Predicting programmed death-ligand 1 (PD-L1) expression with fluorine-18 fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) metabolic parameters in resectable non-small cell lung cancer.

BACKGROUND: Programmed death-ligand 1 (PD-L1) expression is a predictive biomarker for immunotherapy in non-small cell lung cancer (NSCLC). PD-L1 and glucose transporter 1 expression are closely associated, and studies demonstrate correlation of PD-L1 with glucose metabolism. AIM: The aim of this study was to investigate the association of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) metabolic parameters with PD-L1 expression in primary lung tumour and lymph node metastases in resected NSCLC. METHODS: We conducted a retrospective analysis of 210 patients with node-positive resectable stage IIB-IIIB NSCLC. PD-L1 tumour proportion score (TPS) was determined using the DAKO 22C3 immunohistochemical assay. Semi-automated techniques were used to analyse pre-operative [18F]FDG-PET/CT images to determine primary and nodal metabolic parameter scores (including max, mean, peak and peak adjusted for lean body mass standardised uptake values (SUV), metabolic tumour volume (MTV), total lesional glycolysis (TLG) and SUV heterogeneity index (HISUV)). RESULTS: Patients were predominantly male (57%), median age 70 years with non-squamous NSCLC (68%). A majority had negative primary tumour PD-L1 (TPS < 1%; 53%). Mean SUVmax, SUVmean, SUVpeak and SULpeak values were significantly higher (p < 0.05) in those with TPS ≥ 1% in primary tumour (n = 210) or lymph nodes (n = 91). However, ROC analysis demonstrated only moderate separability at the 1% PD-L1 TPS threshold (AUCs 0.58-0.73). There was no association of MTV, TLG and HISUV with PD-L1 TPS. CONCLUSION: This study demonstrated the association of SUV-based [18F]FDG-PET/CT metabolic parameters with PD-L1 expression in primary tumour or lymph node metastasis in resectable NSCLC, but with poor sensitivity and specificity for predicting PD-L1 positivity ≥ 1%. CLINICAL RELEVANCE STATEMENT: Whilst SUV-based fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography metabolic parameters may not predict programmed death-ligand 1 positivity ≥ 1% in the primary tumour and lymph nodes of resectable non-small cell lung cancer independently, there is a clear association which warrants further investigation in prospective studies. TRIAL REGISTRATION: Non-applicable KEY POINTS: • Programmed death-ligand 1 immunohistochemistry has a predictive role in non-small cell lung cancer immunotherapy; however, it is both heterogenous and dynamic. • SUV-based fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) metabolic parameters were significantly higher in primary tumour or lymph node metastases with positive programmed death-ligand 1 expression. • These SUV-based parameters could potentially play an additive role along with other multi-modal biomarkers in selecting patients within a predictive nomogram.

Resectability versus Operability in Early-Stage Non-Small Cell Lung Cancer.

PURPOSE OF REVIEW: With increased detection of early-stage non-small cell lung cancer (NSCLC) owing to screening, determining optimal management increasingly hinges on assessing resectability and operability. Resectability refers to the feasibility of achieving microscopically negative margins based on tumour size, location and degree of local invasion and achieving an anatomical lobar resection. Operability reflects the patient's tolerance for resection based on comorbidities, cardiopulmonary reserve and frailty. Standardized criteria help guide these assessments, but application variability contributes to practice inconsistencies. This review synthesizes a strategic approach to evaluating resectability and operability in contemporary practice. Standardization promises reduced care variability and optimized patient selection to maximize curative outcomes in this new era of early detection. RECENT FINDINGS: Recent pivotal trials demonstrate equivalency of sublobar resection to lobectomy for small, peripheral, node-negative NSCLC, expanding options for parenchymal preservation in borderline surgical candidates. Furthermore, recent phase 3 trials have highlighted the benefit of chemoimmunotherapy as a neoadjuvant treatment with an excellent pathological response and a down staging of the tumour, improving the resectability of the early-stage NSCLC. A good assessment of the operability and resectability is paramount in order to offer the best course of treatment for our patients. European and American societies have issued recommendations to help clinicians assess the cardiopulmonary function and predict the extension of pulmonary resection that could afford the patient. This operability assessment is closely linked with the evaluated tumour resectability which will determine the extension of pulmonary resection that is needed for the patient in order to achieve a good oncological outcome. Some major progresses have been done recently to improve the operability and resectability of patients. For instance, prehabilitation program allows better postoperative morbidity. Some studies have shown a potential good oncological outcome with sublobar resection expending access to surgery for patient with reduced lung function. Some others have identified the neoadjuvant immunochemotherapy as a potential solution for downstaging tumours. Work-up of early-stage NSCLC is a key moment and has to be done thoroughly and in full knowledge of the recent findings in order to propose the most appropriate treatment for the patient.

