Standardized Incidence Ratios Research Articles

Myotonic dystrophy type 1 in South Korea: a comprehensive analysis of cancer and comorbidity risks.

Myotonic dystrophy type 1 (DM1) is an inherited neuromuscular disorder characterized by myotonia and progressive muscle weakness. Beyond the primary symptoms, there is growing concern regarding a higher incidence of certain comorbidities in DM1 patients, including cancer, diabetes, thyroid dysfunction, and cataracts. This study was designed to examine the occurrence of these conditions among patients diagnosed with DM1 in South Korea, using data from the National Health Insurance Service database. The study undertook a comprehensive review of 3,842 patients diagnosed with DM1 between 2012 and 2018. We assessed the incidence of cancer and the prevalence of diabetes, thyroid dysfunction, and cataracts among these patients, comparing their rates to those in the general population. In the study cohort, 463 out of 3,842 DM1 patients (12.04%) were diagnosed with cancer, indicating a substantial elevation in cancer risk with an overall standard incidence ratio of 1.9 (95% CI = 1.6-2.3, p < 0.01) when compared to the expected rates in the general population. Moreover, the prevalence of diabetes (15.2%) and thyroid dysfunction (17.6%) was noteworthy in the DM1 population. The mean age at which DM1 patients underwent cataract surgery was 55.07years, noticeably younger than the mean age of 69.25years for cataract surgery in the general population. DM1 patients have a noteworthy occurrence of several comorbidities such as cancer, diabetes, thyroid dysfunction, and earlier cataract surgery. This highlights the importance of a comprehensive and integrative approach to the management and treatment of DM1, going beyond addressing only the primary neuromuscular symptoms. More research is required to understand the underlying mechanisms contributing to these comorbidities in DM1 patients, which may inform preventative measures and guide improvements in patient care.

Second Neoplasms in Italian Patients with Hairy Cell Leukemia after Treatment with Cladribine: A Multicenter Investigation and Literature Review

Concern has emerged about the prevalence of second cancers among patients with hairy cell leukemia (HCL) treated with purine analogs. We investigated 513 patients with HCL treated with cladribine over the last 30 years at 18 Italian centers and calculated their standardized incidence ratios (SIRs). We identified 24 patients with a second cancer diagnosed at a median time from treatment with cladribine of 59.9 months (range: 9.2–169.7 months). All patients with solid neoplasms presented with a limited-stage disease, except four cases of locally advanced cancer; multiple myeloma patients had a smoldering disease, while lymphoma patients had stage Ie and stage IV diseases. Response to therapy was complete in 19 cases; 1 patient is still receiving treatment for a relapsing bladder disease, while 2 patients progressed during treatment and died. These two patients died from unrelated causes: one from infection and one due to surgery complications. The median OS from HCL was 98.5 months (range: 38.4–409.2 months), while the median OS from second cancer was 27.6 months (range: 1–117.8 months). The SIR was 0.86 (95% CI: 0.54–1.30) for males and 1.13 (95% CI: 0.36–2.73) for females: no statistically significant differences were highlighted. We were not able to demonstrate an excess of second cancer or a significant association with the specific studied neoplasm.

Impact of Indoor Radon Exposure on Lung Cancer Incidence in Slovenia

Indoor radon is an important risk factor for lung cancer, as 3–14% of lung cancer cases can be attributed to radon. The aim of our study was to estimate the impact of indoor radon exposure on lung cancer incidence over the last 40 years in Slovenia. We analyzed the distribution of lung cancer incidence across 212 municipalities and 6032 settlements in Slovenia. The standardized incidence ratios were smoothed with the Besag–York–Mollie model and fitted with the integrated nested Laplace approximation. A categorical explanatory variable, the risk of indoor radon exposure with low, moderate and high risk values, was added to the models. We also calculated the population attributable fraction. Between 2.8% and 6.5% of the lung cancer cases in Slovenia were attributable to indoor radon exposure, with values varying by time period. The relative risk of developing lung cancer was significantly higher among the residents of areas with a moderate and high risk of radon exposure. Indoor radon exposure is an important risk factor for lung cancer in Slovenia in areas with high natural radon radiation (especially in the southern and south-eastern parts of the country).

