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.

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.

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.

Individualized prediction of survival benefit from postoperative radiotherapy for patients with malignant pleural mesothelioma.

OBJECTIVES: The role of postoperative radiotherapy (PORT) in malignant pleural mesothelioma (MPM) remains controversial and the eighth edition TNM staging scheme for MPM has not been fully verified. We aimed to develop an individualized prediction model for identifying optimal candidates for PORT among MPM patients who received surgery plus chemotherapy and externally validate the performance of the new TNM staging scheme. MATERIALS AND METHODS: Detailed characteristics of MPM patients during 2004-2015 were retrieved from SEER registries. Propensity score matching (PSM) was conducted to reduce disparities of baseline characteristics (age, sex, histologic type, stage, and type of surgery) between the PORT group and no-PORT group. A novel nomogram was constructed based on independent prognosticators identified by multivariate Cox regression model. The discriminatory performance and degree of calibration were evaluated. We stratified patients into different risk groups according to nomogram total scores and estimated the survival benefit of PORT in different subgroups in order to identify the optimal candidates. RESULTS: We identified 596 MPM patients, among which 190 patients (31.9%) received PORT. PORT conferred significant survival benefit in the unmatched population, while there was no significant survival difference favoring PORT in the matched population. The C-index of the new TNM staging scheme was closed to 0.5, which represented a poor discriminatory ability. A novel nomogram was constructed based on clinicopathological factors, including age, sex, histology, and N stage. We stratified patients into three risk groups. Subgroup analyses indicated that PORT was beneficial for high-risk group (p = 0.003) rather than low-risk group (p = 0.965) and intermediate-risk group (p = 0.661). CONCLUSION: We established a novel predictive model, which could make individualized prediction of survival benefit of PORT for MPM and could compensate for weakness in TNM staging system.

Peripheral location of lung cancer is associated with higher local disease recurrence.

OBJECTIVES: Our goal was to evaluate the association between the distance of the tumour to the visceral pleura and the rate of local recurrence in patients surgically treated for stage pI lung cancer. METHODS: We conducted a single-centre retrospective review of 578 consecutive patients with clinical stage IA lung cancer who underwent a lobectomy or segmentectomy from January 2010 to December 2019. We excluded 107 patients with positive margins, previous lung cancer, neoadjuvant treatment and pathological stage II or higher status or for whom preoperative computed tomography (CT) scans were not available at the time of the study. The distance between the tumour and the closest visceral pleura area (fissure/mediastinum/lateral) was assessed by 2 independent investigators who used preoperative CT scans and multiplanar 3-dimensional reconstructions. An area under the receiver operating characteristic curve analysis was performed to determine the best threshold for the tumour/pleura distance. Then multivariable survival analyses were used to assess the relationship between local recurrence and this threshold in relation to other variables. RESULTS: Local recurrence occurred in 27/471 patients (5.8%). A cut-off value of 5 mm between the tumour and the pleura was determined statistically. In the multivariable analysis, the local recurrence rate was significantly higher in patients with a tumour-to-pleura distance ≤5 mm compared to patients with a tumour-to-pleura distance >5 mm (8.5% vs 2.7%, hazard ratio 3.36, 95% confidence interval: 1.31-8.59, P = 0.012). Subgroup analyses of patients with pIA and tumour size ≤2 cm identified local recurrences in 4/78 patients treated with segmentectomy (5.1%), with a significantly higher occurrence with tumour-to-pleura distances ≤5 mm (11.4% vs 0%, P = 0.037), and in 16/292 patients treated with lobectomy (5.5%) without significant higher occurrence in tumour-to-pleura distances of ≤5 mm (7.7% vs 3.4%, P = 0.13). CONCLUSIONS: The peripheral location of a lung tumour is associated with a higher rate of local recurrence and should be taken into account during preoperative planning when considering segmental versus lobar resection.

Disparities in Survival Due to Social Determinants of Health and Access to Treatment in US Patients With Operable Malignant Pleural Mesothelioma.

