Population-based Cancer Research Articles

A Glimpse into the Epidemiology of Geriatric Cancers in India: Report from the Indian Population Based Cancer Registries.

Indian population is aging and the cancer rates are rising. Older adults (OAs)(≥60 years) with cancer require specialized care. However, data on geriatric cancer epidemiology is scarce. The study compiled the geriatric cancer data from the published reports(2012-2014) of Indian population-based cancer registries(PBCRs). Of the 1,61,363 cancers registered in the Indian PBCRs, 72,446(44.9%) occur in OAs, with 21,805(30.1%), 18,349(25.3%), 14,645(20.2%), and 17,647(24.4%) occurring in 60-64, 65-69, 70-74, and ≥75year age groups. The truncated incidence rates for OAs are 555.9,404.5, and 481.9 for males, females, and OA populations respectively. The common cancers are lung, prostate, and esophagus cancers in males, breast, cervix, and lung in females. The overall common cancers are lung, prostate, and breast. While >50% of the incident cases of prostate, and bladder cancers occurred in OAs, <20% of Hodgkin lymphoma and thyroid cancers occurred in OAs. OA cancer epidemiology has a regional variation, highest in South India and lowest in Western India. The current study quantifies the cancer burden in the Indian geriatric population. Understanding the epidemiology of geriatric cancers is vital to health program planning and implementation. Increased awareness, focused resource allocation, research, and national policies for streamlining care will all help to improve geriatric cancer outcomes.

Quality assessment of a rural population-based cancer registry (PBCR) at Ratnagiri, Maharashtra, India for the years 2017-18.

Cancer registries are valuable resources for cancer control and research. To justify their purpose, their data should be of satisfactory quality by being comparable internationally, complete in their coverage, valid in their values and timely in reporting. This study aimed to assess the quality of the Ratnagiri Population Based Cancer Registry's data for the years 2017-18 across the four dimensions of data quality. Regarding comparability, the registry procedure was reviewed vis-à-vis the rules they follow for cancer registry operation. We have used four methods for validity: re-abstraction and re-coding, diagnostic criteria methods- like the percentage of microscopically verified (MV%) and of death certificate only (DCO%) cases, missing information like proportion of cases of primary site unknown (PSU%) and internal validity. Semi-quantitative methods were employed for assessing completeness. Timeliness for all years of registry functioning was assessed qualitatively. The overall accuracy rate of the registry was found to be 91.1% (94.7% for demographic and 88% for tumour details). Mortality to incidence ratios were found to be 0.50 for females and 0.59 for males. MV% was found to be 90.8% for males and 91.5% for females. The average number of sources per case was found to be 1.5. DCO% was found to be 2.7%. PSU% was 7.4%. We have positive results regarding the data's validity and comparability, but there is scope for improvement concerning completeness. Continuous training of the registry personnel and monitoring of the registry is recommended.

Risk factors and clinical impact of thrombosis during induction chemotherapy for pediatric acute lymphoblastic leukemia: A report from CYP-C.

Thromboembolism (TE) is associated with reduced survival in pediatric acute lymphoblastic leukemia (ALL). It has been hypothesized that TE might signal leukemic aggressiveness. The objective was to determine risk factors for TE during ALL induction (TEind ) therapy and whether TEind is associated with treatment refractoriness. This retrospective cohort study using the population-based Cancer in Young People Canada (CYP-C) registry included children <15 years of age diagnosed with ALL (2000-2019) and treated at one of 12 Canadian pediatric centers outside of Ontario. Univariate and multivariable logistic regression models were used to determine risk factors for TEind and whether TEind predicted induction failure and ALL treatment intensification. The impact of TEind on overall and event-free survival was estimated using Cox proportional hazard regression models. The study included 2589 children, of which 45 (1.7%) developed a TEind . Age (<1 year and ≥10 years vs. 1-<10 years), T-cell phenotype, high-risk ALL, and central nervous system involvement were all associated with TEind in univariate analysis. Age and T-cell phenotype remained independent predictors of TEind in multivariable analysis. Induction failure occurred in 53 patients (2.1%). TEind was not associated with induction failure (OR: not estimable) or treatment intensification (adjusted OR [95% CI]: 0.66 [0.26-1.69]). TEind was independently associated with overall survival (adjusted HR [95% CI]: 2.54 [1.20-5.03]) but not event-free survival (adjusted HR [95% CI] 1.86 [0.98-3.51]). In this population-based study of children treated with contemporary chemotherapy protocols, TEind was associated with age and T-cell phenotype and mortality but did not predict induction failure.

