Publications by authors named "Raja M Flores"

143 Publications

REPLY: ROBOTIC-ASSISTED LUNG RESECTIONS: OBJECTIVE OBSERVATIONS 20 YEARS LATER.

J Thorac Cardiovasc Surg 2021 Jan 16. Epub 2021 Jan 16.

Department of Thoracic Surgery, Mount Sinai Health System, Icahn School of Medicine at Mount Sinai, New York, NY.

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http://dx.doi.org/10.1016/j.jtcvs.2020.11.153DOI Listing
January 2021

Commentary: Robotic first rib resection: A safe, modern update.

J Thorac Cardiovasc Surg 2020 Oct 13. Epub 2020 Oct 13.

Department of Thoracic Surgery, Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, New York, NY. Electronic address:

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http://dx.doi.org/10.1016/j.jtcvs.2020.10.019DOI Listing
October 2020

Somatic Epigenetic Silencing of Inactivates Necroptosis and Contributes to Chemoresistance in Malignant Mesothelioma.

Clin Cancer Res 2021 Feb 17;27(4):1200-1213. Epub 2020 Nov 17.

Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.

Purpose: Receptor-interacting protein kinase 3 (RIPK3) phosphorylates effector molecule MLKL to trigger necroptosis. Although RIPK3 loss is seen in several human cancers, its role in malignant mesothelioma is unknown. This study aimed to determine whether RIPK3 functions as a potential tumor suppressor to limit development of malignant mesothelioma.

Experimental Design: RIPK3 expression was examined in 66 malignant mesothelioma tumors and cell lines. Promoter methylation and siRNA studies were performed to assess the mode of silencing in RIPK3-deficient malignant mesothelioma cells. Restoration of RIPK3 expression in RIPK3-negative malignant mesothelioma cells, either by treatment with 5-aza-2'-deoxycytidine or lentiviral expression of cDNA, was performed to assess effects on cell viability, necrosis, and chemosensitization.

Results: Loss of RIPK3 expression was observed in 42/66 (63%) primary malignant mesotheliomas and malignant mesothelioma cell lines, and RT-PCR analysis demonstrated that downregulation occurs at the transcriptional level, consistent with epigenetic silencing. RIPK3-negative malignant mesothelioma cells treated with 5-aza-2'-deoxycytidine resulted in reexpression of RIPK3 and chemosensitization. Ectopic expression of RIPK3 also resulted in chemosensitization and led to necroptosis, the latter demonstrated by phosphorylation of downstream target MLKL and confirmed by rescue experiments. Mining of expression and survival outcomes among patients with malignant mesothelioma available from The Cancer Genome Atlas repository revealed that promoter methylation of is associated with reduced expression and poor prognosis.

Conclusions: These data suggest that RIPK3 acts as a tumor suppressor in malignant mesothelioma by triggering necroptosis and that epigenetic silencing of by DNA methylation impairs necroptosis and contributes to chemoresistance and poor survival in this incurable disease.
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http://dx.doi.org/10.1158/1078-0432.CCR-18-3683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887036PMC
February 2021

Taken Together: Effective Multimodal Approaches for Malignant Pleural Mesothelioma.

Thorac Surg Clin 2020 Nov;30(4):481-487

Department of Thoracic Surgery, New York Mesothelioma Program, Mount Sinai Health System, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1023, New York, NY 10029, USA.

Malignant pleural mesothelioma is an aggressive, deadly cancer often requiring input from multiple medical disciplines. Treatment has evolved over the last several decades with increasing evidence and ongoing advances in chemotherapy, radiation, and immunotherapy; however, no standard treatment regimen has yet been defined. Regardless of the overall strategy, surgery remains the foundation of treatment to remove macroscopic disease, and preservation of lung parenchyma via extended pleurectomy/decortication may be preferable to extrapleural pneumonectomy.
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http://dx.doi.org/10.1016/j.thorsurg.2020.08.002DOI Listing
November 2020

Updates in Staging and Management of Malignant Pleural Mesothelioma.

Surg Oncol Clin N Am 2020 Oct 10;29(4):603-612. Epub 2020 Aug 10.

Department of Thoracic Surgery, The Icahn School of Medicine at Mount Sinai, 1190 Fifth Avenue, Box 1023, New York, NY 10029, USA.

While without treatment, malignant pleural mesothelioma (MPM) confers poor survival, cancer-directed surgery as part of multimodality treatment is associated with a 15% 5-year survival. Extrapleural pneumonectomy (EPP) and radical or extended pleurectomy/decortication (P/D) are the 2 types of resection performed in this context. Preoperative staging is critical to patient selection for surgery; P/D is recommended over EPP in most cases. Adjuvant therapy with intraoperative platforms, traditional chemotherapy, hemithoracic radiotherapy resection, and new immunotherapy agents are instrumental in achieving durable long-term results. We outline the latest understanding of disease staging and describe the current state of literature and practice.
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http://dx.doi.org/10.1016/j.soc.2020.06.002DOI Listing
October 2020

The Association of Cerebral Desaturation During One-Lung Ventilation and Postoperative Recovery: A Prospective Observational Cohort Study.

