Mexico Comprehensive Cancer Center Research Articles

Abstract C086: Somatic mutation variations in minority populations at the University of New Mexico Comprehensive Cancer Center

Abstract The global burden of cancer underscores the urgency to understand its genetic underpinnings. Genetic testing has revolutionized clinical practice, identifying driver mutations crucial for tumorigenesis, including TP53, PIK3CA, KRAS, PTEN, and ARID1A. However, minority populations are underrepresented in major genomic projects, hindering tailored therapies. Variations in genetic polymorphisms among ethnicities, exemplified by distinct patterns in mutations like BRCA and EGFR, underscore the imperative for diversity in genomic research. We conducted a retrospective study at the University of New Mexico Comprehensive Cancer Center, analyzing 5,045 patients' genetic testing data. Significant differences in somatic gene mutation frequencies and survival outcomes were observed across racial and ethnic groups, highlighting the importance of personalized approaches in cancer care. Specific gene mutations, such as IDH1, JAK2, KITX11, and TP53, were associated with distinct survival outcomes. Integrating genetic testing into routine practice could enhance patient stratification and treatment efficacy. Future research should explore underlying mechanisms and include larger, diverse populations to advance personalized medicine in oncology. Citation Format: Isabella Doan, Jonathan Coy, Bernard Tawfik. Somatic mutation variations in minority populations at the University of New Mexico Comprehensive Cancer Center [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C086.

Abstract A084: Journey to understanding indigenous peoples engagement in cancer genomic research

Abstract Introduction: Tribal Nations across the Southwest have striking disparities in cancer incidence and mortality. Compounded by disproportionately low rates of cancer screening and limited access to healthcare, Native Americans are more often diagnosed at later stages of disease and have the poorest outcomes in all types of cancer when compared to any other racial and ethnic group in the United States. At the University of New Mexico Comprehensive Cancer Center, the Participant Engagement Cancer Genomic Sequencing (PE-CGS) Center is developing culturally appropriate materials and strategies to enhance the engagement and recruitment of Native Americans into genomic research. This effort aims to determine participant knowledges, attitudes, cultural beliefs, and communication preferences regarding clinical genomics testing. Ultimately, targeting improvement of cancer outcomes in Southwestern Tribal communities. Cultural adaptations are crucial with regards to biospecimen collection, storage, and usage, due to historical mistrust of research among Native communities. (i.e., Havasupai Tribe v. the Arizona Board of Regents). A Tribal Advisory Committee, consisting of Tribal leaders, Native physicians, and patient advocates oversee all aspects of the research study. The goal is to identify appropriate optimized health literacy strategies for engaging Native peoples in cancer genomic research. Methods: The team conducted semi-structured discussions with participants to understand their perspectives on motivations to join, cultural safety components, and effectiveness of engagement strategies. With participant consent, the discussions were recorded and transcribed. Analysis included the transcripts and notes taken by the interviewer and followed Grounded Theory principles. All transcripts and notes followed line-by-line analysis by three of the authors (JS, JR and TG) who met regularly to identify and discuss emergent themes. Results: As of May 31, 2024, the PE-CGS study has enrolled 112 participants and completed 39 discussions. Participants emphasized altruistic motives tied to family and community, echoing traditional values, in their decision to participate in the study. This notion emerged during interactions with Native team members, where comfort stemmed from shared experiences (healthcare system, barriers), use of Native language, and adherence to Native social norms. Additional considerations included present autonomy throughout various stages of the study (sample use, data sharing, discussions). Return of genetic testing results improved understanding of treatment options, hereditary risk, and health literacy. Conclusion: Feedback highlights the importance of aligning cultural beliefs with Western medicine through a strengths-based approach. The findings will inform improvements in respectful engagement, communication, information exchange, and recruitment processes with Native American cancer patients and cancer survivors to genomic testing studies. Citation Format: Jessica Sanchez, Koby Blackwater, Joseph Rodman, Tamar Ginossar, Andrew Sussman, Shiraz Mishra, Cindy Blair, Mallery Quetawki, Debra MacKenzie, V. Shane Pankratz, Ursa Brown-Glaberman, Jeffery Trent, Cheryl Willman. Journey to understanding indigenous peoples engagement in cancer genomic research [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A084.

Stepping Up Summer Fun: the Cancer Research - Scholarship and Training Experience in Population Sciences (C-STEPS) Program.

Over the last two decades, strides in cancer prevention, earlier detection, and novel treatments have reduced overall cancer mortality; however, cancer health disparities (CHD) persist among demographically diverse and intersecting populations. The development of a culturally responsive workforce trained in interdisciplinary, team-based science is a key strategy for addressing these cancer disparities. The Cancer Research - Scholarship and Training Experience in Population Sciences (C-STEPS) program at the University of New Mexico Comprehensive Cancer Center is designed to increase and diversify the biomedical and behavioral research workforce by providing specialized and experiential curricula that highlight team-oriented cancer control and population science. Undergraduate students interested in CHD and in pursuing STEM-H (science, technology, engineering, mathematics, and health) graduate or professional degrees are eligible for the program. C-STEPS students are paired with a UNM faculty mentor, who guides the student's 10-week summer research experience. They receive mentorship and support from three layers-faculty, near-peers (graduate students), and peers (undergraduates who have completed the C-STEPS program previously). Students generate five products, including a capstone presentation, grounded in the research they conduct with their faculty mentors. Since its founding in 2021, C-STEPS has trained three cohorts with a total of 32 students. The C-STEPS program provides a unique team-science approach with multilayer mentoring to create a sustainable pipeline for the development of students interested in STEM-H fields and CHD research. The capstone project led to 47% of students presenting their work at conferences, and two publishing their manuscripts in peer-reviewed journals. Overall, 89% of students were either "satisfied" or "very satisfied" with the program and the same percentage recommended the program to other undergraduates.