The epidemiology of haematological cancers in Sarawak, Malaysia (1996 to 2015)

BackgroundPublished epidemiological studies of haematological cancers are few. Hereby we present a 20-year epidemiological data of haematological cancers in Sarawak from a population-based cancer registry.MethodsHaematological cancer cases with ICD-10 coded C81-C96 and ICD-O coded /3 diagnosed from 1996 to 2015 were retrieved from Sarawak Cancer Registry. Adult was defined as those 15 years and above. Incidence rate (IR) was calculated based on yearly Sarawak citizen population stratified to age, gender, and ethnic groups. Age-standardised IR (ASR) was calculated using Segi World Standard Population.ResultsA total of 3,947 cases were retrieved and analysed. ASR was 10 and male predominance (IR ratio 1.32, 95%CI 1.24,1.41). Haematological cancers generally had a U-shaped distribution with lowest IR at age 10–14 years and exponential increment from age 40 years onwards, except acute lymphoblastic leukaemia (ALL) with highest IR in paediatric 2.8 versus adult 0.5. There was a significant difference in ethnic and specific categories of haematological cancers, of which, in general, Bidayuh (IR ratio 1.13, 95%CI 1.00, 1.27) and Melanau (IR ratio 0.54, 95%CI 0.45, 0.65) had the highest and lowest ethnic-specific IR, respectively, in comparison to Malay. The ASR (non-Hodgkin lymphoma, acute myeloid leukaemia, ALL, chronic myeloid leukaemia, and plasma cell neoplasm) showed a decreasing trend over the 20 years, -2.09 in general, while Hodgkin lymphoma showed an increasing trend of + 2.80. There was crude rate difference between the 11 administrative divisions of Sarawak.ConclusionsThis study provided the IR and ASR of haematological cancers in Sarawak for comparison to other regions of the world. Ethnic diversity in Sarawak resulted in significant differences in IR and ASR.

Cancer survival: left truncation and comparison of results from hospital-based cancer registry and population-based cancer registry.

Cancer survival is an important indicator for evaluating cancer prognosis and cancer care outcomes. The incidence dates used in calculating survival differ between population-based registries and hospital-based registries. Studies examining the effects of the left truncation of incidence dates and delayed reporting on survival estimates are scarce in real-world applications. Cancer cases hospitalized at Nantong Tumor Hospital during the years 2002-2017 were traced with their records registered in the Qidong Cancer Registry. Survival was calculated using the life table method for cancer patients with the first visit dates recorded in the hospital-based cancer registry (HBR) as the diagnosis date (OSH), those with the registered dates of population-based cancer (PBR) registered as the incidence date (OSP), and those with corrected dates when the delayed report dates were calibrated (OSC). Among 2,636 cases, 1,307 had incidence dates registered in PBR prior to the diagnosis dates of the first hospitalization registered in HBR, while 667 cases with incidence dates registered in PBR were later than the diagnosis dates registered in HBR. The 5-year OSH, OSP, and OSC were 36.1%, 37.4%, and 39.0%, respectively. The "lost" proportion of 5-year survival due to the left truncation for HBR data was estimated to be between 3.5% and 7.4%, and the "delayed-report" proportion of 5-year survival for PBR data was found to be 4.1%. Left truncation of survival in HBR cases was demonstrated. The pseudo-left truncation in PBR should be reduced by controlling delayed reporting and maximizing completeness. Our study provides practical references and suggestions for evaluating the survival of cancer patients with HBR and PBR.

Methylated DNA biomarkers and incident cancer in the American Cancer Society (ACS) Cancer Prevention Study-3 (CPS-3) cohort.

3004 Background: Multi-cancer early detection (MCED) tests are being developed to complement current single-cancer screening, and are based on next-generation sequencing of cell-free DNA in blood plasma with subsequent analysis of genomic features by machine-learning algorithms. To evaluate the detectability of cancer signals in individuals without known cancer at the time of blood draw, we assessed pre-diagnostic signals using a previously validated locked, methylation-based assay in plasma samples from the ACS CPS-3 cohort. Methods: CPS-3 is a prospective cohort study of cancer incidence and mortality. Participants (N=294,000) donated a blood sample (36 mL) at enrollment (2006-2013) and are followed for cancer outcomes via routine linkages with population-based cancer and death registries. Selected participants diagnosed with cancer within 3 years (Y) of blood donation and an equivalent number of matched non-cancer participants were chosen for processing. Despite differences in sample collection (tube, protocol) and long storage time in freezer, standard requirements for MCED sample quality were applied. Primary outcome: demonstrate that cancer signal was detectable via the MCED test up to 3Y prior to conventional diagnosis. Secondary outcomes: assess detectability based on time from blood draw and other clinical factors. Sampling weights were considered in the statistical analyses. Results: Of 268,726 CPS-3 participants, 2,850 were selected and assayed by cohort sampling, and 2,754 were included in the primary analysis set. CPS-3 cohort demographics and cancer incidence patterns compared to Surveillance, Epidemiology, and End Results suggested that this cohort is younger and healthier than the U.S. population. The test negative rate was 100% among non-cancers. The test positive rate (TPR) stratified by time between blood draw and clinical diagnosis was 2.3% (3Y), 6.0% (2Y), 15.2% (1Y). For eventually fatal cancers, TPR was 5.1% (3Y), 21.6% (2Y), 55.1% (1Y) vs 1.8%, 4.1%, 10.2% for non-fatal cancers. By stage, within 1Y, TPR was 73.7% for Distant at 4-6 months (M) and 94.1% at 1-3M vs 26.7% for Regional at 4-6M and 71.0% at 1-3M. The overall accuracy of predicting cancer signal origin was 95% (1Y). Many cancers were detected 3Y prior to clinical diagnosis: for example, a case of colon/rectum cancer at Regional stage was detected at 991 days. Conclusions: The ACS CPS-3 cohort includes persons at lower-than-average risk of cancer but offered a biospecimen repository with sufficient plasma samples to assess the preclinical detectability of cancer signals by retrospective evaluation. Rapid changes in detectability over time underscore the short preclinical time scales for aggressive cancers to develop, and therefore to be detected. These insights into cancer biology reinforce the importance of pre-diagnostic samples in the study of cancer signals for early detection.