Abstract LB151: Association of radiotherapy with the risk of subtype-specific lung cancer among breast cancer survivors in the United States

Abstract Background Breast cancer survivors face an elevated risk of subsequent primary lung cancer (SPLC), especially those who received radiotherapy. Nevertheless, the association of radiotherapy for breast cancer and the risk of subtype-specific lung cancer is unknown. Methods Females diagnosed with first primary breast cancer at ages 20-84 years from 1992-2020 were identified from 12 Surveillance, Epidemiology, and End Results registries. Follow-up began at 2 months from breast cancer diagnosis and ended at subsequent lung cancer diagnosis, last known vital status, death, or December 31, 2020. Standardized incidence ratios (SIRs) and excess absolute risks (EARs, per 10,000 women) were calculated for each histological subtype of lung cancer (adenocarcinoma, squamous cell carcinoma, small cell carcinoma, large cell carcinoma, and others) using expected rates of each subtype in the SEER population. Subgroup analyses were conducted by treatment for breast cancer (radiotherapy yes or no/unknown), overall and stratified by the relative position (ipsilateral and contralateral) of the breast and SPLC. Results Of all 550,007 breast cancer survivors (&amp;gt;50 years old, 74%; non-Hispanic Whites, 67%; localized, 51%), 8,014 SPLCs were diagnosed during a mean follow-up of 9.7 years. 52.6% of the participants received radiotherapy treatment. Compared with the general population, breast cancer survivors had a statistically significantly higher risk of lung cancer with subtype-specific SIR being greatest for adenocarcinoma (Observed N=4337; SIR=1.20, 95% Confidence Interval [CI]=1.16-1.24; EAR=1.35), followed by squamous cell carcinoma (Observed N=1368; SIR=1.11, 95% CI=1.05-1.17; EAR=0.26) and small cell carcinoma (Observed N=1026; SIR=1.08, 95% CI=1.02-1.15; EAR=0.14). When stratified by radiotherapy receipt, the increased risk associated with adenocarcinoma did not vary across strata. In contrast, the increased risk for squamous and transitional cell carcinoma and small cell carcinoma were confined to those who received radiotherapy (SIR=1.16, 95% CI=1.08-1.24 vs SIR=1.06, 95% CI=0.98-1.15 for squamous and transitional cell carcinoma; SIR=1.15, 95% CI=1.06-1.25 vs SIR= 1.00, 95% CI=0.91-1.09 for small cell carcinoma). Further analysis by laterality showed that associations of treatment receipt with increased risk of lung cancer were confined to ipsilateral SPLC for these two subtypes. Conclusion Different subtypes of lung cancer may have distinct associations with prior radiation treatment in individuals who have survived breast cancer. The findings have implications for evaluating risks and implementing surveillance for subsequent primary lung cancer in the growing population of breast cancer survivors. Citation Format: Chenxi Jiang, Rachel A. Freedman, Ahmedin Jemal, Hyuna Sung. Association of radiotherapy with the risk of subtype-specific lung cancer among breast cancer survivors in the United States [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB151.

Cancer-Causing Effects of Orthopaedic Metal Implants in Total Hip Arthroplasty.

Metal implants have been preferentially used in THA due to its biocompatibility, mechanical stability and durability. Yet concerns have emerged regarding their potential to release metallic ions, leading to long-term adverse effects, including carcinogenicity. This study aimed to investigate the risk of cancer development in patients with orthopaedic metal implants in total hip arthroplasty (THA). Patients with THA conducted at a local tertiary implant centre from 2001-2008 were linked to the local cancer registry and followed up to the end of 2023. Standardized incidence ratios (SIRs) for cancer incidence and its confidence interval by Poisson distribution were calculated. Survival analysis was depicted using the Kaplan-Meier method, and the log-rank test was used to assess the differences across groups. The study cohort included 388 patients and 53 cancers diagnosed during follow-up, at least 5 years post THA. All-site cancer risks were increased in patients with THA (SIR: 1.97; 95% CI: 1.48-2.46), validated with chi-square analysis (chi-square = 15.2551, N = 100,388, p < 0.01). A statistically significant increase in multiple site-specific cancers including haematological cancers were identified. Patients with THA were found to have an increased risk for cancer compared to the general population during a mean follow-up of 16 years.

A Novel Approach for Conducting a Catchment Area Analysis of Breast Cancer by Age and Stage for a Community Cancer Center.