The Combined Robotic-assisted Laparoscopic and Thoracic Approach in the Management of Diaphragmatic, Pleural, and Pericardial Endometriosis.

STUDY OBJECTIVE: To demonstrate the advantages of a combined robotic-assisted laparoscopic and thoracic approach in the management of extensive diaphragmatic, pleural, and pericardial endometriosis. DESIGN: A video article demonstrating excision of endometriosis from pericardium, diaphragm, and pleura. SETTING: Thoracic endometriosis is the most common site of extrapelvic endometriosis [1]. Surgical treatment aims to excise all visible disease to relief symptoms and prevent recurrence [2-4]. INTERVENTIONS: A 41-year-old lady with cyclical shoulder tip and chest pain and known extensive diaphragmatic endometriosis was referred to our center. The procedure was done jointly by a gynecologist and a thoracic surgeon experienced in robotic-assisted endometriosis excision (Supplemental Video 1). Robotic-assisted laparoscopy revealed extensive full-thickness diaphragmatic endometriosis and a full-thickness pericardial nodule. Pericardial endometriosis excision was performed and a 1 cm defect was left open in the pericardium. Multiple diaphragmatic endometriotic nodules were excised and pleural cavity was entered (Image 2). On robotic-assisted thoracic surgery, further deep endometriotic lesions were detected and excised from the posterior aspect of the diaphragm. These lesions were not identified abdominally despite complete division of falciform ligament, full mobilization of the liver, and the use of a 30-degree scope. Superficial endometriotic lesions on parietal pleura were also detected (Image 3) and excised. The defects on the diaphragm were closed (Image 4). Chest and abdominal drains were left in situ. The patient was discharged on day 4. CONCLUSION: The combined robotic-assisted laparoscopic and thoracic approach is indicated in selected cases and allows full exploration of the thoracic cavity and both sides of the diaphragm, thus preventing incomplete excision of the disease. Robotic surgery also allows smooth dual-surgeon teamwork.

18F FDG PET/CT and Novel Molecular Imaging for Directing Immunotherapy in Cancer.

Immunotherapy has transformed the treatment landscape of many cancers, with durable responses in disease previously associated with a poor prognosis. Patient selection remains a challenge, with predictive biomarkers an urgent unmet clinical need. Current predictive biomarkers, including programmed death-ligand 1 (PD-L1) (measured with immunohistochemistry), are imperfect. Promising biomarkers, including tumor mutation burden and tumor infiltrating lymphocyte density, fail to consistently predict response and have yet to translate to routine clinical practice. Heterogeneity of immune response within and between lesions presents a further challenge where fluorine 18 fluorodeoxyglucose PET/CT has a potential role in assessing response, stratifying treatment, and detecting and monitoring immune-related toxicities. Novel radiopharmaceuticals also present a unique opportunity to define the immune tumor microenvironment to better predict which patients may respond to therapy, for example by means of in vivo whole-body PD-L1 and CD8+ T cell expression imaging. In addition, longitudinal molecular imaging may help further define dynamic changes, particularly in cases of immunotherapy resistance, helping to direct a more personalized therapeutic approach. This review highlights current and emerging applications of molecular imaging to stratify, predict, and monitor molecular dynamics and treatment response in areas of clinical need.

Salvage pulmonary resection in stages IIIb-IV lung cancer after treatment with immune checkpoint inhibitors case series and literature review.

