Changes in sex-specific incidence of lymphoid neoplasms across the lifespan.

Not available.

Developing a company-specific job exposure matrix for the Asbest Chrysotile Cohort Study.

OBJECTIVES: Exposure assessment for retrospective industrial cohorts are often hampered by limited availability of historical measurements. This study describes the development of company-specific job-exposure matrices (JEMs) based on measurements collected over five decades for a cohort study of 35 837 workers (Asbest Chrysotile Cohort Study) in the Russian Federation to estimate their cumulative exposure to chrysotile containing dust and fibres. METHODS: Almost 100 000 recorded stationary dust measurements were available from 1951-2001 (factories) and 1964-2001 (mine). Linear mixed models were used to extrapolate for years where measurements were not available or missing. Fibre concentrations were estimated using conversion factors based on side-by-side comparisons. Dust and fibre JEMs were developed and exposures were allocated by linking them to individual workers' detailed occupational histories. RESULTS: The cohort covered a total of 515 355 employment-years from 1930 to 2010. Of these individuals, 15% worked in jobs not considered professionally exposed to chrysotile. The median cumulative dust exposure was 26 mg/m3 years for the entire cohort and 37.2 mg/m3 years for those professionally exposed. Median cumulative fibre exposure was 16.4 fibre/cm3 years for the entire cohort and 23.4 fibre/cm3 years for those professionally exposed. Cumulative exposure was highly dependent on birth cohort and gender. Of those professionally exposed, women had higher cumulative exposures than men as they were more often employed in factories with higher exposure concentrations rather than in the mine. CONCLUSIONS: Unique company-specific JEMs were derived using a rich measurement database that overlapped with most employment-years of cohort members and will enable estimation of quantitative exposure-response.

Long-term risk of subsequent cancer incidence among hereditary and nonhereditary retinoblastoma survivors.

BACKGROUND: Increased sarcoma and melanoma risks after hereditary retinoblastoma are well established, whereas less is known about epithelial subsequent malignant neoplasms (SMNs) and risks for multiple (≥2) SMNs. METHODS: Leveraging long-term follow-up and detailed histologic information, we quantified incident SMN risk among 1128 hereditary and 924 nonhereditary retinoblastoma survivors (diagnosed 1914-2006; follow-up through 2016). Standardised incidence ratios (SIRs) compared cancer risk after retinoblastoma relative to the general population. We estimated cumulative incidence accounting for competing risk of death. RESULTS: Hereditary survivors had statistically significantly increased SMN risk (N = 239; SIR = 11.9; 95% confidence interval [CI] 10.4-13.5), with SIRs >80-fold for sarcomas, nasal cavity tumours and pineoblastoma. Significantly increased risks were also observed for melanoma and central nervous system, oral cavity and breast SMNs (SIRs = 3.1-17), but not the uterus, kidney, lung, bladder, pancreas or other types. Cumulative incidence 50 years following hereditary retinoblastoma was 33.1% (95% CI 29.0-37.2) for a first SMN and 6.0% (95% CI 3.8-8.2) for a second SMN. SMN risk was not increased after nonhereditary retinoblastoma (N = 25; SIR = 0.8; 95% CI 0.5-1.2). CONCLUSION: Beyond the established sarcoma and melanoma risks after hereditary retinoblastoma, we demonstrate increased risk for a more limited number of epithelial malignancies than previously suggested. Cumulative incidence estimates emphasise long-term SMN burden after hereditary retinoblastoma.

Risk factors for contralateral breast cancer in postmenopausal breast cancer survivors in the NIH-AARP Diet and Health Study.

