Lobar Gross Endobronchial Disease Predicts for Overall Survival and Grade 5 Pulmonary Toxicity in Medically Inoperable Early Stage Non-Small Cell Lung Cancer Patients Treated With Stereotactic Body Radiation Therapy

PurposeStereotactic body radiation therapy (SBRT) is considered standard of care for medically inoperable early stage non-small cell lung cancer (ES-NSCLC). Central tumor location is a known risk factor for severe SBRT related toxicity. Bronchoscopy allows for visualization of the central airways pr...

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Autores principales:	Nima Aghdam, Jonathan W. Lischalk, Monica Pernia Marin, Clare Hall, Timothy O’Connor, Lloyd Campbell, Simeng Suy, Sean P. Collins, Marc Margolis, Rebecca Krochmal, Eric Anderson, Brian T. Collins
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	bronchoscopy gross endobronchial disease inoperable non-small cell lung cancer stereotactic body radiation therapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/1c080e30a5d2415e8484a5dd5a4267bc
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id	oai:doaj.org-article:1c080e30a5d2415e8484a5dd5a4267bc
record_format	dspace
institution	DOAJ
collection	DOAJ
language	EN
topic	bronchoscopy gross endobronchial disease inoperable non-small cell lung cancer stereotactic body radiation therapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	bronchoscopy gross endobronchial disease inoperable non-small cell lung cancer stereotactic body radiation therapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Nima Aghdam Jonathan W. Lischalk Monica Pernia Marin Clare Hall Timothy O’Connor Lloyd Campbell Simeng Suy Sean P. Collins Marc Margolis Rebecca Krochmal Eric Anderson Brian T. Collins Lobar Gross Endobronchial Disease Predicts for Overall Survival and Grade 5 Pulmonary Toxicity in Medically Inoperable Early Stage Non-Small Cell Lung Cancer Patients Treated With Stereotactic Body Radiation Therapy
description	PurposeStereotactic body radiation therapy (SBRT) is considered standard of care for medically inoperable early stage non-small cell lung cancer (ES-NSCLC). Central tumor location is a known risk factor for severe SBRT related toxicity. Bronchoscopy allows for visualization of the central airways prior to treatment. Five fraction SBRT approaches have been advocated to mitigate treatment induced toxicity. In this report, we examine the mature clinical outcomes of a diverse cohort of ES-NSCLC patients with both peripheral and central tumors treated with a conservative 5 fraction SBRT approach and evaluate the role of lobar gross endobronchial disease (LGED) in predicting overall survival and treatment-related death.MethodsMedically inoperable biopsy-proven, lymph node-negative ES-NSCLC patients were treated with SBRT. Bronchoscopy was completed prior to treatment in all centrally located cases. The Kaplan-Meier method was used to estimate overall survival (OS), local control (LC), regional control (RC), distant metastasis free survival (DMFS) and disease-free survival (DFS). Overall survival was stratified based on clinical stage, histology, tumor location and LGED. Toxicities were scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0.ResultsFrom December 2010 to December 2015, 50 consecutive patients were treated uniformly with a 50 Gy in 5 fraction SBRT approach (tumor BED10 ≥ 100 Gy) and followed for a minimum of 5 years or until death. At a median follow up of 42 months for all patients, 3-year OS was 50%. Three-year OS did not statistically differ between stage I and stage II disease (51% vs. 47%; p=0.86), adenocarcinoma and squamous cell carcinoma (50% vs. 45%; p=0.68), or peripheral and central tumors (56% vs. 45%; p=0.46). Five central tumors were found to have LGED, and 3-year OS for this cohort was quite poor at 20%. Cox regression analysis identified LGED as a predictor of OS while controlling for age, stage and location (OR:4.536, p-value=0.038). Despite the relatively low dose delivered, treatment likely contributed to the death of 4 patients with central tumors. Lobar gross endobronchial disease was an independent predictor for grade 5 pulmonary toxicity (n=4, p=0.007). Specifically, 3 of the 5 patients with LGED developed fatal radiation-induced bronchial stricture. Three-year LC, RC, DMFS and DFS results for the group were similar to contemporary studies at 90%, 90%, 82% and 65%.ConclusionsCentral location of ES-NSCLC is a well-established predictor for severe SBRT-related toxicity. Here we identify LGED as a significant predictor of poor overall survival and grade 5 pulmonary toxicity. The relatively high rates of severe treatment-related toxicity seen in patients with central ES-NSCLC may be due in part to LGED. Underlying LGED may cause irreparable damage to the lobar airway, unmitigated by SBRT treatment thus increasing the risk of severe treatment-related toxicity. These findings should be verified in larger data sets. Future prospective central ES-NSCLC clinical trials should require staging bronchoscopy to identify LGED and further assess its clinical significance.
format	article
author	Nima Aghdam Jonathan W. Lischalk Monica Pernia Marin Clare Hall Timothy O’Connor Lloyd Campbell Simeng Suy Sean P. Collins Marc Margolis Rebecca Krochmal Eric Anderson Brian T. Collins
author_facet	Nima Aghdam Jonathan W. Lischalk Monica Pernia Marin Clare Hall Timothy O’Connor Lloyd Campbell Simeng Suy Sean P. Collins Marc Margolis Rebecca Krochmal Eric Anderson Brian T. Collins
author_sort	Nima Aghdam
title	Lobar Gross Endobronchial Disease Predicts for Overall Survival and Grade 5 Pulmonary Toxicity in Medically Inoperable Early Stage Non-Small Cell Lung Cancer Patients Treated With Stereotactic Body Radiation Therapy
