JNCI Cancer Spectrum最新文献

Background: Emerging literature notes the importance of neighborhood-level factors for cancer control behaviors beyond that of individual factors. Markers of neighborhood-level disadvantage have been linked to greater likelihood of nonsalutary cancer control behaviors. There has been less examination of many neighborhood factors simultaneously, which more accurately reflects individuals' daily experiences. We estimated associations of neighborhood deprivation indices with cancer control behaviors, identifying the relative importance of neighborhood-level deprivation index components for these outcomes.

Methods: We used data from the Religion and Health in African Americans study, a national probability sample of African American adults. We separately considered 4 screening and 4 prevention behaviors as outcomes. We constructed neighborhood deprivation indices using census tract-level data and estimated their associations with outcomes using bayesian index models, adjusting for individual-level covariates. We reported odds ratios (ORs), credible intervals, and exceedance probabilities.

Results: Participants in our sample engaged in relatively high levels of screening behaviors and lower levels of prevention behaviors. Neighborhood deprivation indices were statistically significantly associated with a greater likelihood of binge drinking (OR = 1.13, exceedance probability = 98.5%), smoking (OR = 1.07, exceedance probability = 99.4%), and insufficient colonoscopy (exceedance probability = 99.9%), Papanicolaou (exceedance probability = 99.7%), and prostate-specific antigen (exceedance probability = 99.1%) screening. Within neighborhood deprivation indices, median household income, percentage of individuals without some college education, and percentage of individuals unemployed received large estimated importance weights.

Conclusion: We identified statistically significant associations between neighborhood disadvantage and nonsalutary cancer control behaviors as well as important neighborhood-level deprivation index components for each outcome. These and similar findings from future studies should be used to target specific neighborhood factors for specific cancer control behaviors rather than using a one-size-fits-all approach.

Background: Screening represents a cornerstone of cervical cancer control strategy. However, disparities in social determinants of health have perpetuated gaps in screening among racial and ethnic minorities. Social determinants of health including cultural stigma and lack of insurance have contributed to decreased screening among Hispanic women. To increase cancer screening in this population, community-academic partnerships and culturally tailored media have emerged as promising strategies.

Methods: This study assessed the impact of a culturally tailored cervical cancer screening campaign implemented through academic-community-government partnerships. Intercept surveys, conducted from 2015 to 2018 in eastern neighborhoods of Los Angeles, assessed campaign recall, interpretation, and screening intention among Hispanic women aged 21-65 years after exposure to the campaign. Screening intention was evaluated using χ2 and logistic regression by participant characteristics, with thematic analysis for campaign interpretation.

Results: Of 673 participants, 26.1% were uninsured, and 85.9% primarily spoke Spanish at home. Campaign recall was 25.1%, with 64.5% interpreting the campaign's message as cervical cancer screening or health checkups. The campaign's most liked aspect was emphasis on family (cited by 37.1% of participants). Postcampaign, 89.5% of participants overall were likely or extremely likely to schedule a Pap test, including 83.5% of women who had not had a Pap test in the past 3 years.

Conclusions: Our findings underscore several important strategies to reduce cervical cancer disparities: (1) associating positive cultural values with screening to decrease stigma, (2) combining culturally tailored outreach with interventions that target other known screening barriers, (3) facilitating long-term community relationships, and (4) leveraging academic-community-government partnerships.

Background: Black/African Americans experience disproportionate cancer burden and mortality rates. Racial and ethnic variation in cancer burden reflects systemic and health-care inequities, cancer risk factors, and heredity and genomic diversity. Multiple systemic, sociocultural, economic, and individual factors also contribute to disproportionately low Black/African American participation in cancer clinical trials.

Methods: The Participatory Action for Access to Clinical Trials project used a community-based participatory research approach inclusive of Black/African American community-based organizations, Henry Ford Health, and the University of Michigan Urban Research Center. The project aims were to understand Black/African Americans' behavioral intentions to participate in cancer clinical trials and to obtain recommendations for improving participation. Audio-recorded focus group data were transcribed and coded, and searches were conducted to identify themes and subthemes. Representative text was extracted from the transcripts.

Results: Six community focus group discussions (70 participants) and 6 Henry Ford Health patient/survivor focus group discussions (29 participants) were completed. General themes related to trial participation were identified, including (1) systemic issues related to racism, health disparities, and trust in government, health systems, and clinical research; (2) firsthand experiences with health care and health systems; (3) perceived and experienced advantages and disadvantages of clinical trial participation; and (4) recruitment procedures and personal decision-making processes. Specific recommendations on how to address barriers were obtained.

Conclusions: Community-based participatory research is effective in bringing communities equitably to the table. To build trust, health systems must provide opportunities for patients and communities to jointly identify factors affecting cancer clinical trial participation, implement recommendations, and address health disparities.

