Cocaine use and head and neck cancer risk: A pooled analysis in the International Head and Neck Cancer Epidemiology Consortium.

BACKGROUND: Cocaine is an illegal recreational drug used worldwide, yet little is known about whether cocaine inhalation (smoking/snorting) increases the risk of head and neck cancer (HNC). METHODS: The analyses were conducted by pooling data from three case-control studies with 1639 cases and 2506 controls from the International Head and Neck Cancer Epidemiology Consortium. Epidemiologic data, including cocaine use histories, were obtained in face-to-face interviews. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using hierarchical logistic regression models. RESULTS: Controlling for cumulative tobacco and alcohol use, we observed a weak positive association between cocaine use and HNC (ORever vs. never = 1.35, 95% CI: 0.96, 1.90). In stratified analysis, while we did not detect associations among never tobacco or alcohol users due to the limited sample size, the association with cocaine use was observed among tobacco users and alcohol drinkers. ORs for ever and high cumulative use (>18 times) versus never use were 1.40 (95% CI: 0.98, 2.00) and 1.66 (95% CI: 1.03, 2.69) among tobacco users, and 1.34 (95% CI: 0.93, 1.92) and 1.59 (95% CI: 1.00, 2.51) among alcohol drinkers, respectively. CONCLUSION: In this pooled analysis, we observed a weak positive association between cocaine inhalation and HNC risk. Our findings provide preliminary evidence of the potential carcinogenic effect of cocaine on HNC. Because of study limitations, including limited number of cocaine users, confounding, and heterogeneity across studies, future investigations will require larger studies with more detailed information on cocaine use history.

Association of Major Adverse Financial Events and Later-Stage Cancer Diagnosis in the United States.

PURPOSE: This study assessed the prevalence of specific major adverse financial events (AFEs)-bankruptcies, liens, and evictions-before a cancer diagnosis and their association with later-stage cancer at diagnosis. METHODS: Patients age 20-69 years diagnosed with cancer during 2014-2015 were identified from the Seattle, Louisiana, and Georgia SEER population-based cancer registries. Registry data were linked with LexisNexis consumer data to identify patients with a history of court-documented AFEs before cancer diagnosis. The association of AFEs and later-stage cancer diagnoses (stages III/IV) was assessed using separate sex-specific multivariable logistic regression. RESULTS: Among 101,649 patients with cancer linked to LexisNexis data, 36,791 (36.2%) had a major AFE reported before diagnosis. The mean and median timing of the AFE closest to diagnosis were 93 and 77 months, respectively. AFEs were most common among non-Hispanic Black, unmarried, and low-income patients. Individuals with previous AFEs were more likely to be diagnosed with later-stage cancer than individuals with no AFE (males-odds ratio [OR], 1.09 [95% CI, 1.03 to 1.14]; P < .001; females-OR, 1.18 [95% CI, 1.13 to 1.24]; P < .0001) after adjusting for age, race, marital status, income, registry, and cancer type. Associations between AFEs prediagnosis and later-stage disease did not vary by AFE timing. CONCLUSION: One third of newly diagnosed patients with cancer had a major AFE before their diagnosis. Patients with AFEs were more likely to have later-stage diagnosis, even accounting for traditional measures of socioeconomic status that influence the stage at diagnosis. The prevalence of prediagnosis AFEs underscores financial vulnerability of patients with cancer before their diagnosis, before any subsequent financial burden associated with cancer treatment.

Epidemiology of Cancer.

BACKGROUND: Cancers are a large and heterogeneous group of malignant tumors that collectively accounted for approximately 600 000 US deaths in 2020; only heart disease claimed more lives. A large amount of knowledge has accumulated regarding the epidemiology of most cancer types, including their causes. CONTENT: The cancer types most frequently diagnosed among adults in most high-income countries are lung, colorectal, female breast, cutaneous melanoma, and prostate. In general cancer incidence and mortality is very low in children and adolescents, rising exponentially with increasing age during adulthood. There is marked international variation in the incidence of most cancers. The most important causes of cancer are tobacco use (primarily cigarette use), excess alcohol consumption, obesity, lack of physical activity, diets low in fruits and vegetables, infectious agents, and sun exposure. Early detection can reduce the chances that a person will die of cancers of the female breast, uterine cervix, colon and rectum, lung, and prostate. SUMMARY: Although the most common cancers in the United States continue to have a substantial impact on public health, they are caused in whole or part by factors over which people and governments have control through choices they make. Among these are tobacco and alcohol use, obesity, diets low in fruits and vegetables and lack of physical activity, and sun exposure. Thus, a very large proportion of cancer's impact could be ameliorated if more people avoided these exposures.

