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Background: Immune checkpoint inhibitors (ICIs) have become standard-of-care at different stage disease in non-small cell lung cancer (NSCLC). Based on the increasing characterization of molecular aberrations and oncogenic drivers in NSCLC, it is expected that more and more patients will benefit from orally small targeted therapies in NSCLC. However, their concomitant or sequential use is associated with an increased risk of a various toxicity pattern., Methods: Relevant publications were included if they reported data on the question of toxicities associated with sequential or combined use of ICIs and small targeted therapies used in NSCLC treatment. MEDLINE, Google Scholar, and the Cochrane Library were searched for the following request, from database inception until June 2023., Results: This review highlighted a various pattern of toxicities (i.e., interstitial lung disease, hepatitis, dermatoses) in the context of both sequential and concomitant administration of ICIs and small targeted therapies. Such toxicities seem rather a "drug-effect" than a "class-effect" and some of these toxicities are more specific of a small targeted therapy. This review highlights on the impact of treatment sequence administration and emphasis for physicians to be particularly careful whether small targeted therapy is administered within one to three months after last ICIs injection., Conclusion: Physicians have to be aware of severe toxicities in case of both concomitant or sequential ICIs/small targeted therapies administration in NSCLC. Further studies are needed to better understand the mechanisms underlying these toxicities in order to prevent them and to refine ICIs and small targeted therapy sequencing strategy., 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 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In recent years, the concept of spread through air spaces (STAS) has been discussed as an adverse prognostic factor for lung cancer. The aim of our study is to clarify the prognostic role of STAS in relation to the main recognized prognostic factors in a retrospective cohort of 330 European patients who underwent stages I to III lung adenocarcinoma resection. On univariate analysis, the presence of STAS was related to progression-free survival (PFS; hazard ratio [HR]: 1.48; 95% CI: 1.02-2.19; P = 0.038) and overall survival (OS; HR: 1.61; 95% CI: 1.03-2.52; P = 0.50). On multivariate analysis, STAS was related to PFS (HR: 1.51; 95% CI: 1.00-2.17; P = 0.050) and to OS (HR: 1.67; 95% CI: 1.00-2.81; P = 0.050). We showed that the presence of STAS was associated with lower PFS, equivalent to the next pathologic T stage, especially the median PFS of T3 stages without STAS was at 62.8 months while the median PFS of T3 stages with STAS was at 15.7 months, closer to the median PFS of 17.4 months in T4 stages. To conclude, STAS is an independent prognostic factor of PFS in this European cohort and is close to significance for OS. We suggest that the presence of STAS might lead to an upstaging of lung adenocarcinoma., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Since randomised clinical trials demonstrated a survival benefit of adjuvant chemotherapy (AC) following curative-intent lung surgery, AC has been implemented as a standard therapeutic strategy for patients with a completely resected IIA-IIIA non-small cell lung cancer (NSCLC). Regarding the moderate benefit of AC and the lack of literature on AC use in real-life practice, we aimed to evaluate compliance to guidelines, AC safety and efficacy in a less selected population., Methods: Between January 2009 and December 2014, we retrospectively analysed 210 patients with theoretical indication of AC following curative-intent lung surgery for a completely resected IIA-IIIA NSCLC. The primary objective of this retrospective study was to evaluate compliance to AC guidelines. Secondary objectives included safety and efficacy of AC in real-life practice., Results: Among 210 patients with a theoretical indication of AC, chemotherapy administration was validated in multidisciplinary team (MDT) for 62.4% of them and 117 patients (55.7%) finally received AC. Patient's clinical conditions were the main reasons advanced in MDT for no respect to AC guidelines. Most of the patients received cisplatin-vinorelbine (86.3%) and AC was initiated within 8 weeks following lung surgery for 73.5% of patients. One-half of patients who received AC experienced side effects leading to either dose-intensity modification or treatment interruption. In real-life practice, AC was found to provide a survival benefit over surgery alone. Factors related to daily-life practice such as delayed AC initiation or incomplete AC planned dose received were not associated with an inferior survival., Conclusions: Although AC use might differ from guidelines in real-life practice, this retrospective study highlights that AC can be used safely and remains efficient among a less selected population. In the context of immunotherapy and targeted therapies development in peri-operative treatment strategies, the place of AC has to be precised in the future., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-22-345/coif). The authors have no conflicts of interest to declare., (2022 Translational Lung Cancer Research. All rights reserved.)

