Red Flag Signs and Symptoms for Patients With Early-Onset Colorectal Cancer: A Systematic Review and Meta-Analysis.

Importance: Early-onset colorectal cancer (EOCRC), defined as a diagnosis at younger than age 50 years, is increasing, and so-called red flag signs and symptoms among these individuals are often missed, leading to diagnostic delays. Improved recognition of presenting signs and symptoms associated with EOCRC could facilitate more timely diagnosis and impact clinical outcomes. Objective: To report the frequency of presenting red flag signs and symptoms among individuals with EOCRC, to examine their association with EOCRC risk, and to measure variation in time to diagnosis from sign or symptom presentation. Data Sources: PubMed/MEDLINE, Embase, CINAHL, and Web of Science were searched from database inception through May 2023. Study Selection: Studies that reported on sign and symptom presentation or time from sign and symptom presentation to diagnosis for patients younger than age 50 years diagnosed with nonhereditary CRC were included. Data Extraction and Synthesis: Data extraction and quality assessment were performed independently in duplicate for all included studies using Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guidelines. Joanna Briggs Institute Critical Appraisal tools were used to measure risk of bias. Data on frequency of signs and symptoms were pooled using a random-effects model. Main Outcomes and Measures: Outcomes of interest were pooled proportions of signs and symptoms in patients with EOCRC, estimates for association of signs and symptoms with EOCRC risk, and time from sign or symptom presentation to EOCRC diagnosis. Results: Of the 12 859 unique articles initially retrieved, 81 studies with 24 908 126 patients younger than 50 years were included. The most common presenting signs and symptoms, reported by 78 included studies, were hematochezia (pooled prevalence, 45% [95% CI, 40%-50%]), abdominal pain (pooled prevalence, 40% [95% CI, 35%-45%]), and altered bowel habits (pooled prevalence, 27% [95% CI, 22%-33%]). Hematochezia (estimate range, 5.2-54.0), abdominal pain (estimate range, 1.3-6.0), and anemia (estimate range, 2.1-10.8) were associated with higher EOCRC likelihood. Time from signs and symptoms presentation to EOCRC diagnosis was a mean (range) of 6.4 (1.8-13.7) months (23 studies) and a median (range) of 4 (2.0-8.7) months (16 studies). Conclusions and Relevance: In this systematic review and meta-analysis of patients with EOCRC, nearly half of individuals presented with hematochezia and abdominal pain and one-quarter with altered bowel habits. Hematochezia was associated with at least 5-fold increased EOCRC risk. Delays in diagnosis of 4 to 6 months were common. These findings highlight the need to identify concerning EOCRC signs and symptoms and complete timely diagnostic workup, particularly for individuals without an alternative diagnosis or sign or symptom resolution.

MicroRNA panels as diagnostic biomarkers for colorectal cancer: A systematic review and meta-analysis.

Background: Circulating microRNAs (miRNA) have emerged as promising diagnostic biomarkers for several diseases, including cancer. However, the diagnostic accuracy of miRNA panels in colorectal cancer (CRC) remains inconsistent and there is still lack of meta-analyses to determine whether miRNA panels can serve as robust biomarkers for CRC diagnosis. Methods: This study performed a systematic review and meta-analysis to evaluate the clinical utility of miRNA panels as potential biomarkers for the diagnosis of CRC. The investigation systematically searched PubMed, Medline, Web of Science, Cochrane Library, and Google Scholar (21-year span, between 2000 and 2021) to retrieve articles reporting the diagnostic role of miRNA panels in detecting CRC. Diagnostic meta-analysis of miRNA panels used diverse evaluation indicators, including sensitivity, specificity, Positive Likelihood Ratio (PLR), Negative Likelihood Ratio (NLR), Diagnostic Odds Ratio (DOR), and the area under the curve (AUC) values. Results: Among the 313 articles identified, 20 studies met the inclusion criteria. The pooled estimates of miRNA panels for the diagnosis of CRC were 0.85 (95% CI: 0.84-0.86), 0.79 (95% CI: 0.78-0.80), 4.06 (95% CI: 3.89-4.23), 0.20 (95% CI: 0.19-0.20), 22.50 (95% CI: 20.81-24.32) for sensitivity, specificity, PLR, NLR, and DOR, respectively. Moreover, the summary receiver operating characteristics (SROC) curve revealed an AUC value of 0.915 (95% CI: 0.914-0.916), suggesting an outstanding diagnostic accuracy for overall miRNA panels. Subgroup and meta-regression analyses demonstrated that miRNA panels have the highest diagnostic accuracy within serum samples, rather than in other sample-types - with a sensitivity, specificity, PLR, NLR, DOR, and AUC of 0.87, 0.86, 7.33, 0.13, 55.29, and 0.943, respectively. Sensitivity analysis revealed that DOR values did not differ markedly, which indicates that the meta-analysis had strong reliability. Furthermore, this study demonstrated no proof of publication bias for DOR values analyzed using Egger's regression test (P > 0.05) and funnel plot. Interestingly, miR-15b, miR-21 and miR-31 presented the best diagnostic accuracy values for CRC with sensitivity, specificity, PLR, NLR, DOR, and AUC values of 0.95, 0.94, 17.19, 0.05, 324.81, and 0.948, respectively. Conclusion: This study's findings indicated that miRNA panels, particularly serum-derived miRNA panels, can serve as powerful and promising biomarkers for early CRC screening. Systematic review registration: [www.crd.york.ac.uk/prospero], identifier [CRD42021268172].