J Cardiothorac Vasc Anesth 2021 Feb 27;35(2):542-550. Epub 2020 Jul 27.

Department of Anesthesiology, Perioperative and Pain Medicine, Icahn School of Medicine at Mount Sinai, New York, NY.

Objectives: This study was designed to investigate whether cerebral oxygen desaturations during thoracic surgery are predictive of patients' quality of recovery. As a secondary aim, the authors investigated the relationship among cerebral desaturations and postoperative delirium and hospital length of stay.

Design: This study was a prospective observational cohort study.

Setting: A single tertiary-care medical center from September 2012 through March 2014.

Patients: Adult patients scheduled for elective pulmonary surgery requiring one-lung ventilation.

Interventions: All patients were monitored with the ForeSight cerebral oximeter.

Measurements And Main Results: The primary assessment tool was the Postoperative Quality of Recovery Scale. Delirium was assessed using the Confusion Assessment Method. Of the 117 patients analyzed in the study, 60 of the patients desaturated below a cerebral oximetry level of 65% for a minimum of 3 minutes (51.3%). Patients who desaturated were significantly less likely to have cognitive recovery in the immediate postoperative period (p = 0.012), which did not persist in the postoperative period beyond day 0. Patients who desaturated also were more likely to have delirium (p = 0.048, odds ratio 2.81 [95% CI 1.01-7.79]) and longer length of stay (relative duration 1.35, 95% CI 1.05-1.73; p = 0.020).

Conclusions: Intraoperative cerebral oxygen desaturations, frequent during one-lung ventilation, are associated significantly with worse early cognitive recovery, high risk of postoperative delirium, and prolonged length of stay. Large interventional studies on cerebral oximetry in the thoracic operating room are warranted.
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http://dx.doi.org/10.1053/j.jvca.2020.07.065DOI Listing
February 2021

Disparities in COVID-19 Testing and Positivity in New York City.

Am J Prev Med 2020 09 25;59(3):326-332. Epub 2020 Jun 25.

Institute for Translational Epidemiology and Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York; Center for Disaster Health, Trauma, and Resilience, New York, New York; Department of Thoracic Surgery, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address:

Introduction: Existing socioeconomic and racial disparities in healthcare access in New York City have likely impacted the public health response to COVID-19. An ecological study was performed to determine the spatial distribution of COVID-19 testing by ZIP code Tabulation Area and investigate if testing was associated with race or SES.

Methods: Data were obtained from the New York City coronavirus data repository and 2018 American Community Survey 5-year estimates. A combined index of SES was created using principal component analysis and incorporated household income, gross rent, poverty, education, working class status, unemployment, and occupants per room. Multivariable Poisson regressions were performed to predict the number of total tests and the ratio of positive tests to total tests performed, using the SES index, racial composition, and Hispanic composition as predictors.

Results: The number of total tests significantly increased with the increasing proportion of white residents (β=0.004, SE=0.001, p=0.0032) but not with increasing Hispanic composition or SES index score. The ratio of positive tests to total tests significantly decreased with the increasing proportion of white residents in the ZIP code Tabulation Area (β= -0.003, SE=0.000 6, p<0.001) and with increasing SES index score (β= -0.001 6, SE=0.0007, p=0.0159).

Conclusions: In New York City, COVID-19 testing has not been proportional to need; existing socioeconomic and racial disparities in healthcare access have likely impacted public health response. There is urgent need for widespread testing and public health outreach for the most vulnerable communities in New York City.
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http://dx.doi.org/10.1016/j.amepre.2020.06.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316038PMC
September 2020

Disparities in Surgical Recommendation for Stage I Non-Small Cell Lung Cancer.

Am J Clin Oncol 2020 10;43(10):741-747

Department of Population Health Science and Policy, Institute for Translational Epidemiology.

Objectives: Sociodemographic disparities in lung cancer prevalence, treatment options offered, and outcomes have been well documented. In stage I non-small cell lung cancer (NSCLC), the standard of care is surgical resection. This study explores disparities in surgical recommendations in stage I NSCLC, when surgery is considered curative.

Materials And Methods: Patients diagnosed with primary stage I NSCLC from 2007 to 2016 were identified from the Surveillance, Epidemiology, and End Results database (N=56,534). Associations between sociodemographic variables and surgical recommendation were assessed using multivariable logistic regression models. Survival impact was investigated using Cox-proportional hazards regression and propensity matching techniques.

Results: Of the 76.9% patients recommended surgery, 95% underwent surgery. Recommended surgery was inversely associated with increasing age (P<0.01), non-Hispanic Black race (adjusted odds ratio [ORadj] 0.64, 95% confidence interval [CI]: 0.59-0.70), Hispanic ethnicity (ORadj 0.75, 95% CI: 0.67-0.84), nonprivate/Medicare insurance (Medicaid: ORadj 0.55, 95% CI: 0.51-0.60; insured with unknown plan: ORadj 0.74, 95% CI: 0.69-0.79; uninsured: ORadj 0.45, 95% CI: 0.36-0.55), and single status (ORadj 0.66, 95% CI: 0.63-0.70). Patients who were not recommended surgery were at increased risk of death compared with those who were recommended.