Metabolomic and transcriptomic alterations in the colon of mice with metabolic syndrome in the absence of inflammation

Metabolic syndrome (MetS) is characterized by a cluster of conditions including abdominal obesity, elevated blood pressure, altered lipid profiles and high blood sugar levels. These factors collectively elevate risks for cardiovascular diseases, diabetes, and metabolic dysfunction associated steatotic liver disease (MASLD). MetS impacts approximately a third of the US populace and a quarter of the global population. Despite its widespread prevalence, there are no existing medications to specifically treat MetS. With the global rise in MetS cases, understanding its underlying mechanisms is paramount. Our research emphasizes the potential physiological and metabolic disruptions within the gastrointestinal (GI) tract that might contribute to MetS manifestation. Using a mouse model of MetS (MS NASH) and healthy lean controls (C57BL/6J), we investigated the colon environment. 16S rRNA sequencing from fecal samples revealed a distinct microbiota profile in MS NASH mice, highlighted by an increase in the Lactobacillus genus. Colonic metabolome and transcriptome in MS NASH mice displayed an upregulation in anabolic pathways, like glycolysis, the pentose phosphate pathway, and the tryptophan/kynurenine pathway. Subsequent integrated analysis of these datasets unveiled potential compensatory mechanisms and pathway crosstalk, within the colonic environment. Despite these alterations, MS NASH mice showed no signs of intestinal inflammation, a finding confirmed through detailed histological and LCN-2 assessments. Additionally, there were no changes detected in genes typically associated with increased intestinal inflammation or permeability. This study provides insight in the nuanced relationship between the metabolic state, gut microbiota, and potential progression towards other metabolic disorders. Our findings highlight the significance of multi-omics data convergence in understanding the changes within the colonic environment and their implications for MetS onset and/or progression. Supported in part by the National Center for Research Resources and the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH) through grant no. UL1TR001449 (E.F.C.) and in part by NIH grant P20GM121176 (E.F.C.), and the University of New Mexico Comprehensive Cancer Center with grant P30CA118100. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Abstract A111: Summertime fun: Findings from three cohorts of C-STEPS summer research trainees

Abstract Introduction: For the past three summers (2021-2023), a National Cancer Institute-funded R25 research education program has been underway at the University of New Mexico Comprehensive Cancer Center, entitled “Cancer Research—Scholarship and Training Experiences in Population Sciences” (C-STEPS). The program engages a diverse population of undergraduate students from across the nation in hands-on, mentored 10-week summer research education and training in cancer control and population science (CCPS). Methods: Using a data-driven methodology, the C-STEPS team has collected quantitative and qualitative data via REDCap surveys to evaluate program aims and student progress and ascertain how students experience the program to improve it for future cohorts. Students who decline admission are provided a one-time survey about the reasons they declined and asked to prioritize factors in their selection of summer research programs. Students enrolled in the program complete a pre- and post-program survey, pre- and post-seminar surveys, and a bi-annual alumni survey. The pre- and post-seminar surveys reflect expected competencies for each of the eight seminars that are part of the curriculum. The alumni survey captures academic accomplishments and career updates since completion of the summer program. Results: We have collected three years of pre/post-program data and pre/post-seminar data. Student knowledge, confidence, and interest in CCPS has steadily increased within each cohort across each of the three time periods: pre-program, immediately post-program, and alumni (1-3 years after the initial research experience). The pre/post seminar surveys indicated that the structure of the seminars inhibited interactions between the presenter and students and warranted change. We have administered the decliner and alumni survey twice each. Data from the decliner survey suggest that students apply to multiple programs each summer and the timeframe for notification to students about their acceptance may need to be shortened to give students more time to consider their C-STEPS offer in relation to other summer opportunities. Data from the alumni survey indicate that students continue to engage in research with their C-STEPS mentor and present the research at their home institution. Conclusion: Efforts to decrease the length of time between when a student applies and when they are notified of their acceptance are at the forefront of the refinement process for the next cohort. The seminars have been restructured to promote more student-led discussions and interactions between presenters and students. The CCPS research experiences and professional networks students develop during the summer have led to new educational and career opportunities. Initial evidence indicates that the success of C-STEPS extends well beyond the immediate one-time immersive research experience. Citation Format: Shoshana Adler Jaffe, Paige A. Lynch, Judith Sheche, Joseph Rodman, Miria Kano, Shiraz I. Mishra. Summertime fun: Findings from three cohorts of C-STEPS summer research trainees [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A111.

