Taiwan Cancer Registry Research Articles

Risk of retinal vein occlusion in colorectal cancer patients receiving anti-vascular endothelial growth factors – a population-based cohort study

BackgroundAnti−vascular endothelial growth factors (VEGFs) treatment has been associated with an increased risk of thromboembolic events. Therefore, the use of anti−VEGFs for patients with colorectal cancers (CRC) has raised concerns about the potential risk of retinal vein occlusion (RVO), an ocular disease caused by embolism or venous stasis. This study aims to evaluate the risk of RVO in patients with CRC treated with anti−VEGFs.MethodWe conducted a retrospective cohort study using the Taiwan Cancer Registry and National Health Insurance Database. The study cohort comprised patients newly diagnosed with CRC between 2011 and 2017, who received anti-VEGF treatment. For each patient in the study cohort, a control group comprising four patients newly diagnosed with CRC, but not receiving anti-VEGF treatment, was randomly selected. A washout period of 12 months was implemented to identify new cases. The index date was defined as the date of the first prescription of anti-VEGF drugs. The study outcome was the incidence of RVO, as identified by ICD-9-CM (362.35 and 362.36) or ICD-10-CM codes (H3481 and H3483). Patients were followed from their index date until the occurrence of RVO, death or the end of the study period. Covariates, including patients' age at index date, sex, calendar year of CRC diagnosis, stage of CRC and comorbidities related to RVO, were included. Multivariable Cox proportional hazards regression models were used to calculate hazard ratios (HRs) with adjustments for all covariates to compare the risk of RVO between the anti-VEGF and control groups.ResultsWe recruited 6285 patients in the anti-VEGF group and 37,250 patients in the control group, with mean ages of 59.49 ± 12.11 and 63.88 ± 13.17 years, respectively. The incidence rates were 1.06 per 1000 person-years for the anti-VEGF group, and 0.63 per 1000 person-years for the controls. There was no statistically significant difference in RVO risk between the anti-VEGF and control groups (HR: 2.21, 95% CI: 0.87–5.61).ConclusionOur results indicated no association between use of anti-VEGF and occurrence of RVO among CRC patients, although the crude incidence rate of RVO was higher in patients receiving anti-VEGF, compared to control patients. Future study with larger sample size is required to confirm our findings.

Association Between the Use of Topical Calcineurin Inhibitors and the Risk of Cancer Among Patients with Atopic Dermatitis: A Nationwide, Population-Based, Retrospective Cohort Study.

The cancer risks associated with treatment withtopical calcineurin inhibitors (TCIs) in patients with atopic dermatitis (AD) remain controversial, and limited evidence exists regarding the cancer risks among patients with AD treated with TCIs in Asian populations. This study identified the association between TCI use and the risks of developing all cancers, lymphoma, skin cancers, and other cancers. This study was a nationwide, population-based, retrospective cohort study. Taiwan's National Health Insurance Research Database. Patients diagnosed at least twice with ICD-9 code 691 or at least one time with ICD-9 codes 691 or 692.9 within 1 year between 1 January 2003 and 31 December 2010 were included and followed until 31 December 2018. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using the Cox proportional hazard ratio model. Patients using tacrolimus or pimecrolimus were identified in the National Health Insurance Research Database and compared with patients using topical corticosteroids (TCSs). The main outcomes were hazard ratios (HRs) of cancer diagnoses and associated outcomes obtained from the Taiwan Cancer Registry database. After propensity score (PS) matching, the final cohort included 195,925 patients with AD, including 39,185 who were initial TCI users and 156,740 who were TCS users. Propensity score matching was performed according to age, sex, index year, and Charlson Comorbidity Index using a ratio of 1:4. Exceptfor leukemia, HR and 95% CI showed no significant associations between TCI use and the risk of developing all cancer, lymphoma, skin cancers, and other cancers. Sensitivity analysis showed that the lag time HRs for every cancer subtype continued to show no significant association between TCI use and cancer risk, except for leukemia. Our study found no evidence to support an association between TCI use and the risks of almost all cancers compared with TCS use in patients with AD, but physicians should be aware of potentially higher risks of leukemia with TCI use. This study represents the first population-based study focused on the cancer risk of TCI use among patients with AD in an Asian population.

