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A simple and inexpensive shaker/Erlenmeyer flask system for large-scale cultivation of insect cells is described and compared to a commercial spinner system. On the basis of maximum cell density, average population doubling time and overproduction of recombinant protein, a better result was obtained with a simpler and less expensive bioreactor consisting of Erlenmeyer flasks and an ordinary shaker waterbath. Routinely, about 90 mg of pure poly(ADP-ribose) polymerase catalytic domain was obtained for a total of 3 x 109 infected cells in three liters of culture

Background: While immune checkpoint inhibitors (ICIs) are increasingly reshaping the therapeutic landscape of non-small-cell lung cancer (NSCLC), only a limited proportion of patients achieve a relevant and long-lasting benefit with these treatments, calling for the identification of clinical and, ideally modifiable, predictors of efficacy. Body composition phenotypes may reflect aspects of patients' immunology and thereby their ability to respond to ICIs. This study aims to explore the possible association between pre-treatment body composition phenotypes, tumour response, and clinical outcomes in patients receiving first-line pembrolizumab monotherapy for advanced NSCLC., Methods: A retrospective review of consecutive patients with treatment-naïve NSCLC and PD-L1 expression ≥50% undergoing pembrolizumab at three academic institutions was performed. Pre-treatment body composition parameters were measured at the third lumbar vertebra level by computed tomography, defined using pre-established cut-offs. Primary endpoint was objective response rate (ORR), secondary endpoints progression-free survival and overall survival (PFS and OS), compared through the log-rank test and the Cox proportional hazards model., Results: Data from 134 patients (93 males [69.4%] and 41 females [30.6%]) were collected. Median age was 69 years (range 36-85), with a median follow-up of 12 months (range 1-131). The median body mass index (BMI) was 24.5 (IQR 21.5; 26.1) kg/m 2 . Overall, 59.0% and 51.5% of patients met established radiographic criteria for evidence of sarcopenia and myosteatosis, respectively, which occur across the BMI spectrum. Multivariate regression analysis, adjusted for co-morbidities, revealed that sarcopenia (aOR 5.56, 95% CI. 2.46-12.6, P < 0.0001) and low intermuscular adipose tissue (IMAT) area (aOR 1.83, 95% CI. 1.22-2.83, P = 0.001) were associated with a lower rate of ORR (30.4% vs. 70.5%, P < 0.0001 and 30.7% vs. 73.2%, P < 0.0001, respectively). Moreover, both in univariate and multivariate analysis, adjusted for co-morbidities, low performance status according to the Eastern Cooperative Oncology Group scale (ECOG PS), sarcopenia and low IMAT were significantly related to short PFS (ECOG PS: aHR 2.73, 95% CI 1.60-4.66, P < 0.0001; sarcopenia: aHR 2.24, 95% CI 1.37-3.67, P = 0.001; IMAT depot: aHR 2.26, 95% 1.40-3.63, P = 0.002) and OS (ECOG PS: aHR 3.44, 95% CI 1.96-6.01, P < 0.0001; sarcopenia: aHR 4.68, 95% CI 2.44-8.99, P < 0.0001; IMAT depot: aHR 3.18, 95% 1.72-5.88, P < 0.0001)., Conclusions: Skeletal muscle abnormalities, apparently frequent in NSCLC, potentially represent intriguing predictive markers of response to ICIs and survival outcomes. Large prospective trials are needed to validate ICIs responders' clinical biomarkers., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with oncogene-addicted metastatic non-small-cell lung cancer (mNSCLC), published in January 2023, was modified according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with oncogene-addicted mNSCLC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with oncogene-addicted mNSCLC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), co-ordinated by ESMO and the Korean Society for Medical Oncology (KSMO). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different regions of Asia. The latter are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with oncogene-addicted mNSCLC across the different regions of Asia, drawing on the evidence provided by both Western and Asian trials, while respecting the differences in screening practices, molecular profiling and age and stage at presentation. Attention is drawn to the disparity in the drug approvals and reimbursement strategies between the different regions of Asia., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

While recent randomized controlled trials (RCT) have suggested superior overall survival (OS) outcomes with segmentectomy over lobectomy, questions remain regarding the comparability of these surgical procedures for treating early-stage non-small cell lung cancer (NSCLC). This systematic review and meta-analysis aimed to synthetize existing evidence and to compare the survival outcomes observed for stage IA NSCLC following segmentectomy or lobectomy. 40 studies (38 observational, 2 RCTs) encompassing 103,926 patients were analyzed. Primary outcomes included overall survival (OS), disease-free survival (DFS), local recurrences, harvested lymph nodes, postoperative morbidity, and length of hospital stay. Risk of bias was assessed using established tools, and evidence certainty was evaluated using GRADE. Non-RCTs showed an OS HR of 1.10 (95 % CI: 0.94-1.30, p = 0.24) with low certainty, contrasting with RCTs' HR of 0.82 (95 % CI: 0.66-1.02, p = 0.7) with moderate certainty. Local recurrences exhibited OR 1.40 (95 % CI: 0.94-2.08, p = 0.09) in non-RCTs with low certainty, and RR 1.61 (95 % CI: 1.12-2.31, p = 0.01) in RCTs with low certainty. Non-RCTs showed DFS HR 1.13 (95 % CI: 0.95-1.34, p = 0.18) with low certainty, while RCTs yielded HR 1.00 (95 % CI: 0.85-1.18, p = 0.97) with moderate certainty. Lobectomy resulted in more harvested lymph nodes. Postoperative morbidity and length of hospital stay did not differ significantly. While definitive evidence for OS, DFS, and postoperative outcomes differences was inconclusive, a potential increase in local recurrences following lobectomy was noted. Further well-designed studies are warranted to enhance evidence and inform clinical practice in stage I lung cancer surgery., 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 © 2024 Elsevier B.V. All rights reserved.)

Epigenetic dysregulation has long been recognized as a significant contributor to tumorigenesis and tumor maintenance, impacting all recognized cancer hallmarks. Although some epigenetic drugs have received regulatory approval for certain hematological malignancies, their efficacy in treating solid tumors has so far been largely disappointing. However, recent advancements in developing new compounds and a deeper understanding of cancer biology have led to success in specific solid tumor subtypes through precision medicine approaches. Moreover, epigenetic drugs may play a crucial role in synergizing with other anticancer treatments, enhancing the sensitivity of cancer cells to various anticancer therapies, including chemotherapy, radiation therapy, hormone therapy, targeted therapy, and immunotherapy. In this review, we critically evaluate the evolution of epigenetic drugs, tracing their development from initial use as monotherapies to their current application in combination therapies. We explore the preclinical rationale, completed clinical studies, and ongoing clinical trials. Finally, we discuss trial design strategies and drug scheduling to optimize the development of possible combination therapies., Competing Interests: MM reports honoraria from AstraZeneca (

Introduction: To date, for all non-small cell lung cancer (NSCLC) cases, it is recommended to test for driver alterations to identify actionable therapeutic targets. In this light, comprehensive genomic profiling (CGP) with next generation sequencing (NGS) has progressively gained increasing importance in clinical practice. Here, with the aim of assessing the distribution and the real-world frequency of gene alterations and their correlation with patient characteristics, we present the outcomes obtained using FoundationOne (F1CDx) and FoundationLiquid CDx (F1L/F1LCDx) NGS-based profiling in a nationwide initiative for advanced NSCLC patients., Methods: F1CDx (324 genes) was used for tissue samples, and F1L (70 genes) or F1LCDx (324 genes) for liquid biopsy, aiming to explore the real-world occurrence of molecular alterations in aNSCLC and their relationship with patients' characteristics., Results: Overall, 232 advanced NSCLC patients from 11 Institutions were gathered [median age 63 years; never/former or current smokers 29.3/65.9%; adenocarcinoma/squamous 79.3/12.5%; F1CDx/F1L+F1LCDx 59.5/40.5%]. Alterations were found in 170 different genes. Median number of mutated genes per sample was 4 (IQR 3-6) and 2 (IQR 1-3) in the F1CDx and F1L/F1LCDx cohorts, respectively. TP53 (58%), KRAS (22%), CDKN2A/B (19%), and STK11 (17%) alterations were the most frequently detected. Actionability rates (tier I and II) were comparable: 36.2% F1CDx vs. 34% ctDNA NGS assays (29.5% and 40.9% F1L and F1LCDx, respectively). Alterations in KEAP1 were significantly associated with STK11 and KRAS , so as TP53 with RB1 . Median tumor mutational burden was 6 (IQR 3-10) and was significantly higher in smokers. Median OS from metastatic diagnosis was 23 months (IQR 18.5-19.5) and significantly lower in patients harboring ≥3 gene mutations. Conditional three-year survival probabilities increased over time for patients profiled at initial diagnosis and exceeded those of individuals tested later in their clinical history after 12 months., Conclusion: This study confirms that NGS-based molecular profiling of aNSCLC on tissue or blood samples offers valuable predictive and prognostic insights., Competing Interests: MaS declares travel fees from Roche and Sanofi unrelated to the current work. LB declares travel fees from Eli Lilly, Sanofi and Takeda, Advisory Board role from AMGEN, Roche and Takeda, Speaker Honoraria from Amgen and BMS, Research funding from BMS, unrelated to the current work. HS declares advisory board role for BMS, MSD, Roche, Pfizer, Takeda, AstraZeneca, Merck unrelated to the current work. MO declares travel accommodation from Eli Lilly and Advisory Board role/Speaker Honoraria from Astra Zeneca, BMS and MSD, outside the submitted work. ES and SC are employed at Roche. LP is the co-owner and an employee of AdRes, which has received project funding from Roche; outside the submitted work, received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational event from Fresenius Kabi, Janssen Cilag, SINPE; AdRes received grants or contracts from Janssen Cilag, Roche, Novartis, Sanofi, Astellas, Diasorin, Nestlè, Shionogi, Boehringer Ingelheim, GSK, and others, outside the submitted work. CP is employee of Adres. The funder had no role in the data collection and no access to patient level data. UM 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 unrelated to the current work. SN 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. EB received speakers’ and travel fees from MSD, Astra-Zeneca, Celgene, Pfizer, Helsinn, Eli-Lilly, BMS, Novartis, and Roche, institutional research grants from Astra-Zeneca and Roche. SP received honoraria or speakers’ fees from Astra-Zeneca, Eli-Lilly, BMS, MSD, Takeda, Amgen, Novartis, and Roche, unrelated to the current work. The remaining 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 Sposito, Belluomini, Nocini, Insolda, Scaglione, Menis, Simbolo, Lugini, Buzzacchino, Verderame, Spinnato, Aprile, Calvetti, Occhipinti, Marinelli, Veccia, Lombardo, Soto Parra, Ferraù, Savastano, Porta, Pradelli, Sicari, Castellani, Malapelle, Novello, Bria, Pilotto and Milella.)

