Infectious diseases represent a relevant issue in lung cancer patients. Bacterial and viral infections might influence the patients’ prognosis, both directly affecting the immune system and indirectly impairing the outcome of anticancer treatments, mainly immunotherapy. In this analysis, we aimed to review the current evidence in order to clarify the complex correlation between infections and lung cancer. In detail, we mainly explored the potential impact on immunotherapy outcome/safety of (1) bacterial infections, with a detailed focus on antibiotics; and (2) viral infections, discriminating among (a) human immune-deficiency virus (HIV), (b) hepatitis B/C virus (HBV-HCV), and (c) Sars-Cov-2. A series of studies suggested the prognostic impact of antibiotic therapy administration, timing, and exposure ratio in patients treated with immune checkpoint inhibitors, probably through an antibiotic-related microbiota dysbiosis. Although cancer patients with HIV, HBV, and HCV were usually excluded from clinical trials evaluating immunotherapy, some retrospective and prospective trials performed in these patient subgroups reported similar results compared to those described in not-infected patients, with a favorable safety profile. Moreover, patients with thoracic cancers are particularly at risk of COVID-19 severe outcomes and mortality. Few reports speculated about the prognostic implications of anticancer therapy, including immunotherapy, in lung cancer patients with concomitant Sars-Cov-2 infection, showing, to date, inconsistent results. The correlation between infectious diseases and immunotherapy remains to be further explored and clarified in the context of dedicated trials. In clinical practice, the accurate and prompt multidisciplinary management of lung cancer patients with infections should be encouraged in order to select the best treatment options for these patients, avoiding unexpected toxicities, while maintaining the anticancer effect.

On February 23rd, the 1st case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was diagnosed at the University Hospital Trust of Verona, Italy. On March 13th, the Oncology Section was converted into a 22-inpatient bed coronavirus disease (COVID) Unit, and we reshaped our organisation to face the SARS-CoV-2 epidemic, while maintaining oncological activities. We tracked down (i) volumes of oncological activities (January 1st - March 31st, 2020 versus the same period of 2019), (ii) patients' and caregivers' perception and (iii) SARS-CoV-2 infection rate in oncology health professionals and SARS-CoV-2 infection-related hospital admissions of "active"' oncological patients. As compared with the same trimester in 2019, the overall reduction in total numbers of inpatient admissions, chemotherapy administrations and specialist visits in January-March 2020 was 8%, 6% and 3%, respectively; based on the weekly average of daily accesses, reduction in some of the oncological activities became statistically significant from week 11. The overall acceptance of adopted measures, as measured by targeted questionnaires administered to a sample of 241 outpatients, was high (>70%). Overall, 8 of 85 oncology health professionals tested positive for SARS-CoV-2 infection (all but one employed in the COVID Unit, no hospital admissions and no treatment required); among 471 patients admitted for SARS-CoV-2 infection, 7 had an "active"' oncological disease (2 died of infection-related complications). A slight, but statistically significant reduction in oncology activity was registered during the SARS-CoV-2 epidemic peak in Verona, Italy. Organisational and protective measures adopted appear to have contributed to keep infections in both oncological patients and health professionals to a minimum.

Purpose: Physical activity is associated with a reduction in mortality and recurrence risks in patients with cancer. Despite the well-recognized benefits of exercise, patients’ adherence to an exercise program remains a challenge. The present study aimed to assess the experiences of patients with cancer participating in a 12-week exercise program. Methods: A total of 21 survivors participated in focus group discussions after the conclusion of the exercise intervention. Semi-structured interview questions were developed according to the theory of the Health Belief Model. Data were analyzed using thematic analysis and categorized into perceived benefits, barriers, and cues to action. Results: Patients described a series of benefits achieved during the exercise program, from physical to psychological domains. Treatment-related side effects and logistic factors, including distance from the gym facility, were the most commonly reported barriers to adherence. Concerning cues to action, expected benefits from exercise were the most important reason to participate, while a patient-center program, supervised by skilled experts, highly stimulated patients to complete the program. Conclusion: Overall, patients with cancer reported a positive experience participating in a supervised exercise program. A variety of factors influencing participation and adherence were individuated. This study may help design and develop effective and sustainable programs addressing individuals’ needs.

