Leveraging a relationship-based sexual health framework for sexual risk prevention in adolescent men in the United States

Background: Studies link sexual health to lower sexual risk in adolescent women, yet no empirical literature evaluates these associations in adolescent men. Methods: Data were drawn from a longitudinal cohort study of sexual relationships and sexual behaviour among adolescent men (n = 72; 14–16 years) in the US. Participants contributed quarterly partner-specific interviews, from which sexual health information and partnered sexual behaviours were drawn. A multidimensional measure of sexual health was constructed and linked to partnered outcomes, including oral–genital, vaginal and anal sex, condom use, partner concurrency and intimate partner violence. Random intercept, mixed-effects linear, ordinal logistic or binary logistic regression were for analyses. Models controlled for participant age, race/ethnicity and relationship length. Results: Adolescent men contributed 651 unique partner-specific interviews. A higher sexual health score with partners was significantly associated with more frequent oral–genital and vaginal sex, as well as higher condom use, lower partner concurrency and lower received and perpetuated intimate partner violence. Conclusion: Positive sexually related experiences in adolescent men contribute to a core of sexual wellbeing, which in turn is linked to lower levels of sexual risk with partners. The present study data support both developmental and public health applications of sexual health, with attention on promoting healthy sexuality as well as risk reduction. Higher sexual health among adolescent men from the US is associated with more frequent condom use, lower partner concurrency and less frequent intimate partner violence. Young men’s exercising the skills associated with healthy sexuality may also reinforce the skills needed to both enjoy sexuality with partners and to avoid adverse sexual outcomes

Non-invasive Eye Tracking Methods for New World and Old World Monkeys

Eye-tracking methods measure what humans and other animals visually attend to in the environment. In nonhuman primates, eye tracking can be used to test hypotheses about how primates process social information. This information can further our understanding of primate behavior as well as offer unique translational potential to explore causes of or treatments for altered social processing as seen in people with neurodevelopmental disorders such as autism spectrum disorder and schizophrenia. However, previous methods for collecting eye-tracking data in nonhuman primates required some form of head restraint, which limits the opportunities for research with respect to the number of or kinds of primates that can undergo an eye-tracking study. We developed a novel, noninvasive method for collecting eye tracking data that can be used both in animals that are difficult to restrain without sedation as well as animals that are of different ages and sizes as the box size can be adjusted. Using a transport box modified with a viewing window, we collected eye-tracking data in both New (Callicebus cupreus) and Old World monkeys (Macaca mulatta) across multiple developmental time points. These monkeys had the option to move around the box and avert their eyes from the screen, yet, they demonstrated a natural interest in viewing species-specific imagery with no previous habituation to the eye-tracking paradigm. Provided with opportunistic data from voluntary viewing of stimuli, we found that juveniles viewed stimuli more than other age groups, videos were viewed more than static photo imagery, and that monkeys increased their viewing time when presented with multiple eye tracking sessions. This noninvasive approach opens new opportunities to integrate eye-tracking studies into nonhuman primate research

Non-invasive Eye Tracking Methods for New World and Old World Monkeys.

Eye-tracking methods measure what humans and other animals visually attend to in the environment. In nonhuman primates, eye tracking can be used to test hypotheses about how primates process social information. This information can further our understanding of primate behavior as well as offer unique translational potential to explore causes of or treatments for altered social processing as seen in people with neurodevelopmental disorders such as autism spectrum disorder and schizophrenia. However, previous methods for collecting eye-tracking data in nonhuman primates required some form of head restraint, which limits the opportunities for research with respect to the number of or kinds of primates that can undergo an eye-tracking study. We developed a novel, noninvasive method for collecting eye tracking data that can be used both in animals that are difficult to restrain without sedation as well as animals that are of different ages and sizes as the box size can be adjusted. Using a transport box modified with a viewing window, we collected eye-tracking data in both New (Callicebus cupreus) and Old World monkeys (Macaca mulatta) across multiple developmental time points. These monkeys had the option to move around the box and avert their eyes from the screen, yet, they demonstrated a natural interest in viewing species-specific imagery with no previous habituation to the eye-tracking paradigm. Provided with opportunistic data from voluntary viewing of stimuli, we found that juveniles viewed stimuli more than other age groups, videos were viewed more than static photo imagery, and that monkeys increased their viewing time when presented with multiple eye tracking sessions. This noninvasive approach opens new opportunities to integrate eye-tracking studies into nonhuman primate research

Non-invasive Eye Tracking Methods for New World and Old World Monkeys.

