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This is the first case report of a non-small-cell lung cancer (NSCLC) patient harboring HIP1-ALK (H28:A20) and CTNNB1 p.S45del treated with first-line alectinib. Approximately 5% of NSCLC patients are reported to have anaplastic lymphoma kinase (ALK) rearrangements, and among these EML4-ALK is the most frequent fusion variant. However, in recent years the use of next-generation sequencing (NGS) in clinical laboratories has become increasingly widespread, identifying a lot of new ALK fusion partners as well as a large quantity of co-occurring genomic alterations. Unfortunately, the growing number of genomic alterations detected by NGS does not always correspond to adequate knowledge of their clinical significance, often resulting in an empiric treatment of patients harboring uncommon mutations., (© 2024 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

Introduction: Malignant pleural mesothelioma (MPM) is a poor-prognosis disease. Owing to the recent availability of new therapeutic options, there is a need to better assess prognosis. The initial clinical response could represent a useful parameter., Methods: We proposed a transfer learning approach to predict an initial treatment response starting from baseline CT scans of patients with advanced/unresectable MPM undergoing first-line systemic therapy. The therapeutic response has been assessed according to the mRECIST criteria by CT scan at baseline and after two to three treatment cycles. We used three slices of baseline CT scan as input to the pre-trained convolutional neural network as a radiomic feature extractor. We identified a feature subset through a double feature selection procedure to train a binary SVM classifier to discriminate responders (partial response) from non-responders (stable or disease progression)., Results: The performance of the prediction classifiers was evaluated with an 80:20 hold-out validation scheme. We have evaluated how the developed model was robust to variations in the slices selected by the radiologist. In our dataset, 25 patients showed an initial partial response, whereas 13 patients showed progressive or stable disease. On the independent test, the proposed model achieved a median AUC and accuracy of 86.67% and 87.50%, respectively., Conclusions: The proposed model has shown high performance even by varying the reference slices. Novel tools could help to improve the prognostic assessment of patients with MPM and to better identify subgroups of patients with different therapeutic responsiveness., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Fanizzi, Catino, Bove, Comes, Montrone, Sicolo, Signorile, Perrotti, Pizzutilo, Galetta and Massafra.)

