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1. Enhancing NSCLC recurrence prediction with PET/CT habitat imaging, ctDNA, and integrative radiogenomics-blood insights

Author

Sujit, Sheeba J., primary, Aminu, Muhammad, additional, Karpinets, Tatiana V., additional, Chen, Pingjun, additional, Saad, Maliazurina B., additional, Salehjahromi, Morteza, additional, Boom, John D., additional, Qayati, Mohamed, additional, George, James M., additional, Allen, Haley, additional, Antonoff, Mara B., additional, Hong, Lingzhi, additional, Hu, Xin, additional, Heeke, Simon, additional, Tran, Hai T., additional, Le, Xiuning, additional, Elamin, Yasir Y., additional, Altan, Mehmet, additional, Vokes, Natalie I., additional, Sheshadri, Ajay, additional, Lin, Julie, additional, Zhang, Jianhua, additional, Lu, Yang, additional, Behrens, Carmen, additional, Godoy, Myrna C. B., additional, Wu, Carol C., additional, Chang, Joe Y., additional, Chung, Caroline, additional, Jaffray, David A., additional, Wistuba, Ignacio I., additional, Lee, J. Jack, additional, Vaporciyan, Ara A., additional, Gibbons, Don L., additional, Heymach, John, additional, Zhang, Jianjun, additional, Cascone, Tina, additional, and Wu, Jia, additional

Published
2024
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2. Neoadjuvant chemotherapy plus nivolumab with or without ipilimumab in operable non-small cell lung cancer: the phase 2 platform NEOSTAR trial

Author

Tina Cascone, Cheuk H. Leung, Annikka Weissferdt, Apar Pataer, Brett W. Carter, Myrna C. B. Godoy, Hope Feldman, William N. William, Yuanxin Xi, Sreyashi Basu, Jing Jing Sun, Shalini S. Yadav, Frank R. Rojas Alvarez, Younghee Lee, Aditya K. Mishra, Lili Chen, Monika Pradhan, Haiping Guo, Ansam Sinjab, Nicolas Zhou, Marcelo V. Negrao, Xiuning Le, Carl M. Gay, Anne S. Tsao, Lauren Averett Byers, Mehmet Altan, Bonnie S. Glisson, Frank V. Fossella, Yasir Y. Elamin, George Blumenschein, Jianjun Zhang, Ferdinandos Skoulidis, Jia Wu, Reza J. Mehran, David C. Rice, Garrett L. Walsh, Wayne L. Hofstetter, Ravi Rajaram, Mara B. Antonoff, Junya Fujimoto, Luisa M. Solis, Edwin R. Parra, Cara Haymaker, Ignacio I. Wistuba, Stephen G. Swisher, Ara A. Vaporciyan, Heather Y. Lin, Jing Wang, Don L. Gibbons, J. Jack Lee, Nadim J. Ajami, Jennifer A. Wargo, James P. Allison, Padmanee Sharma, Humam Kadara, John V. Heymach, and Boris Sepesi

Subjects
General Medicine, General Biochemistry, Genetics and Molecular Biology
Abstract

Neoadjuvant ipilimumab + nivolumab (Ipi+Nivo) and nivolumab + chemotherapy (Nivo+CT) induce greater pathologic response rates than CT alone in patients with operable non-small cell lung cancer (NSCLC). The impact of adding ipilimumab to neoadjuvant Nivo+CT is unknown. Here we report the results and correlates of two arms of the phase 2 platform NEOSTAR trial testing neoadjuvant Nivo+CT and Ipi+Nivo+CT with major pathologic response (MPR) as the primary endpoint. MPR rates were 32.1% (7/22, 80% confidence interval (CI) 18.7–43.1%) in the Nivo+CT arm and 50% (11/22, 80% CI 34.6–61.1%) in the Ipi+Nivo+CT arm; the primary endpoint was met in both arms. In patients without known tumor EGFR/ALK alterations, MPR rates were 41.2% (7/17) and 62.5% (10/16) in the Nivo+CT and Ipi+Nivo+CT groups, respectively. No new safety signals were observed in either arm. Single-cell sequencing and multi-platform immune profiling (exploratory endpoints) underscored immune cell populations and phenotypes, including effector memory CD8+ T, B and myeloid cells and markers of tertiary lymphoid structures, that were preferentially increased in the Ipi+Nivo+CT cohort. Baseline fecal microbiota in patients with MPR were enriched with beneficial taxa, such as Akkermansia, and displayed reduced abundance of pro-inflammatory and pathogenic microbes. Neoadjuvant Ipi+Nivo+CT enhances pathologic responses and warrants further study in operable NSCLC. (ClinicalTrials.gov registration: NCT03158129.)

Published
2023
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3. Neoadjuvant chemotherapy plus nivolumab with or without ipilimumab in operable non-small cell lung cancer: the phase 2 platform NEOSTAR trial

Author

Cascone, Tina, primary, Leung, Cheuk H., additional, Weissferdt, Annikka, additional, Pataer, Apar, additional, Carter, Brett W., additional, Godoy, Myrna C. B., additional, Feldman, Hope, additional, William, William N., additional, Xi, Yuanxin, additional, Basu, Sreyashi, additional, Sun, Jing Jing, additional, Yadav, Shalini S., additional, Rojas Alvarez, Frank R., additional, Lee, Younghee, additional, Mishra, Aditya K., additional, Chen, Lili, additional, Pradhan, Monika, additional, Guo, Haiping, additional, Sinjab, Ansam, additional, Zhou, Nicolas, additional, Negrao, Marcelo V., additional, Le, Xiuning, additional, Gay, Carl M., additional, Tsao, Anne S., additional, Byers, Lauren Averett, additional, Altan, Mehmet, additional, Glisson, Bonnie S., additional, Fossella, Frank V., additional, Elamin, Yasir Y., additional, Blumenschein, George, additional, Zhang, Jianjun, additional, Skoulidis, Ferdinandos, additional, Wu, Jia, additional, Mehran, Reza J., additional, Rice, David C., additional, Walsh, Garrett L., additional, Hofstetter, Wayne L., additional, Rajaram, Ravi, additional, Antonoff, Mara B., additional, Fujimoto, Junya, additional, Solis, Luisa M., additional, Parra, Edwin R., additional, Haymaker, Cara, additional, Wistuba, Ignacio I., additional, Swisher, Stephen G., additional, Vaporciyan, Ara A., additional, Lin, Heather Y., additional, Wang, Jing, additional, Gibbons, Don L., additional, Jack Lee, J., additional, Ajami, Nadim J., additional, Wargo, Jennifer A., additional, Allison, James P., additional, Sharma, Padmanee, additional, Kadara, Humam, additional, Heymach, John V., additional, and Sepesi, Boris, additional

