Kekoa Taparra, MD, PhD, MPH

All Publications

• The Lahaina Wildfires and 'Aina Connectedness in the Face of Climate Disasters. JAMA internal medicine Taparra, K., Faust, J. S., Batangan, K. 2024

  Abstract

  This Viewpoint examines the disaster response and climate health concepts following the 2023 Lahaina wildfires in Maui through the perspective of Native Hawaiian leaders and health care workers.

  View details for DOI 10.1001/jamainternmed.2024.3325

  View details for PubMedID 39374007

• Identification of High-Incidence Populations in the United States for anti-Epstein Barr Virus Serologic Screening for Nasopharyngeal Carcinoma. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology Clark, P. E., Taparra, K., Miller, J. A. 2024

  Abstract

  BACKGROUND: In the United States (US), Epstein-Barr Virus (EBV)-associated nasopharyngeal carcinoma (NPC) disproportionately impacts Asian Americans (AA) and Native Hawaiians and other Pacific Islanders (NHPI) who have no access to screening. EBV-based screening trials in Asia have detected most cases at early stages. We sought to identify a US target population for NPC screening and hypothesized that once-lifetime screening could be cost-effective.METHODS: We obtained NPC incidence data from the SEER Asian and Pacific Islander datasets. We estimated the number needed to screen, mortality reduction, and resource utilization using a validated model and performance data from trials. Six evaluated strategies incorporated serology, nasopharyngeal swab PCR, and endoscopy or MRI.RESULTS: Intermediate-incidence and high-incidence populations accounted for 10.7% of US person-years yet 42.7% of cases. Anti-BNLF2b screening with selective endoscopy was the preferred strategy. In high-incidence populations, the median NNS to detect one case was 1,992, with a median of 7.12 NPC deaths averted per 100,000 screened. Screening met the willingness-to-pay threshold in all five high-incidence populations (median ICER/GDP 0.82) and among men in intermediate-incidence populations.CONCLUSIONS: Nearly half of NPC in the US arises among the 10% with AA or NHPI ethnicity. A suitable target population for US screening trials would be men and women age 35-65 of Chinese, Samoan, or Southeast Asian ethnicity, or men age 35-60 of Guamanian/Chamorro, Filipino, or Native Hawaiian ethnicity. Once-lifetime anti-BNLF2b screening could be cost-effective.IMPACT: These data may aid the design of US screening trials. Targeted NPC screening might mitigate health disparities.

  View details for DOI 10.1158/1055-9965.EPI-24-0576

  View details for PubMedID 39361358

• Racial and Ethnic Disparities in Age-Specific All-Cause Mortality During the COVID-19 Pandemic. JAMA network open Faust, J. S., Renton, B., Bongiovanni, T., Chen, A. J., Sheares, K. D., Du, C., Essien, U. R., Fuentes-Afflick, E., Haywood, T., Khera, R., King, T., Li, S. X., Lin, Z., Lu, Y., Marshall, A. D., Ndumele, C. D., Opara, I., Loarte-Rodriguez, T., Sawano, M., Taparra, K., Taylor, H. A., Watson, K. E., Yancy, C. W., Krumholz, H. M. 2024; 7 (10): e2438918

  Abstract

  The end of the COVID-19 public health emergency (PHE) provides an opportunity to fully describe pandemic-associated racial and ethnic mortality disparities. Age-specific excess mortality differences have important downstream implications, especially in minoritized race and ethnicity populations.To characterize overall and age-specific all-cause excess mortality by race and ethnicity during the COVID-19 PHE and assess whether measured differences reflected changes from prepandemic disparities.This cross-sectional study analyzed data of all US residents and decedents during the COVID-19 PHE, aggregated by observed race and ethnicity (at time of death) and age. Statistical analysis was performed from March 2020 to May 2023.COVID-19 PHE period (March 2020 to May 2023).All-cause excess mortality (incident rates, observed-to-expected ratios) and all-cause mortality relative risks before and during the PHE.For the COVID-19 PHE period, data for 10 643 433 death certificates were available; mean (SD) decedent age was 72.7 (17.9) years; 944 318 (8.9%) were Hispanic; 78 973 (0.7%) were non-Hispanic American Indian or Alaska Native; 288 680 (2.7%) were non-Hispanic Asian, 1 374 228 (12.9%) were non-Hispanic Black or African American, 52 905 (0.5%) were non-Hispanic more than 1 race, 15 135 (0.1%) were non-Hispanic Native Hawaiian or Other Pacific Islander, and 7 877 996 (74.1%) were non-Hispanic White. More than 1.38 million all-cause excess deaths (observed-to-expected ratio, 1.15 [95% CI, 1.12-1.18]) occurred, corresponding to approximately 23 million years of potential life lost (YPLL) during the pandemic. For the total population (all ages), the racial and ethnic groups with the highest observed-to-expected all-cause mortality ratios were the American Indian or Alaska Native (1.34 [95% CI, 1.31-1.37]) and Hispanic (1.31 [95% CI, 1.27-1.34]) populations. However, higher ratios were observed in the US population aged 25 to 64 years (1.20 [95% CI, 1.18-1.22]), greatest among the American Indian or Alaska Native (1.45 [95% CI, 1.42-1.48]), Hispanic (1.40 [95% CI, 1.38-1.42]), and Native Hawaiian or Other Pacific Islander (1.39 [95% CI, 1.34-1.44]) groups. In the total population aged younger than 25 years, the Black population accounted for 51.1% of excess mortality, despite representing 13.8% of the population. Had the rate of excess mortality observed among the White population been observed among the total population, more than 252 000 (18.3%) fewer excess deaths and more than 5.2 million (22.3%) fewer YPLL would have occurred.In this cross-sectional study of the US population during the COVID-19 PHE, excess mortality occurred in all racial and ethnic groups, with disparities affecting several minoritized populations. The greatest relative increases occurred in populations aged 25 to 64 years. Documented differences deviated from prepandemic disparities.

  View details for DOI 10.1001/jamanetworkopen.2024.38918

  View details for PubMedID 39392630

• Race Disaggregation and Racial and Ethnic Disparities in US Youth Mortality. JAMA Shontell, R. K., Taparra, K., DeVille, N. V. 2024

  View details for DOI 10.1001/jama.2024.15133

  View details for PubMedID 39230887

• Inclusion of American Indian, Alaska Native, Native Hawaiian, and Pacific Islander Patients in Clinical Trial Travel Time. JAMA oncology Gimmen, M. Y., Calac, A. J., Taparra, K. 2024

  View details for DOI 10.1001/jamaoncol.2024.3405

  View details for PubMedID 39172476

• Racial Disparities in Cancer Stage at Diagnosis and Survival for Adolescents and Young Adults. JAMA network open Taparra, K., Kekumano, K., Benavente, R., Roberto, L., Gimmen, M., Shontell, R., Cakobau, H., Deo, N., Kinslow, C. J., Betof Warner, A., Deville, C., Shing, J. Z., Vo, J. B., Patel, M. I., Pollom, E. 2024; 7 (8): e2430975

  Abstract

  There are limited studies assessing stage at diagnosis and risk of death among all 5 federally defined races in the US among adolescent and young adult (AYA) patients with cancer.To identify racial disparities in stage at diagnosis and survival among AYA patients with cancer.This retrospective cohort study used data from a US national hospital-based oncology database on AYA patients, aged 15 to 39 years, with the 10 deadliest cancers among AYA patients who received a diagnosis from January 1, 2004, to December 31, 2017, with 6 months or more of follow-up. Analyses by race were categorized by the 5 federally defined races in the US: American Indian or Alaska Native, Asian, Black, Native Hawaiian or Other Pacific Islander, and non-Hispanic White (hereafter, White). White patients served as the majority reference group. Statistical analysis was performed from November 2022 to September 2023.The primary end points were late stage at diagnosis (logistic regression with adjusted odds ratios [AORs] and 95% CIs) and overall survival (log-rank tests and Cox proportional hazards regression with adjusted hazard ratios [AHRs] and 95% CIs).A total of 291 899 AYA patients (median age, 33 years [IQR, 28-37 years]; 186 549 female patients [64%]; 189 812 [65%] with stage I or II cancers) were evaluated. The cohort included 1457 American Indian or Alaska Native patients (1%), 8412 Asian patients (3%), 40 851 Black patients (14%), 987 Native Hawaiian or Other Pacific Islander patients (0.3%), and 240 192 White patients (82%). Cancers included breast (n = 79 195 [27%]), lymphoma (n = 45 500 [16%]), melanoma (n = 36 724 [13%]), testis (n = 31 413 [11%]), central nervous system (n = 26 070 [9%]), colon or rectum (n = 22 545 [8%]), cervix (n = 20 923 [7%]), sarcoma (n = 14 951 [5%]), ovary (n = 8982 [3%]), and lung (n = 5596 [2%]). Risk of late-stage diagnosis was higher for Asian (AOR, 1.20; 95% CI, 1.14-1.26), Black (AOR, 1.40; 95% CI, 1.36-1.43), and Native Hawaiian or Other Pacific Islander (AOR, 1.34; 95% CI, 1.16-1.55) patients compared with White patients. Overall survival differed by race for all cancer sites, except cancers of the central nervous system and ovary. Risk of death was higher for American Indian or Alaska Native (AHR, 1.15; 95% CI, 1.02-1.30), Black (AHR, 1.22; 95% CI, 1.19-1.26), and Native Hawaiian or Other Pacific Islander (AHR, 1.25; 95% CI, 1.09-1.44) patients but lower for Asian patients (AHR, 0.90; 95% CI, 0.85-0.95) compared with White patients.This cohort study of AYA patients suggests that stage at diagnosis and survival varied across races for the 10 deadliest AYA cancers. These results support the need for tailored interventions and informed public policy to achieve cancer care equity for all races.

  View details for DOI 10.1001/jamanetworkopen.2024.30975

  View details for PubMedID 39212989

  View details for PubMedCentralID PMC11365006

• Indigenous Representation and Belonging in Cardiology. JAMA cardiology Jones, J. E., Taparra, K. 2024

  View details for DOI 10.1001/jamacardio.2024.1706

  View details for PubMedID 38985456

• How Ending Affirmative Action May Affect Radiation Oncology Workforce and Our Patients: A Collaboration of the American Society of Radiation Oncology, Society of Chairs of Academic Radiation Oncology Programs, Association for Directors of Radiation Oncology Programs, and Association of Residents in Radiation Oncology. International journal of radiation oncology, biology, physics LeCompte, M. C., Gibbs, I. C., Taparra, K., Suneja, G., Jr, C. D., Ii, Z. W., MacDuffie, E., Pinnix, C. C., Kamrava, M., Jimenez, R. B., Currey, A. D., Chen, Y., Franco, I. 2024

  View details for DOI 10.1016/j.ijrobp.2024.06.014

  View details for PubMedID 38944312

• Race and Ethnicity Representation in Phase 2/3 Oncology Clinical Trial Publications: A Systematic Review. JAMA health forum Taparra, K., Benavente, R., Shih, J. J., Gimmen, M. Y., Tominez, P., Kekumano, K. E., Pineda, E., Halualani, G., Cakobau, H., Ludmir, E. B., Deville, C. J., Peppercorn, J., Gomez, S. L., Bosserman, L., Chino, F., Patel, M. I., Shah, C. 2024; 5 (6): e241388

  Abstract

  Importance: The five 1997 Office of Management and Budget races in the US include American Indian or Alaska Native, Asian, Black or African American, Native Hawaiian or Other Pacific Islander, and White, with Hispanic ethnicity. Despite the Affordable Care Act mandating Office of Management and Budget-based collecting and reporting standards, race and ethnicity publishing in medical journals is inconsistent, despite being necessary to achieve health equity.Objective: To quantify race and ethnicity reporting rates and calculate representation quotients (RQs) in published oncology clinical trials.Evidence Review: In this systematic review, PubMed and Embase were queried for phase 2/3 clinical trials of the 6 most common noncutaneous solid cancers, published between January 1, 2012, and December 31, 2022, in 4 high-impact journals. Trial characteristics were recorded. The RQs for each race and ethnicity were calculated by dividing the percent of representation in each clinical trial publication by the percent of year-matched, site-specific incident cancers in the US, compared with Kruskal-Wallis tests with Bonferroni correction (BC). Reporting was compared between journal publications and ClinicalTrials.gov.Findings: Among 1202 publications evaluated, 364 met inclusion criteria: 16 JAMA, 241 Journal of Clinical Oncology, 19 Lancet, and 88 New England Journal of Medicine. Publications included 268 209 patients (171 132 women [64%]), with a median of 356 (IQR, 131-800) patients per publication. Reported race and ethnicity included American Indian or Alaska Native in 52 (14%) publications, Asian in 196 (54%), Black or African American in 215 (59%), Hispanic in 67 (18%), Native Hawaiian or Other Pacific Islander in 28 (8%), and White in 254 (70%). Median RQ varied across race (P<.001 BC), with 1.04 (IQR, 0.09-4.77) for Asian, 0.98 (IQR, 0.86-1.06) for White, 0.42 (IQR, 0.12-0.75) for Black or African American, and 0.00 (IQR, 0.00-0.00) for both American Indian or Alaska Native and Native Hawaiian or Other Pacific Islander patients. Sensitivity analyses showed similar findings on subset analysis for US-only clinical trials. There was significantly less race and ethnicity reporting in the clinical trial publications compared with ClinicalTrials.gov documentation for American Indian or Alaska Native (14% vs 45%; P<.001 per McNemar chi2 test with continuity correction [MC]) and Native Hawaiian or Other Pacific Islander (8% vs 43%; P<.001 MC).Conclusions and Relevance: While most phase 2/3 oncology clinical trials published in high-impact journals report race and ethnicity, most did not report American Indian or Alaska Native and Native Hawaiian or Other Pacific Islander racial categories. Our findings support a call to action for consistent journal policies and transparent race and ethnicity reporting, in alignment with Affordable Care Act-concordant race and ethnicity federal reporting requirements.

  View details for DOI 10.1001/jamahealthforum.2024.1388

  View details for PubMedID 38848090

• Evaluating disparities in receptor status, overall survival, and time to hormone therapy among women with breast cancer Taparra, K. A., DeVille, N. V., Melendez-Ramos, A., Blanco-Portillo, J., Ioannidis, A., Patel, M. I., Pollom, E. L., Horst, K. C. LIPPINCOTT WILLIAMS & WILKINS. 2024

  View details for Web of Science ID 001275557402568

• Disparities in stereotactic radiosurgery practice patterns for treatment of brain metastases: A large national cancer database study Taparra, K. A., Shih, J., Patel, M. I., Pollom, E. L. LIPPINCOTT WILLIAMS & WILKINS. 2024

  View details for Web of Science ID 001275557402566

• Site-specific patterns of early-stage cancer diagnosis during the COVID-19 pandemic. JNCI cancer spectrum Kinslow, C. J., DeStephano, D. M., Neugut, A. I., Taparra, K., Horowitz, D. P., Yu, J. B., Cheng, S. K. 2024

  Abstract

  The COVID-19 pandemic caused widespread disruptions in cancer care. We hypothesized that the greatest disruptions in diagnosis occurred in screen-detected cancers. We identified patients (≥18 years) newly diagnosed with cancer from 2019 to 2020 in the United States National Cancer Database and calculated the change in proportion of early to late-stage cancers using a weighted linear regression. Disruptions in early-stage diagnosis were greater than late-stage diagnosis (17% vs 12.5%). Melanoma demonstrated the greatest relative decrease in early- vs late-stage diagnosis (22.9 vs 9.2%), while the decrease was similar for pancreatic cancer. Compared to breast cancer, cervical, melanoma, prostate, colorectal, and lung cancers showed the greatest disruptions in early-stage diagnosis. Uninsured patients experienced greater disruptions than privately insured patients. Disruptions in cancer diagnosis in 2020 had a larger impact on early-stage disease, particularly screen-detected cancers. Our study supports emerging evidence that primary care visits may play a critical role in early melanoma detection.

