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Erratum for Natural History of Non-Small-Cell Lung Cancer with Bone Metastases

http://hdl.handle.net/20.500.11768/96547

Purpose: Lonidamine (LND) can enhance the activity of anthracyclines in patients with metastatic breast cancer. A multicenter, prospective, randomized trial was designed to determine whether the association of LND with high-dose epirubicin plus cyclophosphamide (EC) could improve disease-free survival (DFS) in patients with early breast cancer (BC) compared with EC alone. Granulocyte colony-stimulating factor (G-CSF) was added to maintain the EC dose-intensity. Patients and Methods: From October 1991 to April 1994, 506 patients with stage I/II BC were randomly assigned to four groups: (A) epirubicin 120 mg/m2 and cyclophosphamide 600 mg/m2 administered intravenously on day 1 every 21 days for four cycles (124 patients); (B) EC plus LND 450 mg/d administered orally (125 patients); (C) EC plus G-CSF administered subcutaneously (129 patients); (D) EC plus LND plus G-CSF (128 patients). Results: Median follow-up was 55 months. Five-year DFS rate was similar for LND (B+D groups; 69.6%) versus non-LND arms (A+C groups; 70.3%) and G-CSF (C+D groups; 67.2%) versus non–G-CSF arms (A+B groups; 72.9%). Five-year overall survival (OS) was comparable in LND (79.1%) versus non-LND arms (81.3%) and in G-CSF (80.6%) versus non–G-CSF arms (79.6%). DFS and OS distributions in LND and G-CSF arms did not change according to tumor size, node, receptor, and menopausal status. G-CSF dramatically reduced hematologic toxicity without having a significant impact on dose-intensity (98.1% v 95.5% for C+D and A+B groups, respectively). Conclusion: EC is active and well tolerated in patients with early breast cancer. The addition of LND or G-CSF does not improve DFS or OS.

http://hdl.handle.net/20.500.11768/96536

http://hdl.handle.net/20.500.11768/96442

Lung cancer is the most common cause of cancer deaths in both men and women worldwide and has a poor prognosis. Non-small-cell lung cancer (NSCLC) represents approximately 80% of all lung cancers. Surgery is the only curative treatment of NSCLC but only 15–20% of tumours can be radically resected with a survival of about 40% at 5 years. Considering these disappointing results NSCLC is one of the most frequent subjects of clinical research worldwide. Italy is playing an important role in the clinical research of NSCLC performing phase I, II and III trials, prevalently by cooperative groups, and achieving important results that contributed to define the standard treatment for NSCLC patients. In particular, Italy is leader in the clinical research of the treatment of advanced NSCLC elderly patients. Today, large controlled clinical trials are ongoing. In this paper we analyse and discuss the main trials performed by Italian groups in the fields of NSCLC.

Purpose To study the prognostic value for overall survival of baseline assessment of functional status, comorbidity, and quality of life (QoL) in elderly patients with advanced non—small-cell lung cancer treated with chemotherapy. Patients and Methods Data from 566 patients enrolled onto the phase III randomized Multicenter Italian Lung Cancer in the Elderly Study (MILES) study were analyzed. Functional status was measured as activities of daily living (ADL) and instrumental ADL (IADL). The presence of comorbidity was assessed with a checklist of 33 items; items 29 and 30 of the European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire QLQ-C30 (EORTC QLQ-C30) were used to estimate QoL. ADL was dichotomized as none versus one or more dependency. For IADL and QoL, three categories were defined using first and third quartiles as cut points. Comorbidity was summarized using the Charlson scale. Analysis was performed by Cox model, and stratified by treatment arm. Results Better values of baseline QoL (P = .0003) and IADL (P = .04) were significantly associated with better prognosis, whereas ADL (P = .44) and Charlson score (P = .66) had no prognostic value. Performance status 2 (P = .006) and a higher number of metastatic sites (P = .02) also predicted shorter overall survival. Conclusions Pretreatment global QoL and IADL scores, but not ADL and comorbidity, have significant prognostic value for survival of elderly patients with advanced non—small-cell lung cancer who were treated with chemotherapy. Using these scores in clinical practice might improve prognostic prediction for treatment planning.

