Rates of Downstream Procedures and Complications Associated With Lung Cancer Screening in Routine Clinical Practice : A Retrospective Cohort Study.

BACKGROUND: Lung cancer screening (LCS) using low-dose computed tomography (LDCT) reduces lung cancer mortality but can lead to downstream procedures, complications, and other potential harms. Estimates of these events outside NLST (National Lung Screening Trial) have been variable and lacked evaluation by screening result, which allows more direct comparison with trials. OBJECTIVE: To identify rates of downstream procedures and complications associated with LCS. DESIGN: Retrospective cohort study. SETTING: 5 U.S. health care systems. PATIENTS: Individuals who completed a baseline LDCT scan for LCS between 2014 and 2018. MEASUREMENTS: Outcomes included downstream imaging, invasive diagnostic procedures, and procedural complications. For each, absolute rates were calculated overall and stratified by screening result and by lung cancer detection, and positive and negative predictive values were calculated. RESULTS: Among the 9266 screened patients, 1472 (15.9%) had a baseline LDCT scan showing abnormalities, of whom 140 (9.5%) were diagnosed with lung cancer within 12 months (positive predictive value, 9.5% [95% CI, 8.0% to 11.0%]; negative predictive value, 99.8% [CI, 99.7% to 99.9%]; sensitivity, 92.7% [CI, 88.6% to 96.9%]; specificity, 84.4% [CI, 83.7% to 85.2%]). Absolute rates of downstream imaging and invasive procedures in screened patients were 31.9% and 2.8%, respectively. In patients undergoing invasive procedures after abnormal findings, complication rates were substantially higher than those in NLST (30.6% vs. 17.7% for any complication; 20.6% vs. 9.4% for major complications). LIMITATION: Assessment of outcomes was retrospective and was based on procedural coding. CONCLUSION: The results indicate substantially higher rates of downstream procedures and complications associated with LCS in practice than observed in NLST. Diagnostic management likely needs to be assessed and improved to ensure that screening benefits outweigh potential harms. PRIMARY FUNDING SOURCE: National Cancer Institute and Gordon and Betty Moore Foundation.

Identifying factors and causal chains associated with optimal implementation of Lynch syndrome tumor screening: An application of coincidence analysis.

PURPOSE: This study compared Lynch syndrome universal tumor screening (UTS) across multiple health systems (some of which had two or more distinct UTS programs) to understand multi-level factors that may impact the successful implementation of complex programs. METHODS: Data from 66 stakeholder interviews were used to conduct multi-value coincidence analysis (mv-CNA) and identify key factors that consistently make a difference in whether UTS programs were implemented and optimized at the system level. RESULTS: The selected CNA model revealed combinations of conditions that distinguish 4 optimized UTS programs, 10 non-optimized programs, and 4 systems with no program. Fully optimized UTS programs had both a maintenance champion and a positive inner setting. Two independent paths were unique to non-optimized programs: 1) positive attitudes and a mixed inner setting, or 2) limited planning & engaging among stakeholders. Negative views about UTS evidence or lack of knowledge about UTS led to a lack of planning and engaging, which subsequently prevented program implementation. CONCLUSION: The model improved our understanding of program implementation in health care systems and informed the creation of a toolkit to guide UTS implementation, optimization, and changes. Our findings and toolkit may serve as a use case to increase the successful implementation of other complex precision health programs.

Dietary Factors Differ Between Young-Onset and Older-Onset Colorectal Cancer Patients.

We aimed to evaluate differences in dietary factors between young-onset (diagnosed at ages <50) and older-onset colorectal cancer (CRC). CRC patients diagnosed from 1998 to 2018 reported to the Puget Sound Surveillance, Epidemiology, and End Results registry were recruited using mail and telephone. Consented patients completed questionnaires assessing demographics, medical history, and CRC risk factors, including dietary factors. We used multi-variable logistic regression to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) comparing dietary intake in young-onset vs. older-onset CRC. Analyses included 1,087 young- and 2,554 older-onset CRC patients. Compared to older-onset CRC, young-onset CRC patients had lower intake of vegetables (OR for highest intake vs. lowest = 0.59 CI: 0.55, 0.64) and fruit (OR for highest intake vs. lowest = 0.94 CI: 0.88, 0.99) and higher intake of processed meat (OR for highest intake vs. lowest = 1.82 CI: 1.11, 2.99) and spicy food (OR for highest intake vs. lowest = 1.69 CI: 1.09, 2.61). There was no statistically significant difference between young- and older-onset CRC patients for red meat consumption. Dietary patterns differed between young- and older-onset CRC; young-onset CRC patients had lower intake of vegetables and fruit and higher intakes of processed meat and spicy food.