  View details for DOI 10.1093/jncics/pkae022

  View details for PubMedID 38521544

• Medical Student Intent to Practice in Underserved Areas. JAMA Akimoto, K. S., Taitano-Ritter, D., Taparra, K. 2024; 331 (9): 800-801

  View details for DOI 10.1001/jama.2023.28309

  View details for PubMedID 38441589

• Recombination map tailored to Native Hawaiians may improve robustness of genomic scans for positive selection. Human genetics Dinh, B. L., Tang, E., Taparra, K., Nakatsuka, N., Chen, F., Chiang, C. W. 2023

  Abstract

  Recombination events establish the patterns of haplotypic structure in a population and estimates of recombination rates are used in several downstream population and statistical genetic analyses. Using suboptimal maps from distantly related populations may reduce the efficacy of genomic analyses, particularly for underrepresented populations such as the Native Hawaiians. To overcome this challenge, we constructed recombination maps using genome-wide array data from two study samples of Native Hawaiians: one reflecting the current admixed state of Native Hawaiians (NH map) and one based on individuals of enriched Polynesian ancestries (PNS map) with the potential to be used for less admixed Polynesian populations such as the Samoans. We found the recombination landscape to be less correlated with those from other continental populations (e.g. Spearman's rho=0.79 between PNS and CEU (Utah residents with Northern and Western European ancestry) compared to 0.92 between YRI (Yoruba in Ibadan, Nigeria) and CEU at 50kb resolution), likely driven by the unique demographic history of the Native Hawaiians. PNS also shared the fewest recombination hotspots with other populations (e.g. 8% of hotspots shared between PNS and CEU compared to 27% of hotspots shared between YRI and CEU). We found that downstream analyses in the Native Hawaiian population, such as local ancestry inference, imputation, and IBD segment and relatedness detections, would achieve similar efficacy when using the NH map compared to an omnibus map. However, for genome scans of adaptive loci using integrated haplotype scores, we found several loci with apparent genome-wide significant signals (|Z-score|>4) in Native Hawaiians that would not have been significant when analyzed using NH-specific maps. Population-specific recombination maps may therefore improve the robustness of haplotype-based statistics and help us better characterize the evolutionary history that may underlie Native Hawaiian-specific health conditions that persist today.

  View details for DOI 10.1007/s00439-023-02625-2

  View details for PubMedID 38157018

• Contextualizing Depression in Pacific Islander Sexual and Gender Minority Youth-Location, History, and Culture. JAMA pediatrics Apana, N., DeVille, N. V., Taparra, K. 2023

  View details for DOI 10.1001/jamapediatrics.2023.5073

  View details for PubMedID 37983055

• Rising From Ruin-Revitalizing Native Hawaiian Health. JAMA Taparra, K., Apana, N. K. 2023

  Abstract

  This Viewpoint offers insight into the health effects of the recent fires in Hawaiʻi and what culturally conscious approaches are needed to ensure the health of Native Hawaiians going forward.

  View details for DOI 10.1001/jama.2023.21427

  View details for PubMedID 37930729

• Diversity in Cancer Care: Current Challenges and Potential Solutions to Achieving Equity in Clinical Trial Participation. Cancer journal (Sudbury, Mass.) Akimoto, K., Taparra, K., Brown, T., Patel, M. I. 2023; 29 (6): 310-315

  Abstract

  ABSTRACT: Access to and participation in cancer clinical trials determine whether such data are applicable, feasible, and generalizable among populations. The lack of inclusion of low-income and marginalized populations limits generalizability of the critical data guiding novel therapeutics and interventions used globally. Such lack of cancer clinical trial equity is troubling, considering that the populations frequently excluded from these trials are those with disproportionately higher cancer morbidity and mortality rates. There is an urgency to increase representation of marginalized populations to ensure that effective treatments are developed and equitably applied. Efforts to ameliorate these clinical trial inclusion disparities are met with a slew of multifactorial and multilevel challenges. We aim to review these challenges at the patient, clinician, system, and policy levels. We also highlight and propose solutions to inform future efforts to achieve cancer health equity.

  View details for DOI 10.1097/PPO.0000000000000675

  View details for PubMedID 37963364

• The US Economic Burden of Health Inequities. JAMA Benavente, R. V., Gimmen, M. Y., Taparra, K. 2023; 330 (12): 1190-1191

  View details for DOI 10.1001/jama.2023.13673

  View details for PubMedID 37750886

• Recombination map tailored to Native Hawaiians improves robustness of genomic scans for positive selection. bioRxiv : the preprint server for biology Dinh, B. L., Tang, E., Taparra, K., Nakatsuka, N., Chen, F., Chiang, C. W. 2023

  Abstract

  Recombination events establish the patterns of haplotypic structure in a population and estimates of recombination rates are used in several downstream population and statistical genetic analyses. Using suboptimal maps from distantly related populations may reduce the efficacy of genomic analyses, particularly for underrepresented populations such as the Native Hawaiians. To overcome this challenge, we constructed recombination maps using genome-wide array data from two study samples of Native Hawaiians: one reflecting the current admixed state of Native Hawaiians (NH map), and one based on individuals of enriched Polynesian ancestries (PNS map) with the potential to be used for less admixed Polynesian populations such as the Samoans. We found the recombination landscape to be less correlated with those from other continental populations (e.g. Spearman's rho = 0.79 between PNS and CEU (Utah residents with Northern and Western European ancestry) compared to 0.92 between YRI (Yoruba in Ibadan, Nigeria) and CEU at 50 kb resolution), likely driven by the unique demographic history of the Native Hawaiians. PNS also shared the fewest recombination hotspots with other populations (e.g. 8% of hotspots shared between PNS and CEU compared to 27% of hotspots shared between YRI and CEU). We found that downstream analyses in the Native Hawaiian population, such as local ancestry inference, imputation, and IBD segment and relatedness detections, would achieve similar efficacy when using the NH map compared to an omnibus map. However, for genome scans of adaptive loci using integrated haplotype scores, we found several loci with apparent genome-wide significant signals (|Z-score| > 4) in Native Hawaiians that would not have been significant when analyzed using NH-specific maps. Population-specific recombination maps may therefore improve the robustness of haplotype-based statistics and help us better characterize the evolutionary history that may underlie Native Hawaiian-specific health conditions that persist today.

  View details for DOI 10.1101/2023.07.12.548735

  View details for PubMedID 37503129

• Definitive Treatment of Brain Metastases From a Neuroendocrine Tumor With Peptide Receptor Radionuclide Therapy With 177Lutetium DOTATATE: A Case Report. Cureus Zhang, V., Taparra, K., Fisher, G., Aparici, C., Soltys, S. G. 2023; 15 (9): e45327

  Abstract

  Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare malignancies that arise from secretory endocrine cells of the gastroenteropancreatic system. Clinical outcomes have improved for patients with GEP-NETs due to the development and recent FDA approval of 177Lutetium DOTATATE. However, the response of brain metastases from GEP-NETs from 177Lutetium DOTATATE is unreported. We present the case of an 81-year-old man with low-grade small bowel GEP-NET with liver and brain metastases treated with a total of six cycles of 177Lutetium DOTATATE. With over three years of follow-up from his initial treatment, his brain metastases have had complete or partial responses, with no need for brain radiotherapy or radiosurgery.

  View details for DOI 10.7759/cureus.45327

  View details for PubMedID 37849592

  View details for PubMedCentralID PMC10577096

• Racial Disparities in 30-day Readmissions after Surgery for Head and Neck Cancer. The Laryngoscope Huang, A. E., Shih, J. J., Sunwoo, J. B., Pollom, E., Taparra, K. 2023

  Abstract

  Native Hawaiians and other Pacific Islanders (NHPI) patients with head and neck cancer are often aggregated with Asian individuals despite evidence of heterogeneous health outcomes and mortality. The aim of this study was to determine the association of race with unplanned 30-day hospital readmission rate after head and neck surgery across the five federally recognized racial categories.This retrospective cohort study used a national hospital-based database and included patients ≥18 years old with diagnostically confirmed, nonmetastatic head and neck cancer of any subsite treated surgically between 2004 and 2017. The primary endpoint was unplanned readmission within 30 days of discharge after primary surgery.A total of 365,834 patients were included who were predominantly White (87%), treated at academic cancer centers (47%), lower income (63%), with early-stage disease (60%), and with thyroid (47%) or oral cavity (23%) cancers. Median follow-up duration was 47 months. Of the 10,717 (3%) readmissions, 5,845 (1.6%) were unplanned. Adjusted for confounders and compared with White patients, NHPI patients had the highest likelihood of unplanned (aOR 2.07, 95%CI 1.16-3.40, p = 0.008) readmissions. Within the NHPI group, patients with lower income (aOR 4.27, 95%CI 1.28-20.4, p = 0.035) and those residing in an urban or rural area (aOR 7.42, 95%CI 1.14-49.5, p = 0.034) were more likely to be readmitted.NHPI patients with head and neck cancers experience significantly higher 30-day readmissions following definitive surgical treatment. These results highlight the importance of racial disaggregation in clinical studies.4 Laryngoscope, 2023.

  View details for DOI 10.1002/lary.30997

  View details for PubMedID 37610178

• MGMT promoter methylation predicts overall survival after chemotherapy for 1p/19q-codeleted gliomas. Clinical cancer research : an official journal of the American Association for Cancer Research Kinslow, C. J., Rae, A. I., Taparra, K., Kumar, P., Siegelin, M. D., Grinband, J., Gill, B. J., McKhann, G. M., Sisti, M. B., Bruce, J. N., Canoll, P. D., Iwamoto, F. M., Horowitz, D. P., Kachnic, L. A., Neugut, A. I., Yu, J. B., Cheng, S. K., Wang, T. J. 2023

  Abstract

  PURPOSE: While MGMT promoter methylation (mMGMT) is predictive of response to alkylating chemotherapy and guides treatment decisions in glioblastoma, its role in grade 2 and 3 glioma remains unclear. Recent data suggests that mMGMT is prognostic of progression-free survival in 1p/19q-codeleted oligodendrogliomas, but an effect on overall survival (OS) has not been demonstrated.EXPERIMENTAL DESIGN: We identified patients with newly diagnosed 1p/19q-codeleted gliomas and known MGMT promoter status in the National Cancer Database from 2010-2019. Multivariable Cox proportional hazards regression modeling was used to assess the effect of mMGMT on OS after adjusting for age, sex, race, co-morbidity, grade, extent of resection, chemotherapy, and radiotherapy.RESULTS: We identified 1,297 eligible patients, 938 (72.3%) of whom received chemotherapy in their initial course of treatment. The MGMT promoter was methylated in 1,009 (77.8%) patients. Unmethylated MGMT (uMGMT) was associated with worse survival compared to mMGMT (70% [95%CI 64-77%] vs. 81% [95%CI 78-85%], P<.001, adjusted hazard ratio [aHR] 2.35 [95%CI 1.77-3.14]). uMGMT was associated with worse survival in patients who received chemotherapy (63% [95%CI 55-73%] vs. 80% [95%CI 76-84%], P<.001, aHR 2.61 [95%CI 1.89-3.60]) but not in patients who did not receive chemotherapy (P=.38, HR 1.31 [95%CI 0.71- 2.42]). Similar results were observed regardless of WHO grade and after single- or multiagent chemotherapy.CONCLUSIONS: Our study demonstrates an association between mMGMT and OS in 1p/19qcodeleted gliomas. MGMT promoter status should be considered as a stratification factor in future clinical trials of 1p/19q-codeleted gliomas that use OS as an endpoint.

  View details for DOI 10.1158/1078-0432.CCR-23-1295

  View details for PubMedID 37611077

• Tailored Mentorship for the Underrepresented & Allies in Radiation Oncology: The ARRO Equity and Inclusion Subcommittee Mentorship Experience Saripalli, A. L., Germino, E. A., Taparra, K., Rattani, A., Pointer, K. B., Singh, S. A., Musunuru, H., Shukla, U. C., Vidal, G., Pereira, I. J., Williams, V. M., Elmore, S. C., Franco, I., Chaurasia, A. R., Rivera, A. ELSEVIER SCIENCE INC. 2023: E10

  View details for Web of Science ID 001060221600021

• Racial Disparities among Asian American, Native Hawaiian, and Other Pacific Islander Patients with Cancer Who Refuse Recommended Radiation Therapy or Surgery. Cancers Lau, B., Tominez, P., Shing, J. Z., Vo, J. B., Pollom, E., Taparra, K. 2023; 15 (13)

  Abstract

  Despite radiation therapy (RT) and surgery being the curative treatments, prior work demonstrated that the aggregated Asian American (AA) and Native Hawaiian and Other Pacific Islanders (NHPI) population refuse RT and surgery at a higher rates than other races. Given that AA and NHPI are distinct groups, data disaggregation is necessary to understand racial and ethnic disparities for treatment refusal. We aimed to (1) compare RT and surgery refusal rates between AA and NHPI populations, (2) assess RT and surgery refusal on overall mortality, and (3) determine predictors of refusing RT and surgery using the United States (U.S.) National Cancer Database. Adjusted odds ratios (aOR) and 95% confidence intervals (95%CI) for treatment refusal were calculated using logistic regression. Adjusted hazard ratios (aHR) were calculated for overall survival using Cox proportional hazard models among propensity score-matched groups. The overall rate of RT refusal was 4.8% and surgery refusal was 0.8%. Compared to East AA patients, NHPI patients had the highest risk of both RT refusal (aOR = 1.38, 95%CI = 1.21-1.61) and surgery refusal (aOR = 1.28, 95%CI = 1.00-1.61). RT refusal significantly predicted higher mortality (aHR = 1.17, 95%CI = 1.08-1.27), whereas surgery refusal did not. Predictors of RT and surgery refusal were older patient age, high comorbidity index, and cancer diagnosis between 2011-2017. The results show heterogenous treatment refusal patterns among AA and NHPI populations, suggesting areas for targeted intervention.