Published
2023
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4. Efficacy and clinicogenomic correlates of response to immune checkpoint inhibitors alone or with chemotherapy in non-small cell lung cancer

Author

Hong, Lingzhi, primary, Aminu, Muhammad, additional, Li, Shenduo, additional, Lu, Xuetao, additional, Petranovic, Milena, additional, Saad, Maliazurina B., additional, Chen, Pingjun, additional, Qin, Kang, additional, Varghese, Susan, additional, Rinsurongkawong, Waree, additional, Rinsurongkawong, Vadeerat, additional, Spelman, Amy, additional, Elamin, Yasir Y., additional, Negrao, Marcelo V., additional, Skoulidis, Ferdinandos, additional, Gay, Carl M., additional, Cascone, Tina, additional, Gandhi, Saumil J., additional, Lin, Steven H., additional, Lee, Percy P., additional, Carter, Brett W., additional, Wu, Carol C., additional, Antonoff, Mara B., additional, Sepesi, Boris, additional, Lewis, Jeff, additional, Gibbons, Don L., additional, Vaporciyan, Ara A., additional, Le, Xiuning, additional, Jack Lee, J., additional, Roy-Chowdhuri, Sinchita, additional, Routbort, Mark J., additional, Gainor, Justin F., additional, Heymach, John V., additional, Lou, Yanyan, additional, Wu, Jia, additional, Zhang, Jianjun, additional, and Vokes, Natalie I., additional

Published
2023
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7. Neoadjuvant nivolumab or nivolumab plus ipilimumab in operable non-small cell lung cancer: the phase 2 randomized NEOSTAR trial

Author

Cheuk Hong Leung, Wayne L. Hofstetter, John V. Heymach, Alexandre Reuben, Myrna C.B. Godoy, Ara A. Vaporciyan, Padmanee Sharma, Yasir Elamin, Neda Kalhor, Robert R. Jenq, Junya Fujimoto, Tina Cascone, Anne S. Tsao, William N. William, Charles Lu, Frank E. Mott, Nadim J. Ajami, Don L. Gibbons, Jack A. Roth, David C. Rice, Luisa M. Solis, Hai T. Tran, Brett W. Carter, Lauren Averett Byers, Andrew Futreal, Lorenzo Federico, Annikka Weissferdt, Garrett L. Walsh, Reza J. Mehran, Chantale Bernatchez, George R. Blumenschein, Jennifer A. Wargo, Heather Lin, Cara Haymaker, Xiuning Le, Jonathan M. Kurie, Mehmet Altan, James P. Allison, Stephen G. Swisher, Edwin R. Parra, Boris Sepesi, Hitoshi Dejima, Frank V. Fossella, Jianjun Zhang, Bonnie S. Glisson, Mara B. Antonoff, Abdul Wadud Khan, Apar Pataer, Alejandro Francisco-Cruz, Ignacio I. Wistuba, Humam Kadara, J. Jack Lee, and Ferdinandos Skoulidis

Subjects
Adult, Male, 0301 basic medicine, Oncology, medicine.medical_specialty, Lung Neoplasms, medicine.medical_treatment, Ipilimumab, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, Clinical endpoint, Carcinoma, Humans, Medicine, Lung cancer, Neoadjuvant therapy, Aged, Chemotherapy, business.industry, General Medicine, Middle Aged, medicine.disease, Neoadjuvant Therapy, Clinical trial, Nivolumab, 030104 developmental biology, 030220 oncology & carcinogenesis, Female, business, medicine.drug
Abstract

Ipilimumab improves clinical outcomes when combined with nivolumab in metastatic non-small cell lung cancer (NSCLC), but its efficacy and impact on the immune microenvironment in operable NSCLC remain unclear. We report the results of the phase 2 randomized NEOSTAR trial (NCT03158129) of neoadjuvant nivolumab or nivolumab + ipilimumab followed by surgery in 44 patients with operable NSCLC, using major pathologic response (MPR) as the primary endpoint. The MPR rate for each treatment arm was tested against historical controls of neoadjuvant chemotherapy. The nivolumab + ipilimumab arm met the prespecified primary endpoint threshold of 6 MPRs in 21 patients, achieving a 38% MPR rate (8/21). We observed a 22% MPR rate (5/23) in the nivolumab arm. In 37 patients resected on trial, nivolumab and nivolumab + ipilimumab produced MPR rates of 24% (5/21) and 50% (8/16), respectively. Compared with nivolumab, nivolumab + ipilimumab resulted in higher pathologic complete response rates (10% versus 38%), less viable tumor (median 50% versus 9%), and greater frequencies of effector, tissue-resident memory and effector memory T cells. Increased abundance of gut Ruminococcus and Akkermansia spp. was associated with MPR to dual therapy. Our data indicate that neoadjuvant nivolumab + ipilimumab-based therapy enhances pathologic responses, tumor immune infiltrates and immunologic memory, and merits further investigation in operable NSCLC. Neoadjuvant treatment with nivolumab plus ipilimumab is well tolerated and demonstrates clinical efficacy in patients with early stage lung cancer.

