Long-Term Survival Analysis of Pleural Mesothelioma Patients Undergoing Surgery: Brief Report From a Tertiary Referral Centre.

OBJECTIVES: to date, no consensus has been reached on the surgical gold-standard in pleural mesothelioma (PM). We retrospectively reviewed our experience as a tertiary referral centre, to compare short- and long-term survival of PM patients undergoing different types of surgery. METHODS: in retrospective, observational, single-centre study, we analysed all the patients histologically diagnosed with PM undergoing surgical procedures with palliative or curative intent at IRCCS Istituto Nazionale dei Tumori of Milan, Italy, from January 2003 to December 2020. The primary study endpoint was 10-year overall survival (OS) in three different types of resections: extra-pleural-pneumonectomy (EPP), pleurectomy/decortication (P/D), partial-pleurectomy/pleural-biopsy (PP/B). Secondary endpoints were postoperative hospital stay and postoperative 30-day and 90-day mortality rates. The survival function was estimated using Kaplan-Meier, and the Log-rank test was used for testing differences. Univariable and Multivariable Cox regression models were implemented to estimate Hazard Ratio (HR) for all variables of interest. RESULTS: 243 consecutive patients were enrolled, EPP was performed in 49 (20.2%), P/D in 58 (23.8%), PP/B in 136 (56.0%) patients. The median follow-up time was 19.8 months. 10-year OS was significantly better for P/D group (16%, Log-Rank test p<0.0001) compared to PP/B (1.8%) and EPP (0%). No statistically significant differences were found among the 3 surgical groups in 30- and 90-day mortality rates. At multivariable analysis, gender (male, HR=1.58), type of resection (P/D, HR=0.55) and surgery date (recent years, HR=0.61) were found to be independent prognostic factors for OS. CONCLUSIONS: in PM, lung-sparing curative approach (e.g. P/D) should be preferred in highly selected patients and in highly experienced centres, whenever appropriate. Anyway, when P/D is not indicated, adopting palliative/conservative management (e.g. PP/B) could ensure comparable results as extremely aggressive surgeries (e.g. EPP). The aim of surgery in PM should not be reaching complete resection, but rather accomplishing significant resection allowing to complete the multimodality treatment in highly selected patients in experienced centers.

Routine perioperative blood tests predict survival of resectable lung cancer.

There is growing evidence that inflammatory, immunologic, and metabolic status is associated with cancer patients survival. Here, we built a simple algorithm to predict lung cancer outcome. Perioperative routine blood tests (RBT) of a cohort of patients with resectable primary lung cancer (LC) were analysed. Inflammatory, immunologic, and metabolic profiles were used to create a single algorithm (RBT index) predicting LC survival. A concurrent cohort of patients with resectable lung metastases (LM) was used to validate the RBT index. Charts of 2088 consecutive LC and 1129 LM patients undergoing lung resection were evaluated. Among RBT parameters, C-reactive protein (CRP), lymphocytes, neutrophils, hemoglobin, albumin and glycemia independently correlated with survival, and were used to build the RBT index. Patients with a high RBT index had a higher 5-year mortality than low RBT patients (adjusted HR 1.93, 95% CI 1.62-2.31). High RBT patients also showed a fourfold higher risk of 30-day postoperative mortality (2.3% vs. 0.5%, p 0.0019). The LM analysis validated the results of the LC cohort. We developed a simple and easily available multifunctional tool predicting short-term and long-term survival of curatively resected LC and LM. Prospective external validation of RBT index is warranted.

Salvage Surgery After First-Line Alectinib for Locally-Advanced/Metastatic ALK-Rearranged NSCLC: Pathological Response and Perioperative Results.