Abstract IA016: Best practice strategies for SOGI data collection: Lessons learned from conducting and implementing the Ask SOGI study

Abstract Background: Collection of reliable data on Sexual Orientation and Gender Identity (SOGI) is essential for improving cancer care for Sexual and Gender Minority (SGM) populations that experience health disparities. To address gaps in reliable SOGI data collection, the National Cancer Institute (NCI) funded a series of awards to enhance sexual orientation and gender identity (SOGI) data collection at cancer centers. In August 2022, we launched the “We Ask Because We Care: Enhancing Sexual Orientation and Gender Identity Data Collection in New Mexico Cancer Center” (Ask SOGI) research intervention at the University of New Mexico Comprehensive Cancer Center (UNMCCC). Methods: Our research team used a mixed methods framework that included a cancer center-wide readiness assessment survey and focus groups to: 1) identify potential barriers to the systematic collection of patient SOGI data, incorporate National Academy of Science Engineering Medicine (NASEM) recommended SOGI measures into the UNMCCC Electronic Health Records; 2) tailor future staff/provider-cultural competency/cultural humility educational interventions, and 3) design a patient-facing “We Ask Because We Care” campaign to encourage welcoming and comfortable care for SGM patients and their informal cancer caregivers. Results: Although the study is on-going, initial survey findings suggest that staff and provider concerns regarding the appropriate method and time for asking patients about their SOGI may inhibit data collection at the cancer center. Respondents desired cancer center led education and training for staff and faculty that would include appropriate points and methods for SOGI data collection, demonstrations of SOGI integration and utilization into the electronic health record, and strategies to encourage conversational confidence so staff and providers can engage patients and their caregivers in sensitive topics. Moreover, SGM patients and caregiver focus group participant reviewers of the emerging “We Ask Because We Care” campaign were positive about the visual images, and acknowledged the importance of such efforts for creating affirmative spaces for SGM persons experiencing cancer. Conclusion: Interventions that address multilevel staff and provider, as well as patient and caregiver concerns regarding discussions of sexual orientation and gender identity data collection may increase more consistent collection of SOGI data that can be used to enhance cancer care and health disparities research. Citation Format: Miria Kano, Dolores Guest, Amy Farnbach Pearson, Mikaela Kosich, Kendal A. Jacobson, Shiraz Mishra, Andrew Sussman, Bernard Tawfik, Zoneddy Dayao, NFN Scout, Cathleen Willging. Best practice strategies for SOGI data collection: Lessons learned from conducting and implementing the Ask SOGI study [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr IA016.

Abstract B134: The art of science: Painting a new image of genomic research in the indigenous communities of the Southwest

Abstract Introduction: The Patient Engagement-Cancer Genome Sequencing Research Center (PE-CGS; NCI U2C CA252973) based at the University of New Mexico Comprehensive Cancer Center (UNMCCC) with partners at Mayo Clinic Comprehensive Cancer Center, the Translational Genomics Research Institute, and the Black Hills for American Indian Health Research Center are developing culturally appropriate strategies and methods to address the underrepresentation of American Indians (AIs) in genomic research. Our efforts are directed towards the implementation of tailored cancer prevention, diagnosis, and treatment strategies that reduce cancer health disparities in Tribal communities. Methods: The PE-CGS Center has three units, each tasked with specific research components to engage AI participants in participatory, clinically-meaningful genomic research: 1) the Participant Engagement Unit; 2) the Genomics Characterization Unit; and 3) the Engagement Optimization Unit (EOU). The Center also has a Tribal Advisory Committee, composed of Tribal Governors, Presidents, and tribal health advocates and experts, who provide direction on all research matters. The PE-CGS EOU uses iterative rapid-cycle research techniques to optimize engagement and shares these strategies with other units for timely implementation. To date, the EOU has developed and implemented three key efforts. First, to aid in recruiting participants for the study, the EOU tailored a series (6) of participant-facing informational materials that include artwork from a local AI artist who combined her traditional and scientific knowledge to prepare complementary imagery. Second, the EOU is currently implementing a series of semi-structured discussions to document participant perceptions on criteria including engagement, communication, and education. Lastly, the EOU implemented a survey among UNMCCC providers on their return of results processes. Results: EOU discussions are ongoing and have provided important perspectives on participant satisfaction and areas for improvement. Participants have commended study staff on their efforts to make enrollment straightforward. Participants report discussing the study with family prior to enrolling, highlighting the importance of continuing to engage with the entire community on the goals of the study. The provider return of results survey is complete (n=42/62, response rate=68%); one key finding was that providers who return somatic test results rarely provide participants with a hard copy of the results or utilize complementary materials that might enhance their explanation of the test findings. Conclusion: The EOU serves an innovative function through its rapid-cycle methods to optimize participant engagement. Although participants are generally pleased with their study participation, there are numerous opportunities for improvement. The informational materials represent a novel contribution to the field of genomic research. Efforts will continue to implement optimized processes for effective engagement of AI communities in genomic research and cancer care delivery. Citation Format: Shoshana Adler Jaffe, Kendal Jacobson, Joseph Rodman, Cindy Blair, Debra MacKenzie, Mallery Quetawki, Tamar Ginossar, V. Shane Pankratz, Andrew Sussman, Ursa Brown-Glabermen, Jeffrey Trent, Cheryl Willman, Shiraz I. Mishra. The art of science: Painting a new image of genomic research in the indigenous communities of the Southwest [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B134.

