treatment days to 72 Gy/42 fractions/6 weeks. Of the 1113 patients entered, 1073 patients were analyzable for outcome. The median follow-up was 23 months for all analyzable patients and 41.2 months for patients alive. Results: Patients treated with hyperfractionation and accelerated fractionation with concomitant boost had significantly better local-regional control (p = 0.045 and p = 0.050 respectively) than those treated with standard fractionation. There was also a trend toward improved disease-free survival (p = 0.067 and p = 0.054 respectively) although the difference in overall survival was not significant. Patients treated with accelerated fractionation with split had similar outcome to those treated with standard fractionation. All three altered fractionation groups had significantly greater acute side effects compared to standard fractionation. However, there was no significant increase of late effects. Conclusions: Hyperfractionation and accelerated fractionation with concomitant boost are more efficacious than standard fractionation for locally advanced head and neck cancer. Acute but not late effects are also increased.

Fractionated Stereotactic Radiotherapy for 111 Patients with Residual Lesion after First Course of Radiation Therapy for Nasopharyngeal Carcinoma

Article

Sep 2008
INT J RADIAT ONCOL

Radiotherapy alone in patients with advanced nasopharyngeal cancer: comparison with an intergroup study

Article

Dec 2000
INT J RADIAT ONCOL

Five compared with six fractions per week of conventional radiotherapy of squamous-cell carcinoma of head and neck: DAHANCA 6&7 randomized controlled trial

Article

Oct 2003

Although head and neck cancer can be cured by radiotherapy, the optimum treatment time for locoregional control is unclear. We aimed to find out whether shortening of treatment time by use of six instead of five radiotherapy fractions per week improves the tumour response in squamous-cell carcinoma. We did a multicentre, controlled, randomised trial. Between January, 1992, and December, 1999, of 1485 patients treated with primary radiotherapy alone, 1476 eligible patients were randomly assigned five (n=726) or six (n=750) fractions per week at the same total dose and fraction number (66-68 Gy in 33-34 fractions to all tumour sites except well-differentiated T1 glottic tumours, which were treated with 62 Gy). All patients, except those with glottic cancers, also received the hypoxic radiosensitiser nimorazole. Analysis was by intention to treat. More than 97% of the patients received the planned total dose. Median overall treatment times were 39 days (six-fraction group) and 46 days (five-fraction group). Overall 5-year locoregional control rates were 70% and 60% for the six-fraction and five-fraction groups, respectively (p=0.0005). The whole benefit of shortening of treatment time was seen for primary tumour control (76 vs 64% for six and five fractions, p=0.0001), but was non-significant for neck-node control. Six compared with five fractions per week improved preservation of the voice among patients with laryngeal cancer (80 vs 68%, p=0.007). Disease-specific survival improved (73 vs 66% for six and five fractions, p=0.01) but not overall survival. Acute morbidity was significantly more frequent with six than with five fractions, but was transient. The shortening of overall treatment time by increase of the weekly number of fractions is beneficial in patients with head and neck cancer. The six-fractions-weekly regimen has become the standard treatment in Denmark.

The predictive value of the 1997 American Joint Committee on Cancer stage classification in determining failure patterns in nasopharyngeal carcinoma

Article

Dec 2001
CANCER-AM CANCER SOC

BACKGROUNDA retrospective analysis of treatment outcomes in patients with nasopharyngeal carcinoma (NPC) was performed in which the newly revised 1997 American Joint Committee on Cancer (AJCC) stage classification was applied and compared with the 1988 AJCC and Ho stage classifications, with emphasis on the predictive value of different staging systems in determining failure patterns in NPC.METHODS Three hundred and twenty-four patients with newly diagnosed NPC treated between September 1989 and August 1991 and originally staged according to Ho stage classification were re-staged according to the 1988 and 1997 AJCC stage classifications. In addition to stage grouping, patients were also classified into the following prognostic categories to study the failure patterns: early disease group (T1-2N0-1), advanced local disease group (T3-4N0-1), advanced nodal disease group (T1-2N2-3), and advanced locoregional disease group (T3-4N2-3). The overall survival (OAS), relapse-free survival (RFS), local relapse-free survival, nodal relapse-free survival, and distant metastases-free survival were compared among different stage groups and prognostic categories in the three staging systems.RESULTSIn the new AJCC system, the percentages of patients with Stage I, II, III, and IV disease were 15.1%, 31.5%, 28.1%, and 25.3%, respectively, whereas most patients were classified as having Stage IV disease (65.7%) in the old AJCC system and Stage II or III disease (74.1%) in the Ho system. The 5 year OAS rates in the 1997 AJCC Stage I, II, III, and IV disease were 97.7%, 78.7%, 79.5%, and 61.4%, respectively. The corresponding 5 year RFS rates were 95.7%, 64.7%, 54.5%, and 41.1%. Using the 1997 AJCC system to define the four prognostic categories, the early disease group had the lowest incidence of relapse (27.6%) and death (18.4%), whereas the advanced locoregional disease group had the highest incidence of relapse (61.4%) and death (43.2%). Both the advanced local disease group and the advanced nodal disease group had similar rates of relapse (46.7% vs. 47.2%), but local relapse was the major cause of failure in the former group (61.8%), whereas distant metastases was the major cause in the latter group (44%).CONCLUSIONS Using the 1997 AJCC staging system, the authors observed a better distribution of patient numbers as well as segregation of survival curves among different stage groups. Moreover, prognostic categories with distinct prognosis and failure patterns were definable by the new system, which has important implications in selecting appropriate patient treatment strategies. Cancer 2001;92:2845–55. © 2001 American Cancer Society.

Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: Phase III Randomized Intergroup Study 0099

Article

Apr 1998

The Southwest Oncology Group (SWOG) coordinated an Intergroup study with the participation of Radiation Therapy Oncology Group (RTOG), and Eastern Cooperative Oncology Group (ECOG). This randomized phase III trial compared chemoradiotherapy versus radiotherapy alone in patients with nasopharyngeal cancers. Radiotherapy was administered in both arms: 1.8- to 2.0-Gy/d fractions Monday to Friday for 35 to 39 fractions for a total dose of 70 Gy. The investigational arm received chemotherapy with cisplatin 100 mg/m2 on days 1, 22, and 43 during radiotherapy; postradiotherapy, chemotherapy with cisplatin 80 mg/m2 on day 1 and fluorouracil 1,000 mg/m2/d on days 1 to 4 was administered every 4 weeks for three courses. Patients were stratified by tumor stage, nodal stage, performance status, and histology. Of 193 patients registered, 147 (69 radiotherapy and 78 chemoradiotherapy) were eligible for primary analysis for survival and toxicity. The median progression-free survival (PFS) time was 15 months for eligible patients on the radiotherapy arm and was not reached for the chemo-radiotherapy group. The 3-year PFS rate was 24% versus 69%, respectively (P < .001). The median survival time was 34 months for the radiotherapy group and not reached for the chemo-radiotherapy group, and the 3-year survival rate was 47% versus 78%, respectively (P = .005). One hundred eighty-five patients were included in a secondary analysis for survival. The 3-year survival rate for patients randomized to radiotherapy was 46%, and for the chemoradiotherapy group was 76% (P < .001). We conclude that chemoradiotherapy is superior to radiotherapy alone for patients with advanced nasopharyngeal cancers with respect to PFS and overall survival.

