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BackgroundSurvival from metastatic cutaneous melanoma is substantially lower than for localized disease. Treatments for metastatic melanoma have been limited, but remarkable clinical improvements have been reported in clinical trials in the last decade. We described the characteristics of US patients diagnosed with cutaneous melanoma during 2001-2013 and assessed trends in short-term survival for distant-stage disease.MethodsTrends in 1-year net survival were estimated using the Pohar Perme estimator, controlling for background mortality with life tables of all-cause mortality rates by county of residence, single year of age, sex, and race for each year 2001-2013. We fitted a flexible parametric survival model on the log-hazard scale to estimate the effect of race on the hazard of death because of melanoma and estimated 1-year net survival by race.ResultsOnly 4.4% of the 425 915 melanomas were diagnosed at a distant stage, cases diagnosed at a distant stage are more commonly men, older patients, and African Americans. Age-standardized, 1-year net survival for distant-stage disease was stable at approximately 43% during 2001-2010. From 2010 onward, survival improved rapidly, reaching 58.9% (95% confidence interval = 56.6% to 61.2%) for patients diagnosed in 2013. Younger patients experienced the largest improvement. Survival for distant-stage disease increased in both Blacks and Whites but was consistently lower in Blacks.ConclusionsOne-year survival for distant-stage melanoma improved during 2001-2013, particularly in younger patients and those diagnosed since 2010. This improvement may be a consequence of the introduction of immune-checkpoint-inhibitors and other targeted treatments for metastatic and unresectable disease. Persistent survival inequalities exist between Blacks and Whites, suggesting differential access to treatment.

© 2015 The Society for Investigative Dermatology, Inc Solid organ transplant recipients, who are medically immunosuppressed to prevent graft rejection, have increased melanoma risk, but risk factors and outcomes are incompletely documented. We evaluated me

Aims: To evaluate cancer incidence among workers at two facilities in the USA that made semiconductors and electronic storage devices.Methods: 89 054 men and women employed by International Business Machines (IBM) were included in the study. We compared employees' incidence rates with general population rates and examined incidence patterns by facility, duration of employment, time since first employment, manufacturing era, potential for exposure to workplace environments other than offices and work activity.Results: For employees at the semiconductor manufacturing facility, the standardised incidence ratio (SIR) for all cancers combined was 81 (1541 observed cases, 95% confidence interval (CI) 77 to 85) and for those at the storage device manufacturing facility the SIR was 87 (1319 observed cases, 95% CI 82 to 92). The subgroups of employees with > or =15 years since hiring and > or =5 years worked had 6-16% fewer total incidents than expected. SIRs were increased for several cancers in certain employee subgroups, but analyses of incidence patterns by potential exposure and by years spent and time since starting in specific work activities did not clearly indicate that the excesses were due to occupational exposure.Conclusions: This study did not provide strong or consistent evidence of causal associations with employment factors. Data on employees with long potential induction time and many years worked were limited. Further follow-up will allow a more informative analysis of cancer incidence that might be plausibly related to workplace exposures in the cohort. [ABSTRACT FROM AUTHOR]

Abstract Background The Gene Ontology (GO) Consortium organizes genes into hierarchical categories based on biological process, molecular function and subcellular localization. Tools such as GoMiner can leverage GO to perform ontological analysis of microarray and proteomics studies, typically generating a list of significant functional categories. Two or more of the categories are often redundant, in the sense that identical or nearly-identical sets of genes map to the categories. The redundancy might typically inflate the report of significant categories by a factor of three-fold, create an illusion of an overly long list of significant categories, and obscure the relevant biological interpretation. Results We now introduce a new resource, RedundancyMiner, that de-replicates the redundant and nearly-redundant GO categories that had been determined by first running GoMiner. The main algorithm of RedundancyMiner, MultiClust, performs a novel form of cluster analysis in which a GO category might belong to several category clusters. Each category cluster follows a "complete linkage" paradigm. The metric is a similarity measure that captures the overlap in gene mapping between pairs of categories. Conclusions RedundancyMiner effectively eliminated redundancies from a set of GO categories. For illustration, we have applied it to the clarification of the results arising from two current studies: (1) assessment of the gene expression profiles obtained by laser capture microdissection (LCM) of serial cryosections of the retina at the site of final optic fissure closure in the mouse embryos at specific embryonic stages, and (2) analysis of a conceptual data set obtained by examining a list of genes deemed to be "kinetochore" genes.

Abstract Background Over 60% of protein-coding genes in vertebrates express mRNAs that undergo alternative splicing. The resulting collection of transcript isoforms poses significant challenges for contemporary biological assays. For example, RT-PCR validation of gene expression microarray results may be unsuccessful if the two technologies target different splice variants. Effective use of sequence-based technologies requires knowledge of the specific splice variant(s) that are targeted. In addition, the critical roles of alternative splice forms in biological function and in disease suggest that assay results may be more informative if analyzed in the context of the targeted splice variant. Results A number of contemporary technologies are used for analyzing transcripts or proteins. To enable investigation of the impact of splice variation on the interpretation of data derived from those technologies, we have developed SpliceCenter. SpliceCenter is a suite of user-friendly, web-based applications that includes programs for analysis of RT-PCR primer/probe sets, effectors of RNAi, microarrays, and protein-targeting technologies. Both interactive and high-throughput implementations of the tools are provided. The interactive versions of SpliceCenter tools provide visualizations of a gene's alternative transcripts and probe target positions, enabling the user to identify which splice variants are or are not targeted. The high-throughput batch versions accept user query files and provide results in tabular form. When, for example, we used SpliceCenter's batch siRNA-Check to process the Cancer Genome Anatomy Project's large-scale shRNA library, we found that only 59% of the 50,766 shRNAs in the library target all known splice variants of the target gene, 32% target some but not all, and 9% do not target any currently annotated transcript. Conclusion SpliceCenter http://discover.nci.nih.gov/splicecenter provides unique, user-friendly applications for assessing the impact of transcript variation on the design and interpretation of RT-PCR, RNAi, gene expression microarrays, antibody-based detection, and mass spectrometry proteomics. The tools are intended for use by bench biologists as well as bioinformaticists.

Abstract Background There are many fewer genes in the human genome than there are expressed transcripts. Alternative splicing is the reason. Alternatively spliced transcripts are often specific to tissue type, developmental stage, environmental condition, or disease state. Accurate analysis of microarray expression data and design of new arrays for alternative splicing require assessment of probes at the sequence and exon levels. Description SpliceMiner is a web interface for querying Evidence Viewer Database (EVDB). EVDB is a comprehensive, non-redundant compendium of splice variant data for human genes. We constructed EVDB as a queryable implementation of the NCBI Evidence Viewer (EV). EVDB is based on data obtained from NCBI Entrez Gene and EV. The automated EVDB build process uses only complete coding sequences, which may or may not include partial or complete 5' and 3' UTRs, and filters redundant splice variants. Unlike EV, which supports only one-at-a-time queries, SpliceMiner supports high-throughput batch queries and provides results in an easily parsable format. SpliceMiner maps probes to splice variants, effectively delineating the variants identified by a probe. Conclusion EVDB can be queried by gene symbol, genomic coordinates, or probe sequence via a user-friendly web-based tool we call SpliceMiner (http://discover.nci.nih.gov/spliceminer). The EVDB/SpliceMiner combination provides an interface with human splice variant information and, going beyond the very valuable NCBI Evidence Viewer, supports fluent, high-throughput analysis. Integration of EVDB information into microarray analysis and design pipelines has the potential to improve the analysis and bioinformatic interpretation of gene expression data, for both batch and interactive processing. For example, whenever a gene expression value is recognized as important or appears anomalous in a microarray experiment, the interactive mode of SpliceMiner can be used quickly and easily to check for possible splice variant issues.

