A somato-cognitive action network alternates with effector regions in motor cortex.

Motor cortex (M1) has been thought to form a continuous somatotopic homunculus extending down the precentral gyrus from foot to face representations1,2, despite evidence for concentric functional zones3 and maps of complex actions4. Here, using precision functional magnetic resonance imaging (fMRI) methods, we find that the classic homunculus is interrupted by regions with distinct connectivity, structure and function, alternating with effector-specific (foot, hand and mouth) areas. These inter-effector regions exhibit decreased cortical thickness and strong functional connectivity to each other, as well as to the cingulo-opercular network (CON), critical for action5 and physiological control6, arousal7, errors8 and pain9. This interdigitation of action control-linked and motor effector regions was verified in the three largest fMRI datasets. Macaque and pediatric (newborn, infant and child) precision fMRI suggested cross-species homologues and developmental precursors of the inter-effector system. A battery of motor and action fMRI tasks documented concentric effector somatotopies, separated by the CON-linked inter-effector regions. The inter-effectors lacked movement specificity and co-activated during action planning (coordination of hands and feet) and axial body movement (such as of the abdomen or eyebrows). These results, together with previous studies demonstrating stimulation-evoked complex actions4 and connectivity to internal organs10 such as the adrenal medulla, suggest that M1 is punctuated by a system for whole-body action planning, the somato-cognitive action network (SCAN). In M1, two parallel systems intertwine, forming an integrate-isolate pattern: effector-specific regions (foot, hand and mouth) for isolating fine motor control and the SCAN for integrating goals, physiology and body movement.

A genome-wide association study of contralateral breast cancer in the Women's Environmental Cancer and Radiation Epidemiology Study.

BACKGROUND: Contralateral breast cancer (CBC) is the most common second primary cancer diagnosed in breast cancer survivors, yet the understanding of the genetic susceptibility of CBC, particularly with respect to common variants, remains incomplete. This study aimed to investigate the genetic basis of CBC to better understand this malignancy. FINDINGS: We performed a genome-wide association analysis in the Women's Environmental Cancer and Radiation Epidemiology (WECARE) Study of women with first breast cancer diagnosed at age < 55 years including 1161 with CBC who served as cases and 1668 with unilateral breast cancer (UBC) who served as controls. We observed two loci (rs59657211, 9q32, SLC31A2/FAM225A and rs3815096, 6p22.1, TRIM31) with suggestive genome-wide significant associations (P < 1 × 10-6). We also found an increased risk of CBC associated with a breast cancer-specific polygenic risk score (PRS) comprised of 239 known breast cancer susceptibility single nucleotide polymorphisms (SNPs) (rate ratio per 1-SD change: 1.25; 95% confidence interval 1.14-1.36, P < 0.0001). The protective effect of chemotherapy on CBC risk was statistically significant only among patients with an elevated PRS (Pheterogeneity = 0.04). The AUC that included the PRS and known breast cancer risk factors was significantly elevated. CONCLUSIONS: The present GWAS identified two previously unreported loci with suggestive genome-wide significance. We also confirm that an elevated risk of CBC is associated with a comprehensive breast cancer susceptibility PRS that is independent of known breast cancer risk factors. These findings advance our understanding of genetic risk factors involved in CBC etiology.

Agreement of medical record abstraction and self-report of breast cancer treatment with an extended recall window.

BACKGROUND: Medical record abstraction (MRA) and self-report questionnaires are two methods frequently used to ascertain cancer treatment information. Prior studies have shown excellent agreement between MRA and self-report, but it is unknown how a recall window longer than 3 years may affect this agreement. METHODS: The Women's Environmental Cancer and Radiation Epidemiology (WECARE) Study is a multicenter, population-based case-control study of controls with unilateral breast cancer individually matched to cases with contralateral breast cancer. Participants who were diagnosed with a first primary breast cancer from 1985 to 2008 before the age of 55 years completed a questionnaire that included questions on treatment. First primary breast cancer treatment information was abstracted from the medical record from radiation oncology clinic notes for radiation treatment and from systemic adjuvant treatment reports for hormone therapy and chemotherapy. Agreement between MRA and self-reported treatment was assessed with the kappa statistic and corresponding 95% confidence intervals (CIs). RESULTS: A total of 2808 participants with MRA and self-reported chemotherapy treatment information, 2733 participants with MRA and self-reported hormone therapy information, and 2905 participants with MRA and self-reported radiation treatment information were identified. The median recall window was 12.5 years (range, 2.8-22.2 years). MRA and self-reported treatment agreement was excellent across treatment modalities (kappachemo, 98.5; 95% CI, 97.9-99.2; kappahorm, 87.7; 95% CI, 85.9-89.5; kapparad, 97.9; 95% CI, 97.0-98.7). There was no heterogeneity across recall windows (pchemo = .46; phorm = .40; prad = .61). CONCLUSIONS: Agreement between self-reported and MRA primary breast cancer treatment modality information was excellent for young women diagnosed with breast cancer and was maintained even among women whose recall window was more than 20 years after diagnosis.

