Search

Breast metastasis from extramammary malignancy is rare, with a reported incidence rate of 0.4% to 1.3% in the published literature. The primary malignancies that most commonly metastasize to the breast are leukemia, lymphoma, and malignant melanoma. Here, we report a very rare case of metastatic EGFR-mutated non-small cell lung cancer (NSCLC) in the breast detected by screening mammography. The patient had initially been diagnosed with a clinical stage IIIA NSCLC and had been treated with neoadjuvant chemoradiation followed by curative-intent surgery. Several interesting aspects of the case, along with a discussion of evolving adjuvant and frontline metastatic management options in EGFR-mutated NSCLC, will be presented.

BackgroundGEN-009 adjuvanted personalized cancer vaccine contains up to 20 neoantigens selected by ATLAS™, an ex vivo bioassay screening autologous T-cells for immune responses against both neoantigens and Inhibigens™. Inhibigen-specific T-cells suppress immunity, have been shown to accelerate tumor progression in mice, and are excluded from GEN-009. In cohort A, all patients immunized in the adjuvant setting with GEN-009 monotherapy developed immune responses. Ninety-nine percent of selected peptides were immunogenic: ex vivo CD4+ and CD8+ fluorospot responses specific for 51% and 41% of immunized peptides, respectively.1 Six of 8 patients continue without progression with a median follow up >2 years.MethodsGEN-009 was administered to patients with advanced cancer who received standard-of-care (SOC) PD-1 inhibitor as monotherapy or in combination therapy during vaccine manufacturing. Five vaccine doses were administered over 24 weeks in combination with single agent anti-PD-1. Patients who progressed prior to vaccination received salvage therapy followed by GEN-009 in combination. Peripheral T-cell responses were measured by ex vivo and in vitro stimulated fluorospot assays. Circulating tumor (ct) DNA levels were evaluated in a subset of patients pre- and post-GEN-009 administration.Results15 patients received GEN-009 in combination with PD-1 inhibitor; 1 patient received GEN-009 monotherapy. Median number of neoantigens per vaccine was 14 (range 5–18). GEN-009-related adverse events were limited to vaccine injection site reactions, mild myalgias or fatigue. Sequential vaccination with GEN-009 had an additive effect on the magnitude of ex vivo T-cell responses, that persisted in some patients for 12+ months post first vaccine dose. An association between proportion of peptides eliciting significant cytokine responses and RECIST response is apparent. Epitope spread was detected in CD8+ T-cells from CPI-sensitive patients, but not refractory patients. Four patients who responded to PD-1 inhibition followed by disease stabilization then demonstrated further tumor reduction after GEN-009 vaccination. Seven of 9 CPI responsive patients are progression-free 7 to 18 months after first vaccine dose. Three of 7 CPI-refractory patients have experienced unexpected prolonged stable disease, with 2 PR and 1 SD after vaccination lasting up to 10 months. Plasma ctDNA kinetics mirrored RECIST responses in each tested patient; in some responders, all evidence of ctDNA disappeared, including non-targeted antigens.ConclusionsVaccination with GEN-009 alone or in combination with anti-PD-1 was well tolerated. Preliminary data demonstrate induction of robust, durable neoantigen-specific immune responses and epitope spreading in the presence of PD-1 CPI. Broad immunity against tumor specific targets and encouraging patient outcomes support further study.Trial Registration clinicaltrials.gov identifier: NCT03633110ReferencesLam H, et al. An empirical antigen selection method identifies neoantigens that either elicit broad anti-tumor response or drive tumor growth. Cancer Discovery 2021 March;11(3):696–713.Ethics ApprovalThis study was approved by Western Institutional Review Board, approval number 1-1078861-1

The NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates to the targeted therapy and immunotherapy sections in the NCCN Guidelines. For the 2018 update, a new section on biomarkers was added.

This selection from the NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) focuses on targeted therapies and immunotherapies for metastatic NSCLC, because therapeutic recommendations are rapidly changing for metastatic disease. For example, new recommendations were added for atezolizumab, ceritinib, osimertinib, and pembrolizumab for the 2017 updates.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) focuses on the principles of radiation therapy (RT), which include the following: (1) general principles for early-stage, locally advanced, and advanced/metastatic NSCLC; (2) target volumes, prescription doses, and normal tissue dose constraints for early-stage, locally advanced, and advanced/palliative RT; and (3) RT simulation, planning, and delivery. Treatment recommendations should be made by a multidisciplinary team, including board-certified radiation oncologists who perform lung cancer RT as a prominent part of their practice.

Lung cancer screening with LDCT is a complex and controversial topic, with inherent risks and benefits. Results from the large, prospective, randomized NLST show that lung cancer screening with LDCT can decrease lung cancer–specific mortality by 20% and even decrease all-cause mortality by 7%.8 The NLST results indicate that to prevent one death from lung cancer, 320 high-risk individuals must be screened with LDCT. However, the NLST findings have not been replicated yet in a separate cohort. Further analysis of the NLST is underway, including comparative effectiveness modeling. The cost-effectiveness and true benefit-to-risk ratio for lung cancer screening still must be determined. At some point, an acceptable level of risk will have to be deemed appropriate for the benefits of screening. The NCCN Lung Cancer Screening Panel recommends helical LDCT screening for select patients at high risk for lung cancer based on the NLST results, nonrandomized studies, and observational data. These guidelines discuss in detail the criteria for determining which patients are at high risk, and the algorithm provides recommendations for evaluating and following-up nodules detected on LDCT screening (e.g., solid and part-solid nodules). Smokers should always be encouraged to quit smoking tobacco (http://www.smokefree.gov/). Programs using behavioral counseling combined with medications that promote smoking cessation (approved by the FDA) can be very useful (see Treating Tobacco Use and Dependence: Quick Reference Guide for Clinicians; http://www.surgeongeneral.gov/tobacco/tobaqrg.htm). When considering lung cancer screening, it is important to have a full understanding of all risks and benefits related to screening with LDCT. As policies for implementing lung screening programs are designed, a focus on multidisciplinary programs (incorporating primary care doctors, pulmonologists, radiologists, thoracic surgeons, medical oncologists, and pathologists) will be helpful to optimize decision-making and minimize interventions for patients with benign lung disease.

