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Abstract: Background: More than 50% of brain metastases (BMs) occur in advanced non-small cell lung cancer (NSCLC) patients. Untreated patients with BMs have a poor prognosis with a median survival of 2 months. In most cases BMs are multiple and their optimal therapy is whole-brain radiation therapy (WBRT). The role of systemic therapies for these patients is still a matter for investigation due to concerns about the ability of these drugs to cross the blood–brain barrier (BBB). Cisplatin (CDDP) remains the backbone for medical treatment of NSCLC and fotemustine (FTM) is a nitrosurea able to cross the BBB. Methods: Patients with advanced NSCLC, ECOG performance status (PS) 0–1 and multiple BMs not amenable to surgery or stereotactic radiotherapy were treated with 2 cycles of FTM 80mg/m2 days 1, 8 and CDDP 80mg/m2 day 1, every 3 weeks followed by WBRT 30Gy (3Gy daily in 10 fractions). Radiological restaging was performed before WBRT to assess the role of chemotherapy both for cranial and extracranial disease. Patients with disease control (DC: complete response plus partial response) received 4 more cycles. To assess the basic activities of daily living (ADL), the Barthel ADL Index was used to score patients’ performance every 2 cycles. The trial design provides a two-step evaluation according to the optimal two-stage design of Simon. In the first phase 29 patients were enrolled in order to verify if this schedule showed more than 25% response rate both for cranial and extracranial disease. If so, enrolment added up to a total of 81 patients. Results: After the first evaluation 4 out of 29 patients were excluded from the study (3 untreated/1 not included for administrative reasons). At the time of the planned interim analysis patient''s characteristics were the following: median age 61 years (range 44–70), M/F=16/9, adenocarcinoma 11, squamous 5, large cell 2, undefined NSCLC 7; PS 0/1 in 11/14 cases, median Barthel Index score was 20 . Three (12%) partial responses were observed, 9 subjects (36%) with stable disease and 13 (52%) showing disease progression. These data did not satisfy the pre-planned hypothesis and the study was stopped. At the time of the first evaluation before WBRT 12/25 (48%) patients had a systemic DC in contrast with 15/25 (60%) patients with BMs DC. Chemotherapy was relatively well tolerated with a prevalence of asthenia as the most relevant specific toxicity while the haematological toxicity was mild. Conclusion: CDDP and FTM combined with WBRT do not represent a therapeutic option for patients with NSCLC. Therefore further studies to evaluate the combination of systemic treatments with WBRT are warranted. [Copyright &y& Elsevier]

Background: Several video-assisted techniques have been used to treat primary spontaneous pneumothorax (PSP). The aim of this study was to evaluate the results of thoracoscopic pleural abrasion for PSP.Methods: From 1991 to 2003, 185 consecutive patients, 143 male and 42 female, aged 15 to 60 years (average 31.6) underwent thoracoscopic pleural abrasion for PSP. The indications for surgery were as follows: a first episode with persistent air leak in 33 patients (17.9%), a recurrent ipsilateral pneumothorax in 122 patients (65.9%), a previous contralateral pneumothorax in 23 patients (12.4%), and recurrence after surgical treatment in seven patients (3.8%). Bullae were resected in 163 patients (88.1%). Mechanical pleural abrasion was performed in all cases.Results: There were no deaths. Intraoperative hemorrhage occurred in three patients. It was controlled via thoracotomy in one patient and via thoracoscopy in two patients. The postoperative complication rate was 8.1% (15/185). Complications included prolonged air leak in eight patients (4.3%), pleural effusion in two (1.1%), extrapleural hematoma in one (0.5%), chest wall infection in one (0.5%), atelectasis in one (0.5%), and hemorrhage in two (1.1%). Postoperative hospital stay ranged between 2 and 17 days (mean, 5). Mean duration of drainage was 3.8 days (range; 1-16). Postoperatively, 111 patients were contacted, with a mean follow-up of 36.5 months. Four of them had a recurrence (3.6%) that did not require reoperation.Conclusion: Thoracoscopic pleural abrasion associated with bullae resection is a safe and efficient treatment for PSP. Results remain stable in the long term. [ABSTRACT FROM AUTHOR]