Published
2021
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8. Intestinal Metaplasia in the Esophageal Remnant Is Rare After Ivor Lewis Esophagectomy

Author

Mara B. Antonoff, Wayne L. Hofstetter, Garrett L. Walsh, Boris Sepesi, Jack A. Roth, Ravi Rajaram, Ara A. Vaporciyan, David C. Rice, Stephen G. Swisher, Kyle G. Mitchell, Erin M. Corsini, Nicolas Zhou, and Reza J. Mehran

Subjects
medicine.medical_specialty, business.industry, medicine.medical_treatment, Gastroenterology, Reflux, Intestinal metaplasia, medicine.disease, digestive system diseases, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Esophagectomy, Interquartile range, 030220 oncology & carcinogenesis, Internal medicine, Metaplasia, Barrett's esophagus, Medicine, Adenocarcinoma, 030211 gastroenterology & hepatology, Surgery, medicine.symptom, Esophagus, business
Abstract

Most patients undergoing esophagectomy will experience intermittent reflux of gastric and biliary content into the remnant esophagus postoperatively. The incidence of new or recurrent intestinal metaplasia following chemoradiation and surgery has not been well-described. Furthermore, post-resection guidelines do not exist regarding surveillance for metaplasia in the esophageal remnant. Patients undergoing Ivor Lewis esophagectomy after concurrent chemoradiation for a diagnosis of esophageal adenocarcinoma from 2006 to 2018 were identified. Pathology records were reviewed for the presence of intestinal metaplasia on pretreatment biopsies, surgical specimen, or post-resection biopsies. In total, 619 patients met inclusion criteria, including 267 (43%) who had intestinal metaplasia noted either prior to or at the time of esophagectomy. The median duration of metaplastic disease prior to resection was 4.4 months. During a median follow-up time of 28 months (interquartile range, 12–60), intestinal metaplasia was noted in the remnant esophagus in 12 (2%) patients, 7 of whom had a prior history of metaplasia. Local recurrence of adenocarcinoma was also uncommon, and occurred in 37/577 (6%) of patients with complete resections, with similar event rates among those with and without a prior history of metaplasia (14/249 [6%] vs. 23/328 [7%], p = 0.614). Our findings suggest that despite several factors predisposing to mucosal damage following esophagectomy, occurrence of new intestinal metaplasia after trimodality therapy in our patient population appears to be rare, even among patient with a previous history of this pathologic finding, which may have significant implications for surveillance and cost-savings after resection.

Published
2021
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9. CD73 expression defines immune, molecular, and clinicopathological subgroups of lung adenocarcinoma

Author

Pedro Rocha, Dzifa Y. Douse, Lixia Diao, Humam Kadara, Jianjun Zhang, Debora A. Ledesma, Jose Luis Solorzano, John V. Heymach, Ruth Salazar, Luisa M. Solis, Neda Kalhor, Barbara Mino, J. Jack Lee, Don L. Gibbons, Cesar A. Moran, David C. Rice, Carmen Behrens, Pamela Villalobos, Ara A. Vaporciyan, Jiexin Zhang, Hitoshi Dejima, Annikka Weissferdt, Kyle G. Mitchell, Tina Cascone, Edwin Parra-Cuentas, Boris Sepesi, Xiuning Le, and Ignacio I. Wistuba

Subjects
Male, Lung adenocarcinoma, Cancer Research, Lung Neoplasms, medicine.medical_treatment, Immune profiling, Atypical hyperplasia, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, Immunology and Allergy, 5'-Nucleotidase, Neoadjuvant therapy, Aged, 80 and over, 0303 health sciences, biology, Immunosuppression, Middle Aged, Prognosis, Oncology, 030220 oncology & carcinogenesis, Adenocarcinoma, Immunohistochemistry, Female, Original Article, medicine.symptom, Adult, PD-L1, Immunology, Adenocarcinoma of Lung, Inflammation, GPI-Linked Proteins, 03 medical and health sciences, Immune system, Biomarkers, Tumor, medicine, Humans, Immunologic Factors, Aged, Retrospective Studies, 030304 developmental biology, business.industry, Correction, medicine.disease, Adenosinergic pathway, CD73, Cancer research, biology.protein, business, Follow-Up Studies
Abstract

Introduction CD73 is a membrane-bound enzyme crucial in adenosine generation. The adenosinergic pathway plays a critical role in immunosuppression and in anti-tumor effects of immune checkpoint inhibitors (ICI). Here, we interrogated CD73 expression in a richly annotated cohort of human lung adenocarcinoma (LUAD) and its association with clinicopathological, immune, and molecular features to better understand the role of this immune marker in LUAD pathobiology. Materials and methods Protein expression of CD73 was evaluated by immunohistochemistry in 106 archived LUADs from patients that underwent surgical treatment without neoadjuvant therapy. Total CD73 (T +) was calculated as the average of luminal (L +) and basolateral (BL +) percentage membrane expression scores for each LUAD and was used to classify tumors into three groups based on the extent of T CD73 expression (high, low, and negative). Results CD73 expression was significantly and progressively increased across normal-appearing lung tissue, adenomatous atypical hyperplasia, adenocarcinoma in situ, minimally invasive adenocarcinoma, and LUAD. In LUAD, BL CD73 expression was associated with an increase in PD-L1 expression in tumor cells and increase of tumor-associated immune cells. Stratification of LUADs based on T CD73 extent also revealed that tumors with high expression of this enzyme overall exhibited significantly elevated immune infiltration and PD-L1 protein expression. Immune profiling demonstrated that T-cell inflammation and adenosine signatures were significantly higher in CD73-expressing lung adenocarcinomas relative to those lacking CD73. Conclusion Our study suggests that higher CD73 expression is associated with an overall augmented host immune response, suggesting potential implications in the immune pathobiology of early stage lung adenocarcinoma. Our findings warrant further studies to explore the role of CD73 in immunotherapeutic response of LUAD.

