Patterns of Care and Outcomes for Hepatocellular Carcinoma and Pancreatic Cancer Based on Rurality of Patient's Residence in a Rural Midwestern State.

BACKGROUND: Although advancements in surgical planning and multidisciplinary care have improved the survival of patients with hepatopancreatic cancers in recent years, the impact of the rurality of patient residence on care received and survival is not well known. We aimed to assess the association between the rurality of patient's residence and cancer-specific survival outcomes among patients with hepatocellular carcinoma (HCC) and pancreatic cancer (PC) in Iowa, hypothesizing that patients in rural areas would experience lower survival. METHODS: Adult patients diagnosed with HCC or PC between 2010-2020 were identified using the Iowa Cancer Registry. Chi-square tests were used to compare categorical variables by rural/urban status. Logistic regression was used to examine factors associated with receiving surgery. Multivariable-adjusted Cox proportional hazards regression was used to determine associations with cancer-specific mortality. RESULTS: Of 1,877 patients with HCC, 58%, 27%, and 16% resided in metropolitan, micropolitan, and rural areas, respectively. Nearly 70% of patients in rural areas traveled≥50 miles for definitive care. Additionally, those residing in rural areas had the highest proportion of patients receiving definitive care at non-Commission on Cancer (CoC) centers (12.6% Metro vs. 14% Micro vs. 22.2% Rural, P<0.001). In multivariable-adjusted analysis of patients with stage I-III disease, definitive care at a non-CoC center was independently associated with lower odds of surgery (95% CI: 0.23 [0.12-0.45], P<0.0001) and higher mortality risk (1.39 [95% CI: 1.07-1.79], P=0.01), though rural residence was not. For PC, 5,465 patients were diagnosed, and 51%, 28%, and 20% resided in metropolitan, micropolitan, and rural areas, respectively. Similar to HCC, although rural residence was neither associated with odds of surgery nor with mortality risk, receiving definitive care at non-CoC accredited centers was associated with significantly lower odds of receiving surgery (95% CI: 0.17 [0.11-0.26], P<0.0001) and higher mortality risk (1.48 [95% CI: 1.23-1.77], P<0.0001). CONCLUSION: Rural residents with hepatopancreatic cancer have the highest proportion of patients receiving definitive care at non-CoC centers, which is associated with lower odds of receiving surgery and higher odds of mortality. This highlights the importance of standardizing complex cancer care and the need to foster collaboration between specialized and non-specialized centers.

The Carbon Isotope Ratio as an Objective Biomarker of Added Sugar Intake: A Scoping Review of Current Evidence in Human Nutrition.

Objective biomarkers of dietary intake are needed to advance nutrition research. The carbon isotope ratio (C13/C12; CIR) holds promise as an objective biomarker of added sugar (AS) and sugar-sweetened beverage (SSB) intake. This systematic scoping review presents the current evidence on CIRs from human studies. Search results (through April 12, 2024) yielded 6297 studies and 24 final articles. Studies were observational (n = 12), controlled feeding (n = 10), or dietary interventions (n = 2). CIRs were sampled from blood (n = 23), hair (n = 5), breath (n = 2), and/or adipose tissue (n = 1). Most (n = 17) conducted whole tissue (that is, bulk) analysis, 8 used compound specific isotope analysis (CSIA), and/or 2 studies used methods appropriate for analyzing breath. Studies were conducted in 3 concentrated geographic regions of the United States (n = 7 Virginia; n = 5 Arizona; n = 4 Alaska), with only 2 studies conducted in other countries. Studies that used CSIA to examine the CIR from the amino acid alanine (CIR-Ala; n = 4) and CIR analyzed from breath (n = 2) provided the most robust evidence for CIR as an objective biomarker of AS and SSBs (R2 range 0.36-0.91). Studies using bulk analysis of hair or blood showed positive, but modest and more variable associations with AS and SSBs (R2 range 0.05-0.48). Few studies showed no association, particularly in non-United States populations and those with low AS and SSB intakes. Two studies provided evidence for CIR to detect changes in SSB intake in response to dietary interventions. Overall, the most compelling evidence supports CIR-Ala as an objective indicator of AS intake and breath CIR as an indicator of short-term AS intake. Considering how to adjust for underlying dietary patterns remains an important area of future work and emerging methods using breath and CSIA warrant additional investigation. More evidence is needed to refine the utility and specificity of CIRs to measure AS and SSB intake.