  View details for DOI 10.3390/cancers15133358

  View details for PubMedID 37444468

• Racial disparities in survival and stage at diagnosis among adolescent and young adult patients with cancer Taparra, K. A., Kekumano, K., Benevente, R., Gimmen, M. Y., Kinslow, C., Deville, C., Pollom, E. L. LIPPINCOTT WILLIAMS & WILKINS. 2023

  View details for Web of Science ID 001053772003334

• Race and ethnicity reporting by US federal standards in high-impact phase 2/3 oncology clinical trial publications Taparra, K. A., Benevente, R., Shih, J., Gimmen, M. Y., Tominez, P., Kekumano, K., Pineda, E., Sherman, R., Deville, C., Peppercorn, J. M., Gomez, S. L., Bosserman, L. D., Chino, F., Patel, M. I., Shah, C. S. LIPPINCOTT WILLIAMS & WILKINS. 2023

  View details for Web of Science ID 001053772000314

• Association of MGMT Promotor Methylation With Survival in Low-grade and Anaplastic Gliomas After Alkylating Chemotherapy. JAMA oncology Kinslow, C. J., Mercurio, A., Kumar, P., Rae, A. I., Siegelin, M. D., Grinband, J., Taparra, K., Upadhyayula, P. S., McKhann, G. M., Sisti, M. B., Bruce, J. N., Canoll, P. D., Iwamoto, F. M., Kachnic, L. A., Yu, J. B., Cheng, S. K., Wang, T. J. 2023

  Abstract

  O6-methylguanine-DNA methyltransferase (MGMT [OMIM 156569]) promoter methylation (mMGMT) is predictive of response to alkylating chemotherapy for glioblastomas and is routinely used to guide treatment decisions. However, the utility of MGMT promoter status for low-grade and anaplastic gliomas remains unclear due to molecular heterogeneity and the lack of sufficiently large data sets.To evaluate the association of mMGMT for low-grade and anaplastic gliomas with chemotherapy response.This cohort study aggregated grade II and III primary glioma data from 3 prospective cohort studies with patient data collected from August 13, 1995, to August 3, 2022, comprising 411 patients: MSK-IMPACT, EORTC (European Organization of Research and Treatment of Cancer) 26951, and Columbia University. Statistical analysis was performed from April 2022 to January 2023.MGMT promoter methylation status.Multivariable Cox proportional hazards regression modeling was used to assess the association of mMGMT status with progression-free survival (PFS) and overall survival (OS) after adjusting for age, sex, molecular class, grade, chemotherapy, and radiotherapy. Subgroups were stratified by treatment status and World Health Organization 2016 molecular classification.A total of 411 patients (mean [SD] age, 44.1 [14.5] years; 283 men [58%]) met the inclusion criteria, 288 of whom received alkylating chemotherapy. MGMT promoter methylation was observed in 42% of isocitrate dehydrogenase (IDH)-wild-type gliomas (56 of 135), 53% of IDH-mutant and non-codeleted gliomas (79 of 149), and 74% of IDH-mutant and 1p/19q-codeleted gliomas (94 of 127). Among patients who received chemotherapy, mMGMT was associated with improved PFS (median, 68 months [95% CI, 54-132 months] vs 30 months [95% CI, 15-54 months]; log-rank P < .001; adjusted hazard ratio [aHR] for unmethylated MGMT, 1.95 [95% CI, 1.39-2.75]; P < .001) and OS (median, 137 months [95% CI, 104 months to not reached] vs 61 months [95% CI, 47-97 months]; log-rank P < .001; aHR, 1.65 [95% CI, 1.11-2.46]; P = .01). After adjusting for clinical factors, MGMT promoter status was associated with chemotherapy response in IDH-wild-type gliomas (aHR for PFS, 2.15 [95% CI, 1.26-3.66]; P = .005; aHR for OS, 1.69 [95% CI, 0.98-2.91]; P = .06) and IDH-mutant and codeleted gliomas (aHR for PFS, 2.99 [95% CI, 1.44-6.21]; P = .003; aHR for OS, 4.21 [95% CI, 1.25-14.2]; P = .02), but not IDH-mutant and non-codeleted gliomas (aHR for PFS, 1.19 [95% CI, 0.67-2.12]; P = .56; aHR for OS, 1.07 [95% CI, 0.54-2.12]; P = .85). Among patients who did not receive chemotherapy, mMGMT status was not associated with PFS or OS.This study suggests that mMGMT is associated with response to alkylating chemotherapy for low-grade and anaplastic gliomas and may be considered as a stratification factor in future clinical trials of patients with IDH-wild-type and IDH-mutant and codeleted tumors.

  View details for DOI 10.1001/jamaoncol.2023.0990

  View details for PubMedID 37200021

  View details for PubMedCentralID PMC10196932

• Racial Disparities in Brachytherapy Treatment among Women with Cervical and Endometrial Cancer in the United States. Cancers Taparra, K., Ing, B. I., Ewongwo, A., Vo, J. B., Shing, J. Z., Gimmen, M. Y., Keli'i, K. M., Uilelea, J., Pollom, E., Kidd, E. 2023; 15 (9)

  Abstract

  Brachytherapy improves clinical outcomes among women diagnosed with cervical and endometrial cancers. Recent evidence demonstrates that declining brachytherapy boosts for women with cervical cancer were associated with higher mortality. In this retrospective cohort study, women diagnosed with endometrial or cervical cancer in the United States between 2004 and 2017 were selected from the National Cancer Database for evaluation. Women ≥18 years of age were included for high intermediate risk (PORTEC-2 and GOG-99 definition) or FIGO Stage II-IVA endometrial cancers and FIGO Stage IA-IVA-non-surgically treated cervical cancers. The aims were to (1) evaluate brachytherapy treatment practice patterns for cervical and endometrial cancers in the United States; (2) calculate rates of brachytherapy treatment by race; and (3) determine factors associated with not receiving brachytherapy. Treatment practice patterns were evaluated over time and by race. Multivariable logistic regression assessed predictors of brachytherapy. The data show increasing rates of brachytherapy for endometrial cancers. Compared to non-Hispanic White women; Native Hawaiian and other Pacific Islander (NHPI) women with endometrial cancer and Black women with cervical cancer were significantly less likely to receive brachytherapy. For both NHPI and Black women, treatment at community cancer centers was associated with a decreased likelihood of brachytherapy. The data suggest racial disparities among Black women with cervical cancer and NHPI women with endometrial cancer and emphasize an unmet need for brachytherapy access within community hospitals.

  View details for DOI 10.3390/cancers15092571

  View details for PubMedID 37174037

• Cancer mortality rates by racial/ethnic groups in the United States, 2018-2020. Journal of the National Cancer Institute Haque, A. T., Berrington de Gonzalez, A., Chen, Y., Haozous, E. A., Inoue-Choi, M., Lawrence, W. R., McGee-Avila, J. K., Napoles, A. M., Perez-Stable, E. J., Taparra, K., Vo, J. B., Freedman, N. D., Shiels, M. S. 2023

  Abstract

  BACKGROUND: Starting in 2018, national death certificates included a new racial classification system that accounts for multiple-race decedents and separates Native Hawaiian and Pacific Islander (NHPI) individuals from Asian individuals. We estimated cancer death rates across updated racial/ethnic categories, sex, and age.METHODS: Age-standardized U.S. cancer mortality rates and rate ratios from 2018-2020 among ≥20-year-olds were estimated with national death certificate data by race/ethnicity, sex, age, and cancer site.RESULTS: In 2018, there were approximately 597,000 cancer deaths, 598,000 in 2019, and 601,000 in 2020. Among men, cancer death rates were highest in Black men (298.2/100,000; n=105,632), followed by White (250.8; n=736,319), American Indian/Alaska Native (AI/AN) (249.2; n=3,376), NHPI (205.6; n=1,080), Latino (177.2; n=66,167), and Asian (147.9; n=26,591) men. Among women, Black women had the highest cancer death rates (206.5/100,000; n=104,437), followed by NHPI (192.1; n=1,141), AI/AN (189.9; n=3,239), White (183.0; n=646,865), Latina (128.4; n=61,579), and Asian women (111.4; n=26,396). The highest death rates by age group occurred among NHPI individuals aged 20-49years, and Black individuals aged 50-69 and ≥70years. Asian individuals had the lowest cancer death rates across age groups. Compared to Asian individuals, total cancer death rates were 39% higher in NHPI men and 73% higher in NHPI women.CONCLUSIONS: There were striking racial/ethnic disparities in cancer death rates during 2018-2020. Separating NHPI and Asian individuals revealed large differences in cancer mortality between two groups that were previously combined in vital statistics data.

  View details for DOI 10.1093/jnci/djad069

  View details for PubMedID 37074947

• SUPPORT: SUrvey of Parental Leave POlicies of RadiaTion Oncology Programs and Residency Applicants. Advances in radiation oncology Baniel, C. C., Qu, V., Ponce, S. B., Taparra, K., Beadle, B., Currey, A., Lichter, K. E., Frank, J., Bagshaw, H., Soltys, S., Pollom, E. 2023; 8 (4): 101207

  Abstract

  Recruitment to radiation oncology training programs has recently declined, and gender inequities persist in radiation oncology. Policies that promote inclusivity, such as the updated American College of Graduate Medical Education parental leave policy establishing minimum parental leave requirements, may support recruitment to radiation oncology.We surveyed 2021-2022 radiation oncology residency applicants and program directors (PDs) about program-specific parental leave policies, transparency of parental leave information during the residency application and interview process, and perceptions of the effect of parenthood on residency training, career advancement, and well-being.Of 89 radiation oncology PDs, 29 (33%) completed the survey. Of 154 residency applicants (current fourth-year medical students, international applicants, or postdoctoral fellows) surveyed, 62 (40%) completed the survey. Most applicants planned to start a family during residency (53%) and reported perceived flexibility to start a family influenced their decision to pursue radiation oncology over other career specialties (55%). Many applicants viewed time in residency (nonresearch, 22%), in research (33%), and as early career faculty (24%) as the best time to start a family. A small number of applicants used program-specific parental leave policy information in determining their rank list (11%), and many applicants sought information regarding fertility health care benefits (55%). Many applicants obtained parental leave information verbally, despite expressing a preference for objective means (slide deck, 63%; website, 50%; or handout, 42%) of information sharing. PDs were all supportive of a 6-week maternity leave policy (100% agree or strongly agree with the policy) and did not feel parental leave would negatively affect a resident's ability to pursue an academic (100%) or private practice career (100%).Many radiation oncology residency applicants plan to start families during training, seek and value program-specific parental leave information and health benefits, and prefer objective means of information sharing. These findings likely reflect those who have strong views of parental leave policies.

  View details for DOI 10.1016/j.adro.2023.101207

  View details for PubMedID 37124316

  View details for PubMedCentralID PMC10130339

• Cancer Disparities among Pacific Islanders: A Review of Sociocultural Determinants of Health in the Micronesian Region. Cancers Pineda, E., Benavente, R., Gimmen, M. Y., DeVille, N. V., Taparra, K. 2023; 15 (5)

  Abstract

  It is well appreciated that the social determinants of health are intimately related with health outcomes. However, there is a paucity of literature that explores these themes comprehensively for the indigenous people within Micronesia. Certain Micronesia-specific factors, such as transitions from traditional diets, the consumption of betel nut, and exposure to radiation from the nuclear bomb testing in the Marshall Islands, have predisposed certain Micronesian populations to an increased risk of developing a variety of malignancies. Furthermore, severe weather events and rising sea levels attributed to climate change threaten to compromise cancer care resources and displace entire Micronesian populations. The consequences of these risks are expected to increase the strain on the already challenged, disjointed, and burdened healthcare infrastructure in Micronesia, likely leading to more expenses in off-island referrals. A general shortage of Pacific Islander physicians within the workforce reduces the number of patients that can be seen, as well as the quality of culturally competent care that is delivered. In this narrative review, we comprehensively underscore the health disparities and cancer inequities faced by the underserved communities within Micronesia.

  View details for DOI 10.3390/cancers15051392

  View details for PubMedID 36900185

• HPV-Associated Cancer Incidence by Disaggregated Asian American, Native Hawaiian, and Other Pacific Islander Ethnicity. JNCI cancer spectrum Shing, J. Z., Corbin, J., Kreimer, A. R., Carvajal, L. J., Taparra, K., Shiels, M. S., Vo, J. B. 2023

  Abstract

  BACKGROUND: Asian Americans (AAs) and Native Hawaiians and other Pacific Islanders (NHPIs) have suboptimal human papillomavirus (HPV) vaccination and cancer screening rates. AAs and NHPIs are often aggregated, masking disparities characterized by varying colonization/immigration patterns and cultural/religious beliefs between populations and ethnicities. We examined the incidence of HPV-associated cancers across disaggregated AA and NHPI ethnicities.METHODS: Using the Surveillance, Epidemiology, and End Results "Detailed Asian/Pacific Islander" Database, we calculated 1990-2014 sex-specific age-standardized HPV-associated cancer incidence of cervical carcinoma, oropharyngeal squamous cell carcinoma (SCC), vulvar SCC, vaginal SCC, anal SCC, and penile SCC, by ethnicity: Asian Indian/Pakistani, Chinese, Filipino, Japanese, Kampuchean, Korean, Laotian, Native Hawaiian, other Pacific Islander, and Vietnamese. Trends by calendar period (1990-1996, 1997-2002, 2003-2008, 2009-2014) were estimated using Joinpoint regression.RESULTS: The most common HPV-associated cancer was cervical carcinoma in women and oropharyngeal SCC in men. During 1990-2014, cervical carcinoma incidence per 100,000 ranged from 4.5 (Asian Indian/Pakistani) to 20.7 (Laotian). Cervical carcinoma incidence only statistically significantly declined for Asian Indian/Pakistani, Filipino, Korean, Laotian, and Vietnamese women (range=19.9%-44.1% decline per period). Among men, oropharyngeal SCC incidence per 100,000 ranged from 1.1 (Chinese) to 5.1 (Native Hawaiian). Oropharyngeal SCC incidence only statistically significantly increased for Japanese men (31.0% increase per period). Heterogeneity across ethnicities were observed for other cancer sites.CONCLUSIONS: HPV-associated cancer incidence varied widely between AAs and NHPIs and by ethnicity, underscoring the need for improved data capture of ethnic groups in research and more tailored interventions to better address health disparities between AA and NHPI populations.

  View details for DOI 10.1093/jncics/pkad012

  View details for PubMedID 36790075

• Tailored Mentorship for the Underrepresented & Allies in Radiation Oncology: The ARRO Equity and Inclusion Subcommittee Mentorship Experience. International journal of radiation oncology, biology, physics Germino, E. A., Saripalli, A. L., Taparra, K., Rattani, A., Pointer, K. B., Singh, S. A., Musunuru, H. B., Shukla, U. C., Vidal, G., Pereira, I. J., Williams, V. M., Elmore, S. N., Franco, I., Chaurasia, A. R., Rivera, A. 2023

  Abstract

  PURPOSE: There are limited opportunities for mentorship for Underrepresented in Medicine (URM) trainees and physicians in radiation oncology (RO). The purpose of this study was to create and evaluate a formal mentorship program open to URMs and allies with interests in diversity, equity, and inclusion (DEI).METHODS AND MATERIALS: A mentorship program incorporating a virtual platform was designed by the Association of Residents in Radiation Oncology (ARRO) Equity and Inclusion Subcommittee (EISC). It was structured to include 6 sessions over 6 months with matched mentor/mentee pairs based on responses to a publicized online interest form. A compilation of evidence-based guidelines was provided to optimize the mentorship relationship. Linked pre- and post-program surveys were administered to collect demographic data, define baseline goals and level of support, and evaluate program satisfaction.RESULTS: Thirty-five mentor-mentee pairs were matched; 31 mentees completed the pre-program survey and 17 completed the post-program survey. Pre-program, only 3 mentees (9.7%) reported satisfaction with current mentorship and 5 (16%) reported mechanisms or mentorship in place at their program to support URMs. On the post-program survey, mentees reported high satisfaction with areas of mentorship, mentor attributes, and the program overall. Opportunities for improvement include implementation of mechanisms to enhance communication with mentor-mentee pairs and maintain longitudinal engagement.CONCLUSIONS: In the first-ever tailored mentorship program in RO for URMs and those with DEI interests, our results demonstrate that there is self-reported interest for better mentorship for URMs in RO, and that a nationwide structured mentorship program can address participants' goals with high satisfaction. Program expansion could provide URMs and allies in RO more opportunities for career development and promote a greater sense of community and inclusion within the field.