Nasopharyngeal Carcinoma: The Significance of Neck Node Involvement in Relation to the Pattern of Distant Failure

Article

Mar 1990

The pattern of distant failure of 759 Stage I-IV cases of nasopharyngeal carcinoma was studied. The most common sites of distant metastasis were, in descending order, bone, lung and liver. The N stage, T stage and the characteristics (size and degree of fixation) of the neck nodes involved were found to be significant prognostic factors determining the development of distant metastasis. The bilaterality of neck node involvement, sex, age, haemoglobin and white blood count at diagnosis were not significant. The discriminating effect of N stage holds true in patient groups stratified for the node size and degree of fixation. The superiority of the Ho stage classification was confirmed. The high incidence of distant failure in patients with T3, N3, or bulky or fixed neck node involvement warrants further clinical trials to explore the role of adjuvant chemotherapy.

Management of local residual primary lesion of nasopharyngeal carcinoma: II. Results of prospective randomized trial on booster dose

Article

Mar 1990
INT J RADIAT ONCOL

Although the question of booster dose for residual primary lesion arises in only 5% of nasopharyngeal carcinoma patients receiving radiotherapy, it poses a difficult problem for clinicians and should be followed. Hence, to test the validity of booster dose for residual primary lesion of nasopharyngeal carcinoma, a prospective randomized trial has been designed and carried out since January 1980. All patients who had a residual lesion in the nasopharynx at 70 Gy were biopsied. Those pathologically positive for cancer were randomized into two groups: (a) positive radiation group (PRG): patients were given further irradiation to a total dose of 90 Gy by the cone-down and assault technique, and (b) positive observation group (POG): patients were given no more irradiation but were followed periodically together with those who were pathology negative (NOG). A total of 78 patients were entered. The validity of booster dose was shown by the 5-year survival rates of the PRG, POG and NOG groups: 75% (3/4), 33% (1/3), and 58% (14/24), respectively. The total local recurrence rates of these groups were 6% (1/16), 36% (5/14), and 4% (2/48), respectively. The authors believe that booster dose for pathology positive residual lesion in the nasopharynx is necessary. The four factors leading to the development of a local recurrence are: (a) residual primary lesion proved positive by pathology but left unboosted, (b) well differentiated squamous cell carcinoma in the original primary lesion, (c) mild radio-response in the cancer parenchyma, and (d) mild radio-response in the interstitial tissue.

Management of Local Residual Primary Lesion of Nasopharyngeal Carcinoma (NPC): Are Higher Doses Beneficial?

Article

Jul 1989
INT J RADIAT ONCOL

One hundred and eighty-two nasopharyngeal carcinoma (NPC) patients, treated from March 1958 through 1978, received 70 Gy or more and were left with gross residual lesion in the nasopharynx, were retrospectively analyzed. Ninety-two patients were given a boost by reduced portals to a total of 90-120 Gy (boost group) whereas for the other non-randomized 90 patients, the treatment was stopped at 70 Gy (observation group). The local recurrence, distant metastasis and 5-year survival rates of the two groups are: 35% (32/92) vs. 58% (52/90), 20% (18/92) vs. 43% (39/90), and 54% (50/92) vs. 21% (19/90), respectively. The benefit of boost is more apparent in patients with T1-2 than T3-4 lesions (p less than 0.001), at increased risk of radiation encephalo-myelitis from 5.5% to 17%. The authors believe that boost be given to patients with early Stage T or small residual lesion at the primary site of NPC.

Analysis of 1379 patients with nasopharyngeal carcinoma treated by radiation

Article

Apr 1988

One thousand three hundred seventy-nine nasopharyngeal carcinoma (NPC) patients were treated from March 1958 to December 1978. Twenty-two percent had stage I or II and 78% Stage III or IV had lesions. Two hundred twenty-Kv radiographs were used before 1960; and telecobalt was used from 1961 to 1978. Factors influencing the 5-year survival rate favorably are youth of patient, being female, pathologic condition (poorly differentiated carcinoma, 45.1% versus adenocarcinoma, 13%), stage (Stage I, 86%, Stage II, 59.5%; Stage III, 45.8%; Stage IV, 29.2%), decade admitted for treatment in the past (31% in the 1950s, 48.6% in the 1970s), total dose delivered to the nasopharynx (40 to 49 Gy, 46%; 70 to 79 Gy, 54.1%; 90 Gy or more, 64%) and prophylactic radiation to the neck regions (with prophylactic irradiation, 53.8%, without prophylactic irradiation, 23%). This implies that prophylactic radiation of the neck is crucial even without positive clinical metastasis. For those who have a residual tumor in the primary site when 70 Gy has been delivered, the total dose may be boosted to more than 90 Gy with the cone-down technique or on basis of adding 20 Gy to the dose at which the primary lesion disappeared grossly. The common postirradiation complications are: radiation myelitis, trismus, and otitis media. Because disease recurred in some patients after the fifth year, NPC patients should be followed for at least 10 years.

