Prognostic Value Of Fdg-Pet Metrics For Advanced Nsclc Patients Treated With First-Line Immunotherapy

Measures of disease burden on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) have prognostic value for advanced non–small cell lung cancer (NSCLC) patients treated with chemotherapy. Here we explore the prognostic value of FDG-PET for patients treated with first-line immunotherapy and if PET-guided radiotherapy (RT) should be explored in those patients. Patients treated at our institution between 2015 and 2019 with first-line immune checkpoint inhibitors targeting the PD-1/PD-L1 axis (with or without chemotherapy) for advanced/metastatic NSCLC who underwent PET staging 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. Number of hypermetabolic lesions (nLesions) and total metabolic tumor volume (MTV, log-transformed) were tested as predictors of progression-free survival (PFS) and overall survival (OS) duration in univariate Cox proportional hazards models. Among patients who received RT near the time of diagnosis, the proportion of disease treated with RT was tested as prognostic factor as well. Actuarial PFS and OS rates were calculated using the Kaplan-Meier Method, and comparisons between subgroups were performed using log rank testing. Seventy-two patients met inclusion criteria. Thirty-two patients (44%) received immunotherapy as monotherapy, and 40 (56%) received immunotherapy with chemotherapy. PD-L1 tumor proportion score (TPS) was below 50% in 38 patients, 50-100% in 24 patients, and unknown for ten patients. The median number of hypermetabolic lesions identified for each patient was 6 (range 1 to 39). The median MTV was 93 cc (range 13 to 1,306 cc). Nineteen patients received RT near the time of immunotherapy initiation, with target volumes encompassing <1% to >99% of the total MTV (median 25%). The median follow-up duration for living patients is 11 months. MTV was a significant predictor of OS (HR 1.30 per two-fold increase, 95% CI 1.00 to 1.69, p = 0.047). The actuarial 12-month OS rate was 87% for patients with MTV less than or equal to 173 cc, compared to 74% for other patients. nLesions was a significant predictor of both OS (HR 1.05 per lesion, 95% CI 1.00 to 1.11, p = 0.045) and PFS (HR 1.05 per lesion, 95% CI 1.01 to 1.08, p = 0.005). Among patients who received RT near the time of diagnosis, RT targeting less than 25% of the total MTV was associated with inferior OS (12-month OS 36% v. 100%, log rank p = 0.011). PET-based measures of disease burden (MTV) and multifocality (nLesions) may be important prognostic factors for advanced NSCLC patients treated with first-line immunotherapy. Disease ‘debulking’ with RT could be explored as an adjunct to immunotherapy. Validation of our findings with larger datasets is planned.