Cancer Control Research Articles

A double-edged sword effect of silver nanoparticles on angiogenesis in 4T1 breast cancer-bearing mice.

Silver nanoparticles (AgNPs) are increasingly known to have anticancer effects, but few studies have examined their adverse effects, so the underlying mechanisms are not yet fully understood. The current study investigated the critical influence of AgNPs on angiogenesis in 4T1 breast cancer-bearing mice. The sub-lethal dose of AgNPs (0.25mg/kg) was carried out. Female BALB/c mice (N = 35) were divided into 7 groups; normal control, cancer control, AgNPs control (one dose of (0.25mg/kg) AgNPs), single dose AgNPs before cancer, single dose AgNPs after cancer, 5 doses AgNPs after cancer, and doxorubicin. 4T1 breast cancer cell induction was performed subcutaneously on the left flank. Intraperitoneal (IP) administration of AgNPs and doxorubicin was carried out for all studied groups. Weight gain was normal in all study groups except the doxorubicin-treated group. Administering AgNPs before cancer induction promotes tumorigenesis, raises MMP-2 and MMP-9 activity, and increases CD31 and Ki67 expression. The cancer control group experienced the same outcomes. On the other hand, depending on the administered doses, the injection of AgNPs after tumor induction resulted in a notable decrease in tumor volume.In the doxorubicin-treated group, similar results were observed, while a dose of AgNPs‌ before cancer induction lead to increasing tumor volume compared to the cancer control group. The differences of biochemical markers including LDH, ALP, AST, ALT, BUN, and Cr between different groups were not significant. Significant differences were seen among all studied groups except doxorubicin and single dose AgNPs before cancer groups for serum TAC levels. It appears that AgNPs are considered a double-edged sword in the fight against cancer. AgNPs not only have anti-cancer effects on tumor size and angiogenesis, but they also might have cancer-stimulating roles. To confirm this conclusion, more detailed investigations are needed.

TET2 regulates early and late transitions in exhausted CD8+ T cell differentiation and limits CAR T cell function.

CD8+ T cell exhaustion hampers control of cancer and chronic infections and limits chimeric antigen receptor (CAR) T cell efficacy. Targeting TET2 in CAR T cells provides therapeutic benefit; however, TET2's role in exhausted T cell (TEX) development is unclear. In chronic lymphocytic choriomeningitis virus (LCMV) infection, TET2 drove conversion from stem cell-like TEX progenitors toward terminally differentiated and effector (TEFF)-like TEX. TET2 also enforced a terminally differentiated state in the early bifurcation between TEFF and TEX, indicating broad roles for TET2 in acquisition of effector biology. To exploit the therapeutic potential of TET2, we developed clinically actionable TET2-targeted CAR T cells by disrupting TET2 via knock-in of a safety switch alongside CAR knock-in at the TRAC locus. TET2-targeted CAR T cells exhibited restrained terminal exhaustion in vitro and enhanced antitumor responses in vivo. Thus, TET2 regulates fate transitions in TEX differentiation and can be targeted with a safety mechanism in CAR T cells for improved tumor control.

Advancing Global Pharmacoequity in Oncology.

Limited availability and affordability of cancer drugs contribute to staggering disparities in cancer survival between high-income and low- and middle-income countries (LMICs). As infrastructure for cancer care rapidly develops, there is an urgent need to reduce prices and improve access to cancer medicines in LMICs to advance pharmacoequity globally. Prior strategies to expand access to cancer medicines in LMICs have primarily relied on charity or differential pricing and have yielded limited results. Policymakers at the World Health Assembly recently proposed several strategies to increase global access to cancer drugs. Reviewing empirical data and lessons learned from medication access programs for HIV, COVID-19, and other infectious diseases, 3 strategies that multilateral organizations can use to reduce prices of cancer drugs in LMICs are discussed herein. These include (1) building regional technology transfer and manufacturing hubs, (2) expanding and streamlining use of compulsory licenses, and (3) implementing global standards for drug price transparency. Counterpoints to the critiques of these policies are critiqued and how programs can use these strategies to build on existing disease-centered initiatives is discussed. Lessons learned from the global response to HIV and COVID-19 show that international collaboration and support from the World Health and Trade Organizations can ensure a unified, coordinated agenda for advancing access to care in LMICs. Building on these lessons and implementing similar approaches for cancer drugs can play a critical role in expanding accessibility and affordability of cancer medicines in LMICs. With a growing burden of cancer morbidity and mortality in LMICs, redoubled efforts to deliver essential cancer medications to LMICs would have an immense impact on global cancer control and achieving the United Nations Sustainable Development Goals.