Outcomes in solid organ transplant recipients with a pretransplant diagnosis of melanoma.

Melanoma causes significant morbidity in solid organ transplant recipients (SOTRs). Melanomas diagnosed before transplantation can recur with intensive immunosuppression, but outcomes have not been well studied. We evaluated 901 non-Hispanic White SOTRs with a pretransplant melanoma identified using linked transplant and cancer registry data in the United States. Most pretransplant melanomas were invasive (60.7%), and the median time from diagnosis to transplantation was 5.1 years. After transplantation, 41 SOTRs developed a new invasive melanoma, corresponding to 9-fold increased risk compared with the general population (standardized incidence ratio, 9.2; 95% confidence interval [CI], 6.6-12). Twenty-two SOTRs died from melanoma after transplantation, corresponding to 52-fold increased risk (standardized mortality ratio, 52; 95% CI, 33-79). Risk factors for posttransplant melanoma included age at transplantation (adjusted hazard ratio [HR], 2.86; 95% CI, 1.24-6.60; for age 55+ vs <55 years) and maintenance immunosuppression with cyclosporine/azathioprine (adjusted HR, 2.53; 95% CI, 1.08-5.90). Melanoma mortality was strongly elevated after a posttransplant melanoma diagnosis (HR, 35.6; 95% CI, 14.0-90.4; adjusted for cyclosporine/azathioprine maintenance therapy and calendar year of transplantation). In conclusion, SOTRs with a pretransplant melanoma are at risk of adverse melanoma-related outcomes after transplantation. These findings support thorough dermatologic evaluation prior to transplantation and frequent posttransplant surveillance.

Mortality among solid organ transplant recipients with a pretransplant cancer diagnosis.

Little is known about the outcomes among solid organ transplant recipients with a pretransplant cancer diagnosis. We used linked data from the Scientific Registry of Transplant Recipients with 33 US cancer registries. Cox proportional hazards models assessed associations of pretransplant cancer with overall mortality, cancer-specific mortality, and development of a new posttransplant cancer. Among 311 677 recipients, the presence of a single pretransplant cancer was associated with increased overall mortality (adjusted hazard ratio [aHR], 1.19; 95% CI, 1.15-1.23) and cancer-specific mortality (aHR, 1.93; 95% CI, 1.76-2.12); results for 2+ pretransplant cancers were similar. Cancer-specific mortality was not significantly increased for uterine, prostate, or thyroid cancers (aHRs were 0.83, 1.22, and 1.54, respectively) but strongly elevated for lung cancer and myeloma (aHRs were 3.72 and 4.42, respectively). A pretransplant cancer diagnosis was also associated with increased risk of developing posttransplant cancer (aHR, 1.32; 95% CI, 1.23-1.40). Among 306 recipients whose cancer death was confirmed by cancer registry data, 158 deaths (51.6%) were from a de novo posttransplant cancer and 105 (34.3%) from the pretransplant cancer. Pretransplant cancer diagnoses are associated with increased mortality after transplantation, but some deaths are related to posttransplant cancers and other causes. Improved candidate selection and cancer screening and prevention may reduce mortality in this population.

Association of contralateral breast cancer risk with mammographic density defined at higher-than-conventional intensity thresholds.