Patients with advanced non-small-cell lung cancer (NSCLC) treated with immune checkpoint blockers (ICBs) ultimately progress either rapidly (primary resistance) or after durable benefit (secondary resistance). The cancer vaccine OSE2101 may invigorate antitumor-specific immune responses after ICB failure. The objective of ATALANTE-1 was to evaluate its efficacy and safety in these patients. ATALANTE-1 was a two-step open-label study to evaluate the efficacy and safety of OSE2101 compared to standard-of-care (SoC) chemotherapy (CT). Patients with human leukocyte antigen (HLA)-A2-positive advanced NSCLC without actionable alterations, failing sequential or concurrent CT and ICB were randomized (2 : 1) to OSE2101 or SoC (docetaxel or pemetrexed). Primary endpoint was overall survival (OS). Interim OS futility analysis was planned as per Fleming design. In April 2020 at the time of interim analysis, a decision was taken to prematurely stop the accrual due to coronavirus disease 2019 (COVID-19). Final analysis was carried out in all patients and in the subgroup of patients with ICB secondary resistance defined as failure after ICB monotherapy second line ≥12 weeks. Two hundred and nineteen patients were randomized (139 OSE2101, 80 SoC); 118 had secondary resistance to sequential ICB. Overall, median OS non-significantly favored OSE2101 over SoC {hazard ratio (HR) [95% confidence interval (CI)] 0.86 [0.62-1.19], P = 0.36}. In the secondary resistance subgroup, OSE2101 significantly improved median OS versus SoC [11.1 versus 7.5 months; HR (95% CI) 0.59 (0.38-0.91), P = 0.017], and significantly improved post-progression survival (HR 0.46, P = 0.004), time to Eastern Cooperative Oncology Group (ECOG) performance status deterioration (HR 0.43, P = 0.006) and Quality of Life Questionnaire Core 30 (QLQ-C30) global health status compared to SoC (P = 0.045). Six-month disease control rates and progression-free survival were similar between groups. Grade ≥3 adverse effects occurred in 11.4% of patients with OSE2101 and 35.1% in SoC (P = 0.002). In HLA-A2-positive patients with advanced NSCLC and secondary resistance to immunotherapy, OSE2101 increased survival with better safety compared to CT. Further evaluation in this population is warranted. • The study compared survival with cancer vaccine OSE2101 versus CT in NSCLC patients after immunotherapy failure. • In patients with secondary resistance to sequential CT-ICB, survival was improved with OSE2101 compared to CT. • Quality of life, preservation of ECOG performance status 0 or 1 and safety were statistically better with OSE2101 compared to CT. • OSE2101 had a favorable benefit/risk versus CT in NSCLC patients with secondary resistance that merits further evaluation. [ABSTRACT FROM AUTHOR]

Pulmonary hyalinising granulomas (PHG) are rare. They are defined by the presence of collagen lamellar fibrosis. One third are associated with retroperitoneal or mediastinal fibrosis. Two cases of PHG are presented. They were revealed by dysphagia due to tight oesophageal stricture from associated mediastinal fibrosis. PHG are considered as a benign and slowly evolving disease, but associated mediastinal fibrosis may evolve on its own. Only steroid therapy may slow down progression. This makes an accurate diagnosis necessary. It relies on large surgical biopsies. [Copyright &y& Elsevier]

