Revisiting Exclusion of Prior Cancer in Clinical Trials of Male Breast Cancer

Background: Eligibility criteria for cancer clinical trials present challenges to enrollment. Many trials exclude patients with a prior cancer. This common practice may be especially detrimental to trials of rare cancers, such as male breast cancer, that struggle to accrue adequate numbers of participants. Objectives: to estimate prevalence of prior cancer among men newly diagnosed with breast cancer and describe characteristics of men with prior cancer compared to those without. Methods: We identified men diagnosed with breast cancer between 2011-2015 using population-based data from National Cancer Institute\u27s Surveillance, Epidemiology, and End Results program of cancer registries. We used sequence number and diagnosis year to identify cancers diagnosed prior to breast cancer (inclusive of prior breast, different, and unknown types of cancer). We compared sociodemographic, tumor, and treatment characteristics of men with and without prior cancer using chi-square tests. Results: Among 2317 men, nearly one quarter (24.3%) had any prior cancer, and the majority (58.7%) of these were of a different cancer type. A higher proportion of men with a prior cancer of a different type were older, had smaller (≤ 2 cm) breast tumors, were diagnosed with stage 0-1 breast cancer, and did not receive surgery compared to men without any prior cancer; there were no statistically significant differences by race and ethnicity, county median income, hormone receptor status, or surgery type. Conclusion: Given prevalence of prior cancer in this rare and understudied population of men diagnosed with breast cancer, including men with prior cancer in clinical trials may improve accrual

Birth Cohort Colorectal Cancer (Crc): Implications For Research and Practice

Colorectal cancer (CRC) epidemiology is changing due to a birth cohort effect, first recognized by increasing incidence of early onset CRC (EOCRC, age \u3c50 \u3eyears). In this paper, we define birth cohort CRC as the observed phenomenon, among individuals born 1960 and later, of increasing CRC risk across successive birth cohorts, rising EOCRC incidence, increasing incidence among individuals aged 50 to 54 years, and flattening of prior decreasing incidence among individuals aged 55 to 74 years. We demonstrate birth cohort CRC is associated with unique features, including increasing rectal cancer (greater than colon) and distant (greater than local) stage CRC diagnosis, and increasing EOCRC across all racial/ethnic groups. We review potential risk factors, etiologies, and mechanisms for birth cohort CRC, using EOCRC as a starting point and describing importance of viewing these through the lens of birth cohort. We also outline implications of birth cohort CRC for epidemiologic and translational research, as well as current clinical practice. We postulate that recognition of birth cohort CRC as an entity-including and extending beyond rising EOCRC-can advance understanding of risk factors, etiologies, and mechanisms, and address the public health consequences of changing CRC epidemiology

Potential Impact of Revised Nci Eligibility Criteria Guidance: Prior Malignancy Exclusion in Breast Cancer Clinical Trials

BACKGROUND: Many individuals with cancer have survived a prior cancer and for this reason may have been excluded from clinical trials. Recent NCI guidance recommends including these individuals, especially when the risk of the prior malignancy interfering with either safety or efficacy endpoints is very low. Using breast cancer as an example, we determined the potential effect this policy change may have on clinical trial accrual. PATIENTS AND METHODS: We reviewed protocols of NCI-sponsored breast cancer clinical trials activated in 1991 through 2016. We quantified prevalence of prior cancer-related exclusion criteria and assessed the association with trial characteristics using Fisher\u27s exact tests. Using SEER data, we estimated the prevalence and timing of prior primary (nonbreast) cancer diagnoses among patients with breast cancer. RESULTS: Among 87 clinical trials (total target enrollment, 137,253 patients), 77% excluded individuals with prior cancer, most commonly (79%) within the preceding 5 years. Among trials with radiographic response or toxicity endpoints, 69% excluded prior cancer. In SEER data, the prevalence of a prior (nonbreast) cancer diagnosis ranged from 5.7% to 7.7%, depending on breast cancer stage, of which 39% occurred within 5 years of the incident breast cancer. For trials excluding prior cancer, the estimated proportion of patients excluded for this reason ranged from 1.3% to 5.8%, with the estimated number of excluded patients ranging from 1 to 288. CONCLUSIONS: More than three-fourths of NCI-sponsored breast cancer clinical trials exclude patients with prior cancer, including almost 70% of trials with response or toxicity endpoints. Given that \u3e5% of patients with breast cancer have a history of prior cancer, in large phase III trials this practice may exclude hundreds of patients. Following recent NCI eligibility guidance, the inclusion of patients with prior cancer on breast cancer trials may have a meaningful impact on accrual

