177 - "No Phase III? No Worries!": Analysis of over 1100 Inoperable Early-Stage Lung Cancer Patients Treated with Either Single- or Three-Fraction SBRT to Reveal a Standard of Care
Presenter(s)
G. M. Videtic1, C. A. Reddy2, T. Djemil3, P. Xia4, and K. L. Stephans4; 1Department of Radiation Oncology, Cleveland Clinic Foundation, Cleveland, OH, 2Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, OH, 3Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH, 4Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH
Purpose/Objective(s): A drafted but never activated RTOG phase III trial planned to compare RTOG 0915 single-fraction (SF) to RTOG 0236 three-fraction (TF) lung stereotactic body radiotherapy (SBRT) for inoperable peripheral early-stage lung cancer (ESLC) patients (pts), with a primary endpoint of 3-year (yr) overall survival (OS). We analyzed our large single institution database to investigate this question and other relevant cancer- and treatment-related outcomes.
Materials/Methods: We surveyed our institutional review board-approved prospective lung SBRT data registry from 2003 to 2025 for SF [34 Gy] and TF [60 Gy (or 54 Gy with heterogeneous planning (HP)] ESLC pts treated, on and off protocol. OS, rates of local failure (LF), distant failure (DF) and toxicity were assessed. Prognostic factors for LF and DF were identified with competing risk regression with all-cause mortality defined as a competing event. Factors associated with OS were identified with Cox proportional hazards regression.
Results: For the 22-year interval, 1107 pts met study criteria for this retrospective analysis, with the SF cohort having 685 pts (61.9%) and the TF 422 pts (38.1%). 38.8% pts were alive at analysis. Median follow up for all, SF, and TF pts was 28.2, 23.0 and 41.5 months, respectively (p= <0.0001). Patient characteristics included: female (52.6%); median age 73.5 years, median KPS 80; 27.0% still smoking; inoperability by lung co-morbidities in 52.5%; with no differences by fractionation (Fx). Tumor characteristics included: median size 1.8 cm; median PET SUVmax 6.5; 71.2% with biopsy proven cancer and the majority adenocarcinoma at 45.4% with no differences by Fx. TF SBRT was 60 Gy and 54Gy for 81.5% and 18.5% pts, respectively. Median, 3-yr and 5-yr OS by SF and TF were: 44.4 months, 57.7% and 38.0%; 44.2 months, 57.6% and 40.9%, respectively(p=0.52). At 5 yr, failure patterns by SF and TF were: LF 4.5% vs. 3.0% (p=0.15) and DF 21.4% vs. 24.0% (p=0.21), respectively. Grade 3 and higher toxicity was reported in 2.7% of total pts, with no significant difference by Fx (p=0.55). Grade 3 and higher chest wall toxicity was: SF 0.4% and TF 0.9%. Each Fx cohort had grade 5 in 1 pt (both as pneumonitis). Multivariate analysis (MVA) for LF and DF revealed no pt, tumor or treatment associations by Fx. MVA for OS was significantly associated with age at SBRT (p=0.0008), KPS (p=<0.0001), gender (p=<0.0001) and tumor size (p=0.0012).
Conclusion: This large single institution analysis of over 1100 pts revealed no differences in OS between SF and TF lung SBRT pts and specifically none at the proposed RTOG phase III endpoint of 3-yr OS. LF, DM and grade 3 and higher toxicity rates [including chest wall] were similar between Fx schedules. This suggests that SF should be the standard lung SBRT option for inoperable ESLC.