BACKGROUND: The role of salvage surgery after tyrosine kinase inhibitors in advanced oncogene-addicted non-small cell lung cancer is largely unexplored. PATIENTS: We aimed to describe the pathological features and surgical early-outcomes of Anaplastic Lymphome Kinase anaplastic lymphome kinase positive non-small cell lung cancer patients undergoing surgery after first-line alectinib treatment. We retrospectively collected and analyzed multicentric data of 10 patients treated with alectinib for advanced-stage anaplastic lymphome kinase positive lung adenocarcinoma who underwent anatomical surgical resection from January 2020 to Decemeber 2021. All patients were treatment naive and received alectinib (600 mg twice daily). Surgery was always proposed after multidisciplinary discussion. The primary endpoints were pathological response and surgical feasibility (technical intraoperative complications, postoperative outcomes). RESULTS: Alectinib was received for a mean of 212 days before surgery (42-415 days) and was generally interrupted about one week before surgery (range: 0-32 days) with no patient experienced grade 4 toxicity. All patients received an R0 resection with surgery consisting of lobectomy in 8 cases with bilobectomy and (left) pneumonectomy in 1 case each. Intra-operative difficulties were described in 7 cases (70%), mostly due to perivascular fibrosis or thickening of mediastinal lymph nodal tissues. Major and minor complications occurred in 0 and 3 cases (30%), respectively. A pathological complete response and major pathological response (defined as 0% and < 10% viable tumor cells, respectively) were observed in 50% and 90% of cases, respectively. Despite short follow-up, only one tumor recurrence was observed (in the only patient who did not resume alectinib after surgery). INTERPRETATION: Despite some technical intraoperative difficulties, salvage surgery was safe and feasible after Alectinib for advanced lung adenocarcinoma.

Long term outcome of complex surgical resection and reconstruction for rare thoracic cancers.

BACKGROUND: Complex surgical resection and reconstruction for rare thoracic cancers (RTCs) represent a major challenge, given their very low frequency, extreme variability of presentation, multi-modality treatment options and inadequate outcome prediction. We analysed the experience of a tertiary referral centre on a consecutive series of patients with thoracic germ cell tumours, thymomas and sarcomas, with the aim of reporting the long-term outcome by cancer type and complexity of surgical procedures. METHODS: From Jan 2003 to Dec 2018, 768 surgical procedures were performed with curative intent on 644 RTC patients. Study endpoints were: post-operative hospital stay (Pod), 30-day and 90-day mortality, 5-year and 10-year overall survival (OS). Median follow-up of alive patients was 7.2 years. RESULTS: Median Pod was 7 days, with a 1.2% 30-day and 2.9% 90-day mortality. OS was 90.8% at one year, 74.2% at five years and 62.8% at 10 years. Ten-year OS was 73.0% in low, 65.3% in intermediate, and 55.6% in high complexity score (Log-rank tests p<0.0001); 66.6% in patients with one or two reconstructions and 46.4% in patients with three or more reconstructions (p<0.0001); 46.0% with vascular and 50.0% with chest wall reconstruction; 71.8% in germ cell tumours, 64.6% in thymoma and 51.3% in sarcoma (p<0.0001). CONCLUSION: Complex surgical resection and reconstruction was associated with acceptable 90-day mortality and good 10-year survival in all RTC types. A predictive score based on surgical complexity and cancer type can help the clinical decision making.

Lung metastasectomy for osteosarcoma in children, adolescents, and young adults: proof of permanent cure.

INTRODUCTION: Surgical resection of pulmonary metastases has been associated with increased survival at 5 years for osteosarcoma, but limited information is available on long-term outcome, role of repeated metastasectomies, and surgical sequelae in a pediatric population. We analyzed a consecutive series of children, adolescents, and young adults (AYA) treated by repeated lung metastasectomies during a period >40 years to estimate the clinical benefit and potential cure rate of salvage surgery. METHODS: All patients who underwent lung metastasectomy for osteosarcoma at the IRCCS Istituto Ortopedico Rizzoli of Bologna, University of Modena, and IRCCS Istituto Nazionale Tumori of Milan from May 1973 to January 2014 were included. Overall survival (OS) at 20 years from the first metastasectomy was calculated. RESULTS: A total of 463 consecutive children and AYA were analyzed. Median age was 15.9 years (range 0.2-23.2 years) and median follow-up 18.6 years. The 5- and 20-year OS were 34.0% and 29.7% (95% CI 25.5-34.0%). Among the 138 (29.8%) alive patients, 42 (30.4%) had disease recurrence cured by repeated metastasectomies. Disease-free interval from primary tumor, number of metastases, and complete resection were the most relevant survival predictors at multivariable model analysis. DISCUSSION: The extended follow-up of this consecutive series shows that repeated lung metastasectomy can achieve a permanent cure when offered to properly selected patients with metastases from osteosarcoma.

Validation of a prognostic model including the number of harvested lymph-nodes in the setting of non-small cell lung cancer patients undergoing curative resection: a multicenter analysis.

