Surgery For Malignant Pleural Mesothelioma Research Articles

Strategies to address recruitment to a randomised trial of surgical and non-surgical treatment for cancer: results from a complex recruitment intervention within the Mesothelioma and Radical Surgery 2 (MARS 2) study

ObjectivesRecruiting to randomised trials is often challenging particularly when the intervention arms are markedly different. The Mesothelioma and Radical Surgery 2 randomised controlled trial (RCT) compared standard chemotherapy with or...

Salvage pleurectomy/decortication following immunotherapy for malignant pleural mesothelioma.

Salvage surgery following immunotherapy is a promising treatment option for advanced malignant tumour. However, only a few cases of salvage surgery for malignant pleural mesothelioma (MPM) have been reported. This retrospective study was conducted to assess the feasibility of salvage surgery following immunotherapy for initially unresectabele MPM. Among 61 patients who received pleurectomy/decortication (P/D) for MPM, 7 patients received salvage P/D after immunotherapy. Surgical indication of salvage P/D was conversion to resectability in 5 patients and local relapse in 2 patients, and macroscopic complete resection was achieved in all patients. Although salvage P/D was associated with longer operation time (median, 507 min), higher intraoperative blood loss (median, 2573 mL) and higher morbidity (≥ grade 3, 29%), no patient died after surgery. Radiographic response to immunotherapy was well correlated with pathologic response, as all 4 patients with partial response showed significant pathologic response (viable cells, ≤50%). With the median postoperative follow-up duration of 9.0 months, all patients were alive mostly without tumour recurrence as local recurrence developed in 1 patient. To conclude, salvage P/D after immunotherapy may be a feasible treatment option for selected patients with advanced MPM, which should be validated in future multi-institutional studies. In addition, a long-term follow-up is essential to reveal the clinical benefit achieved with salvage P/D following immunotherapy.

Comparison of video-assisted pleurectomy/decortication surgery plus hyperthermic intrathoracic chemotherapy with VATS talc pleurodesis for the treatment of malignant pleural mesothelioma: A pilot study

Hyperthermic intrathoracic chemotherapy (HITHOC) adjunct to surgery for Malignant Pleural Mesothelioma (MPM) has no definite role. The primary objective of this pilot-trial was to evaluate the feasibility for future large studies. The study design was a prospective randomized three-centric pilot trial. We recruited patients diagnosed with MPM and prospectively assigned them to two groups: Group A: Video Assisted Thoracic Surgery (VATS) talc pleurodesis or Group B: Video-assisted P/D plus HITHOC. From November-2011 to July-2017 24 males and 3 females, with a median age of 68-years were enrolled (recruitment rate 5 patients/year). Preoperative stage was I-II, and 18 had epithelioid type. 14 patients were in the Group A. Operative mortality was 0. Follow-up ranged 6–80 months. The median overall survival time started to diverge at 20 months, being 19 months (95% CI 12–25) in Group A and 28 months (95% CI 0–56) in Group B. Survival rate for the epithelioid type was 15 months (95% CI 0–34) in Group A and 45 months (95% CI 0–107) in the Group B. These findings suggest that video-assisted P/D plus HITHOC may improve survival time in MPM patients undergoing surgical treatment and support the need for a larger multicenter randomized clinical trial.

The Effects of Preserving the Diaphragm on Early and Late Outcome of Lung-Sparing Radical Surgery for Malignant Pleural Mesothelioma.