Brizel DM, Dodge RK, Clough RW, Dewhirst MWOxygenation of head and neck cancer: changes during radiotherapy and impact on treatment outcome. Radiother Oncol 53: 113-117

Article

Nov 1999
RADIOTHER ONCOL

To evaluate the long term clinical significance of tumor oxygenation in a population of head and neck cancer patients receiving radiotherapy and to assess changes in tumor oxygenation during the course of treatment. Patients with head and neck cancer receiving primary RT underwent pretreatment polarographic tumor oxygen measurement of the primary site or a metastatic neck lymph node. Treatment consisted of once daily (2 Gy/fraction to a total dose of 66-70 Gy) or twice daily irradiation (1.25 Gy/fraction to 70-75 Gy) to the primary site. Twenty-seven patients underwent a second series of measurements early in the course of irradiation. Sixty-three patients underwent pretreatment tumor oxygen assessment (primary site, n = 24; nodes, n = 39). The median pO2 for primary lesions was 4.8 mmHg, and it was 4.3 mmHg for cervical nodes. There was a weak association between anemia and more poorly oxygened tumors, but many non-anemic patients still had poorly oxygenated tumors. Repeat assessments of tumor oxygenation after 10-15 Gy were unchanged compared to pretreatment baselines. Poorly oxygenated nodes pretreatment were more likely to contain viable residual disease at post-radiation neck dissection. Median follow-up time for surviving patients was 20 months (range 3-50 months). Hypoxia (tumor median pO2 <10 mmHg) adversely affected 2 year local-regional control (30 vs. 73%, P = 0.01), disease-free survival (26 vs. 73%, P = 0.005), and survival (35 vs. 83%, P = 0.02). Tumor oxygenation affects the prognosis of head and neck cancer independently of other known prognostic variables. This parameter may be a useful tool for the selection of patients for investigational treatment strategies.

Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer

Article

Mar 2000

Despite more than 70 randomised trials, the effect of chemotherapy on non-metastatic head and neck squamous-cell carcinoma remains uncertain. We did three meta-analyses of the impact of survival on chemotherapy added to locoregional treatment. We updated data on all patients in randomised trials between 1965 and 1993. We included patients with carcinoma of the oropharynx, oral cavity, larynx, or hypopharynx. The main meta-analysis of 63 trials (10,741 patients) of locoregional treatment with or without chemotherapy yielded a pooled hazard ratio of death of 0.90 (95% CI 0.85-0.94, p<0.0001), corresponding to an absolute survival benefit of 4% at 2 and 5 years in favour of chemotherapy. There was no significant benefit associated with adjuvant or neoadjuvant chemotherapy. Chemotherapy given concomitantly to radiotherapy gave significant benefits, but heterogeneity of the results prohibits firm conclusions. Meta-analysis of six trials (861 patients) comparing neoadjuvant chemotherapy plus radiotherapy with concomitant or alternating radiochemotherapy yielded a hazard ratio of 0.91 (0.79-1.06) in favour of concomitant or alternating radiochemotherapy. Three larynx-preservation trials (602 patients) compared radical surgery plus radiotherapy with neoadjuvant chemotherapy plus radiotherapy in responders or radical surgery and radiotherapy in non-responders. The hazard ratio of death in the chemotherapy arm as compared with the control arm was 1.19 (0.97-1.46). Because the main meta-analysis showed only a small significant survival benefit in favour of chemotherapy, the routine use of chemotherapy is debatable. For larynx preservation, the non-significant negative effect of chemotherapy in the organ-preservation strategy indicates that this procedure must remain investigational.

Randomized clinical trial on 7-day continuous accelerated irradiation (CAIR) of head and neck cancer. Report on 3-year tumour control and normal tissue toxicity

Article

May 2001
CANCER RADIOTHER

Examining prognostic factors and patterns of failure in nasopharyngeal carcinoma following concomitant radiotherapy and chemotherapy: Impact on future clinical trials

Article

Jul 2001
INT J RADIAT ONCOL

Concomitant chemotherapy and radiotherapy (CCRT), followed by adjuvant chemotherapy, has improved the outcome of nasopharyngeal carcinoma (NPC). However, the prognosis and patterns of failure after this combined-modality treatment are not yet clear. In this report, the prognostic factors and failure patterns we observed with CCRT may shed new light in the design of future trials. One hundred forty-nine (149) patients with newly diagnosed and histologically proven NPC were prospectively treated with CCRT followed by adjuvant chemotherapy between April 1990 and December 1997. One hundred and thirty-three (89.3%) patients had MRI of head and neck for primary evaluation before treatment. Radiotherapy was delivered either at 2 Gy per fraction per day up to 70 Gy or 1.2 Gy per fraction, 2 fractions per day, up to 74.4 Gy. Chemotherapy consisted of cisplatin and 5-fluorouracil. According to the AJCC 1997 staging system, 32 patients were in Stage II, 53 in Stage III, and 64 in Stage IV (M0). Univariate analysis revealed that WHO (World Health Organization) Type II histology, T4 classification, and parapharyngeal extension were poor prognostic factors for locoregional control. Multivariate analysis revealed that T4 disease was the most important adverse factor that affects locoregional control, the risk ratio being 5.965 (p = 0.02). Univariate analysis for distant metastasis revealed that T4 and N3 classifications, serum LDH level > 410 U/L (normal range, 180-460), parapharyngeal extension, and infiltration of the clivus were significantly associated with poor prognosis. Multivariate analysis, however, revealed that T4 classification and N3 category were the only two factors that predicted distant metastasis; the risk ratios were 3.994 (p = 0.02) and 3.390 (p = 0.01), respectively. Therefore, based on the risk factor analysis, we were able to identify low-, intermediate-, and high-risk patients. Low-risk patients were those without the risk factors mentioned above. They consisted of Stage II patients with T2aN0, T1N1, and T2aN1 categories and of Stage III patients with T1N2 and T2aN2 categories. Their risk of recurrence is low (4%). Intermediate-risk patients were those with at least one univariate risk factor. They are Stage II patients with T2bN0 and T2bN1 categories and Stage III patients with T2bN2 and T3N0-2 categories. The risk of recurrence is modest (18%). High-risk patients have risk factors by multivariate analysis. They are stage T4 or N3 patients. Their risk of recurrence is high (36%). Low-risk patients have an excellent outcome. Future trials should focus on reducing treatment-associated toxicities and complications and reevaluate the benefit of sequential adjuvant chemotherapy. The recurrence in treatment of intermediate-risk patients is modest; CCRT and adjuvant chemotherapy may be the best standard for them. Patients with T4 and N3 disease have poorer prognosis. Hyperfractionated radiotherapy may be considered for the T4 patients. Future study in these high-risk patients should also address the problem of distant spread of the disease.

