Radiation Therapy for Colorectal Liver Metastasis: The Effect of Radiation Therapy Dose and Chemotherapy on Local Control and Survival

Ishita Chen; Jeho Jeong; Paul B Romesser; Lara Hilal; John Cuaron; Melissa Zinovoy; Carla Hajj; T Jonathan Yang; Jillian Tsai; Yoshiya Yamada; Abraham J Wu; Charlie White; Megan Fiasconaro; Neil H Segal; Nancy E Kemeny; Zhigang Zhang; Christopher H Crane; Marsha Reyngold

doi:10.1016/j.adro.2023.101382

Radiation Therapy for Colorectal Liver Metastasis: The Effect of Radiation Therapy Dose and Chemotherapy on Local Control and Survival

Adv Radiat Oncol. 2023 Oct 2;9(2):101382. doi: 10.1016/j.adro.2023.101382. eCollection 2024 Feb.

Authors

Ishita Chen¹, Jeho Jeong², Paul B Romesser¹, Lara Hilal¹, John Cuaron¹, Melissa Zinovoy¹, Carla Hajj¹, T Jonathan Yang¹, Jillian Tsai¹, Yoshiya Yamada¹, Abraham J Wu¹, Charlie White³, Megan Fiasconaro³, Neil H Segal⁴, Nancy E Kemeny⁴, Zhigang Zhang³, Christopher H Crane¹, Marsha Reyngold¹

Affiliations

¹ Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
² Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York.
³ Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
⁴ Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.

Abstract

Purpose: Colorectal liver metastases (CLMs) represent a radioresistant histology. We aimed to investigate CLM radiation therapy (RT) outcomes and explore the association with treatment parameters.

Methods and materials: This retrospective analysis of CLM treated with RT at Memorial Sloan Kettering Cancer Center used Kaplan-Meier analysis to estimate freedom from local progression (FFLP), hepatic progression-free, progression-free, and overall survival (OS). Cox proportional hazards regression was used to evaluate association with clinical factors. Dose-response relationship was further evaluated using a mechanistic tumor control probability (TCP) model.

Results: Ninety patients with 122 evaluable CLMs treated 2006 to 2019 with a variety of RT fractionation schemes with a median biologically effective dose (α/β = 10; BED10) of 97.9 Gy (range, 43.2-187.5 Gy) were included. Median lesion size was 3.5 cm (0.7-11.8 cm). Eighty-seven patients (97%) received prior systemic therapy, and 73 patients (81%) received prior liver-directed therapy. At a median follow-up of 26.4 months, rates of FFLP and OS were 62% (95% CI, 53%-72%) and 75% (66%-84%) at 1 year and 42% (95% CI, 32%-55%) and 44% (95% CI, 34%-57%) at 2 years, respectively. BED10 below 96 Gy and receipt of ≥3 lines of chemotherapy were associated with worse FFLP (hazard ratio [HR], 2.69; 95% CI, 1.54-4.68; P < .001 and HR, 2.67; 95% CI, 1.50-4.74; P < .001, respectively) and OS (HR, 2.35; 95% CI, 1.35-4.09; P = .002 and HR, 4.70; 95% CI, 2.37-9.31; P < .001) on univariate analyses, which remained significant or marginally significant on multivariate analyses. A mechanistic Tumor Control Probability (TCP) model showed a higher 2-Gy equivalent dose needed for local control in patients who had been exposed to ≥ 3 lines of chemotherapy versus 0 to 2 (250 ± 29 vs 185 ± 77 Gy for 70% TCP).

Conclusions: In a large single-institution series of heavily pretreated patients with CLM undergoing liver RT, low BED10 and multiple prior lines of systemic therapy were associated with lower local control and OS. These results support continued dose escalation efforts for patients with CLM.

Grants and funding

P30 CA008748/CA/NCI NIH HHS/United States