Objectives: PsA and gout are two prevalent rheumatic diseases, that can be associated as part of a rheumatism known as 'Psout'. Both conditions are associated with cardiovascular (CV) risk, thus their co-occurrence could have significant implications for the management of CV risks and patient care. This study aimed to determine the prevalence of gout within a PsA patient cohort and, consequently, to identify factors associated with this pathological association., Methods: This is an observational, descriptive, cross-sectional, single-center study, including patients diagnosed with PsA. Demographic, clinical, biological and imaging data were collected. We identified the proportion of patients simultaneously affected by PsA and gout and compared characteristics between those with and without gout., Results: The prevalence of gout among PSA patients was 9.8% (12/122), with a prevalence of 23% for asymptomatic hyperuricemia and 7.4% presenting with specific US signs of gout. Significant associated factors in the univariate analysis included weight, hypertension, diabetes, certain medications (diuretics, aspirin, lipid-lowering agents), impaired renal function, elevated fasting blood glucose, lipid abnormalities and specific US signs of gout., Conclusion: Our study has described the existence of patients simultaneously affected by PsA and gout ('Psout'). Performing joint US along with uric acid level measurements in PsA patients can enable personalized therapeutic care., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Introduction: The LIPI, based on pretreatment derived neutrophils/[leukocytes-neutrophils] ratio (dNLR) and LDH, is associated with immune checkpoint inhibitors (ICI) outcomes in advanced non-small-cell lung cancer (NSCLC). We aimed to assess baseline LIPI correlation with durvalumab consolidation outcomes in the locally advanced setting., Material and Methods: Multicentre retrospective study (330 patients) with stage III unresectable NSCLC treated with durvalumab after chemo-radiotherapy between April 2015 and December 2020; 65 patients treated with chemo-radiotherapy only. Baseline LIPI characterized 3 groups: good (dNLR≤3+LDH≤ULN), intermediate (dNLR>3/LDH>ULN) and poor (dNLR>3+LDH>ULN). Primary endpoint was overall survival (OS)., Results: In the durvalumab cohort, median age was 67 years, 95% smokers, 98% with a performance status of 0-1; 60% had nonsquamous histology and 16% a PD-L1 expression <1%. Radiotherapy was delivered concurrently in 81%. LIPI was evaluable in 216 patients: 66% good, 31% intermediate, 3% poor. LIPI significantly correlated with median OS (median follow-up: 19 months): 18.1 months vs. 47.0 months vs. not reached in poor, intermediate and good LIPI groups, respectively (P = .03). A trend between objective response rate and LIPI groups was observed: 0% vs. 41% vs. 45%, respectively (P = .05). The pooled intermediate/poor LIPI group was associated with shorter OS (HR 1.97; P = .03) and higher risk of progressive disease (OR 2.68; P = .047). Survivals and response were not influenced in the control cohort., Conclusion: Baseline LIPI correlated with outcomes in patients with locally advanced NSCLC treated with durvalumab consolidation, but not in those who only received chemo-radiotherapy, providing further evidence of its prognostic and potential predictive role of ICI benefit in NSCLC., Competing Interests: Disclosure VAA: Lectures and educational activities: Bristol-Myers Squibb, AstraZeneca, MSD; Travel, Accommodations, Expenses: Takeda, Sanofi, Janssen; RL: Personal fees: AstraZeneca, Bristol-Myers Squibb. Travel, Accommodations: Roche, Italfarmaco; RLC: Consulting, advisory role or lectures: Amgen, Bristol-Myers Squibb, Pierre-Fabre, Boehringer Ingelheim, Novartis, Roche. Honoraria: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Pierre-Fabre, MSD, Novartis, Pfizer, Roche, Takeda. Clinical trials research: AstraZeneca, Roche. Travel, Accommodations, Expenses: Roche, Novartis, Takeda, Boehringer Ingelheim; JBB: Reports grants and personal fees from Roche and Pfizer, and personal fees from MSD, BMS, AstraZeneca, Boehringer-Ingelheim, Sanofi, and Novartis, outside the submitted work; SP: Consulting, advisory role or lectures: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Roche, Amgen, Takeda (outside the submitted manuscript); MT: Travel, accommodation, expenses: Roche, Bristol-Myers Squibb, AstraZeneca, Takeda, Eli Lilly. Honoraria as medical writer: Novartis, Amgen, MSD. None related to the current manuscript; MS: Speaker, Advisory Role: Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi Avemtis, Siemens Healthineers, Takeda; Research support (institutional): Amgen, BMS, Dracen Pharmaceuticals, Janssen, Novartis, Pfizer, Siemens Healthiness; EN: has participated in lectures and advisory boards from Roche, Bristol Myers Squibb, Merck Sharp & Dohme, Merck Serono, Pfizer, Lilly, Amgen, Boehringer Ingelheim, AstraZeneca, Takeda, Sanofi and Bayer. E. N. has received research funding support from Pfizer, Roche, Merck Serono, Bristol Myers Squibb and Nanostring; GL: Honorary from Boehringer Ingelheim, Blueprint Medicines, AstraZeneca, Merck, Janssen; Consulting and advisory role from Pfizer and AstraZeneca; Research funding from AstraZeneca, Lucence, Xilis, Merck Sharp and Dohme, EMD Serono, Blueprint Medicines, Tesaro, Vavarian Nordic, Novartis, G1 Therapeutics. AdaptImmune, BMS, GSK, Abbvie, Rgenix, Pfizer, Roche, Genentech, Lilly, Janssen; travel, accommodations and expenses from Boehringer Ingelheim, Pfizer, Squibb Sons, Janssen, Seattle Genetics, Celgene, Ibsen, Pharmacyclocs, Merck, AstraZeneca, Seagen; DS: Consulting, advisory role: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Merck Sharp & Dohme, Sanofi. Honoraria: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Roche, Merck Sharp & Dohme. Principal Investigator in clinical trial sponsored by Bristol-Myers Squibb, Merck Sharp & Dohme, Eli Lilly. Travel, Accommodations: AstraZeneca, Roche, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer; RGC: Consulting, advisory role or lectures from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Takeda, Janseen, MSD, Roche, Pfizer, Eli Lilly, Amgen, Sanofi; honoraria (self) from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Pfizer, Roche, MSD, Takeda, Eli Lilly, Novartis; clinical trials research from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, Medimmun, Sanofi-Aventis; VB: Consulting, advisory role: AstraZeneca, Bristol-Myers Squibb, MSD, Merck, Novartis, Pfizer, Roche. Clinical trials research: AstraZeneca, MSD, Roche; MC: Advisory or Consultancy role: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, EUSA Pharma, Lilly, Roche. Honoraria, lectures: Abbot, AstraZeneca, Bristol-Myers Squibb, EUSA Pharma, Ipsen, Merck, Sharp & Dohme, Novartis, Pfizer, Pierre Fabre, Roche, Takeda. Travel expenses: Ipsen, Lilly, Merck, Pfizer, Pierre Fabre. Institutional financial interests: Astra Zeneca, Merck, Pfizer, Roche; BB: Sponsored Research at Gustave Roussy Cancer Center, Abbvie, Amgen, AstraZeneca, Biogen, Blueprint Medicines, BMS, Celgene, Eli Lilly, GSK, Ignyta, IPSEN, Merck KGaA, MSD, Nektar, Onxeo, Pfizer, Pharma Mar, Sanofi, Spectrum Pharmaceuticals, Takeda, Tiziana Pharma; DP: Consulting, advisory role or lectures: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche. Honoraria: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche. Clinical trials research: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, Medimmun, Sanofi-Aventis, Taiho Pharma, Novocure, Daiichi Sankyo. Travel, Accommodations, Expenses: AstraZeneca, Roche, Novartis, prIME Oncology, Pfizer; LM: Research grant/Funding (self): Bristol Myers Squibb, Boehringer Ingelheim, Amgen, Stilla, Inivata; Advisory/Consultancy: Roche Diagnostics, Takeda; Honoraria (self): Bristol Myers Squibb, Tecnofarma, Roche; Travel/Accommodation/Expenses: Roche, Boehringer Ingelheim, Takeda, AstraZeneca. The remaining authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aims: SCLC is the most aggressive lung cancer histology with a 5-year OS <10%. At the diagnosis, almost two-thirds of the SCLC an Extended Disease presentation. Two randomized studies (CASPIAN and ImPower133) demonstrated an OS improvement, when immunotherapy was prescribed as maintenance therapy after standard chemotherapy. To date, SABR has had a limited indication in managing metastatic SCLC, although recent reports proposed it as a valid treatment option in selected patients. We propose a retrospective multicentric analysis of patients treated with SABR for oligometastatic SCLC., Method: Data of patients affected by oligometastatic-SCLC treated with SABR between 2017 and 2022 in 11 Italian centers were collected. Clinical and therapeutic variables together with OS and time to next treatment were analyzed. Univariate analysis with Kaplan-Meier curve were calculated, and log-rank test were applied. Cox proportional hazard model was used for multivariate analysis., Results: Data from 93 patients and 132 metastatic lesions were analyzed. The median age was 64 years (36-86) and all but 1 had Performance Status 0 or 1. Fifty-two patients presented ED at diagnosis. The first line treatment was radiochemotherapy in 42%, CHT alone in 24% and CHT-IO in 28%, others treatment accounts for 4% and only 2% of patients underwent best supportive care. Of the 132 lesions treated with SBRT 55 were in brain, 27 in lung, 11 in liver, 10 in lymph nodes, 8 in bones and 20 in adrenal gland. Median OS was 14 months, 1 year-OS and 2 years OS were 53% and 27%, respectively. The median TtNT was 14 months for the entire population. Of all the analyzed variables only, the anatomical site of the metastases and their number showed statistical significance in the univariate analysist, confirmed in the subsequent multivariate., Conclusion: SABR seems to play a role in delaying further systemic lines in oligometastatic disease and to extend the use of ongoing treatment in oligoprogressive state. Prospective studies are needed to confirm these findings., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Treatment with 3 years of adjuvant osimertinib is considered a new standard in patients with completely resected stage I to IIIA NSCLC harboring a common sensitizing EGFR mutation. This therapeutic approach significantly prolonged the disease-free survival and the overall survival versus placebo and revealed a significant role in preventing the occurrence of brain metastases. However, many unanswered questions remain, including the optimal duration of this therapy, whether all patients benefit from adjuvant osimertinib, and the role of adjuvant chemotherapy in this population. Indeed, there is a renewed interest in neoadjuvant strategies with targeted therapies in resectable NSCLC harboring oncogenic drivers. In light of these considerations, we discuss the past and current treatment options, and the clinical challenges that should be addressed to optimize the treatment outcomes in this patient population., (Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

