Intensified MR-guided pulsed adaptive cancer treatment- a potential new treatment option for large(>5cm) central non-small cell lung cancer, a case report.

Abstract

There are currently no effective treatment options for large, inoperable, centrally located thoracic lesions with poor or suboptimal response to immunotherapy. The use of SBRT for tumors larger than 5 cm in this location is limited by toxicity. Therefore, new and innovative treatment strategies are a major unmet medical need. Adaptive radiotherapy (ART) guided by MR-Linac systems, enables real-time adjustment of the treatment plan according to daily anatomical changes and tumor response. This approach is particularly beneficial in thoracic oncology, where tumor shrinkage and respiratory motion can significantly affect dose delivery. Moreover, ART may enhance the therapeutic synergy between radiotherapy and immunotherapy. We report the case of a 65-year-old woman diagnosed with stage IV non-small cell lung cancer (NSCLC) of mixed squamous and adenocarcinoma histology. The patient initially presented with seizures, and an MRI revealed 10 intracranial metastases alongside a 55 mm tumor in the left lung. Following stereotactic brain radiotherapy and the initiation of nivolumab plus ipilimumab, the treatment was continued with nivolumab monotherapy due to grade 3 pulmonary toxicity. Imaging demonstrated a tumor progression limited to the lung. She was then qualified for MR-guided adaptive stereotactic radiotherapy (3 × 10 Gy), delivered at 10-day intervals. Significant tumor regression required redefinition of the GTV before fractions 2 and 3. No acute or late toxicity was observed. A 6-month follow-up PET-CT revealed marked regression in tumor size (from 79 mm to 17 mm) and metabolic activity (SUVmax reduced from 33.1 to 5.13). Comparative imaging showed less extensive post-radiation lung changes than typically observed after conventional radiotherapy. This case illustrates the potential of MR-guided adaptive radiotherapy to enhance treatment precision, reduce toxicity, and enable immune-radiotherapy synergy. Integration of the PULSAR concept-with spaced fractions and immunotherapy-may improve tumor response. Further clinical trials are required to confirm these benefits on larger patient populations.