17 results on '"Katherine Van Loon"'
Search Results
2. Supplementary Table 2 from Cell-Free DNA Next-Generation Sequencing in Pancreatobiliary Carcinomas
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Eric A. Collisson, AmirAli Talasaz, Pamela N. Munster, Trever G. Bivona, Margaret A. Tempero, Andrew H. Ko, Katherine Van Loon, Robin K. Kelley, Chloe E. Atreya, Zhen Wang, Andrew E. Hendifar, Mary Vu, Jim Leng, Lai Mun Siew, Dragan Sebisanovic, Claire Greene, and Oliver A. Zill
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Complete patient-level and mutation-level concordance information, mutation identities, and monitoring status for each patient in study.
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- 2023
3. Supplementary Figure 1 from Cell-Free DNA Next-Generation Sequencing in Pancreatobiliary Carcinomas
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Eric A. Collisson, AmirAli Talasaz, Pamela N. Munster, Trever G. Bivona, Margaret A. Tempero, Andrew H. Ko, Katherine Van Loon, Robin K. Kelley, Chloe E. Atreya, Zhen Wang, Andrew E. Hendifar, Mary Vu, Jim Leng, Lai Mun Siew, Dragan Sebisanovic, Claire Greene, and Oliver A. Zill
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Comparisons of CA 19-9 concentration and cfDNA mutant allele fractions in plasma. (A-E) cfDNA mutant allele fractions ("cfDNA percentage") versus CA 19-9 units per milliliter (U/mL) were determined at similar times for five patients with three or more serial blood draws. cfDNA percentage represents the mutant allele fraction of the most abundant cfDNA mutation, as determined at time zero, for each patient. (F) cfDNA mutant allele fractions and CA 19-9 marker measurements for patient 56 over the course of four time points while on therapy (gemcitabine nab-paclitaxel). Note that draw number 1 occurred 17 days after diagnosis.
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- 2023
4. Supplementary Table 4 from Cell-Free DNA Next-Generation Sequencing in Pancreatobiliary Carcinomas
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Eric A. Collisson, AmirAli Talasaz, Pamela N. Munster, Trever G. Bivona, Margaret A. Tempero, Andrew H. Ko, Katherine Van Loon, Robin K. Kelley, Chloe E. Atreya, Zhen Wang, Andrew E. Hendifar, Mary Vu, Jim Leng, Lai Mun Siew, Dragan Sebisanovic, Claire Greene, and Oliver A. Zill
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List of genes and exons captured in the Guardant360 cfDNA sequencing test.
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- 2023
5. Supplementary Table 1 from Cell-Free DNA Next-Generation Sequencing in Pancreatobiliary Carcinomas
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Eric A. Collisson, AmirAli Talasaz, Pamela N. Munster, Trever G. Bivona, Margaret A. Tempero, Andrew H. Ko, Katherine Van Loon, Robin K. Kelley, Chloe E. Atreya, Zhen Wang, Andrew E. Hendifar, Mary Vu, Jim Leng, Lai Mun Siew, Dragan Sebisanovic, Claire Greene, and Oliver A. Zill
- Abstract
Characteristics of the 26 patients in study.
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- 2023
6. Supplementary Figures 1-9 from A Phase I First-in-Human Study of Nesvacumab (REGN910), a Fully Human Anti–Angiopoietin-2 (Ang2) Monoclonal Antibody, in Patients with Advanced Solid Tumors
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Lillian L. Siu, A. Thomas DiCioccio, Bo Gao, Pamela A. Trail, Ana Kostic, Israel Lowy, Carrie M. Brownstein, Lieve Adriaens, Muralidhar Beeram, Ariceli A. Alfaro, Philippe L. Bedard, Amita Patnaik, Katherine Van Loon, Albiruni R. Abdul Razak, Anthony W. Tolcher, Robin Kate Kelley, and Kyriakos P. Papadopoulos
- Abstract