High burden of invasive and non-invasive cancer among women aged 20–49 years: the situation in Geneva, Switzerland

BackgroundThe pattern of cancer among young adults aged 20–49 years is different than that observed in other age groups, most notably women present higher rates than those observed among men. Estimations of the burden of cancer disease among women of this age group, however, rarely include both invasive and non-invasive disease.MethodsWe calculated incidence rates of invasive and non-invasive cancers for women and men aged 20–49 years and by cancer site for the period 2014–2018 in the canton of Geneva, Switzerland using data from the population-based cancer registry.ResultsBetween 2014 and 2018, the incidence rates of invasive and non-invasive cancers among women were 177.6/100,000 and 166.4/100,000, respectively. The rates among men of the same age were 110.6/100,000 and 31.8/100,000, respectively. Just three cancers, breast, thyroid and melanoma accounted for 70% of all invasive cancers among women. In situ cervical cancer represented over 70% of non-invasive disease.ConclusionCancer among women aged 20–49 years is quite frequent. This is primarily a result of increasing risk, increased diagnosis or both and highlights the need for better primary prevention strategies, personalized risk assessment and tailored screening, as well as increased awareness of women and health professionals about health risks in young adults.

The Association Between Cancer and Alzheimer's-Type Neuropathology: A Community-Based Cohort Study

Background: Cancer and Alzheimer's disease are common diseases in aging populations. Intriguingly, prior research has reported a lower incidence of Alzheimer's disease dementia among individuals with a history of cancer. Both are prevalent and lethal conditions. The current study was conducted to investigate the association of cancer history with neuropathological and cognitive features. Methods: Data were drawn from elderly, longitudinally evaluated participants in a community-based cohort study of aging and dementia who came to autopsy at the University of Kentucky Alzheimer's Disease Research Center. The data were linked to the Kentucky Cancer Registry, which is a population-based state cancer surveillance system, to obtain cancer-related data. We examined the relationship between cancer history, clinical dementia diagnoses, Mini-Mental State examination test scores, and neuropathological features using inverse probability weighting to address confounding and selection bias. Results: Included participants (n = 785) had a mean ±SD age of death of 83.8 ±8.6 years; 60.1% were female. Positive cancer history was determined in 190 (24.2%) participants. The prevalence of at least one APOE ε4 allele was lower among participants with cancer history compared to cancer-free participants (32.6% vs 42.0%, P = 0.0063). Participants with cancer history had lower odds of MCI/Dementia, and higher cognitive test scores (e.g., comparing MMSE scores evaluated at six and &amp;lt; two years prior to death., P &amp;lt; 0.001). Cancer history was also associated with reduced odds of intermediate (III/IV) or severe (V/VI) Braak Neurofibrillary tangle stages, moderate/frequent neuritic plaques, moderate/frequent diffuse plaques, and moderate/severe cerebral amyloid angiopathy (all P&amp;lt;0.05). By contrast, TDP-43, √é±-synuclein, and cerebrovascular pathologies were not associated with cancer history. Conclusion: In this study, we showed that cancer history was associated with a lower burden of Alzheimer's disease pathology and clinical dementia. These findings provide an additional basis of support for prior epidemiological research reporting a protective association between cancer and Alzheimer's disease-type dementia.

Abstract 1434: Molecular characteristics of breast cancer patients subjected to screening for germline predisposition in a population-based observational study

Abstract An estimated 5-10% of breast cancer cases carry germline mutations in genes associated with a moderate to strong breast cancer risk, like BRCA1 and BRCA2. These mutations can influence disease onset, progression, biology of the tumor, potential for therapy, risk of recurrence and cancer risk of close relatives. This warrants clinical germline screening for such gene variants according to national guidelines on patient selection. In this study we aimed to molecularly and clinicopathologically contrast clinically screened patients and their tumors against unscreened patients. For this we used a population-based breast cancer cohort from southern Sweden with 6660 patients (14% of which had been screened) with accompanying RNA-sequencing and clinicopathological registry data. Screening subsets were analyzed within five clinically relevant breast cancer subgroups based on hormone receptor and lymph node status. Among other features, we investigated clinicopathological characteristics, risk of tumor recurrence, survival outcomes, tumor proliferation markers, immune cell content, genes differentially expressed and the pathways in which they were involved. Most differences were found in the triple negative breast cancer (TNBC) subgroup: when compared to patients that had not been screened, the screened subset contained younger individuals showing better overall survival, more proliferative tumors with upregulated genes that belong to DNA replication and double-strand break repair processes, lower proportion of M2 macrophages and higher proportion of T-helper 2 cells. As so, Swedish screening guidelines divide TNBC cases into two separate subsets possibly by selecting distinct underlying biological and mutational mechanisms associated with DNA repair deficiency (e.g., through BRCA1/2-deficiency), a disparity not seen in other breast cancer clinical subgroups. Understanding the molecular landscape of defined screening populations may improve future guideline updates, which in turn would also improve patient and resource handling. Citation Format: Deborah F. Nacer de Oliveira, Johan Vallon-Christersson, Hans Ehrencrona, Anders Kvist, Åke Borg, Johan Staaf. Molecular characteristics of breast cancer patients subjected to screening for germline predisposition in a population-based observational study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1434.