Background: Mesenchymal-epithelial transition (MET) exon 14 (METex14) skipping mutation is a rare alteration in non-small-cell lung cancer (NSCLC), occurring in about 3%-4% of cases. Here we report disease and patient characteristics, and efficacy and tolerability of MET inhibitors among advanced METex14 NSCLC patients from the Italian real-world registry ATLAS., Materials and Methods: Clinical-pathological and molecular data, and treatment efficacy/tolerability outcomes were retrospectively collected from the ATLAS registry., Results: From July 2020 to July 2023 a total of 146 METex14 advanced NSCLC patients were included across 27 Italian centers. Median age was 74 years, and most patients were male (52%), with an Eastern Cooperative Oncology Group performance status < 2 (72%) and adenocarcinoma subtype (83%). One hundred and twenty-five out of 146 (86%) patients received at least one line of systemic anticancer therapy. Fifty-six (38%) were treated with capmatinib and 34 (23%) with tepotinib. 29% and 52% of them received targeted treatment in the first and second line, respectively. In the cohort of patients treated with MET inhibitors, the response rate (RR) was 37% (33% in previously treated patients and 46% in treatment-naïve) with a disease control rate of 62%. With a median follow-up of 10.8 months, progression-free survival was 6.6 months [95% confidence interval (CI) 4.3-8.3 months] and overall survival was 10.7 months (95% CI 7.2-19.3 months). In patients with measurable brain metastases (17 cases), the intracranial RR was 41%. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 12% of patients with grade 3 peripheral edema in 7% of cases. A fatal adverse reaction occurred in one patient due to pneumonitis. TRAEs-related dose reduction and discontinuation were reported in 6% and 8% of cases, respectively., Conclusion: Capmatinib and tepotinib represent an effective treatment option in NSCLC patients with METex14. Real-world efficacy outcomes are worse than those reported in prospective clinical trials. Their activity is more pronounced in the treatment-naïve population, suggesting that this is the right setting in the management of patients with METex14., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Older patients have similar immune checkpoint inhibitor efficacy and rates of adverse events as younger patients, but appear to have decreased tolerability, particularly in the oldest patient cohort (>80 years), often leading to early cessation of therapy. We aimed to determine whether early discontinuation impacts efficacy of anti-PD-1 therapy in patients ≥80 years old. In this retrospective, multicenter, international cohort study, we examined 773 patients with 4 tumor types who were at least 80 years old and treated with anti-PD-1 therapy. We determined response rate, overall survival (OS), and progression-free survival (PFS) in patients who discontinued therapy early (<12 months) for reasons other than progression or death. We used descriptive statistics for demographics, response, and toxicity rates. Survival statistics were described using Kaplan Meier curves. Median (range) age at anti-PD-1 initiation was 83.0 (75.8-97.0) years. The cancer types included were melanoma (n = 286), non-small cell lung cancer (NSCLC) (n = 345), urothelial cell carcinoma (UCC) (n = 108), and renal cell carcinoma (RCC) (n = 34). Of these, 102 met the primary endpoint of <12 months to discontinuation for reasons other than death or progression. Median PFS and OS, respectively, for these patients were 34.4 months and 46.6 months for melanoma, 15.8 months and 23.4 months for NSCLC, and 10.4 months and 15.8 months for UCC. This study suggests geriatric patients who have demonstrated therapeutic benefit and discontinued anti-PD-1 therapy at less than 12 months of duration for reasons other than progression may have durable clinical benefit without additional therapy., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Alessio Cortellini declares grants for consultancies/advisory boards from MSD, OncoC4, IQVIA, AstraZeneca, Access Infinity, Ardelis-Health, Alpha Sight, Roche, REGENERON; speaker fees from AstraZeneca, Eisai, Pierre-Fabre, MSD, Sanofi/REGENERON; writing/editorial activity from BMS, MSD; travel support from Sanofi, MSD. Anwaar Saaed reports research grants (to institution) from AstraZeneca, Bristol-Myers Squibb, Merck, Clovis, Exelixis, Actuate therapeutics, Incyte Corporation, Daiichi Sankyo, Five prime therapeutics, Amgen, Innovent biologics, Dragonfly therapeutics, Oxford biotherapeutics, KAHR medical, Biontech, and advisory board/consulting fees from AstraZeneca, Bristol-Myers Squibb, Merck, Xilio therapeutics, Arcus therapeutics, Exelixis, Pfizer, and Daiichi Sankyo. Akiva Diamond served on an Advisory Board for Incyte. Christopher Hoimes has served on advisory boards or as a consultant for BMS, Merck, Seagen. Amin H. Nassar receives honoraria from OncLive, TEMPUS, and Korean Society for Medical Oncology and received consulting fees from Guidepoint Global. Dwight Owen discloses research funding (to institution) from BMS, Merck, Genentech, Palobiofarma, and Onc.AI. Toni Choueiri reports institutional and/or personal, paid and/or unpaid support for research, advisory boards, consultancy, and/or honoraria past 5 years, ongoing or not, from: Alkermes, AstraZeneca, Aravive, Aveo, Bayer, Bristol Myers-Squibb, Calithera, Circle Pharma, Deciphera Pharmaceuticals, Eisai, EMD Serono, Exelixis, GlaxoSmithKline, Gilead, HiberCell, IQVA, Infinity, Ipsen, Jansen, Kanaph, Lilly, Merck, Nikang, Nuscan, Novartis, Oncohost, Pfizer, Roche, Sanofi/Aventis, Scholar Rock, Surface Oncology, Takeda, Tempest, Up-To-Date, CME events (Peerview, OncLive, MJH, CCO and others), outside the submitted work. TC also reports institutional patents filed on molecular alterations and immunotherapy response/toxicity, and ctDNA; equity: Tempest, Pionyr, Osel, Precede Bio, CureResponse, InnDura Therapeutics, Primium; committees: NCCN, GU Steering Committee, ASCO/ESMO, ACCRU, KidneyCan; medical writing and editorial assistance support may have been funded by Communications companies in part; no speaker's bureau. TC entored several non-US citizens on research projects with potential funding (in part) from non-US sources/Foreign Components. The institution of TC (Dana-Farber Cancer Institute) may have received additional independent funding of drug companies or/and royalties potentially involved in research around the subject matter. David J Pinato declares the following competing interests: Lecture fees: Bayer Healthcare, Astra Zeneca, EISAI, Bristol Myers-Squibb, Roche, Ipsen; Travel expenses: Bristol Myers-Squibb, Roche, Bayer Healthcare; Consulting fees: Mina Therapeutics, Boeringer Ingelheim, Ewopharma, EISAI, Ipsen, Roche, H3B, Astra Zeneca, DaVolterra, Mursla, Starpharma, Avammune Therapeutics, LiFT Biosciences, Exact Sciences; Research funding (to institution): MSD, BMS, GSK. Thomas Marron currently or has previously served on Advisory and/or Data Safety Monitoring Boards for Rockefeller University, Regeneron, AbbVie, Merck, Bristol-Meyers Squibb, Boehringer Ingelheim, Atara, AstraZeneca, Genentech, Celldex, Chimeric, DrenBio, Glenmark, Simcere, Surface, G1 Therapeutics, NGMbio, DBV Technologies, Arcus, Fate, Ono, Larkspur, and Astellas. Abdul Rafeh Naqash receives funding for trials he is PI on: Loxo@Lilly, Surface Oncology, ADC Therapeutics, IGM Biosciences, EMD Serono, Aravive, Nikang Therapeutics, Inspirna, Exelexis, Revolution Medicine, Jacobio, Pionyr, Jazz Pharmaceuticals, and NGM Biopharmaceuticals. ARN also received Consultant Editor Compensation from JCO Precision Oncology, Travel Compensation from: SITC/AACR/Conquer Cancer Foundation/BinayTara Foundation and Foundation Med, Caris Life Sciences, and serves on the Advisory Board for Foundation Med. Douglas Johnson has served on advisory boards or as a consultant for BMS, Mallinckrodt, Merck, Mosaic ImmunoEngineering, Novartis, Oncosec, Pfizer, Targovax, and Teiko, and has received research funding from BMS and Incyte., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Evidence demonstrates that physical exercise confers several psycho-physical benefits on patients with cancer. This study aims to investigate the role of oncologists in exercise promotion., Patients and Methods: A multicenter, cross-sectional study was conducted by distributing an anonymous, self-administered questionnaire to patients with cancer. The questionnaire enclosed demographic, health, and exercise variables. The exercise-related questions included in the study used the Godin-Shephard Leisure-Time Physical Activity Questionnaire to measure the amount of physical exercise. In addition, the survey gathered information on whether exercise was discussed with patients, and whether oncologists followed the assess, advise, reinforce, and refer (AARR) process regarding exercise. The survey also asked if patients preferred that exercise be discussed during their consultations. Descriptive statistics and logistic regression were applied., Results: With a response rate of 75%, a total of 549 patients completed the survey. Regarding the exercise discussion, 38% of patients stated that their oncologist initiated an exercise discussion, 14% started the discussion themselves, and 48% said that the issue was not considered. Overall, 35% of patients reported that the oncologist assessed their exercise level, 22% and 42% received advice or reinforcement to increase their exercise, respectively, and 10% were referred to a dedicated service. Regarding preferences, 72% of patients thought that the oncologists should initiate an exercise discussion, 2% that only patients should start the discussion, and 26% thought that the issue should not be discussed. Similarly, 74% of patients are willing to receive the exercise assessment, 59% and 75% the advice and reinforcement to increase their exercise, and 46% to be referred to an exercise service., Conclusions: Although exercise promotion rates are low, patients are willing to receive exercise information. Dedicated strategies should be developed to support oncologists in promoting exercise to their patients., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aims: To date, precision medicine has revolutionized the clinical management of Non-Small Cell Lung Cancer (NSCLC). International societies approved a rapidly improved mandatory testing biomarkers panel for the clinical stratification of NSCLC patients, but harmonized procedures are required to optimize the diagnostic workflow. In this context a knowledge-based database (Biomarkers ATLAS, https://biomarkersatlas.com/) was developed by a supervising group of expert pathologists and thoracic oncologists collecting updated clinical and molecular records from about 80 referral Italian institutions. Here, we audit molecular and clinical data from n = 1100 NSCLC patients collected from January 2019 to December 2020., Methods: Clinical and molecular records from NSCLC patients were retrospectively collected from the two coordinating institutions (University of Turin and University of Naples). Molecular biomarkers (KRAS, EGFR, BRAF, ROS1, ALK, RET, NTRK, MET) and clinical data (sex, age, histological type, smoker status, PD-L1 expression, therapy) were collected and harmonized., Results: Clinical and molecular data from 1100 (n = 552 mutated and n = 548 wild-type) NSCLC patients were systematized and annotated in the ATLAS knowledge-database. Molecular records from biomarkers testing were matched with main patients' clinical variables., Conclusions: Biomarkers ATLAS (https://biomarkersatlas.com/) represents a unique, easily managing, and reliable diagnostic tool aiming to integrate clinical records with molecular alterations of NSCLC patients in the real-word Italian scenario., Competing Interests: Declaration of competing interest Umberto Malapelle has received personal fees (as consultant and/or speaker bureau) from Boehringer Ingelheim, Roche, MSD, Amgen, Thermo Fisher Scientific, Eli Lilly, Diaceutics, GSK, Merck and AstraZeneca, Janssen, Diatech, Novartis and Hedera for work performed. Francesco Passiglia Francesco declared consultant/advisory fee from Astrazaneca, Janssen, Amgen, Sanofi, Brystol Myer Squibb, Merck Sharp and Dohne, Roche, Beigene, Novartis, Thermofisher Scientific. Pasquale Pisapia reports speaking fees from Novartis outside the submitted work. Diego Cortinovis has received personal fees (as consultant and/or speaker bureau) from Advisory Amgen, AstraZeneca, BMS, MSD, Novartis, Roche, Jannsen, Sanofi Genzyme.Domenico Galetta has received personal fees (as consultant and/or speaker bureau) from Astra-Zeneca, Pfizer, Eli-Lilly, BMS, MSD, Novartis, Amgen, Roche for work performed outside of the current study. Paolo Graziano has received personal fees (as consultant and/or speaker bureau) from: Amgen, AstraZeneca, BMS, Eli Lilly, MSD, Novartis, Roche, Pfizer, Boehringer Ingelheim unrelated to the current work. Fabio Pagni has received personal fees (as consultant and/or speaker bureau) from Novartis, Roche, MSD, Amgen, GSK and AstraZeneca, for work performed outside of the current study. Giulia Pasello has received personal fees (as consultant and/or speaker bureau) from: Amgen, AstraZeneca, BMS, Eli Lilly, MSD, Novartis, Roche, Jannsen, AstraZeneca, Roche unrelated to the current work. Sara Pilotto reports personal fees (invited speaker, advisory board) from AstraZeneca, Eli-Lilly, Novartis, AMGEN, Takeda, Sanofi, Bristol Myers Squibb, MSD and Roche; and research grants from AstraZeneca, Bristol Myers Squibb and Roche outside the submitted work. Marcello Tiseo reports personal fees (as consultant and/or speaker bureau) from Astra-Zeneca, Pfizer, Eli-Lilly, BMS, Novartis, Roche, MSD, Boehringer Ingelheim, Otsuka, Takeda, Pierre Fabre, Amgen, Merck, Sanofi. M.T. He received institutional research grants from Astra-Zeneca, Boehringer Ingelheim un related to the current work. Luisella Righi declared consultant/advisory fee from AstraZeneca, Novartis, Roche, Eli Lilly and Boehringer Ingelheim. Giancarlo Troncone reports personal fees (as speaker bureau or advisor) from Roche, MSD, Pfizer and Bayer, unrelated to the current work. Silvia Novello reports personal fees (as speaker bureau or advisor) from Eli Lilly, MSD, Roche, BMS, Takeda, Pfizer, Astra Zeneca and Boehringer Ingelheim, unrelated to the current work., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The pathologic diagnosis of pleural mesothelioma is generally based on international guidelines, but no compulsory points based on different drugs approvals in different European countries are required to be reported. According to the last (2021) edition of the World Health Organization classification of pleural tumors, the nuclear grade of epithelioid-type mesothelioma should be always inserted in the pathologic report, while the presence of BRCA-associated protein-1 (BAP1) (clone C4) loss and a statement on the presence of the sarcomatoid/nonepithelioid component are fundamental for both a screening of patients with suspected BAP1 tumor predisposition syndrome and the eligibility to perform first-line immunotherapy at least in some countries. Several Italian experts on pleural mesothelioma who are deeply involved in national scientific societies or dedicated working groups supported by patient associations agreed that the pathology report of mesothelioma of the pleura should always include the nuclear grade in the epithelioid histology, which is an overt statement on the presence of sarcomatoid components (at least 1%, in agreement with the last classification of pleural mesothelioma) and the presence of BAP1 loss (BAP1-deficient mesothelioma) or not (BAP1-retained mesothelioma) in order to screen patients possibly harboring BAP1 tumor predisposition syndrome. This review aims to summarize the most recent data on these three important elements to provide evidence regarding the possible precision needs for mesothelioma.

Recently, the fifth edition of the WHO classification recognized the thoracic SMARCA4 -deficient undifferentiated tumor (SMARCA4-UT) as a separate entity from conventional non-small cell lung cancer with SMARCA4 deficiency because of the different clinicopathological characteristics of these two diseases. SMARCA4-UT mainly occurs in young to middle-aged adults and involves a large mass compressing the tissues surrounding the mediastinum and lung parenchyma. Unfortunately, SMARCA4-UT shows a high probability of recurrence after upfront surgery as well as radiotherapy resistance; moreover, chemotherapy has low efficacy. Moreover, given the recent classification of SMARCA4-UT, no data concerning specific clinical trials are currently available. However, several case reports show immunotherapy efficacy in patients with this disease not only in a metastatic setting but also in a neoadjuvant manner, supporting the development of clinical trials. In addition, preclinical data and initial clinical experiences suggest that inhibiting pathways such as CDK4/6, AURKA, ATR, and EZH2 may be a promising therapeutic approach to SMARCA4-UT.