This study describes the characteristics of 337 patients seen by the fracture liaison service of the Amiens University Hospital for at least two osteoporotic fractures between 2009 and 2019. Results showed that recurrent fracture occurs rapidly after the index fracture. Rheumatological and therapeutic managements are not sufficient, mainly because of cognitive disorders or patients' refusal., Purpose: The aim of this study was to describe the characteristics of patients taken in charge by a fracture liaison service and sustaining a recurrent osteoporotic fracture., Methods: This was a retrospective and monocentric study based on the dataset of patients included in the FLS of the Department of Rheumatology of the Amiens University Hospital. To be included in the study cohort, patients must have had at least two consecutive osteoporotic fractures between January 2009 and December 2019., Results: Three hundred thirty-seven patients were included. The mean age at index fracture was 77.3 ± 12.5 years. Eighty-four percent of the patients were women. 89.3% of the patients had a Charlson comorbidity index between 1 and 4. Nearly half of the patients had cognitive disorders. Femoral neck was the most frequent site for both index and recurrent fractures. Thirty-seven percent of patients benefited from a consultation in Rheumatology after their index fracture. The main reasons for the lack of follow-up were cognitive disorders and patient rejection., Conclusion: Our study showed that recurrent fracture occurs rapidly after the index fracture and that rheumatological and therapeutic managements are not sufficient, mainly because of cognitive disorders or patients' refusal impairing the patients to benefit from specialized management., (© 2023. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Competing Interests: The authors declare no competing interests.

Competing Interests: Disclosure LEH reports personal fees as an invited speaker from Benecke, Medtalks and VJOncology; personal fees for participation in mentorship programme funded by AstraZeneca; personal fees for travel support from Roche; personal fees as member of the committee that revised the Dutch guidelines on NSCLC, brain metastases and leptomeningeal metastases; fees paid to her institution for an educational webinar from Janssen; fees paid to her institution for advisory board membership from Amgen, Bristol Myers Squibb (BMS), Boehringer Ingelheim, Janssen, Lilly, Merck, Merck Sharp & Dohme (MSD), Novartis, Pfizer, Roche and Takeda; fees paid to her institution as an invited speaker from AstraZeneca, Bayer, high5oncology, Lilly and MSD; fees paid to her institution for interview sessions from Roche; fees paid to her institution for podcast appearance from Takeda; institutional research grants from AstraZeneca, Boehringer Ingelheim, Roche, Takeda, Pfizer and Merck; institutional funding as a local principal investigator (PI) from AbbVie, AstraZeneca, Blueprint Medicines, Gilead, GlaxoSmithKline (GSK), Merck Serono, Mirati, MSD, Novartis, Roche and Takeda; non-remunerated roles as chair for metastatic NSCLC of the lung cancer group for European Organisation for Research and Treatment of Cancer (EORTC) and as the secretary of the studies foundation for NVALT (Nederlandse Vereniging van Artsen voor Longziekten en Tuberculose). KMK reports personal fees as an invited speaker from Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, Medscape, Merck Serono, MSD, Novartis, Pfizer, Prime Oncology, Roche and Roche Diagnostics/Ventana; personal fees for consultancy and advisory board membership from AbbVie, Amgen, AstraZeneca, Bayer, Debiopharm, Diaceutics, Janssen, Merck Serono, MSD, Novartis, Pfizer, Regeneron, Roche and Roche Diagnostics/Ventana; non-remunerated roles as the past Pathology Committee Chair for IASLC (International Association for the Study of Lung Cancer) and member of the UK Lung Cancer Consortium. JM reports fees paid to her institution as an invited speaker from AstraZeneca, Boehringer Ingelheim, BMS, MSD and Roche; fees paid to her institution for expert testimony from AstraZeneca, Boehringer Ingelheim and MSD; fees paid to her institution for travel expenses from Ipsen. TSM reports personal fees as an invited speaker from AbbVie, ACEA Pharma, Alpha Biopharma, Amgen, Amoy Diagnostics, BeiGene, Boehringer Ingelheim, BMS, Daiichi Sankyo, Daz Group, Eli Lilly, Fishawack Facilitate, InMed Medical Communication, Janssen, Jiahui Holdings Co., LiangYiHui Healthcare, Lucene Health Inc., Lunit USA, Inc., MD Health, Medscape/WebMD, Merck Serono, MSD, MiRXES, Novartis, OrigiMed, PeerVoice, PER, Permanyer SL, Pfizer, Prime Oncology, Research to Practice, Roche, Sanofi-Aventis, Shanghai BeBirds Translation & Consulting Co., Taiho Pharmaceutical Co., Takeda and Touch Medical Media; personal fees for advisory board membership from AbbVie, ACEA Pharma, Alpha Biopharma, Amgen, Amoy Diagnostics, BeiGene, Berry Oncology, Blueprint Medicines, Boehringer Ingelheim, BMS, C4 Therapeutics, Cirina Ltd., Covidien LP, CStone Pharma, Curio Science, D3 Bio Ltd., Da Volterra, Daiichi Sankyo, Eisai, Eli Lilly, Fishawack Facilitate, G1 Therapeutics, Gilead Sciences, Gritstone Oncology, Guardant Health, Hengrui, Ignyta, Incyte, Inivata, IQVIA, Janssen, Lakeshore Biotech, Loxo Oncology, Lucene Health Inc., Lunit USA, Inc., Medscape/WebMD, Merck Serono, Mirati Therapeutics, MiRXES, MoreHealth, MSD, Novartis, OrigiMed, OSE Immunotherapeutics, Pfizer, Puma Tech, Qiming Development, Roche, Roche/Genentech, Sanofi-Aventis, SFJ Pharmaceutical Ltd., Synergy Research, Takeda, Tigermed, Vertex Pharmaceuticals, Virtus Medical and Yuhan; personal fees as the Chairman for ACT Genomics-Sanomics Group; personal fees as a member of the board of directors from AstraZeneca and HutchMed; holds stocks/shares from AstraZeneca, Aurora Tele-Oncology, Biolidics Ltd., HutchMed and Sanomics Ltd.; institutional funding from AstraZeneca, BMS, Clovis Oncology, G1 Therapeutics, Merck Serono, MSD, Novartis, Pfizer, Roche, SFJ Pharmaceuticals, Takeda and XCovery; non-remunerated roles as an invited speaker with AstraZeneca, Aurora Tele-Oncology, Lunit USA, Inc. and Sanomics Ltd. and for an advisory role with geneDecode; non-remunerated leadership roles with ASCO (American Society of Clinical Oncology), ATORG (Asian Thoracic Oncology Research Group), CLCRF (Chinese Lung Cancer Research Foundation Limited), CSCO (Chinese Society of Clinical Oncology), HKCF (Hong Kong Cancer Fund), HKCTS (Hong Kong Cancer Therapy Society), IASLC and St. Stephen’s College & Prep School (Hong Kong). UN reports fees paid to her institution as an invited speaker from MSD; fees paid to her institution for advisory board membership and a writing engagement from AstraZeneca; institutional funding as a coordinating PI for Bayer; non-remunerated roles as a PI for clinical trials funded by Deutsche Krebshilfe and as a member of the board of directors and vice-chair of ‘Strahlenschutzkommission’ from the German Commission on Radiological Protection. AP reports personal fees as an invited speaker from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Mundipharma and Takeda; personal fees for advisory board membership from AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, Janssen, MSD, Pfizer and Roche; non-remunerated activities with AIOM (Italian Association of Medical Oncology) as member of the Scientific Committee for lung cancer guidelines. SP reports personal fees for an editorial role as an Associate Editor for Annals of Oncology; fees paid to her institution as an invited speaker from AstraZeneca, BMS, Boehringer Ingelheim, e-cancer, Eli Lilly, Fishawack, Illumina, Imedex, Medscape, Mirati, MSD, Novartis, OncologyEducation, PER, Pfizer, PRIME, RMEI, Roche/Genentech, RTP, Sanofi and Takeda; fees paid to her institution for advisory board membership from AbbVie, Amgen, Arcus, AstraZeneca, Bayer, BeiGene, Bio Invent, Biocartis, Blueprint Medicines, BMS, Boehringer Ingelheim, Daiichi Sankyo, Debiopharm, Eli Lilly, F-Star, Foundation Medicine, Genzyme, Gilead, GSK, Illumina, Incyte, IQVIA, iTeos, Janssen, Merck Serono, Mirati, MSD, Novartis, Novocure, Pfizer, PharmaMar, Phosplatin Therapeutics, Regeneron, Roche/Genentech, Sanofi, Seattle Genetics, Takeda and Vaccibody; institutional funding as a steering committee member from AstraZeneca, BeiGene, BMS, iTeos, Mirati, MSD, PharmaMar, Phosplatin Therapeutics and Roche/Genentech; institutional funding as a coordinating PI from AstraZeneca; institutional funding as a trial chair from GSK and Roche/Genentech; non-remunerated role as President and Council Member for the Ballet Béjart Lausanne Foundation; non-remunerated leadership roles as President of ESMO (2020-2022), Vice-President of SAMO (Swiss Academy of Multidisciplinary Oncology), Vice-President of Lung Group for SAKK (Swiss Group for Clinical Cancer Research); non-remunerated role as PI involved in academic trials for ETOP (European Thoracic Oncology Platform)/EORTC/SAKK; non-remunerated role as Council Member and Scientific Committee Chair for ETOP/IBCSG Partners (International Breast Cancer Study Group); member of AACR (American Association for Cancer Research), ASCO, ASMAC/VSAO (Association of Swiss Interns and Residents), FMH (Association of Swiss Physicians) and IASLC. DP reports personal fees as an invited speaker from AbbVie, AstraZeneca, Janssen, Novartis, Peer CME, Pfizer, priME Oncology and Samsung; personal fees for advisory board membership from AbbVie, AstraZeneca, BMS, Celgene, Daiichi Sankyo, Janssen, Merck, Novartis, Pfizer, Roche and Samsung; institutional funding as a PI from AbbVie, AstraZeneca, BMS, Daiichi Sankyo, Janssen, Merck, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi and Sanofi-Aventis. EFS reports personal fees as an invited speaker from Boehringer Ingelheim and Daiichi Sankyo; personal fees for advisory board membership from Merck Serono; fees paid to his institution for advisory board membership from AstraZeneca, BMS, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Janssen, MSD, Roche, Sanofi and Takeda; institutional funding as a local PI from AstraZeneca, Genmab, Gilead and Pfizer. BJS reports personal fees as an invited speaker from AstraZeneca, Pfizer and Roche/Genentech; personal fees for advisory board membership from Amgen and Roche/Genentech; fees paid to his institution for advisory board membership from AstraZeneca, BMS, Merck and Novartis; fees paid to his institution for steering committee membership from Novartis, Pfizer and Roche/Genentech; personal fees as a member of the board of directors from Cancer Council Victoria and Thoracic Oncology Group of Australasia; personal fees as a consultant from Peter MacCallum Cancer Centre; royalties from UpToDate. GV reports personal fees as an invited speaker and for advisory board membership from Roche; personal fees as a consultant from Ab Medica; institutional funding as a PI from AIRC (Fondazione AIRC per la ricerca sul cancro ETS) and the Italian Ministry of Health. MR reports personal fees as an invited speaker from Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Lilly, Merck, MSD, Novartis, Roche and Sanofi; personal fees for advisory board membership from Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Mirati, MSD, Pfizer, Roche and Sanofi.