Verification of the association of the cycle threshold (Ct) values from HPV testing on Cobas4800 with the histologic grades of cervical lesions using data from two population-based cervical cancer screening trials

ObjectiveTo verify the association of high-risk human papillomavirus (hrHPV) viral load reflected by cycle threshold (Ct) values from HPV testing on Cobas4800 assay with the histologic grades of cervical lesions via analysis on the combined data from two cervical cancer screening trials and to explore the referability of Ct values in management of the abnormalities from cervical cancer primary screening.MethodsWe analyzed the data from Chinese Multi-Center Screening Trial (CHMUST) and BUJI Cervical Cancer Screening Study Project (BUJI Study). All data to be analyzed in this paper were related to provider-collected samples. One-way ANOVA was performed to compare the Ct values among different histological groups, and Kendall’s tau-b correlation was applied to examine the association between Ct values and cervical lesion grades. The stepwise incidence of CIN2+ and CIN3+ in every 100 HPV positive individuals were calculated according to the descending of the genotype specific Ct values. The highest Ct values related to CIN3+ incidence rate 4% (or 25%) were used as the cutoffs to distinguish low-Ct value cases from the high-Ct value ones.ResultsA total of 1376 women in CHUMUST and BUJI Study who were aged 30–59 and positive of hrHPV for provider-collected samples on Cobas4800 with complete data in terms of the relevant Ct values (CtV) and the histological diagnosis were included for analysis. Our data showed significant difference among different histological grades of cervical lesions in the CtV of hrHPV, HPV16-plus (positive of HPV16 only or HPV16 plus 18 and/or pooled 12-HPV), and pooled 12-HPV (P < 0.05). No significant difference was found among different grades of lesions in term of correlated CtV of HPV18-plus (positive of HPV18 only or HPV18 plus pooled 12-HPV) (P > 0.05). The CIN2+ or CIN3+ incidence per 100 positives significantly increased corresponding to the descending of the CtV of hrHPV, HPV16-plus and pooled 12-HPV. Compared with high-CtV groups (CtV > 33.2 for hrHPV, CtV > 29.6 for pooled 12-HPV), the relevant risks (RRs) of CIN2+ for hrHPV and pooled 12-HPV positive groups with low-CtV (CtV ≤ 33.2 and ≤ 29.6, respectively) were 3.2 (95%CI 2.18–4.80) and 2.3 (95%CI 1.50–3.45). Similarly, the RRs of CIN3+ for hrHPV and pooled 12-HPV positive groups with low-CtV were 6.5 (95%CI 2.83–14.80) and 2.7 (95%CI 1.15–6.39), respectively. The RRs of CIN2+ for medium- (30.3 < CtV ≤ 37.4) and low- (≤ 30.3) CtV HPV16-plus positives were 5.1 (95%CI 0.68–38.38) and 20.6 (95%CI 2.96–143.92) related to high-CtV (> 37.4) groups, and the CIN3+ incidence in low-CtV value group was nine-fold higher of that in medium-CtV ones [RRs, 9.0 (95%CI 2.89–28.10)]. In comparing with the algorithms of “HPV16-plus/18-plus + cytology ≥ ASCUS for pooled 12-HPV”, triage algorithm “HPV16-plus/18-plus + Ct value ≤ 33.2 for pooled 12-HPV” could achieve a comparable sensitivity of 93.2%.ConclusionHPV viral loads reflected by Ct values for hrHPV, HPV16-plus and pooled 12-HPV from Cobas4800 HPV testing were directly associated with the severity of cervical lesions. A lower HPV genotype-specific Ct value prompted a significantly high CIN3+ risk of 4% or higher in women positive of hrHPV, HPV16-plus or pooled 12-HPV, indicating that HPV viral load reflected by Ct values on Cobas4800 may be a promising risk indicator in management of abnormalities from primary cervical cancer screening.

Suicide risk among patients with cancer in the United States, 2000-2016.

