Highest Standardized Incidence Ratios Research Articles

Comparison of the standardized incidence ratio of tuberculosis among workers at medical and educational institutions: a nationwide LTBI observational cohort study

BackgroundThe objective of this study was to determine the incidence of tuberculosis (TB) among workers at medical institutions based on interferon-gamma release assay (IGRA) and compare it with that of workers at educational institutions and the general population. MethodsFrom March 2017 to December 2020, we used a cohort of workers from medical and educational institutions in Korea, who underwent IGRA as part of a national screening program for latent tuberculosis infection (LTBI). After connecting to the National Health Insurance Service (NHIS) database to detect for any actual cases of active TB, we estimated standardized incidence ratio (SIR) and the expected number of cases to compare the incidence of TB with that of the general population. ResultsSignificant disparities in TB incidence were revealed among workers in medical and educational institutions, based on IGRA results, age, and occupation. Individuals positive for IGRA in medical institutions displayed substantially higher SIR for TB, 7.19 (6.15–8.41), compared to counterparts in educational institutions, 3.69 (3.02–4.51). Comparing by age group, we see that the SIRs are higher in younger age groups compared to older ones, with 37.30 (28.11–49.50) and 11.89 (7.28–19.41) for IGRA-positive medical and education workers under 30 years of age, respectively. In the results by occupation within the medical institutions, nurses had the highest SIR at 14.17 (11.14–18.04). ConclusionsHealthcare workers in medical institutions are more likely to develop actual TB after a positive result of LTBI screening in Korea. Intensive management and surveillance programs should be reinforced.

HPV-associated cancers among people living with HIV: nationwide population-based retrospective cohort study 2004–21 in Estonia

Abstract Cancers represent the primary cause of mortality among people living with HIV (PLWH). However, comprehensive nationwide data regarding cancer incidence remains limited. Our objective was to evaluate the incidence rates of cancers, particularly those associated with human papillomavirus (HPV), within a nationwide study cohort. Using data from the Estonian Health Insurance Fund and the National Cancer Registry from 2004 to 2021, we calculated standardized incidence ratios (SIRs) for various cancer types among PLWH to compare to the general population with special emphases on HPV-associated cancers. A total of 7011 individuals (65.7% men) diagnosed with HIV were identified. HPV-associated cancers accounted for 21.4% of all incident cancer cases among PLWH. SIRs for HPV-associated cancers were 3.7 [95% confidence interval (CI) 2.2–6.2] among men living with HIV (MLWH) and 5.7 (95% CI 4.0–7.9) among women living with HIV (WLWH). In MLWH, the highest SIRs were for penile 12.5 (95% CI 4.0–38.7), followed by oropharyngeal 3.6 (95% CI 1.7–7.6) and anal–rectal cancers 2.7 (95% CI 1.1–6.4) in comparison to the general population. In WLWH, an increased incidence of cervical (SIR = 5.8, 95% CI 3.9–8.5), oropharyngeal (SIR = 6.1, 95% CI 1.5–24.3), and anal–rectal (SIR = 3.6, 95% CI 1.2–11.2) cancers was observed. A significantly increased risk of AIDS-defining and non-AIDS-defining cancers is reported. We demonstrate a substantially heightened risk of HPV-associated cancers among PLWH compared to the general population, underscoring the imperative for intensified screening and scaled-up vaccination along with improvement in adherence to antiretroviral therapy.

6893 The Interaction Effect Between BMI, Diabetes, and Age at Diabetes Onset on the Risk of Thyroid Cancer: A Population-Based Cohort Study

Abstract Disclosure: T. Hou: None. Y. Li: None. J. Tian: None. Z. Bloomgarden: None. Y. Shi: None. ObjectiveThe relationship between type 2 diabetes mellitus (T2DM) and thyroid cancer was confounded by some characteristics of diabetes. We aimed to determine the association of the presence of diabetes and, among persons with diabetes, the age at T2DM onset, BMI, and the interactive effect with the subsequent thyroid cancer risk. MethodsWe conducted a population-based longitudinal cohort study including 428,568 persons with new-onset T2DM matched with the general population (100,649,346 person-years). Risk of thyroid cancer by subgroups were calculated based on standardized incidence ratio (SIR), hazard ratio (HR), and Cox proportional hazards models. ResultsIn T2DM patients, 1142 thyroid cancer cases were identified during eight years of follow-up, with an incidence rate of 59.01/100,000 person-years and a higher SIR: 1.21 (95% CI: 1.14-1.28) compared to the general population. New-onset T2DM had an overall 21% higher risk of thyroid cancer. Both the earlier age at T2DM onset and higher BMI were associated with a significant increasing risk of thyroid cancer independently (T2DM onset age <50: SIR 1.46 (1.27-1.69); BMI ≥30.0 Kg/m2 SIR: 1.93 (1.57-2.38)). The highest risk of cancer appeared in the patients with both BMI ≥30.0 Kg/m2 and T2DM onset age <50 years (SIR=3.91, HR=3.04). Among patients with T2DM onset age <60 years, SIR shows an increasing trend of cancer risk with higher BMI levels, while no significant increasing trends with higher BMI in T2DM onset age ≥60 years. For patients with BMI ≥25.0 Kg/m2, SIR of cancer risk decreases with an later T2DM onset age, whereas no significant decreasing trends of cancer risk in BMI <24.9 Kg/m2 group. Obese (BMI ≥30.0 Kg/m2) patients had a significant higher HR of thyroid cancer only when T2DM onset age <60 years. ConclusionsBoth earlier age of T2DM onset (<50 years) and higher BMI (≥30 Kg/m2) contributed to higher risk of thyroid cancer. These results suggest that earlier screening of thyroid cancer might be appropriate in patients diagnosed with T2DM, especially in individuals with young-onset T2DM and obesity. Presentation: 6/3/2024