These NCCN Guidelines Insights focus on recent updates to the 2015 NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC). Appropriate targeted therapy is very effective in patients with advanced NSCLC who have specific genetic alterations. Therefore, it is important to test tumor tissue from patients with advanced NSCLC to determine whether they have genetic alterations that make them candidates for specific targeted therapies. These NCCN Guidelines Insights describe the different testing methods currently available for determining whether patients have genetic alterations in the 2 most commonly actionable genetic alterations, notably anaplastic lymphoma kinase (ALK) gene rearrangements and sensitizing epidermal growth factor receptor (EGFR) mutations.

Background: Empyema remains a cause of morbidity and mortality. Thoracoscopy has proved its versatility in the management of pleural space disorders. The suitability of video-assisted thoracic surgery (VATS) for decortication in the management of the fibrotic stage of empyema is unclear. Methods: VATS evacuation of empyema and decortication was performed on seventeen patients presenting with pleural space infections. A retrospective review was performed and constitutes the basis of this report. Results: VATS evacuation of empyema and decortication was successfully performed in 13 of 17 patients. Blood loss was 325 ± 331 cc. Mean hospital stay was 18 ± 10 days. Postoperative hospitalization was 11 ± 7 days. Chest tubes remained in place for 7 ± 3 days. There were no operative mortalities. Conclusions: Video-assisted evacuation of empyema and decortication is an effective modality in the management of the exudative and fibrinopurulent stages of empyema. An organized empyema should be approached thoracoscopically, but may require open decortication.

Summary: Purpose: We wished to assess organ transplant recipients, who incur a significant risk for seizures. Method: We reviewed 85 lung transplants performed in 81 patients at the University of North Carolina hospitals between 1991 and 1994. All patients were reviewed for age, reason for transplant, detailed description of seizures, neurological examination, medications, and laboratory results, including cyclosporine level, EEG, and brain imaging. Results: Eighteen of 81 (22%) patients experienced seizures. Patients aged

Lymphoma is an unusual cause of tracheoesophageal fistula (TEF). Most fistulas develop after radiation therapy and are a rare occurrence in patients treated with chemotherapy alone. The presence of a TEF is usually indicative of active lymphoma. This report describes a tracheoesophageal fistula that developed during chemotherapy for diffuse large cell lymphoma.

Background: The role of surgical staging of patients with non-small cell lung cancer (NSCLC) continues to evolve. This report describes our findings utilizing routine cervical mediastinoscopy in the evaluation of peripheral T1 ( Methods: Retrospectively 30 patients with peripheral T1 lesions and CT scans negative for pathologic adenopathy were identified over a 3-year period. Cervical mediastinoscopy was performed prior to VATS/thoracotomy during the same operative session. Results: Mediastinoscopy was performed in 29 of 30 patients. For patients with malignancy (27 of 30), 3 of 27 (11%) had mediastinoscopy positive for malignancy and no further resection performed. Overall the subgroup of patients with bronchogenic carcinomas had positive mediastinal involvement identified in 5 of 24 (21%) after mediastinoscopy or complete resection. Conclusions: A significant number of patients with small peripheral lung cancers harbor radiographically occult lymph node involvement. Mediastinoscopy facilitates identification of patients with regionally advanced disease prior to resection, allowing neoadjuvant therapy and avoiding unnecessary resections.

Reexpansion pulmonary edema is a well-described complication of treatment for pleural effusion and pneumothorax. It is very rarely described in association with anesthesia and video-assisted thoracoscopic surgery. The etiology is unclear but several mechanisms have been proposed. We report a case of reexpansion pulmonary edema after video-assisted thoracoscopic surgery treated successfully with continuous positive airway pressure.

Patients with cystic fibrosis pose particular challenges for lung transplantation surgeons. Earlier reports from North America centers suggested that patients with cystic fibrosis were greater risk for heart-lung or isolated lung transplantation than other patients with end-stage pulmonary disease. During a 3 ½ year period, 44 patients with end-stage lung disease resulting from cystic fibrosis underwent double lung transplantation at this institution. During the same interval, 18 patients with cystic fibrosis, died while waiting for a double lung transplantation. The ages of the recipients ranged from 8 to 45 years, and mean forced expiratory volume in 1 second was 21% predicted. Seven patients had Pseudomonas cepacia bacteria before transplantation. Bilateral sequential implantation with omentopexy was used in all patients. There were no operative deaths, although two patients required urgent retransplantation because of graft failure. Cardiopulmonary bypass was necessary in six procedures in five patients and was associated with an increased blood transfusion requirement, longer postoperative ventilation, and longer hospital stay. Actuarial survival rate was 85% at 1 year and 67% at 2 years. Infection was the most common cause of death within 6 months of transplantation ( Pseudomonas cepacia pneumonia was the cause of death in two patients), and bronchitis obliterans was the most common cause of death after 6 months. Actuarial freedom form development of clinically significant bronchiolitis obliterans was 59% at 2 years. Results of pulmonary function tests improved substantially in survivors, with forced expiratory volume in 1 second averaging 78% predicted 2 years after transplantation. Double lung transplantation can be accomplished with acceptable morbidity and mortality in patients with cystic fibrosis. (J THORAC CARDIOVAS SURG 1995;109-:204-35)