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Research Letter | Association of VA Surgeons

Radiation Therapy for Unresectable Pancreatic Adenocarcinoma Population-Based Trends in Utilization and Survival Rates in the United States FREE

Mia Shapiro, MD1,2; Naim U. Rashid, PhD2,3; Qin Huang, MD2,4; Shira L. Galper, MD2,5,6; Valia A. Boosalis, MD7,8; Edward E. Whang, MD1,2,9; Jason S. Gold, MD1,2,9
[+] Author Affiliations
1Surgery Services, VA Boston Healthcare System, West Roxbury, Massachusetts
2Harvard Medical School, Boston, Massachusetts
3Dana-Farber Cancer Center, Boston, Massachusetts
4Pathology Services, VA Boston Healthcare System, West Roxbury, Massachusetts
5Radiation Therapy Services, VA Boston Healthcare System, West Roxbury, Massachusetts
6Beth Israel Deaconess Medical Center, Boston, Massachusetts
7Medicine Services, VA Boston Healthcare System, West Roxbury, Massachusetts
8Boston University School of Medicine, Boston, Massachusetts
9Brigham and Women’s Hospital, Boston, Massachusetts
JAMA Surg. 2015;150(3):274-277. doi:10.1001/jamasurg.2014.1837.
Text Size: A A A
Published online

Pancreatic cancer is the fourth most common cause of cancer-related death in the United States. Approximately 30% of patients present with locally unresectable disease. Although early studies demonstrated a survival benefit for chemotherapy,1,2 the added benefit of radiation remains unclear. Two recent prospective randomized trials3,4 specifically examined the contribution of radiation. The Fédération Francophone de Cancérologie Digestive/Société Francophone de Radiothérapie Oncologique trial3 compared patients randomly assigned to receive gemcitabine hydrochloride alone with patients randomly assigned to chemoradiotherapy along with 5-fluorouracil and cisplatin, followed by treatment with gemcitabine in both arms of the trial, and reported increased toxicity with decreased survival in the chemoradiotherapy arm. In contrast, the Eastern Cooperative Oncology Group trial,4 which compared patients randomly assigned to receive gemcitabine with patients randomly assigned to receive gemcitabine plus radiotherapy, found increased survival with radiation but was limited by poor accrual. The goal of our study was to examine the trends and predictors of the use of radiation for localized unresectable pancreatic cancer.

Patients with histologically confirmed nonmetastatic pancreatic adenocarcinoma with invasion of the large vessels by the tumor were selected from the Surveillance, Epidemiology, and End Results database, a population-based cancer registry encompassing 28% of the US population. Those who underwent resection were not included in our study. Patients who received external beam radiotherapy or who did not receive radiation were included. Correlations between clinicopathologic variables were sought using the Pearson χ2 test, the Fisher exact test, and univariate and multivariate logistic regression. Survival rates were compared using the log-rank test and multivariate Cox regression. P < .05 was found to be statistically significant. This study did not require institutional review board approval as the Surveillance, Epidemiology, and End Results database does not contain protected health information.

Between 1988 and 2010, a total of 9786 patients with localized unresectable pancreatic adenocarcinoma were identified. There was a significant decrease in radiation use over time (P < .001; Figure, A). While 52% of patients received radiation between 1988 and 1992, only 39% received radiation during the most recent period (ie, 2008-2010).

Place holder to copy figure label and caption
Figure.
Decrease in Radiation Use Over Time and Association of Radiation Use With Improved Survival

A, Trend in radiation use by time period. The error bars represent 95% CIs for percentages obtained using the adjusted Wald method. B, Kaplan-Meier survival curve comparing overall survival for patients who received radiation with overall survival for patients who did not.

Graphic Jump Location

We found significant variations in the administration of radiotherapy in relation to patient demographics. Geographic region, marital status, ethnicity, race, age, and year of diagnosis were all associated with radiation use on univariate analysis (P < .001; Table). The use of radiation was also associated with tumor grade (P = .03). Tumor size and regional lymph node involvement were not associated with the administration of radiotherapy. In the multivariate model, in addition to time period (P < .001), demographic factors including marital status (P < .001), age (P < .001), Hispanic ethnicity (P < .01), race (P < .01), and geographic region (P < .001) were independently associated with radiation use. Sex, tumor size, and lymph node involvement did not independently correlate with radiotherapy. Tumor grade was initially omitted because more than half the patients had missing data; however, when multivariate analysis was repeated with tumor grade, it was not considered to be statistically significant.

Table Graphic Jump LocationTable.  Association Between Clinicopathologic Variables and Use of Radiation Therapy in Univariate and Multivariate Modelsa

Radiotherapy was used most frequently in the Midwest, followed by the Northeast, and less frequently in the Southeast and Pacific West. Patients were more likely to receive radiation if they were younger than 65 years of age and married. The rate of use of radiation was lower among Hispanic patients and among African American patients. The use of radiation was associated with survival independent of other clinicopathologic variables (P < .001; hazard ratio, 0.69 [95% CI, 0.65-0.73]; median survival of 10 months with radiation compared with 6 months without radiation [Figure, B]).

