Linkage To Cancer Registry Research Articles

Evaluating the quality of prostate cancer diagnosis recording in CPRD GOLD and CPRD Aurum primary care databases for observational research: A study using linked English electronic health records

BackgroundPrimary care data in the UK are widely used for cancer research, but the reliability of recording key events like diagnoses remains uncertain. Although data linkage can improve reliability, its costs, time requirements, and sample size constraints may discourage its use. We evaluated accuracy, completeness, and date concordance of prostate cancer (PCa) diagnosis recording in Clinical Practice Research Datalink (CPRD) GOLD and Aurum compared to linked Cancer Registry (CR) and Hospital Episode Statistics (HES) Admitted Patient Care (APC) in England. MethodsIncident PCa diagnoses (2000–2016) for males aged ≥46 at diagnosis who remained registered with their General Practitioner (GP) by age 65 and were recorded in at least one data source were analysed. Accuracy was the proportion of diagnoses recorded in GOLD or Aurum with a corresponding record in CR or HES. Completeness was the proportion of CR or HES diagnoses with a corresponding record in GOLD or Aurum. ResultsThe final cohorts for comparisons included 29,500 records for GOLD and 26,475 for Aurum. Compared to CR, GOLD was 86 % accurate and 65 % complete, while Aurum was 87 % accurate and 77 % complete. Compared to HES, GOLD was 76 % accurate and 60 % complete, and Aurum was 79 % accurate and 70 % complete. Concordance in diagnosis dates improved over time in both GOLD and Aurum, with 93 % of diagnoses recorded within a year compared to CR, and 66 % (GOLD) and 71 % (Aurum) compared to HES. Delays of 2–3 weeks in primary care diagnosis recording were observed compared to CR, whereas most diagnoses appeared at least 3 months earlier in primary care than in HES. ConclusionsAurum demonstrated better accuracy and completeness for PCa diagnosis recording than GOLD. However, linkage to HES or CR is recommended for improved case capture. Researchers should address the limitations of each data source to ensure research validity.

Abstract 4136285: Large-Scale Proteomics Identifies Novel Shared Biomarkers of Heart Failure and Cancer: the Atherosclerosis Risk in Communities (ARIC) Study

Introduction: There is a bidirectional relationship between cancer and cardiovascular disease risk. Identifying proteins associated with both cancer and heart failure (HF) may provide insight into common biological pathways underlying both conditions. Methods: Among 10,136 participants in the community-based ARIC cohort study who were free of HF and cancer at study visit 2 (1990-92) and had aptamer-based proteomics (SomaScan v4), we assessed the association of 4,955 plasma proteins with incident HF and with incident site-specific cancer ascertained by cancer registry linkage supplemented with medical records (lung, post-menopausal breast, prostate, colorectal, and hematologic) using multivariable Cox models adjusted for demographics, clinical characteristics, and social determinants of health. Two-sample cis-Mendelian randomization ( cis- MR) was performed to evaluate potential causal effects of proteins on HF, left ventricular (LV) function, and site-specific cancer. Results: Mean age at baseline was 56±6; 54% were female; and 24% reported black race. Over a median follow-up of 10 [IQR 10, 10] years, there were 604 incident HF events and 1,207 incident cancers (169 lung, 85 hematologic, 105 colorectal, 206 breast, 288 prostate). Using a Bonferroni significance threshold (p < 1.0x10 -5 ), 23 proteins were associated with both HF and lung cancer, 2 with HF and hematologic malignancy, 1 with HF and colorectal cancer, and none with HF and breast or prostate cancer. Six proteins remained significantly associated with both HF and lung cancer after further adjustment for pack-years of smoking (Figure). In cis- MR of these six proteins, ICAM5 and MMP12 showed potential causal effect on LV volume and lung adenocarcinoma, and PLAUR showed potential causal effect on HF and lung adenocarcinoma. Conclusion: Among various types of cancer, proteins associated with lung cancer showed the greatest overlap with proteins associated with HF, which was largely accounted for by smoking exposure. We uncovered a set of 6 plasma proteins associated with both incident HF and lung cancer after accounting for smoking. MR identified proteins with potential causal effects on both lung adenocarcinoma and LV size (ICAM5, MMP12) and HF (PLAUR).

Abstract 4135985: Association of Plasma Cystatin-C with Cancer Risk in Individuals with and without Cardiovascular and Chronic Kidney Disease: An Atherosclerosis Risk in Communities (ARIC) Study