BACKGROUND: The prognostic role of the extension of lymphadenectomy in non-small-cell lung cancer is still a debated and intriguing issue. The aim of this study is to validate a prognostic score including the number of resected lymph-nodes previously reported using a large multicenter dataset. METHODS: From 01/2002 to 12/2012, data on 4858 NSCLC patients undergoing curative-intent surgery in six institutions were retrospectively reviewed. To test the discriminative ability of the model, composed of a panel of high-risk, pathologic stage, nodal status, age, number of Resected Nodes and intermediate risk factors (gender, grading, histology), was determined. The Kaplan-Meier method was used to estimate overall (OS), cancer-specific (CSS) and disease-free survival (DFS) curves, and the log rank test was adopted to evaluate the differences between groups. RESULTS: Pathological stages were: 1) I in 46.5%, II in 24.1%, III in 27.8% and IV in 1.6% of cases. Overall, 5-year OS, CSS and DFS were 54.6%, 76.7% and 44.8%, respectively. Stratifying the sample of 3948 patients with complete data into low-risk (LR, #107), Intermediate-risk (IR, #1268) and High-Risk (HR, #2573) groups, the optimal prognostic discrimination power of this score was confirmed (C-statistics: 0.71, 95%CI 69-73). Specifically in LR, IR and HR, 5-year OS was 83.5%, 66.4% and 46.2% (P<0.0001), 5y-CSS was 95.8%, 89% and 69% (P<0.0001), and 5y-DFS was 74.7%, 59.1% and 35.5% (P<0.0001), respectively. CONCLUSIONS: Our study confirms the optimal prognostic discrimination power of the previous prognostic model including the number of harvested nodes.

Survival Analysis in Single N2 Station Lung Adenocarcinoma: The Prognostic Role of Involved Lymph Nodes and Adjuvant Therapy.

BACKGROUND: Prognostic factors in patients with single mediastinal station (sN2) involvement continues to be a debated issue. METHODS: Data on 213 adenocarcinoma patients with sN2 involvement and who had undergone complete anatomical lung resection and lymphadenectomy, were retrospectively reviewed. Clinical and pathological characteristics together with adjuvant therapy (AD) and node (N) status classifications (number of resected nodes (#RN), number of metastatic nodes (#MN), and node ratio (#MN/#RN = NR) were analyzed. RESULTS: Univariable analysis confirmed that age (0.009), #MN (0.009), NR (0.003), #N1 involved stations (p = 0.003), and skip metastases (p = 0.005) were related to overall survival (OS). Multivariable analysis confirmed, as independent prognostic factors, age <66 years and NR with a three-year OS (3YOS) of 78.7% in NR < 10% vs. 46.6% in NR > 10%. In skip metastases, NR (HR 2.734, 95% CI 1.417-5.277, p = 0.003) and pT stage (HR2.136, 95% CI 1.001-4.557, p = 0.050) were confirmed as independent prognostic factors. AD did not influence the OS of patients with singular positive lymph nodes (p = 0.41), while in patients with multiple lymph nodes and AD, a significantly better 3YOS was demonstrated, i.e., 49.1% vs. 30% (p = 0.004). In patients with N2 + N1 involvement, age (p = 0.002) and AD (p = 0.022) were favorable prognostic factors. CONCLUSIONS: Adenocarcinoma patients with single N2 station involvement had a favorable outcome in the case of skip metastases and low NR. Adjuvant therapy improves survival with multiple nodal involvement, while its role in single node involvement should be clarified.

Recent Advances in the Management of Typical and Atypical Lung Carcinoids.

Neuroendocrine neoplasms of the lung represent about 20% to 30% of all neuroendocrine tumors. On the basis of clinical and pathologic characteristics, 2 different categories of tumors may be defined: poorly differentiated neuroendocrine neoplasms, characterized by a high rate of recurrences and poor prognosis, and well-differentiated neuroendocrine neoplasms (typical carcinoids and atypical carcinoids), which generally display an indolent course. Lung carcinoids represent only 1% to 5% of all lung malignancies, but their incidence has significantly increased over the past 30 years. Surgery is the reference standard of treatment for lung carcinoids with locoregional disease. For advanced or unresectable lung carcinoids, several therapeutic options are available, but the choice should be shared within a multidisciplinary team to ensure optimal therapeutic outcomes. We describe the current management of these rare neoplasms.