Supplementary Figure 1 Total Nesvacumab (REGN910) and Total Ang2 vs Time (cycle 1) following IV infusion in Patients. Supplementary Figure 2 Serum levels of ESM1, SDF-1, PLGF-1 and sVCAM-1 following Nesvacumab (REGN910) treatment. Supplementary Figure 3 Correlative analysis of baseline serum Ang2, ESM-1, SDF-1 ,PIGF and cVCAM-1 and treatment duration. Supplementary Figure 4 Correlative analysis of baseline Ang2 in tumor vessels and treatment duration/response. Supplementary Figure 5 Ang2 and VEGF-A protein levels in tumor tissue pre and post treatment with Nesvacumab (REGN910). Supplementary Figure 6 Biomarker analysis of archival tumor tissue. Supplementary Figure 7 Microvascular density in tumor tissue pre and post treatment with Nesvacumab (REGN910). Supplementary Figure 8 Tumor cell proliferation in tumor tissue pre and post treatment with Nesvacumab (REGN910). Supplementary Figure 9 TIE-2 protein levels associated with tumor vessels pre and post treatment with Nesvacumab (REGN910)
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- 2023
7. Supplementary Table 1 from A Phase I First-in-Human Study of Nesvacumab (REGN910), a Fully Human Anti–Angiopoietin-2 (Ang2) Monoclonal Antibody, in Patients with Advanced Solid Tumors
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Lillian L. Siu, A. Thomas DiCioccio, Bo Gao, Pamela A. Trail, Ana Kostic, Israel Lowy, Carrie M. Brownstein, Lieve Adriaens, Muralidhar Beeram, Ariceli A. Alfaro, Philippe L. Bedard, Amita Patnaik, Katherine Van Loon, Albiruni R. Abdul Razak, Anthony W. Tolcher, Robin Kate Kelley, and Kyriakos P. Papadopoulos
- Abstract
Supplementary Table 1. Summary of the Most Common (>10%) Treatment-Emergent Adverse Events
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- 2023
8. Data from A Phase I First-in-Human Study of Nesvacumab (REGN910), a Fully Human Anti–Angiopoietin-2 (Ang2) Monoclonal Antibody, in Patients with Advanced Solid Tumors
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Lillian L. Siu, A. Thomas DiCioccio, Bo Gao, Pamela A. Trail, Ana Kostic, Israel Lowy, Carrie M. Brownstein, Lieve Adriaens, Muralidhar Beeram, Ariceli A. Alfaro, Philippe L. Bedard, Amita Patnaik, Katherine Van Loon, Albiruni R. Abdul Razak, Anthony W. Tolcher, Robin Kate Kelley, and Kyriakos P. Papadopoulos
- Abstract
Purpose: Nesvacumab (REGN910) is a fully human immunoglobulin G1 (IgG1) monoclonal antibody that specifically binds and inactivates the Tie2 receptor ligand Ang2 with high affinity, but shows no binding to Ang1. The main objectives of this trial were to determine the safety, tolerability, dose-limiting toxicities (DLT), and recommended phase II dose (RP2D) of nesvacumab.Experimental Design: Nesvacumab was administered intravenously every two weeks with dose escalations from 1 to 20 mg/kg in patients with advanced solid tumors.Results: A total of 47 patients were treated with nesvacumab. No patients in the dose escalation phase experienced DLTs, therefore a maximum tolerated dose (MTD) was not reached. The most common nesvacumab-related adverse events were fatigue (23.4%), peripheral edema (21.3%), decreased appetite, and diarrhea (each 10.6%; all grade ≤ 2). Nesvacumab was characterized by linear kinetics and had a terminal half-life of 6.35 to 9.66 days in a dose-independent manner. Best response by RECIST 1.1 in 43 evaluable patients included 1 partial response (adrenocortical carcinoma) of 24 weeks duration. Two patients with hepatocellular carcinoma had stable disease (SD) > 16 weeks, with tumor regression and >50% decrease in α-fetoprotein. Analyses of putative angiogenesis biomarkers in serum and tumor biopsies were uninformative for treatment duration.Conclusions: Nesvacumab safety profile was acceptable at all dose levels tested. Preliminary antitumor activity was observed in patients with treatment-refractory advanced solid tumors. On the basis of cumulative safety, antitumor activity, pharmacokinetic and pharmacodynamic data, the 20 mg/kg dose was determined to be the RP2D. Clin Cancer Res; 22(6); 1348–55. ©2015 AACR.