The accepted aim of radical surgery for malignant pleural mesothelioma (MPM) is the achievement of macroscopic complete resection (MCR) whilst reducing perioperative morbidity by preserving normal tissue. Whilst preservation of the lung by pleurectomy/decortication (PD) has become widely utilised, there remains debate regarding the management of the diaphragm. Muscle-sparing complete excision of the diaphragmatic pleura is technically challenging; thus, surgeons may proceed to extended PD with phrenectomy and possible increased morbidity or to preserve the diaphragmatic pleura at the expense of MCR with potential survival deficit. We aimed to evaluate the effects of an intentional change in protocol to diaphragm-sparing PD whilst maintaining MCR as the treatment of choice for MPM. In a series of 136 patients (111M:25F, median age 68(63-73) years) undergoing radical surgery for MPM, we identified 28 patients (22M:6F, median age 67(60-71) years) in whom MCR was achieved without phrenectomy (PD group). We compared their perioperative outcomes and survival with a historical control group of 18 patients (18M:0F, median age 69(57-78) years) in whom MCR had been achieved with phrenectomy (EPD group) but in whom there was no histological evidence of diaphragm muscle invasion and who, in retrospect, could have undergone muscle-sparing MCR if this procedure had been attempted. There was no significant intergroup difference in demographics or tumour cell type; the majority of both groups were found to be epithelial (PD 85.7%, EPD 77.8%). The EPD group was found to be more locally advanced (T3 55.56%) than the PD group (T1 46.43%) (p = 0.03). All the following parameters were significantly reduced after PD compared to EPD: operative time (188 vs. 220 min, p = 0.007); duration of air leak (5 vs. 10 days, p = 0.001), duration of inotrope (p = 0.009) and post-operative hospital stay (8 vs. 13 days, p = 0.034). There were no significant differences (p = 0.123) in overall survival (OS) between the two groups, but the median survival in the PD group had not been reached at a median follow up of 33.9 (24.2-46) months. A surgical strategy of attempting to spare the diaphragm whilst still achieving MCR wherever possible is justified by improved perioperative outcomes without compromising OS.

Multimodal therapy of epithelioid pleural mesothelioma: improved survival by changing the surgical treatment approach.

The exact role and type of surgery for malignant pleural mesothelioma (MPM) remains controversial. This study aimed at analyzing a 20-year single center perioperative experience in MPM surgery at our high-volume thoracic surgery center and comparing the overall survival after trimodal extrapleural pneumonectomy (EPP) and extended pleurectomy and decortication combined with hyperthermic intrathoracic chemoperfusion (EPD/HITOC) and adjuvant chemotherapy with that after chemotherapy (CTx) alone. Patients with epithelioid MPM treated with neoadjuvant chemotherapy, EPP and adjuvant radiotherapy within a trimodal concept or EPD/HITOC in combination with adjuvant chemotherapy between 2001 and 2018 were included in this retrospective analysis. Surgical cohorts were compared to patients treated with standard chemotherapy. Overall, 182 patients (69 EPP, 57 EPD/HITOC, 56 CTx) were analyzed. Due to occupational exposure to asbestos for most of the patients, 154 patients (84.6%) were male. The patients in the surgical cohorts were significantly younger than those in the CTx cohort. There was no significant difference between the proportion of patient age and side. The median overall survival of the EPD/HITOC cohort with 38.1 months was significantly longer than that of the EPP and CTx cohorts (24.0 and 15.8 months). Better survival was significantly associated with an ECOG 0 performance status, age below 70 years, and negative lymph node status. In the multivariate analysis, EPD/HITOC was significantly associated with improved overall survival. Perioperative morbidity was lower in the EPD/HITOC group than in the EPP cohort. EPD/HITOC is feasible and safe for localized epithelioid pleural mesothelioma. Changing the surgical approach to a less radical lung-sparing technique may improve overall survival compared to trimodal EPP.

Multifactorial Evaluation following Cytoreductive Surgery for Malignant Pleural Mesothelioma in Patients with High Symptom-Burden.