Report on post-transplantation cancer in southeast Asia from the Thai kidney transplantation cohort

Post-transplantation cancer is a significant cause of mortality among kidney transplant recipients (KTR). The incidence of post-transplantation cancer varies based on geographic region and ethnicity. However, data on KTR from South East Asia, where characteristics differ from other parts of Asia, is lacking. We conducted a retrospective cohort study at a transplant center in Thailand to investigate the incidence of post-transplantation cancer and mortality rates. Factors associated with post-transplantation cancer and patient outcomes were analyzed using competing-risks regression. The study included 1156 KTR with a post-transplant follow-up duration of 5.1 (2.7–9.4) years. The age- and sex-adjusted incidence rate of post-transplant cancer was highest for urothelial cancer (6.9 per 1000 person-years), which also resulted in the highest standardized incidence ratio (SIR) of 42.5 when compared to the general population. Kidney cancer had the second-highest SIR of 24.4. Increasing age was the factor associated with an increased risk of post-transplant cancer (SHR 1.03; 95% CI 1.01–1.05). Human leukocyte antigen (HLA) DR mismatch was associated with a decreased risk of post-transplant cancer (SHR 0.72; 95% CI 0.52–0.98). Post-transplantation cancer was significantly associated with patient mortality (HR 3.16; 95% CI 2.21–4.52). Cancer significantly contributes to KTR mortality, and the risk profile for cancer development in Thai KTRs differs from that of Western and most Asian counterparts. Further research is essential to explore appropriate screening protocols for countries with high rates of urothelial and kidney cancer, including Thailand.

Association Between COVID-19 and Self-Harm: Nationwide Retrospective Ecological Spatiotemporal Study in Metropolitan France.

The COVID-19 pandemic has not been associated with increases in suicidal behavior at the national, regional, or county level. However, previous studies were not conducted on a finer scale or adjusted for ecological factors. Our objective was to assess the fine-scale spatiotemporal association between self-harm and COVID-19 hospitalizations, while considering ecological factors. Using the French national hospital discharge database, we extracted data on hospitalizations for self-harm of patients older than 10 years (from 2019 to 2021) or for COVID-19 (from 2020 to 2021) in metropolitan France. We first calculated monthly standardized incidence ratios (SIRs) for COVID-19 between March 2020 and December 2021, using a Besag, York, and Mollié spatiotemporal model. Next, we entered the SIRs into an ecological regression in order to test the association between hospital admissions for self-harm and those for COVID-19. Lastly, we adjusted for ecological variables with time lags of 0 to 6 months. Compared with a smoothed SIR of ≤1, smoothed SIRs from 1 to 3, from 3 to 4, and greater than 4 for COVID-19 hospital admissions were associated with a subsequent increase in hospital admissions for self-harm, with a time lag of 2 to 4 months, 4 months, and 6 months, respectively. A high SIR for hospital admissions for COVID-19 was a risk factor for hospital admission for self-harm some months after the epidemic peaks. This finding emphasizes the importance of monitoring and seeking to prevent suicide attempts outside the epidemic peak periods.

Somatic and psychiatric comorbidity in people with diagnosed gambling disorder: A Finnish nation-wide register study.