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- 2023
9. Supplementary Data from A Phase I First-in-Human Study of Nesvacumab (REGN910), a Fully Human Anti–Angiopoietin-2 (Ang2) Monoclonal Antibody, in Patients with Advanced Solid Tumors
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Lillian L. Siu, A. Thomas DiCioccio, Bo Gao, Pamela A. Trail, Ana Kostic, Israel Lowy, Carrie M. Brownstein, Lieve Adriaens, Muralidhar Beeram, Ariceli A. Alfaro, Philippe L. Bedard, Amita Patnaik, Katherine Van Loon, Albiruni R. Abdul Razak, Anthony W. Tolcher, Robin Kate Kelley, and Kyriakos P. Papadopoulos
- Abstract
Supplementary Data. Study entry criteria specific to patients with HCC
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- 2023
10. Abstract 42: Patient-Provider Communication in the Setting of Advanced Cancer: Experience and Views from Rwanda
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Pacifique Uwamahoro, Rebecca DeBoer, Hubert Tuyishime, Vincent Kalumire Cubaka, Egide Mpanumusingo, Katherine Van Loon, and Anita Ho
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Epidemiology ,media_common.quotation_subject ,Control (management) ,Advanced cancer ,Oncology ,Nursing ,Quality (business) ,Psychological resilience ,Thematic analysis ,Citation ,Psychology ,Empowerment ,Socioeconomic status ,media_common - Abstract
Purpose: Caring for patients with advanced cancer involves complex patient-provider communication (PPC), including disclosure of diagnosis, discussion of prognosis, decision-making about treatment, delivery of bad news, and transitions in goals of care. Values and norms that influence PPC differ across diverse cultural and socioeconomic contexts. We aimed to characterize PPC experiences and preferences among patients and providers at Butaro Hospital in Rwanda, understand facilitators and barriers to high quality PPC, and collect suggestions for improvement. Methods: We conducted semi-structured interviews with a purposive sample of 11 oncology providers and 11 adult patients with advanced cancer. Interviews were recorded, transcribed, translated to English, coded using software, and analyzed using framework thematic analysis. Results: Participants reported both strengths and opportunities for improvement in PPC at Butaro. Strengths include routine explanation of diagnosis, treatment plan, and potential side effects, aided by a consent form and a dedicated counselor. Patients reported that PPC focuses on symptoms and treatment plan discussion, but is limited in truth telling about prognosis, especially when goals of care transition from curative to palliative. Facilitators to quality PPC include multidisciplinary team commitment, patient trust toward providers, provider communication style, and strong resilience in distressing clinical situations. While patients perceived power imbalance between patients and providers as the main barrier to PPC, providers cited inadequate time due to work overload, discomfort facing sad situations, and unfavorable physical environment as main barriers. Suggestions to improve PPC include training providers in communication skills, patient and family education and empowerment, more time and private spaces, and standardizing approaches to harmonize PPC. Conclusion: PPC at Butaro works well though there is room for improvement. Understanding how cultural norms and values regarding poor prognoses influence patient and provider communication preferences can inform strategies to improve PPC and ensure patient-centered care in Rwanda and similar settings. Citation Format: Pacifique Uwamahoro, Hubert Tuyishime, Vincent Cubaka, Egide Mpanumusingo, Anita Ho, Katherine Van Loon, Rebecca J. DeBoer. Patient-Provider Communication in the Setting of Advanced Cancer: Experience and Views from Rwanda [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 42.
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- 2021
11. A Phase I First-in-Human Study of Nesvacumab (REGN910), a Fully Human Anti–Angiopoietin-2 (Ang2) Monoclonal Antibody, in Patients with Advanced Solid Tumors
- Author
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Kyriakos P. Papadopoulos, Pamela Trail, Anthony W. Tolcher, Ana Kostic, A. Thomas DiCioccio, Robin Kate Kelley, Israel Lowy, Amita Patnaik, Ariceli Alfaro, Lillian L. Siu, Lieve Adriaens, Muralidhar Beeram, Katherine Van Loon, Philippe L. Bedard, Albiruni Ryan Abdul Razak, Bo Gao, and Carrie Brownstein
- Subjects
Adult ,Male ,0301 basic medicine ,Nesvacumab ,Cancer Research ,medicine.medical_specialty ,Maximum Tolerated Dose ,Peripheral edema ,Antineoplastic Agents ,Pharmacology ,Antibodies, Monoclonal, Humanized ,Gastroenterology ,Angiopoietin-2 ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Pharmacokinetics ,Neoplasms ,Internal medicine ,medicine ,Humans ,Aged ,Neoplasm Staging ,Aged, 80 and over ,Dose-Response Relationship, Drug ,business.industry ,Cancer ,Middle Aged ,medicine.disease ,Treatment Outcome ,030104 developmental biology ,Oncology ,Tolerability ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Pharmacodynamics ,Monoclonal ,Female ,medicine.symptom ,business ,Biomarkers - Abstract