Competing Interests: Disclosure LEH reports personal fees as an invited speaker from Benecke, Medtalks and VJOncology; personal fees for participation in mentorship programme funded by AstraZeneca; personal fees for travel support from Roche; personal fees as member of the committee that revised the Dutch guidelines on NSCLC, brain metastases and leptomeningeal metastases; fees paid to her institution for an educational webinar from Janssen; fees paid to her institution for advisory board membership from Amgen, Bristol-Myers Squibb (BMS), Boehringer Ingelheim, Janssen, Lilly, Merck, Merck Sharp & Dohme (MSD), Novartis, Pfizer, Roche and Takeda; fees paid to her institution as an invited speaker from AstraZeneca, Bayer, high5oncology, Lilly and MSD; fees paid to her institution for interview sessions from Roche; fees paid to her institution for podcast appearance from Takeda; institutional research grants from AstraZeneca, Boehringer Ingelheim, Roche, Takeda, Pfizer and Merck; institutional funding as a local principal investigator (PI) from AbbVie, AstraZeneca, Blueprint Medicines, Gilead, GlaxoSmithKline (GSK), Merck Serono, Mirati, MSD, Novartis, Roche and Takeda; non-remunerated roles as chair for metastatic NSCLC of the lung cancer group for European Organisation for Research and Treatment of Cancer (EORTC) and as the secretary of the studies foundation for Nederlandse Vereniging van Artsen voor Longziekten en Tuberculose (NVALT). KK reports personal fees as an invited speaker from Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, Medscape, Merck Serono, MSD, Novartis, Pfizer, Prime Oncology, Roche and Roche Diagnostics/Ventana; personal fees for consultancy and advisory board membership from AbbVie, Amgen, AstraZeneca, Bayer, Debiopharm, Diaceutics, Janssen, Merck Serono, MSD, Novartis, Pfizer, Regeneron, Roche and Roche Diagnostics/Ventana; non-remunerated roles as the past Pathology Committee Chair for International Association for the Study of Lung Cancer (IASLC) and member of the UK Lung Cancer Consortium. JM reports fees paid to her institution as an invited speaker from AstraZeneca, Boehringer Ingelheim, BMS, MSD and Roche; fees paid to her institution for expert testimony from AstraZeneca, Boehringer Ingelheim and MSD; fees paid to her institution for travel expenses from Ipsen. TSM reports personal fees as an invited speaker from AbbVie, ACEA Pharma, Alpha Biopharma, Amgen, Amoy Diagnostics, BeiGene, Boehringer Ingelheim, BMS, Daiichi Sankyo, Daz Group, Eli Lilly, Fishawack Facilitate, InMed Medical Communication, Janssen, Jiahui Holdings Co., LiangYiHui Healthcare, Lucene Health Inc., Lunit USA, Inc., MD Health, Medscape/WebMD, Merck Serono, MIRXES, MSD, Novartis, OrigiMed, PeerVoice, PER, Permanyer SL, Pfizer, Prime Oncology, Research to Practice, Roche, Sanofi-Aventis, Shanghai BeBirds Translation & Consulting Co., Taiho Pharmaceutical Co., Takeda and Touch Medical Media; personal fees for advisory board membership from AbbVie, ACEA Pharma, Alpha Biopharma, Amgen, Amoy Diagnostics, BeiGene, Berry Oncology, Blueprint Medicines, Boehringer Ingelheim, BMS, C4 Therapeutics, Cirina Ltd, Covidien LP, CStone Pharma, Curio Science, D3 Bio Ltd, Da Volterra, Daiichi Sankyo, Eisai, Eli Lilly, Fishawack Facilitate, G1 Therapeutics, Gilead Sciences, Gritstone Oncology, Guardant Health, Hengrui, Ignyta, Incyte, Inivata, IQVIA, Janssen, Lakeshore Biotech, Loxo Oncology, Lucene Health Inc., Lunit USA, Inc., Medscape/WebMD, Merck Serono, Mirati Therapeutics, MiRXES, MoreHealth, MSD, Novartis, OrigiMed, OSE Immunotherapeutics, Pfizer, Puma Tech, Qiming Development, Roche, Roche/Genentech, Sanofi-Aventis, SFJ Pharmaceutical Ltd, Synergy Research, Takeda, Tigermed, Vertex Pharmaceuticals, Virtus Medical and Yuhan; personal fees as the Chairman for ACT Genomics-Sanomics Group; personal fees as a member of the board of directors from AstraZeneca and HutchMed; holds stocks/shares from AstraZeneca, Aurora Tele-Oncology, Biolidics Ltd, HutchMed and Sanomics Ltd.; institutional funding from AstraZeneca, BMS, Clovis Oncology, G1 Therapeutics, Merck Serono, MSD, Novartis, Pfizer, Roche, SFJ Pharmaceuticals, Takeda and XCovery; non-remunerated roles as an invited speaker with AstraZeneca, Aurora Tele-Oncology, Lunit USA, Inc. and Sanomics Ltd and for an advisory role with geneDecode; non-remunerated leadership roles with American Society of Clinical Oncology (ASCO), Asian Thoracic Oncology Research Group (ATORG), Chinese Lung Cancer Research Foundation Limited (CLCRF), Chinese Society of Clinical Oncology (CSCO), Hong Kong Cancer Fund (HKCF), Hong Kong Cancer Therapy Society (HKCTS), IASLC and St. Stephen’s College & Prep School (Hong Kong). UN reports fees paid to her institution as an invited speaker from MSD; fees paid to her institution for advisory board membership and a writing engagement from AstraZeneca; institutional funding as a coordinating PI for Bayer; non-remunerated roles as a PI for clinical trials funded by Deutsche Krebshilfe and as a member of the board of directors and vice-chair of ‘Strahlenschutzkommission’ from the German Commission on Radiological Protection. AP reports personal fees as an invited speaker from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Mundipharma and Takeda; personal fees for advisory board membership from AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, Janssen, MSD, Pfizer and Roche; non-remunerated activities with Italian Association of Medical Oncology (AIOM) as member of the Scientific Committee for lung cancer guidelines. SP reports personal fees for an editorial role as an Associate Editor for Annals of Oncology; fees paid to her institution as an invited speaker from AstraZeneca, BMS, Boehringer Ingelheim, ecancer, Eli Lilly, Fishawack, Illumina, Imedex, Medscape, Mirati, MSD, Novartis, OncologyEducation, Physician’s Education Resource (PER), Pfizer, Partnerships in International Medical Education (PRIME), RMEI Medical Education, LLC (RMEI), Roche/Genentech, Research To Practice (RTP), Sanofi and Takeda; fees paid to her institution for advisory board membership from AbbVie, Amgen, Arcus, AstraZeneca, Bayer, BeiGene, Bio Invent, Biocartis, Blueprint Medicines, BMS, Boehringer Ingelheim, Daiichi Sankyo, Debiopharm, Eli Lilly, F-Star, Foundation Medicine, Genzyme, Gilead, GSK, Illumina, Incyte, IQVIA, iTeos, Janssen, Merck Serono, Mirati, MSD, Novartis, Novocure, Pfizer, PharmaMar, Phosplatin Therapeutics, Regeneron, Roche/Genentech, Sanofi, Seattle Genetics, Takeda and Vaccibody; institutional funding as a steering committee member from AstraZeneca, BeiGene, BMS, iTeos, Mirati, MSD, PharmaMar, Phosplatin Therapeutics and Roche/Genentech; institutional funding as a coordinating PI from AstraZeneca; institutional funding as a trial chair from GSK and Roche/Genentech; non-remunerated role as President and Council Member for the Ballet Béjart Lausanne Foundation; non-remunerated leadership roles as President of ESMO (2020-2022), Vice- President of Swiss Academy of Multidisciplinary Oncology (SAMO), Vice-President of Lung Group for Swiss Group for Clinical Cancer Research (SAKK); non-remunerated role as PI involved in academic trials for European Thoracic Oncology Platform (ETOP)/EORTC/SAKK; non-remunerated role as Council Member and Scientific Committee Chair for ETOP/International Breast Cancer Study Group (IBCSG) Partners member of American Association of Cancer Research (AACR), ASCO, Association Suisse des médecines-assistant(e)s et chef(fe)s de Clinique (ASMAC)/Verband Schweizerischer Assistenz- und Oberärztinnen und- ärzte (VSAO), Fédération des médecins suisses (FMH) and IASLC. DP reports personal fees as an invited speaker from AbbVie, AstraZeneca, Janssen, Novartis, Peer CME, Pfizer, priME Oncology and Samsung; personal fees for advisory board membership from AbbVie, AstraZeneca, BMS, Celgene, Daiichi Sankyo, Janssen, Merck, Novartis, Pfizer, Roche and Samsung; institutional funding as a PI from AbbVie, AstraZeneca, BMS, Daiichi Sankyo, Janssen, Merck, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi and Sanofi-Aventis. ES reports personal fees as an invited speaker from Boehringer Ingelheim and Daiichi Sankyo; personal fees for advisory board membership from Merck Serono; fees paid to his institution for advisory board membership from AstraZeneca, BMS, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Janssen, MSD, Roche, Sanofi and Takeda; institutional funding as a local PI from AstraZeneca, Genmab, Gilead and Pfizer. BJS reports personal fees as an invited speaker from AstraZeneca, Pfizer and Roche/Genentech; personal fees for advisory board membership from Amgen and Roche/Genentech; fees paid to his institution for advisory board membership from AstraZeneca, BMS, Merck and Novartis; fees paid to his institution for steering committee membership from Novartis, Pfizer and Roche/Genentech; personal fees as a member of the board of directors from Cancer Council Victoria and Thoracic Oncology Group of Australasia; personal fees as a consultant from Peter MacCallum Cancer Centre; royalties from UpToDate. GV reports personal fees as an invited speaker and for advisory board membership from Roche; personal fees as a consultant from Ab Medica; institutional funding as a PI from Fondazione AIRC per la ricerca sul cancro ETS (AIRC) and the Italian Ministry of Health. MR reports personal fees as an invited speaker from Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Lilly, Merck, MSD, Novartis, Roche and Sanofi; personal fees for advisory board membership from Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Mirati, MSD, Pfizer, Roche and Sanofi.

