Nomogram using intratumoral and peritumoral radiomics for the preoperative prediction of visceral pleural invasion in clinical stage IA lung adenocarcinoma.

BACKGROUND: Accurate prediction of visceral pleural invasion (VPI) in lung adenocarcinoma before operation can provide guidance and help for surgical operation and postoperative treatment. We investigate the value of intratumoral and peritumoral radiomics nomograms for preoperatively predicting the status of VPI in patients diagnosed with clinical stage IA lung adenocarcinoma. METHODS: A total of 404 patients from our hospital were randomly assigned to a training set (n = 283) and an internal validation set (n = 121) using a 7:3 ratio, while 81 patients from two other hospitals constituted the external validation set. We extracted 1218 CT-based radiomics features from the gross tumor volume (GTV) as well as the gross peritumoral tumor volume (GPTV5, 10, 15), respectively, and constructed radiomic models. Additionally, we developed a nomogram based on relevant CT features and the radscore derived from the optimal radiomics model. RESULTS: The GPTV10 radiomics model exhibited superior predictive performance compared to GTV, GPTV5, and GPTV15, with area under the curve (AUC) values of 0.855, 0.842, and 0.842 in the three respective sets. In the clinical model, the solid component size, pleural indentation, solid attachment, and vascular convergence sign were identified as independent risk factors among the CT features. The predictive performance of the nomogram, which incorporated relevant CT features and the GPTV10-radscore, outperformed both the radiomics model and clinical model alone, with AUC values of 0.894, 0.828, and 0.876 in the three respective sets. CONCLUSIONS: The nomogram, integrating radiomics features and CT morphological features, exhibits good performance in predicting VPI status in lung adenocarcinoma.

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.

OBJECTIVES: Recruiting 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 without (extended) pleurectomy decortication surgery for malignant pleural mesothelioma. Anticipating recruitment difficulties, a QuinteT Recruitment Intervention was embedded in the main trial phase to unearth and address barriers. The trial achieved recruitment to target with a 4-month COVID-19 pandemic-related extension. This paper presents the key recruitment challenges, and the strategies delivered to optimise recruitment and informed consent. DESIGN: A multifaceted, flexible, mixed-method approach to investigate recruitment obstacles drawing on data from staff/patient interviews, audio recorded study recruitment consultations and screening logs. Key findings were translated into strategies targeting identified issues. Data collection, analysis, feedback and strategy implementation continued cyclically throughout the recruitment period. SETTING: Secondary thoracic cancer care. RESULTS: Respiratory physicians, oncologists, surgeons and nursing specialists supported the trial, but recruitment challenges were evident. The study had to fit within a framework of a thoracic cancer service considered overstretched where patients encountered multiple healthcare professionals and treatment views, all of which challenged recruitment. Clinician treatment biases, shaped in part by the wider clinical and research context alongside experience, adversely impacted several aspects of the recruitment process by restricting referrals for study consideration, impacting eligibility decisions, affecting the neutrality in which the study and treatment was presented and shaping patient treatment expectations and preferences. Individual and group recruiter feedback and training raised awareness of key equipoise issues, offered support and shared good practice to safeguard informed consent and optimise recruitment. CONCLUSIONS: With bespoke support to overcome identified issues, recruitment to a challenging RCT of surgery versus no surgery in a thoracic cancer setting with a complex recruitment pathway and multiple health professional involvement is possible. TRIAL REGISTRATION NUMBER: ISRCTN ISRCTN44351742, Clinical Trials.gov NCT02040272.

Anaesthetic and perioperative considerations for extrapleural pneumonectomy and extended pleurectomy/decortication: a scoping review protocol.