  View details for DOI 10.1016/j.ijrobp.2023.02.003

  View details for PubMedID 36787853

• A National Cancer Disparities Analysis of Predictors for Radiation Therapy Refusal by Race. International journal of radiation oncology, biology, physics Taparra, K., Qu, V., Lau, B., Pollom, E. 2023

  Abstract

  PURPOSE: Radiation therapy (RT) refusal by patients with cancer is infrequent but is significant because it portends poor outcomes. No prior study has evaluated all five federally defined racial categories with respects to RT refusal. Here we use a large nationally representative population with cancer to determine: 1) which race of patients refuse RT the most and 2) predictive factors for RT refusal by race.MATERIALS/METHODS: A retrospective study included patients ≥18 years old with diagnostically confirmed cancer between 2004-2017, using the National Cancer Database. All patients included were offered RT for first course treatment. Multivariable logistic regression assessed RT refusal (adjusted odds ratio [aOR]) with 95% confidence intervals (95%CI). Analyses were adjusted for patient factors (age, rurality, income, education, and comorbidities) and cancer characteristics (stage, cancer type, facility type, year of diagnosis, and region). Median overall survival was calculated using the Kaplan-Meier method.RESULTS: Of 11,609,044 patients, 2,759,753 patients were included and recommended for RT by the treating physician. Median follow-up was 50 months. RT was refused by 139,383 patients (5.0%), varying by race: 416 NHPI (7.2%), 489 AIAN (5.8%), 118,186 Non-Hispanic White (5.0%), 17,427 Black (4.8%), and 2,865 Asian (4.8%) patients. The rates of annual RT refusal were increasing, especially among NHPI patients. The populations with the highest likelihood of refusing RT were NHPI (aOR=1.53, 95%CI=1.36-1.71), AIAN (aOR=1.24, 95%CI=1.12-1.37), and Black (aOR=1.11, 95%CI=1.09-1.14) patients, compared to Non-Hispanic White patients. Older age and higher comorbidity burden predicted RT refusal across all races. Median overall survival was 81 months and 144 months for patients who refused RT and received RT, respectively.CONCLUSION: Indigenous and Black patients are more likely to refuse RT, which may contribute to inferior cancer outcomes. Understanding NHPI and AIAN patient perspectives and perceptions may elucidate interventions to mitigate these disparities.

  View details for DOI 10.1016/j.ijrobp.2023.01.033

  View details for PubMedID 36764491

• Griseofulvin Radiosensitizes Non-Small Cell Lung Cancer Cells and Activates cGAS. Molecular cancer therapeutics Wang, X., Raman, N., Lemtiri-Chlieh, G., Chang, J., Jagtap, S., Chowdhury, D. D., Ballew, M., Carrieri, F. A., Nguyen, T., Nugent, K., Peck, T., Levine, M. S., Chan, A., Lam, C., Malek, R., Hoang, T., Phillips, R., Cheng, Z., Taparra, K., Connis, N., Hann, C. L., Holland, A., Tran, P. T., Lafargue, A., Wang, H. 2023

  Abstract

  Extra copies of centrosomes are frequently observed in cancer cells. To survive and proliferate, cancer cells have developed strategies to cluster extra-centrosomes to form bipolar mitotic spindles. The aim of this study was to investigate whether centrosome clustering (CC) inhibition (CCi) would preferentially radiosensitize non-small cell lung cancer (NSCLC). Griseofulvin (GF; FDA approved treatment) inhibits CC, and combined with radiation therapy (RT) resulted in a significant increase in the number of NSCLC cells with multipolar spindles, and decreased cell viability and colony formation ability in vitro. In vivo, GF treatment was well tolerated by mice, and the combined therapy of GF and RT resulted in a significant tumor growth delay. Both GF and RT treatment also induced the generation of micronuclei (MN) in vitro and in vivo and activated cyclic GMP-AMP synthase (cGAS) in NSCLC cells. A significant increase in downstream cGAS-STING pathway activation was seen after combination treatment in A549 radioresistant cells that was dependent on cGAS. In conclusion, GF increased RT efficacy in lung cancer preclinical models in vitro and in vivo. This effect may be associated with the generation of MN and the activation of cGAS. These data suggest that the combination therapy of CCi, RT and immunotherapy could be a promising strategy to treat NSCLC.

  View details for DOI 10.1158/1535-7163.MCT-22-0191

  View details for PubMedID 36752776

• From Ashes to Action - Indigenous Health Perspectives on the Lahaina Fires. The New England journal of medicine Taparra, K., Purdy, M., Raphael, K. L. 2023

  View details for DOI 10.1056/NEJMp2309966

  View details for PubMedID 37733295

• Attrition of Indigenous Medical Students Requires Swift Institutional Response. JAMA internal medicine Calac, A. J., Taparra, K. 2022

  View details for DOI 10.1001/jamainternmed.2022.4933

  View details for PubMedID 36315122

• Mental Health and Substance Use Among US Homeless Adolescents. JAMA Taparra, K., Egan, A., Kanagusuku, L. 2022; 328 (9): 889-890

  View details for DOI 10.1001/jama.2022.11622

  View details for PubMedID 36066525

• Mental Health and Substance Use Among US Homeless Adolescents RESPONSE JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Taparra, K., Egan, A., Kanagusuku, L. 2022; 328 (9): 889-890

  View details for Web of Science ID 000855171700028

• Longitudinal Analysis of a Social Media Campaign to Increase Awareness and Engagement Among Radiation Oncologists for Black History Month (BHM) Ewongwo, A., Pereira, I., White, Z., LeCompte, M., Washington, C., Taparra, K., Ponce, S., Elbanna, M., Bajaj, A., Sim, A., Balogun, O., Rivera, A., Chaurasia, A., Vidal, G., Franco, I. LIPPINCOTT WILLIAMS & WILKINS. 2022: S46-S47

  View details for Web of Science ID 000847787800099

• Outcomes of patients with stage I-II Hodgkin lymphoma who had uniform pre-treatment staging with PET/CT and treatment with limited field radiation therapy after chemotherapy. Blood cancer journal Frechette, K. M., Lester, S. C., Taparra, K., Breen, W. G., Martenson, J. A., Hoppe, B. S., Peterson, J. L., Rule, W. G., Stafford, S. L., Stish, B. J., Habermann, T. M., Young, J. R., Harmsen, W. S., Laack, N. N. 2022; 12 (8): 121

  View details for DOI 10.1038/s41408-022-00711-8

  View details for PubMedID 35995767

• Disparities in Survival and Comorbidity Burden Between Asian and Native Hawaiian and Other Pacific Islander Patients With Cancer. JAMA network open Taparra, K., Qu, V., Pollom, E. 2022; 5 (8): e2226327

  Abstract

  Improper aggregation of Native Hawaiian and other Pacific Islander individuals with Asian individuals can mask Native Hawaiian and other Pacific Islander patient outcomes. A comprehensive assessment of cancer disparities comparing Asian with Native Hawaiian and other Pacific Islander populations is lacking.To compare comorbidity burden and survival among East Asian, Native Hawaiian and other Pacific Islander, South Asian, and Southeast Asian individuals with non-Hispanic White individuals with cancer.This retrospective cohort study used a national hospital-based oncology database enriched with Native Hawaiian and other Pacific Islander and Asian populations. Asian, Native Hawaiian and other Pacific Islander, and White individuals diagnosed with the most common cancers who received treatment from January 1, 2004, to December 31, 2017, were included. Patients younger than 18 years, without pathologic confirmation of cancer, or with metastatic disease were excluded. Data were analyzed from January to May 2022.The primary end points were comorbidity burden by Charlson-Deyo Comorbidity Index and overall survival (OS).In total, 5 955 550 patients were assessed, including 60 047 East Asian, 11 512 Native Hawaiian and other Pacific Islander, 25 966 South Asian, 42 815 Southeast Asian, and 5 815 210 White patients. The median (IQR) age was 65 (56-74) years, median (IQR) follow-up was 58 (30-96) months, and 3 384 960 (57%) were women. Patients were predominantly from metropolitan areas (4 834 457 patients [84%]) and the Southern United States (1 987 506 patients [34%]), with above median education (3 576 460 patients [65%]), and without comorbidities (4 603 386 patients [77%]). Cancers included breast (1 895 351 patients [32%]), prostate (948 583 patients [16%]), kidney or bladder (689 187 patients [12%]), lung (665 622 patients [11%]), colorectal (659 165 patients [11%]), melanoma (459 904 patients [8%]), endometrial (307 401 patients [5%]), lymphoma (245 003 patients [4%]), and oral cavity (85 334 patients [1%]) malignant neoplasms. Native Hawaiian and other Pacific Islander patients had the highest comorbidity burden (adjusted odds ratio [aOR], 1.70; 95% CI, 1.47-1.94) compared with Asian and White groups. Asian patients had superior OS compared with White patients for most cancers; only Southeast Asian patients with lymphoma had inferior survival (adjusted hazard ratio [aHR], 1.26; 95% CI, 1.16-1.37). In contrast, Native Hawaiian and other Pacific Islander patients demonstrated inferior OS compared with Asian and White patients for oral cavity cancer (aHR, 1.56; 95% CI, 1.14-2.13), lymphoma (aHR, 1.35; 95% CI, 1.11-1.63), endometrial cancer (aHR, 1.30; 95% CI, 1.12-1.50), prostate cancer (aHR, 1.29; 95% CI, 1.14-1.46), and breast cancer (aHR, 1.09; 95% CI, 1.00-1.18). No cancers among Native Hawaiian and other Pacific Islander patients had superior OS compared with White patients.In this cohort study, compared with White patients with the most common cancers, Asian patients had superior survival outcomes while Native Hawaiian and other Pacific Islander patients had inferior survival outcomes. Native Hawaiian and other Pacific Islander patients had significantly greater comorbidity burden compared with Asian and White patients, but this alone did not explain the poor survival outcomes. These results support the disaggregation of these groups in cancer studies.

  View details for DOI 10.1001/jamanetworkopen.2022.26327

  View details for PubMedID 35960520

• Do no harm: A call to action on COVID-19 and mask requirements. Cancer Patel, M. I., Wood, E. H., Charlot, M., Florez, N., Duron, Y., Jeames, S. E., Taparra, K. A., Velazquez Manana, A., Jain, S. 2022

  View details for DOI 10.1002/cncr.34411

  View details for PubMedID 35913498

• Data aggregation hides Pacific Islander health disparities. Lancet (London, England) Taparra, K., ʻOiwi, K., Pellegrin, K. 2022

  View details for DOI 10.1016/S0140-6736(22)01100-X

  View details for PubMedID 35717993

• Disaggregation of Asian American and Pacific Islander Women With Stage 0-II Breast Cancer Unmasks Disparities in Survival and Surgery-to-Radiation Intervals: A National Cancer Database Analysis From 2004 to 2017. JCO oncology practice Taparra, K., Dee, E. C., Dao, D., Patel, R., Santos, P., Chino, F. 2022: OP2200001

  Abstract

  Aggregation of Asian Americans (AAs) with Native Hawaiians and Other Pacific Islanders (NHPIs) masks significant health disparities. We evaluated overall survival (OS) and surgery-to-radiation intervals (STRIs) among AA and NHPI women with early-stage breast cancer.This National Cancer Database study included women with stage 0-II breast cancer diagnosed between 2004 and 2017. STRI was defined as days from surgery to radiation. Patients were stratified by adjuvant treatment. AAs were disaggregated into geographically relevant subpopulations: East, South, and Southeast Asians. Kaplan-Meier estimates and log-rank tests assessed survival. Cox proportional hazard and linear regression were adjusted for clinical and sociodemographic factors.In total, 578,927 women were included (median age 61 years, median follow-up 65 months, and 10-year OS 83%). AA and NHPI 10-year OS was 91% overall; subpopulation 10-year OS was 92% for East Asian, 90% for South Asian, 90% for Southeast Asian, and 83% for NHPI. On multivariable analysis, compared with non-Hispanic White, NHPI women had worse survival (adjusted hazard ratio [aHR] = 1.38; 95% CI, 1.09 to 1.77); all AA subpopulations had improved survival: East Asian (aHR = 0.57; 95% CI, 0.48 to 0.69), South Asian (aHR = 0.66; 95% CI, 0.51 to 0.84), and Southeast Asian (aHR = 0.78; 95% CI, 0.65 to 0.94). The AA and NHPI median STRI for was 73 days overall; the disaggregated median STRI was 68 days for East Asian, 80 days for South Asian, 77 days for Southeast Asians, and 81 days for NHPI. On adjusted analysis, compared with non-Hispanic White, Southeast Asians and NHPI had longer STRI by 6.6 (95% CI, 4.3 to 8.9) and 10.0 (95% CI, 5.8 to 14) days, respectively.Breast cancer disparities exist among disaggregated AA and NHPI subpopulations. Data disaggregation insights may lead to interventions to overcome these disparities, such as optimizing time-to-treatment for select populations.

  View details for DOI 10.1200/OP.22.00001

  View details for PubMedID 35594493

• Ancestral Stem Cell Reprogramming Genes Active in Hemichordate Regeneration FRONTIERS IN ECOLOGY AND EVOLUTION Humphreys, T., Weiser, K., Arimoto, A., Sasaki, A., Uenishi, G., Fujimoto, B., Kawashima, T., Taparra, K., Molnar, J., Satoh, N., Marikawa, Y., Tagawa, K. 2022; 10

  View details for DOI 10.3389/fevo.2022.769433

  View details for Web of Science ID 000763643300001

• Disaggregating Asian American and Pacific Islanders unmasks disparities in survival, time-to-surgery, and surgery-to-radiation intervals among women with Stage I-III breast cancer: An NCDB analysis from 2004-2016 Taparra, K., Dee, E., Dao, D., Patel, R., Santos, P., Chino, F. AMER ASSOC CANCER RESEARCH. 2022

  View details for DOI 10.1158/1538-7755.DISP21-PR-15

  View details for Web of Science ID 000788061800299

• Low-Cost, Multi-Center, Longitudinal Remote Training Improves Confidence in Head and Neck Contouring Li, B., Hirata, E. Y., Baclay, J. M., Henson, L., Flores, J., Taparra, K., Hu, K. S., Reddy, J., Mcgee, L. A., Patel, S. H., Sanghvi, P. ELSEVIER SCIENCE INC. 2021: E348

  View details for Web of Science ID 000715803800707

• The Impact of COVID-19 on Radiation Oncology Residency Applicant Away Rotations, Interviews, and Rank Lists: A Comparison Between the 2020 Match and 2021 Match. Advances in radiation oncology Taparra, K., Ebner, D. K., Cruz, D. D., Holliday, E. B. 2021: 100842

  Abstract

  Background: The COVID-19 pandemic modified the Residency Match process for fourth-year medical students. In-person away rotations were discouraged, interviews were virtual, and traditional factors used to rank programs were absent. Here, we compare survey results administered to both the 2020 and 2021 Match applicants to assess the influence of the pandemic on the RO Match process.Methods: An Institutional Review Board approved prospective cross-sectional study was conducted. The 2020 and 2021 RO Match applicants at a large RO program were invited to participate. Descriptive summary statistics were assessed.Results: The 2020 and 2021 Matches each had seventy-six applicants complete the survey with response rates of 54% and 57%, respectively. The two groups were predominantly white, cisgender male, single, and without children. While 11% of 2020 applicants did not complete away rotations, 45% of 2021 applicants did not. For 2021 Match applicants, 65% of away rotations were performed virtually while 51% were not for medical school credit. 84% of applicants were satisfied with virtual interviews and 72% felt cost savings were worth not having in-person interviews. While 49% of Match 2020 applicants spent >$5,000 in interview costs, 0% of the Match 2021 applicants did so, with 45% spending <$100. Post-interview communications from programs increased during the pandemic from 36% to 42% in 2020 Match and 2021 Match, respectively. While program culture was the most common factor influencing 2021 Match applicants program rankings, half of applicants did not gain a sense of program culture during virtual interviews.Conclusions: We find 2021 Match applicants completed fewer away rotations, were satisfied with virtual interviews/reduced costs, and did not gain a sense of program culture through virtual rotations/interviews despite it being the most important ranking factor reported. This study supports further exploration of virtual away rotations and virtual interviews moving forward beyond the pandemic.