Spatial Analysis of Lung Cancer Patients and Associated Influencing Factors from the Perspective of Urban Sustainable Development: A Case Study of Jiangsu Province, China

With global environmental changes, lung cancer has become one of the most common types of cancer worldwide, posing a significant public health challenge. Jiangsu Province, located in the eastern part of China, is an economically and socially developed region. According to the latest cancer registration data in Jiangsu Province, lung cancer ranks first in both incidence and mortality of cancer in the province. Thus, studying the spatiotemporal distribution of lung cancer cases and analyzing the influence of various factors on this distribution are crucial for the effective prevention and control of the disease in Jiangsu Province. This study takes the statistical data of lung cancer patients in Jiangsu Province in 2020 as the research object, uses Geographic Information System (GIS) visualization and spatial analysis to study the spatial distribution characteristics of lung cancer patients in Jiangsu Province, and employs the geographical detector to numerically express the impact of various environmental factors on the distribution of lung cancer patients in Jiangsu Province. The results reveal a notable spatial clustering of lung cancer cases, with high-incidence areas concentrated in Suzhou, Nanjing, and Xuzhou cities. Among the seven environmental factors examined, PM2.5, SO2, and PM10 concentration exert the most significant influence. This study employs multifactorial spatial analysis to elucidate the intricate relationships between people’s health and air quality, medical resource distribution, and lung cancer incidence in the process of pursuing sustainable development in cities and provides an important reference for the improvement in lung cancer prevention and control strategies.

Abstract B003: Dogs with cancer have higher plasma exosome concentrations compared with healthy dogs in the COED (canine osteosarcoma early detection) study

Abstract Background: Osteosarcoma a common cancer in dogs that can serve as a translational model for certain aspects of human osteosarcoma. We previously developed a serum exosome gene signature in dogs with osteosarcoma capable of detecting minimal residual disease and predicting prognosis after therapy. Our goal is to continue expanding our understanding of exosomes for liquid biopsy applications in dogs with cancer, and to leverage this information in the design of liquid biopsy tests to address risk, early detection, and management of human cancer patients. For this study, we hypothesized that dogs with cancer would have higher plasma exosome concentrations compared with healthy control dogs. Methods: Plasma exosomes were enriched from 29 dogs with cancer, including 8 dogs with osteosarcoma, and 26 healthy control dogs. Exosome size and concentration in the plasma samples were characterized with nanoparticle tracking analysis. Wilcoxon rank sum tests were performed to assess differences between groups. Results: Dogs with cancer had a higher mean exosome concentration at 1.4 x 1012 (+/- 1.1 x 1012) particles/ml, compared with 5.0 x 1011 (+/- 2.7 x 1011) particles/ml in healthy control dogs (p = 0.0046). There was no difference in exosome size between dogs with cancer (mean diameter = 99.9 nm) and healthy control dogs (107.8 nm; p = 0.16) when all cancer types were included. However, exosomes enriched from healthy control samples were found to be significantly larger when compared to the exosomes enriched from the subset of cancer dogs that had osteosarcoma (mean exosome diameter = 83.9 nm; p = 0.0065). Similarly, when comparing exosome size between dogs with osteosarcoma and dogs with other cancers, plasma exosomes were larger in the dogs with other cancers (107.4 nm; p = 0.023). Conclusions: In this population, dogs with cancer have higher plasma exosome concentrations compared with healthy control dogs. Interestingly, we also found that dogs with osteosarcoma had significantly smaller exosome size than dogs with other cancers and healthy control dogs. Though the size of exosomes from dogs with osteosarcoma was found to be smaller, it is possible that the larger exosome concentration in dogs with osteosarcoma results in a similar total exosomal mass. Ongoing work includes analysis of exosomal cargo to develop a liquid biopsy test capable of assessing risk of osteosarcoma development in dogs, and applying similar methodology to determine exosomal genes associated with prognosis in pediatric osteosarcoma. The higher exosome concentrations in dogs with cancer suggests that this feature, combined with analysis of exosomal cargo, may have utility in development of a liquid biopsy cancer test in dogs. Citation Format: Kelly M. Makielski, Jaron M. Magstadt, Courtney H. Labe, Ali Khammanivong, Meagan Wojtysiak, Kyle Duval, Mitzi Lewellen, Amber Winter, Kelly Reid, Andrea Chehadeh, Michelle Buettner, Caitlin Feiock, Aaron K. Rendahl, Gary R. Cutter, Logan G. Spector, Brenda J. Weigel, Jaime F. Modiano. Dogs with cancer have higher plasma exosome concentrations compared with healthy dogs in the COED (canine osteosarcoma early detection) study [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B003.