ackground: The combination of cisplatin (CDDP) and 5-Fluorouracil (5-FU) is a standard regimen for the treatment of recurrent and metastatic head and neck squamous cell carcinoma (HNSCC). This combination shows a relevant toxicity and new chemotherapy associations with a more favourable toxicity profile are awaited. Carboplatin (CB) is a platinum derivative with less toxicity than CDDP. Raltitrexed (R) is a potent and specific thymidylate synthase inhibitor with activity comparable to that of 5-FU in colorectal cancer; moreover, it showed activity as a single agent in HNSCC. Materials and Methods: Since 2001, a multicentre, phase II trial has been underway to evaluate the efficacy and toxicity of the CB+R combination in untreated patients with recurrent or metastatic HNSCC. Thirty-two patients were enrolled and included in an intent-to-treat analysis. Toxicity was graded according to NCI criteria. Patients had a histo/cytologically proven recurrent or metastatic HNSCC; patients with locally advanced disease not amenable to CDDP+5-FU treatment were also included. Patients had to be > 18 years old with ECOG PS of 0-2 and adequate bone marrow, renal and liver functions. CB (AUC 5) and R (3 mg/m 2) were administered intravenously every 3 weeks. The median age was 62 years (range 43-71), 29 M/3 F. The median PS was 1 (0-2). Twelve patients were staged III and 20 were metastatic (10 recurrent). The oral cavity/oropharynx were the primary site in 20 patients and the larynx in 10 patients. The median number of cycles delivered was 3, while globally 115 cycles were administered. The median time to progression was 4.2 months and median duration of survival was 9.8 months. Results: Seven patients achieved a partial response (22%), 10 patients showed a stable disease (31%), while 13 patients (48%) had progressive disease. Eight patients (25%) had a G 3-4 neutropenia, while G 3-4 anaemia was observed in 2 patients and thrombocytopenia in 1 patient. No extrahaematological G 3-4 toxicities were observed. A persistent G 2 hepatic toxicity led a patient to drop out from the study. Conclusion: In our phase II trial, CB in combination with R showed a moderate activity with safe administration on an outpatient basis

Bronchopleural fistula (BPF) is a well recognized and potentially fatal complication of major thoracic surgery and several strategies regarding its prevention and subsequent management have been described. An immediate BPF occurring intraoperatively after bronchial closure is a rare event and is usually treated by bronchial stump reamputation and/or hand-suture reinforcement by mattress suture, or myoplasty. We report a simple and successful technique, using azygous vein flaps, to repair an intraoperative BPF associated to a small bronchial dehiscence occurred after a right pneumonectomy in a 70-year-old diabetic man receiving induction chemotherapy treatment.

The aim of this study was to evaluate the safety of continuous nonabsorbable (3/0 polypropylene) sutures for sleeve lobectomy, and the influence of induction chemotherapy on postoperative outcome in patients with lung malignancies.A review of a prospective database of a single surgeon identified 41 consecutive patients who underwent sleeve lobectomy from May 1998 to July 2003. Bronchial reconstruction was done placing two 3/0 polypropylene sutures at the far side of the cartilaginous wall and subsequently fixed. Afterwards, two running sutures were performed in order to obtain a telescopic anastomosis.Twenty-four patients (59%) underwent induction chemotherapy. There were 31 right upper, 3 left lower ''reverse'', and 7 left upper sleeve lobectomies with radical lymph node dissection. Eight patients underwent reconstruction of the pulmonary artery. There were 34 non-small cell lung cancers, 3 limited small cell lung cancers, 1 neuroendocrine large cell carcinoma, and 3 bronchial carcinoid tumors. N2, N1, and N0 diseases were found in 13, 12 and 16 patients, respectively. Post-operative morbidity and mortality were 14.5% (n=6) and 4.8% (n=2) (1 patient, 4%, after induction chemotherapy). The rate of postoperative anastomotic complications was 2.4% (n=1). Late bronchial stenosis developed in 3 cases, but all were successfully medically treated. Twenty-nine patients are still alive, 27 without evidence of disease. The overall 2-year probability of survival (Kaplan-Meier) was 59%. Induction chemotherapy did not influence postoperative morbidity/mortality (chi2 test: P=0.64/P=0.56).Continuous nonabsorbable suture for sleeve lobectomy is quick and technical easy to perform, with low postoperative morbidity/mortality; induction chemotherapy does not influence postoperative outcome in these patients.

