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Background: Combined endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and endoscopic ultrasound-guided tissue acquisition (EUS-TA) are accurate procedures for the diagnosis and staging of mediastinal lymph nodes (MLNs) in lung cancer. However, the respective contribution of separate and combined procedures in diagnosis and staging has not been fully studied. The aim of this study was to assess their respective performances., Methods: Patients with suspected malignant MLNs in lung cancer or recurrence identified by PET-CT who underwent combined EBUS-TBNA and EUS-TA were retrospectively reviewed., Results: A total of 141 patients underwent both procedures. Correct diagnosis was obtained in 82% with EBUS-TBNA, 91% with EUS-TA, and 94% with the combined procedure. The overall sensitivity, specificity, and positive and negative predictive values (PPV and NPV) of EBUS-TBNA, EUS-TA, and the combined procedure for diagnosing malignancy were [75%, 100%, 100%, 58%], [87%, 100%, 100%, 75%], and [93%, 100%, 100%, 80%], respectively, with a significantly better sensitivity of the combined procedure ( p < 0.0001). Staging (82/141 patients) was correctly assessed in 74% with EBUS-TBNA, 68% with EUS-TA, and 85% with the combined procedure. The overall sensitivity, specificity, PPV, and NPV of EBUS-TBNA, EUS-TA, and the combined procedure for lung cancer staging were [62%, 100%, 100%, 55%], [54%, 100%, 100%, 50%], and [79%, 100%, 100%, 68%], respectively, significantly better in terms of sensitivity for the combined procedure ( p < 0.001)., Conclusion: The combined EBUS-EUS approach in lung cancer patients showed better accuracy and sensitivity in diagnosis and staging when compared with EBUS-TBNA and EUS-TA alone.

Background: Restin is a member of the melanoma-associated antigen (MAGE) superfamily. Its expression has been reported to be up- or downregulated in cancer. Preclinical data suggest it is a tumor suppressor. In this study, we aimed to evaluate restin expression and prognostic value in non-small cell lung cancer (NSCLC)., Methods: Restin expression was analyzed by immunohistochemistry in three tissue microarrays consisting of formalin-fixed/paraffin-embedded NSCLC specimens from 113 patients, represented in triplicate. Restin staining H-score was the result of the staining intensity (0-no, 1-weak, 2-moderate, and 3-strong) multiplied by the percentage of stained tumor cells; it was defined as low if 1-100, moderate if 101-200, and strong if 201-300. Haverage-score was the average H-score in the triplicate. Restin Haverage-scores were tested for correlations with clinical and pathological characteristics and patient outcome., Results: Restin expression was localized to the cytoplasm, with nuclear enhancement, of 112/113 (99.1%) NSCLCs. Restin Haverage-scores were 0 in 1/113 (0.88%), low in 15/113 (13.3%), moderate in 48/113 (42.5%), and strong in 49/113 (43.4%) NSCLCs. Restin Haverage-scores did not correlate with NSCLC histological subtype, disease stage, recurrence/progression-free, or overall survival., Conclusion: Restin is moderately to strongly expressed in the majority of NSCLC tumors but its expression has no prognostic value in patients with NSCLC., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: Interstitial lung disease (ILD) is associated with a higher lung cancer (LC) risk and may impact cancer's clinical characteristics, treatment strategies, and outcomes. This impact's extent is unclear, particularly in Caucasians., Methods: In this retrospective observational study, we reviewed the files of all LC patients diagnosed in a 38-month period. Expert radiologists reviewed the computed tomography scans performed at diagnosis. Patients with LC and ILD ( n = 29, 7%) were compared to those without ILD ( n = 363, 93%) for population and cancer characteristics, treatments, and clinical outcomes., Results: Patients with LC and ILD were older (73 ± 8 vs. 65 ± 11 years; p < 0.001). There was no significant difference in LC histology, localization, stage, or treatment modalities. The respiratory complication rate after cancer treatment was significantly higher in the ILD group (39% vs. 6%; p < 0.01). Overall survival rates were similar at 12 (52% vs. 59%; p = 0.48) and 24 months (41% vs. 45%; p = 0.64) but poorer in the ILD group at 36 months, although not statistically significant (9% vs. 39%; p = 0.06). The ILD group had a higher probability of death (hazard ratio (HR) = 1.49 [0.96;2.27]), but this was not statistically significant ( p = 0.06). In a Cox regression model, patients with ILD treated surgically had a significantly higher mortality risk (HR = 2.37 [1.1;5.09]; p = 0.03)., Conclusions: Patients with combined LC and ILD have worse clinical outcomes even when similar treatment modalities are offered.