Association of Social Risk Factors With Mortality among Us adults With a New Cancer Diagnosis

This cohort study examines the associations of multiple social risk factors with mortality risk among patients newly diagnosed with cancer in the US

An age-period-cohort analysis of obesity and incident esophageal adenocarcinoma among white males

The incidence of esophageal adenocarcinoma (EAC) has increased in recent decades. Increases in incidence have been attributed to changes in the prevalence of risk factors for EAC; however, the extent to which these changes explain increases in EAC incidence has not been studied in detail. We used age-period-cohort analysis to estimate changes in the incidence of EAC among white males by age, time period, and birth cohort. Incidence rates per 100,000 individuals were analyzed from 1973 to 2012. Hierarchical Poisson models were used to estimate age, period, and cohort effects, whereby age-specific incidence rates were nested within periods and cohorts. The prevalence of obesity for each time period and birth cohort was included in the model as a fixed-effect. Incidence increased with advancing age (β = 0.12, P <0.01). There were significant period and birth cohort effects, although the period effect was much larger than the cohort effect. The period effect decreased dramatically when obesity was included as a fixed effect, while the small cohort effect remained unchanged. Results suggest much of the increase in the incidence of EAC can be attributed to a period effect, which may be due to changes in the prevalence of obesity over time

Persistent Disparities in Colorectal Cancer Screening: a Tell-Tale Sign For Implementing New Guidelines in Younger adults

BACKGROUND: In May 2021, the U.S. Preventive Services Task Force began recommending initiating colorectal cancer screening at age 45 (vs. 50) years. METHODS: We estimated prevalence of colorectal cancer screening (by colonoscopy, sigmoidoscopy, CT colonography, or stool-based tests) in adults ages 50 to 75 years using data from the National Health Interview Survey in 2000, 2003, 2005, 2008, 2010, 2013, 2015, and 2018. For each survey year, we estimated prevalence by age, race/ethnicity, educational attainment, family income, and health insurance. We also compared increases in prevalence of screening from 2000 to 2018 in 5-year age groups (50-54, 55-59, 60-64, 65-69, and 70-75 years). RESULTS: Overall, prevalence of colorectal cancer screening increased from 36.7% in 2000 to 66.1% in 2018. Screening prevalence in 2018 was lowest for age 50 to 54 years (47.6%), Hispanics (56.5%), Asians (57.1%), and participants with less than a high school degree (53.6%), from low-income families (56.6%), or without insurance (39.7%). Increases in prevalence over time differed by five-year age group. For example, prevalence increased from 28.2% in 2000 to 47.6% in 2018 (+19.4%; 95% CI, 13.1-25.6) for age 50 to 54 years but from 46.4% to 78.0% (+31.6%; 95% CI, 25.4%-37.7%) for age 70 to 75 years. This pattern was consistent across race/ethnicity, educational attainment, family income, and health insurance. CONCLUSIONS: Prevalence of colorectal cancer screening remains low in adults ages 50 to 54 years. IMPACT: As new guidelines are implemented, care must be taken to ensure screening benefits are realized equally by all population groups, particularly newly eligible adults ages 45 to 49 years. See related commentary by Brawley, p. 1671

in Utero Exposure to antiemetic and Risk of adult-Onset Colorectal Cancer

BACKGROUND: Incidence rates of colorectal cancer (CRC) are increasing among adults born in and after the 1960s, implicating pregnancy-related exposures introduced at that time as risk factors. Dicyclomine, an antispasmodic used to treat irritable bowel syndrome, was initially included in Bendectin (comprising doxylamine, pyridoxine, and dicyclomine), an antiemetic prescribed during pregnancy in the 1960s. METHODS: We estimated the association between in utero exposure to Bendectin and risk of CRC in offspring of the Child Health and Development Studies, a multigenerational cohort that enrolled pregnant women in Oakland, CA, between 1959 and 1966 (n = 14 507 mothers and 18 751 liveborn offspring). We reviewed prescribed medications from mothers\u27 medical records to identify those who received Bendectin during pregnancy. Diagnoses of CRC in adult (aged ≥18 years) offspring were ascertained by linkage with the California Cancer Registry. Cox proportional hazards models were used to estimate adjusted hazard ratios, with follow-up accrued from birth through cancer diagnosis, death, or last contact. RESULTS: Approximately 5% of offspring (n = 1014) were exposed in utero to Bendectin. Risk of CRC was higher in offspring exposed in utero (adjusted hazard ratio = 3.38, 95% confidence interval [CI] = 1.69 to 6.77) compared with unexposed offspring. Incidence rates of CRC were 30.8 (95% CI = 15.9 to 53.7) and 10.1 (95% CI = 7.9 to 12.8) per 100 000 in offspring exposed to Bendectin and unexposed, respectively. CONCLUSIONS: Higher risk of CRC in offspring exposed in utero may be driven by dicyclomine contained in the 3-part formulation of Bendectin used during the 1960s. Experimental studies are needed to clarify these findings and identify mechanisms of risk