External validation of the N descriptor in the proposed tumour-node-metastasis subclassification for lung cancer: the crucial role of histological type, number of resected nodes and adjuvant therapy.

OBJECTIVES: Overlapping survival curves for N1b (multiple N1 stations), N2a2 (single N2 station + N1 involvement) and N2a1 (skip N2 metastasis) limit the current tumour-node-metastasis (TNM) node (N) subclassification for node involvement. We validated externally the proposed subclassification. METHODS: Clinical records from a multicentric database comprising 1036 patients with pulmonary adenocarcinoma (ADC) or squamous cell carcinoma with N1/N2 involvement who underwent, from January 2002 to December 2014, complete lung resections were retrospectively reviewed. Patients were categorized according to the 8th TNM N subclassification proposal. Histological type, number of resected nodes (#RN) and adjuvant therapy (ADJ) were considered limiting factors. RESULTS: No difference in the 5-year overall survival (-OS) was noted between N1b and N2a1 (49.6% vs 44.8%, P = 0.72); instead, the 5-year-OS was significantly improved in patients with squamous cell carcinoma (63% in N1b vs 30.7% in N2a1, P = 0.04). In patients with ADC, the 5-year-OS was better in those with N2a1 than with N1b (50.6% vs 37.5%, P = 0.09). When we compared N1b with N2a2, the 5-year-OS was statistically significant (49.6% vs 32.8%, P = 0.02); considering only patients with squamous cell carcinoma (63% vs 25.8%, P = 0.003), #RN >10 (63.2% vs 35.3%, P = 0.05) and without ADJ (56.4% vs 24.5%, P = 0.02), the 5-year-OS was significantly different. Differences were not significant for ADC, #RN <10 and ADJ. Finally, the 5-year-OS was statistically significant when we compared N2a1 with N2a2 of the total cohort (44.8% vs 32.8%, P = 0.04), in ADC (5-year-OS 50.6% vs 36.5%, P = 0.04) and #RN >10 (5-year-OS 49.8% vs 32.1%, P = 0.03) without ADJ. CONCLUSIONS: Histological type, ADJ and #RN are relevant prognostic factors in N + non-small-cell lung cancer. Considering these results, we may better interpret the prognosis prediction limits of the proposed 8th TNM subclassification for the N descriptor.

Prognostic score for survival with pulmonary carcinoids: the importance of associating clinical with pathological characteristics.

OBJECTIVES: Lung carcinoids (LCs) are staged using the non-small-cell lung cancer tumour/node/metastasis staging system; the possibility of an LC-specific staging system is still being debated. The goal of our study was to construct a composite prognostic score for LC. METHODS: From January 2002 to December 2014, data from 293 patients who underwent surgical treatment for LC in 7 research institutes were retrospectively analysed. A panel of established prognostic factors in addition to lymph node metastasis patterns (single/multiple N1-N2 station, skip metastasis, lobe specific), numbers of lymph nodes resected and the ratio between the numbers of metastatic lymph nodes and the numbers of lymph nodes resected (node ratio) were correlated to overall survival (OS) and disease-free survival (DFS). The log-hazard ratio (HR), obtained from the Cox model, was used to derive weighting factors for a continuous prognostic index, designed to identify differential outcome risks. The score was dichotomized according to maximally selected log-rank statistics. RESULTS: Pathological analysis showed typical carcinoids in 223 (76.1%) and atypical carcinoids in 70 (23.9%) patients; the tumour/node/metastasis pattern was stage I in 72.4%, stage II in 18.1%, stage III in 9.5% and stage IV in 0.03% cases. The median numbers of lymph nodes resected was 12 (range 0-53); hilar and mediastinal node metastases were identified in 14% and 6.8% of cases, respectively. Overall, the 5-year OS and 5-year DFS rates were 90.6% and 76.7%, respectively. At multivariable analysis, sex, age, pathological T stage and node ratio were significantly related to a better OS; age, histological type, pathological T stage and node ratio were related to DFS. These factors were used to generate the prognostic score, which showed statistically significant differences between the high-risk and low-risk groups: 5-year OS = 96.6% if score <3.1 vs 63.5% if score ≥3.1 [P < 0.0001; HR 17.56, 95% confidence interval (CI) 5.45-56.53]; 5-year DFS 92.3% if score <1.5 vs 52.5% if score ≥ 1.5 (P < 0.0001; HR 7.95, 95% CI 3.48-18.16). CONCLUSIONS: The proposed prognostic scores seem to be effective in predicting outcomes for patients with LCs.