Glaser CM, Millesi W, Kornek GV, Long S, Schull B, Watzinger F, Selzer E, Lavey RSImpact of hemoglobin level and use of recombinant erythropoietin on efficacy of preoperative chemoradiation therapy for squamous cell carcinoma of the oral cavity and oropharynx. Int J Radiat Oncol Biol Phys 50: 705-715

Article

Jul 2001
INT J RADIAT ONCOL

We assessed the influence of hemoglobin level and r-HuEPO administration on response to chemoradiotherapy, locoregional tumor control, and overall survival in patients treated with neoadjuvant chemoradiotherapy and surgery for a squamous cell carcinoma of the oral cavity or oropharynx. The 191 study patients were treated with mitomycin C (15 mg/m(2) day 1), 5-fluorouracil (750 mg/m(2)/day, days 1-5), and radiotherapy (50 Gy in 25 fractions weeks 1-5), followed by resection of the primary tumor bed and neck dissection at the General Hospital Vienna, Austria, between November 1989 and October 1998 for a T2-4, N0-3, M0 SCC of the oral cavity or oropharynx. Starting in May 1996, patients with a low hemoglobin (Hgb) before or during chemoradiotherapy received r-HuEPO 10,000 IU/kg s.c. 3-6 times/week until the week of surgery. On multivariate analysis, Hgb level and use of r-HuEPO were independent prognostic factors for response to chemoradiotherapy and locoregional tumor control (p < 0.01). Pathologic response to neoadjuvant therapy was also predictive of locoregional control (p < 0.001). Patients with a pretreatment Hgb > or = 14.5 g/dL had significantly higher complete response, locoregional control, and survival rates than the patients with a pretreatment Hgb < 14.5 g/dL who did not receive r-HuEPO (p < 0.05). The response, control, and survival rates in patients with a pretreatment Hgb < 14.5 g/dL given r-HuEPO were significantly higher than in low Hgb patients not given r-HuEPO (p < or = 0.001) and equivalent to patients with a pretreatment Hgb > 14.5 g/dL (p > or = 0.3). Low pretreatment Hgb is a negative prognostic factor for oral cavity and oropharyngeal SCCA patients, but was completely abrogated by r-HuEpo administration during neoadjuvant chemoradiotherapy. Randomized trials of radiation and/or chemotherapy with or without r-HuEPO for patients whose Hgb level is either low at the start of therapy or is anticipated to become low during therapy are indicated.

The predictive value of the 1997 American Joint Committee on Cancer stage classification in determining failure patterns in nasopharyngeal carcinoma

Article

Jan 2002

A retrospective analysis of treatment outcomes in patients with nasopharyngeal carcinoma (NPC) was performed in which the newly revised 1997 American Joint Committee on Cancer (AJCC) stage classification was applied and compared with the 1988 AJCC and Ho stage classifications, with emphasis on the predictive value of different staging systems in determining failure patterns in NPC. Three hundred and twenty-four patients with newly diagnosed NPC treated between September 1989 and August 1991 and originally staged according to Ho stage classification were re-staged according to the 1988 and 1997 AJCC stage classifications. In addition to stage grouping, patients were also classified into the following prognostic categories to study the failure patterns: early disease group (T1-2N0-1), advanced local disease group (T3-4N0-1), advanced nodal disease group (T1-2N2-3), and advanced locoregional disease group (T3-4N2-3). The overall survival (OAS), relapse-free survival (RFS), local relapse-free survival, nodal relapse-free survival, and distant metastases-free survival were compared among different stage groups and prognostic categories in the three staging systems. In the new AJCC system, the percentages of patients with Stage I, II, III, and IV disease were 15.1%, 31.5%, 28.1%, and 25.3%, respectively, whereas most patients were classified as having Stage IV disease (65.7%) in the old AJCC system and Stage II or III disease (74.1%) in the Ho system. The 5 year OAS rates in the 1997 AJCC Stage I, II, III, and IV disease were 97.7%, 78.7%, 79.5%, and 61.4%, respectively. The corresponding 5 year RFS rates were 95.7%, 64.7%, 54.5%, and 41.1%. Using the 1997 AJCC system to define the four prognostic categories, the early disease group had the lowest incidence of relapse (27.6%) and death (18.4%), whereas the advanced locoregional disease group had the highest incidence of relapse (61.4%) and death (43.2%). Both the advanced local disease group and the advanced nodal disease group had similar rates of relapse (46.7% vs. 47.2%), but local relapse was the major cause of failure in the former group (61.8%), whereas distant metastases was the major cause in the latter group (44%). Using the 1997 AJCC staging system, the authors observed a better distribution of patient numbers as well as segregation of survival curves among different stage groups. Moreover, prognostic categories with distinct prognosis and failure patterns were definable by the new system, which has important implications in selecting appropriate patient treatment strategies.

Chow E, Payne D, O'Sullivan B, Pintilie M, Liu FF, Waldron J, Warde P, Cummings BRadiotherapy alone in patients with advanced nasopharyngeal cancer: comparison with an intergroup study Is combined modality treatment really necessary? Radiother Oncol 63: 269-274

Article

Jul 2002
RADIOTHER ONCOL

To examine the outcome of radiotherapy (RT) alone in patients with advanced nasopharyngeal cancer (NPC) and to compare the results with those reported by the Intergroup study 0099 (IGS) comparing RT to combined modality therapy (CMT). During the period 1985-1992, 198 NPC patients presenting without distant metastatic disease were treated for cure. Of these, 172 had stage III/IV (UICC 1987, 1992). Planned RT was 2 Gy/day fraction to 60-66 Gy to the primary tumor, with 50 and 60 Gy to the node negative and to palpable nodes, respectively. Outcomes included overall survival (OS) and disease-free survival (DFS), defined from the time of registration at our institution. The TNM categories and other prognostic factors were similar to the IGS, though 80% had stage IV compared to 91% in IGS. The 5 year OS and DFS for the 172 patients with stage III/IV disease were 62 and 48%, respectively, as compared to the IGS results of OS 37% and DFS 29% for RT alone, and OS 67% and DFS 58% for the CMT arm of IGS. When the distribution of adverse prognostic factors was balanced between both studies the comparative results were unchanged. The early results for RT alone of this single institution experience are superior to those of the IGS control arm (RT), while somewhat inferior to those reported in the chemo-radiotherapy arm. The surprisingly poor outcome of the IGS/RT control arm may have resulted by chance, suggesting the need for a confirmatory randomized trial to fully establish the role of combined chemotherapy and radiation, as used in the IGS.

Using technology to decrease xerostomia for head and neck cancer patients treated with radiation therapy

Article

Jan 2003
SEMIN ONCOL

The treatment of head and neck cancer has evolved from conventional fields encompassing large volumes of normal tissue to focused treatment aimed at conforming the dose around the target while avoiding normal tissue. Intensity modulated radiation therapy has changed the way radiation oncologists think about head and neck cancer. Using the concepts of conformal treatment and avoidance, the therapeutic ratio can be improved and technology exploited to the patients' advantage. This is particularly evident with head and neck irradiation, where a common side effect is xerostomia. By decreasing xerostomia through conformal avoidance of the parotid glands, we can improve patient satisfaction and quality of life. In this study, xerostomia is assessed through a subjective salivary gland function questionnaire. This article examines the use of intensity modulated radiation therapy in the treatment of head and neck cancer to decrease xerostomia. The purpose of this article is to evaluate the significance of parotid gland dosimetry in relation to subjective salivary gland function.