PURPOSE: The role of established breast cancer risk factors and clinical characteristics of the first breast cancer in the development of contralateral breast cancer (CBC) among postmenopausal women is unclear. METHODS: We identified 10,934 postmenopausal women diagnosed with a first primary breast cancer between 1995 and 2011 in the NIH-AARP Diet and Health Study. CBC was defined as a second primary breast cancer diagnosed in the contralateral breast ≥ 3 months after the first breast cancer. Exposures included pre-diagnosis risk factors (lifestyle, reproductive, family history) and clinical characteristics of the first breast cancer. We used multivariable Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Over a median follow-up of 6.8 years, 436 women developed CBC. We observed an increasing trend in CBC risk by age (p-trend = 0.002) and decreasing trend by year of diagnosis (p-trend = 0.001) of the first breast cancer. Additional risk factor associations were most pronounced for endocrine therapy (HR 0.68, 95% CI 0.53-0.87) and family history of breast cancer (HR 1.38, 95% CI 1.06-1.80, restricted to invasive first breast cancer). No associations were found for lifestyle (body mass index, physical activity, smoking, alcohol) or reproductive factors (age at menarche, parity, age at first birth, age at menopause). CONCLUSIONS: This study suggests that clinical characteristics of the first breast cancer and family history of breast cancer, but not pre-diagnosis lifestyle and reproductive factors, are strongly associated with CBC risk among postmenopausal women. Future studies are needed to understand how these factors contribute to CBC etiology and to identify further opportunities for prevention.

Racial and ethnic differences in risk of second primary cancers among prostate cancer survivors.

PURPOSE: Previous studies have shown an overall decreased risk of second cancers among prostate cancer survivors, but this has not been comprehensively examined by race/ethnicity. We conducted a retrospective cohort study of 716,319 one-year survivors of prostate cancer diagnosed at ages 35-84 during 2000-2015 as reported to 17 US Surveillance, Epidemiology and End Results (SEER) registries. METHODS: We estimated standardized incidence ratios (SIRs) for second primary non-prostate malignancies by race/ethnicity (non-Latino white, Black, Asian/Pacific Islander [API] and Latino), by Gleason, and by time since prostate cancer diagnosis. Poisson regression models were used to test heterogeneity between groups with the expected number as the offset. RESULTS: 60,707 second primary malignancies were observed. SIRs for all second cancers combined varied significantly by race/ethnicity: SIRwhite: 0.88 (95% confidence interval: 0.87-0.89), SIRLatino: 0.92 (0.89-0.95), SIRBlack: 0.97 (0.95-0.99), and SIRAPI: 1.05 (1.01-1.09) (p-heterogeneity < 0.001). SIRs for all cancers combined were higher among survivors of higher vs. lower Gleason prostate cancers irrespective of race/ethnicity. We observed significant heterogeneity by race/ethnicity in SIRs for 9 of 14 second cancer types investigated including lung, bladder, kidney, and liver. CONCLUSIONS: Our results confirm that most prostate cancer survivors have lower risks of second cancers than expected, but the magnitude varied by race/ethnicity. Exceptionally, API men had small but significantly increased risk. Further research to understand drivers of the observed race/ethnicity heterogeneity is warranted.

Tobacco smoking among chrysotile asbestos workers in Asbest in the Russian Federation.

OBJECTIVES: A historical cohort study of cancer mortality is being conducted among workers in a chrysotile mine and its enrichment factories in the town of Asbest, Russian Federation. Because individual-level information on tobacco use is not available for Asbest Chrysotile Cohort members, a cross-sectional survey of smoking behaviours was conducted among active and retired workers. METHODS: Self-administered questionnaires were completed by active workers during meetings organised by occupational safety personnel. Retired workers completed questionnaires during meetings of the Veterans Council or were interviewed via telephone or in person. Of the respondents, 46% could be linked to the Asbest Chrysotile Cohort. Among those, logistic regression models were used to assess associations between smoking and cumulative dust exposure. RESULTS: Among men, smoking prevalence was high and relatively consistent across birth decades (average, 66%), and was similar in workers across all levels of cumulative dust exposure (p trend, 0.44). Among women, the prevalence increased from <10% in those born before 1960 to 30% in those born after 1980, and smoking was associated with exposure to dust versus not exposed to dust (p value, 0.006), but did not vary appreciably across workers in different cumulative dust exposure categories (p trend, 0.29). CONCLUSIONS: Our study suggests that cross-sectional surveys may be a useful tool for understanding the potential health impact from smoking in occupational cohorts, including possible confounding by smoking. This survey showed that adjustment at the age group level among women is needed to reduce residual confounding and account for smoking patterns, which have changed substantially over time.

Radiotherapy for ductal carcinoma in situ and risk of second non-breast cancers.

