Improved Accuracy and Sensitivity in Diagnosis and Staging of Lung Cancer with Systematic and Combined Endobronchial and Endoscopic Ultrasound (EBUS-EUS): Experience from a Tertiary Center.

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.

Treatment and Prognosis of Patients with Lung Cancer and Combined Interstitial Lung Disease.

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.

Long-term complete remission after severe pembrolizumab-induced immune-related encephalitis in metastatic lung adeno-squamous carcinoma: A case report.

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.

Restin protein expression in non-small cell lung cancer.

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.

Systemic Inflammation/Nutritional Status Scores Are Prognostic but Not Predictive in Metastatic Non-Small-Cell Lung Cancer Treated with First-Line Immune Checkpoint Inhibitors.

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.

Case report: BRAF A598-T599insV mutation as a potential resistance mechanism to alectinib in ALK-rearranged lung adenocarcinoma.

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.

Bronchotracheal Stenting Management by Rigid Bronchoscopy under Extracorporeal Membrane Oxygenation (ECMO) Support: 10 Years of Experience in a Tertiary Center.

Purpose: Airway stenting offers good palliation and improves the quality of life in patients with inoperable bronchotracheal stenosis. However, in some cases, the management of stenting can be life-threatening. Hence, a strategy for maintaining oxygenation and hemodynamic stability should be anticipated to avoid critical situations. Herein, we report the use of extracorporeal membrane oxygenation (ECMO) in bronchotracheal stenting management to secure oxygenation and facilitate interventions. Methods: We retrospectively reviewed all patients who underwent rigid bronchoscopy under ECMO support for the management of bronchotracheal stenting at CHU UCL Namur hospital (Belgium), between January 2009 and December 2019. Results: We included 14 bronchoscopy cases performed on 11 patients (3 patients underwent 2 bronchoscopies) in this study; 12 were performed on males and 2 on females. The median age was 54 years. There were 11 benign and 3 malignant etiologies for the central airway obstruction/stenosis. Eight cases were supported by venovenous ECMO and six by venoarterial ECMO. The median ECMO time was 267 minutes. The weaning of ECMO support was successful in all cases. In most cases, the procedures were performed effectively and safely. Only two local complications caused by the cannulation of ECMO were reported, and anticoagulation was adapted to avoid bleeding at the operating site and clot formation in the system. Conclusion: Elective ECMO support was helpful and safe for the high-risk management of bronchotracheal stenting with rigid bronchoscopy and was not associated with any additional significant complications.

Long term outcome after 48 Gy stereotactic ablative body radiotherapy for peripheral stage I non-small cell lung cancer.

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.

Complete tumor response of a locally advanced lung large-cell neuroendocrine carcinoma after palliative thoracic radiotherapy and immunotherapy with nivolumab.

Lung large-cell neuroendocrine carcinoma (L-LCNEC) is a rare subset of lung carcinoma associated with poor overall survival. Due to its rarity, little has been established about its optimal treatment in the advanced stage. We report the case of a 41-year-old woman diagnosed with an unresectable locally advanced L-LCNEC who presented an impressive tumor response to immunotherapy with nivolumab after non-curative thoracic radiotherapy. Salvage surgery was then performed, and pathologic analysis of the resected piece revealed the absence of residual viable tumor cells. Based on this case report, we discuss the literature regarding the efficacy of inhibitors of programmed death-1 protein (PD-1) in L-LCNEC and their use in association with radiotherapy and in the neoadjuvant setting.

Reassessing the BODE score as a criterion for listing COPD patients for lung transplantation.

BACKGROUND: The BODE score (incorporating body mass index, airflow obstruction, dyspnea and exercise capacity) is used for the timing of listing for lung transplantation (LTx) in COPD, based on survival data from the original BODE cohort. This has limitations, because the original BODE cohort differs from COPD patients who are candidates for LTx and the BODE does not include parameters that may influence survival. Our goal was to assess whether parameters such as age, smoking status and diffusion indices significantly influence survival in the absence of LTx, independently of the BODE. METHODS: In the present cohort study, the BODE was prospectively assessed in COPD patients followed in a tertiary care hospital with an LTx program. The files of 469 consecutive patients were reviewed for parameters of interest (age, gender, smoking status and diffusing capacity of the lungs for carbon monoxide [DL,CO]) at the time of BODE assessment, as well as for survival status. Their influence on survival independent of the BODE score was assessed, as well as their ability to predict survival in patients aged less than 65 years. RESULTS: A Cox regression model showed that the BODE score, age and DL,CO were independently related to survival (P-values <0.001), as opposed to smoking status. Survival was better in patients aged less than 65 in the first (P=0.004), third (P=0.002) and fourth BODE quartiles (P=0.008). The difference did not reach significance in the second quartile (P=0.13). Median survival for patients aged less than 65 in the fourth BODE quartile was 55 months. According to a receiver operating characteristic curve analysis, the BODE score as well as FEV1 and DL,CO fared similarly in predicting survival status at 5 years in patients aged less than 65 years. CONCLUSION: Age and DL,CO add to the BODE score to predict survival in COPD. Assessing survival using tools tested in cohorts of patients younger than 65 years is warranted for improving the listing of patients for LTx.

Diagnostic Accuracy and Safety of CT-Guided Percutaneous Transthoracic Needle Biopsies: 14-Gauge versus 22-Gauge Needles.

PURPOSE: To compare the diagnostic accuracy and safety of a 14-gauge core needle versus a 22-gauge fine needle in the evaluation of thoracic lesions by CT-guided percutaneous transthoracic needle biopsy (TTNB). MATERIALS AND METHODS: Medical charts of all patients who underwent CT-guided percutaneous transthoracic core-needle biopsies (CNBs) with a 14-gauge Spirotome device (99 patients, 102 procedures) and fine-needle biopsies (FNBs) with a 22-gauge Rotex needle (92 patients, 102 procedures) between 2007 and 2013 at a single academic institution were retrospectively reviewed. Variables that could influence diagnostic accuracy and safety were collected. RESULTS: The overall and cancer-specific diagnostic accuracy rates were 90% and 94%, respectively, with CNB, versus 82% and 89% with FNB. Precise cancer type/subtype was provided by 97% of CNBs versus 65% of FNBs (P < .001). In patients with lung cancer considered for targeted therapy, biomarker analyses were feasible in 80% of CNBs versus 0% of FNBs (P < .001). The rate of pneumothorax was significantly higher with CNB versus FNB (31% vs 19%; P = .004), but chest tube insertion rates were similar (10% vs 11%, respectively). Major bleeding complications occurred in 1% of CNBs versus 2% of FNBs and were associated with one death in the CNB group. CONCLUSIONS: Percutaneous transthoracic CNB with a 14-gauge Spirotome needle provided better characterization of cancer lesions and allowed biomarker analyses without a significant increase in major procedural complications.