The present study describes supportive care (SC) in patients with advanced non-small-cell lung cancer (NSCLC), evaluating whether it is affected by concomitant chemotherapy, patient's performance status (PS) and age. Data of patients enrolled in three randomised trials of first-line chemotherapy, conducted between 1996 and 2001, were pooled. The analysis was limited to the first three cycles of treatment. Supportive care data were available for 1185 out of 1312 (90%) enrolled patients. Gastrointestinal drugs (45.7%), corticosteroids (33.4%) and analgesics (23.8%) were the most frequently observed categories. The mean number of drugs per patient was 2.43; 538 patients (45.4%) assumed three or more supportive drugs. Vinorelbine does not produce substantial variations in the SC pattern, while cisplatin-based treatment requires an overall higher number of supportive drugs, with higher use of antiemetics (41 vs 27%) and antianaemics (10 vs 4%). Patients with worse PS are more exposed to corticosteroids (42 vs 30%). Elderly patients require drugs against concomitant diseases significantly more than adults (20 vs 7%) and are less frequently exposed to antiemetics (12 vs 27%). In conclusion, polypharmacotherapy is a relevant issue in patients with advanced NSCLC. Chemotherapy does not remarkably affect the pattern of SC, except for some drugs against side effects. Elderly patients assume more drugs for concomitant diseases and receive less antiemetics than adults.

Background Nivolumab has shown a survival benefit compared with docetaxel as second-line treatment for patients with previously treated advanced squamous non-small cell lung cancer (NSCLC) in a randomized phase III trial. The experiences of patients and physicians in routine clinical practice are often different from those in a controlled clinical trial setting. We present data from the entire Italian cohort of patients with squamous NSCLC enrolled in a worldwide nivolumab NSCLC expanded access program. Patients and Methods Patients with pretreated advanced squamous NSCLC received nivolumab 3 mg/kg every 2 weeks for up to 24 months. Safety was monitored throughout; efficacy data collected included objective tumor response, date of progression, and survival information. Results The Italian cohort comprised 371 patients who received at least one dose of nivolumab. In the overall population, the objective response rate (ORR) was 18%, the disease control rate (DCR) was 47%, and median overall survival (OS) was 7.9 months (95% confidence interval 6.2–9.6). In subgroup analyses, ORR, DCR, and median OS were, respectively, 17%, 48%, and 9.1 months in patients previously treated with two or more lines of therapy (n = 209) and 8%, 40%, and 10.0 months in patients treated beyond disease progression (n = 65). In the overall population, the rate of any-grade and grade 3–4 adverse events was 29% and 6%, respectively. Treatment-related adverse events led to treatment discontinuation in 14 patients (5%). There were no treatment-related deaths. Conclusion To date, this report represents the most extensive clinical experience with nivolumab in advanced squamous NSCLC in current practice outside the controlled clinical trial setting. These data suggest that the efficacy and safety profiles of nivolumab in a broad, real-world setting are consistent with those obtained in clinical trials. Implications for Practice Nivolumab is approved in the U.S. and Europe for the treatment of advanced non-small cell lung cancer (NSCLC) after failure of prior platinum-based chemotherapy. In this cohort of Italian patients with previously treated, advanced squamous NSCLC treated in a real-world setting as part of the nivolumab expanded access program, the efficacy and safety of nivolumab was consistent with that previously reported in nivolumab clinical trials.

Renal Cell Carcinoma (RCC) is generally characterized by low-FDG avidity, and [18F]FDG-PET/CT is not recommended to stage the primary tumor. However, its role to assess metastases is still unclear. The aim of this study was to evaluate the diagnostic accuracy of [18F]FDG-PET/CT in correctly identifying RCC lung metastases using histology as the standard of truth. The records of 350 patients affected by RCC were retrospectively analyzed. The inclusion criteria were: (a) biopsy- or histologically proven RCC; (b) Computed Tomography (CT) evidence of at least one lung nodule; (c) [18F]FDG-PET/CT performed prior to lung surgery; (d) lung surgery with histological analysis of surgical specimens; (e) complete follow-up available. A per-lesion analysis was performed, and diagnostic accuracy was reported as sensitivity and specificity, using histology as the standard of truth. [18F]FDG-PET/CT semiquantitative parameters (Standardized Uptake Value [SUVmax], Metabolic Tumor Volume [MTV] and Total Lesion Glycolysis [TLG]) were collected for each lesion. Sixty-seven patients with a total of 107 lesions were included: lung metastases from RCC were detected in 57 cases (53.3%), while 50 lesions (46.7%) were related to other lung malignancies. Applying a cut-off of SUVmax ≥ 2, the sensitivity and the specificity of [18F]FDG-PET/CT in detecting RCC lung metastases were 33.3% (95% CI: 21.4–47.1%) and 26% (95%CI: 14.6–40.3%), respectively. Although the analysis demonstrated a suboptimal diagnostic accuracy of [18F]FDG-PET/CT in discriminating between lung metastases from RCC and other malignancies, a semiquantitative analysis that also includes volumetric parameters (MTV and TLG) could support the correct interpretation of [18F]FDG-PET/CT images.