Eye-tracking methods measure what humans and other animals visually attend to in the environment. In nonhuman primates, eye tracking can be used to test hypotheses about how primates process social information. This information can further our understanding of primate behavior as well as offer unique translational potential to explore causes of or treatments for altered social processing as seen in people with neurodevelopmental disorders such as autism spectrum disorder and schizophrenia. However, previous methods for collecting eye-tracking data in nonhuman primates required some form of head restraint, which limits the opportunities for research with respect to the number of or kinds of primates that can undergo an eye-tracking study. We developed a novel, noninvasive method for collecting eye tracking data that can be used both in animals that are difficult to restrain without sedation as well as animals that are of different ages and sizes as the box size can be adjusted. Using a transport box modified with a viewing window, we collected eye-tracking data in both New (Callicebus cupreus) and Old World monkeys (Macaca mulatta) across multiple developmental time points. These monkeys had the option to move around the box and avert their eyes from the screen, yet, they demonstrated a natural interest in viewing species-specific imagery with no previous habituation to the eye-tracking paradigm. Provided with opportunistic data from voluntary viewing of stimuli, we found that juveniles viewed stimuli more than other age groups, videos were viewed more than static photo imagery, and that monkeys increased their viewing time when presented with multiple eye tracking sessions. This noninvasive approach opens new opportunities to integrate eye-tracking studies into nonhuman primate research

The impact of SBF2 on taxane-induced peripheral neuropathy.

Taxane-induced peripheral neuropathy (TIPN) is a devastating survivorship issue for many cancer patients. In addition to its impact on quality of life, this toxicity may lead to dose reductions or treatment discontinuation, adversely impacting survival outcomes and leading to health disparities in African Americans (AA). Our lab has previously identified deleterious mutations in SET-Binding Factor 2 (SBF2) that significantly associated with severe TIPN in AA patients. Here, we demonstrate the impact of SBF2 on taxane-induced neuronal damage using an ex vivo model of SBF2 knockdown of induced pluripotent stem cell-derived sensory neurons. Knockdown of SBF2 exacerbated paclitaxel changes to cell viability and neurite outgrowth while attenuating paclitaxel-induced sodium current inhibition. Our studies identified paclitaxel-induced expression changes specific to mature sensory neurons and revealed candidate genes involved in the exacerbation of paclitaxel-induced phenotypes accompanying SBF2 knockdown. Overall, these findings provide ex vivo support for the impact of SBF2 on the development of TIPN and shed light on the potential pathways involved

Abstract GS5-02: Detection of circulating tumor DNA (ctDNA) after neoadjuvant chemotherapy is significantly associated with disease recurrence in early-stage triple-negative breast cancer (TNBC): Preplanned correlative results from clinical trial BRE12-158

Abstract Background: A significant proportion of patients with early-stage TNBC are treated with neoadjuvant chemotherapy (NAC). Sequencing of ctDNA after surgery can be used to detect minimal residual disease and predict which patients may experience clinical recurrence. Methods: BRE12-158 is a recently completed Phase II clinical trial which randomized early-stage TNBC patients with residual disease after NAC to post-neoadjuvant genomically-directed therapy vs treatment of physician choice. 151 patients had a plasma sample collected at the time of treatment assignment (after surgery and radiation). ctDNA was successfully sequenced in 150 patients. 148 of the 150 sequenced patients had clinical follow-up. Sequencing was performed by Foundation Medicine using the FoundationOne Liquid assay which profiles for 70 commonly mutated oncogenes. Presence of mutated ctDNA was associated with distant disease free survival (DDFS) and overall survival (OS) in univariate analysis using the Log-Rank test, and in multi-variate analysis using Cox proportional hazards model. Results: Mutated ctDNA was detected in 94 of 148 sequenced patients (64%). TP53 was the most commonly mutated gene consistent with prior genomic studies of TNBC. At 16.7 months of median follow-up, detection of ctDNA was significantly associated with an inferior DDFS (median DDFS 32.5 months vs. Not Reached, p=0.0030). At 24 months, the DDFS probability was 53% in ctDNA-positive patients as compared to 81% in ctDNA-negative patients. In multi-variate analysis, when considering significant covariates, including: residual cancer burden (RCB); number of positive lymph nodes; tumor size; stage; grade; age; and race; detection of ctDNA remained independently associated with inferior DDFS (HR=3.1, CI: 1.4-6.8, p=0.0048). Similarly, detection of ctDNA was associated with inferior OS in univariate (p=0.021) and multi-variate analysis (HR=2.7, CI:1.1-6.2, p=0.022). Lastly, we observed a correlation between higher maximum somatic allele frequency and a shorter DDFS interval in multivariate analysis (HR=4.7, CI: 1.04-21.1, p=0.044) and shorter OS (HR=4.9, CI:1.06-22.4, p=0.041), suggesting that the quantitative degree of ctDNA burden is associated with clinical outcome. Conclusions: Detection of ctDNA in early-stage TNBC after neoadjuvant chemotherapy is an independent predictor of disease recurrence, and represents an important novel stratification factor for future post-neoadjuvant trials. Citation Format: Milan Radovich, Guanglong Jiang, Christopher Chitambar, Rita Nanda, Carla Falkson, Filipa C. Lynce, Christopher Gallagher, Claudine Isaacs, Marcelo Blaya, Elisavet Paplomata, Radhika Walling, Karen Daily, Reshma Mahtani, Michael A. Thompson, Robert Graham, Maureen E. Cooper, Dean C. Pavlick, Lee Albacker, Jeff Gregg, Casey L. Bales, Bradley A. Hancock, Erica Cantor, Fei Shen, Anna Maria V. Storniolo, Sunil Badve, Tarah Ballinger, Kathy D. Miller, Bryan P. Schneider. Detection of circulating tumor DNA (ctDNA) after neoadjuvant chemotherapy is significantly associated with disease recurrence in early-stage triple-negative breast cancer (TNBC): Preplanned correlative results from clinical trial BRE12-158 [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr GS5-02

