Intensity modulated radiation therapy after extra‐pleural pneumonectomy for malignant pleural mesothelioma is feasible without fatal pulmonary toxicity and provides good survival

Jhavar, Sameer; Pruszynski, Jessica; Gowan, Alan; Boyle, Teresa; Deb, N.; Patel, Mehul

doi:10.1111/ajco.12680

Cited by 3 publications

(4 citation statements)

References 41 publications

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“…Reasearchers from the National Cancer Institute of Aviano have published a series of prospective studies (6)(7)(8) proving that radical intensity-modulated radiation therapy, after lung-sparing surgery, leads to excellent locoregional control and survival in MPM patients. A median overall survival (OS) of 25.6 months and a 2-year OS rate of 58% are among the best results observed in recent studies (9)(10)(11), supporting the idea that this approach represents a concrete therapeutic option for MPM.…”

Section: Introductionmentioning

confidence: 64%

Biological Pathways Associated With the Development of Pulmonary Toxicities in Mesothelioma Patients Treated With Radical Hemithoracic Radiation Therapy: A Preliminary Study

et al. 2021

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Radical hemithoracic radiotherapy (RHR), after lung-sparing surgery, has recently become a concrete therapeutic option for malignant pleural mesothelioma (MPM), an asbestos-related, highly aggressive tumor with increasing incidence and poor prognosis. Although the toxicity associated to this treatment has been reduced, it is still not negligible and must be considered when treating patients. Genetic factors appear to play a role determining radiotherapy toxicity. The aim of this study is the identification of biological pathways, retrieved through whole exome sequencing (WES), possibly associated to the development of lung adverse effects in MPM patients treated with RHR. The study included individuals with MPM, treated with lung-sparing surgery and chemotherapy, followed by RHR with curative intent, and followed up prospectively for development of pulmonary toxicity. Due to the strong impact of grade 3 pulmonary toxicities on the quality of life, compared with less serious adverse events, for genetic analyses, patients were divided into a none or tolerable pulmonary toxicity (NoSTox) group (grade ≤2) and a severe pulmonary toxicity (STox) group (grade = 3). Variant enrichment analysis allowed us to identify different pathway signatures characterizing NoSTox and Stox patients, allowing to formulate hypotheses on the protection from side effects derived from radiotherapy as well as factors predisposing to a worst response to the treatment. Our findings, being aware of the small number of patients analyzed, could be considered a starting point for the definition of a panel of pathways, possibly helpful in the management of MPM patients.

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Section: Introductionmentioning

confidence: 64%

Biological Pathways Associated With the Development of Pulmonary Toxicities in Mesothelioma Patients Treated With Radical Hemithoracic Radiation Therapy: A Preliminary Study

et al. 2021

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“…Reasearchers from the National Cancer Institute of Aviano have published a series of prospective studies (6)(7)(8) proving that radical intensity modulated radiation therapy, after lung-sparing surgery, leads to excellent loco-regional control and survival in MPM patients. A median overall survival (OS) of 25.6 months and a 2-year OS rate of 58% are among the best results observed in recent studies (9)(10)(11), supporting the idea that this approach represents a concrete therapeutic option for MPM.…”

Section: Introductionmentioning

confidence: 64%

Molecular Signatures Associated With the Development of Pulmonary Toxicities in Mesothelioma Patients Treated With Radical Hemithoracic Radiation Therapy

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Muraro

et al. 2021

Preprint

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Background. Radical Hemithoracic Radiotherapy (RHR), after lung-sparing surgery, has recently become a concrete therapeutic option for malignant pleural mesothelioma (MPM), an asbestos-related, highly aggressive tumor with increasing incidence and poor prognosis. Although the toxicity associated to this treatment has been reduced, it is still not negligible and must be considered when treating patients. Genetic factors appear to play a role determining radiotherapy toxicity. The aim of this study is the identification of genetic markers able to predict the relative susceptibility for newly diagnosed MPM patients to develop lung adverse effects if they were to be treated with RHR. Methods. The study included individuals with MPM, treated with lung-sparing surgery and neoadjuvant chemotherapy, followed by RHR with curative intent, and followed up prospectively for development of pulmonary toxicity. Due to the impact of grade 3 pulmonary toxicities on the quality of life, for further genetic analyses patients were divided into a none or tolerable pulmonary toxicity group (Grade ≤2) and a severe pulmonary toxicity group (Grade=3). Whole exome sequencing (WES) was performed to identify genetic variants in biological pathways associated to pulmonary toxicity after radiotherapy.Results. We identified crucial pathways driving the lung response to ionizing radiations in patients affected by mesothelioma: by affecting both the fibrinolytic activity and RNA editing pathways, irradiation could be responsible of the severe toxicity events reported by some patients, who present specific mutations in genes involved in these pathways. Conclusions. Our preliminary results could pave the way for the definition of a panel of predictive genomic variants, capable of supporting the management of MPM patients. By allowing for early identification of patients at high risk for treatment-dependent pulmonary toxicity, this predictive tool could play a major role in the design of new therapeutic combinations.