Purpose: Nesvacumab (REGN910) is a fully human immunoglobulin G1 (IgG1) monoclonal antibody that specifically binds and inactivates the Tie2 receptor ligand Ang2 with high affinity, but shows no binding to Ang1. The main objectives of this trial were to determine the safety, tolerability, dose-limiting toxicities (DLT), and recommended phase II dose (RP2D) of nesvacumab. Experimental Design: Nesvacumab was administered intravenously every two weeks with dose escalations from 1 to 20 mg/kg in patients with advanced solid tumors. Results: A total of 47 patients were treated with nesvacumab. No patients in the dose escalation phase experienced DLTs, therefore a maximum tolerated dose (MTD) was not reached. The most common nesvacumab-related adverse events were fatigue (23.4%), peripheral edema (21.3%), decreased appetite, and diarrhea (each 10.6%; all grade ≤ 2). Nesvacumab was characterized by linear kinetics and had a terminal half-life of 6.35 to 9.66 days in a dose-independent manner. Best response by RECIST 1.1 in 43 evaluable patients included 1 partial response (adrenocortical carcinoma) of 24 weeks duration. Two patients with hepatocellular carcinoma had stable disease (SD) > 16 weeks, with tumor regression and >50% decrease in α-fetoprotein. Analyses of putative angiogenesis biomarkers in serum and tumor biopsies were uninformative for treatment duration. Conclusions: Nesvacumab safety profile was acceptable at all dose levels tested. Preliminary antitumor activity was observed in patients with treatment-refractory advanced solid tumors. On the basis of cumulative safety, antitumor activity, pharmacokinetic and pharmacodynamic data, the 20 mg/kg dose was determined to be the RP2D. Clin Cancer Res; 22(6); 1348–55. ©2015 AACR.
- Published
- 2016
12. Abstract A18: Feasibility and acceptability of the Survivor Choices for Eating and Drinking (SUCCEED) digital health dietary intervention after colorectal cancer (CRC): A randomized pilot trial
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Erin L. Van Blarigan, Stacey A. Kenfield, June M. Chan, Alan Paciorek, Li Zhang, Hilary Chan, Marissa Savoie, Andrea Grace Bocobo, Louis X. Wong, Angela Laffan, Katherine Van Loon, Chloe Atreya, Anthony Riberi, Olivier Riberi, Christine Miaskowski, Yoshimi Fukuoka, Jeffrey A. Meyerhardt, and Alan P. Venook
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Oncology ,Epidemiology - Abstract
Background: Dietary factors after CRC are associated with risk of recurrence and death. Our objective was to develop a digital health intervention to help individuals with CRC adopt healthy dietary habits. Methods: We conducted an unblinded 12-week (wk) pilot randomized trial to determine the feasibility and acceptability of a web-based dietary intervention with text messaging among individuals with CRC at the University of California, San Francisco. Eligible patients (pts) had colon or rectal adenocarcinoma, were not receiving chemotherapy, were disease-free or had stable disease, were able to speak and read English, and had a mobile phone. We excluded pts meeting ≥4 of the 6 target dietary behaviors. Pts were randomized 1:1 to intervention or control. All pts received print materials on diet after CRC. Pts in the intervention group received 12 wks of access to a website and daily text messaging that recommended ≥5 servings (serv)/day (d) of vegetables, ≥3 serv/d of whole grains, ≥2 serv/wk of fish, ≤2 alcoholic drinks/d for men and ≤1 alcoholic drinks/d for women, and no processed meat or sugar-sweetened beverages. Pts were encouraged to use the website to track intake of target dietary factors. Primary outcomes included feasibility (enrollment, time spent on website, text message response rate) and acceptability (self-administered online questionnaire). Secondarily, we estimated the effect of the intervention on diet using 4-d diet records, body size, blood pressure, and fasting C-reactive protein, hemoglobin A1c, glucose, cholesterol, and triglycerides using linear regression. Results: We screened 94 pts for eligibility; 75 were eligible and we randomized 50 to intervention (25) or control (25) between April 2017-May 2018. Over the course of the 12-wk study, the intervention arm accessed the website on a median of 2 d [interquartile range (IQR): 1-9 d] and spent a median of 28 min on the site (IQR: 4-51 min). Pts responded to a median of 15/21 text messages that asked for a reply (IQR: 8-20). 