Joseph Cicenia

ALK Status Testing in Non–Small-Cell Lung Carcinoma by FISH on ThinPrep Slides with Cytology Material

Introduction: Oncogenic anaplastic lymphoma kinase (ALK) gene rearrangements in non–small-cell lung carcinomas (NSCLC) provide the basis for targeted therapy with crizotinib and other specific ALK inhibitors. Treatment eligibility is conventionally determined by the Food and Drug Administration–approved companion diagnostic fluorescence in situ hybridization (FISH) assay on paraffin-embedded tissue (PET). On limited samples such as fine needle aspiration–derived cytoblocks, FISH for ALK is often uninformative. FISH performed on liquid-based ThinPrep slides (ThinPrep-FISH) may represent a robust alternative. Methods: Two hundred thirty cytology samples from 217 patients with advanced NSCLC, including a consecutive series of 179 specimens, were used to generate matched ThinPrep slides and paraffin cytoblocks. The same ThinPrep slides used for cytologic diagnosis were assessed by standard ALK break-apart two-color probe FISH, after etching of tumor areas. Ultrasensitive ALK immunohistochemistry (IHC) on corresponding cytoblocks [D5F3 antibody, OptiView signal amplification] served as the reference data set. Results: ThinPrep-FISH ALK signals were robust in 228 of 230 cases and not compromised by nuclear truncation inherent in paraffin-embedded tissue–FISH; only two samples displayed no signals. Nine of 178 informative cases (5%) in the consecutive series and 18 of 228 informative cases (7.8%) overall were ALK rearranged by ThinPrep-FISH. In 154 informative matched ThinPrep-FISH and cytoblock-IHC samples, 152 were concordant (10, 6.5% ALK status positive; 142, 92.2% ALK status negative), and two (1.3%) were ThinPrep-FISH positive but IHC negative (sensitivity 100%, specificity 98.6%, overall agreement 98.7%). Conclusion: Detection of ALK gene rearrangements in liquid cytology ThinPrep slides derived from patients with NSCLC can be confidently used for clinical ALK molecular testing.

EGFR mutational genotyping of liquid based cytology samples obtained via fine needle aspiration (FNA) at endobronchial ultrasound of non-small cell lung cancer (NSCLC)

OBJECTIVES Epidermal growth factor receptor (EGFR) gene mutation status should be determined in all patients with advanced, non-squamous non-small cell lung carcinoma (NSCLC) to guide targeted therapy with EGFR tyrosine kinase inhibitors. EGFR mutations are commonly tested by Sanger sequencing or allele specific polymerase chain reaction (ASPCR) on formalin-fixed paraffin-embedded (FFPE) samples including cell blocks (CB) that may fail due to absence of tumor cells. The cell pellet from cytology specimens obtained at the time of endobronchial guided ultrasound fine needle aspiration (EBUS FNA) (EBUS-TBNA, transbronchial needle aspiration) represents an alternative resource for additional tissue. Here we demonstrate the utility of using the FNA cell pellet versus for the detection of EGFR mutations in NSCLC. MATERIALS AND METHODS For internal validation, 39 cytology samples from patients with NSCLC referred for EGFR testing were analyzed using the EGFR rotor-gene Q (RGQ) PCR assay (Qiagen). Thereafter, a consecutive series of 228 EBUS FNA samples were tested. RESULTS The ASPCR assay demonstrated acceptable intra-assay, inter-assay and inter-lot reproducibility, sensitivity, and specificity. For the consecutive series, only 6/228 (2.6%) failed analysis (5 due to insufficient DNA yield). Of 228 EBUS FNA cell pellets tested 32 (14.0%) demonstrated clinically relevant mutations. RESULTS AND CONCLUSION ASPCR can reliably detect EGFR gene mutations in FNA preparations from patients with NSCLC obtained at EBUS.

