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Mid/Distal Esophageal Cancer and Gastroesophageal Junction Cancer (Siewert Type I and II)

January 2018

January 2018

DOI:10.1007/978-3-319-64900-9_2

In book: Gastrointestinal Malignancies (pp.21-50)

Authors:

Anupam Rishi

Moffitt Cancer Center

Michael Chuong

University of Maryland, Baltimore

Jessica M Frakes

Moffitt Cancer Center

The management of mid/distal esophageal and gastroesophageal junction (GEJ) cancer is challenging with only one-third patient presenting with a potentially resectable disease at diagnosis. Surgery alone treatments result in disappointing outcomes, and its utility as monotherapy has been challenged. Combined modality approach with the incorporation of neoadjuvant chemoradiation is the current standard of care for resectable patients, while definitive chemoradiation is used for locally advanced disease. The radiation techniques have evolved tremendously over past decade with the development of modern radiotherapy delivery techniques capable of safely delivering intensified treatment. This chapter provides a practical guide for evidence and treatment planning for radiation treatment strategies in the context of multimodality setting. The natural history and management of mid/lower esophageal cancer are not very different from GEJ (Siewert type I and II) cancers, and therefore, will be discussed together in this chapter.

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Prognostic Value of 18F-FDG PET/CT Metabolic Tumor Volume for Complete Pathologic Response and Clinical Outcomes after Neoadjuvant Chemoradiation Therapy for Locally Advanced Esophageal Cancer

Article

Full-text available

Jan 2016

Purpose/Objective: The prognostic value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) has not yet been defined in locally advanced esophageal cancer (LAEC). This study aims to elucidate the prognostic role of PET/CT for patients treated with neoadjuvant chemoradiation (CRT) followed by esophagectomy. Materials/Methods: We retrospectively evaluated patients with LAEC treated from 2006 to 2014 with neoadjuvant CRT followed by esophagectomy. A 76 patients had pre-CRT and post CRT PET/CT scans. PET parameters maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), peak standardized uptake value (SUVpeak), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were recorded for both pre-CRT and post-CRT scans. The correlation of the measured parameters with pathologic complete response (pCR) and clinical outcomes was analyzed. Results: Receiver operating characteristic (ROC) analysis was performed to determine the optimal cutoff values for predicting pCR. Binomial logistic regression using these optimal cutoff values was performed for pCR. A pre CRT MTV <33.1 was 4 times more likely to have a pCR (OR 4.20 95%CI 1.60 to 11.0, p=0.004). Pre CRT TLG <153 was 4.7 times more likely to have a pCR (OR 4.71 95%CI 1.78 to 12.4, p=0.002), and post CRT TLG <53.1 was 4.5 times more likely to have a pCR (OR 4.52 95%CI 1.60 to 12.7, p=0.004). On MVA, pre-CRT MTV and pre CRT TLG remained significant (p=0.006 and p=0.039, respectively). Percent change in MTV independently predicted for OS (p=0.034). By contrast, SUVmax and SUVpeak did not predict for pCR or survival. Conclusions: Pre CRT MTV and pre CRT TLG were independently predictive of pCR, and percentage change in MTV independently predicted for OS in LAEC. Further study is needed to determine if MTV and TLG values can help define which patients will most benefit from radiation dose escalation and esophagectomy

Clinical outcomes and toxicities of proton radiotherapy for gastrointestinal neoplasms: A systematic review