22/25 intervention pts completed the feedback survey; 82% were satisfied or very satisfied with the text messages. When asked to rate the quality of the website on a scale from 0-100, the median rating was 72 (IQR: 55-83). Diet records were available at baseline and 12 wks for 23 control and 22 intervention pts. Comparing baseline and 12 wks, intervention pts increased intake of whole grains (0.7 serv/d to 1.6 serv/d) and fatty fish (0 serv/d to 0.4 serv/d); controls did not change intake of whole grains (0.7 and 0.6 serv/d) or fatty fish (0.1 and 0 serv/d). We did not observe changes in either arm for other dietary factors, body size, blood pressure, or circulating markers. Conclusion: Individuals with CRC participating in a digital health dietary intervention engaged with text messaging more than a study website. The intervention led to changes in certain dietary behaviors. Additional work is needed to find strategies to increase engagement and modify other dietary factors. Trial Registration: NCT02965521 Funding: 5K07CA197077. Citation Format: Erin L. Van Blarigan, Stacey A. Kenfield, June M. Chan, Alan Paciorek, Li Zhang, Hilary Chan, Marissa Savoie, Andrea Grace Bocobo, Louis X. Wong, Angela Laffan, Katherine Van Loon, Chloe Atreya, Anthony Riberi, Olivier Riberi, Christine Miaskowski, Yoshimi Fukuoka, Jeffrey A. Meyerhardt, Alan P. Venook. Feasibility and acceptability of the Survivor Choices for Eating and Drinking (SUCCEED) digital health dietary intervention after colorectal cancer (CRC): A randomized pilot trial [abstract]. In: Proceedings of the AACR Special Conference on Modernizing Population Sciences in the Digital Age; 2019 Feb 19-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(9 Suppl):Abstract nr A18.
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- 2020
13. Abstract D111: Incidence and survival patterns of gastroenteropancreatic neuroendocrine neoplasms in California
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Alan Paciorek, Emily K. Bergsland, Meg McKinley, Li Zhang, Brandon E. Shih, Insoo Suh, Iona Cheng, Ann Griffin, Claire K. Mulvey, Katherine Van Loon, Eric K. Nakakura, and Quan-Yang Duh
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Epidemiology ,business.industry ,Incidence (epidemiology) ,Cancer ,medicine.disease ,Primary tumor ,Additional research ,Confidence interval ,Annual Percent Change ,Cancer registry ,Oncology ,Medicine ,Pacific islanders ,business ,Demography - Abstract
Background. Neuroendocrine neoplasms (NEN) are a heterogeneous group of rare tumors. There is a paucity of epidemiologic data regarding risk factors. We aimed to characterize the burden of NEN in California with its diverse racial/ethnic populations. Methods Using California Cancer Registry, we identified all newly diagnosed NEN from gastroenteropancreatic (GEP) sites 1992-2015. Annual age-adjusted incidence rates (AIR) per 100,000 person-years were compared, and average annual percent change (APC) in rates were compared according to sex, race-ethnicity (non-Hispanic (NH) white, NH black, Asian/Pacific Islander, American Indian, Hispanic), primary tumor site (stomach, small intestine, colon or rectum, appendix, pancreas), stage, and type of county of residence (urban, suburban, rural) using incidence rate ratios (IRR). Overall survival from diagnosis to death by any cause was estimated by Kaplan-Meier method and compared using log-rank tests. Results There were 23,983 GEP NEN incident cases and 9,910 deaths 1992-2015. All AIRs increased over the 24 years, with the greatest increase in Hispanics with pancreatic NEN (APC 8.9). Rates for the period 2011-2015 varied according to primary tumor site: colorectal (AIR 1.41); small intestinal (AIR 0.97); pancreatic (AIR 0.92); stomach (AIR 0.44); and appendiceal (AIR 0.36). Comparing rates by populations the greatest disparities were for NH blacks vs. Asians with small intestinal NEN (IRR 7.01 95% confidence interval (CI) [5.37-9.21]) or appendiceal NEN (IRR 3.74 95% CI [2.34-6.08]), for NH whites vs. Asians with small intestinal NEN (IRR 4.34 95% CI [3.44-5.53]) or appendiceal NEN (IRR 5.10 95% CI [3.54-7.59]), for NH blacks vs. NH whites with colorectal NEN (IRR 2.59 95% CI [2.27-2.94]), and for NH whites vs. Hispanics with appendiceal NEN (IRR 2.54 95% CI [2.08-3.12]). Statistically significantly longer survival estimates were observed in women (median 13.1 years) vs. men (11.6 years), and in Asians/Pacific Islanders (20.7 years) and Hispanics (16.7 years) vs. NH blacks (12.3 years) and NH whites (9.6 years). No significant survival differences were detected across county types. Survival estimates were significantly different across primary tumor sites: colorectal (median 19.9 years); appendiceal (16.0 years); small intestinal (10.1 years); stomach (9.7 years); and pancreatic (4.4 years). Conclusions Incidence rates of GEP NEN in California steadily increase from 1992 through 2015 for all populations. Recent AIRs for particular race-ethnicities and primary tumor sites are more than double others, exposing large disparities. Survival estimates differ significantly by primary tumor site, sex, race-ethnicity, and stage, but not by county. These findings show some higher incidence rates and longer survival than in previously published estimates nationwide and add information about GEP NEN in Hispanic and Asian/Pacific Islander populations in California. Additional research is needed to clarify reasons for the disparities. Citation Format: Alan Paciorek, Brandon Shih, Meg McKinley, Iona Cheng, Li Zhang, Claire Mulvey, Ann Griffin, Eric Nakakura, Quan-Yang Duh, Insoo Suh, Katherine Van Loon, Emily Bergsland. Incidence and survival patterns of gastroenteropancreatic neuroendocrine neoplasms in California [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D111.
