Dose escalation of radiotherapy in unresectable extrahepatic cholangiocarcinoma

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.

Prognostic Makers Including Immune and Inflammatory Factors Predict Outcomes in Patients Receiving Postoperative Radiation Therapy for Cholangiocarcinoma

“…The most frequent sites of local recurrence were the hepatectomy stump, the anastomosis, or both. Several reports that determined the sites of local recurrence with or without adjuvant chemotherapy found that the most common are biliary anastomosis, the liver incision, and choledochojejunostomy, with recurrence rates ranging from 36.4-59% [1,30,31]. Thus, the frequencies of local recurrence sites are similar with or without RT; however, our present data indicate that the recurrence rates were lower for patients administered adjuvant RT.…”

“…Age is a prognostic factor for CCA [1]. Moreover, some studies show that tumor size and multiple tumors (satellite tumor) are prognostic factors of CCA [1,30,31]. In the present study, there was no signi cant difference in tumor size (data not shown), and patients did not have detectable satellite tumors.…”

“…Comparisons with previous studies may be di cult because of their different populations and stages. Patients with an elevated NLR experience shorter survival [1,[33][34][35]. However, we show a signi cant association between LCR and PFS.…”

“…Patients with unresectable extrahepatic cholangiocarcinoma (EHCC) treated with radiation therapy using 3D-CRT, intensity-modulated radiation therapy (IMRT), or proton beam therapy experience an MST of 18.7 months [1]. In our present study, 2-year OS rates were 59.5%; those of CSS, PFS, and LRC were 62.0%, 40.1%, and 66.7%, respectively; and MST was 29.5 months.…”

Prognostic nomogram to predict overall survival for patients with perihilar cholangiocarcinoma: A population-based study of SEER database

“…The regimen of gemcitabine and cisplatin was recommended for inoperable or postoperative pCCA patients [4,37], but detailed chemotherapy regimen information were unavailable in SEER database. Patients with extrahepatic cholangiocarcinoma may be offered chemoradiation therapy, which was administered with a dose of 45 Gy to regional lymphatics and 54 to 59.4 Gy to the tumor bed [38,39]. With respect to the radiotherapy for perihilar cholangiocarcinoma, Leng et al [40] argued that adjuvant radiotherapy was of no association with survival improvement for resected pCCA groups.…”