• Pleomorphic lung carcinoma (PLC) is a rare histotype of lung cancer. • PLC is characterized by aggressive clinical course and poor prognosis. • 18F-FDG PET/CT can be helpful in stratification of patients. • Metabolic parameters such as SUVmax, MTV and TLG provide additional information. Pleomorphic lung carcinoma (PLC) is a rare histotype of non-small cell lung cancer (NSCLC) characterized by aggressive clinical course, poor response to therapy and poor prognosis. Therefore, aim of our study is to analyze with 18F-FDG PET/CT a subset of patients affected by PLC to evaluate their metabolic characteristics in terms of SUVmax, MTV and TLG, in order to correlate them with overall survival (OS) and disease-free survival (DFS). We retrospectively analyzed 49 consecutive patients with histologically defined PLC occurred to our Institution between 2003 and 2014. All patients underwent F18-FDG PET-CT before surgery and primary tumor was automatically segmented using an isocontour threshold method. SUV threshold for tumor segmentation was defined as the 41 % of lesion SUVmax. Total volume of the segmented VOI (MTV, centimeters cubed) and average SUV (SUVavg, grams per milliliter) in the segmented VOI were measured. In our population men were significantly more affected than women (42:7). According to Youden criteria, SUVmax, MTV41 and TLG41 best cut-off values to predict 2-year mortality were, 18.95, 27.89 and 290.45, respectively, with TLG41 showing best specificity (85 %) and positive predictive value (82.4 %). As concerning 2-year recurrence, SUVmax, MTV41 and TLG41 best cut-off values were 10.08, 27.89 and 134.85, with SUVmax showing best sensitivity (96.7 %) and negative predictive value (85.7 %). ROC curves confirmed that SUVmax, MTV41 and TLG41 were equally accurate to predict 2-year mortality and 2-year recurrence in our population. Metabolic biomarkers such as SUVmax, MTV and TLG can be used as a prognostic index for disease progression, recurrence and death in patients with PLC, independently from other clinical/pathological prognostic elements. [ABSTRACT FROM AUTHOR]

Purpose: Chemotherapy-induced nausea and vomiting (CINV) still represents a common side-effect of chemotherapy, and often, its perception differs between patients and healthcare professionals. The aim of this study was to evaluate the agreement on the perception of CINV and other items among clinicians, patients, and nurses.Methods: This observational prospective study was part of an evaluation program promoted by the Women Against Lung Cancer in Europe (WALCE) Onlus. From August 2015 to February 2016, a survey was administered in 11 oncologic institutions to 188 stage IV lung cancer patients and to their oncologists and nurses during first-line chemotherapy. Our survey investigated 11 aspects: anxiety, mood, weakness, appetite, nausea, vomiting, pain, drowsiness, breath, general condition, and trust in treatments. These items were assessed through Numerical Rating Scale at four consecutive evaluations: at T0 (immediately prior to the first cycle), at T1 (immediately prior to the second cycle), at T2 (immediately prior to the third cycle), and at T3 (immediately prior to the fourth cycle). Clinician versus patient (CvP), nurse versus patient (NvP), and clinician versus nurse (CvN) agreements were estimated applying Weighted Cohen's kappa. A multivariate logistic model and generalized equation estimates were applied to evaluate factors possibly influencing CINV development.Results: The incidence of patients reporting CINV varied from 40% at T0 to 71% at T3. Both CvP and NvP agreement on the investigated items were mainly moderate, slightly increasing over time, and becoming substantial for some items, in particular for NvP. Pre-chemotherapy anxiety in its mild, moderate, and severe manifestations, as well as mild, moderate, and severe anxiety experienced after chemotherapy start, exposed patients to a higher risk of anticipatory and acute/delayed CINV, respectively.Conclusions: Despite clinical staff awareness of patients' status and perceptions, CINV still represents a clinical problem. This study confirms that particular attention should be paid to anxiety due to its key role in CINV development. [ABSTRACT FROM AUTHOR]