Phase III Study of Concurrent Chemoradiotherapy Versus Radiotherapy Alone for Advanced Nasopharyngeal Carcinoma: Positive Effect on Overall and Progression-Free Survival

Article

Feb 2003

Nasopharyngeal carcinoma (NPC) is a radiosensitive and chemosensitive tumor. This randomized phase III trial compared concurrent chemoradiotherapy (CCRT) versus radiotherapy (RT) alone in patients with advanced NPC. From December 1993 to April 1999, 284 patients with 1992 American Joint Committee on Cancer stage III to IV (M0) NPC were randomly allocated into two arms. Similar dosage and fractionation of RT was administered in both arms. The investigational arm received two cycles of concurrent chemotherapy with cisplatin 20 mg/m(2)/d plus fluorouracil 400 mg/m(2)/d by 96-hour continuous infusion during the weeks 1 and 5 of RT. Survival analysis was estimated by the Kaplan-Meier method and compared by the log-rank test. Baseline patient characteristics were comparable in both arms. After a median follow-up of 65 months, 26.2% (37 of 141) and 46.2% (66 of 143) of patients developed tumor relapse in the CCRT and RT-alone groups, respectively. The 5-year overall survival rates were 72.3% for the CCRT arm and 54.2% for the RT-only arm (P =.0022). The 5-year progression-free survival rates were 71.6% for the CCRT group compared with 53.0% for the RT-only group (P =.0012). Although significantly more toxicity was noted in the CCRT arm, including leukopenia and emesis, compliance with the combined treatment was good. The second cycle of concurrent chemotherapy was refused by nine patients and was delayed for > or = 1 week for another nine patients. There were no treatment-related deaths in either arm. We conclude that CCRT is superior to RT alone for patients with advanced NPC in endemic areas.

Treatment outcome after radiotherapy alone for patients with Stage I-II nasopharyngeal carcinoma

Article

Jul 2003

The objective of this study was to review the long-term treatment outcome of patients with American Joint Committee on Cancer (AJCC) 1997 Stage I-II nasopharyngeal carcinoma (NPC) who were treated with radiotherapy alone. One hundred forty-one patients with NPC had AJCC 1997 Stage I-II disease (Stage I NPC, 50 patients; Stage II NPC, 91 patients) after restaging and were treated with radiotherapy alone between September 1989 and August 1991. Fifty-seven patients had lymph node disease, and the median greatest lymph node dimension was 3 cm. The median dose to the nasopharynx was 65 grays. The median follow-up was 82 months (range, 4-141 months). Patients who had Stage I disease had an excellent outcome after radiotherapy. The 10-year disease specific survival, recurrence free survival (RFS), local RFS, lymph node RFS, and distant metastasis free survival rates were 98%, 94%, 96%, 98%, and 98%, respectively. Patients who had Stage II disease had a worse outcome compared with patients who had Stage I disease: The corresponding 10-year survival rates were 60%, 51%, 78%, 93%, and 64%. The differences all were significant except for lymph node control. Among patients who had Stage II disease, those with T1-T2N1 NPC appeared to have a worse outcome compared with patients who had T2N0 NPC. No significant differences in survival rates were found with respect to lymph node size or status for patients with T1-T2N1 disease. When patients with NPC had their disease staged according to the AJCC 1997 classification system, patients with Stage I disease had an excellent outcome after they were treated with radiotherapy alone. Patients with Stage II disease, especially those with T1-T2N1 disease, had a relatively worse outcome, and more aggressive therapy, such as combined-modality treatment, may be indicated for those patients.

Henke M, Laszig R, Rube C, Schafer U, Haase KD, Schilcher B, Mose S, Beer KGT, Burger U, Dougherty C, Frommhold HErythropoietin to treat head and neck cancer patients with anaemia undergoing radiotherapy: randomised, double-blind, placebo-controlled trial. Lancet 362: 1255-1260

Article

Nov 2003
LANCET

Anaemia is associated with poor cancer control, particularly in patients undergoing radiotherapy. We investigated whether anaemia correction with epoetin beta could improve outcome of curative radiotherapy among patients with head and neck cancer. We did a multicentre, double-blind, randomised, placebo-controlled trial in 351 patients (haemoglobin <120 g/L in women or <130 g/L in men) with carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx. Patients received curative radiotherapy at 60 Gy for completely (R0) and histologically incomplete (R1) resected disease, or 70 Gy for macroscopically incompletely resected (R2) advanced disease (T3, T4, or nodal involvement) or for primary definitive treatment. All patients were assigned to subcutaneous placebo (n=171) or epoetin beta 300 IU/kg (n=180) three times weekly, from 10-14 days before and continuing throughout radiotherapy. The primary endpoint was locoregional progression-free survival. We assessed also time to locoregional progression and survival. Analysis was by intention to treat. 148 (82%) patients given epoetin beta achieved haemoglobin concentrations higher than 140 g/L (women) or 150 g/L (men) compared with 26 (15%) given placebo. However, locoregional progression-free survival was poorer with epoetin beta than with placebo (adjusted relative risk 1.62 [95% CI 1.22-2.14]; p=0.0008). For locoregional progression the relative risk was 1.69 (1.16-2.47, p=0.007) and for survival was 1.39 (1.05-1.84, p=0.02). Epoetin beta corrects anaemia but does not improve cancer control or survival. Disease control might even be impaired. Patients receiving curative cancer treatment and given erythropoietin should be studied in carefully controlled trials.