Background: While previous studies suggested a relationship between circulating Cystatin-C (Cys-C), a cysteine protease inhibitor involved in regulating tissue inflammation and a renal filtration marker, and both cancer and CVD, they often lacked long-term follow-up or did not account for the impact of CVD on the relationship between Cys-C and cancer. Methods: We included participants from the Atherosclerosis Risk in Communities (ARIC) study followed from visit 2 (1990-1992) through 2015. Plasma Cys-C level was measured by SomaScan. Other renal filtration markers beta-2 microglobulin (B2M) and beta-trace protein (BTP) were used to compare their cancer association with Cys-C. Incident cancer was ascertained by state cancer registry linkage supplemented with medical records. After adjusting for age, sex, race, and study center, adjusted hazard ratios (aHR) of total and site-specific cancers were estimated using Cox proportional hazards regression stratified by baseline chronic kidney disease (CKD) and CVD status. Results: Among 10,869 individuals (median age of 56.9 years, 55% female, 25% Black, 74% White), 3352 incident cancers were ascertained over a median follow-up of 22.9 years. Among 9585 individuals with no history of CKD or CVD, higher Cys-C was significantly associated with a higher risk of total (aHR 1.22, 95%CI 1.02-1.46), bladder, lung, colorectal, and hematologic malignancies. Among 1,050 individuals with CVD, but not CKD, Cys-C level was not associated with total cancer (aHR 1.22, 95%CI 0.74-2.01), but was significantly inversely associated with colorectal (aHR 0.19, 95%CI 0.05-0.76) and positively associated with post-menopausal breast (aHR 4.52, 95%CI 1.05-19.40) cancer risk. In individuals with CKD but not CVD, Cys-C was negatively associated with bladder (HR 0.08, 95%CI 0.0-0.77) and lung (0.23, 95%CI 0.06-0.82) cancers. Lastly, those with both CKD and CVD showed higher hematopoietic and lymphatic cancer with higher Cys-C (HR 4.68, 95%CI 1.32-16.60). Similar patterns were observed for B2M and BTP proteins. Conclusions: Our study highlights the intricate relationship between various renal filtration markers and cancer risk. It suggests that they may play a significant role in cancer development among the general population and CVD patients but not CKD patients. Further research should explore the biological mechanism underlying these associations with even more CKD cases to refine risk estimates. Funding: NHLBI, NCI, NPCR

Abstract 4136755: Associations of Pulmonary Hypertension and Lung Cancer: A Prospective Cohort Study of Half a Million UK Biobank Participants

Background: Pulmonary hypertension (PH) and lung cancer (LC) are both significant public health issues with substantial morbidity and mortality. Recent studies suggest potential associations between pulmonary vascular diseases and LC due to shared risk factors and pathophysiological mechanisms, yet comprehensive research in large populations is scarce. Methods: This prospective cohort study utilized data from the UK Biobank, with baseline assessment between 2006 and 2010 and follow-up until November 30, 2023, for England and Scotland, and May 31, 2022, for Wales. We included 6,425 participants with LC, identified using linked cancer registry data, and followed them for the incidence of PH over a period of 10 years. We adjusted for potential confounders including age, ethnics, sex, smoking status, BMI, and histologic subtypes of LC. Statistical analyses were performed using Time-dependent Cox proportional hazards models to estimate the associations between PH and LC. Results: Of 502,173 participants in this prospective cohort, 6,425 were diagnosed with LC, while 494,451 did not receive the LC diagnosis. The prevalence of PH in the LC cohort and the no-LC cohort were 0.64% (1,494 of 3,142 women [47.55%]) and 2.40% (59 of 154 women [38.31%]), respectively, with significant difference between the two groups (p<0.001). In the LC cohort, the mortality rates of patients without PH and with PH were 69.18% and 77.92% (p=0.020). Among the patients diagnosed with LC and PH, 33.12% were diagnosed with LC after PH (PH-LC), while 66.88% were diagnosed with LC before PH (LC-PH). And the mortality rates of the PH-LC group and the LC-PH group were 78.43% and 77.67%, respectively, with no significant difference between the two groups (p=0.915). Time-dependent Cox regression analysis showed that PH shows an increasing trend in risk (5th year HR: 3.22, 95% CI: 2.09-4.99, p-value < 0.001), highlighting its significant impact on LC long-term prognosis. Conclusion: To conclude, the presence of PH significantly increased the risk of mortality in participants with LC, especially for the long-term LC survivors. And certain percentage of patients were diagnosed with LC before PH, but they had no significant difference between the patients with LC after PH.

Costs and benefits of a formal quality framework for colonoscopy: Economic evaluation.

Background and study aims Reduction of colorectal cancer morbidity and mortality is one of the primary objectives of colonoscopy. Post-colonoscopy colorectal cancers (PCCRCs) are critical outcome parameters. Analysis of PCCRC rates can validate quality assurance measures in colonoscopy. We assessed the effectiveness of implementing a gastroenterologist-led quality framework that monitors key procedure quality indicators (i.e., bowel preparation quality, adenoma detection rates, or patient satisfaction) by comparing the PCCRC rate before and after implementation. Patients and methods Individuals who had a colonoscopy between 2010 and 2017 at a single tertiary center in Queensland, Australia, were included and divided into two groups: baseline (2010-2014) and redesign phase (2015-2017). Data linkage of the state-wide cancer registry and hospital records enabled identification of subjects who developed colorectal cancers within 5 years of a negative colonoscopy. Costs associated with quality improvement were assessed for effectiveness. Results A total of 19,383 individuals had a colonoscopy during the study period. Seventeen PCCRCs were detected. The PCCRC rate was 0.376 per 1,000 person-years and the average 5-year PCCRC risk ranged from 0.165% to 0.051%. The rate of PCCRCs was higher at the beginning (0.166%; 95% confidence interval [CI] 0.15%-0.17%) compared with the later period with full implementation of quality control measures (0.027%; 95% CI 0.023%-0.03%). The quality process determined an incremental cost-effectiveness ratio of -$5,670.53 per PCCRC avoided. Conclusions This large cohort study demonstrated that a formal gastroenterologist-led quality assurance framework embedded into the routine operations of a clinical department not only reduces interval cancers but is also cost-effective regarding life years gained and quality-adjusted life years.