Background. The aim of our study was to evaluateretrospectively in a large single institution setting allcases of lung resections for colorectal metastases from1998 to 2008 and to assess clinicopathologic factorsinfluencing outcome.Methods. In all, 199 patients, 125 men and 74 women,with lung metastases of colorectal cancer, 120 colon and 79rectum, underwent resection with curative intent; meaninterval between primary surgery and lung metastasis was35 months. Carcinoembryonic antigen preoperative valuewas abnormal in 52 patients; K-RAS wild-type wasdetected in 60 of 97 examined cases; 75 patients receivedpreoperative or postoperative chemotherapy or both. Asolitary lesion was described in 95 patients (47.7%), two orthree metastases in 72 (36.2%), and more than three metastasesin 26 (13.1%). Nodal status was reported in 130patients (73%). One hundred twenty patients (60.3%) underwentwedge resection, 27 (13.6%) underwent segmentectomy,and 52 (26.1%) had lobectomy. An R0 resectionwas achieved in 178 cases (89.4%).Results. Median overall survival was 4.2 years (95%confidence interval: 3.1 to 5.1) with a 5-year overallsurvival of 43% (95% confidence interval: 36% to 50%).An R1 resection (log rank p [ 0.0001), thoracic nodalinvolvement (log rank p [ 0.0002), and preoperativeabnormal carcinoembryonic antigen value (log rankp < 0.001) were significantly associated with pooroutcome in univariate analysis. In multivariate analysis,the same variables plus the number of lesions(single versus multiple, p [ 0.04) were shown to affectoutcome.Conclusions. An R0 resection, preoperative carcinoembryonicantigen, nodal involvement, and number oflesions represent strong prognostic factors in patient withlung metastases of colorectal cancer. The role of systemictreatments and biomolecular tests deserve future prospectiveinvestigations.

Palliative airway treatments are essential to improve quality and length of life in lung cancer patients with central airway obstruction. Rigid bronchoscopy has proved to be an excellent tool to provide airway access and control in this cohort of patients. The main indication for rigid bronchoscopy in adult bronchology remains central airway obstruction due to neoplastic or non-neoplastic disease. We routinely use negative pressure ventilation (NPV) under general anaesthesia to prevent intraoperative apnoea and respiratory acidosis. This procedure allows opioid sparing, a shorter recovery time and avoids manually assisted ventilation, thereby reducing the amount of oxygen needed, while maintaining optimal surgical conditions. The major indication for NPV rigid bronchoscopy at our institution has been airway obstruction by neoplastic tracheobronchial tissue, mainly treated by laser-assisted mechanical dissection. When strictly necessary, we use silicone stents for neoplastic or cicatricial strictures, reserving metal stents to cover tracheo-oesophageal fistulae. NPV rigid bronchoscopy is an excellent tool for the endoscopic treatment of locally advanced tumours of the lung, especially when patients have exhausted the conventional therapeutic resources. Laser-assisted mechanical resection and stent placement are the most effective procedures for preserving quality of life in patients with advanced stage cancer.