Evaluating Factors Affecting Knowledge Sharing Among Health Care Professionals in the Medical Imaging Departments of 2 Cancer Centers: Concurrent Mixed Methods Study.

Knowledge sharing is a crucial part of any knowledge management implementation. It refers to sharing skills and experience among team members in an organization. In a health care setting, sharing knowledge, whether tacit or explicit, is important and can lead to better health care services. In medical imaging departments, knowledge sharing can be of particular importance. There are several factors that affect knowledge-sharing practices in medical imaging departments: individual, departmental, and technological. Evaluating the importance of these factors and understanding their use can help with improving knowledge-sharing practices in medical imaging departments. We aimed to assess the level of motivation, identify current knowledge-sharing tools, and evaluate factors affecting knowledge sharing in the medical imaging departments of 2 cancer centers, The Christie, United Kingdom, and the Kuwait Cancer Control Center (KCCC). A concurrent mixed methods study was conducted through nonprobability sampling techniques between February 1, 2023, and July 30, 2023. Semistructured interviews were used to validate the results of the quantitative analysis. Data were collected using an electronic questionnaire that was distributed among health care professionals in both cancer centers using Qualtrics. Semistructured interviews were conducted online using Microsoft Teams. The quantitative data were analyzed using the Qualtrics MX software to report the results for each question, whereas the qualitative data were analyzed using a thematic approach with codes classified through NVivo. In total, 56 respondents from the KCCC and 29 from The Christie participated, with a 100% response rate (56/56, 100% and 29/29, 100%, respectively) based on the Qualtrics survey tool. A total of 59% (17/29) of health care professionals from The Christie shared their knowledge using emails and face-to-face communication as their main tools on a daily basis, and 57% (32/56) of health care professionals from the KCCC used face-to-face communication for knowledge sharing. The mean Likert-scale score of all the components that assessed the factors that affected knowledge-sharing behaviors fell between "somewhat agree" and "strongly agree" in both centers, excepting extrinsic motivation, which was rated as "neither agree nor disagree." This was similar to the results related to incentives. It was shown that 52% (15/29) of health care professionals at The Christie had no incentives to encourage knowledge-sharing practices. Therefore, establishing clear policies to manage incentives is important to increase knowledge-sharing practices. This study offered an evaluation of factors that affect knowledge sharing in 2 cancer centers. Most health care professionals were aware of the importance of knowledge-sharing practices in enhancing health care services. Several challenges were identified, such as time constraints, a lack of staff, and the language barrier, which limit knowledge-sharing practices. Therefore, establishing a clear policy for knowledge sharing is vital to practicing knowledge-sharing behaviors and facing any challenges that limit this practice.