Mesothelioma has a scant prognosis and a great impact on symptoms and the quality of life. Pleurectomy/decortication and extrapleural pneumonectomy are the two cytoreductive surgical strategies, with different invasiveness, but achieving similar oncological results. Hereafter, the two surgical procedures effects on symptoms and the quality of life are compared in a high symptom-burden population. Between 2003 and 2017, 55 consecutive patients underwent pleurectomy/decortication (n = 26) or extrapleural pneumonectomy (n = 29), both followed by adjuvant chemo-radiotherapy. Cardio-pulmonary function, symptoms and the quality of life (Short-Form-36 and St.George's questionnaires) were evaluated pre- and 3-, 6-, 12- and 24-months postoperatively. Extrapleural pneumonectomy demonstrated lower pain at 12 months but a higher decrement of forced vital capacity at 24 months than pleurectomy/decortication. Both procedures revealed a 3-months improvement of many symptoms and the quality of life determinants. Improvement in physical, social and pain-related measured parameters lasted for a longer time-spawn in the extrapleural pneumonectomy group. No differences were found in chemotherapy compliance and survival between groups. Age-at-presentation (p = 0.02) and non-epitheliod histology (p = 0.10) were the only significant prognosticators. Surgery, despite poor survival results, improved symptoms and the quality of life in patients with mesothelioma with high symptom-burden at diagnosis. Therefore, extrapleural pneumonectomy demonstrated the most durable effects.

Sarcopenia as a Predictor of Short- and Long-Term Outcomes in Patients Surgically Treated for Malignant Pleural Mesothelioma.

Simple SummaryMalignant pleural mesothelioma (MPM) is an aggressive asbestos-related tumor with a poor prognosis. Surgery, often considered in the context of multimodality treatment, may be burdened by high morbidity, and for this reason, it should be reserved for patients who have a good pre-operative performance status. Sarcopenia, a well-established predictor of negative outcomes in several clinical settings, is still underinvestigated in MPM. The aim of the study is to elucidate the prognostic impact of muscular loss on surgical outcomes in patients with MPM. We demonstrated that, respectively, pre- and post-operative sarcopenia strongly affects the risk of post-operative complications and long-term survival after surgery for MPM. This finding will help clinicians to perform a better selection of patients, taking into consideration the enrollment in dedicated rehabilitation programs before surgery.Surgery for malignant pleural mesothelioma (MPM) should be reserved only for patients who have a good performance status. Sarcopenia, a well-known predictor of poor outcomes after surgery, is still underinvestigated in MPM. The aim of this study is to evaluate the role of sarcopenia as a predictor of short-and long-term outcomes in patients surgically treated for MPM. In our analysis, we included patients treated with a cytoreductive intent in a multimodality setting, with both pre- and post-operative CT scans without contrast available. We excluded those in whom a complete macroscopic resection was not achieved. Overall, 86 patients were enrolled. Sarcopenia was assessed by measuring the mean muscular density of the bilateral paravertebral muscles (T12 level) on pre-and post-operative CTs; a threshold value of 30 Hounsfield Units (HU) was identified. Sarcopenia was found pre-operatively in 57 (66%) patients and post-operatively in 61 (74%). Post-operative sarcopenic patients had a lower 3-year overall survival (OS) than those who were non-sarcopenic (34.9% vs. 57.6% p = 0.03). Pre-operative sarcopenia was significantly associated with a higher frequency of post-operative complications (65% vs. 41%, p = 0.04). The evaluation of sarcopenia, through a non-invasive method, would help to better select patients submitted to surgery for MPM in a multimodality setting.

Phase III study with atezolizumab versus placebo in patients with malignant pleural mesothelioma after pleurectomy/decortication (AtezoMeso study).

