Prognostic Significance and Biomarker Identification by Progression Patterns in Patients With Small Cell Lung Cancer...

Chemoimmunotherapy for small cell lung cancer (SCLC) is initially effective; however, relapse is common. Patterns of progression may serve to prognosticate outcomes and identify biomarkers for relapsed SCLC.

Electronic medical records of patients with SCLC who progressed after chemoimmunotherapy were reviewed. Response was classified into oligoprogression (OP, ≤ 5 progressive or new lesions in ≤ 2 organs) and non-oligoprogression (non-OP) for comparison of outcomes. Tissue biopsies at diagnosis and liquid biopsies at progression were evaluated.

Females and patients with fewer de novo metastatic sites were more likely to have OP (P < .05). OP associated with improved overall survival (17.5 vs. 8.6 months, P < .001), survival after progression (11.1 vs. 2.3 months, P < .001), and progression-free survival with subsequent therapy (4.6 vs. 1.8 months, P < .01). Patients with non-OP were more likely to be hospitalized (29.8% vs. 66.7%, P < .001), transition to hospice within three months (6.4% vs. 50%, P < .001), and receive fewer subsequent therapies (89.4% vs. 58.3%, P = .01). Surprisingly, the chemotherapy-free interval (CTFI) was not significantly associated with post-progression overall survival (HR 1.62, 95% CI, 0.82-3.18; P = .16). Biomarker analysis identified hypermethylation at 8 CpGs annotating HOXA5 (P < .01), which correlates with non-OP and predicts inferior survival in an independent patient cohort (HR 0.44, P = .02).

PD patterns are an excellent tool to identify patients with relapsed SCLC who are at high risk of mortality, hospitalization, clinical decline, and poor outcomes with subsequent therapies. Such patients should be prioritized for clinical trial enrollment. Prospective validation for outcomes with chemoimmunotherapy by HOXA5 status is warranted.