Background: Consolidative thoracic radiotherapy (TRT) has been commonly used in the management of extensive-stage small cell lung cancer (ES-SCLC). Nevertheless, phase III trials exploring first-line chemoimmunotherapy have excluded this treatment approach. However, there is a strong biological rationale to support the use of radiotherapy (RT) as a boost to sustain anti-tumor immune responses. Currently, the benefit of TRT after chemoimmunotherapy remains unclear. The present report describes the real-world experiences of 120 patients with ES-SCLC treated with different chemoimmunotherapy combinations. Preclinical data supporting the hypothesis of anti-tumor immune responses induced by RT are also presented., Methods: A total of 120 ES-SCLC patients treated with chemoimmunotherapy since 2019 in the South of Italy were retrospectively analyzed. None of the patients included in the analysis experienced disease progression after undergoing first-line chemoimmunotherapy. Of these, 59 patients underwent TRT after a multidisciplinary decision by the treatment team. Patient characteristics, chemoimmunotherapy schedule, and timing of TRT onset were assessed. Safety served as the primary endpoint, while efficacy measured in terms of overall survival (OS) and progression-free survival (PFS) was used as the secondary endpoint. Immune pathway activation induced by RT in SCLC cells was explored to investigate the biological rationale for combining RT and immunotherapy., Results: Preclinical data supported the activation of innate immune pathways, including the STimulator of INterferon pathway (STING), gamma-interferon-inducible protein (IFI-16), and mitochondrial antiviral-signaling protein (MAVS) related to DNA and RNA release. Clinical data showed that TRT was associated with a good safety profile. Of the 59 patients treated with TRT, only 10% experienced radiation toxicity, while no ≥ G3 radiation-induced adverse events occurred. The median time for TRT onset after cycles of chemoimmunotherapy was 62 days. Total radiation dose and fraction dose of TRT include from 30 Gy in 10 fractions, up to definitive dose in selected patients. Consolidative TRT was associated with a significantly longer PFS than systemic therapy alone (one-year PFS of 61% vs. 31%, p<0.001), with a trend toward improved OS (one-year OS of 80% vs. 61%, p=0.027)., Conclusion: Multi-center data from establishments in the South of Italy provide a general confidence in using TRT as a consolidative strategy after chemoimmunotherapy. Considering the limits of a restrospective analysis, these preliminary results support the feasibility of the approach and encourage a prospective evaluation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Longo, Della Corte, Russo, Spinnato, Ambrosio, Ronga, Marchese, Del Giudice, Sergi, Casaluce, Gilli, Montrone, Gristina, Sforza, Reale, Di Liello, Servetto, Lipari, Longhitano, Vizzini, Manzo, Cristofano, Paolelli, Nardone, De Summa, Perrone, Bisceglia, Derosa, Nardone, Viscardi, Galetta and Vitiello.)

Background: Sotorasib showed a significant improvement of progression free survival (PFS), safety and quality of life over docetaxel in patients with KRASp.G12C-mutated advanced non-small-cell lung cancer (NSCLC) within the CodeBreak-200 study. Here we report real-world efficacy and tolerability data from NSCLC patients who received sotorasib within the Italian expanded access program (EAP)., Methods: Sotorasib (960 mg, orally, once daily) was available on physician request for KRASp.G12C mutant advanced NSCLC patients. Clinical-pathological and molecular data were collected from the Italian ATLAS real-world registry. Patients underwent CT-scan and responses were evaluated by RECIST criteria. Efficacy and tolerability outcomes have been assessed., Results: A total of 196 advanced NSCLC patients were treated across 30 Italian centers. Median age was 69 years old (range 33-86). Most patients were male (61 %), former (49 %) or current smokers (43 %), with ECOG-PS 0/1 (84 %) and adenocarcinoma subtype (90 %). 45 % and 32 % of patients received sotorasib in 2nd and 3rd line, respectively. Overall, response rate was 26 % and the median duration of response was 5.7 months (95 % CI: 4.4-7.0). Median PFS and OS were 5.8 months (95 % CI: 5 - 6.5) and 8.2 months (95 % CI: 6.3 - 9.9). Grade 3-4 TRAEs occurred in 16.5 % of patients, with Grade ≥ 3 liver enzyme increase and TRAEs-related discontinuation reported in 12 % and 4.6 % of cases., Conclusion: Real-world data from the Italian EAP confirm the tolerability and effectiveness of sotorasib in patients with KRASp.G12C-mutated advanced NSCLC and highlight the value of the national ATLAS network as source of real-world evidence driving the clinical management of NSCLC patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Sleeve lobectomy with bronchoplasty is a safe surgical technique for the management of lung cancer and endobronchial localization of extrapulmonary cancers. However, anastomotic complications can occur, and treatment strategies are not standardized., Methods: Data from 280 patients subjected to bronchoplasty were retrospectively analyzed, focusing on surgical techniques, anastomotic complications, and their management. Multivariate analysis was performed, and Kaplan-Meier curves were used to determine survival., Results: Ninety percent of 280 surgeries were for lung cancer. Anastomotic complications occurred in 6.42% of patients: late stenosis in 3.92% and broncho-pleural fistula in 1.78%. The median survival was 65.90 months (95% CI = 41.76-90.97), with no difference ( p = 0.375) for patients with (51.28 months) or without (71.03 months) anastomotic complications. Mortality at 30 days was higher with anastomotic complications (16.7% vs. 3%, p = 0.014). Multivariable analysis confirmed pathological stage (N+) as a risk factor for anastomotic complications ( p = 0.016). Our mortality (3.93%) and morbidity rate (41.78%) corresponded to recent series results., Conclusions: In our experience, surgery is preferred to avoid life-threatening complications in bronchopleural fistulas. Bronchoscopic balloon dilatation is preferred for benign strictures. The nodal stage is related to complications ( p = 0.0014), reflecting the aggressiveness of surgery, which requires extended radical lymphadenectomy.

Medical treatment has changed drastically in recent years, especially for advanced stages of non-small-cell lung cancer (NSCLC), for which the development of immunotherapy and molecular targeted therapy significantly increased survival and quality of life. This single-center retrospective study aimed to analyze the outcome predictors, the surrogate outcomes, and the patient-reported outcomes after neoadjuvant immunotherapy for initially unresectable NSCLC. Patients affected by an initially unresectable NSCLC and identified between March 2014 and December 2021 who received immunotherapy alone or in combination with platinum-based chemotherapy and/or radiotherapy were collected. Overall survival (OS) and disease-free survival (DFS) were estimated according to the Kaplan-Meier method. Patient-reported outcomes were recorded using the European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life (QoL) Group questionnaire-Lung Cancer 29 Module to compare differences in symptoms and QoL at two different times, 30 days and 1 year after surgery. Surgical, pathological records, and patient-reported outcomes (at 30 days and 1 year after surgery) were reviewed. Complete pathological remission was achieved in 7 patients (36.8%) and major pathological remission in 3 patients (15.7%). The median overall survival in the study group is 19 months (range: 2-57.4). Of 19 patients, 16 (84.2%) are alive to date, of which 2 (10.5%) have a local recurrence. At 30 days from surgery, the main symptoms reported by EORTC Module were coughing, shortness of breath, the side effect of treatment, fear of progression, and surgery-related problems. Induction immunotherapy with or without chemotherapy can be considered for unresectable locally advanced NSCLC, and after the downstaging, the possibility of surgery could be re-evaluated in a multidisciplinary setting with high rates of R0 resection. In this selected and highly motivated group of patients, the QoL and symptoms after salvage surgeries are acceptable and even better than those reported in the literature., (© 2023. Italian Society of Surgery (SIC).)

Non-Small cell lung cancer (NSCLC) is one of the most dangerous cancers, with 85% of all new lung cancer diagnoses and a 30-55% of recurrence rate after surgery. Thus, an accurate prediction of recurrence risk in NSCLC patients during diagnosis could be essential to drive targeted therapies preventing either overtreatment or undertreatment of cancer patients. The radiomic analysis of CT images has already shown great potential in solving this task; specifically, Convolutional Neural Networks (CNNs) have already been proposed providing good performances. Recently, Vision Transformers (ViTs) have been introduced, reaching comparable and even better performances than traditional CNNs in image classification. The aim of the proposed paper was to compare the performances of different state-of-the-art deep learning algorithms to predict cancer recurrence in NSCLC patients. In this work, using a public database of 144 patients, we implemented a transfer learning approach, involving different Transformers architectures like pre-trained ViTs, pre-trained Pyramid Vision Transformers, and pre-trained Swin Transformers to predict the recurrence of NSCLC patients from CT images, comparing their performances with state-of-the-art CNNs. Although, the best performances in this study are reached via CNNs with AUC, Accuracy, Sensitivity, Specificity, and Precision equal to 0.91, 0.89, 0.85, 0.90, and 0.78, respectively, Transformer architectures reach comparable ones with AUC, Accuracy, Sensitivity, Specificity, and Precision equal to 0.90, 0.86, 0.81, 0.89, and 0.75, respectively. Based on our preliminary experimental results, it appears that Transformers architectures do not add improvements in terms of predictive performance to the addressed problem., (© 2023. The Author(s).)

Background: Geriatric patients (≥80 years) are underrepresented in immune checkpoint inhibitor (ICIs) clinical trials. However, their unique biology may affect their response to ICIs. There are currently no established biomarkers of the response to ICIs in adult patients with cancer that can help with patient selection., Methods: We built a multicenter, international retrospective study of 885 patients (<80 years: n = 417, 47.12%; ≥80 years: n = 468, 52.88%) with different tumor types treated with ICIs between 2011 and 2021 from 11 academic centers in the U.S. and Europe. The main outcome measures were objective response rates (ORR), progression-free survival (PFS) and overall survival (OS) stratified by age and circulating inflammatory levels (neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammatory index (SII))., Results: Patients ≥80 years with low NLR (NLR-L) and SII (SII-L) had significantly higher ORR (vs. high NLR [NLR-H], p < 0.01 and SII-H, p < 0.05, respectively). At median follow-ups (13.03 months), and compared to SII-H, patients with SII-L had significantly longer median PFS and OS in patients <80 ( p < 0.001), and ≥80 years ( p < 0.001). SII-L was independently associated with longer PFS and OS (HR: 0.61 and 0.62, respectively, p < 0.01)., Conclusion: Lower inflammation pre-ICI initiation may predict an improved response and survival in geriatric patients with cancer.

