June 2024
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7 Reads
Radiotherapy and Oncology
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June 2024
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7 Reads
Radiotherapy and Oncology
October 2023
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15 Reads
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2 Citations
International Journal of Radiation Oncology*Biology*Physics
July 2023
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25 Reads
Background Intrahepatic cholangiocarcinoma (ICC) is a challenging primary liver cancer with a poor prognosis, especially in unresectable cases. Traditional palliative irradiation is limited in reducing liver doses. This study aimed to evaluate the efficacy and toxicity of respiratory-gated proton beam therapy without fiducial markers for intrahepatic cholangiocarcinoma. Methods Between October 2011 and February 2022, 24 patients (median [range] age, 71 [41–88] years) were evaluated at our institution. Twelve patients were pathologically diagnosed with ICC. All patients underwent respiratory-gated proton beam therapy at a dose of 48–83.6 (relative biological effectiveness) in 20–38 fractions with four-dimensional computed tomography planning. The median follow-up period was 18.5 (range, 2.0–74.0) months. The median tumor size was 41 (range, 10–125) mm. Twenty-one patients were classified as having Child–Pugh class A, and three patients were classified as having Child–Pugh class B. Local progression was defined as any growth of the irradiated tumor. Results The median survival time was 28 months for all patients. The Kaplan–Meier estimates of the 2-year overall survival, progression-free survival, and local tumor control rates were 51%, 26%, and 73%, respectively. Local tumor control rates were non-inferior to those reported in previous studies using fiducial markers. One patient had grade 4 pleural effusion; however, whether this was an adverse event due to the proton beam therapy was unclear. Conclusions Respiratory-gated proton beam therapy without fiducial markers is an effective and less invasive treatment option for ICC, showing potential for improved local control and tolerable adverse effects.
May 2023
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24 Reads
Journal of Radiation Research
This study presents the first data of a Japanese nationwide multi-institutional cohort and compares them with the findings of systematic literature reviews on radiation therapies and inoperable stage III non-small cell lung cancer (NSCLC) conducted by the Lung Cancer Working Group in the Particle Beam Therapy (PBT) Committee and Subcommittee at Japanese Society for Radiation Oncology. The Lung Cancer Working Group extracted eight reports and compared their data with those of the PBT registry from May 2016 to June 2018. All the analyzed 75 patients aged ≤80 years underwent proton therapy (PT) with concurrent chemotherapy for inoperable stage III NSCLC. The median follow-up period of the surviving patients was 39.5 (range, 1.6-55.6) months. The 2- and 3-year overall survival (OS) and progression-free survival rates were 73.6%/64.7% and 28.9%/25.1%, respectively. During the follow-up period, six patients (8.0%) had adverse events of Grade ≥ 3, excluding abnormal laboratory values. These included esophagitis in four patients, dermatitis in one and pneumonitis in one. Adverse events of Grade ≥ 4 were not observed. The results of these PBT registry data in patients with inoperable stage III NSCLC suggest that the OS rate was at least equivalent to that of radiation therapy using X-rays and that the incidence of severe radiation pneumonitis was low. PT may be an effective treatment to reduce toxicities of healthy tissues, including the lungs and heart, in patients with inoperable stage III NSCLC.
