Although black women experienced greater cervical cancer incidence and mortality rate reduction in recent years, they continue to have higher incidence rates than whites. Great variations also exist among geographic regions of the US, with the South having both the highest incidence and mortality rates compared to other regions. The present study explores the question of whether living in the South is associated with greater racial disparity in cervical cancer incidence and mortality by examining race- and region-specific rates and the trend between 2000 and 2012. The Surveillance, Epidemiology, and End Results (SEER) 18 Program data was used. Cervical cancer incidence and mortality rates, annual percent changes, and disparity ratios were calculated using SEER*Stat software and Joinpoint regression for four groups: US14-Non-Hispanic White (NHW), US14-Non-Hispanic Black (NHB), South-NHW, and South-NHB, where South included 4 registries from Georgia and Louisiana and US14 were 14 US registries except the four South registries. The average age-adjusted cervical cancer incidence rate was the highest among South-NHBs (11.1) and mortality rate was the highest among US14-NHBs (5.4). In 2012, the degree of racial disparities between South-NHBs and South-NHWs was greater in terms of mortality rates (NHB:NHW = 1.80:1.35) than incidence rates (NHB:NHW = 1.45:1.15). While mortality disparity ratios decreased from 2000–2012 for US14-NHB (APC: -1.9(-2.3,-1.4), mortality disparity ratios for South-NHWs (although lower than NHBs) increased compared to US14-NHW. Incidence rates for NHBs continued to increase with increasing age, whereas rates for NHWs decreased after age 40. Mortality rates for NHBs dramatically increased at age 65 compared to a relatively stable trend for NHWs. The increasing racial disparity with increasing age in terms of cervical cancer incidence rates became more pronounced when corrected for hysterectomy prevalence. Black race and South region were associated with higher cervical cancer incidence and mortality. Cervical cancer rates uncorrected for hysterectomy may underestimate regional and racial disparities. Increasing incidence rates for older NHBs compared to NHWs warrant further research to determine whether screening should continue for NHBs over age 65.

EFFECT OF LONG-TERM EXPOSURE TO LOWER LOW-DENSILIPOPROTEIN CHOLESTEROL BEGINNING EARLY IN LIFE ON THE RISK OF CORONARY HEART DISEASE. A MENDELIAN RANDOMIZATION ANALYSIS

Myeloproliferative neoplasm (MPN) patients often report high symptom burden that persists despite the best available pharmacologic therapy. Meditation has gained popularity in recent decades as a way to manage cancer patient symptoms. The aim of this study was to examine the feasibility of 2 different consumer-based meditation smartphone apps in MPN patients and to examine the limited efficacy of smartphone-based meditation on symptoms compared with an educational control group. Patients (n=128) were recruited nationally through organizational partners and social media. Eligible and consented patients were enrolled into 1 of 4 groups, 2 of which received varying orders of 2 consumer-based apps (10% Happier and Calm) and 2 that received one of the apps alone for the second 4 weeks of the 8-week intervention after an educational control condition. Participants were asked to perform 10 min of meditation per day irrespective of the app and the order in which they received the apps. Feasibility outcomes were measured at weeks 5 and 9 with a Web-based survey. Feasibility outcomes were acceptability, demand, and limited efficacy for depression, anxiety, pain intensity, sleep disturbance, sexual function, quality of life, global health, and total symptom burden. A total of 128 patients were enrolled across all 4 groups, with 73.4% (94/128) patients completing the intervention. Of the participants who completed the 10% Happier app, 61% (46/76) enjoyed it, 66% (50/76) were satisfied with the content, and 77% (59/76) would recommend to others. Of those who completed the Calm app, 83% (56/68) enjoyed it, 84% (57/68) were satisfied with the content, and 97% (66/68) would recommend to others. Of those who completed the educational control, 91% (56/61) read it, 87% (53/61) enjoyed it, and 71% (43/61) learned something. Participants who completed the 10% Happier app averaged 31 (SD 33) min/week; patients completing the Calm app averaged 71 (SD 74) min/week. 10% Happier app participants saw small effects on anxiety (P<.001 d=-0.43), depression (P=.02; d=-0.38), sleep disturbance (P=.01; d=-0.40), total symptom burden (P=.13; d=-0.27), and fatigue (P=.06; d=-0.30), and moderate effects on physical health (P<.001; d=0.52). Calm app participants saw small effects on anxiety (P=.29; d=-0.22), depression (P=.09; d=-0.29), sleep disturbance (P=.002; d=-0.47), physical health (P=.005; d=0.44), total symptom burden (P=.13; d=-0.27), and fatigue (P=.13; d=-0.27). Educational control participants (n=61) did not have effects on any patient-reported outcome except for a moderate effect on physical health (P<.001; d=0.77). Delivering meditation via the Calm app is feasible and scored higher in terms of feasibility when compared with the 10% Happier app. The Calm app will be used to implement a randomized controlled trial, testing the effects of meditation on symptom burden in MPNs. ClinicalTrials.gov NCT03726944; https://clinicaltrials.gov/ct2/show/NCT03726944 (Archived by WebCite at http://www.webcitation.org/77MVdFJwM).