Prenatal exposure to maternal smoking and adult lung cancer risk: a nested case-control study using peripheral blood leukocyte DNA methylation prediction of exposure.

A prior study reported no association between prenatal smoking methylation scores and adult lung cancer risk adjusting for methylation-predicted adult smoking, without considering maternal smoking trends by birth cohort. To address this gap, we examined the association between prenatal smoking methylation scores and adult lung cancer, independent of methylation-predicted adult packyears and by birth cohort, in a study nested in CLUE II. Included were 208 incident lung cancer cases ascertained by cancer registry linkage and 208 controls matched on age, sex, and smoking. DNA methylation was measured in prediagnostic blood. We calculated two prenatal smoking scores, using 19 (Score-19) and 15 (Score-15) previously identified CpGs and a methylation-predicted adult packyears score. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) adjusting for adult packyears score and batch effects. Score-15 was positively associated with lung cancer (per standard deviation, OR = 1.40, 95% CI = 1.10-1.79, P-trend = .006), especially in the 1930-1938 birth cohort (OR = 3.43, 95% CI = 1.55-7.60, P-trend = .002). Score-19 was associated only in the 1930-1938 birth cohort (OR = 2.12, 95% CI = 1.15-3.91). Participants with both prenatal scores below the median (vs all other combinations) had lower risk (OR = 0.44, 95% CI = 0.27-0.72), especially in the 1930-1938 birth cohort (OR = 0.16, 95% CI = 0.04-0.62). Among ever smokers, participants with higher prenatal smoking scores had higher risk, irrespective of adult packyears (low: OR = 2.81, 95% CI = 1.38-5.72, high: OR = 2.67, 95% CI = 1.03-6.95). This prospective study suggests a positive association between prenatal smoking exposure and adult lung cancer risk, especially in the 1930-1938 birth cohort, independent of active smoking. Future studies with multiple birth cohorts are needed.

Abstract 3434: Effect modification by levels of sex hormones in the association between adiposity and cancer incidence in the UK Biobank

Abstract Introduction: The association between adiposity and cancer risk differs between sexes for some cancer types. Methods: We prospectively examined adiposity in relation to cancer incidence according to sex hormones in the UK Biobank. Adiposity was assessed by body mass index (BMI) and visceral adipose tissue (VAT), the latter predicted using determinants of age, height, weight, hip circumference, waist circumference, and race. Serum sex hormone binding globulin (SHBG), testosterone, and estradiol were measured using a biochemistry assay and were classified as high or low based on median levels. Cancer incidence was ascertained using ICD-10 codes through cancer registry linkage. For cancer types showing a sex difference in the association between adiposity and cancer incidence, we assessed multiplicative and additive interaction with sex hormones in men and women separately and corrected for multiple testing using false discovery rate. We used Cox regression to calculate the multivariable hazard ratio (HR) of cancer per increase between the 90th to 10th percentile of adiposity (BMI or predicted VAT). Results: During a median follow-up of 13.1 years, we documented 23,964 and 21,045 incident cancer cases among 217,460 men and 256,163 women, respectively. Adiposity showed a much stronger association with higher risk of colorectal, esophageal, and liver cancers in men than women. In men, BMI was more strongly associated with higher risk of colorectal cancer in low vs. high levels of SHBG (HR (95%CI) of 1.47 (1.31-1.64) vs. 1.12 (0.94-1.33) (adjusted Pinteraction = 0.027). In contrast, BMI showed a stronger association in high vs. low levels of SHBG with esophageal (HR = 2.39 vs. 1.62) and liver cancers (HR = 3.24 vs 1.96) in men (adjusted Pinteraction = 0.038 and 0.027, respectively). Among women, BMI was associated with a higher risk of esophageal cancer in those with low SHBG (HR=1.68) but not in those with high SHBG (HR=0.64) (adjusted Pinteraction = 0.025). Similar patterns were observed for predicted VAT. Men with high SHBG levels and high adiposity (BMI and predicted VAT) had 7.63 (5.08-11.46) and 8.92 (5.72 to 13.90), respectively, times higher risk of liver cancer compared to men with low SHBG levels and low adiposity. No effect modification by estradiol or testosterone was detected for any of the cancers studied. Conclusions: The association between adiposity and colorectal, esophageal, and liver cancer differed by sex. SHBG may be an important factor underlying these differences. Citation Format: LeeAnn Lucas, Yujia Lu, Edward L. Giovannucci, Mingyang Song. Effect modification by levels of sex hormones in the association between adiposity and cancer incidence in the UK Biobank [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3434.

