|
内容記述 |
PurposeAdvanced hepatocellular carcinoma (HCC) with macrovascular invasion (MVI) carries an extremely poor prognosis, necessitating novel therapeutic strategies. This phase Ib trial evaluated the safety and preliminary efficacy of combining carbon-ion radiotherapy (C-ion RT) with immune checkpoint inhibitors (ICIs) in patients with advanced HCC with MVI.Patients and MethodsFifteen patients with MVI-positive advanced HCC were enrolled (Cohort A: durvalumab monotherapy, n = 3; Cohort B: durvalumab plus tremelimumab, n = 12). C-ion RT (60 Gy, 4 fractions) was delivered to the MVI-containing primary tumor, while systemic therapy with durvalumab (+ tremelimumab) was administered concurrently. The primary endpoints included dose-limiting toxicities (DLTs) and adverse events (AEs). Secondary endpoints included progression-free survival (PFS) and overall survival (OS).ResultsNo DLTs were observed, and the combination exhibited a manageable safety profile. The most common adverse events were pyrexia, rash, and elevated lipase levels. Grade 3–4 AEs occurred in 53.3%, including cytokine release syndrome (CRS) and meningitis. Median PFS and OS were 4.7 and 10.4 months, respectively. While C-ion RT achieved effective local control of irradiated lesions, non-irradiated lesions showed limited systemic immune responses.ConclusionsThe combination of MVI-targeted C-ion RT and ICIs demonstrated safety and effective local tumor control in advanced HCC. This novel approach of selective irradiation to MVI-containing tumors, combined with systemic immunotherapy, warrants further investigation to optimize the synergistic effects and enhance systemic efficacy in this poor-prognosis population.Impact and implicationsAdvanced hepatocellular carcinoma (HCC) with macrovascular invasion (MVI) has a poor prognosis, highlighting the need for new therapeutic strategies. Our phase Ib study suggests that carbon-ion radiotherapy (C-ion RT) targeting MVI combined with immune checkpoint inhibitors is feasible and achieves sustained local tumor control. RNA sequencing revealed that immune activation pathways were enriched in responders, while resistance was associated with mesenchymal and angiogenesis signatures. These results reinforce the potential of MVI-targeted irradiation combined with ICIs as a promising treatment strategy for this high-risk patient population, warranting further investigation to improve systemic tumor control. |
