Commission on Cancer Standards for Lymph Node Sampling and Oncologic Outcomes after Lung Resection.

BACKGROUND: The newest Commission on Cancer (CoC) standards recommend sampling 3 mediastinal and 1 hilar lymph node station, 3(N2)1(N1), for lung cancer resections. However, the relationship between the CoC standards and outcomes has not been thoroughly investigated. METHODS: A prospective institutional database was queried for clinical stage I-III lung resections prior to the implementation of the new standards. The relationship between the 3(N2)1(N1) standard ("guideline concordant") and outcomes (upstaging, complications, receipt of adjuvant therapy, locoregional/distant recurrence, and survival) were assessed using multivariable models and stratified by stage. RESULTS: Of 9,289 pulmonary resections 3048 (33%) were guideline concordant and 6241 (67%) were not. Compared to non-concordant, those who were guideline-concordant had higher rates of nodal upstaging (21% vs 13%; OR 1.32 [95% CI 1.14-1.51] p<0.001) and in-hospital complications (34% vs 27%), (OR 1.17 [95% CI 1.05-1.30], p=0.004), but similar adjuvant systemic therapy administration (19% vs 13%; OR 1.09 [95% CI 0.95-1.24], p=0.2), (98% chemotherapy). Locoregional and distant recurrence were not significantly improved with guideline concordance across clinical stage I, II and III subsets. Overall survival was similar in clinical stages I and II but improved survival was observed among guideline concordant clinical stage III patients (HR 0.85 [95% CI 0.74-0.97], p=0.02). CONCLUSIONS: Sampling 3(N2)1(N1) was associated with increased upstaging and complications but not with decreased recurrence or mortality in clinical stage I or II patients. Survival was improved among concordant, clinical stage III patients. Further study is indicated to determine the ideal lymph node sampling strategy across heterogeneous lung cancer patients.

Tumor-Targeted Nonablative Radiation Promotes Solid Tumor CAR T-cell Therapy Efficacy.

Infiltration of tumor by T cells is a prerequisite for successful immunotherapy of solid tumors. In this study, we investigate the influence of tumor-targeted radiation on chimeric antigen receptor (CAR) T-cell therapy tumor infiltration, accumulation, and efficacy in clinically relevant models of pleural mesothelioma and non-small cell lung cancers. We use a nonablative dose of tumor-targeted radiation prior to systemic administration of mesothelin-targeted CAR T cells to assess infiltration, proliferation, antitumor efficacy, and functional persistence of CAR T cells at primary and distant sites of tumor. A tumor-targeted, nonablative dose of radiation promotes early and high infiltration, proliferation, and functional persistence of CAR T cells. Tumor-targeted radiation promotes tumor-chemokine expression and chemokine-receptor expression in infiltrating T cells and results in a subpopulation of higher-intensity CAR-expressing T cells with high coexpression of chemokine receptors that further infiltrate distant sites of disease, enhancing CAR T-cell antitumor efficacy. Enhanced CAR T-cell efficacy is evident in models of both high-mesothelin-expressing mesothelioma and mixed-mesothelin-expressing lung cancer-two thoracic cancers for which radiotherapy is part of the standard of care. Our results strongly suggest that the use of tumor-targeted radiation prior to systemic administration of CAR T cells may substantially improve CAR T-cell therapy efficacy for solid tumors. Building on our observations, we describe a translational strategy of "sandwich" cell therapy for solid tumors that combines sequential metastatic site-targeted radiation and CAR T cells-a regional solution to overcome barriers to systemic delivery of CAR T cells.

Imaging CAR T-cell kinetics in solid tumors: Translational implications.

Success in solid tumor chimeric antigen receptor (CAR) T-cell therapy requires overcoming several barriers, including lung sequestration, inefficient accumulation within the tumor, and target-antigen heterogeneity. Understanding CAR T-cell kinetics can assist in the interpretation of therapy response and limitations and thereby facilitate developing successful strategies to treat solid tumors. As T-cell therapy response varies across metastatic sites, the assessment of CAR T-cell kinetics by peripheral blood analysis or a single-site tumor biopsy is inadequate for interpretation of therapy response. The use of tumor imaging alone has also proven to be insufficient to interpret response to therapy. To address these limitations, we conducted dual tumor and T-cell imaging by use of a bioluminescent reporter and positron emission tomography in clinically relevant mouse models of pleural mesothelioma and non-small cell lung cancer. We observed that the mode of delivery of T cells (systemic versus regional), T-cell activation status (presence or absence of antigen-expressing tumor), and tumor-antigen expression heterogeneity influence T-cell kinetics. The observations from our study underscore the need to identify and develop a T-cell reporter-in addition to standard parameters of tumor imaging and antitumor efficacy-that can be used for repeat imaging without compromising the efficacy of CAR T cells in vivo.