Importance: Outcomes of localized malignant pleural mesothelioma (MPM) remain poor despite multimodality therapy. It is unclear what role disparities have in the overall survival (OS) of patients with operable MPM. Objective: To examine survival disparities associated with social determinants of health (SDOHs) and treatment access in patients with malignant pleural mesothelioma. Design, Setting, and Participants: In this observational, retrospective cohort study, patients with MPM diagnosed between January 1, 2004, and December 31, 2017, were identified from the National Cancer Database with a maximum follow-up time of 13.6 years. The analysis was conducted from February 16, 2022, to July 29, 2022. Patients were included if they were diagnosed with potentially resectable clinical stage I to IIIA MPM, had epithelioid and biphasic histologic subtypes, and received chemotherapy. Patients were excluded if they could not receive curative surgery, were 75 years or older, or had metastasis, unknown stage, or tumor extension to the chest wall, mediastinal tissues, or organs. Exposures: Chemotherapy alone vs chemotherapy with curative surgery in the form of pleurectomy and decortication or extrapleural pneumonectomy. Main Outcomes and Measures: The primary end point was OS. Cox proportional hazards regression models were used to determine hazard ratios (HRs) for OS, including univariable and multivariable models controlling for potential confounders, including demographic, comorbidity, clinical, treatment, tumor, and hospital-related variables, as well as SDOHs. Results: A total of 1389 patients with MPM were identified (median [IQR] age, 66 [61-70] years; 1024 [74%] male; 12 [1%] Asian, 49 [3%] Black, 74 [5%] Hispanic, 1233 [89%] White, and 21 [2%] of other race). The median OS was 1.7 years (95% CI, 1.6-1.8). Risk factors associated with worse OS included older age, male sex, Black race, low income, and low educational attainment. Factors associated with greater odds of survival included receipt of surgical therapy, recent year of treatment, increased distance to travel, and treatment at high-volume academic hospitals. The risk factors most strongly associated with poor OS included Black race (HR, 1.96; 95% CI, 1.43-2.69) and male sex (HR, 1.60; 95% CI, 1.38-1.86). Surgical treatment in addition to systemic chemotherapy (HR, 0.70; 95% CI, 0.61-0.81) was independently associated with improved OS, as were chemotherapy initiation (HR, 0.93; 95% CI, 0.87-0.99) and greater travel distance from the hospital (HR, 0.92; 95% CI, 0.86-0.98). Conclusions and Relevance: In this retrospective cohort study of patients with operable MPM, there was significant variability in access to care by SDOHs. Addressing disparities in access to multimodality therapy can help ensure equity of care for patients with MPM.

Surgical considerations in the resection of solitary fibrous tumors of the pleura.

Solitary fibrous tumors (SFTs) are rare mesenchymal pleural neoplasms with an overall good prognosis and low recurrence rate if completely resected and if degree of differentiation is favorable. Within the last decade, advances in research have led to more reliable methods of differentiating SFTs from other soft tissue tumors. Historically, several markers were used to distinguish SFTs from similar tumors, but these markers had poor specificity. Recent evidence showed NAB2-STAT6 fusion gene to be a distinct feature of SFTs with 100% specificity and sensitivity. Surgical resection, with an emphasis on obtaining negative margins, is the mainstay of treatment for SFTs. Preoperative planning with detailed imaging is imperative to delineate the extent of disease and vascular supply. One important radiologic distinction to aid delineation of a pleural-based tumor compared to a pulmonary parenchymal-based tumor is the angle that the tumor forms with the chest wall, which is obtuse for a pleural-based tumor, and acute for tumors of the lung parenchyma. Often, preoperative tissue diagnosis is not available, and surgery is both diagnostic and curative. Intraoperatively, emphasis should be on complete resection with negative margins. SFTs are resected via several approaches: thoracotomy, sternotomy with the option of hemi-clamshell extension, video-assisted thoracoscopic surgery, and robotic approach, which is increasingly being used and is our preference. We recommend a minimally invasive approach for most lesions, and have resected SFTs of the pleura that are up to 12 cm with the robotic approach. However, the current literature often cites 5 cm as the cut off for an open thoracotomy. Nevertheless, even with larger tumors, a minimally invasive robotic approach is our preference and practice. For giant SFTs (> 20 cm), an open approach may be preferable. Multiple thoracotomies and rib resection may be required to gain adequate exposure and ensure complete resection in these tumors. However, it is noteworthy that most of these tumors have a soft consistency and thus, once bagged, can easily be removed minimally invasively, and thus minimally invasive approach should not be completely ruled out. Recurrence in SFTs usually results from incomplete resection and redo surgery may portend a favorable prognosis.

