Stage 4 ALK-rearranged lung cancer: complete response with alectinib and SBRT

What happened, in summary

A 73-year-old East Asian woman was evaluated in November 2022 after an abnormal chest CT was found during routine imaging. She had no cough or shortness of breath, had never smoked, and had no family history of cancer. CT showed a 1.1 cm spiculated nodule in the right middle lobe, multiple pleural nodules with mild pleural thickening, and fibrotic changes in the right upper lobe. EBUS-guided biopsy of lymph node station 7 showed metastatic adenocarcinoma. Molecular testing found an ALK rearrangement, specifically an EML4-ALK fusion, with EGFR wild-type status. PET-CT confirmed pleural and lymph node metastases, and she was diagnosed with Stage IV lung cancer, T2N2M1a. She started alectinib, an ALK-targeted therapy. Over 18 months, CT scans showed the right middle-lobe tumor and pleural metastatic lesions regressed. In July 2024, however, the original lesions were no longer visible but a new right upper-lobe consolidation with ground-glass opacity appeared. Biopsy of this new lesion confirmed adenocarcinoma again, but the molecular profile was different: there was no ALK rearrangement, and the tumor carried EGFR L858R and T790M co-mutations plus TP53 L194R. The case was considered metachronous lung cancer rather than simple recurrence of the original ALK-driven tumor. Because the ALK-positive disease remained controlled and there were no newly enlarged lymph nodes or other lesions outside the right upper lobe, she continued alectinib and received stereotactic body radiation therapy to the new lesion. This supported local treatment to the new lesion instead of changing systemic therapy immediately. Follow-up CT showed marked reduction with residual scarring only, and PET-CT showed no hypermetabolic lung lesion.