Mammographic dense area (MDA) is an established predictor of future breast cancer risk. Recent studies have found that risk prediction might be improved by redefining MDA in effect at higher-than-conventional intensity thresholds. We assessed whether such higher-intensity MDA measures gave stronger prediction of subsequent contralateral breast cancer (CBC) risk using the Women's Environment, Cancer, and Radiation Epidemiology (WECARE) Study, a population-based CBC case-control study of ≥1 year survivors of unilateral breast cancer diagnosed between 1990 and 2008. Three measures of MDA for the unaffected contralateral breast were made at the conventional intensity threshold ("Cumulus") and at two sequentially higher-intensity thresholds ("Altocumulus" and "Cirrocumulus") using the CUMULUS software and mammograms taken up to 3 years prior to the first breast cancer diagnosis. The measures were fitted separately and together in multivariable-adjusted logistic regression models of CBC (252 CBC cases and 271 unilateral breast cancer controls). The strongest association with CBC was MDA defined using the highest intensity threshold, Cirrocumulus (odds ratio per adjusted SD [OPERA] 1.40, 95% CI 1.13-1.73); and the weakest association was MDA defined at the conventional threshold, Cumulus (1.32, 95% CI 1.05-1.66). In a model fitting the three measures together, the association of CBC with Cirrocumulus was unchanged (1.40, 95% CI 0.97-2.05), and the lower brightness measures did not contribute to the CBC model fit. These results suggest that MDA defined at a high-intensity threshold is a better predictor of CBC risk and has the potential to improve CBC risk stratification beyond conventional MDA measures.

Life-years lost due to cancer among solid organ transplant recipients in the United States, 1987 to 2014.

BACKGROUND: Solid organ transplant recipients have an elevated risk of cancer. Quantifying the life-years lost (LYL) due to cancer provides a complementary view of the burden of cancer distinct from other metrics and may identify subgroups of transplant recipients who are most affected. METHODS: Linked transplant and cancer registry data were used to identify incident cancers and deaths among solid organ transplant recipients in the United States (1987-2014). Data on LYL due to cancer within 10 years posttransplant were derived using mean survival estimates from Cox models. RESULTS: Among 221,962 transplant recipients, 13,074 (5.9%) developed cancer within 10 years of transplantation. During this period, the mean LYL due to cancer were 0.16 years per transplant recipient and 2.7 years per cancer case. Cancer was responsible for a loss of 1.9% of the total life-years expected in the absence of cancer in this population. Lung recipients had the highest proportion of total LYL due to cancer (0.45%) followed by heart recipients (0.29%). LYL due to cancer increased with age, from 0.5% among those aged birth to 34 years at transplant to 3.2% among those aged 50 years and older. Among recipients overall, lung cancer was the largest contributor, accounting for 24% of all LYL due to cancer, and non-Hodgkin lymphoma had the next highest contribution (15%). CONCLUSIONS: Transplant recipients have a shortened lifespan after developing cancer. Lung cancer and non-Hodgkin lymphoma contribute strongly to LYL due to cancer within the first 10 years after transplant, highlighting opportunities to reduce cancer mortality through prevention and screening.

Cancer risk in living kidney donors.

Living kidney donors are screened for transmissible diseases including cancer. Outcomes following donation are excellent, but concern exists regarding development of chronic kidney disease, and cancer risk is unknown. We used linked transplant and cancer registry data to identify incident cancers among 84,357 kidney donors in the United States (1995-2017). We compared risk with the general population using standardized incidence ratios (SIRs). For selected cancers, we used Poisson regression to compare donors with 47,451 Adventist Health Study 2 (AHS-2) participants, who typically have healthy lifestyles. During follow-up, 2843 cancers were diagnosed in donors, representing an overall deficit (SIR 0.79, 95%CI 0.76-0.82). None of 46 specified cancer sites occurred in excess relative to the general population, and 15 showed significant deficits (SIR < 1.00). Compared with AHS-2 participants, donors had similar incidence of liver cancer, melanoma, breast cancer, and non-Hodgkin lymphoma but, starting 7 years after donation, elevated incidence of colorectal cancer (adjusted incidence rate ratio 2.07, 95%CI 1.54-2.79) and kidney cancer (2.97, 1.58-5.58, accounting for the presence of a single kidney in donors). Elevated kidney cancer incidence may reflect adverse processes in donors' remaining kidney. Nonetheless, cancer risk is lower than in the general population, suggesting that enhanced screening is unnecessary.

Influence of rurality on lymph node assessment among women diagnosed with ductal carcinoma in situ and treated with mastectomy, SEER 2000-2015.