Mediastinal Up-Staging During Surgery in Non-Small-Cell Lung Cancer: Which Mediastinal Lymph Node Metastasis Patterns Better Predict The Outcome? A Multicenter Analysis.

BACKGROUND: Unexpected N2 involvement occurs in approximately 10% to 20% of patients with non-small-cell lung cancer (NSCLC) and patients' prognostic factors remain unclear. The aim of this study was to evaluate prognostic factors in these patients. METHODS: From January 2002 to December 2012, we retrospectively analyzed data of 550 patients with NSCLC with preoperative negative, but pathologic positive N2 involvement, who underwent anatomical lung resection and hilo-mediastinal lymphadenectomy, obtained from 6 institutions. An established prognostic factor panel and N2-type involvement were correlated to overall (OS), cancer-specific (CSS), and disease-free survival (DFS) using multivariate Cox Regression model. The following lymph node patterns were analyzed: number of resected nodes (#RNs), metastatic nodes (#MNs), ratio between #MNs and #RNs (NR), N2 subgroups proposed for the eighth TNM edition, and lobe-specific versus nonspecific metastasis. RESULTS: Regarding our cohort, 419 patients were staged IIIA (T1-2N2), 131 IIIB (T3-4 N2), 113 pT1, 306 pT2, 94 pT3, and 37 pT4; 5-year OS, DFS, and CSS were 34.1%, 20.1%, and 64.6%, respectively. Independent prognostic factor for OS, in the multivariable analysis, were as follows: NR <17% (P = .009), proposed N2 classification subgroups (P = .014), age <66 (P < .001), and pT (P = .005); for DFS: NR <17% (P = .003), adjuvant treatment (P = .026), and pT (P = .026); and for CSS: NR <17% (P = .008), grading (P = .001), and adjuvant treatment (P < .001). CONCLUSION: Our study confirms that adjuvant therapy is fundamental and NR, in patients with unexpected N2 involvement, has a strong prognostic factor. In particular, a NR cutoff value of 17% could predict OS, DFS, and CSS in patients with NSCLC.

The Prognostic Role of TNM Staging Compared With Tumor Volume and Number of Pleural Sites in Malignant Pleural Mesothelioma.

BACKGROUND: Age, sex, stage, histotype, and surgery are the most recognized prognostic factors for malignant pleural mesothelioma (MPM). Tumor volume (TV) was suggested as an alternative prognostic evaluation. We aimed to assess the prognostic role of Tumor, Node, Metastases (TNM) versus TV and number of pleural sites (NPS). PATIENTS AND METHODS: Information on stage, TV, and NPS was collected for 52 MPM patients (pts) at our institution from 2009 to 2012. Baseline computed tomography imaging was performed to define TNM, TV, and NPS. Pts were divided in 3 stage groups: early (I-II), III, and IV. A dedicated computer system calculated TV. Pts were divided in 2 groups according to mean baseline TV (483 cm3). NPS was defined on the basis of the NPS macroscopically involved by disease (1-3). The association between TNM, tumor size (T), TV, NPS, TV and NPS, and overall survival was assessed using Cox models adjusted for age, sex, histology, and treatment. RESULTS: Most pts were male; mean age was 62 years. We showed an association between TV, TNM, and T. Stage III (hazard ratio [HR], 4.71; P = .02) and IV (HR, 7.40; P < .01), T3 (HR, 5.07; P < .01) and T4 (HR, 5.09; P < .01), TV > 483 cm3 (HR, 3.47; P < .01) and NPS 2 (HR, 3.00; P = .08) and 3 (HR, 6.05; P < .01) were predictive of worse survival. However, the TV and NPS combination performed better than TV, NPS, and TNM alone as a prognostic classifier. CONCLUSION: We showed that TV is related to TNM staging and T, in particular. Improved prognostic performance might be achievable using quantitative clinical staging combining TV and NPS.

Baseline and Postoperative C-reactive Protein Levels Predict Long-Term Survival After Lung Metastasectomy.