Informal Providers-Ground Realities in South Asian Association for Regional Cooperation Nations: Toward Better Cancer Primary Care: A Narrative Review.

PURPOSE: South Asian Association for Regional Cooperation (SAARC) nations are a group of eight countries with low to medium Human Development Index values. They lack trained human resources in primary health care to achieve the WHO-stated goal of Universal Health Coverage. An unregulated service sector of informal health care providers (IPs) has been serving these underserved communities. The aim is to summarize the role of IPs in primary cancer care, compare quality with formal providers, quantify distribution in urban and rural settings, and present the socioeconomic milieu that sustains their existence. METHODS: A narrative review of the published literature in English from January 2000 to December 2021 was performed using MeSH Terms Informal Health Care Provider/Informal Provider and Primary Health Care across databases such as Medline (PubMed), Google Scholar, and Cochrane database of systematic reviews, as well as World Bank, Center for Global Development, American Economic Review, Journal Storage, and Web of Science. In addition, citation lists from the primary articles, gray literature in English, and policy blogs were included. We present a descriptive overview of our findings as applicable to SAARC. RESULTS: IPs across the rural landscape often comprise more than 75% of primary caregivers. They provide accessible and affordable, but often substandard quality of care. However, their network would be suitable for prompt cancer referrals. Care delivery and accountability correlate with prevalent standards of formal health care. CONCLUSION: Acknowledgment and upskilling of IPs could be a cost-effective bridge toward universal health coverage and early cancer diagnosis in SAARC nations, whereas state capacity for training formal health care providers is ramped up simultaneously. This must be achieved without compromising investment in the critical resource of qualified doctors and allied health professionals who form the core of the rural public primary health care system.

Association of Prediagnosis Obesity and Postdiagnosis Aspirin With Survival From Stage IV Colorectal Cancer.

Importance: The potential relationship between obesity and colorectal cancer (CRC) outcome is poorly understood in patients with late-stage disease. Increased body mass index may negate aspirin use for cancer prevention, but its role as a factor on the effectiveness of postdiagnosis aspirin use is unclear. Objective: To evaluate how prediagnosis obesity and postdiagnosis aspirin use may be associated with overall survival in patients with late-stage colorectal cancer. Design, Setting, and Participants: This cross-sectional study used self-reported data from patients with metastatic or treatment-refractory disease who consented to a clinical protocol at MD Anderson Cancer Center, a large US cancer treatment center. Patients were enrolled between 2010 and 2018 and followed up for mortality through July 2020. Analyses were conducted through March 2022. Exposures: Body mass index in the decade prior to initial diagnosis and regular aspirin use at survey completion. Main Outcomes and Measures: Overall survival was measured from stage IV diagnosis until death or last follow-up. Cox proportional hazards models were constructed to estimate associations of prediagnosis obesity and postdiagnosis aspirin use with overall survival. Results: Of 656 patients included in this analysis, 280 (42.7%) were women, 135 (20.6%) were diagnosed with CRC before age 45 years, 414 (63.1%) were diagnosed between ages 45 and 65 years, and 107 (16.3%) were diagnosed at 65 years or older; 105 patients (16.0%) were Black or Hispanic, and 501 (76.4%) were non-Hispanic White. Controlling for age, sex, race, stage at initial diagnosis, and weight change between prediagnosis and survey date, patients with obesity in the decade prior to CRC diagnosis had significantly higher likelihood of death (hazard ratio, 1.45; 95% CI, 1.11-1.91) compared with those with normal prediagnosis body mass index. Furthermore, only patients with normal prediagnosis body mass index experienced significant survival benefit with postdiagnosis aspirin use (hazard ratio, 0.59; 95% CI, 0.39-0.90). Conclusions and Relevance: In this cross-sectional study, our findings suggest potentially differential tumor development in the long-term physiologic host environment of obesity. Confirmation and further evaluation are needed to determine whether prediagnosis body mass index may be used to estimate the benefit from postdiagnosis aspirin use.