This is the first nation-wide register study based on a total population sample measuring the gender-specific incidences of chronic diseases and conditions among adults diagnosed with gambling disorder (GD). The study used aggregated data for 2011-22 retrieved from the Register of Primary Health Care visits, Care Register for Health Care and Care Register for Social Welfare, including specialized outpatient and inpatient health care, inpatient social care and institutional care and housing services with 24-hour or part-time assistance, set in mainland Finland. Participants comprised people aged 18-90+ years with GD diagnosis [corresponding to pathological gambling, International Classification of Diseases 10th revision (ICD-10) code F63.0, n = 3605; men n = 2574, women n = 1031]and the general population (n = 4 374 192). Incidences of somatic diseases and psychiatric disorders were calculated for the people with diagnosed GD and for the general population, separately for women and men. After standardizing for age, the incidence of each diagnostic group was systematically higher for people with GD compared with the general population, except for cancer. The highest standardized incidence ratio (SIR) values were for psychiatric disorders [SIR = 234.2; 95% confidence interval (CI) = 226.1-242.4], memory disorders (SIR = 172.1; 95% CI = 119.1-234.8), nervous system diseases (SIR = 162.8; 95% CI = 152.8-173.1), chronic respiratory diseases (SIR = 150.6; 95% CI = 137.6-164.2), diabetes (SIR = 141.4; 95% CI = 127.9-155.5) and digestive diseases (SIR = 134.5; 95% CI = 127.1-142.2). In Finland, the incidence of chronic diseases and conditions among people with gambling disorder is higher compared with the general population, apart from cancer.

A Comparative Review of Standardized Incidence Ratios of De Novo Malignancies Post Liver Transplantation in Males Versus Females

After liver transplantation (LTx), the most common cause of death in the long-term is de-novo malignancy (DNM). The aim is to review the gender differences in the standardized incidence ratio (SIR) of DNM within the same geographical locations. MethodsFour studies were identified comparing post-LTx SIR between males and females. ResultsFrom 6663 males and 2780 females LTx recipients, the mean SIR from each of the four studies for males is 2.8, 2.0, 1.94, and 3.4, and 3.5, 1.3, 1.95, and 2.3 for females. On meta-analysis using a random effect model for each gender group. No significant difference was revealed after logarithmic transformation and subgroup meta-analysis. Overall mean SIR with 95% Confidence Interval (CI) for males is 2.53 (95% CI 1.65-3.88) and 2.3 (1.25-4.24) for females. lung malignancy, 1.97 (1.14-3.41) for males and 2.65 (0.67-10.47) for females. For colorectal malignancy, the combined SIR for males is 1.98 (0.58-6.78) and 1.85 (1.02-3.37) for females. The SIR for female gender-specific malignancies; SIR for breast is 1.1±4.4, cervix 2.9±1.9, uterus 2.8, and ovarian 0.7, and for males, testis 1.6±1.3, prostate 1.2±0.4. However, rare malignancies, male breast cancers (n=1, SIR, 22.6), and Kaposi's sarcoma, in males (n=6) and in females (n=1), had SIR 120. and 212.7, respectively ConclusionOverall, there are no statistical differences between male and female DNM. Female-specific cervix, uterus, ovarian, and male-specific testis and prostate have similar SIR. Rare malignancies have very high SIR.

Outcomes of 10 years of PSA screening for prostate cancer in Norwegian men with Lynch syndrome.

Pathogenic germline variants in the mismatch repair (MMR) genes are associated with an increased risk of prostate cancer (PCa). Since 2010 we have recommended MMR carriers annual PSA testing from the age of 40. Prospective studies of the outcome of long-term PSA screening are lacking. This study aimed to investigate the incidence and characteristics of PCa in Norwegian MMR carriers attending annual PSA screening (PSA threshold >3.0 ng/mL) to evaluate whether our recommendations should be continued. This is a prospective observational study of 225 male MMR carriers who were recommended annual PSA screening by the Section of Inherited Cancer, Oslo University Hospital from 2010 and onwards. Incidence and tumor characteristics (age, PSA at diagnosis, Gleason score, TNM score) were described. IHC and MSI-analyses were done on available tumors. Standardized incidence ratio (SIR) was calculated based on data from the Cancer Registry of Norway. Twenty-two of 225 (9.8%) had been diagnosed with PCa, including 10/69 (14.5%) MSH2 carriers and 8/61 (13.1%) MSH6 carriers. Ten of 20 (50%) tumors had Gleason score ≥4 + 3 on biopsy and 6/11 (54.5%) had a pathological T3a/b stage. Eight of 17 (47.1%) tumors showed abnormal staining on IHC and 3/13 (23.1%) were MSI-high. SIR was 9.54 (95% CI 5.98-14.45) for all MMR genes, 13.0 (95% CI 6.23-23.9) for MSH2 and 13.74 for MSH6 (95% CI 5.93-27.08). Our results indicate that the MMR genes, and especially MSH2 and MSH6, are associated with a significant risk of PCa, and a high number of tumors show aggressive characteristics. While the impact of screening on patient outcomes remains to be more firmly established, the high SIR values we observe provide support for continued PSA screening of MSH2 and MSH6 carriers. Studies are needed to provide optimal recommendations for PSA-threshold and to evaluate whether MLH1 and PMS2 carriers should not be recommended screening.