Immune checkpoint inhibitors became the treatment of choice, in monotherapy or in association with platinum-based doublet chemotherapy, in first-line therapy for advanced-stage non-small-cell lung cancer without oncogenic driver. Nevertheless, it can be associated with diverse immune-related adverse events; several immune-related adverse events can also follow each other involving multiple organ systems, leading to immune checkpoint inhibitors discontinuation and immunosuppressive therapy that could compromise the prognosis of patients, with the exception of rare situations such as this clinical case. This case report illustrates a succession of immune-related adverse events including a rare and severe pembrolizumab-induced immune-related encephalitis in a patient with metastatic lung adeno-squamous carcinoma in whom we could observe a long-term and complete remission despite discontinuation of treatment and high-dose corticosteroids. In metastatic non-small-cell lung cancer, a disease with a poor initial prognosis, some patients can benefit from immune checkpoint inhibitors and can even now present a long-term and complete remission and this despite severe and rare immune-related adverse events, high-dose corticosteroids and an early discontinuation of treatment., Competing Interests: 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., (© 2023 The Authors.)

Biomarkers of systemic inflammation/nutritional status have been associated with outcomes in advanced-stage non-small-cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). However, most of them were not tested in cohorts of patients treated with ICIs in combination with chemotherapy (CT) (ICI + CT) or with CT alone, making it impossible to discriminate a predictive from a prognostic effect. We conducted a single-center retrospective study to search for associations between various baseline biomarkers/scores that reflected the systemic inflammation/nutritional status (Lung Immune Prognostic Index, Modified Lung Immune Prognostic Index, Scottish Inflammatory Prognostic Score, Advanced Lung Cancer Inflammation Index, EPSILoN, Prognostic Nutritional Index, Systemic Immune-Inflammation Index, Gustave Roussy Immune Score, Royal Marsden Hospital Prognostic Score, Lung Immuno-oncology Prognostic Score 3, Lung Immuno-oncology Prognostic Score 4, score published by Holtzman et al., and Glasgow Prognostic Score) and outcomes in metastatic NSCLC treated in a first-line setting either with ICI in monotherapy (cohort 1; n = 75), ICI + CT (cohort 2; n = 56), or CT alone (cohort 3; n = 221). In the three cohorts, the biomarkers/scores were moderately associated with overall survival (OS) and progression-free survival (PFS). Their prognostic performance was relatively poor, with a maximum c-index of 0.66. None of them was specific to ICIs and could help to choose the best treatment modality. The systemic inflammation/nutritional status, associated with outcomes independently of the treatment, is therefore prognostic but not predictive in metastatic NSCLC.

Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have improved the prognosis of advanced-stage non-small cell lung cancer (NSCLC) with ALK rearrangement, but resistance mechanisms limit their efficacy. We describe the case of a 63-year-old man with a stage cIVA ALK -rearranged lung adenocarcinoma who developed a BRAF A598-T599insV mutation as a potential resistance mechanism to alectinib, a second-generation ALK TKI. He was treated with an association of BRAF and MEK inhibitors but death occurred two months after treatment initiation in a context of tumor progression and toxicity. Based on this first report of BRAF A598-T599insV mutation occurring in lung cancer, we discuss resistance mechanisms to ALK TKIs, implications of BRAF mutation in NSCLC, and BRAF A598-T599insV mutation in other cancers., 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 Pasau, Wauters, Wauters, Duplaquet, Pirard, Pop-Stanciu, D’Haene, Dupont, Vander Borght, Rondelet and Ocak.)