INTRODUCTION: Extrapleural pneumonectomy (EPP) and extended pleurectomy/decortication (ePD) are surgical cytoreductive techniques aimed at achieving macroscopic resection in malignant pleural tumours such as pleural mesothelioma, non-mesothelioma pleural malignancies such as thymoma and sarcoma, and rarely for pleural tuberculosis, in a more limited fashion. Despite extensive studies on both surgical techniques and consequences, a significant knowledge gap remains regarding how best to approach the perioperative anaesthesia challenges for EPP and ePD.It is unknown if the risk stratification processes for such surgeries are standardised or what types of functional and dynamic cardiac and pulmonary tests are employed preoperatively to assist in the perioperative risk stratification. Further, it is unknown whether the types of anaesthesia and analgesia techniques employed, and the types of haemodynamic monitoring tools used, impact on outcomes. It is also unknown whether individualised haemodynamic protocols are used to guide the rational use of fluids, vasoactive drugs and inotropes.Finally, there is a dearth of evidence regarding how best to monitor these patients postoperatively or what the most effective enhanced recovery protocols are to best mitigate postoperative complications and accelerate hospital discharge. To increase our knowledge of the perioperative and anaesthetic treatment for patients undergoing EPP/ePD, this scoping review attempts to synthesise the literature and identify these knowledge gaps. METHODS AND ANALYSIS: This scoping review will be conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Extension for Scoping Review Protocols methodology. Electronic databases, OVID Medline, EMBASE and the Cochrane Library, will be systematically searched for relevant literature corresponding to EPP or ePD and perioperative or anaesthetic management. Data will be analysed and summarised descriptively and organised according to the three perioperative stages: preoperative, intraoperative and postoperative factors in clinical care. ETHICS AND DISSEMINATION: Ethics approval was not required. The findings will be disseminated through professional networks, conference presentations and publications in scientific journals.

Aerostasis to limit air leak following extended pleurectomy-decortication.

Extended pleurectomy-decortication is a cytoreductive surgical treatment for malignant pleural mesothelioma. Prolonged air leak remains a major postoperative challenge, lengthening hospital stay and increasing morbidity. In this video report, we present a stepwise approach for visceral decortication and introduce the concept of aerostasis by construction of an artificial neopleura. Our results suggest that improved aerostasis results in shortened air leak duration.

Extended pleurectomy decortication and chemotherapy versus chemotherapy alone for pleural mesothelioma (MARS 2): a phase 3 randomised controlled trial.

BACKGROUND: Extended pleurectomy decortication for complete macroscopic resection for pleural mesothelioma has never been evaluated in a randomised trial. The aim of this study was to compare outcomes after extended pleurectomy decortication plus chemotherapy versus chemotherapy alone. METHODS: MARS 2 was a phase 3, national, multicentre, open-label, parallel two-group, pragmatic, superiority randomised controlled trial conducted in the UK. The trial took place across 26 hospitals (21 recruiting only, one surgical only, and four recruiting and surgical). Following two cycles of chemotherapy, eligible participants with pleural mesothelioma were randomly assigned (1:1) to surgery and chemotherapy or chemotherapy alone using a secure web-based system. Individuals aged 16 years or older with resectable pleural mesothelioma and adequate organ and lung function were eligible for inclusion. Participants in the chemotherapy only group received two to four further cycles of chemotherapy, and participants in the surgery and chemotherapy group received pleurectomy decortication or extended pleurectomy decortication, followed by two to four further cycles of chemotherapy. It was not possible to mask allocation because the intervention was a major surgical procedure. The primary outcome was overall survival, defined as time from randomisation to death from any cause. Analyses were done on the intention-to-treat population for all outcomes, unless specified. This study is registered with ClinicalTrials.gov, NCT02040272, and is closed to new participants. FINDINGS: Between June 19, 2015, and Jan 21, 2021, of 1030 assessed for eligibility, 335 participants were randomly assigned (169 to surgery and chemotherapy, and 166 to chemotherapy alone). 291 (87%) participants were men and 44 (13%) women, and 288 (86%) were diagnosed with epithelioid mesothelioma. At a median follow-up of 22·4 months (IQR 11·3-30·8), median survival was shorter in the surgery and chemotherapy group (19·3 months [IQR 10·0-33·7]) than in the chemotherapy alone group (24·8 months [IQR 12·6-37·4]), and the difference in restricted mean survival time at 2 years was -1·9 months (95% CI -3·4 to -0·3, p=0·019). There were 318 serious adverse events (grade ≥3) in the surgery group and 169 in the chemotherapy group (incidence rate ratio 3·6 [95% CI 2·3 to 5·5], p<0·0001), with increased incidence of cardiac (30 vs 12; 3·01 [1·13 to 8·02]) and respiratory (84 vs 34; 2·62 [1·58 to 4·33]) disorders, infection (124 vs 53; 2·13 [1·36 to 3·33]), and additional surgical or medical procedures (15 vs eight; 2·41 [1·04 to 5·57]) in the surgery group. INTERPRETATION: Extended pleurectomy decortication was associated with worse survival to 2 years, and more serious adverse events for individuals with resectable pleural mesothelioma, compared with chemotherapy alone. FUNDING: National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (15/188/31), Cancer Research UK Feasibility Studies Project Grant (A15895).