Risk of Cancer in Patients With Diverticular Disease: A Population-Based Cohort Study

Several studies have investigated the association between diverticular disease (DD) and colorectal cancer. However, whether there is an association between DD and malignancies other than those in the colorectum remains uncertain. For the 1978-2019 period, we conducted a nationwide, population-based cohort study using national Danish health care data. We followed patients with DD for up to 20 years, beginning 1 year after the date of DD diagnosis until the first occurrence of incident cancer, emigration, death, 20 years of follow-up, or December 31, 2019. We calculated cumulative incidence proportions of cancer and standardized incidence ratios (SIRs) comparing cancer incidence among patients with DD with that in the general population. We identified 200,639 patients with DD, of whom 20,498 were diagnosed with cancer during the 1-20 years after their DD diagnosis. The SIRs were increased for most cancer sites except for those in the colorectum (SIR, 0.75; 95% confidence interval, 0.72-0.78). The highest SIRs were observed for cancers of the lung, bronchi, and trachea (SIR, 1.20; 95% confidence interval, 1.15-1.24) and kidney (SIR, 1.27; 95% confidence interval, 1.16-1.39). Our findings show an increased long-term relative risk of cancer following a diagnosis of DD. These findings are likely caused by prevalence of numerous risk factors in patients with DD that confer an increased risk of cancer. The decreased relative risk of colorectal cancer might be explained by an increased likelihood of patients with DD undergoing colonoscopy with polypectomy.

Association between pharmacotherapy and secondary vertebral fracture managed with a brace in a real-world setting: A nationwide database study in Japan.

This retrospective cohort study assessed the association between the incidence of secondary vertebral fracture managed with a brace (SVF) and pharmacotherapy. The association between the incidence of SVF and the presence, type, and medication possession ratio (MPR) of pharmacotherapy was investigated using medical insurance data acquired from the National Database of Health Insurance Claims and Specific Health Checkups of Japan. The data of female patients (n = 637 303) were analyzed. The 2-year incidence of SVF was 73.5 per 10 000 patients (n = 4687). Approximately 0.73% of patients without medications and 0.74% with medications had SVF. Patients taking bisphosphonates (0.87), denosumab (0.77), and selective estrogen receptor modulators (0.88) had significantly lower standardized incidence ratios (SIRs) than patients not taking medications after the occurrence of primary fracture; meanwhile, patients taking parathyroid hormone medications had considerably higher SIRs than those not taking medications. The non-SVF group (59.1%) had a significantly higher mean MPR than the SVF group (55.5%). Patients taking denosumab in the non-SVF group (68.2%) had the highest mean MPR. The proportion of patients taking denosumab with an MPR of ≥80% in the non-SVF group was significantly higher than that in the SVF group. Patients taking medications were at a lower risk of developing SVF than those not taking medications. Although this study did not compare the medications' SVF prevention effects, patients taking denosumab had a 0.77 SIR of SVF in Japan. The effect of pharmacotherapy on SVF prevention might be affected by the MPR of each medication. Geriatr Gerontol Int 2024; 24: 390-397.

Incidence of Tuberculosis Among Immigrants in Korea Who Participated in a Latent Tuberculosis Infection Screening Program.

With a rapid decrease in tuberculosis (TB) incidence, the significance of latent tuberculosis infection (LTBI) has been underscored in South Korea. Although South Korea does not have a high proportion of immigrants compared to other countries, there is a growing argument that it should actively embrace immigrants as a solution to address issues of low birth rates and population aging. This study aimed to assess TB incidence among immigrants who participated a pilot LTBI screening program in South Korea. Records of immigrants participated in a pilot LTBI screening program in South Korea between 2018 and 2019 were linked with Korean National TB Surveillance System to determine TB development. Participants underwent interferon-gamma release assay (IGRA) and chest X-rays. Standardized incidence ratios (SIRs) stratified by age, country of origin's TB burden was calculated with a reference group of general South Korean population. Of a total of 9,517 participants, 14 TB cases were identified. Participants with positive IGRA results who did not initiate LTBI treatment showed TB incidence of 312.5 per 100,000 person-years, whereas those with negative results showed TB incidence of 34.4 per 100,000 person-years, resulting in an incidence rate ratio of 9.08 (95% confidence interval [CI], 2.50-32.99). SIR of TB among total participants including those with negative IGRA results was 2.60 (95% CI, 1.54-4.38; P < 0.001), whereas SIR among those with positive IGRA results was 5.86 (95% CI, 3.15-10.89; P < 0.001). In the calculation of SIR among participants with positive IGRA results, those aged under 35 from high TB-burden countries or intermediate TB-burden countries showed a high SIR (18.08; 95% CI, 2.55-128.37; P = 0.004), and 11.30 (95% CI, 2.82-45.16; P < 0.001), respectively). Contrary to previous reports that suggest the majority of elderly population with a positive IGRA result were due to remote infection and had a lower TB risk compared to younger ages, SIR among those aged 65 or over from intermediate TB-burden countries was 6.15 (95% CI, 0.87-43.69; P = 0.069), which was comparable to that in younger participants aged between 35 and 49 (SIR, 4.87; 95% CI, 1.22-19.49; P = 0.025) or those aged between 50 and 64 (SIR, 4.62; 95% CI, 1.73-12.31; P = 0.002). Young immigrants with positive IGRA results from countries with high or intermediate TB burden showed a relatively high TB risk compared to a general South Korea population. In addition, unexpected high TB risk was observed among elderly immigrants with positive IGRA results. In establishing future policies for LTBI in immigrants in South Korea, screenings should primarily focus on younger age group (who aged under 35). Additionally, further research is needed on the high TB risk observed in elderly immigrants.

