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Role of Preoperative 5-Fluorouracil, Doxorubicin and Streptozotocin Therapy in the Treatment of Localized Pancreatic Neuroendocrine Tumors
Laura R. Prakash*, Priya Bhosale, James Yao, Arvind Dasari, Thomas Aloia, Jeffrey E. Lee, Jean-Nicolas Vauthey, Jason B. Fleming, Matthew H. Katz
MD Anderson Cancer Center, Houston, TX
INTRODUCTION: We previously showed that 5-fluorouracil, doxorubicin and streptozotocin (FAS) leads to a 39% response rate among patients with inoperable—primarily metastatic—pancreatic neuroendocrine tumors (pNETs). Induction treatment with FAS may be recommended for patients with locally/local-regionally advanced or borderline resectable pNET on this basis in an attempt to reduce the anatomic extent of the tumor prior to surgical resection. We sought to characterize the response of localized pNETs to FAS.
PATIENTS: We identified all patients who presented between 2000 and 2012 to a single high-volume institution with localized or local-regional pNET. Pretreatment and posttreatment CT images of patients who received FAS as initial therapy were re-reviewed by a faculty radiologist. Diameters of the primary tumor and regional lymph nodes and the interfaces between the primary tumor and adjacent structures were measured to determine changes in tumor load (RECIST) and anatomic extent of disease in response to FAS.
RESULTS: 1115 patients presented with pNET during the study period. Among 356 (32%) patients who had localized tumors, 40 (11%) received FAS as initial therapy. 29 (72%) patients had evaluable images prior to and following receipt of FAS and comprise the study population. At baseline, an interface between the primary tumor and SMA, celiac trunk or hepatic artery was observed in 19 (66%) patients and either an interface with the SMV-PV or thrombus within the vein was observed in 24 (83%) patients. Following a median of 4 (range 1-11) months of therapy, 17 (89%) patients’ tumors still had an interface with the SMA, celiac trunk or hepatic artery and 24 (100%) still had an SMV-PV interface or thrombus. No patients experienced tumor progression, 2 (7%) patients had a RECIST PR and 27 (93%) had SD (Figure 1). Fourteen (48%) patients underwent pancreatectomy following FAS. Six (40%) resected patients required concomitant management of the SMV-PV by either (3) thrombectomy or (3) vascular resection, one required hepatic artery resection and 9 (64%) operations were R0. The median OS of all, unresected and resected patients was 107 (95% CI, 68-145) months, 41 (95% CI, 16-65) months, 112 (95% CI, 104-119) months respectively.
CONCLUSIONS: A radiographic response to neoadjuvant FAS was observed in only 7% of patients with localized pNET in this series. Nonetheless, 48% underwent subsequent pancreatectomy. While preoperative patients receiving preoperative FAS for localized pNET are unlikely to progress during systemic therapy, significant “downstaging” is likely to occur only in a minority of patients.
 Figure 1: Change in target lesion. Blue = resected, red = not resected. *Underwent noncurative pancreatectomy for palliation years after therapy.
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