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Dose-Response Relationship between Radiation Dose and Loco-regional Control in Patients with Stage II-III Esophageal Cancer Treated with Definitive Chemoradiotherapy.

ABSTRACT: The correlation between radiation dose and loco-regional control (LRC) was evaluated in patients with stage II-III esophageal cancer treated with definitive concurrent chemoradiotherapy (CRT).Medical records of 236 stage II-III esophageal cancer patients treated with definitive CRT at Yonsei Cancer Center between 1994 and 2013 were retrospectively reviewed. Among these, 120 received a radiation dose of < 60 Gy (standard-dose group), while 116 received ≥ 60 Gy (high-dose group). The median doses of radiation in the standard- and high-dose groups were 50.4 and 63 Gy, respectively. Concurrent 5-fluorouracil/cisplatin chemotherapy was administered to most patients.There were no differences in patient characteristics between the two groups except for high Karnofsky performance status and lower-thoracic lesions being more prevalent in the standard-dose group. The median progression-free survival (PFS) and overall survival (OS) times were 13.2 months and 26.2 months, respectively. Patients in the high-dose group had significantly better 2-year LRC (69.1% vs. 50.3%, p=0.002), median PFS (16.7 months vs. 11.7 months, p=0.029), and median OS (35.1 months vs. 22.3 months, p=0.043). Additionally, LRC exhibited a dose-response relationship and the complete response rate was significantly higher in the high-dose group (p=0.006). There were no significant differences in treatment-related toxicities between the groups.A higher radiation dose (> 60 Gy) is associated with increased LRC, PFS, and OS in patients with stage II-III esophageal cancer treated with definitive CRT.

SUBMITTER: Kim HJ

PROVIDER: S-EPMC5512369 | biostudies-other | 2017 Jul

REPOSITORIES: biostudies-other

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Project description:Background Treatment with definitive chemoradiotherapy (CRT) is the best option for patients with locally advanced esophageal tumors considered unresectable or for patients without clinical conditions to undergo surgical treatment. Technological advances in radiotherapy in the last decades have made treatment more accurate with less toxicity, and the association with more effective systemic treatment has been gradually improving survival rates. Aim Evaluate clinical prognostic factors for progression-free survival (PFS) and overall survival (OS) in patients with esophageal cancer treated with definitive radiotherapy (RT) and chemotherapy (ChT). Material and methods The clinical records of 60 patients treated from April 2011 until December 2019 with esophageal cancer considered unresectable and/or without clinical conditions for surgery, treated with definitive CRT, were analyzed. All patients had upper digestive endoscopy (UDE) with positive biopsy, neck, chest, and abdominal CT scan, and 18F-fluorodeoxyglucose positron-emission tomography (PET-CT). Patients were followed with physical examination and CTs every three months in the first and second years and every six months from the third year of follow-up. UDE was made every three to six months after the end of the treatment or in suspicion of tumor recurrence. PET-CT was also performed in the follow-up when clinically necessary. Local and regional failure (LRF) was defined as abnormalities in the image tests within the planning target volume (PTV) and/or positive biopsy on UDE. Any other failure was defined as a distant failure (DF). PFS was defined in the record of the first tumor recurrence site and OS in the death record from the date of the start of treatment. Results The median age of the patients was 66 years (range: 33 to 83 years) and 46 patients (76.7%) were male. Squamous cell carcinoma (SCC) was the most frequent histological type (85%). Most patients had tumors located in the mid-thoracic esophagus (53.3%) and stage III or IV (59.9%). All patients were treated using 3D (76.7%) or intensity-modulated radiotherapy (IMRT; 23.3%). The median total dose was 50.4Gy (41.4-50.4). All patients received platinum-based ChT concomitant with RT. The most common regimen used was carboplatin and paclitaxel, with a median of five cycles. With a median follow-up of 19 months, the median PFS and OS were 10 and 20 months, respectively. LRF and DF as the first site of failure were observed in 22 (36.6%) and 26 (43.3%) patients, respectively. In the univariate analysis, tumor length lower than 2.6 cm, gross tumor volume (GTV) volume lower than 28 cm3, clinical tumor stages T1 and T2, clinical node stage N0, clinical prognostic stage groups I and II, and complete response to treatment, were statistically significant factors for better PFS and OS. In the multivariate analysis, the presence of clinical nodal stage N0 was related to better PFS (p=0.02). Conclusion Node clinical status was the most important clinical factor for PFS. Despite all the technical progress observed in radiotherapy, treatments concomitant with platinum-based chemotherapy are associated with high levels of LRF and DF. New strategies in systemic therapy and radiotherapy are necessary for improving outcomes.

Project description:IntroductionThere are currently two recommended radiation strategies for clinical stage III NSCLC: a lower "preoperative" (45-54 Gy) and a higher "definitive/nonsurgical" (60-70 Gy) dose. We sought to determine if definitive radiation doses should be used in the preoperative setting given that many clinical stage III patients planned for surgery are ultimately managed with chemoradiation alone.MethodsUsing the National Cancer Database data from 2006 to 2016, we performed a comparative effectiveness analysis of stage III N2 patients who received chemoradiotherapy. Patients were stratified into subgroups across 2 parameters: (1) radiation dose: lower (45-54 Gy) and higher (60-70 Gy); and (2) the use of surgery (i.e., surgical and nonsurgical treatment approaches). Long-term survival and perioperative outcomes were evaluated using multivariable Cox proportional hazards and logistic regression models.ResultsA cohort of 961 patients received radiation before surgery including 321 who received a higher dose and 640 who received a lower dose. A higher preoperative dose revealed similar long-term mortality risk (hazard ratio = 0.99, 95% confidence interval: 0.82-1.21, p = 0.951) compared with a lower dose. There was no significant association between radiation dose and 90-day mortality (p = 0.982), 30-day readmission (p = 0.931), or prolonged length of stay (p = 0.052) in the surgical cohort. A total of 17,904 clinical-stage IIIA-N2 patients were treated nonsurgically, including 15,945 receiving higher and 1959 treated with a lower dose. A higher dose was associated with a reduction in long-term mortality risk (hazard ratio = 0.64, 95% confidence interval: 0.60-0.67, p < 0.001) compared with a lower dose.ConclusionsFor clinical stage III NSCLC, the administration of 60 to 70 Gy of radiation seems to be more effective than the lower dose for nonsurgical patients without compromising surgical safety for those that undergo resection. This evidence supports the implementation of 60 to 70 Gy as a single-dose strategy for both preoperative and definitive chemoradiotherapy.

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Dose-Response Relationship between Radiation Dose and Loco-regional Control in Patients with Stage II-III Esophageal Cancer Treated with Definitive Chemoradiotherapy.

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