Cancer research provides a model for advancing clinical trials in dementia in the era of disease-modifying Alzheimer's-type dementia therapies.

Dementia and cancer are multifactorial, widely-feared, age-associated clinical syndromes that are increasing in prevalence. There have been major breakthroughs in clinical cancer research leading to some effective treatments, whereas the field of dementia has achieved comparatively limited success in clinical research. The lessons of cancer research may help those in the dementia research field in confronting some of the dilemmas faced when the clinical care regimen is not entirely safe or efficacious. Cancer clinical trials have assumed that untreated individuals with cancer are at high risk for morbidity and mortality after primary diagnoses. Thus, patients deserve a choice of clinical interventions, either standard of care or experimental, even if the benefits are not certain and the therapy's side effects are potentially severe. The prognosis for many individuals at risk for dementia carries a correspondingly high level of risk for both mortality and severe morbidity, particularly if one focuses on "health-span" rather than lifespan. Caregivers and patients can be strongly impacted by dementia and the many troubling associated symptoms that often go well beyond amnesia. Polls, surveys, and a literature on "dementia worry" strongly underscore that the public fears dementia. While there are institutional and industry hurdles that complicate enrollment in randomized trials, the gravity of the future morbidity and mortality inherent in a dementia diagnosis may require reconsideration of the current protective stance that limits the freedom of at-risk individuals (either symptomatic or asymptomatic) to participate and potentially benefit from ongoing clinical research. There is also evidence from both cancer and dementia research that individuals enrolled in the placebo arms of clinical trials have unexpectedly good outcomes, indicating that participation in clinical trial can have medical benefits to enrollees. To highlight aspects of cancer clinical research that may inform present and future dementia clinical research, this review highlights three main themes: the risk of side effects should be weighed against the often dire consequences of non-treatment; the desirability of long-term incremental (rather than "magic bullet") clinical advances; and, the eventual importance of combination therapies, reflecting that the dementia clinical syndrome has many underlying biological pathways.

NCI SEER-Linked Virtual Tissue Repository Pilot.

BACKGROUND: The Surveillance, Epidemiology, and End Results (SEER) Program with the National Cancer Institute tested whether population-based cancer registries can serve as honest brokers to acquire tissue and data in the SEER-Linked Virtual Tissue Repository (VTR) Pilot. METHODS: We collected formalin-fixed, paraffin-embedded tissue and clinical data from patients with pancreatic ductal adenocarcinoma (PDAC) and breast cancer (BC) for two studies comparing cancer cases with highly unusual survival (≥5 years for PDAC and ≤30 months for BC) to pair-matched controls with usual survival (≤2 years for PDAC and ≥5 years for BC). Success was defined as the ability for registries to acquire tissue and data on cancer cases with highly unusual outcomes. RESULTS: Of 98 PDAC and 103 BC matched cases eligible for tissue collection, sources of attrition for tissue collection were tissue being unavailable, control paired with failed case, second control that was not requested, tumor necrosis ≥20%, and low tumor cellularity. In total, tissue meeting the study criteria was obtained for 70 (71%) PDAC and 74 (72%) BC matched cases. For patients with tissue received, clinical data completeness ranged from 59% for CA-19-9 after treatment to >95% for margin status, whether radiation therapy and chemotherapy were administered, and comorbidities. CONCLUSIONS: The VTR Pilot demonstrated the feasibility of using SEER cancer registries as honest brokers to provide tissue and clinical data for secondary use in research. Studies using this program should oversample by 45% to 50% to obtain sufficient sample size and targeted population representation and involve subspecialty matter expert pathologists for tissue selection.

Scrotal Cancer Incidence Rates and Trends-United States, 1999-2020.

OBJECTIVE: To examine population-level scrotal cancer incidence rates and trends among adult men in the United States. METHODS: Data from the United States Cancer Statistics, covering approximately 96% of the United States population, were analyzed to calculate age-standardized incidence rates of scrotal cancer among men aged 18 years and older from 1999 to 2020. Trends in incidence rates were evaluated by age, race and ethnicity, Census region, and histology using joinpoint regression. RESULTS: Overall, 4669 men were diagnosed with scrotal cancer (0.20 per 100,000). Incidence rates were highest among men aged 70 years and older (0.82 per 100,000). Rates were higher among non-Hispanic Asian or Pacific Islander men (0.31 per 100,000) compared to other race and ethnicity groups. The most common histologic subtypes were squamous cell carcinoma (35.9%), extramammary Paget disease (20.8%), and sarcoma (20.5%). Incidence rates decreased by 2.9% per year from 1999 to 2019 for non-Hispanic Asian or Pacific Islander men, decreased by 8.1% per year from 1999 to 2006 for basal cell carcinomas, and increased by 1.8% per year from 1999 to 2019 for extramammary Paget disease; otherwise, rates remained stable for all other variables examined. CONCLUSION: While scrotal cancer incidence rates were higher than previously reported, rates were still low and stable over time.

Population-level incidence of human papillomavirus-positive oropharyngeal, cervical, and anal cancers, by smoking status.