Prevalence of comorbidities and their impact on survival among older adults with the five most common cancers in Taiwan: a population study

Because of the cancer incidence increase and population aging in Taiwan, we aimed to assess the cancer prevalence, to summarize the comorbidities of older patients with the five most common cancers (i.e., breast, colorectal, liver, lung, and oral), and to develop a Taiwan cancer comorbidity index (TCCI) for studying their actual prognosis. The linkage of the Taiwan Cancer Registry, Cause of Death Database, and National Health Insurance Research Database was used. We followed the standard statistical learning steps to obtain a survival model with good discriminatory accuracy in predicting death due to noncancer causes, from which we obtained the TCCI and defined comorbidity levels. We reported the actual prognosis by age, stage, and comorbidity level. In Taiwan, cancer prevalence nearly doubled in 2004–2014, and comorbidities were common among older patients. Stage was the major predictor of patients' actual prognoses. For localized and regional breast, colorectal, and oral cancers, comorbidities correlated with noncancer-related deaths. Compared with the US, the chances of dying from comorbidities in Taiwan were lower and the chances of dying from cancer were higher for breast, colorectal, and male lung cancers. These actual prognoses could help clinicians and patients in treatment decision-making and help policymakers in resource planning.

Double-contrast barium enema is no longer justified as a backup examination for colonoscopy in the population screening program: Population study in an organized fecal immunochemical test-based screening program.

Currently, some countries still acknowledge double-contrast barium enema (DCBE) as a backup confirmatory examination when colonoscopy is not feasible or incomplete in colorectal cancer (CRC) screening programs. This study aims to compare the performance of colonoscopy and DCBE in terms of the risk of incident CRC after negative results in the fecal immunochemical test (FIT)-based Taiwan Colorectal Cancer Screening Program. Subjects who had positive FITs and received confirmatory exams, either colonoscopy or DCBE, without the findings of neoplastic lesions from 2004 to 2013 in the screening program comprised the study cohort. Both the colonoscopy and DCBE subcohorts were followed until the end of 2018 and linked to the Taiwan Cancer Registry to identify incident CRC cases. Multivariate analysis was conducted to compare the risk of incident CRC in both subcohorts after controlling for potential confounders. A total of 102 761 colonoscopies and 5885 DCBEs were performed after positive FITs without neoplastic findings during the study period. By the end of 2018, 2113 CRCs (2.7 per 1000 person-years) and 368 CRCs (7.6 per 1000 person-years) occurred in the colonoscopy and DCBE subcohorts, respectively. After adjusting for major confounders, DCBE had a significantly higher risk of incident CRC than colonoscopy, with an adjusted HR of 2.81 (95% CI=2.51-3.14). In the FIT screening program, using DCBE as a backup examination was associated with a nearly threefold risk of incident CRC compared with colonoscopy, demonstrating that it is no longer justified as a backup examination for incomplete colonoscopy.

Statin Use During Concurrent Chemoradiotherapy With Improved Survival Outcomes in Esophageal Squamous Cell Carcinoma: A Propensity Score-Matched Nationwide Cohort Study

IntroductionTo determine the effect of statin use during concurrent chemoradiotherapy (CCRT) on overall survival and esophageal squamous cell carcinoma (ESCC)-specific survival in patients with ESCC receiving standard CCRT. MethodsIn this propensity score-matching cohort study, we used data from the Taiwan Cancer Registry Database and National Health Insurance Research Database to investigate the effects of statin use during the period of CCRT on overall survival and ESCC-specific survival. ResultsStatin use during the period of CCRT was found to be a considerable and independent prognostic factor for overall survival and ESCC-specific survival. The adjusted hazard ratio (aHR) for all-cause mortality in the statin group compared with that of the non-statin group was 0.65 (95% confidence interval: 0.51–0.84, p = 0.0009). The aHR for ESCC-specific mortality in the statin group compared with that of the non-statin group was 0.63 (95% confidence interval: 0.47–0.84, p = 0.0016). The use of hydrophilic statins such as rosuvastatin and pravastatin was associated with the greatest survival benefits. A dose-response relationship was also found, with higher cumulative defined daily doses and higher daily intensity of statin use associated with lower mortality. ConclusionsThis study is the first to reveal that statin use during the period of CCRT for ESCC is associated with improvement in overall survival and ESCC-specific survival. In addition, we found that use of rosuvastatin, pravastatin, and simvastatin was associated with better survival outcomes for patients with ESCC receiving CCRT. Furthermore, we found a dose-response relationship of statin use associated with lower ESCC-specific mortality.

