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Concurrent Versus Sequential Neoadjuvant Chemoradiotherapy Followed by Surgery in Locally Advanced Carcinoma Gallbladder Patients: A Prospective Pilot Study
 
Ameet Kumar1, Rajesh Panwar1, Sujoy Pal1, Nihar Ranjan Dash1, Atul Sharma2, Raju Sharma3, Prateek Kinra4, Bidhu Kalyan Mohanti5, Siddharth Dattagupta4, Peush Sahni1, Tushar Kanti Chattopadhyay1  
1Department of Gastrointestinal Surgery and Liver Transplantation, All India Institute of Medical Sciences, New Delhi, India. 2Department of Medical Oncology, Dr B.R. Ambedkar Institute-Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India. 3Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India. 4Department of Pathology, All India Institute of Medical Sciences, New Delhi, India. 5Department of Radiotherapy, Dr B.R. Ambedkart Institute-Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India.


Corresponding Author
:
Dr Sujoy Pal
Email: sujoypal@hotmail.com


Abstract

Background: A multimodality approach to locally advanced gallbladder cancer (LA-GBC) may improve their dismal survival. We did a pilot study to evaluate safety and efficacy of neoadjuvant chemoradiotherapy (NACRT) in LA-GBC. 
Methods: Patients with cytologically proven, resectable LA-GBC (stage III=12, IVA=4), no metastasis at laparoscopy, were allocated to sequential (n=8) and concurrent (n=8) NACRT. Sequential group received gemcitabine 900 mg/m2 and oxaliplatin 
80 mg/m2 on days 1, 8, 22 and 29. Concurrent group received gemcitabine 300 mg/m2 and oxaliplatin 50 mg/m2 weekly for 4 weeks. Radiotherapy (35 Gy/15 fractions/3 weeks) was given to both groups. Patients were reassessed by CT scan before surgery. In sequential group, radiological complete response (rCR), partial response (rPR) and progressive disease (rPD) were seen in 1, 2 and 4 patients, respectively. One patient died before response assessment. 
Results: In concurrent group, rCR, rPR and stable disease were seen in 1, 6 and 1 patients, respectively. The overall response rates was better in concurrent arm (8/8 versus 3/7; p=0.025). Grade III toxicity occurred in 1 patient (concurrent). Eight patients (sequential 2,concurrent 6) underwent resection (R0 in all). Pathological complete response (pCR) was seen in 1 (sequential) while 7 patients (sequential 1,concurrent 6) showed partial response. At a minimum follow-up of 5 years for surviving patients, the median overall survival was 8.6 months and 28.8 months in sequential and concurrent groups respectively. 
Conclusion: Although both sequential and concurrent NACRT were safe and effective in LA-GBC, response rates, resectability and long term survival were somewhat better in the Concurrent group. A larger study would be  required to confirm these results in LA-GBC.