Abstract PD9-10: BRE12-158: A post-neoadjuvant, randomized phase 2 trial of personalized therapy vs. treatment of physician’s choice for patients with residual triple negative breast cancer

Abstract Purpose: Patients with triple negative breast cancer (TNBC) with residual disease after neoadjuvant chemotherapy (NAC) have high risk of recurrence with prior data suggesting improved outcomes with capecitabine. Targeted agents have demonstrated activity across multiple cancer types. BRE12-158 was a phase 2, multicenter trial that randomized TNBC patients with residual disease after NAC to genomically-directed therapy vs. treatment of physician choice (TPC). Patients and Methods: From March 2014 to December 2018, 197 patients were enrolled. Residual tumors were sequenced using a next generation sequencing (NGS) test. A molecular tumor board adjudicated all results. Patients were randomized to 4 cycles of genomically-directed therapy (arm A) vs. TPC (arm B). Patients without a target were assigned to arm B. Primary endpoint was 2-year disease free survival (DFS) among randomized patients. Secondary/exploratory endpoints included: distant disease free survival (DDFS), overall survival (OS), toxicity assessment, time-based evolution of therapy, and drug-specific outcomes. Results: 193 patients were randomized or were assigned to arm B. The estimated 2-year DFS was 56.6% (95%CI:0.45-0.70) for arm A vs. 62.4% (95%CI:0.52-0.75) for randomized arm B. No difference was seen in DFS, DDFS, or OS for the entire or randomized populations. There was increased uptake of capecitabine for TPC over time. Patients randomized later had less distant recurrences. ctDNA status remained a significant predictor of outcome with some patients demonstrating clearance with post-neoadjuvant therapy. Conclusion: Genomically directed therapy was not superior to TPC for patients with residual TNBC after NAC. Capecitabine should remain the standard of care; however, the activity of other agents in this setting provides rationale for testing optimal combinations to improve outcomes for this high-risk population. ctDNA should be considered a standard covariate for trials in this setting. Citation Format: Bryan P Schneider, Guanglong Jiang, Tarah J Ballinger, Fei Shen, Christopher Chitambar, Rita Nanda, Carla Falkson, Filipa C Lynce, Christopher Gallagher, Claudine Isaacs, Marcelo Blaya, Elisavet Paplomata, Radhika Walling, Karen Daily, Reshma Mahtani, Michael A Thompson, Robert Graham, Maureen E Cooper, Dean C Pavlick, Lee A Albacker, Jeffery Gregg, Jeffery P Solzak, Yu-Hsiang Chen, Casey L Bales, Erica Cantor, Bradley A Hancock, Nawal Kassem, Paul Helft, Bert O'Neil, Anna Maria Storniolo, Sunil Badve, Kathy D Miller, Milan Radovich. BRE12-158: A post-neoadjuvant, randomized phase 2 trial of personalized therapy vs. treatment of physician’s choice for patients with residual triple negative breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD9-10

BRE12-158: A postneoadjuvant, randomized phase II trial of personalized therapy versus treatment of physician\u27s choice for patients with residual triple-negative breast cancer

Purpose: Patients with triple-negative breast cancer (TNBC) with residual disease after neoadjuvant chemotherapy (NAC) have high risk of recurrence with prior data suggesting improved outcomes with capecitabine. Targeted agents have demonstrated activity across multiple cancer types. BRE12-158 was a phase II, multicenter trial that randomly allocated patients with TNBC with residual disease after NAC to genomically directed therapy versus treatment of physician choice (TPC). Patients and methods: From March 2014 to December 2018, 193 patients were enrolled. Residual tumors were sequenced using a next-generation sequencing test. A molecular tumor board adjudicated all results. Patients were randomly allocated to four cycles of genomically directed therapy (arm A) versus TPC (arm B). Patients without a target were assigned to arm B. Primary end point was 2-year disease-free survival (DFS) among randomly assigned patients. Secondary/exploratory end points included distant disease-free survival, overall survival, toxicity assessment, time-based evolution of therapy, and drug-specific outcomes. Results: One hundred ninety-three patients were randomly allocated or were assigned to arm B. The estimated 2-year DFS for the randomized population only was 56.6% (95% CI, 0.45 to 0.70) for arm A versus 62.4% (95% CI, 0.52 to 0.75) for arm B. No difference was seen in DFS, distant disease-free survival, or overall survival for the entire or randomized populations. There was increased uptake of capecitabine for TPC over time. Patients randomly allocated later had less distant recurrences. Circulating tumor DNA status remained a significant predictor of outcome with some patients demonstrating clearance with postneoadjuvant therapy. Conclusion: Genomically directed therapy was not superior to TPC for patients with residual TNBC after NAC. Capecitabine should remain the standard of care; however, the activity of other agents in this setting provides rationale for testing optimal combinations to improve outcomes. Circulating tumor DNA should be considered a standard covariate for trials in this setting