Published
2021
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10. 18F-fluorodeoxyglucose positron emission tomography correlates with tumor immunometabolic phenotypes in resected lung cancer

Author

Tina Cascone, Brett W. Carter, Ara A. Vaporciyan, Kyle G. Mitchell, David Piwnica-Worms, Carmen Behrens, Stephen G. Swisher, Edwin R. Parra, Weiyi Peng, Jing Wang, Yunfei Wang, Alexandre Reuben, John V. Heymach, Cesar A. Moran, Wayne L. Hofstetter, Pamela Villalobos, Annikka Weissferdt, Behrang Amini, Myrna C.B. Godoy, Boris Sepesi, William N. William, Don L. Gibbons, J. Jack Lee, Garrett L. Walsh, Junya Fujimoto, Patrick Hwu, Humam Kadara, and Ignacio I. Wistuba

Subjects
Cancer Research, Tumor microenvironment, medicine.diagnostic_test, business.industry, T cell, Immunology, Cell, Gene signature, medicine.disease, Article, Immune system, medicine.anatomical_structure, Oncology, Positron emission tomography, medicine, Cancer research, Immunology and Allergy, Immunohistochemistry, Lung cancer, business
Abstract

Enhanced tumor glycolytic activity is a mechanism by which tumors induce an immunosuppressive environment to resist adoptive T cell therapy; therefore, methods of assessing intratumoral glycolytic activity are of considerable clinical interest. In this study, we characterized the relationships among tumor (18)F-fluorodeoxyglucose (FDG) retention, tumor metabolic and immune phenotypes, and survival in patients with resected non-small cell lung cancer (NSCLC). We retrospectively analyzed tumor preoperative positron emission tomography (PET) (18)F-FDG uptake in 59 resected NSCLCs and investigated correlations between PET parameters (SUV(Max), SUV(Total), SUV(Mean), TLG), tumor expression of glycolysis- and immune-related genes, and tumor-associated immune cell densities that were quantified by immunohistochemistry. Tumor glycolysis-associated immune gene signatures were analyzed for associations with survival outcomes. We found that each (18)F-FDG PET parameter was positively correlated with tumor expression of glycolysis-related genes. Elevated (18)F-FDG SUV(Max) was more discriminatory of glycolysis-associated changes in tumor immune phenotypes than other (18)F-FDG PET parameters. Increased SUV(Max) was associated with multiple immune factors characteristic of an immunosuppressive and poorly immune infiltrated tumor microenvironment, including elevated PD-L1 expression, reduced CD57(+) cell density, and increased T cell exhaustion gene signature. Elevated SUV(Max) identified immune-related transcriptomic signatures that were associated with enhanced tumor glycolytic gene expression and poor clinical outcomes. Our results suggest that (18)F-FDG SUV(Max) has potential value as a noninvasive, clinical indicator of tumor immunometabolic phenotypes in patients with resectable NSCLC and warrants investigation as a potential predictor of therapeutic response to immune-based treatment strategies.

Published
2020
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11. Therapeutic targeting of the PI4K2A/PKR lysosome network is critical for misfolded protein clearance and survival in cancer cells

Author

Neil R. Cashman, Steven H. Lin, Jing Wang, Steven S. Plotkin, Ru Ping Shao, Ignacio I. Wistuba, Apar Pataer, Bulent Ozpolat, Nashwa N. Kabil, Bingliang Fang, Mourad Majidi, Jack A. Roth, Ara A. Vaporciyan, Charles E. Samuel, Stephen G. Swisher, and Mien Chie Hung

Subjects
0301 basic medicine, Protein Folding, Cancer Research, viruses, Mice, SCID, Exosomes, environment and public health, Mice, eIF-2 Kinase, 0302 clinical medicine, Neoplasms, Databases, Genetic, virus diseases, Prognosis, 3. Good health, Survival Rate, Phosphotransferases (Alcohol Group Acceptor), medicine.anatomical_structure, 030220 oncology & carcinogenesis, Female, Programmed cell death, Cell Survival, Antineoplastic Agents, Biology, Article, Minor Histocompatibility Antigens, 03 medical and health sciences, Cell Line, Tumor, Target identification, Lysosome, Genetics, medicine, Animals, Humans, Molecular Biology, Cancer, biochemical phenomena, metabolism, and nutrition, medicine.disease, Xenograft Model Antitumor Assays, Protein kinase R, Microvesicles, 030104 developmental biology, Cell culture, Proteolysis, Cancer cell, Unfolded Protein Response, Cancer research, Unfolded protein response, Lysosomes, Non-small-cell lung cancer
Abstract

The role of RNA-dependent protein kinase R (PKR) and its association with misfolded protein expression in cancer cells are unclear. Herein we report that PKR regulates misfolded protein clearance by preventing it release through exosomes and promoting lysosomal degradation of misfolded prion proteins in cancer cells. We demonstrated that PKR contributes to the lysosome function and regulates misfolded prion protein clearance. We hypothesized that PKR-associated lysosome function is critical for cancer but not normal cell survival, representing an effective approach for highly targeted cancer therapy. In screening a compound library, we identified two PKR-associated compounds 1 and 2 (Pac 1 and 2) did not affect normal cells but selectively induced cell death in cancer cells depending on their PKR expression status. Pac 1 significantly inhibited the growth of human lung and breast xenograft tumors in mice with no toxicity. Pac 1 binds to PI4K2A and disrupts the PKR/PI4K2A-associated lysosome complex, contributing to destabilization of cancer cell lysosomes and triggering cell death. We observed that PKR and PI4K2A play significant prognostic roles in breast cancer patients. These results demonstrate that targeting of a PI4K2A/PKR lysosome complex may be an effective approach for cancer therapy.

Published
2019
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12. Predictors of the response of operating room personnel to surgeon behaviors

Author

Jessica G.Y. Luc, Mara B. Antonoff, Kyle G. Mitchell, Ara A. Vaporciyan, Nadine S. Turner, and Erin M. Corsini

Subjects
Male, Operating Rooms, medicine.medical_specialty, Health Personnel, Sexism, Random Allocation, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, Gender bias, Humans, Medicine, Prospective randomized study, Prospective Studies, Patient Care Team, Surgeons, Response rate (survey), Behavior, Surgical team, business.industry, General Medicine, Sex bias, surgical procedures, operative, 030220 oncology & carcinogenesis, Family medicine, Workforce, Female, 030211 gastroenterology & hepatology, Surgery, business
Abstract

Several studies have assessed the physician–nurse relationship, particularly between females working together. While the surgeon workforce is increasingly represented by females, gendered relationships and biases in the operating room remain largely unstudied. We performed a prospective randomized study in which operative support staff, including nurses, surgical technologists, and surgical assistants, assessed scenarios describing questionable surgeon behaviors. Respondents were randomized to a survey that either discussed a female or male surgeon. For each scenario, one of the four standardized responses was selected. The respondents’ assessments of surgeon behaviors were analyzed. The response rate was 4.4% (3128/71143). Females were more likely than males to deem the surgeon’s behavior inappropriate regardless of surgeon sex (p = 0.001). The likelihood of writing up the surgeon was predicted by role, with technologists, nurses, and assistants reporting surgeons at frequencies of 65.5%, 53.2%, and 48.8%, respectively (p = 0.008). While the overall respondents did not show a propensity to write-up either sex differentially (p = 0.070), technologists were significantly more likely to report female surgeons than male surgeons (p = 0.006). Characteristics of operative personnel were correlated with varying tolerance of surgeon behaviors, with specific subgroups more critical of female surgeons than males. Further exploration of these perceptions will serve to improve interactions in a diverse workplace.