Abstract 4118178: Echocardiographic Measure of Right Ventricular-Pulmonary Arterial Coupling Predicts Survival in Lung Cancer

Background: Echocardiographic indicators of pulmonary hypertension have been reported to predict decreased survival in lung cancer. We sought to test the hypothesis that this may be associated with impaired right ventricular (RV)-systolic pulmonary arterial pressure (sPAP) coupling, further enhancing the prognostic strength of echocardiography in lung cancer. Methods: This prospective observational study included 220 patients with non-small cell lung cancer (NSCLC) examined by Doppler, strain and 3D echocardiography before starting therapy. Prediction of overall survival was assessed by univariable analysis followed by multivariate Cox regression, receiver operating characteristic (ROC) curves and Kaplan-Meier analyses. Results: Echocardiographic examination was on average within normal limits, even though 30% of the patients had sPAP ≥35 mm Hg. In univariable analysis, overall survival was associated with measures of RV systolic function and probability of pulmonary hypertension. In multivariate Cox regression, only RV global longitudinal strain (GLS)/sPAP (HR: 5.766 [95% CI: 1.025–32.443]) and Eastern Cooperative Oncology Group performance status <2 (HR: 0.332 [95% CI: 0.171–0.644]) independently predicted survival. The optimal ROC curve-derived RV GLS/sPAP cut-off to predict survival was −0.54%/mm Hg. Among patients in Union for International Cancer Control (UICC) stage 4, those with impaired RV-arterial coupling (RV GLS/sPAP >−0.54%/mm Hg) had worse survival than those with maintained RV-arterial coupling (HR: 2.8 [95% CI: 1.5–5.3]); the latter subgroup had similar survival compared with patients in UICC stage 3 (HR: 0.57 [95% CI: 0.28–1.14]). Conclusion: RV GLS/sPAP as an echocardiographic measure of RV-arterial coupling adds to prognostication by the UICC status in NSCLC.

Thibang Diphatlha: a sequential multiple assignment randomized trial designed to increase timely adoption of cervical cancer treatment in Botswana.

Delays and missed opportunities for timely treatment contribute significantly to stark inequities in cervical cancer mortality in low- and middle-income countries (LMICs) compared to high-income countries. The vast majority (approximately 90%) of new cases and deaths occur in LMICs, particularly those with high rates of HIV such as Botswana. To date, most of the implementation and cancer control research in Botswana and other LMICs has focused on cancer prevention and screening, with limited focus on cancer treatment. As such, there is a critical need to identify effective strategies to ensure timely care, and to understand contextual factors that shape the response to strategies. Without this fundamental knowledge, cervical cancer will remain a public health crisis in Botswana and other LMICs. To help fill this known gap, this study tests the effectiveness of adaptive strategies on timely treatment adoption using a hybrid (type III) Sequential Multiple Assignment Randomized Trial (SMART) design and evaluate contextual mechanisms contributing to the success or failure of each adaptive strategy. The adaptive strategies are designed to target contextual determinants identified in our prior work, including delayed communication of results to patients, individual and structural barriers to accessing treatment, and suboptimal care coordination between referring and cancer treatment clinics, and are supported by systematic evidence of the effectiveness of nudge strategies in clinical care. The primary implementation outcome is adoption, defined as the initiation of treatment within 90days. Secondary outcomes include fidelity, reach, acceptability, implementation costs, and cancer and HIV-related clinical outcomes. The rationale for the study is that enhancing coordination, communication, and navigation through centralized outreach will both increase timely treatment adoption and be scalable and sustainable after the project is completed. This innovative study seeks to decrease cervical cancer mortality in LMICs by developing and implementing effective and sustainable strategies that can be sustained and adapted to other contexts. Additionally, this study seeks to advance the long-term impact of global implementation science through strong and sustained partnerships in Botswana and other LMICs. ClinicalTrials.govNCT05952141. Registered on July 11, 2023. https://clinicaltrials.gov/study/NCT05952141 PROTOCOL VERSION AND DATE: Version 1 (September 28, 2024).

