Standardized Incidence Ratios Research Articles

Risk of second primary cancers after a diagnosis of first primary cancer: A pan-cancer analysis and Mendelian randomization study.

The risk of second primary cancers (SPC) is increasing after the first primary cancers (FPC) are diagnosed and treated. The underlying causal relationship remains unclear. We conducted a pan-cancer association (26 cancers) study in the Surveillance, Epidemiology, and End Results (SEER) database (non-Hispanic whites). The standardized incidence ratio (SIR) was estimated as the risk of SPCs in cancer survivors based on the incidence in the general population. Furthermore, the causal effect was evaluated by two-sample Mendelian Randomization (MR, 13 FPCs) in the UK Biobank (UKB, n=459,136,, European whites) and robust analysis (radial MR and Causal Analysis Using Summary Effect estimates, CAUSE). We found 11 significant cross-correlations among different cancers after harmonizing SIR and MR results. Whereas only 4 of them were confirmed by MR to have a robust causal relationship. In particular, patients initially diagnosed with oral pharyngeal cancer would have an increased risk of non-Hodgkin lymphoma (SIRSEER = 1.18, 95%Confidence Interval [CI]:1.05-1.31, ORradial-MR=1.21, 95% CI:1.13-1.30, p=6.00 × 10-3; ORcause = 1.17, 95% CI:1.05-1.31, p=8.90 × 10-3). Meanwhile, ovary cancer was identified to be a risk factor for soft tissue cancer (SIRSEER = 1.72, 95%Confidence Interval [CI]:1.08-2.60, ORradial-MR=1.39, 95% CI:1.22-1.58, p=1.07 × 10-3; ORcause = 1.36, 95% CI:1.16-1.58, p=0.01). And kidney cancer was likely to cause the development of lung cancer (SIRSEER = 1.28, 95%Confidence Interval [CI]:1.22-1.35, ORradial-MR=1.17, 95% CI:1.08-1.27, p=6.60 × 10-3; ORcause = 1.16, 95% CI:1.02-1.31, p=0.05) and myeloma (SIRSEER = 1.54, 95%Confidence Interval [CI]:1.33-1.78, ORradial-MR=1.72, 95% CI:1.21-2.45, p=0.02; ORcause = 1.49, 95% CI:1.04-2.34, p=0.02). A certain type of primary cancer may cause another second primary cancer, and the profound mechanisms need to be studied in the future. This work was in supported by grants from National Natural Science Foundation of China (Grant No. 81972645), Innovative research team of high-level local universities in Shanghai, Shanghai Youth Talent Support Program, intramural grant of The University of Hong Kong to Dr. Rong Na, and Shanghai Sailing Program (22YF1440500) to Dr. Da Huang.

Cardiovascular-Related Mortality Risk in Primary Myelofibrosis in Pre-Ruxolitinib and Ruxolitinib Eras

Background Ruxolitinib, a Janus Kinase inhibitor, was approved in 2011 for the treatment of primary myelofibrosis (PMF) and has shown improved survival since its introduction. However, there are reports of possible cardiotoxicity linked to the medication. 1,2 Previous studies have shown that cardiovascular disease (CVD) was the third most common cause of death in PMF. 3 Given that patients with PMF may need therapy for several years, the cardiovascular safety profile of ruxolitinib has been the subject of increased scrutiny. Our goal was to compare the cardiovascular-related mortality (CVM) risk in patients with PMF in the pre-ruxolitinib (pre-Rux) and ruxolitinib (Rux) eras. Methods Using the Surveillance, Epidemiology, and End-result (SEER) Research Plus Data, 17 Registries and Multiple Primary Standardized Incidence Ratio (MP-SIR) registries (2000 - 2020), a retrospective study of patients diagnosed with PMF between 2003 and 2019 was conducted. This period was split into the pre-Rux (2003-2010) and post-approval Rux eras (2012-2019) and compared the standard mortality ratios (SMRs) of CVD in both periods. SMR was expressed as the ratio of cardiovascular deaths observed in PMF to those expected in the general population. Descriptive statistics (frequencies) were compared with Chi-square. The Kaplan-Meier method was used to estimate cumulative relative survival (CRS), and the sub-distribution hazard model for competing risk analysis was used to predict CVM; the significance test was set at <0.05. Results 4,509 patients with PMF were identified between the two study periods (2003-2010 and 2012-2019). As shown in Table 1, a higher proportion of older patients aged 65+ years (67.2% vs. 62.9%, p=0.003) and Non-Hispanic Blacks (8.9% vs. 7.5%, p=0.025) were diagnosed in the Rux era. More patients were alive (49.6% vs. 16.6%, p<0.001), and 5-year CRS was higher in the Rux period (57.1% vs. 47.6%). There was no significant difference in the proportion of deaths due to cardiovascular disease between the two periods. Compared to the general population, patients with PMF had a higher overall CVM independent of the era of diagnosis ( Figure 1). However, there was a decrease in SMR of overall CVD in the post-Rux period (SMR=2.67; 95% CI: 2.28-3.10) compared to the pre-Rux (SMR: 3.42; 95% CI: 2.79-4.15). In terms of specific CVD, the SMRs of diseases of the heart, hypertension without heart diseases, and cerebrovascular disease were higher in the pre-RUX period compared to the Rux era, where SMR was higher only in diseases of the heart, which was still lower than the pre-Rux period (SMR: 2.73 [2.28-3.24] vs. 3.57 [2.84-4.44]). There was no significant difference in the mortality risk from other CVD compared to the general population in both periods. On multivariate analysis, after adjusting for age, sex, race and era of diagnosis, factors associated with reduced odds of CVM were diagnosis of PMF in the RUX era ( HR=0.76; 95% CI: 0.61-0.94, p=0.012), female gender ( HR=0.72; 95% CI: 0.58-0.89, p=0.002) and younger age (<65 years, HR= 0.12; 95% CI: 0.09-0.17, p<0.001. Non-Hispanic Black race was an independent predictor of increased CVM. Conclusion The risk of CVM in PMF compared to the general population did not seem to have increased in the era following the approval of ruxolitinib. The SMRs for overall and some specific cardiovascular diseases appear to be lower in the ruxolitinib era compared to the period before its approval. Lastly, the period following the introduction of ruxolitinib was associated with reduced death from cardiovascular diseases. Hence, ruxolitinib may have had some mortality benefits from cardiovascular disease in PMF; however, further studies are needed to examine and validate this observation.