  View details for DOI 10.1016/j.adro.2021.100842

  View details for PubMedID 34729444

• Disaggregating Pacific Islanders and major Asian subpopulations to reveal hidden breast cancer disparities Taparra, K., Dee, E., Dao, D., Patel, R., Santos, P. G., Chino, F. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2020.39.28_suppl.80

  View details for Web of Science ID 000707130200079

• Racial and Ethnic Disparities in Rates of Invasive Second Breast Cancer Among Women With Ductal Carcinoma In Situ in Hawai'i. JAMA network open Taparra, K., Fukui, J., Killeen, J., Sumida, K., Loo, L. W., Hernandez, B. Y. 2021; 4 (10): e2128977

  Abstract

  Importance: Women with ductal carcinoma in situ (DCIS) may develop a subsequent invasive second breast cancer (SBC). Understanding the association of racial and ethnic factors with the development of invasive SBC may help reduce overtreatment and undertreatment of women from minority groups.Objective: To evaluate risk factors associated with developing invasive ipsilateral SBC (iiSBC) and invasive contralateral SBC (icSBC) among women with an initial diagnosis of DCIS who are from racial and ethnic minority populations.Design, Setting, and Participants: This retrospective cohort study used deidentified data from the Hawai'i Tumor Registry of 6221 female Hawai'i residents aged 20 years or older who received a diagnosis of DCIS between January 1, 1973, and December 31, 2017. The 5 most populous ethnic groups were compared (Chinese, Filipino, Japanese, Native Hawaiian, and White). Data analysis was performed from 2020 to 2021.Exposures: Patient demographic and clinical characteristics and the first course of treatment.Main Outcome and Measures: The a priori study outcome was the development of invasive SBC. Logistic regression was used to identify factors associated with invasive SBC. Factors that were significant on unadjusted analyses were included in the adjusted models (ie, age, race and ethnicity, diagnosis year, DCIS histologic characteristics, laterality, hormone status, and treatment).Results: The racial and ethnic distribution of patients with DCIS across the state's most populous groups were 2270 Japanese women (37%), 1411 White women (23%), 840 Filipino women (14%), 821 Native Hawaiian women (13%), and 491 Chinese women (8%). Women of other minority race and ethnicity collectively comprised 6% of cases (n=388). A total of 6221 women (age range, 20 to ≥80 years) were included in the study; 4817 (77%) were 50 years of age or older, 4452 (72%) received a diagnosis between 2000 and 2017, 2581 (42%) had well or moderately differentiated histologic characteristics, 2383 (38%) had noninfiltrating intraductal DCIS, and 2011 (32%) were treated with mastectomy only. Of these 6221 women, 444 (7%) developed invasive SBC; 190 developed iiSBC (median time to SBC diagnosis, 7.8 years [range, 0.5-30 years]) and 254 developed icSBC (median time to SBC diagnosis, 5.9 years [range, 0.5-28.8 years]). On adjusted analysis, women who developed iiSBC were more likely to be younger than 50 years (adjusted odds ratio [aOR], 1.49; 95% CI, 1.08-2.06), Native Hawaiian (aOR, 3.28; 95% CI, 2.01-5.35), Filipino (aOR, 1.94; 95% CI, 1.11-3.42), Japanese (aOR, 1.58; 95% CI, 1.01-2.48), and untreated (aOR, 2.29; 95% CI, 1.09-4.80). Compared with breast-conserving surgery (BCS) alone, there was a decreased likelihood of iiSBC among women receiving BCS and radiotherapy (aOR, 0.45; 95% CI, 0.27-0.75), BCS and systemic treatment with or without radiotherapy (aOR, 0.40; 95% CI, 0.23-0.69), mastectomy only (aOR, 0.23; 95% CI, 0.13-0.39), and mastectomy and systemic treatment (aOR, 0.57; 95% CI, 0.33-0.96). Women who developed an icSBC were more likely to be Native Hawaiian (aOR, 1.69; 95% CI, 1.10-2.61) or Filipino (aOR, 1.70; 95% CI, 1.10-2.63). Risk of both iiSBC and icSBC decreased in the later years of diagnosis (2000-2017) compared with the earlier years (1973-1999).Conclusions and Relevance: This study suggests that Native Hawaiian and Filipino women who initially received a diagnosis of DCIS were more likely to subsequently develop both iiSBC and icSBC. Japanese women and younger women were more likely to develop iiSBC. Subpopulation disaggregation may help guide clinical treatment and screening decisions for at-risk subpopulations.

  View details for DOI 10.1001/jamanetworkopen.2021.28977

  View details for PubMedID 34668945

• Health care costs for adolescents and young adults with cancer: a Wisconsin community-based hospital study between 2005 and 2020. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer Taparra, K., Fitzsimmons, A., Frankki, S., De Wall, A., Chino, F., Peters, A. 2021

  Abstract

  INTRODUCTION: Adolescents and young adults (AYA) with cancer are at risk of high cumulative healthcare system costs potentially associated with poor health and financial outcomes. Although this has been studied at academic centers, little data on AYA costs at community-based practices exist. The goals of this study were to understand direct health care costs for AYA patients, identify factors for high costs, and assess how total health care costs may relate to survival.METHODS: AYA patients (15-39years) treated at a community hospital in Wisconsin (USA) between 2005 and 2020 were identified. Patient demographics, cancer characteristics, therapies, support services, and all direct health care charges (including up to 1year prior to diagnosis to capture any diagnostic workup) were collected. Logistic and Cox proportional hazard regression models identified factors associated with high costs and survival, respectively.RESULTS: The 388 AYA patients had a median follow-up of 9years (97% survival). Most were 30-39years (62%), female (61%), white (95%), diagnosed early-stage (85%), and underwent surgery (83%). Complete health care costs were available for 233 patients (60%). Median total costs per patient were $123K (range, $73-$215K). On adjusted analysis, higher direct health care costs (>$125K) were associated with greater odds of hospital admissions (odds ratio [OR]=1.7, 95% CI=1.35-2.27), chemotherapy (OR=4.1, 95% CI=1.44-12.70), and breast cancer diagnosis (OR=3.8, 95% CI=1.07-14.70). Living farther from the hospital (OR=0.1, 95% CI=0.02-0.50), later year of diagnosis (OR=0.7, 95% CI=0.55-0.77), and uninsured/unknown insurance status (OR=0.1, 95% CI=0.01-0.57) were associated with decreased odds of having higher health care costs. On adjusted analysis, death was associated with greater odds of higher direct health care costs per $125K (hazards ratio [HR]=7.9, 95% CI=2.22-27.80) and radiation (HR=31.8, 95% CI=3.15-321) but lower odds of hormone therapy (HR=0.1, 95% CI=0.01-0.72) and later year of diagnosis (HR=0.3, 95% CI=0.12-0.60).CONCLUSION: High direct health care costs among AYA patients are associated with hospital admissions, chemotherapy, breast cancer diagnosis, hospital proximity, and earlier year of diagnosis. Death was associated with high direct health care costs, earlier years of diagnosis, and radiation therapy. Total health care costs in community-based hospitals should be considered in the context of AYA patients with cancer.

  View details for DOI 10.1007/s00520-021-06584-0

  View details for PubMedID 34564776

• Native Hawaiian and Other Pacific Islander Representation Among US Allopathic Medical Schools, Residency Programs, and Faculty Physicians. JAMA network open Taparra, K., Deville, C. J. 2021; 4 (9): e2125051

  View details for DOI 10.1001/jamanetworkopen.2021.25051

  View details for PubMedID 34542620

• Why an Increasing Number of Unmatched Residency Positions in Radiation Oncology? A Survey of Fourth-Year Medical Students ADVANCES IN RADIATION ONCOLOGY Blitzer, G. C., Parekh, A. D., Chen, S., Taparra, K., Kahn, J. M., Fields, E. C., Stahl, J. M., Rosenberg, S. A., Buatti, J. M., Laucis, A. M., Wang, Y., Mayhew, D. L., McDonald, A. M., Harari, P. M., Brower, J. 2021; 6 (5): 100743

  Abstract

  The number of US fourth-year medical students applying to radiation oncology has decreased during the past few years. We conducted a survey of fourth-year medical students to examine factors that may be influencing the decision to pursue radiation oncology.An anonymous online survey was sent to medical students at 9 participating US medical schools.A total of 232 medical students completed the survey. Of the 153 students who stated they were never interested in radiation oncology, 77 (50%) reported never having been exposed to the specialty as their reason for not pursuing radiation oncology. The job market was the most commonly cited factor among students who said they were once interested in but ultimately chose not to pursue radiation oncology. Conversely, the recent low pass rates for board examinations and a perception of a lack of diversity within radiation oncology had the least influence.Despite discussion of potential measures to address this disquieting trend, there have been minimal formal attempts to characterize and address potential causes of a decreasing interest in radiation oncology. This study's data are consistent with previous research regarding the trend of decreased medical student interest in radiation oncology and may be used as part of ongoing introspective assessment to inform future change within radiation oncology.

  View details for DOI 10.1016/j.adro.2021.100743

  View details for Web of Science ID 000702562300002

  View details for PubMedID 34466713

  View details for PubMedCentralID PMC8385400

• Away Rotations, Interviews, and Rank Lists: Radiation Oncology Residency Applicant Perspectives on the 2020 Match Process ADVANCES IN RADIATION ONCOLOGY Taparra, K., Ebner, D. K., De La Cruz, D., Holliday, E. B. 2021; 6 (4): 100696

  Abstract

  Using 2020 match applicants, the purpose of this study was to identify baseline applicant perspectives on the match process surveying (1) away rotations, (2) interview/postinterview communications, and (3) factors influencing applicant rank order lists.Applicants in the 2020 match cycle at a large radiation oncology (RO) residency program received a questionnaire covering demographics and the match process: away rotations, interview/postinterview communications, and ranking. Univariable and multivariable logistic regression analyses were used to identify factors associated with completing fewer away rotations.Of 141 surveys sent, 76 were completed, for a response rate of 54%. Most applicants were White, male, and matched into RO. One in 3 applicants did not have a home RO program. Most applicants completed 2 RO rotations (ie, a home rotation and an additional away rotation; range, 0-4 total rotations); RO rotations influenced the applicant rank order lists and the ultimate match result for 94% and 79% of applicants, respectively. Forty-seven percent of applicants reported being asked inappropriate questions during the interview (eg, parental or marital status). Applicants did not perceive a consistent message regarding postinterview communications from program directors. Most applicants were contacted postinterview. Interviews cost most applicants more than $5000. Thirty-seven percent of respondents reported submitting a letter of interest after the interview, hoping to improve their rank. When applying to programs, general reputation and location were the most common influential factors mentioned. When ranking programs, informal conversations with residents and program culture observations were the most common influential factors mentioned. Based on multivariable analysis, applicants who completed fewer RO rotations (including away rotations) had greater odds of matching to their home program (odds ratio [OR], 12.05; 95% CI, 1.27-206.69), lower odds of program location influencing where to apply (OR, 0.04; 95% CI, 0.003-0.37), and lower odds of the program's general reputation affecting their rank list (OR, 0.04; 95% CI, 0.001-0.47).The results suggest that medical students perceive away rotations as an important influencer of their match process. Although applicants and program directors both participate in postinterview communications, interactions with residents influence rank order lists. These data may serve as an up-to-date baseline to evaluate the influence of the COVID-19 pandemic on the RO match process.

  View details for DOI 10.1016/j.adro.2021.100696

  View details for Web of Science ID 000692613400036

  View details for PubMedID 34113741

  View details for PubMedCentralID PMC8170351

• Metastasis-directed Therapy Prolongs Efficacy of Systemic Therapy and Improves Clinical Outcomes in Oligoprogressive Castration-resistant Prostate Cancer EUROPEAN UROLOGY ONCOLOGY Deek, M. P., Taparra, K., Phillips, R., Velho, P., Gao, R. W., Deville, C., Song, D. Y., Greco, S., Carducci, M., Eisenberger, M., DeWeese, T. L., Denmeade, S., Pienta, K., Paller, C. J., Antonarakis, E. S., Olivier, K. R., Park, S. S., Tran, P. T., Stish, B. J. 2021; 4 (3): 447-455

  Abstract

  Available therapies for castrate-resistant prostate cancer (CRPC) confer minimal survival advantage; thus, there is interest in metastasis-directed therapy (MDT) for oligometastatic or oligoprogressive disease to improve outcomes. Here, we describe outcomes of oligoprogressive CRPC treated with stereotactic ablative radiotherapy (SABR).To report outcomes of oligoprogressive CRPC treated with MDT using SABR.Patients with oligoprogressive CRPC were retrospectively evaluated, and outcomes following MDT were reported. Outcomes were additionally compared with oligoprogressive CRPC treated with change in systemic therapy alone.SABR to oligoprogressive lesions.Outcomes of interest were time to prostate-specific antigen (PSA) failure, time to next intervention (TTNI), distant metastasis-free survival (DMFS), and overall survival. Survival analysis was performed using the Kaplan-Meier method, and univariable analysis and multivariable analysis (MVA) were performed.A total of 68 patients were included. After MDT, median time to PSA recurrence, TTNI, and DMFS were 9.7, 15.6, and 10.8 months, respectively. A total of 112 lesions were treated, and the cumulative incidences of local failure at 12 and 24 months were 2.1% and 13.8%, respectively. Factors associated with the risk of local recurrence on univariable analysis were age (hazard ratio [HR] 1.07, p =  0.03) and Gleason grade group (HR 2.20, p =  0.07). Compared with change in systemic therapy alone (n = 52), MDT (n = 31) was associated with improved median time to PSA failure (9.7 vs 4.2 months, p =  0.066)), TTNI (14.9 vs 8.8 months, p =  0.025), and DMFS (12.7 vs 8.9 months, p = 0.045), and remained associated with improved outcomes on MVA.In a retrospective cohort of oligoprogressive CRPC patients, MDT was associated with favorable outcomes and improved cancer control as compared with change in systemic treatment alone. Future prospective trials are needed to confirm these findings.In this report, we retrospectively analyzed outcomes of patients with oligoprogressive castrate-resistant prostate cancer treated with radiation therapy to progressing lesions. Our results suggest that treatment of these lesions with radiation therapy can result in sustained periods of disease-free survival and might add benefit in addition to systemic therapy at the time of progression. These results need to be verified in a prospective trial to identify the optimal integration of radiation therapy into metastatic castrate-resistant prostate cancer.