Correction: Zhang et al. Association between Body Mass Index and Immune-Related Adverse Events (irAEs) among Advanced-Stage Cancer Patients Receiving Immune Checkpoint Inhibitors: A Pan-Cancer Analysis. Cancers 2021, 13, 6109.

Subha Madhavan (S.M.) and Anas Belouali (A.B.) were not included as authors in the published article [...].

Hyperammonemia in lung transplant patients and its management: a review.

Objective: To synthesize the evidence for incidence, pathophysiology, etiology, and protocol-based management of hyperammonemia in lung transplant patients. Background: Elevated ammonia levels are toxic to the brain, and hyperammonemia results in a potentially fatal complication for lung transplant recipients. The hallmark of this condition is ammonia production being way out of proportion to the degree of liver derangement. While there are many hypotheses, the cause remains obscure. Methods: A retrospective review of patients with hyperammonemia following lung transplantation was done to understand the pathophysiology, various treatment modalities, and its impact on patient mortality and morbidity. Studies in the English literature were identified through an electronic database search from PubMed/MEDLINE, Ovid Embase, Google Scholar, Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, Web of Science, and ClinicalTrials.gov until June 2020. No restriction of dates were used, and the search was up until June 2020. Discussion: Mortality among patients with hyperammonemia following lung transplantation is high. Multi-modal treatment approaches include avoiding nephrotoxic drugs, use of bowel decontamination, nitrogen scavengers, branched-chain amino acids, adjustment of immunosuppression, antibiotics like fluoroquinolones or azithromycin, and renal replacement therapy. However, there remains a scarcity of preoperative screening protocol for patients at risk of hyperammonemia as well evidence-based post-operative management guidelines. Intermittent hemodialysis, compared to continuous venovenous hemodialysis, provides better patient outcomes. Conclusion: Early detection of patients at risk by appropriate screening, along with maintaining a high degree of suspicion for hyperammonemia and multi-modal treatment approach, is the key to successful patient outcomes. Further prospective observational studies would facilitate development of protocol-based treatment of this potentially fatal condition.

Patients Recently Treated for B-lymphoid Malignancies Show Increased Risk of Severe COVID-19.

Patients with B-lymphoid malignancies have been consistently identified as a population at high risk of severe COVID-19. Whether this is exclusively due to cancer-related deficits in humoral and cellular immunity, or whether risk of severe COVID-19 is increased by anticancer therapy, is uncertain. Using data derived from the COVID-19 and Cancer Consortium (CCC19), we show that patients treated for B-lymphoid malignancies have an increased risk of severe COVID-19 compared with control populations of patients with non-B-lymphoid malignancies. Among patients with B-lymphoid malignancies, those who received anticancer therapy within 12 months of COVID-19 diagnosis experienced increased COVID-19 severity compared with patients with non-recently treated B-lymphoid malignancies, after adjustment for cancer status and several other prognostic factors. Our findings suggest that patients recently treated for a B-lymphoid malignancy are at uniquely high risk for severe COVID-19. SIGNIFICANCE: Our study suggests that recent therapy for a B-lymphoid malignancy is an independent risk factor for COVID-19 severity. These findings provide rationale to develop mitigation strategies targeted at the uniquely high-risk population of patients with recently treated B-lymphoid malignancies. This article is highlighted in the In This Issue feature, p. 171.

Coinfections in Patients With Cancer and COVID-19: A COVID-19 and Cancer Consortium (CCC19) Study.