Background: 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., Patients and Methods: 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., Results: 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)., Conclusions: 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., Competing Interests: Disclosure BB: research funding, institution: Abbvie, Amgen, AstraZeneca, Chugai pharmaceutical, Daiichi-Sankyo, Ellipse pharma, EISAI, Genmab, Genzyme Corporation, Hedera Dx, Inivata, IPSEN, Janssen, MSD, Pharmamar, Roche-Genentech, Sanofi, Socar research, Taiho Oncology, Turning Point Therapeutics. EF: consulting or advisory role, personal: Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Lilly, GlaxoSmithKline, Janssen, Merck Serono, Novartis, Pfizer, Sanofi, Takeda, Peptomyc, Daiichi Sankyo Europe GmbH, F. Hoffmann LaRoche, Merck Sharp & Dohme; speakers’ bureau, personal: AstraZeneca, Bristol-Myers Squibb, Lilly, Medscape, Merck Sharp & Dohme, PeerVoice, Pfizer, Takeda, Amgen, F. Hoffmann LaRoche, Janssen, Medical Trends, Merck Serono, Sanofi, Touch ONCOLOGY; other relationship, personal: GRIFOLS; research funding, institution: Merck, Merck KGaA. RGC: consulting or advisory role, personal: Roche/Genentech, MSD Oncology, AstraZeneca, Bristol-Myers Squibb, Pfizer, Novartis, Takeda, Boehringer Ingelheim, Janssen Oncology; speakers’ bureau, personal: Roche, AstraZeneca, Bristol-Myers Squibb, Pfizer, Novartis, Takeda, Boehringer Ingelheim, MSD Oncology, Sanofi/Aventis, Janssen Oncology, Amgen, Lilly; travel, accommodations, expenses, personal: Roche/Genentech, MSD Oncology, Pfizer. CM: consulting or advisory role, personal: Roche, Sanofi, Takeda, Pfizer, Bristol-Myers Squibb, MSD, AstraZeneca, Kephren, AMGEN, Janssen, GlaxoSmithKline; honoraria, personal: Roche, AstraZeneca, Kephren, Bristol-Myers Squibb, Pfizer, Sanofi, MSD, Takeda, Janssen; travel, accommodations, expenses, personal: MSD; other, uncompensated relationships: Boehringer Ingelheim. FC: consulting or advisory role, personal: Roche/Genentech, AstraZeneca/MedImmune, Pfizer, Bristol-Myers Squibb, Takeda, Lilly, MSD Oncology, Bayer, Amgen, Sanofi, PharmaMar, Novocure; honoraria, personal: Pfizer, Roche/Genentech, AstraZeneca/MedImmune, Lilly, MSD Oncology, Bristol-Myers Squibb, Takeda, Bayer, Amgen, Sanofi, PharmaMar, Novocure; travel, accommodations, expenses, personal: OSE Immunotherapeutics. WH: consulting or advisory role, personal: AstraZeneca, Janssen; honoraria, personal: MSD Oncology. FD: consulting or advisory role, institution: SIVAN Innovation; honoraria, personal: AstraZeneca, MSD, Ipsen, Roche Belgium, Pfizer/EMD Serono, Takeda; stock and other ownership interests, institution: Kelindi; other relationship, personal: Takeda, Novartis, Ipsen, Janssen-Cilag, Merck Serono, Chugai Pharma, Ferring. SV: consulting or advisory role, personal: Roche; company: Bristol-Myers Squibb, Janssen, Takeda, Reddy Pharma Iberia, Merck KGaA, Puma Biotechnology; speakers’ bureau, personal: Bristol-Myers Squibb, Roche, MSD, AstraZeneca Spain; travel, accommodations, expenses, personal: Roche, MSD, Merck KGaA. DD: consulting or advisory role, personal: BMS, OSE Immunotherapeutics, Amgen, AstraZeneca; honoraria, personal: AstraZeneca, BMS, Janssen, Amgen, Novartis, Sanofi Aventis, Ipsen, MSD, GSK, Hoffmann-La Roche, Pfizer, OSE Immunotherapeutics; research funding, institution: AstraZeneca, Chugaï, Hoffmann-La Roche, Lilly, BMS, MSD, Boehringer-Ingelheim, Pfizer, Takeda, Bayer, Janssen, Sanofi-Aventis; travel, accommodations, expenses, personal: Amgen, BMS, AstraZeneca, MSD, Novartis, Roche, Pfizer, Janssen, Takeda. DG: consulting or advisory role, personal: Eli Lilly, Novartis, AZ, BMS, Pfizer; speakers’ bureau, personal: Eli Lilly, Takeda, Novartis, BMS, MSD, Roche; travel, accommodations, expenses, personal: Amgen. GR: consulting or advisory role, personal: MSD, Astra Zeneca, BMS; honoraria, personal: Roche, MSD, Astra Zeneca; research funding, institution: Roche; travel, accommodations, expenses, personal: Roche, MSD, Astra Zeneca. MM: consulting or advisory role, personal: Alfasigma, Amgen, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Incyte, Lilly, Merck Serono, MSD, Pierre Fabre, Roche, Sanofi; honoraria: Alfasigma, Amgen, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Lilly, Merck Serono, MSD, Pierre Fabre, Roche, Sanofi, SciClone; stock and other ownership interests: Epigen Therapeutics, Theravance. AD: consulting or advisory role, personal: Novartis, Pfizer, Immunocore; research funding, institution: MSD; travel, accommodations, expenses, personal: MSD. BR: consulting or advisory role, personal: Amgen, AstraZeneca, BMS, Chugaï, Lilly, Roche, Takeda; speaker’s bureau: BMS, Roche; travel, accommodations, expenses, personal: BMS, Amgen, MSD, Roche, Novartis. WS: consulting or advisory role, personal: Roche, MSD, Novartis; honoraria, personal: Roche, MSD, Novartis. AZ: consulting or advisory role, personal: Boehringer Ingelheim, Roche, MSD, Oncotest/Rhenium, Lilly; honoraria, personal: MSD, Roche, AstraZeneca, Takeda, Novartis; stock and other ownership interests, personal: Nixio; research funding, institution: Bristol-Myers Squibb; travel, accommodations, expenses, personal: AstraZeneca, MSD, Roche. DC: employment, personal: OSE Immunotherapeutics; leadership, personal: OSE Immunotherapeutics; stock and other ownership interests, personal: OSE Immunotherapeutics. BV: employment, personal: OSE Immunotherapeutics; patents, royalties, other intellectual property, personal: uses of anti-SIRPa antibodies in the treatment of cancer; stock and other ownership interests, personal: OSE Immunotherapeutics. RD: consulting or advisory role, personal: Regeneron, Karyopharm Therapeutics; honoraria, personal: Roche/Genentech, Novartis, Pfizer, Bristol-Myers Squibb, Takeda, AstraZeneca, MSD Oncology, Boehringer Ingelheim, Seattle Genetics; travel, accommodations, expenses, personal: Roche, AstraZeneca. GG: consulting or advisory role, personal: Daiichi Sankyo, Novartis, Radiomics, Janssen Oncology, Sanofi, Eisai, Spectrum Pharmaceuticals, Sanofi/Regeneron; research funding, institution: MedImmune, Karyopharm Therapeutics, Cantargia AB; starting in September 2022, employee of Amgen. All other authors have declared no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Immune checkpoint inhibitors (ICIs) represent the cornerstone of the current treatment of non-small cell lung cancer (NSCLC). However, the occurrence of concomitant infections might hamper success. All consecutive patients with advanced NSCLC who started ICIs as a first- or second-line therapy from January 1, 2017 to June 30, 2020 were retrospectively evaluated. The occurrence of infectious events during ICIs was correlated with clinical characteristics, including previous Cytotoxic Chemotherapy (CC), occurrence of immune-related-adverse-events (irAEs). A total of 211 patients were included, 46 (22%) females, with a median (q1-q3) age of 69 (62-76) years. Overall, 85 patients (40%) received ICIs as a first treatment line and 126 (60%) as a second line; 40 patients (19%) had at least one infection during ICIs, and 17 (8%) more than one. Notably, autoimmune diseases (P < .005), neutropenia (P = .001) or infections during previous CC (P = .001), irAEs (P = .006), or steroid therapy for irAEs (P < .001) were associated with infection development. By multivariate Cox-regression, autoimmune diseases (aHR = 6.27; 95%CI = 2.38-16.48; P < .001) and steroid therapy for irAEs (aHR = 2.65; 95%CI = 1.27-5.52; P < .009) were associated with a higher risk of infection during ICIs. Interestingly, autoimmune diseases were confirmed as risk factors in patients treated with ICIs as a first line, while previous infections were the only independent predictor of infections in patients treated with ICIs as a second line. Patients with NSCLC treated with ICIs with concurrent autoimmune disease, receiving steroid therapy for management of irAEs, or having a history of previous infections during CC should be actively monitored for the risk of developing infectious complications., (© 2023 The Authors. Scandinavian Journal of Immunology published by John Wiley & Sons Ltd on behalf of The Scandinavian Foundation for Immunology.)