Histone deacetylase (HDAC) inhibitors have garnered considerable interest for the treatment of adult and pediatric malignant brain tumors. However, owing to their broad-spectrum nature and inability to effectively penetrate the blood-brain barrier, HDAC inhibitors have failed to provide substantial clinical benefit to patients with glioblastoma (GBM) to date. Moreover, global inhibition of HDACs results in widespread toxicity, highlighting the need for selective isoform targeting. Although no isoform-specific HDAC inhibitors are currently available, the second-generation hydroxamic acid–based HDAC inhibitor quisinostat possesses subnanomolar specificity for class I HDAC isoforms, particularly HDAC1 and HDAC2. It has been shown that HDAC1 is the essential HDAC in GBM. This study analyzed the neuropharmacokinetic, pharmacodynamic, and radiation-sensitizing properties of quisinostat in preclinical models of GBM. It was found that quisinostat is a well-tolerated and brain-penetrant molecule that extended survival when administered in combination with radiation in vivo. The pharmacokinetic-pharmacodynamic-efficacy relationship was established by correlating free drug concentrations and evidence of target modulation in the brain with survival benefit. Together, these data provide a strong rationale for clinical development of quisinostat as a radiosensitizer for the treatment of GBM.

Rapid growth of mobile technologies has resulted in a proliferation of lifestyle-oriented mobile phone apps. However, most do not have a theoretical framework and few have been developed using a community-based participatory research approach. A community academic team will develop a theory-based, culturally tailored, mobile-enabled, Web-based app-the Mobile Cancer Prevention App (mCPA)-to promote adherence to dietary and physical activity guidelines. The aim of this study is to develop mCPA content with input from breast cancer survivors. Members of SISTAAH (Survivors Involving Supporters to Take Action in Advancing Health) Talk (N=12), treated for Stages I-IIIc breast cancer for less than 1 year, 75 years of age or younger, and English-speaking and writing, will be recruited to participate in the study. To develop the app content, breast cancer survivors will engage with researchers in videotaped and audiotaped sessions, including (1) didactic instructions with goals for, benefits of, and strategies to enhance dietary intake and physical activity, (2) guided discussions for setting individualized goals, monitoring progress, and providing or receiving feedback, (3) experiential nutrition education through cooking demonstrations, and (4) interactive physical activity focused on walking, yoga, and strength training. Qualitative (focus group discussions and key informant interviews) and quantitative (sensory evaluation) methods will be used to evaluate the participatory process and outcomes. Investigators and participants anticipate development of an acceptable (frequency and duration of usage) feasible (structure, ease of use, features), and accessible mobile app available for intervention testing in early 2017. Depending on the availability of research funding, mCPA testing, which will be initiated in Miami, will be extended to Chicago, Houston, Philadelphia, and Los Angeles.

Purpose: Ceritinib is an orally bioavailable, small-molecule inhibitor of anaplastic lympoma kinase (ALK), insulin-like growth factor 1 receptor (IGFR1), and focal adhesion kinase (FAK), which are highly expressed in glioblastoma and many brain metastases. Preclinical and clinical studies indicate that ceritinib has antitumor activity in central nervous system (CNS) malignancies. This phase 0 trial measured the tumor pharmacokinetics (PK) and pharmacodynamics (PD) of ceritinib in patients with brain metastasis or recurrent glioblastoma. Patients and Methods: Preoperative patients with brain tumors demonstrating high expression of pSTAT5b/pFAK/pIGFR1 were administered ceritinib for 10 days prior to tumor resection. Plasma, tumor, and cerebrospinal fluid (CSF) samples were collected at predefined timepoints following the final dose. Total and unbound drug concentrations were determined using LC-MS/MS. In treated tumor and matched archival tissues, tumor PD was quantified through IHC analysis of pALK, pSTAT5b, pFAK, pIGFR1, and pIRS1. Results: Ten patients (3 brain metastasis, 7 glioblastoma) were enrolled and no dose-limiting toxicities were observed. Ceritinib was highly bound to human plasma protein [median fraction unbound (Fu), 1.4%] and to brain tumor tissue (median Fu, 0.051% and 0.045% in gadolinium-enhancing and -nonenhancing regions respectively). Median unbound concentrations in enhancing and nonenhancing tumor were 0.048 and 0.006 μmol/L, respectively. Median unbound tumor-to-plasma ratios were 2.86 and 0.33 in enhancing and nonenhancing tumor, respectively. No changes in PD biomarkers were observed in the treated tumor samples as compared to matched archival tumor tissue. Conclusions: Ceritinib is highly bound to plasma proteins and tumor tissues. Unbound drug concentrations achieved in brain metastases and patients with recurrent glioblastoma were insufficient for target modulation.