MulTI-domain self-management in older People wiTh OstEoarthritis and multi-morbidities: protocol for the TIPTOE randomised controlled trial.

BACKGROUND: Four out of five people living with osteoarthritis (OA) also suffer with at least one other long-term health condition. The complex interaction between OA and multiple long-term conditions (MLTCs) can result in difficulties with self-care, restricted mobility, pain, anxiety, depression and reduced quality of life. The aim of the MulTI-domain Self-management in Older People wiTh OstEoarthritis and Multi-Morbidities (TIPTOE) trial is to evaluate the clinical and cost-effectiveness of the Living Well self-management support intervention, co-designed with people living with OA, integrated into usual care, in comparison to usual care alone. METHODS: TIPTOE is a multi-centre, two-arm, individually randomised controlled trial where 824 individuals over 65 years old with knee and/or hip joint pain from their OA affected joint and at least one other long-term health condition will be randomised to receive either the Living Well Self-Management support intervention or usual care. Eligible participants can self-refer onto the trial via a website or be referred via NHS services across Wales and England. Those randomised to receive the Living Well support intervention will be offered up to six one-to-one coaching sessions with a TIPTOE-trained healthcare practitioner and a co-designed book. Participants will be encouraged to nominate a support person to assist them throughout the study. All participants will complete a series of self-reported outcome measures at baseline and 6- and 12-month follow-up. The primary outcome is symptoms and quality of life as assessed by the Musculoskeletal Health Questionnaire (MSK-HQ). Routine data will be used to evaluate health resource use. A mixed methods process evaluation will be conducted alongside the trial to inform future implementation should the TIPTOE intervention be found both clinically and cost-effective. An embedded 'Study Within A Project' (SWAP) will explore and address barriers to the inclusion of under-served patient groups (e.g. oldest old, low socioeconomic groups, ethnic groups). DISCUSSION: TIPTOE will evaluate the clinical and cost-effectiveness of a co-designed, living well personalised self-management support intervention for older individuals with knee and/or hip OA and MLTCs. The trial has been designed to maximise inclusivity and access. TRIAL REGISTRATION: ISRCTN 16024745 . Registered on October 16, 2023.

Clinical Outcomes from the Alaska Native Tribal Health Consortium Colorectal Cancer Control Program: 2009-2015.

The Alaska Native Tribal Health Consortium (ANTHC) participated in the United States Centers for Disease Control and Prevention Colorectal Cancer Control Program (CRCCP) from 2009 to 2015. We conducted a descriptive evaluation of ANTHC CRCCP demographics, quality measures, and clinical outcomes, including screening methods employed within the program and screening outcomes. There were 6981 program screenings completed, with the majority (81.3%) of people screened in the 50-75 year age group. Colonoscopy was the primary screening test used, accounting for 6704 (96.9%) of the screening tests. Quality of colonoscopy was high: adequate bowel preparation was reported in 98.2% of colonoscopies, cecal intubation rate was 98.9%, and the adenoma detection rate was 38.9%. A high proportion (58.9%) of colonoscopies had an initial finding of polyps or lesions suspicious for cancer; 41.2% of all colonoscopies had histological confirmation of either adenomatous polyps (40.6%) or cancer (0.5%). The ANTHC CRCCP successfully increased CRC screening among American Indian and Alaska Native peoples living in Alaska; this was achieved primarily through high-quality colonoscopy metrics. These data support a continued focus by the Alaska Native Tribal Health Consortium and its tribal health partners on increasing CRC screening and reducing cancer mortality among Alaska Native peoples.

LGBTQ+ cancer: priority or lip service? A qualitative content analysis of LGBTQ+ considerations in U.S. state, jurisdiction, and tribal comprehensive cancer control plans.