Disparities in cancer incidence and mortality for individuals incarcerated in Massachusetts (MA) state prisons compared to the general population.

187 Background: More than 10 million people are incarcerated annually in the US. Incarcerated individuals are disproportionately affected by cancer disparities, yet receive healthcare while in prison which may offer opportunities for enhanced cancer screening and treatment. Little research has evaluated disparities in cancer incidence and survival among incarcerated patients. Methods: Name, birth date, and sex were obtained for individuals incarcerated in MA state prisons from 2010-2019 from the MA Department of Corrections and matched to MA state cancer registry data. Patients diagnosed with an incident cancer were classified as currently incarcerated (CI), formerly incarcerated (FI), or never incarcerated (NI) based upon incarceration status at diagnosis. We examined crude cancer incidence, standardized incidence ratios (SIR) and crude overall survival (OS) by incarceration status, and evaluated survival differences with Cox proportional hazards models adjusted for age, sex, race, ethnicity, diagnosis year and cancer type. Results: Of 416,267 cancers diagnosed in 2010-2019, 288 (0.1%) CI, 785 (0.2%) FI and 415,194 (99.7%) NI patients were diagnosed with cancer. Demographics differed by incarceration status (median age: 57 vs 54 vs 66 years for CI, FI and NI, respectively; males: 92.4% vs 71.6% vs 46.4%; and Whites: 69.8% vs 77.3% vs 89.4%; all P≤0.01). The most common cancers detected are in Table. Detection of screenable cancers were highest in CI and NI patients (51.4% and 51.0%) and lowest in FI patients (46.2%; p=0.03). However, of those diagnoses, 25.6% of CI and 22.6% of FI were diagnosed with Stage IV disease, compared with 16.4% of NI patients (p=<0.0001). Crude incidence per 100,000 patient years was 271.7 for CI, 267.9 for FI and 773.2 for NI patients. Compared to NI men, the SIR was 97.6 (95% CI 86.2-110.1) for CI men and 109.5 (95% CI 100.6-118.9) for FI men. Unadjusted 1-year all-cause OS was 68.1% for CI, 72.6% for FI and 76.5% for NI patients, while 5-year OS was 36.4% for CI, 53.2% for FI and 60.9% for NI patients (Table). In adjusted models, CI and FI patients had statistically worse OS, compared with NI (CI vs. NI: HR 2.17, 95% CI 1.84-2.56; FI vs. NI: HR 1.85, 95% CI 1.66-2.07). Conclusions: In MA, CI and NI patients are more likely than FI patients to have screenable cancers detected. However, CI and FI patients are more likely to be diagnosed with stage IV disease, and have worse all-cause OS, compared to NI patients. Research on cancer screening and treatment in prisons is needed to improve cancer outcomes for CI and FI patients.[Table: see text]

Adverse events from HPV vaccination in Taiwan

The safety of human papillomavirus (HPV) vaccines has been evaluated continuously in pre-licensure clinical trials, post-marketing surveillance systems, and observational studies. Most studies have found no significant association between serious adverse events and HPV vaccination. However, these studies have focused on Western populations; similar studies focusing on Asian populations are insufficient. Our retrospective cohort study used the HPV-vaccination records of junior high-school adolescent girls aged 12–15 years between 2013 and 2018 in Taiwan’s National Immunization Information System and linked them to a registry for beneficiaries in Taiwan’s National Health Insurance Database (NHID) to establish the vaccinated group. We selected 19 serious diseases as serious adverse events. We compared the incidence rates of these serious adverse events between the vaccinated group and girls in the same age group population, and we calculated the standardized incidence ratio (SIR) to evaluate the risk of serious adverse events after HPV vaccination. Because of the onset of different types of diseases, we set three periods after the subjects received HPV vaccination: within 3 months, within 1 year, and during the study period (2013–2018). The results showed the incidence rates and the SIRs of 19 selected adverse events. Among the 19 selected serious adverse events, the disease with the highest incidence rate during the study period was fibromyalgia (73.23 cases per million population), and the disease with the lowest incidence rate during the study period was Crohn’s disease (0.15 cases per million population). The results showed no statistically significant increases in the risk of 19 selected serious adverse events and indicated no association between HPV vaccination and serious adverse events. Given the benefits and safety of HPV vaccination, our research can reduce concerns about vaccine side effects, inform health policies and improve public and clinician’s acceptance of HPV vaccine policy.