Abstract 3442: Factors modifying the association between hormonal contraception and risk of early-onset breast cancer

Abstract Breast cancer rates among women younger than 50 years-old have been steadily increasing since the mid-1990s. There is consistent evidence that use of combination estrogen and progesterone oral contraceptives (OCs)—including contemporary formulations with lower estrogen—increases breast cancer risk. It is unclear, however, if this risk varies by factors such as progestin type in the OC formulation, timing of OC use, histopathologic characteristics of the breast cancer, or individual patient characteristics. This study included premenopausal women aged <50 years and cancer-free when they enrolled in the U.S.-based American Cancer Society Cancer Prevention Study-3 cohort between 2006 and 2013 (n=101,838 women). At enrollment participants responded to a detailed life history questionnaire including questions about type, brand, duration, and recency of OC use. Incident breast cancers diagnosed between 2006-2018 were identified through cancer registry linkages (n=759). Participants were followed until the first of 1) breast cancer diagnosis, 2) age >50 years, or 3) December 31, 2018. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were used to estimate associations between OC use and breast cancer risk. On average, participants were 39.3 years at baseline and were followed for 5.7 years (up to 12.3 years). Current versus never use of OCs for 10+ years was associated with a higher risk of breast cancer (10-<20 years: HR=1.46, 95% CI: 1.03-2.07; 20-<30 years: HR=1.66, 95% CI: 1.14-2.41; 30+ years HR= 2.51, 95% CI: 0.77-8.16). Cessation of OC use progressively attenuated the association down to the null 15 years after discontinuation of use (HR=1.04, 95% CI: 0.73-1.49). Associations with current OC use varied by generation of progestin in the formulation (first generation: HR=1.37, 95% CI: 0.93-2.02; second: HR=1.79, 95% CI: 1.20-2.67; third: HR=1.65, 95% CI: 1.13-2.42; fourth: HR= 0.91, 95% CI: 0.49-1.67). The strongest associations were observed for use of formulations with norgestrel: HR=2.82, 95% CI: 1.54-5.19; norgestimate: HR=1.80, 95% CI: 1.19-2.72; and levonorgestrel: HR=1.56, 95% CI: 1.00-2.43. The OC-breast cancer associations were primarily limited to localized, grade 1 or 2, and ER+ disease. Race, income, body mass index, physical activity, alcohol use, cigarette smoking, parity, and breastfeeding did not appear to modify the associations. There were also no clear differences in the associations based on age at first or last OC use or timing relative to pregnancy. Current, long-term OC use was associated with increased risk of early-onset breast cancer. These data suggest that risks may vary with progestin content, and future studies are needed to define formulations that minimize breast cancer risk while still maximizing protection against other female cancers. Citation Format: Lauren R. Teras, Emily L. Deubler, Mark E. Sherman, Clara Bodelon, Lauren E. McCullough, James M. Hodge, Sicha Chantaprasopsuk, Alpa V. Patel. Factors modifying the association between hormonal contraception and risk of early-onset breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3442.

Cancer Treatment Disparities in People With HIV in the United States, 2001-2019.

People with HIV (PWH) have worse cancer outcomes, partially because of inequities in cancer treatment. We evaluated cancer treatment disparities among PWH, including an assessment of changes in disparities over time. We used data from the HIV/AIDS Cancer Match Study, a population-based HIV and cancer registry linkage to examine diffuse large B-cell lymphoma (DLBCL), Hodgkin lymphoma (HL), and cancers of the cervix, lung, anus, prostate, colon, and female breast. Outcomes included receipt of (1) any cancer treatment and (2) standard therapy among patients with local-stage cancer. We assessed associations between HIV and each outcome by estimating adjusted prevalence odds ratios (aORs) with 95% CI and trends over time. We identified predictors of nonreceipt of cancer treatment in PWH. From 2001 to 2019, compared with people with cancer without HIV (n = 2,880,955), PWH (n = 16,334) were more likely to not receive cancer treatment for cervical cancer (aOR, 2.03 [95% CI, 1.52 to 2.70]), DLBCL (aOR, 1.53 [95% CI, 1.38 to 1.70]), HL (aOR, 1.39 [95% CI, 1.19 to 1.63]), lung cancer (aOR, 1.79 [95% CI, 1.65 to 1.93]), prostate cancer (aOR, 1.32 [95% CI, 1.21 to 1.44]), colon cancer (aOR, 1.73 [95% CI, 1.43 to 2.08]), and breast cancer (aOR, 1.38 [95% CI, 1.07 to 1.77]). Similar associations were observed in PWH with local-stage cancers although no difference was observed for anal cancers. The association between HIV and nonreceipt of cancer treatment significantly decreased over time for breast, colon, and prostate cancers (all P trend <.0001), but PWH remained less likely to receive treatment in 2014-2019 for DLBCL, cervix, and lung cancers. Among PWH, Black individuals, people who inject drugs, and those 65 years and older were less likely to receive cancer treatment. Disparities in receipt of cancer treatment persist for PWH in the United States in contemporary time periods. Solutions to address inequitable receipt of cancer treatment among PWH are urgently needed.

Commercial Versus Medicaid Insurance and Use of High-Priced Anticancer Treatments.