BACKGROUND: The frequency of coinfections and their association with outcomes have not been adequately studied among patients with cancer and coronavirus disease 2019 (COVID-19), a high-risk group for coinfection. METHODS: We included adult (≥18 years) patients with active or prior hematologic or invasive solid malignancies and laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection, using data from the COVID-19 and Cancer Consortium (CCC19, NCT04354701). We captured coinfections within ±2 weeks from diagnosis of COVID-19, identified factors cross-sectionally associated with risk of coinfection, and quantified the association of coinfections with 30-day mortality. RESULTS: Among 8765 patients (hospitalized or not; median age, 65 years; 47.4% male), 16.6% developed coinfections: 12.1% bacterial, 2.1% viral, 0.9% fungal. An additional 6.4% only had clinical diagnosis of a coinfection. The adjusted risk of any coinfection was positively associated with age >50 years, male sex, cardiovascular, pulmonary, and renal comorbidities, diabetes, hematologic malignancy, multiple malignancies, Eastern Cooperative Oncology Group Performance Status, progressing cancer, recent cytotoxic chemotherapy, and baseline corticosteroids; the adjusted risk of superinfection was positively associated with tocilizumab administration. Among hospitalized patients, high neutrophil count and C-reactive protein were positively associated with bacterial coinfection risk, and high or low neutrophil count with fungal coinfection risk. Adjusted mortality rates were significantly higher among patients with bacterial (odds ratio [OR], 1.61; 95% CI, 1.33-1.95) and fungal (OR, 2.20; 95% CI, 1.28-3.76) coinfections. CONCLUSIONS: Viral and fungal coinfections are infrequent among patients with cancer and COVID-19, with the latter associated with very high mortality rates. Clinical and laboratory parameters can be used to guide early empiric antimicrobial therapy, which may improve clinical outcomes.

Breast biopsy patterns and findings among older women undergoing screening mammography: The role of age and comorbidity.

INTRODUCTION: Limited evidence exists on the impact of age and comorbidity on biopsy rates and findings among older women. MATERIALS AND METHODS: We used data from 170,657 women ages 66-94 enrolled in the United States Breast Cancer Surveillance Consortium (BCSC). We estimated one-year rates of biopsy by type (any, fine-needle aspiration (FNA), core or surgical) and yield of the most invasive biopsy finding (benign, ductal carcinoma in situ (DCIS) and invasive breast cancer) by age and comorbidity. Statistical significance was assessed using Wald statistics comparing coefficients estimated from logistic regression models adjusted for age, comorbidity, BCSC registry, and interaction between age and comorbidity. RESULTS: Of 524,860 screening mammograms, 9830 biopsies were performed following 7930 exams (1.5%) within one year, specifically 5589 core biopsies (1.1%), 3422 (0.7%) surgical biopsies and 819 FNAs (0.2%). Biopsy rates per 1000 screens decreased with age (66-74:15.7, 95%CI:14.8-16.8), 75-84:14.5(13.5-15.6), 85-94:13.2(11.3,15.4), ptrend < 0.001) and increased with Charlson Comorbidity Score (CCS = 0:14.4 (13.5-15.3), CCS = 1:16.6 (15.2-18.1), CCS ≥2:19.0 (16.9-21.5), ptrend < 0.001).Biopsy rates increased with CCS at ages 66-74 and 75-84 but not 85-94. Core and surgical biopsy rates increased with CCS at ages 66-74 only. For each biopsy type, the yield of invasive breast cancer increased with age irrespective of comorbidity. DISCUSSION: Women aged 66-84 with significant comorbidity in a breast cancer screening population had higher breast biopsy rates and similar rates of invasive breast cancer diagnosis than their counterparts with lower comorbidity. A considerable proportion of these diagnoses may represent overdiagnoses, given the high competing risk of death from non-breast-cancer causes among older women.

Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life Years for 29 Cancer Groups From 2010 to 2019: A Systematic Analysis for the Global Burden of Disease Study 2019.

IMPORTANCE: The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden. OBJECTIVE: To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019. EVIDENCE REVIEW: The GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite measure of educational attainment, income per capita, and total fertility rate for those younger than 25 years. Estimates include 95% uncertainty intervals (UIs). FINDINGS: In 2019, there were an estimated 23.6 million (95% UI, 22.2-24.9 million) new cancer cases (17.2 million when excluding nonmelanoma skin cancer) and 10.0 million (95% UI, 9.36-10.6 million) cancer deaths globally, with an estimated 250 million (235-264 million) DALYs due to cancer. Since 2010, these represented a 26.3% (95% UI, 20.3%-32.3%) increase in new cases, a 20.9% (95% UI, 14.2%-27.6%) increase in deaths, and a 16.0% (95% UI, 9.3%-22.8%) increase in DALYs. Among 22 groups of diseases and injuries in the GBD 2019 study, cancer was second only to cardiovascular diseases for the number of deaths, years of life lost, and DALYs globally in 2019. Cancer burden differed across SDI quintiles. The proportion of years lived with disability that contributed to DALYs increased with SDI, ranging from 1.4% (1.1%-1.8%) in the low SDI quintile to 5.7% (4.2%-7.1%) in the high SDI quintile. While the high SDI quintile had the highest number of new cases in 2019, the middle SDI quintile had the highest number of cancer deaths and DALYs. From 2010 to 2019, the largest percentage increase in the numbers of cases and deaths occurred in the low and low-middle SDI quintiles. CONCLUSIONS AND RELEVANCE: The results of this systematic analysis suggest that the global burden of cancer is substantial and growing, with burden differing by SDI. These results provide comprehensive and comparable estimates that can potentially inform efforts toward equitable cancer control around the world.