Future cancer risk after urgent suspected cancer referral in England when cancer is not found: a national cohort study

Following referral for investigation of urgent suspected cancer within the English National Health Service referral system, 7% of referred individuals are diagnosed with cancer. This study aimed to investigate the risk of cancer occurrence within 1-5 years of finding no cancer following an urgent suspected cancer referral. This national cohort study used urgent suspected cancer referral data for England from the Cancer Waiting Times dataset and linked it with cancer diagnosis data from the National Cancer Registration dataset. Data were extracted for the eight most commonly referred to urgent suspected cancer referral pathways (breast, gynaecological, head and neck, lower and upper gastrointestinal, lung, skin, and urological) for the period April 1, 2013, to March 31, 2014, with 5-year follow-up for individuals with no cancer diagnosis within 1 year of referral. The primary objective was to investigate the occurrence and type of subsequent cancer in years 1-5 following an urgent suspected cancer referral when no cancer was initially found, both overall and for each of the eight referral pathways. The numbers of subsequent cancers were compared with expected cancer incidence in years 1-5 following referral, using standardised incidence ratios (SIRs) based on matched age-gender distributions of expected cancer incidence in England for the same time period. The analysis was repeated, stratifying by referral group, and by calculating the absolute and expected rate of all cancers and of the same individual cancer as the initial referral. Among 1·18 million referrals without a cancer diagnosis in years 0-1, there were 63 112 subsequent cancers diagnosed 1-5 years post-referral, giving an absolute rate of 1338 (95% CI 1327-1348) cancers per 100 000 referrals per year (1038 [1027-1050] in females, 1888 [1867-1909] in males), compared with an expected rate of 1054 (1045-1064) cancers per 100 000 referrals per year (SIR 1·27 [95% CI 1·26-1·28]). The absolute rate of any subsequent cancer diagnosis 1-5 years after referral was lowest following suspected breast cancer referral (746 [728-763] cancers per 100 000 referrals per year) and highest following suspected urological (2110 [2070-2150]) or lung cancer (1835 [1767-1906]) referral. For diagnosis of the same cancer as the initial referral pathway, the highest absolute rates were for the urological and lung pathways (1011 [984-1039] and 638 [598-680] cancers per 100 000 referrals per year, respectively). The highest relative risks of subsequent diagnosis of the same cancer as the initial referral pathway were for the head and neck pathway (SIR 3·49 [95% CI 3·22-3·78]) and lung pathway (3·00 [2·82-3·20]). Cancer risk was higher than expected in the 5 years following an urgent suspected cancer referral. The potential for targeted interventions, such as proactive monitoring, safety-netting, and cancer awareness or risk reduction initiatives should be investigated. Cancer Research UK.

Low-dose CT for lung cancer early-detection in China: Findings from a screening program in Shanghai

Abstract Background Low-dose computed tomography (LDCT) has been recommended for lung cancer screening in high-risk populations. This study is aimed to evaluate the effects of LDCT screening for lung cancer in Chinese populations. Methods A total of 26124 subjects aged over 40 years were enrolled from the Minhang District of Shanghai, China, 2013-2017. The detection of lung cancer and the survival status of cases up to Dec 31,2018 were obtained. Standardized incidence ratio (SIR) was calculated for the screened populations relative to the local general population. Three-year survival rates and proportion of early-stage (stage 0-I) cancer were estimated for all cases from general population and for screen-detected cases. For 12184 high-risk individuals in the screened population, a total of 12184 matched controls without LDCT were identified using propensity score matching (PSM), lung cancer mortality and all-cause mortality were calculated and compared between groups. Results The crude incidence of lung cancer in the screened population was 426.6 (95%CI: 387.4-470.2) per 100000 person-years, with an overall SIR of 2.3 (95%CI: 2.0-2.5). The SIR decreased with the highest level in the first year [3.8 (95%CI: 3.3-4.3)], and a lower level over 3 years [0.6 (95%:CI: 0.5-0.7)]. Early-stage lung cancer accounted for 26.3% of screen-detected cases, significantly higher than 15.3% in all cases during the same period. The 3-year survival rate was also higher in screen-detected cases (60.4%) than all cases (50.9%). Compared with the matched control group, the screened group had a 32.0% (95%CI: 0.47- 0.99) reduced lung cancer mortality and a 56% (95%CI: 0.37-0.52) decreased all-cause mortality. The proportion of early-stage lung cancer was also higher in cases screened-detected than in non-screened (28.9% vs 11.8%, p < 0.05). Conclusions Our results prove the benefits of LDCT screening and its great potential in reducing the disease burden of lung cancer in Chinese populations. Key messages • LDCT screening improved the detection of lung cancer in Chinese populations, and increased the proportion of early-stage cancer and 3-year survival rate of detected lung cancer cases. • LDCT screening decreased 32% of lung cancer mortality and 56% of all-cause mortality in Chinese populations.

