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Should Lung-Sparing Surgery Be the Standard Procedure for Malignant Pleural Mesothelioma?

ABSTRACT: BACKGROUND:Surgical procedures for malignant pleural mesothelioma (MPM) include extrapleural pneumonectomy (EPP), extended pleurectomy/decortication (P/D) and P/D. EPP has been applied to MPM for a long time, but the postoperative status is extremely poor due to the loss of one whole lung. We compared the mortality, morbidity and median survival time (MST) of lung-sparing surgery (extended P/D or P/D) and lung-sacrificing surgery (EPP) for MPM by performing a systematic review. METHODS:We extracted the number of events and patients from the literature identified in electronic databases. Ultimately, 15 reports were selected, and 2674 MPM patients, including 1434 patients undergoing EPP and 1240 patients undergoing extended P/D or P/D, were analyzed. RESULTS:Our systematic review showed that lung-sparing surgery was significantly superior to lung-sacrificing surgery in both the surgical-related mortality (extended P/D vs. EPP: 3.19% vs. 7.65%, p < 0.01; P/D vs. EPP: 1.85% vs. 7.34%, p < 0.01) and morbidity (extended P/D vs. EPP: 35.7% vs. 60.0%, p < 0.01; P/D vs. EPP: 9.52% vs. 20.89%, p < 0.01). Lung-sparing surgery was not inferior to EPP in terms of MST. CONCLUSION:Although no prospective randomized controlled trial has been conducted, it may be time to change the standard surgical method for MPM from lung-sacrificing surgery to lung-sparing surgery.

SUBMITTER: Ichiki Y

PROVIDER: S-EPMC7408715 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Should Lung-Sparing Surgery Be the Standard Procedure for Malignant Pleural Mesothelioma?

Ichiki Yoshinobu Y Goto Hidenori H Fukuyama Takashi T Nakanishi Kozo K

Journal of clinical medicine 20200708 7

<h4>Background</h4>Surgical procedures for malignant pleural mesothelioma (MPM) include extrapleural pneumonectomy (EPP), extended pleurectomy/decortication (P/D) and P/D. EPP has been applied to MPM for a long time, but the postoperative status is extremely poor due to the loss of one whole lung. We compared the mortality, morbidity and median survival time (MST) of lung-sparing surgery (extended P/D or P/D) and lung-sacrificing surgery (EPP) for MPM by performing a systematic review.<h4>Method ...[more]

PMID: 32650433

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Project description:ObjectivesThere is a resurgence of interest in lung-sparing extirpative surgery for malignant pleural mesothelioma with recent reports of better survival and fewer adverse consequences than with extrapleural pneumonectomy. However, these operations are not well-characterized and to offer evidence-based clinical recommendations and to plan future trials a summary of what is already known is required.DesignA formal literature search was performed and all recovered titles were sequentially sifted by title, abstract and full-text reading according to prespecified criteria. Papers were selected if they contained data relevant to the area of enquiry. Quantitative synthesis and textual analysis, appropriate to the material, were performed.SettingFollow-up studies of patients undergoing surgery for malignant pleural mesothelioma in specialist thoracic or cardiothoracic units.ParticipantsAmong the operated patients described in these papers, a total of 1270 patients had undergone lung-sparing surgery for mesothelioma.ResultsThere were no randomized trials or other forms of controlled studies. From 464 titles, 26 papers contained sufficient data on 1270 patients to be included in the systematic review. Operative descriptions for all series were extracted and tabulated and variation was found in the nature of surgery within and between series, and the degree of detail with which it was described. There was more operative detail in recent papers. All available numerical data were extracted, tabulated and summarized using quantitative methods. The average survival at 1, 2, 3, 4 and 5 years was 51%, 26%, 16%, 11% and 9%, respectively. There were no data on patients' performance status, symptomatic change, or other patient reported outcomes.ConclusionsIn the absence of any form of control data, no conclusions can be drawn concerning survival differences or symptomatic benefits attributable to surgery. As mesothelioma surgery is restricted to a selected minority of patients who often have multiple therapies, future research will require controlled studies with explicit definitions of the clinical and surgical intent.

Project description:PurposeTo determine clinically helpful dose-volume and clinical metrics correlating with symptomatic radiation pneumonitis (RP) in malignant pleural mesothelioma (MPM) patients with 2 lungs treated with hemithoracic intensity modulated pleural radiation therapy (IMPRINT).Methods and materialsTreatment plans and resulting normal organ dose-volume histograms of 103 consecutive MPM patients treated with IMPRINT (February 2005 to January 2015) to the highest dose ≤50.4 Gy satisfying departmental normal tissue constraints were uniformly recalculated. Patient records provided maximum RP grade (Common Terminology Criteria for Toxicity and Adverse Event version 4.0) and clinical and demographic information. Correlations analyzed with the Cox model were grade ≥2 RP (RP2+) and grade ≥3 RP (RP3+) with clinical variables, with volumes of planning target volume (PTV) and PTV-lung overlap and with mean dose, percent volume receiving dose D (VD), highest dose encompassing % volume V, (DV), and heart, total, ipsilateral, and contralateral lung volumes.ResultsTwenty-seven patients had RP2+ (14 with RP3+). The median prescription dose was 46.8 Gy (39.6-50.4 Gy, 1.8 Gy/fraction). The median age was 67.6 years (range, 42-83 years). There were 79 men, 40 never-smokers, and 44 with left-sided MPM. There were no significant (P≤.05) correlations with clinical variables, prescription dose, total lung dose-volume metrics, and PTV-lung overlap volume. Dose-volume correlations for heart were RP2+ with VD (35 ≤ D ≤ 47 Gy, V43 strongest at P=.003), RP3+ with VD (31 ≤ D ≤ 45 Gy), RP2+ with DV (5 ≤ V ≤ 30%), RP3+ with DV (15 ≤ V ≤ 35%), and mean dose. Significant for ipsilateral lung were RP2+ with VD (38 ≤ D ≤ 44 Gy), RP3+ with V41, RP2+ and RP3+ with minimum dose, and for contralateral lung, RP2+ with maximum dose. Correlation of PTV with RP2+ was strong (P<.001) and also significant with RP3+.ConclusionsHeart dose correlated strongly with symptomatic RP in this large cohort of MPM patients with 2 lungs treated with IMPRINT. Planning constraints to reduce future heart doses are suggested.