Conclusion: In a cohort of NSCLC patients, nonclinical factors identified a subgroup of patients who were less likely to be recommended surgery.
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http://dx.doi.org/10.1097/COC.0000000000000740DOI Listing
October 2020

Lifestyle behaviors and intervention preferences of early-stage lung cancer survivors and their family caregivers.

Support Care Cancer 2021 Mar 20;29(3):1465-1475. Epub 2020 Jul 20.

Department of Medicine, Baylor College of Medicine, Houston, TX, USA.

Purpose: Lung cancer (LC) is a highly prevalent disease with more survivors diagnosed and treated at earlier stages. There is a need to understand psychological and lifestyle behavior needs to design interventions for this population. Furthermore, understanding the needs and role of family caregivers, especially given the risks associated with second-hand smoke, is needed.

Methods: Thirty-one early-stage (stages I or IIA) LC survivors of (52% men) and 22 (50% women) caregivers (N = 53 total) completed surveys after surgery (baseline) and at 3- and 6-month follow-ups. Participants reported on psychological functioning, smoking, and physical activity (PA) as well as intervention preferences.

Results: Survivors reported low levels of psychological distress and 3% were current smokers during the study. Approximately 79% were sedentary and not meeting national PA guidelines. Caregivers also reported minimal psychological distress and were sedentary (62% not meeting guidelines), but a larger proportion continued to smoke following the survivor's cancer diagnosis (14%). Both survivors and caregivers expressed interest in home-based PA interventions but differed regarding preferred format for delivery. Most (64%) caregivers preferred a dyadic format, where survivors and caregivers participate in the intervention together. However, most survivors preferred an individual or group format (57%) for intervention delivery.

Conclusion: Both LC survivors and family caregivers could benefit from PA interventions, and flexible, dyadic interventions could additionally support smoking cessation for family caregivers.
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http://dx.doi.org/10.1007/s00520-020-05632-5DOI Listing
March 2021

Reply from authors: Robotic segmentectomy: Benefit?

J Thorac Cardiovasc Surg 2020 08;160(2):e89

Department of Thoracic Surgery, Icahn School of Medicine at Mount Sinai, New York, NY.

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http://dx.doi.org/10.1016/j.jtcvs.2020.04.091DOI Listing
August 2020

Surgical care of thoracic malignancies during the COVID-19 pandemic in México: An expert consensus guideline from the Sociedad Mexicana de Oncología (SMeO) and the Sociedad Mexicana de Cirujanos Torácicos Generales (SMCTG).

Thorac Cancer 2020 08 6;11(8):2370-2375. Epub 2020 Jul 6.

Thoracic Oncology Unit, Instituto Nacional de Cancerologia, Mexico City, Mexico.

To date, the impact, timeline and duration of COVID-19 pandemic remains unknown and more than ever it is necessary to provide safe pathways for cancer patients. Multiple triage systems for nonemergent surgical procedures have been published, but potentially curative cancer procedures are essential surgery rather than elective surgery. In the present and future scenario of our country, thoracic oncology teams may have the difficult decision of weighing the utility of surgical intervention against the risk for inadvertent COVID-19 exposure for patients and medical staff. In consequence, traditional pathways of surgical care must be adjusted to reduce the risk of infection and the use of resources. It is recommended that all thoracic cancer patients should be offered treatment according to the accepted standard of care until shortage of services require a progressive reduction in surgical cases. Here, we present a consensus of recommendations discussed by a multidisciplinary panel of experts on thoracic oncology and based on the best available evidence, and hope it will provide a modifiable framework of guidance for local strategy planners in thoracic cancer care services in Mexico. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: This article provides recommendations to guarantee the continuity of surgical care for thoracic oncology cases during COVID-19 pandemic, whilst maintaining the safety of patients and medical staff. WHAT THIS STUDY ADDS: This guideline is the result of an expert consensus on thoracic surgical oncology with recommendations adapted to medical, economic and social realities of Mexico.
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http://dx.doi.org/10.1111/1759-7714.13546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361744PMC
August 2020

Pre-surgical assessment of mediastinal lymph node metastases in Stage IA non-small-cell lung cancers.

Clin Imaging 2020 Dec 15;68:61-67. Epub 2020 Jun 15.

Department of Radiology, Mount Sinai School of Medicine, NY, NY, USA; Phoenix Veterans Affairs Health Care System, Phoenix, AZ, USA.

Objective: Evaluation of sensitivity and specificity of CT and fluorodeoxyglucose-positron emission tomography for pre-surgical staging of mediastinal lymph node metastases (N2/N3) of non-small-cell-lung-cancers ≤30 mm.

Methods: We reviewed a total of 263 patients from a prospective cohort study, who underwent resection including mediastinal lymph nodes, for first primary non-small-cell-lung-cancer ≤30 mm in maximum diameter on pre-surgical CT. Cutoff criteria for short-axis diameter on CT of the largest N2/N3 node of 10, 15, and 20 mm and positron emission uptake of 2.5, 3.0, and 4.0 were evaluated using Area-Under-the-Curve (AUC) assessment. Accuracy criterion was used to determine the optimal cutoffs.