Primary tumor volume of nasopharyngeal carcinoma: Prognostic significance for local control

Article

May 2004
INT J RADIAT ONCOL

To study the prognostic significance of primary tumor volume on local control of nasopharyngeal carcinoma. Between 1998 and 2001, 308 consecutive patients with nasopharyngeal carcinoma treated with radical intent were staged with MRI. On the basis of the extent of tumor infiltration outlined by a diagnostic radiologist, the gross tumor volume of the primary and involved retropharyngeal nodes (GTV-P) was delineated by a radiation oncologist for three-dimensional conformal radiotherapy to the nasopharyngeal region using the Helax-TMS Planning System. All patients were treated with 2 Gy daily to a total dose of 70 Gy in 6-7 weeks. Additionally, chemotherapy was given to 128 patients (42%). The median GTV-P for the whole series was 22 cm(3) (range, 1.4-218 cm(3)). Although the GTV-P varied substantially within each T stage, the overall correlation between these two parameters was strongly significant (p <0.01), with the median GTV-P 2.7 cm(3) for T1, 13.2 cm(3) for T2, 28.1 cm(3) for T3, and 65.5 cm(3) for T4. With a median follow-up of 1.9 years (range, 0.1-3.9 years), the 3-year local failure-free rate was 87%. The 3-year local failure-free rate was 97% for patients with a GTV-P <15 cm(3) compared with 82% for those with a GTV-P > or =15 cm(3) (p <0.01). On multivariate analysis (with T stage as a covariate), GTV-P remained an independent prognostic factor for the local failure-free rate (hazard ratio, 1.01; 95% confidence interval, 1.00-1.02; p <0.01). Our data suggested that GTV-P is a strongly significant factor for predicting local control of nasopharyngeal carcinoma. The risk of local failure was estimated to increase by 1% for every 1 cm(3) increase in primary tumor volume.

Concurrent and Adjuvant Chemotherapy for Nasopharyngeal Carcinoma: A Factorial Study

Article

Jul 2004

To study the efficacy of concurrent chemoradiotherapy (CRT) and adjuvant chemotherapy (AC) for nasopharyngeal carcinoma (NPC). Patients with Ho's stage T3 or N2/N3 NPC or neck node > or = 4 cm were eligible. Patients were randomly assigned to have radiotherapy (RT) or CRT with uracil and tegafur and to have AC or no AC after RT/CRT. AC comprised alternating cisplatin, fluorouracil, vincristine, bleomycin, and methotrexate for six cycles. There were four treatment groups: A, RT; B, CRT; C, RT and AC; D, CRT and AC. For CRT versus RT, groups B and D were compared with groups A and C. For AC versus no AC, groups C and D were compared with groups A and B. Three-year failure-free survival (FFS) and overall survival (OS) for CRT versus RT were 69.3% versus 57.8% and 86.5% versus 76.8%, respectively (P =.14 and.06; n = 110 v 109). Distant metastases rate (DMR) was significantly reduced with CRT (14.8% v 29.4%; P =.026). Locoregional failure rates (LRFR) were similar (20% v 27.6%; P =.39). Three-year FFS and OS for AC versus no AC were 62.5% versus 65% and 80.4% versus 83.1%, respectively (P =.83 and.69; n = 111 v 108). DMR and LRFR were not reduced with AC (P =.34 and.15, respectively). Cox model showed CRT to be a favorable prognostic factor for OS (hazard ratio, 0.42; P =.009). An improvement in OS with CRT was observed but did not achieve statistical significance. The improvement seemed to be associated with a significant reduction in DMR. AC did not improve outcome.

Hyperfractionated Accelerated Chemoradiation With Concurrent Fluorouracil-Mitomycin Is More Effective Than Dose-Escalated Hyperfractionated Accelerated Radiation Therapy Alone in Locally Advanced Head and Neck Cancer: Final Results of the Radiotherapy Cooperative Clinical Trials Group of the German Cancer Society 95-06 Prospective Randomized Trial

Article

Mar 2005

To report the results and corresponding acute and late reactions of a prospective, randomized, clinical study in locally advanced head and neck cancer comparing concurrent fluorouracil (FU) and mitomycin (MMC) chemotherapy and hyperfractionated accelerated radiation therapy (C-HART; 70.6 Gy) to hyperfractionated accelerated radiation therapy alone (HART; 77.6 Gy). Three hundred eighty-four stage III (6%) and IV (94%) oropharyngeal (59.4%), hypopharyngeal (32.3%), and oral cavity (8.3%) cancer patients were randomly assigned to receive either 30 Gy (2 Gy every day) followed by 1.4 Gy bid to a total of 70.6 Gy concurrently with FU (600 mg/m(2), 120 hours continuous infusion) days 1 through 5 and MMC (10 mg/m(2)) on days 5 and 36 (C-HART) or 14 Gy (2 Gy every day) followed by 1.4 Gy bid to a total dose of 77.6 Gy (HART). The data were analyzed on an intent-to-treat basis. At 5 years, the locoregional control and overall survival rates were 49.9% and 28.6% for C-HART versus 37.4% and 23.7% for HART, respectively (P = .001 and P = .023, respectively). Progression-free and freedom from metastases rates were 29.3% and 51.9% for C-HART versus 26.6% and 54.7% for HART, respectively (P = .009 and P = .575, respectively). For C-HART, maximum acute reactions of mucositis, moist desquamation, and erythema were lower than with HART, whereas no differences in late reactions and overall rates of secondary neoplasms were observed. C-HART (70.6 Gy) is superior to dose-escalated HART (77.6 Gy) with comparable or less acute reactions and equivalent late reactions, indicating an improvement of the therapeutic ratio.

Treatment results for nasopharyngeal carcinoma in the modern era: The Hong Kong experience

Article

Apr 2005
INT J RADIAT ONCOL

To analyze the treatment results achievable for nasopharyngeal carcinoma in the modern era to identify the key failures for future improvement and to provide an updated baseline for future trials. The results of 2687 consecutive patients treated at all public oncology centers in Hong Kong during 1996-2000 were retrospectively analyzed. The stage distribution (by American Joint Committee on Cancer and International Union Against Cancer staging system, 1997) was 7% Stage I, 41% Stage II, 25% Stage III, and 28% Stage IVA-B. All patients were irradiated with 6-MV photons and the median total dose was 66 Gy. Only 23% of patients had additional treatment with chemotherapy. The 5-year local, nodal, and distant failure-free rates were 85%, 94%, and 81%, respectively; patients with local failure had significantly higher risk of nodal and distant failures. The 5-year progression-free, overall, and cancer-specific survival rates were 63%, 75%, and 80%, respectively. The presenting stage was the most important prognostic factor for all endpoints: with overall survival decreasing from 90% for Stage I to 58% for Stage IVA-B. The results achieved by the 2070 patients treated by radiotherapy alone were almost identical to that of the whole series, the distant failure-free rate among patients with locoregional control was 89% for Stage I-II and 75% for Stage III-IVB. The 860 patients (32%) staged with magnetic resonance imaging achieved significantly better results than those staged by computed tomography, the overall survival being 93% vs. 83% for Stages I-II, and 72% vs. 63% for Stages III-IVB (p = 0.001). Treatment results for nasopharyngeal carcinoma have substantially improved in the modern era; future trials should be based on updated baseline results. Further reduction of distant failure is important for future breakthrough, particularly for patients with advanced disease.