12119 Background: Individuals diagnosed with cancer have elevated suicide risk in the US, although little is known about risk associated with state of residence, health insurance coverage, or time since diagnosis by cancer types. This study used a recent national dataset to examine a wide range of patients’ sociodemographic and clinical factors that may be associated with suicide risks. Methods: We identified patients diagnosed with cancer from 43 population-based state cancer registries in 2000-2016 with follow-up through Dec 31, 2016. Standardized Mortality Ratios (SMR) and 95% confidence intervals (95CI) were calculated by state of residence, attained age group, sex, and race/ethnicity to compare suicide risks in the cohort vs. the general US population. Hazard Ratios (HR) and 95CI from multivariable Cox proportional hazard models were derived to identify cancer-specific risk factors of suicide among the cohort, controlling for competing risks from other causes of death. Results: Among 16,771,397 patients, 7,972,782 (47.5%) died during the study period, and 20,792 (0.3%) from suicide. The overall SMR for suicide was 1.26 (95CI = 1.24-1.28), decreasing from 1.67 (95CI 1.47-1.88) in 2000 to 1.16 (95CI 1.11-1.21) in 2016. Patients from Alaska, Colorado and Idaho, those aged 65-69 years (SMR = 1.44, 95CI = 1.39-1.50), Hispanic patients (SMR = 1.48, 95CI = 1.38-1.58), those uninsured (SMR = 1.66, 95CI = 1.53-1.80) or insured with Medicaid (SMR = 1.72, 95CI = 1.61-1.84) or ≤64 years of age with Medicare (SMR = 1.94, 95CI = 1.80-2.07) had the highest suicide risks compared to the general population. Moreover, the highest suicide risk occurred within two years of diagnosis (SMR [95CI] = 7.19 [6.97-7.41], 5.60 [5.35-5.84] and 4.18 [4.03-4.33] for ≤5 months, 6-11 months, and 12-23 months after cancer diagnosis, respectively). In the first two years following diagnosis, the risk of suicide was higher in patients diagnosed with distant-stage than early-stage diseases (HR = 1.29, 95CI = 1.21-1.37), and in patients with more cancer types with poor prognoses and high symptom burdens, such as cancers of oral cavity &amp; pharynx, esophagus, stomach, brain, lung and pancreas (HRs ranged 1.23-2.10 vs. colorectal cancer, all P≤0.001). After two years, patients diagnosed with cancers subject to long-term quality of life impairment, such as cancers of oral cavity &amp; pharynx, female breast, bladder, and leukemia (HRs ranged 1.17-1.54 vs. colorectal cancer, all P≤0.01), had higher suicide risks. Conclusions: Suicide risk among patients diagnosed with cancer decreased during the past two decades but remained elevated compared to the general population. Different geographic, racial/ethnic, socioeconomic, and clinical factors, some of which are modifiable, contribute to increased suicide risk among patients diagnosed with cancer. Tailored social and psych-oncological interventions are warranted for suicide prevention in this vulnerable population.

The influence of metabolic factors and ethnicity on breast cancer risk, treatment and survival: The Oslo ethnic breast cancer study

Background Breast cancer risk remains higher in high-income compared with low-income countries. However, it is unclear to what degree metabolic factors influence breast cancer development in women 30 years after immigration from low- to a high-incidence country. Methods Using Cox regression models, we studied the association between pre-diagnostic metabolic factors and breast cancer development, and whether this association varied by ethnicity among 13,802 women participating in the population-based Oslo Ethnic Breast Cancer Study. Ethnic background was assessed and pre-diagnostic metabolic factors (body mass index, waist:hip ratio, serum lipids and blood pressure) were measured. A total of 557 women developed invasive breast cancer, and these women were followed for an additional 7.7 years. Results Among women with an unfavorable metabolic profile, women from south Asia, compared with western European women, had a 2.3 times higher breast cancer risk (HR 2.30, 95% CI 1.18–4.49). Compared with the western European women, the ethnic minority women were more likely to present with triple-negative breast cancer (TNBC) (OR 2.11, 95% CI 0.97–4.61), and less likely to complete all courses of planned taxane treatment (OR 0.26, 95% CI 0.08–0.82). Among TNBC women, above-median triglycerides:HDL-cholesterol (>0.73) levels, compared with below-median triglycerides:HDL-cholesterol (≤0.73) levels, was associated with 2.9 times higher overall mortality (HR 2.88, 95% CI 1.02–8.11). Conclusions Our results support the importance of metabolic factors when balancing breast cancer prevention and disease management among all women, and in particular among non-western women migrating from a breast cancer low-incidence to a high-incidence country.

Mammography classification model trained from image labels only

The Cancer Registry of Norway organises a population-based breast cancer screening program, where 250 000 women participate each year. The interpretation of the screening mammograms is a manual process, but deep neural networks are showing potential in mammographic screening. Most methods focus on methods trained from pixel-level annotations, but these require expertise and are time-consuming to produce. Through the screenings, image level annotations are however readily available. In this work we present a few models trained from image level annotations from the Norwegian dataset: a holistic model, an attention model and an ensemble model. We compared their performance with that of pretrained models based on pixel-level annotations, trained on international datasets. From this we found that models trained on our local data with image-level annotation gave considerably better performance than the pretrained models from external data, although based on pixel-level annotations.