Exploring the spatial pattern of animal bites in Iran (2021–2022)

ObjectiveKnowledge of the spatial pattern of animal bites can be helpful for targeted resource allocation and to develop and deliver effective intervention programs. The aim of this study was to explore the spatial pattern of the animal bites in Iran during 2021–2022. MethodsAnimal bite cases from all provinces and counties in Iran were obtained from a nationally based registry. Global Moran's I was applied to check spatial autocorrelation. The spatially adjusted standardized incidence ratios (SIRs) were estimated using the Besag, York, and Mollie (BYM) model. Spatial clusters were identified by local indicators of spatial association (LISA) and purely spatial scan statistic. ResultsA total of 260,470 animal bites were registered during the study period. There was a positive spatial autocorrelation (global Moran's I=0.27, p-value=0.001). The majority of SIRs greater than 1.00 was found in counties in the northern belt of Iran (e.g., observed greater than expected animal bites). LISA found that approximately 7% of counties in the north and northeast, 18% in the west and south, and 3% in the central part of Iran were significant hot spots, cold spots, and spatial outliers (p-value≤0.05). Spatial scan statistic detected primary hot spot cluster in the counties in the Mazandaran and Alborz provinces (Relative Risk=2.56, p-value<0.001), while primary cold spot cluster involved counties in Kurdistan and Kermanshah province (0.37, <0.001). ConclusionAnimal bites were unevenly distributed in Iran. Further prevention and control programs as well as appropriately resource allocation are needed in order to reduce the observed animal bites spatial disparity.

Cancer risk, disease-modifying therapy, and age in multiple sclerosis: A retrospective population-based cohort study

BackgroundLong-term population-based safety studies are needed to investigate cancer outcomes in people with multiple sclerosis (MS) treated with modern disease-modifying therapy (DMT). ObjectivesTo investigate if exposure to DMT increases the risk of invasive cancer in MS. MethodsWe used population-based administrative health data from Alberta, Canada between 2008 and 2018. DMT exposure was defined in two ways: first as exposure to any DMT, and second by DMT type (modulating, sequestering, depleting). Study outcome was time to first diagnosis of invasive cancer. Cancer risk was compared to the general population using standardized incidence ratios (SIRs) and to the unexposed MS cases using hazard ratios (HRs). ResultsThe analysis included 14,313 MS cases: 5,801 (40.5 %) were exposed to DMT. Median (interquartile range) follow-up was 8.4 (4.3, 10.4) years. Compared to the general population, there was no difference in cancer risk for the overall MS population (SIR: 0.94, 95 % confidence interval [CI]: 0.87, 1.02) or the DMT-exposed MS cases (SIR: 0.89; 95 % CI: 0.75, 1.05). Compared to unexposed MS cases, we found an interaction with age for exposure to any DMT (p = 0.001) and modulating DMT (p = 0.001), indicating that a difference in the risk of cancer associated with DMT depends on age. Cancer risk was not associated with exposure to sequestering DMT (HR: 1.28, 95 % CI: 0.78, 2.08) or depleting DMT (HR: 2.29, 95 % CI: 0.86, 6.14). ConclusionsCancer risk for MS patients was similar to the general population. In the MS population, the age-dependent effect of DMT for cancer risk suggests a higher risk of cancer with age 62 or older and a protective effect at younger age. Further investigation is required to clarify whether the interaction between DMT exposure and age is a causal effect.

Second Hematologic Malignancies Associated With Primary Mediastinal Germ Cell Tumors: A Population-based Study.

Studies addressing second hematologic malignancies (SHMs) in patients with primary mediastinal germ cell tumors (PMGCTs) are scarce. To better describe this phenomenon, we analyzed a large case series from a population-based registry. The Surveillance, Epidemiology, and End Results database was used to report the clinical characteristics and incidence of SHMs in patients with PMGCT. Among 1297 PMGCTs, 27 cases (2.08%) of SHM were found, with a median latency period of 12 months (95% CI: 5-41). All SHM occurred in males, 20 of whom (74.1%) had a previous nonseminomatous tumor. Acute myeloid leukemia was the most frequent SHM, accounting for 13 cases, 4 of which were acute megakaryoblastic leukemia that occurred within 5 months of diagnosis. The median survival after the diagnosis of SHM was 6 months (95% CI: 2-41). The risk of SHM was significantly higher than expected for the reference population, with a standardized incidence ratio of 6.21 (95% CI: 3.31-10.62) and an absolute excess risk of 19.19 per 10,000 person-years. Patients with PMGCT are at a higher risk of developing SHMs than the general population, particularly acute myeloid leukemia. This risk ranges from synchronous diagnosis of acute megakaryoblastic leukemia to the later onset of other hematological disorders that might be related to PMGCT therapies. Our findings may help create follow-up schedules for patients with PMGCT and raise the level of suspicion surrounding this association.

Incidence and Geographical Distribution of Adrenocortical Carcinoma: Retrospective Analysis of a State Cancer Registry

ObjectiveAdrenocortical carcinoma (ACC) is a rare malignancy without established association with environmental risk factors. ACC incidence is stable based on large surgical databases while referral centers data reported increasing number of cases seen. We studied ACC incidence and distribution at a county level to find potential ACC “hot spots” that could be linked to environmental exposures. MethodsA retrospective analysis of Texas Cancer Registry that included ACC patients diagnosed between 2000 and 2018. County-level heatmaps were created and compared with breast, prostate, and lung cancer. ResultsWe identified 448 ACC cases during the study period. Cases were registered in 110 of the 254 counties (43.3%) in Texas, representing 92.74% of the total population. The median incidence was 23 new cases/y (range 14-33). The mean population-adjusted ACC incidence rate was 0.104 per 100 000 per year (standard deviation 0.005; 95% CI, 0.092-0.116). Seven counties (6.3%) accounted for 215 (48.0%) cases, with more than 10 cases each and median standardized incidence ratio (SIR) of 0.1 (range, 0.0-0.9). One hundred three counties (93.7%) accounted for the remaining 233 cases (52%), with fewer than 10 cases per county. The highest standardized incidence ratios were found in counties with a median population of fewer than 14 000 residents and with only one reported case. ConclusionOur analysis is the first report to create ACC heatmap and could not detect any geographic clustering of ACC in Texas. The incidence of ACC remained stable and consistent with data from other large databases.