The U.S. Preventive Services Task Force recently issued an updated draft recommendation statement to initiate breast cancer (BC) screening at age 40, reflecting well-documented disparities in BC mortality that disproportionately impact younger Black women. This study applied a novel approach to identify hotspots of BC diagnosed before age 50 and/or at an advanced stage to improve BC detection within these communities. Cancer registry data for 3,497 women with invasive BC diagnosed or treated between 2012 and 2020 at the Helen F. Graham Cancer Center & Research Institute (HFGCCRI) and who resided in the HFGCCRI catchment area, defined as New Castly County, Delaware, were geocoded and analyzed with spatial intensity. Standardized incidence ratios stratified by age and race were calculated for each hotspot. Four hotspots were identified, two for BC diagnosed before age 50, one for advanced BC, and one for advanced BC diagnosed before age 50. Younger Black women were overrepresented in these hotspots relative to the full catchment area. The novel use of spatial methods to analyze a community cancer center catchment area identified geographic areas with higher rates of BC with poor prognostic factors and evidence that these areas made an outsized contribution to racial disparities in BC. Identifiying and prioritizing hotspot BC communities for community outreach and engagement activities designed to improve BC detection has the potential to reduce the overall burden of BC and narrow racial disparities in BC.

Biopsy-verified vulvar lichen sclerosus: Incidence trends 1997-2022 and increased risk of vulvar squamous precancer and squamous cell carcinoma.

Population-based data on the epidemiology of vulvar lichen sclerosus (LS) are sparse and only few prospective studies have investigated the malignant potential of the disease. We used the nationwide Danish Pathology Registry to first assess the incidence of biopsy-verified vulvar LS in the period 1997-2022 and second to examine the incidence of vulvar high-grade squamous precancer and squamous cell carcinoma (SCC) in women with biopsy-verified vulvar LS (1978-2019) compared with that expected in the general female population. For the latter aim, we computed standardized incidence ratios (SIRs) with 95% confidence intervals (CIs). During our study period, the age-standardized incidence rate of vulvar LS increased from 5.0 (1997-1998) to 35.7 (2021-2022) per 100,000 person-years. Compared with the general female population, women with biopsy-verified vulvar LS had significantly increased rates of vulvar high-grade squamous precancer (SIR = 8.5; 95% CI: 7.2-10.0) and SCC (SIR = 16.2; 95% CI: 14.2-18.4). The SIRs of vulvar high-grade squamous precancer and SCC did not vary substantially according to length of follow-up. This nationwide and population-based study shows a 7-fold increase in the incidence of biopsy-verified vulvar LS since 1997. Data also show that women with biopsy-verified vulvar LS have 8.5 and 16 times higher than expected incidence of vulvar high-grade squamous precancer and SCC, respectively. The substantially increased incidence of vulvar high-grade squamous precancer and SCC following LS is important in relation to the clinical management and follow-up of LS patients.

Abstract 843: The burden of Merkel cell carcinoma attributable to immunosuppression, ultraviolet radiation, and Merkel cell polyomavirus in the United States

Abstract Background: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer. No published study has estimated the contribution of the major potentially modifiable risk factors, such as immunosuppression, ultraviolet radiation (UVR) and infection with Merkel cell polyomavirus (MCPyV), to the burden of MCC in the US. We estimated the population attributable fractions (PAFs) for MCC associated with immunosuppression (HIV and organ transplantation), MCPyV, and UVR in the US during 2001-2020. Methods: We calculated PAFs for immunosuppression and UVR using the formula: prevalence in cases (Pc)*[(Relative risk, RR-1)/RR]. The proportion of MCC cases among organ recipients and people with HIV (Pc) were derived from US cancer registries in the HIV/AIDS Cancer Match Study, Transplant Cancer Match Study, and the Surveillance Epidemiology and End Results (SEER) Program data. To approximate the RRs, we calculated standardized incidence ratios (SIRs) comparing MCC incidence in people with HIV and organ recipients to the general population. We merged SEER data on MCC cases by county with data on ambient UVR levels in order to create population quintiles of UVR exposure. Since only non-Hispanic White individuals showed elevated IRRs for increased ambient UVR exposure, we estimated the PAF of UVR by calculating incidence rate ratios (IRR ≈ RR) comparing MCC incidence in non-Hispanic White individuals to all other races/ethnicities (at any UVR level) as the reference; here, Pc was the proportion of non-Hispanic White patients in each quintile. To estimate the PAF of MCPyV, we meta-analyzed US studies reporting on MCPyV prevalence in MCC tissues (here PAF ≈ Pc). Results: Over the study period (2001-2020), 40,571 MCCs were diagnosed in the US. Compared to the general population, organ recipients had 13 times higher (SIR=12.7, CI: 11.3-14.2) and people with HIV had three times higher (SIR=2.78, CI: 2.01-3.75) risk of MCC. Due to the rarity of these exposures (HIV Pc = 0.4%; Transplant Pc = 1.9%), only 0.2% of MCC cases were attributable to HIV and 1.7% were attributable to organ transplantation. Compared with people in other racial/ethnic groups, the IRRs of non-Hispanic White individuals at the various levels of ambient UVR for MCC arising on the head and neck ranged from 4.24 to 5.03 and for other primary sites ranged from 2.81 to 3.36. After combining the PAFs for these sites, the overall PAF for UVR was 65.8%. Meta-analyzing 20 studies with 984 MCC cases combined, we found that 66.1% (CI: 58.0-72.2%) of MCCs were attributable to MCPyV. Conclusions: While a small proportion of MCCs were due to immunosuppression from HIV infection and organ transplantation, UVR and MCPyV played a major role in MCC burden. Future research is required to assess the combined impact of these risk factors on MCC incidence. Citation Format: Jacob T. Tribble, Karena Volesky-Avellaneda, Qianlai Luo, Michael R. Sargen, Isaac Brownell, Elizabeth K. Cahoon, Meredith Shiels, Ruth Pfeiffer, Adrianne Moreno, Brenda Y. Hernandez, Eric Engels. The burden of Merkel cell carcinoma attributable to immunosuppression, ultraviolet radiation, and Merkel cell polyomavirus in the United States [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 843.