Combination of calretinin, MALAT1, and GAS5 as a potential prognostic biomarker to predict disease progression in surgically treated mesothelioma patients.

BACKGROUND: The role of cytoreductive surgery for epithelioid pleural mesothelioma within a multimodal treatment approach remains controversial. Carefully selected patients benefit from cytoreductive surgery and adjuvant chemotherapy, but there is no established biomarker to predict tumor recurrence or progression during the course of the disease. The aim of this study was to identify potential biomarkers to predict therapeutic response in terms of progression-free survival. METHODS: Between 03/2014 and 08/2022, preoperative blood samples were collected from 76 patients with epithelioid pleural mesothelioma who underwent cytoreductive surgery as part of a multimodal treatment approach. Identification of potential biomarkers was performed by determination of mesothelin and calretinin, as well as specific long non-coding RNAs and microRNAs. Receiver operating characteristic analysis, Kaplan-Meier survival analysis, and Cox regression were used to assess the association between biomarker concentrations and patient recurrence status and survival. RESULTS: MALAT1, GAS5, and calretinin showed statistically significant increased biomarker levels in patients with recurrence in contrast to recurrence-free patients after surgical treatment (p < 0.0001, p = 0.0190, and p = 0.0068, respectively). The combination of the three biomarkers resulted in a sensitivity of 68 % and a specificity of 89 %. CONCLUSION: MALAT1, GAS5, and calretinin could be potential biomarkers for the prediction of tumor recurrence, improving the benefit from multimodal treatment including cytoreductive surgery.

Extrapleural pneumonectomy for sarcoma: Outcomes of adult patients at a specialized center.

BACKGROUND: Extrapleural pneumonectomy (EPP) is a complex surgical procedure involving en-bloc resection of the parietal and visceral pleura, lung, pericardium, and ipsilateral diaphragm. Small case series of pleural-based sarcoma of predominantly pediatric patients suggest EPP may be a life-prolonging surgical option. We aimed to describe the characteristics and outcomes of adults who underwent EPP at a specialized sarcoma center. METHODS: Clinicopathologic variables, surgical details, and follow-up information were extracted for patients undergoing EPP for pleural-based sarcoma between August 2017 and December 2020. Primary outcomes were event-free survival (EFS) and overall survival (OS) from the date of EPP. Secondary outcomes were disease-free interval (DFI) prior to EPP, and early and late postoperative complications. RESULTS: Eight patients were identified, seven with soft tissue sarcoma and one with bone sarcoma. Patients had either localized disease with a primary thoracic sarcoma, sarcoma recurrent to the thorax, or de novo metastatic disease. All patients underwent resection of their pleural-based sarcoma by an experienced cardiothoracic surgeon, and some patients had pre or postoperative treatment. The perioperative morbidity was comparable with previously published reports of EPP performed in mesothelioma patients. At median follow-up of 22.5 months, median EFS was 6.0 months and OS was 20.7 months. Six patients (75%) had disease recurrence; five (62.5%) died of progressive disease. Two patients (25%) had not recurred: one died of a radiation-related esophageal rupture, and one was alive with no evidence of disease at 37.0 months. Characteristics of those with the longest EFS included low-grade histology and achieving a metabolic response to preoperative chemotherapy. CONCLUSIONS: In adults with pleural-based sarcoma, EPP is rarely curative but appears to be a feasible salvage procedure when performed at specialized centers. Patient selection is critical with strong consideration given to multimodal therapy to optimize patient outcomes. In the absence of a confirmed response to neoadjuvant treatment, long term survival is poor and EPP should not be recommended.