The use of radiotherapy for patients with locally unresectable pancreatic carcinoma has decreased in the United States over the past 20 years. Disparities exist in the use of radiation based on patient demographics. In contrast, tumor characteristics were not independently associated with radiation. Radiotherapy was associated with improved survival, although selection bias cannot be excluded because data on patients’ comorbidities and use of chemotherapy were not available.

The use of radiation is likely on the decline owing to the proven efficacy of chemotherapy for locally unresectable pancreatic cancer without convincing data showing an additive effect for radiotherapy. Despite the limitations in our survival analysis, there may be a cohort of patients with localized unresectable pancreatic cancer who could benefit from radiation, and this is worthy of further investigation. If radiotherapy is thought to be of benefit, efforts should be made to minimize disparities in its use.

Corresponding Author: Jason S. Gold, MD, Surgery Services, VA Boston Healthcare System (112), 1400 VFW Pkwy, West Roxbury, MA 02132 (jgold4@partners.org).

Published Online: January 28, 2015. doi:10.1001/jamasurg.2014.1837.

Author Contributions: Drs Shapiro and Gold had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Shapiro, Huang, Gold.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Shapiro, Rashid, Huang, Gold.

Critical revision of the manuscript for important intellectual content: Shapiro, Galper, Boosalis, Whang, Gold.

Statistical analysis: Shapiro, Rashid, Gold.

Administrative, technical, or material support: Huang, Gold.

Study supervision: Galper, Whang, Gold.

Conflict of Interest Disclosures: None reported.

Funding/Support: This work is supported by the Department of Veterans Affairs Office of Research and Development through a Career Development Award 2 (Dr Gold).

Role of the Funder/Sponsor: The Department of Veterans Affairs Office of Research and Development had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Previous Presentation: This paper was presented at the 38th Annual Surgical Symposium of the Association of VA Surgeons; April 7, 2014; New Haven, Connecticut.

Additional Contributions: We thank Charles H. Yoon, MD, PhD, at the Department of Surgery of Brigham and Women’s Hospital and Harvard Medical School and Mandeep S. Saund, MD, at the Department of Surgery of Beth Israel Deaconess Medical Center, Harvard Vanguard Medical Associates, and Harvard Medical School for their advice on and contributions to this work. There was no compensation awarded to these additional contributors.

Haslam  JB, Cavanaugh  PJ, Stroup  SL.  Radiation therapy in the treatment of irresectable adenocarcinoma of the pancreas. Cancer. 1973;32(6):1341-1345.
PubMed   |  Link to Article
Moertel  CG, Frytak  S, Hahn  RG,  et al.  Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation + 5-fluorouracil: the Gastrointestinal Tumor Study Group. Cancer. 1981;48(8):1705-1710.
PubMed   |  Link to Article
Chauffert  B, Mornex  F, Bonnetain  F,  et al.  Phase III trial comparing intensive induction chemoradiotherapy (60 Gy, infusional 5-FU and intermittent cisplatin) followed by maintenance gemcitabine with gemcitabine alone for locally advanced unresectable pancreatic cancer: definitive results of the 2000-01 FFCD/SFRO study. Ann Oncol. 2008;19(9):1592-1599.
PubMed   |  Link to Article
Loehrer  PJ  Sr, Feng  Y, Cardenes  H,  et al.  Gemcitabine alone vs gemcitabine plus radiotherapy in patients with locally advanced pancreatic cancer: an Eastern Cooperative Oncology Group trial. J Clin Oncol. 2011;29(31):4105-4112.
PubMed   |  Link to Article

Figures

Place holder to copy figure label and caption
Figure.
Decrease in Radiation Use Over Time and Association of Radiation Use With Improved Survival

A, Trend in radiation use by time period. The error bars represent 95% CIs for percentages obtained using the adjusted Wald method. B, Kaplan-Meier survival curve comparing overall survival for patients who received radiation with overall survival for patients who did not.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable.  Association Between Clinicopathologic Variables and Use of Radiation Therapy in Univariate and Multivariate Modelsa

References

Haslam  JB, Cavanaugh  PJ, Stroup  SL.  Radiation therapy in the treatment of irresectable adenocarcinoma of the pancreas. Cancer. 1973;32(6):1341-1345.
PubMed   |  Link to Article
Moertel  CG, Frytak  S, Hahn  RG,  et al.  Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation + 5-fluorouracil: the Gastrointestinal Tumor Study Group. Cancer. 1981;48(8):1705-1710.
PubMed   |  Link to Article
Chauffert  B, Mornex  F, Bonnetain  F,  et al.  Phase III trial comparing intensive induction chemoradiotherapy (60 Gy, infusional 5-FU and intermittent cisplatin) followed by maintenance gemcitabine with gemcitabine alone for locally advanced unresectable pancreatic cancer: definitive results of the 2000-01 FFCD/SFRO study. Ann Oncol. 2008;19(9):1592-1599.
PubMed   |  Link to Article
Loehrer  PJ  Sr, Feng  Y, Cardenes  H,  et al.  Gemcitabine alone vs gemcitabine plus radiotherapy in patients with locally advanced pancreatic cancer: an Eastern Cooperative Oncology Group trial. J Clin Oncol. 2011;29(31):4105-4112.
PubMed   |  Link to Article

Correspondence

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