Lung neuroendocrine tumors are catalogued in four categories by the World Health Organization (WHO 2004) classification. Its reproducibility and prognostic efficacy was disputed. The WHO 2010 classification of digestive neuroendocrine neoplasms is based on Ki67 proliferation assessment and proved prognostically effective. This study aims at comparing these two classifications and at defining a prognostic grading system for lung neuroendocrine tumors. The study included 399 patients who underwent surgery and with at least 1 year follow-up between 1989 and 2011. Data on 21 variables were collected, and performance of grading systems and their components was compared by Cox regression and multivariable analyses. All statistical tests were two-sided. At Cox analysis, WHO 2004 stratified patients into three major groups with statistically significant survival difference (typical carcinoid vs atypical carcinoid (AC), PZ0.021; AC vs large-cell/small-cell lung neuroendocrine carcinomas, P<0.001). Optimal discrimination in three groups was observed by Ki67% (Ki67% cutoffs: G1 <4, G2 4-<25, G3 R≥25; G1 vs G2, P=0.021; and G2 vs G3, P≤0.001), mitotic count (G1 ≤2, G2 >2-47, G3 >47; G1 vs G2, P≤0.001; and G2 vs G3, P≤0.001), and presence of necrosis (G1 absent, G2 <10% of sample, G3 >10% of sample; G1 vs G2, P≤0.001; and G2 vs G3, P≤0.001) at uni and multivariable analyses. The combination of these three variables resulted in a simple and effective grading system. A three-tiers grading system based on Ki67 index, mitotic count, and necrosis with cutoffs specifically generated for lung neuroendocrine tumors is prognostically effective and accurate. [ABSTRACT FROM AUTHOR]

Background: In literature there are only a few descriptions of the typical presentation of solitary fibrous tumours (SFT) and only a few case reports showing its unusual clinical and radiological features. Methods: We retrospectively evaluated the computed tomography scans of 36 patients presenting with a histological diagnosis of SFT between 1998 and 2008. Results: We present five cases of SFT with an atypical clinical presentation and radiological features. Conclusions: SFT can occasionally present with unusual radiological features making a differential diagnosis difficult. Even thought imaging plays a fundamental role in the initial diagnostic approach, final diagnosis in only confirmed by biopsy and histology. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The purpose of this study was to evaluate the efficacy of a protein-based pattern in serum previously determined by MALDI-TOF-MS (Matrix Assisted Laser Desorption Ionization-Time of Flight) and considered potentially useful for prediction of clinical outcome of EGFR (epidermal growth factor receptor) TKIs (tyrosine kinase inhibitors) treated patients. Design and methods: We generated SELDI-TOF (Surface Enhanced Laser Desorption Ionization-Time of Flight) spectra in sera of 11 advanced NSCLC treated with Gefitinib. We detected the clusters with m/z 5843, 11445, 11529, 11685, 11759 and 11903 which were previously reported to be potential predictors of response to Gefitinib treatment. Results: Four cluster peaks with m/z 5843, 11445, 11529, 11685 corresponded to SAA (serum amyloid A) protein on the basis on their calculated molecular weight, peptide fingerprinting and antibodies recognition. Conclusions: We confirm that several proteins already reported were isoforms of SAA but further studies are in development in order to evaluate the predictive value of such algorithm. [Copyright &y& Elsevier]

Background: Prolonged air leak after pulmonary lobectomy is a common time- and cost-consuming complication. Its prevention may significantly reduce hospitalization length and costs offering patients a standard uneventful postoperative course. The aim of the present study is to identify predictors of prolonged postoperative air leak and to stratify preoperative risk factors. Methods: From July 2004 to December 2007 241 consecutive standard lobectomies were performed with curative intent for lung cancer. After excluding patients not fulfilling the inclusion criterion, 58 patients were enrolled in the "prolonged air leak" group and 63 patients were enrolled in the "standard outcome" group. Results: Total lung capacity (p=0.0038) and percentage emphysema (p=0.0050) calculated by computed tomography were both significantly related to prolonged postoperative air leak; the values of 4773cc and 0.4% showed the highest predictive value in terms of sensitivity (84.5% and 75.9% respectively). Multivariate logistic regression disclosed that male sex (p=0.0006), right side of operation (p=0.0010) and age (p=0.0082) were significantly related to prolonged postoperative air leak. Preoperative chemotherapy (p=0.0940) did not affect air leak status. Conclusions: Computed tomography quantification of emphysema is the best predictor of prolonged air leak. Age, male sex and right side lobectomy are correlated to this complication. Preoperative chemotherapy is not an additional risk factor. [ABSTRACT FROM AUTHOR]