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- 2020
14. Abstract A108: Differences in incidence by sex and race/ethnicity of adrenocortical carcinomas and malignant pheochromocytomas and paragangliomas in California
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Ann Griffin, Meg McKinley, Dawn Pearson, Iona Cheng, Alan Paciorek, Chienying Liu, Li Zhang, Emily K. Bergsland, Claire K. Mulvey, Sanziana A. Roman, Katherine Van Loon, Brandon E. Shih, Quan-Yang Duh, Insoo Suh, and Julie Ann Sosa
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Race ethnicity ,Oncology ,Epidemiology ,business.industry ,Incidence (epidemiology) ,Medicine ,business ,Demography - Abstract
Background: Malignant pheochromocytomas (PHEO), paragangliomas (PGL), and adrenocortical carcinomas (ACC) are rare endocrine malignancies with limited data regarding risk factors. To further elucidate their epidemiology, we sought to characterize the burden of malignant PHEO, PGL, and ACC in California. Methods: Using the population-based California Cancer Registry, we identified all new diagnoses of malignant PHEO, PGL, and ACC in California from 1992-2016 (ICD-O-3 codes 8700/3, 8680/3, and 8393/3). We calculated age-adjusted incidence rates (AIR) standardized to the 2000 United States census. We compared AIRs by sex, race/ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic, and Asian/Pacific Islander), and county of residence (categorized as urban versus suburban/rural) using SEER*Stat and generated IR ratios (IRR). Results: Between 1992-2016, there were 261 incident cases of malignant PHEO, 271 of malignant PGL, and 866 of ACC in California. Overall AIR per 100,000 person-years were 0.03 for PHEO, 0.03 for PGL, and 0.10 for ACC. Incidence differed by both sex and race/ethnicity. Men had a higher incidence of PGL than women (IRR 1.49, 95% confidence interval [CI] 1.13-1.98; p Citation Format: Claire K. Mulvey, Alan Paciorek, Brandon Shih, Meg McKinley, Dawn Pearson, Iona Cheng, Li Zhang, Ann Griffin, Quan-Yang Duh, Sanziana Roman, Julie Ann Sosa, Insoo Suh, Chienying Liu, Katherine Van Loon, Emily Bergsland. Differences in incidence by sex and race/ethnicity of adrenocortical carcinomas and malignant pheochromocytomas and paragangliomas in California [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr A108.