Colorectal cancer pre-diagnostic symptoms are associated with anatomic cancer site.

BACKGROUND: Signs and red flag symptoms in colorectal cancer (CRC) patients who are below the recommended screening age are often overlooked, leading to delayed diagnosis and worse prognosis. This study investigates how patient pre-diagnostic symptoms are associated with anatomic site of their cancer and whether the association varies by age at CRC diagnosis. METHODS: We ascertained CRC patients' experienced symptoms and screening through medical abstractions from an ongoing population-based study of CRC patients identified through a SEER cancer registry (N = 626). We used logistic regression to estimate odds ratios and 95% confidence intervals for the association between symptoms and CRC anatomic site. Additional analyses were stratified by age at diagnosis. Early-onset was defined as less than 50 years of age at CRC diagnosis. RESULTS: Participants who experienced blood in stool were more likely (odds ratio (95% confidence interval)) to have rectal (vs. colon) cancer (4.37 (3.02, 6.33)), as were patients who experienced changes to stool (1.78 (1.21, 2.60)). Patients diagnosed with colon cancer were more likely to present with abdominal pain (0.30 (0.19, 0.47)), anemia (0.40 (0.21, 0.75)), other symptoms (0.33 (0.19, 0.55)) and no symptoms (0.68 (0.44, 1.04)). When stratifying by age at diagnosis, we found that the association between blood in stool and rectal tumor location was particularly pronounced for patients with early-onset CRC (6.48 (2.73, 15.41)). CONCLUSIONS: Common pre-diagnostic red flag symptoms are associated with CRC anatomic site. These findings can inform best practices for gastroenterologist triage of care and early evaluation of CRC and are of key importance given the rise of early-onset (pre-screening age) CRC. TRIAL REGISTRATION: Not applicable to this study and analysis.

Depression, anxiety, & loneliness among cancer survivors during the COVID-19 pandemic.

PURPOSE: To assess the impact of the COVID-19 pandemic on depression, anxiety, and loneliness between those with and without a history of cancer. DESIGN: This prospective observational study used a quantitative approach. PARTICIPANTS: Adult members of the Kaiser Permanente Research Bank (N = 104,640). METHODS: Participants completed a series of surveys from May to December 2020. The difference in score of depression, anxiety, and loneliness were estimated using linear mixed regression. FINDINGS: Among cancer survivors, 21% and 19% met the thresholds for increased risk of depression and anxiety. Among cancer survivors, younger age groups and females reported increased depression, anxiety, and loneliness scores. CONCLUSIONS: This study highlights the continued necessity of addressing mental health needs and social support in cancer survivors during and after a public health emergency. IMPLICATIONS FOR PSYCHOSOCIAL PROVIDERS: Cancer survivors may need particular resources after cancer treatment to strengthen resilience and improve quality of life.

Quantitative Pathologic Analysis of Digitized Images of Colorectal Carcinoma Improves Prediction of Recurrence-Free Survival.