Background and Aim: Psoriatic arthritis (PsA) is a polymorphic disease associated with numerous comorbidities. The objective of this study was to describe the main clinicobiological and imaging characteristics of a population of PsA and to extract any disparities between men and women., Methods: A total of 132 patients in the rheumatology department of Amiens University Hospital with a confirmed diagnosis of PsA according to the CASPAR criteria were included over a period of 4 months. All data were collected retrospectively in this observational and single-center study., Results: The sex ratio was 1 and the average age at inclusion was 54.9 years. Peripheral PsA was the predominant clinical form. Axial PsA represented 12.1% of cases. Enthesitis was noted in 52.3% of cases while dactylitis was identified in 29.5% of cases. Moreover, 12.1% had a joint symptomatology preceding the appearance of cutaneous signs. HLA-B*27 positivity was found in 33.3% of cases. Chronic hyperuricemia accounted for 10% of our population. Sacroiliitis was observed in 41% of cases. The disparities between men and women are multiple and consistent with the literature: Polyarticular form, enthesitis, obesity, more intensive prescription of s-DMARDs, and b-DMARDs are more associated with the female population. Oligoarticular form, psoriatic nail dystrophy, radiological axial involvement, and chronic hyperuricemia are more encountered in the male population., Conclusions: Our study found a very heterogeneous disease, with marked differences between men and women. Peripheral PsA remains predominant but the search for associated axial involvement, which is probably underestimated, seems essential., Relevance for Patients: This work studied the main characteristics of patients with PsA followed in real life, in a regional university reference center. We have highlighted a very heterogeneous disease as well as some gender disparities, not well described in the literature, which should be taken into account in order to optimize therapeutic management., Competing Interests: The authors declare no competing interest on this study or its publication., (Copyright: © 2023 Author(s).)

We performed an updated meta-analysis to explore the role of maintenance therapy in SCLC. Clinical trials with randomization to maintenance/consolidation (V) placebo or observation or best supportive care in SCLC, both extended and limited disease were searched from January 2009 to March 2022. The hazard ratios (HR) for progression-free survival (PFS) and overall survival (OS) with the relative 95% confidence interval (CI) were extracted from each study. Summary HR was calculated using random- or fixed-effects models, depending on the heterogeneity of the included studies. A total of 9 studies were identified. Neither PFS nor OS were improved with maintenance/consolidation (PFS: random-effect; HR 0.93; 95% CI 0.71-1.21; P=0.10; OS: fixed-effect; HR 0.98; 95% CI 0.89-1.08; P=0.14). Among the different strategies, immunotherapy maintenance showed a significantly decreased risk of progression (V)standard of care (random-effect; HR 0.80; 95% CI 0.66-0.97; P=0.03). The current updated meta-analysis did not demonstrate a benefit of maintenance/consolidation therapy in SCLC, with only a PFS benefit for immunotherapy approach., Competing Interests: Conflicts of interest S.P. received honoraria or speaker's fees from Astra-Zeneca, BMS, Boehringer Ingelheim, MSD, Roche and Istituto Gentili. C.C. received honoraria or speaker's fees from Pfizer, Ipsen, Janssen, MSD. E.B. received speaker's and travel fees from MSD, Astra-Zeneca, Celgene, Pfizer, Helsinn, Eli-Lilly, BMS, Novartis and Roche. E.B received consultant fees from Roche, Pfizer. E.B. received institutional research grants from Astra-Zeneca and Roche. All other authors declare they have no conflicts of interest to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Selpercatinib is a RET selective tyrosine kinase inhibitor with nanomolar potency against diverse RET alterations, including fusions, activating point mutations, and acquired resistance mutations. Rearranged during transfection (RET) gene is a validated target in non-small-cell lung cancer (NSCLC). Selpercatinib is currently approved for adult patients with metastatic RET fusion-positive NSCLC., Areas Covered: This review summarizes the efficacy and safety data of selpercatinib in the treatment landscape of RET fusion-positive NSCLC., Expert Opinion: Globally considered, selpercatinib is an optimal treatment choice, in terms of both (systemic and intracranial) efficacy and safety, in patients affected by advanced NSCLC harboring RET fusions as a driver mechanism. Future challenges include the identification of the most appropriate placement for selpercatinib in the treatment algorithm of RET fusion-positive NSCLC (including early stages), the clarification of resistance mechanisms, as well as of its role in EGFR-mutant NSCLC undergoing progression during osimertinib driven by RET alterations.

Objectives: Exercise has been reported to alleviate disease as well as treatment impact in patients with lung cancer. Nevertheless, there is limited information available regarding the perception of lung cancer dedicated healthcare professionals' and their advice on exercise., Materials and Methods: An online survey exploring healthcare professionals' practice patterns, perceptions, barriers, and facilitators of exercise in patients with lung cancer was conducted within members of the EORTC Lung Cancer Group (LCG)., Results: One hundred forty-one healthcare providers completed the survey, mainly medical and radiation oncologists. Overall, 63% of the study participants declared that they frequently assessed exercise level in their patients, and 43% of them reinforced the importance of exercise. However, only 10% referred patients to an exercise program or specialist. Although the majority of the respondents had a positive perception regarding the benefits and safety of exercise (even in patients with advanced disease and/or bone metastasis), two-thirds of clinicians reported not having adequate training about exercise counselling. Moreover, 53% reported to lack of knowledge of guidelines referring to exercise in patients with cancer. Several obstacles and facilitators to improve exercise promotion in lung cancer care were identified., Conclusion: Healthcare providers recognize the relevance and feasibility of exercise as part of cancer treatment intervention, but specific pathways to do the referral are frequently missing. Future structured and well-designed strategies and initiatives are needed to support an effective referral in order to implement exercise interventions routinely in clinical practice., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Neuroendocrine carcinomas are very aggressive tumors with few treatment options. DLL3 seems to be an optimal target for therapeutic intervention, as it is expressed mainly on the membrane of tumor cells with neuroendocrine origin., Areas Covered: In this article, we outline the preclinical and clinical studies published in the last years on DLL3 in neuroendocrine neoplasm, above all of lung origin. Furthermore, we review the current literature on the interaction between DLL3 and the tumor microenvironment., Expert Opinion: Several DLL3-targeting strategies have been proposed in the last years with mixed results. Understanding the influence of DLL3 on the tumor (immune) microenvironment and developing adoptive therapies directed against this optimal target might represent the key strategy. Building on the clinical data obtained so far, future trials on in vivo diagnostic tools for predictive purpose and new specific therapies are needed.

