Tumor inflammatory microenvironment contribution to survival in resected upstaged adenocarcinomas.

INTRODUCTION: Tumor Inflammatory microenvironment (TIME) encompasses several immune pathways modulating cancer development and escape that are not entirely uncoded. The results achieved with immunotherapy elicited the scientific debate on TIME also in non-small cell lung cancer (NSCLC). We aimed to investigate whether TIME (in terms of PD-L1 expression and/or Tumor Infiltrating Lymphocytes - TILs) played a separate role in terms of survival (OS) in resected upstaged lung adenocarcinomas (ADCs), excluding other perioperative variables as confounders. MATERIALS AND METHODS: This retrospective study included 50 patients with a clinically resectable lung ADC, undergoing surgery (lobectomy or segmentectomy) at the Thoracic Unit of Padova University Hospital between 2016 and 2022 and receiving an unexpected pathological upstaging (IIB or higher). RESULTS: Despite microscopical variables increasing from IIB to IIIB, survival was not significantly related to them. OS was better in TIME-active patients (defined as the presence of positive PD-L1 and/or TILs>10 %) than double negatives (PD-L1-/TILs-) (p = 0.01). In IIB or higher ADCs, TIME-active patients showed an improved survival compared to double negatives, merging the current TIME theories. CONCLUSION: TIME seems to be associated with survival independently from other microscopical parameter, even in case of resected upstaged adenocarcinomas.

Significance of Spread Through Air Spaces and Vascular Invasion in Early-stage Adenocarcinoma Survival: A Comprehensive Clinicopathologic Study of 427 Patients for Precision Management.

Spread through air spaces (STAS) is a novel invasive pattern of lung cancer associated with poor prognosis in non-small cell cancer (NSCLC). We aimed to investigate the incidence of STAS in a surgical series of adenocarcinomas (ADCs) resected in our thoracic surgery unit and to identify the association of STAS with other clinicopathological characteristics. We retrospectively enrolled patients with stage cT1a-cT2b who underwent resection between 2016 and 2022. For each case, a comprehensive pathologic report was accessible which included histotype, mitoses, pleural invasion, fibrosis, tumor infiltrating lymphocytes, necrosis, inflammation, vascular and perineural invasion, as well as STAS. PD-L1 expression was also investigated. A total of 427 patients with ADCs underwent surgery. Regarding overall survival (OS), no significant difference was observed between the STAS positive (STAS+) and STAS negative (STAS-) groups ( P =0.44). However, vascular invasion (VI) was associated with a poorer survival probability ( P =0.018). STAS+/VI+ patients had tendentially worse survival compared with STAS+/VI- ( P =0.089). ADCs with pathologic evidence of immune system (IS) activation (TILs>10% and PD-L1≥1) demonstrated significantly increased OS compared with ADCs with no IS and VI. In terms of recurrence rate, no statistical differences were found between the STAS+ and STAS- samples ( P =0.2). VI was also linked to a significantly elevated risk of recurrence ( P =0.0048). Our study suggests that in resected early-stage ADCs, STAS+ does not seem to influence recurrence or mortality. VI was instead an adverse pathologic prognostic factor for both survival and recurrence, whereas IS seemed to be protective.

Three-Dimensional Imaging-Guided Lung Anatomic Segmentectomy: A Single-Center Preliminary Experiment.

Background and objectives: VATS segmentectomy has been proven to be effective in the treatment of stage I NSCLC, but its technical complexity remains one of the most challenging aspects for thoracic surgeons. Furthermore, 3D-CT reconstruction images can help in planning and performing surgical procedures. In this paper, we present our personal experience of 11 VATS anatomical resections performed after accurate pre-operative planning with 3D reconstructions. Materials and methods: A 3D virtual model of the lungs, airways, and vasculature was obtained, starting from a 1.25 mm 3-phase contrast CT scan, and the original images were used for the semi-automatic segmentation of the lung parenchyma, airways, and tumor. Results: Six males and five females were included in this study. The median diameter of the pulmonary lesion at the pre-operative chest CT scan was 20 mm. The surgical indication was confirmed in seven patients: in three cases, a lobectomy, instead of a segmentectomy, was needed due to intraoperative findings of nodal metastasis. Meanwhile, only in one case, we performed a lobectomy because of inadequate surgical resection margins. Skin-to-skin operative average time was 142 (IQR 1-3 105-182.5) min. The median post-operative stay was 6 (IQR 1-3 3.5-7) days. The mean value of the closest surgical margin was 13.7 mm. Conclusion: Image-guided reconstructions are a useful tool for surgeons to perform complex resections in order to spare healthy parenchyma and to ensure disease-free margins. Nevertheless, human skill and surgeon experience still remain fundamental for the final decisions regarding the proper resection to perform.

