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Background: Androgen deprivation therapy (ADT) inhibits prostate cancer growth. However, ADT causes loss of bone mineral density (BMD) and an increase in fracture risk; effective interventions for ADT‐induced bone loss are limited. Methods: A phase 2 randomized controlled trial investigated the feasibility, safety, and preliminary efficacy of high‐dose weekly vitamin D (HDVD, 50,000 IU/week) versus placebo for 24 weeks in patients with prostate cancer receiving ADT, with all subjects receiving 600 IU/day vitamin D and 1000 mg/day calcium. Participants were ≥60 years (mean years, 67.7), had a serum 25‐hydroxyvitamin D level <32 ng/mL, and initiated ADT within the previous 6 months. At baseline and after intervention, dual‐energy x‐ray absorptiometry was used to assess BMD, and levels of bone cell, bone formation, and resorption were measured. Results: The HDVD group (N = 29) lost 1.5% BMD at the total hip vs. 4.1% for the low‐dose group (N = 30; p =.03) and 1.7% BMD at the femoral neck vs. 4.4% in the low‐dose group (p =.06). Stratified analyses showed that, for those with baseline 25‐hydroxyvitamin D level <27 ng/mL, the HDVD group lost 2.3% BMD at the total hip vs 7.1% for the low‐dose group (p <.01). Those in the HDVD arm showed significant changes in parathyroid hormone (p <.01), osteoprotegerin (p < 0.01), N‐terminal telopeptide of type 1 collagen (p < 0.01) and C‐terminal telopeptide of type 1 collagen (p < 0.01). No difference in adverse events or toxicity was noted between the groups. Conclusions: HDVD supplementation significantly reduced hip and femoral neck BMD loss, especially for patients with low baseline serum 25‐hydroxyvitamin D levels, although demonstrating safety and feasibility in prostate cancer patients on ADT. Patients with prostate cancer on androgen deprivation therapy often suffer rapid bone loss during the initiation of treatment. Supplementation with high‐dose vitamin D (50,000 IU/week plus 800 IU/day) significantly and safely decreased the amount of bone loss compared with vitamin D supplementation using the recommended daily allowance (800 IU/day). [ABSTRACT FROM AUTHOR]

Hydroxyurea is approved for treating children and adults with sickle cell anemia (SCA). Despite its proven efficacy, concerns remain about its mutagenic and carcinogenic potential that hamper its widespread use. Cell culture‐ and animal‐based investigations indicate that hydroxyurea's genotoxic effects are due to indirect clastogenicity in select cell types when high dose and time thresholds are exceeded (reviewed by Ware & Dertinger, 2021). The current study extends these preclinical observations to pediatric patients receiving hydroxyurea for treatment of SCA. First, proof‐of‐principle experiments with testicular cancer patients exposed to a cisplatin‐based regimen validated the ability of flow cytometric blood‐based micronucleated reticulocyte (MN‐RET) and PIG‐A mutant reticulocyte (MUT RET) assays to detect clastogenicity and gene mutations, respectively. Second, these biomarkers were measured in a cross‐sectional study with 26 SCA patients receiving hydroxyurea and 13 SCA patients without exposure. Finally, a prospective study was conducted with 10 SCA patients using pretreatment blood samples and after 6 or 12 months of therapy. Cancer patients exposed to cisplatin exhibited increased MN‐RET within days of exposure, while the MUT RET endpoint required more time to reach maximal levels. In SCA patients, hydroxyurea induced MN‐RET in both the cross‐sectional and prospective studies. However, no evidence of PIG‐A gene mutation was found in hydroxyurea‐treated children, despite the fact that the two assays use the same rapidly‐dividing, highly‐exposed cell type. Collectively, these results reinforce the complementary nature of MN‐RET and MUT RET biomarkers, and indicate that hydroxyurea can be clastogenic but was not mutagenic in young patients with SCA. [ABSTRACT FROM AUTHOR]