Because the markups on cancer drugs vary by payor, providers' financial incentive to use high-price drugs is differential according to each patient's insurance type. We evaluated the association between patient insurer (commercial vs Medicaid) and the use of high-priced cancer treatments. We linked cancer registry, administrative claims, and demographic data for individuals diagnosed with cancer in North Carolina from 2004 to 2011, with either commercial or Medicaid insurance. We selected cancers with multiple FDA-approved, guideline-recommended chemotherapy options and large price differences between treatment options: advanced colorectal, lung, and head and neck cancer. The outcome was a receipt of a higher-priced option, and the exposure was insurer: commercial versus Medicaid. We estimated risk ratios (RRs) for the association between insurer and higher-priced treatment using log-binomial models with inverse probability of exposure weights. Of 812 patients, 209 (26%) had Medicaid. The unadjusted risk of receiving higher-priced treatment was 36% (215/603) for commercially insured and 27% (57/209) for Medicaid insured (RR: 1.31, 95% CI: 1.02-1.67). After adjustment for confounders the association was attenuated (RR: 1.15, 95% CI: 0.81-1.65). Exploratory subgroup analysis suggested that commercial insurance was associated with increased receipt of higher-priced treatment among patients treated by non-NCI-designated providers (RR: 1.53, 95% CI: 1.14-2.04). Individuals with Medicaid and commercial insurance received high-priced treatments in similar proportion, after accounting for differences in case mix. However, modification by provider characteristics suggests that insurance type may influence treatment selection for some patient groups. Further work is needed to determine the relationship between insurance status and newer, high-price drugs such as immune-oncology agents.

Oral prednisolone and warfarin and risk of oesophageal cancer: A case-control study.

A recent epidemiological study systematically screened 250 prescription medications for associations with oesophageal cancer risk, using Scottish data, and identified an increased risk with use of prednisolone and warfarin. We investigated whether oral prednisolone or warfarin use was associated with increased oesophageal cancer risk. A case-control study was conducted within the Clinical Practice Research Datalink. In the primary analysis oesophageal cancer cases were identified from linked cancer registry records. Up to 5 cancer-free controls were matched to each case (based upon sex, birth year, GP practice and year of GP registration). Prednisolone and warfarin medications were identified from prescribing records. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression after adjusting for covariates including demographics, comorbidities and medication use. There were 4552 oesophageal cancer cases and 22,601 matched control participants. Overall, there was no evidence of an increased risk of oesophageal cancer with oral prednisolone use (unadjusted OR=1.16 95% CI 1.06, 1.27 and adjusted OR=0.99 95% CI 0.89, 1.11) or warfarin use (unadjusted OR=1.12 95% CI 0.99, 1.28 and adjusted OR=1.08 95% CI 0.92, 1.27). In this large population-based study, oral prednisolone and warfarin were not associated with oesophageal cancer risk.

An Updated Evaluation of Atrazine-Cancer Incidence Associations among Pesticide Applicators in the Agricultural Health Study Cohort.

Atrazine is a common agricultural herbicide in the United States. Few epidemiologic studies have evaluated cancer risks. Previous analyses within the Agricultural Health Study (AHS) have found some evidence of associations with cancer at some sites. We updated exposure information, incident cases, and follow-up time to assess the associations between atrazine use and cancer at specific sites in the AHS. Information about lifetime pesticide use was reported at enrollment (1993-1997) and follow-up (1999-2005). Among 53,562 pesticide applicators in North Carolina and Iowa, we identified 8,915 incident cases through cancer registry linkages through 2014 (North Carolina)/2017 (Iowa). We used Poisson regression to evaluate the association between ever/never and intensity-weighted lifetime days of atrazine use and incident cancer risk controlling for several confounders. We also evaluated lagged exposures and age-stratified risk. Approximately 71.2% of applicators reported ever using atrazine, which was associated with lung cancer [; 95% confidence interval (CI): 1.04, 1.46]. Aggressive prostate cancer risk was increased in the highest quartile (; 95% CI: 0.95, 1.52; ), particularly among those years old (; 95% CI: 1.61, 5.75; ; ). Among applicators years of age, ever-atrazine use was associated with non-Hodgkin lymphoma (NHL) (; 95% CI: 1.10, 5.38; ). For soft tissue sarcoma, there was an elevated risk in the highest tertile of exposure (: 2.54; 95% CI: 0.97, 6.62; ). In analyses with exposure lagged by 25 years, there was an elevated risk of pharyngeal (; 95% CI: 1.45, 6.36; ) and kidney (; 95% CI: 1.15, 2.29; ) cancers. We observed suggestive associations with some malignancies in overall, age-specific, and lagged analyses. Associations with aggressive prostate cancer and NHL were apparent among those diagnosed at younger ages and with cancers of the pharynx and kidney, and soft tissue sarcomas were observed in lagged analyses. Further work is needed to confirm these observed associations and elucidate potential underlying mechanisms. https://doi.org/10.1289/EHP13684.

Estimated incidence of disruptions to event-free survival from non-metastatic cancers in New South Wales, Australia - a population-wide epidemiological study of linked cancer registry and treatment data.