- Published
- 2020
15. Abstract B06: Investigating the microbial etiology of Tanzanian esophageal squamous cell carcinoma
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Larry Akoko, Katherine Van Loon, Eric Collisson, Yulia Newton, Elia John Mmbaga, Jason Nomburg, Msiba Seleka, Amie Radenbuagh, Susan Bullman, Beatrice Mushi, James A. DeCaprio, Charles J. Vaske, and Matthew Meyerson
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Cancer Research ,biology ,Colorectal cancer ,Human microbiome ,Esophageal cancer ,medicine.disease ,biology.organism_classification ,medicine.disease_cause ,digestive system diseases ,Oncology ,Fusobacterium ,medicine ,Cancer research ,Prevotella ,Microbiome ,Oral Microbiome ,Carcinogenesis - Abstract
Background: Esophageal cancer is a leading cause of cancer-associated deaths worldwide. Notably, there is a disproportionately high incidence of esophageal squamous cell carcinoma (ESCC) throughout the eastern corridor of Africa. One possible explanation for the unique geographic distribution of ESCC may be the human microbiome, which has been shown to influence other gastrointestinal (GI) cancers, including gastric and colorectal cancer (CRC). Methods: To address this question, we conducted RNA sequencing (RNAseq) and whole-genome sequencing (WGS) of samples from 61 Tanzanian ESCC patients. We used the computational microbial identification and classification software PathSeq to conduct a microbial abundance analysis of these samples. Next, we implemented linear discriminant analysis with LEfSe to determine which, if any, microbial taxa are enriched in the ESCC tumors of Tanzanian patients relative to ESCC samples from North America patients available through The Cancer Genome Atlas (TCGA). Results: Analysis of these RNAseq and WGS data reveals an extremely high abundance of Fusobacterium, Prevotella, and Streptococcus in the tumors of a subset of these patients. Based on the WGS data in particular, 14, 45, and 27 of the 61 ESCC samples maintain at least 10% relative abundance of Fusobacterium, Prevotella, and Streptococcus, respectively. The RNAseq data are consistent and reveal that as much as 75% of all bacterially derived reads in these samples are from these genera. Furthermore, LEfSe analysis suggest that these bacteria are significantly enriched in Tanzanian ESCC samples compared to North American ESCC samples. Discussion: These data suggest that the microbiome may be involved in ESCC incidence in Tanzania. Fusobacterium, Prevotella, and Streptococcus are notable for their association with CRC and are correlated with distinct clinical and molecular CRC characteristics. Members of these bacterial genera have been observed to modulate the carcinogenesis of GI cancers in a variety of ways, including through the selective stimulation or inhibition of various classes of immune cells. Furthermore, species within these genera have been observed invasively within cancerous GI tissues. Current studies are under way to visualize these microorganisms in tumor tissue, to characterize their association with molecular subtypes of ESCC, and to understand the relationship between tumor-associated bacteria and bacteria in the oral microbiome of ESCC patients in Tanzania. Citation Format: Jason Nomburg, Susan Bullman, Eric Collisson, Beatrice Mushi, Msiba Seleka, Charlie Vaske, Yulia Newton, Amie Radenbuagh, Larry Akoko, James A. DeCaprio, Matthew Meyerson, Elia J. Mmbaga, Katherine Van Loon. Investigating the microbial etiology of Tanzanian esophageal squamous cell carcinoma [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr B06.
- Published
- 2020
16. Abstract 2522: RNA rescue somatic mutations and RNA editing in esophageal cancer
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Amie J. Radenbaugh, J Zachary Sanborn, Yulia Newton, Charlie Vaske, Katherine Van Loon, and Eric Collisson
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Cancer Research ,Oncology - Abstract
The detection of somatic single nucleotide variants is a crucial component to the characterization of the cancer genome. Traditional mutation calling algorithms have focused on comparing the normal and tumor DNA from the same individual. For projects like The Cancer Genome Atlas (TCGA), it became routine to also sequence the tumor RNA. Our computational method, RADIA (RNA and DNA Integrated Analysis), combines the patient-matched normal and tumor DNA with the tumor RNA to detect somatic mutations. The inclusion of the RNA increases the power to detect somatic mutations, especially at low DNA allelic frequencies or when tumor purity is low. By integrating an individual’s DNA and RNA, we are able to detect mutations that would otherwise be missed by traditional algorithms that examine only the DNA. Mutations with high support in the RNA and low support in the DNA are termed RNA Rescue mutations. RNA editing is a post-transcriptional modification of pre-mRNA that has recently been identified as an additional epigenetic mechanism relevant to cancer development and progression. Using patient-matched normal and tumor DNA along with tumor RNA, we are able to identify RNA editing events across the entire transcriptome. There exists a remarkable geographic variability observed in incidence rates for Esophageal Cancer where more than 80% of cases and deaths occur in developing countries. There is an urgent demand to address the unmet clinical needs for these regions. Mutation of the tumor suppressor gene TP53 is the most frequent genetic alteration in both Esophageal Squamous Cell Cancer (ESCC) and Esophageal Adenocarcinoma (EAC). In a previous study of 59 tumors in Malawi a high proportion of tumors without TP53 mutations was reported. Here, we apply RADIA to a cohort of 61 tumors from Tanzania, and identify RNA Rescue Mutations that were previously missed by DNA mutation callers in significantly mutated genes such as TP53, CDK6, NOTCH1, VEGFA, KMT2D. RNA Editing events in the 3’UTR regions of genes are very common, especially when Alu elements are present, and are known to deregulate microRNA mediated gene regulation. MDM2 is a key oncogene in the p53 pathway with elevated gene expression in many tumor types and is known to be transcriptionally repressed by microRNAs. Here we detect transcriptome-wide RNA Editing events, and identify RNA Editing events in the seed regions of microRNA target sites of genes such as MDM2. We will also show how RNA Editing of certain genes are significantly associated with an RNA-Seq clustering solution. These genes show significantly differential expression between RNA-Seq clusters, indicating that these editing events have a functional impact on the genes they affect. We will further investigate these functional effects and downstream implications on the molecular characterization of the RNA-Seq subtypes. Citation Format: Amie J. Radenbaugh, J Zachary Sanborn, Yulia Newton, Charlie Vaske, Katherine Van Loon, Eric Collisson. RNA rescue somatic mutations and RNA editing in esophageal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2522.