Mammography adherence in relation to function-related indicators in older women.

Prior studies of screening mammography patterns by functional status in older women show inconsistent results. We used Breast Cancer Surveillance Consortium-Medicare linked data (1999-2014) to investigate the association of functional limitations with adherence to screening mammography in 145,478 women aged 66-74 years. Functional limitation was represented by a claims-based function-related indicator (FRI) score which incorporated 16 items reflecting functional status. Baseline adherence was defined as mammography utilization 9-30 months after the index screening mammography. Longitudinal adherence was examined among women adherent at baseline and defined as time from the index mammography to end of the first 30-month gap in mammography. Multivariable logistic regression and Cox proportional hazards models were used to investigate baseline and longitudinal adherence, respectively. Subgroup analyses were conducted by age (66-70 vs. 71-74 years). Overall, 69.6% of participants had no substantial functional limitation (FRI score 0), 23.5% had some substantial limitations (FRI score 1), and 6.8% had serious limitations (FRI score ≥ 2). Mean age at baseline was 68.5 years (SD = 2.6), 85.3% of participants were white, and 77.1% were adherent to screening mammography at baseline. Women with a higher FRI score were more likely to be non-adherent at baseline (FRI ≥ 2 vs. 0: aOR = 1.13, 95% CI = 1.06, 1.20, p-trend < 0.01). Similarly, a higher FRI score was associated with longitudinal non-adherence (FRI ≥ 2 vs. 0: aHR = 1.16, 95% CI = 1.11, 1.22, p-trend < 0.01). Effect measures of FRI did not differ substantially by age categories. Older women with a higher burden of functional limitations are less likely to be adherent to screening mammography recommendations.

Association of Childhood Socioeconomic Status with Leukocyte Telomere Length Among African Americans and the Mediating Role of Behavioral and Psychosocial Factors: Results from the GENE-FORECAST Study.

PURPOSE: We examined if childhood socioeconomic status (SES) was related to adult leucocyte telomere length (TL) using the data of 361 African American (AA) participants from the GENE-FORECAST Study. We also assessed the mediating role of behavioral and psychosocial factors in the association between childhood SES and adult TL. METHODS: Childhood SES was assessed individually by using participant's mother's education and occupation, father's education and occupation, parental home ownership, and family structure. TL was assessed using the quantitative polymerase chain reaction method. Information on potential confounders and mediators were collected. The associations of childhood SES with TL were assessed using multivariable linear regression models. We used path analysis to quantify and test the share of these associations that was statistically explained by each of the mediators (participant's educational attainment, smoking status, physical activity, dietary habit, perceived stress, and depressive symptoms). RESULTS: Mother's education was associated with longer average TL (ß: 0.021; 95% CI: 0.001, 0.04, p=0.038) in confounder adjusted models. Once mediators were introduced in the model, the estimates were reduced and remained marginally significant (ß: 0.017; 95% CI: -0.003, 0.038, p=0.061). According to path model, approximately 19% of the effect of mother's education on TL (ß: 0.004; 95% CI: -0.001, 0.01, p < 0.10) was mediated through participant's own education level. No significant mediation effect was observed for any other mediators. CONCLUSIONS: These data provide evidence that participant's mother's education was positively linked to adult TL in AA population. Participant's own educational level partially explained this association.

Cost-Effectiveness of Screening Mammography Beyond Age 75 Years : A Cost-Effectiveness Analysis.