BACKGROUND: The addition of cyclo-oxygenase-2 (COX-2) inhibitors and prolonged constant infusion (PCI) of gemcitabine to treatment for advanced non-small-cell lung cancer (NSCLC) might improve treatment efficacy. We aimed to assess whether the addition of rofecoxib or PCI gemcitabine could improve overall survival compared with first-line treatment with cisplatin plus gemcitabine given by standard infusion. METHODS: Patients with stage IV or IIIb (with supraclavicular nodes or pleural effusion) NSCLC who were under 70 years of age and who had performance status 0 or 1 were eligible for this multicentre, prospective, open-label, randomised phase III trial with 2x2 factorial design. Patients were randomly assigned to one of four treatment groups: group A, gemcitabine 1200 mg/m(2) in a 30-min intravenous infusion on days 1 and 8 and intravenous cisplatin 80 mg/m(2) on day 1, every 21 days for six cycles; group B, the same treatments as group A plus oral rofecoxib 50 mg/day until disease progression; group C, intravenous PCI gemcitabine 1200 mg/m(2) in a 120-min infusion on days 1 and 8 and intravenous cisplatin 80 mg/m(2) on day 1, every 21 days for six cycles; group D, the same drugs as group C plus oral rofecoxib 50 mg/day until disease progression. The primary endpoint was overall survival; secondary endpoints were progression-free survival, response rate, quality of life, and toxicity. Analyses were intention-to-treat. This trial is registered on the clinical trials site of the US National Institutes of Health website http://clinicaltrials.gov/ct/show/NCT00385606. FINDINGS: Between Jan 30, 2003, and May 3, 2005, 400 patients were enrolled. Median age was 60 years (range 29-71). PCI gemcitabine did not improve overall survival (median 47 weeks [95% CI 40-55] vs 44 [36-52], with standard gemcitabine infusion, hazard ratio (HR) of death 0.93 [0.74-1.17], p=0.41), progression-free survival, nor any other secondary endpoint. Vomiting and fatigue were significantly worse with PCI gemcitabine. The two rofecoxib groups were closed early (on Oct 1, 2004) due to withdrawal of the drug because of safety issues. With intention-to-treat statistical analyses limited to 240 patients (ie, those randomised before July 1, 2004) who had at least 3 months of treatment, rofecoxib did not prolong overall survival (median 44 weeks [CI 36-55] vs 44 [40-54] without rofecoxib, and HR of death 1.00 [0.75-1.34], p=0.85), or progression-free survival, but did improve response rate (41%vs 26%, p=0.02), global quality of life, physical, emotional and role functioning, fatigue, and sleeping. Rofecoxib significantly increased the incidence of diarrhoea and decreased constipation, fatigue, fever, weight loss, and pain, and analgesic consumption. Severe cardiac ischaemia was more frequent with rofecoxib than without; however, the difference was not statistically significant in the primary analysis (p=0.06) and became significant when patients who were randomised between July 1, 2004, and Sept 30, 2004, were included in the analysis (p=0.03). INTERPRETATION: Neither PCI gemcitabine nor rofecoxib prolonged survival in the patients in this study. Rofecoxib improved response rate and several quality-of-life items, including pain-related items and global quality of life. Further studies with less cardiotoxic COX-2 inhibitors are needed in NSCLC. [ABSTRACT FROM AUTHOR]