Severity of Chronic Graft-versus-Host Disease and Late Effects Following Allogeneic Hematopoietic Cell Transplantation for Adults with Hematologic Malignancy

The study aimed to determine the association of chronic graft-versus-host disease (cGVHD) diagnosis and severity with the development of subsequent neoplasms (SN) and nonmalignant late effects (NM-LE) in 2-year disease-free adult survivors following hematopoietic cell transplantation (HCT) for a hematologic malignancy. To do so, we conducted a retrospective analysis of 3884 survivors of HCT for hematologic malignancy in the Center of International Blood and Marrow Transplant Research database. We conducted a landmark analysis at the 2-year post-transplantation date, comparing first SN and NM-LE in survivors with and without cGVHD. The cumulative incidence (CuI) of SN and NM-LE were estimated through 10 years post-HCT in both groups, with death or disease relapse as a competing risk. Cox proportional hazards models were used to evaluate the associations of cGVHD and its related characteristics with the development of SN and NM-LE. The estimated 10-year CuI of SN in patients with GVHD (n=2669) and patients without cGVHD (n=1215) was 15% (95% confidence interval [CI], 14% to 17%) versus 9% (7.2% to 11%) (P < .001). cGVHD by 2 years post-HCT was independently associated with SN (hazard ratio [HR], 1.94; 95% CI, 1.53 to 2.46; P < .0001) with a standardized incidence ratio of 3.2 (95% CI, 2.9 to 3.5; P < .0001). Increasing severity of cGVHD was associated with an increased risk of SN. The estimated 10-year CuI of first NM-LE in patients with and without cGVHD was 28 (95% CI, 26% to 30%) versus 13% (95% CI, 11% to 15%) (P < .001). cGVHD by 2 years post-HCT was independently associated with NM-LE (HR, 2.23; 95% CI, 1.81 to 2.76; P < .0001). Multivariate analysis of cGVHD-related factors showed that increasing severity of cGVHD, extensive grade, having both mucocutaneous and visceral involvement, and receiving cGVHD treatment for >12 months were associated with the greatest magnitude of risk for NM-LE. cGVHD was closely associated with both SN and NM-LE in adult survivors of HCT for hematologic malignancy. Patients identified as having more severe involvement and both mucocutaneous and visceral organ involvement may warrant enhanced monitoring and screening for SNs and NM-LEs. However, caution is warranted when interpreting these results, as patients with cGVHD may have more vigilant post-transplantation health care and surveillance for late effects.

Risks of non-ovarian cancers in women with borderline ovarian tumor: a national cohort study in Sweden

BackgroundAssociations between different cancer types are known. The affirmation of the risk for non-ovarian cancer after ovarian borderline tumors (BOT) is, however, sparse.AimTo analyze the risk of subsequent or simultaneous cancers in women with BOTs compared with the general female Swedish population.MethodsAn open cohort study (1995–2018) was conducted where a diagnosis of BOTs as well as subsequent or simultaneous cancer diagnoses were obtained from the Swedish Cancer Register and matched to the Total Population Register. Each woman with BOT was followed until non-ovarian cancer, death or emigration and could only be included once for the outcome. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) for specific non-ovarian cancers were analyzed.ResultsThe 4998 women with serous and mucinous BOTs were diagnosed during 1995–2018 with a mean age of 55.7 years (SD 16.0) at diagnosis. Compared with the general female population, women with BOTs had increased risks for non-ovarian cancer in colon (SIR = 2.5; 95% CI 2.0–3.1), rectum (SIR = 1.7; 95% CI 1.1–2.5), small intestine (SIR = 5.0; 95% CI 2.3–9.5), cervix (SIR = 2.5; 95% CI 1.4–4.2), endometrium (SIR = 2.4; 95% CI 1.9–3.1), pancreas (SIR = 2.3; 95% CI 1.4–3.5), upper aerodigestive tract (SIR = 2.2; 95% CI 1.2–3.8), lung (SIR = 1.8; 95% CI 1.4–2.3), kidney (SIR = 2.3; 95% CI 1.4–3.7) and bladder (SIR = 1.8; 95% CI 1.1–2.8). Among women with serous BOTs, the risk of thyroid gland cancer (SIR = 3.1; 95% CI 1.2–6.4) was also increased. Lung and pancreas cancer showed increased risks more than 1 year after a diagnosis of BOT.ConclusionsThis Swedish population-based study demonstrated an increased risk of multiple malignancies including lung and pancreatic cancers beyond the first year of diagnosis in patients with borderline ovarian tumors (BOTs), suggesting a potential shared etiology.

Thyroid cancer risk after radiation exposure in adults-systematic review and meta-analysis.