Post-diagnostic beta blocker use and breast cancer-specific mortality: a population-based cohort study

PurposeBeta blockers (BB) have been associated with improved, worsened, or unchanged breast cancer outcomes in previous studies. This study examines the association between the post-diagnostic use of BBs and death from breast cancer in a large, representative sample of New Zealand (NZ) women with breast cancer.MethodsWomen diagnosed with a first primary breast cancer between 2007 and 2016 were identified from four population-based regional NZ breast cancer registries and linked to national pharmaceutical data, hospital discharges, and death records. The median follow-up time was 4.51 years. Cox proportional hazard models were used to estimate the hazard of breast cancer-specific death (BCD) associated with any post-diagnostic BB use.ResultsOf the 14,976 women included in analyses, 21% used a BB after diagnosis. BB use (vs non-use) was associated with a small and nonstatistically significant increased risk of BCD (adjusted hazard ratio: 1.11; 95% CI 0.95–1.29). A statistically significant increased risk confined to short-term use (0–3 months) was seen (HR = 1.40; 1.14–1.73), and this risk steadily decreased with increasing duration of use and became a statistically significant protective effect at 3 + years of use (HR = 0.55; 0.34–0.88).ConclusionOur findings suggest that any increased risk associated with BB use may be driven by risk in the initial few months of use. Long-term BB use may be associated with a reduction in BCD.

Real-world evidence of patient-reported outcomes following definitive radiation therapy for prostate cancer: Findings from an Australian population-based clinical outcomes registry.

244 Background: We aimed to evaluate patient-reported functional outcomes (PRO) following definitive radiation therapy (RT) for prostate cancer (PCa) in a real-life population-based setting. Methods: The population-based Victorian Prostate Cancer Outcomes Registry (PCOR-Vic) captures approximately 90% of all PCa cases in the state. From 2015 onwards, all men in PCOR-Vic were contacted to complete the Expanded Prostate Cancer Index Composite short-form 26 (EPIC-26) at 12-month post-treatment. The EPIC-26 included urinary incontinence, urinary obstructive, bowel, sexual and hormonal function domain scores, ranging from 0 to 100, with higher score representing better outcomes. We estimated differences in the EPIC-26 domain scores between different RT techniques using linear regression, adjusting for patient, tumor, and treatment related factors, including the use of androgen deprivation therapy (ADT). The nature of recruitment methods and data collection in PCOR-Vic precluded us from measuring EPIC-26 prior to treatment, and hence this was not adjusted for in our analyses. Results: Between 2015 and 2020, there were 1,898 men treated with definitive RT who completed the EPIC-26 questionnaires and were included in this study – 1551 (82%) had external beam radiation therapy (EBRT) alone, 91 (5%) had EBRT with brachytherapy boost (EBRT+BT), 204 (11%) had low-dose-rate brachytherapy (LDR-BT) alone, and 52 (3%) had high-dose-rate brachytherapy (HDR-BT) alone. There were 1,140 (60%) men who had ADT with RT – 68% with EBRT alone, 76% with EBRT+BT, 4% with LDR-BT, and 21% with HDR-BT (P &lt; 0.001). Compared to men who had EBRT alone, men who had LDR-BT had higher adjusted mean EPIC-26 urinary incontinence (8.6 points; 95%CI: 5.3-12.0; P &lt; 0.001), sexual (13.5 points; 95%CI: 9.2-17.8; P &lt; 0.001) and hormonal score (6.8 points; 95%CI: 3.5-10.1; P &lt; 0.001) at 12-month post-treatment. Compared to men who had EBRT alone, there were no statistically significant differences in all five EPIC-26 domain scores in men who had EBRT+BT or HDR-BT alone. Conclusions: This is the first Australian real-world evidence on PRO for different RT modalities for PCa on a population-based level. We observed better urinary incontinence, sexual and hormonal function in men who had LDR-BT compared to EBRT, but no significant differences between men who had EBRT, EBRT+BT or HDR-BT.

Abstract P3-18-03: Long-term outcomes for breast conservation plus radiotherapy versus mastectomy in early breast cancer after neoadjuvant systemic therapy: Results from the Swedish national breast cancer register (NKBC)