Trends in thyroid cancer burden in Taiwan over two decades

Thyroid cancer incidence has increased over recent decades with considerable geographic variations in incidence patterns. Here, we analyzed temporal trends in the incidence and mortality rates of thyroid cancer in Taiwan. We obtained age-standardized rates at a national level using data from the Taiwan Cancer Registry annual reports from 1995 to 2019. Trends in age-standardized rates were characterized by joinpoint regression analysis. The age-standardized incidence rate of thyroid cancer increased from 3.00 per 100,000 person-years in 1995 to 15.46 per 100,000 person-years in 2019 (p < 0.001). Significant upward trends were observed in virtually all age groups, including adolescents and the geriatric population. The average annual percent changes were 7.97%, 2.60%, 2.77%, and 1.43% for papillary, follicular, medullary, and anaplastic thyroid cancers, respectively. The mortality rate from thyroid cancer decreased over time in women but remained stable in men. The incidence rates of thyroid cancer have steadily increased across gender, age groups, and tumor types over the past two decades. Future studies are needed to investigate potential etiological factors other than overdiagnosis that may drive these trends.

Prior treated tuberculosis and mortality risk in lung cancer.

Lung cancer is one of the leading causes of cancer death worldwide, and tuberculosis (TB) is a common pre-existing disease. However, there is scarce literature studying the mortality risk in patients with prior TB and subsequent lung cancer. We recruited lung cancer patients from the Taiwan Cancer Registry from 2011 to 2015 and classified them into two groups according to presence or absence of prior TB. We then matched them in a ratio of 1:4 using the exact matching approach. The mortality risk within 3 years after diagnosis of lung cancer was analyzed and compared between these two groups. During the study period, 43,472 patients with lung cancer were recruited, and of these, 1,211 (2.79%) patients had prior TB. After matching, this cohort included 5,935 patients with lung cancer in two groups: patients with prior TB before lung cancer (n = 1,187) and those without (n = 4,748). After controlling for demographic factors and comorbidities, the patients with prior TB had increased adjusted hazard ratios of 1.13 (95% CI: 1.04-1.23) and 1.11 (1.02-1.21) for all-cause and cancer-specific 3-year mortality, respectively, compared to the lung cancer patients without prior TB. Duration between TB and lung cancer (<1 year vs. 1-3 years vs. >3 years) had no differences for mortality risk. In the present study, 2.79% patients with lung cancer had prior TB, which was associated with higher 3-year mortality after they developed lung cancer. The mortality risk with prior TB did not decrease even if >3 years passed before diagnosis of lung cancer.

The impacts of the scope of benefits expansion on hospice care among adult decedents: a nationwide longitudinal observational study

ObjectivesCompared to aggressive treatment for patients at the end stage of life, hospice care might be more likely to satisfy such patients’ need and benefits and improve their dignity and quality of life. Whether the reimbursement policy expansion affect the use of hospice care among various demographics characteristics and health status was unknown. Therefore, the purpose of this study was to explore the impacts of reimbursement policy expansion on hospice care use, and to investigate the effects on people with various demographics characteristics and health status.MethodsWe used the 2001–2017 Taiwan NHI claims data, Death Registry, and Cancer Registry in this study, and we included people who died between 2002 and 2017. The study period was divided into 4 sub-periods. hospice care use and the initiation time of 1st hospice care use were used as dependent variables; demographic characteristics and health status were also collected.ResultsThere were 2,445,781 people who died in Taiwan during the study period. The results show that the trend of hospice care use increased over time, going steeply upward after the scope of benefits expansion, but the initiation time of 1st hospice care use did not increase after the scope of benefits expansion. The results also show that the effects of expansion varied among patients by demographic characteristics.ConclusionThe scope of benefits expansion might induce people’s needs in hospice care, but the effects varied by demographic characteristics. Understanding the reasons for the variations in all populations would be the next step for Taiwan’s health authorities.