April 2023
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16 Reads
Medical Physics
Background It is important to have precise image guidance throughout proton therapy in order to take advantage of the therapy's physical selectivity. Purpose We evaluated the effectiveness of computed tomography (CT)‐image guidance in proton therapy for patients with hepatocellular carcinoma (HCC) by assessing daily proton dose distributions. The importance of daily CT image‐guided registration and daily proton dose monitoring for tumors and organs at risk (OARs) was investigated. Methods A retrospective analysis was conducted using 570 sets of daily CT (dCT) images throughout whole treatment fractions for 38 HCC patients who underwent passive scattering proton therapy with either a 66 cobalt gray equivalent (GyE)/10 fractions (n = 19) or 76 GyE/20 fractions (n = 19) protocol. The actual daily delivered dose distributions were estimated by forward calculation using the dCT sets, their corresponding treatment plans, and the recorded daily couch correction information. We then evaluated the daily changes of the dose indices D99%, V30GyE, and Dmax for the tumor volumes, non‐tumorous liver, and other OARs, that is, stomach, esophagus, duodenum, colon, respectively. Contours were created for all dCT sets. We validated the efficacy of the dCT‐based tumor registrations (hereafter, “tumor registration”) by comparing them with the bone registration and diaphragm registration as a simulation of the treatment based on the positioning using the conventional kV X‐ray imaging. The dose distributions and the indices of three registrations were obtained by simulation using the same dCT sets. Results In the 66 GyE/10 fractions, the daily D99% value in both the tumor and diaphragm registrations agreed with the planned value with 3%–6% (SD), and the V30GyE value for the liver agreed within ±3%; the indices in the bone registration showed greater deterioration. Nevertheless, tumor‐dose deterioration occurred in all registration methods for two cases due to daily changes of body shape and respiratory condition. In the 76 GyE/20 fractions, in particular for such a treatment that the dose constraints for the OARs have to be cared in the original planning, the daily D99% in the tumor registration was superior to that in the other registration (p < 0.001), indicating the effectiveness of the tumor registration. The dose constraints, set in the plan as the maximum dose for OARs (i.e., duodenum, stomach, colon, and esophagus) were maintained for 16 patients including seven treated with re‐planning. For three patients, the daily Dmax increased gradually or changed randomly, resulting in an inter‐fractional averaged Dmax higher than the constraints. The dose distribution would have been improved if re‐planning had been conducted. The results of these retrospective analyses indicate the importance of daily dose monitoring followed by adaptive re‐planning when needed. Conclusions The tumor registration in proton treatment for HCC was effective to maintain the daily dose to the tumor and the dose constraints of OARs, particularly in the treatment where the maintenance for the dose constraints needs to be considered throughout the treatment. Nevertheless daily proton dose monitoring with daily CT imaging is important for more reliable and safer treatment.
April 2023
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42 Reads
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2 Citations
Journal of Radiation Research
Japanese national oncological experts convened to evaluate the efficacy and safety of particle beam therapy (PT) for pulmonary, liver and lymph node oligometastases (P-OM, L-OM and LN-OM, respectively) and to conduct a statistically comparative analysis of the local control (LC) rate and overall survival (OS) rate of PT versus those of X-ray stereotactic body radiotherapy (X-SBRT) and X-ray intensity-modulated radiotherapy (X-IMRT). They conducted [1] an analysis of the efficacy and safety of metastasis-directed therapy with PT for P-OM, L-OM and LN-OM using a Japanese nationwide multi-institutional cohort study data set; [2] a systematic review of X-ray high-precision radiotherapy (i.e. X-SBRT/X-IMRT) and PT for P-OM, L-OM and LN-OM; and [3] a statistical comparison between LC and OS of the cohort data set in PT and that of the extracted historical data set in X-SBRT/X-IMRT from the preceding systematic review. Safety was evaluated as the incidence of grade ≥ 3 adverse events, while statistical comparisons of LC and OS were conducted by estimating the incidence rate ratios (IRR) for local progression and mortality, respectively. This study demonstrated that PT provided durable LC (3-year LC rate: 72.8-83.2%) with acceptable OS (3-year OS rate: 38.5-68.1%) and risk of severe toxicity incidence of 0.8-3.5% in radical metastasis-directed therapy for P-OM, L-OM and LN-OM. Compared to LC with X-SBRT or X-IMRT, LC with PT was potentially superior for P-OM; superior for L-OM; and equivalent for LN-OM. In particular, this study demonstrated that PT may be a new treatment option for L-OM tumors measuring > 5 cm.
January 2023
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46 Reads
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4 Citations
Simple Summary Surgery has shown that early-stage esophageal cancer is accompanied by extensive lymph node metastasis. Therefore, elective nodal irradiation is indispensable for chemoradiotherapy instead of surgery for the radical cure of esophageal cancer. In contrast, attention must be paid to adverse effects when applying radiation to a wide area. Adverse events are generally more intense with high-dose irradiation. Therefore, determining the appropriate dose for prophylactic irradiation to the elective nodal area is important. However, the appropriate dose has not been fixed. In this study, the therapeutic effects and adverse events of a group of 36 Gy elective nodal irradiation doses were similar to those of 40 Gy or higher. This study’s results indicate that preventing lymph node metastasis at lower doses is possible, thus suppressing adverse events. Abstract We evaluated elective nodal irradiation (ENI) doses during radical chemoradiotherapy (CRT) for esophageal cancer (EC). A total of 79 patients (65 men and 14 women) aged 52–80 years with T1-3, N0-3, and M0 (including M1ly) who underwent CRT for EC during November 2012–September 2019 were eligible for this retrospective analysis. Patients were divided into two groups: the high-dose group (HG), including 38 patients who received ≥40 Gy as ENI; and the low-dose group (LG), including 41 patients who received <40 Gy. The median doses were 40.0 and 36.0 Gy in HG and LG, respectively. During the follow-up (median: 36.7 months), no lymph node recurrence was observed in the ENI field in all patients. Lymph node recurrence near the ENI field was observed in six patients. No significant differences were observed between the two groups in median overall survival, progression-free survival, and local control. Grade 3–4 acute and late adverse events were observed in five patients of HG and six patients of LG, respectively. No ulceration or stricture was observed in the ENI field on endoscopy examined with 58 Gy irradiation. In conclusion, an ENI dose of 36 Gy could be considered to control the elective nodes of EC.