Background: Improvement in radiotherapy techniques and expected outcomes, as well as in understanding the underlying biological mechanisms contributing to its action (immunomodulation in primis), led to the integration of this therapeutical approach in the current management of advanced non-small cell lung cancer (NSCLC), not only in oncogene-driven tumors, but also in non-oncogene addicted NSCLC where the combination of platinum-based chemotherapy plus pembrolizumab represents nowadays the pivotal strategy. In this light, we have designed a randomized phase II (ESPERa) trial to evaluate the efficacy and safety of adding Stereotactic Body Radiotherapy (SBRT) to pembrolizumab-pemetrexed maintenance in advanced NSCLC patients experiencing disease response or stability after chemo-immunotherapy induction., Patients and Methods: Advanced non-oncogene addicted NSCLC patients with ECOG performance status of 0 or 1, who obtained disease response or stability after 4 cycles of platinum-based chemotherapy plus pembrolizumab will be randomized 2:1 to receive pembrolizumab-pemetrexed maintenance plus SBRT vs pembrolizumab-pemetrexed alone. The primary endpoint is progression-free survival (PFS). Concomitant translational researches will be performed to identify potential prognostic and/or predictive biomarkers, as well as to analyze and monitor tumour microenvironment and tumor-host interactions., Conclusions: Although available data suggest the safety and efficacy of combining immunotherapy and radiotherapy, their systematic integration in the current first-line landscape still remains to be explored. If the pre-planned endpoints of the ESPERa trial will be achieved, the addition of SBRT to pembrolizumab-pemetrexed maintenance as a strategy to consolidate and ideally improve the awaited benefit could be considered as a promising strategy in NSCLC undergoing first-line therapy, as well as an interesting approach to be evaluated in other disease setting, as well as in other oncological malignancies where immunotherapy represents nowadays the standard-of-care., Competing Interests: Disclosure M.M. reports personal fees from Pfizer, EUSA Pharma and Astra Zeneca, outside the submitted manuscript. S.P. received honoraria or speakers’ fee from Astra-Zeneca, Eli-Lilly, BMS, Boehringer Ingelheim, MSD and Roche, outside the submitted manuscript. All remaining authors have declared no conflicts of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Durvalumab is the standard-of-care as consolidation therapy after chemo-radiotherapy in stage III unresectable non-small cell lung cancer (NSCLC); however, its activity across patients with NSCLC harbouring driver genomic alterations (dGA) is poorly characterised., Material and Methods: Multicentre retrospective study including patients with stage III unresectable NSCLC treated with durvalumab after chemo-radiotherapy between April 2015 and October 2020 at 26 centres in Europe and America. Clinical and biological data were collected; dGA included: EGFR/BRAF/KRAS mutations (m) and ALK/ROS1 rearrangements (r). We evaluated progression-free survival (PFS) and overall survival (OS) based on dGA., Results: Out of 323 patients included, 43 patients had one dGA: KRASm (n = 26; 8 G12C), EGFRm (n = 8; 6 del19/ex21), BRAFm (n = 5; 4 V600E) and ALKr (n = 4). The median age was 66 years [39-84], gender ratio 1:1, with 98% performance status (PS) 0-1 and 19% non-smokers; 88% had adenocarcinoma. PD-L1 was positive in 85% (n = 4 missing). In the whole cohort, the median PFS was 17.5 months (mo.) (95% CI, 13.2-24.9) and median OS 47 mo (95%CI, 47-not reached [NR]). No statistically significant differences in terms of the median PFS were observed between patients with dGA vs. non-dGA: 14.9 mo (95% CI, 8.1-NR) vs. 18 mo. (95% CI, 13.4-28.3) (P = 1.0); however, when analysed separately: the median PFS was NR (11.3-NR) in the KRASm G12C vs. 8.1 mo (5.8-NR) in the EGFRm del19/ex21 vs. 7.8 mo (7.7-NR) in the BRAFm V600E/ALKr (P = 0.02)., Conclusions: We observed limited activity of durvalumab consolidation in patients with stage III unresectable NSCLC with EGFR/BRAFm and ALKr but not for those harbouring KRASm. Larger prospective studies are needed to confirm these findings., Competing Interests: Conflict of interest statement MMj: advisory and consultancy honoraria from Roche, Merck, BristolMyers Squibb, AstraZeneca, Amgen, Boehringer, Sanofi and Takeda; speaker honoraria from Roche, Merck, Bristol-Myers Squibb, AstraZeneca, Bayer, Amgen, Pfizer and Boehringer; grants from AstraZeneca and BristolMyers Squib, and travel/accommodation expenses from Roche, Merck and Lilly. RLC: honoraria from Kyowa Kirin, Pierre-Fabre, Takeda, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Novartis, Roche, Merck Serono, Pfizer; consulting or advisory role from Roche, Astra-Zeneca, Boehringer Ingelheim, Aristo, Novartis; research funding from Roche, Bristol-Myers Squibb, MSD, Boehringer Ingelheim, AstraZeneca. JBB: grants and personal fees from Roche-Genentech, Pfizer, MSD, BMS, Astrazeneca, Novartis, Boehringer-Ingelheim, Vifor, Sanofi, LEO Pharma, outside the submitted work. SP: Consulting, advisory role or lectures from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Roche, Amgen. MT: travel grants from Roche, Bristol-Myers Squibb, AstraZeneca, Takeda; honoraria as medical writer from Novartis, Amgen. GZ: research grants from Roche-France, Bristol-Myers Squibb, and Takeda outside of the submitted work; perceived fees from Bristol-Myers Squibb, AstraZeneca, Pfizer, and Boehringer Ingelheim outside the submitted work; and reimbursement for international meetings assistance from AbbVie, Merck Sharp & Dohme, AstraZeneca, Bristol-Myers Squibb, and Roche-France. XM-R: Research grant funding from Brystol-Myers Squibb; consulting, advisory role or lectures from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim; honoraria (self) from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Pfizer, Roche, MSD; clinical trials research from Boehringer Ingelheim, Pfizer, Roche, Abbvie; travel, accommodations and expenses from Roche, Pfizer, Brysto-Myers Squibb. JB: educational grants by AMGEN. MSch: speaker and advisory role honoraria, travel accommodations from AMGEN, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Janssen, Novartis, Pfizer, Roche, Takeda; personal research support from AMGEN, Dracen Pharmaceuticals, Siemens Healthineers; institutional research support from Boehringer Ingelheim, Bristol-Myers Squibb, MSD, Novartis, Pfizer, Roche. EN: research support from Roche, Merck Serono, Bristol Myers Squibb and Pfizer and participated in advisory boards or lectures from Bristol Myers Squibb, Merck Serono, Merck Sharpe & Dohme, Lilly, Roche, Pfizer, Takeda, Bayer, Boehringer Ingelheim, Amgen and AstraZeneca. DS: Consulting, advisory role, honoraria from AstraZeneca, Merck Sharp & Dohme, Bristol-Myers Squibb, Boehringer Ingelheim, Sanofi, Eli Lilly; travel grants from Roche. RGC: Consulting, advisory role or lectures from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Takeda, Janseen, MSD, Roche, Pfizer, Eli Lilly, Amgen, Sanofi; honoraria (self) from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Pfizer, Roche, MSD, Takeda, Eli Lilly, Novartis; clinical trials research from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, Medimmun, Sanofi-Aventis. JMe: Advisory Boards/Honoraria/Speakers’ fee/Consultant for Astra-Zeneca, Boeringher Ingelheim, BMS, Roche, MSD; travel grants from Astra-Zeneca, Boeringher Ingelheim, BMS, Ipsen, Roche, MSD. VB: Clinical trial research from AstraZeneca, Roche, MSD; advisory role/consulting/speaker from Pfizer, MSD, AstraZeneca, Roche, Bristol, Merck, Takeda. MC: Advisory or Consultancy role from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, EUSA Pharma, Lilly, Roche; honoraria, lectures from Abbot, Bristol-Myers Squibb, EUSA Pharma, Ipsen, Novartis, Pfizer, Pierre Fabre, Roche; travel, expenses from Ipsen, Lilly, Merck, Pfizer, Pierre Fabre; institutional financial interests from Astra Zeneca, Merck, Roche, Pfizer. GR: consulting, advisory role or lectures from AstraZeneca, Bayer, Bristol-Myers Squibb, Janssen, Merck Sharp & Dome, Pfizer, Roche, Takeda; sponsored Research Amgen and Janssen. BB: sponsored research at Gustave Roussy Cancer Centre Abbvie, Amgen, AstraZeneca, Biogen, Blueprint Medicines, BMS, Celgene, Eli Lilly, GSK, Ignyta, IPSEN, Merck KGaA, MSD, Nektar, Onxeo, Pfizer, Pharma Mar, Sanofi, Spectrum Pharmaceuticals, Takeda, Tiziana Pharma. DP: consulting, advisory role or lectures from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche; honoraria from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche; clinical trials research from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, Medimmun, Sanofi-Aventis, Taiho Pharma, Novocure, Daiichi Sankyo; travel, accommodations, expenses from AstraZeneca, Roche, Novartis, prIME Oncology, Pfizer. LM: research grant/Funding (self) from Bristol Myers Squibb, Boehringer Ingelheim, Amgen, Stilla, Inivata; advisory/consultancy from Roche, Takeda; honoraria (self) from Bristol Myers Squibb, Roche, Takeda, AstraZeneca; travel/Accommodation/Expenses from Roche, Bristol Myers Squibb, Takeda, AstraZeneca; non-remunerated activity/ies from AstraZeneca. MR, EA, MMo, ND, EE, RL, JMo, FA, SP, AD, MSp, EM, RR, JCB, LL, BD, AdG, CAV and GL declare no conflicts of interest., (Copyright © 2022. Published by Elsevier Ltd.)

