Faculty Bibliography

Data regarding the association between photodynamic therapy (PDT) and mortality in lung cancer patients are limited. We analyzed the association between PDT and mortality in patients with stage III or IV non-small cell lung cancer (NSCLC) using data from the National Cancer Database (NCDB) between 2004 and 2016. From the NCDB, we identified patients receiving laser ablation/cryosurgery or local tumor destruction/excision (which includes PDT). From Medicare and Medicaid claims between 2000 and 2013, we identified NSCLC patients receiving PDT and those receiving bronchoscopy, then used these to confirm the PDT treatment. From NCDB, we extracted NSCLC patients who received radiation with chemotherapy, radiation alone or chemotherapy alone. We used survival analysis to determine the association between PDT and mortality. Between 2004 and 2016, 457,556 NSCLC patients with stage III or stage IV were identified, of which 147 received PDT with radiation and chemotherapy, 227,629 received radiation with chemotherapy, 106,667 had radiation therapy alone and 122,193 received chemotherapy alone. Compared to the radiation alone group, the PDT group and radiation with chemotherapy group had lower hazard of mortality (50% and 53% lower, respectively). Among the NSCLC patients with stage III or stage IV disease, the addition of PDT to radiation therapy offers survival benefit over radiation therapy alone.

This study investigated the geographic variation and the clustering of lung cancer incidence rates in Philadelphia and the surrounding areas using addresses at the time of diagnosis. Using 60,844 cases from Pennsylvania Cancer Registry, we calculated and mapped the age-adjusted incidence rates for five Pennsylvania (PA) counties near Philadelphia between 1998-2007 and 2008-2017. We identified ZIP codes with significantly higher incidence rates than the state rates and examined their demographic and exposure characteristics. Further, we tested for spatial autocorrelation and identified spatial clusters using Moran's I statistic. Our results showed that approximately one in four ZIP codes had an incidence rate that was significantly higher than the PA state rate in each period studied. Clusters of higher incidences were detected in the southeastern part of PA bordering New Jersey. These areas tended to be more populated, of lower socioeconomic status, and closer to manufacturing facilities and major highways. Possibly driven by the community and environmental factors, the observed differences in disease incidence suggest the importance of including residential location in risk assessment tools for lung cancer.

BACKGROUND:Bronchoscopy is commonly used to evaluate suspicious lung lesions. The yield is likely dependent on patient, radiographic, and bronchoscopic factors. Few studies have assessed these factors simultaneously while also including the preprocedure physician-assessed probability of cancer (pCA) when assessing yield. METHODS:This study is a secondary data analysis from a prospective multicenter trial. Diagnostic yield of standard bronchoscopy with biopsy ± fluoroscopy, endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA), electromagnetic navigation, and combination bronchoscopies was assessed. Definitions for diagnostic and nondiagnostic bronchoscopies were rigorously predefined. The association of diagnostic yield with individual variables was examined by using univariate and multivariate logistic regression analyses where appropriate. RESULTS:A total of 687 patients were included from 28 sites. Overall diagnostic yield was 69%; 80% for EBUS, 55% for bronchoscopy with biopsy ± fluoroscopy, 57% for electromagnetic navigation, and 74% for combination procedures (P < .001). Patients with larger, central lesions with adenopathy were significantly more likely to undergo a diagnostic bronchoscopy. Patients with pCA < 10% and 10% to 60% had lower yields (44% and 42%, respectively), whereas pCA > 60% yielded a positive result in 77% (P < .001). In multivariate logistic regression, the use of EBUS-TBNA, larger sized lesions, and central location were significantly associated with a diagnostic bronchoscopy. Seventeen percent of those with a malignant diagnosis and 28% of those with a benign diagnosis required secondary procedures to establish a diagnosis. CONCLUSIONS:This study is the first to assess the yield of bronchoscopy according to physician-assessed pCA in a large, prospective multicenter trial. The yield of bronchoscopy varied greatly according to physician suspicion that cancer is present, the patients' clinical/radiographic features, and the type of procedure performed. Of the procedures performed, EBUS-TBNA was the most likely to provide a diagnosis.

Novel diagnostic techniques for lung cancer are rapidly evolving. Specifically, several novel changes to bronchoscopy are reaching clinical evaluation. It is critical to think about historical standards for evaluating new diagnostic testing, and put those concepts into the framework of lung cancer. Often a thorough evaluation of new technology is not performed as a part of regulatory marketing clearance. Therefore, we must consider how to best study novel testing beyond these regulatory minimums. There are several methodological principles that can achieve this goal such as using a control arm, more thorough reporting of enrolled patients, consecutive patient enrollment, and adequate sample size. We hope clinicians, particularly those performing bronchoscopy for lung nodules, will feel empowered to critically appraise the evaluation of new diagnostic testing for lung cancer moving forward.