- Published
- 2019
17. Abstract B39: A pilot study to establish procedures for DNA and RNA isolation from African esophageal tumor specimens
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Elia John Mmbaga, Charles William Cahalane, Beatrice Mushi, Ali Mwanga, John Greer, Eric A. Collisson, Katherine Van Loon, Msiba Selekwa, and Larry Akoko
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.diagnostic_test ,Cancer ,RNA ,Transit time ,RNA integrity number ,Biology ,medicine.disease ,Transcriptome Sequencing ,chemistry.chemical_compound ,chemistry ,Internal medicine ,Biopsy ,medicine ,RNA extraction ,DNA - Abstract
Objective: We propose to utilize tumor biospecimens from patients with esophageal squamous cell carcinoma (ESCC) to identify possible genetic, molecular, and infectious determinants of this high-incidence disease in East Africa. However, laboratory technologies in East Africa are not available to support DNA and RNA extraction and genome and transcriptome sequencing from patient specimens. In preparation for establishment of a biorepository for African ESCC specimens, we compared different fixation and preservation media for transportability over long distances and success in preserving the genetic integrity and expression profiles of ESCC. Methods: Patients with a suspected diagnosis of ESCC at Muhimbili National Hospital in Dar es Salaam, Tanzania were identified and consented prior to endoscopic evaluations. For patients with endoscopic findings consistent with ESCC, tumor biopsies were obtained and stored using two different fixation and preservation media: PAXgene® Tissue Container (n=2) and RNAlater® (n=2). All specimens were shipped at room temperature from Dar es Salaam to San Francisco. DNA and RNA quantity was measured by nanodrop method and DNA was further confirmed by picogreen method, yielding measures of total DNA and RNA acquired (ug). DNA quality was measured as percent of total DNA degradation to between 200-1000 bp. RNA quality measure was determined by bioanalyzer output measure RNA Integrity Number (RIN). Results: Specimens for our first 10 patients were analyzed. Average transit time of biopsy specimens in preservative at room temperature was 6.2 days (range 3.5-9.0). Tumor specimens preserved with PAXgene® yielded a mean of 7.7 ug total DNA and 8.6 ug total RNA. Tumor specimens preserved with RNAlater® yielded a mean 1.4 ug of DNA and 8.2 ug of RNA. DNA degradation products were 0% of total with PAXgene® versus 6% of total with RNAlater®. Specimens preserved with PAXgene® yielded a mean RIN of 4, while RNAlater® yielded a mean RIN of 9. DNA and RNA quality were not associated with length of time at room temperature, up to a maximum of 9 days. Conclusion: Tissue preserved using the PAXgene® Tissue Container yielded higher DNA quantity and quality than tissue preserved in RNAlater®. RNA quantity was comparable for both mediums, but RNAlater® resulted in superior RNA quality versus PAXgene®. Both mediums allowed for flexible transport of specimens at room temperature and merit further inquiry into their potential as cost-effective methods to facilitate molecular analyses for geographically isolated diseases in Africa. Based upon our pilot data, each medium offers unique advantages. Our expanded study will continue to utilize both mediums to optimize isolation of both DNA and RNA. We will plan to present data for an enriched sample size. Funding source: National Institutes of Health, National Cancer Institute Cancer Center Administrative Supplement to Promote Cancer Prevention and Control Research in Low and Middle Income Countries, A119617, [CA-0082629]. Citation Format: Beatrice Paul Mushi, John Greer, Charles William Cahalane, II, Msiba Selekwa, Ali Mwanga, Larry Akoko, Elia Mmbaga, Eric Collisson, Katherine Van Loon. A pilot study to establish procedures for DNA and RNA isolation from African esophageal tumor specimens [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr B39.
- Published
- 2017
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