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Dosimetric Correlates of Pulmonary Toxicity in Patients with Malignant Pleural Mesothelioma Receiving Radiation Therapy to the Intact Lungs.

ABSTRACT: PURPOSE:We aimed to determine dose-volume constraints that correlate with severe (grade ?3) radiation pneumonitis (RP) in patients diagnosed with malignant pleural mesothelioma, treated using volumetric modulated arc therapy. METHODS AND MATERIALS:Data from 40 patients with malignant pleural mesothelioma who underwent pleurectomy decortication and adjuvant radiation therapy at our institution between December 2010 and October 2016 were retrospectively analyzed. Dosimetric variables for the absolute volume and percentage volume of the ipsilateral lung, contralateral lung, and heart were recorded. Events of RP were assessed using the Common Terminology Criteria for Toxicity and Adverse Events, version 4.0. The statistical analysis with Wilcoxon rank-sum, Spearman rank correlation, and receiver operating characteristic curves was computed using MATLAB V9.1, RV3.4, and SAS V9.4. RESULTS:Of the 40 patients, 26 patients (65%) were male. The median age at the time of diagnosis was 66.5 years (range, 44-84 years). The median prescription dose was 45 Gy (range, 30-54 Gy). Five patients (12.5%) had grade ?3 RP. The incidence of grade? 3 RP showed a significant correlation (P < .05) with the absolute volume and percentage volume of the ipsilateral lung spared of ?20 Gy (55 cc; 7%) and spared of ?30 Gy (200 cc; 23%). Dosimetric variables of the contralateral lung, total lung, and heart did not show a correlation with incidence of grade ?3 RP. CONCLUSIONS:In our cohort, sparing the ipsilateral lung of at least 55 cc of 20 Gy and 200 cc of 30 Gy correlated with a reduced incidence of severe (grade ?3) RP.

SUBMITTER: Thompson MR

PROVIDER: S-EPMC6500743 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Dosimetric Correlates of Pulmonary Toxicity in Patients with Malignant Pleural Mesothelioma Receiving Radiation Therapy to the Intact Lungs.

Thompson Marcher R MR Dumane Vishruta A VA Lazarev Stanislav A SA Zia Yaseen Y Rosenzweig Kenneth E KE

Practical radiation oncology 20190115 3

<h4>Purpose</h4>We aimed to determine dose-volume constraints that correlate with severe (grade ≥3) radiation pneumonitis (RP) in patients diagnosed with malignant pleural mesothelioma, treated using volumetric modulated arc therapy.<h4>Methods and materials</h4>Data from 40 patients with malignant pleural mesothelioma who underwent pleurectomy decortication and adjuvant radiation therapy at our institution between December 2010 and October 2016 were retrospectively analyzed. Dosimetric variable ...[more]

PMID: 30654090

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Project description:PurposeWe previously reported our technique for delivering intensity modulated radiation therapy (IMRT) to the entire pleura while attempting to spare the lung in patients with malignant pleural mesothelioma (MPM). Herein, we report a detailed pattern-of-failure analysis in patients with MPM who were unresectable or underwent pleurectomy/decortication (P/D), uniformly treated with hemithoracic pleural IMRT.Methods and materialsSixty-seven patients with MPM were treated with definitive or adjuvant hemithoracic pleural IMRT between November 2004 and May 2013. Pretreatment imaging, treatment plans, and posttreatment imaging were retrospectively reviewed to determine failure location(s). Failures were categorized as in-field (within the 90% isodose line), marginal (<90% and ≥50% isodose lines), out-of-field (outside the 50% isodose line), or distant.ResultsThe median follow-up was 24 months from diagnosis and the median time to in-field local failure from the end of RT was 10 months. Forty-three in-field local failures (64%) were found with a 1- and 2-year actuarial failure rate of 56% and 74%, respectively. For patients who underwent P/D versus those who received a partial pleurectomy or were deemed unresectable, the median time to in-field local failure was 14 months versus 6 months, respectively, with 1- and 2-year actuarial in-field local failure rates of 43% and 60% versus 66% and 83%, respectively (P=.03). There were 13 marginal failures (19%). Five of the marginal failures (38%) were located within the costomediastinal recess. Marginal failures decreased with increasing institutional experience (P=.04). Twenty-five patients (37%) had out-of-field failures. Distant failures occurred in 32 patients (48%).ConclusionsAfter hemithoracic pleural IMRT, local failure remains the dominant form of failure pattern. Patients treated with adjuvant hemithoracic pleural IMRT after P/D experience a significantly longer time to local and distant failure than patients treated with definitive pleural IMRT. Increasing experience and improvement in target delineation minimize the incidence of avoidable marginal failures.

Project description:Malignant pleural mesothelioma (MPM) is a highly lethal, poorly understood neoplasm that is typically associated with asbestos exposure. We performed transcriptional profiling using high-density oligonucleotide microarrays containing approximately 22,000 genes to elucidate potential molecular and pathobiological pathways in MPM using discarded human MPM tumor specimens (n=40), normal lung specimens (n=4), normal pleura specimens (n=5), and MPM and SV40-immortalized mesothelial cell lines (n=5). In global expression analysis using unsupervised clustering techniques, we found two potential subclasses of mesothelioma which correlate loosely with tumor histology. We also identified sets of genes with expression levels that distinguish between multiple tumor subclasses, normal and tumor tissues, and tumors with different morphologies. Microarray gene expression data were confirmed using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and protein analysis for three novel candidate oncogenes (NME2, CRI1, and PDGFC) and one candidate tumor suppressor (GSN). Finally, we used bioinformatics tools (i.e. software) to create and explore complex physiological pathways that may be relevant in mesothelioma tumorigenesis, pathobiology, or both. Tissues and cell lines profiled using microarrays. Discarded MPM surgical specimens (n=40), normal pleura specimens (n=5), and normal lung specimens (n=4) were freshly collected (and snap frozen) from patients who underwent surgery at Boston's Brigham and Women's Hospital (BWH) between October 1998 and August 2000. All of these patients underwent extrapleural pneumonectomy with heated intra-pleural cisplatin chemotherapy delivered after the specimens were removed. All normal specimens were obtained from patients who were never diagnosed with MPM. Two human MPM cell lines (MS589 and MS428) were kindly provided by Jonathan A. Fletcher, M.D., Department of Pathology, BWH. The JMN1B MPM cell line19,20 has been described previously. The SV40-immortalized, non-tumorigenic mesothelial cell line (Met-5A)21 and the MPM cell line MSTO-211H22 were purchased from the American Type Culture Collection. Normal tissues were obtained from additional consented patients undergoing treatment for diseases other than MPM. All MPM samples used in these studies contained relatively pure tumor (greater than 50% tumor cells per high power field examined in a section adjacent to the tissue used). The microscopic slides from the patients' resection specimens were reviewed by one of the authors (J.G.), and the diagnosis and histologic subclassification of MPM confirmed in all cases. Linked clinical and pathological data were obtained for all patients who contributed tumor specimens. Specimens and data were rendered anonymous to protect patient confidentiality. Studies utilizing human tissues were approved by and conducted in accordance with the policies of the Institutional Review Board at BWH.

Dataset Information

Dosimetric Correlates of Pulmonary Toxicity in Patients with Malignant Pleural Mesothelioma Receiving Radiation Therapy to the Intact Lungs.

Publications

Dosimetric Correlates of Pulmonary Toxicity in Patients with Malignant Pleural Mesothelioma Receiving Radiation Therapy to the Intact Lungs.

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