PURPOSE: Radiotherapy for ductal carcinoma (DCIS) is increasing, but the risks and benefits of the treatment remain uncertain. We aimed to investigate the relationship between radiotherapy for DCIS and risk of second non-breast cancers in a large US cohort. METHODS: We conducted a retrospective cohort study of 52,556 women in 12 U.S. population-based cancer registries diagnosed with first primary DCIS during 1992-2008 at age 25-79 years. We estimated relative risks (RRs), attributable risks (AR), and excess absolute risks (EAR) of second non-breast cancers associated with radiotherapy using Poisson regression adjusted for age at year of diagnosis, grade, hormonal therapy (yes/no or unknown), and time since diagnosis. RESULTS: Approximately half of the women (46.3%) received radiotherapy. Radiotherapy was associated with an increased risk of all second non-breast cancers combined [RR 1.17, 95% confidence interval (CI) 1.08-1.28] and all in-field, radiation-related second cancers combined (RR 1.37, 95% CI 1.15-1.63), driven by second lung cancers (RR 1.33, 95% CI 1.10-1.60) and non-CLL leukemia (RR 1.71, 95% CI 1.02-2.86). The estimated cumulative excess risk of all second non-breast cancers was 0.8% by 15 years after DCIS diagnosis. CONCLUSIONS: Radiotherapy was associated with an increased risk of second non-breast cancers. The specific excess of cancers at sites likely in/near the radiotherapy field suggests the findings are unlikely due exclusively to confounding, but further research into factors related to receipt of radiotherapy is needed. Our risk estimates can be used to help assess the balance of the risks and benefits of radiotherapy for DCIS and to inform clinical practice.

Childhood cancer incidence patterns by race, sex and age for 2000-2006: a report from the South African National Cancer Registry.

Higher childhood cancer incidence rates are generally reported for high income countries although high quality information on descriptive patterns of childhood cancer incidence for low or middle income countries is limited, particularly in Sub-Saharan Africa. There is a need to quantify global differences by cancer types, and to investigate whether they reflect true incidence differences or can be attributed to under-diagnosis or under-reporting. For the first time, we describe childhood cancer data reported to the pathology report-based National Cancer Registry of South Africa in 2000-2006 and compare our results to incidence data from Germany, a high income country. The overall age-standardized incidence rate (ASR) for South Africa in 2000-2006 was 45.7 per million children. We observed substantial differences by cancer types within South Africa by racial group; ASRs tended to be 3-4-fold higher in South African Whites compared to Blacks. ASRs among both Black and White South Africans were generally lower than those from Germany with the greatest differences observed between the Black population in South Africa and Germany, although there was marked variation between cancer types. Age-specific rates were particularly low comparing South African Whites and Blacks with German infants. Overall, patterns across South African population groups and in comparison to Germans were similar for boys and girls. Genetic and environmental reasons may probably explain rather a small proportion of the observed differences. More research is needed to understand the extent to which under-ascertainment and under-diagnosis of childhood cancers drives differences in observed rates.

Meeting report: suggestions for studies on future health risks following the Fukushima accident.

In October 2013, the Radiation Medical Science Center of the Fukushima Medical University and the Section of Environment and Radiation of the International Agency for Research on Cancer held a joint workshop in Fukushima, Japan to discuss opportunities and challenges for long-term studies of the health effects following the March 2011 Fukushima Daiichi Nuclear Power Plant Accident. This report describes four key areas of discussion -- thyroid screening, dosimetry, mental health, and non-radiation risk factors -- and summarizes recommendations resulting from the workshop. Four recommendations given at the workshop were to: 1) build-up a population-based cancer registry for long-term monitoring of the cancer burden in the prefecture; 2) enable future linkage of data from the various independent activities, particularly those related to dose reconstruction and health status ascertainment; 3) establish long-term observational studies with repeated measurements of lifestyle and behavioural factors to disentangle radiation and non-radiation factors; and 4) implement primary prevention strategies targeted for populations affected by natural disasters, including measures to better understand and address health risk concerns in the affected population. The workshop concluded that coordinated data collection between researchers from different institutes and disciplines can both reduce the burden on the population and facilitate efforts to examine the inter-relationships between the many factors at play.