Introduction: Breast cancer is the leading cause of cancer death among women in the industrialized countries. The incidence of local recurrences after mastectomy and breast-conserving therapy varies between 5% and 40% depending on risk factors and primary therapy. Methods: From April 1999 to April 2011, 40 patients underwent chest wall resection and reconstruction for locally recurrent breast carcinoma with chest wall invasion. The main goal of surgery was local disease control to palliate clinical symptoms. Results: Local radical resection was achieved in 26 patients (65%). One, 2 and 5 year overall survival rates were 94.4%, 82.0% and 68.5%; 1, 2 and 5 year disease-free survival rates were 94.4%, 73.6% and 45.5% respectively.Univariate analysis indicated age (p = 0.002) and synchronous distant metastases (p = 0.020) as factors having a negative impact on overall survival; multivariate analysis disclosed age (p = 0.052) and synchronous metastases (p = 0.059) as factors with a slight negative impact on overall survival. Older age was associated with improved overall survival.Univariate analysis indicated synchronous distant metastases (p = 0.029) and the need of post resectional additional treatments (p = 0.022) as factors adversely conditioning disease-free survival or time to progression; multivariate analysis disclosed the need of post resectional additional treatments (p = 0.036) as the only factor adversely conditioning disease-free survival or time to progression. Conclusions: Chest wall resection and reconstruction for locally recurrent breast cancer is a feasible and safe procedure providing adequate local disease control and an excellent palliation of very disabling symptoms in a selected group of patients.

Introduction: Available information on perioperative blood transfusion practices in oncologic thoracic surgery is scant and outdated. The purpose of this study was to investigate transfusion requirements in patients undergoing curative resection for lung cancer and to identify possible factors predictive of perioperative blood transfusion in our cohort of patients. Methods: From 1st January 2009 to 31st December 2009, 317 patients underwent anatomic pulmonary resection. Patients who received at least 1 unit of red blood cells comprised the "transfused" group. Each case in this group was matched for surgical procedure with a control subject who did not require blood transfusion and was operated on during the same year; these patients comprised the "not transfused" group. Results: A total of 75 patients (23.6%) received at least 1 unit of red blood cells during the perioperative period. Factors conditioning perioperative blood transfusion were: preoperative hemoglobin level (p < 0.0001); procedure duration (p = 0.017); body mass index (p < 0.001); induction therapies (p = 0.017); redo procedure (p = 0.021). Age, sex, histology, stage, ASA score, side, intraoperative blood loss, and fluid infusion did not affect perioperative blood transfusion practices. Conclusions: Preoperative hemoglobin level is the major risk factor for perioperative blood transfusion practices in oncologic thoracic surgery; procedure duration, body mass index, induction therapies, and redo procedure may condition transfusional needs, although they were actually not predictive on multivariate analysis. © 2011 Society of Surgical Oncology.

Objective Tracheal sleeve pneumonectomy is a challenge in lung cancer management and in achieving long-term oncological results. In November 2018, we started a prospective study on the role of extracorporeal membrane oxygenation (ECMO) in tracheal sleeve pneumonectomy. We aim to present our preliminary results. Methods From November 2018 to November 2019, six patients (three men and three women; median age: 61 years) were eligible for tracheal sleeve pneumonectomy for lung cancer employing the veno-venous ECMO during tracheobronchial anastomosis. Results Only in one patient, an intrapericardial pneumonectomy without ECMO support was performed, but cannulas were maintained during surgery. The median length of surgery was 201 minutes (range: 162–292 minutes), and the average duration of the apneic phase was 38 minutes (range: 31–45 minutes). No complications correlated to the positioning of the cannulas were recorded. There was only one major postoperative complication (hemothorax). At the time of follow-up, all patients were alive; one patient alive with bone metastasis was being treated with radiotherapy. Conclusion ECMO-assisted oncological surgery was rarely described, and its advantages include hemodynamic stability with low bleeding complications and a clean operating field. As suggested by our preliminary data, ECMO-assisted could be a useful alternative strategy in select lung cancer patients.

OBJECTIVES A few studies have already demonstrated survival benefits for local treatment in solitary metastatic non-small-cell lung cancer (NSCLC). The aim of this study is to retrospectively investigate the role of surgery in patients with oligometastatic (OM) NSCLC. METHODS Between January 1998 and December 2018, 57 patients with OM stage IV NSCLC (1 or 2) underwent a multidisciplinary approach including lung cancer surgery, local treatment of the distant metastasis (DM) and systemic medical treatments. RESULTS All patients had DM synchronous to lung cancer. Fifty-one (90%) patients had a single DM whereas 6 (11%) patients had 2 DMs. Forty-eight (84%) patients underwent induction chemotherapy. We performed 47 (82%) lobectomies, 4 (7%) segmentectomies and 6 (11%) pneumonectomies. Pathological lymph node involvement was evident in 28 (49%) patients. Adjuvant chemotherapy was administered in 20 (35%) patients. Forty-six (81%) patients had local treatment of the DM before lung resection, and 11 (19%) patients had after lung resection; 6 (11%) patients had both treatments. The median overall survival (OS) was 30 months, with the 2-, 3- and 5-year OS of 57%, 50% and 30%, respectively. OS was significantly related to lymph node involvement (P = 0.04), size of the primary tumour (P CONCLUSIONS Multidisciplinary approach is the gold standard in OM patients. Patients with no lymph node involvement are the best candidates, with an acceptable OS. Thus, patients with OM-NSCLC should not be excluded from surgery as a matter of principle.