Extensive surgical resections for rare pleural neoplasms: a single-center experience with a yolk sac tumor and synovial sarcoma.

BACKGROUND: Pleural neoplasms are rare and can be subdivided into pleural metastasis and primary pleural neoplasms. Non-mesothelioma primary pleural neoplasms are a diverse group of extremely rare pathologies. CASE PRESENTATION: In this case series, we describe the presentation and management of two rare primary pleural neoplasms. A first case describes a primary pleural yolk sac tumor treated with neoadjuvant chemotherapy, extended pleurectomy decortication, and hyperthermic intrathoracic chemotherapy. In a second case we describe the management of a primary pleural synovial sarcoma by neoadjuvant chemotherapy and extrapleural pneumonectomy. A complete resection was obtained in both cases and the post-operative course was uncomplicated. No signs of tumor recurrence were noted during follow-up in the first patient. In the second patient a local recurrence was diagnosed 6 months after surgery. CONCLUSION: Neo-adjuvant chemotherapy followed by extensive thoracic surgery, including hyperthermic intrathoracic chemotherapy, is a feasible treatment strategy for non-mesothelioma primary pleural neoplasms, but careful follow-up is required.

Risk factors influencing postoperative pleural empyema in patients with pleural mesothelioma: a retrospective single-centre analysis.

OBJECTIVES: Postoperative empyema is a severe, potentially lethal complication also present, but poorly studied in patients undergoing surgery for pleural mesothelioma. We aimed to analyse which perioperative characteristics might be associated with an increased risk for postoperative empyema. METHODS: From September 1999 to February 2023 a retrospective analysis of consecutive patients undergoing surgery for pleural mesothelioma at the University Hospital of Zurich was performed. Uni- and multivariable logistic regression was used to identify associated risk factors of postoperative empyema after surgery. RESULTS: A total of 400 PM patients were included in the analysis, of which n = 50 patients developed empyema after surgery (12.5%). Baseline demographics were comparable between patients with (Eyes) and without empyema (Eno). 39% (n = 156) patients underwent extrapleural pneumonectomy (EPP), of whom 22% (n = 35) developed postoperative pleural empyema; 6% (n = 15) of the remaining 244 patients undergoing pleurectomy and decortication (n = 46), extended pleurectomy and decortication (n = 114), partial pleurectomy (n = 54) or explorative thoracotomy (n = 30) resulted in postoperative empyema. In multivariable logistic regression analysis, EPP (odds ratio 2.8, 95% confidence interval 1.5-5.4, P = 0.002) emerged as the only risk factor associated with postoperative empyema when controlled for smoking status. Median overall survival was significantly worse for Eyes (16 months, interquartile range 5-27 months) than for Eno (18 months, interquartile range 8-35 months). CONCLUSIONS: Patients undergoing EPP had a significantly higher risk of developing postoperative pleural empyema compared to patients undergoing other surgery types. Survival of patients with empyema was significantly shorter.

Safety and efficacy of percutaneous cryoablation for primary and metastatic pleural based tumors.

