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2. Genetic factors associated with prostate cancer conversion from active surveillance to treatment

Author

Jiang, Yu, Meyers, Travis J, Emeka, Adaeze A, Cooley, Lauren Folgosa, Cooper, Phillip R, Lancki, Nicola, Helenowski, Irene, Kachuri, Linda, Lin, Daniel W, Stanford, Janet L, Newcomb, Lisa F, Kolb, Suzanne, Finelli, Antonio, Fleshner, Neil E, Komisarenko, Maria, Eastham, James A, Ehdaie, Behfar, Benfante, Nicole, Logothetis, Christopher J, Gregg, Justin R, Perez, Cherie A, Garza, Sergio, Kim, Jeri, Marks, Leonard S, Delfin, Merdie, Barsa, Danielle, Vesprini, Danny, Klotz, Laurence H, Loblaw, Andrew, Mamedov, Alexandre, Goldenberg, S Larry, Higano, Celestia S, Spillane, Maria, Wu, Eugenia, Carter, H Ballentine, Pavlovich, Christian P, Mamawala, Mufaddal, Landis, Tricia, Carroll, Peter R, Chan, June M, Cooperberg, Matthew R, Cowan, Janet E, Morgan, Todd M, Siddiqui, Javed, Martin, Rabia, Klein, Eric A, Brittain, Karen, Gotwald, Paige, Barocas, Daniel A, Dallmer, Jeremiah R, Gordetsky, Jennifer B, Steele, Pam, Kundu, Shilajit D, Stockdale, Jazmine, Roobol, Monique J, Venderbos, Lionne DF, Sanda, Martin G, Arnold, Rebecca, Patil, Dattatraya, Evans, Christopher P, Dall’Era, Marc A, Vij, Anjali, Costello, Anthony J, Chow, Ken, Corcoran, Niall M, Rais-Bahrami, Soroush, Phares, Courtney, Scherr, Douglas S, Flynn, Thomas, Karnes, R Jeffrey, Koch, Michael, Dhondt, Courtney Rose, Nelson, Joel B, McBride, Dawn, Cookson, Michael S, Stratton, Kelly L, Farriester, Stephen, Hemken, Erin, Stadler, Walter M, Pera, Tuula, Banionyte, Deimante, Bianco, Fernando J, Lopez, Isabel H, Loeb, Stacy, Taneja, Samir S, Byrne, Nataliya, Amling, Christopher L, Martinez, Ann, Boileau, Luc, Gaylis, Franklin D, Petkewicz, Jacqueline, Kirwen, Nicholas, Helfand, Brian T, Xu, Jianfeng, Scholtens, Denise M, Catalona, William J, and Witte, John S

Subjects
Biological Sciences, Genetics, Prostate Cancer, Prevention, Human Genome, Urologic Diseases, Cancer, Aging, Cancer Genomics, 2.1 Biological and endogenous factors, genetics, genome-wide association study, prostate, prostatic neoplasms
Abstract

Men diagnosed with low-risk prostate cancer (PC) are increasingly electing active surveillance (AS) as their initial management strategy. While this may reduce the side effects of treatment for prostate cancer, many men on AS eventually convert to active treatment. PC is one of the most heritable cancers, and genetic factors that predispose to aggressive tumors may help distinguish men who are more likely to discontinue AS. To investigate this, we undertook a multi-institutional genome-wide association study (GWAS) of 5,222 PC patients and 1,139 other patients from replication cohorts, all of whom initially elected AS and were followed over time for the potential outcome of conversion from AS to active treatment. In the GWAS we detected 18 variants associated with conversion, 15 of which were not previously associated with PC risk. With a transcriptome-wide association study (TWAS), we found two genes associated with conversion (MAST3, p = 6.9×10-7 and GAB2, p = 2.0×10-6). Moreover, increasing values of a previously validated 269-variant genetic risk score (GRS) for PC was positively associated with conversion (e.g., comparing the highest to the two middle deciles gave a hazard ratio [HR] = 1.13; 95% Confidence Interval [CI]= 0.94-1.36); whereas, decreasing values of a 36-variant GRS for prostate-specific antigen (PSA) levels were positively associated with conversion (e.g., comparing the lowest to the two middle deciles gave a HR = 1.25; 95% CI, 1.04-1.50). These results suggest that germline genetics may help inform and individualize the decision of AS-or the intensity of monitoring on AS-versus treatment for the initial management of patients with low-risk PC.

