Shorter Course of Radiation Has Benefits in Pancreatic Cancer

Veronica Hackethal, MD

May 21, 2015

High-dose, short-term radiation therapy delivered as a 5-day course of stereotactic body radiation therapy (SBRT) may be as effective, or even better, than standard radiotherapy delivered during 6 weeks for the treatment of locally advanced pancreatic cancer (LAPC). The conclusion is based on two recent studies by researchers at Johns Hopkins University, Stanford University, and Memorial Sloan Kettering Cancer Center.

The standard of care for LAPC is chemotherapy followed by standard chemotherapy and radiation, explained Joseph Herman, MD, codirector of the Pancreatic Cancer Multidisciplinary Clinic at Johns Hopkins University, in Baltimore, Maryland, who is an author on both of the studies. The treatment takes about 6 weeks and can be "very challenging" for patients, Dr Herman said. Although the standard regimen can be effective, it also has high rates of acute toxicity, such as nausea, vomiting, and diarrhea.

SBRT, on the other hand, uses higher doses of targeted radiation delivered during a shorter period, usually 5 days, which could be desirable for patients with unresectable pancreatic cancer, whose median survival is about 12 months.

"Even if we can't demonstrate an improvement in survival with a newer, shorter form of radiation, if we can show that it can be at least as effective, with less toxicity and over a shorter period of time, then that would be an important advancement," Dr Herman said.

Another advantage of SBRT may be its price.

"It is cheaper to do SBRT than standard radiotherapy. In a time of limited resources for oncology care, I think that these results are important," Dr Herman emphasized. "My hope is that insurance companies will consider this as a standard option for these patients and that we can make SBRT more of a mainstream treatment."

SBRT is recommended mainly for locally advanced or unresectable and borderline resectable pancreatic cancer with blood vessel involvement, Dr Herman explained. Patients with involvement of the stomach or duodenum are not good candidates for SBRT, unless they are definitely having surgery.

Randomized trials are needed, though. Dr Herman's group is working to initiate a national randomized trial comparing chemotherapy with the combination of chemotherapy and SBRT.

"For pancreatic cancer, it's really important to continue to encourage clinical trial enrollment, given that it's a very rare cancer and the mortality rate is so high," he emphasized.

Study Details

The first study, a single-arm, multicenter, phase 2 trial, was published in April 2015 in Cancer. It is the first prospective, multicenter study to look at SBRT in pancreatic cancer.

"The acute and chronic toxicity were very acceptable. The acute toxicity was almost nothing," commented Dr Herman, who was first author on the article. "In addition, we didn't see any decrease in quality of life [before or after treatment]. There was a significant improvement in pain scores for these patients."

The 5-day course of SBRT may also be more effective, Dr Herman suggested. Compared with the results of a recent trial of standard radiotherapy, survival with SBRT in this phase 2 trial appeared to be "a little bit better," he pointed out, and toxicity rates were lower.

"I think that this will hopefully help establish SBRT as a standard option for these patients," Dr Herman said.

The study included 49 patients with locally advanced pancreatic cancer treated at Johns Hopkins University, Stanford University, and Memorial Sloan Kettering Cancer Center. Participants received three doses of gemcitabine (Gemzar, Eli Lilly and Company) (1000 mg/m2), then went 1 week without medication, after which they received SBRT (33.0 Gy in five doses) during 1 to 2 weeks.

Results showed that 2% of patients developed acute and 11% developed late grade ≥2 GI side effects. Quality of life scores, as reported on questionnaires, had a median change of 0 on follow-up at 4 weeks and 4 months after treatment (P < .05 for both). Pain scores also significantly improved at 4 weeks after SBRT (P = .001). Median overall survival was 13.9 months (95% confidence interval [CI], 10.2 - 16.7 months); median progression-free survival was 7.8 months (95% CI, 5.8 - 10.2 months). Freedom from local disease progression at 1 year was 78% (95% CI, 60% - 89%). Four patients (8%) were able to undergo margin-negative and lymph-node negative resections.

The second study, published in the January issue of the Annals of Surgical Oncology, looked at acute and late toxicity of SBRT in locally advanced (LAPC) and borderline resectable (BRPC) pancreatic cancer.

"What we showed in this study was that a large proportion of patients, despite being unresectable, were able to go to surgery, and the pathologic response was very favorable with SBRT," commented Dr Herman, who was senior author on the article. "In fact, there were several patients who had a complete response, meaning there was no tumor left behind."

"This is pretty unique. We don't see this kind of response typically with standard radiation and with chemotherapy alone," he continued, "so it's exciting that this short course of 5 days of radiation is giving us at least equivalent or better survival, less toxicity, and better pathologic response rates than what we would see with standard treatment."

The researchers reviewed charts of all patients with pancreatic cancer who received SBRT at Johns Hopkins between 2010 and 2014. Seventy-seven patients received pre-SBRT chemotherapy (gemcitabine only, n = 45; gemcitabine-based regimens, n = 14; FOLFIRINOX, n = 18). Patients received a total dose of 25 to 33 Gy SBRT in five separate doses.

The analysis included 88 patients, 74 (84%) of whom had LAPC, and 14 (16%) of whom had BRPC. The median overall survival was 18.4 months, the median progression-free survival was 9.9 months (95% CI, 8.0 - 12.3), and the median local progression-free survival was 13.9 months (95% CI, 12.02 - 17.87).

Only 3.4% (n = 3) of patients experienced acute grade ≥3 toxicity ; 5.7% (n = 5) experienced late grade ≥2 GI toxicity.

Nineteen (21.6%) patients had surgery, of whom 16% had pathologic complete response, 10% had near response, and 74% had partial response.

Dr Sugar has received a grant from the Viragh Family Foundation Inc and from the National Cancer Institute.

Cancer. 2015:121;1128-1137. Full text

Ann Surg Oncol. Published online Jan. 15, 2015. Abstract

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