LAUSR

We appreciate the thoughtful response provided by Lamberti et al, there is certainly still hope for adjuvant therapy in resected gastroenteropancreatic neuroendocrine tumors (GEP NETs). Given that cytotoxic chemotherapy has been extensively studied in only advanced disease or in limited numbers in resected disease,3‐5 we hypothesized that analysis of the data from the US Neuroendocrine Tumor Study Group (the largest known GEP NET registry in the United States) might reveal certain patient populations for which adjuvant therapy might be studied prospectively. Certainly, there are limitations and challenges related to our dataset, perhaps most notably that because adjuvant therapy for resected GEP NET is not considered the standard of care; thus, we have a very limited number of patients ultimately included in our analysis. In addition, as highlighted by Lamberti et al we were unable to stratify by cytotoxic chemotherapy (although when known, FOLFOX or cisplatin/ etoposide were the commonest regimens) type nor were we able to study GEP NETs by organ. Although aware of the inherent selection bias in such methodology, significant effort was made to account for clinically and pathologically‐relevant factors in the multivariable model. Numerous models were employed during exploratory data analysis to detect variables that either differed significantly between the cohorts or were significantly associated with overall survival or recurrence‐free survival. However, ultimately, there is no question that patients receiving cytotoxic chemotherapy had more advanced disease, both clinically and in terms of tumor biology. We agree with Lamberti et al that larger, or loco‐regional pancreatic NETs would be a reasonable population in which to prospectively study the utility of adjuvant therapy. We hope that as larger national and international GEP NET datasets become available, similar analyses might inform patient or disease factors that may benefit from adjuvant therapy. And ideally, a large multicenter prospective randomized trial will be conducted, focused on a high‐risk patient population that may actually benefit—as the editorialists have suggested. In the meantime, however, we must be cautious in the use of adjuvant therapy for resected GEP NETs until more evidence suggestive of benefit becomes available. James R. Barrett MD Daniel E. Abbott MD