1051 - Efficacy and Safety of Twice-Daily (BID) Re-Irradiation (Re-RT) of Thoracic Malignancies

08:20am - 08:25am PT

Room 155/157

Presenter(s)

Victoria Doss, MD - Johns Hopkins Medicine, Baltimore, MD

V. L. Doss¹, C. F. P. M. de Sousa¹, E. Hales¹, T. Trent¹, E. Hagan², T. Gebre², A. Obaideen², M. Negassa², D. Liu¹, C. Hu³, A. N. Viswanathan¹, H. Li¹, K. R. Voong¹, X. Jia¹, T. R. McNutt¹, R. K. Hales¹, and R. Ger¹; ¹Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, ²Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, ³Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD

Purpose/Objective(s): Re-RT is increasing as cancer care advances. Concern for cumulative dose to organs at risk (OAR) may prompt BID fractionation, yet data is scarce for its application in thoracic re-RT. This study characterizes the safety and efficacy of BID re-RT for thoracic malignancies.

Materials/Methods: All BID thoracic re-RT cases since 2012 were reviewed. Doses were deformably registered, and a custom script calculated cumulative EQD2 (a/ß = 3). Maximum overall toxicity was graded per CTCAE v5.0 and evaluated for relationship to radiation. Cumulative incidence of local failure (LF) was calculated. Kaplan Meier curves were generated for overall survival (OS) and progression-free survival (PFS) and compared with the log-rank test.

Results: Sixty-five BID re-RT cases were reviewed. Most patients (77%) received 45Gy in 30 fractions (range 30Gy/20 to 60Gy/40). Median follow-up was 13.4 months. Table 1 shows adverse event incidence and median cumulative delivered OAR dose vs ARS and ACR cumulative dose recommendations. Ten patients (15.4%) had a G3 toxicity, totaling 15 events: five cardiovascular, six gastrointestinal, and four respiratory. Of 24 OAR doses exceeding ARS/ACR cumulative dose recommendations, only one case had toxicity =G3: a G3 esophageal obstruction (composite esophagus D_max 111.7Gy). No G4 events occurred. One G5 esophageal perforation occurred with a tumor invading the esophageal wall (cumulative esophagus D_max 99.9Gy).

Median time to LF was not reached (12-month: 27.6%, 24-month: 42.9%). Median PFS was 8.0 months (12-month: 32.4%, 24-month: 14.1%). Median OS was 18.5 months. There were no significant differences in PFS or OS by histology, dose >45Gy or metastatic status. Of the 39 patients who progressed, 28% were in the thorax, 44% distant only, and 28% mixed. At the end of follow-up, 24 patients were alive, and 15 had no evidence of disease.

Conclusion: BID thoracic re-RT is effective for durable control with low G3+ toxicity despite high-risk scenarios. Our analysis supports BID re-RT for thoracic malignancies, and its demonstrated safety advocates for investigation of dose-escalation along a definitive re-RT paradigm for tumors often considered radioresistant.

Abstract 1051 - Table 1: Median cumulative delivered OAR dose vs ARS/ACR composite dose recommendations (EQD2, a/ß=3)

OAR	ARS/ACR Composite Dose Constraint	Cumulative Delivered Dose: Median (Range)	Percentage of Patients with Adverse Event (max grade for patient)	Cases Exceeding ARS/ACR Constraint
Heart	V40Gy <50%	6.0% (0 - 43.8)	Pericarditis G1 (1.5%), G3 (3.1%)	0
Esophagus	V60Gy <40% D_max < 100Gy	4.0% (0 - 50.7) 70.5 Gy (21.4 - 111.7)	Esophagitis G1 (27.8%), G2 (24.6%), G3 (3.1%)	2 5
Lung	V20Gy <40%	20.0% (3.1 - 48.3)	Pneumonitis G1 (12.3%), G2 (7.7%)	4
Great Vessel	D_max <120Gy	105.9 Gy (84.9 - 150.5)	-	2
Large Airway	D_max <110Gy	91.8 Gy (2.7 - 169.1)	Respiratory Stricture G1 (6.2%), G3 (1.5%)	8
Brachial Plexus	D_max <85Gy	42.9 Gy (2.4 - 99.2)	Plexopathy G2 (1.5%)	1
Spinal Cord	D_max <57Gy	33.4 Gy (7.0 - 61.5)	-	2