The National Comprehensive Cancer Control Program, a Centers for Disease Control and Prevention funded program, supports cancer coalitions across the United States (US) in efforts to prevent and control cancer including development of comprehensive cancer control (CCC) plans. CCC plans often focus health equity within their priorities, but it is unclear to what extent lesbian, gay, bisexual, transgender, queer/questioning, plus (LGBTQ+) populations are considered in CCC plans. We qualitatively examined to what extent LGBTQ+ populations were referenced in 64 U.S. state, jurisdiction, tribes, and tribal organization CCC plans. A total of 55% of CCC plans mentioned LGBTQ+ populations, however, only one in three CCC plans mentioned any kind of LGBTQ+ inequity or LGBTQ+ specific recommendations. Even fewer plans included mention of LGBTQ+ specific resources, organizations, or citations. At the same time almost three fourths of plans conflated sex and gender throughout their CCC plans. The findings of this study highlight the lack of prioritization of LGBTQ+ populations in CCC plans broadly while highlighting exemplar plans that can serve as a roadmap to more inclusive future CCC plans. Comprehensive cancer control plans can serve as a key policy and advocacy structure to promote a focus on LGBTQ+ cancer prevention and control.

Evidence-based screening, clinical care and health education recommendations for Alaska Native peoples with prediabetes living in southcentral Alaska: findings from the Alaska EARTH follow-up study.

Pre-diabetes (pre-DM) is a strong predictor of diabetes (DM) over time. This study investigated how much of the recent increase in pre-DM identified among Alaska Native (AN) peoples living in urban southcentral Alaska may be due to changes in diagnostic methods. We used clinical and demographic data collected at baseline between 2004 and 2006 and at follow-up collected between 2015 and 2017 from the urban southcentral Alaska Education and Research Towards Health (EARTH) cohort. We used descriptive statistics and logistic regression to explore differences in demographic and clinical variables among the identified pre-DM groups. Of 388 participants in the follow-up study, 243 had A1c levels indicating pre-DM with only 20 demonstrating pre-DM also by fasting blood glucose (FBG). Current smoking was the sole predictor for pre-DM by A1c alone while abdominal obesity and elevated FBG-predicted pre-DM by A1c+FBG. No participants had an elevated FBG without an A1c elevation. A substantial portion of the rise in pre-DM found among urban southcentral AN peoples in the EARTH follow-up study was due to the addition of A1c testing. Pre-DM by A1c alone should be used to motivate behavioural changes that address modifiable risk factors, including smoking cessation, physical activity and weight management.

Identifying predictors of COVID-related delays in cancer-specific medical care.

PURPOSE: Evidence of the impact of the COVID-19 pandemic on cancer prevention and control is growing, but little is known about patient-level factors associated with delayed care. We analyzed data from a survey focused on Iowan cancer patients' COVID-19 experiences in the early part of the pandemic. METHODS: Participants were recruited from the University of Iowa Holden Comprehensive Cancer Center's Patients Enhancing Research Collaborations at Holden (PERCH) program. We surveyed respondents on demographic characteristics, COVID-19 experiences and reactions, and delays in any cancer-related health care appointment, or cancer-related treatment appointments. Two-sided significance tests assessed differences in COVID-19 experiences and reactions between those who experienced delays and those who did not. RESULTS: There were 780 respondents (26% response), with breast, prostate, kidney, skin, and colorectal cancers representing the majority of respondents. Delays in cancer care were reported by 29% of respondents. In multivariable-adjusted models, rural residents (OR 1.47; 95% CI 1.03, 2.11) and those experiencing feelings of isolation (OR 2.18; 95% CI 1.37, 3.47) were more likely to report any delay, where experiencing financial difficulties predicted delays in treatment appointments (OR 5.72; 95% CI 1.96, 16.67). Health insurance coverage and concern about the pandemic were not statistically significantly associated with delays. CONCLUSION: These findings may inform cancer care delivery during periods of instability when treatment may be disrupted by informing clinicians about concerns that patients have during the treatment process. Future research should assess whether delays in cancer care impact long-term cancer outcomes and whether delays exacerbate existing disparities in cancer outcomes.

