Abstract
PurposeTo evaluate the effect of escalated dose radiation therapy (EDR, defined as doses >50.4 Gy in 28 fractions [59.5 Gy BED]) on overall survival (OS), freedom from local progression (FFLP), and freedom from distant progression (FFDP) of patients with unresectable extrahepatic cholangiocarcinoma (EHCC).MethodsA consecutive cohort of 80 patients who underwent radiotherapy for unresectable EHCC from 2001 to 2015 was identified. Demographic, tumor, treatment, toxicity, and laboratory variables were collected. The maximal RT doses ranged from 30 to 75 Gy (median 50.4 Gy, at 1.8‐4.5 Gy/fraction). Gross tumor volume (GTV) coverage by maximal dose in EDR group ranged from 38% to 100%. Kaplan–Meier method was used to estimate OS, FFLP, and FFDP. Univariate and multivariate Cox regression models were analyzed.ResultsAfter radiotherapy, median OS, FFLP, and FFDP were 18.7, 22.6, and 24.3 months, respectively. There was no significant difference in OS or FFLP between patients who received EDR to portions of the GTV and patients who did not. On multivariate analysis, bigger GTV, age, and ECOG performance status were independently associated with shorter OS. Local progression on chemotherapy prior to RT was independently associated with shorter FFLP. High baseline neutrophil/lymphocyte ratio (>5.3) was independently associated with shorter FFDP. Toxicity grades were similar in EDR and lower doses except lymphopenia which was higher in EDR (P = 0.053).Conclusions EDR to selective portions of the GTV may not benefit patients with unresectable EHCC despite having acceptable toxicity. New methods to improve local control and survival for unresectable EHCC are needed.
Highlights
Extrahepatic cholangiocarcinoma (EHCC) is a rare and lethal malignancy that originates from the epithelial cells of the extrahepatic bile ducts
In a series of 52 patients with locally advanced EHCC treated at our institution, we previously identified the limitations of conventional doses of radiotherapy in this disease and suggested that a possible way to overcome that would be escalated dose radiotherapy (EDR)
We reviewed our experience with patients with unresectable EHCC who were treated with radiotherapy with or without concurrent chemotherapy, looking for evidence of long-term local tumor control, and overall survival
Summary
Extrahepatic cholangiocarcinoma (EHCC) is a rare and lethal malignancy that originates from the epithelial cells of the extrahepatic bile ducts. EHCC can be further divided according to its location into perihilar and distal types. According to a Surveillance, Epidemiology, and End Results (SEER) review from 1975 to 2013, the incidence is 1.9 cases per 100 000 people, and the incidence appears to be increasing. The prognosis of EHCC is poor, with a 5-year survival rate of 16.9%.1. Complete surgical resection is the only potentially curative treatment for anatomically resectable tumors, but most patients present with unresectable locally advanced or metastatic disease due to late presentation and nonspecific symptoms.. Resectability is determined by local extent of the tumor including vascular involvement, estimated magnitude of pancreatic or liver resection, and metastatic disease.. The prognosis of EHCC is poor, with a 5-year survival rate of 16.9%.1 Currently, complete surgical resection is the only potentially curative treatment for anatomically resectable tumors, but most patients present with unresectable locally advanced or metastatic disease due to late presentation and nonspecific symptoms. Resectability is determined by local extent of the tumor including vascular involvement, estimated magnitude of pancreatic or liver resection, and metastatic disease. Effective treatment options for these patients are needed
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