Abstract A109: The growth and evolution of GMaP Region 3 Technical Training Summits

Abstract Introduction: The Geographic Management of Cancer Health Disparities Program (GMaP) is a national program funded by the National Cancer Institute’s (NCI) Center to Reduce Cancer Health Disparities with the mission to expand and diversify the pipeline of cancer researchers. GMaP Region 3 is one of seven regions, and is comprised of members from seven Southwestern US states. The University of New Mexico Comprehensive Cancer Center serves as the hub for GMaP Region 3, and has hosted three seminal training Summits. Methods: GMaP Technical Training Summits provided hands-on learning experiences for cancer health disparities (CHD) trainees and promoted collaboration among Region 3’s NCI-designated cancer centers. GMaP Region 6 collaborated with Region 3 to host the final two Summits. Each of the three Summits had differing aims, but the core goals were to strengthen grant writing skills, enhance professional development, in addition to providing opportunities for networking and mentorship. Summit activities included keynote addresses by senior researchers, many of whom are members of historically underrepresented populations, interactive grant writing sessions, and mock grant reviews. Attendee feedback was captured via REDCap surveys and qualitative experience summary reports. Results: Each Summit had increasing attendance: 2016 Summit, n=29, 2019 Summit, n=35; 2023 Summit, n=48. Summit length grew from 1 full day to 2.5 days of sessions. Although the majority of participants were from Regions 3 and 6 there were also attendees from Region 2 and 5 demonstrating the desirability of this type of intensive grant writing training. Attendees were largely satisfied with their experience and in 2023 the overall reception of the summit material was 87% positive. Attendees highlighted the benefits of receiving individualized feedback on their Specific Aims page and the ability to meet people doing similar work. Summits were described as “invigorating” and “motivational”. Participants across the years highlighted the value of hearing from influential researchers in the field and cited these keynote addresses as being “inspirational”. Challenges of hosting these Summits included logistical barriers specifically pertaining to ensuring that scholars had the financial support they needed to attend prior to each event. In addition, tailoring the Summit curriculum and coordinating appropriate speakers was an ongoing learning process. Recommendations: Grant writing is both a science and an art and many scholars, particularly those from underrepresented groups, do not have access to the focused training necessary to develop successful proposals. The GMaP Region 3 Summits provided opportunities for scholars to learn from experienced grant writers and network with their peers. Future efforts to provide tailored grant writing education to newer cancer researchers should be prioritized to support their career development and diversify the types of CHD research proposed and ultimately funded. Citation Format: Shoshana Adler Jaffe, Dolores D. Guest, John Torres, Miria Kano, Andrew Sussman, Shiraz I. Mishra. The growth and evolution of GMaP Region 3 Technical Training Summits [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A109.

Abstract C019: Comparing the effectiveness of different community education approaches on colorectal cancer knowledge

Abstract Introduction: Colorectal cancer (CRC) incidence and mortality varies greatly among racial/ethnic groups nationally. Community outreach and education are effective strategies to enhance knowledge of CRC and have been shown to increase screening for CRC. The University of New Mexico Comprehensive Cancer Center implements Screen to Save, a community-based CRC screening initiative through the National Outreach Network Program. During the COVID-19 pandemic, restrictions on in-person engagement led to the development and implementation of alternative delivery strategies. Our site continued in-person education as possible, and added Zoom and fully self-paced via QR code options for community member participation. Very little is known regarding the effectiveness of different delivery modes. The purpose of this research is to examine the relationship between method of education session delivery and participant CRC knowledge. Methods: Participants were recruited via community organizations, Facebook advertising, and referrals from local stakeholders. Both before and after a standardized health education session, participants completed a survey assessing their knowledge of CRC risk and screening recommendations. Participant demographics were descriptively summarized. Estimates of mean changes, and 95% confidence intervals (CI), were obtained for each content delivery type. Differences in these changes were compared using ANCOVA approaches. Results: There were 239 participants who completed the educational sessions in-person (n=81), via Zoom (n=66), or using the self-paced module (n=92), Groups did not differ significantly in composition for age (p=0.72) or gender (p=0.33), but did differ in race, ethnicity, and education level (p<0. 001). Those who participated in any delivery method improved their knowledge scores by 11.6 (95% CI: 9.9-13.3) percentage points. For in-person, Zoom, and self-paced groups, the improvements were 14.1 (95% CI: 10.6-17.6, p<0.001), 11.5 (95% CI: 9.1-13.8, p<0.001), and 9.4 (95% CI: 6.7-12.1, p<0.001) percentage points, respectively. When comparing pre vs post score differences among session types while adjusting for pre scores, and for baseline differences in race, ethnicity, and education, the differences in improvement for the three different session types were not significantly different (p=0.68). For in-person, Zoom, and self-paced groups adjusted improvements were 9.2 (95% CI: 0.5-17.5), 11.1 (95% CI: 1.9-19.8), and 10.1 (95% CI: 1.5-18.3) percentage points, respectively. Conclusion: Health education sessions delivered in person, via Zoom, and by self-paced online modules are associated with increases in participant knowledge of CRC. As Cancer Centers expand community outreach and engagement to address cancer health disparities in their catchment areas, a better understanding of the relative effectiveness of different delivery strategies is needed. Further research will help to discern population characteristics predictive of different strategies and link these approaches to screening uptake. Citation Format: Lila A. Baca, Yadira Aguero, Angelica Solares, Vernon Shane Pankratz, Shiraz I. Mishra, Miria Kano, Andrew L. Sussman. Comparing the effectiveness of different community education approaches on colorectal cancer knowledge [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C019.

Impact of audio-visual tool on patient comfort level at a comprehensive cancer center infusion suite: Preliminary results.