Small cell lung cancer (SCLC) is treated as a homogeneous disease, although the expression of NEUROD1, ASCL1, POU2F3, and YAP1 identifies distinct molecular subtypes. The MYC oncogene, amplified in SCLC, was recently shown to act as a lineage-specific factor to associate subtypes with histological classes. Indeed, MYC-driven SCLCs show a distinct metabolic profile and drug sensitivity. To disentangle their molecular features, we focused on the co-amplified PVT1, frequently overexpressed and originating circular (circRNA) and chimeric RNAs. We analyzed hsa&#95;circ&#95;0001821 (circPVT1) and PVT1/AKT3 (chimPVT1) as examples of such transcripts, respectively, to unveil their tumorigenic contribution to SCLC. In detail, circPVT1 activated a pro-proliferative and anti-apoptotic program when over-expressed in lung cells, and knockdown of chimPVT1 induced a decrease in cell growth and an increase of apoptosis in SCLC in vitro. Moreover, the investigated PVT1 transcripts underlined a functional connection between MYC and YAP1/POU2F3, suggesting that they contribute to the transcriptional landscape associated with MYC amplification. In conclusion, we have uncovered a functional role of circular and chimeric PVT1 transcripts in SCLC; these entities may prove useful as novel biomarkers in MYC-amplified tumors., (© 2022 Wiley Periodicals LLC.)

Non-small cell lung cancer (NSCLC) represents 85% of all new lung cancer diagnoses and presents a high recurrence rate after surgery. Thus, an accurate prediction of recurrence risk in NSCLC patients at diagnosis could be essential to designate risk patients to more aggressive medical treatments. In this manuscript, we apply a transfer learning approach to predict recurrence in NSCLC patients, exploiting only data acquired during its screening phase. Particularly, we used a public radiogenomic dataset of NSCLC patients having a primary tumor CT image and clinical information. Starting from the CT slice containing the tumor with maximum area, we considered three different dilatation sizes to identify three Regions of Interest (ROIs): CROP (without dilation), CROP 10 and CROP 20. Then, from each ROI, we extracted radiomic features by means of different pre-trained CNNs. The latter have been combined with clinical information; thus, we trained a Support Vector Machine classifier to predict the NSCLC recurrence. The classification performances of the devised models were finally evaluated on both the hold-out training and hold-out test sets, in which the original sample has been previously divided. The experimental results showed that the model obtained analyzing CROP 20 images, which are the ROIs containing more peritumoral area, achieved the best performances on both the hold-out training set, with an AUC of 0.73, an Accuracy of 0.61, a Sensitivity of 0.63, and a Specificity of 0.60, and on the hold-out test set, with an AUC value of 0.83, an Accuracy value of 0.79, a Sensitivity value of 0.80, and a Specificity value of 0.78. The proposed model represents a promising procedure for early predicting recurrence risk in NSCLC patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Bove et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-1722/coif). DG serves as an unpaid editorial board member of Journal of Thoracic Disease from October 2022 to September 2024. The other authors have no conflicts of interest to declare.

Many new treatment modalities for non-small-cell carcinoma (NSCLC) have been described in the last two decades. Surgical resections remain the gold standard for early stages and may be considered for locally advanced tumors. Medical treatment has changed drastically in recent years, especially for advanced stages, for which the development of immunotherapy and molecular targeted therapy significantly increased survival and quality of life. The addition of radical surgical resection following immunotherapy or immuno-chemotherapy is feasible and safe with low surgical-related mortality and morbidity in selected patients with initially unresectable NSCLC. However, data from multiple ongoing trials with overall survival as the primary endpoint should be awaited before this strategy is introduced into the standard of care.

Background: The addition of immune checkpoint inhibitors (ICIs) to chemotherapy is the new standard of care in the first-line treatment of small cell lung cancer (SCLC). However, although the concomitant use of immunotherapy and chemotherapy can increase the antitumor efficacy, it can also increase toxicity. The present study evaluated the tolerability of immune-based combinations in the first-line treatment of SCLC., Methods: Relevant trials were identified by searching electronic databases and conference meetings. Seven phase II and III randomized controlled trials and 3766 SCLC patients were included in the meta-analysis (immune-based combinations = 2133; chemotherapy = 1633). Outcomes of interest included treatment-related adverse events (TRAEs) and the rate of discontinuation due to TRAEs., Results: Immune-based combination treatment was associated with a higher risk of grade 3-5 TRAEs (odds ratio [OR], 1.16; 95% confidence interval [CI]: 1.01-1.35). Immune-based combinations were associated with a higher risk of TRAEs leading to discontinuation (OR, 2.30; 95% CI: 1.17-4.54). No differences were observed in grade 5 TRAEs (OR, 1.56; 95% CI: 0.93-2.63)., Conclusion: This meta-analysis indicates that the addition of immunotherapy to chemotherapy in SCLC patients is associated with a higher risk of toxicity and probably of treatment discontinuation. Tools for identifying SCLC patients that would not benefit from immune-based therapy are urgently needed., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for approximately 80% of all lung cancers, and most NSCLC is diagnosed in the advanced stage. The advent of immune check point inhibitors (ICIs) changed the therapeutic scenario both in metastatic disease (in first and subsequent lines) and earlier settings. Comorbidities, reduced organ function, cognitive deterioration, and social impairment give reasons for a greater probability of adverse events, making the treatment of elderly patients challenging. The reduced toxicity of ICIs compared to standard chemotherapy makes this approach attractive in this population. The effectiveness of ICIs varies according to age, and patients older than 75 years may benefit less than younger patients. This may be related to the so-called immunosenescence, a phenomenon that refers to the reduced activity of immunity with older age. Elders are often under-represented in clinical trials, even if they are a large part of the patients in a clinical practice. In this review, we aim to explore the biological aspects of immunosenescence and to report and analyze the most relevant and recent literature findings on the role of immunotherapy in elderly patients with NSCLC.

(1) Objective: the purpose of this study was to evaluate and quantify the stress to which a surgeon is subjected during his/her surgical activity; we compared the individual clinical and psychological responses to stress of two surgeons during their surgical activities via robotic and open approaches. (2) Materials and methods: This was a prospective observational study in which we progressively collected data concerning the surgical performances of two different thoracic surgeons (October 2021-June 2022). We evaluated 20 lung resections performed via robot-assisted surgery and 20 lung resections performed via an open approach by each surgeon; in particular, we evaluated a panel of pre-, peri-, and postoperative data concerning the interventions, the patients, and other outcomes concerning the autonomic nervous system (ANS) and psychological responses to stress of the surgeons during their surgical activities. (3) Results: When analyzing data concerning the ANS activity of two surgeons, during robotic activity we found lower maximum, minimum, and mean heart rates; lower mean respiratory frequencies; lower body temperatures; and lower mean desaturations compared to the open approach activity for both surgeons. The psychological monitoring showed that the open approach created more physical fatigue and frustration but higher levels of satisfaction and performance evaluation. The robot-assisted surgeries showed higher levels of anxiety. (4) Conclusions: for different reasons, the robotic approach stimulated the ANS to a lesser degree, causing less stress for surgeons and ensuring greater comfort.

Renal Cell Carcinoma (RCC) is generally characterized by low-FDG avidity, and [ 18 F]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 [ 18 F]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) [ 18 F]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. [ 18 F]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 [ 18 F]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 [ 18 F]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 [ 18 F]FDG-PET/CT images.

Objectives: Superior sulcus tumour, which affects the lung's apex, is an uncommon subtype of non-small cell lung cancer (NSCLC). The current study examined the clinical characteristics and management of superior sulcus NSCLC patients in a high-volume referral oncological centre over 22 years., Methods: Retrospective review of 100 surgeries with curative intent for superior sulcus NSCLC over 22 years (July 1998 - December 2020). The surgical approach was defined according to the lesion site and the anatomy of the thoracic inlet. Survival curves, including non-cancer-related deaths, were drawn using the Kaplan-Meier methods, and the log-rank test was used to evaluate differences in survival across groups of patients. Cox proportional hazards regression was used to assess the association between selected clinical and pathologic characteristics on OS., Results: 54 patients received induction treatments. The surgical approach was anterior thoracotomy in 53 patients, Paulson incision in 30, and a combined in 8. The median postoperative length of stay was 11 days (range: 5 - 27 days). Overall 90-day mortality was 6.93%. The median OS was 24.3 months. After a median follow-up of 3 years, 5-year and 10-year OS rates were 33.9% and 26.4%, respectively. A significantly lower 5-year OS was observed in patients with the nodal disease (46.6% in pN0 vs 13.2% in pN+; p = 0.024), without preoperative treatments (41.0% in patients without preoperative treatments versus 17.4%; p = 0.09) and anteriorly located tumour (anterior vs posterior: 17.4% vs 49.1%; p = 0.032). Cox proportional hazards regression showed better survival in the pT1 stage (HR = 4.6; 95% CI: 1.9 - 11.2; p = 0.00076) and in R0 (HR = 4.2; 95% CI: 1.4 - 12.5; p = 0.010)., Conclusions: Superior sulcus tumours still represent a life-threatening condition that, while curable in a significant proportion of cases, requires complex procedures with high surgical risks and a multimodality treatment setting. An optimal surgical approach should be planned to maximise resection completeness and survival. Other factors affecting survival are related to tumour staging, emphasising the importance of a meticulous preoperative workup and candidate selection to identify those expected to benefit from a survival benefit., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bertolaccini, Casiraghi, Galetta, Petrella, Mazzella, Lo Iacono, Girelli, Bardoni, Mohamed, Musso, Sedda and Spaggiari.)

