PD-L1, Tumor Mutational Burden, and Outcomes in NSCLC With Brain Metastases: A Brief Report
Elio Adib1, Amin H Nassar2, Elias Bou Farhat3
1Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts.
Introduction:
Patients with NSCLC and brain metastases have a poor prognosis. Combining brain-directed radiation therapy (RT) with immune checkpoint inhibitors (ICIs) may be synergistic. Nevertheless, predictors of response and toxicity are lacking.
Methods:
This retrospective study conducted at Dana-Farber Brigham Cancer Center from 2015 to 2023 included patients with non-EGFR and non-ALK-altered NSCLC and newly diagnosed brain metastases starting ICI within 90 days of brain-directed RT. We assessed all-cause mortality, systemic and neurologic death, systemic and intracranial progression at the patient level, and local recurrence and radiation necrosis at the metastasis level.
Results:
Among the 178 patients with 536 brain metastases, the median age was 64 years, and 53% were female individuals. The median number of brain metastases detected at diagnosis was three. Most patients received pembrolizumab (93%) and were treated with stereotactic radiation (81%). Higher programmed death-ligand 1 (PD-L1) expression was associated with improved all-cause mortality (median survival: PD-L1 less than 1%: 10.7 mo, 1%-49%: 14.3 mo, more or equal to 50%: 29.5 mo), driven by longer time to systemic death. Higher PD-L1 was also associated with improved systemic progression-free survival (p ≥50% versus <1% = 0.02) and distant intracranial disease-free survival (p ≥50% versus <1% = 0.02). The rate of local recurrence was low across all groups (1%-4% at 2 y). Patients with higher PD-L1 had numerically higher radiographic radiation necrosis rates (2.3%, 5.5%, 9.3% at 2 y for PD-L1 <1%, 1%-49%, and ≥50%, respectively, p ≥50% versus <1% = 0.08) and significantly higher symptomatic radiation necrosis rates (p ≥50% versus <1% = 0.04).
Conclusions:
The combination of brain-directed RT and ICI is effective in treating patients with NSCLC and brain metastases. Although high PD-L1 levels are associated with longer survival and improved intracranial control, radiation necrosis occurs more frequently in patients with high PD-L1 expression. Clinicians should be aware of long-term treatment-related toxicities in this population.
Insights
Combining radiation therapy and immune checkpoint inhibitors improves outcomes for non-small cell lung cancer patients with brain metastases. Higher PD-L1 expression correlates with better survival but also increased radiation necrosis risk.
Area of Science:
- Oncology
- Radiotherapy
- Immunotherapy
Background:
- Non-small cell lung cancer (NSCLC) with brain metastases carries a poor prognosis.
- Combining brain-directed radiation therapy (RT) with immune checkpoint inhibitors (ICIs) shows potential synergy.
- Predictors for response and toxicity in this combined treatment setting are currently lacking.
Purpose of the Study:
- To evaluate the efficacy and toxicity of combining brain-directed RT with ICIs in NSCLC patients with brain metastases.
- To identify predictors of treatment response and adverse events, specifically radiation necrosis.
- To assess survival outcomes and disease progression in this patient cohort.
Main Methods:
- Retrospective study at Dana-Farber Brigham Cancer Center (2015-2023).
- Included patients with non-EGFR/ALK-altered NSCLC and newly diagnosed brain metastases receiving ICI within 90 days of brain-directed RT.
- Assessed all-cause mortality, systemic/neurologic death, systemic/intracranial progression, local recurrence, and radiation necrosis.
Main Results:
- Higher programmed death-ligand 1 (PD-L1) expression was linked to improved overall survival (median survival: 29.5 months for PD-L1 ≥50% vs. 10.7 months for <1%).
- Higher PD-L1 correlated with better systemic progression-free survival and distant intracranial disease-free survival.
- While local recurrence was low, higher PD-L1 was associated with increased symptomatic radiation necrosis (p=0.04).
Conclusions:
- The combination of brain-directed RT and ICIs is effective for NSCLC with brain metastases.
- High PD-L1 expression predicts longer survival and better intracranial control but also a higher risk of radiation necrosis.
- Clinicians must consider long-term toxicities, such as radiation necrosis, in patients with high PD-L1 expression receiving this combined therapy.
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