348 Background: Patients receiving chemotherapy often experience anxiety which may result in dissatisfaction with care and decreased adherence to treatment, subsequently leading to unfavorable outcomes. Patient education is shown to ameliorate the anxiety and improve patient comfort. However, retention of information by patients may be sub-optimal in this setting and utilization of multiple information sources may enhance patient recall. We hypothesized that a short “welcome video” on what to expect at an infusion visit, in addition to nursing- patient education would improve patient comfort level. Methods: We conducted a single center prospective pre-post study at the University of New Mexico Comprehensive Cancer Center (UNMCCC) to evaluate the impact of an educational audio-visual tool on the comfort level of patients. An introductory welcome video was developed and made available on: (i) the UNMCCC website (ii) on iPads All patients receiving infusions are asked to complete a survey prior to their infusion. In the phase 1 patients completed surveys prior to the “welcome video” being released. In the phase 2, the video has been introduced. We plan to compare the comfort level of the two populations before and after the video release. Study was reviewed and approved by University of New Mexico Health Sciences IRB. Results: In the first phase, 43 patients completed the survey. Overall, patients felt to have a good understanding of what to expect on their infusion day (average score - 8.9/10), felt somewhat nervous (average score: 3/10), and were interested to learn more about treatment side effects (average score: 5/10), on the 10-point Likert scale (1- strongly disagree, 10- strongly agree (table 1). In the phase 2, preliminary data collection on 40 surveyed patients showed that only 15% (6/40) watched the welcome video. Strategies planned to enhance access including a text message link to the video at patient registration are being implemented as we continue to collect phase 2 survey results. Conclusions: At our center, patients already demonstrate a strong sense of comprehension regarding what to anticipate on their infusion day, primarily through nursing-patient education. Our goal is to further enhance their understanding by improving the delivery of our welcome video and refining the survey questions to yield more informative insights.[Table: see text]

Unfolded Protein Response Factor ATF6 Augments T Helper Cell Responses and Promotes Mixed Granulocytic Airway Inflammation

Abstract The unfolded protein response (UPR) plays a critical role in many diseases, including airway inflammation. Several recent studies demonstrated a pathogenic role of Activating transcription factor 6a (ATF6a or ATF6), one of the essential arms of UPR, in airway structural cells. However, its role in T helper (TH) cells has not been well examined. In this study, we found that ATF6 was selectively induced by STAT6 and STAT3 in TH2 and TH17 cells, respectively. ATF6 upregulated UPR genes and promoted the differentiation and cytokine production of TH2 and TH17 cells. T cell-specific Atf6-deficiency impaired TH2 and TH17 responses in vitro and in vivo and attenuated mixed granulocytic experimental asthma. ATF6 inhibitor Ceapin A7 suppressed ATF6 downstream gene expression and TH cell cytokine expression in both murine and human memory CD4 +T cells. Administration of Ceapin A7 lessened both TH2 and TH17 responses in vivo, leading to alleviation of both airway neutrophilia and eosinophilia. Thus, our results demonstrate a novel role of ATF6 in TH2 and TH17 cell-driven mixed granulocytic airway disease, suggesting a novel option to combat steroid-resistant mixed and even T2-low endotypes of asthma through targeting ATF6. This work was supported in part by NIH grants HL148337 and AI142200 (X.O.Y.), and DK110439 and DK132643 (M.L.). We acknowledge the University of New Mexico Comprehensive Cancer Center Flow Cytometry Core supported by NIH CA118100 and the Autophagy, Inflammation, and Metabolism in Disease Center Inflammation and Metabolism Core supported by NIH GM121176

Outcomes of responders to PD-1/PD-L1 inhibitors who discontinue therapy after sustained disease control.

PD-1/PD-L1 immune checkpoint inhibitors (ICIs) are widely used in the treatment of metastatic malignancies. Judiciously balancing disease control (DC) against development of immune-related adverse events (irAE) remains a crucial aspect of treatment. The effect of treatment discontinuation after sustained disease control (SDC) is unknown. The purpose of this analysis was to evaluate outcomes of responders to ICI who discontinue treatment after a minimum of 12 months (SDC). We retrospectively reviewed the database of the University of New Mexico Comprehensive Cancer Center (UNMCCC) between 2014 and 2021 and identified patients who had received ICI. Patients with metastatic solid tumors who had stopped ICI therapy after achieving SDC [stable disease, partial response, complete response (SD, PR, CR)] were selected and outcomes reviewed from their electronic health records. We identified 204 patients who were treated with ICI for various solid cancers. Forty-four patients (21.6%) met the criteria, of whom 35 with follow-up data were included in the final analysis; including 11 melanoma, 5 non-small cell lung, 4 head & neck, 8 renal, 4 urothelial, 1 anal, 1 Merkel cell carcinoma, and 1 liposarcoma. Patients were divided into two groups: those who stopped ICI due to an irAE [irAE group, n = 14, median treatment time (MTT), 16.6 mo] and those who stopped due to other reasons (eg completion of 2 years of therapy, n = 20, non-cancer related surgery, n = 1) (non-irAE group, n = 21, MTT, 23.7 mo). Among the irAE group, the most common irAE included pneumonitis, rash, transaminitis, and fatigue. As of data cutoff date, 9 of 14 (64%) patients continued to show SDC. Only 5 of 14 (36%) patients in this group experienced progression of disease (PD), with 1 of 2 patients achieving DC (median follow-up of 19.2 mo after last dose of treatment, range 3-50.2 mo). Among the non-irAE group, 13 of 21 (62%) continued to have SDC. Eight of 21 (38%) experienced PD after stopping treatment, 7 of whom received ICI rechallenge, with 2 of 7 achieving DC (median follow-up of 22.2 mo, range 3.6-54.8 mo). At a median follow-up of 21.3 mo from stopping ICI therapy (range, 3-54.8 mo), 10 patients (71%) from the irAE group and 13 (61.9%) from the non-irAE group are in DC and have not experienced PD. We demonstrate that 22 (66%) patients experienced SDC, regardless of cancer type or development of irAE. After including patients who were re-challenged with ICI due to PD, 25 (71%) remain in DC. Future prospective malignancy-specific trials are warranted to evaluate optimal treatment duration.