Notably, the growing use of radionuclear technology, especially in diagnostic and therapeutic procedures involving radiation exposure, raises concerns about the health effects of radiation. Although epidemiological studies have provided strong evidence for elevated thyroid cancer risk after radiation exposure in childhood, the risk of thyroid cancer associated with adult exposure remains to be investigated. We conducted a systematic review and meta-analysis of relevant studies on the risk of developing thyroid cancer after radiation exposure in adulthood. The PubMed and Web of Science databases were used to select eligible articles. After screening, a total of 15 studies were identified in which estimates of the standardized incidence ratio (SIR) and the relative risk (RR) of thyroid cancer were available in 8 and 11 studies, respectively. The overall SIR estimated by the random effects model was 2.19 [95% confidence interval (CI), 1.54, 3.10]. Cochran's Q test showed significant heterogeneity in the SIRs (Q= 178, P< 0.0001). The overall RR at 10mGy was 1.0038 (95% CI, 0.9991, 1.0085), with no significant heterogeneity (Q= 9.30, P= 0.5041). The total SIR, as well as that from each study, indicated a statistically significant excess, which could be related to screening bias. Radiation-related thyroid cancer risk was elevated in a few studies; however, the overall estimate of the RR at 10mGy was not significant. This study demonstrates no strong epidemiological evidence for the risk of thyroid cancer in radiation exposure during adulthood; however, further research is needed.

Retinal vascular occlusion risks during the COVID-19 pandemic and after SARS-CoV-2 infection

The coronavirus disease 2019 (COVID-19) has been reported to affect vascular networks including the eye. However, evidence on the causal relationship between COVID-19 infection and retinal vascular occlusions remains limited. This study aimed to determine the change in retinal vascular occlusion incidence during COVID-19 era and whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces retinal vascular occlusion. Retinal vein occlusion (RVO) and retinal artery occlusion (RAO) incidences during 2018–2019 and 2020–July 2021 were compared, those in confirmed and suspected COVID-19 patients diagnosed from 2020 to January 2021 were calculated, and those in COVID-19 patients during 180 days prior and 180 days after diagnosis were assessed. Additionally, the standardized incidence ratio of RVOs in COVID-19 patients was analyzed. Incidence rates per 100,000 people/year of RVO during 2018–2019 and 2020–2021 was 102.0 and 98.8, respectively. RAO incidence rates during 2018–2019 and 2020–2021 were 11.7 and 12.0, respectively. In both confirmed and suspected COVID-19 patients, the incidence of RVO and RAO did not change significantly from 180 days before to after diagnosis in the adjusted model. RVO incidence slightly decreased while RAO incidence increased during the COVID-19 pandemic. SARS-CoV-2 infection did not significantly increase RVO or RAO incidence.

SAT416 The Incidence Of Autoimmune Disease In Transgender People After Initiation Of Gender-Affirming Hormone Therapy

Abstract Disclosure: C. Wiepjes: Advisory Board Member; Self; Novartis Pharmaceuticals. M. Den Heijer: None. Background Autoimmune diseases are more common in women than in men, possibly caused by differences in sex hormones. Generally, estrogen has an immunoenhancing effect, while testosterone has an immunosuppressive effect. However, it is not known whether gender-affirming hormone therapy in transgender people affects the risk of developing autoimmune diseases. Therefore, we aimed to compare the incidence of autoimmune diseases in trans women and trans men during hormone therapy with rates from the general population. Methods All people who visited the gender identity clinic in Amsterdam, the Netherlands, between 1972 and 2018 were included (n=8831). The medical records were screened for the occurrence of autoimmune diseases. In addition, the cohort was linked to a nationwide health data registry with medical diagnoses, as not all people received their check-ups at our clinic and in order to compare with a control population. These additional diagnoses were available from 2012-2017 and based on Diagnosis-Treatment-Combination codes. People were excluded for analyses if they did not use gender-affirming hormones (n=3022), did not have a follow-up visit (n=345), could not be linked with the nationwide health data registry (n=630), used alternating testosterone and estradiol (n=38), or had an autoimmune disease before start of hormone therapy (n=112). Standardized incidence ratios (SIR) were computed for trans women and trans men compared with the general population. Results In total, 4684 people were included, of which 2830 trans women and 1854 trans men. Median age at start of hormone therapy was 29 years (IQR 22 to 40) in trans women and 22 years (IQR 18 to 29) in trans men. Median follow-up time was 10 years (IQR 3 to 22, max 59) in trans women (total 38326 person years) and 4 years (IQR 1 to 13, max 48) in trans men (total 16548 person years). In total, 55 trans women and 48 trans men developed an autoimmune disease, after a median duration of hormone therapy of 7 years (IQR 2 to 17) in trans women and 5 years (IQR 1 to 12) in trans men. In the analyses with first autoimmune disease between 2012 and 2017, 25 trans women had an event, while 31 cases (SIR 0.81, 95%CI 0.52 to 1.16) were expected compared to cis men and 47 cases (SIR 0.54, 95%CI 0.35 to 0.77) compared to cis women. In trans men, 27 people had an event, while 15 cases were expected compared to cis men (SIR 1.81, 95%CI 1.19 to 2.55) and 23 cases were expected compared to cis women (SIR 1.16, 95%CI 0.77 to 1.64). Conclusion The risk of developing autoimmune diseases in trans women using gender-affirming hormones was similar to the risk in cis men, whereas trans men had a similar risk as cis women. This implies that gender-affirming hormone therapy does not influence the risk of developing autoimmune diseases. For further research it is interesting to see whether the severity of autoimmune diseases changes in trans people starting gender-affirming hormones. Presentation: Saturday, June 17, 2023

FRI191 Changes In The Incidence And Geographical Distribution Of Adrenocortical Carcinoma: A Retrospective Analysis Of A State Cancer Registry