Published
2019
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13. Author Correction: Multi-region exome sequencing reveals genomic evolution from preneoplasia to lung adenocarcinoma

Author

Alexandre Reuben, John V. Heymach, Humam Kadara, Kishio Kuroda, Edwin R. Parra, Runzhe Chen, Stephen G. Swisher, Rebecca Thornton, Ignacio I. Wistuba, Chi-Wan Chow, J. Jack Lee, Latasha Little, J.S. Hu, Emily Roarty, Wenyong Sun, Samantha Tippen, Nicholas McGranahan, Xin Hu, Mara B. Antonoff, Brett W. Carter, P. Andrew Futreal, Junya Fujimoto, Lei Shi, Jianhua Zhang, Kazuto Ashizawa, Jianjun Zhang, Curtis Gumbs, Xu Wang, Xingzhi Song, Waun Ki Hong, Paul Scheet, Edwin J. Ostrin, Myrna C.B. Godoy, Harvey I. Pass, Dan Su, Carmen Behrens, Xizeng Mao, Junya Fukuoka, Ara A. Vaporciyan, Lisha Ying, Kazuhiro Tabata, and Jun Li

Subjects
Multidisciplinary, Lung, Science, MEDLINE, General Physics and Astronomy, General Chemistry, Computational biology, Biology, medicine.disease, General Biochemistry, Genetics and Molecular Biology, medicine.anatomical_structure, medicine, Adenocarcinoma, Exome sequencing
Published
2021
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14. Nodal immune flare mimics nodal disease progression following neoadjuvant immune checkpoint inhibitors in non-small cell lung cancer

Author

Cascone, Tina, primary, Weissferdt, Annikka, additional, Godoy, Myrna C. B., additional, William, William N., additional, Leung, Cheuk H., additional, Lin, Heather Y., additional, Basu, Sreyashi, additional, Yadav, Shalini S., additional, Pataer, Apar, additional, Mitchell, Kyle G., additional, Khan, Md Abdul Wadud, additional, Shi, Yushu, additional, Haymaker, Cara, additional, Solis, Luisa M., additional, Parra, Edwin R., additional, Kadara, Humam, additional, Wistuba, Ignacio I., additional, Sharma, Padmanee, additional, Allison, James P., additional, Ajami, Nadim J., additional, Wargo, Jennifer A., additional, Jenq, Robert R., additional, Gibbons, Don L., additional, Lee, J. Jack, additional, Swisher, Stephen G., additional, Vaporciyan, Ara A., additional, Heymach, John V., additional, and Sepesi, Boris, additional

Published
2021
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15. Author Correction: Multi-region exome sequencing reveals genomic evolution from preneoplasia to lung adenocarcinoma

Author

Hu, Xin, primary, Fujimoto, Junya, additional, Ying, Lisha, additional, Fukuoka, Junya, additional, Ashizawa, Kazuto, additional, Sun, Wenyong, additional, Reuben, Alexandre, additional, Chow, Chi-Wan, additional, McGranahan, Nicholas, additional, Chen, Runzhe, additional, Hu, Jinlin, additional, Godoy, Myrna C., additional, Tabata, Kazuhiro, additional, Kuroda, Kishio, additional, Shi, Lei, additional, Li, Jun, additional, Behrens, Carmen, additional, Parra, Edwin Roger, additional, Little, Latasha D., additional, Gumbs, Curtis, additional, Mao, Xizeng, additional, Song, Xingzhi, additional, Tippen, Samantha, additional, Thornton, Rebecca L., additional, Kadara, Humam, additional, Scheet, Paul, additional, Roarty, Emily, additional, Ostrin, Edwin Justin, additional, Wang, Xu, additional, Carter, Brett W., additional, Antonoff, Mara B., additional, Zhang, Jianhua, additional, Vaporciyan, Ara A., additional, Pass, Harvey, additional, Swisher, Stephen G., additional, Heymach, John V., additional, Lee, J. Jack, additional, Wistuba, Ignacio I., additional, Hong, Waun Ki, additional, Futreal, P. Andrew, additional, Su, Dan, additional, and Zhang, Jianjun, additional

Published
2021
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16. Immune evolution from preneoplasia to invasive lung adenocarcinomas and underlying molecular features

Author

Dejima, Hitoshi, primary, Hu, Xin, additional, Chen, Runzhe, additional, Zhang, Jiexin, additional, Fujimoto, Junya, additional, Parra, Edwin R., additional, Haymaker, Cara, additional, Hubert, Shawna M., additional, Duose, Dzifa, additional, Solis, Luisa M., additional, Su, Dan, additional, Fukuoka, Junya, additional, Tabata, Kazuhiro, additional, Pham, Hoa H. N., additional, Mcgranahan, Nicholas, additional, Zhang, Baili, additional, Ye, Jie, additional, Ying, Lisha, additional, Little, Latasha, additional, Gumbs, Curtis, additional, Chow, Chi-Wan, additional, Estecio, Marcos Roberto, additional, Godoy, Myrna C. B., additional, Antonoff, Mara B., additional, Sepesi, Boris, additional, Pass, Harvey I., additional, Behrens, Carmen, additional, Zhang, Jianhua, additional, Vaporciyan, Ara A., additional, Heymach, John V., additional, Scheet, Paul, additional, Lee, J. Jack, additional, Wu, Jia, additional, Futreal, P. Andrew, additional, Reuben, Alexandre, additional, Kadara, Humam, additional, Wistuba, Ignacio I., additional, and Zhang, Jianjun, additional