BACKGROUND: The cost-effectiveness of screening mammography beyond age 75 years remains unclear. OBJECTIVE: To estimate benefits, harms, and cost-effectiveness of extending mammography to age 80, 85, or 90 years according to comorbidity burden. DESIGN: Markov microsimulation model. DATA SOURCES: SEER (Surveillance, Epidemiology, and End Results) program and Breast Cancer Surveillance Consortium. TARGET POPULATION: U.S. women aged 65 to 90 years in groups defined by Charlson comorbidity score (CCS). TIME HORIZON: Lifetime. PERSPECTIVE: National health payer. INTERVENTION: Screening mammography to age 75, 80, 85, or 90 years. OUTCOME MEASURES: Breast cancer death, survival, and costs. RESULTS OF BASE-CASE ANALYSIS: Extending biennial mammography from age 75 to 80 years averted 1.7, 1.4, and 1.0 breast cancer deaths and increased days of life gained by 5.8, 4.2, and 2.7 days per 1000 women for comorbidity scores of 0, 1, and 2, respectively. Annual mammography beyond age 75 years was not cost-effective, but extending biennial mammography to age 80 years was ($54 000, $65 000, and $85 000 per quality-adjusted life-year [QALY] gained for women with CCSs of 0, 1, and ≥2, respectively). Overdiagnosis cases were double the number of deaths averted from breast cancer. RESULTS OF SENSITIVITY ANALYSIS: Costs per QALY gained were sensitive to changes in invasive cancer incidence and shift of breast cancer stage with screening mammography. LIMITATION: No randomized controlled trials of screening mammography beyond age 75 years are available to provide model parameter inputs. CONCLUSION: Although annual mammography is not cost-effective, biennial screening mammography to age 80 years is; however, the absolute number of deaths averted is small, especially for women with comorbidities. Women considering screening beyond age 75 years should weigh the potential harms of overdiagnosis versus the potential benefit of averting death from breast cancer. PRIMARY FUNDING SOURCE: National Cancer Institute and National Institutes of Health.

Findings of living donation experiences shared on a digital storytelling platform: A thematic analysis.

Objectives: To identify common experiences and emotional changes shared by living donors and kidney recipients about their living donation experiences on a digital storytelling platform. Methods: 82 donors and 36 recipients submitted prompt-guided videos to the platform. Two coders analyzed transcripts for motivations, common themes, and emotions expressed. Results: Storytellers shared their stories to advocate for living donation and contribute to others facing similar challenges. Pre-surgery, recipients recalled their dialysis experiences and how they sought living donors while donors discussed their motivations and common fears. Post-surgery, recipients discussed changes in their relationship with the donor and quality life, while donors described how they benefited. Learning they needed a transplant, recipients reported feeling fear (33.3%) while donors felt sadness (48.8%). Post-transplant, recipients and donors reported feeling happiness (85.4%, 38.9%) and relief (29.3%, 22.2%). Conclusion: Online digital storytelling libraries increase access to real-life living donation experiences. Since stories are highly personal, additional living donor kidney transplant risk-benefit education is needed. Innovation: Stories can supplement traditional education and be incorporated into advocacy efforts; campaigns could capitalize upon the personal aspect of stories to gently introduce and encourage living kidney donation among the general public.

Celecoxib Colorectal Bioavailability and Chemopreventive Response in Patients with Familial Adenomatous Polyposis.

Why celecoxib exerts chemopreventive activity in only some familial adenomatous polyposis (FAP) patients remains poorly understood. We conducted a phase II clinical study to identify potential predictive biomarkers for celecoxib chemopreventive activity in FAP. Twenty-seven patients with FAP completed a 6-month oral course of 400 mg of celecoxib twice a day; they underwent colonoscopies before and after celecoxib treatment to assess colorectal polyp tumor burden and to obtain normal and polyp colorectal biopsies to measure celecoxib, 13-S-hydroxyoctadecadienoic acid (13-HODE), 15-HETE, 12-HETE, and LTB4 levels by LC/MS-MS. Celecoxib levels in sera from those patients were also measured before treatment and after 2, 4, and 6 months of treatment. Nineteen of the 27 patients experienced a response to celecoxib, with a ≥ 28% reduction of colonic polyp burden on the basis of a reproducible quantitative assessment of colonoscopy results. Celecoxib levels were significantly lower in polyp tissues than in normal colorectal tissues. Celecoxib levels in sera and normal colorectal tissues were correlated in patients who experienced a response to celecoxib but not in those who did not. Among the measured lipoxygenase products, only 13-HODE levels were significantly lower in polyp tissues than in normal tissues. Our findings demonstrate the differential bioavailability of celecoxib between normal and polyp tissues and its potential effects on clinical response in patients with FAP. PREVENTION RELEVANCE: This study evaluated potential predictive biomarkers for celecoxib chemopreventive activity in patients with FAP. Our findings demonstrated the differential bioavailability of celecoxib between normal and polyp tissues and its potential effects on clinical chemopreventive response in patients with FAP. See related Spotlight, p. 205.

Low-dose CT lung cancer screening uptake: A rural-urban comparison.