Population cancer registries record primary cancer incidence, mortality and survival for whole populations, but not more timely outcomes such as cancer recurrence, secondary cancers or other complications that disrupt event-free survival. Nonetheless, indirect evidence may be inferred from treatment data to provide indicators of recurrence and like events, which can facilitate earlier assessment of care outcomes. The present study aims to infer such evidence by applying algorithms to linked cancer registry and treatment data obtained from hospitals and universal health insurance claims applicable to the New South Wales (NSW) population of Australia. Primary invasive cancers from the NSW Cancer Registry (NSWCR), diagnosed in 2001-2018 with localized or regionalized summary stage, were linked to treatment data for five common Australian cancers: breast, colon/rectum, lung, prostate, and skin (melanomas). Clinicians specializing in each cancer type provided guidance on expected treatment pathways and departures to indicate remission and subsequent recurrence or other disruptive events. A sample survey of patients and clinicians served to test initial population-wide results. Following consequent refinement of the algorithms, estimates of recurrence and like events were generated. Their plausibility was assessed by their correspondence with expected outcomes by tumor type and summary stage at diagnosis and by their associations with cancer survival. Kaplan-Meier product limit estimates indicated that 5-year cumulative probabilities of recurrence and other disruptive events were lower, and median times to these events longer, for those staged as localized rather than regionalized. For localized and regionalized cancers respectively, these were: breast - 7% (866 days) and 34% (570 days); colon/rectum - 15% (732 days) and 25% (641 days); lung - 46% (552 days) and 66% (404 days); melanoma - 11% (893 days) and 38% (611 days); and prostate - 14% (742 days) and 39% (478 days). Cases with markers for these events had poorer longer-term survival. These population-wide estimates of recurrence and like events are approximations only. Absent more direct measures, they nonetheless may inform service planning by indicating population or treatment sub-groups at increased risk of recurrence and like events sooner than waiting for deaths to occur.

Abstract B128: Cancer treatment inequities in people with HIV in the United States, 2001-2019

Abstract Background: People with HIV (PWH) are at increased risk of both AIDS-defining (i.e., Kaposi sarcoma, non-Hodgkin lymphoma, cervical cancer) and non-AIDS-defining cancers. Prior work with data from 1996-2010 reported that PWH with cancer in the US were less likely to receive cancer treatment. However, an updated analysis is warranted to see if the disparity in receipt of cancer treatment persists for PWH. Methods: We used data from the HIV/AIDS Cancer Match (HACM) Study, a population-based HIV and cancer registry linkage in 13 U.S. states to examine diffuse large B-cell lymphoma (DLBCL), Hodgkin-lymphoma (HL), and cancers of the cervix, lung, anal, prostate, colon, and breast. For each cancer type, we estimated adjusted prevalence odds ratios (aOR) and 95% confidence intervals using logistic regression to assess the relationship between HIV status and cancer treatment adjusted for race, age at cancer diagnosis, sex, cancer stage, year of cancer diagnosis and region. In addition, we used logistic regression to identify predictors of cancer treatment receipt in PWH by cancer site, including race, age at cancer diagnosis, sex, HIV mode of transmission, cancer stage, calendar year period of cancer diagnosis and region. Results: We evaluated 11,657 PWH with cancer and 2,687,946 patients with cancer without HIV. A total of 9,030 PWH with cancer received any cancer treatment (77.5%) compared to 2,218,200 individuals with cancer, without HIV (82.5%) who received any cancer treatment. HIV was associated with lower odds of receiving cancer treatment compared to people with cancer and no HIV for cervical cancer (aOR=0.46 95% CI: 0.35-0.60), DLBCL (0.55, 0.50-0.62), HL (0.64,0.53-0.76), lung cancer (0.57, 0.52-0.62), prostate cancer (0.74, 0.66-0.83), and colon cancer (0.60, 0.50-0.74). Non-Hispanic (NH)-Black PWH with lung cancer were less likely to receive cancer treatment compared to NH-White PWH. People who inject drugs (PWID), PWID/men who have sex with men (MSM) and heterosexual PWH were less likely to be treated for DLBCL, lung cancer and prostate cancer compared to MSM. In contrast, PWID were more likely to receive cancer treatment for anal cancer than MSM. For PWH with DLBCL, those diagnosed in 2011-2014 were 46% more likely to receive treatment (aOR=1.46, 1.00-2.12) compared to those diagnosed in 1996-2000. Conclusion: Inequities in receipt of cancer treatment persist for PWH in the US. We saw for some cancers, PWH had lower odds of receiving cancer treatment, even after controlling for important factors. Beginning in 2018, the National Comprehensive Cancer Network (NCCN) published cancer treatment guidelines explicit for PWH. Despite improvements in HIV-related treatment, inequitable receipt of cancer treatment will continue to prolong and exacerbate disparities among people with cancer with and without HIV. Citation Format: Jennifer K. McGee-Avila, Gita Suneja, Qianlai Luo, Marie Josephe Horner, Ann Rositch, Eric Engels, Meredith S. Shiels, Jessica Islam. Cancer treatment inequities in people with HIV in the United States, 2001-2019 [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B128.

Decline in the Incidence of Distant Recurrence of Breast Cancer: A Population-Based Health Record Linkage Study, Australia 2001-2016.