Article

Full-text available

Aug 2016
J Gastrointest Oncol

Background: Proton beam radiotherapy (PBT) is frequently shown to be dosimetrically superior to photon radiotherapy (RT), though supporting data for clinical benefit are severely limited. Because of the potential for toxicity reduction in gastrointestinal (GI) malignancies, we systematically reviewed the literature on clinical outcomes (survival/toxicity) of PBT. Methods: A systematic search of PubMed, EMBASE, abstracts from meetings of the American Society for Radiation Oncology, Particle Therapy Co-Operative Group, and American Society of Clinical Oncology was conducted for publications from 2000-2015. Thirty-eight original investigations were analyzed. Results: Although results of PBT are not directly comparable to historical data, outcomes roughly mirror previous data, generally with reduced toxicities for PBT in some neoplasms. For esophageal cancer, PBT is associated with reduced toxicities, postoperative complications, and hospital stay as compared to photon radiation, while achieving comparable local control (LC) and overall survival (OS). In pancreatic cancer, numerical survival for resected/unresected cases is also similar to existing photon data, whereas grade ≥3 nausea/emesis and post-operative complications are numerically lower than those reported with photon RT. The strongest data in support of PBT for HCC comes from phase II trials demonstrating very low toxicities, and a phase III trial of PBT versus transarterial chemoembolization demonstrating trends towards improved LC and progression-free survival (PFS) with PBT, along with fewer post-treatment hospitalizations. Survival and toxicity data for cholangiocarcinoma, liver metastases, and retroperitoneal sarcoma are also roughly equivalent to historical photon controls. There are two small reports for gastric cancer and three for anorectal cancer; these are not addressed further. Conclusions: Limited quality (and quantity) of data hamper direct comparisons and conclusions. However, the available data, despite the inherent caveats and limitations, suggest that PBT offers the potential to achieve significant reduction in treatment-related toxicities without compromising survival or LC for multiple GI malignancies. Several randomized comparative trials are underway that will provide more definitive answers.

Randomized Trial of Preoperative Chemoradiation Versus Surgery Alone in Patients With Locoregional Esophageal Carcinoma

Article

Jan 2001

PURPOSE: A pilot study of 43 patients with potentially resectable esophageal carcinoma treated with an intensive regimen of preoperative chemoradiation with cisplatin, fluorouracil, and vinblastine before surgery showed a median survival of 29 months in comparison with the 12-month median survival of 100 historical controls treated with surgery alone at the same institution. We designed a randomized trial to compare survival for patients treated with this preoperative chemoradiation regimen versus surgery alone. MATERIALS AND METHODS: One hundred patients with esophageal carcinoma were randomized to receive either surgery alone (arm I) or preoperative chemoradiation (arm II) with cisplatin 20 mg/m²/d on days 1 through 5 and 17 through 21, fluorouracil 300 mg/m²/d on days 1 through 21, and vinblastine 1 mg/m²/d on days 1 through 4 and 17 through 20. Radiotherapy consisted of 1.5-Gy fractions twice daily, Monday through Friday over 21 days, to a total dose of 45 Gy. Transhiatal esophagectomy with a cervical esophagogastric anastomosis was performed on approximately day 42. RESULTS: At median follow-up of 8.2 years, there is no significant difference in survival between the treatment arms. Median survival is 17.6 months in arm I and 16.9 months in arm II. Survival at 3 years was 16% in arm I and 30% in arm II (P = .15). This study was statistically powered to detect a relatively large increase in median survival from 1 year to 2.2 years, with at least 80% power. CONCLUSION: This randomized trial of preoperative chemoradiation versus surgery alone for patients with potentially resectable esophageal carcinoma did not demonstrate a statistically significant survival difference.

Prognostic value of 18F-FDG PET/CT metabolic tumor volume for complete pathologic response and clinical outcomes after neoadjuvant chemoradiation therapy for locally advanced esophageal cancer.

Article

Feb 2016

150 Background: The prognostic value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) has not yet been defined in locally advanced esophageal cancer (LAEC). This study aims to elucidate the prognostic role of PET/CT for patients treated with neoadjuvant chemoradiation (CRT) followed by esophagectomy. Methods: We retrospectively evaluated patients with LAEC treated from 2006 to 2014 with neoadjuvant CRT followed by esophagectomy. 86 patients had pre-CRT and post CRT PET/CT scans performed at our institution. These scans were imported into an image analysis program. PET parameters maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), mean standardized uptake value (SUVmean), and peak standardized uptake value (SUVpeak) were recorded for both pre-CRT and post-CRT scans. MTV was defined using a previously described liver method. The correlation of these parameters with pathologic complete response (pCR) and clinical outcomes was analyzed using binomial lo...

