Safety and Success of Repeat Lung Needle Biopsies in Patients with Epidermal Growth Factor Receptor-Mutant Lung Cancer.

BACKGROUND: Postprogression repeat biopsies are critical in caring for patients with lung cancer with epidermal growth factor receptor (EGFR) mutations. However, hesitation about invasive procedures persists. We assessed safety and tissue adequacy for molecular profiling among repeat postprogression percutaneous transthoracic needle aspirations and biopsies (rebiopsies). MATERIALS AND METHODS: All lung biopsies performed at our hospital from 2009 to 2017 were reviewed. Complications were classified by Society of Interventional Radiology criteria. Complication rates between rebiopsies in EGFR-mutants and all other lung biopsies (controls) were compared using Fisher's exact test. Success of molecular profiling was recorded. RESULTS: During the study period, nine thoracic radiologists performed 107 rebiopsies in 75 EGFR-mutant patients and 2,635 lung biopsies in 2,347 patients for other indications. All biopsies were performed with computed tomography guidance, coaxial technique, and rapid on-site pathologic evaluation (ROSE). The default procedure was to take 22-gauge fine-needle aspirates (FNA) followed by 20-gauge tissue cores. Minor complications occurred in 9 (8.4%) rebiopsies and 503 (19.1%; p = .004) controls, including pneumothoraces not requiring chest tube placement (4 [3.7%] vs. 426 [16.2%] in rebiopsies and controls, respectively; p < .001). The only major complication was pneumothorax requiring chest tube placement, occurring in zero rebiopsies and 38 (1.4%; p = .4) controls. Molecular profiling was requested in 96 (90%) rebiopsies and successful in 92/96 (96%). CONCLUSION: At our center, repeat lung biopsies for postprogression molecular profiling of EGFR-mutant lung cancers result in fewer complications than typical lung biopsies. Coaxial technique, FNA, ROSE, and multiple 20-gauge tissue cores result in excellent specimen adequacy. IMPLICATIONS FOR PRACTICE: Repeat percutaneous transthoracic needle aspirations and biopsies for postprogression molecular profiling of epidermal growth factor receptor (EGFR)-mutant lung cancer are safe in everday clinical practice. Coaxial technique, fine-needle aspirates, rapid on-site pathologic evaluation, and multiple 20-gauge tissue cores result in excellent specimen adequacy. Although liquid biopsies are increasingly used, their sensitivity for analysis of resistant EGFR-mutant lung cancers remains limited. Tissue biopsies remain important in this context, especially because osimertinib is now in the frontline setting and T790M is no longer the major finding of interest on molecular profiling.

Evolution of Body Composition Following Autologous and Allogeneic Hematopoietic Cell Transplantation: Incidence of Sarcopenia and Association with Clinical Outcomes.

Sarcopenia, the loss of muscle mass, has been identified as a potential risk factor for adverse outcomes in hematopoietic cell transplantation (HCT) recipients. However, much remains unknown about change in body composition following HCT. We retrospectively evaluated computed tomography (CT) imaging from 315 lymphoma patients undergoing HCT at our institution between 2000 and 2014. Cross-sectional areas of lean muscle, subcutaneous adipose tissue, and visceral adipose tissue were measured on CT at the level of the third lumbar vertebral body before HCT, 1-year post-HCT, and 2.5 years post-HCT. The incidence of sarcopenia before HCT was 47% in the autologous HCT (auto-HCT) cohort (n = 218) and 55% in the allogeneic HCT (allo-HCT) cohort (n = 97). Older age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.01 to 1.04; P < .001) and male sex (OR, 4.59; 95% CI, 1.42 to 4.93; P < .001) were associated with sarcopenia before HCT. Increasing body mass index (OR, .78; 95% CI, .73 to .84; P < .001) was protective against sarcopenia before HCT. A significant decline in total lean body mass (ß = 1.96; 95% CI, .79 to 3.13; P = .001) and increased sarcopenia incidence (OR, 1.72; 95% CI, 1.13 to 2.62, P = .012) was observed over time for patients in the allo-HCT cohort when compared with the trend in the auto-HCT cohort. Both auto-HCT and allo-HCT recipients experienced an increase in total body fat mass over time (ß = 3.75; 95% CI, 2.77 to 4.73; P < .001). In multivariate analysis of patients undergoing allo-HCT, the presence of sarcopenia on baseline imaging before HCT was associated with a lower risk of acute graft-versus-host disease (OR, .30; 95% CI, .09 to .98; P = .047). In conclusion, we found that total body fat mass increases after both auto-HCT and allo-HCT. Following allo-HCT, total lean body mass significantly decreases corresponding to increased incidence of sarcopenia. Future studies are needed to further characterize changes in body composition in HCT recipients and investigate its impact on HCT outcomes.