TPS8591 Background: Surgery for malignant pleural mesothelioma (MPM) is indicated mainly in multimodal approaches and in clinical trial settings. Different studies have shown significantly lower complication rates, lower peri-operative morbidity and mortality with pleural/decortication (P/D), with similar overall survival rates. The biology of mesothelioma shows significant heterogeneity. Surgical tumor reduction may create a host environment more amenable to immunotherapy by reducing the ratio of tumor cells versus antitumor effector T lymphocytes, reducing the quantities of intratumor and/or systemic immunosuppressive cells, and ablating tumor-derived paracrine factors that promote local recruitment of immunosuppressive cells. Encouraging clinical data emerging in the field of tumor immunotherapy have demonstrated that therapies focused on enhancing T-cell responses against cancer can result in a significant survival benefit. The AtezoMeso Study evaluates the introduction of atezolizumab-ATEZO in MPM, patients (pts) after P/D and platinum/pemetrexed perioperative therapy. Methods: This is a double-blind, placebo controlled, phase III trial, in 20 Italian centers. Main inclusion criteria are P/D without macroscopic residual and ECOG-PS 0-1. Pts who underwent to P/D without macroscopic residual disease and have received at least 4 cycles of perioperative therapy with cisplatin/carboplatin and pemetrexed, will be randomized (2:1) to receive ATEZO or placebo. Therapy will be administered at dose of 1,200 mg iv, every 21 days, for 12 months or until recurrence, unacceptable toxicity or patient/physician decision. Randomization will be done through a centralized system, using histology (epithelioid vs nonepithelioid) and stage (I vs > I) as stratification factors. Pts will be radiologically evaluated after surgical before starting therapy and then every 12 weeks for 24 months or until recurrence. Quality of life (QoL) will be evaluated with the EQ-5D questionnaire administered at baseline and every 12 weeks. Tissue tumor samples will be centrally analyzed to determinate the genomic profile using FoundationOne CDx platform. The primary endpoint is the evaluation of the atezolizumab efficacy in terms of disease free survival (DFS). Secondary endpoints include the safety and efficacy in terms of overall survivall and QoL. Assuming a median DFS equal to 9 months in placebo arm, an accrual time of 24 months and a follow-up time of 24 months, a sample size of 162 pts will allow to detect true hazard ratios of 0.62 with power 0.8, at a confidence level of 95%. At February 14th, 2022, 3 pts have been enrolled. Clinical trial information: 2020-003762-39; GOIRC-02-2019.

96 The impact of radiographic tumor thickness on the complexity of the tumor immune microenvironment in malignant pleural mesothelioma

BackgroundMalignant pleural mesothelioma (MPM) is a rare and aggressive cancer associated with exposure to asbestos with limited treatment strategies and poor prognosis.1 There is no curative treatment for MPM, and patients follow standard treatment options.2,3 Radiographic tumor thickness (TT) has recently emerged as a surrogate marker associated with overall survival,4 however, the influence of TT on the complexity of the immune component within tumor microenvironment is unknown. Our aim was to perform comprehensive profiling of the tumor immune microenvironment (TIME) relative to the TT to understand of this relationship to guide the design of novel treatment strategies.MethodsTumor specimens (n=29) were obtained from surgically managed MPM patients. Analysis was performed based on the median tumor thickness of 80mm, which defined thick vs thin groups. Additional analysis used TT as a continuous variable for correlations with immune features. The immune cell composition in the TIME was determined by flow cytometry (n=23). Transcriptomic profiling (n=20) was assessed using Nanostring nCounter Tumor Signaling 360 panel. Expanded tumor-infiltrating lymphocytes (TIL) were utilized for further characterization by 10x Genomics single cell RNA-seq profiling (n=8) and cytotoxicity assays (n=18). Level of significance was determined using unpaired non-parametric statistical test.ResultsFresh tumor tissue cytometry showed substantial differences in the immune profiles for thick versus thin tumors, highlighting a relationship of the TT and its immune composition. Thin tumors contained more Tregs, and higher OX40 expression (p=0.081 for non-Treg CD4+ and p<0.05 for CD8+ T cells), CTLA4, LAG3, TIGIT and Ki67 in TIL, while PD-1 expression was not associated with TT. Gene expression profiling suggested an impaired adaptive immune response in thin tumors compared to thick tumors characterized by the exhausted CD8 score (p=0.0252), T-cell co-stimulation score (p=0.0387) and TNF superfamily member score (p=0.0159) and a subset with a myeloid immune evasion score (p=0.0387). TIL expansion was not impacted by baseline TT. However, TIL cytotoxicity, as measured in a redirected lysis assay, showed IFN-gamma response was negatively correlated with baseline TT (p=0.023, R2=0.28). Expanded TIL clustering based upon single cell profiling is underway.ConclusionsUtilizing multi-platform immune profiling approaches, we observed a distinct relationship between the TT and immune signatures. Understanding underlying immune signatures underpinning the biology of thick versus thin MPM tumors provides insights to potential responsiveness to immune-based therapies and may inform on the design for future novel strategies relative to the disease extent based on TT.ReferencesBibby AC, Tsim S, Kanellakis N, Ball H, Talbot DC, Blyth KG, Maskell NA, Psallidas I. Malignant pleural mesothelioma: an update on investigation, diagnosis and treatment. Eur Respir Rev 2016;25(142):472–86.Faig J, Howard S, Levine EA, Casselman G, Hesdorffer M, Ohar JA. Changing pattern in malignant mesothelioma survival. Transl Oncol 2015;8(1):35–9.Alpert N, van Gerwen M, Taioli E. Epidemiology of mesothelioma in the 21st century in Europe and the United States, 40 years after restricted/banned asbestos use. Transl Lung Cancer R 2020;9:S28-S38.de Perrot M, Dong Z, Bradbury P, Patsios D, Keshavjee S, Leighl NB, Hope A, Feld R, Cho J. Impact of tumour thickness on survival after radical radiation and surgery in malignant pleural mesothelioma. Eur Respir J 2017;49(3).Ethics ApprovalThis study was approved by the University of Texas MD Anderson Cancer Center‘s IRB; approval number LAB08-0380; participants gave informed consent before taking part.