PURPOSE: Assess safety and local tumor progression-free survival (LTPFS) of percutaneous cryoablation for pleural-based thoracic malignancies. MATERIALS AND METHODS: Retrospective study of 46 patients (17 treated for palliation; 9 for oligoprogression; 20 for curative intent), with 62 pleural-based thoracic lesions, treated in 59 cryoablation sessions. Patients were treated from 9/2005-11/2021 with CryoCare CS (Varian, Irvine, CA) or IceFORCE (Boston Scientific, Marlborough, MA) systems. For tumors treated with curative intent and/or oligoprogression, LTPFS of the treated tumor(s) and overall survival (OS) were estimated using Kaplan-Meier method. Post-operative complications were reported for all sessions, including those with palliative intent; univariate analyses were used to calculate factors associated with increased complication risk. RESULTS: Median number of tumors treated in a single treatment session was 1 (range 1-4). Largest dimension of the treated tumor was 2.1 cm [IQR:0.9-5 cm]. Of the 59 treatments, 98.3 % were technically successful. Median LTPFS was 14.4 (95 % CI: 9.4-25.6) months. Tumor size was a significant predictor of LTPFS (HR: 1.21, 95 % CI: 1.03-1.44, p = 0.023). Median OS was 52.4 (28.1-NR) months. Complications occurred in 28/59 sessions (47.5 %); 2/59 (3.4 %) were ≥ grade D by Society of Interventional Radiology adverse event criteria (death; hypoxia requiring supplemental oxygen upon discharge). Pain and pneumothorax were the most common complications. The length of lung parenchyma traversed was a significant predictor of pneumothorax: HR 0.48 (95 %CI: 0.14-0.83), p = 0.0024. CONCLUSION: Percutaneous cryoablation for pleural lesions is associated with a long duration of local control and most complications were minor and self-limited.

Circulating SMRP and CA-125 before and after pleurectomy decortication for pleural mesothelioma.

BACKGROUND: Tumor recurrence remains the main barrier to survival after surgery for pleural mesothelioma (PM). Soluble mesothelin-related protein (SMRP) and cancer antigen 125 (CA-125) are established blood-based biomarkers for monitoring PM. We prospectively studied the utility of these biomarkers after pleurectomy decortication (PD). METHODS: Patients who underwent PD and achieved complete macroscopic resection with available preoperative SMRP levels were included. Tumor marker levels were determined within 60 days of three timepoints: (1) preoperation, (2) post-operation, and (3) recurrence. RESULTS: Of 356 evaluable patients, 276 (78%) had recurrence by the end of follow-up interval. Elevated preoperative SMRP levels were associated with epithelioid histology (p < 0.013), advanced TNM (p < 0.001) stage, and clinical stage (p < 0.001). Preoperative CA-125 levels were not significantly associated with clinical covariates. Neither biomarker was associated with survival or disease-free survival. With respect to nonpleural and nonlymphatic recurrences, mean SMRP levels were elevated in patients with pleural (p = 0.021) and lymph node (p = 0.042) recurrences. CA-125 levels were significantly higher in patients with abdominal (p < 0.001) and lymph node (p = 0.004) recurrences. Among patients with all three timepoints available, we observed an average decrease in SMRP levels by 1.93 nmol/L (p < 0.001) postoperatively and again an average increase at recurrence by 0.79 nmol/L (p < 0.001). There were no significant changes in levels of CA-125 across the study timepoints (p = 0.47). CONCLUSIONS: Longitudinal changes in SMRP levels corresponded with a radiographic presence of disease in a subset of patients. SMRP surveillance could aid in detection of local recurrences, whereas CA-125 could be helpful in recognizing abdominal recurrences.

Solitary fibrous tumours of the pleura: do we need a different perspective on malignancy?

OBJECTIVES: Solitary fibrous tumours of the pleura (SFTP) are historically considered to be benign soft tissue neoplasms. However, a clinical relevant number of these neoplasms have malignant histological features. The objective of this study was to evaluate the percentage of SFTP presenting unfavourable clinical behaviour in order to predict negative long-term outcome. METHODS: A retrospective review of 74 patients treated at 4 hospitals between 1990 and 2013 was performed. The median follow-up was 10 years (range: 1-20 years). Risk of tumour recurrence and metastases (unfavourable clinical behaviour) with regard to histology using the Kaplan-Meier and Cox proportional hazards methods. RESULTS: The mean age was 61 years (SD 12.75 years). There were 31 male patients (58%) and 43 female patients (42%). Tumour size ranged from 1 to 30 cm (mean 9.09 cm; SD 6.22 cm). Complete resection (R0) was achieved by minimally invasive thoracoscopic resection in 29% and thoracotomy in 57%; 25% of SFTPs showed histological evidence of malignancy, according to England criteria. Recurrence occurred in 21% and 10% of patients had metastases; 83% of patients with metastases and 39% of patients with recurrence died within 5 years. The median recurrence-free survival for histologically benign SFTP was not reached, compared to 8 years for malignant SFTP. The five-year overall survival rate was 84%. Mitotic rate ≥1/10 HPF, high cellularity, nuclear atypia, Ki-67 level >5% and poorly circumscribed (sessile) growth pattern were associated with poor long-term outcome. CONCLUSIONS: Pathological differentiation of SFTP morphology into pedunculated, well circumscribed and poorly circumscribed (sessile) growth pattern is recommended. Due to the misleading classification into histologically benign and malignant, all unpedunculated SFTP should be classified as potentially aggressive. Lifelong follow-up is mandatory.