Abstract 7321: Second primary cancer risks following breast cancer in BRCA1/2 pathogenic variant carriers

Abstract Background: Second primary cancer (SPC) risk estimates in breast cancer (BC) survivors carrying germline BRCA1/2 pathogenic variants (PVs) remain uncertain. We estimated relative and absolute SPC risks following BC in BRCA1/2 PV carriers using genetic testing laboratory data in England, linked for the first time to population-scale electronic health records data from the National Disease Registration Service and Hospital Episode Statistics. Material and methods: The cohort contained 27,154 women diagnosed with primary BC and tested for germline BRCA1/2 PVs between 1995-2019. Follow-up began at the latest of the genetic test dates and one year following the BC diagnosis and continued until the first SPC diagnosis, death, migration, relevant surgery, and the end of 2020, whichever came first. We estimated overall and site-specific standardized incidence ratios (SIRs) by comparing observed and expected SPC counts, with expected counts calculated using incidences for the general English population accounting for calendar year, SPC site, age, and gender. We stratified the SIRs by age, estrogen-receptor status, and cancer site. We further assessed associations using Cox regression adjusted for age at BC diagnosis and estrogen-receptor status of the first BC, and estimated 10-year absolute SPC risks with Kaplan-Meier analysis. Results: There were 1909 BRCA1 (138 with SPCs) and 1926 BRCA2 (101 with SPCs) PV carriers, with mean follow-up lengths of 4.2 and 4.4y and median follow-up lengths of 3.4 and 3.6y. In BRCA1 PV carriers, there were elevated contralateral BC (SIR:15.3, 95%CI:11.5-19.8), ovarian (SIR:43.3, 95%CI:30.9-58.9), non-breast and non-ovarian combined (SIR:2.23, 95%CI:1.63-2.98), colorectal (SIR:4.72, 95%CI:2.58-7.92) and uterine (SIR:3.42, 95%CI:1.25-7.44) SPC risks. In BRCA2 PV carriers, there were increased contralateral BC (SIR:7.53, 95%CI:5.33-10.3), ovarian (SIR:16.5, 95%CI:10.1-25.5), non-breast and non-ovarian (SIR:1.72, 95%CI:1.27-2.27) and pancreatic (SIR:6.57, 95%CI:2.63-13.5) SPC risks. Consistently, when we compared BC survivors carrying a BRCA1 PV to BC survivors without a PV in either gene, they were at elevated contralateral BC (HR:3.94, 95%CI:2.91-5.33), ovarian (HR:35.7, 95%CI:21.3-60.0), non-breast and non-ovarian (HR:1.53, 95%CI:1.11-2.12) and colorectal (HR:2.95, 95%CI:1.56-5.55) SPC risks, whereas BRCA2 PV carriers were at increased contralateral BC (HR:2.59, 95%CI:1.83-3.65), ovarian (HR:12.3, 95%CI:6.93-21.9) and pancreatic (HR:5.32, 95%CI:2.30-12.3) SPC risks. We estimated 10-year cumulative contralateral BC, ovarian, and non-breast and non-ovarian SPC risks of 15%, 6.3%, and 7.8% in BRCA1 PV carriers and 12%, 2.9%, and 6.2% in BRCA2 PV carriers. Conclusions: Cancer risks were increased, at combined and specific sites, following BC in BRCA1/2 PV carriers. These findings could aid the clinical management of BC survivors carrying BRCA1/2 PVs. Citation Format: Isaac Allen, Hend Hassan, Yvonne Walburga, Catherine Huntley, Lucy Loong, Tameera Rahman, Beth Torr, Andrew Bacon, Craig Knott, Sophie Jose, Sally Vernon, Margreet Lüchtenborg, Joanna Pethick, Francesco Santaniello, Shilpi Goel, Sophie Allen, Katrina Lavelle, Fiona McRonald, Diana M. Eccles, Eva Morris, Steven Hardy, Clare Turnbull, Marc Tischkowitz, Paul Pharoah, Antonis C. Antoniou. Second primary cancer risks following breast cancer in BRCA1/2 pathogenic variant carriers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7321.

