whole breast radiation than in all of the previously reported randomized IORT studies in previous decades (4). In see more parallel with this resurgence in IORT interest spawned by technological advances, there have been advances in chemotherapeutic management of systemic disease that has made it increasingly important to achieve effective and durable control of the primary disease with

local therapies, thus providing a shot in the arm for intensification of radiation Inhibitors,research,lifescience,medical treatment via techniques such as IORT. The accompanying article by Ashman et al. reports the Mayo Clinic Scottsdale experience with preoperative chemoradiation therapy combined with a mobile electron accelerator IORT for locally advanced and borderline resectable pancreatic cancer

patients (5). Among 48 patients treated between 2002 and 2010 with chemoradiation therapy with the intent of resection and IORT, 31 patients underwent an attempted resection. Sixteen of these patients were able to undergo a R0/R1 Inhibitors,research,lifescience,medical resection whereas one patient underwent an R2 resection and the remaining 14 patients did not undergo resection. Twenty eight of these thirty one operated patients received IORT. Patients who had R0/R1 resections (with IORT) had significantly better median overall survival durations (23 vs. 10 months, P=0.002) than those Inhibitors,research,lifescience,medical Inhibitors,research,lifescience,medical who had R2 resection or no resection (with IORT). Since there were no patients without IORT who were part of the study, it remains unclear what role the IORT played in the survival outcomes achieved. It also remains unclear whether the inability of nearly half of all patients (16 of 31) to receive chemotherapy after IORT may have adversely affected overall survival of these patients. What might seem, on the surface, easier to discern is whether the additional IORT improved local control? While recognizing that comparisons to historical controls are fraught with flaws and that assessment/reporting of Inhibitors,research,lifescience,medical local control

is particularly challenging many in pancreatic cancer patients, the reported local failure rate of 29% in unresected patients who underwent IORT seems to compare favorably to that reported for locally advanced pancreatic cancers who do not undergo IORT. While this hints at a potential local control benefit from escalated doses of radiation to the retroperitoneal margin, given the competing risk for frequent and rapid metastatic dissemination of these aggressive tumors, it is not surprising that a potential local control benefit does not translate to a survival benefit. Similar findings were reported in a recent multi-institutional retrospective analysis of IORT for resected pancreatic cancer patients where local control was excellent but there was no improvement in overall survival (6).