Background/aim: Lung cancer is one of the most common malignant neoplastic diseases and by far the leading cause of cancer death worldwide. Recently, immune checkpoint inhibitors (ICIs) have received increasing attention for playing a crucial role in non-small cell lung cancer (NSCLC). Biomarkers, such as programmed cell death-ligand 1 (PD-L1) and tumor mutational burden (TMB), seemed to be helpful in selecting patients who are more likely to benefit from ICI treatment: however, their role has not yet been fully clarified., Patients and Methods: In this retrospective study, we evaluated the relationship between pre-treatment peripheral blood neutrophil-to-lymphocyte ratio (NLR) and survival in 252 patients suffering from advanced NSCLC who had received pembrolizumab as their first-line immunotherapy., Results: Compared to their NLR low counterparts who had a median overall survival (OS) of 34.8 months, patients with NLRs above 4.8 had a median OS of 7.6 months (HR=3.26, 95%Cl=2.3-4.6, p-value<0.0000001). In multivariate Cox regression analysis, alongside other variables, such as metastatic sites, age, and sex, NLR and PD-L1 predicted progression-free survival and OS; furthermore, a very high NLR - over 10 - seemed to forecast a very dismal prognosis in patients undergoing immunotherapy, with sudden deaths in the days immediately following therapy (median OS=3.8 months)., Conclusion: NLR acts as a valuable and reliable prognostic factor in non-small cell lung carcinoma patients undergoing first line immunotherapy with pembrolizumab. Additional investigation is necessary to fully elucidate the underlying biological rationale, which can be found in myeloid derived suppressor cells, a heterogeneous population of cells with neutrophil-like immunophenotypic features., Competing Interests: The Authors have no conflicts of interest to declare in relation to this study., (Copyright 2023, International Institute of Anticancer Research.)

Background: Alectinib is a second generation of ALK -tyrosine kinase inhibitors ( ALK -TKIs), which has attracted much attention in the treatment of ALK -positive non-small cell lung cancer (NSCLC). At present, there are few reports on the efficacy and safety of alectinib in Chinese population. Moreover, biomarkers reflecting prognosis and efficacy are exceedingly needed. This study assessed the efficacy of alectinib in patients with ALK -positive NSCLC and analyzed the prognostic factors., Methods: Patients with ALK -positive NSCLC who were confirmed by histopathology or cytology at the Affiliated Cancer Hospital of Nanjing Medical University between October 2018 and October 2021 were enrolled. All patients were treated with alectinib. The clinical characteristics and circulating tumor biomarkers before and after treatment were collected. Kaplan-Meier test was used to calculate the progression-free survival (PFS). Univariate and multivariate Cox regression analyses were used to explore the influencing factors on PFS. Incidence of adverse events was observed., Results: Twenty patients progressed after first-line treatment (n=59) with alectinib, and 21 patients progressed following second-line treatment (n=36) with alectinib. The median PFS of first-line treatment patients was not achieved, and the median PFS of patients undergoing second-line treatment was 15.0 months [95% confidence interval (CI): 0.00-32.23]. The most common adverse reactions were liver dysfunction (37.50%), anemia (37.50%), and constipation (20.83%). The incidence of grade III and above adverse reactions was 6.25%. Univariate analysis showed that neutrophil-to-lymphocyte ratio [NLR; hazard ratio (HR) =0.424, P=0.005] carcinoembryonic antigen (CEA; HR =0.482, P=0.029), lactate dehydrogenase (LDH; HR =0.327, P<0.001), carbohydrate antigen (CA)199 (HR =0.313, P=0.002), and circulating cell free DNA (cfDNA; HR =0.229, P=0.008) concentration levels were associated with PFS, and multivariate analysis showed that NLR (HR =3.058, P=0.034) was independent prognostic factor. After three months of treatment, CEA, CA199, NLR, and LDH, could further predict the prognosis of alectinib treatment., Conclusions: The efficacy and safety of alectinib as a first-line or second-line treatment for ALK -positive NSCLC in keeping with published prospective studies. CEA, CA199, NLR, and LDH within the normal range after three months of treatment were associated with good prognosis. Detection of serum tumor markers can indicate therapeutic success in patients treated with alectinib., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-22-857/coif). AR declares consulting fees form AstraZeneca, participation on advisory board (Takeda), supporting for attending to meetings form Thermofisher and BMS. BGMH declares Advisory Board of Merck, Sharpe and Dohme, Eisai, Pfizer, Sanofi and Takeda. The other authors have no conflicts of interest to declare., (2022 Translational Lung Cancer Research. All rights reserved.)

Background: Potential relationships with the prognosis of patients with extensive-stage non-small cell lung cancer (ES-SCLC) have been investigated without valid results., Methods: A retrospective analysis of real-world data of consecutive patients with ES-SCLC admitted to our Medical Thoracic Oncology Unit was carried out from 2010 to 2020, focusing on identification of prognostic factors. Kaplan-Meier analysis was used to represent progression-free survival (PFS) and overall survival (OS). Univariable and multivariable Cox models were used to investigate prognostic factors., Results: The analysis included 244 patients. The median OS was 8 months (95% confidence interval [CI]: 8-10) and the median PFS was 5 months (95% CI: 5-6). The univariable analysis showed that factors associated with shorter OS were older age (p = 0.047), TNM stage 4 versus 3 (p < 0.001), Eastern Cooperative Oncology Group (ECOG) performance status (PS) 1 and 2 versus 0 (p < 0.001), and >2 metastatic sites (p = 0.004). Mediastinal radiotherapy (RT) (p < 0.001), >1 irradiated site (p = 0.026), 3 and 4 chemotherapy (CT) lines versus 1 (p = 0.044 and 0.001, respectively), prophylactic cranial irradiation (PCI) (p < 0.001), and surgery (p = 0.001) correlated with longer OS. The multivariable analysis revealed statistically significant associations for TNM, ECOG PS 2 versus 0, number of CT lines, PCI, and surgery. A total of 23 patients (9.4%) survived ≥24 months, 39% of whom had received four CT lines and 48% had mediastinal RT., Conclusions: Our data suggest that tumor burden, PS, and mediastinal RT strongly correlate with outcome. With the addition of immunotherapy to CT, the identification of new biomarkers as predictive factors is urgently required., (© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Mast cells (MCs) are multifunctional immune cells implicated in both physiological and pathological processes. Among the latter, MCs play a crucial role in cancer. Many studies have shown a correlation between MCs and tumor progression in several solid and hematological malignancies. In particular, MCs can directly promote tumor growth via c-kit/stem cell factor-dependent signaling and via the release of histamine, which modulate tumor growth through H1 and H2 receptors. At the same time, MCs can increase tumor progression by stimulating angiogenesis via both proangiogenic cytokines stored in their cytoplasm, and by acting on the tumor microenvironment and extracellular matrix. With regard to NSCLC, the role of MCs has not yet been established, with studies showing a correlation with a poor prognosis on the one hand and suggesting a protective effect of MCs on the other hand. These controversial evidences are at least, in part, due to the heterogeneity of the studies exploring the role of MCs in NSCLC, with some studies describing only the MC count without specification of the activation and degranulation state, and without reporting the intratumoral localization and the proximity to other immune and cancer cells. A better knowledge of the role of MCs in NSCLC is mandatory, not only to define their prognostic and predictive proprieties but also because targeting them could be a possible therapeutic strategy., (© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Introduction: Anaplastic lymphoma kinase (ALK) fusions identify a limited subset of non-small cell lung cancer (NSCLC) patients, whose therapeutic approach have been radically changed in recent years. However, diagnostic procedures and clinical-radiological responses to specific targeted therapies remain heterogeneous and intrinsically resistant or poor responder patients exist., Methods: A total of 290 patients with advanced NSCLC defined as ALK+ by immunohistochemistry (IHC) and/or fluorescent in situ hybridisation (FISH) test and treated with single or sequential multiple ALK inhibitors (ALKi) from 2011 to 2017 have been retrospectively retrieved from a multicentre Italian cancer network database. In 55 patients with enough leftover tumour tissue, specimens were analysed with both targeted and customised next generation sequencing panels. Identified fusion variants have been correlated with clinical outcomes., Results: Of the 55 patients, 24 received crizotinib as first-line therapy, 1 received ceritinib, while 30 received chemotherapy. Most of the patients (64%) received ALKi in sequence. An ALK fusion variant was identified in 73% of the cases, being V3 variant (E6A20) the most frequent, followed by V1 (E13A20) and more rare ones (e.g. E6A19). In three specimens, four new EML4-ALK fusion breakpoints have been reported. Neither fusion variants nor brain metastases were significantly associated with overall survival (OS), while it was predictably longer in patients receiving a sequence of ALKi. The presence of V1 variant was associated with progression-free survival (PFS) improvement when crizotinib was used (p = 0.0073), while it did not affect cumulative PFS to multiple ALKi., Conclusion: Outcomes to sequential ALKi administration were not influenced by fusion variants. Nevertheless, in V1+ patients a prolonged clinical benefit was observed. Fusion variant identification by NGS technology may add relevant information about rare chromosomal events that could be potentially correlated to worse outcomes., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Completion pneumonectomy (CP) is associated with high morbidity and mortality. We reviewed our experience to evaluate whether induction treatment (IT) may affect postoperative outcomes and analyzed factors influencing long-term results., Methods: Between 1998 and 2020, 69 patients with lung cancer underwent CP (50 males, median age 63 years, right CP in 47 patients). A total of 23 patients (33.3%) received IT (chemotherapy in 15, chemoradiotherapy in 7, and radiation in 1). Surgery included 25 (36.2%) extended resections and five (7.2%) tracheal sleeve CP., Results: The 30-day mortality rate was 7.2% (5/69), and overall morbidity was 37.6%. Major complications occurred in five patients (7.2%): one cardiac dislocation, one diaphragmatic hernia, one transient ischemic attack (TIA), and two bronchopleural fistulas. Minor complications occurred in 21 cases (30.4%): pulmonary in 12, cardiac in 7, and neurological in 2. The median hospital stay was 8 days (range, 5-56 days). IT did not influence postoperative morbidity and mortality. Pathological staging included 19 (27.5%) stage I, 36 (52.2%) stage II, and 14 (20.3%) stage III. Overall 5-year survival was 51.7%. Factors influencing survival were IT ( p = 0.01), extension of resection ( p = 0.04), histology ( p = 0.01), pathological stage ( p = 0.03), and T and N factors ( p = 0.2, respectively). Factors affecting survival in multivariate analysis included IT ( p = 0.02) and histology ( p = 0.03)., Conclusions: In our experience, CP had a low mortality, acceptable morbidity, and good long-term survival, which justifies this surgical procedure. Postoperative complications were not influenced by IT. Long-term survival was adversely influenced by the absence of IT, the presence of extended resection, the presence of squamous cell carcinoma, and cancers at advanced stages.