MA04.05 Survival Benefit of Multiagent Chemotherapy With and Without Curative Surgery for Malignant Pleural Mesothelioma

There is limited evidence demonstrating a survival advantage of curative-intent surgery for malignant pleural mesothelioma over systemic therapy. This radical surgery (pleurectomy, decortication or extra pleural pneumonectomy) carries a significant risk of increased morbidity and mortality. We sought to evaluate if the addition of curative intent surgery is associated with better survival over multiagent chemotherapy alone in a large population-based study.

OA04.02 Diaphragm and Phrenic Nerve Preservation During Lung-Sparing Surgery for Malignant Pleural Mesothelioma: The Impact on Patient Outcomes

Lung-sparing surgery for malignant pleural mesothelioma (MPM) is associated with a difficult and prolonged recovery due to the extensive nature of the procedure. For a select group of patients, prolonged survival rates have been reported. A clear understanding of which patients will benefit from lung-sparing surgery is currently unknown. Despite having favorable tumor histologies, limited tumor burden and being deemed physically fit for surgery, some patients will still experience increased morbidity and/or mortality.

Examining the impact of physical function performance in predicting patient outcomes after lung-sparing surgery for malignant pleural mesothelioma

ABSRACT Purpose The purpose of this study was to examine the impact of physical function performance and pulmonary function on patient outcomes after lung-sparing surgery for malignant pleural mesothelioma (MPM). Materials and methods A retrospective review of 54 patients with MPM from 2015 to 2020 was performed. The primary objective was to assess whether physical function, as measured by the Eastern Cooperative Oncology Group Performance Status (ECOG), and pulmonary function tests were predictive of postoperative patient outcomes (ventilator days, chest tube days, hospital length of stay). A secondary objective was to explore demographic and preoperative variables that best predict postoperative physical function and patient outcomes. Results Data include 54 patients who underwent extended pleurectomy-decortication. Preoperative ECOG was a significant predictor of postoperative patient outcomes while preoperative lung function lacked predictive ability. Preoperative ECOG was also predictive of preoperative lung function. Age on the day of surgery was the best predictor of postoperative physical function, which was significantly reduced postoperatively. Conclusions Preoperative physical function performance was a significant predictor of postoperative outcomes. The results of our study highlight the importance of physical function in patients with MPM and support the need for early rehabilitation and further research to determine optimal rehabilitation interventions. IMPLICATIONS FOR REHABILITATION Preoperative physical function can predict outcomes after lung-sparing surgery for malignant pleural mesothelioma (MPM). Physical function in patients with MPM should be carefully examined. To accurately reflect patients’ abilities, patient assessment should include both patient-reported outcomes and performance-based measures. Patients with MPM should receive rehabilitation early after diagnosis and throughout the continuum of care.