Abstract Disclosure: V.B. Brondani: None. A.M. Griffin: None. T.J. Owen: None. K.W. Merriman: None. J.M. Varghese: None. C. Jimenez: None. S.G. Waguespack: None. P.H. Graham: None. M.T. Campbell: None. M.M. Hassan: None. M.A. Habra: None. Background: Adrenocortical carcinoma (ACC) is a rare malignancy with an annual incidence of 0.102 cases per 100,000 persons per year in the United States. At our tertiary cancer center, we have observed increasing numbers of cases, but to date there has been no study exploring ACC incidence at a populational level to validate our observations. Furthermore, the possibility of geographic ACC clusters has not been studied. Our objectives were to evaluate the incidence and geographical distribution of ACC cases in Texas. Methods: Cases of ACC between 2000 and 2018 were retrospectively identified from the Texas Cancer Registry (TCR). Cases were registered in 110 of Texas' 254 counties (43.3%), representing 92.74% of the total population of Texas. SEER Stat software was used to pool demographic and clinical characteristics and calculate incidence rates. Kaplan-Meier overall survival curve and Pearson's correlations were calculated using SPSS. P values &amp;lt; .05 were considered significant. ACC county-level heatmaps were created with Tableau software to identify clusters. Breast, prostate, lung cancer incidences and their geographic distribution were compared to ACC data. Results: TCR registered 448 cases of ACC in the study period, with a median of 23 new cases/year (range 14-33). Thirty-three (7.4%) patients were aged 19 years or younger (15 were under 5 years), 293 (65.4%) patients were between 20 and 64 years, and 122 (27.23%) were 65 years or older. The majority were female (270 cases [60.3%]), and White (393 [87.7%]). One hundred (22.3%) patients were Hispanic. In 155 evaluable cases, the proportions of patients with stage I, II, III, and IV disease at diagnosis were 7.7%, 27.7%, 16.1%, and 48.4%, respectively. The median overall survival was two years (range, 0-19 years). The mean adjusted population ACC incidence rate was 0.104 per 100,000 per year (std = 0.005; 95% CI, 0.092-0.116). Seven counties (6.3%) accounted for 215 (48.0%) cases, with more than 10 cases each (median, 34 cases per county; range, 11-66) and a median standardized incidence ratio (SIR) of 0.1 (range, 0.0-0.9). One hundred three counties (93.7%) accounted for the remaining 233 cases (52%), with fewer than 10 cases per county (median, 1 case; range, 1-9 cases). The highest SIRs (corresponding to &amp;gt;10, range, 11.2-30.8) were found in counties with a median population of fewer than 14,000 and with only one reported case. We could not detect any geographic clustering of ACC. Counties with a high frequency of breast, prostate, lung cancer cases also had more cases of ACC (Pearson correlation .982, .981, and .982, respectively; P &amp;lt; .01 for all tests). Conclusion: The incidence of ACC in Texas remained relatively stable through the years and consistent with the US annual incidence. We did not observe any obvious ACC cluster, and SIRs may not be useful for analyzing this rare disease. Presentation: Friday, June 16, 2023

Cancer incidence among visual artists: 45 years of follow-up in four Nordic countries

Introduction Professional visual artists constitute a heterogeneous vocational group, including, but not limited to painters, photographers, textile artists, and sculptors who may face exposure to workplace hazardous substances and lifestyle factors that may contribute to the development of selected cancers. The objective of this registry-based cohort study was to assess the cancer incidence among Nordic visual artists. Materials and methods This study is based on data from the Nordic Occupational Cancer (NOCCA) project that combines census data of 15 million people from all Nordic countries and cancer registries from 1961 to 2005. For the present study we selected a cohort of visual artists from Finland, Iceland, Norway, and Sweden. Standardized incidence ratio (SIR) analyses were conducted with the cancer incidence rates for the entire national study populations used as reference rates. Results In male visual artists, there were statistically significant excesses in cancers of the tongue (SIR 2.91, 95% confidence interval 1.74–4.55), oral cavity (2.09, 1.26–3.27), pharynx (2.18, 1.45-–3.15), testis (1.91, 1.11–3.05), renal pelvis (2.48, 1.42–4.03) and bladder (1.33, 1.14–1.55). The risk was significantly decreased for cancers of the lip (0.45, 0.18-0.93) and stomach (0.65, 0.50–0.84). In female visual artists, the only significantly increased risk was observed for breast cancer (1.29, 1.13–1.48) and the only significantly decreased risk for stomach cancer (0.43, 0.17–0.88). The incidence of lung cancer was close to the population average in both sexes. Conclusions The non-elevated incidence of lung cancer suggests a similar prevalence of smoking between visual artists and the general population, while the elevated risk of cancers of mouth and pharynx among male visual artists is suggestive of more widespread alcohol drinking. The excess risk of urogenital cancers might be associated with exposure to solvents.

Safety of JAK and IL-6 inhibitors in patients with rheumatoid arthritis: a multicenter cohort study.

