1048 - Adaptive vs. Non-Adaptive Radiation Dose Escalation in Locally Advanced Non-Small Cell Lung Cancer (LA-NSCLC): Indirect Comparison of NRG-RTOG 0617 and 1106 Individual Patient Data

08:05am - 08:10am PT

Room 155/157

Presenter(s)

Joseph Miccio, MD - Penn State Hershey Medical Center, Hershey, PA

J. A. Miccio¹, C. Hu², F. M. Kong³, P. Samson⁴, D. Gelblum⁵, B. W. Loo Jr⁶, G. M. Videtic⁷, S. Faria⁸, S. Jolly⁹, S. Tian¹⁰, D. E. Gerber¹¹, J. W. Welsh¹², I. Nakhoul¹³, E. M. Gore¹⁴, J. Lyness¹⁵, J. D. Bradley¹⁶, and M. Machtay¹; ¹Penn State Cancer Institute and College of Medicine, Hershey, PA, ²Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, ³The University of Hong Kong, Hong Kong, China, ⁴Washington University School of Medicine in St. Louis, Department of Radiation Oncology, St. Louis, MO, ⁵Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, ⁶Stanford University, Palo Alto, CA, ⁷Department of Radiation Oncology, Cleveland Clinic Foundation, Cleveland, OH, ⁸McGill University Health Centre, Division of Radiation Oncology, Montreal, QC, Canada, ⁹Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, ¹⁰Department of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, ¹¹University of Texas Southwestern Medical Center, Dallas, TX, ¹²Department of Thoracic Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, ¹³Southeast Clinical Oncology Research, Kingsport, TN, ¹⁴Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, ¹⁵NRG Oncology Statistics and Data Management Center, Philadelphia, PA, ¹⁶University of Pennsylvania/Abramson Cancer Center, Philadelphia, PA

Purpose/Objective(s): NRG-RTOG 0617 found non-adaptive radiation therapy (naRT) dose escalation to 74 Gy worsened overall survival (OS) compared to 60 Gy, while NRG-RTOG 1106 showed PET-adapted RT dose escalation (aRT) was safe. This study indirectly compares aRT vs. naRT in LA-NSCLC.

Materials/Methods:

Patients (pts) from RTOG 0617 and 1106 randomized to dose-escalation arms were included. All received concurrent carboplatin/paclitaxel chemotherapy; none received post-chemoradiotherapy immunotherapy.

Outcomes were OS, progression-free survival (PFS), freedom from local-regional progression (FFLRP), and toxicity. Propensity score-based inverse probability of treatment weighting (IPTW) adjusted for imbalances in baseline clinical, demographic and tumor characteristics. Kaplan-Meier methods estimated OS, PFS, and FFLRP, with hazard ratios (HRs) derived from Cox models, both unweighted and weighted. Grade 3+ toxicity was analyzed using logistic regression with odds ratios (ORs). Statistical significance was defined as p < 0.05.

Results:

Eighty-four pts received aRT and 207 received naRT (median radiation dose 71 Gy vs. 74 Gy, respectively). naRT had more males (59% vs. 43%, p=0.016), white pts (86% vs. 70%, p=0.003), and current smokers (51% vs. 38%, p=0.042), with better performance status (59% vs. 44% Zubrod 0, p=0.025). aRT pts had higher intensity-modulated radiation therapy (IMRT) use (92% vs. 47%, p<0.001) and PET-based staging (100% vs. 89%, p=0.002).

Unweighted, aRT showed numerically higher OS (3-year 39% vs. 27%, hazard ratio [HR]=0.73, 95% confidence interval [CI] 0.53-1.01, p=0.053) and FFLRP (3-year 46% vs. 37%, HR=0.68, 95% CI 0.46-1.01, p=0.056), while PFS was similar (3-year 20% vs. 21%, HR=0.96, 95% CI 0.73-1.28, p=0.790). Weighted, trends persisted for OS (3-year 39% vs. 27%, HR=0.70, 95% CI 0.46-1.07, p=0.097), FFLRP (3-year 49% vs. 39%, HR=0.65, 95% CI 0.39-1.10, p=0.110), and PFS (3-year 24% vs. 22%, HR=0.87, 95% CI 0.59-1.30, p=0.500).

Unweighted, aRT had lower rates of grade 3+ esophagitis (6% vs. 21%, odds ratio [OR]=0.25, 95% CI 0.10-0.67, p=0.005) and blood/bone marrow toxicity (11% vs. 54%, OR=0.11, 95% CI 0.05-0.23, p<0.001), with a trend toward lower cardiac toxicity (1% vs. 7%, OR=0.17, 95% CI 0.02-1.34, p=0.092). Weighted, cardiac toxicity (OR=0.08, 95% CI 0.01-0.62, p=0.017) and blood/bone marrow toxicity (OR=0.10, 95%CI 0.04-0.25, p<0.001) were significantly lower, while pneumonitis trended lower (OR=0.12, 95% CI 0.02-1.06, p=0.057).

Conclusion:

aRT with mandatory IMRT/IGRT and PET-based staging/planning resulted in significantly lower grade 3+ toxicity vs. naRT. OS and FFLRP trended higher with aRT, but PFS was similar. Ongoing analyses include dosimetric comparisons and in-field control evaluation.