BACKGROUND & AIMS: To examine whether quantitative pathologic analysis of digitized hematoxylin and eosin slides of colorectal carcinoma (CRC) correlates with clinicopathologic features, molecular alterations, and prognosis. METHODS: A quantitative segmentation algorithm (QuantCRC) was applied to 6468 digitized hematoxylin and eosin slides of CRCs. Fifteen parameters were recorded from each image and tested for associations with clinicopathologic features and molecular alterations. A prognostic model was developed to predict recurrence-free survival using data from the internal cohort (n = 1928) and validated on an internal test (n = 483) and external cohort (n = 938). RESULTS: There were significant differences in QuantCRC according to stage, histologic subtype, grade, venous/lymphatic/perineural invasion, tumor budding, CD8 immunohistochemistry, mismatch repair status, KRAS mutation, BRAF mutation, and CpG methylation. A prognostic model incorporating stage, mismatch repair, and QuantCRC resulted in a Harrell's concordance (c)-index of 0.714 (95% confidence interval [CI], 0.702-0.724) in the internal test and 0.744 (95% CI, 0.741-0.754) in the external cohort. Removing QuantCRC from the model reduced the c-index to 0.679 (95% CI, 0.673-0.694) in the external cohort. Prognostic risk groups were identified, which provided a hazard ratio of 2.24 (95% CI, 1.33-3.87, P = .004) for low vs high-risk stage III CRCs and 2.36 (95% CI, 1.07-5.20, P = .03) for low vs high-risk stage II CRCs, in the external cohort after adjusting for established risk factors. The predicted median 36-month recurrence rate for high-risk stage III CRCs was 32.7% vs 13.4% for low-risk stage III and 15.8% for high-risk stage II vs 5.4% for low-risk stage II CRCs. CONCLUSIONS: QuantCRC provides a powerful adjunct to routine pathologic reporting of CRC. A prognostic model using QuantCRC improves prediction of recurrence-free survival.

Evaluation of Harms Reporting in U.S. Cancer Screening Guidelines.

BACKGROUND: Cancer screening should be recommended only when the balance between benefits and harms is favorable. This review evaluated how U.S. cancer screening guidelines reported harms, within and across organ-specific processes to screen for cancer. OBJECTIVE: To describe current reporting practices and identify opportunities for improvement. DESIGN: Review of guidelines. SETTING: United States. PATIENTS: Patients eligible for screening for breast, cervical, colorectal, lung, or prostate cancer according to U.S. guidelines. MEASUREMENTS: Information was abstracted on reporting of patient-level harms associated with screening, diagnostic follow-up, and treatment. The authors classified harms reporting as not mentioned, conceptual, qualitative, or quantitative and noted whether literature was cited when harms were described. Frequency of harms reporting was summarized by organ type. RESULTS: Harms reporting was inconsistent across organ types and at each step of the cancer screening process. Guidelines did not report all harms for any specific organ type or for any category of harm across organ types. The most complete harms reporting was for prostate cancer screening guidelines and the least complete for colorectal cancer screening guidelines. Conceptualization of harms and use of quantitative evidence also differed by organ type. LIMITATIONS: This review considers only patient-level harms. The authors did not verify accuracy of harms information presented in the guidelines. CONCLUSION: The review identified opportunities for improving conceptualization, assessment, and reporting of screening process-related harms in guidelines. Future work should consider nuances associated with each organ-specific process to screen for cancer, including which harms are most salient and where evidence gaps exist, and explicitly explore how to optimally weigh available evidence in determining net screening benefit. Improved harms reporting could aid informed decision making, ultimately improving cancer screening delivery. PRIMARY FUNDING SOURCE: National Cancer Institute.

"Go ahead and screen" - advice to healthcare systems for routine lynch syndrome screening from interviews with newly diagnosed colorectal cancer patients.