Preoperative thoracic muscle area on computed tomography predicts long-term survival following pneumonectomy for lung cancer.

OBJECTIVES: To assess the prognostic role of thoracic muscle as quantified on preoperative computed tomography (CT) for the estimation of overall survival (OS) following pneumonectomy. METHODS: Muscle cross-sectional area (CSA) at the level of the fifth (T5) and eighth (T8) thoracic vertebra was measured on CT scans of consecutive patients with lung cancer prior to pneumonectomy. We stratified patients into high and low muscle groups using the gender-specific median of muscle CSA as separator and estimated associations of muscle CSA and OS using the Kaplan-Meier analysis. Multivariable logistic regression adjusted for body mass index, Charlson comorbidity index (includes age), forced expiratory volume in the first second as a % of predicted, sex, race, smoking status, tumour stage and prior lung cancer treatment was performed. RESULTS: A total of 128 patients were included (61.0 ± 10.6 years of age, mean body mass index of 26.9 kg/m2, 55.5% men). The T8 level showed fewer artefacts and strong correlation with the T5 level (Pearson's rho = 0.904). T8 CSA was therefore used for subsequent analyses. Mean T8 CSA was 118.5 cm2 (median 115.3 cm2) in men and 75.2 cm2 (median 74.0 cm2) in women. During a median follow-up of 23.6 months (interquartile range 39.3), 65 patients (50.8%) died, of whom 41 were in the low muscle group. The Kaplan-Meier analysis showed significantly longer OS in the high muscle group (log-rank P = 0.02). Multivariable analysis showed an independent association of muscle CSA and OS (P = 0.02) with a hazard ratio of 0.80 (confidence interval 0.67-0.98) per 10-cm2 increment. CONCLUSIONS: Thoracic muscle is independently associated with long-term overall survival following pneumonectomy for lung cancer and may contribute to refined survival estimates in this population. IRB PROTOCOL: Protocol #2017P000650, approved 21 April 2017.

Microstructured thin-film electrode technology enables proof of concept of scalable, soft auditory brainstem implants.

Auditory brainstem implants (ABIs) provide sound awareness to deaf individuals who are not candidates for the cochlear implant. The ABI electrode array rests on the surface of the cochlear nucleus (CN) in the brainstem and delivers multichannel electrical stimulation. The complex anatomy and physiology of the CN, together with poor spatial selectivity of electrical stimulation and inherent stiffness of contemporary multichannel arrays, leads to only modest auditory outcomes among ABI users. Here, we hypothesized that a soft ABI could enhance biomechanical compatibility with the curved CN surface. We developed implantable ABIs that are compatible with surgical handling, conform to the curvature of the CN after placement, and deliver efficient electrical stimulation. The soft ABI array design relies on precise microstructuring of plastic-metal-plastic multilayers to enable mechanical compliance, patterning, and electrical function. We fabricated soft ABIs to the scale of mouse and human CN and validated them in vitro. Experiments in mice demonstrated that these implants reliably evoked auditory neural activity over 1 month in vivo. Evaluation in human cadaveric models confirmed compatibility after insertion using an endoscopic-assisted craniotomy surgery, ease of array positioning, and robustness and reliability of the soft electrodes. This neurotechnology offers an opportunity to treat deafness in patients who are not candidates for the cochlear implant, and the design and manufacturing principles are broadly applicable to implantable soft bioelectronics throughout the central and peripheral nervous system.