The ORAL Surveillance trial showed a potentially higher incidence of malignancy and major adverse cardiovascular events (MACEs) associated with tofacitinib than those associated with tumor necrosis factor (TNF) inhibitors (TNFis). However, few studies have compared the safety of non-TNFis or other Janus kinase (JAK) inhibitors (JAKis). This study was aimed at comparing the incidence rates (IRs) of malignancies and MACEs in patients with rheumatoid arthritis (RA) treated using interleukin-6 (IL-6) inhibitors (IL-6is) or JAKis. We retrospectively analyzed 427 patients with RA who were treated using an IL-6i (n = 273) or a JAKi (n = 154). We determined the IRs of malignancy and MACEs, and the standardized incidence ratio (SIR) of malignancies and investigated factors related to malignancy and MACEs. After adjusting the clinical characteristic imbalance by propensity score matching (PSM), we compared the IRs of adverse events between the JAKi and IL-6i groups. After PSM, the observational period was determined to be 605.27 patient-years (PY), and the median observational period was determined to be 2.28 years. We identified seven cases of malignancy (IR: 2.94 per 100 PY) in the JAKi-treated group and five cases (IR: 1.36 per 100 PY) in the IL-6i-treated group after PSM. The IR of MACEs was 2.56 and 0.83 (per 100 PY) in the JAKi- and IL-6i-treated groups. The IRRs of JAKi-treated patients versus IL-6i-treated patients were 2.13 (95% confidence interval (CI): 0.67-7.42) for malignancy and 3.03 (95% CI: 0.77-15.21) for MACE. There were no significant differences in IRR for malignancy and MACE between both groups after PSM. Univariate and multivariable Cox regression analyses revealed that older age and JAKi use were independent risk factors for malignancy, while older age, hypertension, and JAKi use were independent risk factors for MACEs. The overall malignancy SIR was significantly higher in the JAKi-treated group compared to the general population (2.10/100 PY, 95% CI: 1.23-2.97). The IRs of malignancy and MACE in patients with RA after PSM were comparable between IL-6i-treated and JAKi-treated patients. However, the SIR of malignancy in JAKi treatment was significantly higher than in the general population; therefore, further safety studies comparing JAKi to non-TNFi biologic disease-modifying antirheumatic drugs (bDMARDs) are needed.

Risk of second cancer in esophageal squamous cell carcinoma and adenocarcinoma survivors: a population-based analysis in SEER dataset.

Previous studies have reported increased risk of second cancer in both esophageal squamous cell cancer (ESCC) and esophageal adenocarcinoma (EAC) survivors. This study aimed to examine the risk and influential factors of second cancer in ESCC and EAC patients. This population-based cohort study included 7,297 ESCC patients and 11,812 EAC patients who were in 1992-2019 from the Surveillance, Epidemiology, and End Results (SEER) program in the United States. These patients were followed up until diagnosis of second cancer, death, or end of the study (December 31, 2019). We calculated standard incidence ratio (SIR) and 95% confidence interval (CI) of second cancer and performed competing-risk regression to estimate the subdistribution hazard ratios (sHR) comparing categories of patients' characteristics. After a total of 49,509.38 person-years of follow-up, 431 (5.9%) ESCC patients and 636 (5.9%) EAC patients developed a second cancer. An overall increased risk of second cancer was observed in both ESCC patients (SIR: 1.66, 95% CI: 1.51-1.83) and EAC patients (SIR: 1.11, 95% CI: 1.02-1.20). ESCC patients were at increased risk of second malignancy in oral cavity and pharynx (SIR: 12.57, 95% CI: 9.87-15.79), stomach (SIR: 3.03, 95% CI: 1.77-4.85), nose and larynx (SIR: 4.79, 95% CI: 2.47-8.37), and lung and bronchus (SIR: 2.44, 95% CI: 1.96-2.99), but decreased risk of prostate cancer (SIR: 0.73, 95% CI: 0.52-0.99). EAC patients had increased risk of second malignancies in stomach (SIR: 4.41, 95% CI: 3.23-5.89), lung and bronchus (SIR: 1.26, 95% CI: 1.02-1.54), and kidney (SIR: 1.57, 95% CI: 1.05-2.25). The risk of second cancer was higher in female ESCC patients than in males (sHR: 1.34, 95% CI: 1.11-1.63) and decreased with more advanced tumor stage in both ESCC patients (sHR: 0.62, 95% CI: 0.50-0.76 for regional stage; sHR: 0.27, 95% CI: 0.20-0.36 for distant stage) and EAC patients (sHR: 0.47, 95% CI: 0.40-0.56 for regional stage; sHR: 0.10, 95% CI: 0.07-0.13 for distant stage). Both ESCC and EAC patients are at considerable risk of certain types of second cancer.

Risk of Cancer in Patients With Crohn's Disease 30 Years After Diagnosis (the IBSEN Study).

Patients with Crohn's disease (CD) are most often diagnosed as young adults; therefore, long-term studies are needed to assess the risk of cancer over their lifetime. Thus, the aims of the present study were to determine the risk of cancer in a Norwegian population-based cohort (the Inflammatory Bowel South Eastern Norway [IBSEN] study), 30 years after diagnosis, and to assess whether patients with CD were at an increased risk of specific cancer types. The IBSEN cohort prospectively included all incident patients diagnosed between 1990 and 1993. Data on cancer incidence were obtained from the Cancer Registry of Norway. Overall and cancer-specific hazard ratios (HRs) for CD patients compared with age- and sex-matched controls were modeled using Cox regression. Standardized incidence ratios (SIRs) were estimated compared to the general population. In total, the cohort included 237 patients with CD, and 36 of them were diagnosed with cancer. Compared to the general Norwegian population, patients with CD had an increased overall risk of cancer (HR = 1.56, 95% CI: 1.06-2.28), particularly male patients (HR = 1.85, 95% CI: 1.08-3.16). The incidence of lung cancer and nonmelanoma skin cancer was increased; however, the difference was not statistically significant (SIR = 2.29, 95% CI: 0.92-4.27 and SIR = 2.45, 95% CI: 0.67-5.37, respectively). After 30 years of follow-up, the risk of all cancers in patients with CD was increased compared to the general population.