Ohio State University Hospital

Abstract Background The rising incidence of Breast cancer (BC) in young women requires further genomic characterization, as only a fraction carry a germline mutation. Given the growing interest in therapies targeting the phosphoinositide 3-kinase/AKT (PI3K/AKT), mammalian target of rapamycin (mTOR), and phosphatase and tensin homolog (PTEN) pathways, central to BC pathogenesis, we evaluated whether PI3K/AKT/mTOR pathway alterations and gene expression differed by age at BC diagnosis. Methods: In this analysis of patients’ tumor/germline whole exome DNA and RNA sequencing data from the Ohio State University Total Cancer Care registry, 71 profiled patients were young adults (YA) aged < 40 years, and 675 were non-YA aged ≥40 years. Descriptive statistics characterized the frequency and co-occurrence of BC-specific alterations and mRNA expression profiles by age groups. Results The prevalence of these BC-relevant mutations are reported in Table 1 Table: Prevalence of BC-relevant mutations by age cohort Mutation Age Group % of Patients with Mutation Fisher's Exact Test p-value (<40 vs ≥ 40) PIK3CA <40 16.9% (12/71) 0.0002 ≥ 40 39% (263/675) AKT1 <40 5.6% (4/71) 0.220 ≥40 10.8% (73/675) mTOR <40 16.9% (12/71) 0.450 ≥40 21.5% (145/675) PTEN <40 12.7% (9/71) 0.550 ≥40 10.5% (71/675) . PIK3CA mutation occurred more frequently in non-YA patients (16.9% YA versus (vs) 39% non-YA; p<0.0002). The frequency of driver mutations were similar between cohorts (73% in YA vs 82% in non-YA). Most hotspot mutations were enriched in non-YA group, particularly H1047R (15.11% n=102 non-YA vs 4.23%, n=3 YA; p= 0.01). Others include: E545K (6.52%, n=44 vs 2.82%, n=2, p=0.302), E542K (4.59%, n=31 vs 1.41%, n=1; p=0.352); H1047L (1.93%, n=13 vs none, p=0.625) and N345K (1.78%, n=12 vs 1.41% n=1; p=1.00). There were no age-based differences in AKT1 mutation (5.6% YA vs 10.8% non-YA patients; p=0.220). Hotspot alterations E17K, E17G, and L52R were numerically enriched, albeit nonsignificant, in non-YA. There were no significant differences in the presence of mTOR by age (16.9% YA and 21.5% non-YA; p=0.450). Most alterations in both groups were variants of unknown significance (17/17 in YA, 157/159 in non-YA). YA and non-YA cohorts had similar frequency of PTEN mutations (12.7% YA vs 10.5% non-YA; p=0.550). The proportion of PTEN driver mutations also did not differ (82% YA and 93% non-YA). Conclusion PIK3CA mutations were more prevalent among non-YAs highlighting potential age-associated oncogenic drivers. Although AKT1, mTOR, and PTEN gene mutations did not differ between age groups, in general, oncogenic/hotspot mutations occurred more frequently in patients ≥40 years. As management of BC evolves to incorporate PI3K/AKT/mTOR inhibitors, age-specific somatic alterations may uncover therapeutic vulnerabilities and inform customized treatment. Citation Format: N. Lopetegui-Lia, A. Davenport, J. Gill, A. M. Roy, S. Myers, D. Agnese, E. Burke, T. Y. Andraos, D. M. Schimming, S. Hulett, H. LeFebvre, M. Gatti-Mays, D. Stover. Age-driven genomic differences in breast cancer: relevance for PI3K-pathway [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-03-03.

Black patients with metastatic prostate cancer have higher mortality rates compared to non-Hispanic White patients. There are no data on outcomes with [177Lu]Lu-PSMA-617 (LuPSMA) across racial groups. We evaluated the association between race and outcomes with LuPSMA in a multi-institutional cohort of consecutive patients with mCRPC treated with LuPSMA. The primary outcomes were PSA-50 rate, PSA-progression-free survival (PSA-PFS), and overall survival (OS). Statistical models were adjusted for age, number of prior therapies, sites of metastases, and baseline PSA. A total of 654 patients were included; 593 (91%) were White, 45 (7%) were Black and 16 (2%) were another non-Black minority (NBM). There were no statistically significant differences in PSA-50 rates, PSA-PFS and OS between the groups. Black and White patients treated with LuPSMA had similar clinical outcomes; efforts are needed to ensure Black and NBM patients have equal access to life prolonging therapies to narrow disparities in outcomes.