Background: Despite the large number of men diagnosed with localized prostate cancer, there is as yet no consensus concerning appropriate treatment. The purpose of this study was to describe the initial treatment patterns for localized prostate cancer in a population-based sample and to determine the clinical and patient characteristics associated with initial treatment and overall survival.Methods: The analysis included 3,300 patients from seven states, diagnosed with clinically localized prostate cancer in 1997. We examined the association of sociodemographic and clinical characteristics with four treatment options: radical prostatectomy, radiation therapy, hormone therapy, and watchful waiting. Diagnostic and treatment information was abstracted from medical records. Socioeconomic measures were derived from the 2000 Census based on the patient's residence at time of diagnosis. Vital status through December 31, 2002, was obtained from medical records and linkages to state vital statistics files and the National Death Index. Multiple logistic regression analysis and Cox proportional hazards models identified factors associated with initial treatment and overall survival, respectively.Results: Patients with clinically localized prostate cancer received the following treatments: radical prostatectomy (39.7%), radiation therapy (31.4%), hormone therapy (10.3%), or watchful waiting (18.6%). After multivariable adjustment, the following variables were associated with conservative treatment (hormone therapy or watchful waiting): older age, black race, being unmarried, having public insurance, having non-screen detected cancer, having normal digital rectal exam results, PSA values above 20, low Gleason score (2-4), comorbidity, and state of residence. Among patients receiving definitive treatment (radical prostatectomy or radiation therapy), older age, being unmarried, PSA values above 10, unknown Gleason score, state of residence, as well as black race in patients under 60 years of age, were associated with receipt of radiation therapy. Overall survival was related to younger age, being married, Gleason score under 8, radical prostatectomy, and state of residence. Comorbidity was only associated with risk of death within the first three years of diagnosis.Conclusions: In the absence of clear-cut evidence favoring one treatment modality over another, it is important to understand the factors that inform treatment selection. Since state of residence was a significant predictor of both treatment as well as overall survival, true regional differences probably exist in how physicians and patients select treatment options. Factors affecting treatment choice and treatment effectiveness need to be further explored in future population-based studies. [ABSTRACT FROM AUTHOR]

Purpose: Unlike most childhood cancers, therapy for ALL includes a prolonged maintenance phase during which children typically resume regular activities. Physicians need data regarding the persistent impact of COVID-19 in this population to help guide families after the pandemic., Methods: The Pediatric Oncology COVID-19 Case Report (POCC) collects deidentified data (sociodemographics, clinical data [cancer, COVID-19 course]) on children, adolescents, and young adults with cancer and COVID-19 from 104 US pediatric oncology institutions. The analysis presented here compares children (≤21 years) with ALL in maintenance (ALL-MTN) with all other children with cancer and COVID-19. Multivariable analyses adjust for age, race/ethnicity, insurance, absolute neutrophil count at the time of infection, vaccination, and comorbidities., Results: Compared with other children reported to POCC (n = 1,190), those in ALL-MTN (n = 481) were less often hospitalized (23% v 29%, P = .01) or admitted to the intensive care unit (ICU: 3% v 5%, P = .01); these findings persisted in multivariable analysis (hospitalization: odds ratio [OR], 0.7 [95% CI, 0.6 to 0.9]; ICU: OR, 0.5 [95% CI, 0.2 to 0.8]). However, cancer-directed therapy was changed more often for children in ALL-MTN (50% v 33%, P ≤ .01; OR, 2.0 [95% CI, 1.6 to 2.5[). Vaccination was an independent prognostic factor in our multivariable model, decreasing odds of hospitalization (OR, 0.7 [95% CI, 0.5 to 0.9])., Conclusion: Children in ALL-MTN required fewer hospitalizations and ICU admissions but more therapy modifications than other children with cancer. Vaccination against COVID-19 reduced the odds of hospitalization.

Adolescents and young adults (ie, individuals aged 15-39 years, known as AYAs) with cancer face unique vulnerabilities yet remain underrepresented in clinical trials, including adult registries of COVID-19 in cancer (AYAs: 8%-12%). We used the Pediatric Oncology COVID-19 Case Report to examine the clinical course of COVID-19 among AYAs with cancer. The Pediatric Oncology COVID-19 Case Report collects deidentified clinical and sociodemographic data regarding individuals aged from birth to 39 years with cancer (37%) and COVID-19 from more than 100 institutions. Between April 1, 2020, and November 28, 2023, 191 older AYAs (individuals 22-39 years of age) and 640 younger AYAs (individuals 15-21 years of age) were captured. Older AYAs were less often hospitalized (P < .001), admitted to the intensive care unit (P = .02), and required respiratory support (P = .057). In multivariable analyses, older AYAs faced 80% lower odds of intensive care unit admission but 2.3-times greater odds of changes to cancer-directed therapy. Unvaccinated patients had 5.4-times higher odds of intensive care unit admission. Among AYAs with cancer, the COVID-19 course varies by age. These findings can inform oncology teams directing COVID-19 management and prevention in AYA patients with cancer., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: As the February 2022 Surveillance, Epidemiology, and End Results (SEER) Call for Data deadlines approached, the New York State Cancer Registry had received reports for approximately 10% fewer consolidated incident cases for 2020 than expected. We used claims data to examine changes in the volume of cancer claim records during the COVID-19 pandemic and possible contributors to the deficit in cancer reports., Methods: The New York State (NYS) Statewide Planning and Research Cooperative System (SPARCS) requires reporting of all patient encounters from licensed ambulatory surgery, emergency department, and hospital inpatient and outpatient providers. Each record includes patient demographics and up to 17 diagnosis codes from the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM). For this project, we extracted 6,725,416 SPARCS records with any malignant neoplasm code for 2018 through June 2021 for NYS residents. Using SAS 9.4, we focused on comparing the cancer-related records for 2020 to the records from 2019., Results: Overall, there were 5% more cancer-related records in 2019 than in 2018 (2,009,600 vs 1,914,364), but 8.2% fewer records in 2020 (1,844,054 total) than in 2019. Looking by month and year, the number of claims in the first 2 months of 2020 exceeded the numbers from 2019 by 5%. However, a decrease in the number of claims started in March 2020, with the biggest drop in April 2020, where there was a deficit of 38.8% for cancer-related encounter reports relative to the same month the previous year. Although the numbers rose after April, the number of claims for the last half of 2020 was still 4% lower than the same time frame in 2019. There were substantial decreases in the number of records in 2020 for all encounter types and across levels of each covariate examined, including age, sex, race/ethnicity, and facility region of NYS. In analyses of all reporting facilities, facilities in New York City had a more pronounced and more prolonged drop in reporting in 2020 than facilities in the rest of the state., Conclusion: Although SPARCS data do not provide definitive evidence of decreases in incident cancer diagnoses, these data suggest that there were fewer cancers diagnosed among NYS residents in 2020. Additional analyses are needed to assess the impacts of COVID-19-related delays in cancer diagnosis and treatment on stage at diagnosis and outcomes., (© 2022 National Cancer Registrars Association.)

