Patients with pancreatic cancer who receive external beam radiotherapy survive longer than those who are treated with surgery alone, according to the results of a retrospective analysis published in the Journal of Clinical Oncology.

Management of patients with pancreatic cancer is an ongoing challenge because despite improvements in surgical technique and the introduction of new treatment regimens, prognosis remains extremely poor. 5-year survival rates after attempts at curative surgery range from just 14% to 27%.

The reason so many patients die soon after surgery is partly because of high rates of recurrence, both at sites near the original tumour and in distant locations. Reflecting the importance of systemic disease to overall survival, chemotherapy after surgery can improve outcomes to some extent. But it is not yet clear whether radiation after surgery confers similar benefits. To further refine the role of radiation treatment in patients with pancreatic cancer, Avo Artinyan and colleagues did a retrospective study using the US-based Surveillance, Epidemiology, and End results database, which includes information from 18 registries around the country.

All patients who had undergone surgery for pancreatic cancer between the years 1988 and 2003 were identified from the database, along with details of overall survival, adjuvant treatments, local extent of disease, grade, tumour location, and demographic information. Deciding to focus on patients who did not have any traces of disease in their lymph nodes during surgery---the group the authors reasoned would be most likely to benefit from the localized treatment effects of radiotherapy---a total of 1930 patients who met the study's inclusion criteria were identified.

Around 40% of patients received radiation at some point during their treatment. Patients who received neoadjuvant radiation, intraoperative radiation, adjuvant radiation in the form of radioisotopes or radioactive implants, and were excluded from the survival analyses and 13 of the 674 patients in the adjuvant radiation group who were treated with radioisotopes, radioactive implants, or an unknown radiation source were allowed in the descriptive portion of the study, but excluded from further analysis.

Therefore, the final intervention population consisted of 661 patients who had node-negative disease and who had received external beam radiotherapy after undergoing surgery. The control group consisted of the remaining 1137 patients who had undergone surgery but received no radiation therapy. Median survival for the total patient population was 17 months. Comparing the two groups of patients, those who received adjuvant radiation had significantly better survival than the nonradiation group, with median survival times of 20 versus 15 months, respectively. Univariate analysis showed that adjuvant radiation, age at diagnosis, tumour location, grade, and T classification were all associated significantly with survival. In a multivariate analysis, external beam radiotherapy was associated with around a 30% decrease in the risk of death.

In a further calculation designed to eliminate the skewing effect of including patients with very poor survival in the study---for whom adjuvant therapy probably was not considered due to their state of health before or after surgery---the researchers repeated the analysis after excluding patients with survival less than 3 months. After exclusion of early deaths, there was no significant difference in overall survival between patients who did and did not receive external beam radiotherapy (median 20 months versus 19 months, respectively). But in a multivariate analysis, this intervention was again associated with improved survival, after adjusting for the other covariates. The authors explain that "the discrepancy between univariate and multivariate findings may have been related to a slightly greater incidence of higher T classification lesions in the irradiated group."

"Our results demonstrated a survival advantage in patients who received adjuvant EBRT compared with non-irradiated patients…[which] persisted after adjusting for several relevant clinical factors, such as age, T classification, grade, and tumor location," note the authors. However, they caution, the SEER registry does not collect data regarding chemotherapy meaning that some of the survival advantage observed in the study may be the result of treatment with adjuvant chemotherapy rather than radiation. What is more, the database includes no information about dosing schedules or the size of the area treated with radiation, and since these factors influence outcome, this dearth of data is a further source of uncertainty.

"In conclusion," write the authors, "there appears to be a small but significant benefit in survival with the administration of adjuvant EBRT for patients who have N0 pancreatic cancer in the U.S. population. This survival advantage is independent of several established prognostic factors for outcome….[Therefore,] radiation therapy as a potential component of adjuvant treatment, either in the standard or trial setting, cannot be dismissed."

Improved survival with adjuvant external-beam radiation therapy in lymph node-negative pancreatic cancer: a United States population-based assessment

Artinyan A, Hellan M, Mojica-Manosa P, Chen Y-J, Pezner R, Ellenhorn JDI, Kim J. Cancer 2008; 112: 34-42
Cancer Research Summaries are overviews of important cancer research findings that have been reported in leading cancer publications. The Cancer Research Summaries are provided by the Cancer Media Service (CMS) in collaboration with Nature Clinical Practice Oncology.

This summary is provided by the Cancer Media Service which is operated by The European School of Oncology.

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