Results: Of 263 patients, 9 had nonsolid, 42 part-solid, and 212 solid non-small-cell-lung-cancers. Post-surgically, none of the 51 patients with nonsolid or part-solid cancers had mediastinal lymph node metastases. Among the 212 patients with solid cancers, 23 had N2 node metastases. For the 212 patients with solid cancers, the AUC for CT lymph node measurements was 0.67 (95% CI: 0.57-0.77), significantly higher (p = 0.001) than chance alone, while the AUC for SUVmax measurements, 0.56 (95% CI: 0.48-0.65), was not (p = 0.13). Optimal CT cutoff was >20 mm had low sensitivity of 30.4% (95% CI: 11.6%-49.2%) but high specificity of 99.5% (95% CI: 98.4%-100.0%).

Conclusion: Based on these results, clinical Stage IA for non-small-cell-lung-cancers with nonsolid, part-solid, or solid consistency should be based on pre-surgical CT maximum tumor diameter and lymph node short-axis measurements on CT ≤20 mm. Further prospective evaluation of these clinical Stage IA staging criteria is needed.
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http://dx.doi.org/10.1016/j.clinimag.2020.06.016DOI Listing
December 2020

REPLY: ROBOTIC-ASSISTED SEGMENTECTOMY: DOING IT SIMPLY BECAUSE WE CAN?

J Thorac Cardiovasc Surg 2020 09 11;160(3):e176. Epub 2020 Jun 11.

Department of Thoracic Surgery, Icahn School of Medicine at Mount Sinai, New York, NY.

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http://dx.doi.org/10.1016/j.jtcvs.2020.04.162DOI Listing
September 2020

Serum cotinine verification of self-reported smoking status among adults eligible for lung cancer screening in the 1999-2018 National Health and Nutrition Examination Survey.

Lung Cancer 2020 06 23;144:49-56. Epub 2020 Apr 23.

Institute for Translational Epidemiology and Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Thoracic Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Background: Self-reported smoking behavior is widely used in identifying the eligibility for lung cancer screening (LCS). In clinical trials, self-reported smoking status was shown to be a reliable measure, while its effectiveness outside of trial settings remains to be clarified. We aimed to verify self-reported smoking status with serum cotinine levels among LCS-eligible adults from the National Health and Nutrition Examination Survey (NHANES).

Methods: From the combined 1999-2018 NHANES data, we selected adults (aged ≥18 years) with complete data on serum cotinine and smoking behavior, and determined their LCS eligibility according to the United States Preventive Services Task Force recommendation. Using established race/ethnicity specific cotinine cutpoints as the gold standard, we verified self-reported current smoking status with five measures: sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), and reliability Kappa. We also compared these performance measures in subgroups stratified by sex, race/ethnicity, education, family income to poverty ratio, health insurance, and secondhand smoking exposure (SHS) at home. All analyses took into account the complex survey design.

Results: Approximately 9.3% (n = 2335, equivalent to 8.82 million weighted population) of all adults who currently smoke or formerly smoked were eligible for LCS. The prevalence of current smoking was 52.6% and 60.8% based on self-report and cotinine, respectively. The Se and Sp were 86.4% (95%CI: 83.9%-88.9%) and 99.7% (95%CI: 99.4%-100%), respectively; PPV and NPV were 99.8% (95%CI: 99.6%-100%) and 82.6% (95%CI: 79.4%-85.7%), respectively; and Kappa was 0.83 (95%CI: 0.80-0.86). The reliability Kappa was higher among females than males (0.87 (95%CI: 0.82-0.93)) vs 0.80 (95%CI: 0.77-0.84), the lowest among non-Hispanic white (0.82 (95%CI: 0.78-0.86)), and higher among those with SHS (0.72 (95%CI: 0.63-0.80) vs (0.68 (95%CI: 0.61-0.76)).

Conclusion: Self-reported smoking status is reasonably reliable among adults with high risk for developing lung cancer in the general population.
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http://dx.doi.org/10.1016/j.lungcan.2020.04.019DOI Listing
June 2020

Perioperative chemoimmunotherapy in a patient with stage IIIB non-small cell lung cancer.

Ann Transl Med 2020 Mar;8(5):245

Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China.

We present a case of a 56-year-old male patient with stage IIIB (T3N2M0) poorly differentiated squamous cell carcinoma of the lung. Four cycles of chemotherapy were first applied, and the patient had stable disease. However, the patient refused to receive radiotherapy, therefore second-line treatment chemotherapy combined with anti-PD-1 immunotherapy was applied. Partial response was reached at the 4 cycle of chemotherapy combined with anti-PD-1 immunotherapy. The neoadjuvant strategy was prolonged to 10 cycles but no significant change was observed on tumor size. The patient then underwent video-assisted thoracoscopic left lower lobectomy. Eight cycles of adjuvant PD-1 immunotherapy were applied postoperatively. Perioperative immunotherapy demonstrated good curative effect in this patient and no recurrence was observed at the clinic 40 months following surgery. Here we intend to explore the concept of immunotherapy combined with chemotherapy and surgery in neoadjuvant and adjuvant setting, and to investigate the possibility of extending this strategy in patients with stage IIIB non-small cell lung cancer (NSCLC).
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http://dx.doi.org/10.21037/atm.2020.01.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7154428PMC
March 2020

Commentary: Robot-assisted segmentectomy is safe and expensive-What is the debate?