BACKGROUND AND OBJECTIVES: The role of salvage thoracic surgery in managing advanced-stage lung cancer following treatment with immune checkpoint inhibitors is currently unclear. We present a series of nine patients with advanced non-small-cell lung cancer who underwent pulmonary resection following treatment with pembrolizumab. METHODS: We performed a single-institution retrospective analysis of pulmonary resection undertaken following treatment with pembrolizumab for advanced-stage lung cancer. Nine patients met the inclusion criteria. RESULTS: In six cases, surgery was indicated for persistent localized disease after treatment, and in three cases for nonresponsive synchronous/metachronous lung nodules while on treatment for stage IV lung cancer. Dense hilar fibrosis was present in all patients. Minimal access surgery was achieved in five cases (video-assisted n = 2, robotic-assisted n = 3). There was no in-hospital mortality. One patient died within 60 days from community-acquired COVID-19 pneumonitis. Seven patients remain free of disease between 5 and 22 months follow-up. CONCLUSIONS: Pulmonary resection is safe and technically feasible following treatment with immune checkpoint inhibitors. Surgical challenges relate to postimmunotherapy fibrosis, but with increased experience and a robotic approach, minimal access surgery is achievable. Further prospective studies are required to assess the surgical impact on disease control and overall survival in this patient cohort.

Diaphragmatic paralysis post COVID-19 treated with robot-assisted plication reinforced with acellular dermal matrix: a report of two cases.

Coronavirus disease 2019 (COVID-19) continues to be a disease of global importance, with an increasing array of sequelae attributed to infection by the severe acute respiratory syndrome coronavirus-2. One such complication that has been rarely documented thus far is diaphragmatic dysfunction. Here, we report the cases of 2 individuals who developed diaphragmatic paralysis post COVID-19, which failed to respond to conservative management. Both patients proceeded to undergo robot-assisted thoracoscopic plication of the diaphragm reinforced with a bovine acellular dermal matrix. In both cases, there was significant improvement in symptomatology, namely dyspnoea and fatigue. We conclude that robot-assisted diaphragmatic plication should be considered for the treatment of refractory diaphragmatic paralysis post COVID-19.

Three-Dimensional Printing for Chest Wall Reconstruction in Thoracic Surgery: Building on Experience.

OBJECTIVES: Patients undergoing surgery for locally advanced lung cancer involving the chest wall require anatomical lung with extensive en-bloc chest wall resection and appropriate reconstruction.In this proof-of-concept study, we aimed to produce personalized three-dimensional (3D)-printed chest wall prosthesis for a patient undergoing chest wall resection and reconstruction using clinically obtained computed tomography (CT) data. METHODS: Preoperative CT scans of three patients undergoing chest wall resection were analyzed and the areas of resection segmented. This was then used to produce a 3D print of the chest wall and a silicone mold was created from the model. This mold was sterilized and used to produce methyl methacrylate prostheses which were then implanted into the patients. RESULTS: Three patients had their chest wall reconstructed using this technique to produce a patient specific prosthesis. There were no early complications or deaths. CONCLUSIONS: It is possible to use 3D printing to produce a patient specific chest wall reconstruction for patients undergoing chest wall resection for malignancy that is cost-effective. This chest wall is thought to provide stability in the form of prosthetic ribs as well compliance in the form of an expanded polytetrafluoroethylene patch. Further research is required to measure chest wall compliance during the respiratory cycle and long-term follow-up from this method.

Retrospective Observational Study into the Early Causes of Death Following Surgery for NSCLC.