Pelvic Neoadjuvant Radiotherapy for Stage M1a Rectal Adenocarcinoma Patients Treated With Systemic Therapy Followed by Proctectomy and Metastasectomy: A Nationwide Retrospective Cohort Study.

The effect of pelvic neoadjuvant radiotherapy (nRT) for stage M1a rectal adenocarcinoma patients treated with systemic therapy followed by proctectomy and metastasectomy was scarcely investigated in the literatures. The eligible rectal cancer patients diagnosed between 2011-2019 were identified via the Taiwan Cancer Registry. In the primary analysis, we used propensity score weighting to balance observable potential confounders and compared the hazard ratio (HR) of death for the nRT group vs. without RT group. We also compared the incidence of rectal cancer mortality (IRCM) and performed various supplementary analyses. Our primary analyses included 145 patients. nRT was associated with improved OS (HR=0.51, p=0.01). The numerical trends remained similar for IRCM and in supplementary analyses. nRT was associated with improved OS in our study population.

Effect of esophageal cancer screening on mortality among patients with oral cancer and second primary esophageal cancer in Taiwan

ObjectiveOral and esophageal cancer are the fourth and fifth leading causes of cancer deaths among men in Taiwan. Despite a good prognosis for oral cavity cancer patients, survival is worse for those who develop second primary esophageal cancer. There remains no consensus regarding early prevention of potential second primary esophageal cancer in patients with oral cavity cancer. Our study aimed to compare 5-year mortality between endoscopically screened and non-screened patients with oral cavity cancer and second primary esophageal cancer. Materials and methodsThis study identified patients with incident oral cavity cancer and second primary esophageal cancer during 2004 and 2013 using the Taiwan Cancer Registry and National Health Insurance Research Database. We compared 5-year mortality from the second primary esophageal cancer diagnosis date between screened and non-screened groups of patients with oral cavity cancer and second primary esophageal cancer. ResultsA total of 217 screened and 305 non-screened oral cavity cancer patients with second primary esophageal cancer were studied. Endoscopic screening significantly improved early detection of second primary esophageal cancer (adjusted odds ratio: 0.34, 95 % confidence interval [CI]: 0.23–0.49) and reduced all-cause mortality (adjusted hazard ratio: 0.80; 95 % CI: 0.66–0.98). ConclusionsOral cavity cancer patients with second primary esophageal cancer may have worse overall survival than those without. Early detection of second primary esophageal cancer is a crucial mediator between endoscopic screening and mortality. Endoscopic screening after the diagnosis of incident oral cavity cancer significantly increased early detection and reduced all-cause mortality.

Association of smoking and ALK tyrosine-kinase inhibitors on overall survival in treatment-naïve ALK-positive advanced lung adenocarcinoma.

Anaplastic lymphoma kinase (ALK) fusion mutation is more common in younger and never-smoking lung cancer patients. The association of smoking and ALK-tyrosine kinase inhibitors (TKIs) on overall survival (OS) of treatment-naïve ALK-positive advanced lung adenocarcinoma remains unclear in real-world. This retrospective study evaluated all 33170 lung adenocarcinoma patients registered in the National Taiwan Cancer Registry from 2017 to 2019, of whom 9575 advanced stage patients had ALK mutation data. Among the 9575 patients, 650 (6.8%) patients had ALK mutation with the median follow-up survival time 30.97 months (median age, 62 years; 125 [19.2%] were aged ≥75 years; 357 (54.9%) females; 179 (27.5) smokers, 461 (70.9%) never-smokers, 10 (1.5%) with unknown smoking status; and 544 (83.7%) with first-line ALK-TKI treatment). Overall, of 535 patients with known smoking status who received first-line ALK-TKI treatment, never-smokers and smokers had a median OS of 40.7 months (95% confidence interval (CI), 33.1-47.2 months) and 23.5 months (95% CI, 11.5-35.5 months) (P=0.015), respectively. Among never-smokers, those who received first-line ALK-TKI treatment had a median OS of 40.7 months (95% CI, 22.7-57.8 months), while those ALK-TKI not as first-line treatment had a median OS of 31.7 months (95% CI, 15.2-42.8 months) (P=0.23). In smokers, the median OS for these patients was 23.5 months (95% CI, 11.5-35.5 months) and 15.6 months (95% CI, 10.2-21.1 months) (P=0.026), respectively. For patients with treatment-naïve advanced lung adenocarcinoma, the ALK test should be performed irrespective of smoking status and age. Smokers had shorter median OS than never-smokers among treatment-naïve-ALK-positive patients with first-line ALK-TKI treatment. Furthermore, smokers not receiving first-line ALK-TKI treatment had inferior OS. Further investigations for the first-line treatment of ALK-positive smoking advanced lung adenocarcinoma patients are needed.

