Effectiveness of pemetrexed-based chemotherapy and radiation therapy in RET-rearranged lung adenocarcinoma: a mono-institutional case series

: Rearranged during Transfection gene (RET) fusions occur in 0.7–2% of non-small cell lung cancer (NSCLC) representing a novel target for oncogene addicted disease. Retrospective analyses showed remarkable response to the chemotherapic anti-folate drug Pemetrexed in patients affected by RET-fusion NSCLC, while immunotherapy does not assure remarkable efficacy. Nowadays, novel therapies are enriching the number of specific anti-RET strategies. The present mono-institutional case series reports significant responses to Pemetrexed, and radiation therapies performed on previously identified or oligo-progressing metastatic sites. Next Generation Sequencing conducted on histological tissue in two cases and on blood specimen in one case detected RET fusion in the clinical course after chemotherapy. As other oncogene addicted subtypes of NSCLC, such as EGFR mutated, ALK and ROS1 rearranged, radiation treatment of residual or oligo-progressing lesions appeared to prolong the clinical benefit from oncological treatments. Despite specific anti-RET treatments are under evaluation for RET-positive non squamous NSCLC, Pemetrexed assured optimal and durable clinical response. The addition of loco-regional treatment of residual or oligo-progressive disease prolonged the time to chemotherapy failure. The present manuscript aims at arising the hypothesis that loco-regional treatment could be considered for oligo-metastatic disease with consolidation extent and could allow beyond progression Pemetrexed-based therapy for oligo-progressive disease.