We investigated differences in cumulative incidence of first distant recurrence (DR) following non-metastatic breast cancer over a time period when new adjuvant therapies became available in Australia. We conducted a health record linkage study of females with localized (T1-3N0) or regional (T4 or N+) breast cancer in the New South Wales Cancer Registry in 2001 to 2002 and 2006 to 2007. We linked cancer registry records with administrative records from hospitals, dispensed medicines, radiotherapy services, and death registrations to estimate the 9-year cumulative incidence of DR and describe use of adjuvant treatment. The study included 13,170 women (2001-2002 n = 6,338, 2006-2007 n = 6,832). The 9-year cumulative incidence of DR was 3.6% [95% confidence interval (CI), 2.3%-4.9%] lower for 2006-2007 diagnoses (15.0%) than 2001-2002 (18.6%). Differences in the annual hazard of DR between cohorts were largest in year two. DR incidence declined for localized and regional disease. Decline was largest for ages <40 years (absolute difference, 14.4%; 95% CI, 8.3%-20.6%), whereas their use of adjuvant chemotherapy (2001-2002 49%, 2006-2007 75%) and HER2-targeted therapy (2001-2002 0%, 2006-2007 16%) increased. DR did not decline for ages ≥70 years (absolute difference, 0.9%; 95% CI, -3.6%-1.8%) who had low use of adjuvant chemotherapy and HER2-targeted therapy. This whole-of-population study suggests that DR incidence declined over time. Decline was largest for younger ages, coinciding with changes to adjuvant breast cancer therapy. Study findings support the need for trials addressing questions relevant to older people and cancer registry surveillance of DR to inform cancer control programs.

Type 2 Diabetes and Colorectal Cancer Risk

Type 2 diabetes and colorectal cancer (CRC) disproportionately burden indviduals of low socioeconomic status and African American race. Although diabetes is an emerging CRC risk factor, associations between diabetes and CRC in these populations are understudied. To determine if diabetes is associated with CRC risk in a cohort representing understudied populations. This cohort study uses data from the prospective Southern Community Cohort Study in the US, which recruited from 2002 to 2009 and completed 3 follow-up surveys by 2018. Of about 85 000 participants, 86% enrolled at community health centers, while 14% were enrolled via mail or telephone from the same 12 recruitment states. Participants with less than 2 years of follow-up, previous cancer diagnosis (excluding nonmelanoma skin cancer) at enrollment, missing enrollment diabetes status, diabetes diagnosis before age 30, and without diabetes at enrollment with no follow-up participation were excluded. Data were analyzed from January to September 2023. Physician-diagnosed diabetes and age at diabetes diagnosis were self-reported via survey at enrollment and 3 follow-ups. Diabetes diagnosis was hypothesized to be positively associated with CRC risk before analysis. Incident CRC was assessed via state cancer registry and National Death Index linkage. Hazard ratios and 95% CIs were obtained via Cox proportional hazard models, using time-varying diabetes exposure. Among 54 597 participants, the median (IQR) enrollment age was 51 (46-58) years, 34 786 (64%) were female, 36 170 (66%) were African American, and 28 792 (53%) had income less than $15 000 per year. In total, 289 of 25 992 participants with diabetes developed CRC, vs 197 of 28 605 participants without diabetes. Diabetes was associated with increased CRC risk (hazard ratio [HR], 1.47; 95% CI, 1.21-1.79). Greater associations were observed among participants without colonoscopy screening (HR, 2.07; 95% CI, 1.16-3.67) and with smoking history (HR, 1.62; 95% CI, 1.14-2.31), potentially due to cancer screening differences. Greater associations were also observed for participants with recent diabetes diagnoses (diabetes duration <5 years compared with 5-10 years; HR, 2.55; 95% CI, 1.77-3.67), possibly due to recent screening. In this study where the majority of participants were African American with low socioeconomic status, diabetes was associated with elevated CRC risk, suggesting that diabetes prevention and control may reduce CRC disparities. The association was attenuated for those who completed colonoscopies, highlighting how adverse effects of diabetes-related metabolic dysregulation may be disrupted by preventative screening.

Disparities in time to initiation of treatment among patients with metastatic solid tumors in Washington state.

153 Background: Timely initiation of cancer treatment can improve quality of life and survival. As part of a large, statewide effort aimed at improving cancer care quality, we estimated time from diagnosis to initial treatment among patients with newly diagnosed metastatic cancers. Methods: Using an established linkage of Washington state cancer registry records with claims data from commercial insurers, Medicare, and Medicaid, we identified patients diagnosed with metastatic solid tumors diagnosed between 2017 and 2019. Time to first treatment with chemotherapy (CT), radiation therapy (RT) or hormone therapy (HT) was measured as the number of days from first visit at an oncology clinic to the date of first treatment. Patients seen at multiple oncology clinics were assigned to the clinic with the greatest number of physician visits. We used linear regression to evaluate factors associated with timeliness of care (tumor type, age, sex, race/ethnicity, insurance type, resident neighborhood deprivation, comorbidity). Results: 3,237 patients met inclusion criteria with median time to initial treatment of 34 days (CT 35 days; RT 28 days; HT 37 days). Mean time to treatment was 45.2 days (CT 47.6 days; RT 39.4 days; HT 49.0 days). Factors that were significantly associated with time to initiation of treatment are shown in the Table. Conclusions: Black and Medicaid-enrolled patients with metastatic cancers experience significantly longer times to first treatment. Future research will focus on identifying factors underlying the observed differences so that interventions can be designed to reduce these disparities.[Table: see text]

BRCA1/2 germline testing among eligible persons with breast cancer in Washington state: A retrospective study using state cancer registry and claims data.