Gastric herniation due to rupture of diaphragmatic prosthesis in the postoperative period of pleuropneumonectomy due to mesothelioma: A complication to consider.

Extrapleural pneumonectomy, usually associated with pericardial and diaphragmatic reconstruction with prosthetic material, is one of the surgical techniques used in the treatment of malignant pleural mesothelioma. Herniation of the abdominal viscera towards the thorax through the prosthetic material at the diaphragmatic level is a rare but potentially serious complication of these procedures, which must be diagnosed quickly for urgent repair. We present the case of a patient who presented with gastric herniation in the early postoperative period of a left pneumonectomy due to pleural mesothelioma. The clinical findings were mild, but supported by imaging tests, they confirmed the diagnostic hypothesis and facilitated the solution of the condition. Possible contributing factors are reviewed and the need for early diagnosis and treatment is emphasized to avoid ischemia of herniated abdominal viscera in the thoracic cavity, due to the risk of necrosis and contamination by fecaloid material.

A Case of Primary Epithelioid Sarcoma of the Pleura.

BACKGROUND Epithelioid sarcoma is a rare tumor and that is extremely rare as a primary pleural neoplasm. On imaging, it may appear similar to malignant pleural mesothelioma; thus, it can be difficult to diagnose. CASE REPORT A 64-year-old Asian woman, who had a treatment history of cervix adenocarcinoma, was admitted with dyspnea and right massive pleural effusion. Chest drainage was performed, and malignant cells were found in the pleural effusion. The malignant cells were thought to be metastasized from previous cervical cancer. We continued pleural drainage; however, the volume of the pleural effusion did not decrease. On the 5th hospital day, the chest tube became occluded. Computed tomography showed structures similar to empyema. Pleural irrigation and fibrinolytic therapy did not improve her condition. Empyema curettage was performed on the 14th hospital day. The resected pleura was submitted for pathological examination and showed tumor lesion but not metastatic adenocarcinoma of the cervix. The intrathoracic tumor grew extremely rapidly, and the patient died of respiratory failure on postoperative day 8 (22nd hospital day) before a diagnosis could be made. The final pathological diagnosis obtained on the 34th hospital day was epithelioid sarcoma. CONCLUSIONS For patients who appear to have empyema complicated by neoplastic lesions, a histopathological examination should also be performed to ensure accurate diagnosis. In addition, if a tumorous lesion is detected and it is neither metastatic nor malignant pleural mesothelioma, pleural epithelioid sarcoma should be added to the differential diagnosis in the presence of a rapidly growing and histologically difficult-to-diagnose pleural tumor.

Contemporary issues in the surgical management of pleural mesothelioma.

The surgical management of pleural mesothelioma (PM) can be divided into diagnostic, staging, palliation, and cytoreductive surgery. In the cytoreductive surgical setting, the combination of different treatment modalities has led to better outcomes than surgery alone. The scarcity of high-quality studies has led to heterogeneity in management of PM across the mesothelioma treatment centers. Here, we review the literature regarding the most important open questions and ongoing clinical trials.

Does mediastinal lymph node involvement influence the surgical outcome in malign pleural mesothelioma?

BACKGROUND: This study examined the effect of metastatic mediastinal lymph node involvement on the prognosis of patients with malignant pleural mesothelioma (MPM) who underwent extrapleural pneumonectomy (EPP) or extended pleurectomy (E/P) and also to assess the effect of metastatic mediastinal lymph node involvement on the prognosis of patients with MPM in these group of patients. METHODS: This retrospective study included 84 patients with MPM (66 men [78.6%] and 18 women [21.4%]) who underwent EPP (n = 44) or E/P (n = 40) at our institution between January 2001 and July 2019. Survival analyses were performed according to histopathology, nodal status, and surgical approach. RESULTS: In the EPP group, patients with T2-N2 status had a significantly better mean survival (17 ± 2.1 months) than patients with T3-N2 (7.3 ± 1.6 months) or T4-N2 (3.2 ± 1.1 months) status (p = .001). In the E/P group, patients with T2-N2 status had a mean survival of 18 ± 1.1 months, while patients with T3-N2 and T4-N2 status had mean survival durations of 6.6 ± 1.6 and 4.8 ± 1.2 months, respectively (p = .159). In both treatment groups, the survival rates of patients with epithelial tumors were better than those of patients with non-epithelial tumors, independent of N status. None of the patients with N2 disease survived until 5 years postoperatively. CONCLUSION: In summary, our results suggested that mediastinal lymph node metastasis negatively influenced the prognosis of patients with T3 MPM, regardless of treatment by EPP or E/P. Under these circumstances, preoperative cervical mediastinoscopy or endobronchial ultrasound-guided transbronchial needle aspiration may be considered for patients with high-stage MPM who are scheduled for surgery with curative intent. In our study, N2 status was spotted as a significant factor affecting survival, nevertheless its significance in survival of pleural mesothelioma patients should be analyzed in multi-centered studies.