Small cell lung cancer (SCLC) represents about 13%-15% of all lung cancers. It has a particularly unfavorable prognosis and in about 70% of cases occurs in the advanced stage (extended disease). Three phase III studies tested the combination of immunotherapy (atezolizumab, durvalumab with or without tremelimumab, and pembrolizumab) with double platinum chemotherapy, with practice-changing results. However, despite the high tumor mutational load and the chronic pro-inflammatory state induced by prolonged exposure to cigarette smoke, the benefit observed with immunotherapy is very modest and most patients experience disease recurrence. Unfortunately, biological, clinical, or molecular factors that can predict this risk have not yet been identified. Thanks to these clinically meaningful steps forward, SCLC is no longer considered an "orphan" disease. Innovative treatment strategies and combinations are currently under investigation to further improve the expected prognosis of patients with SCLC. Following the recent therapeutic innovations, we have reviewed the available literature data about SCLC management, with a focus on current unmet needs and potential predictive factors. In detail, the role of radiotherapy; fragile populations, such as elderly or low-performance status patients (ECOG PS 2), usually excluded from randomized studies; predictive factors of response useful to optimize and guide therapeutic choices; and new molecular targets and future combinations have been explored and revised., 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 © 2022 Belluomini, Calvetti, Inno, Pasello, Roca, Vattemi, Veccia, Menis and Pilotto.)

Introduction: Bone metastases (BMs) are a negative prognostic factor in patients with non-small cell lung cancer (NSCLC). Although immune-checkpoint inhibitors (ICIs) have dramatically changed the therapeutic landscape of NSCLC, little information is available on BMs from NSCLC treated with ICIs alone or in association with bone-targeted therapy (BTT) such as zoledronate or denosumab., Methods: From 2014 to 2020, 111 of the 142 patients with BMs secondary to NSCLC extrapolated from the prospective multicenter Italian BM Database were eligible for analysis. Information on blood count, comorbidities, and toxicity was retrospectively collected. The neutrophil-to-lymphocyte ratio (NLR) pre- and post-treatment was calculated. Survival was analyzed using the Kaplan-Meier method, with statistical significance of survival differences assessed using the log-rank test., Results: Median age was 66 (range, 42-84) years. Performance status (PS) Eastern Cooperative Oncology Group (ECOG) was 0-1 in 79/111 patients. The majority of patients (89.2%) had adenocarcinoma histology. At a median follow-up of 47.4 months, median progression-free (mPFS) and overall survival (mOS) was 4.9 (95%CI, 2.8-10.0) and 11.9 (95%CI, 8.2-14.4) months, respectively. Forty-six (43.4%) patients with BM NSCLC underwent first- or further-line therapy with ICIs: 28 (60.8%) received nivolumab, 9 (19.6%) pembrolizumab, and 9 (19.6%) atezolizumab. Of the 46 patients treated with ICIs, 30 (65.2%) underwent BTT: 24 (80.0%) with zoledronate and 6 (20.0%) with denosumab. The ICI-alone group had an mOS of 15.8 months [95%CI, 8.2-not evaluable (NE)] vs . 21.8 months (95%CI, 14.5-not evaluable) for the ICI plus BTT group and 7.5 (95%CI, 6.1-10.9) months for the group receiving other treatments (p < 0.001). NLR ≤5 had a positive impact on OS., Conclusion: BTT appears to have a synergistic effect when used in combination with ICIs, improving patient survival., 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 © 2021 Bongiovanni, Foca, Menis, Stucci, Artioli, Guadalupi, Forcignanò, Fantini, Recine, Mercatali, Spadazzi, Burgio, Fausti, Miserocchi and Ibrahim.)

Background : The current treatment landscape of early stage lung cancer is rapidly evolving, particularly in EGFR mutant non-small cell lung cancer (NSCLC), where target therapy is moving to early stages. In the current review, we collected the available data exploring the impact of EGFR targeting in both neoadjuvant and adjuvant settings, underlying lights and shadows and discussing the existing open issues. Methods : We performed a comprehensive search using PubMed and the proceedings of major international meetings to identify neoadjuvant/adjuvant trials with EGFR tyrosine kinase inhibitors (TKIs) in NSCLC. Results : Limited data are available so far about the activity/efficacy of neoadjuvant TKIs in EGFR mutant NSCLC, with only modest downstaging and pathological complete response rates reported. Differently, the ADAURA trial already proposed osimertinib as a potential new standard of care in resected NSCLC harboring an activating EGFR mutation. Conclusion : Anticipating targeted therapy to early stage EGFR mutant NSCLC presents great opportunities but also meaningful challenges in the current therapeutic/diagnostic pathway of lung cancer care. Appropriate endpoint(s) selection for clinical trials, disease progression management, patients' and treatment selection, as well as need to address the feasibility of molecular profiling anticipation, represent crucial issues to face before innovation can move to early stages.

Purpose: This meta-analysis aims to combine and analyze randomized clinical trials comparing computed tomography lung screening (CTLS) versus either no screening (NS) or chest x-ray (CXR) in subjects with cigarette smoking history, to provide a precise and reliable estimation of the benefits and harms associated with CTLS., Materials and Methods: Data from all published randomized trials comparing CTLS versus either NS or CXR in a highly tobacco-exposed population were collected, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Subgroup analyses by comparator (NS or CXR) were performed. Pooled risk ratio (RR) and relative 95% CIs were calculated for dichotomous outcomes. The certainty of the evidence was assessed using the GRADE approach., Results: Nine eligible trials (88,497 patients) were included. Pooled analysis showed that CTLS is associated with: a significant reduction of lung cancer-related mortality (overall RR, 0.87; 95% CI, 0.78 to 0.98; NS RR, 0.80; 95% CI, 0.69 to 0.92); a significant increase of early-stage tumors diagnosis (overall RR, 2.84; 95% CI 1.76 to 4.58; NS RR, 3.33; 95% CI, 2.27 to 4.89; CXR RR, 1.52; 95% CI, 1.04 to 2.23); a significant decrease of late-stage tumors diagnosis (overall RR, 0.75; 95% CI, 0.68 to 0.83; NS RR, 0.67; 95% CI, 0.56 to 0.80); a significant increase of resectability rate (NS RR, 2.57; 95% CI, 1.76 to 3.74); a nonsignificant reduction of all-cause mortality (overall RR, 0.99; 95% CI, 0.94 to 1.05); and a significant increase of overdiagnosis rate (NS, 38%; 95% CI, 14 to 63). The analysis of lung cancer-related mortality by sex revealed nonsignificant differences between men and women ( P = .21; I-squared = 33.6%)., Conclusion: Despite there still being uncertainty about overdiagnosis estimate, this meta-analysis suggested that the CTLS benefits outweigh harms, in subjects with cigarette smoking history, ultimately supporting the systematic implementation of lung cancer screening worldwide., Competing Interests: Francesco PassigliaConsulting or Advisory Role: AstraZeneca, MSD Oncology, AmgenTravel, Accommodations, Expenses: MSD Oncology, Roche Marzia Del ReConsulting or Advisory Role: Sanofi, Celgene, Janssen-Cilag, Ipsen, Roche Molecular DiagnosticsSpeakers' Bureau: Sanofi, Pfizer, Novartis, Janssen-Cilag, Ipsen, AstraZeneca, Astellas Pharma Francesco FacchinettiOther Relationship: Roche, Bristol Myers Squibb Roberto FerraraConsulting or Advisory Role: Merck Sharp & Dohme Tindara FranchinaHonoraria: Novartis, AstraZenecaConsulting or Advisory Role: Boehringer Ingelheim, Merck Sharp & Dohme Anna R. LariciSpeakers' Bureau: Boehringer Ingelheim Umberto MalapelleConsulting or Advisory Role: Boehringer Ingelheim, Roche, Merck Sharp & Dohme, Amgen, Thermo Fisher Scientific, Lilly, Diaceutics, GlaxoSmithKline, Merck, AstraZenecaSpeakers' Bureau: Boehringer Ingelheim, AstraZeneca, Roche, Merck Sharp & Dohme, Amgen, Merck, Thermo Fisher Scientific, Lilly, Diaceutics, GlaxoSmithKline Jessica MenisConsulting or Advisory Role: MSD Oncology, Roche/Genentech, Boehringer Ingelheim, AstraZeneca, Bristol Myers Squibb/PfizerSpeakers' Bureau: AstraZeneca/MedImmune, Bristol Myers Squibb/Pfizer, Boehringer Ingelheim, MSD Oncology, Roche/GenentechTravel, Accommodations, Expenses: Boehringer Ingelheim Antonio PassaroConsulting or Advisory Role: Roche/Genentech, Bristol Myers Squibb, AstraZeneca, MSD Oncology, Pfizer, Boehringer IngelheimTravel, Accommodations, Expenses: Roche/Genentech, Bristol Myers Squibb Sara PilottoHonoraria: Bristol Myers Squibb, Boehringer Ingelheim, AstraZenecaSpeakers' Bureau: Bristol Myers Squibb, Boehringer Ingelheim, Roche, MSD Oncology, AstraZenecaResearch Funding: AstraZenecaTravel, Accommodations, Expenses: Bristol Myers Squibb, Roche, AstraZeneca Sara RamellaHonoraria: AstraZeneca, AmgenConsulting or Advisory Role: AstraZeneca, Roche, Ipsen Rocco TrisoliniHonoraria: Pentax Medical Devices Silvia NovelloConsulting or Advisory Role: SanofiSpeakers' Bureau: AstraZeneca, Merck Sharp & Dohme, Bristol Myers Squibb, Roche, Pfizer, Lilly, Takeda, AbbVie, Boehringer Ingelheim, Bayer, Amgen, BeigeneNo other potential conflicts of interest were reported.

Introduction : Cachexia represents a relevant issue in oncological care, which is still lacking effective therapies. Although the incidence of cancer cachexia varies across cancer types, it is responsible for approximately a quarter of cancer-related deaths. The pathophysiology of this syndrome is multifactorial, including weight loss, muscle atrophy and impairment of the pro-/anti-inflammatory balance. Areas covered : Diagnostic criteria and optimal endpoints for cachexia-dedicated trials are still debated, slowing the identification of interventions counteracting cachexia sequaele . The multifaceted features of this syndrome support the rationale for personalized therapy. A multimodal approach is likely to offer the best option to address key cachexia-related issues. Pharmacologic agents, physical exercise, nutritional and psycho-social interventions may have a synergistic effect, and improve quality of life. Expert opinion : A personalized multimodal intervention could be the best strategy to effectively manage cancer cachexia. To offer such a comprehensive approach, a specialized staff, including health professionals with different expertise, is necessary. Each specialist plays a specific role inside the multimodal intervention, with the aim of delivering the best cancer care and access to the most effective therapeutic options for each patient.

