Neoadjuvant chemoradiotherapy for locally advanced pancreas cancer does not lead to tumor regression

Neo-adjuvant chemo-radiotherapy is proposed to improve resectability of locally-advanced/borderline-resectable pancreas cancer (LAPC). The ability of neo-adjuvant therapy to provide tumor regression has not been reported. We reviewed pre and post treatment CT scans of patients undergoing neo-adjuvant chemo-radiotherapy (cisplatin, interferon-alpha, 5-FU, radiation) in a phase II clinical trial for LAPC between 2005 and 2008. Response to therapy was assessed. 15 patients (median age 61years, males 66%) received neo-adjuvant therapy for LAPC during 2005-08. Mean tumor size was 3.9cm. Indications for neo-adjuvant treatment included one or more of the following: Involvement of superior mesenteric artery (SMA) (≤180deg-3 patients, >180deg-1 patient), celiac axis (≤180deg-2 patients, >180deg-3 patients), hepatic artery (HA) (>180deg-6 patients), and/or superior mesenteric vein/portal vein (SMV/PV) (≤180deg-6 patients, >180deg-7 patients). 4 of 9 (44.4%) patients with borderline resectable disease (tumor involving ≤ 180deg circumference of the SMA, short-segment encasement/abutment of the common HA, or short-segment occlusion of SMV/PV) were resected after neo-adjuvant therapy. Regression of major vascular involvement was not observed in any patients. No patient with >180deg arterial involvement had tumor regression or resection. Five patients (33%) had disease progression during neo-adjuvant therapy. Pre-treatment and post-treatment tumor density (Hounsfield units) was similar (Pre-treatment HU: 60.4±6.48, post-treatment HU: 62.2±6.5, p=0.369). Neo-adjuvant treatment does not provide tumor regression of LAPC with major vascular involvement. Patient selection for neo-adjuvant trial enrollment should remain focused on borderline disease which may have potential for surgical resection

Neoadjuvant chemoradiotherapy for locally advanced pancreas cancer rarely leads to radiological evidence of tumour regression

Neo‐adjuvant chemo‐radiotherapy has been proposed to improve resectability of locally‐advanced pancreatic cancer (LAPC). However, the ability of neo‐adjuvant therapy to induce radiological tumour regression has not been reported. Pre‐ and post‐treatment computed tomography (CT) scans of patients undergoing neo‐adjuvant chemo‐radiotherapy for LAPC were reviewed. LAPC was sub‐classified into borderline resectable disease [≤180° involvement of the superior mesenteric artery (SMA); short‐segment encasement/abutment of the common hepatic artery; or tumour‐associated deformity, abutment or short‐segment occlusion of the superior mesenteric vein (SMV)/ portal vein (PV) that was amenable to vascular resection and reconstruction] and locally advanced un‐resectable pancreatic cancer (vascular involvement more than that described for borderline resectable pancreatic cancer). The radiological response and surgical resection rates were assessed. Sixteen patients received neo‐adjuvant therapy for LAPC during 2005–2008. Regression of major vascular involvement, i.e. un‐encasement or regression of abutment of any involved vessels was not observed in any patient. Pre‐ and post‐treatment tumour densities were not statistically different. Fifty per cent of patients with borderline resectable disease and none of the patients with locally advanced un‐resectable pancreatic cancer eventually underwent surgical resection. Neo‐adjuvant treatment does not induce radiological tumour regression of LAPC with major vascular involvement. Patient selection for neo‐adjuvant trial enrolment should remain focused on borderline disease which may have a potential for surgical resection

RNA sequencing of pancreatic adenocarcinoma tumors yields novel expression patterns associated with long‐term survival and reveals a role for ANGPTL4

Background Pancreatic adenocarcinoma patients have low survival rates due to late‐stage diagnosis and high rates of cancer recurrence even after surgical resection. It is important to understand the molecular characteristics associated with survival differences in pancreatic adenocarcinoma tumors that may inform patient care. Results RNA sequencing was performed for 51 patient tumor tissues extracted from patients undergoing surgical resection, and expression was associated with overall survival time from diagnosis. Our analysis uncovered 323 transcripts whose expression correlates with survival time in our pancreatic patient cohort. This genomic signature was validated in an independent RNA‐seq dataset of 68 additional patients from the International Cancer Genome Consortium. We demonstrate that this transcriptional profile is largely independent of markers of cellular division and present a 19‐transcript predictive model built from a subset of the 323 transcripts that can distinguish patients with differing survival times across both the training and validation patient cohorts. We present evidence that a subset of the survival‐associated transcripts is associated with resistance to gemcitabine treatment in vitro, and reveal that reduced expression of one of the survival‐associated transcripts, Angiopoietin‐like 4, impairs growth of a gemcitabine‐resistant pancreatic cancer cell line. Conclusions Gene expression patterns in pancreatic adenocarcinoma tumors can distinguish patients with differing survival outcomes after undergoing surgical resection, and the survival difference could be associated with the intrinsic gemcitabine sensitivity of primary patient tumors. Thus, these transcriptional differences may impact patient care by distinguishing patients who would benefit from a non‐gemcitabine based therapy