November 2022
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27 Reads
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1 Citation
We report here the long-term results of marker-less respiratory-gated proton therapy (PT), without fiducial markers for hepatocellular carcinoma (HCC), which was planned using a four-dimensional computed tomography technique. Local tumor control (LTC) and overall survival (OS) were estimated using the Kaplan–Meier method. Toxicity was graded per CTCAE v5.0. Patients (n = 105; median age 73 years, range 38–90 years) with 128 lesions were treated. The median radiation dose was 66 gray relative biological effectiveness (GyRBE) (range, 52.8–82.5 GyRBE) delivered in 2.0 to 6.6 GyRBE fractions, depending on lesion volume, the involved liver, and the patient’s condition. The median follow-up of surviving patients was 63 months (range, 1–126 months), and the 5-year LTC and OS rates were 93.2% and 40.4%, respectively. Univariate and multivariate analyses identified tumors near the gastrointestinal tract as an independent risk factor for local recurrence and revealed that hepatic reserve, tumor stage, performance status, operability, sex, and portal vein thrombosis were independent risk factors for OS. Acute and late treatment-related grade 3 toxicities were experienced by eight patients (7.6%). Adverse events ≥ grade 4 were not evident. Marker-less respiratory-gated PT for HCC is a safe and effective treatment without severe complications.
March 2022
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27 Reads
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3 Citations
International Journal of Clinical Oncology
Background: This multi-institutional clinical trial evaluated the feasibility of intensity-modulated radiotherapy (IMRT) for patients with locally advanced non-small cell lung cancer (NSCLC). Methods: The major inclusion criteria were clinical stage III NSCLC, age 20-74 years, and Eastern Cooperative Oncology Group performance status 0-1. Patients were treated with either cisplatin + S-1 (CS; four cycles every 4 weeks) or carboplatin + paclitaxel (CP; administered weekly with thoracic radiotherapy [RT], plus two consolidation cycles) concurrently with IMRT (60 Gy in 30 fractions). The primary endpoint was a treatment completion rate, defined as at least two cycles of CS or five cycles of CP during IMRT and completing 60 Gy IMRT within 56 days after the start of treatment, assumed its 90% confidence interval exceeds 60%. RT quality assurance was mandatory for all the patients. Results: Twenty-two patients were registered. One patient withdrew due to pulmonary infection before starting treatment. RT plans were reviewed and none was judged as a protocol violation. Grade 2 and 3 pneumonitis occurred in four (19%) and one (5%) patients, respectively. Seventeen patients met the primary endpoint, with a treatment completion rate of 77.3% (90% confidence interval [CI] 58.0%-90.6%). Four patients failed to complete chemotherapy due to chemotherapy-related adverse events, but 20 patients completed IMRT. There were no treatment-related deaths. The 2-year progression-free and overall survival rates were 31.8% (95% CI 17.3%-58.7%) and 77.3% (95% CI 61.6%-96.9%), respectively. Conclusion: The treatment completion rate did not meet the primary endpoint, but 20 of 22 patients completed IMRT.
November 2020
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8 Reads
International Journal of Radiation Oncology*Biology*Physics
... Despite these promising developments, challenges remain, including the need for continued research to better understand the long-term outcomes and comparative effectiveness of particle beam therapy relative to other treatment modalities for lung cancer. Furthermore, accessibility and cost-effectiveness issues must be addressed to ensure this advanced technology's widespread availability and affordability for all patients who may benefit from it [22,23]. ...
October 2023
International Journal of Radiation Oncology*Biology*Physics
... Although the excellent physical characteristics and the greater radiobiological potential, especially for hypoxic, radioresistant tumours, as well as homologous recombination deficiency and wild-type BRCA tumours [1,[60][61][62][63][64][65], there is still limited evidence about CIRT in the management of oligometastatic disease. In this challenging scenario, a recent nationwide multi-institutional cohort study explored the role of particle beam RT ( proton and CIRT) in the management of 614 patients ( for a total of 841 oligometastases), including 13 cases of ovarian and 45 cases of uterine cancers [66]. This large cohort study showed an overall durable LC (72.8-83.2% at 3 years), superior to stereotactic RT in the case of the liver (incidence rate ratio [IRR], 0.52 ;95% CI, 0.37-0.72; ...