INTRODUCTION: Respiratory failure has historically been the major cause of mortality after elective lung resections. With improved intubation using fiber-optic scopes, better preoperative respiratory risk assessment, more advanced anesthetic single lung ventilation, and minimally invasive surgical technique, this may have changed. Our objective was to assess the main causes of mortality over the past 10 years in patients undergoing elective lung surgery in a major UK center. MATERIALS AND METHODS: A retrospective unit data search was made for all deaths during the 10-year period between January 2007 and December 2016 inclusive. All inpatient deaths within 30 days of an elective anatomical lung resection for lung malignancies were included. RESULTS: Three-thousand three-hundred sixteen lung resections for malignancy were performed in the 10-year period. There were 44 (1.3%) deaths during this period, 27 (61.4%) after open lobectomies, 8 (18.2%) after video-assisted thoracoscopic surgery lobectomies, 5 (11.4%) after sleeve lobectomies, and 4 (9%) after pneumonectomies. Causes of death included 24 (54.5%) respiratory failure, 10 (22.7%) ischemic bowel, 4 (9%) coronary events, 2 (4.5%) strokes, 2 (4.5%) on table hemorrhage, 1 (2.3%) massive pulmonary embolus, and 1 (2.3%) postoperative hemorrhage. CONCLUSION: Although respiratory failure is still a major cause of mortality in the postoperative patient, bowel ischemia has been found to be the second greatest cause of death. This study highlights the need to identify those at risk of this fatal complication during preoperative assessment and their postoperative management.

TUSC3 accelerates cancer growth and induces epithelial-mesenchymal transition by upregulating claudin-1 in non-small-cell lung cancer cells.

Lung cancer is the most frequent cause of cancer-related deaths worldwide, but its molecular pathogenesis is poorly understood. The tumor suppressor candidate 3 (TUSC3) gene is located on chromosome 8p22 and is universally acknowledged as a cancer suppressor. However, our research has demonstrated that TUSC3 expression is significantly upregulated in non-small-cell lung cancer compared to benign controls. In this study, we analyzed the consequences of TUSC3 knockdown or overexpression on the biological functions of non-small-cell lung cancer cell lines. To identify the molecules and signaling pathways with which TUSC3 might interact, we completed immunoblotting, quantitative polymerase chain reaction, microarray, co-immunoprecipitation, and immunofluorescence assays. We demonstrated that TUSC3 knockdown leads to decreased proliferation, migration, and invasion, and reduced xenograft tumor growth of non-small-cell lung cancer cell lines, whereas opposite results were observed with overexpression of TUSC3. In addition, TUSC3 knockdown suppressed epithelial-mesenchymal transition by downregulating the expression of claudin-1, which plays an indispensable role in EMT progress. On the contrary, overexpression of TUSC3 significantly enhanced EMT progress by upregulating claudin-1 expression. Overall, our observations suggest that TUSC3 accelerates cancer growth and induces the epithelial-mesenchymal transition in non-small-cell lung cancer cells; we also identified claudin-1 as a target of TUSC3.

Treatment and prognostic factors of patients with thymic epithelial tumors at first recurrence or progression.

AIM: The treatment of patients with recurrent or progressive thymic epithelial tumors remains uncertain due to limited data in this rare disease. MATERIALS & METHODS: A retrospective 10-year monoinstitutional analysis was conducted on 25 patients with first recurrence or disease progression following primary treatment. RESULTS: Twenty patients had thymoma, five thymic carcinomas. Ten patients (40%) received surgery, four (40%) following chemotherapy; 17 (68%) had chemotherapy, with a combination regimen in 16 of them (94%). Surgery had a significant effect both on overall survival and progression-free survival-2 by univariate analysis (p = 0.04), combination chemotherapy only on progression-free survival-2 (p = 0.03). CONCLUSION: Combination chemotherapy and surgery at first recurrence/progression of thymic epithelial tumors were associated with improved survival. DISCUSSION: Although several limitations may have affected this retrospective study on a relatively small number of patients with this rare entity of recurrent thymic malignancies, we suggest the use of combination chemotherapy and surgery at their first recurrence may have contributed to the high overall and progression-free survival observed with adequate follow-up and deserve further investigations in broader retrospective and comparative studies.

Does Previous Surgical Training Impact the Learning Curve in Video-Assisted Thoracic Surgery Lobectomy for Trainees?