Dysregulation of the PRUNE2/PCA3 genetic axis in human prostate cancer: from experimental discovery to validation in two independent patient cohorts.

We have previously shown that the long non-coding (lnc)RNA prostate cancer associated 3 (PCA3; formerly prostate cancer antigen 3) functions as a trans-dominant negative oncogene by targeting the previously unrecognized prostate cancer suppressor gene PRUNE2 (a homolog of the Drosophila prune gene), thereby forming a functional unit within a unique allelic locus in human cells. Here, we investigated the PCA3/PRUNE2 regulatory axis from early (tumorigenic) to late (biochemical recurrence) genetic events during human prostate cancer progression. The reciprocal PCA3 and PRUNE2 gene expression relationship in paired prostate cancer and adjacent normal prostate was analyzed in two independent retrospective cohorts of clinically annotated cases post-radical prostatectomy: a single-institutional discovery cohort (n=107) and a multi-institutional validation cohort (n=497). We compared the tumor gene expression of PCA3 and PRUNE2 to their corresponding expression in the normal prostate. We also serially examined clinical/pathological variables including time to disease recurrence. We consistently observed increased expression of PCA3 and decreased expression of PRUNE2 in prostate cancer compared with the adjacent normal prostate across all tumor grades and stages. However, there was no association between the relative gene expression levels of PCA3 or PRUNE2 and time to disease recurrence, independent of tumor grades and stages. We concluded that upregulation of the lncRNA PCA3 and targeted downregulation of the protein-coding PRUNE2 gene in prostate cancer could be early (rather than late) molecular events in the progression of human prostate tumorigenesis but are not associated with biochemical recurrence. Further studies of PCA3/PRUNE2 dysregulation are warranted. We received support from the Human Tissue Repository and Tissue Analysis Shared Resource from the Department of Pathology of the University of New Mexico School of Medicine and a pilot award from the University of New Mexico Comprehensive Cancer Center. RP and WA were supported by awards from the Levy-Longenbaugh Donor-Advised Fund and the Prostate Cancer Foundation. EDN reports research fellowship support from the Brazilian National Council for Scientific and Technological Development (CNPq), Brazil, and the Associação Beneficente Alzira Denise Hertzog Silva (ABADHS), Brazil. This work has been funded in part by the NCI Cancer Center Support Grants (CCSG; P30) to the University of New Mexico Comprehensive Cancer Center (CA118100) and the Rutgers Cancer Institute of New Jersey (CA072720).

Outcomes of responders to PD-1/PD-L1 inhibitors who discontinue therapy after sustained disease control.

2586 Background: PD-1/PD-L1 immune checkpoint inhibitors (ICIs) are widely used in the treatment of metastatic malignancies. Judiciously balancing disease control (DC) against development of immune-related adverse events (irAE) remains a crucial aspect of treatment. The effect of treatment discontinuation after sustained disease control (SDC) is unknown. The purpose of this analysis was to evaluate outcomes of responders to ICI who discontinue treatment after a minimum of 12 months (SDC). Methods: We retrospectively reviewed the database of the University of New Mexico Comprehensive Cancer Center between 2014 and 2021 and identified patients who had received ICI. Patients with metastatic solid tumors who had stopped ICI therapy after achieving SDC [stable disease, partial response, complete response (SD,PR,CR)] were selected and outcomes reviewed from their electronic health records. Results: We identified 204 patients who were treated with ICI for various solid cancers. Forty-four patients (21.6%) met the criteria, of whom 35 with follow-up data were included in the final analysis; including 11 melanoma, 5 non-small cell lung, 4 head & neck, 8 renal, 4 urothelial, 1 anal, 1 Merkel cell carcinoma, and 1 liposarcoma. Patients were divided into two groups: those who stopped ICI due to an irAE [irAE group, n=14, median treatment time (MTT), 16.6 mo] and those who stopped due to other reasons (eg completion of 2 years of therapy, n=20, non-cancer related surgery, n=1) (non-irAE group, n=21, MTT, 23.7 mo). Among the irAE group, the most common irAE included pneumonitis, rash, transaminitis, and fatigue. As of data cutoff date, 10 of 14 (71%) patients continued to show SDC. Only 4 of 14 (28.6%) patients in this group experienced progression of disease (PD), one of whom was re-challenged with nivolumab and achieved DC (median follow-up of 19.2 mo after last dose of treatment, range 3-50.2 mo). Among the non-irAE group, 13 of 21 (62%) continued to have SDC. Eight of 21 (38%) experienced PD after stopping treatment, 7 of whom received ICI rechallenge, with 2 of 7 achieving DC (median follow-up of 22.2 mo, range 3.6-54.8 mo). At a median follow-up of 21.3 mo from stopping ICI therapy (range, 3-54.8 mo), 10 patients (71%) from the irAE group and 13 (61.9%) from the non-irAE group are in DC and have not experienced PD. Conclusions: We demonstrate that 23 (66%) patients experienced SDC, regardless of cancer type or development of irAE. After including patients who were re-challenged with ICI due to PD, 26 (74%) remain in DC. Future prospective malignancy-specific trials such as NCT04637594 are warranted to evaluate optimal treatment duration. [Table: see text]

Abstract PO-080: Reaching the “hard to reach” sexual and gender diverse communities for population-based research in cancer prevention