BACKGROUND: Lynch syndrome (LS) is the most common cause of inherited colorectal cancer (CRC). Universal tumor screening (UTS) of newly diagnosed CRC cases is recommended to aid in diagnosis of LS and reduce cancer-related morbidity and mortality. However, not all health systems have adopted UTS processes and implementation may be inconsistent due to system and patient-level complexities. METHODS: To identify barriers, facilitators, and suggestions for improvements of the UTS process from the patient perspective, we conducted in-depth, semi-structured interviews with patients recently diagnosed with CRC, but not screened for or aware of LS. Patients were recruited from eight regionally diverse US health systems. Interviews were conducted by telephone, 60-minutes, audio-recorded, and transcribed. An inductive, constant comparative analysis approach was employed.  RESULTS: We completed 75 interviews across the eight systems. Most participants were white (79%), about half (52%) were men, and the mean age was 60 years. Most self-reported either no (60%) or minimal (40%) prior awareness of LS. Overall, 96% of patients stated UTS should be a routine standard of care for CRC tumors, consistently citing four primary motivations for wanting to know their LS status and engage in the process for LS identification: "knowledge is power"; "family knowledge"; "prevention and detection"; and "treatment and surveillance." Common concerns pertaining to the process of screening for and identifying LS included: creating anticipatory worry for patients, the potential cost and the accuracy of the genetic test, and possibly having one's health insurance coverage impacted by the LS diagnosis. Patients suggested health systems communicate LS results in-person or by phone from a trained expert in LS; offer proactive verbal and written education about LS, the screening steps, and any follow-up surveillance recommendations; and support patients in communicating their LS screening to any of their blood relatives. CONCLUSION: Our qualitative findings demonstrate patients with CRC have a strong desire for healthcare systems to regularly implement and offer UTS. Patients offer key insights for health systems to guide future implementation and optimization of UTS and other LS screening programs and maximize diagnosis of individuals with LS and improve cancer-related surveillance and outcomes. TRIAL REGISTRATION: Not available: not a clinical trial.

An Update on the Epidemiology, Molecular Characterization, Diagnosis, and Screening Strategies for Early-Onset Colorectal Cancer.

Rising trends in the incidence and mortality of early-onset colorectal cancer (CRC) in those who are younger than 50 years have been well established. These trends have spurred intense investigation focused on elucidating the epidemiology and characteristics of early-onset CRC, as well as on identifying strategies for early detection and prevention. In this review, we provide a contemporary update on early-onset CRC with a particular focus on epidemiology, molecular characterization, red flag signs and symptoms, and screening for early-onset CRC.

The Kaiser Permanente Research Bank Cancer Cohort: a collaborative resource to improve cancer care and survivorship.

BACKGROUND: The Kaiser Permanente Research Bank (KPRB) is collecting biospecimens and surveys linked to electronic health records (EHR) from approximately 400,000 adult KP members. Within the KPRB, we developed a Cancer Cohort to address issues related to cancer survival, and to understand how genetic, lifestyle and environmental factors impact cancer treatment, treatment sequelae, and prognosis. We describe the Cancer Cohort design and implementation, describe cohort characteristics after 5 years of enrollment, and discuss future directions. METHODS: Cancer cases are identified using rapid case ascertainment algorithms, linkage to regional or central tumor registries, and direct outreach to KP members with a history of cancer. Enrollment is primarily through email invitation. Participants complete a consent form, survey, and donate a blood or saliva sample. All cancer types are included. RESULTS: As of December 31, 2020, the cohort included 65,225 cases (56% female, 44% male) verified in tumor registries. The largest group was diagnosed between 60 and 69 years of age (31%) and are non-Hispanic White (83%); however, 10,076 (16%) were diagnosed at ages 18-49 years, 4208 (7%) are Hispanic, 3393 (5%) are Asian, and 2389 (4%) are Black. The median survival time is 14 years. Biospecimens are available on 98% of the cohort. CONCLUSIONS: The KPRB Cancer Cohort is designed to improve our understanding of treatment efficacy and factors that contribute to long-term cancer survival. The cohort's diversity - with respect to age, race/ethnicity and geographic location - will facilitate research on factors that contribute to cancer survival disparities.

Patient and tumour characteristics of screening-age adults diagnosed with screen-detected versus symptomatic colon cancer.