Post-transcriptional control drives Aurora kinase A expression in human cancers.

Aurora kinase A (AURKA) is a major regulator of the cell cycle. A prominent association exists between high expression of AURKA and cancer, and impairment of AURKA levels can trigger its oncogenic activity. In order to explore the contribution of post-transcriptional regulation to AURKA expression in different cancers, we carried out a meta-analysis of -omics data of 18 cancer types from The Cancer Genome Atlas (TCGA). Our study confirmed a general trend for increased AURKA mRNA in cancer compared to normal tissues and revealed that AURKA expression is highly dependent on post-transcriptional control in several cancers. Correlation and clustering analyses of AURKA mRNA and protein expression, and expression of AURKA-targeting hsa-let-7a miRNA, unveiled that hsa-let-7a is likely involved to varying extents in controlling AURKA expression in cancers. We then measured differences in the short/long ratio (SLR) of the two alternative cleavage and polyadenylation (APA) isoforms of AURKA mRNA across cancers compared to the respective healthy counterparts. We suggest that the interplay between APA and hsa-let-7a targeting of AURKA mRNA may influence AURKA expression in some cancers. hsa-let-7a and APA may also independently contribute to altered AURKA levels. Therefore, we argue that AURKA mRNA and protein expression are often discordant in cancer as a result of dynamic post-transcriptional regulation.

Surgery versus radiation for clinically positive nodal prostate cancer in an other cause mortality risk weighted cohort.

This study examined cancer control metrics between surgery and radiation for clinically positive nodal prostate cancer in an other-cause mortality weighted cohort, to circumvent limitations in previous studies. The Surveillance, Epidemiology, and End Results Research Plus database was queried to identify men with clinically positive nodal prostate cancer at diagnosis between 2004 and 2017 who were treated with surgery or radiation. A competing-risks regression model was used to calculate the 10-year other-cause mortality risk using available covariates, including treatment type. Inverse probability of treatment weighting was then used to balance covariates, including other-cause mortality risk. Then, competing-risks cumulative incidence curves and multivariable models, which were weighted on the calculated other-cause mortality risk, were used to examine the impact of treatment type on cancer-specific mortality, after accounting for covariates. 4739 patients underwent surgery whereas 1039 underwent radiation. The median follow-up was 4.7years (2.6-8.2). Other-cause mortality was statistically different between treatment arms in the unweighted cohort (Gray's p = 0.005), but that difference disappeared in the weighted cohort (Gray's p = 0.2). At 10years, the cancer-specific mortality rate was 27.6% (22.2-33.9) for radiation versus 18.1% (16.2-20.3) for surgery (p < 0.001). On competing-risks multivariable analysis, radiation had 1.86-fold (95% CI 1.69-2.12) higher hazard likelihood from one year to the next compared to surgery (p < 0.001). Clinically positive nodal patients treated with radiation fare worst cancer-specific mortality than those that underwent surgery, using calculated other-cause mortality risk.

Personal Networks and Cervical Cancer Screening among Black Immigrant Women.

