Whole Liver Radiotherapy for Multiple Liver Metastases in Thoracic Malignancies

Abstract

Liver metastases (LM) are common in advanced thoracic cancer patients with dismal oncological outcomes. Even in the modern era of novel systemic therapy, LM led to a 21% increased mortality risk compared with those without. Options for progressive multiple LM after systemic therapy are limited. Therefore, a different treatment modality is urgently needed to overcome such a predicament. Herein, we renovate the classical whole liver radiotherapy (WLRT) and evaluate its efficacy and safety in treating thoracic cancer patients with progressive multiple LM. Patients with lung or thymic cancer who had multiple LM treated by WLRT between 2018 and 2022 were enrolled. Radiotherapy (RT) was delivered with a median dose of 24 Gy (range 8-25 Gy) in 8 fractions (range 1-16) at the discretion of treating physicians. Overall survival (OS) and cumulative incidence of intrahepatic progression were calculated from the completion of WLRT till death or progression by Kaplan-Meier and competing risk analyses, respectively. Twenty-four patients were enrolled in this retrospective study. Eleven patients (46%) had lung adenocarcinoma, of which nine patients had oncogenic mutations. Six patients (25%) had small cell lung cancer (SCLC), four patients (17%) had thymic squamous cell carcinoma (SqCC), two patients (8%) had lung SqCC, and one patient (4%) had mixed histology. Eighteen patients (75%) were under systemic therapy treatment before the diagnosis of LM, and fifteen (63%) received LM biopsy. The median time from the diagnosis of LM to WLRT was 7.5 months (range, 0.5-33.9 months). Eleven patients (46%) had concurrent RT and systemic therapy. With a median follow-up of 3.1 months, the 3-, 6- and 12-month OS were 57%, 38%, and 15%, respectively. After adjusting death as a competing risk, the cumulative incidence of LM progression at 3, 6, and 12 months were 10%, 19%, and 44%, respectively. Within three months after the completion of RT, one patient (4%) had grade 5 radiation-induced liver disease (RILD), one patient (4%) had grade 4 abnormal liver function test (LFT), three patients (13%) had grade 3 abnormal LFT, and twelve patients (50%) had ≤ grade 2 abnormal LFT. The patient who had Gr.5 RILD expired 51 days after the completion of RT with 24 Gy in 8 fractions concurrently with topotecan. He had primary SCLC with viral hepatitis B. His LFT was around the normal upper limit before WLRT. WLRT provided favorable intrahepatic control with acceptable radiation-related toxicities and could be considered a treatment option for patients with progressive LM under systemic therapy. Further investigation with a larger cohort is warranted to identify patients at a high risk of developing severe RILD.