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.)

Patients with oligometastatic disease (OMD) non-small cell lung cancer (NSCLC) are considered as a subgroup of metastatic NSCLC that can obtain long-term survival or even cure. Oligometastatic refers to a state of a limited number of metastases in a limited number of organs. In clinical guidelines it is stated that patients with oligometastatic NSCLC can benefit from the addition of local radical therapy (LRT) to systemic therapy. With the introduction of minimally invasive surgery, advances in interventional radiology and stereotactic radiotherapy (SRT), LRT is becoming feasible for more and more patients. Furthermore, the introduction of immune checkpoint inhibitors (ICI) in the treatment landscape of advanced NSCLC has improved the survival of these patients. Importantly, the use of ICI in combination with LRT is also of interest in the subgroup of NSCLC patients with OMD. For example, it has been suggested that SRT may synergize with ICI as several preclinical studies reported an increased tumor antigen release, improved antigen presentation, and T-cell infiltration in irradiated tumors. In this narrative review, we describe the current evidence of immunotherapy treatment in OMD NSCLC, with a focus on future trial design and problems that need to be addressed., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-20-1065). The series “Oligometastatic NSCLC: definition and treatment opportunities” was commissioned by the editorial office without any funding or sponsorship. JR serves as an unpaid editorial board member of Translational Lung Cancer Research from September 2019 to September 2021. AL serves as an unpaid editorial board member of Translational Lung Cancer Research from September 2019 to September 2021. JR reports other from OSE PHARMA, ASTRA ZENECA, MSD, PFIZER and ROCHE, outside the submitted work. JM reports grants, personal fees and other from Boehringer-Ingelheim, grants and other from MSD, Roche, Astrazeneca, Ipsen and BMS, outside the submitted work. DDR reports grants from Brsitol-Myers Squibb, AstraZeneca, Boehringer Ingelheim, Philips, Olink, Celgene, Seattle Genetics, Roche/Genentech and Merck/Pfizer, outside the submitted work. LH reports other from boehringer ingelheim, BMS, Roche Genentech and BMS, grants from Roche Genentech and Boehringer Ingelheim, other from AstraZeneca, personal fees from Quadia, grants from Astra Zeneca, other from Eli Lilly, Roche Genentech, Pfizer, MSD and Takeda, non-financial support from AstraZeneca, Novartis, BMS, MSD/Merck, GSK, Takeda, Blueprint Medicines and Roche Genentech, other from Amgen, outside the submitted work. The authors have no other conflicts of interest to declare., (2021 Translational Lung Cancer Research. All rights reserved.)

Objective: In this review, we aim to collect and discuss available data about the role and composition of tumor microenvironment (TME) in oligometastatic (OMD) and oligoprogressive (OPD) non-small cell lung cancer (NSCLC). Furthermore, we aim to summarize the ongoing clinical trials evaluating as exploratory objective the TME composition, through tissue and/or blood samples, in order to clarify whether TME and its components could explain, at least partially, the oligometastatic/oligoprogressive process and could unravel the existence of predictive and/or prognostic factors for local ablative therapy (LAT)., Background: OMD/OPD NSCLC represent a heterogeneous group of diseases. Several data have shown that TME plays an important role in tumor progression and therefore in treatment response. The crucial role of several types of cells and molecules such as immune cells, cytokines, integrins, protease and adhesion molecules, tumor-associated macrophages (TAMs) and mesenchymal stem cells (MSCs) has been widely established. Due to the peculiar activation of specific pathways and expression of adhesion molecules, metastatic cells seem to show a tropism for specific anatomic sites (the so-called "seed and soil" hypothesis). Based on this theory, metastases appear as a biologically driven process rather than a random release of cancer cells. Although the role and the function of TME at the time of progression in patients with NSCLC treated with tyrosine-kinase inhibitors and immune checkpoint inhibitors (ICIs) have been investigated, limited data about the role and the biological meaning of TME are available in the specific OMD/OPD setting., Methods: Through a comprehensive PubMed and ClinicalTrials.gov search, we identified available and ongoing studies exploring the role of TME in oligometastatic/oligoprogressive NSCLC., Conclusions: Deepening the knowledge on TME composition and function in OMD/OPD may provide innovative implications in terms of both prognosis and prediction of outcome in particular from local treatments, paving the way for future investigations of personalized approaches in both advanced and early disease settings., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-20-1134). The series “Oligometastatic NSCLC: definition and treatment opportunities” was commissioned by the editorial office without any funding or sponsorship. EB serves as an unpaid editorial board member of Translational Lung Cancer Research from September 2019 to September 2021. MM reports honoraria or speakers’ fee from Pfizer, EUSA Pharma and Astra Zeneca, outside the submitted manuscript. SP reports honoraria or speakers’ fee from Astra-Zeneca, Eli-Lilly, BMS, Boehringer Ingelheim, MSD and Roche, outside the submitted manuscript. The authors have no other conflicts of interest to declare., (2021 Translational Lung Cancer Research. All rights reserved.)

Background: To describe the incidence and the clinical characteristics of oligometastatic non-small cell lung cancer (NSCLC) patients. Oligometastatic NSCLC is gaining recognition as a clinical condition with a different prognosis compared to multi metastatic disease. Usually, four different scenarios of oligometastatic disease can be described but not epidemiological data are available. To date, it is difficult to delineate an exhaustive epidemiological scenario because no uniform or shared definition of oligometastatic status exists, even though a recent consensus defined synchronous oligometastatic disease as having a maximum of 5 metastases in 3 different organs., Methods: A systematic review and a pooled analysis of literature were performed. Article selection was based on the following characteristics: focus on lung cancers; dealing with oligometastatic settings and providing a definition of oligometastatic disease; number of metastatic lesions with or without the number of organs involved; providing some incidence or clinical characteristics of oligometastatic NSCLC patients. Series focusing on a specific single metastatic organ were excluded. The research was launched in MEDLINE (OvidSP) in March 2020. Full articles were individually and collectively read by the authors according to the previous criteria. Each author inspected the reference list included in the eligible articles. If the selection criteria were recognized, the article was reviewed by all authors and then included. Data on patient clinical features were pooled together from 31 articles selected., Results: A total number of 31 articles have been selected for the analysis. The following variables were extracted from the publications: (I) number of metastases, (II) number of organs involved, (III) number of patients, (IV) number and percentage of males and females, (V) number and percentage of squamous and non-squamous histology, (VI) T and N status and/or stage of primary disease for oligometastatic setting. The data collected have been analyzed according to the oligometastatic setting., Conclusions: Oligometastatic status is globally identified as a different clinical condition from multi metastatic NSCLC, although the clinical characteristics were consistent in the general metastatic population, even with a lower-than-expected TN status. The brain and bones were the most frequent organs involved. Lacking consensus definition, these results must be interpreted cautiously and a prospective evaluation is urgently needed., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/tlcr-20-982). The series “Oligometastatic NSCLC: definition and treatment opportunities” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2021 Translational Lung Cancer Research. All rights reserved.)

Aims: This study describes real-world outcomes of pretreated EGFR T790M-positive (T790M + ) advanced non-small-cell lung cancer patients progressing after first- or second-generation tyrosine kinase inhibitors and receiving osimertinib, compared with T790M-negative (T790M - ) patients. We have also described progression patterns and treatment sequences. Patients & methods: This is a retrospective multicenter Italian observational study including consecutive Caucasian patients referred between 2014 and 2018. Results: 167 patients were included. Median progression-free survival was 9.8 months (95% CI: 8.3-13.3) for T790M + and 6.0 months (95% CI: 4.9-7.2) for T790M - patients, respectively. Median overall survival was 20.7 months (95% CI: 18.9-28.4) for T790M + and 10.6 months (95% CI: 8.6-23.6) for T790M - patients, respectively. The T790M mutation correlated with absence of new sites of disease. After progression, most T790M + patients continued osimertinib, whereas most T790M - patients received a different treatment line. Conclusion: Better outcomes were shown in patients receiving osimertinib. A more limited progression pattern for T790M + was suggested.

Introduction: The COVID-19 pandemic has proved to be a historic challenge for healthcare systems, particularly with regard to cancer patients. So far, very limited data have been presented on the impact on integrated care pathways (ICPs)., Methods: We reviewed the ICPs of lung cancer patients who accessed the Veneto Institute of Oncology (IOV)/University Hospital of Padua (Center 1) and the University Hospital of Verona (Center 2) before and after the COVID-19 pandemic, through sixteen indicators chosen by the members of a multidisciplinary team (MDT)., Results: Two window periods (March and April 2019 and 2020) were chosen for comparison. Endoscopic diagnostic procedures and major resections for early stage NSCLC patients increased at Center 1, where a priority pathway with dedicated personnel was established for cancer patients. A slight decrease was observed at Center 2 which became part of the COVID unit. Personnel shortage and different processing methods of tumor samples determined a slightly longer time for diagnostic pathway completion at both Centers. Personnel protection strategies led to a MDT reshape on a web basis and to a significant selection of cases to be discussed in both Centers. The optimization of patient access to healthcare units reduced first outpatient oncological visits, patient enrollment in clinical trials, and end-of-life cancer systemic treatments; finally, a higher proportion of hypofractionation was delivered as a radiotherapy approach for early stage and locally advanced NSCLC., Conclusions: Based on the experience of the two Centers, we identified the key steps in ICP that were impacted by the COVID-19 pandemic so as to proactively put in place a robust service provision of thoracic oncology., 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 © 2021 Pasello, Menis, Pilotto, Frega, Belluomini, Pezzuto, Caliò, Sepulcri, Cernusco, Schiavon, Infante, Damin, Micheletto, Del Bianco, Giovannetti, Bonanno, Fantoni, Guarneri, Calabrese, Rea, Milella and Conte.)