Ludmila Fridel

Histological diagnosis of interstitial lung diseases by cryo-transbronchial biopsy.

The gold standard for the histological diagnosis of interstitial lung diseases (ILD) is an open lung biopsy (OLB). Tissue samples obtained by forceps transbronchial lung biopsies (TBB) are usually too small. We aim to evaluate the efficacy and safety of cryo‐TBB for the diagnosis of ILD and to explore its role as substitute for OLB.

Transbronchial cryo-biopsy in lung transplantation patients: first report.

Transbronchial lung biopsies remain the gold standard to establish the presence of allograft rejection or infection after lung transplantation. The aim of this study was to evaluate the efficacy and safety of cryo‐transbronchial biopsies (cryo‐TBB) in lung transplantation patients.

Safety of Cryo-Transbronchial Biopsy in Diffuse Lung Diseases: Analysis of Three Hundred Cases

Background: Transbronchial biopsy (TBB) which is performed with metal forceps (forceps TBB) has been accepted as a useful technique in establishing diagnoses of diffuse lung diseases (DLDs). The use of cryoprobes to obtain alveolar tissue (cryo-TBB) is a new method which is currently used by our institute as well as others with excellent results. Objectives: To assess the safety of cryo-TBB compared with conventional forceps TBB. Methods: We performed a retrospective data evaluation of 300 consecutive patients who underwent cryo-TBB between January 2012 and April 2014 and compared them with historical cases treated with forceps TBB between 2010 and 2012. The results of both diagnostic modalities were compared based on pathological reports. The major complications (significant bleeding and pneumothorax) were compared, along with postprocedural hospitalization. Results: Pneumothorax was observed in 15 cases (4.95%) treated with cryo-TBB versus 9 cases (3.15%) treated with forceps TBB, with no significant difference (p = 0.303). The insertion of a chest tube was necessary in 6 (2%) and 4 (1.3%) of the cases having undergone cryo-TBB or forceps TBB, respectively (p = 0.8). In the cryo-TBB group, bleeding was encountered in 16 cases (5.2%), and it occurred in 13 cases (4.5%) of the forceps TBB group, with no significant difference in rates (p = 0.706). Also, there was no significant difference in hospital admission rates between the groups [cryo-TBB: 10 (3.3%); forceps TBB: 4 (1.44%); p = 0.181]. The safety profile of cryo- and forceps TBB remained the same even when stratified according to indications for TBB, i.e. immunocompromised hosts, patients after lung transplantation and those with DLDs. Conclusion: In patients with DLDs, cryo-TBB is as safe as forceps TBB.

ALK-Rearranged Non–Small-Cell Lung Cancer Is Associated With a High Rate of Venous Thromboembolism

Background Patients with lung cancer are at increased risk for venous thromboembolism (VTE), particularly those receiving chemotherapy. It is estimated that 8% to 15% of patients with advanced non–small‐cell lung cancer (NSCLC) experience a VTE in the course of their disease. The incidence in patients with specific molecular subtypes of NSCLC is unknown. We undertook this review to determine the incidence of VTE in patients with ALK (anaplastic lymphoma kinase)‐rearranged NSCLC. Patients and Methods We identified all patients with ALK‐rearranged NSCLC diagnosed and/or treated at the Princess Margaret Cancer Centre (PM CC) in Canada between July 2012 and January 2015. Retrospective data were extracted from electronic medical records. We then included a validation cohort comprising all consecutive patients with ALK‐rearranged NSCLC treated in 2 tertiary centers in Israel. Results Within the PM CC cohort, of 55 patients with ALK‐rearranged NSCLC, at a median follow‐up of 22 months, 23 (42%) experienced VTE. Patients with VTE were more likely to be white (P = .006). The occurrence of VTE was associated with a trend toward worse prognosis (overall survival hazard ratio = 2.88, P = .059). Within the validation cohort (n = 43), the VTE rate was 28% at a median follow‐up of 13 months. Combining the cohorts (n = 98), the VTE rate was 36%. Patients with VTE were younger (age 52 vs. 58 years, P = .04) and had a worse Eastern Cooperative Oncology Group performance status (P = .04). VTE was associated with shorter overall survival (hazard ratio = 5.71, P = .01). Conclusion The rate of VTE in our ALK‐rearranged cohort was 3‐ to 5‐fold higher than previously reported for the general NSCLC population. This warrants confirmation in larger cohorts. Micro‐Abstract We examined the rate of venous thromboembolism in a cohort of consecutive patients with ALK‐rearranged non–small‐cell lung cancer (NSCLC) at a single center and found it to be 3‐ to 5‐fold higher than previously reported in the setting of advanced NSCLC. The results were comparable when we included a validation cohort of consecutive patients at 2 other centers, with an overall rate of 36%. Prospective confirmation is warranted.