Prior research has linked personal network characteristics with cancer screening uptake including Papanicolaou (Pap) screening, but less is known about the experiences of Black immigrant women (BIW) in the USA. We examined the relationship between network characteristics and Pap screening among BIW and explored how their network members influence their cancer related knowledge and prevention behaviors. A mixed methods study of BIW, aged 21-65years, in southeastern US included a cross-sectional survey (N = 204) and in-depth individual interviews (N = 13). We examined whether high-social connectedness, contact frequency, and social support were associated with Pap screening, using multivariable logistic regression models. Thematic analysis further assessed the roles of personal network factors on BIW's cancer preventive behaviors. Pap screening was more likely among BIW with high- versus low-social connectedness (OR: 2.68, CI: 1.12, 6.46). However, the impact of high-social connectedness was attenuated, after adjusting for demographic factors and health insurance. Our qualitative findings revealed that both BIW and their personal networks had limited knowledge on cancer and related prevention measures. Close network members, particularly mother-figures, provided support for BIW's care seeking efforts, including cancer screening, although some participants mentioned a lack of screening support. These findings suggest that Black immigrant communities may benefit from tailored cancer prevention interventions among close network members, to improve knowledge and support for cancer control behaviors.

Rural-Urban Disparities and Trends in Cancer Screening: An Analysis of Behavioral Risk Factor Surveillance System Data (2018-2022).

Despite evidence of the benefit of routine cancer screenings, data show a concerning decline in cancer screening uptake for multiple cancer screenings. This analysis aimed to examine rural-urban differences in recent trends for being up to date with screenings for breast, cervical, and colorectal cancers. We used 2018, 2020, and 2022 Behavioral Risk Factor Surveillance System data to assess up-to-date cancer screening status among eligible U.S. adults. We calculated weighted prevalence estimates overall and stratified by county-level rural-urban classification. We used survey-weighted multivariable logistic regression models to examine rural-urban disparities in cancer screening up-to-date status by year. Prevalence of being up to date with each cancer screening was lower in 2022 than it was in 2018. The largest decline in screening overall was for cervical cancer that dropped from 81.89% in 2018 to 47.71% in 2022. Rural-urban disparities were observed for breast cancer screening from 2018 to 2022 with the odds of up-to-date screening being 14% to 27% lower for rural populations than urban populations. For colorectal and cervical cancer, the odds of being up to date with screenings were lower for rural populations in 2018 and 2020, but there was no significant difference observed in 2022 (colorectal screening OR = 0.96; 95% CI: 0.90, 1.02) (cervical screening OR = 0.97; 95% CI: 0.93, 1.03). There is a concerning trend of decreasing uptake of cancer screenings, which will challenge future efforts in cancer prevention and control efforts. Efforts are needed to better understand factors contributing to the declining uptake of cancer screenings.

Factors of interobserver variability in prostate tumor MRI delineation: impact of PI-QUAL score.

Prostate cancer ranks as the second most common cancer in men worldwide. Dose escalation to the tumor and/or the prostate improves biochemical recurrence-free survival. However, interobserver variability in lesion contouring poses a significant limitation to such therapeutic approaches. Therefore, a study of factors influencing this variability is necessary. Three independent readers delineated the index prostate lesion (DIL) using T2w and ADC sequences for each patient. Clinical data were retrospectively collected for all participants. Logistic regression analysis was employed to examine the correlation between clinical features and a mean DICE coefficient > 0.7. Features exhibiting a p value < 0.05 on univariate analysis were subjected to multivariate analysis. The study comprised 68 patients, with a median DICE coefficient of 0.69 (95% CI 0.65-0.71), wherein 42.6% (29/68) attained a mean DICE > 0.7. Univariate analysis identified the PI-QUAL score, maximum diameter of DIL, and mean DIL volume as significant (p < 0.05) predictors. In multivariate analysis, only the PI-QUAL score (p = 0.008) remained statistically associated with a DICE coefficient > 0.7. The PI-QUAL score emerges as the primary predictive factor for minimizing inter-reader variability in intraprostatic dominant lesion segmentation. These findings underscore the importance of considering PI-QUAL scores when devising focal treatment plans. Adoption of a multi-reader approach involving diverse medical specialists (radiologists, radiotherapists, urologists) is advocated, particularly for MRIs with low PI-QUAL scores. Radiotherapy is a major treatment for patients with localized prostate cancer. Dose escalation to the tumor leads to improved cancer control. Precise delineation of the dominant intraprostatic lesion (DIL) remains a limitation to focal treatments. Features influencing inter-reader variability were never evaluated. In this study, we identified that the PI-QUAL score was the sole predictor of the inter-reader delineation variability of the DIL.

