Evaluation of Rigid Bronchoscopy–Guided Percutaneous Dilational Tracheostomy. A Pilot Study

Rationale: Rigid bronchoscopy–guided (RBG) percutaneous tracheostomy has been used in patients with morbid obesity, prior neck surgery, distorted airway anatomy, and uncorrected coagulopathy where standard percutaneous dilational tracheostomy (PDT) is relatively contraindicated. Objectives: This study aims to describe a standardized approach to incorporate RBG-PDT in clinical practice. Methods and Measurements: Retrospective case series of patients who underwent RBG-PDT from 2008 to 2012 at Beth Israel Deaconess Medical Center. Patient medical records were reviewed for demographics, comorbid conditions, American Society of Anesthesiologists classification, indication for tracheostomy, duration of procedure, and periprocedural complications. Main Results: A total of 35 patients underwent RBG-PDT, including 24 men, with a mean age of 66 years (611 yr; range, 42–88 yr). The mean body mass index was 34 kg/m2. The mean procedure time was 32 (610) minutes, with a median of 33 minutes. The most common indication for tracheostomy was failure to wean from mechanical ventilation, followed by tracheal stenosis and tracheobronchomalacia. The most common indications for RBG-PDT were complex airway, obesity, and coagulopathy. There were no periprocedural complications of consequence, or mortality associated with the procedure. Conclusions: RBG-PDT is safe and effective in a population of high-risk patients who are otherwise not considered good candidates for standard PDT

Shape-sensing robotic-assisted bronchoscopy for pulmonary nodules: initial multicenter experience using the Ion™ Endoluminal System

BACKGROUND: Traditional bronchoscopy provides limited approach to peripheral nodules. Shape-sensing robotic-assisted bronchoscopy (SSRAB, Ion™ Endoluminal System) is a new tool for minimally invasive peripheral nodule biopsy. We sought to answer the research question: Does SSRAB facilitate sampling of pulmonary nodules during bronchoscopists\u27 initial experience? METHODS: The lead-in stage of a multicenter, single-arm, prospective evaluation of the Ion Endoluminal System (PRECIsE) is described. Enrolled subjects ≥ 18 years old had recent computed tomography evidence of one or more solid or semi-solid pulmonary nodules ≥ 1.0 to ≤ 3.5 cm in greatest dimension and in any part of the lung. Subjects were followed at 10- and 30-days post-procedure. This stage provided investigators and staff their first human experience with the SSRAB system; safety and procedure outcomes were analyzed descriptively. Neither diagnostic yield nor sensitivity for malignancy were assessed in this stage. Categorical variables are summarized by percentage; continuous variables are summarized by median/interquartile range (IQR). RESULTS: Sixty subjects were enrolled across 6 hospitals; 67 nodules were targeted for biopsy. Median axial, coronal and sagittal diameters were \u3c 18 mm with a largest cardinal diameter of 20.0 mm. Most nodules were extraluminal and distance from the outer edge of the nodule to the pleura or nearest fissure was 4.0 mm (IQR: 0.0, 15.0). Median bronchial generation count to the target location was 7.0 (IQR: 6.0, 8.0). Procedure duration (catheter-in to catheter-out) was 66.5 min (IQR: 50.0, 85.5). Distance from the catheter tip to the closest edge of the virtual nodule was 7.0 mm (IQR: 2.0, 12.0). Biopsy completion was 97.0%. No pneumothorax or airway bleeding of any grade was reported. CONCLUSIONS: Bronchoscopists leveraged the Ion SSRAB\u27s functionality to drive the catheter safely in close proximity of the virtual target and to obtain biopsies. This initial, multicenter experience is encouraging, suggesting that SSRAB may play a role in the management of pulmonary nodules. Clinical Trial Registration identifier and date NCT03893539; 28/03/2019

Electromagnetic navigation bronchoscopy in the European cohort of the prospective, multicenter NAVIGATE study

n/

Rapidly fatal advanced EGFR -mutated lung cancers and the need for rapid tumor genotyping in clinical practice

Use of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is associated with dramatic, durable, and tolerable responses and side effect profiles, respectively, when applied for palliation of advanced EGFR-mutated non-small-cell lung cancers (NSCLCs). Expert guidelines recommend that EGFR mutation testing results should be available within 10 working days of receipt of tumor specimen by the testing laboratory; in circumstances where the tumor specimen needs to be sent to an external laboratory for testing, the sample should be sent within 3 working days of receiving the request for testing. We report here 2 cases, out of 109 EGFR-mutated (exon 19 deletion or L858R) NSCLCs seen at our institution, experiencing rapid clinical deterioration and death within the window of time prescribed by consensus testing guidelines. We hypothesize that a faster turn-around time may have changed the clinical outcome. Improving rapid turnaround times for tumor genotyping may afford more optimal palliation vis-à-vis early initiation of oral targeted therapy in patients with advanced EGFR-mutated NSCLC

