Neoadjuvant Stereotactic Body Radiotherapy plus Immune Therapy Favorably Remodels the Hepatocellular Carcinoma Tumor Microenvironment
Mené sur 8 patients atteints d'un carcinome hépatocellulaire avancé, cet essai pilote évalue la sécurité d'un traitement préopératoire combinant une radiothérapie stéréotaxique corporelle et 2 cycles d'atézolizumab-bévacizumab
Although immunotherapy regimens have significantly improved treatment options for patients with advanced hepatocellular carcinoma (HCC), the optimal use of these regimens in earlier disease stages remains poorly defined.We conducted a single-institution, single-arm pilot study (NCT04857684) of neoadjuvant stereotactic body radiotherapy (SBRT) followed by 2 cycles of atezolizumab plus bevacizumab and subsequent surgical resection in patients with initially resectable HCC (n = 8). The primary endpoint was safety as defined by the proportion of patients with grade 3 to 4 treatment-related adverse events (trAE) by Common Terminology Criteria for Adverse Events v5.0. Furthermore, we dissected the detailed remodeling of the tumor immune microenvironment following treatment using single-cell resolution spatial transcriptomic method.Only 1 patient experienced a grade 3 trAE. Seven of 8 patients proceeded to surgery, and all achieved margin-negative (R0) resection; 1 patient did not proceed because of subsequent disagreement of resectability. One patient achieved a pathologic complete response, and all resected patients were relapse-free at data cutoff (median follow-up, 16.3 months; range, 2.1–19.9). Compared with unmatched treatment-naïve HCC specimens, posttreatment specimens showed significantly higher anticancer immune infiltration, including organized peritumoral aggregates. Immune infiltration and its proximity to tumor cells correlated with preoperative radiographic response.This study provides proof of concept that neoadjuvant SBRT and immunotherapy is safe and provides a clear rationale for additional prospective clinical studies utilizing this strategy.
Clinical Cancer Research , résumé, 2026