PURPOSE: Despite recommendations from national organizations supporting the use of lymph node assessment (LNA) among patients with ductal carcinoma in situ (DCIS) at time of mastectomy, variation in practice patterns across the United States has been observed. However, few studies have evaluated LNA differences and rurality. METHODS: Data from the SEER Patterns of Care studies were used to identify women who underwent mastectomy for newly diagnosed DCIS during 2000, 2005, 2010, and 2015. Weighted multivariate logistic regression was used to evaluate the association between rural-urban residence and the use of LNA. A subgroup analysis was performed comparing the use of axillary lymph node dissection (ALND) versus sentinel lymph node biopsy (SLNB). RESULTS: Of the 504 patients included in the analysis, approximately 81% underwent LNA at time of mastectomy with lower rates of use observed among rural patients (66%) versus urban patients (82%). In multivariate analysis, LNA increased over time (p < 0.0001), and rural patients were less likely to receive LNA compared to urban patients [adjusted odds ratio (aOR) = 0.19; 95% confidence interval (CI) 0.06-0.66]. However, the likelihood of undergoing ALND relative to SLNB was lower among rural compared to urban patients (aOR = 0.16; 95% CI 0.03-0.73). CONCLUSIONS: Over time, the use of LNA with mastectomy has increased among DCIS patients. However, significant rural-urban differences in the use and type of LNA persist. The findings of this study highlight the importance of continued research aimed at examining the impact of rurality on the receipt of high-quality cancer care.

Gynecologic oncologist impact on adjuvant chemotherapy care for stage II-IV ovarian cancer patients.

OBJECTIVE: We aim to evaluate the impact gynecologic oncologists have on ovarian cancer adjuvant chemotherapy care from their role as surgeons recommending adjuvant chemotherapy care and their role as adjuvant chemotherapy providers while considering rural-urban differences. METHODS: Multivariable adjusted logistic regressions and Cox proportional hazards models were developed using a population-based, retrospective cohort of stage II-IV and unknown stage ovarian cancer patients diagnosed in Iowa, Kansas, and Missouri in 2010-2012 whose medical records were abstracted in 2017-2018. RESULTS: Gynecologic oncologist surgeons (versus other type of surgeon) were associated with increased odds of adjuvant chemotherapy initiation (adjusted odds ratio (OR) 2.18; 95% confidence interval (CI) 1.10-4.33) and having a gynecologic oncologist adjuvant chemotherapy provider (OR 10.0; 95% CI 4.58-21.8). Independent of type of surgeon, rural patients were less likely to have a gynecologic oncologist chemotherapy provider (OR 0.52; 95% CI 0.30-0.91). Gynecologic oncologist adjuvant chemotherapy providers (versus other providers) were associated with decreased surgery-to-chemotherapy time (rural: 6 days; urban: 8 days) and increased distance to chemotherapy (rural: 22 miles; urban: 11 miles). Rural women (versus urban) traveled 38 miles farther when their chemotherapy provider was a gynecologic oncologist and 27 miles farther when it was not. CONCLUSION: Gynecologic oncologist surgeons may impact adjuvant chemotherapy initiation. Gynecologic oncologists serving as adjuvant chemotherapy providers were associated with some care benefits, such as reduced time from surgery-to-chemotherapy, and some care barriers, such as travel distance. The barriers and benefits of having a gynecologic oncologist involved in adjuvant chemotherapy care, including rural-urban differences, warrant further research in other populations.

Estimated Regional White Matter Hyperintensity Burden, Resting State Functional Connectivity, and Cognitive Functions in Older Adults.

OBJECTIVE: White matter hyperintensities (WMH) are linked to deficits in cognitive functioning, including cognitive control and memory; however, the structural, and functional mechanisms are largely unknown. We investigated the relationship between estimated regional disruptions to white matter fiber tracts from WMH, resting state functional connectivity (RSFC), and cognitive functions in older adults. DESIGN: Cross-sectional study. SETTING: Community. PARTICIPANTS: Fifty-eight cognitively-healthy older adults. MEASUREMENTS: Tasks of cognitive control and memory, structural MRI, and resting state fMRI. We estimated the disruption to white matter fiber tracts from WMH and its impact on gray matter regions in the cortical and subcortical frontoparietal network, default mode network, and ventral attention network by overlaying each subject's WMH mask on a normative tractogram dataset. We calculated RSFC between nodes in those same networks. We evaluated the interaction of regional WMH burden and RSFC in predicting cognitive control and memory. RESULTS: The interaction of estimated regional WMH burden and RSFC in cortico-striatal regions of the default mode network and frontoparietal network was associated with delayed recall. Models predicting working memory, cognitive inhibition, and set-shifting were not significant. CONCLUSION: Findings highlight the role of network-level structural and functional alterations in resting state networks that are related to WMH and impact memory in older adults.

Referrals and Decision-Making Considerations Involved in Selecting a Surgeon for Rectal Cancer Treatment in the Midwestern United States.