INTRODUCTION: Robotic-assisted surgery has become the first choice for several conditions since its introduction in clinical practice in 2000. However, the U.S. Food and Drug Administration has recently raised a warning against the use of robotic surgical approaches for the cure and prevention of cancer following the publication of two studies focused on endometrial cancer. We conducted an internal audit to retrospectively analyze our experience to assess the safety and feasibility of robotic-assisted surgery compared to open surgery. METHODS: We selected a 5-year period to guarantee at least 2 years of follow-up (2011-2016) and identified 1139 patients who underwent lobectomy for non-small-cell lung cancer (NSCLC) in our division. The primary data set analyzed included 544 early-stage clinical N0 patients (348 open and 196 robotic surgeries). We compared 131 patients of each group individually matched, with demographic and clinical characteristics almost identical. RESULTS: No difference was observed between the cohorts, either in terms of recurrence-free survival (hazard ratio: 1.09; p = 0.55) or overall survival (hazard ratio: 0.86; p = 0.36). The 5-year recurrence of disease risk and overall survival were 24.9% and 83.2%, respectively, in the open group and 24.6% and 86.1%, respectively, in the robotic group. CONCLUSIONS: These data underline that robotic-assisted lobectomy for early NSCLC is a safe and feasible technique with adequate long-term and progression-free survival compared to open surgery.

Rat sarcoma (RAS) oncogenes have intensively been investigated during the last decades. Taking into account all human tumours, Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) gene is the most frequently mutated (about 22%) among the three isoforms, followed by Neuroblastoma RAS Viral Oncogene Homolog (NRAS) (8%) and Harvey Rat Sarcoma Viral Oncogene Homolog (HRAS) (3%). In the last years, careful attention has been paid on KRAS and NRAS gene mutations in non-small-cell lung cancer (NSCLC) and colorectal cancer (CRC) patients because of their prognostic and predictive roles. In particular, a large body of literature data has been generated investigating clinical outcomes of targeted treatments in NSCLC and CRC KRAS- and NRAS-mutated patients. The latest evidences are here reviewed, providing also an overview of the real-world RAS mutation testing practice across different Italian laboratories. On this basis, we propose a knowledge-based system, www.rasatlas.com, to support the healthcare personnel in the management of patients featuring RAS gene mutations in the landscape of precision oncology.

Despite promising results obtained in the early diagnosis of several pathologies, breath analysis still remains an unused technique in clinical practice due to the lack of breath sampling standardized procedures able to guarantee a good repeatability and comparability of results. The most diffuse on an international scale breath sampling method uses polymeric bags, but, recently, devices named Mistral and ReCIVA, able to directly concentrate volatile organic compounds (VOCs) onto sorbent tubes, have been developed and launched on the market. In order to explore performances of these new automatic devices with respect to sampling in the polymeric bag and to study the differences in VOCs profile when whole or alveolar breath is collected and when pulmonary wash out with clean air is done, a tailored experimental design was developed. Three different breath sampling approaches were compared: (a) whole breath sampling by means of Tedlar bags, (b) the end-tidal breath collection using the Mistral sampler, and (c) the simultaneous collection of the whole and alveolar breath by using the ReCIVA. The obtained results showed that alveolar fraction of breath was relatively less affected by ambient air (AA) contaminants (p-values equal to 0.04 for Mistral and 0.002 for ReCIVA Low) with respect to whole breath (p-values equal to 0.97 for ReCIVA Whole). Compared to Tedlar bags, coherent results were obtained by using Mistral while lower VOCs levels were detected for samples (both breath and AA) collected by ReCIVA, likely due to uncorrected and fluctuating flow rates applied by this device. Finally, the analysis of all data also including data obtained by explorative analysis of the unique lung cancer (LC) breath sample showed that a clean air supply might determine a further confounding factor in breath analysis considering that lung wash-out is species-dependent.