Background: Individuals with a history of cancer may be more susceptible to severe COVID-19 due to immunosuppression, comorbidities, or ongoing treatment. We linked inpatient claims data on COVID-19 hospitalizations to cancer diagnoses from the New York State Cancer Registry (NYSCR) to examine associations between prior cancer diagnoses and hospitalizations for COVID-19, and factors associated with death at discharge after COVID-19 hospitalization., Methods: New York State (NYS) residents diagnosed with invasive cancer before July 1, 2021, who were alive on January 1, 2020, were identified from NYSCR data. We obtained claims data for discharge year 2020 and the first half of 2021 from NYS's Statewide Planning and Research Cooperative System (SPARCS), and we linked inpatient records with COVID-19 as the primary diagnosis to cancer data from the NYSCR using deterministic matching methods. We calculated descriptive statistics and conducted multivariable-adjusted logistic regression analyses to examine associations of cancer case characteristics with COVID-19 hospitalization and with vital status at discharge among patients with a history of cancer. All analyses were conducted in SAS 9.4., Results: Our analysis included 1,257,377 individuals with a history of cancer, 10,210 of whom had a subsequent primary COVID-19 hospitalization. Individuals with a history of cancer were 16% more likely to be hospitalized with COVID-19, compared to the general population of NYS, after adjusting for age and sex (95% CI, 14%-19%). Factors independently associated with COVID-19 hospitalization among cancer patients included older age, male sex, non-Hispanic Black race or Hispanic ethnicity, diagnosis with late-stage cancer or with multiple tumors, more recent cancer diagnosis, and New York City (NYC) residency at the time of cancer diagnosis. Factors independently associated with death at discharge among individuals with COVID-19 hospitalization and a prior cancer diagnosis included older age, male sex, non-Hispanic Black or non-Hispanic Asian/Pacific Islander race or Hispanic ethnicity, residence in NYC at the time of COVID-19 hospitalization, and an active cancer diagnosis claim code at the time of COVID-19 hospitalization., Conclusion: This claims-based study identified higher risks of COVID-19 hospitalization and death at discharge among individuals with a history of cancer, and particularly those in certain demographic and diagnostic groups., (© 2022 National Cancer Registrars Association.)

Background: We examined the impact of race/ethnicity and age on survival in a publicly insured cohort of children and adolescent/young adults (AYA; 15-39 years) with Hodgkin lymphoma, adjusting for chemotherapy using linked Medicaid claims. Materials and Methods: We identified 1231 Medicaid-insured patients <1-39 years diagnosed with classical Hodgkin lymphoma between 2005 and 2015, in the New York State Cancer Registry. Chemotherapy regimens were based on contemporary therapeutic regimens. Cox proportional hazards regression models quantified associations of patient, disease, and treatment variables with overall survival (OS) and disease-specific survival (DSS), and are presented as hazard ratios (HR) with confidence intervals (95% CIs). Results: At median follow-up of 6.6 years, N  = 1108 (90%) patients were alive; 5-year OS was 92% in children <15 years. In multivariable models, Black (vs. White) patients had 1.6-fold increased risk of death (HR: 1.58, 95% CI: 1.02-2.46; p  = 0.042). Stage III/IV (vs. I/II) was associated with 1.9-fold increased risk of death (HR: 1.86, 95% CI: 1.25-2.78; p  = 0.002) and treatment at a non-National Cancer Institute (NCI) affiliate was associated with worse DSS (HR: 2.71, 95% CI: 1.47-4.98; p  = 0.001). Conclusions: In this Medicaid-insured cohort of children and AYAs with Hodgkin lymphoma, Black race/ethnicity remained associated with inferior OS in multivariable models adjusted for disease, demographic, and treatment data. Further work is needed to identify dimensions of health care access not mediated by insurance, as findings suggest additional factors are contributing to observed cancer disparities in vulnerable pediatric and AYA populations.

Purpose of Review: This study aims to describe what is currently known about how children with cancer have been affected by the COVID-19 pandemic, including morbidity and mortality, interruptions in cancer care and delays in diagnosis, and psychosocial effects. Here we summarize the literature on how this patient population has fared during the pandemic, reviewing multiple smaller reports along with two large registries., Recent Findings: Although children with cancer generally have better outcomes with COVID-19 infection than adults with cancer, their risks of hospitalization, ICU admission, and death are greatly increased compared to the general pediatric population. There are socioeconomic and ethnic disparities present in these effects. Children with cancer experience significant risks from the COVID-19 pandemic. It has yet to be seen how delays and interruptions of cancer treatment and direct organ toxicities caused by the virus itself may affect long-term outcomes in these patients., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Statistically significantly increased cancer incidence has been reported from 3 cohorts of World Trade Center (WTC) disaster rescue and recovery workers. We pooled data across these cohorts to address ongoing public concerns regarding cancer risk 14 years after WTC exposure., Methods: From a combined deduplicated cohort of 69 102 WTC rescue and recovery workers, a sample of 57 402 workers enrolled before 2009 and followed through 2015 was studied. Invasive cancers diagnosed in 2002-2015 were identified from 13 state cancer registries. Standardized incidence ratios (SIRs) were used to assess cancer incidence. Adjusted hazard ratios (aHRs) were estimated from Cox regression to examine associations between WTC exposures and cancer risk., Results: Of the 3611 incident cancers identified, 3236 were reported as first-time primary (FP) cancers, with an accumulated 649 724 and 624 620 person-years of follow-up, respectively. Incidence for combined FP cancers was below expectation (SIR = 0.96, 95% confidence interval [CI] = 0.93 to 0.99). Statistically significantly elevated SIRs were observed for melanoma-skin (SIR = 1.43, 95% CI = 1.24 to 1.64), prostate (SIR = 1.19, 95% CI = 1.11 to 1.26), thyroid (SIR = 1.81, 95% CI = 1.57 to 2.09), and tonsil (SIR = 1.40, 95% CI = 1.00 to 1.91) cancer. Those arriving on September 11 had statistically significantly higher aHRs than those arriving after September 17, 2001, for prostate (aHR = 1.61, 95% CI = 1.33 to 1.95) and thyroid (aHR = 1.77, 95% CI = 1.11 to 2.81) cancers, with a statistically significant exposure-response trend for both., Conclusions: In the largest cohort of 9/11 rescue and recovery workers ever studied, overall cancer incidence was lower than expected, and intensity of WTC exposure was associated with increased risk for specific cancer sites, demonstrating the value of long-term follow-up studies after environmental disasters., (© The Author(s) 2022. Published by Oxford University Press.)

