International Journal of Radiation Oncology*Biology*Physics
Clinical InvestigationRadiotherapy Is Associated With Improved Survival in Adjuvant and Palliative Treatment of Extrahepatic Cholangiocarcinomas
Introduction
Cholangiocarcinomas are rare malignancies that arise from the epithelial cells that line the bile ducts and constitute approximately 3% of all gastrointestinal cancers (1). Cholangiocarcinomas can be classified by their location within the biliary tree as intrahepatic, hilar (Klatskin's tumor), or distal, each with different resectability rates and outcomes. Whether this is because of a biologic difference dependent on tumor location is under debate (2). The present study focused on the use of radiotherapy (RT) for extrahepatic cholangiocarcinoma (EHC). Distal EHCs constitute approximately 20–30% of cholangiocarcinomas, with hilar cholangiocarcinomas accounting for an additional 50–60% (3). The incidence of EHCs appears to be decreasing; however, approximately 7,500 new cases of EHCs were diagnosed in the United States in 2005 4, 5. A gradual improvement in the 5-year survival rates has occurred for patients with EHCs but the prognosis remains poor, with a 5-year survival rate of 12.5–40% 3, 5, 6, 7, 8, 9, 10, 11.
Surgical resection is the only curative treatment for EHC; however, most patients have unresectable disease or have positive surgical margins after resection 3, 6, 12, 13, 14. It has been suggested that RT may be of benefit in patients with EHCs in both the adjuvant and palliative setting; however, this remains controversial 15, 16, 17, 18, 19. Because of the low incidence of EHC, large randomized trials evaluating the effectiveness of RT in the postoperative and palliative settings are unavailable. The present study was designed to examine the role of RT in the postoperative and palliative setting in a large group of patients from the Surveillance, Epidemiology, and End Results (SEER) database.
Section snippets
Patient selection and treatment
The SEER database of the National Cancer Institute is a national cancer registry that collects information about the incidence and survival of cancer cases from 13 cancer registries. It includes approximately 26% of the U.S. population and is representative of national demographics. The SEER database was queried for the diagnosis of cholangiocarcinoma between 1988 and 2003. The “International Classification of Diseases for Oncology” (ICD-0-2 [1972–2000] and ICD-0-3 [2000–2002]) codes were used
Baseline patient characteristics
A total of 7,640 patients with EHC were identified for the period between 1973 and 2003. After eliminating all patients diagnosed before 1988, a total of 5,345 patients were available for analysis. RT details were lacking for 168 patients who were excluded from the analysis. Finally, after eliminating patients without surgical information, a total of 4,758 patients were available for analysis.
The patient demographics are listed by treatment category in Table 1; 52.5% of the patients were white
Discussion
Patients with EHC, treated with palliative RT, had a significant improvement in OS compared with patients treated with no RT or surgery on both multivariate and propensity score analyses. The results demonstrated a 5-month improvement in median OS and a 44% reduction in the risk of death. Surgery plus RT was associated with a 7-month improvement in median OS and a 5% reduction in the risk of mortality compared with surgery alone. However, after adjusting for potential confounders using the
Conclusion
It is possible that with careful patient selection, such as selecting those with positive margins, RT would be of benefit. To better define the role of RT in the adjuvant setting, additional prospective trials are needed. Given the locally aggressive nature of this disease, multimodality treatment should be investigated. Toxicity remains a problem; however, proton therapy might be a way to limit the dose to critical structures and allow both RT and concurrent chemotherapy doses to be increased
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Cited by (70)
Proton beam therapy for extrahepatic biliary tract cancer: Analysis with prospective multi-institutional patients’ registration database, Proton-Net
2023, Clinical and Translational Radiation OncologyThe effect of trans arterial chemoembolization in the management of intrahepatic cholangiocarcinoma. A systematic review and meta-analysis
2022, European Journal of Surgical OncologyAdjuvant systemic treatment in resected biliary tract cancer: State of the art, controversies, and future directions
2021, Cancer Treatment and Research CommunicationsCitation Excerpt :A large retrospective series assessed the role of adjuvant radiotherapy in 3839 patients with iCCA [42]; median OS was 11 months (95% CI, 9–13) and 6 months (95% CI, 5–6) for patients receiving surgery followed by adjuvant radiotherapy or surgery alone, respectively. When the authors adjusted for other prognostic factors in the multivariable analysis, differences were significant [42]. Of note, international guidelines supported the use of adjuvant therapy on the basis of a pivotal meta-analysis by Horgan and colleagues [28].
Italian Clinical Practice Guidelines on Cholangiocarcinoma – Part II: Treatment
2020, Digestive and Liver DiseaseCitation Excerpt :This benefit was predominantly observed in patients with positive margins, who were more represented among those undergoing radiotherapy [105]. In general, available literature [37,106–132] regarding radiation therapy is scarce and of low quality due to the low number of patients enrolled, the heterogeneity of patients and combined treatments, and the retrospective nature of most studies. The vast majority of studies were on pCCA.
Current standards and future perspectives in adjuvant treatment for biliary tract cancers
2020, Cancer Treatment ReviewsRadiotherapy for Biliary Tract Cancers
2018, Seminars in Radiation Oncology
Funded, in part, by a grant from the Pennsylvania Department of Health.
The Pennsylvania Department of Health specifically disclaims responsibility for any analysis, interpretations, or conclusions. Nandita Mitra was also funded by the Abramson Cancer Center of the University of Pennsylvania Core Support Grant, NIH grant P30-CA016520.
Conflict of interest: none.