Risk of Myelodysplastic Syndromes (MDS) in Adolescents and Young Adults with Cancers Treated with Chemotherapy with or without Radiotherapy

Introduction The risk of MDS among adolescents and young adults (AYA) with cancer treated with chemotherapy with or without radiotherapy in the US is not well understood. Method We interrogated NCI's Surveillance, Epidemiology and End Result (SEER)-17 registries to identify patients (pts) between the ages of 15-39 years (AYA) diagnosed with MDS at least one year after diagnosis of a primary unrelated cancer treated with chemotherapy and or radiotherapy over a twenty-year period (January 2000 to December 2020). All cancers, including MDS, were identified using ICD-O-3/WHO-2008 histology codes. We excluded all leukemia and MDS entities from index cancer sites. The risk of MDS was estimated by standardized incidence ratio (SIR), defined as the ratio of observed MDS cases in the AYA pts treated for first cancers to the expected number of MDS cases in the general US population during this period. A referent rate file for MDS incidence in age, gender, race and calendar-year matched US population available in SEER*Stat software (version 8.4.0) was used for SIR calculation. We calculated exact, 2-sided Poisson-based 95% confidence intervals (CIs) about the SIRs. We stratified the risk using 5- calendar year periods, and latency after index cancer diagnosis. SIR and time to MDS development was calculated for six most common index cancers using R(v4.2.2)-software. Result Of a total of 168,078 AYA pts eligible for analysis, with 1,290,803-person years at risk during 2000 to 2020, 66 pts developed MDS during this period. The median age at diagnosis of index cancer and MDS were 34 years (yrs) (interquartile range (IQR), 27-37 yrs) and 38 yrs (IQR, 32-44 yrs), respectively. There were 680% more cases of MDS in the AYA cohort compared to that expected in the matched general US population [SIR (95% CI): 7.80 (6.03-9.92), p&amp;lt;0.05)]. A higher SIR was observed for males (12.19) compared to females (5.82) and among all race/ethnicity, highest among black males [(SIR (95%CI): 18.99 (6.17-44.32), p&amp;lt;0.05]. We analyzed SIR for top-six index cancer sites that contributed to most MDS cases. Lymphomas [Non-Hodgkin (NHL) and Hodgkin (HL)] and breast accounted for 54.5% of all MDS cases. SIR for MDS in pts with NHL was 22.07 (95% CI: 12.61-35.84), in HL pts was 10.75 (95% CI: 4.64-21.18), and in breast cancer pts was 2.79 (95% CI:2.22-7.51). Even though the absolute number of cases was low, pts with brain, as well as bone and joint cancers had highest SIRs for MDS. When stratified by 5-calendar year periods, the SIR of MDS was elevated compared to general population through all periods and was highest during 2000-2005 (27.44; 95% CI: 11.03-56.53), and declined for the subsequent time periods. When analyzed by latency period, the SIR for MDS was highest at 1-3 years after index cancer diagnosis (21.46: 95% CI 13.45-32.50) and then showed a steady decline with increasing latency over a period of 15-20 years but never reached the rates observed in general population (Figure 1). Among the six most common index sites, pts with bone and joint cancer had earliest time to occurrence of MDS, whereas the longest latency to developing MDS was observed in pts with testicular cancer (Figure 2). Conclusion AYA cancer cohort treated with chemotherapy or radiotherapy have nearly 8-fold higher risk of future development of MDS compared to the same age matched general US population. This risk is highest during the initial 1-3 years of diagnosis of index cancer, declines over time, but never reaches the rates in the general population. These findings warrant further investigation to understand the biology behind this observation and have potential treatment and surveillance implications.