Rescue/recovery workers who responded to the World Trade Center (WTC) attacks were exposed to known/suspected carcinogens. Studies have identified a trend toward an elevated risk of cutaneous melanoma in this population; however, few found significant increases. Furthermore, temporal aspects of the association have not been investigated. A total of 44,540 non-Hispanic White workers from the WTC Combined Rescue/Recovery Cohort were studied between March 12, 2002 and December 31, 2015. Cancer data were obtained through linkages with 13 state registries. Poisson regression was used to estimate hazard ratios and 95% confidence intervals using the New York State population as the reference; change points in hazard ratios were estimated using profile likelihood. We observed 247 incident cases of melanoma. No increase in incidence was detected during 2002-2004. From 2005 to 2015, the hazard ratio was 1.34 (95% confidence interval = 1.18-1.52). A dose‒response relationship was observed by arrival time at the WTC site. Risk was elevated just over 3 years after the attacks . Whereas WTC-related exposures to UVR or other agents might have contributed to this result, exposures other than those at the WTC site, enhanced medical surveillance, and lack of a control group with a similar proportion of rescue/recovery workers cannot be discounted. Our results support continued study of this population for melanoma., (© 2021 The Authors.)

Background: The World Trade Center (WTC) attacks on 11 September 2001 created a hazardous environment with known and suspected carcinogens. Previous studies have identified an increased risk of prostate cancer in responder cohorts compared with the general male population., Objectives: To estimate the length of time to prostate cancer among WTC rescue/recovery workers by determining specific time periods during which the risk was significantly elevated., Methods: Person-time accruals began 6 months after enrolment into a WTC cohort and ended at death or 12/31/2015. Cancer data were obtained through linkages with 13 state cancer registries. New York State was the comparison population. We used Poisson regression to estimate hazard ratios and 95% CIs; change points in rate ratios were estimated using profile likelihood., Results: The analytic cohort included 54 394 male rescue/recovery workers. We observed 1120 incident prostate cancer cases. During 2002-2006, no association with WTC exposure was detected. Beginning in 2007, a 24% increased risk (HR: 1.24, 95% CI 1.16 to 1.32) was observed among WTC rescue/recovery workers when compared with New York State. Comparing those who arrived earliest at the disaster site on the morning of 11 September 2001 or any time on 12 September 2001 to those who first arrived later, we observed a positive, monotonic, dose-response association in the early (2002-2006) and late (2007-2015) periods., Conclusions: Risk of prostate cancer was significantly elevated beginning in 2007 in the WTC combined rescue/recovery cohort. While unique exposures at the disaster site might have contributed to the observed effect, screening practices including routine prostate specific antigen screening cannot be discounted., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: A recent study of World Trade Center (WTC)-exposed firefighters and emergency medical service workers demonstrated that elevated thyroid cancer incidence may be attributable to frequent medical testing, resulting in the identification of asymptomatic tumors. We expand on that study by comparing the incidence of thyroid cancer among three groups: WTC-exposed rescue/recovery workers enrolled in a New York State (NYS) WTC-medical monitoring and treatment program (MMTP); WTC-exposed rescue/recovery workers not enrolled in an MMTP (non-MMTP); and the NYS population., Methods: Person-time began on 9/12/2001 or at enrollment in a WTC cohort and ended at death or on 12/31/2015. Cancer data were obtained through linkages with 13 state cancer registries. We used Poisson regression to estimate rate ratios (RRs) and 95% confidence intervals (CIs) for MMTP and non-MMTP participants. NYS rates were used as the reference. To estimate potential changes over time in WTC-associated risk, change points in RRs were estimated using profile likelihood., Results: The thyroid cancer incidence rate among MMTP participants was more than twice that of NYS population rates (RR = 2.31; 95% CI = 2.00-2.68). Non-MMTP participants had a risk similar to NYS (RR = 0.96; 95% CI = 0.72-1.28). We observed no change points in the follow-up period., Conclusion: Our findings support the hypothesis that no-cost screening (a benefit provided by WTC-MMTPs) is associated with elevated identification of thyroid cancer. Given the high survival rate for thyroid cancer, it is important to weigh the costs and benefits of treatment, as many of these cancers were asymptomatic and may have been detected incidentally., (© 2021 Wiley Periodicals LLC.)

Background: World Trade Center (WTC)-exposed responders may be eligible to receive no-cost medical monitoring and treatment for certified conditions, including cancer. The survival of responders with cancer has not previously been investigated., Methods: This study compared the estimated relative survival of WTC-exposed responders who developed cancer while enrolled in two WTC medical monitoring and treatment programs in New York City (WTC-MMTP responders) and WTC-exposed responders not enrolled (WTC-non-MMTP responders) to non-responders from New York State (NYS-non-responders), all restricted to the 11-southernmost NYS counties, where most responders resided. Parametric survival models estimated cancer-specific and all-cause mortality. Follow-up ended at death or on December 31, 2016., Results: From January 1, 2005 to December 31, 2016, there were 2,037 cancer cases and 303 deaths (248 cancer-related deaths) among WTC-MMTP responders, 564 cancer cases, and 143 deaths (106 cancer-related deaths) among WTC-non-MMTP responders, and 574,075 cancer cases and 224,040 deaths (158,645 cancer-related deaths) among the NYS-non-responder population. Comparing WTC-MMTP responders with NYS-non-responders, the cancer-specific mortality hazard ratio (HR) was 0.72 (95% confidence interval [CI] = 0.64-0.82), and all-cause mortality HR was 0.64 (95% CI = 0.58-0.72). The cancer-specific HR was 0.94 (95% CI = 0.78-1.14), and all-cause mortality HR was 0.93 (95% CI = 0.79-1.10) comparing WTC-non-MMTP responders to the NYS-non-responder population., Conclusions: WTC-MMTP responders had lower mortality compared with NYS-non-responders, after controlling for demographic factors and temporal trends. There may be survival benefits from no-out-of-pocket-cost medical care which could have important implications for healthcare policy, however, other occupational and socioeconomic factors could have contributed to some of the observed survival advantage., (© 2021 The Authors. American Journal of Industrial Medicine Published by Wiley Periodicals LLC.)

Three cohorts including the Fire Department of the City of New York (FDNY), the World Trade Center Health Registry (WTCHR), and the General Responder Cohort (GRC), each funded by the World Trade Center Health Program have reported associations between WTC-exposures and cancer. Results have generally been consistent with effect estimates for excess incidence for all cancers ranging from 6 to 14% above background rates. Pooling would increase sample size and de-duplicate cases between the cohorts. However, pooling required time consuming steps: obtaining Institutional Review Board (IRB) approvals and legal agreements from entities involved; establishing an honest broker for managing the data; de-duplicating the pooled cohort files; applying to State Cancer Registries (SCRs) for matched cancer cases; and finalizing analysis data files. Obtaining SCR data use agreements ranged from 6.5 to 114.5 weeks with six states requiring >20 weeks. Records from FDNY ( n = 16,221), WTCHR ( n = 29,372), and GRC ( n = 33,427) were combined de-duplicated resulting in 69,102 unique individuals. Overall, 7894 cancer tumors were matched to the pooled cohort, increasing the number cancers by as much as 58% compared to previous analyses. Pooling resulted in a coherent resource for future research for studies on rare cancers and mortality, with more representative of occupations and WTC- exposure.