Impact of a standardized protocol for chest tube management after VATS pulmonary resections on post-operative outcomes and complications.

Chest tube management represents a major issue after lung surgery as no protocol is widely accepted and tube management is generally based on local or personal habits. Aim of this study is to evaluate the impact of a standardized protocol for chest tube management after pulmonary resections on the post-operative outcomes. We performed a single center retrospective analysis of all adult patients undergoing thoracoscopic pulmonary resection from January 2020 to December 2021. Starting from January 2021 a standardized protocol of chest tube management was applied after all procedures. Patients were divided into two groups according to the chest tube management strategy. he two groups had similar pre-operative characteristics and the extent of lung resection was comparable. Intervention group had significantly shorter time to chest tube removal (median 1 vs 3 days, p < 0.001) and post-operative length of stay (median 3 vs 4 days, p < 0.001). Despite earlier chest tube removal, there was not an increased incidence of post-removal complications. On multivariable analysis, the new chest drain management strategy was an independent predictor of earlier chest tube removal. A standardized protocol of chest tube management allows for an earlier chest tube removal and a shorter hospital stay, without an increase in post-operative complications.

Perioperative outcomes in redo VATS for pulmonary ipsilateral malignancy: A single center experience.

BACKGROUND: The role of video-assisted thoracoscopic surgery for oncological major pulmonary resections is now well established; however, the literature within pulmonary re-operations is still limited. The purpose of this study is to evaluate the safety and efficacy of redo thoracoscopic resections for ipsilateral pulmonary malignancy. METHODS: Data from patients undergoing video-assisted thoracoscopic surgery at the Unit of Thoracic Surgery of Padua were analyzed, comparing the results between the first and second ipsilateral surgery. The retrospective study included patients who underwent 2 thoracoscopic surgeries for oncological reasons between 2015 and 2022. The variables considered included patients' baseline characteristics, pre, intra, and postoperative data. RESULTS: The study enrolled 51 patients undergoing ipsilateral thoracoscopic re-operation. The statistical analysis showed that surgical time (95min vs 115min; p = 0.009), the presence of intrapleural adhesions at second surgery (30 % vs 76 %; p < 0.001), overall pleural fluid output (200 vs 560 ml; p = 0.003), time with pleural drainage (2 vs 3 days; p = 0.027), air leaks duration time (p = 0.004) and post-operative day of discharge (3 vs 4 days; p = 0.043) were significantly higher in the re-operation group. No statistical differences were observed between the 2 groups respect to R0 resection rate (90.2 % vs 89.1 %; p=>0.9) and complications (5.8 % vs 15.6 %; p = 0.11). The conversion rate to open surgery was 11.8 %. CONCLUSION: Although some differences emerged between the first and second intervention, they had minimal impact on the clinical course of the patients. Therefore, thoracoscopic surgery has been shown to be safe and effective in re-operations with satisfying perioperative outcomes. To achieve such results, these procedures should be reserved for experienced surgeons.

Microscopical Variables and Tumor Inflammatory Microenvironment Do Not Modify Survival or Recurrence in Stage I-IIA Lung Adenocarcinomas.

