Improved Survival Outcomes in Medically Fit Patients With Early-Stage Non-Small-Cell Lung Cancer Undergoing Stereotactic Body Radiotherapy.

INTRODUCTION: Stereotactic body radiotherapy (SBRT) has been shown to result in excellent disease control rates for early-stage non-small-cell lung cancer (NSCLC). It remains unknown which patients would most benefit from SBRT in treating NSCLC. PATIENTS AND METHODS: We conducted a retrospective analysis of 346 patients treated with SBRT for early-stage NSCLC at 2 institutions (86 patients from City of Hope National Medical Center and 260 patients from The Newport Beach Radiosurgery Center/Hoag Hospital) from February 2010 to July 2019. The primary endpoint was overall survival (OS). The omnibus test of model coefficients was performed to study the associations between clinical factors and OS. Survival analyses were performed by the log-rank test and Cox proportional hazards regression. RESULTS: Under the univariate analysis, variables associated with a decreased likelihood of death included age < 65 years (P = .040) and being a surgical candidate (P = .010). Multivariate analysis found that surgical candidates still had a significantly decreased likelihood of death compared to nonsurgical candidates (Hazard ratio 0.360, 95% confidence interval 0.153-0.848, P = .019). Median OS was significantly increased for surgical candidates versus nonsurgical candidates (83 vs 53 months, P = .017). The local failure rate was 9.1%, the locoregional failure rate was 12.7%, and the distant failure rate was 10.7%. CONCLUSION: Patients who are deemed to be candidates for surgery have improved OS compared to those who are not when treated with SBRT. This raises the question of selection bias in trials comparing surgery with SBRT in NSCLC, as patients who are deemed to be surgical candidates and then go on to undergo surgery may have an inherent OS benefit.

Complex Oncological Decision-Making Utilizing Fast-and-Frugal Trees in a Community Setting-Role of Academic and Hybrid Modeling.

Non-small cell lung cancer is a devastating disease and with the advent of targeted therapies and molecular testing, the decision-making process has become complex. While established guidelines and pathways offer some guidance, they are difficult to utilize in a busy community practice and are not always implemented in the community. The rationale of the study was to identify a cohort of patients with lung adenocarcinoma at a City of Hope community site (n = 11) and utilize their case studies to develop a decision-making framework utilizing fast-and-frugal tree (FFT) heuristics. Most patients had stage IV (N = 9, 81.8%) disease at the time of the first consultation. The most common symptoms at initial presentation were cough (N = 5, 45.5%), shortness of breath (N = 3, 27.2%), and weight loss (N = 3, 27.2%). The Eastern Cooperative Oncology Group (ECOG) performance status ranged from 0-1 in all patients in this study. Distribution of molecular drivers among the patients were as follows: EGFR (N = 5, 45.5%), KRAS (N = 2, 18.2%), ALK (N = 2, 18.2%), MET (N = 2, 18.2%), and RET (N = 1, 9.1%). Seven initial FFTs were developed for the various case scenarios, but ultimately the decisions were condensed into one FFT, a molecular stage IV FFT, that arrived at accurate decisions without sacrificing initial information. While these FFT decision trees may seem arbitrary to an experienced oncologist at an academic site, the simplicity of their utility is essential for community practice where patients often do not get molecular testing and are not assigned proper therapy.

Selected Case From the Arkadi M. Rywlin International Pathology Slide Seminar: Atypical Thymoma With Rhabdomyomatous Differentiation.

Thymic epithelial neoplasms with foci of rhabdomyomatous differentiation are rare. A case is presented of a primary thymic epithelial neoplasm showing the features of an atypical spindle cell thymoma that contained foci of bland-appearing rhabdomyomatous cells. The histologic and immunohistochemical features of this tumor are discussed along with a review of the literature and the comments from the AMR members to the case.

Robotic Lobectomy Utilizing the Robotic Stapler.

A drawback of robotic lobectomy is the inability of the operating surgeon to perform stapler division of the pulmonary vessels and bronchi. With the advent of the robotic stapler, the surgeon is able to control this instrument from the console. The robotic stapler presents certain challenges. This article outlines techniques to use the robotic stapler for the safe and predictable performance of lobectomies.

Electromagnetic navigation bronchoscopy performed by thoracic surgeons: one center's early success.