Cytoreductive surgery with hyperthermic intrathoracic chemotherapy for malignant pleural mesothelioma: a systematic review.

INTRODUCTION: Cytoreductive surgery has been used a part of multimodality treatment in patients with malignant pleural mesothelioma (MPM). The residual microscopic disease that remains will lead to disease progression in the majority of patients. Delivery of hyperthermic intrathoracic chemotherapy at the time of surgery has been used to address this microscopic disease, however it's effect and place in the multimodality treatment sphere is unknown. The aim of this systematic review was to assess the effect of surgery and hyperthermic intrathoracic chemotherapy in patients with MPM on overall survival and disease-free interval. METHODS: Ovid MEDLINE, Embase, Web of Science and the Cochrane Database of Systematic Reviews were searched from database inception through to June 2021. Studies reporting overall survival and/or disease-free interval in patients with MPM undergoing cytoreductive surgery with hyperthermic intrathoracic chemotherapy were considered. Study quality was assessed using the Newcastle-Ottawa Scale. A narrative review was performed. RESULTS: Fifteen studies were eligible for inclusion comprising 598 patients. Surgery with hyperthermic intrathoracic chemotherapy was associated with a median overall survival and disease-free interval ranging from 11 to 75 months and 7.2 to 57 months, respectively. These appeared to be superior to patients not receiving hyperthermic intrathoracic chemotherapy (overall survival: 5-36 months and disease-free interval: 12.1-21 months). A higher dose of hyperthermic intrathoracic chemotherapy was associated with an improvement in overall survival compared with a lower dose: 18-31 months versus 6-18 months, respectively. The most common morbidity was atrial fibrillation followed by renal complications. CONCLUSION: Surgery with hyperthermic intrathoracic chemotherapy offers a safe and effective therapy with an improvement in disease-free interval and overall survival, particularly when hyperthermic intrathoracic chemotherapy is administered at a higher dose. PROSPERO REGISTRATION NUMBER: CRD42019129002.

The Impact of Adjuvant Hemithoracic Radiation on Outcomes in Patients With Stage I-III Malignant Pleural Mesothelioma: A Dual Registry Analysis.

BACKGROUND: The outcomes associated with receipt of adjuvant radiation in patients after surgery for MPM are poorly understood. OBJECTIVE: The objective of this study was to use 2 registries to compare the outcomes of patients receiving adjuvant radiation or no radiation after definitive surgery for pathologic stage I-III MPM. METHODS: Patients with resected pathologic stage I-III MPM were identified from the Duke University registry (1996-2016) and National Cancer Database (NCDB) (2004-2015). The primary outcome was overall survival. Propensity score-matched and landmark subgroup analyses were performed. RESULTS: A total of 212 institutional and 1615 NCDB patients met criteria. In both cohorts, patients who underwent radiation were more likely to have margin-negative resection and more advanced pathologic stage. At a landmark time of 4.4 and 4.7 months from surgery, Duke [hazard ratio (HR) 1.14; 95% confidence interval (CI) 0.62-2.11] and NCDB patients (HR 0.97; 95% CI 0.81-1.17) who received adjuvant radiation did not experience improved survival compared to those who did not receive radiation in multivariable analysis. Duke patients who received radiation had similar incidence of recurrence and time to both overall recurrence and ipsilateral recurrence (HR 0.87; 95% CI 0.43-1.77) compared to those who did not. Duke patients experienced 100 grade 1/2, 21 grade 3/4, and one grade 5 toxicity events during radiation. CONCLUSIONS: In this dual registry analysis of patients with resected stage I-III MPM, the receipt of adjuvant hemithoracic radiation was not associated with improved survival compared to no radiation.