Background To analyze if the number of open lung resections performed by trainees before starting video-assisted thoracic surgery (VATS) lobectomy training program has any impact on intraoperative and postoperative outcomes. Materials and Methods Retrospective analysis of 46 consecutive patients who underwent VATS lobectomies between December 2011 and September 2012 by two trainees (A.B. and L.O.). The previous surgical experience of the two trainees was evaluated to assess for any difference in terms of learning curve. Group A comprised 25 VATS lobectomies performed by one trainee (A.B.) and group B comprised 21 VATS lobectomies performed by the other trainee (L.O.). Results There was no statistical difference in terms of operating time and intraoperative bleeding between the two groups (p = 0.16 and p = 0.6). The conversion rate was 8% (2 out of 25 cases) in group A and 23.8% (5 out of 21 cases) in group B (p = 0.002). Evaluation of vascular injury showed no difference in the conversion rate (p = 0.56). The median length of the drainage and of hospital stay were 4 days and 7 days in group A and 4 days and 8 days in group B, respectively (p = 0.36 and p = 0.24). The complication rate was 44% in group A and 47.6% in group B (p = 0.52). A.B. had performed 139 and L.O. 70 operations as first operator before starting their VATS lobectomy training; the surgical experience had an impact only on the conversion rate. Conclusion Our study showed that a training program in VATS lobectomy is feasible, and previous surgical training has a minimal impact on intraoperative and postoperative outcomes.

Survival following Pulmonary Metastasectomy for Sarcoma.

OBJECTIVES: The aim of this study is to report the overall survival after pulmonary metastasectomy in patients with metastatic sarcoma and prognostic factors for survival. METHODS: This is a retrospective observational study of consecutive patients having pulmonary metastasectomy for sarcoma over a 5-year period. Survival was calculated by Kaplan-Meier method. RESULTS: Between August 2007 and January 2014, a total of 80 pulmonary metastasectomies were performed on 66 patients with metastatic sarcoma. There were no postoperative in-hospital deaths. The median age was 51 years (range, 16-79) and 39 (59%) patients were male. Fourteen patients had bilateral lung operations and surgical access was by video-assisted thoracoscopic surgery in 48 (73%) cases. The median number of metastases resected was 3 (range, 1-9). The median disease-free interval was 25 months (range, 0-156). Median overall survival was 25.5 months (range, 1-60). At follow-up, 19 patients (29%) were dead with a median follow-up of 31 months (range, 1-60). Recurrence of metastases significantly affected survival: median of 25.5 months (95% confidence interval [CI], 17.7-33.4) versus 48.4 months (95% CI, 42.5-54.4) in patients with no recurrent metastases (p = 0.004). There was no significant difference in survival between patients with high-grade versus low-grade tumors (p = 0.13), histological type (osteosarcoma vs. other soft tissue sarcoma types, p = 0.14), unilateral versus bilateral lung metastases (p = 0.48), or lung metastases alone versus lung and other sites of metastases (p = 0.5). CONCLUSION: In selected patients, pulmonary metastasectomy for sarcoma is safe and may confer a good medium-term survival. Recurrent metastasis after resection confers a poor prognosis.

Lymph node dissection in lung cancer surgery.

Lung cancer, a leading cause of cancer-related death, often requires surgical resection for early-stage cases, with recent data supporting less invasive resections for tumors smaller than 2 cm. Central to resection is lymph node assessment, an area of controversy worldwide, compounded by advances in minimally invasive techniques. The review aims to assess current standards for lymph node assessment, recent data from the surgical era, and the immunobiological basis of how lymph node metastases impact patient outcomes. The British Thoracic Society guidelines recommend systematic nodal dissection during lung cancer resection, without specifying node removal or sampling. Historical data on mediastinal lymph node dissection (MLND) survival benefits are inconclusive, although proponents argue for lower recurrence rates. Recent trials such as ACOSOG Z0030 found no survival difference between MLND and nodal sampling, reinforcing the need for robust staging. While lobe-specific dissection strategies have been proposed, they currently lack consensus. JCOG1413 aims to compare the clinical benefits of lobe-specific and systematic dissection. TNM-9 staging revisions emphasize the prognostic significance of single-station N2 involvement. Robotic surgery shows promise, with trials such as RAVAL, which reported comparable outcomes to video-assisted thoracic surgery (VATS) and improved lymph node sampling. Immunobiological insights suggest preserving key immunological sites during lymphadenectomy, especially for patients receiving adjuvant immunotherapy. In conclusion, the standard lymph node resection strategy remains unsettled. The debate between systematic and selective dissection continues, with implications for staging accuracy and patient outcomes. As minimally invasive techniques evolve, robotic surgery emerges as an effective and low-risk approach to delivering optimal lymph node assessment.