J Thorac Cardiovasc Surg 2020 11 25;160(5):1373-1374. Epub 2020 Jan 25.

Department of Thoracic Surgery, Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, New York, NY. Electronic address:

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http://dx.doi.org/10.1016/j.jtcvs.2020.01.014DOI Listing
November 2020

Serum cotinine levels and nicotine addiction potential of e-cigarettes: an NHANES analysis.

Carcinogenesis 2020 Oct;41(10):1454-1459

Institute for Translational Epidemiology and Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

This study aims to compare serum cotinine levels in e-cigarette and combustible cigarette smokers, in an attempt to quantify the potential chronic nicotine addiction risk that e-cigarettes pose. We analyzed 428 participants in 2015-2016 NHANES: 379 (87.03%) smoked combustible cigarettes alone and 49 (12.97%) smoked e-cigarettes. Serum cotinine levels were measured by isotope-dilution high-performance liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometric method with a detection limit of 0.015 ng/ml. Electronic cigarette smokers were younger than combustible cigarette smokers (mean age 36.79 versus 42.69 years, P = 0.03), more likely to be male (64.93% versus 48.32%, P = 0.09) and significantly less likely to live with other smokers (50.17% versus 90.07%, P < 0.01). Serum cotinine levels increased linearly with self-reported days of smoking in both electronic cigarette and combustible cigarette smokers, after accounting for living with a smoker. The analysis of the subgroup who reported daily use show non-statistically significantly higher serum cotinine levels in electronic cigarette smokers versus combustible cigarette smokers (β adj = 52.50, P = 0.10). This analysis of recent US data demonstrates that electronic cigarettes expose users to nicotine levels proportionate to, and potentially higher than combustible cigarettes, and thus pose a serious risk of chronic nicotine addiction. This could be particularly relevant in otherwise tobacco naive individuals; future risk of tobacco-related dependence, addiction and relapse, as well as of tobacco-related cancers in these subjects needs to be investigated.
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http://dx.doi.org/10.1093/carcin/bgaa015DOI Listing
October 2020

Is survival after sublobar resection lobectomy made equivalent by extent of lymphadenectomy?

Ann Transl Med 2019 Sep;7(Suppl 6):S191

Department of Thoracic Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

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http://dx.doi.org/10.21037/atm.2019.07.33DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789343PMC
September 2019

Intratumoral lymph vessel invasion as a predictive risk factor for nodal metastasis in non-small cell lung cancer: should L-1 status obligate adjuvant chemotherapy?

J Thorac Dis 2019 Sep;11(Suppl 15):S1990-S1991

Department of Thoracic Surgery, Mount Sinai Health System, Icahn School of Medicine, New York, NY, USA.

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http://dx.doi.org/10.21037/jtd.2019.06.73DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6783737PMC
September 2019

Disparities in surgery for early-stage cancer: the impact of refusal.

Cancer Causes Control 2019 Dec 19;30(12):1389-1397. Epub 2019 Oct 19.

Institute for Translational Epidemiology and Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Background: For early-stage cancer surgery is often curative, yet refusal of recommended surgical interventions may be contributing to disparities in patient treatment. This study aims to assess predictors of early-stage cancers surgery refusal, and the impact on survival.

Methods: Patients recommended surgery with primary stage I and II lung, prostate, breast, and colon cancers, diagnosed between 2007-2014, were identified in the Surveillance, Epidemiology and End Results database (n = 498,927). Surgery refusal was reported for 5,757 (1.2%) patients. Associations between sociodemographic variables and surgery refusal by cancer type were assessed in adjusted multivariable logistic regression models. The impact of refusal on survival was investigated using adjusted Cox-Proportional Hazard regression in a propensity score-matched cohort.

Results: Increasing age (p < 0.0001 for all four cancer types), non-Hispanic Black race/ethnicity (OR 2.00, 95% CI 1.68-2.39; OR 3.04, 95% CI 2.17-4.26; OR 2.19, 95% CI 1.77-2.71; OR 2.02, 95% CI 1.86-2.20; vs non-Hispanic White), insurance status (uninsured: OR 2.75, 95% CI 1.89-3.99; OR 2.10, 95% CI 1.72-2.56; vs insured), marital status (OR 2.16, 95% CI 1.85-2.51; OR 1.56, 95% CI 1.16-2.10; OR 2.11, 95% CI 1.80-2.47; OR 1.94, 95% CI 1.81-2.09), and stage (OR 1.94, 95% CI 1.70-2.22; OR 0.13, 95% CI 0.09-0.18; OR 0.71, 95% CI 0.52-0.96) were all associated with refusal; patients refusing surgery were at increased risk of death compared to patients who underwent surgery.