BACKGROUND: Despite evidence of superior outcomes for rectal cancer at high-volume, multidisciplinary cancer centers, many patients undergo surgery in low-volume hospitals. OBJECTIVE: This study aimed to examine considerations of former patients with rectal cancer when selecting their surgeon and to evaluate which considerations were associated with surgery at high-volume hospitals. DESIGN: In this retrospective cohort study, patients were surveyed about what they considered when selecting a cancer surgeon. SETTINGS: Study data were obtained via survey and the statewide Iowa Cancer Registry. PATIENTS: All eligible individuals diagnosed with invasive stages II/III rectal cancer from 2013 to 2017 identified through the registry were invited to participate. MAIN OUTCOME MEASURES: The primary outcomes were the characteristics of the hospital where they received surgery (ie, National Cancer Institute designation, Commission on Cancer accreditation, and rectal cancer surgery volume). RESULTS: Among respondents, 318 of 417 (76%) completed surveys. Sixty-nine percent of patients selected their surgeon based on their physician's referral/recommendation, 20% based on surgeon/hospital reputation, and 11% based on personal connections to the surgeon. Participants who chose their surgeon based on reputation had significantly higher odds of surgery at National Cancer Institute-designated (OR 7.5; 95% CI, 3.8-15.0) or high-volume (OR 2.6; 95% CI, 1.2-5.7) hospitals than those who relied on referral. LIMITATIONS: This study took place in a Midwestern state with a predominantly white population, which limited our ability to evaluate racial/ethnic associations. CONCLUSION: Most patients with rectal cancer relied on referrals in selecting their surgeon, and those who did were less likely to receive surgery at a National Cancer Institute-designated or high-volume hospitals compared to those who considered reputation. Future research is needed to determine the impact of these decision factors on clinical outcomes, patient satisfaction, and quality of life. In addition, patients should be aware that relying on physician referral may not result in treatment from the most experienced or comprehensive care setting in their area. See Video Abstract at http://links.lww.com/DCR/B897.REMISIONES Y CONSIDERACIONES PARA LA TOMA DE DECISIONES RELACIONADAS CON LA SELECCIÓN DE UN CIRUJANO PARA EL TRATAMIENTO DEL CÁNCER DE RECTO EN EL MEDIO OESTE DE LOS ESTADOS UNIDOSANTECEDENTES:A pesar de la evidencia de resultados superiores para el tratamiento del cáncer de recto en centros oncológicos de gran volumen y multidisciplinarios, muchos pacientes se someten a cirugía en hospitales de bajo volumen.OBJETIVOS:Examinar las consideraciones de los antiguos pacientes con cáncer de recto al momento de seleccionar a su cirujano y evaluar qué consideraciones se asociaron con la cirugía en hospitales de gran volumen.DISEÑO:Encuestamos a los pacientes sobre qué aspectos consideraron al elegir un cirujano oncológico para completar este estudio de cohorte retrospectivo.AJUSTE:Los datos del estudio se obtuvieron mediante una encuesta y el Registro de Cáncer del estado de Iowa.PACIENTES:Se invitó a participar a todas las personas elegibles diagnosticadas con cáncer de recto invasivo en estadios II/III entre 2013 y 2017 identificadas a través del registro.PRINCIPALES MEDIDAS DE RESULTADO:Los resultados principales fueron las características del hospital donde fue realizada la cirugía (es decir, designación del Instituto Nacional del Cáncer, acreditación de la Comisión de Cáncer y volumen de cirugía del cáncer de recto).RESULTADOS:Hubo 318 de 417 (76%) encuestas completadas. El sesenta y nueve por ciento seleccionó a su cirujano en función de la referencia / recomendación de su médico, el 20% por la reputación del cirujano/hospital, y el 11% por sus conexiones personales con el cirujano. Los participantes que eligieron a su cirujano en función a la reputación tuvieron probabilidades significativamente más altas de cirugía en el Instituto Nacional del Cáncer designado (OR = 7,5, IC del 95%: 3,8-15,0) o en hospitales de alto volumen (OR = 2,6, IC del 95%: 1,2-5,7) que aquellos que dependían de la derivación.LIMITACIONES:Este estudio se llevó a cabo en un estado del medio oeste con una población predominantemente blanca, lo que limitó nuestra capacidad para evaluar las asociaciones raciales/étnicas.CONCLUSIONES:La mayoría de los pacientes con cáncer de recto dependían de las derivaciones para seleccionar a su cirujano, y los que lo hacían tenían menos probabilidades de recibir cirugía en un hospital designado por el Instituto Nacional del Cáncer o en hospitales de gran volumen en comparación con los que consideraban la reputación. Se necesitan investigaciones a futuro para determinar el impacto de estos factores de decisión en los resultados clínicos, la satisfacción del paciente y la calidad de vida. Además, los pacientes deben ser conscientes de que depender de la remisión de un médico puede no resultar en el tratamiento más experimentado o integral en su área. Consulte Video Resumen en http://links.lww.com/DCR/B897. (Traducción-Dr Osvaldo Gauto).