Entecavir versus tenofovir on prognosis of hepatitis B virus‐related hepatocellular carcinoma after curative hepatectomy

There is still controversy about whether tenofovir disoproxil fumarate (TDF) and entecavir (ETV) have different effects on the outcomes of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). The aim of this study was to compare the prognoses between ETV and TDF treatment among patients with HBV-related HCC after hepatectomy. An analysis was done on data from the Taiwan Cancer Registry, which was linked to Taiwan National Health Insurance Research Database, for the years 2011-2016. We identified 7107 patients with HBV-related HCC after curative hepatectomy, and 25.3% of them used ETV or TDF after surgery. After propensity score overlap weighting, 1797 patients treated with ETV (n=1365) or TDF (n=432) were included for analyses. Cox proportional hazards models were used to compare the efficacy of ETV and TDF for recurrence and overall survival (OS). After hepatectomy, the recurrence rate per 100 person-years was 14.87 for the ETV group and 9.25 for the TDF group. The risk of recurrence was similar in the TDF group and the ETV group (HR [95% CI]: 0.91 [0.69-1.19; p=0.479]), as was the risk of all-cause mortality (HR [95% CI]: 0.67 [0.42-1.07]; p=0.091). When considering early recurrence (<2 years) and late recurrence (≧2 years), the TDF and ETV groups showed no significant differences. Subgroup analyses and sensitivity analyses demonstrated consistent results. Both TDF and ETV showed similar health benefits in terms of recurrence and OS in patients with HBV-related HCC patients after hepatectomy.

Latency period of aristolochic acid-induced upper urinary tract urothelial carcinoma.

Aristolochic acid (AA) is a carcinogen in upper urinary tract urothelial carcinoma (UTUC). This study investigated the latency period between AA exposure and UTUC development. This population-based cohort study was designed using record linkage of the National Health Insurance Research Database (NHIRD), Taiwan Cancer Registry Dataset, and cause-of-death data in Taiwan. Those aged 40-79 years were enrolled in this study. Patients who died or had renal insufficiency or UTUC before 2005 were excluded. The doses of AA exposure and rates of comorbidities between 2000 and 2005 were obtained. The Cox proportion hazard model was used to estimate the risk of UTUC between 2005 and 2016. In addition, the Cox model with time-varying coefficient of AA was used to measure the latency period of UTUC. Of the 752,232 participants enrolled from the NHIRD, 520,871 (68.29%), 210,447 (27.59%), and 31,415 (4.12%) were exposed to cumulative AA doses of 0-1 mg, 1-150 mg, and >150 mg, respectively. A total of 1,147 (0.15%) patients were diagnosed with UTUC between 2005 and 2016. The latency periods of UTUC in middle-aged (40-59 years old) men with cumulative AA doses of 1-150 mg and middle-aged women with cumulative AA doses of 1-150 mg and >150 mg were 8, 9, and 7 years, respectively. Among the aged (60-79 years) individuals, no time-varying effect was observed, and the latency period could not be measured. A decreased risk of UTUC was observed after the ban on AA in Taiwan, especially in middle-aged women with moderate to high doses of AA exposure and men with moderate doses of AA exposure. The latency period of UTUC varies with age, the dose of AA exposure, and sex.

Adjuvant chemotherapy compared with observation in patients with T2aN0 stage IB lung adenocarcinoma.