154 Background: Clinical practice guidelines have recommended germline testing certain groups of breast cancer patients (men, younger women, and triple negative) for pathogenic BRCA1/2 mutations since 1996. We linked cancer registry records with enrollment and claims records from public and commercial insurers in Washington state to assess factors associated with BRCA1/2 testing among eligible persons with breast cancer. Methods: The database consisted of Washington SEER and state cancer registry records linked with claims records from commercial insurers (Premera Blue Cross, Regence Blue Shield), Medicare, Medicaid, and the Washington State Employee Benefit Plan. Eligible patients were diagnosed with breast cancer between 2017-2019 and were age &lt;= 50 female, any age male, or with triple negative cancer. Other inclusion criteria included first primary cancer, alive at least 3 months following diagnosis, and continuous insurance enrollment from 2 months prior to 24 months following diagnosis. We used multivariable logistic regression to examine factors associated with BRCA1/2 testing. In a secondary analysis, we examined whether receipt of testing was associated with bilateral mastectomy. Results: The study population included 1,358 women and 43 men (80.2% were non-Hispanic White, 4.1% non-Hispanic Black, 11.7% non-Hispanic Asian, and 4.9% Hispanic.) The insurance composition was as follows: 56% commercial, 15% Medicare, 19% Medicaid; 10% multiple insurers. Overall, 63% received BRCA1/2 testing. Factors that were significantly associated with testing are shown in the table. In the secondary regression model, the association between BRCA1/2 testing and bilateral mastectomy was positive (OR 1.45, 95% CI 1.07-1.98). Conclusions: Despite a trend towards more testing over time, BRCA1/2 germline testing remains underutilized among persons who are eligible for testing, with significant disparities among Medicaid and Medicare enrollees. Testing may influence management, but further study is required. Patients would benefit from more effective integration of clinical guidelines into practice.[Table: see text]

Clinical Outcomes in Patients With Refractory Anemia With Excess Blasts (RAEB) Who Receive Hypomethylating Agents (HMAs)

BackgroundWe sought to understand the clinical effectiveness associated with use of hypomethylating agents (HMAs) azacitidine (AZA) and decitabine (DEC) for patients with refractory anemia with excess blasts (RAEB; an established proxy for higher-risk myelodysplastic syndromes/neoplasms) in contemporary and representative real-world settings. Patients and methodsWe used the Surveillance, Epidemiology and End Results (SEER)-Medicare database, a linkage of cancer registry and Medicare claims data, to identify patients aged ≥ 66 years diagnosed with RAEB, between 2009 and 2017 in the United States, and who received AZA or DEC as first-line therapy. Outcomes measured were overall survival (OS), event-free survival (EFS), and incidence of progression-related acute myeloid leukemia (AML). ResultsOf 973 eligible patients, 738 (75.8%) received AZA and 235 (24.2%) received DEC; 6.4% received hematopoietic cell transplantation during follow-up. In the overall population, median OS was 13.9 months (95% confidence interval [CI]: 12.9-15.0), median EFS was 5.2 months (95% CI: 4.9-5.7), and 38.0% of patients progressed to AML. Incidences of AML progression and death were 25.6% and 29.9%, respectively, at Year 1, and 34.3% and 44.8%, respectively, at Year 2. There were no significant differences in clinical benefits between AZA and DEC. ConclusionMedian OS with both HMAs remained significantly shorter than in the AZA-001 clinical trial, highlighting how patient outcomes vary between clinical and real-world settings. Further research is required to understand why these disparities exist.

Real-World Treatment Patterns of Older Adults with Locally Advanced SCCHN Using SEER-Medicare

Roughly 50-67% of patients with squamous cell carcinomas of the head and neck (SCCHN) present with locally advanced (LA) disease and 65% of them relapse after initial therapy. The standard of care for LA SCCHN is definitive therapy (DT), a combination of surgery and or radiation therapy (RT), with or without platinum-based chemotherapy/cetuximab (chemo), that has been shown to optimize long term disease control. Few published analyses have characterized recent real-world treatment (Tx) patterns of older adults with LA SCCHN in the US. We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, a linkage of cancer registry and claims data, to identify patients diagnosed with LA SCCHN (first and only cancer) from 2010 to 2017 who initiated a relevant Tx (Tx initiation date defined as index date) and were continuously enrolled in Medicare Parts A, B, and D from 12 months pre-index until death or 12 months post-index. We used clinical guidelines regarding timing and frequency of treatments to build an algorithm that used Medicare claims to categorize initial Tx as non-DT, non-surgical DT (concomitant chemo+RT (cCRT) or chemotherapy before RT/cCRT), or surgical DT (surgery then RT/cCRT ± prior chemo). We identified 1052 older adults with LA SCCHN (median age 73 years, 37% female, and 81% non-Hispanic white) whose initial treatment was started a median of 26 days after initial diagnosis. Of the 610 patients who received a DT as their initial Tx, 23.3% of patients had a subsequent Tx: 3.8% received immunotherapy-containing regimens (IO), and the most common subsequent Tx were surgery only (7.7%), chemotherapy only (3.6%), and RT only (3.4%). The median time to next Tx (TTNT) differed by DT category and primary tumor site. (Table 1) CONCLUSION: In this descriptive analysis, we provided an update on the Tx patterns of older adults with LA SCCHN in the US, for whom there have been no novel FDA approvals in over a decade. We found that a large proportion (42%) of patients did not receive DT regimens in the real-world setting despite known benefits in LA SCCHN. Roughly a quarter of patients required subsequent Tx. Availability of IO was low due to approvals after 2017. These findings suggest a need for novel therapies that can improve outcomes in LA SCCHN.