We estimated the population-level incidence of human papillomavirus (HPV)-positive oropharyngeal, cervical, and anal cancers by smoking status. We combined HPV DNA genotyping data from the Centers for Disease Control and Prevention's Cancer Registry Sentinel Surveillance System with data from the Kentucky Cancer Registry and Behavioral Risk Factor Surveillance System across smoking status. During 2004-2005 and 2014-2015 in Kentucky, most cases of oropharyngeal (63.3%), anal (59.7%), and cervical (54.9%) cancer were among individuals who ever smoked. The population-level incidence rate was higher among individuals who ever smoked than among those who never smoked for HPV-positive oropharyngeal (7.8 vs 2.1; adjusted incidence rate ratio = 2.6), cervical (13.7 vs 6.8; adjusted incidence rate ratio = 2.0), and anal (3.9 vs 1.6; adjusted incidence rate ratio = 2.5) cancers. These findings indicate that smoking is associated with increased risk of HPV-positive oropharyngeal, cervical, and anal cancers, and the population-level burden of these cancers is higher among individuals who ever smoked.

Undiagnosed Cancer Cases in the US During the First 10 Months of the COVID-19 Pandemic.

Importance: The COVID-19 pandemic disrupted the normal course of cancer screening and detection in the US. A nationwide analysis of the extent of this disruption using cancer registry data has not been conducted. Objective: To assess the observed and expected cancer rate trends for March through December 2020 using data from all 50 US states and the District of Columbia. Design, Settings, and Participants: This was a population-based cross-sectional analysis of cancer incidence trends using data on cases of invasive cancer diagnosis reported to the US Cancer Statistics from January 1, 2018, through December 31, 2020. Data analyses were performed from July 6 to 28, 2023. Exposure(s): Age, sex, race, urbanicity, and state-level response to the COVID-19 pandemic at the time of cancer diagnosis. Main Outcomes and Measures: Used time-series forecasting methods to calculate expected cancer incidence rates for March 1 through December 31, 2020, from prepandemic trends (January 2018-February 2020). Measured relative difference between observed and expected cancer incidence rates and numbers of potentially missed cancer cases. Results: This study included 1 297 874 cancer cases reported in the US from March 1 through December 31, 2020, with an age-adjusted incidence rate of 326.5 cases per 100 000 population. Of the observed cases, 657 743 (50.7%) occurred in male patients, 757 106 (58.3%) in persons 65 years or older, and 1 066 566 (82.2%) in White individuals. Observed rates of all-sites cancer incidence in the US were 28.6% (95% prediction interval [PI], 25.4%-31.7%) lower than expected during the height of the COVID-19 pandemic response (March-May 2020); 6.3% (95% PI, 3.8%-8.8%) lower in June to December 2020; and overall, 13.0% (95% PI, 11.2%-14.9%) lower during the first 10 months of the pandemic. These differences indicate that there were potentially 134 395 (95% PI, 112 544-156 680) undiagnosed cancers during that time frame. Prostate cancer accounted for the largest number of potentially missed cases (22 950), followed by female breast (16 870) and lung (16 333) cancers. Screenable cancers saw a total rate reduction of 13.9% (95% PI, 12.2%-15.6%) compared with the expected rate. The rate of female breast cancer showed evidence of recovery to previous trends after the first 3 months of the pandemic, but levels remained low for colorectal, cervical, and lung cancers. From March to May 2020, states with more restrictive COVID-19 responses had significantly greater disruptions, yet by December 2020, these differences were nonsignificant for all sites except lung, kidney, and pancreatic cancer. Conclusions and Relevance: This cross-sectional analysis of cancer incidence trends found a substantial disruption to cancer diagnoses in the US during the first 10 months of the COVID-19 pandemic. The overall and differential findings can be used to inform where the US health care system should be looking to make up ground in cancer screening and detection.

Human Papillomavirus Detection in Scrotal Squamous Cell Carcinoma: Case Series from a Population-Based Cancer Registry.

Introduction: Scrotal squamous cell carcinomas (SCCs) are rare malignancies that are not considered to be associated with the human papillomavirus (HPV) by the International Agency for Research on Cancer. However, recent studies have detected HPV in these cancers. We sought to determine the presence of HPV types among scrotal cancer cases identified through population-based cancer registries. Methods: Primary scrotal SCCs diagnosed from 2014 to 2015 were identified, and tissue sections from formalin-fixed, paraffin-embedded tissue blocks were obtained for laboratory testing. A pathology review was performed to confirm morphology. HPV testing was performed using L1 consensus polymerase chain reaction analysis. Immunohistochemistry was used to evaluate p16INK4a (p16) expression. Results: Five cases of scrotal SCC were identified from 1 cancer registry. Age at diagnosis ranged from 34 to 75 years (median, 56 years). Four cases were non-Hispanic White, and 1 was non-Hispanic Black. The morphologic subtype of 4 cases was keratinizing (usual), and 1 case was verrucous (warty) histologic subtype. Two of the usual cases of SCC were HPV-negative and p16-negative, and 2 were positive for HPV16 and p16. The verrucous (warty) SCC subtype case was HPV6-positive and p16-negative. Conclusions: The presence of HPV16 and p16 overexpression in the examined tissue specimens lends additional support for the role of HPV in the etiology of scrotal SCC.