Treatment outcomes and late complications of 849 patients with nasopharyngeal carcinoma treated with radiotherapy alone

Article

Aug 2005
INT J RADIAT ONCOL

The objective of this study was to describe the treatment outcomes and treatment-related complications of nasopharyngeal carcinoma (NPC) patients treated with radiotherapy alone. Retrospective analysis was performed on 849 consecutive NPC patients treated between 1983 and 1998 in our institution. Potentially significant patient-related and treatment-related variables were analyzed. Radiation-related complications were recorded. The 5-year overall and disease-free survival rates of these patients were 59% and 52%, respectively. Advanced parapharyngeal space (PPS) invasion showed stronger prognostic value than PPS invasion. Multiple neck lymph node (LN) involvement was demonstrated to be one of the most powerful independent prognostic factors among all LN-related parameters. External beam radiation dose more than 72 Gy was associated with significantly higher incidence of hearing impairment, trismus, and temporal lobe necrosis. We recommend that the extent of PPS should be clarified and stratified. Multiple neck LN involvement could be integrated into the N-classification in further revisions of the American Joint Committee on Cancer stage. Boost irradiation is not suggested for node-negative necks. For node-positive necks, boost irradiation is indicated and a longer interval between initial and boost irradiation would reduce the incidence of neck fibrosis without compromising the neck control rate.

Intensity-modulated radiotherapy in nasopharyngeal carcinoma: dosimetric advantage over conventional plans and feasibility of dose escalation

Article

Jun 2003
INT J RADIAT ONCOL

To compare intensity-modulated radiotherapy (IMRT) with two-dimensional RT (2D-RT) and three-dimensional conformal radiotherapy (3D-CRT) treatment plans in different stages of nasopharyngeal carcinoma and to explore the feasibility of dose escalation in locally advanced disease. Three patients with different stages (T1N0M0, T2bN2M0 with retrostyloid extension, and T4N2M0) were selected, and 2D-RT, 3D-CRT, and IMRT treatment plans (66 Gy) were made for each of them and compared with respect to target coverage, normal tissue sparing, and tumor control probability/normal tissue complication probability values. In the Stage T2b and T4 patients, the IMRT 66-Gy plan was combined with a 3D-CRT 14-Gy boost plan using a 3-mm micromultileaf collimator, and the dose-volume histograms of the summed plans were compared with their corresponding 66-Gy 2D-RT plans. In the dosimetric comparison of 2D-RT, 3D-CRT, and IMRT treatment plans, the T1N0M0 patient had better sparing of the parotid glands and temporomandibular joints with IMRT (dose to 50% parotid volume, 57 Gy, 50 Gy, and 31 Gy, respectively). In the T2bN2M0 patient, the dose to 95% volume of the planning target volume improved from 57.5 Gy in 2D-RT to 64.8 Gy in 3D-CRT and 68 Gy in IMRT. In the T4N2M0 patient, improvement in both target coverage and brainstem/temporal lobe sparing was seen with IMRT planning. In the dose-escalation study for locally advanced disease, IMRT 66 Gy plus 14 Gy 3D-CRT boost achieved an improvement in the therapeutic ratio by delivering a higher dose to the target while keeping the normal organs below the maximal tolerance dose. IMRT is useful in treating all stages of nonmetastatic nasopharyngeal carcinoma because of its dosimetric advantages. In early-stage disease, it provides better parotid gland sparing. In locally advanced disease, IMRT offers better tumor coverage and normal organ sparing and allows room for dose escalation.

Dosimetric predictors of xerostomia for head-and-neck-cancer patients treated with SMART (simultaneous modulated accelerated radiation therapy) boost technique

Article

Jun 2003
INT J RADIAT ONCOL

To evaluate the predictors of xerostomia in the treatment of head-and-neck cancers treated with intensity-modulated radiation therapy (IMRT), using the simultaneous modulated accelerated radiation therapy (SMART) boost technique. Dosimetric parameters of the parotid glands are correlated to subjective salivary gland function. Between January 1996 and June 2000, 30 patients with at least 6 months follow-up were evaluated for subjective xerostomia after being treated definitively for head-and-neck cancer with the SMART boost technique. Threshold limits for the ipsilateral and contralateral parotid glands were 35 Gy and 25 Gy, respectively. Dosimetric parameters to the parotid glands were evaluated. The median follow-up time was 38.5 months (mean 39.9 months). The results of the dosimetric parameters and questionnaire were statistically correlated. Xerostomia was assessed with a 10-question subjective salivary gland function questionnaire. The salivary gland function questionnaire (questions 1, 2, 3, 4, 6, and 9) correlated significantly with the dosimetric parameters (mean and maximum doses and volume and percent above tolerance) of the parotid glands. These questions related to overall comfort, eating, and abnormal taste. Questions related to thirst, difficulty with speech or sleep, and the need to carry water daily did not correlate statistically with the dosimetric parameters of the parotid glands. Questions regarding overall comfort, eating, and abnormal taste correlated significantly with the dosimetric parameters of the parotid glands. Questions related to thirst, difficulty with speech or sleep, and the need to carry water daily did not correlate statistically with the dosimetric parameters of the parotid glands. Dosimetric sparing of the parotid glands improved subjective xerostomia. IMRT in the treatment of head-and-neck cancer can be exploited to preserve the parotid glands and decrease xerostomia. This is feasible even with an accelerated treatment regimen like the SMART boost. More patients need to be evaluated using IMRT to identify relevant dosimetric parameters.

Retrospective analysis of 934 primary nasopharyngeal carcinoma (NPC) patients treated with conventional external beam radiotherapy alone

Article

Nov 2005

To analyze the clinical outcome of 934 primary nasopharyngeal carcinoma treated with conventional external beam radiotherapy alone. 34 patients were treated from Jan. 1, 1999 to Dec. 31, 1999. The radiation fields were delineated according to the CT/MRI imaging findings on disease extent. Two lateral opposing isocentric portals with customized blockings were used for the nasopharynx and upper neck. The dose delivered to tumor in the nasopharynx was 68-70 Gy/2 Gy fraction/7 weeks. The doses delivered to the neck was 60-70 Gy/6-7 weeks for patients with positive lymph nodes and 50 Gy/5 weeks for the patients with negative lymph node. The 1-, 2-, 3- and 4-year overall survival rate (OS) was 89.5%, 81.9%, 78.1% and 75.7%, and metastasis-free survival rate (MFS) was 84.0%, 77.2%, 74.4% and 72.0%, respectively. The 1-, 2-, 3- and 4-year disease-free survival rate (DFS) was 80.8%, 73.1%, 68.5% and 65.1%, and the relapse-free survival rate (RFS) was 95.5%, 92.7%, 90.3% and 87.3%, respectively. The overall failure rate was 30.9% (289/934). At the end of the radiotherapeutic course, the percentage of residual disease was 14.6%. The 4-year loco-regional recurrence and distant metastasis rates after radiotherapy were 7.2% and 9.2% with a median time of 19.3 months and 12.8 months. It may be helpful to improve radiotherapy curative effect when the target is individually designed through improving irradiation technique according to CT/MRI findings and by shortening the overall course time, enhancing irradiation dose and strictly implementing QA/QC measures.