Pleural epithelioid hemangioendothelioma in a 39-Year-old female: a case report.

BACKGROUND: Epithelioid hemangioendothelioma (EHE) is a rare malignancy of vascular origin which can be primarily be seen in various tissues. EHE originating from the pleura is an even more uncommon subtype which may mimic mesothelioma and pleural carcinomatosis. The prognosis of pleural EHE is poor and there is no consensus on the optimal therapeutic approach. CASE PRESENTATION: A 39-year-old middle-eastern female presented with progressive dyspnea and left shoulder discomfort. Chest computed tomography scan revealed a left side pleural effusion and pleural thickening. Pleuroscopy was done and biopsies were taken which were positive for CD31, CD34, CK, factor 8-R-antigen, and vimentin. Patient was diagnosed with pleural epithelioid hemangioendothelioma (PEHE) and chemotherapy was started and underwent extrapleural pneumonectomy 7 months later. Unfortunately, the patient passed away 10 months after diagnosis due to disease complications. CONCLUSIONS: Once PEHE is suspected in histology it can be confirmed with immunohistochemistry. Chemotherapy, surgery or a combination of both is currently used as the treatment but the standard treatment remains a question.

A Rare Presentation of Minimally Invasive Mesothelioma as a Large Tension Pneumothorax.

Development of mesothelioma is associated with asbestos exposure. Common presentations are with pleural-based plaques invading the chest wall and/or pleural effusion on chest imaging. The intent of this case report is to describe a rare presentation of mesothelioma, which presented atypically as a large tension pneumothorax. A 93-year-old male presented with a history of dyspnea that started after a coughing episode. On physical examination he was hemodynamically stable, but was hypoxic requiring 2L of supplemental oxygen. Computed tomography of the chest revealed a large right tension pneumothorax. A chest tube was placed and connected to suction (-20cmH20), but he continued to have an unresolving air leak over the following 2-week period. Upon video-assisted thoracotomy there were no blebs or adhesions seen. Right apical wedge resection and talc pleurodesis were performed. Pathologic examination revealed an atypical mesothelial cell proliferation with minimal, focal invasion into the pulmonary parenchyma. Tumor spread along the visceral pleura was thought to be the underlying cause of the pneumothorax. The surgical margins were uninvolved by the tumor, and the patient was later discharged home in stable condition. This was a rare presentation of what could best be described as minimally invasive mesothelioma arising in a background of probable mesothelioma in situ, which presented atypically as a large tension pneumothorax. This case highlighted the importance of establishing a pathologic diagnosis from pleural effusion cytology and/or pleural biopsy in persons presenting with spontaneous pneumothorax, and the difficulty in confirming a pathologic diagnosis of early mesothelial neoplasia.

Genomic profiling of tissue and blood predicts survival outcomes in patients with resected pleural mesothelioma.

PURPOSE: Pleural mesothelioma (PM) is an aggressive tumor still considered incurable, in part due to the lack of predictive biomarkers. Little is known about the clinical implications of molecular alterations in resectable PM tissues and blood. Here, we characterized genetic alterations to identify prognostic and predictive biomarkers in patients with resected PM. EXPERIMENTAL DESIGN: Targeted next-generation sequencing was performed in retrospective pleural tumor tissue and paired plasma samples from stage IB-IIIB resected PM. Association between prognosis and presence of specific mutations was validated in silico. RESULTS: Thirty PM tissues and paired blood samples from 12 patients were analyzed. High tissue tumor mutational burden (TMB) (>10 mutations/Mb), tissue median minor allele frequency (MAF) (>9 mutations/Mb), and blood TMB (>6 mutations/Mb), tissue KMT2C, PBRM1, PKHD1,EPHB1 and blood LIFR mutations correlated with longer disease-free survival and/or overall survival. High concordance (>80%) between tissue and blood was found for some mutations. CONCLUSIONS: Tissue TMB and MAF, blood TMB, and specific mutations correlated with outcomes in patients with resected PM and should be further studied to validate their role as prognostic biomarkers and potentially predictive factors for combinations with immune-checkpoint inhibitors. This suggest that molecular profiling could identify longer survivors in patients with resected PM.