Hyperthermic Intrathoracic Chemotherapy for Malignant Pleural Mesothelioma: The Forefront of Surgery-Based Multimodality Treatment.

Introduction: Malignant Pleural Mesothelioma (MPM) is characterized by an aggressive behavior and an inevitably fatal prognosis, whose treatment is still far from being standardized. The role of surgery is questionable since a radical resection is unattainable in most cases. Hyperthermic IntraTHOracic Chemotherapy (HITHOC) combines the advantages of antitumoral effects together with those of high temperature on the exposed tissues with the aim to improve surgical radicality. Material and Methods: this is a narrative review on the role of HITHOC in the management of MPM patients. To provide data on the beginnings and the historical evolution of this technique, we searched the available literature by selecting the more exhaustive papers on this topic. Results: from 1994 to date different authors experimented HITHOC following a cytoreductive surgery in MPM, obtaining in most cases a good local control and a better overall survival associated to very low complication rate. Conclusions: HITHOC may be considered as a safe, feasible and effective procedure although there is a high heterogeneity between different protocols adopted worldwide. More structured studies are needed to reach a unanimous consensus on this technique.

Non-incisional pleurectomy/decortication for malignant pleural mesothelioma.

Pleurectomy/decortication has been preferably employed as a curative-intent surgery for malignant pleural mesothelioma. However, visceral pleurectomy during pleurectomy/decortication provides technical challenges. For visceral pleurectomy, pleural incisions are commonly made to create a dissection plane between the visceral pleura and the lung parenchyma, which may cause tumor dissemination and may not allow en bloc complete resection of the entire pleura. To overcome such potential disadvantages, we have developed a novel surgical technique without any pleural incision (non-incisional pleurectomy/decortication) to achieve en bloc removal of the entire pleura. A total of 36 consecutive patients who underwent non-incisional pleurectomy/decortication for malignant pleural mesothelioma from January 2017 through December 2020 in our institute were retrospectively reviewed to assess the feasibility. Macroscopic complete resection was achieved in 31 patients (86.1%) with non-incisional pleurectomy/decortication. In the majority of patients (n = 29), en bloc complete resection of the entire pleura was achieved (without pleural laceration in 10 and with some pleural laceration in 19 patients). The total operation time and the duration of visceral pleurectomy were significantly shorter as compared with those for conventional pleurectomy/decortication (median, 350 versus 506min [P = 0.011], and 43 versus 97 min [P < 0.001], respectively). Among 36 patients who underwent non-incisional pleurectomy/decortication, postoperative complications developed in 13 patients (36.1%), and one patient died on the postoperative day 95 caused by aggressive tumor progression of residual tumor. Non-incisional pleurectomy/decortication is a fast and feasible technique to achieve en bloc macroscopic complete resection for malignant pleural mesothelioma.

Japanese Current Status of Curative-Intent Surgery for Malignant Pleural Mesothelioma

BackgroundFew reports about surgical outcomes in malignant pleural mesothelioma (MPM) have been based on reliable nationwide databases. Here, we analyzed the incidence, surgical outcome, and operative risk factors using Japanese nationwide database. MethodsCharacteristics and perioperative data from 622 patients who underwent curative-intent surgery for MPM between January 2014 and December 2017 were recorded from National Clinical Database of Japan. We analyzed the incidence, surgical outcomes, and risk factors for surgical complications after 2 surgical procedures (extrapleural pneumonectomy [EPP] and pleurectomy/decortication [P/D]). ResultsDuring 4 years, EPP was performed in 279 patients and P/D in 343. EPP was more frequently performed in institutions less experienced in MPM, while P/D was more frequently performed in institutions well experienced in MPM (P < .001), especially in high-volume centers with more than 10 cases during this period. P/D was more frequently performed, especially in high-volume centers. The morbidity rates were 45.2% in EPP and 35.9% in P/D. Heart failure and pneumonia were most frequent in EPP, while prolonged air leakage was most frequent in P/D. Thirty-day and in-hospital mortality rates were 1.1% and 3.2% (EPP) and 1.2% and 3.2% (P/D), respectively. Regression analyses revealed that higher age (>65 years) was associated with operative complications in EPP (odds ratio, 3.56 [95% confidence interval, 1.26-8.56]), whereas no risk factor was observed in P/D. ConclusionsIn Japanese nationwide annual database, P/D was more frequently performed, especially in high-volume centers. Morbidity was higher in EPP than P/D; however, the mortality rates were quite low in Japan regardless surgical procedures.

