Vikas Ostwal1, Sandip Basu2, Prabhat Bhargava1, Minit Shah1, Rahul Vithalrao Parghane2, Sujay Srinivas1, Vikram Chaudhari3, Manish S Bhandare3, Shailesh V Shrikhande3, Anant Ramaswamy4. 1. Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, India. 2. Radiation Medicine Centre, Babha Atomic Research Centre, Tata Memorial Hospital Annexe, Homi Bhabha National Institute (HBNI), Mumbai, India. 3. GI and HPB Surgery, Tata Memorial Hospital (Homi Bhabha National Institute), Mumbai, India. 4. Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, India, anantr13@gmail.com.
Abstract
INTRODUCTION: Capecitabine-temozolomide (CAPTEM) chemotherapy, alone or with concurrent peptide receptor radionuclide therapy (PRRT), has activity in advanced WHO grade 2 and grade 3 neuroendocrine neoplasms (NENs). The objective of this study was to evaluate the activity of the CAPTEM in patients with grade 2 and grade 3 NENs and identify prognostic factors. MATERIALS AND METHODS: A retrospective analysis of patients with metastatic grade 2 and grade 3 NENs, who were having baseline significant dual uptake on 68Ga-DOTATATE/18F-fluorodeoxyglucose (FDG)-PET-CT scan and treated with CAPTEM chemotherapy between January 2014 and December 2019 at Tata Memorial Hospital, was conducted. The clinical variables and survival data were collected. Progression-free survival (PFS) was estimated using the Kaplan-Meier method. RESULTS: A total of 68 patients received the CAPTEM regimen, of whom 29 patients (43%) received CAPTEM alone and 39 patients (57%) received concurrent PRRT. The primary sites were pancreas in 32 (47%) and small intestine in 12 (18%) patients. Mean Ki-67 index was 12.6% (range: 3-50). Forty-five patients (65%) were treatment naïve. There were no significant differences in baseline clinical variables between patients treated with CAPTEM alone or with CAPTEM-PRRT. Both regimens were well tolerated. With a median follow-up of 22.1 months, the median PFS for the entire cohort was 27.5 months. There was no statistical difference in the median PFS between patients receiving CAPTEM alone or CAPTEM-PRRT (33.7 vs. 22 months; p = 0.199). A Ki-67 index of >5% predicted for inferior PFS on multivariate analysis (24 versus 73.8 months; p = 0.04; hazard ratio -3.77; 95% confidence interval: 1.07-13.26). CONCLUSION: CAPTEM, alone or concurrent with PRRT, has a significant activity in grade 2 and grade 3 NENs with dual SSTR and 18FDG expression. A Ki-67 index >5% predicts strongly for inferior outcomes and should be further explored as a prognostic cutoff in grade 2 NENs. Early initiation of CAPTEM should be considered in this group of tumors with significant baseline 18FDG expression.
INTRODUCTION: Capecitabine-temozolomide (CAPTEM) chemotherapy, alone or with concurrent peptide receptor radionuclide therapy (PRRT), has activity in advanced WHO grade 2 and grade 3 neuroendocrine neoplasms (NENs). The objective of this study was to evaluate the activity of the CAPTEM in patients with grade 2 and grade 3 NENs and identify prognostic factors. MATERIALS AND METHODS: A retrospective analysis of patients with metastatic grade 2 and grade 3 NENs, who were having baseline significant dual uptake on 68Ga-DOTATATE/18F-fluorodeoxyglucose (FDG)-PET-CT scan and treated with CAPTEM chemotherapy between January 2014 and December 2019 at Tata Memorial Hospital, was conducted. The clinical variables and survival data were collected. Progression-free survival (PFS) was estimated using the Kaplan-Meier method. RESULTS: A total of 68 patients received the CAPTEM regimen, of whom 29 patients (43%) received CAPTEM alone and 39 patients (57%) received concurrent PRRT. The primary sites were pancreas in 32 (47%) and small intestine in 12 (18%) patients. Mean Ki-67 index was 12.6% (range: 3-50). Forty-five patients (65%) were treatment naïve. There were no significant differences in baseline clinical variables between patients treated with CAPTEM alone or with CAPTEM-PRRT. Both regimens were well tolerated. With a median follow-up of 22.1 months, the median PFS for the entire cohort was 27.5 months. There was no statistical difference in the median PFS between patients receiving CAPTEM alone or CAPTEM-PRRT (33.7 vs. 22 months; p = 0.199). A Ki-67 index of >5% predicted for inferior PFS on multivariate analysis (24 versus 73.8 months; p = 0.04; hazard ratio -3.77; 95% confidence interval: 1.07-13.26). CONCLUSION: CAPTEM, alone or concurrent with PRRT, has a significant activity in grade 2 and grade 3 NENs with dual SSTR and 18FDG expression. A Ki-67 index >5% predicts strongly for inferior outcomes and should be further explored as a prognostic cutoff in grade 2 NENs. Early initiation of CAPTEM should be considered in this group of tumors with significant baseline 18FDG expression.
Authors: Elettra Merola; Andrea Michielan; Umberto Rozzanigo; Marco Erini; Sandro Sferrazza; Stefano Marcucci; Chiara Sartori; Chiara Trentin; Giovanni de Pretis; Franca Chierichetti Journal: World J Gastrointest Surg Date: 2022-02-27