Abstract Background In patients with hypertrophic cardiomyopathy (HCM), the prognostic value of native T1 and extracellular volume fraction (ECV) for adverse cardiovascular events has not been well defined. Methods Consecutive 663 participants with HCM who underwent cardiovascular magnetic resonance (CMR) were recruited. The follow-up endpoints included heart failure (HF)-related death and sudden cardiac death (SCD) or aborted SCD. Results During the median follow-up time of 44 months (interquartile range [IQR]: 23 to 66.0 months), 56 (8.4%) participants reached composite endpoints including 38 (5.7%) with SCD or aborted SCD, 16 (2.4%) with HF-related death and 2 (0.3%) with heart transplantation. On multivariable Cox proportional hazards regression analyses, native T1 including late gadolinium enhancement (LGE) from three short axes were significantly associated with cardiac death (basal native T1: hazard ratio [HR], 1.06 per 10 ms increase; 95% confidence interval [CI], 1.02 to 1.09; middle native T1: HR, 1.05 per 10 ms increase; 95% CI, 1.01 to 1.09; apical native T1: HR, 1.04 per 10 ms increase; 95% CI, 1.02 to 1.07; all P < 0.05) after adjustment for non-sustained ventricular tachycardia, history of syncope, the extent of LGE, left atrial size, and NYHA class. Conversely, only basal ECV was associated with cardiac death (basal ECV including LGE area: HR, 1.08 per 1% increase, 95%CI, 1.03 to 1.13, P = 0.001; basal ECV excluding LGE: HR, 1.1 per 1% increase; 95%CI, 1.04 to 1.16; P < 0.001) In addition, participants with increased mean native T1 (≥1349.4 ms) or basal ECV(≥ 29.4%) were more likely to suffer from cardiac death in the entire study cohort or the subgroup with low LGE extent (<15%) or low ESC risk score (<6%) (all P < 0.05). Furthermore, the addition of mean LV native T1 (≥1349.4 ms) or basal ECV (≥ 29.4%) to current risk factors in the guidelines could further improve prediction for the composite endpoint (C-index increased to 0.719 from 0.521 for the AHA/ACC risk model, P < 0.001; C index increased to 0.709 from 0.514 for the ESC risk model; P < 0.001). Conclusions In this study of patients with HCM, mean native T1 of three short axes and basal ECV were independently associated with cardiac death and added incremental value to conventional clinical predictors for patients with HCM.Figure 1.Demonstrative images.Figure 2 Incremental Value of T1 mapping

This chapter discusses how custodial sentences can be more efficient and effective by engaging those detained with interventions consistent with the Risk, Needs, Responsivity (RNR) evidence base. It discusses key features of best practice interventions with persons in jails, prisons, psychiatric hospitals and civil commitment facilities. Secure settings are one among a continuum of distinct tertiary prevention settings. Efficacy is highly impacted by the length and conditions of mandated institutionalisation. Designing interventions for sex offending populations must consider both efficacy and ethics. RNR-based interventions effectively reduce sexual recidivism, as much as by 69%. Challenges and opportunities for implementing What Works with individuals mandated to secure settings for sexual offending problems are grouped for the RNR principles. Adhering to the Need principle in secure settings means that amply trained, qualified staff assess participants' Needs, using empirically validated structured assessment tools. Implementing the Responsivity principle can be particularly challenging in secure settings.