title_short	Lobar Gross Endobronchial Disease Predicts for Overall Survival and Grade 5 Pulmonary Toxicity in Medically Inoperable Early Stage Non-Small Cell Lung Cancer Patients Treated With Stereotactic Body Radiation Therapy
title_full	Lobar Gross Endobronchial Disease Predicts for Overall Survival and Grade 5 Pulmonary Toxicity in Medically Inoperable Early Stage Non-Small Cell Lung Cancer Patients Treated With Stereotactic Body Radiation Therapy
title_fullStr	Lobar Gross Endobronchial Disease Predicts for Overall Survival and Grade 5 Pulmonary Toxicity in Medically Inoperable Early Stage Non-Small Cell Lung Cancer Patients Treated With Stereotactic Body Radiation Therapy
title_full_unstemmed	Lobar Gross Endobronchial Disease Predicts for Overall Survival and Grade 5 Pulmonary Toxicity in Medically Inoperable Early Stage Non-Small Cell Lung Cancer Patients Treated With Stereotactic Body Radiation Therapy
title_sort	lobar gross endobronchial disease predicts for overall survival and grade 5 pulmonary toxicity in medically inoperable early stage non-small cell lung cancer patients treated with stereotactic body radiation therapy
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/1c080e30a5d2415e8484a5dd5a4267bc
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spelling	oai:doaj.org-article:1c080e30a5d2415e8484a5dd5a4267bc2021-12-01T13:40:41ZLobar Gross Endobronchial Disease Predicts for Overall Survival and Grade 5 Pulmonary Toxicity in Medically Inoperable Early Stage Non-Small Cell Lung Cancer Patients Treated With Stereotactic Body Radiation Therapy2234-943X10.3389/fonc.2021.728519https://doaj.org/article/1c080e30a5d2415e8484a5dd5a4267bc2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.728519/fullhttps://doaj.org/toc/2234-943XPurposeStereotactic body radiation therapy (SBRT) is considered standard of care for medically inoperable early stage non-small cell lung cancer (ES-NSCLC). Central tumor location is a known risk factor for severe SBRT related toxicity. Bronchoscopy allows for visualization of the central airways prior to treatment. Five fraction SBRT approaches have been advocated to mitigate treatment induced toxicity. In this report, we examine the mature clinical outcomes of a diverse cohort of ES-NSCLC patients with both peripheral and central tumors treated with a conservative 5 fraction SBRT approach and evaluate the role of lobar gross endobronchial disease (LGED) in predicting overall survival and treatment-related death.MethodsMedically inoperable biopsy-proven, lymph node-negative ES-NSCLC patients were treated with SBRT. Bronchoscopy was completed prior to treatment in all centrally located cases. The Kaplan-Meier method was used to estimate overall survival (OS), local control (LC), regional control (RC), distant metastasis free survival (DMFS) and disease-free survival (DFS). Overall survival was stratified based on clinical stage, histology, tumor location and LGED. Toxicities were scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0.ResultsFrom December 2010 to December 2015, 50 consecutive patients were treated uniformly with a 50 Gy in 5 fraction SBRT approach (tumor BED10 ≥ 100 Gy) and followed for a minimum of 5 years or until death. At a median follow up of 42 months for all patients, 3-year OS was 50%. Three-year OS did not statistically differ between stage I and stage II disease (51% vs. 47%; p=0.86), adenocarcinoma and squamous cell carcinoma (50% vs. 45%; p=0.68), or peripheral and central tumors (56% vs. 45%; p=0.46). Five central tumors were found to have LGED, and 3-year OS for this cohort was quite poor at 20%. Cox regression analysis identified LGED as a predictor of OS while controlling for age, stage and location (OR:4.536, p-value=0.038). Despite the relatively low dose delivered, treatment likely contributed to the death of 4 patients with central tumors. Lobar gross endobronchial disease was an independent predictor for grade 5 pulmonary toxicity (n=4, p=0.007). Specifically, 3 of the 5 patients with LGED developed fatal radiation-induced bronchial stricture. Three-year LC, RC, DMFS and DFS results for the group were similar to contemporary studies at 90%, 90%, 82% and 65%.ConclusionsCentral location of ES-NSCLC is a well-established predictor for severe SBRT-related toxicity. Here we identify LGED as a significant predictor of poor overall survival and grade 5 pulmonary toxicity. The relatively high rates of severe treatment-related toxicity seen in patients with central ES-NSCLC may be due in part to LGED. Underlying LGED may cause irreparable damage to the lobar airway, unmitigated by SBRT treatment thus increasing the risk of severe treatment-related toxicity. These findings should be verified in larger data sets. Future prospective central ES-NSCLC clinical trials should require staging bronchoscopy to identify LGED and further assess its clinical significance.Nima AghdamJonathan W. LischalkMonica Pernia MarinClare HallTimothy O’ConnorLloyd CampbellSimeng SuySean P. CollinsMarc MargolisRebecca KrochmalEric AndersonBrian T. CollinsFrontiers Media S.A.articlebronchoscopygross endobronchial diseaseinoperablenon-small cell lung cancerstereotactic body radiation therapyNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)

Lobar Gross Endobronchial Disease Predicts for Overall Survival and Grade 5 Pulmonary Toxicity in Medically Inoperable Early Stage Non-Small Cell Lung Cancer Patients Treated With Stereotactic Body Radiation Therapy

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