  View details for DOI 10.1016/j.euo.2020.05.004

  View details for Web of Science ID 000656890300016

  View details for PubMedID 32536574

  View details for PubMedCentralID PMC7788526

• Racial disparities among women who develop invasive secondary breast cancer. Taparra, K., Fukui, J., Killeen, J., Sumida, K. M., Loo, L., Hernandez, B. Y. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2021.39.15_suppl.e18523

  View details for Web of Science ID 000708120303126

• Health care costs among adolescent young adults with cancer at a community-based hospital. Taparra, K., Fitzsimmons, A., Frankki, S. M., DeWall, A., Chino, F., Peters, A. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2021.39.15_suppl.e18857

  View details for Web of Science ID 000708120304085

• The transactivation domain of TWIST1 is required for TWIST1-induced aggressiveness in non-small cell lung cancer. Lafargue, A., Wang, H., Chettiar, S. T., Gajula, R. P., Smack, C., Siddiqui, I., Taparra, K., Lam, C., Carrieri, F., Nugent, K., Zachara, N., Tran, P. T. AMER ASSOC CANCER RESEARCH. 2021

  View details for Web of Science ID 000641160600095

• Radiation Oncology Application and Match Patterns, Pre- and Post-SOAP (Supplemental Offer and Acceptance Program) from 2012 to 2020 PRACTICAL RADIATION ONCOLOGY Chowdhary, M., Taparra, K., Bates, J. E., Royce, T. J. 2021; 11 (2): 152-153

  View details for DOI 10.1016/j.prro.2020.05.009

  View details for Web of Science ID 000631929900012

  View details for PubMedID 33158778

• The Game Continues: Seeking Clarity in the Radiation Oncology Match. Advances in radiation oncology Ebner, D. K., Taparra, K., Olivier, K. R. 2021; 6 (2): 100627

  Abstract

  Though the previous Gaming the Match agreement offered guidance to programs on how best to approach the Match process, guidance for applicants remains inconsistent. Here we review and propose guidelines by which the spirit of the Match may better be achieved for both program directors and applicants alike.

  View details for DOI 10.1016/j.adro.2020.11.012

  View details for PubMedID 33851062

• Navigating Native Hawaiian and Pacific Islander Cancer Disparities From a Cultural and Historical Perspective JCO ONCOLOGY PRACTICE Taparra, K., Miller, R. C., Deville, C. 2021; 17 (3): 130-+

  View details for DOI 10.1200/OP.20.00831

  View details for Web of Science ID 000655506700022

  View details for PubMedID 33497251

• Patterns of Recurrence and Modes of Progression After Metastasis-Directed Therapy in Oligometastatic Castration-Sensitive Prostate Cancer INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Deek, M. P., Taparra, K., Dao, D., Chan, L., Phillips, R., Gao, R. W., Kwon, E. D., Deville, C., Song, D. Y., Greco, S., Carducci, M. A., Eisenberger, M., DeWeese, T. L., Denmeade, S., Pienta, K., Paller, C. J., Antonarakis, E. S., Olivier, K. R., Park, S. S., Stish, B. J., Tran, P. T. 2021; 109 (2): 387-395

  Abstract

  Metastasis-directed therapy (MDT) is increasingly used in castration-sensitive oligometastatic prostate cancer because it prolongs progression-free survival (PFS) and androgen deprivation free survival. Here we describe patterns of recurrence and identify modes of progression after MDT using SABR.Two hundred fifty-eight patients with castration-sensitive oligometastatic prostate cancer (≤5 lesions at staging) were retrospectively identified from a multi-institutional database. Descriptive patterns of recurrence and modes of progression were reported. Other outcomes including median time to prostate-specific antigen (PSA) recurrence, time to next intervention, distant metastasis-free survival, overall survival, and biochemical PFS (bPFS) were reported. Survival analysis was performed using the Kaplan-Meier method, and multivariable analysis was performed.Median follow-up was 25.2 months, and 50.4% of patients received concurrent androgen deprivation. Median time to PSA recurrence was 15.7 months, time to next intervention was 28.6 months, distant metastasis-free survival was 19.1 months, and bPFS was 16.1 months. Two-year overall survival was 96.8%. On multivariable analysis, factors associated with bPFS included age (hazard ratio [HR], 1.03; P = .04), N1 disease at diagnosis (HR, 2.00; P = .02), M1 disease at diagnosis (HR, 0.44; P = .01), initial PSA at diagnosis (HR, 1.002; P = <.001), use of androgen deprivation therapy (HR, 0.41; P < .001), pre-SABR PSA (HR, 1.02; P = .01), and use of enhanced imaging for staging (HR, 2.81; P = .001). Patterns of progression favored an osseous component at recurrence; in patients initially treated to a bone lesion alone, the vast majority (86.5%) experienced a recurrence that included an osseous site. Patients treated initially to a nodal site alone tended to recur in a node only (64.5%); however, there was also a significant minority with an osseous component of recurrence at progression (32.3%). Modes of progressors were class I (patients with long term control [no recurrence ≥18 months after therapy]) occurring in 40.9%, class II (oligoprogressors [≤3 lesions at recurrence]) occurring in 36% (including 7.9% of patients with PSA recurrence but no metastatic disease), and class III (polyprogressors [>3 lesions]) occurring in 23.1% of patients.After MDT, the majority of patients have long-term control or oligoprogression (class I or II). Recurrence tended to occur in osseous sites. These findings, if validated, have implications for future integration of MDT and clinical trial design.

  View details for DOI 10.1016/j.ijrobp.2020.08.030

  View details for Web of Science ID 000607368300014

  View details for PubMedID 32798608

  View details for PubMedCentralID PMC7856169

• Pacific Islanders Searching for Inclusion in Medicine. JAMA health forum Taparra, K. 2021; 2 (2): e210153

  View details for DOI 10.1001/jamahealthforum.2021.0153

  View details for PubMedID 36218798

• Prostate Cancer Disparities in Risk Group at Presentation and Access to Treatment for Asian Americans, Native Hawaiians, and Pacific Islanders: A Study With Disaggregated Ethnic Groups. JCO oncology practice Jain, B., Ng, K., Santos, P. M., Taparra, K., Muralidhar, V., Mahal, B. A., Vapiwala, N., Trinh, Q. D., Nguyen, P. L., Dee, E. C. 2021: OP2100412

  Abstract

  We identified (1) differences in localized prostate cancer (PCa) risk group at presentation and (2) disparities in access to initial treatment for Asian American, Native Hawaiian, and Pacific Islander (AANHPI) men with PCa after controlling for sociodemographic factors.We assessed all patients in the National Cancer Database with localized PCa with low-, intermediate-, and high-risk disease who identified as Thai, White, Asian Indian, Chinese, Vietnamese, Korean, Japanese, Filipino, Hawaiian, Pacific Islander, Laotian, Pakistani, Kampuchean, and Hmong. Multivariable logistic regression defined adjusted odds ratios (AORs) with 95% CI of (1) presenting at progressively higher risk group and (2) receiving treatment or active surveillance with intermediate- or high-risk disease, adjusting for sociodemographic and clinical factors.Among 980,889 men (median age 66 years), all AANHPI subgroups with the exception of Thai (AOR = 0.84 [95% CI, 0.58 to 1.21], P > .05), Asian Indian (AOR = 1.12 [95% CI, 1.00 to 1.25], P > .05), and Pakistani (AOR = 1.34 [95% CI, 0.98 to 1.83], P > .05) men had greater odds of presenting at a progressively higher PCa risk group compared with White patients (Chinese AOR = 1.18 [95% CI, 1.11 to 1.25], P < .001; Japanese AOR = 1.36 [95% CI, 1.26 to 1.47], P < .001; Filipino AOR = 1.37 [95% CI, 1.29 to 1.46], P < .001; Korean AOR = 1.32 [95% CI, 1.18 to 1.48], P < .001; Vietnamese AOR = 1.20 [95% CI, 1.07 to 1.35], P = .002; Laotian AOR = 1.60 [95% CI, 1.08 to 2.36], P = .018; Hmong AOR = 4.07 [95% CI, 1.54 to 10.81], P = .005; Kampuchean AOR = 1.55 [95% CI, 1.03 to 2.34], P = .036; Asian Indian or Pakistani AOR = 1.15 [95% CI, 1.07 to 1.24], P < .001; Native Hawaiians AOR = 1.58 [95% CI, 1.38 to 1.80], P < .001; and Pacific Islanders AOR = 1.58 [95% CI, 1.37 to 1.82], P < .001). Additionally, Japanese Americans (AOR = 1.46 [95% CI, 1.09 to 1.97], P = .013) were more likely to receive treatment compared with White patients.Our findings suggest that there are differences in PCa risk group at presentation by race or ethnicity among Asian American, Native Hawaiian, and Pacific Islander subgroups and that there exist disparities in treatment patterns. Although AANHPI are often studied as a homogenous group, heterogeneity upon subgroup disaggregation underscores the importance of further study to assess and address barriers to PCa care.

  View details for DOI 10.1200/OP.21.00412

  View details for PubMedID 34709962

• Healing and Health Equity for Asian American, Native Hawaiian, and Pacific Islander Populations. JAMA Taparra, K., Harding, M., Deville, C. 2021; 326 (23): 2432-2433

  View details for DOI 10.1001/jama.2021.19243

  View details for PubMedID 34932087

• Metastasis Directed Therapy Prolongs Efficacy of Systemic Therapy and Improves Clinical Outcomes in Oligoprogressive Castration-Resistant Prostate Cancer Deek, M. P., Taparra, K., Phillips, R., Velho, P., Gao, R. W., Deville, C., Song, D., Greco, S. C., Carducci, M., Eisenberger, M., DeWeese, T. L., Denmeade, S., Pienta, K., Paller, C., Antonarakis, E. S., Olivier, K., Park, S. S., Tran, P. T., Stish, B. J. ELSEVIER SCIENCE INC. 2020: E893-E894

  View details for Web of Science ID 000582521503121

• Modes of Failure Following Metastasis Directed Therapy in Patients with Oligometastatic Hormone Sensitive Prostate Cancer: A Multi-institutional Analysis Taparra, K., Deek, M. P., Dao, D., Chan, L., Phillips, R., Velho, P., Gao, R. W., Deville, C., Song, D., Greco, S. C., Carducci, M., Eisenberger, M., DeWeese, T. L., Denmeade, S., Pienta, K., Paller, C., Antonarakis, E. S., Park, S. S., Tran, P. T., Stish, B. J. ELSEVIER SCIENCE INC. 2020: E869-E870

  View details for Web of Science ID 000582521503068

• Reducing Heart Dose with Protons and Cardiac Substructure Sparing for Mediastinal Lymphoma Treatment INTERNATIONAL JOURNAL OF PARTICLE THERAPY Taparra, K., Lester, S. C., Harmsen, W., Petersen, M., Funk, R. K., Blanchard, M. J., Young, P., Herrmann, J., Hunzeker, A., Schultz, H., McCollough, C., Tasson, A., Leng, S., Martenson, J. A., Whitaker, T. J., Williamson, E., Laack, N. N. 2020; 7 (1): 1-12

  Abstract

  Electrocardiogram-gated computed tomography with coronary angiography can be used for cardiac substructure sparing (CSS) optimization, which identifies and improves avoidance of cardiac substructures when treating with intensity modulated radiotherapy (IMRT). We investigated whether intensity modulated proton therapy (IMPT) would further reduce dose to cardiac substructures for patients with mediastinal lymphoma.Twenty-one patients with mediastinal lymphoma were enrolled and underwent electrocardiogram-gated computed tomography angiography during or shortly after simulation for radiotherapy planning. Thirteen patients with delineated cardiac substructures underwent comparative planning with both IMPT and IMRT. Plans were normalized for equivalent (95%) target volume coverage for treatment comparison.Thirteen patients met criteria for this study. The median size of the mediastinal lymphadenopathy was 7.9 cm at the greatest diameter. Compared with IMRT-CSS, IMPT-CSS significantly reduced mean dose to all cardiac substructures, including 3 coronary arteries and 4 cardiac valves. Use of IMPT significantly reduced average whole-heart dose from 9.6 to 4.9 Gy (P < .0001), and average mean lung dose was 9.7 vs 5.8 Gy (P < .0001). Prospectively defined clinically meaningful improvement was observed in at least 1 coronary artery in 9 patients (69%), at least 1 cardiac valve in 10 patients (77%), and whole heart in all 13 patients.For patients with mediastinal lymphoma, IMPT-CSS treatment planning significantly reduced radiation dose to cardiac substructures. The significant improvements outlined in this study for proton therapy suggest possible clinical improvement in alignment with previous analyses of CSS optimization.

  View details for DOI 10.14338/IJPT-20-00010.1

  View details for Web of Science ID 000610832000001

  View details for PubMedID 33094130

  View details for PubMedCentralID PMC7574827

• O-GlcNAcylation is required for mutant KRAS-induced lung tumorigenesis. Shiraishi, T., Tran, P. T., Malek, R., Lafargue, A., Barbhuiya, M., Wang, X., Simons, B., Ballew, M., Nugent, K., Groves, J., Williams, R., Wang, H., Verdone, J., Yildirir, G., Henry, R., Zhang, B., Wong, J., Wang, K., Nelkin, B., Pienta, K., Felsher, D., Zachara, N., Taparra, K. AMER ASSOC CANCER RESEARCH. 2020: 59

  View details for Web of Science ID 000531799600091

• Baroreceptor Reflex Failure after Curative Chemoradiation for Oropharyngeal Cancer: A Potential Use of an Established Therapy Kim, H., Taparra, K., Holland, J. M. ELSEVIER SCIENCE INC. 2020: 1218

  View details for Web of Science ID 000580656800270

• Electrocardiogram-Gated Computed Tomography with Coronary Angiography for Cardiac Substructure Delineation and Sparing in Patients with Mediastinal Lymphomas Treated with Radiation Therapy PRACTICAL RADIATION ONCOLOGY Lester, S. C., Taparra, K., Petersen, M. M., Funk, R. K., Blanchard, M. J., Young, P. M., Herrmann, J., Hunzeker, A. E., Schultz, H. L., McCollough, C., Tasson, A. M., Leng, S., Martenson, J. A., Deisher, A. J., Whitaker, T. J., Williamson, E. E., Laack, N. N. 2020; 10 (2): 104-111

  Abstract

  (1) Demonstrate feasibility of electrocardiogram-gated computed tomography with coronary angiography (E-CTA) in treatment planning for mediastinal lymphoma and (2) assess whether inclusion of cardiac substructures in the radiation plan optimization (CSS optimization) results in increased cardiac substructure sparing.Patients with mediastinal lymphomas requiring radiation therapy were prospectively enrolled in an observational study. Patients completed a treatment planning computed tomography scan and E-CTA in the deep inspiration breath hold position. Avoidance structures (eg, coronary arteries and cardiac valves) were created in systole and diastole and then merged into a single planning organ-at-risk volume based on a cardiac substructure contouring atlas. In the photon cohort, 2 volumetric modulated arc therapy plans were created per patient with and without CSS optimization. Dosimetric endpoints were compared.In the photon cohort, 7 patients were enrolled. For all 7 patients, the treating physician elected to use the CSS optimization plan. At the individual level, 2 patients had reductions of 10.8% and 16.2% of the right coronary artery receiving at least 15 Gy, and 1 had a reduction of 9.6% of the left anterior descending artery receiving 30 Gy. No other differences for coronary arteries were detected between 15 and 30 Gy. Conversely, 5 of 7 patients had >10% reductions in dose between 15 to 30 Gy to at least 1 cardiac valve. The greatest reduction was 22.8% of the aortic valve receiving at least 30 Gy for 1 patient. At the cohort level, the maximum, mean, and 5-Gy increment analyses were nominally similar between planning techniques for all cardiac substructures and the lungs.Cardiac substructure delineation using E-CTA was feasible, and inclusion in optimization led to modest improvements in sparing of radiosensitive cardiac substructures for some patients.