AIM: International studies have shown that most colon cancers are diagnosed among people with symptoms, but research is limited in the United States. Here, we conducted a retrospective study of adults aged 50-85 years diagnosed with stage I-IIIA colon cancer between 1995 and 2014 in two US healthcare systems. METHODS: Mode of detection (screening or symptomatic) was ascertained from medical records. We estimated unadjusted odds ratios (OR) and 95% confidence intervals (CI) comparing detection mode by patient factors at diagnosis (year, age, sex, race, smoking status, body mass index [BMI], Charlson score), prediagnostic primary care utilization, and tumour characteristics (stage, location). RESULTS: Of 1,675 people with colon cancer, 38.4% were screen-detected, while 61.6% were diagnosed following symptomatic presentation. Screen-detected cancer was more common among those diagnosed between 2010 and 2014 versus 1995-1999 (OR 1.65, 95% CI: 1.19-2.28), and those with a BMI of 25-<30 kg/m2 (OR 1.54, 95% CI: 1.21-1.98) or ≥30 kg/m2 (OR 1.52, 95% CI: 1.18-1.96) versus <25 kg/m2 . Screen-detected cancer was less common among people aged 76-85 (OR 0.50, 95% CI: 0.39-0.65) versus 50-64, those with comorbidity scores >0 (OR 0.71, 95% CI: 0.56-0.91 for score = 1, OR 0.34, 95% CI: 0.26-0.45 for score = 2+), and those with 2+ prediagnostic primary care visits (OR 0.53, 95% CI: 0.37-0.76) versus 0 visits. The odds of screen detection were lower among patients diagnosed with stage IIA (OR 0.33, 95% CI = 0.27-0.41) or IIB (OR 0.12, 95% CI: 0.06-0.24) cancers versus stage I. CONCLUSIONS: Most colon cancers among screen-eligible adults were diagnosed following symptomatic presentation. Even with increasing screening rates over time, research is needed to better understand why specific groups are more likely to be diagnosed when symptomatic and identify opportunities for interventions.

The association of bowel function, participation in life activities, and quality of life in rectal cancer survivors.

PURPOSE: To evaluate whether limited participation in life activities is associated with quality of life (QOL) in rectal cancer survivors, and if so, whether this association is independent of bowel function difficulties. METHODS: We surveyed rectal cancer survivors from four healthcare systems about their QOL, bowel function, and participation in life activities. Additional demographic and clinical variables were extracted from the electronic health record. We examined independent associations between bowel function, participation in life activities, and QOL, controlling for potential confounders. We also identified factors, including ostomy status, that correlate with participation in life activities. RESULTS: Of the 527 respondents, 52% were male, 80% were non-Hispanic white, and the mean age was 63. In fully adjusted models for all rectal cancer survivors, participation in life activities was positively associated with QOL, while bowel function was not. Bowel function retained an independent association with QOL for those who previously had an ostomy and were therefore more likely to have a low rectal anastomosis. Lower participation in life activities was correlated with lower self-reported physical and cognitive function, younger age, financial difficulty, and being non-Hispanic white. CONCLUSIONS: Rectal cancer survivors' participation in life activities was strongly associated with QOL, even when controlling for numerous confounders, including bowel function. Identifying ways to improve participation in life activities may be critical to developing rehabilitative and other supportive interventions that optimize QOL among rectal cancer survivors.

Associations between molecular characteristics of colorectal serrated polyps and subsequent advanced colorectal neoplasia.

PURPOSE: BRAF mutation and DNA hypermethylation have linked sessile serrated adenomas/polyps (SSA/Ps) to serrated colorectal cancer (CRC) in cross-sectional studies, but they have not been evaluated in a longitudinal study. We aimed to evaluate the associations between molecular markers of serrated polyps and subsequent advanced colorectal neoplasia. METHODS: Study subjects included Kaiser Permanente Washington members aged 20-75 years who received an index colonoscopy between 1/1/1998 and 12/31/2007 and had hyperplastic polyps (HPs) or SSA/Ps according to study pathology review. Polyps from index colonoscopies were removed and assayed for BRAF mutation, CpG island methylator phenotype (CIMP), and MLH1 methylation. Pathology reports and biopsies from the subsequent lower gastrointestinal endoscopy through 1/1/2013 were reviewed for advanced colorectal neoplasia. We identified additional incident CRC cases through linkage to the Seattle-Puget Sound Surveillance Epidemiology and End Results registry. We used generalized estimating equations to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI) for subsequent advanced colorectal neoplasia, comparing index serrated polyps with different molecular markers. RESULTS: We included 553 individuals with index serrated polyps (420 HPs and 133 SSA/Ps) and 795 subsequent endoscopies. The prevalence of BRAF-mutant, CIMP-high, and MLH1-methylated serrated polyps were 51%, 4%, and 2%, respectively. BRAF and CIMP were not associated with subsequent advanced colorectal neoplasia. MLH1-methylated SSP/As were significantly more likely to have subsequent advanced neoplasia (OR = 4.66, 95% CI 1.06-20.51). CONCLUSION: Our results suggest that BRAF-mutant and CIMP-high serrated polyps are not associated with subsequent advanced colorectal neoplasia. Among SSA/Ps, MLH1 methylation may be an important marker to identify high-risk CRC precursors.