Microscopical predictors and Tumor Immune Microenvironment (TIME) have been studied less in early-stage NSCLC due to the curative intent of resection and the satisfactory survival rate achievable. Despite this, the emerging literature enforces the role of the immune system and microscopical predictors as prognostic variables in NSCLC and in adenocarcinomas (ADCs) as well. Here, we investigated whether cancer-related microscopical variables and TIME influence survival and recurrence in I-IIA ADCs. We retrospectively collected I-IIA ADCs treated (lobectomy or segmentectomy) at the University Hospital (Padova) between 2016 and 2022. We assigned to pathological variables a cumulative pathological score (PS) resulting as the sum of them. TIME was investigated as tumor-infiltrating lymphocytes (TILs < 11% or ≥11%) and PD-L1 considering its expression (<1% or ≥1%). Then, we compared survival and recurrence according to PS, histology, TILs and PD-L1. A total of 358 I-IIA ADCs met the inclusion criteria. The median PS grew from IA1 to IIA, indicating an increasing microscopical cancer activity. Except for the T-SUVmax, any pathological predictor seemed to be different between PD-L1 < 1% and ≥1%. Histology, PS, TILs and PD-L1 were unable to indicate a survival difference according to the Log-rank test (p = 0.37, p = 0.25, p = 0.41 and p = 0.23). Even the recurrence was non-significant (p = 0.90, p = 0.62, p = 0.97, p = 0.74). According to our findings, resection remains the best upfront treatment in I-IIA ADCs. Microscopical cancer activity grows from IA1 to IIA tumors, but it does not affect outcomes. These outcomes are also unmodified by TIME. Probably, microscopical cancer development and immune reaction against cancer are overwhelmed by an adequate R0-N0 resection.

Video-assisted thoracoscopic lobectomy after neoadjuvant chemotherapy for non-small cell lung cancer: a multicenter propensity-matched study.

BACKGROUND: The role of video-assisted thoracoscopic surgery for the treatment of non-small-cell lung cancer after neoadjuvant chemotherapy remains controversial. The aim of this study is to demonstrate the reliability of video-assisted lobectomy compared to the open approach by evaluating perioperative and long-term outcomes. METHODS: In this retrospective, multicentric study from January 2010 to December 2018, we included all patients with non-small-cell lung cancer who underwent lobectomy through the video-assisted or open approach after neoadjuvant chemotherapy. The perioperative outcomes, including data concerning the feasibility of the surgical procedure, the occurrence of any medical and surgical complications and long-term oncological evidence, were collected and compared between the two groups. To minimize selection bias, propensity score matching was performed. RESULTS: A total of 286 patients were enrolled: 193 underwent thoracotomy lobectomy, and 93 underwent VATS lobectomy. The statistical analysis showed that surgical time (P < 0.001), drainage time (P < 0.001), days of hospitalization (P < 0.001) and VAS at discharge (P = 0.042) were lower in the VATS group. The overall survival and disease-free survival were equivalent for the two techniques on long-term follow-up. CONCLUSIONS: VATS lobectomy represents a valid therapeutic option in patients affected by non-small-cell lung cancer after neoadjuvant chemotherapy. The VATS approach in our experience seems to be superior in terms of the perioperative outcomes, while maintaining oncological efficacy.

Comparison of operative and postoperative characteristics and outcomes between thoracoscopic segmentectomy and lobectomy for non-small-cell lung cancer: a propensity score matching study from the Italian VATS Group Registry.