Published
2021
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17. Correction to: CD73 expression defines immune, molecular, and clinicopathological subgroups of lung adenocarcinoma

Author

Rocha, Pedro, primary, Salazar, Ruth, additional, Zhang, Jiexin, additional, Ledesma, Debora, additional, Solorzano, Jose L., additional, Mino, Barbara, additional, Villalobos, Pamela, additional, Dejima, Hitoshi, additional, Douse, Dzifa Y., additional, Diao, Lixia, additional, Mitchell, Kyle Gregory, additional, Le, Xiuning, additional, Zhang, Jianjun, additional, Weissferdt, Annikka, additional, Parra-Cuentas, Edwin, additional, Cascone, Tina, additional, Rice, David C., additional, Sepesi, Boris, additional, Kalhor, Neda, additional, Moran, Cesar, additional, Vaporciyan, Ara, additional, Heymach, John, additional, Gibbons, Don L., additional, Lee, J. Jack, additional, Kadara, Humam, additional, Wistuba, Ignacio, additional, Behrens, Carmen, additional, and Solis, Luisa Maren, additional

Published
2021
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18. Identification of distinct immune landscapes using an automated nine-color multiplex immunofluorescence staining panel and image analysis in paraffin tumor tissues

Author

Parra, Edwin R., primary, Zhai, Jie, additional, Tamegnon, Auriole, additional, Zhou, Nicolas, additional, Pandurengan, Renganayaki Krishna, additional, Barreto, Carmelia, additional, Jiang, Mei, additional, Rice, David C., additional, Creasy, Caitlin, additional, Vaporciyan, Ara A., additional, Hofstetter, Wayne L., additional, Tsao, Anne S., additional, Wistuba, Ignacio I., additional, Sepesi, Boris, additional, and Haymaker, Cara, additional

Published
2021
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19. Neoadjuvant nivolumab or nivolumab plus ipilimumab in operable non-small cell lung cancer: the phase 2 randomized NEOSTAR trial

Author

Cascone, Tina, primary, William, William N., additional, Weissferdt, Annikka, additional, Leung, Cheuk H., additional, Lin, Heather Y., additional, Pataer, Apar, additional, Godoy, Myrna C. B., additional, Carter, Brett W., additional, Federico, Lorenzo, additional, Reuben, Alexandre, additional, Khan, Md Abdul Wadud, additional, Dejima, Hitoshi, additional, Francisco-Cruz, Alejandro, additional, Parra, Edwin R., additional, Solis, Luisa M., additional, Fujimoto, Junya, additional, Tran, Hai T., additional, Kalhor, Neda, additional, Fossella, Frank V., additional, Mott, Frank E., additional, Tsao, Anne S., additional, Blumenschein, George, additional, Le, Xiuning, additional, Zhang, Jianjun, additional, Skoulidis, Ferdinandos, additional, Kurie, Jonathan M., additional, Altan, Mehmet, additional, Lu, Charles, additional, Glisson, Bonnie S., additional, Byers, Lauren Averett, additional, Elamin, Yasir Y., additional, Mehran, Reza J., additional, Rice, David C., additional, Walsh, Garrett L., additional, Hofstetter, Wayne L., additional, Roth, Jack A., additional, Antonoff, Mara B., additional, Kadara, Humam, additional, Haymaker, Cara, additional, Bernatchez, Chantale, additional, Ajami, Nadim J., additional, Jenq, Robert R., additional, Sharma, Padmanee, additional, Allison, James P., additional, Futreal, Andrew, additional, Wargo, Jennifer A., additional, Wistuba, Ignacio I., additional, Swisher, Stephen G., additional, Lee, J. Jack, additional, Gibbons, Don L., additional, Vaporciyan, Ara A., additional, Heymach, John V., additional, and Sepesi, Boris, additional

Published
2021
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20. Correction to: CD73 expression defines immune, molecular, and clinicopathological subgroups of lung adenocarcinoma

Author

Barbara Mino, J. Jack Lee, John V. Heymach, David C. Rice, Lixia Diao, Boris Sepesi, Luisa M. Solis, Debora A. Ledesma, Ruth Salazar, Humam Kadara, Ignacio I. Wistuba, Pamela Villalobos, Neda Kalhor, Cesar A. Moran, Annikka Weissferdt, Xiuning Le, Don L. Gibbons, Pedro Rocha, Dzifa Y. Douse, Carmen Behrens, Edwin Parra-Cuentas, Ara A. Vaporciyan, Hitoshi Dejima, Kyle G. Mitchell, Jianjun Zhang, Jiexin Zhang, Tina Cascone, and Jose Luis Solorzano

Subjects
Cancer Research, Lung, business.industry, Immunology, MEDLINE, medicine.disease, Text mining, Immune system, medicine.anatomical_structure, Oncology, Expression (architecture), Cancer research, Immunology and Allergy, Medicine, Adenocarcinoma, business
Abstract

The original version of this article unfortunately contained a mistake.

Published
2021
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21. Evolution of DNA methylome from precancerous lesions to invasive lung adenocarcinomas

Author

Hu, Xin, primary, Estecio, Marcos R., additional, Chen, Runzhe, additional, Reuben, Alexandre, additional, Wang, Linghua, additional, Fujimoto, Junya, additional, Carrot-Zhang, Jian, additional, McGranahan, Nicholas, additional, Ying, Lisha, additional, Fukuoka, Junya, additional, Chow, Chi-Wan, additional, Pham, Hoa H. N., additional, Godoy, Myrna C. B., additional, Carter, Brett W., additional, Behrens, Carmen, additional, Zhang, Jianhua, additional, Antonoff, Mara B., additional, Sepesi, Boris, additional, Lu, Yue, additional, Pass, Harvey I., additional, Kadara, Humam, additional, Scheet, Paul, additional, Vaporciyan, Ara A., additional, Heymach, John V., additional, Wistuba, Ignacio I., additional, Lee, J. Jack, additional, Futreal, P. Andrew, additional, Su, Dan, additional, Issa, Jean-Pierre J., additional, and Zhang, Jianjun, additional