Regional variations in German mesothelioma mortality rates: 2000­2010.

PURPOSE: Germany has one of the highest age-adjusted mesothelioma mortality rates worldwide. As mesothelioma occurs ≥ 30 years after asbestos exposure, contemporary rates likely reflect exposures in the 1960-1970s. During this period, political division between West and East Germany led to differences regarding the import and consumption of asbestos. It is unclear whether mesothelioma rates also differ between these formerly separate countries which are now served by similar health and mortality reporting systems, thereby facilitating regional comparisons. METHODS: We examined regional, temporal, and sex variations in mesothelioma mortality rates in Germany in 2000-2010, collapsing the federal states into West Germany, East Germany, and Berlin. We calculated truncated (≥ 40 years) age-standardized mesothelioma mortality rates (ASRs(40+)) per 100,000 person-years, estimated sex-stratified mortality rate ratios (MRRs) (95 % confidence intervals (CIs)), adjusted for age and calendar year from Poisson models, and fitted age-period-cohort models. RESULTS: There were 12,854 mesothelioma deaths at ages ≥ 40 years in Germany during 2000-2010. ASRs(40+) were higher in West (males 4.4; females 0.8) than East (males 1.7; females 0.6) Germany. MRRs for West versus East Germany were 2.68 (95 % CI 2.48-2.88) among males and 1.42 (95 % CI 1.27-1.59) among females. In both regions, mortality rates increased for birth cohorts until the mid 1940s and subsequently declined. The country's peak mesothelioma burden is predicted to occur by 2020. CONCLUSIONS: Geographical differences in mesothelioma mortality rates are consistent with heterogeneous historical asbestos exposures. Differences may exist for other asbestos-related cancers and should be investigated in analytic studies with individual asbestos exposure information.

Association between diabetes and subsequent malignancy risk among older breast cancer survivors.

Type II diabetes is associated with cancer risk in the general population but has not been well studied as a risk factor for subsequent malignancies among cancer survivors. We investigated the association between diabetes and subsequent cancer risk among older (66-84 years), 1-year breast cancer survivors within the linked Surveillance Epidemiology and End Results (SEER)-Medicare database using Cox regression analyses to quantify hazard ratios (HR) and corresponding 95% confidence intervals (95% CI). Among 133 324 women, 29.3% were diagnosed with diabetes before or concurrent with their breast cancer diagnosis, and 10 452 women developed subsequent malignancies over a median follow-up of 4.3 years. Diabetes was statistically significantly associated with liver (HR = 2.35, 95% CI = 1.48 to 3.74), brain (HR = 1.94, 95% CI = 1.26 to 2.96), and thyroid cancer risks (HR = 1.38, 95% CI = 1.01 to 1.89). Future studies are needed to better understand the spectrum of subsequent cancers associated with diabetes and the role of diabetes medications in modifying subsequent cancer risk, alone or in combination with cancer treatments.

Survival of adult AML patients treated with chemotherapy in the U.S. population by age, race and ethnicity, sex, calendar-year period, and AML subgroup, 2001-2019.

Background: Population-based survival studies of adult acute myeloid leukemia (AML) have not simultaneously evaluated age at diagnosis, race and ethnicity, sex, calendar period or AML subtypes/subgroups among chemotherapy-treated patients. Methods: For 28,473 chemotherapy-treated AML patients diagnosed at ages ≥20 years in population-based cancer registry areas of the Surveillance, Epidemiology, and End Results Program (2001-2018, followed through 2019), we evaluated 1-month through 5-year relative survival (RS) and 95% confidence intervals (95% CI) using the actuarial method in the SEER∗Stat Survival Session and overall survival (OS) using multivariable Cox regression to estimate proportional hazard ratios (HR) and 95% CI. Findings: RS decreased with increasing age (20-39, 40-59, 60-74, 75-84, ≥85 years) at AML diagnosis. RS declined substantially within the first month and, except for acute promyelocytic leukemia, decreasing patterns continued thereafter for core binding factor AML, AML with antecedent condition/therapy, and all other AML. For all ages, acute promyelocytic leukemia RS stabilized after the first year. For total AML the hazard of death was significantly increased for non-Hispanic (NH)-Black (HR = 1.18, 95% CI = 1.12-1.24) and NH-Pacific Islander patients (HR = 1.31, 95% CI = 1.11-1.55) compared with NH-White patients. In contrast, NH-Asian and Hispanic patients had similar OS to NH-White patients across all ages and most AML subgroups. Males had significantly inferior survival to females with some exceptions. Compared to 2001-2006, in 2013-2018 OS improved for all age and AML subgroups. Interpretation: Chemotherapy-treated U.S. adults with AML have notable differences in survival by age, race and ethnicity, sex, calendar-year period, and AML subgroup. Despite survival gains over time, our findings highlight the need for improving early outcomes across all AML subgroups, older ages, and Black and Pacific Islander patients and long-term outcomes among most treated groups. Funding: Intramural Research Program of the U.S. National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, and the U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Surveillance and Epidemiology.

