Consolidation Radical Chest Radiotherapy in Induced Oligo-persistent Disease Improves Overall Survival in Metastatic...

In the context of metastatic disease, most studies have focused on ConRT for oligo-progressive disease, while data on outcomes with radical Con-RT in oligopersistent disease remain limited. We have been practicing Con-RT in patients who responded to first-line systemic therapy, including both oncogene addicted and non-addicted patients. To gain insight into the outcomes with Con-RT, we audited our real-world data in a resource-constrained setting.

Metastatic NSCLC (2016-2022) who responded to first-line chemotherapy or targeted therapy and had oligo-persistent disease were offered radical chest RT (60Gy/30#/55Gy/20# or 45Gy/25#). The primary endpoint was Overall Survival (OS) and progression-free survival, which was derived with KM survival curves. Prognostic factors affecting OS were analyzed with a Cox regression model. A Propensity Score Analysis (PSA) was performed to adjust for potential confounding factors.

Among 190 patients (71% males), 54% had adenocarcinoma. Metastatic staging included M1a (30%), M1b (13.6%), M1c (47.8%), and Mx (10%). First-line treatment comprised chemotherapy (50%), targeted therapy (14%), or CT/targeted therapy followed by Con-RT (21%); 3% received palliative RT alone, and 15% did not receive further treatment. Factors significant on univariate analysis for OS were smokers with median OS (4 mo. vs 6 mo., p =0.01), women (8 mo. vs 5 mo., p =0.05), M status (M1a 8 mo; M1b 6 mo; M1c 4 mo., p =0.05), type of treatment (No treatment 2 mo.; CT 4 mo; targeted 6 mo; Con RT 18 mo, p =0.001), and Con RT 18 mo vs No-RT 4 mo, p =0.001). On multivariate analysis, factors retained as significant were smokers HR 1.7 (95%CI, 1.2-2.5 p =0.004) and Con RT [HR 0.28 (95%CI 0.14-0.55) p=0.001]. On univariate analysis, factors significantly affecting the Progression-Free Survival (PFS) were females with median PFS (05 mo. vs 0 mo., p =0.02), type of treatment (No treatment 0 mo.; CT 0 mo.; targeted therapy 4 mo.; Con-RT 8 mo, palliative RT 6 mo., p =0.001), and Con-RT [Yes vs No] (10 mo. vs 0 mo, p =0.001). In the multivariate analysis, factors retained significant were females with HR 1.5 (95% CI 1.08-2.1, p =0.01), and Con-RT with HR 0.42 (95% CI 0.22-0.82, p <0.01). The OS benefit was similar even after PSA (Mean OS 21 mo. [Con-RT] vs 7 mo. [No-RT], p =<0.001). Local failures were significantly reduced, and the ratio of local versus distant recurrences was 1:4. The rates of grade 3 pneumonitis and grade 3 esophagitis were 7% and 2%, respectively.

Our results show that radical intent Con-RT in responders to first-line systemic therapy yields a favorable survival benefit at no added cost of toxicity.

Our real-world data demonstrates that Radical Con RT significantly improves OS and PFS in oligo-persistent metastatic NSCLC. These results are practice-changing and should be further evaluated in extensive prospective studies.