For patients with T2aN0 stage IB lung adenocarcinoma, benefits of adjuvant chemotherapy remain controversial. Here, we aimed to evaluate such benefits. This retrospective cohort study was conducted on the database of the National Taiwan Cancer Registry. We analyzed patients with T2aN0 stage IB lung adenocarcinoma (re-classified by AJCC 8th edition) diagnosed during the period from January 2011 to December 2017. They were divided into two groups: (1) group 1: tumor <=3 cm with visceral pleural invasion (VPI); (2) group 2: tumor >3 cm, but <=4 cm. Overall survival (OS) and cancer specific survival (CSS) were evaluated. Risk factors for survival were determined. A total of 2,100 patients with T2aN0 stage IB lung adenocarcinoma (1,265 in group 1 and 835 in group 2) were enrolled for study. The proportions of patients receiving adjuvant chemotherapy in group 1 and 2 were 39.1% and 68.6%, respectively. Amongst group 1 patients, adjuvant chemotherapy was not an independent risk factor for OS and CSS. Amongst group 2 patients, high-grade histologic findings and receiving sublobar resection were two risk factors for poorer survival. Adjuvant chemotherapy was also associated with an OS (adjusted hazard ratio (aHR), 0.52; 95% confidence interval (CI), 0.38-0.72; P<0.001) and CSS (aHR, 0.54; 95% CI, 0.37-0.78; p=0.001) benefit regardless of the presence or absence of risk factors. For patients with T2aN0 stage IB lung adenocarcinoma, adjuvant chemotherapy improved OS and CSS in those with tumors >3 cm, but <=4 cm.For patients with tumors <=3 cm with VPI, adjuvant chemotherapy had no survival benefit.

Comparison of healthcare utilization and life-sustaining interventions between patients with glioblastoma receiving palliative care or not: A population-based study

Background: Palliative care has historically been under-utilized in patients with glioblastoma. Furthermore, literature on the utilization of healthcare and life-sustaining interventions during the late-stage of glioblastoma has been limited. Aim: To identify and compare healthcare utilization and life-sustaining interventions between patients with glioblastoma who received palliative care and who did not based on patients identified retrospectively from Taiwan Cancer Registry between January 2007 and December 2017. Design: In this study, palliative care was defined on the basis of claims submitted to the National Health Insurance, which has a specific code for it. Variables included demographic characteristics, the utilization of healthcare services, and invasive life-sustaining interventions. Setting/participants: Of the 1994 patients with glioblastoma identified, 1784 fulfilled the inclusion criteria, 613 (34%) of whom received palliative care. Results: The survival of patients with glioblastoma under palliative care was significantly longer than that of those without palliative care. Those without palliative care had significantly more frequent intensive care unit admissions and a longer cumulative length of intensive care unit stay. Regarding cardiopulmonary or respiratory treatments, patients without palliative care had significantly more invasive interventions than those with palliative care. Patients receiving palliative care had significantly lower odds than those without life-sustaining interventions. Conclusions: Our retrospective analysis reveals that glioblastoma patients without palliative care had greater odds of receiving life-sustaining treatments within 1 year before their death, although no gains in survival as compared to those that received palliative care. These findings highlight the urgent need for palliative care in caring for patients with glioblastoma.

Renin-Angiotensin-Aldosterone System Inhibitors and Development of Gynecologic Cancers: A 23 Million Individual Population-Based Study.