OBJECTIVES: Only few studies compared the surgical morbidity and mortality of thoracoscopic segmentectomy versus lobectomy for non-small-cell lung cancer, in particular, by relating the segmental resections with the corresponding anatomical lobes. METHODS: We enrolled a total of 7487 patients who underwent VATS lobectomy (7269) or segmentectomy (218) from January 2014 to July 2019. A propensity score matching approach was used to account for potential confounding factors between the 2 groups. After matching, 349 lobectomies and 208 segmentectomies were included in the analysis. We analysed the operative and postoperative outcomes of video-assisted anatomical segmentectomy compared with video-assisted lobectomy and, in details, the results of segmentectomy with its corresponding lobectomy in a large cohort of patients from the Italian VATS Group Registry. RESULTS: The overall conversion rate to thoracotomy was not statistically different between the groups (27 patients 8% vs 7 patients 3%, P = 0.1). The lobectomy group had a greater number of resected lymph nodes (median 11 vs 8, P = 0.006). No significant differences were detected in 30-day mortality (1.4%, 5 patients vs 0.9%, 2 patients), overall complications (18%, 62 patients vs 14%, 29 patients) and prolonged air leakage (31 patients, 9% vs 12 patients, 6%) between lobectomy and segmentectomy, respectively. No statistical differences were found regarding the median duration of drainage (3.2 days, P = 1) and the overall median length of hospital stay (6.4 days, P = 0.1) between the 2 groups. In the context of segmentectomy versus corresponding lobectomy, the right upper lobectomy compared with right upper segmentectomy showed a higher number of resected lymph nodes (P = 0.027). No statistical differences were reported in terms of conversion rate and postoperative complication and mortality. CONCLUSIONS: Segmentectomy could be considered a safe procedure without significant differences compared to thoracoscopic lobectomy in terms of postoperative morbidity and mortality.

Short- and Long-Term Impact of Smoking Donors in Lung Transplantation: Clinical and Pathological Analysis.

BACKGROUND: The use of smoking donors (SD) is one strategy to increase the organ pool for lung transplantation (LT), but the benefit-to-risk ratio has not been demonstrated. This study aimed to evaluate the impact of SD history on recipient outcomes and graft alterations. METHODS: LTs in 293 patients were retrospectively reviewed and divided into non-SD (n = 225, group I), SD < 20 pack-years (n = 45, group II), and SD ≥ 20 pack-years (n = 23, group III) groups. Moreover, several lung donor biopsies before implantation (equally divided between groups) were evaluated, focusing on smoking-related lesions. Correlations were analyzed between all pathological data and smoking exposure, along with other clinical parameters. RESULTS: Among the three groups, donor and recipient characteristics were comparable, except for higher Oto scores and age in group III. Group III showed a longer intensive care unit (ICU) and hospital stay compared with the other two groups. This finding was confirmed when SD history was considered as a continuous variable. However, survival and other mid- and long-term major outcomes were not affected by smoking history. Finally, morphological lesions did not differ between the three groups. CONCLUSIONS: In our study, SDs were associated with a longer post-operative course, without affecting graft aspects or mid- and long-term outcomes. A definition of pack-years cut-off for organ refusal should be balanced with the other extended criteria donor factors.

Lobectomy With Artery Reconstruction and Pneumonectomy for Non-Small Cell Lung Cancer: A Propensity Score Weighting Study.

BACKGROUND: The treatment of non-small cell lung cancer is based, when suitable, on surgical resection. Pneumonectomy has been considered the standard surgical procedure for locally advanced lung cancers but it is associated with high mortality and morbidity rates. Reconstruction of the pulmonary artery, associated with parenchyma-sparing techniques, is meant to be an alternative to pneumonectomy. METHODS: This retrospective single-center study is based on a detailed and comprehensive analysis of the clinical and oncologic data of patients treated between 2004 and 2016 through pneumonectomy or lobectomy with reconstruction of the pulmonary artery. A propensity score weighting approach, based on the preoperative characteristics of two groups of 124 patients each was performed. The subsequent statistical analysis evaluated long-term and short-term clinical outcomes together with risk factors analysis. RESULTS: The comparison between pneumonectomy and pulmonary artery reconstructions showed a higher 30-day (P = .02) and 90-day (P = .03) mortality rate in the pneumonectomy group, together with a higher incidence of major complications (P = .004). Long-term results have shown comparable outcomes, both in terms of 5-year disease-free survival (52.2% for pneumonectomy vs 46% for pulmonary artery reconstructions, P = .57) and overall 5-year survival (41.9% vs 35.6%, respectively; P = .57). Risk factors analysis showed that cancer-specific survival was related to lymph node status (P < .01) and absence of adjuvant therapy (P = .04). Lymph node status also influenced the risk of recurrence (P < .01). CONCLUSIONS: Lobectomy with reconstruction of the pulmonary artery is a valuable and oncologically safe alternative to pneumonectomy, with lower short-term mortality and morbidity, without affecting long-term oncologic results.