BACKGROUND: Blood level of C-reactive protein (CRP) at diagnosis is a well-know prognostic bio-marker in different primary tumors, but its role has not been investigated in resectable lung metastases. The aim of our study is to assess the predictive value of baseline (CRP0) and 3rd postoperative day (CRP3) levels on long-term survival of patients undergoing lung metastasectomy. METHODS: A total of 846 consecutive patients underwent the first pulmonary resection for lung metastases between January 2003 and December 2015, including 611 (72%) single surgical procedures, 235 (28%) multiple metastasectomies, 501 (59%) epithelial primary tumors, 276 (33%) sarcomas, 66 (8%) melanomas, 286 (33.8%) with 0 risk factors (CRP0 ≤ 2 and CRP3 ≤ 84 mg/L) and 560 (66.2%) with ≥ 1 risk factor (CRP0 > 2 and/or CRP3 > 84 mg/L). RESULTS: Cumulative 5-year survival was 57% in patients with low CRP (0 risk factors) versus 43% in high CRP (≥ 1 risk factor, p < 0.0002), 62% versus 50% respectively for epithelial tumors (p < 0.0140), and 51% versus 34% for sarcomas (p < 0.0111). Multivariable Cox analysis confirmed a mortality hazard ratio of 2.5 at 1-year and 1.5 at 5-years in patients with high CRP. CONCLUSIONS: Baseline and postoperative CRP levels predict survival of patients with resectable lung metastases. These data provide a rationale for prospective clinical trials testing the efficacy of anti-inflammatory or immune-modulating agents as "adjuvant" therapy after lung metastasectomy, in patients with elevated pre- and/or postoperative CRP levels.

Lymph-node ratio predicts survival among the different stages of non-small-cell lung cancer: a multicentre analysis†.

OBJECTIVES: The prognostic role of the number of resected and metastatic lymph nodes in non-small-cell lung cancer (NSCLC) is still being debated. The aim of this study was to evaluate the impact of lymphadenectomy in addition to the already validated variables in NSCLC survival. METHODS: From January 2002 to December 2012, data on 4858 patients with NSCLC undergoing anatomical lung resection and hilomediastinal lymphadenectomy in 6 institutions were analysed retrospectively. Established prognostic factors in addition to the number of resected lymph nodes and the ratio between the number of metastatic lymph nodes and the number of resected lymph nodes (NR) were correlated to overall survival (OS) and disease-free survival (DFS) using the multivariable Cox regression model. Harrell's C-statistic with the 95% confidence interval (CI) was determined. Analysis by means of maximally selected log-rank statistics was performed to find optimal cut-off points in order to split patients into groups with different outcome probabilities. RESULTS: The median numbers of resected lymph nodes and of metastatic lymph nodes were 17 (range 6-85) and 2 (1-36), respectively. Hilar (N1) and mediastinal (N2) metastases were identified in 21.3% and 20.0% of cases, respectively. Overall, the 5-year OS and DFS rates were 54.6% and 44.8%, respectively. At multivariable analysis, age, gender, pathological stage, R0 resection, type of surgery and NR correlated with longer OS rates; the same variables plus tumour grading were further related to DFS. C-statistics were 66.0 (95% CI 62.7-69.4) for DFS and 60.5 (95% CI 58.3-62.6) for OS. An NR <40% significantly correlated with a higher 5-year survival rate in the total sample (OS 57.6% vs 23.8%, P < 0.001; DFS 48.2% vs 11.4, P < 0.001) and in patients with N1 (OS 47.9% vs 36.1%, P = 0.03; DFS 39% vs 24.2%, P = 0.02) and N2 (OS 36.9% vs 21.8%, P < 0.001 DFS 23.9% vs 9.1%, P < 0.001). CONCLUSIONS: Our study confirms that the number of resected lymph nodes is a strong prognostic indicator in NSCLC. In particular, an NR cut-off value of 40% may predict both OS and DFS.

Best practices for the management of thymic epithelial tumors: A position paper by the Italian collaborative group for ThYmic MalignanciEs (TYME).