INT 0123 (Radiation Therapy Oncology Group 94-05) Phase III Trial of Combined-Modality Therapy for Esophageal Cancer: High-Dose Versus Standard-Dose Radiation Therapy

Article

Mar 2002

PURPOSE: To compare the local/regional control, survival, and toxicity of combined-modality therapy using high-dose (64.8 Gy) versus standard-dose (50.4 Gy) radiation therapy for the treatment of patients with esophageal cancer. PATIENTS AND METHODS: A total of 236 patients with clinical stage T1 to T4, N0/1, M0 squamous cell carcinoma or adenocarcinoma selected for a nonsurgical approach, after stratification by weight loss, primary tumor size, and histology, were randomized to receive combined-modality therapy consisting of four monthly cycles of fluorouracil (5-FU) (1,000 mg/m²/24 hours for 4 days) and cisplatin (75 mg/m² bolus day 1) with concurrent 64.8 Gy versus the same chemotherapy schedule but with concurrent 50.4 Gy. The trial was stopped after an interim analysis. The median follow-up was 16.4 months for all patients and 29.5 months for patients still alive. RESULTS: For the 218 eligible patients, there was no significant difference in median survival (13.0 v 18.1 months), 2-year survival (31% v 40%), or local/regional failure and local/regional persistence of disease (56% v 52%) between the high-dose and standard-dose arms. Although 11 treatment-related deaths occurred in the high-dose arm compared with two in the standard-dose arm, seven of the 11 deaths occurred in patients who had received 50.4 Gy or less. CONCLUSION: The higher radiation dose did not increase survival or local/regional control. Although there was a higher treatment-related mortality rate in the patients assigned to the high-dose radiation arm, it did not seem to be related to the higher radiation dose. The standard radiation dose for patients treated with concurrent 5-FU and cisplatin chemotherapy is 50.4 Gy.

Final Results of NRG Oncology RTOG 0246: An Organ Preserving Selective Resection Strategy in Esophageal Cancer Patients Treated with Definitive Chemoradiation

Article

Oct 2016

Introduction: The impact of selective surgical resection for esophageal cancer patients treated with definitive chemoradiation has not been clearly evaluated long-term. Methods: NRG Oncology RTOG 0246 was a multi-institutional, single arm, open-label, non-randomized phase II study, which enrolled forty-three patients from Sept 2003 to March 2008 with clinical stage T1-4N0-1M0 squamous cell or adenocarcinoma of the esophagus or gastroesophageal junction (GEJ) from 19 sites. Patients (pts) received induction chemotherapy with 5-FU (650 mg/m(2)/d), cisplatin (15 mg/m(2)/d) and paclitaxel (200 mg/m(2)/d) for 2 cycles followed by concurrent chemoradiation with 50.4 Gy (1.8 Gy/Fx) and daily 5-FU (300 mg/m(2)/d) with cisplatin (15 mg/m(2)/d) over the first five days. Following definitive chemoradiation pts were evaluated for residual disease. Selective esophagectomy was considered only for pts with residual disease after chemoradiation (Clin Non-CR) or recurrent disease on surveillance. Results: This report looks at the long-term outcome of this selective surgical strategy. With a median follow-up of 8.1 yrs (for 12 alive patients, min-max: 7.2 - 9.8 yrs), the estimated 5 and 7-yr survival rates are 36.6% (CI, 22.3%-51.0%) and 31.7% (CI, 18.3%-46.0%). Clin CR was achieved in 15 pts (37%) with 5 and 7-yr survival rates of 53.3% (CI, 26.3%-74.4%) and 46.7% (CI, 21.2%-68.7%). Esophageal resection was not required in 20/41 pts (49%) on this trial. Conclusions: The long-term results of NRG Oncology RTOG 0246 demonstrate promising efficacy of a selective surgical resection strategy and suggest the need for larger randomized studies to further evaluate this organ preserving approach.