Hospital Rurality and Gene Expression Profiling for Early-Stage Breast Cancer among Iowa Residents (2010-2018).

Objective: Given the challenges rural cancer patients face in accessing cancer care as well as the slower diffusion and adoption of new medical technologies among rural providers, the aim of our study was to examine trends in gene expression profiling (GEP) testing and evaluate the association between hospital rurality and receipt of GEP testing. Methods: Data from the Iowa Cancer Registry (ICR) were used to identify women with newly diagnosed, histologically confirmed breast cancer from 2010 through 2018 who met eligibility criteria for GEP testing. Patients were allocated to the hospitals where their most definitive surgical treatment was received, and Rural-Urban Commuting Area codes were used to categorize hospitals into urban (N = 43), large rural (N = 16), and small rural (N = 48). Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression to evaluate the association between hospital rurality and GEP test use, adjusting for demographic and clinical characteristics. The association between test result and treatment received was assessed among patients who received Oncotype DX (ODX) testing. Results: Of 6,726 patients eligible for GEP test use, 46% (N = 3,069) underwent testing with 95% receiving ODX. While overall GEP testing rates increased over time from 42% between 2010 and 2012 to 51% between 2016 and 2018 (P trend < 0.0001), use continued to be the lowest among patients treated at hospitals in small rural areas. The odds of GEP testing remained significantly lower among patients treated at hospitals located in small rural areas (aOR 0.55; 95% CI 0.43-0.71), after adjusting for demographic and clinical characteristics. ODX recurrence scores were highly correlated with chemotherapy use across all strata of hospital rurality. Conclusions: GEP testing continues to be underutilized, especially among those treated at small rural hospitals. Targeted interventions aimed at increasing rates of GEP testing to ensure the appropriate use of adjuvant chemotherapy may improve health outcomes and lower treatment-related costs.

Race, ethnicity and risk of second primary contralateral breast cancer in the United States.

Breast cancer survivors have a high risk of a second primary contralateral breast cancer (CBC), but there are few studies of CBC risk in racial/ethnic minority populations. We examined whether the incidence and risk factors for CBC differed by race/ethnicity in the United States. Women with a first invasive Stage I-IIB breast cancer diagnosis at ages 20-74 years between 2000 and 2015 in the Surveillance, Epidemiology, and End Results Program (SEER) 18 registries were followed through 2016 for a diagnosis of invasive CBC ≥1 year after the first breast cancer diagnosis. We used cause-specific Cox proportional hazards models to test the association between race/ethnicity and CBC, adjusting for age, hormone receptor status, radiation therapy, chemotherapy and stage at first diagnosis, and evaluated the impact of contralateral prophylactic mastectomy, socioeconomic status, and insurance status on the association. After a median follow-up of 5.9 years, 9247 women (2.0%) were diagnosed with CBC. Relative to non-Hispanic (NH) White women, CBC risk was increased in NH Black women (hazard ratio = 1.44, 95% CI 1.35-1.54) and Hispanic women (1.11, 95% CI 1.02-1.20), with the largest differences among women diagnosed at younger ages. Adjustment for contralateral prophylactic mastectomy, socioeconomic status and health insurance did not explain the associations. Therefore, non-Hispanic Black and Hispanic women have an increased risk of CBC that is not explained by clinical or socioeconomic factors collected in SEER. Large studies of diverse breast cancer survivors with detailed data on treatment delivery and adherence are needed to inform interventions to reduce this disparity.

Prevalence of human papillomavirus genotypes in high-grade cervical precancer and invasive cervical cancer from cancer registries before and after vaccine introduction in the United States.

