Genomic Classifier for Guiding Treatment of Intermediate-Risk Prostate Cancers to Dose-Escalated Image Guided Radiation Therapy Without Hormone Therapy.

PURPOSE: The National Comprehensive Cancer Network (NCCN) has recently endorsed the stratification of intermediate-risk prostate cancer (IR-PCa) into favorable and unfavorable subgroups and recommend the addition of androgen deprivation therapy (ADT) to radiation therapy (RT) for unfavorable IR-PCa. Recently, more accurate prognostication was demonstrated by integrating a 22-feature genomic classifier (GC) to the NCCN stratification system. Here, we test the utility of the GC to better identify patients with IR-PCa who are sufficiently treated by RT alone. METHODS AND MATERIALS: We identified a novel cohort comprising 121 patients with IR-PCa treated with dose-escalated image guided RT (78 Gy in 39 fractions) without ADT. GC scores were derived from tumors sampled in diagnostic biopsies. Multivariable analyses, including both NCCN subclassification and GC scores, were performed for biochemical failure (prostate-specific antigen nadir + 2 ng/mL) and metastasis occurrence. RESULTS: By NCCN subclassification, 33 (27.3%) and 87 (71.9%) of men were classified as having favorable and unfavorable IR-PCa, respectively (1 case unclassifiable). GC scores were high in 3 favorable IR-PCa and low in 60 unfavorable IR-PCa. Higher GC scores, but not NCCN risk subgroups, were associated with biochemical relapse (hazard ratio, 1.36; 95% confidence interval [CI], 1.09-1.71] per 10% increase; P = .007) and metastasis (hazard ratio, 2.05; 95% CI, 1.24-4.24; P = .004). GC predicted biochemical failure at 5 years (area under the curve, 0.78; 95% CI, 0.59-0.91), and the combinatorial NCCN + GC model significantly outperformed the NCCN alone model for predicting early-onset metastasis (area under the curve for 5-year metastasis of 0.89 vs 0.86 [GC alone] vs 0.54 [NCCN alone]). CONCLUSIONS: We demonstrated the accuracy of the GC for predicting disease recurrence in IR-PCa treated with dose-escalated image guided RT alone. Our findings highlight the need to evaluate this GC in a prospective clinical trial investigating the role of ADT-RT in clinicogenomic-defined IR-PCa subgroups.

Bringing it all together: effective maternal and child health practice as a means to improve public health.

Effective maternal and child health (MCH) practice requires skillfully combining a number of theoretical models and frameworks to support systems addressing the health needs of women, children, and families. This paper describes three perspectives relevant to current MCH practice: the federal Maternal & Child Health Bureau's Pyramid of MCH Health Services [1], Frieden's Health Impact Pyramid [Frieden in Am J Public Health 100(4):590-595, (2010)], and life course theory [Halfon in Milbank Quart, 80:433-79, (2002); Kotelchuck in Matern Child Health J, 7:5-11, (2003); Pies (2009)], an emerging conceptual framework that addresses a number of pressing maternal and child health issues including health disparities and the social determinants of health. While developed independently, a synthesis of these three frameworks provides an important analytical perspective to assess the adequacy and comprehensiveness of current public health programs and systems supporting maternal and child health improvement. Synthesizing these frameworks from the specific vantage point of MCH practice provides public health practitioners with important and dynamic opportunities to promote improvements in health, especially for state and local governmental health agencies with the statutory authority and public accountability for improving the health of women, children, and families in their jurisdictions. A crucial finding of this synthesis is that significant improvements in MCH outcomes at the state and local levels are the result of collaborative, integrated, and synergistic implementation of many different interventions, programs and policies that are carried out by a number of stakeholders, and administered in many different settings. MCH programs have a long history of coordinating disparate sectors of the health care and public health enterprise to create systems of services that improve maternal and child health. Future improvements in MCH build on this legacy but will come from a "paradigm shift" in MCH practice that blends (1) evidence-based interventions and best practices that improve the health of individuals, communities, and populations, and crosscuts health service settings with (2) public policies that promote and improve maternal and child health needs at the local, state, and national levels, and (3) supports MCH leadership to implement such changes in MCH systems nationwide. As such, the challenge presented by this synthesis is not merely technical, i.e. having the scientific and organizational capacity to address identified MCH needs. Instead, a more pressing challenge is providing effective leadership in the coordination and integration of these frameworks and using them in practice to develop a vision that guides programs and policies to improve maternal and child health nationwide.