Background: Immunosuppressed solid organ transplant recipients (SOTRs) have elevated rates of certain rare cancers caused by viruses. Evaluating risk of rare cancers among SOTRs may provide etiological clues for additional cancers linked to poor immunity and viral infections., Methods: We performed a cohort study of 262 455 SOTRs (1987-2014) from the US SOTR registry linked to 17 population-based cancer registries. First cancers in SOTRs were categorized using an established classification scheme based on site and histology. Standardized incidence ratios (SIRs) compared risk in SOTRs with the general population. We used Poisson regression to calculate incidence rate ratios according to immune-related SOTR characteristics, including time since transplant (ie, duration of immunosuppression). All statistical tests were 2-sided., Results: We examined 694 distinct cancer subtypes, with 33 manifesting statistically significantly elevated SIRs (Bonferroni P < 7.2 × 10-5). All 33 are rare (incidence <6 per 100 000 person-years) and several have known viral etiology (eg, Merkel cell carcinoma: SIR = 24.7, 95% confidence interval [CI] = 20.8 to 29.1). Additional cancers that were increased include squamous cell carcinomas of the lip (SIR range = 18.3-19.8), eye and adnexa (SIR = 13.8, 95% CI = 7.9 to 22.3), salivary gland (SIR = 9.3, 95% CI = 6.1 to 13.5), and nasal cavity and sinuses (SIR = 4.5, 95% CI = 2.8 to 6.8); sebaceous adenocarcinoma (SIR = 34.3, 95% CI = 26.3 to 44.0); malignant fibrous histiocytoma (15.4); and subtypes of bladder, kidney, lung, and colon cancer (SIR range = 3.2-13.3). Incidence of several cancers increased over time since transplant (Ptrend < .05), including squamous cell carcinomas of the lip, salivary gland, and anogenital sites., Conclusions: SOTRs experience elevated rates of several rare cancers. Because some of these cancers exhibit aggressive behavior with poor outcomes, it is important to further characterize the role of immunity and the potential involvement of oncogenic viruses to improve prevention and treatment., (© The Author(s) 2020. Published by Oxford University Press.)

Human immunodeficiency virus (HIV)-infected people and solid organ transplant recipients have elevated risk of anaplastic large cell lymphoma (ALCL). Little is known regarding ALCL risk factors in immunosuppressed populations. We used data from US cancer registries linked to HIV registries (1996-2016) and to the national transplant registry (1992-2017). ALCL risk in HIV-infected people and transplant recipients relative to the general population was calculated as a standardized incidence ratio (SIR). ALCL risk factors were evaluated using Poisson regression. We identified 121 incident ALCL cases in the HIV (n = 86) and transplant (n = 35) populations. We reviewed pathology reports for 45 cases and most (86·7%) were confirmed as ALCL. Epstein-Barr virus tested positive in 1/8 (12·5%) cases. Compared to the general population, ALCL risk was strongly elevated among HIV-infected people [SIR 5·43; 95% confidence interval (CI) 4·27-6·81] and transplant recipients (5·96; 4·03-8·49). Among HIV-infected people, ALCL incidence was strongly related to CD4 count [adjusted incidence rate ratio (aIRR) 0·15 for ≥500 vs. <200 cells/μl; P trend < 0·001]. Among transplant recipients, risk was highest within the first year (aIRR 6·82) and 10+ years post-transplant (5·99). In conclusion, ALCL risk is strongly increased in these immunosuppressed populations but may be unrelated to EBV infection based on limited reports., (© 2020 British Society for Haematology and John Wiley & Sons Ltd.)

Hydrogels derived from decellularized lungs are promising materials for tissue engineering in the development of clinical therapies and for modeling the lung extracellular matrix (ECM) in vitro . Characterizing and controlling the resulting physical, biochemical, mechanical, and biologic properties of decellularized ECM (dECM) after enzymatic solubilization and gelation are thus of key interest. As the role of enzymatic pepsin digestion in effecting these properties has been understudied, we investigated the digestion time-dependency on key parameters of the resulting ECM hydrogel. Using resolubilized, homogenized decellularized pig lung dECM as a model system, significant time-dependent changes in protein concentration, turbidity, and gelation potential were found to occur between the 4 and 24 h digestion time points, and plateauing with longer digestion times. These results correlated with qualitative scanning electron microscopy images and quantitative analysis of hydrogel interconnectivity and average fiber diameter. Interestingly, the time-dependent changes in the storage modulus tracked with the hydrogel interconnectivity results, while the Young's modulus values were more closely related to average fiber size at each time point. The structural and biochemical alterations correlated with significant changes in metabolic activity of several representative lung cells seeded onto the hydrogels with progressive decreases in cell viability and alterations in morphology observed in cells cultured on hydrogels produced with dECM digested for >12 and up to 72 h of digestion. These studies demonstrate that 12 h pepsin digest of pig lung dECM provides an optimal balance between desirable physical ECM hydrogel properties and effects on lung cell behaviors.

Solid organ transplant recipients have an increased risk of lip cancer, but the reasons are uncertain. Using data from the Transplant Cancer Match Study, we describe the epidemiology of lip cancer among 261 500 transplant recipients in the United States. Two hundred thirty-one lip cancers were identified, corresponding to elevated risks for both invasive and in situ lip cancers (standardized incidence ratios of 15.3 and 26.2, respectively). Invasive lip cancer incidence was associated with male sex (adjusted incidence rate ratio [aIRR] 2.01, 95% CI 1.44-2.82), transplanted organ (0.33, 0.20-0.57, for liver transplants and 3.07, 1.96-4.81, for lung transplants, compared with kidney transplants), and racial/ethnic groups other than non-Hispanic whites (0.09, 0.04-0.2). In addition, incidence increased with age and during the first 3 years following transplant, and was higher in recipients prescribed cyclosporine/azathioprine maintenance therapy (aIRR 1.79, 95% CI 1.09-2.93, compared with use of tacrolimus/mycophenolate mofetil) and following a diagnosis of cutaneous squamous cell carcinoma (4.21, 2.69-0.94). The elevation in lip cancer incidence is consistent with an effect of immunosuppression. Notably, the very strong associations with white race and history of prior skin cancer point to an important role for ultraviolet radiation exposure, and cyclosporine and azathioprine may contribute as photosensitizing or DNA damaging agents., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Cancer risk is increased in persons living with human immunodeficiency virus (HIV) (PLWH). Improved survival has led to an aging of PLWH. We evaluated the cancer risk in older PLWH (age ≥50 years)., Methods: We included data from the HIV/AIDS Cancer Match Study (1996-2012) and evaluated risks of Kaposi sarcoma (KS), non-Hodgkin lymphoma (NHL), Hodgkin lymphoma, and cervical, anal, lung, liver, oral cavity/pharyngeal, breast, prostate, and colon cancers in older PLWH with risk in the general population by calculating standardized incidence ratios (SIRs) and excess absolute risks (EARs). Cancer risk by time since HIV diagnosis was estimated using Poisson regression., Results: We identified 10371 cancers among 183542 older PLWH. Risk was significantly increased for KS (SIR, 103.34), NHL (3.05), Hodgkin lymphoma (7.61), and cervical (2.02), anal (14.00), lung (1.71), liver (2.91), and oral cavity/pharyngeal (1.66) cancers, and reduced for breast (0.61), prostate (0.47), and colon (0.63) cancers. SIRs declined with age for all cancers; however, EARs increased with age for anal, lung, liver, and oral cavity/pharyngeal cancers. Cancer risk was highest for most cancers within 5 years after HIV diagnosis; risk decreased with increasing time since HIV diagnosis for KS, NHL, lung cancer, and Hodgkin lymphoma., Conclusions: Cancer risk is elevated among older PLWH. Although SIRs decrease with age, EARs are higher for some cancers, reflecting a greater absolute excess in cancer incidence among older PLWH. High risk in the first 5 years after HIV diagnosis for some cancers highlights the need for early HIV diagnosis and rapid treatment initiation.