Purpose: Deficits in speech understanding constitute one of the most severe consequences of hearing loss. Here we investigate the clinical and genetic risk factors for symmetric deterioration of speech recognition thresholds (SRT) among cancer survivors treated with cisplatin. Methods: SRT was measured using spondaic words and calculating the mean of measurements for both ears with symmetric SRT values. For clinical associations, SRT‐based hearing disability (SHD) was defined as SRT≥15 dB hearing loss and clinical variables were derived from the study dataset. Genotyped blood samples were used for GWAS with rank‐based inverse normal transformed SRT values as the response variable. Age was used as a covariate in association analyses. Results: SHD was inversely associated with self‐reported health (p = 0.004). Current smoking (p = 0.002), years of smoking (p = 0.02), BMI (p < 0.001), and peripheral motor neuropathy (p = 0.003) were positively associated with SHD, while physical activity was inversely associated with SHD (p = 0.005). In contrast, cumulative cisplatin dose, peripheral sensory neuropathy, hypertension, and hypercholesterolemia were not associated with SHD. Although no genetic variants had an association p value < 5 × 10−8, 22 genetic variants were suggestively associated (p < 10−5) with SRT deterioration. Three of the top variants in 10 respective linkage disequilibrium regions were either positioned within the coding sequence or were eQTLs for genes involved in neuronal development (ATE1, ENAH, and ZFHX3). Conclusion: Current results improve our understanding of risk factors for SRT deterioration in cancer survivors. Higher BMI, lower physical activity, and smoking are associated with SHD. Larger samples would allow for expansion of the current findings on the genetic architecture of SRT. [ABSTRACT FROM AUTHOR]

This report summarizes the presentations, discussions, and recommendations of the most recent American Geriatrics Society and National Institute on Aging research conference, "Cancer and Cardiovascular Disease," on October 18–19, 2021. The purpose of this virtual meeting was to address the interface between cancer and heart disease, which are the two leading causes of death among older Americans. Age‐related physiologic changes are implicated in the pathogenesis of both conditions. Emerging data suggest that cancer‐related cardiovascular disease (CVD) involves disrupted cell signaling and cellular senescence. The risk factors for CVD are also risk factors for cancer and an increased likelihood of cancer death, and people who have both cancer and CVD do more poorly than those who have only cancer or only CVD. Issues addressed in this bench‐to‐bedside conference include mechanisms of cancer and CVD co‐development in older adults, cardiotoxic effects of cancer therapy, and management of comorbid cancer and CVD. Presenters discussed approaches to ensure equitable access to clinical trials and health care for diverse populations of adults with CVD and cancer, mechanisms of cancer therapy cardiotoxicity, and management of comorbid CVD and cancer, including the role of patient values and preferences in treatment decisions. Workshop participants identified many research gaps and questions that could lead to an enhanced understanding of comorbid CVD and cancer and to better and more equitable management strategies. [ABSTRACT FROM AUTHOR]

Purpose: Cisplatin is a critical component of first‐line chemotherapy for several cancers, but causes peripheral sensory neuropathy, hearing loss, and tinnitus. We aimed to identify comorbidities for cisplatin‐induced neurotoxicities among large numbers of similarly treated patients without the confounding effect of cranial radiotherapy. Methods: Utilizing linear and logistic regression analyses on 1680 well‐characterized cisplatin‐treated testicular cancer survivors, we analyzed associations of hearing loss, tinnitus, and peripheral neuropathy with nongenetic comorbidities. Genome‐wide association studies and gene‐based analyses were performed on each phenotype. Results: Hearing loss, tinnitus, and peripheral neuropathy, accounting for age and cisplatin dose, were interdependent. Survivors with these neurotoxicities experienced more hypertension and poorer self‐reported health. In addition, hearing loss was positively associated with BMIs at clinical evaluation and nonwork‐related noise exposure (>5 h/week). Tinnitus was positively associated with tobacco use, hypercholesterolemia, and noise exposure. We observed positive associations between peripheral neuropathy and persistent vertigo, tobacco use, and excess alcohol consumption. Hearing loss and TXNRD1, which plays a key role in redox regulation, showed borderline significance (p = 4.2 × 10−6) in gene‐based analysis. rs62283056 in WFS1 previously found to be significantly associated with hearing loss (n = 511), was marginally significant in an independent replication cohort (p = 0.06; n = 606). Gene‐based analyses identified significant associations between tinnitus and WNT8A (p = 2.5 × 10−6), encoding a signaling protein important in germ cell tumors. Conclusions: Genetics variants in TXNRD1 and WNT8A are notable risk factors for hearing loss and tinnitus, respectively. Future studies should investigate these genes and if replicated, identify their potential impact on preventive strategies. [ABSTRACT FROM AUTHOR]