Real-world Clinical Implementation of Lung Cancer Screening-Evaluating Processes to Improve Screening Guidelines-Concordance.

BACKGROUND: Lung cancer screening (LCS) requires complex processes to identify eligible patients, provide appropriate follow-up, and manage findings. It is unclear whether LCS in real-world clinical settings will realize the same benefits as the National Lung Screening Trial (NLST). OBJECTIVE: To evaluate the impact of process modifications on compliance with LCS guidelines during LCS program implementation, and to compare patient characteristics and outcomes with those in NLST. DESIGN: Retrospective cohort study. SETTING: Kaiser Permanente Colorado (KPCO), a non-profit integrated healthcare system. PATIENTS: A total of 3375 patients who underwent a baseline lung cancer screening low-dose computed tomography (S-LDCT) scan between May 2014 and June 2017. MEASUREMENTS: Among those receiving an S-LDCT, proportion who met guidelines-based LCS eligibility criteria before and after LCS process modifications, differences in patient characteristics and outcomes between KPCO LCS patients and the NLST cohort, and factors associated with a positive screen. RESULTS: After modifying LCS eligibility confirmation processes, patients receiving S-LDCT who met guidelines-based LCS eligibility criteria increased from 45.6 to 92.7% (P < 0.001). Prior to changes, patients were older (68 vs. 67 years; P = 0.001), less likely to be current smokers (51.3% vs. 52.5%; P < 0.001), and less likely to have a ≥ 30-pack-year smoking history (50.0% vs. 95.3%; P < 0.001). Compared with NLST participants, KPCO LCS patients were older (67 vs. 60 years; P < 0.001), more likely to currently smoke (52.3% vs. 48.1%; P < 0.001), and more likely to have pulmonary disease. Among those with a positive baseline S-LDCT, the lung cancer detection rate was higher at KPCO (9.4% vs. 3.8%; P < 0.001) and was positively associated with prior pulmonary disease. CONCLUSION: Adherence to LCS guidelines requires eligibility confirmation procedures. Among those with a positive baseline S-LDCT, comorbidity burden and lung cancer detection rates were notably higher than in NLST, suggesting that the study of long-term outcomes in patients undergoing LCS in real-world clinical settings is warranted.

A population-based survey to assess the association between cannabis and quality of life among colorectal cancer survivors.

BACKGROUND: As more states legalize cannabis for medical and recreational use, people increasingly use cannabis to treat medical conditions and associated symptoms. The prevalence and utility of cannabis for cancer-related symptoms may be clarified by examining cannabis use among patients with a common cancer diagnosis. We aimed to determine the prevalence of cannabis use among colorectal cancer (CRC) survivors and its associations with quality of life (QoL) and cancer-related symptomatology. METHODS: A cross-sectional survey of patient-reported QoL outcomes and behaviors, including cannabis use, was conducted within the Patient Outcomes To Advance Learning network's (PORTAL) CRC Cohort. The cohort included a population-based sample of healthcare system members ≥18 years old diagnosed with adenocarcinoma of the colon or rectum from 2010 through 2016. We assessed the association between cannabis use and QoL using the European Organization for Research and Treatment of Cancer QLQ-C30 summary score. RESULTS: Of the 1784 respondents, 293 (16.4%) reported cannabis use following CRC diagnosis. Current tobacco smokers were more likely to use cannabis compared to former or never tobacco smokers (adjusted odds ratio [aOR] 2.71, 95% confidence interval [CI] 1.56 to 4.70). Greater alcohol use (> 4 drinks per month versus ≤4 drinks per month) was associated with cannabis use (aOR 2.17, 95% CI 1.65 to 2.85). There was an association between cannabis use and cancer stage at diagnosis, with stage 3 or 4 CRC patients more likely to use cannabis than stage 1 or 2 CRC patients (aOR 1.68, 95% CI 1.25 to 2.25). After adjusting for demographics, medical comorbidities, stage and site of CRC diagnosis, and prescription opioid use, people who used cannabis had significantly lower QoL than people who did not use cannabis (difference of - 6.14, 95% CI - 8.07 to - 4.20). CONCLUSION: Among CRC survivors, cannabis use was relatively common, associated with more advanced stages of disease, associated with tobacco and alcohol use, and not associated with better QoL. Clinicians should inquire about cannabis use among their patients and provide evidence-based recommendations for cancer-related symptoms.

