Intraoperative RT Useful in Unresectable Pancreatic Cancer

SALT LAKE CITY-Intraoperative electron beam radiation therapy (IOERT) may prolong the survival of patients who have unresectable but nonmetastatic pancreatic cancers that are small, according to a retrospective study reported at the 45th Annual Meeting of the American Society for Therapeutic Radiology and Oncology (abstract 159). Among patients who received this radiation therapy as part of their comprehensive treatment, nearly one-fifth of those with small cancers were still alive 3 years later, but all of those with large cancers had died. "Locally advanced, nonmetastatic pancreatic cancer is a common presentation, and it is associated with profound morbidity and suffering for these patients. Our therapeutic efforts are of a palliative nature," said lead author Christopher G. Willett, MD, clinical director of radiation oncology, Massachusetts General Hospital, and professor of radiation oncology, Harvard Medical School. Dr. Willett noted that various forms of radiation therapy have been used to treat this cancer for more than 30 years. "To improve local control, intraoperative electron beam radiation therapy, typically 20 Gy, has been combined with treatment programs of external beam irradiation, typically on the order of 45 to 50 Gy, and 5-FU [fluorouracil]- based chemotherapy," he said. The investigators studied 150 patients with unresectable, biopsy-proven ductal adenocarcinoma of the pancreas treated with external beam radiation therapy, 5-FU, and IOERT between 1978 and 2001. Pathologists re-reviewed the histologic findings in patients surviving more than 3 years to verify the diagnosis. The patients received a wide range of treatments with respect to both radiation therapy and chemotherapy, Dr. Willett noted. "As we all know, there has been a profound treatment evolution in this disease," he said. "The basic theme, however, is an effort to employ moderate- to highdose external beam irradiation with 5-FU and IOERT at 20 Gy." Survival Benefit The patients had a median and mean survival of 13 and 17 months, respectively, Dr. Willett said. In Kaplan- Meier analysis, their survival rates were 54% at 1 year, 17% at 2 years, and 7% at 3 years. Eight patients were long-term survivors, with three patients still alive 3 to 4 years after treatment, and five patients still alive more than 5 years after treatment. "In an effort to assess tumor volume, we used a surrogate marker- diameter of the electron cone," Dr. Willett said. There was a significant inverse correlation between cone diameter and survival. About one-fifth of the 26 patients treated with cones that were 5 or 6 cm in diameter were still alive at 3 years, compared with none of the 11 patients treated with cones that were 9 cm in diameter (17% vs 0%), he said. Patients treated with cones having a diameter of 7 or 8 cm had intermediate survival. Rates of morbidity and mortality were reasonable, Dr. Willett noted. Overall, 0.6% of patients died during surgery, 20% had postoperative complications, and 15% had late complications. Whereas delayed gastric emptying was fairly common in the perioperative period, abdominal abscesses and fistulas were uncommon. A second laparotomy was necessary in three patients. "Those experienced with electron beam treatment and this type of protocol for pancreatic head carcinomas know that the major issue is GI bleeding due to duodenal treatment, and 16 patients experienced this," he said. A single patient developed duodenal obstruction, and two patients had fatal gastrointestinal bleeding due to late vascular effects. The length of hospital stay for the treatment gradually decreased over the study period, Dr. Willett noted. "In our more recent time points, we were down to about a 5- or 6-day length of stay following a laparotomy, gastric jejunostomy, and IOERT," he said. Despite aggressive local treatment, Dr. Willett said, local control of these cancers is likely to be very problematic. "Clearly, if one is to use IOERT for this group of patients, selection is critical." Dr. Willett noted that routine laparoscopy (to rule out peritoneal disease) and restaging by CT after fulldose preoperative radiation therapy and chemotherapy (to rule out progressive and metastatic disease) have helped identify patients who are good candidates for intraoperative radiation therapy. "Our current protocol is looking at a phase I-II trial employing external beam irradiation with oxaliplatin(Drug information on oxaliplatin) [Eloxatin], gemcitabine(Drug information on gemcitabine) [Gemzar], and restaging, with the appropriate use of IOERT," he said.