PURPOSE: The US Preventive Services Task Force recommends lung cancer screening with Low-Dose Computed Tomography (LDCT) in high-risk individuals. Our objective was to identify demographic, health, and financial factors associated with screening uptake, with a focus on urban-rural differences. METHODS: We analyzed data from the 2018 and 2019 Behavioral Risk Factor Surveillance System and its optional Lung Cancer Screening Module to examine factors associated with screening uptake among 20 states that administered the optional module. We compared differences in factors associated with uptake overall and by geographical regions and conducted multivariable logistic mixed-effects regression, accounting for participant clustering by state to assess the impact of these factors on uptake. FINDINGS: Overall 1,268 participants underwent LDCT screening with no significant differences observed between rural (16.3%) and urban residents (17.7%, p = 0.67). In multivariable models, rural residents did not differ significantly in their LDCT screening uptake (OR = 0.85; 95% CI: 0.67-1.09, p = 0.20), but uptake was significantly higher for participants with underlying chronic respiratory conditions, veterans, those with higher pack-year history, and those with poor/fair general health and prior history of cancer. Uptake declined with age, higher education level, concerns about paying for medical care, and lack of primary care. CONCLUSIONS: Modifiable targets can be leveraged to increase LDCT screening. Based on significant predictors of screening uptake, clinicians should prioritize interventions that effectively consider smoking history as well as those identified as effective in veterans' health settings. Additionally, reducing structural barriers to care related to insurance and income will be key to reducing disparities.

Racial/ethnic disparities in use of surveillance mammogram among breast cancer survivors: a systematic review.

BACKGROUND: Increasing number of breast cancer survivors in the USA have led to greater focus on the long-term health outcomes and surveillance care among these women. However limited evidence exists of use of surveillance mammography among breast cancer survivors and how it varies across racial/ethnic groups. METHODS: We conducted a systematic review of the literature to explore disparities in use of surveillance mammogram among women breast cancer survivors by searching for relevant studies published between 2000 and 2020 from Medline (Ovid), PubMed (National Library of Medicine), and PsycINFO (Ovid) bibliographic databases. Two authors independently screened titles, abstracts, and full texts of all articles that reported surveillance mammography use across racial/ethnic groups. Data on study design, screening eligibility, sample size, operational definition, and/or measure of the use of a surveillance mammogram among breast cancer survivors and the association between race/ethnicity and use of a surveillance mammogram were summarized in the evidence tables. RESULTS: We identified 1544 records from the three databases, and 30 studies examined the use of surveillance mammograms among breast cancer survivors across race/ethnic groups. Of these, 21 provided adjusted estimates of racial/ethnic disparities in use of surveillance mammograms, and 15 of these reported statistically significant disparities. In summary, most studies reported that non-white women (mainly Blacks and Hispanics) were less likely to receive a timely surveillance mammogram compared to White. CONCLUSION: This study extends the evidence of racial/ethnic disparities beyond completion of initial treatment by finding similar disparities in receipt of surveillance mammograms among breast cancer survivors. IMPLICATION FOR CANCER SURVIVORS: Our findings identify a need to improve efforts to increase post-treatment use of surveillance mammography among racial/ethnic minority women to reduce these gaps and improve overall clinical and quality of life outcomes.

Association between Body Mass Index and Immune-Related Adverse Events (irAEs) among Advanced-Stage Cancer Patients Receiving Immune Checkpoint Inhibitors: A Pan-Cancer Analysis.

Evidence regarding the association between body mass index (BMI) and immune-related adverse events (irAEs) among cancer patients receiving immune checkpoint inhibitors (ICIs) is limited. Here, we use cross-sectional hospital-based data to explore their relationship. Pre-treatment BMI was treated as an ordinal variable (<25, 25 to ≤30, ≥30 kg/m2). The outcome of interest was irAEs after ICI initiation. A multivariable logistic regression model estimated the adjusted odds ratio (aOR) and 95% confidence interval (CI) of BMI. A total of 684 patients with stage III or IV cancer were included in the study (lung: 269, melanoma: 204, other: 211). The mean age at the first dose of ICI was 64.1 years (SD = 13.5), 394 patients (57.6%) were male, and over one-third (N = 260, 38.0%) were non-White. Overall, 52.9% of patients had BMI ≥ 25 kg/m2 (25 to ≤30: 217, ≥30: 145) and 288 (42.1%) had irAEs after ICI treatment. Patients with higher BMI tended to have a higher rate of irAEs (<25: 35.7%, 25 to ≤30: 47.0%, ≥30: 49.0%). The multivariable logistic regression yielded consistent results (BMI ≥ 30 vs. BMI < 25: aOR = 1.47, 95% CI = 0.96-2.23; 25 ≤ BMI < 30 vs. BMI < 25: aOR = 1.46, 95% CI = 1.02-2.11, p-trend = 0.04). In conclusion, among patients with advanced cancer receiving ICIs, the rate of irAEs appears to be higher among those with higher BMI.

