Combining IORT With Chemotherapy Improves Survival in Pancreatic Cancer

Pancreatic cancer remains a dreaded disease, with a little less than half the patients presenting with locally advanced, usually unresectable, disease. Even with neoadjuvant chemotherapy, survival remains dismal. A new study conducted at Massachusetts General Hospital (MGH) evaluated the impact of intraoperative radiotherapy (IORT), along with induction chemotherapy and chemo-radiotherapy, in patients with advanced disease, and observed hints of success.

The trial retrospectively analyzed clinical outcomes in patients with locally advanced unresectable or borderline-resectable pancreatic ductal adenocarcinoma (PDAC) to receive the above treatment between 2010 and 2015. Following the neoadjuvant treatment—FOLFIRINOX, gemcitabine with nab-paclitaxel, or FOLFOX with dose-escalation to FOLFIRINOX—patients underwent exploratory laparotomy. A little more than 60% (41) of the enrolled 68 patients underwent resection, 26.5% (18) had unresectable disease, and 13.2% (9) had developed distant metastases. More than half the patients with resectable disease (22) were provided IORT.

The authors discovered that the median overall survival (OS) improved from 26.6 months, for all patients who underwent resection, to 35.1 months in patients who received IORT along with resection. Median OS was 24.5 months in patients who underwent resection alone. The difference in OS was, however, not significant. Median progression-free survival improved from 16.3 months, in patients who underwent resection alone, to 21.0 months in patients who additionally were treated with IORT (P = .09). The rate of developing distant metastases was the same between the 2 groups.

In patients with unresectable disease who received IORT, median OS was 24.8 months and median PFS was 16.1 months.

"We confirm that in the modern era of chemotherapy, IORT is useful in allowing surgeons to attempt resection even when radiographically it appears the vessels are involved. Even in patients who are not resected, median survivals now are similar to patients who were resected when treated with IORT," Theodore (Ted) Sunki Hong, MD, senior author on the study, told The American Journal of Managed Care in an e-mail. Hong is the director of gastrointestinal service in the Department of Radiation Oncology, and associate clinical director in the Department of Radiation Oncology at MGH.

IORT extended patient hospital stay by about half a day compared with the control group (4 versus 3.5 days, respectively), but did not significantly impact operating times or patient morbidity.

Based on their findings, the authors conclude that the addition of IORT to neoadjuvant chemotherapy in patients with PDAC was associated with encouraging median survival rates in patients with unresectable disease or close or positive margins after resection, and that this patient population may benefit from aggressive local therapy that includes IORT.

Plans are underway to initiate a multi-institutional trial based on the MGH protocol to duplicate the results with significantly more patients and other leading pancreatic cancer centers.

Reference

Keane FK, Wo JY, Ferrone CR, et al. Intraoperative radiotherapy in the era of intensive neoadjuvant chemotherapy and chemoradiotherapy for pancreatic adenocarcinoma [published online October 12, 2016]. Am J Clin Oncol. Am J Clin Oncol. doi: 10.1097/COC.0000000000000336.