Young-Onset Colorectal Cancer: Earlier Diagnoses or Increasing Disease Burden?

Colorectal cancer (CRC) incidence and mortality in the United States have changed strikingly in recent decades. Overall, CRC incidence decreased by >30% from 1975 (59.5 per 100,000) to 2013 (37.9 per 100,000). CRC mortality similarly declined from 28.1 per 100,000 in 1975 to 14.5 per 100,000 in 2013—nearly a 50% decrease.1 Screen-eligible populations, particularly those over age 65, have experienced the largest declines in incidence and mortality

No Increase in Risk of Acute Myocardial Infarction in Privately Insured Adults Prescribed Proton Pump Inhibitors vs Histamine-2 Receptor Antagonists (2002–2014)

Background & Aims: Proton pump inhibitors (PPIs) are commonly used medications. Recent studies reported an increased risk of acute myocardial infarction (MI) in PPI users vs non-users. We evaluated MI risk associated with PPIs compared with histamine-2 receptor antagonists (H2RAs) in privately insured adults in the United States. Methods: Using administrative claims from commercial and Medicare Supplemental plans (2001–2014), we compared risk of MI in patients who started a new prescription for PPIs vs H2RAs. Enrollees were followed from their first prescription until MI, medication discontinuation, plan disenrollment, or December 31, 2014. MI was defined using hospital diagnosis codes. Risk differences (RD), risk ratios, and 95% confidence intervals (CIs) were estimated using Kaplan-Meier methods at 3, 12, and 36 months after treatment initiation. Standardized morbidity ratio weights were used to control measured confounding. Analyses were stratified by plan type (commercial vs Medicare Supplemental). Results: We identified more than 5 million new users of prescription PPIs and H2RAs. Median follow-up time was 60 days for patients with commercial insurance and 96 days in patients with Medicare Supplemental insurance. The 12-month weighted risk of MI was low overall (approximately 2 cases per 1000 among patients in commercial plans; 8 per 1000 among patients in Medicare Supplemental plans). In the RD analysis, we found no significant differences in MI risk between patients who started PPIs vs H2RAs for the first 12 months, either in the commercial population (weighted RD per 1000, –0.08; 95% CI, –0.51 to 0.36) or the Medicare Supplemental population (weighted RD per 1000, –0.45; 95% CI, –1.53 to 0.58). Conclusion: In an analysis of administrative claims from commercial and Medicare Supplemental plans, we found no evidence that prescription PPIs increase risk of MI compared with prescription H2RAs. Physicians and patients should not avoid starting a PPI because of concerns related to MI risk

Patterns of Sociodemographic and Clinicopathologic Characteristics of Stages II and III Colorectal Cancer Patients by Age: Examining Potential Mechanisms of Young-Onset Disease

Background and Aims. As a first step toward understanding the increasing incidence of colorectal cancer (CRC) in younger (age < 50) populations, we examined demographic, clinicopathologic, and socioeconomic characteristics and treatment receipt in a population-based sample of patients newly diagnosed with stages II and III CRC. Methods. Patients were sampled from the National Cancer Institute's Patterns of Care studies in 1990/91, 1995, 2000, 2005, and 2010 (n=6,862). Tumor characteristics and treatment data were obtained through medical record review and physician verification. We compared sociodemographic and clinicopathologic characteristics and treatment patterns of younger (age < 50) and older (age 50-69, age ≥ 70) CRC patients. Results. Younger patients were more likely to be black (13%) and Hispanic (15%) than patients aged 50-69 years (11% and 10%, resp.) and ≥70 years (7% each). A larger proportion of young white (41%) and Hispanic (33%) patients had rectal tumors, whereas tumors in the right colon were the most common in young black patients (39%). The majority of younger patients received chemotherapy and radiation therapy, although receipt of microsatellite instability testing was suboptimal (27%). Conclusion. Characteristics of patients diagnosed with young-onset CRC differ considerably by race/ethnicity, with a higher proportion of black and Hispanic patients diagnosed at the age of < 50 years

Propensity score methods to control for confounding in observational cohort studies: a statistical primer and application to endoscopy research

Background and Aims: Confounding is a major concern in nonexperimental studies of endoscopic interventions and can lead to biased estimates of the effects of treatment. Propensity score methods, which are commonly used in the pharmacoepidemiology literature, can effectively control for baseline confounding by balancing measured baseline confounders and risk factors and creating comparable populations of treated and untreated patients. Methods: We propose the following 5-step checklist to guide the use and evaluation of propensity score methods: (1) select covariates, (2) assess “Table 1” balance in risk factors before propensity score implementation, (3) estimate and implement the propensity score in the study cohort, (4) reassess “Table 1” balance in risk factors after propensity score implementation, and (5) critically evaluate differences between matched and unmatched patients after propensity score implementation. We then applied this checklist to an endoscopy example using a study cohort of 411 adults with newly diagnosed eosinophilic esophagitis (EoE), some of whom were treated with esophageal dilation. Results: We identified 156 patients, aged 18 and older, who were treated with esophageal dilation, and 255 patients who were nondilated. We successfully matched 148 (95%) dilated patients to nondilated patients who had a propensity score within 0.1, based on patient age, sex, race, self-reported food allergy, and presence of narrowing at baseline endoscopy. Crude imbalances were observed before propensity score matching in several baseline covariates, including age, sex, and narrowing; however, propensity score matching was successful in achieving balance across all measured covariates. Conclusions: We provide an introduction to propensity score methods, including a straightforward checklist for implementing propensity score methods in nonexperimental studies of treatment effectiveness. Moreover, we demonstrate the advantage of using “Table 1” as a simple but effective diagnostic tool for evaluating the success of propensity score methods in an applied example of esophageal dilation in EoE