Thymic epithelial tumors (TETs) are a heterogenous group of rare tumors, with a complex histopatological classification. Furthermore, the recent introduction of the first TNM staging system, that is scheduled to replace the Masaoka-Koga system, may create further difficulties in TET management, that remains challenging. Several guidelines for treatment of TETs are available and provide recommendations based mainly on non randomized trials and retrospective or limited series. Often the lack of evidence leads to formulation of indications based on expert opinions. As for other rare cancers it is crucial to create networks to coordinate the work among centres involved in treatment of these diseases in order to offer the best diagnostic and therapeutic tools. For this purpose, in 2014 a network named TYME (ThYmic MalignanciEs), was founded in Italy with the aim of improving care and research in TETs. In September 2017 a panel of multidisciplinary experts from TYME network and from other Italian centres strongly involved in TET diagnosis and treatment convened a first Italian Expert meeting together with representatives of association for patients affected by rare thoracic cancers Tu.To.R, to explore how these tumors are managed in the different centres of Italy compared to ESMO guidelines. In this paper we summarize the issues discussed during that meeting and we propose recommandations based on Masaoka Koga and the new TNM staging system.

Prognostic Model for Resected Squamous Cell Lung Cancer: External Multicenter Validation and Propensity Score Analysis exploring the Impact of Adjuvant and Neoadjuvant Treatment.

INTRODUCTION: We developed one of the first clinicopathological prognostic nomograms for resected squamous cell lung cancer (SQLC). Herein, we validate the model in a larger multicenter cohort and we explore the impact of adjuvant and neoadjuvant treatment (ANT). METHODS: Patients with resected SQLC from January 2002 to December 2012 in six institutions were eligible. Each patient was assigned a prognostic score based on the clinicopathological factors included in the model (age, T descriptor according to seventh edition of the TNM classification, lymph node status, and grading). Kaplan-Meier analysis for disease-free survival, cancer-specific survival (CSS), and overall survival was performed according to a three-class risk model. Harrell's C-statistics were adopted for model validation. The effect of ANT was adjusted with propensity score. RESULTS: Data on 1375 patients were gathered (median age, 68 years; male sex, 86.8%; T descriptor 1 or 2 versus 3 or 4, 71.7% versus 24.9%; nodes negative versus positive, 53.4% versus 46.6%; and grading of 1 or 2 versus 3, 35.0% versus 41.1%). Data for survival analysis were available for 1097 patients. With a median follow-up of 55 months, patients at low risk had a significantly longer disease-free survival than did patients at intermediate risk (hazard ratio [HR] = 1.67, 95% confidence interval [CI]: 1.40-2.01) and patients at high risk (HR = 2.46, 95% CI: 1.90-3.19); they also had a significantly longer CSS (HR = 2.46, 95% CI: 1.80-3.36 versus HR = 4.30, 95% CI: 2.92-6.33) and overall survival (HR = 1.79, 95% CI: 1.48-2.17 versus HR = 2.33, 95% CI: 1.76-3.07). A trend in favor of ANT was observed for intermediate-risk/high-risk patients, particularly for CSS (p = 0.06 [5-year CSS 72.7% versus 60.8%]). CONCLUSIONS: A model based on a combination of easily available clinicopathological factors effectively stratifies patients with resected SQLC into three risk classes.

Thirty-day mortality and five-year survival in thoracic surgery: "real-world" assessment of outcomes from a single-institution audit.

BACKGROUND: Accurate measurement of outcomes is essential to monitor the effectiveness of public health policies. In Italy, the Ministry of Health has chosen 30-day mortality after major surgical or medical procedures as the main outcome measure, pooling all pulmonary resections for malignancy in a single category. The present audit evaluated all pulmonary resections performed over a 13-year period in a single institution to assess the immediate (30-day mortality) and long-term (5-year survival) outcomes according to type and stage of disease and extent of surgery. METHODS: We analyzed the results of 4,234 first pulmonary resections performed from 2003 to 2015 for lung cancer (2,636), lung metastases (1,080), other primary cancers (259) and benign diseases (259). The median follow-up of cancer patients was 4.1 years. RESULTS: Overall 30-day mortality was 1.1%, being 1.2% for lung cancer, 0.3% for lung metastases, 3.5% for pneumonectomies, 1% for lobectomies, and 0.5% for sublobar resections. Among lung cancer patients, 30-day mortality was 0.7% for simple anatomical resections, 2.8% for complex resections, 0.7% for stage I, and 1.6% for higher stages. Overall 5-year survival was 56% for lung cancer, 49% for lung metastases, and 53% for other primary cancers (p = 0.03). According to the surgical procedure for lung cancer, 5-year survival was 60%, 55% and 36% for lobectomies, segmentectomies and pneumonectomies, respectively (p<0.0001). CONCLUSIONS: For better monitoring of thoracic surgery outcomes in a real-world setting, we suggest evaluating lung cancer separately from other thoracic malignancies, and including 5-year survival rates stratified by resection volume and surgical procedure complexity.