Brain metastases in patients with EGFR -mutated or ALK -rearranged non-small-cell lung cancers

Introduction—Brain metastases (BM) are common in non-small-cell lung cancer (NSCLC). However, the baseline incidence and evolution of BM over time in oncogene-driven NSCLCs are seldom reported. In this study, we evaluated the frequency of BM in patients with epidermal growth factor receptor (EGFR)-mutated or anaplastic lymphoma kinase (ALK)-rearranged NSCLC. Methods—The presence of BM, clinicopathologic data, and tumor genotype were retrospectively compiled and analyzed from a cohort of 381 patients. Results—We identified 86 EGFR-mutated (90.7% with metastatic disease; 85.9% received an EGFR inhibitor) and 23 ALK-rearranged (91.3% with metastatic disease; 85.7% received an ALK inhibitor) NSCLCs. BM were present in 24.4% of EGFR-mutated and 23.8% of ALK-rearranged NSCLCs at the time of diagnosis of advanced disease. This study did not demonstrate a difference in the cumulative incidence of BM over time between the two cohorts (EGFR/ALK cohort competing risk regression [CRR] coefficient of 0.78 [95% CI 0.44–1.39], p=0.41). In still living patients with advanced EGFR-mutated NSCLC, 34.2% had BM at 1 year, 38.4% at 2 years, 46.7% at 3 years, 48.7% at 4 years, and 52.9% at 5 years. In still living patients with advanced ALKrearranged NSCLC, 23.8% had BM at 1 year, 45.5% at 2 years, and 58.4% at 3 years. Conclusions—BM are frequent in advanced EGFR-mutated or ALK-rearranged NSCLCs, with an estimated >45% of patients with CNS involvement by three years of survival with the use of targeted therapies. These data point toward the CNS as an important unmet clinical need in the evolving schema for personalized care in NSCLC

Fiducial marker placement with electromagnetic navigation bronchoscopy: a subgroup analysis of the prospective, multicenter NAVIGATE study

Fiducial markers (FMs) help direct stereotactic body radiation therapy (SBRT) and localization for surgical resection in lung cancer management. We report the safety, accuracy, and practice patterns of FM placement utilizing electromagnetic navigation bronchoscopy (ENB). Methods: NAVIGATE is a global, prospective, multicenter, observational cohort study of ENB using the superDimension™ navigation system. This prospectively collected subgroup analysis presents the patient demographics, procedural characteristics, and 1-month outcomes in patients undergoing ENB-guided FM placement. Follow up through 24 months is ongoing. Results: Two-hundred fifty-eight patients from 21 centers in the United States were included. General anesthesia was used in 68.2%. Lesion location was confirmed by radial endobronchial ultrasound in 34.5% of procedures. The median ENB procedure time was 31.0 min. Concurrent lung lesion biopsy was conducted in 82.6% (213/258) of patients. A mean of 2.2 ± 1.7 FMs (median 1.0 FMs) were placed per patient and 99.2% were accurately positioned based on subjective operator assessment. Follow-up imaging showed that 94.1% (239/254) of markers remained in place. The procedure-related pneumothorax rate was 5.4% (14/258) overall and 3.1% (8/258) grade ⩾ 2 based on the Common Terminology Criteria for Adverse Events scale. The procedure-related grade ⩾ 4 respiratory failure rate was 1.6% (4/258). There were no bronchopulmonary hemorrhages. Conclusion: ENB is an accurate and versatile tool to place FMs for SBRT and localization for surgical resection with low complication rates. The ability to perform a biopsy safely in the same procedure can also increase efficiency. The impact of practice pattern variations on therapeutic effectiveness requires further study

Experience with targeted next generation sequencing for the care of lung cancer: Insights into promises and limitations of genomic oncology in day-to-day practice