BACKGROUND/OBJECTIVE: Exercise interventions improve anxiety and mood disturbances in patients with cancer. However, studies are limited in older adults with cancer. We assessed the effects of exercise on anxiety, mood, and social and emotional well‐being in older patients with cancer during their first 6 weeks of chemotherapy. DESIGN: Exploratory secondary analysis of a randomized controlled trial (RCT). SETTING: Community oncology practices. PARTICIPANTS: Older patients (aged 60 years or older) undergoing chemotherapy (N = 252). INTERVENTION: Patients were randomized to Exercise for Cancer Patients (EXCAP) or usual care (control) for the first 6 weeks of chemotherapy. EXCAP is a home‐based, low‐ to moderate‐intensity progressive walking and resistance training program. MEASUREMENTS: Analysis of covariance, with study arm as the factor, baseline value as the covariate, and study arm × baseline interaction, was used to evaluate arm effects on postintervention anxiety (State Trait Anxiety Inventory [STAI]), mood (Profile of Mood States [POMS]), and social and emotional well‐being (Functional Assessment of Cancer Therapy–General subscales) after 6 weeks. RESULTS: Median age was 67 years; 77% had breast cancer. Statistically significant group differences were observed in the STAI score (P = .001), POMS score (P = .022), social well‐being (P = .002), and emotional well‐being (P = .048). For each outcome, EXCAP patients with worse baseline scores had larger improvements at 6 weeks; these improvements were clinically significant for STAI score and social well‐being. CONCLUSIONS: Among older cancer patients receiving chemotherapy, a 6‐week structured exercise program improved anxiety and mood, especially among those participants with worse baseline symptoms. Additional RCTs are needed to confirm these findings and evaluate the appropriate exercise prescription for managing anxiety, mood, and well‐being in this patient population. J Am Geriatr Soc 67:1005–1011, 2019. [ABSTRACT FROM AUTHOR]

Objective To describe the management strategies and outcomes of patients with renal medullary carcinoma ( RMC) and characterise predictors of overall survival ( OS). Patients and Methods RMC is a rare and aggressive malignancy that afflicts young patients with sickle cell trait; there are limited data on management to date. This is a study of patients with RMC who were treated in 2000-2015 at eight academic institutions in North America and France. The Kaplan-Meier method was used to estimate OS, measured from initial RMC diagnosis to date of death. Cox regression analysis was used to determine predictors of OS. Results In all, 52 patients (37 males) were identified. The median (range) age at diagnosis was 28 (9-48) years and 49 patients (94%) had stage III/ IV. The median OS for all patients was 13.0 months and 38 patients (75%) had nephrectomy. Patients who underwent nephrectomy had superior OS compared to patients who were treated with systemic therapy only (median OS 16.4 vs 7.0 months, P < 0.001). In all, 45 patients received chemotherapy and 13 (29%) had an objective response; 28 patients received targeted therapies, with 8-week median therapy duration and no objective responses. Only seven patients (13%) survived for >24 months. Conclusions RMC carries a poor prognosis. Chemotherapy provides palliation and remains the mainstay of therapy, but <20% of patients survive for >24 months, underscoring the need to develop more effective therapy for this rare tumour. In this study, nephrectomy was associated with improved OS. [ABSTRACT FROM AUTHOR]

BACKGROUND Survivors of Hodgkin lymphoma (HL) are at an increased risk of developing second malignancies. To the authors' knowledge, the risks of head and neck cancer (HNC) after HL and subsequent survival have not been thoroughly investigated. METHODS From the US population-based Surveillance, Epidemiology, and End Results (SEER) database for 1973 through 2011, survivors of HL who developed HNC as a second cancer were analyzed. Patients with a first primary HNC were used as a comparison group. Observed-to-expected ratios and summary statistics were performed on patients with HL with squamous cell carcinoma (HL-SCC) and salivary gland cancer (HL-SGC). The impact of HL history on overall survival was assessed using a multivariate Cox proportional hazards model. RESULTS The observed-to-expected ratio for SCC among patients with HL was 1.73 (95% confidence interval [95% CI], 1.36-2.16; P<.05), whereas it was 8.56 for SGC (95% CI, 5.82-12.15; P<.05). Using Cox proportional hazards modeling, a history of HL was found to be an adverse prognostic factor for overall survival for SCC (hazard ratio, 1.37; 95% CI, 1.08-1.73 [ P = .009]) but not SGC (hazard ratio, 1.21; 95% CI, 0.82-1.79 [ P = .34]). The inferior survival of the patients in the HL-SCC cohort appears to be attributable to more deaths from HL and other malignancies diagnosed after SCC. CONCLUSIONS There is a significantly increased risk of salivary and nonsalivary HNC after HL, and worse survival for patients with HL-SCC versus those with a first primary SCC. Clinicians should be aware of the risks of HNC after HL. In the absence of evidence-based criteria, the authors recommend that survivors of HL undergo periodic head and neck examination. Cancer 2015;121:1436-1445. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]