Learning curve of robotic surgery for lung cancer: analysis for two surgeons during the COVID-19 pandemic.

OBJECTIVE: To describe and compare the RATS learning curve between two surgeons in one department for lung cancer surgery using the CUSUM method. METHODS: Retrospective analysis using a prospective database on robotic-assisted lung resections performed by two different surgeons in one hospital. The CUSUM method was used to describe the learning curve. RESULTS: 366 consecutives cases were analysed (195 for the first surgeon and 171 for the second surgeon). A traditional 3-phase pattern learning curve was found with a diminution of the operating time throughout the different phases. For Surgeon 1, phase 1 was from case 1 to 59, phase 2 from case 60 to 99 and phase 3 started at case 100. For Surgeon 2, phase 1 was from 1 to 44, phase 2 from case 45 to 79 and phase 3 started at case 80. CONCLUSION: This study described our first experience with the Da Vinci Robotic System in our department. The curves had a similar shape which shows the learning curve of robotic surgery using the CUSUM method is reproducible. Furthermore, our results showed that the learning curve may improve after the programme starts in the department when the different team elements are all trained.

Salvage surgery for recurrent transdiaphragmatic thymoma in a patient not eligible for chemotherapy.

The recurrence rate following thymoma surgery has been reported to be as high as 29%. In cases of localized recurrence, complete resection can result in prolonged patient survival. However, surgery is rarely considered in cases of invasive recurrent thymomas with high disease burden. Here, we present the case of a woman with type B2 thymoma (Masaoka-Koga stage IVa) treated with surgery, chemotherapy, and radiotherapy. The disease recurred 6 years later, with invasion of the left lung and the 12th thoracic vertebra, as well as extension into the retroperitoneum. Due to the development of chemotherapy-associated toxicity, she underwent surgery with complete tumor resection and has remained free of disease at a 12-months follow-up. Radical surgery for recurrent invasive thymoma extending through the diaphragm is a feasible and safe therapeutic option in highly selected patients who are not eligible for systemic treatments.

The International Association for the Study of Lung Cancer Pleural Mesothelioma Staging Project: Proposal for Revision of the TNM Stage Groupings in the Forthcoming (Ninth) Edition of the TNM Classification for Pleural Mesothelioma.

INTRODUCTION: The eighth edition of the TNM classification of pleural mesothelioma (PM) saw substantial changes in T and N components and stage groupings. The International Association for the Study of Lung Cancer collected data into a multinational database to further refine this classification. This ninth edition proposal incorporates changes proposed in the clinical (c)T component but not the pathologic T component, to include size criteria, and further refines TNM stage groupings for PM. METHODS: Data were submitted through electronic data capture or batch transfer from institutional databases. Survival was measured from diagnosis date. Candidate stage groups were developed using a recursive partitioning and amalgamation algorithm applied to all cM0 cases for clinical stage and subsequently for pathologic stage. Cox models were developed to estimate survival for each stage group. RESULTS: Of 3598 submitted cases, 2192 were analyzable for overall clinical stage and 445 for overall pathologic stage. Recursive partitioning and amalgamation generated survival tree on overall survival outcomes restricted to cM0, with newly proposed (ninth edition) cT and cN component-derived optimal stage groupings of stage I (T1N0), II (T1N1; T2N0), IIIA (T1N2; T2N1/2; any T3), IIIB (any T4), and IV (any M1). Although cT and pathologic T descriptors are different in the ninth edition, aligning pathologic stage groupings with clinical stage produced better discrimination than did retaining eighth edition pathologic stage groupings. CONCLUSIONS: To our knowledge, this revision of the clinical TNM classification for PM is the first to incorporate the measurement-based proposed changes in cT category. The pathologic TNM aligns with clinical TNM.

The International Association for the Study of Lung Cancer Mesothelioma Staging Project: Proposals for the "N" Descriptors in the Forthcoming Ninth Edition of the TNM Classification for Pleural Mesothelioma.

