Higher radiation dose improves OS, local control for inoperable cholangiocarcinoma

Higher doses of radiotherapy appeared associated with improved OS and local control among patients with inoperable intrahepatic cholangiocarcinoma, according to the results of a retrospective dose–response analysis.

“Intrahepatic cholangiocarcinoma (IHCC) is an uncommon but lethal disease that arises from the epithelial lining of the intrahepatic biliary tree,” Christopher H. Crane, MD, professor in the department of radiation oncology at The University of Texas MD Anderson Cancer Center, and colleagues wrote. “Surgery is considered the only potentially curative treatment for IHCC, but only approximately 30% of patients have operable disease.”

Non-operative treatment options have significant limitations and have been associated with poor survival outcomes, according to study background. However, advances in radiotherapy techniques and imaging have enabled ablative doses to be delivered to large liver tumors.

Thus, Crane and colleagues sought to evaluate the effects of radiotherapy dose escalation for the treatment of patients with inoperable IHCC.

The researchers identified 79 patients (median age, 63 years; 58% women) treated with definitive radiotherapy between 2002 and 2014. The median tumor size at diagnosis was 7.9 cm (range, 2.2-17).

Eighty-nine percent of patients (n = 70) received systemic chemotherapy prior to radiotherapy. The median radiotherapy dose was 58.05 Gy (range, 35-100) in three to 30 fractions, for a median biologic equivalent dose (BED) of 80.5 Gy (range, 43.75-180). Sixty patients received a BED of 80.5 Gy or lower, whereas 19 patients received a BED higher than the median.

Median follow-up for patients alive at time of analysis was 33 months (range, 11-93). Patients achieved a median OS of 30 months. One-year OS rate was 87%, 2-year OS rate was 61% and 3-year OS rate was 44%.

Median PFS was 30 months. The 1-year PFS rate was 88%, 2-year PFS rate was 61% and 3-year PFS rate was 39%.

Sixty-one percent (n = 48) of patients died, of whom 75% (n = 36) had known causes of death. Hepatic complications served as the most frequent cause of death, including biliary complications (n = 16), vascular complications (n = 10), parenchymal liver failure from disease burden (n = 2) and a combination of these factors (n = 4).

Radiation dose appeared to be the single most influential prognostic factor. As a continuous variable, total radiation dose correlated with improved local control (P = .03) and OS (P = .02).

Patients treated with doses higher than the conventional dose of 50.4 Gy had significantly improved OS compared with those treated with 50.4 Gy or less (43 months vs. 23 months; P = .01).

Further, a significantly greater proportion of patients who received BED greater than 80.5 Gy achieved 3-year OS (73% vs. 38%; P = .017) and local control (78% vs. 45%; P = .04).

As a continuous variable, BED significantly affected local control (P = .009) and OS (P = .004).

The researchers did not observe any significant treatment-related toxicities.

Potential limitations identified by the researchers included the potential for selection bias in favor of patients who received higher radiotherapy doses; the possible underestimation of treatment-related toxicities due to errors in medical recording; and the variety of radiation dose/fractionation schedules used.

“With 79 patients, the current study, to our knowledge, is the largest series of IHCC treated with definitive radiotherapy reported to date,” Crane and colleagues wrote. “Higher total radiotherapy doses and higher doses delivered per fraction to achieve BED greater than 80.5 Gy should be considered for all patients undergoing definitive radiotherapy for IHCC if dose constraints to the liver, bile duct, stomach and bowel can be met and image guidance is used to ensure that the dose is delivered safely.” – by Cameron Kelsall

Disclosure: Crane reports honoraria from and a consultant role with Vertex Pharmaceuticals. Please see the full study for a list of all other researchers’ relevant financial disclosures.