Pathway-based signatures predict patient outcome, chemotherapy benefit and synthetic lethal dependencies in invasive lobular breast cancer.

BACKGROUND: Invasive Lobular Carcinoma (ILC) is a morphologically distinct breast cancer subtype that represents up to 15% of all breast cancers. Compared to Invasive Breast Carcinoma of No Special Type (IBC-NST), ILCs exhibit poorer long-term outcome and a unique pattern of metastasis. Despite these differences, the systematic discovery of robust prognostic biomarkers and therapeutically actionable molecular pathways in ILC remains limited. METHODS: Pathway-centric multivariable models using statistical machine learning were developed and tested in seven retrospective clinico-genomic cohorts (n = 996). Further external validation was performed using a new RNA-Seq clinical cohort of aggressive ILCs (n = 48). RESULTS AND CONCLUSIONS: mRNA dysregulation scores of 25 pathways were strongly prognostic in ILC (FDR-adjusted P < 0.05). Of these, three pathways including Cell-cell communication, Innate immune system and Smooth muscle contraction were also independent predictors of chemotherapy response. To aggregate these findings, a multivariable machine learning predictor called PSILC was developed and successfully validated for predicting overall and metastasis-free survival in ILC. Integration of PSILC with CRISPR-Cas9 screening data from breast cancer cell lines revealed 16 candidate therapeutic targets that were synthetic lethal with high-risk ILCs. This study provides interpretable prognostic and predictive biomarkers of ILC which could serve as the starting points for targeted drug discovery for this disease.

Guideline-concordant breast cancer care by patient race and ethnicity accounting for individual-, facility- and area-level characteristics: a SEER-Medicare study.

PURPOSE: To examine racial-ethnic variation in adherence to established quality metrics (NCCN guidelines and ASCO quality metrics) for breast cancer, accounting for individual-, facility-, and area-level factors. METHODS: Data from women diagnosed with invasive breast cancer at 66+ years of age from 2000 to 2017 were examined using SEER-Medicare. Associations between race and ethnicity and guideline-concordant diagnostics, locoregional treatment, systemic therapy, documented stage, and oncologist encounters were estimated using multilevel logistic regression models to account for clustering within facilities or counties. RESULTS: Black and American Indian/Alaska Native (AIAN) women had consistently lower odds of guideline-recommended care than non-Hispanic White (NHW) women (Diagnostic workup: ORBlack 0.83 (0.79-0.88), ORAIAN 0.66 (0.54-0.81); known stage: ORBlack 0.87 (0.80-0.94), ORAIAN 0.63 (0.47-0.85); seeing an oncologist: ORBlack 0.75 (0.71-0.79), ORAIAN 0.60 (0.47-0.72); locoregional treatment: ORBlack 0.80 (0.76-0.84), ORAIAN 0.84 (0.68-1.02); systemic therapies: ORBlack 0.90 (0.83-0.98), ORAIAN 0.66 (0.48-0.91)). Commission on Cancer accreditation and facility volume were significantly associated with higher odds of guideline-concordant diagnostics, stage, oncologist visits, and systemic therapy. Black residential segregation was associated with significantly lower odds of guideline-concordant locoregional treatment and systemic therapy. Rurality and area SES were associated with significantly lower odds of guideline-concordant diagnostics and oncologist visits. CONCLUSIONS: This is the first study to examine guideline-concordance across the continuum of breast cancer care from diagnosis to treatment initiation. Disparities were present from the diagnostic phase and persisted throughout the clinical course. Facility and area characteristics may facilitate or pose barriers to guideline-adherent treatment and warrant future investigation as mediators of racial-ethnic disparities in breast cancer care.

Patient perspectives of weight stigma across the cancer continuum: A scoping review.