Lymphoid Malignancies in Shwachman-Diamond Syndrome: Incidence, Clinical Features, and Outcomes from the North American SDS Registry

Introduction: Many marrow failure conditions are associated with myeloid malignancy predisposition and a subset carry an increased risk of both myeloid and lymphoid malignancies. The increased risk of myeloid malignancy is known in Shwachman-Diamond syndrome (SDS), however, the risk of lymphoid malignancy in SDS has not been previously reported. Through the North American SDS Registry (SDSR), we identified patients with SDS diagnosed with lymphoma. We report the clinical features and outcomes in these patients as well as the incidence rates of lymphoma, MDS, and AML in this cohort. Methods: Patients with biallelic SBDS mutations enrolled on the SDSR were included for analysis. Age- and sex-specific incidence rates from the SEER Program (2016-2020) were multiplied by person-years of observation to obtain expected numbers of events. The crude rate per 100,000 (100,000*observed number of malignancies/person-years of follow-up) and the standardized incidence ratio (SIR) were calculated. Results: Out of a total of 217 patients with SDS with biallelic SBDS mutations in the SDSR, we identified 3 subjects who developed lymphoma. Case 1: A male patient with biallelic SBDS mutations (c.258 + 2T&amp;gt;C; c.653G&amp;gt;A, p.Arg218Gln) presented with dyspnea and was diagnosed with primary mediastinal B-cell lymphoma at age 16 years. Bone marrow exam was negative for lymphoma but revealed a new del20q clone. He received 6 cycles of R-CHOP. His course was complicated by febrile neutropenia, pleural effusion, deep vein thrombosis, and decreased cardiac ejection fraction requiring subsequent omission of doxorubicin and carvedilol initiation. He is in remission &amp;gt;3 years from diagnosis. Case 2: A male patient with biallelic SBDS mutations (c.258 + 2T&amp;gt;C; c.183_184TA&amp;gt;CT, p.Lys62*) was diagnosed at age 23 years with diffuse large B-cell lymphoma (DLBCL) of the distal stomach and duodenal bulb. Bone marrow exam was negative for malignancy but demonstrated an abnormal karyotype: 46,XY,t(11;16)(q23;q24), del(20)(q11.2q13.3)[9]/46,XY[11]. He received 5 cycles of R-CHOP therapy, which was complicated by febrile neutropenia and S. aureus sepsis. Four years later, he was diagnosed with relapsed DLBCL of the distal ileum and concurrent AML with 5q deletion. He achieved complete remission of both malignancies after 2 cycles of cyclophosphamide, vincristine, prednisone, obinutuzumab, azacitidine, and venetoclax. Therapy was complicated by B. cereus bacteremia with brain abscesses and endocarditis and C. difficile infection. He underwent a matched unrelated donor hematopoietic stem cell transplant and is in remission &amp;gt;180 days from transplant. Case 3: A male patient with biallelic SBDS mutations (c.258 + 2T&amp;gt;C; c.183_184TA&amp;gt;CT, p.Lys62*) was diagnosed with Stage IVB classical Hodgkin lymphoma at age 12 years after presenting with mediastinal syndrome. Bone marrow biopsy was negative for findings suggestive of MDS or malignancy, however, the initial PET-CT was consistent with medullary involvement. He initiated therapy with steroids, doxorubicin, vinblastine, dacarbazine, and brentuximab vedotin and received focal radiation. His course was complicated by recurrent febrile neutropenia, C. difficile colitis, and cellulitis. Due to infectious complications and delayed count recovery after 2 cycles, despite chemotherapy dose reductions, he was transitioned to brentuximab and nivolumab. He demonstrated complete response by Deauville criteria prior to cycle 5 of brentuximab and nivolumab. Among 217 patients with biallelic SBDS mutations in the SDSR, the median age was 12.8 years (range: 0.3 - 52.8). The observed number, rates, and SIR for lymphoma, MDS, and AML are given in Table 1. A high SIR indicates a higher incidence in the SDSR relative to the SEER population in 2016-2020. The observed rate of lymphoma was 28.5 times higher in SDS than the expected rate in the general population. Conclusions: The incidence of lymphoma among patients with SDS is increased relative to the general population but is lower than the incidence of MDS or AML. Increased toxicity with standard therapies was observed in these patients. Given the increased risk of MDS/AML in SDS, which may be further increased by antecedent chemotherapy, non-genotoxic therapies should be investigated for lymphoma in SDS. Our results show that SDS should be added to the list of marrow failure conditions predisposing to both myeloid and lymphoid malignancies.

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.

