RÉSUMÉ
Background: Chemotherapy (CT) is the standard of care for advanced gall bladder cancer (GBC). However, after completion of 6 cycles of CT, a proportion of patients with good performance status progress within a few months. Retrospective data in locally advanced cases revealed that consolidation chemo-radiotherapy (CTRT) in responders to CT and with good performance status improves overall survival. Methods: FNA proven advanced GBC with predefined clinical-radiological features will be administered 4 cycles CT (cisplatin-gemcitabine combination). After completion of CT, those in good Karnofsky performance status (KPS) will be randomised to consolidation CTRT versus observation (standard of care). The primary end point of the study is to compare OS between the two arms. The secondary end point is to compare progression free survival (PFS), toxicity, and quality of life between the two study arms. The trial is designed to detect an improvement in 2-year overall survival (OS) from 8% in the control arm to 25% in study arm with 80.0% power at a 0.05 significance level. The resultant sample size to achieve this aim is 140 (70 in each arm) over a duration of 4-5 years with a 10% attrition rate. Accrual has been from January 2019 to October 2022. Conclusions: This trial aims to assess the incremental gain in outcomes with consolidation CTRT versus observation in responders to first-line CT in advanced GBCs. This is the first randomised study to evaluate role of consolidation chemoradiation. Trial Registration: The trial is registered with clinical trials registry India (CTRI/2019/04/025204) and clinical trials.gov (NCT05493956).
RÉSUMÉ
Introduction: Chemotherapy (CT) is the standard of care in advanced gallbladder cancer (GBC). Should locally advanced GBC (LA-GBC) with response to CT and good performance status (PS) be offered as consolidation chemoradiation (cCTRT) to delay progression and improve survival? There is a scarcity of literature on this approach in the English literature. We present our experience with this approach in LA-GBC. Materials and Methods: After obtaining ethics approval, we reviewed the records of consecutive GBC patients from 2014 to 2016. Out of 550 patients, 145 were LA-GBC who were initiated on chemotherapy. A contrast-enhanced computed tomography (CECT) abdomen was done to evaluate the response to treatment, according to the RECIST (Response Evaluation Criteria in Solid Tumors) criteria. All responders to CT (PR and SD) with good PS but unresectable were treated with cCTRT. Radiotherapy was given to GB bed, periportal, common hepatic, coeliac, superior mesenteric, and para-aortic lymph nodes up to a dose of 45 to 54 Gy in 25 to 28 fractions along with concurrent capecitabine at the rate of 1,250 mg/m2. Treatment toxicity, overall survival (OS), and factors affecting OS were computed based on Kaplan–Meier and Cox regression analysis. Results: The median age of patients was 50 years (interquartile range [IQR] = 43–56 years), and men to women ratio was 1:3. A total of 65% and 35% patients received CT and CT followed by cCTRT, respectively. The incidence of Grade 3 gastritis and diarrhea was 10% and 5%, respectively. Responses were partial response (PR; 65%), stable disease (SD; 12%), progressive disease (PD; 10%), and nonevaluable (NE; 13%) because they did not complete six cycles of CT or were lost to follow-up. Among PR, 10 patients underwent radical surgery (six after CT and four after cCTRT). At a median follow-up of 8 months, the median OS was 7 months with CT and 14 months with cCTRT (P = 0.04). The median OS was 57 months, 12 months, 7 months, and 5 months for complete response (CR) (resected), PR/SD, PD, and NE (P = 0.008), respectively. OS was 10 months and 5 months for Karnofsky performance status (KPS) >80 and <80 (P = 0.008), respectively. PS (hazard ratio [HR] = 0.5), stage (HR = 0.41), and response to treatment (HR = 0.05) were retained as independent prognostic factors.