BACKGROUND: Weight stigma has been defined as the social devaluation and denigration of individuals because of their weight. The purpose of this scoping systematic review was to assess and understand patient experiences with weight stigma in the cancer care setting. METHODS: We conducted a systematic scoping review of studies examining shame, prejudice, bias, and stigma in relation to weight and cancer-related care using five databases: PubMed, CINAHL Plus Full Text (ProQuest), Cochrane Library, PsycINFO (EBSCO), and Scopus. Articles were uploaded into Covidence for de-duplication and screening. Included studies were peer reviewed, reported adult patient experiences in cancer-related care, and were published in English between October 2012 and February 2023. Study characteristics and key findings were abstracted and qualitatively synthesized. RESULTS: Publications meeting inclusion criteria yielded five studies (n = 113 participants). Most focused on the experiences of women (n = 4) and cancers which predominantly impact women (i.e., breast, cervical, endometrial; n = 4). All stages of the cancer continuum were included with studies examining screening (n = 2), treatment (n = 1), and post-treatment survivorship (n = 2). Weight discrimination was discussed in four studies and weight-biased stereotypes were discussed in three studies. Experiences of weight bias internalization were reported in four studies. One study described an instance of implicit weight bias. CONCLUSIONS: Limited studies examine patient experiences of weight stigma in cancer care; however, current evidence suggests that patients do experience weight stigma in cancer-related care. This review highlights critical gaps and a need for more research on the prevalence and impact of weight stigma in cancer screening and care.

Perspectives on Referring for Rectal Cancer Surgery: a Survey Study of Gastroenterologist and General Surgeons in Iowa.

PURPOSE: To understand referral practices for rectal cancer surgical care and to secondarily determine differences in referral practices by two main hypothesized drivers of referral: the rurality of the community endoscopists' practice and their affiliation with a colorectal surgeon. METHODS: Community gastroenterologists and general surgeons in Iowa completed a mailed questionnaire on practice demographics, volume, and referral practices for rectal cancer patients. Rurality was operationalized with RUCA codes. RESULTS: Twenty-two of 53 gastroenterologists (42%) and 120 of 188 general surgeons (64%) (total 144/241, 60%) in Iowa responded. Most performed colonoscopies, including 22 gastroenterologists (100%) and 96 general surgeons (80%). Regular referral of rectal cancer patients to colorectal surgeons was reported for 57% of urban physicians affiliated with a colorectal surgeon, 33% of urban physicians not affiliated with a colorectal surgeon, and 57% and 72% of physicians in large and small rural areas, respectively, who were not affiliated with a colorectal surgeon. High surgeon volume, high hospital volume, and colorectal surgeon specialty were important factors in the referral decisions for over half the physicians. 69% of diagnosing urban general surgeons reported performing rectal cancer surgery about half the time or more, while 85% of small rural and 60% of large rural diagnosing general surgeons reported never or rarely performing rectal cancer surgery. CONCLUSIONS: Diagnosing physicians have variable rectal cancer referral practices, including consistency in referred to surgeon and prioritization of volume and specialization. Prioritizing specialized or high-volume rectal cancer surgical care would require changing existing referring patterns.

Assessing Completeness of Cancer Treatment Data from an Academic Medical Center's Tumor Registry Through Comparison to the Central Registry.

Background: Researchers often rely on hospital tumor registry data to provide comprehensive cancer therapy information. The purpose of this study was to determine the completeness of treatment information found in the abstracted records of patients seen at an academic medical center located in a rural Midwestern state. Approach: The cohort included 846 Iowa residents diagnosed with a single malignant tumor of the female breast, colon/rectum, lung, pancreas, or prostate in 2017-2018 with an abstract recorded by the academic medical center and at least 1 other hospital. Treatment/no treatment agreement between the academic medical center's abstract and the central registry's consolidated abstract was examined for the following summary variables of the North American Association of Central Cancer Registries (NAACCR): surgery of the primary site, chemotherapy, radiation therapy, immunotherapy, and hormone therapy. Treatment summary variables from the academic medical center abstract that agreed with the corresponding variables from the central registry abstract were classified as concordant. The proportion of concordance for each treatment modality was the outcome measure, and 95% confidence intervals were calculated with the Agresti-Coull method. Concordance was also examined at the specific treatment level. Results: There was high concordance between the treatment information recorded in the academic medical center and the central registry records. The average proportion of treatment/no treatment agreement across all treatment modalities and cancer sites was 0.97 (SD, 0.02). Concordance remained high even when examining specific treatments (average concordance, 0.95; SD, 0.04). The lowest treatment/no treatment concordance proportion was 0.92 (95% CI, 0.86-0.96) for chemotherapeutic treatment of pancreatic cancer. We also found that the academic medical center's summary variables captured most treatments given at other facilities, ranging from 74.4% capture of immunotherapy to 88.2% capture of surgery of the primary site. Conclusions: These results indicate that NAACCR-formatted, summary variables from the academic medical center's tumor registry are likely to provide comprehensive treatment information for those individuals diagnosed or treated in this setting. Analyses of either the academic medical record registry records or consolidated records from the central registry should yield similar results. Future research should establish whether similar findings are obtained at other medical centers.