Severity of Complications and Duration of Type 2 Diabetes and the Risk of Cancer: A Population-based Study.

The literature on the association between diabetes severity and cancer risk is limited and inconclusive. The study aimed to evaluate the association between the adapted Diabetes Complications Severity Index (aDCSI) and the duration of type 2 diabetes and cancer risk. Patients aged 20 years or older with newly diagnosed type 2 diabetes between January 1, 2007 and December 31, 2011 were identified from Taiwan National Health Insurance claims data. Standardized incidence ratios (SIRs) were calculated to compare cancer incidence in people with diabetes to that in the general population. Poisson regression was used to examine whether SIRs differed by age, sex, aDSCI, and duration of diabetes. A total of 756,547 patients were included, with a median follow-up of 8.8 years. Excluding the first year after diagnosis, the SIR for overall cancer was 1.18(95% CI 1.17-1.19). Higher aDCSI was associated with increased SIRs for overall(SIR ratio 1.03(1.02-1.03) per point increase), head and neck(1.03(1.01-1.04)), liver(1.04(1.03-1.05)), pancreas(1.03(1.00-1.05)), kidney(1.13(1.10-1.15)) and leukemia(1.09(1.06-1.13)). There was no association between aDCSI and colorectal, extrahepatic biliary tract, uterus and thyroid cancer, and a negative association with breast cancer(0.97(0.95-0.98)). Type 2 diabetes duration was associated with increased SIRs for overall (1.01(1.00-1.02) per year increase), head and neck(1.03(1.01-1.05)) and liver cancer(1.04(1.02-1.05)). The heterogeneity in the association between diabetes severity and diabetes-related cancers suggests diverse underlying connection. Adopting distinct approaches in further research and prevention strategies for different kinds of diabetes-related cancers is important.

Prevalence and features of SARS-CoV-2 infection in prisons in Tuscany.

Prisons can be a reservoir for infectious diseases, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), due to the very intimate nature of the living spaces and the large number of people forced to share them. To investigate the SARS-CoV-2 epidemiology in prisons, this study evaluated the infection incidence rate in prisoners who underwent nasopharyngeal swabs. This is an observational cohort study. Data collection included information on prisoners who underwent nasopharyngeal swab testing for SARS-CoV-2 and the results. Nasopharyngeal swab tests for SARS-CoV-2 were performed between 15 February 2021 and 31 May 2021 for prisoners with symptoms and all new arrivals to the facility. Another section included information on the diagnosis of the disease according to the International Classification of Diseases, Ninth Revision, and Clinical Modification. Up until the 31 May 2021, 79.2% of the prisoner cohort (n = 1744) agreed to a nasopharyngeal swab test (n = 1381). Of these, 1288 were negative (93.3%) and 85 were positive (6.2%). A significant association [relative risk (RR)] was found only for the risk of SARS-CoV-2 infection among foreigners compared to Italians [RR = 2.4, 95% confidence interval (CI): 1.2-4.8]. A positive association with SARS-CoV-2 infection was also found for inmates with at least one nervous system disorder (RR = 4, 95%CI: 1.8-9.1). The SARS-CoV-2 incidence rate among prisoners is significantly lower than in the general population in Tuscany (standardized incidence ratio 0.7, 95%CI: 0.6-0.9). In the prisoner cohort, screening and rapid access to health care for the immigrant population were critical to limiting virus transmission and subsequent morbidity and mortality in this vulnerable population.

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.

Sporadic deficient mismatch repair in colorectal cancer increases the risk for non-colorectal malignancy: A European multicenter cohort study.