Demographic differences in the utilization of clinical and direct-to-consumer genetic testing.

Genetic testing has increased over the last decade due to growth in the number of clinical and direct-to-consumer (DTC) tests. However, there is uncertainty about how increased DTC genetic testing affects disparities. Between November 2017 and February 2018, a nationwide electronic survey on experiences with genetic testing was conducted among adult Kaiser Permanente members. Logistic regression was used to calculate adjusted odds ratios and 95% confidence intervals comparing receipt of clinical and DTC genetic testing between groups by race and ethnicity. Invitations were sent to 57,331 members, and 10,369 surveys were completed. 22% of respondents had received genetic testing (17% DTC and 5% provider-ordered). Non-Hispanic Whites were more likely than other groups to have clinical genetic testing but were similar to Hispanics and non-Hispanic Blacks in rates of DTC genetic testing. Among those who received any health-related genetic test, 10% reported abnormal results. Of these, non-Hispanic Whites were more likely than other racial/ethnic groups to speak to a medical professional about abnormal results. Results suggest that racial/ethnic disparities in the use of clinical genetic services persist. Additional research is needed to identify lessons learned from DTC genetic testing that may increase equity in the use of clinical genetic services.

The association between colorectal sessile serrated adenomas/polyps and subsequent advanced colorectal neoplasia.

PURPOSE: Colorectal cancer (CRC) screening guidelines recommend increased surveillance of individuals with sessile serrated adenomas/polyps (SSA/Ps), but there is uncertainty about the risk associated with SSA/Ps. We aimed to determine the association between SSA/Ps and subsequent advanced colorectal neoplasia. METHODS: This case-control study included Kaiser Permanente Washington (KPWA) members who received an index colonoscopy between 1/1/1998 and 12/31/2007, and had hyperplastic polyps (HPs) or SSA/Ps but no conventional adenomas according to study pathologist histologic review. Subsequent pathology reports and biopsies through 1/1/2013 were reviewed for advanced colorectal neoplasia. We linked to the Seattle-Puget Sound Surveillance Epidemiology and End Results (SEER) registry to identify additional CRC cases. We used generalized estimating equations with a logit link to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for advanced colorectal neoplasia, comparing those with SSA/Ps to those with HPs. RESULTS: There were 161 individuals with index SSA/Ps, 548 with HPs, and 918 subsequent endoscopies included in analyses. Of those with index SSA/Ps, 19 had subsequent advanced colorectal neoplasia; 39 with HPs had subsequent advanced colorectal neoplasia. Compared to those with HPs, those with SSA/Ps were not statistically significantly more likely to have subsequent advanced colorectal neoplasia (adjusted OR 1.79; CI 0.98-3.28). Polyp size ≥ 10 mm, right colon location, and the presence of multiple serrated polyps were also not associated with advanced colorectal neoplasia. CONCLUSIONS: Our results suggest that there is not a strong association between SSA/Ps and subsequent advanced colorectal neoplasia during the 5 years following SSA/P removal.

Treatment patterns and survival differ between early-onset and late-onset colorectal cancer patients: the patient outcomes to advance learning network.