Comparing COVID-19 Response Behaviors between a Cancer Patient Sample and a Population-Based Cancer-Free Sample in a Rural Midwestern State.

INTRODUCTION: The COVID-19 pandemic caused an increase in fear, anxiety, and depressive symptoms globally. For populations at increased risk for adverse outcomes due to illness, such as cancer patients, these worries may have been exacerbated. Understanding how the pandemic impacted cancer patients will inform better preparation for future events that cause disturbances to cancer care delivery. METHODS: This study analyzed data from two surveys to determine whether cancer patients' responses differed from a cancer-free population-based sample in terms of concerns, preventive behaviors, and thoughts on their healthcare provider's communication regarding COVID-19 in a US Midwestern state. In August 2020, a survey was sent to 10,009 Iowans aged 18 and older, randomly selected from the 2018 Iowa voter registration file. In September 2020, a survey was emailed to 2,954 cancer patients aged 18 and older who opted into the University of Iowa Holden Comprehensive Cancer Center's Patients Enhancing Research Collaborations at Holden program. Previously validated and pretested Likert-type and multiple-choice items assessed concern regarding COVID-19, social distancing perception and behaviors, and demographic characteristics of respondents. We used χ2 tests and logistic regression to examine differences between the cancer patient and general population survey responses. RESULTS: We included 3,622 responses from the general population survey and 780 responses from the cancer patient survey in this analysis. Cancer patient survey respondents were more frequently older, lived in urban areas, had Medicare insurance coverage, had a college degree or higher, and were married. Cancer patients were more likely to report engaging in social distancing behaviors and greater concern regarding the pandemic. CONCLUSION: This study suggests differences in the impact of the COVID-19 pandemic on cancer patients compared to cancer-free members of the general population. These results indicate the need for consideration of cancer patients' physical and mental health during large-scale disruptions to cancer care.

Cancer Screening Prevalence among Participants in the Southcentral Alaska Education and Research towards Health (EARTH) Study at Baseline and Follow-Up.

Alaska Native communities are working to prevent cancer through increased cancer screening and early detection. We examined the prevalence of self-reported colorectal (CRC), cervical, and breast cancer screening among Alaska Native participants in the southcentral Alaska Education and Research toward Health (EARTH) study at baseline (2004-2006) and ten-year follow-up (2015-2017); participant characteristics associated with screening; and changes in screening prevalence over time. A total of 385 participants completed questionnaires at follow-up; 72% were women. Of those eligible for CRC screening, 53% of follow-up participants reported a CRC screening test within the past 5 years, significantly less than at baseline (70%) (p = 0.02). There was also a significant decline in cervical cancer screening between baseline and follow-up: 73% of women at follow-up vs. 90% at baseline reported screening within the past three years (p < 0.01). There was no significant difference in reported breast cancer screening between baseline (78%) and follow-up (77%). Colorectal and cervical cancer screening prevalence in an urban, southcentral Alaska Native cohort declined over 10 years of follow-up. Increased cancer screening and prevention are needed to decrease Alaska Native cancer-related morbidity and mortality.

Diagnosing Provider, Referral Patterns, Facility Type, and Patient Satisfaction Among Iowa Rectal Cancer Patients.