Published
2021
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22. CD73 expression defines immune, molecular, and clinicopathological subgroups of lung adenocarcinoma

Author

Rocha, Pedro, primary, Salazar, Ruth, additional, Zhang, Jiexin, additional, Ledesma, Debora, additional, Solorzano, Jose L., additional, Mino, Barbara, additional, Villalobos, Pamela, additional, Dejima, Hitoshi, additional, Douse, Dzifa Y., additional, Diao, Lixia, additional, Mitchell, Kyle Gregory, additional, Le, Xiuning, additional, Zhang, Jianjun, additional, Weissferdt, Annikka, additional, Parra-Cuentas, Edwin, additional, Cascone, Tina, additional, Rice, David C., additional, Sepesi, Boris, additional, Kalhor, Neda, additional, Moran, Cesar, additional, Vaporciyan, Ara, additional, Heymach, John, additional, Gibbons, Don L., additional, Lee, J. Jack, additional, Kadara, Humam, additional, Wistuba, Ignacio, additional, Behrens, Carmen, additional, and Solis, Luisa Maren, additional

Published
2021
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23. 18F-fluorodeoxyglucose positron emission tomography correlates with tumor immunometabolic phenotypes in resected lung cancer

Author

Mitchell, Kyle G., primary, Amini, Behrang, additional, Wang, Yunfei, additional, Carter, Brett W., additional, Godoy, Myrna C. B., additional, Parra, Edwin R., additional, Behrens, Carmen, additional, Villalobos, Pamela, additional, Reuben, Alexandre, additional, Lee, J. Jack, additional, Weissferdt, Annikka, additional, Moran, Cesar A., additional, Fujimoto, Junya, additional, Sepesi, Boris, additional, Walsh, Garrett L., additional, Vaporciyan, Ara A., additional, Hofstetter, Wayne L., additional, William, William N., additional, Gibbons, Don L., additional, Wang, Jing, additional, Hwu, Patrick, additional, Swisher, Stephen G., additional, Piwnica-Worms, David, additional, Kadara, Humam, additional, Wistuba, Ignacio I., additional, Heymach, John V., additional, Peng, Weiyi, additional, and Cascone, Tina, additional

Published
2020
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24. Comprehensive T cell repertoire characterization of non-small cell lung cancer

Author

Reuben, Alexandre, primary, Zhang, Jiexin, additional, Chiou, Shin-Heng, additional, Gittelman, Rachel M., additional, Li, Jun, additional, Lee, Won-Chul, additional, Fujimoto, Junya, additional, Behrens, Carmen, additional, Liu, Xiaoke, additional, Wang, Feng, additional, Quek, Kelly, additional, Wang, Chunlin, additional, Kheradmand, Farrah, additional, Chen, Runzhe, additional, Chow, Chi-Wan, additional, Lin, Heather, additional, Bernatchez, Chantale, additional, Jalali, Ali, additional, Hu, Xin, additional, Wu, Chang-Jiun, additional, Eterovic, Agda Karina, additional, Parra, Edwin Roger, additional, Yusko, Erik, additional, Emerson, Ryan, additional, Benzeno, Sharon, additional, Vignali, Marissa, additional, Wu, Xifeng, additional, Ye, Yuanqing, additional, Little, Latasha D., additional, Gumbs, Curtis, additional, Mao, Xizeng, additional, Song, Xingzhi, additional, Tippen, Samantha, additional, Thornton, Rebecca L., additional, Cascone, Tina, additional, Snyder, Alexandra, additional, Wargo, Jennifer A., additional, Herbst, Roy, additional, Swisher, Stephen, additional, Kadara, Humam, additional, Moran, Cesar, additional, Kalhor, Neda, additional, Zhang, Jianhua, additional, Scheet, Paul, additional, Vaporciyan, Ara A., additional, Sepesi, Boris, additional, Gibbons, Don L., additional, Robins, Harlan, additional, Hwu, Patrick, additional, Heymach, John V., additional, Sharma, Padmanee, additional, Allison, James P., additional, Baladandayuthapani, Veera, additional, Lee, Jack J., additional, Davis, Mark M., additional, Wistuba, Ignacio I., additional, Futreal, P. Andrew, additional, and Zhang, Jianjun, additional

Published
2020
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25. Therapeutic targeting of the PI4K2A/PKR lysosome network is critical for misfolded protein clearance and survival in cancer cells

Author

Pataer, Apar, primary, Ozpolat, Bulent, additional, Shao, RuPing, additional, Cashman, Neil R., additional, Plotkin, Steven S., additional, Samuel, Charles E., additional, Lin, Steven H., additional, Kabil, Nashwa N., additional, Wang, Jing, additional, Majidi, Mourad, additional, Fang, Bingliang, additional, Roth, Jack A., additional, Vaporciyan, Ara A., additional, Wistuba, Ignacio I., additional, Hung, Mien-Chie, additional, and Swisher, Stephen G., additional

Published
2019
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26. Multi-region exome sequencing reveals genomic evolution from preneoplasia to lung adenocarcinoma

Author

Hu, Xin, primary, Fujimoto, Junya, additional, Ying, Lisha, additional, Fukuoka, Junya, additional, Ashizawa, Kazuto, additional, Sun, Wenyong, additional, Reuben, Alexandre, additional, Chow, Chi-Wan, additional, McGranahan, Nicholas, additional, Chen, Runzhe, additional, Hu, Jinlin, additional, Godoy, Myrna C., additional, Tabata, Kazuhiro, additional, Kuroda, Kishio, additional, Shi, Lei, additional, Li, Jun, additional, Behrens, Carmen, additional, Parra, Edwin Roger, additional, Little, Latasha D., additional, Gumbs, Curtis, additional, Mao, Xizeng, additional, Song, Xingzhi, additional, Tippen, Samantha, additional, Thornton, Rebecca L., additional, Kadara, Humam, additional, Scheet, Paul, additional, Roarty, Emily, additional, Ostrin, Edwin Justin, additional, Wang, Xu, additional, Carter, Brett W., additional, Antonoff, Mara B., additional, Zhang, Jianhua, additional, Vaporciyan, Ara A., additional, Pass, Harvey, additional, Swisher, Stephen G., additional, Heymach, John V., additional, Lee, J. Jack, additional, Wistuba, Ignacio I., additional, Hong, Waun Ki, additional, Futreal, P. Andrew, additional, Su, Dan, additional, and Zhang, Jianjun, additional