April 2023
Journal of Radiation Research
... An optimal irradiation range aims to strike a wellbalanced equilibrium between the adverse effects and toxicities associated with radiation therapy (such as radiation esophagitis, radiation pneumonitis, and leukopenia) and the potential survival bene ts; it seeks to maximize treatment outcomes for patients while reducing the chances of complications arising from radiotherapy. Elective nodal irradiation (ENI) was previously the most popular method for outlining LN drainage areas in patients with esophageal cancer; however, this approach can lead to severe radiation side effects [9]. Currently, involved-eld irradiation (IFI) is increasingly employed by radiation oncologists [10]. ...
January 2023
... Adenocarcinoma and squamous cell carcinoma are two common pathological types of lung cancer [3] , also known as nonsmall cell lung cancer (NSCLC). Due to a low early diagnosis rate and resistance to radiotherapy and chemotherapy, the overall prognosis of NSCLC is poor [4,5] . In recent years, the prognosis of some lung adenocarcinoma patients with positive driver genes, such as EGFR, ALK, ROS, PD-1/PD-L1 has significantly improved due to the use of targeted and immunotherapy drugs [6,7] . ...
March 2022
International Journal of Clinical Oncology
... For example, Kinashi et al. [157] reported that DNA repair enzyme O6-methylguanine DNA methyltransferase (MGMT) and tumor suppressor p53 mutations in glioblastoma cells could affect the cell-killing effect of temozolomide combined with BNCT. Another example was published by Tatebe et al. [158] studying BNCT combined with rapamycin. The mammalian target of rapamycin (mTOR) signaling pathway is implicated in resistance to therapy and poor treatment outcomes. ...
August 2020
World Journal of Oncology
... In addition, the KPS is a prognostic factor for terminally ill cancer patients [20,21]. Regarding the NLR ≥5, patients with a low NLR may experience prolonged survival after WBRT for advanced non-SCLC [22]. Similarly, the NLR has been reported to be a prognostic factor after resection [12] and radiation therapy [13] in patients with BM. ...
January 2019
In vivo (Athens, Greece)
... Numerous clinical studies have been conducted in HNC patients using [ 18 F]FMISO PET imaging, evaluating different aspects, such as correlation with other hypoxia biomarkers [7][8][9], the ability to prognosticate in HNC patients [10], and the variation in uptake during serial imaging [11,12]. Although there is a wealth of published literature, it is difficult to summate their outcomes as the studies are heterogenous with regards to study design, image analysis (for example evaluating standardized uptake value (SUV) max versus tumour to background ratio (TBR)) and research question. ...
March 2018
Anticancer Research
... 3,4 Therefore, HPV-positive OPC shows distinct epidemiological, clinical, and molecular features when compared to HPV-negative OPC, and tumor HPV status is recognized as the strongest independent prognostic factor for radiotherapy (RT) outcomes. 1,[4][5][6][7][8] Although the clinical and molecular-genetic characteristics of HPV-positive and HPV-negative OPC clearly differ, whether the prognostic factors for these cancers are also distinct remains unclear. 9 Currently, the eighth edition of the International Union Against Cancer (UICC)/American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) classification system for OPC considers the HPV status. 10 The system accurately reflected the superior survival outcomes of HPV-positive OPC. ...
January 2018
Anticancer Research
... Boron neutron capture reaction ( 10 B (n, α) 7 Li) is, in principle, very effective in destroying tumors, provided that a sufficient amount of 10 B can be accumulated in the target tumor and a sufficient number of very-low-energy thermal neutrons can be delivered [1,2]. The two particles generated in this reaction have a high linear energy transfer (LET) and have a range of roughly the diameter of one or two tumor cells [1,2]. ...
February 2016
... In addition, Liauw et al. revealed that RT for primary prostate cancer was correlated with an increased risk of developing second malignancies (12). Moreover, there are multiple other studies that suggested that patients receiving RT for primary pelvic cancers (PPC) are at an increased risk of second malignancies in adjacent organs like the rectum, bladder, and prostate (13)(14)(15). It is worth noting that the uterus is in a close anatomical relationship with other pelvic target organs, which is within the pelvic irradiation field. ...
November 2012
International Journal of Clinical Oncology