Impact on the Volume of Pathology Reports Before and During the COVID-19 Pandemic in SEER Cancer Registries.

INTRODUCTION: Health care procedures including cancer screening and diagnosis were interrupted due to the COVID-19 pandemic. The extent of this impact on cancer care in the United States is not fully understood. We investigated pathology report volume as a reflection of trends in oncology services pre-pandemic and during the pandemic. METHODS: Electronic pathology reports were obtained from 11 U.S. central cancer registries from NCI's SEER Program. The reports were sorted by cancer site and document type using a validated algorithm. Joinpoint regression was used to model temporal trends from January 2018 to February 2020, project expected counts from March 2020 to February 2021 and calculate observed-to-expected ratios. Results were stratified by sex, age, cancer site, and report type. RESULTS: During the first 3 months of the pandemic, pathology report volume decreased by 25.5% and 17.4% for biopsy and surgery reports, respectively. The 12-month O/E ratio (March 2020-February 2021) was lowest for women (O/E 0.90) and patients 65 years and older (O/E 0.91) and lower for cancers with screening (melanoma skin, O/E 0.86; breast, O/E 0.88; lung O/E 0.89, prostate, O/E 0.90; colorectal, O/E 0.91) when compared with all other cancers combined. CONCLUSIONS: These findings indicate a decrease in cancer diagnosis, likely due to the COVID-19 pandemic. This decrease in the number of pathology reports may result in a stage shift causing a subsequent longer-term impact on survival patterns. IMPACT: Investigation on the longer-term impact of the pandemic on pathology services is vital to understand if cancer care delivery levels continue to be affected.

Use of the Decipher genomic classifier among men with prostate cancer in the United States.

BACKGROUND: Management of localized or recurrent prostate cancer since the 1990s has been based on risk stratification using clinicopathological variables, including Gleason score, T stage (based on digital rectal exam), and prostate-specific antigen (PSA). In this study a novel prognostic test, the Decipher Prostate Genomic Classifier (GC), was used to stratify risk of prostate cancer progression in a US national database of men with prostate cancer. METHODS: Records of prostate cancer cases from participating SEER (Surveillance, Epidemiology, and End Results) program registries, diagnosed during the period from 2010 through 2018, were linked to records of testing with the GC prognostic test. Multivariable analysis was used to quantify the association between GC scores or risk groups and use of definitive local therapy after diagnosis in the GC biopsy-tested cohort and postoperative radiotherapy in the GC-tested cohort as well as adverse pathological findings after prostatectomy. RESULTS: A total of 572 545 patients were included in the analysis, of whom 8927 patients underwent GC testing. GC biopsy-tested patients were more likely to undergo active active surveillance or watchful waiting than untested patients (odds ratio [OR] =2.21, 95% confidence interval [CI] = 2.04 to 2.38, P < .001). The highest use of active surveillance or watchful waiting was for patients with a low-risk GC classification (41%) compared with those with an intermediate- (27%) or high-risk (11%) GC classification (P < .001). Among National Comprehensive Cancer Network patients with low and favorable-intermediate risk, higher GC risk class was associated with greater use of local therapy (OR = 4.79, 95% CI = 3.51 to 6.55, P < .001). Within this subset of patients who were subsequently treated with prostatectomy, high GC risk was associated with harboring adverse pathological findings (OR = 2.94, 95% CI = 1.38 to 6.27, P = .005). Use of radiation after prostatectomy was statistically significantly associated with higher GC risk groups (OR = 2.69, 95% CI = 1.89 to 3.84). CONCLUSIONS: There is a strong association between use of the biopsy GC test and likelihood of conservative management. Higher genomic classifier scores are associated with higher rates of adverse pathology at time of surgery and greater use of postoperative radiotherapy.In this study the Decipher Prostate Genomic Classifier (GC) was used to analyze a US national database of men with prostate cancer. Use of the GC was associated with conservative management (ie, active surveillance). Among men who had high-risk GC scores and then had surgery, there was a 3-fold higher chance of having worrisome findings in surgical specimens.