  View details for DOI 10.1016/j.prro.2019.10.016

  View details for Web of Science ID 000518851800015

  View details for PubMedID 31783172

• Bleomycin Use in the Treatment of Hodgkin Lymphoma (HL): Toxicity and Outcomes in the Modern Era Taparra, K., Liu, H., Polley, M., Ristow, K. M., Habermann, T. M., Ansell, S. M. AMER SOC HEMATOLOGY. 2019

  View details for DOI 10.1182/blood-2019-121488

  View details for Web of Science ID 000577164602061

• Biologics and 30-Day Postoperative Complications After Abdominal Operations for Crohn's Disease: Are There Differences in the Safety Profiles? DISEASES OF THE COLON & RECTUM Lightner, A. L., McKenna, N. P., Alsughayer, A., Harmsen, W. S., Taparra, K., Parker, M. E., Raffals, L. E., Loftus, E. V. 2019; 62 (11): 1352-1362

  Abstract

  The evidence regarding the association of preoperative biologic exposure and postoperative outcomes remains controversial for both antitumor necrosis factor agents and vedolizumab and largely unknown for ustekinumab.The purpose of this study was to determine differences in the rates of 30-day postoperative overall infectious complications and intra-abdominal septic complications among the 3 classes of biologic therapies as compared with no biologic therapy.This was a retrospective review.The study was conducted at an IBD referral center.Adult patients with Crohn's disease who received an antitumor necrosis factor, vedolizumab, ustekinumab, or no biologic therapy within 12 weeks of a major abdominal operation between May 20, 2014, and December 31, 2017, were included.Thirty-day overall postoperative infectious complications and intra-abdominal septic complications were measured.A total of 712 patients with Crohn's disease were included; 272 patients were exposed to an antitumor necrosis factor agents, 127 to vedolizumab, 38 to ustekinumab, and 275 to no biologic therapy within the 12 weeks before an abdominal operation. Patients exposed to a biologic were more likely to be taking a concurrent immunomodulator, but there was no difference in concurrent corticosteroid usage. The particular class of biologic was not independently associated with total overall infectious complications. Vedolizumab was associated with an increased rate of intra-abdominal sepsis on univariate analysis but not on multivariable analysis. Combination immunosuppression was associated with both an increased rate of overall postoperative infectious complications and intra-abdominal sepsis.The study was limited by its retrospective design and single-center data.The overall rate of total infectious complications or intra-abdominal septic complications was not increased based on preoperative exposure to a particular class of biologic. Rates increased with combination immunosuppression of biologic therapy with corticosteroids and previous abdominal resection. See Video Abstract at http://links.lww.com/DCR/B24. BIOLÓGICOS Y COMPLICACIONES POSTOPERATORIAS DE 30 DÍAS DESPUÉS DE LAS OPERACIONES ABDOMINALES PARA LA ENFERMEDAD DE CROHN: ¿EXISTEN DIFERENCIAS EN LOS PERFILES DE SEGURIDAD?:: La evidencia sobre la asociación de la exposición biológica preoperatoria y los resultados postoperatorios sigue siendo controvertida controversial tanto para los agentes del factor de necrosis tumoral (anti-TNF) como para el vedolizumab, y en gran parte desconocida para el ustekinumab.Determinar las diferencias en las tasas de complicaciones infecciosas generales postoperatorias de 30 días y complicaciones sépticas intraabdominales entre las tres clases de terapias biológicas en comparación con ninguna terapia biológica.Revisión retrospectiva.centro de referencia de la enfermedad inflamatoria intestinal.Pacientes adultos con enfermedad de Crohn que recibieron un factor de necrosis antitumoral, vedolizumab, ustekinumab o ningún tratamiento biológico dentro de las 12 semanas de una operación abdominal mayor entre el 5/20/2014 y el 12/31/2017.Complicaciones infecciosas postoperatorias generales de 30 días, complicaciones sépticas intraabdominales.Se incluyeron setecientos doce pacientes con enfermedad de Crohn; 272 pacientes fueron expuestos a un anti-TNF, 127 a vedolizumab, 38 a ustekinumab y 275 a ninguna terapia biológica dentro de las 12 semanas previas a una operación abdominal. Los pacientes expuestos a un producto biológico tenían más probabilidades de tomar un inmunomodulador concurrente, pero no hubo diferencias en el uso simultáneo de corticosteroides. La clase particular de productos biológicos no se asoció de forma independiente con las complicaciones infecciosas totales. Vedolizumab se asoció con una mayor tasa de sepsis intraabdominal en el análisis univariable, pero no en el análisis multivariable. La inmunosupresión combinada se asoció tanto con una mayor tasa de complicaciones infecciosas postoperatorias generales como con sepsis intraabdominal.Diseño retrospectivo, datos de centro único.La tasa general de complicaciones infecciosas totales o complicaciones sépticas intraabdominales no aumentó en función de la exposición preoperatoria a una clase particular de productos biológicos. Las tasas aumentaron con la combinación de inmunosupresión de la terapia biológica con corticosteroides y resección abdominal previa. Vea el Resumen del Video en http://links.lww.com/DCR/B24.

  View details for DOI 10.1097/DCR.0000000000001482

  View details for Web of Science ID 000490158900014

  View details for PubMedID 31567927

• Bleomycin use in the treatment of Hodgkin lymphoma (HL): toxicity and outcomes in the modern era LEUKEMIA & LYMPHOMA Taparra, K., Liu, H., Polley, M., Ristow, K., Habermann, T. M., Ansell, S. M. 2020; 61 (2): 298-308

  Abstract

  One-in-five Hodgkin Lymphoma (HL) patients treated with bleomycin develop bleomycin pulmonary toxicity (BPT). Given bleomycin-omission data with negative interim-PET, we assessed changes in BPT statistics. We retrospectively evaluated 126 ABVD-treated HL patients for overall survival (OS), progression-free survival (PFS), BPT factors, and management. Forty-seven patients developed BPT with 17% BPT-mortality. In univariable analysis, OS was negatively impacted by BPT (HR = 3.6, 95%CI = 1.2-10.6), but not bleomycin-omission (HR = 1.3, 95%CI = 0.5-3.7). In multivariable analysis, BPT was not associated with OS (HR = 3.0, 95%CI = 0.9-9.9). BPT patients were older (46 y vs 33 years) and received less bleomycin (107 vs 215 units) compared to non-BPT patients. BPT was managed primarily with bleomycin-omission. "Recent Era" patients had lower BPT rates (28% vs 48%), mortality (10% vs 21%), and bleomycin doses (7 vs 12 doses), yet higher bleomycin-omission in the absence of the BPT (59% vs 8%) compared to "Early Era". Our data suggest BPT continually impacts OS in ABVD-treated HL patients, however management is changing.

  View details for DOI 10.1080/10428194.2019.1663419

  View details for Web of Science ID 000486469300001

  View details for PubMedID 31517559

• Cancer Therapeutic Strategies and Treatment Resistance PRINCIPLES OF CLINICAL CANCER RESEARCH Taparra, K., Tran, P. T., Mell, L. K., Tran, P. T., Yu, J. B., Zhang, Q. 2019: 108-126

  View details for Web of Science ID 000485118400009

• O-GlcNAcylation is required for mutant KRAS-induced lung tumorigenesis JOURNAL OF CLINICAL INVESTIGATION Taparra, K., Wang, H., Malek, R., Lafargue, A., Barbhuiya, M. A., Wang, X., Simons, B. W., Ballew, M., Nugent, K., Groves, J., Williams, R. D., Shiraishi, T., Verdone, J., Yildirir, G., Henry, R., Zhang, B., Wong, J., Wang, K., Nelkin, B. D., Pienta, K. J., Felsher, D., Zachara, N. E., Tran, P. T. 2018; 128 (11): 4924–37

  Abstract

  Mutant KRAS drives glycolytic flux in lung cancer, potentially impacting aberrant protein glycosylation. Recent evidence suggests aberrant KRAS drives flux of glucose into the hexosamine biosynthetic pathway (HBP). HBP is required for various glycosylation processes, such as protein N- or O-glycosylation and glycolipid synthesis. However, its function during tumorigenesis is poorly understood. One contributor and proposed target of KRAS-driven cancers is a developmentally conserved epithelial plasticity program called epithelial-mesenchymal transition (EMT). Here we showed in novel autochthonous mouse models that EMT accelerated KrasG12D lung tumorigenesis by upregulating expression of key enzymes of the HBP pathway. We demonstrated that HBP was required for suppressing KrasG12D-induced senescence, and targeting HBP significantly delayed KrasG12D lung tumorigenesis. To explore the mechanism, we investigated protein glycosylation downstream of HBP and found elevated levels of O-linked β-N-acetylglucosamine (O-GlcNAcylation) posttranslational modification on intracellular proteins. O-GlcNAcylation suppressed KrasG12D oncogene-induced senescence (OIS) and accelerated lung tumorigenesis. Conversely, loss of O-GlcNAcylation delayed lung tumorigenesis. O-GlcNAcylation of proteins SNAI1 and c-MYC correlated with the EMT-HBP axis and accelerated lung tumorigenesis. Our results demonstrated that O-GlcNAcylation was sufficient and required to accelerate KrasG12D lung tumorigenesis in vivo, which was reinforced by epithelial plasticity programs.

  View details for PubMedID 30130254

• The Impact of PET/CT Staging on the Incidence of Late Hodgkin Lymphoma Relapse for Patients Treated with Limited Radiation Fields Frechette, K. M., Lester, S. C., Taparra, K., Stafford, S. L., Martenson, J. A., Stish, B. J., Laack, N. N. ELSEVIER SCIENCE INC. 2018: E218-E219

  View details for DOI 10.1016/j.ijrobp.2018.07.756

  View details for Web of Science ID 000447811600503

• Exploring Host Germline Genetics to Help Identify Patients with Early Stage Lymphoma Who Might Benefit From the Addition of Radiation Therapy Lester, S. C., Taparra, K., Routman, D. M., Maurer, M. J., Ansell, S. M., Feldman, A. L., Link, B. K., Stish, B. J., Martenson, J. A., Slager, S. L., Stafford, S. L., Habermann, T. M., Cerhan, J. R. ELSEVIER SCIENCE INC. 2018: S122-S123

  View details for DOI 10.1016/j.ijrobp.2018.06.307

  View details for Web of Science ID 000447811602502

• Sparing of the Cardiac Valves and Left Ventricle using Proton Therapy with ECG-gated CT with Coronary Angiography for the Treatment of Mediastinal Lymphoma Lester, S. C., Taparra, K., Hunzeker, A., Funk, K., Blanchard, M., Young, P., Herrmann, J., McCollough, C., Tasson, A., Leng, S., Martenson, J. A., Whitaker, T. J., Williamson, E. E., Laack, N. N. ELSEVIER SCIENCE INC. 2018: E277

  View details for DOI 10.1016/j.ijrobp.2018.07.891

  View details for Web of Science ID 000447811600636

• A Comparison of Proton and X-ray Therapy for Coronary Artery Sparing Using ECG-gated CT with Coronary Angiography for Mediastinal Lymphoma Taparra, K., Lester, S. C., Hunzeker, A., Funk, R. K., Blanchard, M., Young, P., Herrmann, J., Tasson, A., Leng, S., Martenson, J. A., Whitaker, T. J., Williamson, E. E., Laack, N. N. ELSEVIER SCIENCE INC. 2018: S87-S88

  View details for DOI 10.1016/j.ijrobp.2018.06.229

  View details for Web of Science ID 000447811602427

• Associations between perceived medical device-related radiation harm and adherence to mammography screening guidelines Taparra, K., Pepin, K. M., Greenberg-Worisek, A. J. AMER ASSOC CANCER RESEARCH. 2018

  View details for DOI 10.1158/1538-7445.AM2018-4241

  View details for Web of Science ID 000468819502438

• Examining sociodemographic disparities in perceptions of cancer risk from medical imaging radiation Taparra, K., Pepin, K., Moser, R., Hesse, B., Greenberg, A. AMER ASSOC CANCER RESEARCH. 2017

  View details for DOI 10.1158/1538-7445.AM2017-4222

  View details for Web of Science ID 000442513302427

• TWIST1-WDR5-Hottip Regulates Hoxa9 Chromatin to Facilitate Prostate Cancer Metastasis CANCER RESEARCH Malek, R., Gajula, R. P., Williams, R. D., Nghiem, B., Simons, B. W., Nugent, K., Wang, H., Taparra, K., Lemtiri-Chlieh, G., Yoon, A. R., True, L., An, S. S., DeWeese, T. L., Ross, A. E., Schaeffer, E. M., Pienta, K. J., Hurley, P. J., Morrissey, C., Tran, P. T. 2017; 77 (12): 3181-3193

  Abstract

  TWIST1 is a transcription factor critical for development that can promote prostate cancer metastasis. During embryonic development, TWIST1 and HOXA9 are coexpressed in mouse prostate and then silenced postnatally. Here we report that TWIST1 and HOXA9 coexpression are reactivated in mouse and human primary prostate tumors and are further enriched in human metastases, correlating with survival. TWIST1 formed a complex with WDR5 and the lncRNA Hottip/HOTTIP, members of the MLL/COMPASS-like H3K4 methylases, which regulate chromatin in the Hox/HOX cluster during development. TWIST1 overexpression led to coenrichment of TWIST1 and WDR5 as well as increased H3K4me3 chromatin at the Hoxa9/HOXA9 promoter, which was dependent on WDR5. Expression of WDR5 and Hottip/HOTTIP was also required for TWIST1-induced upregulation of HOXA9 and aggressive cellular phenotypes such as invasion and migration. Pharmacologic inhibition of HOXA9 prevented TWIST1-induced aggressive prostate cancer cellular phenotypes in vitro and metastasis in vivo This study demonstrates a novel mechanism by which TWIST1 regulates chromatin and gene expression by cooperating with the COMPASS-like complex to increase H3K4 trimethylation at target gene promoters. Our findings highlight a TWIST1-HOXA9 embryonic prostate developmental program that is reactivated during prostate cancer metastasis and is therapeutically targetable. Cancer Res; 77(12); 3181-93. ©2017 AACR.

