Prospective study assessing the feasibility of hippocampal-sparing radiotherapy in lung cancer patients requiring cranial irradiation.

Background: Lung cancer remains one of the leading causes of cancer-related mortality worldwide, with systemic therapies often limited by poor intracranial penetration, resulting in frequent brain relapses. Whole-brain radiotherapy (WBRT) plays a central role in managing brain metastases and in prophylaxis, although it is frequently associated with significant neurocognitive decline. Hippocampal-sparing WBRT (HSWBRT) represents a strategy to preserve neurocognition and quality of life (QoL) while maintaining disease control. This study evaluated the feasibility and outcomes of HSWBRT in lung cancer patients requiring prophylactic cranial irradiation (PCI) or WBRT.

Methods: In this prospective study (2021-2023), 15 patients with histologically confirmed lung cancer with an indication for PCI or WBRT (lesions > 5 mm from hippocampus) were treated with HSWBRT. Target delineation followed Radiation Therapy Oncology Group (RTOG) guidelines, incorporating a 5-mm isotropic margin for hippocampal avoidance. Prescribed doses were 25 Gy in 10 fractions for PCI and 30 Gy in 10 fractions for brain metastases. Neurocognitive function was assessed using the Montreal Cognitive Assessment (MOCA), Trail Making Test parts A and B (Trail A/B), and the Controlled Oral Word Association Test (COWAT). Quality of life was evaluated with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and EORTC Brain Cancer Module (BN20) at baseline and at 2, 4, 6, 9, and 12 months. Outcomes were compared with a retrospective cohort of 15 patients treated with conventional WBRT. The Kaplan-Meier method was used for survival analysis; comparisons employed log-rank and repeated measures analysis of variance tests.

Results: Median follow-up was 20 months. Intracranial relapse and overall survival rates did not differ significantly between the HSWBRT and WBRT arms. However, self-reported cognitive decline and QoL deterioration were lower in the HSWBRT arm at 12 months (QoL: 83.33 vs. 66.67, p = 0.07). The MOCA scores remained stable, and Trail A/B performance improved post-treatment in the HSWBRT cohort.

Conclusion: Our findings show that HSWBRT appears feasible and effective in preserving neurocognitive function and QoL in lung cancer patients, without compromising intracranial control. Larger randomized studies are needed to validate its role in routine practice.