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

Significant risk of second primary cancer among laryngeal squamous cell carcinoma patients even after 20 years

Background: Evidence on the risk of second primary cancer (SPC) following primary laryngeal squamous cell carcinoma (LSCC) is limited, especially in Europe. Methods: Patients diagnosed with primary LSCC from 1953–2018 were retrieved from the Finnish Cancer Registry. A total of 6241 LSCC patients were identified adding to 49,393 person-years (PY) of follow-up until the end of 2019. Only one patient emigrated and was lost to follow-up. Both standardized incidence ratios (SIR) and excess absolute risk (EAR) per 1000 person-years at risk (PYR) of second primary cancer (SPC) were calculated relative to the general population. Only non-laryngeal SPCs diagnosed six months after diagnosis of primary LSCC were included. Results: A SPC was diagnosed in 1244 LSCC patients (20% of all LSCC patients) over the 65-year period, predominantly in men (92%, n = 1170). Out of all SPCs, 34% were diagnosed within 0.5 to 5 years and 66% after 5 years from primary LSCC. Among male patients, the overall SIR for SPC at any location was 1.61 (95% CI: 1.52–1.71), corresponding to 9.49 excess SPCs per 1000 PYR (95% CI: 8.19–11). The corresponding SIR for women was 1.47 (95% CI: 1.15–1.84), yielding 4.82 excess SPCs per 1000 PYR (95% CI: 2.36–9.84). The risk remained significant even after 20 years of follow-up (SIR for all 1.73, 95% CI: 1.49–2.01 and EAR 16.8 per 1000 PY, 11.88–23.75). The risk for SPC was also significantly elevated in all age groups, except <40. The highest SIRs were for SPCs arising in the mouth/pharynx (SIR for all 3.08, 95% CI: 2.36–3.95 and EAR 0.80 per 1000 PY, 0.55–1.15) and lungs (3.02, 2.75-3.30 and 5.90 per 1000, 5.13–6.78). Conclusion: Patients with LSCC as primary cancer have a 60% excess risk for an SPC, especially for tobacco-associated cancers, remaining significantly elevated even decades after treatment.

Adverse Events Following the BNT162b2 mRNA COVID-19 Vaccine (Pfizer-BioNTech) in Aotearoa New Zealand.

In February 2021, New Zealand began its largest ever immunisation programme with the BNT162b2 mRNA coronavirus disease 2019 (COVID-19) vaccine. We aimed to understand the association between 12 adverse events of special interest (AESIs) and a primary dose of BNT162b2 in the New Zealand population aged ≥5 years from 19 February 2021 through 10 February 2022. Using national electronic health records, the observed rates of AESIs within a risk period (1-21 days) following vaccination were compared with the expected rates based on background data (2014-2019). Standardised incidence ratios (SIRs) were estimated for each AESI with 95% confidence intervals (CIs) using age group-specific background rates. The risk difference was calculated to estimate the excess or reduced number of events per 100,000 persons vaccinated in the risk period. As of 10 February 2022, 4,277,163 first doses and 4,114,364 second doses of BNT162b2 had been administered to the eligible New Zealand population aged ≥5 years. The SIRs for 11 of the 12 selected AESIs were not statistically significantly increased post vaccination. The SIR (95% CI) for myo/pericarditis following the first dose was 2.3 (1.8-2.7), with a risk difference (95% CI) of 1.3 (0.9-1.8), per 100,000 persons vaccinated, and 4.0 (3.4-4.6), with a risk difference of 3.1 (2.5-3.7), per 100,000 persons vaccinated following the second dose. The highest SIR was 25.6 (15.5-37.5) in the 5-19 years age group, following the second dose of the vaccine, with an estimated five additional myo/pericarditis cases per 100,000 persons vaccinated. A statistically significant increased SIR of single organ cutaneous vasculitis (SOCV) was also observed following the first dose of BNT162b2 in the 20-39years age group only. A statistically significant association between BNT162b2 vaccination and myo/pericarditis was observed. This association has been confirmed internationally. BNT162b2 was not found to be associated with the other AESIs investigated, except for SOCV following the first dose of BNT162b2 in the 20-39years age group only, providing reassurances around the safety of the vaccine.

Occupational variation in the incidence of lip cancer in the Nordic countries

Introduction While certain occupations, such as agriculture and fishery, have been associated with an increased risk of lip cancer, the occupational risk profile of lip cancer and its change over time remain poorly known. This study aims to evaluate the incidence of lip cancer across different occupations in the Nordic countries. Methods The Nordic Occupational Cancer Study (NOCCA) covers 14.9 million people and includes 45 years of cancer incidence data, from 1961 to 2005, linked to occupational categories for all the five Nordic populations. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were used to quantify the risk of lip cancer across occupational categories relative to the entire national populations. Results There were a total of 14,477 male and 3008 female lip cancer patients identified during follow up. The highest SIRs were observed among male fishermen (SIR 2.26, 95% CI: 2.04–2.50), gardeners (SIR 1.60, 95% CI: 1.48–1.72), and farmers (SIR 1.60, 95% CI: 1.55–1.66). A significantly reduced risk of lip cancer (SIR < 0.50) was observed among male physicians, teachers, religious workers, artistic workers, journalists, administrators, printers, waiters, and hairdressers. Among women, no occupations were associated with an increased risk of lip cancer. Conclusions The incidence of lip cancer varies widely between outdoor and indoor occupations. Occupations involving outdoor activity and exposure to sunlight show the most elevated SIRs.