Background: Pediatric solid organ transplant recipients have a 100 to 200 times higher risk of non-Hodgkin lymphoma (NHL) than the general pediatric population. Consequently, transplant-related NHL may contribute considerably to the pediatric NHL burden in the United States., Methods: A cohort study using a linkage between the US transplant registry and 16 cancer registries was conducted. Cancer incidence rates were calculated for people less than 20 years old in the transplant and general populations. Rates were applied to transplant registry and US census data to estimate pediatric NHL counts for transplant recipients and the general population., Results: During 1990-2012, an estimated 22,270 NHLs were diagnosed in US children and adolescents; they included 628 cases diagnosed in transplant recipients. Thus, 2.82% of pediatric NHL diagnoses in the general population (95% confidence interval [CI], 2.45%-3.19%) occurred in transplant recipients. Among transplant recipients, the most common subtypes were diffuse large B-cell lymphoma (DLBCL; 64.5% of cases) and Burkitt lymphoma (BL; 8.6%). For DLBCL and BL, transplant recipients contributed 7.62% (95% CI, 6.35%-8.88%) and 0.87% (95% CI, 0.51%-1.23%) of diagnoses, respectively. The proportion of NHLs that occurred in transplant recipients was highest among children less than 5 years old (4.46%; 95% CI, 3.24%-5.69%) and in more recent calendar years (3.73% in 2010-2012; 95% CI, 2.07%-5.39%). DLBCL patterns were similar, with transplant recipients contributing 19.78% of cases among children less than 5 years old (95% CI, 12.89%-26.66%) and 11.4% of cases in 2010-2012 (95% CI, 5.54%-17.28%)., Conclusions: Among children and adolescents, solid organ transplant recipients contribute a substantial fraction of NHL diagnoses, particularly DLBCL diagnoses. This fraction has increased over time. Prevention efforts targeted toward this group could reduce the overall pediatric NHL burden. Cancer 2017;123:4663-4671. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

A variety of refractive surgery techniques, which reshape the corneal stroma using laser energy, have been marketed as simple and safe alternatives to glasses or contact lenses. Laser-assisted in-situ keratomileusis (LASIK) is the most common of these procedures. Although there are few high-quality prospective studies of long-term outcomes, complications, or stability for refractive surgery procedures, there is at least general agreement that more than 90% of appropriately selected patients achieve excellent uncorrected distance vision. In addition to well-recognized contraindications (e.g., unstable refraction, pregnancy and lactation, chronic eye disease, systemic illness, corneal abnormalities), there are other conditions that warrant caution (e.g., excessively dry eyes, contact lens intolerance, chronic pain syndromes). Postoperative dry eye, which may in part represent a corneal neuropathy, usually resolves after six to 12 months but persists in up to 20% of patients. Up to 20% of patients may have new visual disturbances, particularly with night driving. Vision-threatening complications are rare. Intraocular lenses, implanted following cataract extraction, may be an alternative to LASIK in older patients. Although the overall dependence on corrective lenses is markedly reduced, many patients still require glasses or contact lenses after LASIK, particularly in low-light conditions and as they age. Most patients report satisfaction with the results. Family physicians can help patients make informed decisions by exploring their values, preferences, expectations, and tolerance of uncertainty and risk.

Background: The effects of pediatric solid organ transplantation on cancer risk may differ from those observed in adult recipients. We described cancers in pediatric recipients and compared incidence to the general population., Methods: The US transplant registry was linked to 16 cancer registries to identify cancer diagnoses among recipients <18 years old at transplant. Standardized incidence ratios (SIRs) were estimated by dividing observed cancer counts among recipients by expected counts based on the general population rates. Cox regression was used to estimate the associations between recipient characteristics and non-Hodgkin's lymphoma (NHL) risk., Results: Among 17 958 pediatric recipients, 392 cancers were diagnosed, of which 279 (71%) were NHL. Compared with the general population, incidence was significantly increased for NHL (SIR = 212, 95% confidence interval [CI] = 188-238), Hodgkin's lymphoma (SIR = 19, 95% CI = 13-26), leukemia (SIR = 4, 95% CI = 2-7), myeloma (SIR = 229, 95% CI = 47-671), and cancers of the liver, soft tissue, ovary, vulva, testis, bladder, kidney, and thyroid. NHL risk was highest during the first year after transplantation among recipients <5 years old at transplant (SIR = 313), among recipients seronegative for Epstein-Barr virus (EBV) at transplant (SIR = 446), and among intestine transplant recipients (SIR = 1280). In multivariable analyses, seronegative EBV status, the first year after transplantation, intestine transplantation, and induction immunosuppression were independently associated with higher NHL incidence., Conclusions: Pediatric recipients have a markedly increased risk for many cancers. NHL constitutes the majority of diagnosed cancers, with the highest risk occurring in the first year after transplantation. NHL risk was high in recipients susceptible to primary EBV infection after transplant and in intestine transplant recipients, perhaps due to EBV transmission in the donor organ., Competing Interests: POTENTIAL CONFLICT OF INTEREST: Dr Clarke is employed by GRAIL, Inc and has received grant funding from Genentech; the other authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2017 by the American Academy of Pediatrics.)

Background: Population-based cancer survival analyses have traditionally been based on the first primary cancer. Recent studies have brought this practice into question, arguing that varying registry reference dates affect the ability to identify earlier cancers, resulting in selection bias. We used a theoretical approach to evaluate the extent to which the length of registry operations affects the classification of first versus subsequent cancers and consequently survival estimates., Methods: Sequence number central was used to classify tumors from the New York State Cancer Registry, diagnosed 2001-2010, as either first primaries (value=0 or 1) or subsequent primaries (≥2). A set of three sequence numbers, each based on an assumed reference year (1976, 1986 or 1996), was assigned to each tumor. Percent of subsequent cancers was evaluated by reference year, cancer site and age. 5-year relative survival estimates were compared under four different selection scenarios., Results: The percent of cancer cases classified as subsequent primaries was 15.3%, 14.3% and 11.2% for reference years 1976, 1986 and 1996, respectively; and varied by cancer site and age. When only the first primary was included, shorter registry operation time was associated with slightly lower 5-year survival estimates. When all primary cancers were included, survival estimates decreased, with the largest decreases seen for the earliest reference year., Conclusions: Registry operation length affected the identification of subsequent cancers, but the overall effect of this misclassification on survival estimates was small. Survival estimates based on all primary cancers were slightly lower, but might be more comparable across registries., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