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.

Project description:PurposeWe conducted a two-center phase II study to determine the safety of hemithoracic intensity-modulated pleural radiation therapy (IMPRINT) after chemotherapy and pleurectomy-decortication (P/D) as part of a multimodality lung-sparing treatment.Patients and methodsPatients received up to four cycles of pemetrexed plus platinum. If feasible, P/D was performed. Hemithoracic IMPRINT was administered to a planned dose of 50.4 Gy in 28 fractions. The primary end point was the incidence of grade 3 or greater radiation pneumonitis (RP).ResultsA total of 45 patients were enrolled; 18 were not evaluable (because of disease progression before radiation therapy [RT], n = 9; refusal of surgery or RT, n = 5; extrapleural pneumonectomy at time of surgery, n = 2; or chemotherapy complications, n = 2). A total of 26 patients received pemetrexed plus cisplatin, 18 received pemetrexed plus carboplatin, and four received a combination. Thirteen patients (28.9%) had a partial response, 15 patients (33.3%) experienced disease progression, one patient died during chemotherapy, and all others had stable disease. Eight patients underwent P/D or an extended P/D, and 13 underwent a partial P/D. A total of 27 patients started IMPRINT (median dose, 46.8 Gy; range, 28.8 to 50.4 Gy) and were evaluable for the primary end point (median follow-up, 21.6 months). Six patients experienced grade 2 RP, and two patients experienced grade 3 RP; all recovered after corticosteroid initiation. No grade 4 or 5 radiation-related toxicities were observed. The median progression-free survival and overall survival (OS) were 12.4 and 23.7 months, respectively; the 2-year OS was 59% in patients with resectable tumors and was 25% in patients with unresectable tumors.ConclusionsHemithoracic IMPRINT for malignant pleural mesothelioma (MPM) is safe and has an acceptable rate of RP. Its incorporation with chemotherapy and P/D forms a new lung-sparing treatment paradigm for patients with locally advanced MPM.

Project description:BackgroundThis observational study evaluates retrospectively the long-term outcomes after pleurectomy/decortication for pleural mesothelioma, with and without the resection/reconstruction of diaphragm and pericardium.MethodsData from 155 consecutive patients undergoing lung-sparing surgery for epithelial pleural mesothelioma were reviewed. Selection criteria for surgery were cT1-3, cN0-1, good performance status, age <80 years. Perioperative Pemetrexed-Platinum regimen was administered as induction in 101 cases (65.2%) and as adjuvant treatment in 54 cases (34.8%). Extended pleurectomy/decortication was performed in 87 cases (56.12%). In 68 patients (43.87%) standard pleurectomy/decortication was performed without resection/reconstruction of diaphragm and pericardium, when tumour infiltration was deemed absent after intraoperative frozen section. The log-rank test and Cox regression model were used to assess the factors affecting overall survival and recurrence free survival.ResultsMedian follow-up was 20 months. The 2- and 5-year survival rate was 60.9% and 29.2% with a median survival of 34 months. An improved survival was observed when standard pleurectomy/decortication was carried out (P=0.007). A significant impact on survival was found comparing the TNM-stages (P=0.001), pT (P=0.002) and pN variables (P=0.001). Multivariate analysis identified the pN-status (P=0.003) and standard pleurectomy/decortication (P=0.017) as predictive for longer survival. The recurrence-free survival >12 months was strongly related to the overall survival (P<0.001). The macroscopic complete resection (P=0.001), TNM-stage (P=0.003) and pT-status (P=0.001) are related to relapse.ConclusionsWithin multimodal management of pleural mesothelioma, lung-sparing surgery is a valid option even with more conservative technique. A benefit for a longer survival was observed in the early stage of disease, with pN0 and when pleurectomy/decortication is carried out, preserving diaphragm and pericardium. Recurrence is not affected by the type of surgery, and a recurrence-free interval >12 months is predictive of an increased survival when the macroscopic complete resection is achieved.

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Should Lung-Sparing Surgery Be the Standard Procedure for Malignant Pleural Mesothelioma?

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Should Lung-Sparing Surgery Be the Standard Procedure for Malignant Pleural Mesothelioma?

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