BACKGROUND: US population-based cancer registries can be used for surveillance of human papillomavirus (HPV) types found in HPV-associated cancers. Using this framework, HPV prevalence among high-grade cervical precancers and invasive cervical cancers were compared before and after HPV vaccine availability. METHODS: Archived tissue from 2 studies of cervical precancers and invasive cervical cancers diagnosed from 1993-2005 (prevaccine) were identified from 7 central cancer registries in Florida; Hawaii; Iowa; Kentucky; Louisiana; Los Angeles County, California; and Michigan; from 2014 through 2015 (postvaccine) cases were identified from 3 registries in Iowa, Kentucky, and Louisiana. HPV testing was performed using L1 consensus polymerase chain reaction analysis. HPV-type-specific prevalence was examined grouped by hierarchical attribution to vaccine types: HPV 16, 18, HPV 31, 33, 45, 52, 58, other oncogenic HPV types, and other types/HPV negative. Generalized logit models were used to compare HPV prevalence in the prevaccine study to the postvaccine study by patient age, adjusting for sampling factors. RESULTS: A total of 676 precancers (328 prevaccine and 348 postvaccine) and 1140 invasive cervical cancers (777 prevaccine and 363 postvaccine) were typed. No differences were observed in HPV-type prevalence by patient age between the 2 studies among precancers or invasive cancers. CONCLUSIONS: The lack of reduction in vaccine-type prevalence between the 2 studies is likely explained by the low number of cases and low HPV vaccination coverage among women in the postvaccine study. Monitoring HPV-type prevalence through population-based strategies will continue to be important in evaluating the impact of the HPV vaccine.

Hospital and Surgeon Selection for Medicare Beneficiaries With Stage II/III Rectal Cancer: The Role of Rurality, Distance to Care, and Colonoscopy Provider.

OBJECTIVE: To determine factors associated with rectal cancer surgery performed at high-volume hospitals (HVHs) and by high-volume surgeons (HVSs), including the roles of rurality and diagnostic colonoscopy provider characteristics. SUMMARY OF BACKGROUND DATA: Although higher-volume hospitals/surgeons often achieve superior surgical outcomes, many rectal cancer resections are performed by lower-volume hospitals/surgeons, especially among rural populations. METHODS: Patients age 66+ diagnosed from 2007 to 2011 with stage II/III primary rectal adenocarcinoma were selected from surveillance, epidemiology, and end results-medicare data. Patient ZIP codes were used to classify rural status. Hierarchical logistic regression was used to determine factors associated with surgery by HVH and HVS. RESULTS: Of 1601 patients, 22% were rural and 78% were urban. Fewer rural patients received surgery at a HVH compared to urban patients (44% vs 65%; P < 0.0001). Compared to urban patients, rural patients more often had colonoscopies performed by general surgeons (and less often from gastroenterologists or colorectal surgeons), and lived substantially further from HVHs; these factors were both associated with lower odds of surgery at a HVH or by a HVS. In addition, whereas over half of both rural and urban patients received their colonoscopy and surgery at the same hospital, rural patients who stayed at the same hospital were significantly less likely to receive surgery at a HVH or by a HVS compared to urban patients. CONCLUSIONS: Rural rectal cancer patients are less likely to receive surgery from a HVH/HVS. The role of the colonoscopy provider has important implications for referral patterns and initiatives seeking to increase centralization.

Impact of age, rurality and distance in predicting contralateral prophylactic mastectomy for breast cancer in a Midwestern state: a population-based study.

PURPOSE: Iowa is among several rural Midwestern states with the highest proportions of contralateral prophylactic mastectomy (CPM) in women < 45 years of age. We evaluated the role of rurality and travel distance in these surgical patterns. METHODS: Women with unilateral breast cancer (2007-2017) were identified using Iowa Cancer Registry records. Patients and treating hospitals were classified as metro, nonmetro, and rural based on Rural-Urban Continuum Codes. Differences in patient, tumor, and treatment characteristics and median travel distance (MTD) were compared. Characteristics associated with CPM were evaluated with multivariate logistic regression. RESULTS: 22,158 women were identified: 57% metro, 26% nonmetro and 18% rural. Young rural women had the highest proportion of CPM (52%, 39% and 40% for rural, metro, nonmetro women < 40 years). Half of all rural women had surgery at metro hospitals; these women had the longest MTD (62 miles). Among all women treated at metro hospitals, rural women had the highest proportion of CPM (17% rural vs 14% metro/nonmetro, p = 0.007). On multivariate analysis, traveling ≥ 50 miles (ORs 1.43-2.34) and rural residence (OR = 1.29) were independently predictive of CPM. Other risk factors were young age (< 40 years: OR = 7.28, 95% CI 5.97-8.88) and surgery at a metro hospital that offers reconstruction (OR = 2.30, 95% CI 1.65-3.21) and is not NCI-designated (OR = 2.34, 95% CI 1.92-2.86). CONCLUSION: There is an unexpectedly high proportion of CPM in young rural women in Iowa, and travel distance and availability of reconstructive services likely influence decision-making. Improving access to multidisciplinary care in rural states may help optimize decision-making.