Conclusions: More vulnerable patients are at higher risk of refusing recommended surgery, and this decision negatively impacts their survival.
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http://dx.doi.org/10.1007/s10552-019-01240-9DOI Listing
December 2019

Commentary: Minimally invasive thoracic surgery lobectomy: Truth versus hype.

Authors:
Raja M Flores

J Thorac Cardiovasc Surg 2019 Sep 23. Epub 2019 Sep 23.

Department of Thoracic Surgery, Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, New York, NY. Electronic address:

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http://dx.doi.org/10.1016/j.jtcvs.2019.09.017DOI Listing
September 2019

Racial Differences in Treatment and Survival among Veterans and Non-Veterans with Stage I NSCLC: An Evaluation of Veterans Affairs and SEER-Medicare Populations.

Cancer Epidemiol Biomarkers Prev 2020 01 17;29(1):112-118. Epub 2019 Oct 17.

Department of Population Health Science and Policy, Institute for Translational Epidemiology, Icahn School of Medicine at Mount Sinai, New York, New York.

Background: Surgery is the preferred treatment for stage I non-small cell lung cancer (NSCLC), with radiation reserved for those not receiving surgery. Previous studies have shown lower rates of surgery among Blacks with stage I NSCLC than among Whites.

Methods: Black and White men ages ≥65 years with stage I NSCLC diagnosed between 2001 and 2009 were identified in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database and Veterans Affairs (VA) cancer registry. Logistic regression and Cox proportional hazards models were used to examine associations between race, treatment, and survival.

Results: Among the patients in the VA ( = 7,895) and SEER ( = 8,744), the proportion of Blacks was 13% and 7%, respectively. Overall, 16.2% of SEER patients (15.4% of Whites, 26.0% of Blacks) and 24.5% of VA patients received no treatment (23.4% of Whites, 31.4% of Blacks). In both cohorts, Blacks were less likely to receive any treatment compared with Whites [OR = 0.57; 95% confidence interval (CI), 0.47-0.69 for SEER-Medicare; OR = 0.68; 95% CI, 0.58-0.79 for VA]. Among treated patients, Blacks were less likely than Whites to receive surgery only (OR = 0.57; 95% CI, 0.47-0.70 for SEER-Medicare; OR = 0.73; 95% CI, 0.62-0.86 for VA), but more likely to receive chemotherapy only and radiation only. There were no racial differences in survival.

Conclusions: Among VA and SEER-Medicare patients, Blacks were less likely to get surgical treatment. Blacks and Whites had similar survival outcomes when accounting for treatment.

Impact: This supports the hypothesis that equal treatment correlates with equal outcomes and emphasizes the need to understand multilevel predictors of lung cancer treatment disparities.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-0245DOI Listing
January 2020

Second Primary Lung Cancers Demonstrate Similar Survival With Wedge Resection and Lobectomy.

Ann Thorac Surg 2019 12 31;108(6):1724-1728. Epub 2019 Jul 31.

Department of Thoracic Surgery, Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, New York, New York. Electronic address:

Background: Patients who have undergone curative surgery for stage I lung cancer require continued surveillance owing to the risk of a second primary lung cancer developing. Early diagnosis allows for prompt intervention. However, as in primary cancers, the role of wedge vs lobar resections remains controversial.

Methods: The Surveillance Epidemiology and End Results database was examined from 2004 to 2012 and all pathologically proven stage I lung cancer patients who underwent cancer-directed surgery were selected. Cases in which a second primary lung cancer developed 6 or more months after diagnosis of the first cancer were analyzed for survival after surgical treatment.

Results: Second primary lung cancer was identified in 625 patients, of whom 331 (53%) were diagnosed with stage I disease; 43.8% of patients underwent surgery alone, 30.9% received radiation alone, and 21.0% received neither surgery nor radiation. Of the patients who underwent surgery, 57.7% received wedge resection and 36.5% received a lobectomy. Surgical intervention was a positive predictor of survival-both wedge resection and lobectomy exhibited improved outcomes vs no surgery-but there was no statistically significant difference between the two surgical modalities.

Conclusions: Wedge and lobar resections demonstrate similar survival for second primary lung cancers.
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http://dx.doi.org/10.1016/j.athoracsur.2019.06.023DOI Listing
December 2019

A comparison of mutation status in tissue and plasma cell-free DNA detected by ADx-ARMS in advanced lung adenocarcinoma patients.

Transl Lung Cancer Res 2019 Apr;8(2):135-143

The Key Laboratory of Interventional Pulmonology of Zhejiang Province, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China.

Background: Previous studies have shown that there are different methods used to detect the epidermal growth factor receptor () mutation status in plasma cell-free DNA (cfDNA) for advanced lung adenocarcinoma patients including the ADx-Amplification Refractory Mutation System (ADx-ARMS). We explored the performance of the ADx-ARMS in detecting the mutations in cfDNA.