Abstract Purpose Despite about 5% of the US population identifying as Sexual and Gender Diverse (SGD), there is limited research on cancer prevention and control disparities in this population. In New Mexico (NM), population-level data from the Department of Health show differences in cervical and breast cancer screening uptake based on sexual orientation, but these data do not document disparities based on gender identity and for other types of cancer, prompting us to assess cancer prevention practices among NM SGD communities. SGD communities have consistently been considered “hard to reach” and much of the extant SGD studies have been conducted in large urban cities. We present findings on how to implement innovative, multi-pronged, and systematic recruitment strategies to engage SGD communities in NM, a state that is both largely rural and racially classified as “majority-minority” state. Methods Our recruitment efforts focused on four strategies: (1) Every Door Direct Mail program (by the United States Postal Services) was used to mail flyers across targeted (based on residential areas, income below $30,000, and between ages 30-71) mailing routes across NM. (2) These routes were also targeted for study-related ads via Google, Twitter, and Facebook. (3) Email outreach was conducted with SGD-friendly businesses, state cancer coalitions, and the University of New Mexico Comprehensive Cancer Center's Office of Community Outreach and Engagement. (4) Flyers were displayed at clinical and community settings across NM. All flyers, ads, and emails contained QR codes for a pre-survey that determined eligibility for participation in the main survey (i.e. 21-80 years old, NM resident, member of SGD community). Questions on the online survey, provided in both English and Spanish, inquired about the participant's demographics, body organs, physical health, vaccination history, healthcare access, and cancer screening practices. Results A total of 27,369 flyers were distributed and 436,177 impressions were made on social media, resulting in 5,080 surveys from eligible participants. Approximately 68% heard about the study from social media, 17% from email, 16% through friends or family, and 12% from flyers. All eligible participants were then emailed three times and, in a few cases, mailed a survey. This resulted in 3,115 completed surveys. Half of respondents were between 31-40 years, 38% were Black, Hispanic, or American Indian/Alaskan Native, and 48% had an annual household income below $50,000. Eighteen percent identified as lesbian, 30% gay, 28% bisexual, and 18% queer, while 48% were cisgender men, 32% cisgender women, and 13% transgender. Approximately 44% reported residing in rural areas and responses were received from 172 unique NM zip codes. Conclusion To reach state-wide SGD communities and engage them in population-based research, innovative and systematic efforts are needed. Social media and postal flyers may provide successful recruitment opportunities with potential to use these methods for future public health interventions for these populations. Citation Format: Prajakta Adsul, Karen Quezada, Katie Myers, Talya Jaffe, Bernard Tawfik, Emily Wu, Molly McClain, Shiraz Mishra, Miria Kano. Reaching the “hard to reach” sexual and gender diverse communities for population-based research in cancer prevention [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-080.

Comparative Analysis for Effectiveness of Azacitidine Versus Decitabine in Acute Myeloid Leukemia and Myelodysplastic Syndromes in New Mexico: A Single Institution Experience

IntroductionPrognosis of acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS) is still very poor due to limited treatment options. Both azacitidine (AZA) and decitabine (DEC) have to been shown to have a significant overall survival benefit in MDS patients. In recent years, both drugs are increasingly used for relapsed refractory AML as well as de novo AML in elderly patients with multiple comorbidities. However, we do not have the results of prospective clinical trials comparing AZA directly to DEC in AML or MDS patients. The goal of this study is to evaluate the overall survival and response duration of the AML and MDS patients who received at least one cycle of AZA or DEC in University of New Mexico Comprehensive Cancer Center (UNMCC).MethodsA retrospective chart review was performed to identify clinical characteristics, treatment duration and overall survival in AML and MDS patients. AML patients were risk stratified into favorable, intermediate and poor risk categories based on cytogenetics and molecular abnormalities. MDS patients were also risk stratified into low, intermediate and high-risk categories based on International Prognostic Scoring System. A majority of MDS patients in the study were in intermediate to high-risk categories. The primary patient outcome was overall survival (OS), calculated from the date of diagnosis until the date of death or lost to follow-up. Kaplan-Meier method was applied to compare OS between two groups, azacitidine-treated and decitabine-treated patients.ResultsIn this study, 60 patients (82%) received AZA and 13 patients (18%) received DEC as a treatment for either AML or MDS. Median age at diagnosis for AZA group was 69 years old and DEC group was 62 years old. There were 34 females (57%) in AZA group, compared to 6 females (46%) in DEC group. There were 22 patients with therapy related AML in both groups. DEC group had a higher proportion of patients (8 out of 13, 62%) with relapsed refractory AML, compared to only 25 out of 60 (42%) patients in AZA group with the p value of 0.229. There were 35 De novo AML and MDS patients in AZA group and 5 in DEC group.Median duration of treatment was 3.2 months and median number of treatment cycles was 4 for both groups. There was no significant difference in median overall survival between two groups (AZA 18 months vs DEC 17 months, p=0.082). The median overall survival for relapsed refractory AML in both groups was also similar (AZA 16.6 months versus DEC 18.2 months, p=0.932). However, median overall survival was significantly longer for AZA group with MDS or de novo AML patients (AZA 25 months versus DEC 3 months, p=0.001).ConclusionA significant number of patients with MDS and AML received AZA than DEC in UNMCC and it is similar to the previously reported Surveillance, Epidemiology, and End Results-Medicare database analysis which showed a majority of patients (78%) received AZA. Although we have a limited number of patients in both groups, the median overall survival for de novo AML and MDS patients is significantly higher in AZA group than DEC group. We are awaiting results from the ongoing prospective randomized clinical trials comparing azacitidine versus decitabine in AML and MDS patients to confirm these findings. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

First Person Profile: Cheryl Willman, MD: As director and CEO of the University of New Mexico Comprehensive Cancer Center, Dr. Willman has led major health equity initiatives while making pioneering discoveries in precision medicine.