PURPOSE: Our objective was to describe differences in treatment patterns and survival between early-onset (< 50 years old) and late-onset colorectal cancer (CRC) patients in community-based health systems. METHODS: We used tumor registry and electronic health record data to identify and characterize patients diagnosed with adenocarcinoma of the colon or rectum from 2010 to 2014 at six US health systems in the patient outcomes to advance learning (PORTAL) network. We used logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) comparing the distribution of tumor characteristics and treatment patterns in early-onset versus late-onset CRC. Cox regression models were used to estimate adjusted hazard ratios (HRs) and CIs comparing survival between early- and late-onset CRC patients. RESULTS: There were 1,424 early-onset and 10,810 late-onset CRC cases in our analyses. Compared to late-onset CRC, early-onset CRC was significantly associated with advanced-stage disease, high-grade histology, signet ring histology, and rectal or left colon location. After adjusting for differences in tumor and patient characteristics, early-onset patients were more likely than late-onset patients to have > 12 lymph nodes examined (OR 1.60, CI 1.37-1.87), to receive systemic therapy (chemotherapy or immunotherapy) within 6 months of diagnosis (OR 2.84, CI 2.40-3.37), and to have a reduced risk of CRC-specific death (HR 0.66, CI 0.56-0.79). CONCLUSIONS: Early-onset CRC is associated with aggressive tumor characteristics, distal location, and systemic therapy use. Despite some adverse risk factors, these patients tend to have better survival than older onset patients.

Changes in use of opioid therapy after colon cancer diagnosis: a population-based study.

PURPOSE: To describe patterns of opioid use in cancer survivors. METHODS: In a cohort study of colon cancer patients diagnosed during 1995-2014 and enrolled at two Kaiser Permanente regions, we constructed quarterly measures of opioid use from 1 year before cancer diagnosis through 5 years after diagnosis to examine changes in use. Measures included any use, incident use, regular use (use ≥ 45 days in a 91-day quarter), and average daily dose (converted to morphine milligram equivalent, MME). We also assessed temporal trends of opioid use. RESULTS: Of 2,039 colon cancer patients, 11-15% received opioids in the four pre-diagnosis quarters, 68% in the first quarter after diagnosis, and 15-17% in each subsequent 19 quarters. Regular opioid use increased from 3 to 5% pre-diagnosis to 5-7% post diagnosis. Average dose increased from 15 to 17 MME/day pre-diagnosis to 14-22 MME/day post diagnosis (excluding the quarter in which cancer was diagnosed). Among post-diagnosis opioid users, 73-95% were on a low dose (< 20 MME/day). Over years, regular use of opioids increased in survivorship with no change in dosage. CONCLUSION: Opioid use slightly increased following a colon cancer diagnosis, but high-dose use was rare. Research is needed to differentiate under- versus over-treatment of cancer pain.

Cardiovascular medication use and risks of colon cancer recurrences and additional cancer events: a cohort study.

BACKGROUND: Cardiovascular medications may be associated with cancer development, but little is known about their association with cancer recurrence. Medications such as statins and antihypertensives may be commonly used among colon cancer survivors, who are, on average, diagnosed in their mid-60s. We described the associations between statins and antihypertensive medications and colon cancer recurrence in a large, population-based study. METHODS: We conducted a cohort study among adults with stage I-IIIA colon cancer diagnosed in 1995-2014 in two Kaiser Permanente regions, Colorado and Washington. Statin and antihypertensive use were obtained from electronic pharmacy dispensing data. People were classified as medication users on the date of their first dispensing after cohort entry, which started 90 days after completing cancer treatment, continuing through the earliest of death, health plan disenrollment, or chart abstraction. We collected outcome information from medical record abstraction and tumor registries on colon cancer recurrences and second primary cancers. Using Cox proportional hazards multivariable models, we estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for colon cancer recurrences and any cancer event (recurrences and new primaries at any anatomic site) comparing medication users to non-users. RESULTS: Among 2039 people, 937 (46%) used statins and 1425 (70%) used antihypertensives at any point during a median of 4.9 years of follow-up; 460 people had any additional cancer event, including 152 with a colon cancer recurrence. Statin use was not associated with colon cancer recurrence (HR = 1.09, 95%CI = 0.65-1.85) or any cancer event (HR = 1.12, 95%CI = 0.85-1.47), nor was antihypertensive use associated with recurrence (HR = 0.73, 95%CI = 0.44-1.21) or any cancer event (HR = 0.93, 95%CI = 0.70-1.24). CONCLUSIONS: Our results suggest no association between cardiovascular medication use and the risk of recurrence or any additional cancer, and may provide reassurance to colon cancer survivors.