Methods: This prospective cohort study enrolled patients who presented with advanced (stage IIIb/IV) lung adenocarcinoma. mutations in plasma cfDNA and tumor tissues by ADx-ARMS were detected. Next-generation sequencing (NGS) in plasma was performed in patients with inconsistent gene region mutations in the plasma and matched tissue samples. We calculated the clinical parameters of the ADx-ARMS for mutation status in the plasma of cfDNA, using the tumor tissues as the standard for measurement. The objective response rate (ORR) and progression-free survival (PFS) were also calculated for patients receiving first-generation EGFR-tyrosine kinase inhibitors (TKIs) therapy.

Results: In total, 203 patients were included in the final analysis. Mutations were discovered in 58.6% (119/203) of the tumor tissues and 31.0% (63/203) were detected mutations in both tumor tissues and matched plasma. The sensitivity and the specificity setting for detecting the mutations in the plasma using the ADx-ARMS were configured to 52.9% and 98.8%. An ORR of 64.8% was observed among the 71 patients who were identified as being -positive in their tumor tissues, who had received treatments using Gefitinib or Icotinib. Next, the ORR was observed to be 69.0% among the 42 patients with an mutation in their plasma. The median PFS of the patients with an mutation in tumor tissues and plasma were 10.0 11.0 months (P=0.175). The median PFS of the patients with an wild-type in the plasma was 8.7 months, which was significantly shorter than the mutant-type in plasma (P=0.001).

Conclusions: Using ADx-ARMS as an approach with high specificity but moderate sensitivity to detect the mutations in plasma cfDNA and mutation status in plasma cfDNA using the ADx-ARMS can predict the tumor response for EGFR-TKIs.
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http://dx.doi.org/10.21037/tlcr.2019.03.10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6504650PMC
April 2019

Association between the novel classification of lung adenocarcinoma subtypes and EGFR/KRAS mutation status: A systematic literature review and pooled-data analysis.

Eur J Surg Oncol 2019 05 16;45(5):870-876. Epub 2019 Feb 16.

Department of Thoracic Surgery/Oncology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Disease, China State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou, PR China. Electronic address:

Objectives: This study aims to determine the association of EGFR/KRAS mutation status with histological subtypes of lung adenocarcinoma (LAC) based on the IASLC/ATS/ERS classification.

Methods: Pubmed and Cochrane databases were searched from January 2011 to June 2018 for studies that included patients with LAC who underwent surgical resection were classified according to the new IASLC/ATS/ERS classification. EGFR/KRAS status assessment was requireded. The primary outcome was determined by the odds ratio (OR) of the incidence of mutation status of certain of each histological subtype. The reference group consisted of EGFR/KRAS mutation negative patients.

Results: Twenty-seven eligible studies involving 9022 patients with mutation gene detection were included for analysis. Among them, 6717 (74.5%) patients were from the Asian region and, 2305 (25.5%) patients were from Non-Asian regions. The most prevalent subtype was acinar (34.7%), followed by papillary (22.9%), lepidic (18.9%), solid (13.6%), micropapillary (6.3%), and invasive mucinous adenocarcinoma (3.5%). EGFR mutations were more common in patients with resected lepidic predominant adenocarcinoma (OR,1.76; 95%CI, 1.38-2.24;p < 0.01) and were rarely found in solid predominant adenocarcinoma (OR,0.28; 95%CI, 0.23-0.34;p < 0.01) or IMA (OR,0.10; 95%CI, 0.06-0.14;p < 0.01). Conversely, KRAS mutations were characterized by IMA (OR,7.01; 95%CI, 5.11-9.62;p < 0.01), and were less frequently identified in lepidic (OR,0.58; 95%CI, 0.45-0.75;p < 0.01) and acinar (OR,0.65; 95%CI, 0.55-0.78;p < 0.01) predominant subtypes. Further analyses were performed in Asian and Non-Asian groups and the results were consistent.

Conclusions: The current study confirms that the IASLC/ATS/ERS classification is associated with driver gene alterations in resected LAC.
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http://dx.doi.org/10.1016/j.ejso.2019.02.006DOI Listing
May 2019

Survival with Parenchymal and Pleural Invasion of Non-Small Cell Lung Cancers Less than 30 mm.

J Thorac Oncol 2019 05 24;14(5):890-902. Epub 2019 Jan 24.

Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address:

Objective: To determine long-term survival of visceral pleural invasion (VPI) and parenchymal invasion (PAI) (angiolymphatic and/or vascular) on survival of NSCLCs less than 30 mm in maximum diameter.

Methods: Kaplan-Meier survivals for NSCLCs, with and without VPI and/or PAI, were determined for a prospective cohort of screening participants stratified by pathologic tumor size (≤10 mm, 11-20 mm, and 21-30 mm) and nodule consistency. Log-rank test statistics were calculated.