All-Cause and Cause-Specific Mortality Among Low-Risk Differentiated Thyroid Cancer Survivors in the United States.

Background: Despite the excellent disease-specific survival associated with low-risk differentiated thyroid cancer (DTC), its diagnosis and management have been linked to patient concerns about cancer recurrence, treatment-related health risks, and mortality. Lack of information regarding long-term health outcomes can perpetuate these concerns. Therefore, we assessed all-cause and cause-specific mortality in a large cohort of individuals diagnosed with low-risk DTC. Methods: From the U.S. Surveillance, Epidemiology, and End Results-12 cancer registry database (1992-2019), we identified 51,854 individuals (81.8% female) diagnosed with first primary DTC at low risk of recurrence (≤4 cm, localized). We estimated cause-specific cumulative mortality by time since diagnosis, accounting for competing risks. Standardized mortality ratios (SMRs) and CIs were used to compare observed mortality rates in DTC patients with expected rates in the matched U.S. general population, overall and by time since DTC diagnosis. We used Cox proportional hazards models to examine associations between radioactive iodine (RAI) treatment and cause-specific mortality. Results: During follow-up (median = 8.8, range 0-28 years), 3467 (6.7%) deaths were recorded. Thyroid cancer accounted for only 4.3% of deaths (n = 148). The most common causes of death were malignancies (other than thyroid cancer) (n = 1031, 29.7%) and cardiovascular disease (CVD; n = 912, 26.3%). The 20-year cumulative mortality rate from thyroid cancer, malignancies (other than thyroid or nonmelanoma skin cancer), and CVD was 0.6%, 4.6%, and 3.9%, respectively. Lower than expected mortality was observed for all causes excluding thyroid cancer (SMR = 0.69 [CI 0.67-0.71]) and most specific causes, including all malignancies combined (other than thyroid cancer; SMR = 0.80 [CI 0.75-0.85]) and CVD (SMR = 0.64 [CI 0.60-0.69]). However, mortality rates were elevated for specific cancers, including pancreas (SMR = 1.58 [CI 1.18-2.06]), kidney and renal pelvis (SMR = 1.85 [CI 1.10-2.93]), and brain and other nervous system (SMR = 1.62 [CI 0.99-2.51]), and myeloma (SMR = 2.35 [CI 1.46-3.60]) and leukemia (SMR = 1.62 [CI 1.07-2.36]); these associations were stronger ≥10 years after diagnosis. RAI was not associated with risk of cause-specific death, but numbers of events were small and the range of administered activities was likely narrow. Conclusions: Overall, our findings provide reassurance regarding low overall and cause-specific mortality rates in individuals with low-risk DTC. Additional research is necessary to confirm and understand the increased mortality from certain subsequent cancers.

Cancer mortality in chrysotile miners and millers, Russian Federation: main results (Asbest Chrysotile Cohort-Study).