Disparities between tumors arising via different sporadic carcinogenetic pathways have not been studied systematically. This retrospective multicenter cohort study evaluated the differences in the risk for non-colorectal malignancy between sporadic colorectal cancer (CRC) patients from different DNA mismatch repair status. A retrospective European multicenter cohort study including in total of 1706 CRC patients treated between 1996 and 2019 in three different countries. The proficiency (pMMR) or deficiency (dMMR) of mismatch repair was determined by immunohistochemistry. Cases were analyzed for tumor BRAFV600E mutation, and BRAF mutated tumors were further analyzed for hypermethylation status in the promoter region of MLH1 to distinguish between sporadic and hereditary cases. Swedish and Finish patients were matched with their respective National Cancer Registries. For the Czech cohort, thorough scrutiny of medical files was performed to identify any non-colorectal malignancy within 20 years before or after the diagnosis of CRC. Poisson regression analysis was performed to identify the incidence rates of non-colorectal malignancies. For validation purposes, standardized incidence ratios were calculated for the Swedish cases adjusted for age, year, and sex. Of the 1706 CRC patients included in the analysis, 819 were female [48%], median age at surgery was 67 years [interquartile range: 60-75], and sporadic dMMR was found in 188 patients (11%). Patients with sporadic dMMR CRC had a higher incidence rate ratio (IRR) for non-colorectal malignancy before and after diagnosis compared to patients with a pMMR tumor, in both uni- (IRR = 2.49, 95% confidence interval [CI] = 1.89-3.31, p = 0.003) and multivariable analysis (IRR = 2.24, 95% CI = 1.67-3.01, p = 0.004). This association applied whether or not the non-colorectal tumor developed before or after the diagnosis of CRC in both uni- (IRR = 1.91, 95% CI = 1.28-2.98, p = 0.004), (IRR = 2.45, 95% CI = 1.72-3.49, p = 0.004) and multivariable analysis (IRR = 1.67,95% CI = 1.05-2.65, p = 0.029), (IRR = 2.35, 95% CI = 1.63-3.42, p = 0.005), respectively. In this retrospective European multicenter cohort study, patients with sporadic dMMR CRC had a higher risk for non-colorectal malignancy than those with pMMR CRC. These findings indicate the need for further studies to establish the need for and design of surveillance strategies for patients with dMMR CRC.

Risk of Thyroid Cancer in People With Type 1 Diabetes by Autoimmune Thyroid Diseases and Tumor Histology.

Thyroid cancer is the most common endocrine cancer, but little is known about it in type 1 diabetes (T1D) and its potential association with autoimmune diseases. This study aims to assess the risk of thyroid cancer in adults with long-term T1D compared to individuals without diabetes and the proposed association of thyroid autoimmune diseases with thyroid cancer. The study included 4758 individuals with T1D participating in the Finnish Diabetic Nephropathy Study and 12 710 controls. Thyroid cancers were obtained from the Finnish Care Registers for Health Care. 27 (0.57%) individuals with T1D had thyroid cancer compared to 27 (0.21%) in the controls (standardized incidence ratio 2.43; 95% confidence interval 1.59-3.56). The absolute increase in incidence was modest, with a 0.36%-unit rise. This translates to 17 additional cases among 4710 individuals with T1D. Cancer type was papillary in 81.5% of individuals with T1D and 88.9% of the controls; the rest were follicular. In T1D the distribution of hypothyreosis was similar between those with (n = 5, 18.5%) and without (18.1%) cancer, but hyperthyreosis was diagnosed more often with thyroid cancer (n = 3, 11.1%) than without (2.3%, P = .003). None of the thyroid cancers were invasive or had metastatic characteristics. Although there is an excess risk of thyroid cancer, it is only marginally increased (0.36%-unit) in individuals with T1D compared to control individuals and was not associated with increased morbidity or mortality. An overdiagnosis effect due to regular health care contacts is the most likely explanation for the higher risk.

Impact of Risk-Based therapy on late morbidity and mortality in neuroblastoma survivors: a report from the childhood cancer survivor study.