Abstract Background: Population-based studies have consistently shown improved long-term outcomes with breast conserving surgery (BCS) plus radiotherapy (RT) vs. mastectomy in primarily operated breast cancer (BC) patients. However, the survival impact of type of local therapy following modern neoadjuvant systemic therapy (NST) is unclear. Methods: The population-based Swedish National Breast Cancer Register (NKBC), a prospectively collected population-based cohort, was used to identify female BC patients who were diagnosed from January, 2007 until December, 2017 and received NST in the Stockholm region. Patients were divided into BCS+RT and mastectomy groups, and the prognostic factors reflecting the response to NST like pathologic complete response (pCR) and Neo-bioscore calculated by pre/postoperative TNM stage, nuclear grade, and receptors status, were used for stratification. Disease-free survival (DFS), locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were evaluated using inverse probability of treatment weighted (IPTW) Cox proportional hazards model, which enables covariates like age, St Gallen subtypes, cTNM and ypTNM stages to be balanced between the two groups. Results: Among 1,409 eligible women, 456 (32.4%) were treated with BCS+RT, and 953 (67.6%) with mastectomy. Overall, 87 (6.2%) local recurrences, 256 (18.2%) distant metastases, and 282 (20.0%) deaths occurred over a median follow-up of 61 months. Patients diagnosed during later years, younger patients, patients with earlier stage and higher-grade tumors were more likely to receive BCS+RT. After adjusting for age at diagnosis, Neo-bioscore, adjuvant chemotherapy and radiotherapy, significant improvements for BCS+RT compared with mastectomy were observed in DFS (weighted-multivariate hazard ratio (HR), 0.51; 95%CI, 0.28-0.93; median 5-year DFS: 79.1% vs 73.6%) and DMFS (HR, 0.44; 95%CI, 0.23-0.82; median 5-year DMFS: 83.7% vs 74.8%), but no difference was identified in LRFS (HR, 0.94; 95%CI, 0.29-3.07; median 5-year LRFS: 89.9% vs 92.0%) or OS (HR, 0.7; 95%CI, 0.34-1.45; median 5-year OS: 88.4% vs 81.2%). The DFS benefit was observed regardless of pCR status, but varied by Neo-bioscore. Patients with Neo-bioscore 4-7 treated with BCS+RT had better DFS (HR, 0.31; 95%CI, 0.12-0.81) compared with those undergoing mastectomy, whereas low-risk patients with Neo-bioscore 0-3 had similar DFS between the two groups. Both triple negative (N=252; HR for DFS, 0.26; 95%CI, 0.07-0.97) and HER2-positive (N=533; HR for DFS, 0.24, 95%CI, 0.09-0.68) BC patients benefited from BCS+RT, but not patients with luminal tumors (N=589; HR for DFS, 0.82, 95%CI, 0.31-2.18). Similarly, superior DFS with BCS+RT was also seen in patients with neoadjuvant anti-HER2 targeted therapy (N=505; HR, 0.19; 95%CI, 0.05-0.75) or neoadjuvant chemotherapy alone (N=594; HR, 0.47; 95%CI, 0.21-1.06), but not among those receiving neoadjuvant endocrine therapy (N=162; HR, 0.53; 95%CI, 0. 1-2.85). Conclusion: After adjusting for response to NST and other confounders, BCS+RT was associated with reduced risks of tumor recurrence or metastasis compared with mastectomy. This benefit was more pronounced in patients with high Neo-bioscore, indicating that Neo-bioscore rather than pCR status has the potential to tailor breast surgery after NST. Further studies with larger sample size or prospective randomized clinical trials are warranted to confirm our findings. Citation Format: Kang Wang, Aafke Duinmeijer, Alexios Matikas, Renske Altena, Hemming Johansson, Hanna Fredholm, Theodoros Foukakis. Long-term outcomes for breast conservation plus radiotherapy versus mastectomy in early breast cancer after neoadjuvant systemic therapy: Results from the Swedish national breast cancer register (NKBC) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-18-03.

Abstract P3-14-08: The influence of metabolic factors, migration, and ethnic disparities on breast cancer risk and treatment

Abstract Background: Migrant studies have shown an increase in breast cancer incidence rates among immigrants moving from a breast cancer low-incidence to a high-incidence country. However, 30 years after immigration, it remains equivocal to what degree metabolic factors and ethnic disparities affect breast cancer development and treatment. Methods: Using Cox regression models, we examined the association between ethnicity and breast cancer development, and whether this association varied by pre-diagnostic metabolic profiles among 13 802 women, aged 20-75 years, participating in the population-based Oslo Ethnic Breast Cancer Study. Ethnicity was categorized into: women of Western European descent (reference population) and women of non-western ethnicity (ethnic minority). The ethnic minority women were further subclassified into three groups: 1) South Asian, 2) Middle East and North African, and 3) all other non-western origin women. We defined four pre-diagnostic unfavorable metabolic factors (above median body mass index (&amp;gt;24.6 kg/m2), waist:hip ratio (&amp;gt;0.79), triglyceride:HDL-cholesterol ratio (&amp;gt;0.73), and blood pressure (&amp;gt;96.5 mmHg)), which were combined to define three metabolic profiles: (0-2, 3, and 4 unfavorable metabolic factors). A total of 557 women developed invasive breast cancer during a mean 16.5 years of follow-up. Detailed medical records were obtained. Results: Among women with an unfavorable metabolic profile, South Asian women, compared with Western European women, had a 2.3 times higher breast cancer risk (HR 2.30, 95% CI 1.18-4.49). Furthermore, the ethnic minority women, compared with the Western European women, were suggestively more likely to present with triple-negative breast cancer (OR 2.11, 95% CI 0.97-4.61), and less likely to complete all courses of planned taxane treatment (OR 0.26, 95% CI 0.08-0.82). No differences by ethnicity were observed in physicians’ decisions of planned breast cancer treatment, Conclusions: Our results support that metabolic factors, including body composition, serum lipids and blood pressure, are important when balancing breast cancer prevention and disease management among non-western women migrating from a breast cancer low-incidence to a high-incidence country. However, larger studies are needed. Citation Format: Trygve Lofterød, Hanne Frydenberg, Marit Veierød, Anne Karen Jenum, Jon B Reitan, Erik Wist, Inger Thune. The influence of metabolic factors, migration, and ethnic disparities on breast cancer risk and treatment [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-14-08.

