TOPLINE:

In a prospective observational study of a monocentric trial, the combination of stereotactic radiotherapy or radiosurgery (SRT/SRS) with immunotherapy or targeted therapy demonstrated a local control rate of 85.7% for brain metastases at 1 year and a clinical benefit rate of 85.3%, with only 20% of patients experiencing radionecrosis.

METHODOLOGY:

• Researchers conducted a prospective observational study including 45 patients (median age, 53 years; 42.2% men) with 225 brain metastases treated with a combined regimen of targeted therapy, immunotherapy, and SRT/SRS between May 2020 and 2023.
• Primary cancers included melanoma (48.9%), lung cancer (42.2%), and breast cancer (8.9%), with a median time of 12 months from the diagnosis of the primary to the onset of brain metastases.
• Patients were initially followed up at 2 months post-RT, then every 2 months for the first year and every 3 months thereafter, with a median follow-up duration of 23 months.
• Primary endpoints were toxicity and radionecrosis profiles. Secondary endpoints included efficacy outcomes such as local control, the overall response rate, the clinical benefit rate, disease-free survival, overall survival, and distant metastasis-free survival (DMFS).

TAKEAWAY:

• Radionecrosis occurred in 20% of patients (6.7% of lesions), and rates of radionecrosis-free survival were 94.1% at 1 year and 91.9% at 2 years. Intralesional haemorrhage was observed in 8.9% of patients (1.7% of lesions).
• Local control rates were 85.7% at 1 year and 79.8% at 2 years. The absence of comorbidities (adjusted hazard ratio [aHR], 2.798; P = .011), smaller lesions (aHR, 3.631; P < .001), and the achievement of complete response (aHR, 7.749; P = .001) were significant prognostic factors to predict local control.
• The overall response rate was 35.5%, and the clinical benefit rate was 85.3%. Factors such as a higher biologically effective dose (> 50.4 Gy; adjusted odds ratio [aOR], 0.214; P < .001) and a high prescription isodose (> 80%; aOR, 0.249; P < .001) were significantly associated with better chances of achieving a complete response.
• Disease-free survival rates at 1 and 2 years were 37.1% and 27.5%, respectively; overall survival rates were 52.5% and 44.7%, respectively; and DMFS rates were 40.7% and 30.1%, respectively.

IN PRACTICE:

"This approach demonstrates manageable toxicity profiles, with high local control rates and robust response outcomes. However, additional research through multicenter trials with longer follow-up is needed to refine treatment combinations and gain a deeper understanding of their long-term risks and benefits," the authors wrote.

SOURCE:

This study was led by Rossella Di Franco, Istituto Nazionale Tumori - IRCCS Fondazione "G. Pascale," Naples, Italy, and Donato Pezzulla, Responsible Research Hospital, Campobasso, Italy. It was published online on February 13, 2026, in Clinical Oncology.

LIMITATIONS:

The monocentric and prospective nature of this study could have limited the applicability of the findings to broader populations. The modest and heterogeneous sample size, the lack of longer follow-up, and the absence of extended toxicity profile data in larger cohorts hindered definitive conclusions regarding the ideal sequencing and combination of treatments.

DISCLOSURES:

This study did not receive any external funding. The authors reported having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.