Correction to: Predictors of nodal upstaging in patients with cT1-3N0 non-small cell lung cancer (NSCLC): results from the Italian VATS Group Registry.

In the original publication, Carlo Curcio was not included in the author list. The correct author list is included in this Correction.

Bronchus intermedius sleeve resection through a VATS approach.

In recent years, parenchymal sparing techniques for tumor resection have been developed in order to reduce the amount of lung parenchyma that must be removed in cases of centrally located tumors. These techniques maintain oncological radicality while reducing postoperative complications. At the same time, video-assisted thoracoscopic surgery (VATS) has been shown to offer comparable surgical and oncological outcomes to thoracotomy, even in complex cases that require tracheal and bronchial reconstructions. In this video tutorial, we describe a case of an isolated sleeve resection of the bronchus intermedius performed through a VATS approach for a bronchial paraganglioma.

Predictors of nodal upstaging in patients with cT1-3N0 non-small cell lung cancer (NSCLC): results from the Italian VATS Group Registry.

PURPOSE: Accurate staging of early non-small cell lung cancer is fundamental for selecting the best treatment. The aim of this study was to identify risk factors for nodal upstaging after video-assisted thoracoscopic lobectomy for clinical T1-3N0 tumors. METHODS: From 2014 to 2017, 3276 thoracoscopic lobectomies were recorded in the prospective database "Italian VATS Group". Linear and multiple logistic regression models were adapted to identify independent predictors of nodal upstaging and factors associated with progression in postoperative N status. RESULTS: Nodal upstaging was found in 417 cases (12.7%), including 206 cases (6.2%) of N1-positive nodes, 81 cases of N2 nodes (2.4%), and 130 cases (4%) of involvement of both N1 + N2 nodes. A total of 241 (7.3%) patients had single-station nodal involvement, whereas 176 (5.3%) had multiple-station involvement. In the final regression model, the tumor grade, histology, pathologic T status, and > 12 resected nodes were independent predictors of nodal upstaging. CONCLUSIONS: The number of resected lymph nodes seems to predict nodal upstaging better than the type of intraoperative lymph node management. Other preoperative risk factors correspond to those for which the current guidelines of the European Society of Thoracic Surgery recommend more extensive preoperative mediastinal staging.

Two-port intrapericardial left VATS pneumonectomy.

Pneumonectomy is a surgical treatment for locally advanced lung tumors that deeply infiltrate into the pulmonary hilum, and is a major thoracic procedure. An intrapericardial approach may be necessary in cases where it is  impossible to safely deal with the extrapericardial non-invaded sections of the pulmonary vessels. This article describes our technique for intrapericardial left video-assisted thoracoscopic pneumonectomy in a patient with hilar squamous cell carcinoma. The procedure was performed through a two-incision approach and, because of the involvement of the proximal portion of the pulmonary vessels, an intrapericardial isolation and closure of these structures was performed. Radical lymphadenectomy was performed and a pericardial flap was used for coverage of the bronchial stump. This is a complex and challenging procedure, however the patient had an uneventful postoperative course and was discharged on the 7th postoperative day.

Predictors of unexpected nodal upstaging in patients with cT1-3N0 non-small cell lung cancer (NSCLC) submitted to thoracoscopic lobectomy.