Successful Rituximab Therapy in Steroid-Resistant, Cryptogenic Organizing Pneumonia: A Case Series

Cryptogenic organizing pneumonia (COP) is an interstitial lung disease that is usually responsive to corticosteroid treatment. The treatment of COP has not been studied in randomized controlled trials; thus, treatment decisions are based on practice guidelines. We herein present, for the first time, 4 cases of patients with biopsy-proven COP who did not respond to corticosteroids but benefited from rituximab therapy. This report consists of a retrospective case series of patients who experienced steroid-resistant, biopsy-proven COP. Patients included in this case series suffered from acute or chronic COP and did not respond to corticosteroid treatment for a few weeks to months but later responded to rituximab. In a series of 4 patients, 1 patient had a complete radiological and clinical response after rituximab therapy, and the steroids could be gradually tapered. Three patients had a chronic course but had been able to lower steroid dosage or even discontinue the drug after being treated with rituximab. Since 40% of the patients with COP do not respond to or stay dependent on steroids, we think that even the ability to lower the steroid dosage by using rituximab as a steroid-sparing agent with a good safety profile is worth the effort. However, further studies are warranted.

The Pathological Features of Bronchoscopic Lung Volume Reduction Using Sealant Treatment Assessed in Lung Explants of Patients Who Underwent Lung Transplantation

reaction ( fig. 1 ). In the 3 patients who had undergone ELS treatment within 12 months of LTX, deposits of hyalonoid amorphous material, indicative of residual foam sealant, were detected within alveoli ( fig. 2 ). There were no signs of tissue necrosis or dysplasia. Note, there were no histological features of fibrosis in the treatment sites or in adjacent areas. This is the first report in humans of the long-term histological effects of BLVR using ELS therapy. Despite the fact that our conclusions are based on a small number of patients, this histological confirmation regarding the long-term effects of the administered sealant adds important data regarding its safety profile.

Efficacy and safety of trans-bronchial cryo in comparison with forceps biopsy in lung allograft recipients: Analysis of 402 procedures

Trans‐bronchial forceps biopsy (TBFB) is the gold standard to establish the presence of allograft rejection or infection after lung transplantation. We aimed to analyze the diagnostic yield and safety of trans‐bronchial cryobiopsy (TBCB) in lung allografts.

Rare targetable drivers (RTDs) in non-small cell lung cancer (NSCLC): Outcomes with immune check-point inhibitors (ICPi)

OBJECTIVES Efficacy of immune check-point inhibitors (ICPi) in NSCLC with rare targetable drivers (RTDs) is largely unknown. MATERIALS AND METHODS Consecutive patients with NSCLC and RTDs (non-EGFR/ALK, n-82) were selected from the Davidoff Cancer Center database. ORR, PFS, OS with ICPi, OS since advanced disease diagnosis, TMB, MSI, and PD-L1 expression were analyzed; uni- and multivariate PFS and OS analyses were done. OS with ICPi was compared between the RTD cohort and the non-selected NSCLC cohort (n-278). RESULTS Of 50 tumors tested, 32%, 38%, and 30% were associated with ≥50%, 1-49% and <1% PD-L1 expression, respectively. Median TMB (n-48) comprised 4 muts/Mb (0-57); TMB ≥ 10 muts/Mb was seen in 19% of tumors. Both TMB and PD-L1 expression varied across different RTDs. All the 47 tumors were MSI stable. ORR with ICPi (n-44) was 16%, median PFS was 3.2 months (95% CI, 2.6-5.0), median OS was 16.2 months (95% CI, 8.4-NR). No correlation was seen between OS with ICPi and PD-L1 expression (p > 0.4), TMB (p > 0.8), or RTD type (p > 0.3). In the multivariate analysis, ECOG PS (p-0.005), targeted agents exposure (p-0.005), and ICPi exposure (p-0.04) were the only variables which correlated with OS since advanced disease diagnosis. Median OS since advanced disease diagnosis comprised 32 months (95% CI, 19.9-44.9) and 13 months (95% CI, 6.6-15.9) for patients who were and were not exposed to ICPi, respectively (log-rank test-6.3; p-0.01). In the inter-cohort comparison, for patients matched for ECOG PS (0/1), median OS with ICPi comprised 17.5 months (95% CI, 8.1-NR) and 8.6 months (95% CI, 6.7-NR) for RTD and non-selected patients, respectively (log-rank test-2.4, p-0.1). CONCLUSION In NSCLC with RTD, ICPi have favorable efficacy and independent impact on OS. NSCLC with RTD is associated with MSI stable status and variable levels of PD-L1 expression and TMB; their predictive value remains to be determined.