An Intergroup Phase III Comparison of Standard Radiation Therapy and Two Schedules of Concurrent Chemoradiotherapy in Patients With Unresectable Squamous Cell Head and Neck Cancer

Article

Jan 2003

The Head and Neck Intergroup conducted a phase III randomized trial to test the benefit of adding chemotherapy to radiation in patients with unresectable squamous cell head and neck cancer. Eligible patients were randomly assigned between arm A (the control), single daily fractionated radiation (70 Gy at 2 Gy/d); arm B, identical radiation therapy with concurrent bolus cisplatin, given on days 1, 22, and 43; and arm C, a split course of single daily fractionated radiation and three cycles of concurrent infusional fluorouracil and bolus cisplatin chemotherapy, 30 Gy given with the first cycle and 30 to 40 Gy given with the third cycle. Surgical resection was encouraged if possible after the second chemotherapy cycle on arm C and, if necessary, as salvage therapy on all three treatment arms. Survival data were compared between each experimental arm and the control arm using a one-sided log-rank test. Between 1992 and 1999, 295 patients were entered on this trial. This did not meet the accrual goal of 362 patients and resulted in premature study closure. Grade 3 or worse toxicity occurred in 52% of patients enrolled in arm A, compared with 89% enrolled in arm B (P <.0001) and 77% enrolled in arm C (P <.001). With a median follow-up of 41 months, the 3-year projected overall survival for patients enrolled in arm A is 23%, compared with 37% for arm B (P =.014) and 27% for arm C (P = not significant). The addition of concurrent high-dose, single-agent cisplatin to conventional single daily fractionated radiation significantly improves survival, although it also increases toxicity. The loss of efficacy resulting from split-course radiation was not offset by either multiagent chemotherapy or the possibility of midcourse surgery.

Management of local residual primary lesion of nasopharyngeal carcinoma, Part IV: Summary

Jan 1990
139

Jh Yan
Gz Xu
Hu
Yh

Yan JH, Xu GZ, Hu YH, et al. Management of local residual primary lesion of nasopharyngeal carcinoma, Part IV: Summary. Chin J Radiat Oncol 1990;4:139.

Relationship between the treatment result and residual lesion after radiotherapy for patients with nasopharyngeal carcinoma

Jan 2004
150-152

Bw He
Qz Zou
Zhang
Fz

He BW, Zou QZ, Zhang FZ, et al. Relationship between the treatment result and residual lesion after radiotherapy for patients with nasopharyngeal carcinoma. Chin J Radiat Oncol 2004;13:150 –152.

Fractionated radiosurgery for residual lesion after the first course of radiotherapy for nasopharyngeal carcinoma Treatment results for nasopharyngeal carcinoma in the modern era: The Hong Kong experience

Jan 2005
77-801107

Jp Xiao
Gz Xu
L Gao

Xiao JP, Xu GZ, Gao L, et al. Fractionated radiosurgery for residual lesion after the first course of radiotherapy for nasopharyngeal carcinoma. Chin J Radiat Oncol 2005;14:77– 80. 167 Radiotherapy for NPC ● J.-L. YI et al. 23. Lee WM, Sze WM, Au SK, et al. Treatment results for nasopharyngeal carcinoma in the modern era: The Hong Kong experience. Int J Radiat Oncol Biol Phys 2005;61:1107–1116.

Management of local residual primary lesion of nasopharyngeal carcinoma (NPC), Part II: Biopsy, natural history and prognosis

Jan 1989
69-71

Yan Jh Dx Qin
Hu
Yh

Yan JH, Qin DX, Hu YH, et al. Management of local residual primary lesion of nasopharyngeal carcinoma (NPC), Part II: Biopsy, natural history and prognosis. Chin J Radiat Oncol 1989;3:69 –71.

Management of local residual primary lesion of nasopharyngeal carcinoma, Part IV: Sum-mary

Jan 1990
139

Yan Jh Gz Xu
Hu
Yh

Yan JH, Xu GZ, Hu YH, et al. Management of local residual primary lesion of nasopharyngeal carcinoma, Part IV: Sum-mary. Chin J Radiat Oncol 1990;4:139.

Management of local residual primary lesion of nasopharyngeal carcinoma (NPC), Part II: Biopsy, natural history and prognosis

Jan 1989
69-71

J H Yan
D X Qin
Y H Hu

Yan JH, Qin DX, Hu YH, et al. Management of local residual primary lesion of nasopharyngeal carcinoma (NPC), Part II: Biopsy, natural history and prognosis. Chin J Radiat Oncol 1989;3:69 -71.

Management of local residual primary lesion of nasopharyngeal carcinoma, Part IV: Summary

Jan 1990
139

J H Yan
G Z Xu
Y H Hu

Yan JH, Xu GZ, Hu YH, et al. Management of local residual primary lesion of nasopharyngeal carcinoma, Part IV: Summary. Chin J Radiat Oncol 1990;4:139.

Relationship between the treatment result and residual lesion after radiotherapy for patients with nasopharyngeal carcinoma

Jan 2004
150-152

B W He
Q Z Zou
F Z Zhang

He BW, Zou QZ, Zhang FZ, et al. Relationship between the treatment result and residual lesion after radiotherapy for patients with nasopharyngeal carcinoma. Chin J Radiat Oncol 2004;13:150 -152.

Nasopharyngeal carcinoma

Jan 1990
108

Sham

Oxygenation of head and neck cancer

Jan 1999
113

Brizel

Intensity-modulated radiotherapy in nasopharyngeal carcinoma

Jan 2003
145

Relationship between the treatment result and residual lesion after radiotherapy for patients with nasopharyngeal carcinoma

Jan 2004
150

Primary tumor volume of nasopharyngeal carcinoma

Jan 2004
21

Nasopharyngeal carcinoma treated by radical radiotherapy alone: Ten-year experience of a single institution

Abstract

No full-text available

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