Patterns of care amongst older adults diagnosed with locally advanced esophageal cancer: A cohort study

Introduction: Since the early 2010s, neoadjuvant chemoradiation followed by esophagectomy (trimodal therapy) has been a recommended treatment for patients diagnosed with locally advanced esophageal cancer. However, it may also add treatment-related toxicity, particularly for older adults with significant comorbidity and frailty burdens. We examined contemporary patterns of care in older adults, which have not been well characterized. Materials and Methods: We used the Surveillance Epidemiology and End Results-Medicare database to identify a cohort of US adults aged 66 years and older diagnosed with incident locally advanced esophageal cancer between 2004 and 2017. Calendar year age-standardized percentages of treatment receipt were calculated. Joinpoint regression was used to detect temporal trends in treatment receipt. Descriptive associations between patient factors and treatment were assessed. Trend analyses quantified how the percentage of trimodal and definitive chemoradiation (no surgery) patients receiving cisplatin-based, carboplatin-based, and other chemotherapy regimens evolved over time. Results: In total, 4332 adults aged ≥66 years with locally advanced esophageal cancer were included. The age-standardized percentage of patients receiving trimodal therapy increased from 16.7% in 2004 to 26.1% in 2017 (annual percent change = 3.5%; 95% confidence interval [CI], 0.7%–6.4%) in adenocarcinomas and from 7.3% in 2004 to 9.1% in 2017 (annual percent change = 0.4%; 95% CI, −4.1%–5.1%) in squamous cell carcinomas. By 2017, definitive chemoradiation became the most frequently used treatment modality for adenocarcinomas (49.8%; 95% CI, 43.5–56.0) and squamous cell carcinomas (59.5%; 95% CI, 50.8–68.2). Patients with higher comorbidity and frailty burdens were less likely to be treated with trimodal therapy. Amongst patients receiving chemoradiation as part of their treatment, a large and swift channeling away from cisplatin and towards carboplatin-based regimens was observed. Discussion: In practice, definitive chemoradiation is the most commonly received treatment by older adults with locally advanced esophageal cancer. Four out of five older adults do not receive trimodal therapy, some of whom are potentially undertreated

Trimodality Therapy vs Definitive Chemoradiation in Older Adults With Locally Advanced Esophageal Cancer

Background: The comparative effectiveness of trimodality therapy vs definitive chemoradiation for treating locally advanced esophageal cancer in older adults is uncertain. Existing trials lack generalizability to older adults, a population with heightened frailty. We sought to emulate a hypothetical trial comparing these treatments using real-world data. Methods: A cohort of adults aged 66-79 years diagnosed with locally advanced esophageal cancer between 2004 and 2017 was identified in the Surveillance Epidemiology and End Results-Medicare database. The clone-censor-weight method was leveraged to eliminate time-related biases when comparing outcomes between treatments. Outcomes included overall mortality, esophageal cancer-specific mortality, functional adverse events, and healthy days at home. Results: A total of 1240 individuals with adenocarcinomas and 661 with squamous cell carcinomas were identified. For adenocarcinomas, the standardized 5-year risk of mortality was 73.4% for trimodality therapy and 83.8% for definitive chemoradiation (relative risk [RR] = 0.88, 95% confidence interval [CI] = 0.82 to 0.95). Trimodality therapy was associated with mortality risk reduction for squamous cell carcinomas (RR = 0.87, 95% CI = 0.70 to 1.01). The 1-year incidence of functional adverse events was higher in the trimodality group (adenocarcinomas RR = 1.40, 95% CI = 1.22 to 1.65; squamous cell carcinomas RR = 1.21, 95% CI = 1.00 to 1.49). Over 5 years, trimodality therapy was associated with 160 (95% CI = 67 to 229) and 177 (95% CI = 51 to 313) additional home days in individuals with adenocarcinomas and squamous cell carcinomas, respectively. Conclusions: Compared with definitive chemoradiation, trimodality therapy was associated with reduced mortality but increased risk of function-related adverse events. Discussing these tradeoffs may help optimize care plans