  View details for DOI 10.1158/0008-5472.CAN-16-2797

  View details for Web of Science ID 000403328500008

  View details for PubMedID 28484075

  View details for PubMedCentralID PMC5489316

• Therapeutic Targeting of Epithelial Plasticity Programs: Focus on the Epithelial-Mesenchymal Transition Malek, R., Wang, H., Kekoa, T., Tran, P. T. KARGER. 2017: 114-127

  Abstract

  Mounting data points to epithelial plasticity programs such as the epithelial-mesenchymal transition (EMT) as clinically relevant therapeutic targets for the treatment of malignant tumors. In addition to the widely realized role of EMT in increasing cancer cell invasiveness during cancer metastasis, the EMT has also been implicated in allowing cancer cells to avoid tumor suppressor pathways during early tumorigenesis. In addition, data linking EMT to innate and acquired treatment resistance further points towards the desire to develop pharmacological therapies to target epithelial plasticity in cancer. In this review we organized our discussion on pathways and agents that can be used to target the EMT in cancer into 3 groups: (1) extracellular inducers of EMT, (2) the transcription factors that orchestrate the EMT transcriptome, and (3) the downstream effectors of EMT. We highlight only briefly specific canonical pathways known to be involved in EMT, such as the signal transduction pathways TGFβ, EFGR, and Axl-Gas6. We emphasize in more detail pathways that we believe are emerging novel pathways and therapeutic targets such as epigenetic therapies, glycosylation pathways, and immunotherapy. The heterogeneity of tumors and the dynamic nature of epithelial plasticity in cancer cells make it likely that targeting only 1 EMT-related process will be unsuccessful or only transiently successful. We suggest that with greater understanding of epithelial plasticity regulation, such as with the EMT, a more systematic targeting of multiple EMT regulatory networks will be the best path forward to improve cancer outcomes.

  View details for DOI 10.1159/000447238

  View details for Web of Science ID 000394922500006

  View details for PubMedID 28214899

  View details for PubMedCentralID PMC5375029

• SNAII regulates the hexosamine biosynthetic pathway to promote tumorigenesis and oncogene-induced senescence escape in lung cancer Taparra, K., Wang, H., Nugent, K., Malek, R., Groves, J., Yildirir, G., Simons, B., Felsher, D., Zachara, N., Phuoc Tran AMER ASSOC CANCER RESEARCH. 2016

  View details for DOI 10.1158/1538-7445.AM2016-1054

  View details for Web of Science ID 000389941706090

• Hijacking the Hexosamine Biosynthetic Pathway to Promote EMT-Mediated neoplastic Phenotypes FRONTIERS IN ONCOLOGY Taparra, K., Tran, P. T., Zachara, N. E. 2016; 6: 85

  Abstract

  The epithelial-mesenchymal transition (EMT) is a highly conserved program necessary for orchestrating distant cell migration during embryonic development. Multiple studies in cancer have demonstrated a critical role for EMT during the initial stages of tumorigenesis and later during tumor invasion. Transcription factors (TFs) such as SNAIL, TWIST, and ZEB are master EMT regulators that are aberrantly overexpressed in many malignancies. Recent evidence correlates EMT-related transcriptomic alterations with metabolic reprograming in cancer. Metabolic alterations may allow cancer to adapt to environmental stressors, supporting the irregular macromolecular demand of rapid proliferation. One potential metabolic pathway of increasing importance is the hexosamine biosynthesis pathway (HBP). The HBP utilizes glycolytic intermediates to generate the metabolite UDP-GlcNAc. This and other charged nucleotide sugars serve as the basis for biosynthesis of glycoproteins and other glycoconjugates. Recent reports in the field of glycobiology have cultivated great curiosity within the cancer research community. However, specific mechanistic relationships between the HBP and fundamental pathways of cancer, such as EMT, have yet to be elucidated. Altered protein glycosylation downstream of the HBP is well positioned to mediate many cellular changes associated with EMT including cell-cell adhesion, responsiveness to growth factors, immune system evasion, and signal transduction programs. Here, we outline some of the basics of the HBP and putative roles the HBP may have in driving EMT-related cancer processes. With novel appreciation of the HBP's connection to EMT, we hope to illuminate the potential for new therapeutic targets of cancer.

  View details for DOI 10.3389/fonc.2016.00085

  View details for Web of Science ID 000374216600001

  View details for PubMedID 27148477

  View details for PubMedCentralID PMC4834358

• Ganetespib radiosensitization for liver cancer therapy CANCER BIOLOGY & THERAPY Chettiar, S. T., Malek, R., Annadanam, A., Nugent, K. M., Kato, Y., Wang, H., Cades, J. A., Taparra, K., Belcaid, Z., Ballew, M., Manmiller, S., Proia, D., Lim, M., Anders, R. A., Herman, J. M., Tran, P. T. 2016; 17 (4): 457–66

  Abstract

  Therapies for liver cancer particularly those including radiation are still inadequate. Inhibiting the stress response machinery is an appealing anti-cancer and radiosensitizing therapeutic strategy. Heat-shock-protein-90 (HSP90) is a molecular chaperone that is a prominent effector of the stress response machinery and is overexpressed in liver cancer cells. HSP90 client proteins include critical components of pathways implicated in liver cancer cell survival and radioresistance. The effects of a novel non-geldanamycin HSP90 inhibitor, ganetespib, combined with radiation were examined on 3 liver cancer cell lines, Hep3b, HepG2 and HUH7, using in vitro assays for clonogenic survival, apoptosis, cell cycle distribution, γH2AX foci kinetics and client protein expression in pathways important for liver cancer survival and radioresistance. We then evaluated tumor growth delay and effects of the combined ganetespib-radiation treatment on tumor cell proliferation in a HepG2 hind-flank tumor graft model. Nanomolar levels of ganetespib alone exhibited liver cancer cell anti-cancer activity in vitro as shown by decreased clonogenic survival that was associated with increased apoptotic cell death, prominent G2-M arrest and marked changes in PI3K/AKT/mTOR and RAS/MAPK client protein activity. Ganetespib caused a supra-additive radiosensitization in all liver cancer cell lines at low nanomolar doses with enhancement ratios between 1.33-1.78. These results were confirmed in vivo, where the ganetespib-radiation combination therapy produced supra-additive tumor growth delay compared with either therapy by itself in HepG2 tumor grafts. Our data suggest that combined ganetespib-radiation therapy exhibits promising activity against liver cancer cells, which should be investigated in clinical studies.

  View details for DOI 10.1080/15384047.2016.1156258

  View details for Web of Science ID 000375583500016

  View details for PubMedID 26980196

  View details for PubMedCentralID PMC4910914

• Snai1 accelerates Kras driven lung tumorigenesis by overcoming oncogene-induced senescence Taparra, K., Wang, H., Nugent, K., Williams, R., Malek, R., Cades, J., Felsher, D., Phuoc Tran AMER ASSOC CANCER RESEARCH. 2015

  View details for DOI 10.1158/1538-7445.AM2015-2291

  View details for Web of Science ID 000371578504394

• Structure-Function Studies of the bHLH Phosphorylation Domain of TWIST1 in Prostate Cancer Cells NEOPLASIA Gajula, R. P., Chettiar, S. T., Williams, R. D., Nugent, K., Kato, Y., Wang, H., Malek, R., Taparra, K., Cades, J., Annadanam, A., Yoon, A., Fertig, E., Firulli, B. A., Mazzacurati, L., Burns, T. F., Firulli, A. B., An, S. S., Tran, P. T. 2015; 17 (1): 16-31

  Abstract

  The TWIST1 gene has diverse roles in development and pathologic diseases such as cancer. TWIST1 is a dimeric basic helix-loop-helix (bHLH) transcription factor existing as TWIST1-TWIST1 or TWIST1-E12/47. TWIST1 partner choice and DNA binding can be influenced during development by phosphorylation of Thr125 and Ser127 of the Thr-Gln-Ser (TQS) motif within the bHLH of TWIST1. The significance of these TWIST1 phosphorylation sites for metastasis is unknown. We created stable isogenic prostate cancer cell lines overexpressing TWIST1 wild-type, phospho-mutants, and tethered versions. We assessed these isogenic lines using assays that mimic stages of cancer metastasis. In vitro assays suggested the phospho-mimetic Twist1-DQD mutation could confer cellular properties associated with pro-metastatic behavior. The hypo-phosphorylation mimic Twist1-AQA mutation displayed reduced pro-metastatic activity compared to wild-type TWIST1 in vitro, suggesting that phosphorylation of the TWIST1 TQS motif was necessary for pro-metastatic functions. In vivo analysis demonstrates that the Twist1-AQA mutation exhibits reduced capacity to contribute to metastasis, whereas the expression of the Twist1-DQD mutation exhibits proficient metastatic potential. Tethered TWIST1-E12 heterodimers phenocopied the Twist1-DQD mutation for many in vitro assays, suggesting that TWIST1 phosphorylation may result in heterodimerization in prostate cancer cells. Lastly, the dual phosphatidylinositide 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) inhibitor BEZ235 strongly attenuated TWIST1-induced migration that was dependent on the TQS motif. TWIST1 TQS phosphorylation state determines the intensity of TWIST1-induced pro-metastatic ability in prostate cancer cells, which may be partly explained mechanistically by TWIST1 dimeric partner choice.

  View details for DOI 10.1016/j.neo.2014.10.009

  View details for Web of Science ID 000348458300002

  View details for PubMedID 25622896

  View details for PubMedCentralID PMC4309734

• Peroxiredoxin proteins protect MCF-7 breast cancer cells from doxorubicin-induced toxicity INTERNATIONAL JOURNAL OF ONCOLOGY McDonald, C., Muhlbauer, J., Perlmutter, G., Taparra, K., Phelan, S. A. 2014; 45 (1): 219-226

  Abstract

  Peroxiredoxin (Prdx) proteins are thiol-specific antioxidants that protect cells from oxidative stress in many normal and disease states. There are six Prdx proteins expressed in mammals, each with a characteristic tissue expression, subcellular distribution and substrate specificity. Recent studies have revealed elevated Prdx levels in many cancers, suggesting a protective role for these proteins in cancer cell survival. The present study is the first to investigate the function of all six Prdx proteins in the MCF-7 breast cancer cell line. We show that these cells have both higher resistance to doxorubicin-induced toxicity and significantly elevated Prdx levels, compared to the non-cancer MCF-10A cells. Using transient siRNA transfections, we show that Prdx3 suppression leads to decreased MCF-7 cell survival in the absence of doxorubicin. We further demonstrate that individual suppression of four of six of the Prdx proteins leads to increased doxorubicin-induced toxicity by apoptosis. Finally, we show that clonal selection of a doxorubicin-resistant MCF-7 subline by 2-week culture in 0.1 µM doxorubicin resulted in a marked elevation in the expression of several Prdx proteins. Together, these data reveal a protective function for peroxiredoxins in MCF-7 cell survival, and suggest that Prdx overexpression in breast cancer may play a role in doxorubicin-resistance in these, and possibly other, breast cancer cells. This study is the first to investigate the function of the entire Prdx family in a breast cancer cell line.

  View details for DOI 10.3892/ijo.2014.2398

  View details for Web of Science ID 000336881600024

  View details for PubMedID 24789097

• Peroxiredoxin Overexpression in MCF-7 Breast Cancer Cells and Regulation by Cell Proliferation and Oxidative Stress CANCER INVESTIGATION Tehan, L., Taparra, K., Phelan, S. 2013; 31 (6): 374-384

  Abstract

  Peroxiredoxins are thiol-specific antioxidant proteins that protect cells from ROS-induced cell death and are elevated in several cancers. We found that five of the six mammalian peroxiredoxins are overexpressed in MCF-7 breast cancer cells at the mRNA and protein levels, compared to noncancerous MCF-10A cells. Inhibition of MCF-7 proliferation reduced the levels of several peroxiredoxins. In contrast, all six proteins were strongly and transiently induced in MCF-7 cells by H₂O₂. These data suggest that coordinate overexpression of peroxiredoxins may be an important cancer cell adaptation, and that these proteins can be regulated by cell proliferation and oxidative stress.

  View details for DOI 10.3109/07357907.2013.802798

  View details for Web of Science ID 000320866800002

  View details for PubMedID 23758190

• Concurrent versus Sequential Sorafenib Therapy in Combination with Radiation for Hepatocellular Carcinoma PLOS ONE Wild, A. T., Gandhi, N., Chettiar, S. T., Aziz, K., Gajula, R. P., Williams, R. D., Kumar, R., Taparra, K., Zeng, J., Cades, J. A., Velarde, E., Menon, S., Geschwind, J. F., Cosgrove, D., Pawlik, T. M., Maitra, A., Wong, J., Hales, R. K., Torbenson, M. S., Herman, J. M., Tran, P. T. 2013; 8 (6): e65726

  Abstract

  Sorafenib (SOR) is the only systemic agent known to improve survival for hepatocellular carcinoma (HCC). However, SOR prolongs survival by less than 3 months and does not alter symptomatic progression. To improve outcomes, several phase I-II trials are currently examining SOR with radiation (RT) for HCC utilizing heterogeneous concurrent and sequential treatment regimens. Our study provides preclinical data characterizing the effects of concurrent versus sequential RT-SOR on HCC cells both in vitro and in vivo. Concurrent and sequential RT-SOR regimens were tested for efficacy among 4 HCC cell lines in vitro by assessment of clonogenic survival, apoptosis, cell cycle distribution, and γ-H2AX foci formation. Results were confirmed in vivo by evaluating tumor growth delay and performing immunofluorescence staining in a hind-flank xenograft model. In vitro, concurrent RT-SOR produced radioprotection in 3 of 4 cell lines, whereas sequential RT-SOR produced decreased colony formation among all 4. Sequential RT-SOR increased apoptosis compared to RT alone, while concurrent RT-SOR did not. Sorafenib induced reassortment into less radiosensitive phases of the cell cycle through G1-S delay and cell cycle slowing. More double-strand breaks (DSBs) persisted 24 h post-irradiation for RT alone versus concurrent RT-SOR. In vivo, sequential RT-SOR produced the greatest tumor growth delay, while concurrent RT-SOR was similar to RT alone. More persistent DSBs were observed in xenografts treated with sequential RT-SOR or RT alone versus concurrent RT-SOR. Sequential RT-SOR additionally produced a greater reduction in xenograft tumor vascularity and mitotic index than either concurrent RT-SOR or RT alone. In conclusion, sequential RT-SOR demonstrates greater efficacy against HCC than concurrent RT-SOR both in vitro and in vivo. These results may have implications for clinical decision-making and prospective trial design.

  View details for DOI 10.1371/journal.pone.0065726

  View details for Web of Science ID 000321099000098

  View details for PubMedID 23762417

  View details for PubMedCentralID PMC3675179

• Regeneration in the Hemichordate Ptychodera flava ZOOLOGICAL SCIENCE Humphreys, T., Sasaki, A., Uenishi, G., Taparra, K., Arimoto, A., Tagawa, K. 2010; 27 (2): 91-95

  Abstract

  When the body of P. flava is severed, the animal has the ability to regenerate its missing anterior or posterior as appropriate. We have focused on anterior regeneration when the head and branchial regions are severed from the body of the worm. After transection, the body wall contracts and heals closed in 2 to 3 days. By the third day a small blastema is evident at the point of closure. The blastema grows rapidly and begins the process of differentiating into a head with a proboscis and collar. At 5 days the blastema has increased greatly in size and differentiated into a central bulb, the forming proboscis, and two lateral crescents, the forming collar. Between 5 and 7 days a mouth opens ventral to the differentiating blastema. Over the next few days the lateral crescents extend to encircle the proboscis and mouth, making a fully formed collar. By 10 to 12 days a new head, sized to fit the worm's body, has grown attached to the severed site. At about this time the animal regains apparently normal burrowing behavior. After the head is formed, a second blastema-like area appears between the new head and the old body and a new branchial region is inserted by regeneration from this blastema over the next 2 to 3 weeks. The regenerating tissues are unpigmented and whitish such that in-situ hybridization can be used to study the expression of genes during the formation of new tissues.

  View details for DOI 10.2108/zsj.27.91

  View details for Web of Science ID 000274061600005

  View details for PubMedID 20141413