A masked, placebo-controlled, randomized clinical trial evaluating safety and the effect on cardiac function of low-dose rapamycin in 17 healthy client-owned dogs.

Introduction: Geroscience studies of low-dose rapamycin in laboratory species have identified numerous benefits, including reversing age-related cardiac dysfunction. Cardiovascular benefits have been observed in dogs with 10 weeks of treatment, raising questions about possible benefits and adverse effects of long-term use of low-dose rapamycin. The objectives of this study were to assess the impact of 6 months of low-dose rapamycin on echocardiographic indices of cardiac function in healthy dogs and to document the occurrence of adverse events. Methods: Seventeen client-owned dogs aged 6-10 years, weighing 18-36 kg, and without significant systemic disease were included in a prospective, randomized, placebo-controlled, masked clinical trial. Low-dose rapamycin (0.025 mg/kg) or placebo was administered three times per week for 6 months. Baseline, 6-month, and 12-month evaluation included physical examination, cardiology examination, and clinicopathology. Three-month evaluation included physical examination and clinicopathology. Owners completed online questionnaires every 2 weeks. Results: There were no statistically significant differences in echocardiographic parameters between rapamycin and placebo groups at 6 or 12 months. No clinically significant adverse events occurred. In 26.8% of the bi-weekly surveys owners whose dogs received rapamycin reported perceived positive changes in behavior or health, compared to 8.1% in the placebo group (p = 0.04). Discussion: While no clinically significant change in cardiac function was observed in dogs treated with low-dose rapamycin, the drug was well-tolerated with no significant adverse events.

31-Gene Expression Profile Testing in Cutaneous Melanoma and Survival Outcomes in a Population-Based Analysis: A SEER Collaboration.

PURPOSE: The DecisionDx-Melanoma 31-gene expression profile (31-GEP) test is validated to classify cutaneous malignant melanoma (CM) patient risk of recurrence, metastasis, or death as low (class 1A), intermediate (class 1B/2A), or high (class 2B). This study aimed to examine the effect of 31-GEP testing on survival outcomes and confirm the prognostic ability of the 31-GEP at the population level. METHODS: Patients with stage I-III CM with a clinical 31-GEP result between 2016 and 2018 were linked to data from 17 SEER registries (n = 4,687) following registries' operation procedures for linkages. Melanoma-specific survival (MSS) and overall survival (OS) differences by 31-GEP risk category were examined using Kaplan-Meier analysis and the log-rank test. Crude and adjusted hazard ratios (HRs) were calculated using Cox regression model to evaluate variables associated with survival. 31-GEP tested patients were propensity score-matched to a cohort of non-31-GEP tested patients from the SEER database. Robustness of the effect of 31-GEP testing was assessed using resampling. RESULTS: Patients with a 31-GEP class 1A result had higher 3-year MSS and OS than patients with a class 1B/2A or class 2B result (MSS: 99.7% v 97.1% v 89.6%, P < .001; OS: 96.6% v 90.2% v 79.4%, P < .001). A class 2B result was an independent predictor of MSS (HR, 7.00; 95% CI, 2.70 to 18.00) and OS (HR, 2.39; 95% CI, 1.54 to 3.70). 31-GEP testing was associated with a 29% lower MSS mortality (HR, 0.71; 95% CI, 0.53 to 0.94) and 17% lower overall mortality (HR, 0.83; 95% CI, 0.70 to 0.99) relative to untested patients. CONCLUSION: In a population-based, clinically tested melanoma cohort, the 31-GEP stratified patients by their risk of dying from melanoma.

Risk factors for severe acute kidney injury after pediatric hematopoietic cell transplantation.

