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Safety of combining thoracic radiation therapy with concurrent versus sequential immune checkpoint inhibition.

ABSTRACT: Purpose:The objective of this study was to evaluate adverse events (AEs) in patients who received both immune checkpoint inhibitors and thoracic radiation therapy (RT). In particular, we compared the rate of toxicities of concurrent versus sequential delivery of thoracic RT and checkpoint inhibitors. Methods and Materials:Patient and treatment characteristics were collected on all patients at our institution who were treated with programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), and/or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors and underwent thoracic RT (n?=?79). Receiving both treatments within 1 month was considered concurrent (n?=?35; 44%), and any treatment up to 6 months apart was considered sequential (n?=?44; 56%). The primary endpoint of this study was the rate of Grade ?2 AEs from combination therapy (immunotherapy and RT), specifically those that are relevant to thoracic RT: Pneumonitis, other pulmonary events, esophagitis, dermatitis, and fatigue. Further univariate analysis was performed to compare AE rates with clinical and therapy-related variables. Results:A total of 79 patients were identified, with lung cancer (n?=?45) and melanoma (n?=?15) being the most common primary histology. Sixty-two (78%) patients were treated with anti-PD-1 or anti-PD-L1 antibodies, 12 (15%) with anti-CTLA-4 antibodies, and 5 (6%) received both anti-PD-1/PD-L1 and anti-CTLA-4 antibodies. The median follow-up for survivors was 5.9 months (range, 2.4-55.6 months). Grade ?2 AEs included pneumonitis (n?=?5; 6%), esophagitis (n?=?6; 8%), and dermatitis (n?=?8; 10%). No statistically significant correlation was found between these AEs when comparing concurrent versus sequential treatment. The only significant variable was a correlation of immunotherapy drug category with Grade ?2 esophagitis (P?=?.04). Conclusions:Overall, Grade ?2 AE rates of thoracic RT and immunotherapy appeared as expected and acceptable. The lack of significant differences in AE rates with concurrent versus sequential treatment suggests that even concurrent immunotherapy and thoracic RT may be safe.

SUBMITTER: von Reibnitz D

PROVIDER: S-EPMC6128092 | biostudies-literature | 2018 Jul-Sep

REPOSITORIES: biostudies-literature

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Safety of combining thoracic radiation therapy with concurrent versus sequential immune checkpoint inhibition.

von Reibnitz Donata D Chaft Jamie E JE Wu Abraham J AJ Samstein Robert R Hellmann Matthew D MD Plodkowski Andrew J AJ Zhang Zhigang Z Shi Weiji W Dick-Godfrey Rosalind R Panchoo Kelly H KH Barker Christopher A CA Rimner Andreas A

Advances in radiation oncology 20180509 3

<h4>Purpose</h4>The objective of this study was to evaluate adverse events (AEs) in patients who received both immune checkpoint inhibitors and thoracic radiation therapy (RT). In particular, we compared the rate of toxicities of concurrent versus sequential delivery of thoracic RT and checkpoint inhibitors.<h4>Methods and materials</h4>Patient and treatment characteristics were collected on all patients at our institution who were treated with programmed cell death protein 1 (PD-1), programmed ...[more]

PMID: 30202807

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Project description:BackgroundPatients with non-small cell lung cancer may develop pneumonitis after thoracic radiotherapy (RT) and immune checkpoint inhibitors (ICIs). We hypothesized that distinct morphologic features are associated with different pneumonitis etiologies.Materials and methodsWe systematically compared computed tomography (CT) features of RT- versus ICI-pneumonitis. Clinical and imaging features were tested for association with pneumonitis severity. Lastly, we constructed an exploratory radiomics-based machine learning (ML) model to discern pneumonitis etiology.ResultsBetween 2009 and 2019, 82 patients developed pneumonitis: 29 after thoracic RT, 23 after ICI, and 30 after RT + ICI. Fifty patients had grade 2 pneumonitis, 22 grade 3, and 7 grade 4. ICI-pneumonitis was more likely bilateral (65% vs. 28%; p = .01) and involved more lobes (66% vs. 45% involving at least three lobes) and was less likely to have sharp border (17% vs. 59%; p = .004) compared with RT-pneumonitis. Pneumonitis morphology after RT + ICI was heterogeneous, with 47% bilateral, 37% involving at least three lobes, and 40% sharp borders. Among all patients, risk factors for severe pneumonitis included poor performance status, smoking history, worse lung function, and bilateral and multifocal involvement on CT. An ML model based on seven radiomic features alone could distinguish ICI- from RT-pneumonitis with an area under the receiver-operating curve of 0.76 and identified the predominant etiology after RT + ICI concordant with multidisciplinary consensus.ConclusionRT- and ICI-pneumonitis exhibit distinct spatial features on CT. Bilateral and multifocal lung involvement is associated with severe pneumonitis. Integrating these morphologic features in the clinical management of patients who develop pneumonitis after RT and ICIs may improve treatment decision-making.Implications for practicePatients with non-small cell lung cancer often receive thoracic radiation and immune checkpoint inhibitors (ICIs), both of which can cause pneumonitis. This study identified similarities and differences in pneumonitis morphology on computed tomography (CT) scans among pneumonitis due to radiotherapy (RT) alone, ICI alone, and the combination of both. Patients who have bilateral CT changes involving at least three lobes are more likely to have ICI-pneumonitis, whereas those with unilateral CT changes with sharp borders are more likely to have radiation pneumonitis. After RT and/or ICI, severe pneumonitis is associated with bilateral and multifocal CT changes. These results can help guide clinicians in triaging patients who develop pneumonitis after radiation and during ICI treatment.

Dataset Information

Safety of combining thoracic radiation therapy with concurrent versus sequential immune checkpoint inhibition.

Publications

Safety of combining thoracic radiation therapy with concurrent versus sequential immune checkpoint inhibition.

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