En bloc resection of the recurrent pleural mesothelioma and reconstruction of the chest wall after immunotherapy: A case report.

Malignant pleural mesothelioma (MPM) is associated with previous asbestos exposure, while more clinical insights into this disease have come from other case studies. Maximal cytoreduction is critical in disease control and might help to improve the prognosis. Here, a 41-year-old female presented with a 6-month history of a mass detected in the chest wall following resection of a right pleural mesothelioma 2 years previously. A fluorodeoxyglucose positron emission tomography/computed tomography scan showed a right chest wall mass with a blurred boundary 8.9 cm × 3.7 cm in size. The patient had received one cycle of bevacizumab, carboplatin, and pemetrexed, and two cycles of nivolumab, ipilimumab, and gemcitabine 5 months before admission. We subsequently resected the tumor, the involved diaphragm, and the fifth and sixth ribs, and titanium mesh and continuous suture were used to close the thoracic cage. The fixed paraffin-embedded tissues showed epithelioid pleural mesothelioma. The patient received nivolumab and ipilimumab postoperatively, and no recurrence was detected 16 months after surgery. En bloc resection with reconstructive surgery effectively removed the locally advanced malignancy and restored the biological function of the thorax with a favorable prognosis. Neoadjuvant immunotherapy might therefore be conducive to radical resection and perioperative immunotherapy might improve the prognosis.

European Epidemiology of Pleural Mesothelioma-Real-Life Data From a Joint Analysis of the Mesoscape Database of the European Thoracic Oncology Platform and the European Society of Thoracic Surgery Mesothelioma Database.

INTRODUCTION: Pleural mesothelioma (PM) is an aggressive malignancy with increasing prevalence and poor prognosis. Real-life data are a unique approach to reflect the reality of PM epidemiology, treatment, and prognosis in Europe. METHODS: A joint analysis of the European Thoracic Oncology Platform Mesoscape and the European Society of Thoracic Surgeons (ESTS) databases was performed to better understand the characteristics and epidemiology of PM, including histologic subtype, staging, and treatment. Overall survival (OS) was assessed, adjusting for parameters of clinical interest. RESULTS: The analysis included 2766 patients (Mesoscape: 497/10 centers/ESTS: 2269/77 centers). The primary histologic subtype was epithelioid (71%), with 57% patients on stages III to IV. Within Mesoscape, the patients received either multimodality (59%) or palliative intention treatment (41%). The median follow-up was 47.2 months, on the basis of 1103 patients (Mesoscape: 491/ESTS: 612), with 823 deaths, and median OS was 17.4 months. In multivariable analysis, female sex, epithelioid subtype, and lower stage were associated with longer OS, when stratifying by cohort, age, and Eastern Cooperative Oncology Group Performance Status. Within Mesoscape, multimodality treatment including surgery was predictive of longer OS (hazard ratio = 0.56, 95% confidence interval: 0.45-0.69), adjusting for sex, histologic subtype, and Eastern Cooperative Oncology Group Performance Status. Overall, surgical candidates with a macroscopic complete resection had a significantly longer median OS compared with patients with R2 (25.2 m versus 16.4 m; log-rank p < 0.001). CONCLUSIONS: This combined European Thoracic Oncology Platform/ESTS database analysis offers one of the largest databases with detailed clinical and pathologic outcome. Our finding reflects a benefit for selected patients that undergo multimodality treatment, including macroscopic complete resection, and represents a valuable resource to inform the epidemiology and treatment options for individual patients.