Long-Term Adverse Effects and Complications After Prostate Cancer Treatment

Due to the often indolent nature of prostate cancer (PCA), treatment decisions must weigh the risks and benefits of cancer control with those of treatment-associated morbidities. To characterize long-term treatment-related adverse effects and complications in patients treated for PCA compared to a general population of older males. This cohort study used a novel approach linking data from 2 large PCA prevention clinical trials (the Prostate Cancer Prevention Trial and the Selenium and Vitamin-E Cancer Prevention Trial) with Medicare claims records. This analysis included patients with PCA who had been treated with prostatectomy or radiotherapy compared with an untreated control group. Multivariable Cox regression was used, with a time-varying covariate for the occurrence of PCA treatment, adjusted for age, race, and year of time-at-risk initiation, and stratified by study and intervention arm. Data analyses were performed from September 21, 2022, to March 18, 2024. Prostatectomy and radiotherapy occurring after a PCA diagnosis, identified from trial data or Medicare claims records. Ten potential PCA treatment-related complications identified from Medicare claims data. The study sample comprised 29 196 participants (mean [SD] age at time-at-risk initiation, 68.7 [4.8] years). Of these, 3946 participants had PCA, among whom 655 were treated with prostatectomy and 1056 with radiotherapy. The 12-year hazard risk of urinary or sexual complications was 7.23 times greater for those with prostatectomy (95% CI, 5.96-8.78; P < .001) and 2.76 times greater for radiotherapy (95% CI, 2.26-3.37; P < .001) compared to untreated participants. Moreover, among participants treated with radiotherapy, there was a nearly 3-fold greater hazard risk of bladder cancer than in the untreated (hazard ratio [HR], 2.78; 95% CI, 1.92-4.02; P < .001), as well as an approximately 100-fold increased hazard risk of radiation-specific outcomes including radiation cystitis (HR, 131.47; 95% CI, 52.48-329.35; P < .001) and radiation proctitis (HR, 87.91; 95% CI, 48.12-160.61; P < .001). The incidence per 1000 person-years of any 1 of the 10 treatment-related complications was 124.26 for prostatectomy, 62.15 for radiotherapy, and 23.61 for untreated participants. This cohort study found that, even after accounting for age-related symptoms and disease, PCA treatment was associated with higher rates of complications in the 12 years after treatment. Given the uncertain benefit of PCA treatment for most patients, these findings highlight the importance of patient counseling before PCA screening and treatment and provide a rationale for pursuing opportunities for cancer prevention.

Extending the Translational Science Benefits Model to Implementation Science for Cancer Prevention and Control

Extending the Translational Science Benefits Model to Implementation Science for Cancer Prevention and Control

Adjuvant Chemotherapy using S-1 for Resected Biliary Tract Carcinoma

Abstract Objective The benefit of adjuvant chemotherapy for resected biliary tract carcinoma (BTC) is unclear; however, the JCOG1202 trial indicated that S-1 may be effective. This retrospective study evaluated the effectiveness of S-1 adjuvant chemotherapy for resected BTC at a single institute. Methods Seventy-five patients who underwent resection for BTC between 2014 and 2021 were classified as surgery alone (N=29) or surgery plus S-1 (N=46). Outcomes, including relapse-free survival (RFS) and overall survival (OS), were compared between the groups. Results The cohort (mean age, 72.2 years) included 51 men and 24 women. No differences in patient characteristics (age, sex, tumor-node-metastasis classification, Union for International Cancer Control stage, and residual tumor (R) classification) were observed between the groups. Grade 3/4 adverse events were not observed, and relative dose intensity was 84.8%. No differences were observed between the groups regarding RFS and OS, nor in RFS when excluding those with R2 (p=0.599). However, a significant difference was observed in OS between the groups in the latter case (p=0.04), with median survival times of 22.2 months for surgery alone and 64.5 months for surgery plus S-1. Conclusion S-1 adjuvant chemotherapy prolonged OS in patients with BTC treated by curative resection (excluding R2).