PURPOSE: Rectal cancer treatment at high-volume centers is associated with higher likelihood of guideline-concordant care and improved outcomes. Whether rectal cancer patients are referred for treatment at high-volume hospitals may depend on diagnosing provider specialty. We aimed to determine associations of diagnosing provider specialty with treating provider specialty and characteristics of the treating facility for rectal cancer patients in Iowa. METHODS: Rectal cancer patients identified using the Iowa Cancer Registry completed a mailed survey on their treatment experience and decision-making process. Provider type was defined by provider specialty and whether the provider referred patients elsewhere for surgery. Multivariable-adjusted logistic regression models were used to examine predictors of being diagnosed by a general surgeon who also performed the subsequent surgery. RESULTS: Of 417 patients contacted, 381 (76%) completed the survey; our final analytical sample size was 267. Half of respondents were diagnosed by a gastroenterologist who referred them elsewhere; 30% were diagnosed by a general surgeon who referred them elsewhere, and 20% were diagnosed by a general surgeon who performed the surgery. Respondents who were ≥ 65 years old, had less than a college education, and who made < $50,000 per year were more likely to be diagnosed by a general surgeon who performed surgery. In multivariable-adjusted models, respondents diagnosed and treated by the same general surgeon were more likely to have surgery at hospitals with low annual colorectal cancer surgery volume and less likely to be satisfied with their care. CONCLUSIONS: Among rectal cancer patients in Iowa, respondents who were diagnosed and treated by the same provider were less likely to get treatment at a high-volume facility. This study informs the importance of provider referral in centralization of rectal cancer care.

SF3B1 hotspot mutations confer sensitivity to PARP inhibition by eliciting a defective replication stress response.

SF3B1 hotspot mutations are associated with a poor prognosis in several tumor types and lead to global disruption of canonical splicing. Through synthetic lethal drug screens, we identify that SF3B1 mutant (SF3B1MUT) cells are selectively sensitive to poly (ADP-ribose) polymerase inhibitors (PARPi), independent of hotspot mutation and tumor site. SF3B1MUT cells display a defective response to PARPi-induced replication stress that occurs via downregulation of the cyclin-dependent kinase 2 interacting protein (CINP), leading to increased replication fork origin firing and loss of phosphorylated CHK1 (pCHK1; S317) induction. This results in subsequent failure to resolve DNA replication intermediates and G2/M cell cycle arrest. These defects are rescued through CINP overexpression, or further targeted by a combination of ataxia-telangiectasia mutated and PARP inhibition. In vivo, PARPi produce profound antitumor effects in multiple SF3B1MUT cancer models and eliminate distant metastases. These data provide the rationale for testing the clinical efficacy of PARPi in a biomarker-driven, homologous recombination proficient, patient population.

Patterns of Evidence-Based Care for the Diagnosis, Staging, and First-line Treatment of Breast Cancer by Race-Ethnicity: A SEER-Medicare Study.

BACKGROUND: Racial and ethnic disparities in guideline-recommended breast cancer treatment are well documented, however studies including diagnostic and staging procedures necessary to determine treatment indications are lacking. The purpose of this study was to characterize patterns in delivery of evidence-based services for the diagnosis, clinical workup, and first-line treatment of breast cancer by race-ethnicity. METHODS: SEER-Medicare data were used to identify women diagnosed with invasive breast cancer between 2000 and 2017 at age 66 or older (n = 2,15,605). Evidence-based services included diagnostic procedures (diagnostic mammography and breast biopsy), clinical workup (stage and grade determination, lymph node biopsy, and HR and HER2 status determination), and treatment initiation (surgery, radiation, chemotherapy, hormone therapy, and HER2-targeted therapy). Poisson regression was used to estimate rate ratios (RR) and 95% confidence intervals (CI) for each service. RESULTS: Black and American Indian/Alaska Native (AIAN) women had significantly lower rates of evidence-based care across the continuum from diagnostics through first-line treatment compared to non-Hispanic White (NHW) women. AIAN women had the lowest rates of HER2-targeted therapy and hormone therapy initiation. While Black women also had lower initiation of HER2-targeted therapy than NHW, differences in hormone therapy were not observed. CONCLUSIONS: Our findings suggest patterns along the continuum of care from diagnostic procedures to treatment initiation may differ across race-ethnicity groups. IMPACT: Efforts to improve delivery of guideline-concordant treatment and mitigate racial-ethnic disparities in healthcare and survival should include procedures performed as part of the diagnosis, clinical workup, and staging processes.