BACKGROUND: Acute kidney injury (AKI) is common after hematopoietic cell transplantation (HCT) and is associated with poorer outcomes. Risk factors for AKI after pediatric HCT are not fully understood. The study objective was to assess unique risk factors for AKI in the HCT population and evaluate post-HCT AKI patterns. METHODS: We conducted a retrospective cohort study of patients < 21 years of age who underwent HCT at Seattle Children's Hospital/Fred Hutchinson Cancer Center from September 2008 to July 2017 (n = 484). We defined AKI using KDIGO criteria. We collected demographics, baseline HCT characteristics, post-HCT complications, and mortality. Multinomial logistic regression was used to estimate association between AKI and potential risk factors. We used adjusted Cox proportional hazard ratios to evaluate differences in mortality. RESULTS: One hundred and eighty-six patients (38%) developed AKI. Seventy-nine (42%) had severe AKI and 27 (15%) required kidney replacement therapy. Fluid overload was common in all groups and 67% of those with severe AKI had > 10% fluid overload. Nephrology was consulted in less than 50% of those with severe AKI. In multivariable analysis, risk of severe AKI was lower in those taking a calcineurin inhibitor (CNI). Risk of death was higher in severe AKI compared to no AKI (RR 4.6, 95% CI 2.6-8.1). CONCLUSIONS: AKI and fluid overload are common in pediatric patients after HCT. Severe AKI occurred less often with CNI use and was associated with higher mortality. Future interventions to reduce AKI and its associated complications such as fluid overload are approaches to reducing morbidity and mortality after HCT. A higher resolution version of the Graphical abstract is available as Supplementary information.

Using ensembles and distillation to optimize the deployment of deep learning models for the classification of electronic cancer pathology reports.

Objective: We aim to reduce overfitting and model overconfidence by distilling the knowledge of an ensemble of deep learning models into a single model for the classification of cancer pathology reports. Materials and Methods: We consider the text classification problem that involves 5 individual tasks. The baseline model consists of a multitask convolutional neural network (MtCNN), and the implemented ensemble (teacher) consists of 1000 MtCNNs. We performed knowledge transfer by training a single model (student) with soft labels derived through the aggregation of ensemble predictions. We evaluate performance based on accuracy and abstention rates by using softmax thresholding. Results: The student model outperforms the baseline MtCNN in terms of abstention rates and accuracy, thereby allowing the model to be used with a larger volume of documents when deployed. The highest boost was observed for subsite and histology, for which the student model classified an additional 1.81% reports for subsite and 3.33% reports for histology. Discussion: Ensemble predictions provide a useful strategy for quantifying the uncertainty inherent in labeled data and thereby enable the construction of soft labels with estimated probabilities for multiple classes for a given document. Training models with the derived soft labels reduce model confidence in difficult-to-classify documents, thereby leading to a reduction in the number of highly confident wrong predictions. Conclusions: Ensemble model distillation is a simple tool to reduce model overconfidence in problems with extreme class imbalance and noisy datasets. These methods can facilitate the deployment of deep learning models in high-risk domains with low computational resources where minimizing inference time is required.

Evaluation of cognitive function in the Dog Aging Project: associations with baseline canine characteristics.

Canine cognitive dysfunction (CCD) is a neurodegenerative disease in aging dogs. It has been described previously in relatively small cohorts of dogs using multiple different rating scales. This study aimed to use a minimally modified CCD rating scale developed by previous researchers to describe the prevalence of CCD more thoroughly in a large, nationwide cohort of companion dogs participating in the Dog Aging Project (DAP) (n = 15,019). Associations between various canine characteristics, predicted lifespan quartiles, and CCD were examined using univariable and multivariable logistic regression models and receiver operating curve (ROC) analysis. When controlling for all other characteristics, the odds of CCD increased 52% with each additional year of age. Among dogs of the same age, health status, breed type, and sterilization status, odds of CCD were 6.47 times higher in dogs who were not active compared to those who were very active. When controlling for age, breed type, activity level, and other comorbidities, dogs with a history of neurological, eye, or ear disorders had higher odds of CCD. Lifespan quartile analysis showed excellent discriminating ability between CCD positive and negative dogs. Weight-based lifespan quartile estimation could therefore serve as a tool to inform CCD screening by veterinarians.