Early efforts at risk-adapted therapy for neuroblastoma are predicted to result in differential late effects; the magnitude of these differences have not been well-described. Late mortality, subsequent malignant neoplasms (SMN), and severe/life-threatening chronic health conditions (CHCs), graded according to CTCAE v4.03, were assessed among 5-year CCSS survivors of neuroblastoma diagnosed 1987-1999. Using age, stage at diagnosis, and treatment, survivors were classified into risk groups (low [n = 425]; intermediate [n = 252]; high [n = 245]). Standardized mortality ratios (SMR) and standardized incidence ratios (SIR) of SMNs were compared to matched population controls. Cox regression models estimated hazard ratios (HR) and 95% confidence intervals (CI) for CHC compared to 1,029 CCSS siblings. Among survivors (49.8% male; median age 21 years, range 7-42; median follow-up 19.3 years, range 5-29.9), 80% with low-risk disease were treated with surgery alone, while 79.1% with high-risk disease received surgery, radiation, chemotherapy ± autologous stem cell transplant (ASCT). All-cause mortality was elevated across risk groups (SMRhigh=27.7 [21.4-35.8]; SMRintermediate=3.3 [1.7-6.5]; SMRlow=2.8 [1.7-4.8]). SMN risk was increased among high- and intermediate-risk survivors (SIRhigh=28.0 [18.5-42.3]; SIRintermediate=3.7 [1.2-11.3]), but did not differ from the US population for survivors of low-risk disease. Compared to siblings, survivors had an increased risk of grade 3-5 CHCs, particularly among those with high-risk disease (HRhigh=16.1 [11.2-23.2]; HRintermediate=6.3 [3.8-10.5]; HRlow=1.8 [1.1-3.1]). Survivors of high-risk disease treated in the early days of risk stratification carry a markedly elevated burden of late recurrence, SMN, and organ-related multi-morbidity, while survivors of low/intermediate-risk disease have a modest risk of late adverse outcomes.

Incidence of Nonkeratinocyte Skin Cancer After Breast Cancer Radiation Therapy

Previous studies have suggested that radiation therapy may contribute to an increased risk of subsequent nonkeratinocyte (ie, not squamous and basal cell) skin cancers. To test the hypothesis that radiation therapy for breast cancer increases the risk of subsequent nonkeratinocyte skin cancers, particularly when these cancers are localized to the skin of the breast or trunk. This population-based cohort study used longitudinal data from the Surveillance, Epidemiology, and End Results (SEER) Program for January 1, 2000, to December 31, 2019. The SEER database includes population-based cohort data from 17 registries. Patients with newly diagnosed breast cancer were identified and were evaluated for subsequent nonkeratinocyte skin cancer development. Data analysis was performed from January to August 2023. Radiation therapy, chemotherapy, or surgery for breast cancer. The primary outcomes were standardized incidence ratios (SIRs) for subsequent nonkeratinocyte skin cancer development from 2000 to 2019 based on treatment type (radiation therapy, chemotherapy, or surgery), skin cancer site on the body, and skin cancer subtype. Among the 875 880 patients with newly diagnosed breast cancer included in this study, 99.3% were women, 51.6% were aged older than 60 years, and 50.3% received radiation therapy. A total of 11.2% patients identified as Hispanic, 10.1% identified as non-Hispanic Black, and 69.5% identified as non-Hispanic White. From 2000 to 2019, there were 3839 patients with nonkeratinocyte skin cancer, including melanoma (3419 [89.1%]), Merkel cell carcinoma (121 [3.2%]), hemangiosarcoma (104 [2.7%]), and 32 other nonkeratinocyte skin cancers (195 [5.1%]), documented to occur after breast cancer treatment. The risk of nonkeratinocyte skin cancer diagnosis after breast cancer treatment with radiation was 57% higher (SIR, 1.57 [95% CI, 1.45-1.7]) than that of the general population when considering the most relevant site: the skin of the breast or trunk. When risk at this site was stratified by skin cancer subtype, the SIRs for melanoma and hemangiosarcoma were both statistically significant at 1.37 (95% CI, 1.25-1.49) and 27.11 (95% CI, 21.6-33.61), respectively. Receipt of radiation therapy was associated with a greater risk of nonkeratinocyte skin cancer compared with chemotherapy and surgical interventions. In this study of patients with breast cancer, an increased risk of melanoma and hemangiosarcoma after breast cancer treatment with radiation therapy was observed. Although occurrences of nonkeratinocyte skin cancers are rare, physicians should be aware of this elevated risk to help inform follow-up care.

Incidence, risk and prognosis of second primary malignancy of patients with gastric adenocarcinoma

