Characterization of the Entire Metastatic Spectrum for Non-Small Cell Lung Cancer in the Immunotherapy Era

Abstract

Several randomized trials have demonstrated that metastasis-directed therapy for oligometastatic non-small cell lung cancer (NSCLC) improves outcomes. It is not clear what proportion of patients with metastatic disease fall into the oligometastatic category at presentation. Rational design of studies for patients beyond the oligometastatic range will require understanding the numerical and anatomic distributions of metastases in this population. To address this gap in knowledge, we comprehensively characterized the number and distribution of malignant lesions in a modern cohort of advanced NSCLC patients who were staged with FDG-PET/CT and treated with first-line immunotherapy.Advanced NSCLC patients with stage IV disease or recurrent incurable disease who underwent staging PET and were started on first-line immune checkpoint inhibitors targeting the PD-1/PD-L1 axis (with or without chemotherapy) at our institution between 2015 and 2019 were included in this analysis. A commercially available gradient-based segmentation tool was used to contour all visible hypermetabolic extracranial lesions on each staging PET. Counts and anatomic distributions of hypermetabolic lesions were recorded.One hundred twenty-four patients met inclusion criteria. Sixty-six patients (53%) received immunotherapy as monotherapy, and 58 (47%) received immunotherapy with chemotherapy. The median number of hypermetabolic lesions identified for each patient was 6 (range 0 to 53). The distribution of hypermetabolic lesion counts was as follows: 33 (27%) 0-3 lesions, 30 (24%) 4-6 lesions, 25 (20%) 7-10 lesions, 36 (29%) 11 or more lesions. The median number of lung tumors and regional lymph nodes per patient was 4 (range 0 to 33). Excluding parenchymal lung tumors and regional lymph nodes, the median number of distant metastases per patient was 2 (range 0 to 37). The distribution of distant metastasis counts was as follows: 60% 0-3 lesions, 21% 4-6 lesions, 11% 7-10 lesions, 8% 11 or more lesions. Distant metastases were most commonly located in bone (35%), distant lymph nodes (22%), and the liver (10%).To our knowledge, this is the first study to characterize the anatomic disease spectrum in a modern cohort of advanced NSCLC. Most patients had 3 or fewer metastatic lesions, meeting a conservative definition of oligometastatic disease. However, many patients had multifocal thoracic disease. Technological radiotherapy approaches that can efficiently ablate multiple lesions in diverse anatomic locations will enable investigation of aggressive local therapy in a broad NSCLC population.