Published
2022

8. Surgical and Trauma Capacity Assessment in Rural Haryana, India

Author

Bhatia, Manisha B, Mohan, Srivarshini C, Blair, Kevin J, Boeck, Marissa A, Bhalla, Ashish, Sharma, Sristi, Helenowski, Irene, Tatebe, Leah C, Nwomeh, Benedict C, and Swaroop, Mamta

Subjects
Clinical Research, Physical Injury - Accidents and Adverse Effects, Health Services, Health and social care services research, 8.1 Organisation and delivery of services, Generic health relevance, Good Health and Well Being, Delivery of Health Care, Emergency Medical Services, Emergency Service, Hospital, Equipment and Supplies, Hospital, Global Health, Health Resources, Humans, India, Physical Examination, Rural Population, Trauma Centers, Workforce, Wounds and Injuries, Clinical Sciences, General & Internal Medicine
Abstract

BackgroundTrauma is a major global health problem and majority of the deaths occur in low- and middle-income countries (LMICs), at even higher rates in the rural areas. The three-delay model assesses three different delays in accessing healthcare and can be applied to improve surgical and trauma healthcare delivery. Prior to implementing change, the capacities of the rural India healthcare system need to be identified.ObjectiveThe object of this study was to estimate surgical and trauma care capacities of government health facilities in rural Nanakpur, Haryana, India using the Personnel, Infrastructure, Procedures, Equipment and Supplies (PIPES) and International Assessment of Capacity for Trauma (INTACT) tools.MethodsThe PIPES and INTACT tools were administered at eight government health facilities serving the population of Nanakpur in June 2015. Data analysis was performed per tool subsection, and an overall score was calculated. Higher PIPES or INTACT indices correspond to greater surgical or trauma care capacity, respectively.FindingsSurgical and trauma care capacities increased with higher levels of care. The median PIPES score was significantly higher for tertiary facilities than primary and secondary facilities [13.8 (IQR 9.5, 18.2) vs. 4.7 (IQR 3.9, 6.2), p = 0.03]. The lower-level facilities were mainly lacking in personnel and procedures.ConclusionsSurgical and trauma care capacities at healthcare facilities in Haryana, India demonstrate a shortage of surgical resources at lower-level centers. Specifically, the Primary Health Centers were not operating at full capacity. These results can inform resource allocation, including increasing education, across different facility levels in rural India.

Published
2021

25. Implications of Tumor Characteristics and Treatment Modality on Local Recurrence and Functional Outcomes in Children With Chest Wall Sarcoma: A Pediatric Surgical Oncology Research Collaborative Study

Author

Harris, Courtney J., Helenowski, Irene, Murphy, Andrew J., Mansfield, Sara A., LaQuaglia, Michael P., Heaton, Todd E., Cavalli, Michele, Murphy, Joseph T., Newman, Erika A., Overmen, Richard E., Kartal, Tanvi T., Cooke-Barber, J., Donaher, Addison, Malek, Marcus M., Kalsi, Ranjeet, Kim, Eugene S., Zobel, Michael J., Goodhue, Catherine J., Naik-Mathuria, Bindi J., Jefferson, Imory N., Roach, Jonathan P., Mata, Claudia, Piché, Nelson, Joharifard, Shahrzad, Sultan, Serge, Short, Scott S., Meyers, Rebecka L., Bleicher, Josh, Le, Hau D., Janek, Kevin, Bütter, Andreana, Davidson, Jacob, Aldrink, Jennifer H., Richards, Holden W., Tracy, Elisabeth T., Commander, Sarah J., Fialkowski, Elizabeth A., Troutt, Misty, Dasgupta, Roshni, and Lautz, Timothy B.

Published
2022
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39. A Randomized, Double-Blinded, Placebo-Controlled Trial of Simvastatin to Prevent Recurrent Pancreatitis

Author

Goodman, Marc T., Lo, Simon K., Yadav, Dhiraj, Wu, Bechien U., Jamil, Laith H., Kwok, Karl K., Papachristou, Georgios I., Afghani, Elham, Choi-Kuaea, Yunhee, Waldron, Richard T., Lombardi, Christina, Jeon, Christie Y., Helenowski, Irene B., Richmond, Ellen, Benante, Kelly, Habtezion, Aida, Schering, Tia, Khan, Seema A., Rodriguez, Luz M., and Pandol, Stephen J.

Published
2022
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48. Implications of Tumor Characteristics and Treatment Modality on Local Recurrence and Functional Outcomes in Children with Chest Wall Sarcoma: A Pediatric Surgical Oncology Research Collaborative Study

Author

Harris, Courtney J., Helenowski, Irene, Murphy, Andrew J., Mansfield, Sara A., LaQuaglia, Michael P., Heaton, Todd E., Cavalli, Michele, Murphy, Joseph T., Newman, Erika, Overmen, Richard E., Kartal, Tanvi T., Cooke-Barber, Jo, Donaher, Addison, Malek, Marcus M., Kalsi, Ranjeet, Kim, Eugene S., Zobel, Michael J., Goodhue, Catherine J., Naik-Mathuria, Bindi J., Jefferson, Imory N., Roach, Jonathan P., Mata, Claudia, Piché, Nelson, Joharifard, Shahrzad, Sultan, Serge, Short, Scott S., Meyers, Rebecka L., Bleicher, Josh, Le, Hau D., Janek, Kevin, Bütter, Andreana, Davidson, Jacob, Aldrink, Jennifer H., Richards, Holden W., Tracy, Elisabeth T., Commander, Sarah J., Fialkowski, Elizabeth A., Troutt, Misty, Dasgupta, Roshni, and Lautz, Timothy B.

Published
2020
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