The chronic receipt of renin-angiotensin-aldosterone system (RAAS) inhibitors including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been assumed to be associated with a significant decrease in overall gynecologic cancer risks. This study aimed to investigate the associations of long-term RAAS inhibitors use with gynecologic cancer risks. A large population-based case-control study was conducted from claim databases of Taiwan's Health and Welfare Data Science Center (2000-2016) and linked with Taiwan Cancer Registry (1979-2016). Each eligible case was matched with four controls using propensity matching score method for age, sex, month, and year of diagnosis. We applied conditional logistic regression with 95% confidence intervals to identify the associations of RAAS inhibitors use with gynecologic cancer risks. The statistical significance threshold was p < 0.05. A total of 97,736 gynecologic cancer cases were identified and matched with 390,944 controls. The adjusted odds ratio for RAAS inhibitors use and overall gynecologic cancer was 0.87 (95% CI: 0.85-0.89). Cervical cancer risk was found to be significantly decreased in the groups aged 20-39 years (aOR: 0.70, 95% CI: 0.58-0.85), 40-64 years (aOR: 0.77, 95% CI: 0.74-0.81), ≥65 years (aOR: 0.87, 95% CI: 0.83-0.91), and overall (aOR: 0.81, 95% CI: 0.79-0.84). Ovarian cancer risk was significantly lower in the groups aged 40-64 years (aOR: 0.76, 95% CI: 0.69-0.82), ≥65 years (aOR: 0.83, 95% CI: 0.75-092), and overall (aOR: 0.79, 95% CI: 0.74-0.84). However, a significantly increased endometrial cancer risk was observed in users aged 20-39 years (aOR: 2.54, 95% CI: 1.79-3.61), 40-64 years (aOR: 1.08, 95% CI: 1.02-1.14), and overall (aOR: 1.06, 95% CI: 1.01-1.11). There were significantly reduced risks of gynecologic cancers with ACEIs users in the groups aged 40-64 years (aOR: 0.88, 95% CI: 0.84-0.91), ≥65 years (aOR: 0.87, 95% CI: 0.83-0.90), and overall (aOR: 0.88, 95% CI: 0.85-0.80), and ARBs users aged 40-64 years (aOR: 0.91, 95% CI: 0.86-0.95). Our case-control study demonstrated that RAAS inhibitors use was associated with a significant decrease in overall gynecologic cancer risks. RAAS inhibitors exposure had lower associations with cervical and ovarian cancer risks, and increased endometrial cancer risk. ACEIs/ARBs use was found to have a preventive effect against gynecologic cancers. Future clinical research is needed to establish causality.

Urban-Rural Disparity in Birth Cohort Effects on Breast Cancer Incidence.

Breast cancer is the most commonly diagnosed cancer among women worldwide. Studies have reported minimal birth cohort effects on the incidence rates of breast cancer in Western countries but have reported notable birth cohort effects in some Asian countries. The risks of breast cancer may also vary within a country. In the present study, we abstracted female invasive breast cancer data from the Taiwan Cancer Registry for the period 1997-2016. We used the age-period-cohort model to compare birth cohort effects on breast cancer incidence rates between urban and rural regions in Taiwan. We identified a notable urban-rural disparity in birth cohort effects on breast cancer incidence rates in women in Taiwan. The incidence rates in the urban regions were higher than those in the rural regions across all cohorts. However, the incidence rates rose faster in the rural regions than in the urban regions across the cohorts. The risks of breast cancer observed for women born in 1992 were approximately 22 and 11 times than those observed for women born in 1917 in rural and urban regions, respectively. The observed gap in breast cancer incidence rates between the urban and rural regions gradually disappeared across the cohorts. Accordingly, we speculate that urbanization and westernization in Taiwan may be the drivers of female breast cancer incidence rates across birth cohorts.

Incidence Trend of Follicular Lymphoma in Taiwan Compared to Japan and Korea, 2001-2019.

A continuous increase in follicular lymphoma has been observed in Taiwan, Japan, and South Korea over the last few decades. This study aimed to evaluate the difference in incidence trends of follicular lymphoma in Taiwan, Japan, and South Korea between 2001 and 2019. The data for the Taiwanese populations was obtained from the Taiwan Cancer Registry Database, and those for the Japanese and Korean population were retrieved from the Japan National Cancer Registry and some additional reports, both of which included population-based cancer registry data, from Japan and Korea. Follicular lymphoma accounted for 4231 cases from 2002-2019 in Taiwan, 3744 cases from 2001-2008 and 49,731 cases from 2014-2019 in Japan; and 1365 cases from 2001-2012 and 1244 cases from 2011-2016 in South Korea. The annual percentage change for each time period was 3.49% (95% confidence interval: 2.75-4.24%) in Taiwan, 12.66% (95% confidence interval [CI]: 9.59-15.81%) and 4.95% (95% CI: 2.14-7.84%) in Japan, and 5.72% (95% CI: 2.79-8.73%) and 7.93% (95% CI: -1.63-18.42%) in South Korea. Our study confirms that the increasing trends of follicular lymphoma incidence in Taiwan and Japan have been remarkable in recent years, especially the rapid increase in Japan between 2014 and 2019; however, there was no significant in-crease from 2011 to 2015 in South Korea.