Background: In metastatic colorectal cancer (mCRC), improvements in survival from combining leucovorin/fluorouracil/oxaliplatin/irinotecan (FOLFOXIRI) with bevacizumab have come at the risk of increased rates of high-grade toxicities. Trilaciclib is indicated to decrease the incidence of chemotherapy-induced myelosuppression in patients receiving standard-of-care chemotherapy for extensive-stage small cell lung cancer.

Methods: Patients with untreated mCRC were randomly assigned 1:1 to trilaciclib (n = 164) or placebo (n = 162) prior to FOLFOXIRI/bevacizumab for up to 12 cycles (induction), followed by trilaciclib or placebo prior to fluorouracil/leucovorin/bevacizumab (maintenance). Co-primary endpoints were duration of severe (grade 4) neutropenia (DSN) in cycles 1-4 and occurrence of severe neutropenia (SN) during induction. Secondary endpoints included antitumor efficacy, survival, and safety.

Results: The study met its co-primary endpoints. Administering trilaciclib prior to FOLFOXIRI/bevacizumab resulted in significant reductions in DSN in cycles 1-4 vs placebo (mean, 0.1 vs 1.3 days; P < .001) and occurrence of SN during induction (1.3% vs 19.7%; adjusted relative risk [96% CI] = 0.07 [0.0 to 0.3]; P < .001). Grade 3/4 adverse events, including neutropenia, diarrhea, and leukopenia, were less frequent with trilaciclib vs placebo (64.8% vs 73.1%). Trilaciclib was associated with fewer chemotherapy dose reductions and delays and with reduced administration of supportive therapies, compared with placebo. Objective response rate (41.6% vs 57.1%; P = .009) and median progression-free survival (10.3 vs 13.1 months; P < .001) were significantly lower with trilaciclib vs placebo.

Conclusions: Administering trilaciclib prior to FOLFOXIRI/bevacizumab protected the neutrophil lineage from the effects of chemotherapy-induced myelosuppression. However, antitumor efficacy endpoints favored placebo.

Trial registration: ClinicalTrials.gov: NCT04607668.

Background: Breast cancer survivors experience higher rates of cardiovascular disease (CVD) than women without breast cancer, due in part to cardiotoxic cancer treatments and shared lifestyle risk factors. Physical activity is associated with lower mortality risk in breast cancer survivors, but associations with CVD have not been examined in detail.

Methods: The Pathways Study is a prospective cohort study of 4504 women diagnosed with invasive breast cancer between 2005 and 2013. At enrollment, women self-reported their physical activities during the previous 6 months, which were dichotomized as meeting the Centers for Disease Control and Prevention's Physical Activity Guidelines for Americans (≥150 minutes of moderate-intensity or ≥75 minutes of vigorous-intensity activity per week) vs not. Incident CVD events (heart failure, cardiomyopathy, cardiac arrest, ischemic heart disease, stroke) occurring between enrollment and December 2021 were identified from electronic health records. Covariate-adjusted, competing-risks Cox regression models estimated associations between meeting physical activity guidelines and CVD risk.

Results: Compared with women who did not meet physical activity guidelines at their diagnosis, those who did had a 25% lower risk of CVD (HR = 0.75, 95% CI = 0.60 to 0.94). Among the individual CVD outcomes, meeting physical activity guidelines was protective against incident cardiomyopathy (hazard ratio [HR] = 0.54, 95% CI = 0.31 to 0.95), heart failure (HR = 0.66, 95% CI = 0.50 to 0.87), and cardiac arrest (HR = 0.68, 95% CI = 0.49 to 0.99).

Conclusions: Meeting physical activity guidelines at breast cancer diagnosis was associated with lower risk of CVD after diagnosis. Studies investigating changes in physical activity after a breast cancer diagnosis and CVD risk are warranted.

Li-Fraumeni syndrome is a cancer predisposition syndrome caused by pathogenic TP53 germline variants; it is associated with a high lifelong cancer risk. We analyzed the German Li-Fraumeni syndrome registry, which contains data on 304 individuals. Cancer phenotypes were correlated with variants grouped according to their ability to transactivate target genes in a yeast assay using a traditional (nonfunctional, partially functional) and a novel (clusters A, B, and C) classification of variants into different groups. Partially functional and cluster B or C variants were enriched in patients who did not meet clinical testing criteria. Time to first malignancy was longer in carriers of partially functional variants (hazard ratio = 0.38, 95% CI = 0.22 to 0.66). Variants grouped within cluster B (hazard ratio = 0.45, 95% CI = 0.28 to 0.71) or C (hazard ratio = 0.34, 95% CI = 0.19 to 0.62) were associated with later cancer onset than NULL variants. These findings can be used to risk-stratify patients and inform care.