Background: We report the outcomes for unresectable patients with locally advanced or oligometastatic non-small cell lung cancer (NSCLC) treated with tyrosine kinase inhibitor (TKI) or immunotherapy who achieved a clinical downstaging so as to re-enter resectability., Methods: We retrospectively reviewed the clinical, surgical, and pathological data of 42 patients with histologically proven, inoperable NSCLC who received rescue surgery after a good response to TKI or immunotherapy between March 2014 and December 2021., Results: Of 42 patients, 39 underwent pulmonary resection with therapeutic intent (three explorative thoracotomies). There were 26 males, with a median age of 64 years (range, 41-78 years). Twenty-three patients received TKIs and 19 immunotherapies. Anatomic resection was performed in 97.4% of resected patients (38/39) including 30 lobectomies, one right upper sleeve lobectomy, five pneumonectomies, one tracheal sleeve pneumonectomy, and one bilobectomy; a patient underwent wedge resection. Of 10 procedures attempted via a robotic approach, two required conversion to thoracotomy. No intraoperative morbidity/mortality occurred. The median operative time was 190 (range, 80-426) minutes; estimated blood loss was 200 mL (range, 35-780 mL). Morbidity occurred in 13/39 (33.3%). The median length of hospital stay was 6.5 days (range, 4-23 days). Pathologic downstaging was 74.4% (29/39). With a median follow-up of 28.7 months, the 5-year disease-free interval was 46.5%, and the 5-year overall survival was 66.0%; 32/39 patients (82.1%) are alive, 10 with the disease., Conclusions: Lung resection for suspected residual disease after immunotherapy or TKIs is feasible, with encouraging pathological downstaging. Surgical operation may be technically challenging due to the presence of fibrosis, but significant morbidity appears to be rare. Outcomes are encouraging, with reasonable survival during the short-interval follow-up.

This case series aimed to analyze the outcomes of patients referred for salvage pulmonary resections after treatment with chemotherapy and immunotherapy for previously metastatic or unresectable tumors.From October 2016, after multidisciplinary board discussion, eight patients (median: 67 years, range: 52-78 years) underwent medical treatment due to advanced-stage diseases (stage cIIIA-cIVa). Four patients underwent cisplatin-based chemotherapy and, due to progression, were moved to an immunotherapy second line (nivolumab: two patients and pembrolizumab: two patients). Instead, four patients underwent combined cisplatin-based chemotherapy and immune checkpoint inhibitors (atezolizumab: two patients and pembrolizumab: two patients). After a multidisciplinary evaluation for salvage surgery, six patients underwent lobectomies, one patient underwent left pneumonectomy, and one patient underwent upper right lobectomy enlarged to the posterior arches of four ribs. The median duration of surgery was 179 minutes (range: 122-246 minutes). At the final pathological stage, three patients showed a complete major response (ypT0 ypN0), one patient was ypT1a ypN0, one ypT3 ypN0, 2 ypT3 ypN1, and one ypT4 ypN0. The hospital length of stay was 6 days (range: 3-23 days). Two patients had a postoperative complication. At the time of follow-up (median: 15.3 months [range: 1-32 months]), six patients were alive without evidence of the recurrence. Two patients died due to recurrence progression (N3 lymph nodes involvement) of the disease after 6 and 32 months.In stage IIIB-IVA nonsmall cell lung cancer, salvage lung surgeries after chemotherapy and immunotherapy are feasible, with high rates of R0 resection. Surgery can be technically tricky without significant morbidity and encouraging outcomes (even with a short-interval follow-up)., Competing Interests: None declared., (Thieme. All rights reserved.)

Malignant pleural mesothelioma (MPM) is a rare neoplasm whose early diagnosis is challenging and systemic treatments are generally administered as first line in the advanced disease stage. The initial clinical response may represent a useful parameter in terms of identifying patients with a better long-term outcome. In this report, the initial therapeutical response in 46 patients affected with advanced/unresectable pleural mesothelioma was investigated. The initial therapeutic response was assessed by CT scan and clinical examination after 2-3 treatment cycles. Our preliminary evaluation shows that the group of patients treated with regimens including antiangiogenetics and/or immunotherapy had a significantly better initial response as compared to patients only treated with standard chemotherapy, exhibiting a disease control rate (DCR) of 100% (95% IC, 79.40-100%) and 80.0% (95% IC, 61.40-92.30%), respectively. Furthermore, the therapeutic response was correlated with the disease stage, blood leukocytes and neutrophils, high albumin serum levels, and basal body mass index (BMI). Specifically, the patients with disease stage III showed a DCR of 95.7% (95% IC, 78.1-99.9%), whereas for disease stage IV the DCR decreased to 66.7% (95% IC, 34.9-9.1%). Moreover, a better initial response was observed in patients with a higher BMI, who reached a DCR of 96.10% (95% IC, 80.36-99.90%). Furthermore, in order to evaluate in the predictive power of the collected features a multivariate way, we report the preliminary results of a machine learning model for predicting the initial therapeutic response. We trained a state-of-the-art algorithm combined to a sequential forward feature selection procedure. The model reached a median AUC value, accuracy, sensitivity, and specificity of 77.0%, 75%, 74.8%, and 83.3%, respectively. The features with greater informational power were gender, histotype, BMI, smoking habits, packs/year, and disease stage. Our preliminary data support the possible favorable correlation between innovative treatments and therapeutic response in patients with unresectable/advanced pleural mesothelioma. The small sample size does not allow concrete conclusions to be drawn; nevertheless, this work is the basis of an ongoing study that will also involve radiomics in a larger dataset.

After a variable period of activity of the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment, patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR mutations develop resistance to these TKIs. In some cases, an oligoprogression is diagnosed, and its management is still controversial. The oligoprogression represents an intermediate stage of metastatic NSCLC between localized and widely disseminated disease, and is characterized by a limited number and/or sites of metastases in which a disease progression appears, together with a more indolent tumor biology. Currently, the management of oligoprogressed NSCLC involves local treatment, including radiotherapy and/or surgery, to control the progressive lesions. Systemic therapy should also be a potential approach to boost the activity of EGFR-TKIs. However, considering the lack of large trials addressing this topic, the optimal therapeutic strategies remain undefined and should be evaluated on an individualized basis. In this paper, we review the most relevant scientific evidence of continuing the systemic therapy with the same EGFR-TKI for the management of patients with NSCLC harboring EGFR mutations and oligoprogressed to first-line EGFR-TKIs, also discussing the controversies and potential future directions.

Causing a high mortality rate worldwide, lung cancer remains an incurable malignancy resistant to conventional therapy. Despite the discovery of specific molecular targets and new treatment strategies, there remains a pressing need to develop more efficient therapy to further improve the management of this disease. Cancer stem cells (CSCs) are considered the root of sustained tumor growth. This consensus corroborates the CSC model asserting that a distinct subpopulation of malignant cells within a tumor drives and maintains tumor progression with high heterogeneity. Besides being highly tumorigenic, CSCs are highly refractory to standard drugs; therefore, cancer treatment should be focused on eliminating these cells. Herein, we present the current knowledge of the existence of CSCs, CSC-associated mechanisms of chemoresistance, the ability of CSCs to evade immune surveillance, and potential CSC inhibitors in lung cancer, to provide a wider insight to drive a more efficient elimination of this pro-oncogenic and treatment-resistant cell fraction.