Engaging Patients with Late-Stage Non-Small Cell Lung Cancer in Shared Decision Making about Treatment.

Few treatment decision support interventions (DSIs) are available to engage patients diagnosed with late-stage non-small cell lung cancer (NSCLC) in treatment shared decision making (SDM). We designed a novel DSI that includes care plan cards and a companion patient preference clarification tool to assist in shared decision making. The cards answer common patient questions about treatment options (chemotherapy, chemotherapy plus immunotherapy, targeted therapy, immunotherapy, clinical trial participation, and supportive care). The form elicits patient treatment preference. We then conducted interviews with clinicians and patients to obtain feedback on the DSI. We also trained oncology nurse educators to implement the prototype. Finally, we pilot tested the DSI among five patients with NSCLC at the beginning of an office visit scheduled to discuss treatment with an oncologist. Analyses of pilot study baseline and exit survey data showed that DSI use was associated with increased patient awareness of the alternatives' treatment options and benefits/risks. In contrast, patient concern about treatment costs and uncertainty in treatment decision making decreased. All patients expressed a treatment preference. Future randomized controlled trials are needed to assess DSI implementation feasibility and efficacy in clinical care.

Association of Breast Density With Breast Cancer Risk Among Women Aged 65 Years or Older by Age Group and Body Mass Index.

Importance: Breast density is associated with breast cancer risk in women aged 40 to 65 years, but there is limited evidence of its association with risk of breast cancer among women aged 65 years or older. Objective: To compare the association between breast density and risk of invasive breast cancer among women aged 65 to 74 years vs women aged 75 years or older and to evaluate whether the association is modified by body mass index (BMI). Design, Setting, and Participants: This prospective cohort study used data from the Breast Cancer Surveillance Consortium from January 1, 1996, to December 31, 2012, for US women aged 65 years or older who underwent screening mammography. Data were analyzed from January 1, 2018, to December 31, 2020. Exposures: Breast Imaging Reporting and Data System breast density category, age, and BMI. Main Outcomes and Measures: The 5-year cumulative incidence of invasive breast cancer by level of breast density (almost entirely fat, scattered fibroglandular densities, or heterogeneous or extreme density) and age (65-74 vs ≥75 years) was calculated using weighted means. Cox proportional hazards models were fit to estimate the association of breast density with invasive breast cancer risk. The likelihood ratio test was used to test the interaction between BMI and breast density. Results: A total of 221 714 screening mammograms from 193 787 women were included in the study; a total of 38% of the study population was aged 75 years or older. Of the mammograms, most were from women aged 65 to 74 years (64.6%) and non-Hispanic White individuals (81.4%). The 5-year cumulative incidence of invasive breast cancer increased in association with increasing breast density among women aged 65 to 74 years (almost entirely fatty breasts: 11.3 per 1000 women [95% CI, 10.4-12.5 per 1000 women]; scattered fibroglandular densities: 17.2 per 1000 women [95% CI, 16.1-17.9 per 1000 women]; extremely or heterogeneously dense breasts: 23.7 per 1000 women [95% CI, 22.4-25.3 per 1000 women]) and among those aged 75 years or older (fatty breasts: 13.5 per 1000 women [95% CI, 11.6-15.5]; scattered fibroglandular densities: 18.4 per 1000 women [95% CI, 17.0-19.5 per 1000 women]; extremely or heterogeneously dense breasts: 22.5 per 1000 women [95% CI, 20.2-24.2 per 1000 women]). Extreme or heterogeneous breast density was associated with increased risk of breast cancer compared with scattered fibroglandular breast density in both age categories (65-74 years: hazard ratio [HR], 1.39 [95% CI, 1.28-1.50]; ≥75 years: HR, 1.23 [95% CI, 1.10-1.37]). Women with almost entirely fatty breasts had a decrease of approximately 30% (range, 27%-34%) in the risk of invasive breast cancer compared with women with scattered fibroglandular breast density (65-74 years: HR, 0.66 [95% CI, 0.58-0.75]; ≥75 years: HR, 0.73; 95% CI, 0.62-0.86). Associations between breast density and breast cancer risk were not significantly modified by BMI (for age 65-74 years: likelihood ratio test, 2.67; df, 2; P = .26; for age ≥75 years, 2.06; df, 2; P = .36). Conclusions and Relevance: The findings suggest that breast density is associated with increased risk of invasive breast cancer among women aged 65 years or older. Breast density and life expectancy should be considered together when discussing the potential benefits vs harms of continued screening mammography in this population.