SMART: logical radiotherapy and surgery beyond MARS.

The most highly anticipated surgery trial for malignant pleural mesothelioma since the MARS trial 1 Treasure T Lang-Lazdunski L Waller D et al. Extra-pleural pneumonectomy versus no extra-pleural pneumonectomy for patients with malignant pleural mesothelioma: clinical outcomes of the Mesothelioma and Radical Surgery (MARS) randomised feasibility study. Lancet Oncol. 2011; 12: 763-772 Summary Full Text Full Text PDF PubMed Scopus (493) Google Scholar is the mature follow-up of the patients receiving oligofractionated hemithoracic radiotherapy followed by extrapleural pneumonectomy by B C John Cho and colleagues 2 Cho BCJ Donahoe L Bradbury PA et al. Surgery for malignant pleural mesothelioma after radiotherapy (SMART): final results from a single-centre, phase 2 trial. Lancet Oncol. 2021; (published online Jan 12.)https://doi.org/10.1016/S1470-2045(20)30606-9 Summary Full Text Full Text PDF PubMed Scopus (14) Google Scholar published in The Lancet Oncology. MARS, although provocative, forced mesothelioma surgeons to question the role of extrapleural pneumonectomy in trimodality management of pleural mesothelioma, and concluded that extrapleural pneumonectomy within trimodal therapy offers no benefit and possibly harms patients. Therefore, any subsequent trial should be examined carefully with regard to the MARS conclusion. Surgery for malignant pleural mesothelioma after radiotherapy (SMART): final results from a single-centre, phase 2 trialResults from this study suggest that extrapleural pneumonectomy after radiotherapy can be done with good early and long-term results. However, minimising grade 4 events on the protocol is technically demanding and might affect survival beyond the post-operative period. Full-Text PDF

Cancer-directed surgery in malignant pleural mesothelioma: extrapleural pneumonectomy and pleurectomy/decortication

Malignant pleural mesothelioma (MPM) is a primary solid malignancy related to inhalational asbestos exposure. Despite advances in therapy, MPM remains challenging to treat with a post-treatment survival of only 15% at 5-year. In recent years, extra-pleural pneumonectomy has decreased in popularity due to a high morbidity rate and mortality compared to pleurectomy/decortication and other therapeutic alternatives. In this review, we will discuss both procedures, outcomes, ongoing studies, and the roles of surgery in the future treatment of this disease.

Surgery for pleural mesothelioma, when it is indicated and why: arguments against surgery for malignant pleural mesothelioma.

Extrapleural pneumonectomy (EPP) and pleurectomy decortication (PD) are radical operations for malignant pleural mesothelioma (MPM) that remain controversial among thoracic surgeons. There is a lack of randomized evidence to support a survival benefit when major surgical resection is included in multi-modality treatment regimens. Current data from retrospective single institution reviews and prospective trials such as the Surgery for Mesothelioma After Radiation Therapy (SMART) trial are limited by biased patient selection to include only the healthiest patients with most limited disease burden. This patient population predictably has relatively longer survival times than patients with inoperable advanced disease. The only randomized trial to date that has objectively evaluated the true benefit of surgical resection was the Mesothelioma and Radical Surgery (MARS) trial which actually showed shorter survival times among patients who underwent EPP compared with those treated medically. Critics of the MARS trial cite a high perioperative mortality rate for driving these results, however a similar trial has never been repeated to refute the MARS trial results. Finally, it is relevant to consider the high mortality and morbidity rates associated with major operations when recommending these interventions to MPM patients. There is a growing body of literature that identifies patients who clearly obtain no benefit from surgery including those with sarcomatoid or biphasic histology, nodal disease, elevated CRP, elevated platelets and advanced age. Surgery in MPM has risks and is of questionable benefit with outcomes data biased by patient selection of those who will have longer overall survival times regardless of treatment.