BACKGROUND:The capability of bronchoscopy in the diagnosis of peripheral pulmonary nodules (PPNs) remains limited. Despite decades of effort, evidence suggests that the diagnostic accuracy for electromagnetic navigational bronchoscopy (EMN) and radial endobronchial ultrasound (EBUS) approach only 50%. New developments in robotic bronchoscopy (RB) may offer improvements in the assessment of PPNs. METHODS:A prospective single-blinded randomized controlled comparative study to assess success in localization and puncture of PPNs, using an ultrathin bronchoscope with radial EBUS (UTB-rEBUS) vs EMN vs RB in a human cadaver model of PPNs < 2 cm, was performed. The primary end point was the ability to successfully localize and puncture the target nodule, verified by cone-beam CT comparing RB and EMN. Secondary end points included needle to target position "miss" distance, and UTB-rEBUS comparisons. RESULTS:Sixty procedures were performed to target 20 PPNs over the study period. Implanted PPNs were distributed across all lobes, with 80% located within the lung periphery. The target PPN mean diameter was 16.5 ± 1.5 mm, with 50% noted to have a CT bronchus sign. The rate of successful PPN localization and puncture was superior when using RB, compared with EMN (80% vs 45%; P = .02). Among unsuccessful needle passes, the median needle to target "miss" distance was significantly different when comparing UTB-rEBUS, EMN, and RB (P = .0014). CONCLUSIONS:In a cadaver model, use of RB significantly increased the ability to localize and successfully puncture small PPNs when compared with existing technologies. This study demonstrates the potential of RB to precisely reach, localize, and puncture small nodules in the periphery of the lung.

Numerous organizations, including the United States Preventive Services Task Force, recommend annual lung cancer screening (LCS) with low-dose CT for high risk adults who meet specific criteria. Despite recommendations and national coverage for screening eligible adults through the Centers for Medicare and Medicaid Services, LCS uptake in the United States remains low (<4%). In recognition of the need to improve and understand LCS across the population, as part of the larger Population-based Research to Optimize the Screening PRocess (PROSPR) consortium, the NCI (Bethesda, MD) funded the Lung PROSPR Research Consortium consisting of five diverse healthcare systems in Colorado, Hawaii, Michigan, Pennsylvania, and Wisconsin. Using various methods and data sources, the center aims to examine utilization and outcomes of LCS across diverse populations, and assess how variations in the implementation of LCS programs shape outcomes across the screening process. This commentary presents the PROSPR LCS process model, which outlines the interrelated steps needed to complete the screening process from risk assessment to treatment. In addition to guiding planned projects within the Lung PROSPR Research Consortium, this model provides insights on the complex steps needed to implement, evaluate, and improve LCS outcomes in community practice.

BACKGROUND:Despite recent advances in targeted therapy and immunotherapy for advanced non-small cell lung cancer (NSCLC), carboplatin/pemetrexed/bevacizumab remains a commonly used first-line regimen. However, it is unknown whether the addition of bevacizumab to carboplatin/pemetrexed improves overall survival (OS). MATERIALS AND METHODS:Using nationally representative curated electronic health record data from Flatiron Health, we performed a retrospective cohort study of patients diagnosed with advanced nonsquamous NSCLC who received ≥1 cycle of carboplatin/pemetrexed ± bevacizumab as initial systemic therapy for stage IV or metastatic/recurrent disease. The OS impact of adding bevacizumab to carboplatin/pemetrexed was assessed using a Cox proportional hazards model to adjust for age, sex, race, original tumor stage, time between diagnosis of metastatic disease and start of chemotherapy, and performance status. In a secondary analysis of patients at a single academic institution, we also adjusted for the presence of brain metastases, hemoptysis, and anticoagulation. RESULTS:A total of 4,724 patients were included, of which 2,759 patients (58%) received carboplatin/pemetrexed and 1,965 (42%) received carboplatin/pemetrexed/bevacizumab. Median OS was 12.1 months (95% CI, 11.2-12.9 months) in the carboplatin/pemetrexed/bevacizumab group compared with 8.6 months (95% CI, 8.1-9.1 months) in the carboplatin/pemetrexed group (P<.001). Bevacizumab use remained associated with improved OS in a multivariate model (hazard ratio, 0.80; 95% CI, 0.75-0.86; P<.001). In the secondary, institutional analysis (N=539), the effect of bevacizumab was unchanged (hazard ratio, 0.75; 95% CI, 0.59-0.96; P=.02). CONCLUSIONS:In this large, real-world dataset, the addition of bevacizumab to first-line carboplatin/pemetrexed for metastatic nonsquamous NSCLC was associated with improved OS.