12114 Background: Sensory vincristine-related neuropathy is a well-known toxicity of front-line lymphoma treatments, potentially negatively impacting both disease outcomes as well as the long-term quality of life of cancer survivors. Most aggressive non-Hodgkin lymphomas are curable with the multi-agent chemotherapy regimens CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or infusional dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin). This pilot study aimed to characterize and describe chemotherapy-induced peripheral neuropathy (CIPN) outcomes, utilizing patient and clinician-reported outcome measures and neurofilament light chains (NF-L). Nf-L, released in response to axonal damage, is emerging as a sensitive blood-based biomarker for CIPN. Studies in rats have demonstrated repeated vincristine exposure correlated with increased serum NF-L light chains and progressive damage. This has not previously been reported in humans. Methods: A single-center prospective study assessed CIPN toxicity in people with aggressive non-Hodgkin’s lymphoma treated with CHOP and EPOCH. Patient-reported outcome (PRO) measures included the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy Induced Peripheral Neuropathy (EORTC QLQ-CIPN20) questionnaire. Items 19 and 20 were excluded. The clinician-reported outcome measure was the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5.0). Outcomes were evaluated at three time points: (1) Baseline, (2) Immediately before cycle four, and (3) Immediately before cycle six. Blood samples were collected from participants and processed for plasma Nf-L chain analysis. Results: There were 26 participants at baseline (CHOP: n = 17, EPOCH: n = 9), 21 participants at time point 2 (CHOP: n = 17, EPOCH: n = 7), and 16 participants at time point 3 (CHOP: n = 10, EPOCH n = 6). The mean CIPN-18 scores increased at each time point and were not significantly different by chemotherapy type. Five of the 16 participants (31.3%) experienced CIPN ≥ grade 1 at time point 3. A significant relationship existed between the CIPN-18 and the CTCAE (r- 0.39, p =0.002) and between CIPN-18 and Nf-L levels (r= 0.42, p = 0.002). The mean Nf-L levels increased from the first time point (mean = 54.4 pg/mL, 16-187.9 pg/mL) to the second time point (mean = 108.7 pg/mL, 37-232.2 pg/mL) and remained significantly elevated at Time Point 3 (mean = 92pg/mL, 34-172.2 pg/mL). Conclusions: One-third of all participants were experiencing symptoms of CIPN by the third time point (cycle six of therapy), as measured by the CTCAE > 0 and the CIPN-18 > 20. Our study lays the groundwork for using Nf-L as a potential biomarker, in combination with PROs, to identify, recognize, and measure vincristine-induced neurotoxicity.

Introduction: Hypertensive disorders of pregnancy (HDP) are risk factors for cardiovascular disease (CVD). However, associations between subclinical blood pressure (BP) elevations in pregnancy and CVD risk are unknown. Aims: To identify BP patterns during pregnancy among individuals without HDP and determine their association with long-term CVD risk and hypertension (HTN) 2-7 years after delivery. Methods: We included nulliparous individuals from the prospective, multicenter nuMoM2b Study Heart Health Study (nuMoM2b-HHS) who had > 1 BP from each trimester, and excluded those with chronic HTN or HDP. We modeled patterns using group-based trajectory analysis of the mid-BP (average of systolic and diastolic BP) during pregnancy. We selected the final number of groups based on the Bayesian Information Criteria. At 2-7 years after delivery, 30-year predicted CVD risk was estimated using the Framingham risk score; incident HTN was defined as BP > 130/80. Generalized linear models estimated associations between mid-BP trajectory group and CVD risk, adjusting for sociodemographics, adverse pregnancy outcomes, and first-trimester mid-BP. Results: Of 3309 participants, mean age was 27.1 (SD 5.5) years. Five mid-BP groups were identified ( FIGURE ). Incident HTN at mean follow-up of 3.7 years after delivery was 4.2% in low-stable, 11.1% moderate-stable, 21.4% moderate-decreasing, 21.8% moderate increasing, and 44.2% in elevated-stable groups. Compared with the moderate-stable group, adjusted 30-year predicted CVD risk was significantly higher by 0.8% (0.4, 1.1), 1.6% (0.9, 2.3) and 2.6% (2.1, 3.1) in the moderate-decreasing, moderate-increasing and elevated-stable groups, respectively. Conclusions: Among people not meeting HDP criteria, but with elevated mid-BP during pregnancy, nearly half had HTN within 5 years after delivery, and long-term CVD risk was higher. Mid-BP elevations during pregnancy may inform long-term CVD risk even in the absence of HDP.