Dataset Information

A systematic review of lung-sparing extirpative surgery for pleural mesothelioma.

ABSTRACT:

Objectives

There 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.

Design

A 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.

Setting

Follow-up studies of patients undergoing surgery for malignant pleural mesothelioma in specialist thoracic or cardiothoracic units.

Participants

Among the operated patients described in these papers, a total of 1270 patients had undergone lung-sparing surgery for mesothelioma.

Results

There 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.

Conclusions

In 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.

SUBMITTER: Teh E

PROVIDER: S-EPMC3031645 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A systematic review of lung-sparing extirpative surgery for pleural mesothelioma.

Teh Elaine E Fiorentino Francesca F Tan Carol C Treasure Tom T

Journal of the Royal Society of Medicine 20110201 2

<h4>Objectives</h4>There 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.<h4>Design</h4>A formal literature search was performed and all recovered titles were seq ...[more]

PMID: 21282797

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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.

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: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:Malignant pleural mesothelioma (MPM) is a tumour related to a historical exposure to asbestos fibres. Currently, the definite diagnosis is made only by the histological examination of a biopsy obtained through an invasive thoracoscopy. However, diagnosis is made too late for curative treatment because of non-specific symptoms mainly appearing at advanced stage disease. Hence, due to its biologic aggressiveness and the late diagnosis, survival rate is low and the patients' outcome poor. In addition, radiological imaging, like computed tomographic scans, and blood biomarkers are found not to be sensitive enough to be used as an early diagnostic tool. Detection in an early stage is assumed to improve the patients' outcome but is hampered due to non-specific and late symptomology. Hence, there is a need for a new screening and diagnostic test which could improve the patients' outcome. Despite extensive research has focused on blood biomarkers, not a single has been shown clinically useful, and therefore research recently shifted to "breathomics" techniques to recognize specific volatile organic compounds (VOCs) in the breath of the patient as potential non-invasive biomarkers for disease. In this review, we summarize the acquired knowledge about using breath analysis for diagnosing and monitoring MPM and asbestos-related disorders (ARD). Gas chromatography-mass spectrometry (GC-MS), the gold standard of breath analysis, appears to be the method with the highest accuracy (97%) to differentiate MPM patients from at risk asbestos-exposed subjects. There have already been found some interesting biomarkers that are significantly elevated in asbestosis (NO, 8-isoprostane, leukotriene B4, ?-Pinene…) and MPM (cyclohexane) patients. Regrettably, the different techniques and the plethora of studies suffer some limitations. Most studies are pilot studies with the inclusion of a limited number of patients. Nevertheless, given the promising results and easy sampling methods, we can conclude that breath analysis may become a useful tool in the future to screen for MPM, but further research is warranted.

Project description:BackgroundThe effects of extra-pleural pneumonectomy (EPP) on survival and quality of life in patients with malignant pleural mesothelioma have, to our knowledge, not been assessed in a randomised trial. We aimed to assess the clinical outcomes of patients who were randomly assigned to EPP or no EPP in the context of trimodal therapy in the Mesothelioma and Radical Surgery (MARS) feasibility study.MethodsMARS was a multicentre randomised controlled trial in 12 UK hospitals. Patients aged 18 years or older who had pathologically confirmed mesothelioma and were deemed fit enough to undergo trimodal therapy were included. In a prerandomisation registration phase, all patients underwent induction platinum-based chemotherapy followed by clinical review. After further consent, patients were randomly assigned (1:1) to EPP followed by postoperative hemithorax irradiation or to no EPP. Randomisation was done centrally with computer-generated permuted blocks stratified by surgical centre. The main endpoints were feasibility of randomly assigning 50 patients in 1 year (results detailed in another report), proportion randomised who received treatment, proportion eligible (registered) who proceeded to randomisation, perioperative mortality, and quality of life. Patients and investigators were not masked to treatment allocation. This is the principal report of the MARS study; all patients have been recruited. Analyses were by intention to treat. This trial is registered, number ISRCTN95583524.FindingsBetween Oct 1, 2005, and Nov 3, 2008, 112 patients were registered and 50 were subsequently randomly assigned: 24 to EPP and 26 to no EPP. The main reasons for not proceeding to randomisation were disease progression (33 patients), inoperability (five patients), and patient choice (19 patients). EPP was completed satisfactorily in 16 of 24 patients assigned to EPP; in five patients EPP was not started and in three patients it was abandoned. Two patients in the EPP group died within 30 days and a further patient died without leaving hospital. One patient in the no EPP group died perioperatively after receiving EPP off trial in a non-MARS centre. The hazard ratio [HR] for overall survival between the EPP and no EPP groups was 1·90 (95% CI 0·92-3·93; exact p=0·082), and after adjustment for sex, histological subtype, stage, and age at randomisation the HR was 2·75 (1·21-6·26; p=0·016). Median survival was 14·4 months (5·3-18·7) for the EPP group and 19·5 months (13·4 to time not yet reached) for the no EPP group. Of the 49 randomly assigned patients who consented to quality of life assessment (EPP n=23; no EPP n=26), 12 patients in the EPP group and 19 in the no EPP group completed the quality of life questionnaires. Although median quality of life scores were lower in the EPP group than the no EPP group, no significant differences between groups were reported in the quality of life analyses. There were ten serious adverse events reported in the EPP group and two in the no EPP group.InterpretationIn view of the high morbidity associated with EPP in this trial and in other non-randomised studies a larger study is not feasible. These data, although limited, suggest that radical surgery in the form of EPP within trimodal therapy offers no benefit and possibly harms patients.FundingCancer Research UK (CRUK/04/003), the June Hancock Mesothelioma Research Fund, and Guy's and St Thomas' NHS Foundation Trust.

Dataset Information

A systematic review of lung-sparing extirpative surgery for pleural mesothelioma.

Objectives

Design

Setting

Participants

Results

Conclusions

Publications

A systematic review of lung-sparing extirpative surgery for pleural mesothelioma.

Similar Datasets

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