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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Importance: Geriatric (aged ≥80 years) patients are historically underrepresented in cancer clinical trials. Little is known about the efficacy of immune checkpoint inhibitors (ICIs) in geriatric patients. These agents are associated with immune-related adverse events (irAEs), which may be particularly associated with morbidity in this population., Objective: To provide insight into the clinical outcomes and safety of ICIs among geriatric patients (aged ≥80 years) with cancer., Design, Setting, and Participants: A Multicenter, international retrospective study of 928 geriatric patients with different tumors treated with single-agent ICIs between 2010 to 2019 from 18 academic centers in the US and Europe. Analyses were conducted from January 2021 to April 2021., Main Outcomes and Measures: Clinical outcomes and irAE patterns in geriatric patients treated with single-agent ICIs., Results: Median (range) age of the 928 patients at ICI initiation was 83.0 (75.8-97.0) years. Most patients (806 [86.9%]) were treated with anti-programmed cell death 1 therapy. Among the full cohort, the 3 most common tumors were non-small cell lung cancer (NSCLC, 345 [37.2%]), melanoma (329 [35.5%]), and genitourinary (GU) tumors (153 [16.5%]). Objective response rates for patients with NSCLC, melanoma, and GU tumors were 32.2%, 39.3%, and 26.2%, respectively. Median PFS and OS, respectively, were 6.7 and 10.9 months (NSCLC), 11.1 and 30.0 months (melanoma), and 6.0 and 15.0 months (GU). Within histologically specific subgroups (NSCLC, melanoma, and GU), clinical outcomes were similar across age subgroups (aged <85 vs ≥85 years). Among all 928 patients, 383 (41.3%) experienced ≥1 irAE(s), including 113 (12.2%) that were reported to be grade (G) 3 to 4 based on Common Terminology Criteria for Adverse Events (version 5.0). The median time to irAE onset was 9.8 weeks; 219 (57%) occurred within the first 3 months after ICI initiation. Discontinuation of treatment with ICIs owing to irAEs occurred in 137 (16.1%) patients. There was no significant difference in the rate of irAEs among patients aged younger than 85, 85 to 89, and 90 years or older. Despite the similar rate of G3 or higher irAEs, ICIs were discontinued due to irAEs more than twice as often among patients aged 90 years or older compared with patients younger than 90 years (30.9% vs 15.1%, P = .008)., Conclusions and Relevance: The findings of this international cohort study suggest that treatment with ICIs may be effective and generally well tolerated among older patients with cancer, though ICI discontinuation owing to irAEs was more frequent with increasing age.

Background:  Intrathoracic neurogenic tumors (INTs) are uncommon neoplasms arising from nerve tissues. We report our single-center experience in treating these rare INTs., Methods:  Using a prospective institutional database, clinical, surgical, and pathological records of patients receiving resection of INT between May 1998 and June 2018 were analyzed. Survival was calculated by Kaplan-Meier method., Results:  There were 82 patients (24 females) with an average age of 53 years (29-75 years). Mean diameter was 32 mm (range, 12-68 mm). Histology included 49 schwannomas (11 malignant), 15 neurinomas (2 malignant), 14 neurilemmomas, and 4 paragangliomas. Tumor was located in the posterior mediastinum in 52 patients, in the thoracic inlet in 12, in the anterior mediastinum in 7, in the lung parenchyma in 5, and in the chest wall in 3. In three (3.6%) patients, the tumor showed an intraspinal extension. Symptoms were reported in 51 patients (62.2%) and included cough in 23, dyspnea in 15, neurologic symptoms in 11, and wheezing in 2. Operation was performed by thoracotomy in 42 (51.2%) cases and less invasive technique in 40 (48.8%) cases. Resection was completed in 80 patients (97.6%). Postoperative radiotherapy was administered in two cases. Intraoperative and postoperative mortalities were nil. Morbidity occurred in four patients (4.8%) including two prolonged air leaks, one hemothorax, and one chylothorax. Five-year survival was 97% (mean follow-up, 4.9 years). Malignant tumors had a worse prognosis ( p  = 0.02). No recurrence occurred during the follow-up neither for malignant nor for benign tumors., Conclusion:  The treatment of choice for INTs is complete resection which will be tailored to tumor size, location, and extension. Long-term prognosis is favorable for benign neurogenic tumors., Competing Interests: None declared., (Thieme. All rights reserved.)

In developed countries, lung cancer is the leading cause of cancer-related death in both sexes. Although cigarette smoking represents the principal risk factor for lung cancer in females, the higher proportion of this neoplasm among non-smoking women as compared with non-smoking men implies distinctive biological aspects between the two sexes. Gender differences depend not only on genetic, environmental, and hormonal factors but also on the immune system, and all these aspects are closely interconnected. In the last few years, it has been confirmed that the immune system plays a fundamental role in cancer evolution and response to oncological treatments, specifically immunotherapy, with documented distinctions between men and women. Consequently, in order to correctly assess cancer responses and disease control, considering only age and reproductive status, the results of studies conducted in female patients would probably not categorically apply to male patients and vice versa. The aim of this article is to review recent data about gender disparities in both healthy subjects' immune system and lung cancer patients; furthermore, studies concerning gender differences in response to lung cancer immunotherapy are examined.

Small-cell lung cancer (SCLC) is an aggressive malignancy that exhibits a rapid doubling time, a high growth fraction, and the early development of widespread metastases. The addition of immune checkpoint inhibitors to first-line chemotherapy represents the first significant improvement of systemic therapy in several decades. However, in contrast to its effects on non-SCLC, the advantageous effects of immunotherapy addition are modest in SCLC. In particular, only a small number of SCLC patients benefit from immune checkpoint inhibitors. Additionally, biomarkers selection is lacking for SCLC, with clinical trials largely focusing on unselected populations. Here, we review the data concerning the major biomarkers for immunotherapy, namely, programmed death ligand 1 expression and tumour mutational burden. Furthermore, we explore other potential biomarkers, including the role of the immune microenvironment in SCLC, the role of genetic alterations, and the potential links between neurological paraneoplastic syndromes, serum anti-neuronal nuclear antibodies, and outcomes in SCLC patients treated with immunotherapy.

Introduction: The efficacy of immune checkpoint inhibitors in patients with brain metastases (BMs) from non-oncogene addicted non-small cell lung cancer (NSCLC) is under investigation. Here, we sought to determine the optimal management of NSCLCs with PD-L1 ≥ 50% and asymptomatic BMs who were treated with first-line pembrolizumab., Methods: Thirty patients from 15 institutions with PD-L1 ≥ 50% NSCLC had asymptomatic BMs, and met inclusion criteria. Patients were classified based on whether they had undergone upfront local radiotherapy for BMs as well as on the type of brain radiotherapy received., Results: Nine patients were treated with upfront pembrolizumab alone, 8 patients with whole-brain radiotherapy (WBRT) followed by pembrolizumab and 13 patients with stereotactic radiosurgery (SRS) followed by pembrolizumab. Patients' characteristics were similar among the three groups of patients except for a higher number of BMs ≥ 3 in the WBRT group. One complete and 4 partial intracranial responses were observed with upfront pembrolizumab alone. The median survival was not reached for the pembrolizumab and WBRT (n = 8) groups, and it was 7.6 months for the SRS (n = 13) group (P = 0.09), with 12-month survival rates being 55.5%, 62.5%, and 23.0%, respectively. Salvage WBRT was delivered in 1 patient in the upfront pembrolizumab group and in 4 patients in the SRS group., Conclusions: Upfront pembrolizumab showed efficacy in selected patients with PD-L1 ≥ 50% non-oncogene addicted NSCLC and asymptomatic BMs. Prospective studies should address whether pembrolizumab alone, and deferral of radiotherapy, could be pursued in this patient population., (© 2021. Federación de Sociedades Españolas de Oncología (FESEO).)

Background: Pulmonary neuroendocrine tumors include well-differentiated and poorly differentiated histology for which cell type has proved to be a determinant of survival in many studies. In patients diagnosed with bronchial carcinoid and large cell neuroendocrine carcinoma (LCNEC), surgery is the treatment of choice even in the case of locally advanced disease with lymph node involvement., Methods: We retrospectively analyzed patients undergoing anatomic lung resection for bronchial carcinoid or LCNEC with lymph node involvement (N1/N2) at the final pathologic examination (pN+). Characteristics of patients and differences in overall survival and disease-free survival are presented according to tumor type. Overall survival of distinct histologic groups was compared with survival in our institutional experience in stage I patients, without nodal involvement (pN0)., Results: In all, 325 patients underwent surgical resection for neuroendocrine tumors; 89 patients had nodal involvement. Five-year survival was 89% in pN+ bronchial carcinoid both for typical carcinoid and atypical carcinoid but worse for pN+ LCNEC (47%). Cell type did not influence the prognosis in N0 disease, and no differences in survival were evident between N0 and N+ in the bronchial carcinoid group. In the group of LCNEC, 5-year overall survival was much worse for pN+ LCNEC (47%) compared with pN0 LCNEC (91%)., Conclusions: Bronchial carcinoids have the best prognosis, and surgery remains the treatment of choice for both early and locally advanced disease. On the contrary, aggressive forms (LCNEC) with lymph nodal metastasis have a poor prognosis, and they need to be treated with an aggressive multidisciplinary approach., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Giving the potential contribute in cancer initiation and progression, lung microbiota represents a promising topic in cancer research, although still unexplored. We performed a systematic literature search to identify clinical studies evaluating lung microbiota composition, its correlation with lung cancer patients' clinico-pathological features and prognosis. Of the identified 370 studies, 21 were eligible and included. Although studies were heterogeneous, lung cancer resulted to be enriched in peculiar microbial communities, with differences in composition and diversity according to clinico-pathological parameters. Few studies explored how lung microbiota influences cancer outcome. In light of these findings and borrowing the suggestions coming from gut microbiota, we speculate that respiratory microbiome may influence pathogenesis, progression and outcome of lung cancer. Taking advantage of the experience of chronical lung diseases, prospective studies should be designed to evaluate lung microbiota changes throughout any phase of lung cancer course, particularly with the advent of immunotherapy as pivotal treatment., (Copyright © 2021. Published by Elsevier B.V.)

Objectives: 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)., Material and Methods: 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., Results: 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., Conclusion: 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., (Copyright © 2021 Elsevier B.V. All rights reserved.)