BACKGROUND: We investigated mortality in workers of the world's largest chrysotile mine and enrichment factories located in the town of Asbest, Russian Federation. METHODS: This historical cohort study included all workers employed for at least 1 year between 1975 and 2010 and follow-up until the end of 2015. Cumulative exposure to dust was estimated based on workers' complete occupational history linked to dust measurements systematically collected from the 1950s. Exposure to chrysotile fibers was estimated using dust-to-fiber conversion factors. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated as mortality rate ratios in Poisson regression models. RESULTS: A total of 30 445 (32% women) workers accumulated 721 312 person-years at risk and 11 110 (36%) died. Of the workers, 54% had more than 30 years since their first exposure. We found an exposure-response between cumulative dust and lung cancer mortality in men. No clear association with dust exposure but a modest increase in the highest category of fiber exposure was seen for lung cancer in women. Mesothelioma mortality was increased (RR = 7.64, 95% CI = 1.18 to 49.5, to at least 80 fibers per cm3 years and RR = 4.56, 95% CI = 0.94 to 22.1, to at least 150 mg/m3 years [dust]), based on 13 deaths. For colorectal and stomach cancer, there were inconsistent associations. No associations were seen for laryngeal or ovarian cancer. CONCLUSION: In this large-scale epidemiological study in the world's largest active asbestos mine, we confirmed an increased risk of mesothelioma with high fiber exposure and an increasing mortality for lung cancer in men with increasing dust exposure. Less clear-cut increased lung cancer mortality was seen in the women. Continued mortality follow-up is warranted.

Utilization of Autologous Hematopoietic Cell Transplantation Over Time in Multiple Myeloma: A Population-Based Study.

PURPOSE: Autologous hematopoietic cell transplantation (autoHCT) is associated with survival benefits in multiple myeloma (MM), but utilization remains low and differs by sociodemographic factors. Prior population-based studies have not fully captured autoHCT utilization or examined relationships between sociodemographic factors and autoHCT trends over time. PATIENTS AND METHODS: We used a novel data linkage between the California Cancer Registry, Center for International Blood and Marrow Transplant Research, and hospitalizations to capture autoHCT in a population-based MM cohort (n = 29, 109; 1991-2016). Due to interactions by treatment era, stratified multivariable Cox proportional hazards regression models determined factors associated with autoHCT. RESULTS: The frequency of MM patients who received autoHCT increased from 5.7% (1991-1995) to 27.4% (2011-2016). In models by treatment era, patients with public/no (vs. private) health insurance were less likely to receive autoHCT (2011-2016 Medicare hazard ratio (HR) 0.70, 95% confidence interval (CI): 0.63-0.78; Medicaid HR 0.81, CI: 0.72-0.91; no insurance HR 0.56, CI: 0.32-0.99). In each treatment era, Black/African American (vs. non-Hispanic White) patients were less likely to receive autoHCT (2011-2016 HR 0.83, CI: 0.72-0.95). Hispanic patients were less likely to undergo autoHCT, most prominently in the earliest treatment era (1991-1995 HR 0.58, 95% CI: 0.37-0.90; 2011-2016 HR 1.07, CI: 0.96-1.19). Patients in lower socioeconomic status neighborhoods were less likely to utilize autoHCT, but differences decreased over time. CONCLUSIONS: Despite increases in autoHCT utilization, sociodemographic disparities remain. Identifying and mitigating barriers to autoHCT is essential to ensuring more equitable access to this highly effective therapy.

Comparison of Vital Status, Cause of Death, and Follow-Up after Hematopoietic Cell Transplantation in Linked Center for International Blood and Marrow Transplant Research and California Cancer Registry Data, 1991 to 2018.