Treatment of advanced ALK + NSCLC has improved with increasingly effective ALK tyrosine-kinase inhibitors (TKIs). We report real-world treatment patterns and outcomes from the Italian ATLAS registry. Clinical-pathological and treatment data were retrospectively and prospectively collected from 37 Italian centers. 463 ALK + advanced NSCLC patients treated from 2019 to 2024 were included. 431 (93 %) patients received 1st line (1L) ALK TKIs, mostly alectinib (82.5 %). 1L treatment choice, reported in 142 cases, was driven by drug access as first (31 %) or subsequent lines (40.1 %) and by safety (21.8 %). Among 382 patients receiving 1L alectinib overall survival (OS) rate was 88.7 % and 73.3 % at 24 and 60 months, respectively. Median progression-free survival (mPFS) was 43.1 months (95 %CI: 29.5-57.0). Brain was a new site of progression in 11 (3.6 %) patients. Intracranial PFS rate was 73.1 % and 59.1 % at 24 and 36 months with a 64.7 % intracranial response rate. Grade ≥ 3 adverse events occurred in 41 (10.7 %) patients, mainly hepatic toxicity (13, 3.4 %) and asthenia (5, 1.3 %). At progression tissue and/or liquid biopsy were performed in 28 (23.5 %) and 20 (16.8 %) cases, respectively. Out of 80 patients receiving 2nd line therapy after alectinib, 67 (83.8 %) received lorlatinib achieving mPFS 7.5 (95 % CI: 6.2-8.8) and mOS 26.4 months (95 % CI: 19.1-33.7). 17 (15.5 %) patients died without second line therapy. Real-world data confirm the effectiveness and safety of alectinib, used as preferred upfront ALK-TKI. The recent 1L lorlatinib approval might change this scenario. Tissue/liquid biopsy at disease progression are underperformed in clinical practice.

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:Predictive biomarkers of response to immune checkpoint inhibitors (ICI) remain poorly defined in patients with non–small cell lung cancer (NSCLC) without a history of tobacco use and lacking actionable genomic alterations (AGA). We aimed to identify clinical and molecular predictors of response to ICI-based regimens in patients who have never smoked and lack AGAs. Experimental Design:We retrospectively analyzed patients with metastatic, AGA-negative NSCLC who never smoke treated with ICI-based regimens across multiple independent cohorts. Tumor-infiltrating lymphocyte (TIL) densities were quantified using a machine learning–based algorithm, and immune cell biomarkers were assessed with multiplexed immunofluorescence. Transcriptomic correlates of ICI response were analyzed in the Stand Up To Cancer cohort. Results:Among 741 patients with AGA-negative NSCLC and no history of tobacco use, the objective response rate (ORR) was 23.2%, median progression-free survival (mPFS) was 4.5 months, and median overall survival (mOS) was 16.8 months. PD-L1 ≥90% and tumor mutational burden (TMB) ≥90th percentile were independently and significantly associated with improved ORR, mPFS, and mOS (all P <0.01). PD-(L)1 + CTLA-4 combinations outperformed chemoimmunotherapy and PD-(L)1 monotherapy in terms of mPFS and mOS. Transcriptomic analysis revealed enrichment of innate and adaptive immune pathways in responders, including increased MHC class I/II antigen presentation and T-cell activity. High TIL density was also associated with superior ORR and PFS. Multiplexed immunophenotyping confirmed higher immune cell infiltration in patients who experienced durable clinical benefit. Conclusions:We demonstrated how combination therapies may improve ICI outcomes in patients with AGA-negative NSCLC and no history of tobacco exposure. Very high PD-L1, TMB, and immune-enriched phenotypes may guide treatment personalization.