Is Routine Chest Radiography Necessary After Endobronchial Ultrasound-guided Fine Needle Aspiration?

BACKGROUND: Chest radiography is routinely performed after endobronchial ultrasound-guided fine needle aspiration (EBUS-FNA) to detect clinically occult pneumothorax. Because the established rate of postprocedure pneumothorax is low, this study sought to determine whether routine chest radiography can be safely eliminated and to ascertain the potential cost reduction with its omission. METHODS: Patients who underwent EBUS-FNA between January 1, 2017 and December 31, 2018 at Memorial Sloan Kettering Cancer Center (New York, NY) were retrospectively identified. Patient-related factors were summarized using descriptive statistics. Outcomes were compared using the χ2, Fisher exact, and analysis of variance tests. Univariate regression analysis was used to identify factors predictive of postprocedure pneumothorax. RESULTS: A total of 757 patients were included in the study: 72.4% (548 of 757) underwent routine chest radiography in the postanesthesia care unit. Clinically relevant or radiographically evident pneumothorax developed in 1.5% of patients (11 of 757). Of the patients who underwent chest radiography, 0.5% (3 of 548) required unplanned admission for postprocedure pneumothorax, and 0.2% (1 of 548) required tube thoracostomy. Of the 209 patients who did not undergo chest radiography, none experienced a clinically evident pneumothorax. In total, only 1 patient (0.1%) had symptomatic pneumothorax. The pneumothorax event rate was so low that no association with demographic or clinical factors and no predictive factors could be identified. The number of patients needed to be screened by chest radiography to identify 1 patient requiring deviation from routine management is 183. The potential total cost reduction if routine chest radiography had been eliminated was $33,950. CONCLUSIONS: The extremely low rate of postprocedure pneumothorax precluded informative statistical analysis. Routine chest radiography after EBUS-FNA may not be necessary, and its omission may confer a cost savings.

"Two-Birds-One-Stone" Approach for Treating an Infant with Chiari I Malformation and Hydrocephalus: Is Cerebrospinal Fluid Diversion as Sole Treatment Enough?

BACKGROUND: Chiari I malformation (CIM) is a disorder characterized by caudal displacement of the cerebellar tonsils below the foramen magnum. It is often associated with syringomyelia and occasionally with hydrocephalus. CIM is commonly treated by posterior fossa decompression with or without removal of the posterior arch of C1 and duraplasty, but the treatment for infants with symptomatic CIM is not well established. We present a case of symptomatic CIM in an infant that was successfully treated with a ventriculoperitoneal shunt (VPS) and discuss the importance of the pathophysiology in management decisions. CASE DESCRIPTION: A 6-month-old male with a CIM and a cervicothoracic syrinx presented with stridor, lower cranial nerve dysfunction, and increased tone that worsened with crying. Magnetic resonance imaging studies revealed cerebellar tonsillar displacement extending to the level of C3-C4 with a syrinx extending from C4 to T4. In addition, there was compression of the cervicomedullary junction, fourth ventricular outflow obstruction, and obstructive hydrocephalus. The decision was made to place a ventriculoperitoneal shunt (VPS) instead of performing decompressive surgery as the initial treatment intervention. The infant had significant symptomatic relief at 6-, 9-, and 12-month follow-ups. Postoperative magnetic resonance imaging at 6-month follow-up revealed resolution of the syrinx and ventriculomegaly and ascent of the cerebellar tonsils. CONCLUSIONS: Ventriculoperitoneal shunting alone was successfully used to treat an infant with concurrent CIM, syrinx, and hydrocephalus. This case underscores not only the importance of hydrocephalus as the pathogenesis of CIM in some cases but also the possibility of avoiding the morbidity of decompressive surgery in infants.