Mortality of patients with metastatic colorectal cancer who received elective or emergent operation after exposure to bevacizumab: A nationwide database study.

Treatment guidelines for colorectal cancer (CRC) indicate that surgical intervention within 4 weeks or 8 weeks after bevacizumab therapy might increase the risk of postoperative complications and mortality, especially in patients who received emergent operation. Therefore, we aimed to assess the association between different surgical timings, emergent or elective surgery, and the risk of postoperative mortality. Using the Taiwan National Health Insurance Database and Taiwan Cancer Registry, we identified patients with metastatic colorectal cancer (mCRC) who underwent surgery within 1 year of receiving bevacizumab between January 2010 and December 2017. The primary outcomes were 30-day, 60-day, and in-hospital mortality; the secondary outcomes were hospital stay, 30-day readmission rate, and surgical complications. Multivariate analysis was used to adjust for confounders. This study included 2,047 patients. In the multivariate analysis, patients who underwent emergent operation and had higher Charlson scores had a significantly higher mortality rate. Patients with a longer interval to surgery, more cycles of bevacizumab treatment, and distal metastectomy had the opposite result. In subgroup analysis, patients who received emergent operation within 28 days had the highest surgical mortality. The interval to operation among mCRC patients who receive bevacizumab treatment should exceed 4 weeks to avoid additional risk of mortality whether patients receiving elective or emergent operation. Patients who received emergent operation within 28 days of bevcizumab infusion had the highest risk of mortality.

Sidedness and addition of chemotherapy associated with treatment outcomes of regorafenib for metastatic colorectal cancer (mCRC).

36 Background: Regorafenib is one of the options of salvage treatment for mCRC. We aimed to explore the prognostic factors of such regorafenib treatment. Methods: We searched the database of National Health Insurance, Taiwan for patients who initiated regorafenib treatment for mCRC from September 1, 2015, to December 31, 2018. Database interrogation of National Death Registry, Taiwan and Taiwan Cancer Registry was conducted for survival data and clinicopathological variables, respectively. Results: A total of 3,643 patients were included in the analysis. The median age was 61.2 years. The primary tumor was left-sided and KRAS mutant in 75.3% and 54.5% of patients, respectively; 28.9% of patients received chemotherapy simultaneously, with irinotecan as the most common companion. The median time to treatment discontinuation (TTD) was 2.3 months (95% confidence interval [CI]: 95% CI: 2.3-2.3), and the median overall survival (OS) was 7.2 months (95% CI: 6.9-7.4). Patients with left-sided primary tumors, compared with patients with right-sided tumors, exhibited significantly longer TTD (median, 2.4 vs. 2.1 months, p &lt; 0.001) and OS (median, 7.6 vs. 6.1 months, p &lt; 0.001). By contrast, TTD and OS of patients under regorafenib treatment were similar regardless the KRAS mutation status ( p = 0.415 and 0.643, respectively). Patients who received chemotherapy along with regorafenib, compared with patients who did not, also exhibited significantly longer TTD (median, 2.6 vs. 2.2 months, p &lt; 0.001) and OS (median, 8.3 vs. 6.7 months, p &lt; 0.001). In multivariate analysis adjusting age, sex, time from colorectal cancer diagnosis, hospital level, KRAS mutation, and initial regorafenib dose, left-sidedness of the primary tumor remained a predictor for better TTD (hazard ratio [HR]: 0.88, p = 0.002) and OS (HR: 0.92, p = 0.048), as well as addition of chemotherapy (for TTD, HR: 0.86, p &lt; 0.001; for OS, HR: 0.76, p &lt; 0.001). Due to the interaction between sidedness and KRAS mutation, we established separate Cox models and found that left-sided primary tumor was an independent predictor for better TTD and OS for KRAS wild-type tumors, but not for KRAS mutant tumors. Conclusions: In this population-wide cohort study, left-sided primary tumor and addition of chemotherapy were associated with better TTD and OS of regorafenib treatment for mCRC.