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Stereotactic body radiotherapy promising for pancreatic cancer
The addition of stereotactic body radiotherapy to chemotherapy extended OS among patients with unresectable pancreatic cancer, according to data from a retrospective analysis.
Five-year survival rates for patients with pancreatic cancer remain low, at less than 8%. Complete surgical resection extends survival. However, between 80% and 85% of patients present with unresectable disease.
Chemotherapy plus external-beam radiotherapy (EBRT) is standard of care for patients with unresectable pancreatic cancer, but trials of EBRT have shown conflicting results, possibly due to the intrinsic radio resistance of pancreatic cancer cells.
SBRT applies one to five fractions of high-dose radiation to a limited target volume, which offers a potential advantage for patients with pancreatic cancer by overcoming radio resistance. Outcomes with SBRT had not been compared with standard treatment approaches.
Jennifer F. Tseng, MD, MPH, chief of the division of surgical oncology at Beth Israel Deaconess Medical Center, and colleagues identified 204,387 patients with unresected pancreatic adenocarcinoma — diagnosed between 2004 and 2012 — using the National Cancer Data Base. Of them, 14,331 (men, 49.6%) met the inclusion criteria.
Researchers divided patients into four groups based on treatment: chemotherapy alone (n = 5,464) or combined with EBRT (n = 6,418), intensity-modulated radiotherapy (IMRT; n = 2,127) or SBRT (n = 322).
The majority of patients were aged 65 years or older at diagnosis (55.1%), white (79.5%) and had proximal pancreatic tumors (67.4%) and stage III disease (52.2%).
The unadjusted median survival was 10.8 months for the entire cohort; 9.9 months for patients treated with chemotherapy, 10.9 months for chemotherapy with EBRT, 12 months for chemotherapy with IMRT and 13.9 months for chemotherapy with SBRT.
Researchers then used propensity score models — which predicted the odds of a patient receiving SBRT — to control for potential selection bias and match 322 patients who received SBRT to 322 patients each who received chemotherapy alone, EBRT or IMRT.
In the matched analyses, SBRT demonstrated improved median survival (13.9 months) compared with single-agent chemotherapy (10.2 months; P < .0001) and EBRT (11.6 months; P = .0180). Survival did not differ between patients who received SBRT and IMRT in the matched analysis (13.9 months vs. 12.2 months).
Sensitivity analysis showed patients who received multiagent chemotherapy had longer median OS than patients treated with single-agent chemotherapy (11.4 months vs. 8.8 months; P < .001). However, researchers observed no difference in median OS between patients who received the addition of SRBT to multiagent chemotherapy (14.8 months vs. 12.9 months).
“Future trials should evaluate the outcomes of SBRT combined with multiagent chemotherapy vs. multiagent chemotherapy alone or in combination with conventionally fractioned EBRT,” the researchers wrote. “In addition, future trials should also include potentially resectable patients and examine toxicity and quality-of-life measures.” – by Melinda Stevens
Disclosure: The researchers report no relevant financial disclosures.
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This large retrospective study analyzed patients who had received chemotherapy with or without various radiotherapy approaches, including stereotactic body radiotherapy, external-beam radiotherapy (EBRT) and intensity-modulated radiotherapy. The role of radiation in the treatment of pancreatic cancer has remained controversial. Although radiation has the potential to be directly cytotoxic to malignant cells, it can also induce inflammation, which can be a key driver of malignant cell growth in pancreatic cancer.
As such, strategies designed to focus radiation and remove the protumor inflammatory response that can ensue posttreatment may help to better define the potential of radiotherapy in pancreatic cancer. In this study, the researchers provided data to suggest that more focused delivery of radiotherapy by SBRT in combination with chemotherapy improved OS compared with chemotherapy alone and chemotherapy in combination with traditional fractionated EBRT for patients with unresectable pancreatic cancer. The findings are promising, but will require prospective evaluation in a randomized setting.