BACKGROUND: In the last decades, the use of video-assisted thoracoscopic surgery (VATS) lobectomy for the treatment of early stage non-small cell lung cancer is continuously growing. This is mainly due to the development of more advanced surgical devices, to the rising incidence of peripheral lung tumors and is also favored by the increased reliability of preoperative staging techniques. Despite this progress, postoperative unexpected nodal upstaging is still a relevant issue. Aim of this study is to identify possible predictors of unexpected nodal upstaging in patients affected by cT1-3N0 NSCLC submitted to VATS lobectomy. METHODS: A total of 231 cases of cT1-3N0 patients submitted to thoracoscopic lobectomy at our centre between June 2012 and October 2016 were retrospectively reviewed. All data regarding clinical staging by means of computed tomography (CT) and positron-emission tomography (PET)/CT were collected and reviewed. The subsequent pathological staging has been analyzed, with special regards to the possible type of nodal involvement, and the number of pathological nodal stations. RESULTS: Most of the patients included in this study were in a clinical stage cT1aN0, cT1bN0 (stage IA) and cT2aN0 (stage IB), 86 (37.2%) patients, 73 (31.6%) patients and 62 (26.8%) patients, respectively. Postoperative histopathological analysis showed that the most frequent tumor histotype was adenocarcinoma (192 patients, 83.1%). Thirty-eight (16.5%) patients had a nodal upstaging; among these, 17 (7.4%) patients had N2 disease (8 patients with isolated mediastinal nodal involvement, 9 patients with N1 + N2 disease) and 21 (9.1%) patients had an isolated hilar nodal involvement (N1). At bivariate analysis, the clinical T (cT)-parameter (P=0.023), the histotype (P=0.029) and the pathological T (pT)-parameter (P=0.003) were identified as statistically significant predictors of nodal upstaging. Concerning the type of nodal upstaging, the pT was found to be statistically significant (P=0.042). At bivariate analysis for the number of involved nodal stations, a statistical significance was highlighted for the parameters cT (P=0.030) and pT (P=0.027). With linear logistic regression, histology as well as pT reached statistical significance (P=0.0275 and P=0.0382, respectively). No correlation was found between nodal upstaging and the intensity of FDG uptake in the primary lung tumor or with the timing between PET and surgery. CONCLUSIONS: There is a strong correlation between the clinical staging of the parameter T evaluated with CT and the possible unexpected nodal upstaging. The same correlation with nodal upstaging is found for pT. At equal clinical stage, in patients affected by adenocarcinoma of the lung the relative risk of having a postoperative unexpected nodal upstaging is almost 7 times higher than in patients with squamous cell carcinoma.

Is lobectomy really more effective than sublobar resection in the surgical treatment of second primary lung cancer?

OBJECTIVES: Sublobar resection for early-stage lung cancer is still a controversial issue. We sought to compare sublobar resection (segmentectomy or wedge resection) with lobectomy in the treatment of patients with a second primary lung cancer. METHODS: From January 1995 to December 2010, 121 patients with second primary lung cancer, classified by the criteria proposed by Martini and Melamed, were treated at our Institution. We had 23 patients with a synchronous tumour and 98 with metachronous. As second treatment, we performed 61 lobectomies (17 of these were completion pneumonectomies), 38 atypical resections and 22 segmentectomies. Histology was adenocarcinoma in 49, squamous in 38, bronchoalveolar carcinomas in 14, adenosquamous in 8, large cells in 2, anaplastic in 5 and other histologies in 5. RESULTS: Overall 5-year survival from second surgery was 42%; overall operative mortality was 2.5% (3 patients), while morbidity was 19% (22 patients). Morbidity was comparable between the lobectomy group, sublobar resection and completion pneumonectomies (12.8, 27.7 and 30.8%, respectively, P = 0.21). Regarding the type of surgery, the lobectomy group showed a better 5-year survival than sublobar resection (57.5 and 36%, respectively, P = 0.016). Compared with lobectomies, completion pneumonectomies showed a significantly less-favourable survival (57.5 and 20%, respectively, P = 0.001). CONCLUSIONS: From our experience, lobectomy should still be considered as the treatment of choice in the management of second primary lung cancer, but sublobar resection remains a valid option in high-risk patients with limited pulmonary function. Completion pneumonectomy was a negative prognostic factor in long-term survival.

Platinum-based doublet chemotherapy in pre-treated malignant pleural mesothelioma (MPM) patients: a mono-institutional experience.