Health-related quality of life outcomes among breast cancer survivors

Background: Data from a nationwide sample of US breast cancer survivors were used to examine associations between patient characteristics (breast cancer clinical features, prognostic factors, and treatments) and health-related quality of life (HRQOL). Associations between postdiagnosis HRQOL and mortality were then evaluated. Methods: The authors identified female breast cancer survivors (n = 2453) from the Sister Study or Two Sister Study who were at least 1 year from breast cancer diagnosis and who had responded to a survivorship survey in 2012. HRQOL was assessed with the Patient-Reported Outcomes Measurement Information System (PROMIS) Global 10 measures. Multivariable linear regression was used to assess predictors associated with HRQOL. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between HRQOL and all-cause mortality. Results: HRQOL, assessed an average of 4.9 years after the cancer diagnosis (standard deviation of 1.9 years), was negatively associated with a higher cancer stage at diagnosis; a higher comorbidity score at the survey; experience of surgical complications; dissatisfaction with breast surgery; and experience of any recent recurrence, metastasis, or secondary malignancy. Since the completion of the survey, there were 85 deaths (3.5%) during a mean follow-up of 4 years (standard deviation of 0.5 years). In multivariate models, decreases in PROMIS physical T scores and mental T scores were associated with increased mortality (HR for physical T scores, 1.08; 95% CI, 1.05-1.11; HR for mental T scores, 1.03; 95% CI, 1.01-1.06). Conclusions: Prognostic and cancer treatment–related factors affect HRQOL in breast cancer survivors and may inform targeted survivorship care. PROMIS global health measures may offer additional insights into patients' well-being and mortality risk. Lay Summary: Findings from a study suggest that prognostic and cancer treatment–related factors affect health-related quality of life (HRQOL) in breast cancer survivors and that poor HRQOL may increase the mortality risk. The evaluation of HRQOL is important because it may hold potential as a tool for optimizing survivorship care

RE: Colorectal Cancer Incidence Patterns in the United States, 1974–2013

In the latest issue of the Journal, Siegel et al. report that young adults born around 1990 (and so currently age 20 to 29 years) have double and quadruple the risk of colon and rectal cancer (CRC), respectively, compared with the same age group born in 1950. We believe presenting relative increases in incidence isolated from the absolute risk of CRC in younger adults can be misleading. Using relative or ratio measures to communicate risk of young-onset CRC may lead the casual reader or popular press to misinterpret the extent to which incidence is increasing

Long-Term Satisfaction and Body Image After Contralateral Prophylactic Mastectomy

Background: Contralateral prophylactic mastectomy (CPM) rates have been increasing in the US, and although high levels of satisfaction with CPM have been reported, few studies have evaluated the long-term effects on body image, comparing CPM with breast-conserving surgery (BCS) and unilateral mastectomy (UM). Methods: We analyzed responses from a survey of women with both a personal and family history of breast cancer who were enrolled in the Sister Study (n = 1176). Among women who underwent mastectomy, we examined satisfaction with the mastectomy decision, as well as variation in the use of reconstruction and experience of complications. Five survey items, evaluated individually and as a summed total score, were used to compare body image across surgery types (BCS, UM without reconstruction, CPM without reconstruction, UM with reconstruction, and CPM with reconstruction). Results: Participants were, on average, 3.6 years post-diagnosis at the time of survey (standard deviation 1.7). The majority of women (97% of CPM, 89% of UM) were satisfied with their mastectomy decision. Reconstruction was more common after CPM than after UM (70 vs. 47%), as were complications (28 vs. 19%). Body image scores were significantly worse among women who underwent CPM than among women who underwent BCS, with the lowest scores among women who underwent CPM without reconstruction. Conclusions: In our sample, most women were highly satisfied with their mastectomy decision, including those who elected to undergo CPM. However, body image was lower among those who underwent CPM than among those who underwent BCS. Our findings may inform decisions among women considering various courses of surgical treatment

Fertility-related experiences after breast cancer diagnosis in the Sister and Two Sister Studies

Background: Commonly used chemotherapies can be toxic to the ovaries. To the authors’ knowledge, the majority of studies evaluating receipt of fertility counseling for women in their reproductive years have been performed in specific settings, thereby limiting generalizability. Methods: A nationwide sample of US women diagnosed with breast cancer before age 45 years completed a survey assessing the prevalence of fertility counseling. Age-adjusted log-binomial regression was used to estimate prevalence ratios (PRs) and 95% CIs for fertility counseling. Results: Among 432 survivors diagnosed between 2004 and 2011, 288 (67%) had not discussed the effects of treatment on fertility with a health care provider before or during treatment. Fertility discussion was associated with younger age (PR, 3.49 [95% CI, 2.66-4.58] for aged <35 years vs ≥40 years) and lower parity (PR, 1.81 [95% CI, 1.29-2.53] for parity 1 vs 2). Approximately 20% of respondents reported that they were interested in future fertility (87 of 432 respondents) at the time of their diagnosis, but not all of these individuals (66 of 87 respondents) received counseling regarding the impact of treatment on their fertility, and few (8 of 87 respondents) used fertility preservation strategies. Among 68 women with a fertility interest who provided reasons for not taking steps to preserve fertility, reasons cited included concern for an adverse impact on cancer treatment (56%), lack of knowledge (26%), decision to not have a child (24%), and cost (18%). Conclusions: Across multiple treatment settings, the majority of women of reproductive age who are diagnosed with breast cancer did not discuss fertility with a health care provider or use fertility preservation strategies. Discussing the potential impact of cancer treatment on future fertility is an important aspect of patient education