Assessing outcomes following hematopoietic cell transplantation (HCT) poses challenges due to the necessity for systematic and often prolonged patient follow-up. Linking the HCT database of the Center for International Blood and Marrow Transplant Research (CIBMTR) with cancer registry data may improve long-term outcome ascertainment, but the reliability of mortality data in death certificates from cancer registries among HCT recipients remains unknown. We compared the classification of vital status and primary cause of death (COD), as well as the length of follow-up between the CIBMTR and California Cancer Registry (CCR) to assess the possibility of supplementing the CIBMTR with cancer registry data. This retrospective study leveraged a linked CIBMTR-CCR dataset. We included patients who were California residents at the time of HCT and received a first allogeneic (allo) or autologous (auto) HCT for a hematologic malignancy diagnosed during 1991-2016. Follow-up was through 2018. We analyzed 18,450 patients (alloHCT, n = 8232; autoHCT, n = 10,218). The Vital status agreement was 97.7% for alloHCT and 97.2% for autoHCT. Unknown COD was higher in CIBMTR (12.9%) than in CCR (1.6%). After excluding patients with unknown COD information, the overall agreement of primary COD (cancer versus noncancer) was 53.7% for alloHCT and 83.2% for autoHCT. This agreement was lower within the first 100 days post-HCT (alloHCT, 31.0%; autoHCT, 54.6%). Compared with CIBMTR, deaths due to cancer were higher in CCR (alloHCT, 90.0%; autoHCT, 90.1% versus alloHCT, 47.3%; autoHCT, 82.5% in CIBMTR). CIBMTR reports more frequently noncancer-related deaths, including graft-versus-host disease and infections. The cumulative incidence of cancer-specific mortality at 20 years differed, particularly for alloHCT (CCR, 53.7%; CIBMTR, 27.6%). The median follow-up among alive patients was longer in CCR (alloHCT, 6.0 years; autoHCT, 4.7 years) than in CIBMTR (alloHCT, 5.0 years; autoHCT, 3.8 years). Our findings highlight the completeness of vital status data in CIBMTR but reveal substantial disagreement in primary COD. Consequently, caution is required when interpreting HCT studies that use only death certificates to estimate cause-specific mortality outcomes. Improving the accuracy of COD registration and follow-up completeness by developing communication pathways between cancer registries and hospital-based cohorts may enhance our understanding of late effects and long-term outcomes among HCT survivors.

Cumulative incidence estimates for solid tumors after HCT in the CIBMTR and California Cancer Registry.

Compared with the general population, hematopoietic cell transplantation (HCT) survivors are at elevated risk for developing solid subsequent neoplasms (SNs). The Center for International Blood and Marrow Transplant Research (CIBMTR) is a key resource for quantifying solid SN incidence following HCT, but the completeness of SN ascertainment is uncertain. Within a cohort of 18,450 CIBMTR patients linked to the California Cancer Registry (CCR), we evaluated the completeness of solid SN data reported to the CIBMTR during 1991-2018 to understand the implications of using CIBMTR data alone or combined with CCR data to quantify the burden of solid SNs post-HCT. We estimated the cumulative incidence of developing a solid SN, accounting for the competing risk of death. Within the cohort, solid SNs were reported among 724 patients; 15.6% of these patients had an SN reported by CIBMTR-only, 36.9% by CCR-only, and 47.5% by both. The corresponding cumulative incidence of developing a solid SN at 10 years following a first HCT was 4.0% (95% CI=3.5% to 4.4%) based on CIBMTR data only, 5.3% (95% CI=4.9% to 5.9%) based on CCR data only, and 6.3% (95% CI=5.7% to 6.8%) based on both sources combined. The patterns were similar for allogeneic and autologous HCT recipients. Linking detailed HCT information from CIBMTR with comprehensive SN data from cancer registries provides an opportunity to optimize SN ascertainment for informing follow-up care practices and evaluating risk factors in the growing population of HCT survivors.

Genomic characterization of cervical lymph node metastases in papillary thyroid carcinoma following the Chornobyl accident.

Childhood radioactive iodine exposure from the Chornobyl accident increased papillary thyroid carcinoma (PTC) risk. While cervical lymph node metastases (cLNM) are well-recognized in pediatric PTC, the PTC metastatic process and potential radiation association are poorly understood. Here, we analyze cLNM occurrence among 428 PTC with genomic landscape analyses and known drivers (131I-exposed = 349, unexposed = 79; mean age = 27.9 years). We show that cLNM are more frequent in PTC with fusion (55%) versus mutation (30%) drivers, although the proportion varies by specific driver gene (RET-fusion = 71%, BRAF-mutation = 38%, RAS-mutation = 5%). cLNM frequency is not associated with other characteristics, including radiation dose. cLNM molecular profiling (N = 47) demonstrates 100% driver concordance with matched primary PTCs and highly concordant mutational spectra. Transcriptome analysis reveals 17 differentially expressed genes, particularly in the HOXC cluster and BRINP3; the strongest differentially expressed microRNA also is near HOXC10. Our findings underscore the critical role of driver alterations and provide promising candidates for elucidating the biological underpinnings of PTC cLNM.