A Histologic Basis for the Efficacy of SBRT to the lung

Purpose: Stereotactic body radiation therapy (SBRT) is the standard of care for medically inoperable patients with early‐stage NSCLC. However, NSCLC is composed of several histological subtypes and the impact of this heterogeneity on SBRT treatments has yet to be established. Methods: We analyzed 740 patients with early‐stage NSCLC treated definitively with SBRT from 2003 through 2015. We calculated cumulative incidence curves using the competing risk method and identified predictors of local failure using Fine and Gray regression. Results: Overall, 72 patients had a local failure, with a cumulative incidence of local failure at 3 years of 11.8%. On univariate analysis, squamous histological subtype, younger age, fewer medical comorbidities, higher body mass index, higher positron emission tomography standardized uptake value, central tumors, and lower radiation dose were associated with an increased risk for local failure. On multivariable analysis, squamous histological subtype (hazard ratio = 2.4 p = 0.008) was the strongest predictor of local failure. Patients with squamous cancers fail SBRT at a significantly higher rate than do those with adenocarcinomas or NSCLC not otherwise specified, with 3‐year cumulative rates of local failure of 18.9% (95% confidence interval [CI]: 12.7–25.1), 8.7% (95% CI: 4.6–12.8), and 4.1% (95% CI: 0–9.6), respectively. Conclusion: Our results demonstrate an increased rate of local failure in patients with squamous cell carcinoma. Standard approaches for radiotherapy that demonstrate efficacy for a population may not achieve optimal results for individual patients. Establishing the differential dose effect of SBRT across histological groups is likely to improve efficacy and inform ongoing and future studies that aim to expand indications for SBRT.

Histologic and molecular characterization of lung cancer with tissue obtained by electromagnetic navigation bronchoscopy.

Background:Electromagnetic navigation bronchoscopy (ENB) is a catheter-based adjunct to standard bronchoscopic techniques for the sampling of lung lesions. We sought to evaluate the adequacy of ENB-obtained samples for histologic subtyping of lung cancer, epidermal growth factor receptor (EGFR) mutations, and echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) translocations. Methods:We retrospectively analyzed consecutive patients who underwent ENB for the diagnosis of lung lesions between 2008 and 2011. In those proven to be a primary lung cancer by ENB, tissue adequacy for histologic subtyping was recorded. Accuracy was determined by comparison with resected specimens when available. Tissue adequacy for EGFR mutation and/or EML4-ALK analyses was also reviewed. Results:Sixty-five ENB cases resulted in a diagnosis of lung cancer. Tissues obtained were adequate for histologic subtyping in all 65 cases. Forty-three (66.2%) were diagnosed with adenocarcinoma, 19 (29.2%) with squamous cell carcinoma, 3 (4.6%) with small cell carcinoma. In 51 cases (78.5%), subtyping was performed by morphology alone, whereas 11 (21.5%) required immunohistochemical staining. Sixteen of 65 tumors underwent surgical resection. Concordance of histologic subtyping between ENB and surgical specimens was 87.5% (14 tumors). ENB-obtained samples from 15 patients with adenocarcinoma were sent for EGFR mutation analysis, of which 14 (93.3%) were adequate. Samples from 2 patients were evaluated for EML4-ALK gene rearrangements, both of which were adequate for analysis. Conclusions:ENB is effective at obtaining tissue samples adequate for histologic subtyping, EGFR mutation, and EML4-ALK translocation analysis.

Cost effectiveness of bronchial thermoplasty in patients with severe uncontrolled asthma

Abstract Rationale: Based on its clinical effectiveness, bronchial thermoplasty (BT) was approved by the Food and Drug Administration in 2010 for the treatment of severe persistent asthma in patients 18 years and older whose asthma is not well-controlled with inhaled corticosteroids and long-acting beta-agonist medicines. Objective: Assess the 10 year cost-effectiveness of BT for individuals with severe uncontrolled asthma. Methods: Using a Markov decision analytic model, the cost-effectiveness of BT was estimated. The patient population involved a hypothetical cohort of 41-year-old patients comparing BT to usual care over a 10-year time frame. The main outcome measure was cost in 2013 dollars per additional quality adjusted life year (QALY). Results: Treatment with BT resulted in 6.40 QALYs and

Endobronchial Ultrasound-guided Transvascular Needle Aspiration: A Single-Center Experience.

7512 in cost compared to 6.21 QALYs and

The Chef Has a Knife…: Endoscopic Ultrasound-Guided Fine-Needle Aspiration by a Pulmonologist

2054 for usual care. The incremental cost-effectiveness ratio for BT at 10 years was

Endobronchial valves for treatment of bronchopleural fistula in granulomatous polyangitis: a longitudinal case report.

29 821/QALY. At a willingness to pay per QALY of

A Prediction Model to Help with the Assessment of Adenopathy in Lung Cancer (HAL).

50 000, BT continues to be cost effective unless the probability of severe asthma exacerbation drops below 0.63 exacerbation per year or the cost of BT rises above

Iatrogenic pulmonary nodule in a heart transplant recipient.

10 384 total for all three bronchoscopic procedures needed to perform thermoplasty and to cover the entire bronchial tree (baseline =