INTRODUCTION: The International Association for the Study of Lung Cancer developed an international database to inform potential revisions in the ninth edition of the TNM classification of diffuse pleural mesothelioma (PM). This study analyzed the clinical and pathologic N categories to determine whether revisions were indicated relative to the eighth edition staging system. METHODS: Of 7338 PM cases diagnosed from 2013 to 2022 and 3598 met all inclusion criteria for planned analyses. Data on 2836 patients without metastases were included in this study. Overall survival (OS) was measured from date of diagnosis. Patients were included regardless of whether they received neoadjuvant treatment. For the pathologic N analysis, patients who underwent resection (extrapleural pneumonectomy or pleurectomy/decortication) were included. N subgroups were analyzed and OS assessed by the Kaplan-Meier method. RESULTS: The existing eighth edition N categories were performed adequately in the ninth edition data set. A median OS advantage was noted for clinical and pathologic N0 versus N1 patients: 23.2 versus 18.5 and 33.8 versus 25.0 months, respectively. Patients with resected pN0 had a 3-year OS of 48%. No difference in OS was noted for single- versus multiple-station nodal metastases. The number of nodal stations sampled at the time of resection was not associated with a difference in OS. CONCLUSIONS: Data regarding clinical and pathologic N categories corroborate those used in the eighth edition. No changes in the N categories are recommended in the ninth edition of PM staging system.

The International Association for the Study of Lung Cancer Pleural Mesothelioma Staging Project: Expanded Database to Inform Revisions in the Ninth Edition of the TNM Classification of Pleural Mesothelioma.

The International Association for the Study of Lung Cancer collaborated with the International Mesothelioma Interest Group to propose the first TNM stage classification system for diffuse pleural mesothelioma in 1995, accepted by the Union for International Cancer Control and the American Joint Committee on Cancer for the sixth and seventh edition stage classification manuals. The International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee Mesothelioma Domain developed and analyzed an international registry of patients with pleural mesothelioma and updated TNM descriptors for the eighth edition of the stage classification system. To inform revisions for the forthcoming ninth edition of the TNM stage classification system, data submission was solicited for patients diagnosed between 2013 and 2022 with expanded data elements on the basis of the first project's exploratory analyses, including pleural thickness measurements, updated surgical nomenclature, and molecular markers. The resulting database consisted of a total of 3598 analyzable cases from Europe, Australia, Asia, North America, and South America, with a median age of 71 years (range: 18-99 y), 2775 (77.1%) of whom were men. With only 1310 patients (36.4%) undergoing curative-intent operations, this iteration of the database includes far more patients treated nonsurgically compared with prior. Four separate manuscripts on T, N, M, and stage groupings submitted to this journal will summarize analyses of these data and will serve collectively as the primary source of the proposed changes to the upcoming ninth edition of the pleural mesothelioma stage classification system.

The International Association for the Study of Lung Cancer Thymic Epithelial Tumors Staging Project: Proposals for the N and the M Components for the Forthcoming (Ninth) Edition of the TNM Classification of Malignant Tumors.

INTRODUCTION: Stage classification is an important underpinning of management in patients with cancer and rests on a combination of three components-T for tumor extent, N for nodal involvement, and M for distant metastases. This article details the revision of the N and the M components of thymic epithelial tumors for the ninth edition of the TNM classification of malignant tumors proposed by the Thymic Domain of the International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee. METHODS: The N and M components of the eighth edition staging system were verified by a large international collaborative data source through a data-driven analysis. A total of 9147 cases were included for analysis, including 7662 thymomas, 1345 thymic carcinomas, and 140 neuroendocrine thymic tumors. RESULTS: Lymph node involvement rates were 1.5% in thymomas and 17.6% and 27.7% in thymic carcinomas and neuroendocrine thymic tumors, respectively. Rates of lymph node metastasis were increasingly higher in tumors with higher T stage and higher-grade histologic type. Survival analysis validated the differences in the N and M categories proposed in the eighth edition staging system. Good discrimination in overall survival was detected among pathologic (p)N and pM categories in patients with thymoma and thymic carcinoma. CONCLUSIONS: No changes are proposed from the eighth edition for the N and M components. The proposed stage classification will provide a useful tool for management of the disease among the global thymic community.

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).