Presenter(s)
V. L. Doss1, C. D. S. Smith1, E. Hales1, D. Liu1, B. M. Anderson2, H. K. Kooner1, K. Yu3, C. Hu1,4, H. Li1, A. N. Viswanathan1, X. Jia1, R. K. Hales1, T. R. McNutt1, R. Ger1, and K. R. Voong1; 1Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 2University of California San Diego, Department of Radiation Medicine and Applied Sciences, La Jolla, CA, 3Johns Hopkins University Department of Biomedical Engineering, Baltimore, MD, 4Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD
Purpose/Objective(s): Thoracic reirradiation (reRT) for locoregional recurrence (LRR) of lung cancer is increasing, yet predictors of local control remain unclear. We evaluated survival and failure patterns after thoracic reRT by histology and disease extent.
Materials/Methods: We retrospectively reviewed LRR of primary lung cancer cases who received thoracic reRT (2012 – 2025) with overlap of 95% prescription isodose lines. Time-to-event was measured from the end of reRT. Overall survival (OS) was estimated using Kaplan–Meier methods and compared by histology and disease extent (LRR-only vs metastatic) with the log-rank test. Cumulative incidence (CI) of local failure (LF) of the reirradiated tumor was estimated with death as the competing event, compared using Gray’s test and modeled using Fine–Gray subdistributional hazards. All doses are reported in EQD2 (a/ß = 10).
Results: Sixty-two patients were reviewed (23 adenocarcinoma [37.1%]; 20 squamous cell carcinoma [SCC; 32.3%]; 18 small cell lung cancer [SCLC; 29.0%]; one large cell carcinoma [1.6%]). Median age was 70.7 years (range 42 - 89). Median time between RT was 23.0 months and follow-up was 12.5 months. At reRT, 41 patients (66.1%) had LRR only, and 21 (33.9%) had metastatic disease, with a similar distribution by histology (p = 0.871).
Median first RT dose was 63.7 Gy for adenocarcinoma, 62.0 Gy for SCC, and 43.1 Gy for SCLC. Median reRT dose was 48.8 Gy for adenocarcinoma, 43.1 Gy for SCC, and 43.1 Gy for SCLC. Palliative RT (< 35 Gy EQD2) comprised 13%, 20%, and 11.1% of first courses and 26.1%, 35%, and 5.6% of reRT for adenocarcinoma, SCC, and SCLC. Median OS was 12.0 months overall and 21.4 months for non-SCC non-small cell lung cancer (NSCLC), 12.0 months for SCC, and 10.5 months for SCLC. Patients with LRR-only at reRT had superior OS compared to metastatic disease (20.4 vs 4.6 months, p = 0.001). CI of LF differed by histology (Gray’s test p = 0.034). SCC was associated with higher LF versus non-SCC NSCLC (unadjusted sHR 2.45 [1.14–5.26], p = 0.021; adjusted for age and dose <35 Gy EQD2: sHR 2.63 [1.24–5.57], p = 0.012). Median time to LF was not reached for adenocarcinoma nor SCLC and was 12.1 months for SCC. Six-, 12-, and 24-month CI of LF was 4.4%, 8.6%, and 26.5% for adenocarcinoma (8/23 LF events); 13.0%, 49.7%, and 70.0% for SCC (14/20 LF events); and 23.8%, 33.3%, and 38.8% for SCLC (8/18 LF events). Thirty-one patients (62%) died from cancer progression, of whom 74.2% died from intrathoracic progression. Notably, 60% of patients with SCC died from intrathoracic progression versus 29.2% with non-SCC NSCLC and 22.2% with SCLC.Conclusion: Among patients receiving thoracic reRT for LRR of primary lung cancer, SCC was associated with higher CI of LF and intrathoracic cancer-related death. These findings are hypothesis-generating and may suggest potential histology-specific differences in reRT response, warranting prospective evaluation of optimized, histology-adapted reRT strategies, particularly for SCC.