Long-Term Risk of Subsequent Malignant Neoplasms Among Childhood and Adolescent Lymphoma Survivors (1975-2013): A Population-Based Predictive Nomogram.

Studies are needed to assess risk factors pertinent to the incidence of secondary malignancies among childhood and adolescent lymphoma survivors. We aimed to identify risk factors pertinent to the incidence of secondary malignancies and subsequently establish a clinically practical predictive nomogram. A total of 5561 patients who were diagnosed with primary lymphoma below the age of 20 years between 1975 and 2013 and survived for at least 5 years were identified. Standardized incidence ratio (SIR) and excess risk (ER) analysis were performed by sex, age, and year when primary lymphoma was diagnosed, sites and types of primary lymphoma, and therapy strategies. Univariable and multivariable logistic regression were used to identify independent risk factors for adolescent and childhood lymphoma-related secondary malignancies. Based on 5 factors (age, time from lymphoma diagnosis, gender, lymphoma type, and therapy), a nomogram for predicting the risk of a secondary malignancy for patients with childhood and adolescent primary lymphoma was established. Among 5561 lymphoma survivors, 424 developed a secondary malignancy. Females (SIR = 5.34, 95% CI, 4.73-5.99; ER = 50.58) exhibited a higher SIR and ER than males (SIR = 3.28, 95% CI, 2.76-3.87; ER = 15.53). Blacks were at a higher risk than Caucasians or others. Nodular lymphocyte-predominant Hodgkin lymphoma survivors exhibited typically high SIR (13.13, 95% CI, 6-24.92) and ER (54.79) among all lymphoma classifications. Lymphoma survivors who underwent radiotherapy, whether they received chemotherapy or not, had typically higher SIR and ER. Among all types of secondary malignancies, "bone and joint neoplasms" (SIR = 11.07, 95% CI, 5.52-19.81) and "soft tissue neoplasms" (SIR = 12.27, 95% CI, 7.59-18.76) presented significantly high SIR whereas "breast cancer" and "endocrine cancer" associated with higher ER. The median diagnosis age of secondary malignancies was 36 years old, and the median time interval between the diagnosis of two malignancies was 23 years. A nomogram was constructed to predict the risk of secondary malignancies in patients diagnosed with primary lymphoma before 20 years of age. After internal validation, the AUC and C-index of the nomogram are 0.804 and 0.804, respectively. The established nomogram provides a convenient and reliable tool for predicting the risk of a secondary malignancy among childhood and adolescent lymphoma survivors, concluding significant concern for lymphoma survivors with high-risk estimates.

Colorectal cancer and advanced adenoma incidence during post-polypectomy surveillance: a national cohort study in the English Bowel Cancer Screening Programme.

Improved colonoscopy quality has led to debate about whether all post-polypectomy surveillance is justified. We evaluated surveillance within the English Bowel Cancer Screening Programme (BCSP) to determine the yield of surveillance and identify predictive factors for surveillance outcome. We performed a retrospective cohort study of individuals undergoing post-polypectomy surveillance between July 2006 and January 2017. BCSP records were linked to the National Cancer Registration Database to identify interval-type post-colonoscopy colorectal cancers (CRCs). Advanced adenoma and CRC at surveillance were documented. CRC incidence was compared with the general population using standardized incidence ratios (SIRs). Predictors of advanced adenomas at first surveillance (S1), and CRC during follow-up, were identified. 44 151 individuals (23 078 intermediate risk; 21 073 high risk) underwent 64 544 surveillance episodes. Advanced adenoma and CRC yields were, respectively, 10.0 % and 0.5 % at S1, 8.5 % and 0.4 % at S2, and 10.8 % and 0.4 % at S3. S1 yield was lowest in those with one index adenoma ≥ 10 mm (advanced adenoma 6.1 %; CRC 0.3 %). The SIR was 0.76 (95 %CI 0.66-0.88), accounted for by the intermediate risk group (intermediate risk SIR 0.61, 95 %CI 0.49-0.75; high risk SIR 0.95, 95 %CI 0.79-1.15). Adenoma multiplicity, presence of a large nonpedunculated adenoma, and greater villous component were associated with advanced adenoma at S1. Older age and multiplicity were significantly associated with CRC risk. This large, national analysis found low levels of CRC in those undergoing surveillance and low advanced adenoma yield in most subgroups. Less intensive surveillance in some subgroups is warranted, and surveillance may be avoided in those with a single large adenoma.