Intracavitary cisplatin-fibrin chemotherapy after surgery for malignant pleural mesothelioma: A phase I trial

ObjectivesIntracavitary chemotherapy is a promising concept to improve local tumor control for malignant pleural mesothelioma with reported high morbidity rates. We have demonstrated that administration of cisplatin loaded to fibrin increased local drug concentration and reduced systemic toxicity in preclinical models. We present a phase I trial of intracavitary cisplatin-fibrin after surgical tumor resection. MethodsA total of 12 patients (75% International Mesothelioma Interest Group stage III-IV) were treated with 4 dose levels of intracavitary cisplatin-fibrin (11-44 mg/m2 body surface area) in a dose-escalating design. Cisplatin-fibrin was sprayed on the resected surfaces after pleurectomy/decortication. Blood and tissue samples were taken to assess toxicity and pharmacokinetics. Patients were regularly followed up. ResultsNo dose-limiting toxicity was observed. Major morbidity occurred in 4 patients (33%). The 30-day and 90-day mortality were both 0%. Of 80 adverse events, 9 were classified serious, but none of these were related to study treatment. Local cisplatin concentration in the chest wall tissue was high at all dose levels (median, 46.3 μg/g [12-133 μg/g]). In serum, median cisplatin area under the concentration time curve values were always below renal toxicity levels. The median overall survival with 95% confidence interval was 21 months (10-31 months). In 1 patient with epithelioid malignant pleural mesothelioma (International Mesothelioma Interest Group stage I), there was no sign of relapse 48 months after treatment (44 mg/m2 body surface area). ConclusionsThe administration of intracavitary cisplatin-fibrin is safe with favorable pharmacokinetics. Although most patients had advanced disease, long-term outcomes are comparable to other multimodal concepts. A confirmation phase II trial is ongoing.

Outcome of neo-adjuvant chemotherapy in 225 surgical candidates with malignant pleural mesothelioma.

8548 Background: Since any surgery for malignant pleural mesothelioma (MPM) are cytoreductive, effective chemotherapy is a prerequisite for surgery. In this context, we give neo-adjuvant chemotherapy (NAC) to all surgical candidates. Methods: Hyogo College of Medicine MPM Surgery Program mandates all surgical candidates to receive NAC, and only patients with stable disease (SD) or better response proceeds to surgery. The program comprised NAC followed by extrapleural pneumonectomy (EPP) and hemithoracic radiation until 2012, and NAC followed by pleurectomy/decortication (P/D) and postoperative chemotherapy thereafter. Eligibility criteria are histologically confirmed non-sarcomatoid MPM, clinically resectable stage (T1-3N0-1M0), performance status 0–1, and no major comorbidity. Results: From December 2006 to December 2018, 225 patients were enrolled. Of 225, 24 patients (10.7%, Group A) did not proceed to surgery because of progressive disease (n=23) or serious adverse events (n=2). Of the remaining 201 patients with partial response (n=38, 16.9%) or stable disease (n=163, 72.4%), 19 refused surgery (Group B), 16 received exploratory thoracotomy (Group C), and 165 completed surgery (Group D, EPP58, P/D107). Surgical mortality rates at 30 and 90 days were 1.1% (n=2) and 2.8% (n=5), and surgical morbidity (≧grade 3) was 26.0% (n=47). Median survival time and survival rates of each group were shown in the table. Briefly, 2-yr survival competed among Group B,C and D, whereas 5-yr survival rapidly dropped in Group B and C. Conclusions: Approximately 90% of MPM patients with surgical intent successfully underwent either of EPP or P/D after effective chemotherapy with acceptable surgical mortality and morbidity. Comparison of patients who refused or accepted surgery suggested that surgery contributed to long-term survival. [Table: see text]