BACKGROUND: Multiple studies by pulmonologists have demonstrated that electromagnetic navigation bronchoscopy (ENB) can, with high diagnostic yields and low complication rates, diagnose pulmonary lesions. We believe thoracic surgeons can perform this technique with excellent early results. METHODS: A retrospective analysis was conducted of the first consecutive 104 patients undergoing diagnostic ENB by 2 thoracic surgeons between April 2008 and October 2009. Procedures utilized general anesthesia and rapid on-site examination (ROSE) of cytopathology. All pulmonary lesions were suspicious for malignancy. Patients having negative biopsies subsequently underwent additional procedures or follow-up imaging. True negative biopsies were defined as lesions removed surgically and proven benign, lesions that disappeared on subsequent imaging, and lesions demonstrating stability over a 2-year period. RESULTS: Of 104 patients, 3 were excluded due to insufficient follow-up. The remaining 101 patients had a median lesion size of 2.8 cm. Sixty-seven (82%) of the 82 lesions that were determined malignant had a positive diagnosis upon ENB. Of the 34 lesions without a positive ENB biopsy, 19 (56%) were categorized as true negatives: 8 had benign surgical biopsies, 6 disappeared, and 5 demonstrated stability. Consequently, 86 of 101 cases had an accurate ENB biopsy for a diagnostic yield of 85%. There was insufficient evidence to demonstrate an association between lesion size and diagnostic accuracy. There were 6 pneumothoraces (5.8%). CONCLUSIONS: It is possible for thoracic surgeons to perform ENB with early success. The high diagnostic yields in this study may be attributed to the routine utilization of ROSE and general anesthesia, which preserves computed tomographic-to-body divergence.

Mitochondrial requirement for endothelial responses to cyclic strain: implications for mechanotransduction.

Mechanical strain triggers a variety of cellular responses, but the underlying mechanotransduction process has not been established. Endothelial cells (EC) respond to mechanical strain by upregulating adhesion molecule expression through a signaling process involving reactive oxygen species (ROS), but the site of their generation is unknown. Mitochondria anchor to the cytoskeleton and could function as mechanotransducers by releasing ROS during cytoskeletal strain. In human umbilical vein EC (HUVEC), ROS production increased 221 +/- 17% during 6 h of cyclic strain vs. unstrained controls. Mitochondrial inhibitors diphenylene iodonium or rotenone abrogated this response, whereas inhibitors of nitric oxide (NO) synthase (L-nitroarginine), xanthine oxidase (allopurinol), or NAD(P)H oxidase (apocynin) had no effect. The antioxidants ebselen and diethyldithiocarbamate inhibited the increase in ROS, but the NO scavenger Hb had no effect. Thus strain induces ROS release from mitochondria. In other studies, HUVEC were rendered mitochondria deficient (rho0 EC) to determine the requirement for electron transport in the response to strain. Strain-induced 2'7'-dichlorofluorescein fluorescence was attenuated by >80% in rho0 EC compared with HUVEC (43 +/- 7 vs. 221 +/- 17%). Treatment with cytochalasin D abrogated strain-induced ROS production, indicating a requirement for the actin cytoskeleton. Cyclic strain (6 h) increased VCAM-1 expression in wild-type but not rho0 EC. Increases in NF-kappaB activation and VCAM-1 mRNA expression during strain were prevented by antioxidants. These findings demonstrate that mitochondria function as mechanotransducers in endothelium by increasing ROS signaling, which is required for strain-induced increase in VCAM-1 expression via NF-kappaB.

Role of mitochondrial oxidant generation in endothelial cell responses to hypoxia.

Endothelial cells increase their secretion of the cytokine interleukin-6 (IL-6) during hypoxia, which then acts in an autocrine fashion to increase the permeability of cell monolayers. These responses are attenuated by antioxidants, suggesting that reactive oxygen species (ROS) participate in signaling in hypoxic endothelium. We tested whether mitochondria are responsible for these ROS in human umbilical vein endothelial cells exposed to hypoxia. Oxidation of the probe 2', 7'-dichlorodihydrofluorescein to fluorescent dichlorofluorescein or the probe dihydroethidium was used to assess oxidant signaling, whereas permeability was assessed by using transendothelial electrical resistance. Hypoxia elicited increases in dichlorofluorescein and dihydroethidium fluorescence that were abrogated by the mitochondrial electron transport (ET) inhibitors rotenone (2 micromol/L) and diphenyleneiodonium (5 micromol/L). The same ET inhibitors also attenuated hypoxia-induced increases in nuclear factor-kappaB (NF-kappaB) activation, although they did not abrogate NF-kappaB activation in response to endotoxin (lipopolysaccharide). ET inhibition also abolished the hypoxia-induced increases in IL-6 mRNA expression, hypoxia-stimulated IL-6 secretion into the media, and the hypoxia-induced increases in transendothelial electrical resistance of human umbilical vein endothelial cell monolayers. By contrast, the above responses to hypoxia were not significantly affected by treatment with the NAD(P)H oxidase inhibitor apocynin (30 micromol/L), the xanthine oxidase inhibitor allopurinol (100 micromol/L), or the NO synthase inhibitor N-nitro-L-arginine (100 micromol/L). We conclude that ROS signals originating from the mitochondrial ET chain trigger the increase in NF-kappaB activation, the transcriptional activation of IL-6, the secretion of IL-6 into the cell culture media, and the increases in endothelial permeability observed during hypoxia.