Introduction Tumor genotyping using single gene assays (SGAs) is standard practice in advanced non-small-cell lung cancer (NSCLC). We evaluated how the introduction of next generation sequencing (NGS) into day-to-day clinical practice altered therapeutic decision-making. Methods Clinicopathologic data, tumor genotype, and clinical decisions were retrospectively compiled over 6 months following introduction of NGS assay use at our institution in 82 patient-tumor samples (7 by primary NGS, 22 by sequential SGAs followed by NGS, and 53 by SGAs). Results SGAs identified abnormalities in 34 samples, and all patients with advanced EGFR-mutated or ALK-rearranged tumors received approved tyrosine kinase inhibitors (TKIs) or were consented for clinical trials. NGS was more commonly requested for EGFR, ALK, and KRAS-negative tumors (p<0.0001). NGS was successful in 24/29 (82.7%) tumors. Of 17 adenocarcinomas (ACs), 11 (7 from patients with ≤15 pack-years of smoking) had abnormalities in a known driver oncogene. This led to a change in decision-making in 8 patients, trial consideration in 6, and off-label TKI use in 2. Of 7 squamous cell (SC) carcinomas, 1 had a driver aberration (FGFR1); 6 had other genomic events (all with TP53 mutations). In no cases were clinical decisions altered (p=0.0538 when compared to ACs). Conclusions Targeted NGS can identify a significant number of therapeutically-relevant driver events in lung ACs; particularly in never or light smokers. For SC lung cancers, NGS is less likely to alter current practice. Further research into the cost effectiveness and optimal use of NGS and improved provider training in genomic oncology are warranted

Pleural Dye Marking of Lung Nodules by Electromagnetic Navigation Bronchoscopy

IntroductionElectromagnetic navigation bronchoscopy (ENB)‐guided pleural dye marking is useful to localize small peripheral pulmonary nodules for sublobar resection.ObjectiveTo report findings on the use of ENB‐guided dye marking among participants in the NAVIGATE study.MethodsNAVIGATE is a prospective, multicentre, global and observational cohort study of ENB use in patients with lung lesions. The current subgroup report is a prespecified 1‐month interim analysis of ENB‐guided pleural dye marking in the NAVIGATE United States cohort.ResultsThe full United States cohort includes 1215 subjects from 29 sites (April 2015 to August 2016). Among those, 23 subjects (24 lesions) from seven sites underwent dye marking in preparation for surgical resection. ENB was conducted for dye marking alone in nine subjects while 14 underwent dye marking concurrent with lung lesion biopsy, lymph node biopsy and/or fiducial marker placement. The median nodule size was 10 mm (range 4‐22) and 83.3% were <20 mm in diameter. Most lesions (95.5%) were located in the peripheral third of the lung, at a median of 3.0 mm from the pleura. The median ENB‐specific procedure time was 11.5 minutes (range 4‐38). The median time from dye marking to resection was 0.5 hours (range 0.3‐24). Dye marking was adequate for surgical resection in 91.3%. Surgical biopsies were malignant in 75% (18/24).ConclusionIn this study, ENB‐guided dye marking to localize lung lesions for surgery was safe, accurate and versatile. More information is needed about surgical practice patterns and the utility of localization procedures.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151973/1/crj13077_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151973/2/crj13077.pd

Success and failure rates of tumor genotyping techniques in routine pathological samples with non-small-cell lung cancer

Introduction—Identification of some somatic molecular alterations in non-small-cell lung cancer (NSCLC) has become evidence-based practice. The success and failure rate of using commercially-available tumor genotyping techniques in routine day-to-day NSCLC pathology samples is not well described. We sought to evaluate the success and failure rate of EGFR mutation, KRAS mutation, and ALK FISH in a cohort of lung cancers subjected to routine clinical tumor genotype. Methods—Clinicopathologic data, tumor genotype success and failure rates were retrospectively compiled and analyzed from 381 patient-tumor samples. Results—From these 381 patients with lung cancer, the mean age was 65 years, 61.2% were women, 75.9% were white, 27.8% were never smokers, 73.8% had advanced NSCLC and 86.1% had adenocarcinoma histology. The tumor tissue was obtained from surgical specimens in 48.8%, core needle biopsies in 17.9%, and as cell blocks from aspirates or fluid in 33.3% of cases. Anatomic sites for tissue collection included lung (49.3%), lymph nodes (22.3%), pleura (11.8%), bone (6.0%), brain (6.0%), among others. The overall success rate for EGFR mutation analysis was 94.2%, for KRAS mutation 91.6% and for ALK FISH 91.6%. The highest failure rates were observed when the tissue was obtained from image-guided percutaneous transthoracic core-needle biopsies (31.8%, 27.3%, and 35.3% for EGFR, KRAS, and ALK tests, respectively) and bone specimens (23.1%, 15.4%, and 23.1%, respectively). In specimens obtained from bone, the failure rates were significantly higher for biopsies than resection specimens (40% vs 0%, p=0.024 for EGFR) and for decalcified compared to non-decalcified samples (60% vs 5.5%, p=0.021 for EGFR). Conclusions—Tumor genotype techniques are feasible in most samples, outside small imageguided percutaneous transthoracic core-needle biopsies and bone samples from core biopsies with decalcification, and therefore expansion of routine tumor genotype into the care of patients with NSCLC may not require special tissue acquisition or manipulation