Associations between tissue-based CD3+ T-lymphocyte count and colorectal cancer survival in a prospective cohort of older women.

Tumor-infiltrating lymphocytes in colorectal cancer (CRC) predict better survival. However, associations between T-lymphocyte count in histologically normal tissues from patients with CRC and survival remain uncertain. We examined associations of CD3+ T-cells in colorectal tumor and histologically normal tissues with CRC-specific and all-cause mortality in the prospective Iowa Women's Health Study. Tissue microarrays were constructed using paraffin-embedded colorectal tissue samples from 464 women with tumor tissues and 314 women with histologically normal tissues (55-69 years at baseline) diagnosed with incident CRC from 1986 to 2002 and followed through 2014 (median follow-up 20.5 years). Three tumor and two histologically normal tissue cores for each patient were immunostained using CD3+ antibody and quantified, and the counts were averaged across the cores in each tissue. Cox proportional hazards regression estimated hazard ratios (HR) and 95% confidence interval (CI) for CRC-specific and all-cause mortality. After adjustment for age at diagnosis, body mass index, smoking status, tumor grade, and stage, HRs (95% CI) for the highest versus lowest tertile of tumor CD3+ score were 0.59 (0.38-0.89) for CRC-specific mortality and 0.82 (0.63-1.05) for all-cause mortality; for histologically normal CD3+ score, the corresponding HRs (95% CI) were 0.47 (0.19-1.17) and 0.50 (0.27-0.90), respectively. The CD3+ score combining the tumor and histologically normal scores was inversely associated with CRC-specific and all-cause mortality. Although the association between tumor CD3+ score and all-cause mortality was not significant, both higher CD3+ T-lymphocyte counts in tumor and histologically normal scores tended to be associated with lower CRC-specific and all-cause mortality.

Rural disparities in surgical care from gynecologic oncologists among Midwestern ovarian cancer patients.

OBJECTIVE: Up to one-third of women with ovarian cancer in the United States do not receive surgical care from a gynecologic oncologist specialist despite guideline recommendations. We aim to investigate the impact of rurality on receiving surgical care from a specialist, referral to a specialist, and specialist surgery after referral, and the consequences of specialist care. METHODS: We utilized a retrospective cohort created through an extension of standard cancer surveillance in three Midwestern states. Multivariable adjusted logistic regression was utilized to assess gynecologic oncologist treatment of women 18-89 years old, who were diagnosed with primary, histologically confirmed, malignant ovarian cancer in 2010-2012 in Kansas, Missouri and Iowa by rurality. RESULTS: Rural women were significantly less likely to receive surgical care from a gynecologic oncologist specialist (adjusted odds ratio (OR) 0.37, 95% confidence interval (CI) 0.24-0.58) and referral to a specialist (OR 0.37, 95% CI 0.23-0.59) compared to urban women. There was no significant difference in specialist surgery after a referral (OR 0.56, 95% CI 0.26-1.20). Rural women treated surgically by a gynecologic oncologist versus non-specialist were more likely to receive cytoreduction and more complete tumor removal to ≤1 cm. CONCLUSION: There is a large rural-urban difference in receipt of ovarian cancer surgery from a gynecologic oncologist specialist (versus a non-specialist). Disparities in referral rates contribute to the rural-urban difference. Further research will help define the causes of referral disparities, as well as promising strategies to address them.

A Critical, Event-Related Appraisal of Denoising in Resting-State fMRI Studies.

This article advances two parallel lines of argument about resting-state functional magnetic resonance imaging (fMRI) signals, one empirical and one conceptual. The empirical line creates a four-part organization of the text: (1) head motion and respiration commonly cause distinct, major, unwanted influences (artifacts) in fMRI signals; (2) head motion and respiratory changes are, confoundingly, both related to psychological and clinical and biological variables of interest; (3) many fMRI denoising strategies fail to identify and remove one or the other kind of artifact; and (4) unremoved artifact, due to correlations of artifacts with variables of interest, renders studies susceptible to identifying variance of noninterest as variance of interest. Arising from these empirical observations is a conceptual argument: that an event-related approach to task-free scans, targeting common behaviors during scanning, enables fundamental distinctions among the kinds of signals present in the data, information which is vital to understanding the effects of denoising procedures. This event-related perspective permits statements like "Event X is associated with signals A, B, and C, each with particular spatial, temporal, and signal decay properties". Denoising approaches can then be tailored, via performance in known events, to permit or suppress certain kinds of signals based on their desirability.