Association Study between Polymorphisms in DNA Methylation-Related Genes and Testicular Germ Cell Tumor Risk.

BACKGROUND: Testicular germ cell tumors (TGCT), histologically classified as seminomas and nonseminomas, are believed to arise from primordial gonocytes, with the maturation process blocked when they are subjected to DNA methylation reprogramming. SNPs in DNA methylation machinery and folate-dependent one-carbon metabolism genes have been postulated to influence the proper establishment of DNA methylation. METHODS: In this pathway-focused investigation, we evaluated the association between 273 selected tag SNPs from 28 DNA methylation-related genes and TGCT risk. We carried out association analysis at individual SNP and gene-based level using summary statistics from the Genome Wide Association Study meta-analysis recently conducted by the international Testicular Cancer Consortium on 10,156 TGCT cases and 179,683 controls. RESULTS: In individual SNP analyses, seven SNPs, four mapping within MTHFR, were associated with TGCT risk after correction for multiple testing (q ≤ 0.05). Queries of public databases showed that three of these SNPs were associated with MTHFR changes in enzymatic activity (rs1801133) or expression level in testis tissue (rs12121543, rs1476413). Gene-based analyses revealed MTHFR (q = 8.4 × 10-4), methyl-CpG-binding protein 2 (MECP2; q = 2 × 10-3), and ZBTB4 (q = 0.03) as the top TGCT-associated genes. Stratifying by tumor histology, four MTHFR SNPs were associated with seminoma. In gene-based analysis MTHFR was associated with risk of seminoma (q = 2.8 × 10-4), but not with nonseminomatous tumors (q = 0.22). CONCLUSIONS: Genetic variants within MTHFR, potentially having an impact on the DNA methylation pattern, are associated with TGCT risk. IMPACT: This finding suggests that TGCT pathogenesis could be associated with the folate cycle status, and this relation could be partly due to hereditary factors.

Lifetime prevalence of malignant and benign tumours in companion dogs: Cross-sectional analysis of Dog Aging Project baseline survey.

Although cancer is widely regarded as a major contributor to canine morbidity and mortality, its frequency in companion dogs has only infrequently been characterised. We analysed cross-sectional data from the baseline survey of owners of 27 541 living companion dogs enrolled in the Dog Aging Project as of 31 December 2020 to estimate the lifetime prevalence of malignant and benign tumours and several potentially-associated characteristics. Survey questions elicited information on history of 'cancer or tumors' including organ site and histologic type. Owners reported 819 malignant tumours (56% sited in the skin, muscle or other soft tissue) and 404 benign tumours (69% sited in the skin, muscle or other soft tissue). The lifetime prevalence of malignant tumours (29.7/1000 dogs) was approximately double the lifetime prevalence of benign tumours (14.7/1000 dogs). Lifetime prevalence of both malignant and benign tumours increased with dog age at survey completion. There were no statistically discernable differences in age-adjusted lifetime prevalence of malignant (prevalence ratio (PR) = 0.93 [95% confidence interval (CI) 0.82, 1.07] or benign tumours (PR = 1.10, 95% CI 0.91, 1.34) in mixed vs. purebred dogs. The lifetime prevalence of malignant tumours increased with increasing dog size class; compared to toy and small dogs, the age-adjusted PRs (95% CIs) for medium, standard, large, and giant dogs were 1.65 (1.28, 2.11), 2.92 (2.35, 3.64), 3.67 (2.92, 4.62) and 2.99 (1.23, 4.02), respectively. Similar though less pronounced patterns in relation to dog size class were observed for benign tumours. Ongoing prospective data collection will permit future studies on risk factors for canine tumour incidence.

Optimal vocabulary selection approaches for privacy-preserving deep NLP model training for information extraction and cancer epidemiology.