Underuse and Overuse of Colonoscopy for Repeat Screening and Surveillance in the Veterans Health Administration

Regular screening with colonoscopy lowers colorectal cancer incidence and mortality. We aimed to determine patterns of repeat and surveillance colonoscopy and identify factors associated with over- and underuse of colonoscopy

Time to Endoscopy or Colonoscopy among adults Younger Than 50 Years With Iron-Deficiency anemia and/or Hematochezia in the Vha

IMPORTANCE: to date, the diagnostic test completion rate and the time to diagnostic endoscopy or colonoscopy among adults with iron-deficiency anemia (IDA) and/or hematochezia have not been well characterized. OBJECTIVE: to evaluate the diagnostic test completion rate and the time to diagnostic testing among veterans younger than 50 years with IDA and/or hematochezia. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted within the Veterans Health Administration between October 1, 1999, and December 31, 2019, among US veterans aged 18 to 49 years from 2 separate cohorts: those with a diagnosis of IDA (n = 59 169) and those with a diagnosis of hematochezia (n = 189 185). Statistical analysis was conducted from August 2021 to August 2023. EXPOSURES: Diagnostic testing factors included age, sex, race and ethnicity, Veterans Health Administration geographic region, and hemoglobin test value (IDA cohort only). MAIN OUTCOMES AND MEASURES: Primary outcomes of diagnostic testing were (1) bidirectional endoscopy after diagnosis of IDA and (2) colonoscopy or sigmoidoscopy after diagnosis of hematochezia. The association between diagnostic testing factors and diagnostic test completion was examined using Poisson models. RESULTS: There were 59 169 veterans with a diagnosis of IDA (mean [SD] age, 40.7 [7.1] years; 30 502 men [51.6%]), 189 185 veterans with a diagnosis of hematochezia (mean [SD] age, 39.4 [7.6] years; 163 690 men [86.5%]), and 2287 veterans with IDA and hematochezia (mean [SD] age, 41.6 [6.9] years; 1856 men [81.2%]). The cumulative 2-year diagnostic workup completion rate was 22% (95% CI, 22%-22%) among veterans with IDA and 40% (95% CI, 40%-40%) among veterans with hematochezia. Veterans with IDA were mostly aged 40 to 49 years (37 719 [63.7%]) and disproportionately Black (24 480 [41.4%]). Women with IDA (rate ratio [RR], 0.42; 95% CI, 0.40-0.43) had a lower likelihood of diagnostic test completion compared with men with IDA. Black (RR, 0.65; 95% CI, 0.62-0.68) and Hispanic (RR, 0.88; 95% CI, 0.82-0.94) veterans with IDA were less likely to receive diagnostic testing compared with White veterans with IDA. Veterans with hematochezia were mostly White (105 341 [55.7%]). Among veterans with hematochezia, those aged 30 to 49 years were more likely to receive diagnostic testing than adults younger than 30 years of age (age 30-39 years: RR, 1.15; 95% CI, 1.12-1.18; age 40-49 years: RR, 1.36; 95% CI, 1.33-1.40). Hispanic veterans with hematochezia were less likely to receive diagnostic testing compared with White veterans with hematochezia (RR, 0.96; 95% CI, 0.93-0.98). CONCLUSIONS AND RELEVANCE: In the cohorts of veterans younger than 50 years with IDA and/or hematochezia, the diagnostic test completion rate was low. Follow-up was less likely among female, Black, and Hispanic veterans with IDA and Hispanic veterans with hematochezia. Optimizing timely follow-up across social and demographic groups may contribute to improving colorectal cancer outcomes and mitigate disparities