Background: To evaluate the outcome of patients treated with stereotactic ablative body radiotherapy (SABR) with curative intent for stage I non-small cell lung cancer (NSCLC) with regard to local, regional and distant tumor control, disease-free survival (DFS), overall survival (OS) and toxicity., Methods: Data of 300 patients treated with SABR for NSCLC cancer for the period of November 2007 to June 2016 were retrospectively analyzed. Of which, 189 patients had single primary lung lesion and were included in the study. The prescribed dose for the tumor was 48 Gy, given in 12 Gy × 4 fractions for all patients. In 2010, an improved protocol was established in advanced technology for the planning CT, dose calculation and imaging. Cumulative incidence function (CIF) of local, regional, distant or any recurrences were computed using competing risk analysis with death as a competing event. Survivals (DFS and OS) were estimated using the Kaplan-Meier method and Cox proportional regression was used for comparisons. Toxicities were graded according to the common terminology criteria for adverse events version 4.0 (CTCAE v.4)., Results: Diagnosis was histologically confirmed in 42% of the patients (N = 80). At 1, 2 and 4 years, the cumulative incidence function (CIF) of local relapses were 8% [4-13%], 15% [10-21%] and 18% [12-25%], the CIF of regional relapses were 4% [2-8%], 10% [6-16%] and 12% [8-19%], the CIF of distant relapses were 9% [5-14%], 15% [11-22%] and 20% [15-28%] and the CIF of any relapses were 14% [10-20%], 28% [22-36%], 34% [27-43%], respectively. After 1, 2 and 4 years, the OS rates were 83% [95% CI: 78-89%] (N = 128), 65% [95% CI: 57-73%] (N = 78) and 37% [95% CI: 29-47%] (N = 53), respectively. The median survival time was 37 months. The DFS after 1, 2 and 4 years reached 75% [95% CI: 68-81%] (N = 114), 49% [95% CI: 42-58%] (N = 60) and 31% [95% CI: 24-41%] (N = 41), respectively. No grade 4 or 5 toxicity was observed., Conclusions: We observed a long-term local control and survival after SABR for peripheral stage I NSCLC in this large series of patients with the expected low toxicity.

Background: Crizotinib is an approved tyrosine kinase inhibitor in the treatment of advanced-stage non-small-cell lung cancer patients with anaplastic lymphoma receptor tyrosine kinase (ALK) rearrangement. Renal dysfunction after crizotinib administration was recently reported, but the physiopathological explanation and the safety in patients with preexisting renal dysfunction are still not clear., Case Presentation: A 44-year-old female and current smoker was diagnosed with a stage IV lung adenocarcinoma and treated with five lines of chemotherapy during a 4-year period of time. While she developed symptomatic tumor progression with deterioration of her performance status and renal dysfunction after these five lines of treatment, we discovered that her lung cancer was ALK-rearranged. We therefore proposed a treatment with full-dose crizotinib despite the renal impairment (creatinine clearance: 33 mL/min/1.73 m 2 ) of unknown origin. A renal function worsening occurred after the initiation of crizotinib but we did not reduce the dose as recommended and this did not induce further deterioration. During the 15 months under crizotinib, the patient had a good general status, no clinically noticeable side effect, and a stable renal dysfunction, which even improved after the initial worsening and almost returned to the baseline (pre-crizotinib) status., Conclusion: This case report suggests that full-dose crizotinib may be continued even in patients with severe renal dysfunction and deterioration at treatment initiation, in parallel to careful follow-up of renal function and particular attention to avoid the use of concomitant nephrotoxic drugs.

Epidermal growth factor receptor tyrosine kinase inhibitors represent a new treatment option for patients with advanced nonsmall cell lung cancer (NSCLC). This retrospective study examined to what extent previous clinical trial experience matches large-scale Western community implementation of this treatment. In the Belgian expanded access programme, the data from 513 patients with advanced or metastatic NSCLC, not suitable for further chemotherapy and receiving oral gefitinib 250 mg.day(-1) until disease progression, death or unacceptable toxicity, were analysed. The median (range) duration of gefitinib treatment was 2.3 months (0.0-32.7). Its use was predominantly in second- or third-line treatment. The overall response and disease control rates were 8.9 and 41.2%, respectively. In univariate analysis, response was more common in females and never-smokers. In multivariate analysis, female sex was the only significant predictive factor (odds ratio (OR) (95% confidence interval (CI)) 0.329 (0.129-0.839)). Symptom improvement was reported in 108 patients of whom 32 (29.6%) had an objective response, 66 (61.1%) experienced disease stabilisation and 10 (9.3%) progressed. Gefitinib was well tolerated; only 7.8% of the patients reported grade 3 or 4 toxicity. The overall median survival was 4.7 months, with a 1-yr survival rate of 21%. Survival was strongly influenced by a better performance status (PS) (good PS: hazard ratio (HR) (95%CI) 0.110 (0.077-0.157)) and adenocarcinoma with bronchioloalveolar carcinoma features histology (HR (95%CI) 0.483 (0.279-0.834)). In conclusion, the activity of gefitinib was confirmed in the present large Western community implementation study. Response, present in a small subgroup, led to a rewarding survival and could be predicted by sex only. Baseline performance status and adenocarcinoma with bronchioloalveolar carcinoma features histology were significant factors for survival.