Background: Head and neck paragangliomas (HNPGLs) are typically slow-growing, hormonally inactive tumors of parasympathetic paraganglia. Inactivation of prolyl-hydroxylase domain-containing 2 protein causing indirect gain-of-function of hypoxia-inducible factor-2α (HIF-2α), encoded by EPAS1, was recently shown to cause carotid body hyperplasia. We previously described a syndrome with multiple sympathetic paragangliomas caused by direct gain-of-function variants in EPAS1 (Pacak-Zhuang syndrome, PZS) and developed a corresponding mouse model.

Methods: We evaluated a cohort of patients with PZS (n = 9) for HNPGL by positron emission tomography, magnetic resonance imaging, and computed tomography and measured carotid body size compared to literature reference values. Resected tumors were evaluated by histologic sectioning and staining. We evaluated the corresponding mouse model at multiple developmental stages (P8 and adult) for lesions of the head and neck by high resolution ex vivo imaging and performed immunohistochemical staining on histologic sections of the identified lesions.

Results: hree patients had imaging consistent with HNPGL, one of which warranted resection and was confirmed on histology. Three additional patients had carotid body enlargement (Z-score > 2.0), and 3 had carotid artery malformations. We found that 9 of 10 adult variant mice had carotid body tumors and 6 of 8 had a paraganglioma on the cranio-caval vein, the murine homologue of the superior vena cava; these were also found in 4 of 5 variant mice at post-natal day 8. These tumors and the one resected from a patient were positive for tyrosine hydroxylase, synaptophysin, and chromogranin A. Brown fat in a resected patient tumor carried the EPAS1 pathogenic variant.

Conclusions: These findings (1) suggest HNPGL as a feature of PZS and (2) show that these pathogenic variants are sufficient to cause the development of these tumors, which we believe represents a continuous spectrum of disease starting from hyperplasia.

Background: In non-small cell lung cancer (NSCLC), social determinants of health (SDOHs) influence treatment, but SDOHs with geographic precision are infrequently used in real-world research due to privacy considerations. This research aims to characterize the influence of census-tract level SDOHs on treatment for stage I and IIa NSCLC.

Methods: Patients diagnosed between 1/1/17 and 9/30/22 with stages I and IIa NSCLC in the Syapse Learning Health Network had their addresses geocoded and linked to five census tract-level indicators of SDOH (social vulnerability index (SVI), percent (%) housing burden, % broadband internet access, primary care shortage area, and rurality). Clinical and demographic characteristics were ascertained from medical records. Nested multinomial logistic regression models estimated associations between SDOHs and initial treatment using two-sided Wald tests. The collective statistical significance of SDOHs was assessed with a likelihood ratio test (LRT) comparing nested models. Descriptive statistics described time-to-treatment-initiation.

Results: Among 3595 patients, 58% were initially treated with surgery, 29% with radiation, and 12% with "other." Two SDOH variables were associated with increased relative risk ratios (RRR) for radiation therapy compared to surgery: living in primary care shortage areas (RRR 1.61, 95% CI: (1.23-2.10)) and living in non-metropolitan areas (RRR 1.45 (1.02-2.07)). The LRT suggested that the five SDOH variables collectively improved the treatment model. Further, patients in areas with high SVI, low internet access, and high housing-burden initiated treatment later.

Conclusion: When using precise estimates of geospatial SDOHs, these measures were associated with treatment, and should be considered in analyses of cancer outcomes.

Background: People with HIV (PWH) diagnosed with stage-IV cancer are less likely to receive palliative care (PC) compared to those without HIV. Our objective was to evaluate inequities in PC receipt among PWH with stage IV cancer in the US.

Methods: We used the National Cancer Database (2004-2020), including adult (18-89 years) PWH with the 14 most common cancers that occur among PWH. PC was defined as treatment provided with non-curative intent. Our main exposures included % quartiles of adults without a high school degree (educational attainment) and median income quartiles within the patient's zip code. We used hierarchical multivariable Poisson regression to estimate adjusted prevalence ratios(aPR) with 95% confidence intervals (95% CI), adjusting for age, sex, year of diagnosis, race/ethnicity, and cancer type.

Results: Among the included 10,120 PWH with stage IV cancer, 72% were men, 51% were either non-Hispanic(NH)-Black or Hispanic/Latinx, 38% were aged ≥60 years, and 97% resided in urban areas. Fourteen percent received PC. NH-Black PWH living in zip-codes with lower quartiles of educational attainment were more likely to receive PC compared to those in the highest quartile (Q1vs.Q4: aPR:1.93;95% CI:1.29-2,86) For income overall, compared to those in the highest quartile (Q4) of income, those in the lowest quartile had 26% higher likelihood of receiving PC (Q1vs.Q4: aPR:1.26;95% CI:1.05-1.52), particularly among NH-Black adults (Q1vs.Q4: aPR:1.67;95% CI:1.25-2.22; Q2 vs.Q4; aPR:1.48;95% CI:1.09-2.01).

Conclusions: PC use among PWH with stage-IV cancer is low. Contextual poverty plays a role in PC delivery to PWH and cancer, particularly among NH-Black PWH.