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Dose escalation of radiotherapy in unresectable extrahepatic cholangiocarcinoma.

ABSTRACT: PURPOSE:To 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). METHODS:A 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. RESULTS:After 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.

SUBMITTER: Elganainy D

PROVIDER: S-EPMC6198206 | biostudies-other | 2018 Oct

REPOSITORIES: biostudies-other

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Dose escalation of radiotherapy in unresectable extrahepatic cholangiocarcinoma.

Elganainy Dalia D Holliday Emma B EB Taniguchi Cullen M CM Smith Grace L GL Shroff Rachna R Javle Milind M Raghav Kanwal K Kaseb Ahmed A Aloia Thomas A TA Vauthey Jean Nicolas JN Tzeng Ching-Wei D CD Herman Joseph M JM Koong Albert C AC Krishnan Sunil X SX Minsky Bruce D BD Crane Christopher H CH Das Prajnan P Koay Eugene J EJ

Cancer medicine 20180827 10

<h4>Purpose</h4>To 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).<h4>Methods</h4>A consecutive cohort of 80 patients who underwent radiotherapy for unresectable EHCC from 2001 to 2015 was identified. Demographic, tumor, treatment, toxicity, and labo ...[more]

PMID: 30152073

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Project description:IntroductionTumor-related liver failure (TRLF) is the most common cause of death in patients with intrahepatic cholangiocarcinoma (ICC). Though we previously showed that liver radiotherapy (L-RT) for locally advanced ICC is associated with less frequent TRLF and longer overall survival (OS), the role of L-RT for patients with extrahepatic metastatic disease (M1) remains undefined. We sought to compare outcomes for M1 ICC patients treated with and without L-RT.MethodsWe reviewed ICC patients that found to have M1 disease at initial diagnosis at a single institution between 2010 and 2021 who received L-RT, matching them with an institutional cohort by propensity score and a National Cancer Database (NCDB) cohort by frequency technique. The median biologically effective dose was 97.5 Gy (interquartile range 80.5-97.9 Gy) for L-RT. Patients treated with other local therapies or supportive care alone were excluded. We analyzed survival with Cox proportional hazard modeling.ResultsWe identified 61 patients who received L-RT and 220 who received chemotherapy alone. At median follow-up of 11 months after diagnosis, median OS was 9 months (95% confidence interval [CI] 8-11) and 21 months (CI: 17-26) for patients receiving chemotherapy alone and L-RT, respectively. TRLF was the cause of death more often in the patients who received chemotherapy alone compared to those who received L-RT (82% vs. 47%; p = 0.001). On multivariable propensity score-matched analysis, associations with lower risk of death included duration of upfront chemotherapy (hazard ratio [HR] 0.82; p = 0.005) and receipt of L-RT (HR: 0.40; p = 0.002). The median OS from diagnosis for NCDB chemotherapy alone cohort was shorter than that of the institutional L-RT cohort (9 vs. 22 months; p < 0.001).ConclusionFor M1 ICC, L-RT associated with a lower rate of death due to TRLF and longer OS versus those treated with chemotherapy alone. Prospective studies of L-RT in this setting are warranted.

Dataset Information

Dose escalation of radiotherapy in unresectable extrahepatic cholangiocarcinoma.

Publications

Dose escalation of radiotherapy in unresectable extrahepatic cholangiocarcinoma.

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