BACKGROUND: With the use of artificial intelligence and machine learning techniques for biomedical informatics, security and privacy concerns over the data and subject identities have also become an important issue and essential research topic. Without intentional safeguards, machine learning models may find patterns and features to improve task performance that are associated with private personal information. OBJECTIVE: The privacy vulnerability of deep learning models for information extraction from medical textural contents needs to be quantified since the models are exposed to private health information and personally identifiable information. The objective of the study is to quantify the privacy vulnerability of the deep learning models for natural language processing and explore a proper way of securing patients' information to mitigate confidentiality breaches. METHODS: The target model is the multitask convolutional neural network for information extraction from cancer pathology reports, where the data for training the model are from multiple state population-based cancer registries. This study proposes the following schemes to collect vocabularies from the cancer pathology reports; (a) words appearing in multiple registries, and (b) words that have higher mutual information. We performed membership inference attacks on the models in high-performance computing environments. RESULTS: The comparison outcomes suggest that the proposed vocabulary selection methods resulted in lower privacy vulnerability while maintaining the same level of clinical task performance.

A Keyword-Enhanced Approach to Handle Class Imbalance in Clinical Text Classification.

Recent applications ofdeep learning have shown promising results for classifying unstructured text in the healthcare domain. However, the reliability of models in production settings has been hindered by imbalanced data sets in which a small subset of the classes dominate. In the absence of adequate training data, rare classes necessitate additional model constraints for robust performance. Here, we present a strategy for incorporating short sequences of text (i.e. keywords) into training to boost model accuracy on rare classes. In our approach, we assemble a set of keywords, including short phrases, associated with each class. The keywords are then used as additional data during each batch of model training, resulting in a training loss that has contributions from both raw data and keywords. We evaluate our approach on classification of cancer pathology reports, which shows a substantial increase in model performance for rare classes. Furthermore, we analyze the impact of keywords on model output probabilities for bigrams, providing a straightforward method to identify model difficulties for limited training data.

Infection with Human Papilloma Virus (HPV) and risk of subsites within the oral cancer.

BACKGROUND: The aim of this study was to investigate the relationship between high-risk genotypes of Human Papilloma Virus (HPV) and cancer of different subsites of the oral cavity. MATERIAL AND METHODS: A pooled analysis of five studies included on the International Head and Neck Cancer Epidemiology (INHANCE) Consortium was conducted. HPV 16 and HPV 18 were considered. Adjusted odds ratios (ORs) and corresponding 95 % confidence intervals (CIs) for HPV and each oral cavity subsites were simultaneously estimated using multinomial logistic regression models. RESULTS: The analysis included 1157 cases and 3272 controls. This study showed a slightly higher prevalence of HPV infection among oral cancer cases than controls. In particular, an increased risk of other and not otherwise specified (NOS) sites within the oral cavity, oral tongue, palate and floor of mouth cancer was observed for overall HPV16 positivity (OR = 1.66, 95 % CI: 1.01-2.72; OR = 1.97, 95 % CI: 1.36-2.85; OR = 2.48, 95 % CI: 1.50-4.11; OR = 2.71, 95 % CI: 1.06-6.95, respectively). In particular, HPV16E7 was related to cancer of floor of mouth, oral cavity NOS and palate (OR = 2.71, 95 % CI: 1.06-6.95; OR = 3.32, 95 % CI:1.53-7.19; OR = 3.34, 95 % CI:1.38-8.06). Results were inconsistent for HPV18 due to low prevalence of infection. CONCLUSION: Our study suggests that HPV16 infection may increase the risk of developing floor of mouth, gum, tongue, and palate cancers. CLINICAL RELEVANCE: Subjects with HPV infection have a higher risk of cancer from all sites of the oral cavity.

Cancer mortality in a population-based cohort of American Indians - The strong heart study.