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“…Furthermore, developing radiation techniques impacts survival and toxicity outcomes. The IMRT technique makes it possible to deliver a desired dose of radiation that is highly conformal to the target and spares normal tissues by improving dose distribution and dose homogeneity [13,15,16]. Jhavar et al [15] reported good survival outcomes by treatment with IMRT after EPP with a median survival of 38.2 months.…”

Section: Discussionmentioning

confidence: 99%

“…The IMRT technique makes it possible to deliver a desired dose of radiation that is highly conformal to the target and spares normal tissues by improving dose distribution and dose homogeneity [13,15,16]. Jhavar et al [15] reported good survival outcomes by treatment with IMRT after EPP with a median survival of 38.2 months. Shiakh et al [17] evaluated the outcomes of IMRT compared with conventional RT, and concluded that IMRT improved OS (median, 20.2 months vs. 12.3 months) with less toxicity such as esophagitis (Table 4).…”

Section: Discussionmentioning

confidence: 99%

Preliminary results of entire pleural intensity-modulated radiotherapy in a neoadjuvant setting for resectable malignant mesothelioma

et al. 2019

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Purpose The purpose of this study is to evaluate the safety and efficacy of the multimodality treatment with neoadjuvant intensity-modulated radiotherapy (IMRT) for resectable clinical T1-3N0-1M0 malignant pleural mesothelioma (MPM). Materials and Methods A total of eleven patients who received neoadjuvant chemotherapy and radiotherapy between March 2016 and June 2018 were reviewed. Patients received 25 Gy in 5 fractions to entire ipsilateral hemithorax with helical tomotherapy. Results All of patients were men with a median age of 56 years. Epithelioid subtype was found in 10 patients. All patients received neoadjuvant chemotherapy with pemetrexed-cisplatin regimen. Ten patients (90.9%) completed 25 Gy/5 fractions and one (9.0%) completed 20 Gy/4 fractions of radiotherapy. IMRT was well tolerated with only one acute grade 3 radiation pneumonitis. Surgery was performed 1 week (median, 8 days; range, 1 to 15 days) after completing IMRT. Extrapleural pneumonectomy was performed in 4 patients (36.3%), extended pleurectomy/decortication in 2 (18.2%) and pleurectomy/decortications in 5 (63.6%). There was no grade 3+ surgical complication except two deaths after EPP in 1 month. Based on operative findings and pathologic staging, adjuvant chemotherapy was delivered in 7 patients (63.6%), and 2 (18.2%) were decided to add adjuvant radiotherapy. After a median follow-up of 14.6 months (range, 2.8 to 30 months), there were 3 local recurrence (33.3%) and 1 distant metastasis (11.1%). Conclusion Neoadjuvant entire pleural IMRT can be delivered with a favorable radiation complication. An optimal strategy has to be made in resectable MPM patients who would benefit from neoadjuvant radiation and surgery. Further studies are needed to look at long-term outcomes.

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Intensity modulated radiation therapy after extra‐pleural pneumonectomy for malignant pleural mesothelioma is feasible without fatal pulmonary toxicity and provides good survival

Abstract: Intensity-modulated radiation therapy following EPP for MPM resulted in RFS and OS comparable to the published literature without significant toxicity.

Cited by 3 publications

References 41 publications

Biological Pathways Associated With the Development of Pulmonary Toxicities in Mesothelioma Patients Treated With Radical Hemithoracic Radiation Therapy: A Preliminary Study

Biological Pathways Associated With the Development of Pulmonary Toxicities in Mesothelioma Patients Treated With Radical Hemithoracic Radiation Therapy: A Preliminary Study

Molecular Signatures Associated With the Development of Pulmonary Toxicities in Mesothelioma Patients Treated With Radical Hemithoracic Radiation Therapy

Preliminary results of entire pleural intensity-modulated radiotherapy in a neoadjuvant setting for resectable malignant mesothelioma

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