Permeable Nonabsorbable Mesh for Total Diaphragmatic Replacement in Extended Pneumonectomy.

After complex thoracic exenterations, total diaphragmatic resection and reconstruction is challenging. We describe our novel technique for total diaphragmatic replacement with permeable nonabsorbable mesh after extended pneumonectomy.

Baseline and postoperative C-reactive protein levels predict mortality in operable lung cancer.

BACKGROUND: Higher blood levels of C-reactive protein (CRP) have been associated with shorter survival in patients with cardiovascular, chronic obstructive pulmonary disease and cancer. We investigated the impact of baseline and postoperative CRP levels on survival of patients with operable lung cancer (LC). PATIENTS AND METHODS: CRP values at baseline (CRP0) and 3 days after surgery (CRP3) were measured in a consecutive series of 1750 LC patients who underwent complete resection between 2003 and 2015. Patients were classified as having 0 (N = 593), 1 (N = 658) or 2 (N = 553) risk factors: CRP0 and/or CRP3 values above the respective median value. The effect of higher CRP was evaluated by Kaplan-Meier mortality curves and adjusted hazard ratio (HR) with 95% confidence interval (CI), by fitting Cox proportional hazards models. RESULTS: Cumulative proportions of 5-year survival were 67% for 0 risk factors, 58% for 1 risk factor and 41% for 2 risk factors (P < 0.0001). The overall 5-year mortality risk was significantly higher in patients with 1 risk factor (adjusted hazard ratio [aHR] 1.43 [95% CI 1.14-1.79]), or 2 risk factors (aHR 2.49 [95% CI 1.99-3.11]). A significant impact on survival was observed in each tumour-node-metastasis stage group, and in the subset of non-smokers. Postoperative 30-day mortality was significantly higher in patients with 2 risk factors only (aHR 2.2% versus 0.6%, p < 0.0475). CONCLUSIONS: Baseline and postoperative CRP levels predict immediate and long-term mortality in all stages of operable lung cancer. Patients with higher CRP levels could be candidate to randomised adjuvant trials with anti-inflammatory agents.

Pleurectomy-decortication in malignant pleural mesothelioma: are different surgical techniques associated with different outcomes? Results from a multicentre study.

OBJECTIVES: The potential benefit of surgery for malignant pleural mesothelioma (MPM), especially concerning pleurectomy/decortication (P/D), is unclear from the literature. The aim of this study was to evaluate the outcome after multimodality treatment of MPM involving different types of P/D and to analyse the prognostic factors. METHODS: We reviewed 314 patients affected by MPM who were operated on in 11 Italian centres from 1 January 2007 to 11 October 2014. RESULTS: The characteristics of the population were male/female ratio: 3.7/1, and median age at operation was 67.8 years. The epithelioid histotype was observed in 79.9% of patients; neoadjuvant chemotherapy was given to 57% of patients and Stage III disease was found following a pathological analysis in 62.3% of cases. A total of 162 (51.6%) patients underwent extended P/D (EP/D); 115 (36.6%) patients had P/D and 37 (11.8%) received only a partial pleurectomy. Adjuvant radiotherapy was delivered in 39.2% of patients. Median overall survival time after surgery was 23.0 [95% confidence interval (CI): 19.6-29.1] months. On multivariable (Cox) analysis, pathological Stage III-IV [ P = 0.004, hazard ratio (HR):1.34; 95% CI: 1.09-1.64], EP/D and P/D ( P = 0.006, HR for EP/D: 0.46; 95% CI: 0.29-0.74; HR for P/D: 0.52; 95% CI: 0.31-0.87), left-sided disease ( P = 0.01, HR: 1.52; 95% CI: 1.09-2.12) and pathological status T4 ( P = 0.0003, HR: 1.38; 95% CI: 1.14-1.66) were found to be independent significant predictors of overall survival. CONCLUSIONS: Whether the P/D is extended or not, it shows similarly good outcomes in terms of early results and survival rate. In contrast, a partial pleurectomy, which leaves gross tumour behind, has no impact on survival.