Results: The frequency of PAI versus VPI was significantly lower in patients with subsolid nodules than in those with solid nodules (4.9% versus 27.7% [p < 0.0001]), and correspondingly, Kaplan-Meier lung cancer survival was significantly higher among patients with subsolid nodules (99.1% versus 91.3% [p = 0.0009]). Multivariable Cox regression found that only tumor diameter (adjusted hazard ratio [HR] =1.07, 95% confidence interval [CI]: 1.01-1.14, p = 0.02) and PAI (adjusted HR = 3.15, 95% CI: 1.25-7.90, p = 0.01) remained significant, whereas VPI was not significant (p = 0.15). When clinical and computed tomography findings were included with the pathologic findings, Cox regression showed that the risk of dying of lung cancer increased 10-fold (HR = 10.06, 95% CI: 1.35-75.30) for NSCLCs in patients with solid nodules and more than twofold (by a factor of 2.27) in patients with moderate to severe emphysema (HR = 2.27, 95% CI: 1.01-5.11), as well as with increasing tumor diameter (HR = 1.06, 95% CI: 1.01-1.13), whereas PAI was no longer significant (p = 0.19).

Conclusions: Nodule consistency on computed tomography was a more significant prognostic indicator than either PAI or VPI. We propose that patients with NSCLC with VPI and a maximum tumor diameter of 30 mm or less not be upstaged to T2 without further large, multicenter studies of NSCLCs, stratified by the new T status and that classification be considered separately for patients with subsolid or solid nodules.
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http://dx.doi.org/10.1016/j.jtho.2019.01.013DOI Listing
May 2019

Early stage lung cancer survival after wedge resection and stereotactic body radiation.

J Thorac Dis 2018 Oct;10(10):5702-5713

Department of Thoracic Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Background: The comparative effectiveness of stereotactic body radiation therapy (SBRT) and wedge resection in the treatment of early stage lung cancer is still under debate. This meta-analysis compares the 5-year overall survival (OS) of wedge resection and SBRT in patients with stage I non-small cell lung cancer (NSCLC).

Methods: Original research articles published between 1995 and 2017 were identified through the National Library of Medicine and National Institutes of Health PubMed database and through the reference lists of reviewed articles. Data were processed and analyzed in R (version 3.4.2) and a summary estimate that accounted for the sample size of each study was calculated. The combined percent survival was calculated using random effect models. Funnel plots were used to assess publication bias. Heterogeneity was tested using the Q statistic and the I statistic.

Results: There were 16 studies totaling 1,984 patients with stage I NSCLC treated with wedge resection. The meta-estimate was 74% (95% CI, 66-81%), with significant heterogeneity across studies (Q =172.46, P<0.0001; I=91.30%). Thirty-six studies including 3,309 patients with stage I NSCLC treated with SBRT/SABR produced a meta-estimate of 44% (95% CI, 38-50%), with significant heterogeneity (Q =423.55, P<0.0001; I=91.74%). Two articles directly comparing stage I NSCLC patients treated with wedge resection to patients treated with SBRT both reported higher 5-year OS after wedge resection.

Conclusions: SBRT is a treatment option reserved to medically inoperable patients, but could be an alternative to surgery in medically operable patients who prefer a less invasive treatment. More standardized methods for data collection and reporting are necessary to allow better comparisons across published studies.
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http://dx.doi.org/10.21037/jtd.2018.09.140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6236177PMC
October 2018

Systematic review of quality of life following pleurectomy decortication and extrapleural pneumonectomy for malignant pleural mesothelioma.

BMC Cancer 2018 Nov 29;18(1):1188. Epub 2018 Nov 29.

Institute for Translational Epidemiology and Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Background: Few studies have focused on quality of life (QoL) after treatment of malignant pleural mesothelioma (MPM). There are still questions as to which surgical procedure, extrapleural pneumonectomy (EPP) or pleurectomy decortication (P/D) is most effective and results in better survival outcomes, involves fewer complications, and results in better QoL. Here we performed a literature review on MPM patients to assess and compare QoL changes after P/D and EPP.

Methods: Research articles concerning QoL after mesothelioma surgery were identified through May 2018 in Medline. For inclusion, studies were 1) cohort or randomized controlled trials (RCT) design, 2) included standardized QoL instruments, 3) reported QoL measurement after surgery, 4) described the type of surgery performed (EPP or P/D), 5) were written in English. Measures of lung function (FEV1, FVC) and measures from the EORTC-C30 were compared 6 months following surgery with preoperative values.

Results: QoL data was extracted from 17 articles (14 datasets), encompassing 659 patients (102 EPP, 432 P/D); the available evidence was of low quality. While two studies directly compared QoL between the two surgical procedures, additional data was available from one arm of two RCTs, as the RCTs were not comparing EPP and P/D. The remaining data was reported from observational studies. While QoL was still compromised 6 months following surgery, from the limited and low quality data available it would appear that P/D patients had better QoL than EPP patients across all measures. Physical function, social function and global health were better at follow-up for P/D than for EPP, while other indicators such as pain and cough were similar. Forced Expiratory Volume (FEV1) and Forced Vital Capacity (FVC) were reported in one study only, and were higher at follow-up for P/D compared to EPP.

Conclusions: Although the existing evidence is limited and of low quality, it suggests that P/D patients have better QoL than EPP patients following surgery. QoL outcomes should be factored into the choice of surgical procedure for MPM patients, and the possible effects on lung function and QoL should be discussed with patients when presenting surgical treatment options.
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http://dx.doi.org/10.1186/s12885-018-5064-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6267825PMC
November 2018