Due to the long-term low survival rates of gastric adenocarcinoma (GAC) patients, the occurrence and prognosis of second primary malignancies (SPMs) are often underreported and overlooked as a significant concern.To date, only a few studies have addressed this issue in the context of GAC. These studies, however, are limited by their small patient cohorts and lack of substantial, meaningful findings. Our study aims to fill this gap by investigating the incidence, risk factors, and prognostic significance of SPMs among GAC survivors. Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, we analysed data from patients diagnosed with GAC between 2000 and 2020. The study employs the standardized incidence ratio (SIR) to assess the relative risk of SPMs, competing risk regression to identify risk factors for SPM development after GAC, and Kaplan-Meier and COX regression analyses for survival outcomes. Out of 44,041 GAC patients analyzed, 2,032 (4.3%) developed SPMs, with a median latency period of 36 months. The incidence of SPMs was significantly higher in GAC patients (SIR 1.36, 95% CI 1.32-1.4, EAR 53.57) compared to the general population. Key factors including older age, sex, tumor grade, summary stage, and history of surgical and radiation therapy were related to the higher risk of developing SPMs following GAC. Interestingly, GAC patients without SPMs exhibited poorer overall survival compared to those with SPMs. Age, summary stage, and surgical history were identified as independent prognostic factors for GAC patients with SPMs. This comprehensive analysis underscores the necessity of vigilant monitoring and tailored follow-up for SPMs in GAC survivors, highlighting the study's contribution to enhancing GAC survivors care strategies.

Better tools for better estimates: improving approaches to handling missing data in Swiss cancer registries.

Various approaches have been used in the literature to handle missing vital status data in cancer registries. We aimed to compare these approaches to determine which led to the least biased estimates in typical analytic tasks of cancer registries. A simulation study was performed using data from the Swiss National Agency for Cancer Registration for six tumor types. First, 5%, 10% and 15% missingness in the vital status were introduced artificially in the complete data. Second, missing vital status data were handled by applying no, single or multiple imputations. Five-year overall survival estimates, relative survival or standardized incidence ratio were computed. Estimates were compared with the true value. Standardized incidence ratio estimates for colorectal cancer obtained with multiple imputation yielded least biased results (-0.06 to -0.04), but the widest confidence intervals. Single imputation was more biased (-0.32) than using no imputation at all (-0.21). A similar pattern was observed for overall survival and relative survival. This simulation study indicated that often used single imputation (sometimes referred to as simulating follow-up times) techniques to fill in missing vital status data are likely too biased to be useful in practice. Multiple imputation approaches yielded standardized incidence ratio, overall and relative survival estimates with the least bias, indicating reasonable performance that is likely to generalize to other settings.

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 healthcare data. We followed DD patients for up to 20 years, beginning one year after the date of DD diagnosis until the first occurrence of incident cancer, emigration, death, 20 years of follow-up, or December 31st, 2019. We calculated cumulative incidence proportions of cancer and standardized incidence ratios (SIRs) comparing cancer incidence among DD patients 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% CI: 0.72-0.78]). The highest SIRs were observed for cancers of the lung, bronchi, and trachea (SIR, 1.20; 95% CI: 1.15-1.24) and kidney (SIR, 1.27; 95% CI: 1.16-1.39). Our findings show an increased long-term relative risk of cancer following a diagnosis of DD. These findings are likely due to prevalence of numerous risk factors in DD patients that confer an increased risk of cancer. The decreased relative risk of colorectal cancer might be explained by an increased likelihood of DD patients undergoing colonoscopy with polypectomy.

Personal history of cancer as a risk factor for second primary lung cancer: Implications for lung cancer screening.

Personal history of cancer is an independent risk factor for lung cancer but is omitted from existing lung cancer screening eligibility criteria. In this study, we assess the lung cancer risk among cancer survivors and discuss potential implications for screening. This was a retrospective, secondary analysis of data from the Surveillance, Epidemiology and End Results (SEER) registry and the MD Anderson Cancer Center (MDACC). We estimated the standardized incidence ratios (SIRs) for lung cancer by site of first primary cancer using data from SEER. We assessed the lung cancer risk among head and neck cancer survivors from MDACC using cumulative incidence and compared the risk ratios (RR) by individuals' screening eligibility status. Other than first primary lung cancer (SIR: 5.10, 95% CI: 5.01-5.18), cancer survivors in SEER with personal history of head and neck cancer (SIR: 3.71, 95% CI: 3.63-3.80) had the highest risk of developing second primary lung cancer, followed by bladder (SIR: 1.86, 95% CI: 1.81-1.90) and esophageal cancers (SIR: 1.78, 95% CI: 1.61-1.96). Head and neck cancer survivors had higher risk to develop lung cancer compared to the National Lung Screening Trial's subjects, (781 vs. 572 per 100,000 person-years, respectively). Head and neck cancer survivors ineligible for lung cancer screening seen at MDACC had significantly higher lung cancer risk than head and neck cancer survivors from SEER (RR: 1.9, p < 0.001). Personal history of cancer, primarily head and neck cancer, is an independent risk factor for lung cancer and may be considered as an eligibility criterion in future lung cancer screening recommendations.