Radiation Dose Escalation in Esophageal Cancer Revisited: Contemporary Analysis of the National Cancer Data Base, 2004-2012

Article

Aug 2016

Purpose: To evaluate the effect of radiation dose escalation on overall survival (OS) for patients with nonmetastatic esophageal cancer treated with concurrent radiation and chemotherapy. Methods and materials: Patients diagnosed with stage I to III esophageal cancer treated from 2004 to 2012 were identified from the National Cancer Data Base. Patients who received concurrent radiation and chemotherapy with radiation doses of ≥50 Gy and did not undergo surgery were included. OS was compared using Cox proportional hazards regression and propensity score matching. Results: A total of 6854 patients were included; 3821 (55.7%) received 50 to 50.4 Gy and 3033 (44.3%) received doses >50.4 Gy. Univariate analysis revealed no significant difference in OS between patients receiving 50 to 50.4 Gy and those receiving >50.4 Gy (P=.53). The dose analysis, binned as 50 to 50.4, 51 to 54, 55 to 60, and >60 Gy, revealed no appreciable difference in OS within any group compared with 50 to 50.4 Gy. Subgroup analyses investigating the effect of dose escalation by histologic type and in the setting of intensity modulated radiation therapy also failed to reveal a benefit. Propensity score matching confirmed the absence of a statistically significant difference in OS among the dose levels. The factors associated with improved OS on multivariable analysis included female sex, lower Charlson-Deyo comorbidity score, private insurance, cervical/upper esophagus location, squamous cell histologic type, lower T stage, and node-negative status (P<.01 for all analyses). Conclusions: In this large national cohort, dose escalation >50.4 Gy did not result in improved OS among patients with stage I to III esophageal cancer treated with definitive concurrent radiation and chemotherapy. These data suggest that despite advanced contemporary treatment techniques, OS for patients with esophageal cancer remains unaltered by escalation of radiation dose >50.4 Gy, consistent with the results of the INT-0123 trial. Furthermore, these data highlight that many radiation oncologists have not embraced the concept that dose escalation does not improve OS. Although local control, not investigated in the present study, might benefit from dose escalation, novel therapies are needed to improve the OS of patients with esophageal cancer.

Motion-robust intensity-modulated proton therapy for distal esophageal cancer

Article

Mar 2016

Purpose: To develop methods for evaluation and mitigation of dosimetric impact due to respiratory and diaphragmatic motion during free breathing in treatment of distal esophageal cancers using intensity-modulated proton therapy (IMPT).

Radiation modality use and cardiopulmonary mortality risk in elderly patients with esophageal cancer

Article

Dec 2015
CANCER-AM CANCER SOC

Background: It is currently unclear whether the superior normal organ-sparing effect of intensity-modulated radiotherapy (IMRT) compared with 3-dimensional radiotherapy (3D) has a clinical impact on survival and cardiopulmonary mortality in patients with esophageal cancer (EC). Methods: The authors identified 2553 patients aged > 65 years from the Surveillance, Epidemiology, and End Results (SEER)-Medicare and Texas Cancer Registry-Medicare databases who had nonmetastatic EC diagnosed between 2002 and 2009 and were treated with either 3D (2240 patients) or IMRT (313 patients) within 6 months of diagnosis. The outcomes of the 2 cohorts were compared using inverse probability of treatment weighting adjustment. Results: Except for marital status, year of diagnosis, and SEER region, both radiation cohorts were well balanced with regard to various patient, tumor, and treatment characteristics, including the use of IMRT versus 3D in urban/metropolitan or rural areas. IMRT use increased from 2.6% in 2002 to 30% in 2009, whereas the use of 3D decreased from 97.4% in 2002 to 70% in 2009. On propensity score inverse probability of treatment weighting-adjusted multivariate analysis, IMRT was not found to be associated with EC-specific mortality (hazard ratio [HR], 0.93; 95% confidence interval [95% CI], 0.80-1.10) or pulmonary mortality (HR, 1.11; 95% CI, 0.37-3.36), but was significantly associated with lower all-cause mortality (HR, 0.83; 95% CI, 0.72-0.95), cardiac mortality (HR, 0.18; 95% CI, 0.06-0.54), and other-cause mortality (HR, 0.54; 95% CI, 0.35-0.84). Similar associations were noted after adjusting for the type of chemotherapy, physician experience, and sensitivity analysis removing hybrid radiation claims. Conclusions: In this population-based analysis, the use of IMRT was found to be significantly associated with lower all-cause mortality, cardiac mortality, and other-cause mortality in patients with EC. Cancer 2015. © 2015 American Cancer Society.

Improving Outcomes for Esophageal Cancer using Proton Beam Therapy

Article

Dec 2015

Mid/Distal Esophageal Cancer and Gastroesophageal Junction Cancer (Siewert Type I and II)

Abstract

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