First Person Profile: Cheryl Willman, MD: As director and CEO of the University of New Mexico Comprehensive Cancer Center, Dr. Willman has led major health equity initiatives while making pioneering discoveries in precision medicine.

Developing a survivorship care plan (SCP) delivery process for patients and primary care providers serving poor, rural, and minority patients with cancer.

BackgroundSurvivorship care plans (SCPs) summarize patients’ treatment and act as an education and communication tool between oncologists and primary care providers (PCPs). But creation and delivery of SCPs are challenging, labor intensive, and costly. The University of New Mexico Comprehensive Cancer Center (UNM CCC) treats a poor, rural, and minority patient population, and our purpose was to implement and evaluate a process to create and deliver SCPs to patients and PCPs.MethodsProviders placed an electronic SCP order, basic information was imported, and staff compiled treatment details. Flagged SCPs were then ready for delivery, providers approved of and delivered the SCP at the next encounter, and the SCP was sent to the PCP.ResultsBy April 2020, 283 SCPs were ordered, 241 (85.2%) were created by the designated staff, and 97 (34.2%) were given to patients after definitive therapy for breast cancer (59.1%), gynecological cancers (10.8%), prostate cancer (7.4%), colorectal cancer (5.1%), and lymphomas (4.8%). Of 97 SCPs eligible to be sent to PCPs, 75 (77.3%) were mailed or sent via EMR. Of the 41 (48.9%) SCPs sent via mail or fax, only 8 (8.3%) were received and 5 (5.2%) integrated.ConclusionsThis study shows that SCPs can be delivered to patients in a poor, rural, and minority patient population but that PCP receipt and integration of SCPs are poor. Future efforts need to ensure that an oncologist to PCP education and communication tool is able reach and be integrated by PCPs.

Targeted phage display-based pulmonary vaccination in mice and non-human primates

The extensive alveolar capillary network of the lungs is an attractive route for administration of several agents. One key functional attribute is the rapid onset of systemic action due to the absence of first-pass metabolism. Here we applied a combinatorial approach for ligand-directed pulmonary delivery as a unique route for systemic targeting in vaccination. We screened a phage display random peptide library in vivo to select, identify, and validate a ligand (CAKSMGDIVC) that specifically targets and is internalized through its receptor, α3β1 integrin, on the surface of cells lining the lung airways and alveoli and mediates CAKSMGDIVC-displaying phage binding and systemic delivery without compromising lung homeostasis. As a proof-of-concept, we show that the pulmonary delivery of targeted CAKSMGDIVC-displaying phage particles in mice and non-human primates elicit a systemic and specific humoral response. This broad methodology blueprint represents a robust and versatile platform tool enabling new ligand-receptor discovery with many potential translational applications. Cancer Center Support Grants to the University of Texas M.D. Anderson Cancer Center (CA016672), University of New Mexico Comprehensive Cancer Center (CA118100), Rutgers Cancer Institute of New Jersey (CA072720), research awards from the Gillson Longenbaugh Foundation, and National Institutes of Health (NIH) grant no. 1R01CA226537.

Abstract B015: Women in survivorship health using Project ECHO: Creating a model for navigated care transitions

Abstract There are currently over 15 million cancer survivors in the US, and this number is expected to exceed 20 million by 2026 due to population aging and growth. The majority of these patients are older; many are ethnically diverse and face unique health care challenges and comorbidities due to their cancer treatment. Despite this recognition, research clearly documents the persistence of unmet needs among cancer survivors, including less than optimal preventive and cancer surveillance screening rates. Several barriers have been identified in the effort to achieve optimal survivorship care: the current health care system is fragmented, difficult to navigate, and communication between oncologists and primary care providers is often minimal. While research has been devoted to developing integrated care models, systematic reviews conclude that no standard of care exists for survivorship models. Further, given the variability of cancer survivors in terms of health needs, socioeconomic circumstances, and health care environment, it is likely that such models will need to be adaptive. Building on prior formative research, our research team at the University of New Mexico Comprehensive Cancer Center (UNMCCC) is creating a survivorship care model for implementation. New Mexico, a large, rural, minority-majority state, with deep socioeconomic disparities that limit access to care, presents an ideal environment to address the current evidence gap in survivorship care transitions. Our developing research program features the following major components to this survivorship care model: 1) identifying risk-stratified patients at the UNMCCC and delivering a survivorship care plan; 2) using the Project ECHO telementoring platform, implement a survivorship care training curriculum with primary care providers; 3) an oncology nurse navigator based at the UNMCCC will actively navigate patients to the community-based providers; and 4) all components of the model will be assessed using implementation science research and evaluation strategies. We are in the early phases of developing and implementing this model and we will report on the content and process associated with each of the major components. Identified outcomes pertain to feasibility and acceptability of implementation, and we will categorize these using the RE-AIM and Consolidated Framework for Implementation Research frameworks. Citation Format: Andrew L. Sussman, Teresa Rutledge, Zoneddy Dayao, Miria Kano, Amy Gundelach, Stephanie McGirt, Jolene Lobo, Shiraz Mishra. Women in survivorship health using Project ECHO: Creating a model for navigated care transitions [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B015.