Survival and Toxicity in Patients With Unresectable/Inoperable Biliary Cancers Treated with SBRT vs. Conventionally Fractionated Chemoradiation.

Abstract

<h3>Purpose/Objective(s)</h3> The mainstay of treatment for unresectable/inoperable biliary cancers (UIBC) is chemotherapy (CHT) and radiotherapy (RT). We report our single institution clinical efficacy and safety in patients with UIBC treated with SBRT versus conventionally fractionated radiation (CRT). <h3>Materials/Methods</h3> Patients with UIBC treated with SBRT (n = 18) or CRT (n = 23) between 2006 and 2020 were identified. Additional management included neoadjuvant, adjuvant and/or concurrent CHT. Kaplan-Meier estimates of progression free survival (PFS), overall survival (OS) and locoregional control (LRC) were compared with log rank tests. Toxicities during treatment and follow up were based on the CTCAE v5.0. Acute toxicity was defined as adverse events < 6 months from initiation of RT. Differences by RT in patient and treatment characteristics and toxicities were assessed with Chi-square and Fisher's exact tests. Given the small sample, differences with significance of <i>P</i> < 0.10 were considered of potential clinical relevance. <h3>Results</h3> Of the 41 patients analyzed 54% were male, and 20% were non-white. CRT patients were younger than SBRT (median age 64 vs 76 yrs., <i>P</i> < 0.001). Tumor sites included 58% intrahepatic, 27% extrahepatic and 15% gallbladder. There were more > 5 cm tumors in the SBRT (51%) group than CRT (22%). The median SBRT dose was 60 Gy in 5 fractions and the median dose for CRT was 50 Gy in 25 fractions. SBRT dose was dichotomized into BED₁₀ ≥ 100 Gy and < 100 Gy. Of all patients, 29% did not receive any CHT, 24% received neoadjuvant CHT, 44% received adjuvant CHT and 51% received concurrent CHT. Overall, 26 patients died. Median follow-up of those alive was 8.2 months with no difference by RT type. The 1-yr PFS was 31.5% (95% CI 8.5-58.1) for SBRT and 18.8% (95% CI 5.9-37.3) for CRT (<i>P</i> = 0.042). Gallbladder and intrahepatic locations were associated with higher PFS compared to extrahepatic disease (<i>P</i> = 0.002). The 1-yr OS was 68.4% (95% CI 33.9-87.5) for SBRT and 67.0% (95% CI 42.7-82.8) for CRT (<i>P</i> = 0.151). BED₁₀ ≥ 100 Gy had higher OS than CRT or low dose SBRT (<i>P</i> = 0.014). Improved ECOG status was associated with higher OS (<i>P</i> = 0.044). LRC was 42.0% (95 CI 11.3-70.8) for SBRT and 26.1% (95% CI: 7.1-50.6) for CRT (<i>P</i> = 0.149). There was a trend towards improved LRC in tumors > 5 cm (<i>P</i> = 0.097). For acute toxicity, both treatments were well tolerated overall with only 1 patient with grade 3+ toxicity. 74% of CRT patients had an acute toxicity compared to 39% of SBRT patients (<i>P</i> = 0.024). There was no difference in late toxicity between the two groups. There was no grade 3+ late toxicity. <h3>Conclusion</h3> In this single-institution retrospective study, there was improved PFS in UIBC treated with SBRT. There was a trend towards improved LRC in larger tumors. Dose escalation to BED₁₀ ≥ 100 Gy in this series improved OS. SBRT was also better tolerated than CRT.