An interventional pulmonologist possesses expertise in minimally invasive diagnostic and therapeutic procedures involving the airways, lungs and pleura. A malignant pleural effusion (MPE), which occurs in 20% of cancer patients, can be a daunting diagnostic challenge insofar as the pleural cavity is a closed cavity. In these patients, treatment may consequently be delayed before a precise diagnosis can be given. In the meantime, an interventional pulmonologist is called upon to carry out a wide range of examinations in order to establish the etiological diagnosis and to treat the symptoms of an MPE patient. Classical medical thoracoscopy, also called "pleuroscopy", is the reference method in MPE diagnosis because it allows visualization of the pleural cavity, pleural biopsy under direct visual control, providing excellent diagnostic yield. Over the past decade, new diagnostic methods have emerged, such as ultrasound-guided biopsy, as well as different interventions, such as indwelling pleural catheters, aimed at improving the quality of life of MPE patients, for whom therapeutic options are limited. The objective of this review of the literature is to point out the role of the interventional pulmonologist in the management of MPE by detailing the various diagnostic and therapeutic methods he possesses at the present time., (Copyright © 2022 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Background: Pleural metastatic disease is a common disease with dismal prognosis. The immune microenvironment of metastatic pleural tissue remains largely unknown. Thus, we aimed to investigate the presence of different immune cell populations, and to compare them with clinical characteristics., Methods: We included 70 patients with lung and breast adenocarcinoma (ADC) diagnosed with pleural metastasis during a 2-year period with the primary endpoint to investigate if the main immune cell populations are present in pleural metastases and if they have any prognostic role. Secondary endpoints were to detect any differences in their presence between lung and breast primaries and to search for any correlation with the macroscopic (thoracoscopic) findings. We used immunohistochemical techniques for the detection of CD4 + , CD8 + , CD20 + , CD163 + and S100 + cells in whole tissue pleural biopsies of lung and breast metastases., Results: Primary endpoint: all these populations are present in the biopsies from lung and higher stromal and intratumoral CD4 counts, as well as higher stromal CD20 cells were positive prognostic factors for lung cancer metastases, while higher S100 intratumoral counts were positive prognostic factors in lung and marginally breast cancer metastases. Secondary endpoints: significant higher values for the stromal CD163 group (P=0.04) and for the intratumoral S100 group (P=0.006) were seen in lung compared to breast metastases. Interesting correlations were also noted between thoracoscopic findings (nodules, masses, pachypleuritis) and the different factors studied., Conclusions: Our data show that the immune microenvironment may be important in this advanced tumoral setting and that possible targets of the nowadays numerous treatment strategies implicating the immune system may merit further exploration in this poor prognosis disease., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-21-6326/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Although KRAS- activating mutations represent the most common oncogenic driver in non-small cell lung cancer (NSCLC), various attempts to inhibit KRAS failed in the past decade. KRAS mutations are associated with a poor prognosis and a poor response to standard therapeutic regimen. The recent development of new therapeutic agents ( i.e. , adagrasib, sotorasib) that target specifically KRAS G12C in its GDP-bound state has evidenced an unprecedented success in the treatment of this subgroup of patients. Despite providing pre-clinical and clinical efficacy, several mechanisms of acquired resistance to KRAS G12C inhibitors have been reported. In this setting, combined therapeutic strategies including inhibition of either SHP2, SOS1 or downstream effectors of KRAS G12C seem particularly interesting to overcome acquired resistance. In this review, we will discuss the novel therapeutic strategies targeting KRAS G12C and promising approaches of combined therapy to overcome acquired resistance to KRAS G12C inhibitors., Competing Interests: AS received honoraria from Amgen for participation in Board meetings. 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 Désage, Léonce, Swalduz and Ortiz-Cuaran.)

Malignant pleural mesothelioma (MPM) is a rare and aggressive tumour with a poor prognosis, associated with asbestos exposure. Nowadays, treatment is based on chemotherapy with a median overall survival of less than two years. This review highlights the main characteristics of the immune microenvironment in MPM with special emphasis on recent biological advances. The MPM microenvironment is highly infiltrated by tumour-associated macrophages, mainly M2-macrophages. In line with infiltration by M2-macrophages, which contribute to immune suppression, other effectors of innate immune response are deficient in MPM, such as dendritic cells or natural killer cells. On the other hand, tumour infiltrating lymphocytes (TILs) are also found in MPM, but CD4+ and CD8+ TILs might have decreased cytotoxic effects through T-regulators and high expression of immune checkpoints. Taken together, the immune microenvironment is particularly heterogeneous and can be considered as mainly immunotolerant or immunosuppressive. Therefore, identifying molecular vulnerabilities is particularly relevant to the improvement of patient outcomes and the assessment of promising treatment approaches.