US transplant centers are required to report cancers in transplant recipients to the transplant network. The accuracy and completeness of these data, collected in the Scientific Registry of Transplant Recipients (SRTR), are unknown. We compared diagnoses in the SRTR and 15 linked cancer registries for colorectal, liver, lung, breast, prostate and kidney cancers; melanoma; and non-Hodgkin lymphoma (NHL). Among 187 384 transplants, 9323 cancers were documented in the SRTR or cancer registries. Only 36.8% of cancers were in both, with 47.5% and 15.7% of cases additionally documented solely in cancer registries or the SRTR, respectively. Agreement between the SRTR and cancer registries varied (kappa = 0.28 for liver cancer and kappa = 0.52-0.66 for lung, prostate, kidney, colorectum, and breast cancers). Upon evaluation, some NHLs documented only in cancer registries were identified in the SRTR as another type of posttransplant lymphoproliferative disorder. Some SRTR-only cases were explained by miscoding (colorectal cancer instead of anal cancer, metastases as lung or liver cancers) or missed matches with cancer registries, partly due to recipients' outmigration from catchment areas. Estimated sensitivity for identifying cancer was 52.5% for the SRTR and 84.3% for cancer registries. In conclusion, SRTR cancer data are substantially incomplete, limiting their usefulness for surveillance and research., (© Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Cancer incidence in exposed rescue/recovery workers (RRWs) and civilians (non-RRWs) was previously reported through 2008., Methods: We studied occurrence of first primary cancer among World Trade Center Health Registry enrollees through 2011 using adjusted standardized incidence ratios (SIRs), and the WTC-exposure-cancer association, using Cox proportional hazards models., Results: All-cancer SIR was 1.11 (95% confidence interval (CI) 1.03-1.20) in RRWs, and 1.08 (95% CI 1.02-1.15) in non-RRWs. Prostate cancer and skin melanoma were significantly elevated in both populations. Thyroid cancer was significantly elevated only in RRWs while breast cancer and non-Hodgkin's lymphoma were significantly elevated only in non-RRWs. There was a significant exposure dose-response for bladder cancer among RRWs, and for skin melanoma among non-RRWs., Conclusions: We observed excesses of total and specific cancers in both populations, although the strength of the evidence for causal relationships to WTC exposures is somewhat limited. Continued monitoring of this population is indicated. Am. J. Ind. Med. 59:709-721, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Solid organ transplant recipients, who are medically immunosuppressed to prevent graft rejection, have increased melanoma risk, but risk factors and outcomes are incompletely documented. We evaluated melanoma incidence among 139,991 non-Hispanic white transplants using linked US transplant-cancer registry data (1987-2010). We used standardized incidence ratios (SIRs) to compare incidence with the general population and incidence rate ratios (IRRs) from multivariable Poisson models to assess risk factors. Separately, we compared post-melanoma survival among transplant recipients (n=182) and non-recipients (n=131,358) using multivariable Cox models. Among transplant recipients, risk of invasive melanoma (n=519) was elevated (SIR=2.20, 95% CI 2.01-2.39), especially for regional stage tumors (SIR=4.11, 95% CI 3.27-5.09). Risk of localized tumors was stable over time after transplantation but higher with azathioprine maintenance therapy (IRR=1.35, 95% CI 1.03-1.77). Risk of regional/distant stage tumors peaked within 4 years following transplantation and increased with polyclonal antibody induction therapy (IRR=1.65, 95% CI 1.02-2.67). Melanoma-specific mortality was higher among transplant recipients than non-recipients (hazard ratio 2.98, 95% CI 2.26-3.93). Melanoma exhibits increased incidence and aggressive behavior under transplant-related immunosuppression. Some localized melanomas may result from azathioprine, which acts synergistically with UV radiation, whereas T-cell-depleting induction therapies may promote late-stage tumors. Our findings support sun safety practices and skin screening for transplant recipients.

Efforts to develop more effective therapies for acute leukemia may benefit from high-throughput screening systems that reflect the complex physiology of the disease, including leukemia stem cells (LSCs) and supportive interactions with the bone marrow microenvironment. The therapeutic targeting of LSCs is challenging because LSCs are highly similar to normal hematopoietic stem and progenitor cells (HSPCs) and are protected by stromal cells in vivo. We screened 14,718 compounds in a leukemia-stroma co-culture system for inhibition of cobblestone formation, a cellular behavior associated with stem-cell function. Among those compounds that inhibited malignant cells but spared HSPCs was the cholesterol-lowering drug lovastatin. Lovastatin showed anti-LSC activity in vitro and in an in vivo bone marrow transplantation model. Mechanistic studies demonstrated that the effect was on target, via inhibition of HMG-CoA reductase. These results illustrate the power of merging physiologically relevant models with high-throughput screening.

Purpose: Stage at diagnosis is an important prognostic factor for the majority of cancers; it may be an indicator for quality of access to health care and is usually correlated with socioeconomic status (SES) and ethnicity/race. We aimed to investigate the association between stage of cancer at diagnosis with neighborhood of residence (as proxy for SES) and ethnicity/race, while controlling for each other, in selected areas of New York City (NYC)., Methods: The cancer summary data (1999-2008) were provided by the New York State Cancer Registry. Multinomial logistic regression models were applied to calculate risk estimates for being diagnosed with late- or unknown-stage (versus early-stage) cancers in two low-SES and two high-SES neighborhoods of NYC and among several ethnic/racial groups for all cancers combined and cancers of the female breast, lung, colorectum, and prostate, with additional adjustments for sex (for all cancers combined), age, and year of diagnosis., Results: A total of 34,981 cancer cases were included in this study. There were significant and independent ethnic/racial and neighborhood disparities in stage of cancer at diagnosis of most of the cancers studied. The effect of ethnicity/race on the disparity appeared stronger than the effect of neighborhood. There was an overall decreasing trend in the proportion of late-stage cancers, particularly for colorectal cancer, and to a greater extent in the proportion of cancers without staging information., Conclusions: In this population, ethnicity/race seems to be a stronger predictor for late stage at diagnosis than SES, stressing the need for ethnicity/race-oriented programs for cancer screening and improved access to care.

Background: Multiple dates of diagnosis are often received from different reporting sources at a central cancer registry. Resolving these inconsistencies can be a labor-intensive task. To our knowledge, no algorithms for the consolidation of diagnosis dates have been published. We present such an algorithm here., Methods: The algorithm uses a "take the best" heuristic approach, incorporating the reported dates of diagnosis, class of case, service type (a New York-specific item similar to type of reporting source), and the date of first contact. The algorithm was evaluated by comparing results to those obtained with manual review by experienced certified tumor registrars (CTRs)., Results: From a sample of 209,907 tumors with multiple diagnosis dates reported to the New York State Cancer Registry (NYSCR), the algorithm determined a single date for 94.7 percent of these, with the balance designated for manual review. Of a sample of 636 tumors that were manually reviewed to evaluate the algorithm, the algorithm obtained the same year as the CTRs for 621 tumors (97.6 percent), the same month and year for 572 tumors (89.9 percent) and the same month, year, and day for 518 tumors (81.4 percent). There was much lower agreement between the manually derived dates and the originally consolidated dates., Conclusion: The algorithm presented here is accurate, efficient, and reliable, and hopefully will help the cancer registry community move toward standard practices for record consolidation.