Published
2019
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28. Predictors for Locoregional Recurrence for Clinical Stage III-N2 Non-small Cell Lung Cancer with Nodal Downstaging After Induction Chemotherapy and Surgery

Author

Randall L. Baldassarre, Andreas Rimner, Jack A. Roth, Feiran Lou, Ara A. Vaporciyan, Stephen G. Swisher, Steven H. Lin, James Huang, Arya Amini, and Arlene M. Correa

Subjects
Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, Lung Neoplasms, Biopsy, medicine.medical_treatment, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Multimodal Imaging, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Surgical oncology, Carcinoma, Non-Small-Cell Lung, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, In patient, Stage (cooking), Thoracic Oncology, Radionuclide Imaging, Lung cancer, Aged, Neoplasm Staging, Proportional Hazards Models, Retrospective Studies, Aged, 80 and over, Chemotherapy, business.industry, Induction chemotherapy, Middle Aged, medicine.disease, Neoadjuvant Therapy, Surgery, 3. Good health, Chemotherapy, Adjuvant, Lymphatic Metastasis, 030220 oncology & carcinogenesis, Multivariate Analysis, Female, Non small cell, Neoplasm Recurrence, Local, NODAL, business
Abstract

7043 Background: Pathologic downstaging following induction chemotherapy in patients with stage III-N2 NSCLC is a well-known positive prognostic indicator. However, the predictive factors for locoregional recurrence (LRR) in these patients are largely unknown. Methods: Between 1998-2008, 153 patients with clinically or pathologically-staged III-N2 NSCLC from two cancer centers in the United States were treated with induction chemotherapy and surgery. All patients had pathologic N0-1 disease, and no one received postoperative radiotherapy. LRR were defined as disease recurrence at the surgical site, lymph nodes (levels 1-14 including supraclavicular) or both. Overall survival (OS) was calculated using the Kaplan and Meier method and comparisons were made using the log-rank test. Univariate and multivariate Cox proportional hazards model were used to assess the association of LRR and risk factors. Results: The median follow up time for survivors was 39.3 months. Baseline pretreatment N2 nodal involvement was staged by either pathologic confirmation (18.2%) or PET/CT (81.8%). Overall, the 5 year LRR rate was 30.8% (n=38), with LRR being the first site of failure in 51% (22 of 43). The 5 year OS for patients with LRR compared to those without was 21% versus 60.1%, respectively (p

Published
2012
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29. Comparison of Clinical Stage, Therapy Response, and Patient Outcome Between Squamous Cell Carcinoma and Adenocarcinoma of the Esophagus

Author

David C. Rice, Jaffer A. Ajani, Garrett L. Walsh, Arlene M. Correa, Pooja R. Rohatgi, Norio Fukami, Zhongxing Liao, Jack A. Roth, Stephen G. Swisher, Ara A. Vaporciyan, and Tsung T. Wu

Subjects
Male, Oncology, medicine.medical_specialty, Esophageal Neoplasms, medicine.medical_treatment, Antineoplastic Agents, Adenocarcinoma, Gastroenterology, Disease-Free Survival, Endocrinology, Recurrence, Internal medicine, medicine, Humans, Basal cell, Neoplasms, Squamous Cell, Treatment Failure, Sex Distribution, Esophagus, Stage (cooking), Neoplasm Staging, business.industry, Incidence (epidemiology), medicine.disease, Combined Modality Therapy, Texas, Radiation therapy, stomatognathic diseases, Treatment Outcome, medicine.anatomical_structure, Cohort, Disease Progression, Female, business, Chemoradiotherapy
Abstract

Purpose: To analyze the differences in clinical stage, pathologic response to chemoradiotherapy, patterns of failure, and overall survival (OS) between patients with squamous cell carcinoma (SCC) and adenocarcinoma (ACA) of the esophagus. Patients and Methods: We stratified patients by two histologies, ACA and SCC, and statistically compared their clinical stage, post-therapy pathologic response, patterns of failure, and OS. Results: Of the 235 patients who underwent preoperative chemoradiotherapy, 42 (18%) had SCC and 193 (82%) had ACA. Among the ACA patients, a significantly larger proportion was male (93% vs 7%; p

Published
2005
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33. Predictors for Locoregional Recurrence for Clinical Stage III-N2 Non-small Cell Lung Cancer with Nodal Downstaging After Induction Chemotherapy and Surgery

Author

Amini, Arya, primary, Lou, Feiran, additional, Correa, Arlene M., additional, Baldassarre, Randall, additional, Rimner, Andreas, additional, Huang, James, additional, Roth, Jack A., additional, Swisher, Stephen G., additional, Vaporciyan, Ara A., additional, and Lin, Steven H., additional

Published
2012
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35. Impact of Induction Chemotherapy and Preoperative Chemoradiotherapy on Operative Morbidity and Mortality in Patients with Locoregional Adenocarcinoma of the Stomach or Gastroesophageal Junction

Author

Fujitani, Kazumasa, primary, Ajani, Jaffer A., additional, Crane, Christopher H., additional, Feig, Barry W., additional, Pisters, Peter W., additional, Janjan, Nora, additional, Walsh, Garrett L., additional, Swisher, Stephen G., additional, Vaporciyan, Ara A., additional, Rice, David, additional, Welch, Angela, additional, Baker, Jackie, additional, Faust, Josephine, additional, and Mansfield, Paul F., additional

Published
2007
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36. Comparison of Clinical Stage, Therapy Response, and Patient Outcome Between Squamous Cell Carcinoma and Adenocarcinoma of the Esophagus

Author

Rohatgi, Pooja R., primary, Swisher, Stephen G., additional, Correa, Arlene M., additional, Wu, Tsung-T., additional, Liao, Zhongxing, additional, Walsh, Garrett L., additional, Vaporciyan, Ara A., additional, Rice, David C., additional, Fukami, Norio, additional, Roth, Jack A., additional, and Ajani, Jaffer A., additional

Published
2005
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