Dose-Escalated Radiation Therapy with a Simultaneous Integrated Boost with or without Adjuvant Immunotherapy for Locally Advanced Non-Small Cell Lung Cancer

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International Journal of Radiation Oncology • Biology • Physics


Purpose/Objective(s): Cancer-specific outcomes for locally advanced lung cancer have improved significantly with the advent of immunotherapy (IT). As patients live longer, local control will be an increasingly important determinant of survival. Here we compare oncological outcomes among patients treated with a simultaneous integrated boost to those treated with a SIB and adjuvant IT. Materials/Methods: Patients with Stage IIA-IIIC (cT1-T4, cN0-N3, cM0) NSCLC who underwent radiation therapy using a simultaneous integrated boost (SIB; 60 Gy PTV, 70 Gy GTV_ITV in 30 fractions) technique with concurrent chemotherapy from 2016-2019 were included; 37 received adjuvant IT. Patterns of failure along with overall survival (OS), diseasefree survival (DFS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), and distant metastasis-free survival (DMFS) are reported and compared between groups. Baseline characteristics between were compared using c2 for categorical data. Univariate analysis of patient and treatment characteristics impact on clinical outcomes was performed using the Kaplan-Meier. All statistics were completed using RStudio. Results: 103 patients were included, with a median follow-up of 15.6 months and age at diagnosis of 71 years. Normal tissue dose volume constraints were met according to current RTOG/national guidelines. Patterns of failure are shown below. Intrathoracic only failure was 11-12% using the SIB and represented 26-44% of those progressing; extrathoracic failures predominated in the SIB alone subset. There were no statistically significant differences in LR, RR or LRR between SIB and SIB+IT; 2y LR was 18.6% and LRR 26%. Although RR was higher than expected, only 1/ 10 with RR had mediastinoscopy and the remaining had mean of 1.3 lymph nodes sampled at EBUS. SIB+IT had lower DM (2y 17.3 v 40.6%, p Z 0.03) and higher OS (2y OS 53 v 69%). There was no significant difference in any acute/late toxicity in the presence of IT. MVA for OS showed higher OS for R-sided tumors (HR 0.4, p Z 0.009), IT (HR 0.23, p Z 0.002), and heart V5 < Z 72% (HR 0.4, p Z 0.005). Conclusion: This single institution study demonstrates that dose escalation using an SIB technique while maintaining normal tissue dose constraints showed favorable OS and a lower LR and intrathoracic failure rate than those reported using standard dose RT+IT. Addition of IT did not impact LRR but was associated with a change from a predominant intrathoracic to extrathoracic failure pattern with isotoxicity, potentially increasing the rate of salvageable failures after chemoradiation.





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