BACKGROUND: Cancer mortality among American Indian (AI) people varies widely, but factors associated with cancer mortality are infrequently assessed. METHODS: Cancer deaths were identified from death certificate data for 3516 participants of the Strong Heart Study, a population-based cohort study of AI adults ages 45-74 years in Arizona, Oklahoma, and North and South Dakota. Cancer mortality was calculated by age, sex and region. Cox proportional hazards model was used to assess independent associations between baseline factors in 1989 and cancer death by 2010. RESULTS: After a median follow-up of 15.3 years, the cancer death rate per 1000 person-years was 6.33 (95 % CI 5.67-7.04). Cancer mortality was highest among men in North/South Dakota (8.18; 95 % CI 6.46-10.23) and lowest among women in Arizona (4.57; 95 % CI 2.87-6.92). Factors independently associated with increased cancer mortality included age, current or former smoking, waist circumference, albuminuria, urinary cadmium, and prior cancer history. Factors associated with decreased cancer mortality included Oklahoma compared to Dakota residence, higher body mass index and total cholesterol. Sex was not associated with cancer mortality. Lung cancer was the leading cause of cancer mortality overall (1.56/1000 person-years), but no lung cancer deaths occurred among Arizona participants. Mortality from unspecified cancer was relatively high (0.48/100 person-years; 95 % CI 0.32-0.71). CONCLUSIONS: Regional variation in AI cancer mortality persisted despite adjustment for individual risk factors. Mortality from unspecified cancer was high. Better understanding of regional differences in cancer mortality, and better classification of cancer deaths, will help healthcare programs address cancer in AI communities.

Utilization of Systemic Therapy in Patients With Cancer Near the End of Life in the Pre- Versus Postimmune Checkpoint Inhibitor Eras.

PURPOSE: Systemic therapy use in the last 30 days of life (DOL) for patients with advanced cancer is a low-value medical practice. We hypothesized that systemic therapy use in the last 30 DOL increased after approval of antiprogrammed cell death protein 1 immune checkpoint inhibitors (ICIs) and has contributed to increased health care utilization and spending. METHODS: We investigated the change in prevalence of any systemic therapy use in the last 30 DOL among patients with advanced solid tumors in the 4 years before and after antiprogrammed cell death protein 1 ICI approval in 2014. We used cases from the Western Washington Cancer Surveillance System linked to commercial and Medicare insurance. We calculated the difference in prevalence between the pre- and post-ICI periods. We also calculated the annual prevalence of any systemic therapy and ICI use in the last 30 DOL and measured health care utilization (emergency department visits and hospitalizations) and costs during the last 30 DOL. RESULTS: Eight thousand eight hundred seventy-one patients (median age 73 years) were included; 34% and 66% in the pre-and post-ICI period, respectively. Systemic therapy use in the last 30 DOL was lower in the post-ICI versus pre-ICI period (12.4% v 14.4%; difference -2.0% [95% CI, -3.5 to -0.5]). The annual prevalence of systemic therapy use in the last 30 DOL also declined, although ICI use rose. Patients treated with ICIs in last 30 DOL had more emergency department visits, hospitalizations, and higher costs. CONCLUSION: Systemic therapy use in the last 30 DOL was lower in the period after ICI approval. However, ICI use rose over time and had higher utilization and costs in the last 30 DOL. Systemic therapy use in the last 30 DOL warrants monitoring, especially as more ICI indications are approved.

Genetically Inferred Telomere Length and Testicular Germ Cell Tumor Risk.

BACKGROUND: Studies evaluating the association between peripheral blood leukocyte telomere length (LTL) and testicular germ cell tumor (TGCT) risk have produced conflicting results. METHODS: Using available genotype data from the Testicular Cancer Consortium (TECAC), polygenic risk score and Mendelian randomization analyses of genetic variants previously associated with LTL were used to assess potential etiologic associations between telomere length and TGCT risk. RESULTS: Genetically inferred telomere length was not associated with TGCT risk among 2,049 cases and 6,921 controls with individual-level genotype data (OR, 1.02; 95% confidence interval, 0.97-1.07). Mendelian randomization analyses using summary statistic data further indicated no evidence for an association between telomere length and TGCT risk among all available TECAC participants (3,558 cases and 13,971 controls). CONCLUSIONS: Our analyses in the largest molecular genetic testicular cancer study to date provide no evidence for an association between genetically inferred peripheral blood LTL and TGCT risk. IMPACT: The lack of evidence for an overall association indicates that peripheral blood LTL is likely not a strong biomarker for TGCT risk.

Correction: Incorporating Breast Cancer Recurrence Events Into Population-Based Cancer Registries Using Medical Claims: Cohort Study.

[This corrects the article DOI: 10.2196/18143.].