Radiation Is Effective for Palliative Treatment of Pancreatic Neuroendocrine Tumors
By Roxanne Nelson
Medscape Medical News
November 26, 2009 — Radiation therapy is effective in achieving local control and palliation in patients with pancreatic neuroendocrine tumors (PNTs), and it produces high rates of symptomatic palliation.
In the November?15 issue of the International Journal of Radiation Oncology-Biology-Physics, researchers report that PNTs were sensitive to treatment with external-beam radiotherapy (EBRT), despite the fact that this type of tumor is often considered to be radioresistant.
We believe that it is a good palliative therapy.
The authors note that this perception is "somewhat surprising," considering the fact that the management of PNTs is limited to anecdotal experiences. They also point out that data from published case reports suggest just the opposite — that PNTs might be responsive to radiation therapy and chemoradiotherapy, and that PNTs often present as unresectable tumors, making EBRT an attractive option for managing the disease.
"There are misconceptions about the use of radiation, but we believe that it is a good palliative therapy," said study author Edgar Ben-Josef, MD, associate professor in the Department of Radiation Oncology at the University of Michigan in Ann Arbor. "We conducted this study to evaluate our experience with it."
High Rate of Response and Palliation
The team reviewed records for 35 patients, which is thought to be the largest case series of PNTs to be treated with EBRT. They found that 39% of patients experienced a response to radiation therapy, the actuarial 3-year local freedom from progression rate was 49%, and symptom palliation was achieved in 90% of the cohort.
"We recommend that physicians consider radiation therapy for these patients," Dr. Ben-Josef told Medscape Oncology. "It is an effective tool but is underutilized."
Largest Series to Date
These patients were treated with radiation therapy at 49 sites between 1986 and 2006. Of the 35 patients for whom records were available, 14 received radiation treatment to the primary tumor or tumor resection bed. Within this group, 8 patients had unresectable tumors and 6 underwent surgical resection with either gross residual disease left behind/positive margin (n?= 3) or multiple positive lymph nodes (n?= 3). The other 21 patients had only been treated at the sites of distant metastasis, predominantly the liver or bone.
Nearly all of the patients (n?= 13) in the group treated for a primary tumor were chemotherapy naive, and the majority (n?= 20) of those who received radiation treatment to metastatic sites had undergone at least 1 course of cytotoxic chemotherapy. The median dose delivered to the primary and metastatic sites was 58.4 and 24.6?Gy, respectively, and 32 patients in this cohort were treated for symptoms or for progressive disease.
Follow-up computed tomography scans were performed to evaluate the disease in 23 patients who received treatment at 26 sites — 10 to the primary tumor and 16 to metastatic sites. Of this group, 13% had a complete response, 26% had a partial response, 56% had stable disease, and 4% had progressive disease.
Higher Doses for Improved Response
There was a definite dose-related response, Dr. Ben-Josef said. For the purposes of comparison, all radiation doses were converted to a 2?Gy/fraction biologically equivalent dose (BED). The interval to radiographic disease progression was determined for patients receiving either greater than or less than the median BED2Gy of 49.6. The authors observed a significant difference between these 2 groups (P?< .01), and all cases of radiographic progression occurred in patients who had received a radiation dose of 32 BED2Gy or less.
"We need to use higher doses to achieve a better response rate," said Dr. Josef. "We recommend sophisticated planning techniques, as well as appropriate dose fractionation regimens."
There is a potential for adverse events, especially with more aggressive therapy. "We don't want to harm patients, of course, but our data showed a dose-response-related response to therapy," Dr. Josef explained.
There were 2 cases of acute grade?4 toxicities, and 3 late toxicities (2 that were grade?3 and 1 that was grade?5); all toxicities occurred in patients who had undergone both an open surgical procedure and radiation therapy to the primary site. All 5 patients received a radiation dose of more than 50.4?Gy.
The median overall survival was 2 years and, at the time this analysis was conducted, 30 of the patients had died. Although there were no significant differences between patients who were treated at a primary site and those treated at a metastatic site, and there was a trend for improved 1-year survival in those treated at the primary site (86% vs 62%).
"Survival was not the primary focus of our study, but we can say that the patients had a rather long survival," said Dr. Josef.
The authors have disclosed no relevant financial relationships.