BACKGROUND: The major clinical problems of MPM management are the short duration of response and the early relapse. Currently, after the first-line standard pemetrexed/platinum combination there is not a defined regimen for the second line treatment of MPM, and the clinical benefits in fit patients are uncertain. We analyzed the feasibility of gemcitabine/platinum chemotherapy in pretreated MPM patients. METHODS: Eligible patients should have relapsed after first-line chemotherapy with pemetrexed plus cisplatin (24%) or carboplatin (76%); 53% of the patients had previously received trimodality treatment, 18% neoadjuvant chemotherapy followed by pleurectomy/decortication, 29% were inoperable. Patients had to have PS=0-2, adequate organ function, measurable disease. Chemotherapy was gemcitabine 1000 mg/m(2) days 1, 8 associated to the alternative platinum compound respect to 1st line, i.e. cisplatin 75 mg/m(2) or carboplatin AUC 5 day 1 every 3 weeks, for 3-6 cycles. Baseline staging and reassessment after cycles 3 and 6 were performed with CT-scan. RESULTS: Since 2006 17 relapsed MPM patients were referred to our centre. Patients were 12 males and 5 females; median age: 61 years (range 47-74); histology: 12 epithelial, 4 sarcomatoid and 1 biphasic. PS 1-2 (15:2). The combination of gemcitabine with carboplatin/cisplatin was administered as second line treatment in 13 (76%) patients, as third line in 4 (24%) patients. Two patients were lost to follow-up without re-evaluation, therefore radiologic and clinical response was assessable in 15 (88%) patients. Among evaluable patients 10 (67%) showed stable disease and 5 (33%) progressive disease. Symptoms improved in 8 (53%) cases. In the intent-to-treat population median survival was 28 weeks (range 13-168) and median time-to-treatment failure 15 weeks (range 3-75). Toxicity profile showed 2 (13%) grade 4 and 6 (40%) grade 3 thrombocytopenia, 4 (27%) grade 3 leucopenia, 3 (20%) grade 3 anaemia and 6 (40%) of grade 3 neutropenia. Grade 3 non haematological toxicities were nausea (14%) and asthenia (21%). CONCLUSION: Gemcitabine-platinum regimens are able to control symptoms and disease progression with a modest toxicity profile. The present results from a small series of patients should be confirmed by a prospective trial in a larger cohort of patients.

Effect of induction chemotherapy on lung function and exercise capacity in patients affected by malignant pleural mesothelioma.

OBJECTIVES: The effect of induction chemotherapy (IC) on lung function and exercise capacity in patients with malignant pleural mesothelioma (MPM) has not been largely examined. The aim of this study was to evaluate the changes in pulmonary function and oxygen consumption following IC in patients with MPM. METHODS: Between 2004 and 2009, 36 consecutive patients (mean age 62.1 + or - 1.5 years, M/F = 25/11) were prospectively investigated. Data concerning medical history, histology, staging and response to chemotherapy were collected. All patients underwent pulmonary function test before (in the absence of pleural effusion) and after chemotherapy (platinum-based agent plus pemetrexed); 23 out of 36 patients also performed a cardiopulmonary incremental exercise test. RESULTS: An epithelioid histotype was documented in 88.8% of patients. A partial response to chemotherapy was observed in 44.5% of cases and 36.1% of patients experienced grade 2-3 toxicity. A significant improvement in forced expiratory volume in 1s (FEV(1)) (0.13 + or - 0.30 l; P = 0.01), in VO(2) peak (1.76 + or - 2.91 ml kg(-1) min(-1); P = 0.005), in PaO(2) at rest (4.76 + or - 9.84 mmHg; P = 0.03) and in PaO(2) at peak exercise (6.26 + or - 12.72 mmHg; P = 0.04) was detected. The diffusion capacity of the lung for carbon monoxide (DLCO) also increased (1.25 + or - 4.68 ml min(-1) mmHg(-1)), although not significantly (P = 0.20). The stratified analysis based on the response to IC showed a significant improvement in FEV(1), forced vital capacity (FVC) and vital capacity (VC) (both absolute and percentage of predicted values) only in patients with a partial response. CONCLUSIONS: An improvement in lung function and exercise capacity was seen after IC in patients with MPM. These data suggest that IC does not compromise cardiopulmonary performance in this subset of patients.