Diet quality is positively associated with intake of traditional foods and does not differ by season in remote Yup'ik communities.

This study evaluated whether traditional food intake and diet quality differed by season in Yup'ik communities and examined the relationship between intake of traditional food groups and diet quality. Data were collected from 38 participants, ages 14-79 years, from two Yup'ik communities in Southwest Alaska from 2008 to 2010. Self-reported intake (24-h recalls) and dietary biomarker (nitrogen stable isotope ratio) data were collected twice in distinct seasons. Diet quality was assessed using the Healthy Eating Index. A paired sample t-test was used to test for seasonal differences in traditional food intake and diet quality, and linear regression was used to evaluate associations between traditional food intake and diet quality. Total traditional food intake and overall diet quality did not significantly differ by season, but there were differences in traditional food group intake and diet quality component scores. Diet quality was strongly associated with intake of traditional food groups including fish, tundra greens, and berries. Given the strong relationship between traditional food intake and diet quality, policies should aim to ensure continued access to traditional foods in Yup'ik communities amid environmental changes in the circumpolar North.

Key takeaways for knowledge expansion of early-career scientists conducting Transdisciplinary Research in Energetics and Cancer (TREC): a report from the TREC Training Workshop 2022.

The overall goal of the annual Transdisciplinary Research in Energetics and Cancer (TREC) Training Workshop is to provide transdisciplinary training for scientists in energetics and cancer and clinical care. The 2022 Workshop included 27 early-to-mid career investigators (trainees) pursuing diverse TREC research areas in basic, clinical, and population sciences. The 2022 trainees participated in a gallery walk, an interactive qualitative program evaluation method, to summarize key takeaways related to program objectives. Writing groups were formed and collaborated on this summary of the 5 key takeaways from the TREC Workshop. The 2022 TREC Workshop provided a targeted and unique networking opportunity that facilitated meaningful collaborative work addressing research and clinical needs in energetics and cancer. This report summarizes the 2022 TREC Workshop's key takeaways and future directions for innovative transdisciplinary energetics and cancer research.

Effect of rurality and travel distance on contralateral prophylactic mastectomy for unilateral breast cancer.

PURPOSE: Despite lack of survival benefit, demand for contralateral prophylactic mastectomy (CPM) to treat unilateral breast cancer remains high. High uptake of CPM has been demonstrated in Midwestern rural women. Greater travel distance for surgical treatment is associated with CPM. Our objective was to examine the relationship between rurality and travel distance to surgery with CPM. METHODS: Women diagnosed with stages I-III unilateral breast cancer between 2007 and 2017 were identified using the National Cancer Database. Logistic regression was used to model likelihood of CPM based on rurality, proximity to metropolitan centers, and travel distance. A multinomial logistic regression model compared factors associated with CPM with reconstruction versus other surgical options. RESULTS: Both rurality (OR 1.10, 95% CI 1.06-1.15 for non-metro/rural vs. metro) and travel distance (OR 1.37, 95% CI 1.33-1.41 for those who traveled 50 + miles vs. < 30 miles) were independently associated with CPM. For women who traveled 30 + miles, odds of receiving CPM were highest for non-metro/rural women (OR 1.33 for 30-49 miles, OR 1.57 for 50 + miles; reference: metro women traveling < 30 miles). Non-metro/rural women who received reconstruction were more likely to undergo CPM regardless of travel distance (ORs 1.11-1.21). Both metro and metro-adjacent women who received reconstruction were more likely to undergo CPM only if they traveled 30 + miles (ORs 1.24-1.30). CONCLUSION: The impact of travel distance on likelihood of CPM varies by patient rurality and receipt of reconstruction. Further research is needed to understand how patient residence, travel burden, and geographic access to comprehensive cancer care services, including reconstruction, influence patient decisions regarding surgery.