Epidermal growth factor receptor (EGFR) exon 20 insertions occur rarely among different cancer types, with the highest frequency reported among non-small-cell lung cancer (NSCLC) patients, particularly adenocarcinomas (ADCs). Exon 20 insertions fall back in the tyrosine kinase domain, and can be clustered into two principal groups represented by in frame insertions and three to 21 bp (corresponding to 1–7 amino acids) duplications within amino acids 762 and 774. The identification of these alterations is key for an adequate management of NSCLC patients due to the possibility to treat these patients with specific targeted therapies. Next generation sequencing (NGS) technology, able to detect several hotspot gene mutations for different patients simultaneously, is the best detection approach due to its higher sensitivity and specificity compared to other techniques. Here we reviewed the principal biological characteristics, the main detection technologies and treatment options for NSCLC patients harbouring EGFR exon 20 insertions.

Objectives While the best approach to malignant pleural mesothelioma has yet to be demonstrated, surgery remains the mainstay of treatment. We analysed a group of candidates for trimodality treatment, aiming to identify prognostic factors guiding patient selection. Methods Between 2003 and 2015, 83 (31.6%) of the 283 patients with malignant pleural mesothelioma were considered for trimodality treatment to perform induction chemotherapy, extrapleural pneumonectomy and adjuvant radiotherapy. All patients underwent cisplatin-based chemotherapy. Radiotherapy was administered at a mean dose of 50.4 Gy. Results Thirty-six patients (43.4%) had 3 cycles of chemotherapy, whereas 21 (25.3%) had more than 3. Progression to chemotherapy was observed in 10.9% (9 of 83) of patients, partial response in 30.1% (25 of 83) and stable disease in 59% (49 of 83). Sixty-three patients underwent extrapleural pneumonectomy. Fifty-five patients (87.3%) had epithelial tumour. Forty-two patients (66.7%) were in pathological Stage 3. Major complications after extrapleural pneumonectomy were observed in 28 patients (44.4%), whereas 30-day postoperative mortality was 11.1% (7/63). Radiotherapy was not administered in 24 patients (38.1%) due to major complications after surgery or patient intolerance. Two patients (3.2%) died within 90 days after the end of radiotherapy. The trimodality treatment was completed in 37 (44.6%) patients. Median overall survival was 35.6 months, with 1- and 3-year overall survival of 82% and 48% for patients who completed the trimodality treatment compared with 32% and 14% for patients who did not undergo radiotherapy. Conclusions Only 45% of patients completed the planned trimodality treatment, and morbidity/mortality remained high. Nonetheless, the patients who completed treatment showed good loco-regional disease control and better overall survival.

OBJECTIVES The aim of this study was to assess the postoperative outcomes of robotic-assisted lobectomy in obese patients to determine the impact of the robotic approach on a high-risk population who were candidates for major pulmonary resection for non-small-cell lung cancer (NSCLC). METHODS Between January 2007 and August 2018, we retrospectively reviewed the medical records of 224 obese patients (body mass index ≥ 30) who underwent pulmonary lobectomy at our institution via robotic-assisted thoracic surgery (RATS, n = 51) or lateral muscle-sparing thoracotomy (n = 173). RESULTS Forty-two patients were individually matched with those who had the same pathological tumour stage and similar comorbidities and presurgical treatment. The median operative time was significantly longer in the RATS group compared to that in the thoracotomy group (200 vs 158 min; P = 0.003), whereas the length of stay was significantly better for the RATS group (5 vs 6 days; P = 0.047). Postoperative complications were significantly more frequent after open lobectomy than in the RATS group (42.9% vs 16.7%; P = 0.027). After a median follow-up of 4.4 years, the 5-year overall survival rate was 67.6% [95% confidence interval (CI) 45.7–82.2] for the RATS group, and 66.1% (95% CI 46.8–79.9) for the open surgery group (log-rank P = 0.54). The 5-year cumulative incidence of cancer-related deaths was 24.8% (95% CI 9.7–43.5) for the RATS group and 23.6% (95% CI 10.8–39.2) for the open surgery group (Gray’s test, P = 0.69). CONCLUSIONS RATS is feasible and safe for obese patients with NSCLC with advantages compared to open surgery in terms of early postoperative outcomes. In addition, the long-term survival rate was comparable to that of the open approach.