SIGNIFICANCE: We demonstrate that combining large-scale GWA meta-analysis findings across cancer types can identify completely new risk loci common to breast, ovarian, and prostate cancers. We show that the identification of such cross-cancer risk loci has the potential to shed new light on the shared biology underlying these hormone-related cancers. Cancer Discov; 6(9); 1052-67. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 932.
Methods: This is a multinational, multicenter, longitudinal, and observational registry of PC patients presenting to participating tertiary-care hospitals in eight Asian countries (www.clinicaltrials.gov NCT02546908. Registry Identifier: NOPRODPCR4001). Approximately 3500-4000 eligible patients with existing or newly diagnosed high-risk localized PC (cohort 1), nonmetastatic biochemically recurrent PC (cohort 2), or metastatic PC (cohort 3) will be consecutively enrolled and followed-up for 5 years. An enrollment cap of 600 patients each will be applied to cohorts 1 and 2. Disease status is collected at enrollment, and outcome variables captured at 3-monthly intervals include diagnostic/staging, treatments including reason for change, laboratory results, comorbidities, and concomitant medications. Treatments and survival outcomes will be captured real time until study end. Patient-reported quality-of-life will be measured every 6 months, and medical resource utilization summarized at study end. Data analysis will include exploratory analyses of potential associations between multiple risk factors and socioeconomic variables with disease progression and evaluation of various treatments for PC including novel therapies on clinical outcome and health-related quality-of-life outcomes.
Results: 3636 men with PC were enrolled until July 2018; 416 in cohort 1, 399 in cohort 2 and 2821 in cohort 3.
Discussion: A total of 3636 patients were enrolled until July 2018. The prospective disease registry will provide comprehensive and wide-ranging real-world information on how PC is diagnosed and treated in Asia. Such information can be used to inform policy development for best practice and direct clinical study design evaluating new treatments.
MATERIALS AND METHODS: We searched PubMed and Scopus electronic databases to identify eligible reports on cognitive changes following PT of PBT according to PRISMA guidelines. Reports were extracted for information on demographics and cognitive outcomes. Then, they were systematically reviewed based on three themes: (1) comparison with photon therapy, (2) comparison with baseline cognitive measures, to population normative mean or radiotherapy-naïve PBT patients and (3) effects of dose distribution to cognition.
RESULTS: Thirteen reports (median size (range): 70 (12-144)) were included. Four reports compared the cognitive outcome between PBT patients treated with proton to photon therapy and nine compared with baseline/normative mean/radiotherapy naïve from which two reported the effects of dose distribution. Reports found significantly poorer cognitive outcome among patients treated with photon therapy compared with proton therapy especially in general cognition and working memory. Craniospinal irradiation (CSI) was consistently associated with poorer cognitive outcome while focal therapy was associated with minor cognitive change/difference. In limited reports available, higher doses to the hippocampus and temporal lobes were implicated to larger cognitive change.
CONCLUSION: Available evidence suggests that PT causes less cognitive deficits compared with photon therapy. Children who underwent focal therapy with proton were consistently shown to have low risk of cognitive deficit suggesting the need for future studies to separate them from CSI. Evidence on the effect of dose distribution to cognition in PT is yet to mature.