GSOR06 Presentation Time: 11:55 AM: Dosimetric Analysis and Machine Learning Predictive Modeling of Local Control in Cervical Cancer

GSOR06 Presentation Time: 11:55 AM: Dosimetric Analysis and Machine Learning Predictive Modeling of Local Control in Cervical Cancer

Single-dose human papillomavirus vaccination: an update.

Human papillomavirus (HPV) vaccines received regulatory approval and were recommended for use in young girls nearly 2 decades ago. Uptake is mostly high in resource-rich settings. In resource-limited settings, where the burden of cervical cancer is disproportionately high, access to and uptake of HPV vaccines are nowhere near satisfactory, despite evidence that HPV vaccination is highly cost-effective and a significant value-for-money investment. The discovery that only a single dose of the HPV vaccines may be needed to confer adequate protection may make equitable access to HPV vaccines possible. Indeed, the recent World Health Organization recommendation allowing for 1 or 2 doses is already gaining traction. This monograph aims to update the state of the science related to single-dose HPV vaccine protection and includes both primary data and modeling efforts that address key gaps in the knowledge regarding 1) durability of protection of a single dose of the HPV vaccine, 2) single-dose HPV vaccine effectiveness in both high-income and low-income settings, 3) implementation of single-dose HPV vaccination, and 4) how to accelerate control of cervical cancer by integrating a 1-time screen for cervical disease. The content published in this monograph will continue to advance the science of HPV vaccination and will be vital as new countries make informed decisions about how best to use this remarkable vaccine.

A cervical cancer control strategy for lower-resource settings: interventions to complement one-dose HPV vaccination.

One-dose prophylactic HPV vaccination of pre-adolescents may reduce cervical cancer deaths dramatically in lower-resource settings, but the benefits of achieving immediate high coverage among pre-adolescents would not be realized for 20 to 40 years. Prophylactic vaccine efficacy is reduced after sexual debut, and current therapeutic intervention candidates designed to treat existing HPV infections or precancerous lesions have yielded insufficient evidence to warrant widespread use. However, we are developing a feasible, scalable, high-quality cervical screening approach that could prevent hundreds of thousands of deaths, while we work to achieve high coverage of one-dose vaccination for adolescent cohorts. A time-limited "one screen" campaign approach for lower-resource settings could complement parallel efforts to achieve high coverage with one-dose vaccination. This screen-triage-treat strategy would target the highest risk groups of screening age (ie, 25 to 49 years) for once-in-a-lifetime HPV testing of self-collected samples using a low-cost accurate HPV test; subsequent triage relying on extended genotyping and a validated deep-learning algorithm for automated visual evaluation (AVE) would stratify management based on risk to provide treatment for those most likely to develop cancer without overburdening health care systems. Early efficacy of this approach has been demonstrated in 9 countries within the HPV-AVE (PAVE) Study Consortium. We estimate that the cost per death averted of a screen-triage-treat campaign is of similar magnitude to prophylactic vaccination. We do not envision perpetual investment in ubiquitous brick-and-mortar screening programs if "one dose, one screen" is implemented with high coverage and targets the highest-risk populations. In collaboration with in-country stakeholders, efforts to ensure acceptability, risk communication, and cost-effectiveness are underway.

Cost–benefit analysis of mammography screening: the perspective of Nigerian healthcare providers

IntroductionThere is no national breast cancer screening implemented in Nigeria. The National Cancer Control Plan (NCCP) has a goal of making screening services and early detection of cancer available for...