Context: The terrorist attacks of September 11, 2001, resulted in the release of known and suspected carcinogens into the environment. There is public concern that exposures may have resulted in increased cancers., Objective: To evaluate cancer incidence among persons enrolled in the World Trade Center Health Registry., Design, Setting, and Participants: Observational study of 55,778 New York State residents enrolled in the World Trade Center Health Registry in 2003-2004, including rescue/recovery workers (n = 21,850) and those not involved in rescue/recovery (n = 33,928), who were followed up from enrollment through December 31, 2008. Within-cohort comparisons using Cox proportional hazards models assessed the relationship between intensity of World Trade Center exposure and selected cancers., Main Outcome Measures: Cases were identified through linkage with 11 state cancer registries. Standardized incidence ratios (SIRs) adjusted for age, race/ethnicity, and sex were computed with 2003-2008 New York State rates as the reference, focusing on cancers diagnosed in 2007-2008 as being most likely to be related to exposure during September 11 and its aftermath. The total and site-specific incidence rate differences (RDs) per 100,000 person-years between the study population and the New York State population in 2007-2008 also were calculated., Results: There were 1187 incident cancers diagnosed, with an accumulated 253,269 person-years (439 cancers among rescue/recovery workers and 748 among those not involved in rescue/recovery). The SIR for all cancer sites combined in 2007-2008 was not significantly elevated (SIR, 1.14 [95% CI, 0.99 to 1.30]; RD, 67 [95% CI, -6 to 126] per 100,000 person-years among rescue/recovery workers vs SIR, 0.92 [95% CI, 0.83 to 1.03]; RD, -45 [95% CI, -106 to 15] per 100,000 person-years among those not involved in rescue/recovery). Among rescue/recovery workers, the SIRs had significantly increased by 2007-2008 for 3 cancer sites and were 1.43 (95% CI, 1.11 to 1.82) for prostate cancer (n = 67; RD, 61 [95% CI, 20 to 91] per 100,000 person-years), 2.02 (95% CI, 1.07 to 3.45) for thyroid cancer (n = 13; RD, 16 [95% CI, 2 to 23] per 100,000 person-years), and 2.85 (95% CI, 1.15 to 5.88) for multiple myeloma (n = 7; RD, 11 [95% CI, 2 to 14] per 100,000 person-years). No increased incidence was observed in 2007-2008 among those not involved in rescue/recovery. Using within-cohort comparisons, the intensity of World Trade Center exposure was not significantly associated with cancer of the lung, prostate, thyroid, non-Hodgkin lymphoma, or hematological cancer in either group., Conclusions: Among persons enrolled in the World Trade Center Health Registry, there was an excess risk for prostate cancer, thyroid cancer, and myeloma in 2007-2008 compared with that for New York State residents; however, these findings were based on a small number of events and multiple comparisons. No significant associations were observed with intensity of World Trade Center exposures. Longer follow-up for typically long-latency cancers and attention to specific cancer sites are needed.

Background: Advances in treatment have improved ovarian cancer survival for most women, although less for the elderly. We report on this disparity and add further evidence about the relationship among age, comorbidity, and survival after ovarian cancer., Methods: To examine age and comorbidity, Centers for Disease Control and Prevention (CDC)-funded cancer registries examined 2367 women residing in New York and Northern California diagnosed with epithelial ovarian cancer (1998-2000). Subjects were identified through tumor registries, treatment data were supplemented with physician survey, and comorbidity was identified through hospital discharge database linkages. Proportional hazards modeling was used to estimate the risk of death by age and comorbidity, adjusting for clinical and sociodemographic factors., Results: Crude survival at 1 year and 3 years was 71.9% and 50.1%, respectively. Within stage, age-specific survival rates were lower in the oldest groups, particularly for those with advanced disease. For age 75+, 3-year survival was 13% vs. 50% in those <35 (stage IV). For all stages, women without comorbidity had higher survival rates than those with comorbidity. Older age and comorbidity were both associated with advanced stage and less aggressive treatment. The adjusted risk of death was 40%, and it was 80% higher for the 65-74 and 75+ groups, respectively, compared to women 35-64 (p<0.00). Comorbidity increased the risk of death by 40% (p<0.00)., Conclusions: This study confirmed the independent adverse effects of age and comorbidity on survival following ovarian cancer. As the population ages, the co-occurrence of ovarian cancer and comorbidity will increase. Further work identifying critical conditions that impact survival could potentially inform complex treatment decisions.

This study examines whether midlife change in episodic memory predicts hippocampal volume in old age. From the Seattle Longitudinal Study we retrospectively identified 84 healthy, cognitively normal individuals, age 52 to 87, whose episodic memory had reliably declined (n = 33), improved (n = 28) or remained stable (n = 23) over a 14-year period in midlife (age 43-63). Midlife memory improvement was associated with 13% larger hippocampal volume (p < 0.01) in old age (age 66-87), compared with old age individuals whose midlife episodic memory had either declined or remained stable during midlife. Midlife memory change did not predict total hippocampal volume for those currently in late middle age (age 52-65). The pattern of findings was not modified by gender, apolipoprotein ε4 status, education or current memory performance. Change in midlife memory scores over 14 years, but not any single assessment, predicted hippocampal volumes in old age, emphasizing the importance of longitudinal data in examining brain-cognition relationships. These findings suggest that improvement in memory in midlife is associated with sparing of hippocampal volume in later life., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Thyroid cancer incidence in New York State has increased rapidly in recent years, particularly in New York City and its surrounding metropolitan area. In 2007 among white non-Hispanics, incidence rates were about 40% higher in the New York City metropolitan area than in the rest of the state. Here we explore the extent to which living in neighborhoods with a high percentage of highly observant Jews may be associated with this pattern., Methods: We identify neighborhoods with concentrations of highly observant Jewish persons based on the use of Yiddish among children and the location of Orthodox synagogues. Thyroid cancer risk is modeled as a function of living in such a neighborhood, adjusting for age, sex, and other factors. The model was repeated for small (<2 cm) and large (≥2 cm) tumors to assess the role of diagnostic improvements in driving the spatial-temporal patterns., Results: A moderate association with thyroid cancer was found among those living in Jewish neighborhoods and downstate New York. A lesser association was found among those who live in neighborhoods of high levels of people born in Russia, Belarus, or Ukraine. Similar elevated rate ratios were seen for small and large tumors in Jewish neighborhoods, providing evidence against differences in diagnostic practices in this group. Smaller tumors were more pronounced among women and persons diagnosed more recently., Conclusions: The associations found do not seem to be diagnostically driven, but rather due to environmental, genetic, or cultural factors in the highly observant population of New York State.

Objectives: The objectives of this study were to determine the adequacy of surgical staging performed on surgically treated epithelial ovarian cancer (EOC) patients with apparent early stage disease and to determine if receipt of surgical staging had an influence on survival., Methods: Detailed surgical staging information was collected from medical records for 721 patients diagnosed between 1998 and 2000 with EOC. Patients resided in California or New York and were identified through population-based cancer registries., Results: Nearly 90% of patients had removal of the omentum and evaluation of bowel serosa and mesentery but only 72% had assessment of retroperitoneal lymph nodes and the majority of patients did not receive biopsies of other peritoneal locations. Only lymph node assessment (as well as node assessment combined with washings and omentectomy) had a statistically significant association with improved survival. The 5-year survival for women with node sampling was 84.2% versus 69.6% for those without this surgical procedure, and patients who did not have lymph node assessment had nearly twice the risk of death as those who did. When patients were stratified by receipt of chemotherapy, lack of node sampling had an effect only on patients who also had no chemotherapy (adjusted HR=2.2, CI=1.0-4.5)., Conclusions: The results of this population-based study confirm the prognostic importance of surgical staging for women with EOC, and the important role of gynecologic oncologists in treating these patients. Adjuvant chemotherapy does not appear to further improve survival for those women who receive adequate surgical staging., (Copyright © 2011 Elsevier Inc. All rights reserved.)