Can second-generation multitarget stool DNA panels reliably detect colorectal cancer and advanced precancerous lesions?

63 Background: Population-based colorectal cancer (CRC) screening can reduce mortality by detecting and removing advanced precancerous lesions (APL) and early-stage invasive disease. One guideline-included strategy is the multi-target stool DNA test (mt-sDNA), which combines detection of methylation DNA markers (MDMs), KRAS mutations, and fecal hemoglobin. Since the mt-sDNA pivotal study was conducted, novel biomarkers have been discovered. A panel of highly discriminant MDMs ( LASS4, LRRC4, PPP2R5C, and reference marker ZDHHC1) was identified through a blinded, case-control study of archival specimens. Here, we evaluated the performance of this novel mt-sDNA panel, combined with fecal hemoglobin, in archival stool samples weighted to early-stage CRC and prospectively collected APL, simulating a screening population. Methods: The verification study featured 777 samples—210 cases (112 CRC [49 stage I, 38 stage II, 17 stage III, and 8 stage IV] and 98 APL) and 567 controls (176 non-APL and 391 colonoscopy-negative)—from three trials (NCT01397747, NCT01260168, and NCT02503631). Median APL size was 12 mm (interquartile range: 10 mm to 15 mm), with 86.7% adenomas (n = 85) and 13.3% sessile serrated polyps (SSPs; n = 13). The average age was 65.5 years for cases (57% men) and 63.2 for controls (47% men). Samples were processed through homogenization, targeted MDM capture, bisulfite conversion, and MDM quantitation using Long‐probe Quantitative Amplified Signal (LQAS). Fecal hemoglobin was quantified using enzyme-linked immunosorbent assay (ELISA). Samples were split into stratified 75%/25% training-testing sets and model outcomes were cross-validated 1,000 times. Results: Mean performance from the cross-validation analysis is summarized in the table below. Overall sensitivity was 95.2% for CRC and 57.2% for APL, with specificities of 89.8% (no CRC/APL) and 92.4% (no neoplasia). Subgroup analyses showed high sensitivity for early-stage CRC, with 93.4% at stage I and 94.2% at stage II. By APL subtype, sensitivity was 82.9% for high-grade dysplasia, 73.4% for villous lesions, 49.8% for tubular lesions, and 30.2% for SSPs. Conclusions: These data support high sensitivity and specificity for a second-generation mt-sDNA panel. A multicenter pivotal trial evaluating the panel is underway (NCT04144738). [Table: see text]

Results and efforts of population-based breast cancer screening in Fukushima Prefecture

Results and efforts of population-based breast cancer screening in Fukushima Prefecture

Rare Childhood Cancer Burden in a Tertiary Care Hospital of Dhaka, Bangladesh

Background: Accurate childhood cancer burden data are crucial for resource planning and health policy prioritization. In Bangladesh we have no national population based cancer registry. Data about the total burden of childhood cancer in our country is unknown. But a hospital based cancer registry is the cheapest way to assess the tumor burden of a nation. So we investigate the total pediatric cancer burden and the percentage of different types of rare childhood cancers (RCC) of National Institute of Cancer Research and Hospital (NICRH), Dhaka, during the year 2014 – 2018. Aim: To investigate the total number of pediatric cancers, frequency of different types of rare cancer and percentage of rare childhood cancer in the Pediatric Hematology and Oncology (PHO) department. Methods: Data were collected from all pediatric (0-17 years) patients between the year 2014 and 2018 prospectively. Definitive diagnosis of cases were established by histopathological and or immunohistochemical study. As we have no population-based cancer registry, we considered the rare tumors in our study according to the Children's Oncology Group (COG) and the German Childhood Cancer Registry (GCCR). Results: Total number of childhood cancers and RCC was 2242 and 351 respectively. Percentage of rare tumors was 15.66% in our center. Benign rare tumors were 18.52% (N-65) cases. Common age group was the 5-9 years group (54.13 %). Most common RCC groups were Non-Rhabdomyosarcoma soft tissue sarcoma (NRSTS) constituting 49.29 %, followed by Malignant epithelial neoplasms and melanomas (38.18%). Diagnostic delay was 3.52 months. Most common malignancy was Synovial Sarcoma (N-40, 11.39%), Peripheral Neuroectodermal Tumor (N-39, 11.11%), Nasopharyngeal carcinoma (N-35, 9.97%), Malignant small round cell tumor (N-31, 8.83%) and Carcinoma rectum and colon (N-23, 6.55%). Conclusion: We have found that our Institutional (NICRH) rare tumor rate (15.66%) was a bit higher than US national RCC (15%). Though Institutional cancer data reflect the national burden, to estimate the accurate number and percentage of RCC, National Cancer Registry is needed.