Doctor of Philosophy, California Institute of Technology, Bioengineering (2017)
Michael Snyder, Postdoctoral Faculty Sponsor
Very High-Risk Localized Prostate Cancer: Outcomes Following Definitive Radiation
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
2016; 94 (2): 254-262
Existing definitions of high-risk prostate cancer consist of men who experience significant heterogeneity in outcomes. As such, criteria that identify a subpopulation of National Comprehensive Cancer Network (NCCN) high-risk prostate cancer patients who are at very high risk (VHR) for poor survival outcomes following prostatectomy were recently developed at our institution and include the presence of any of the following disease characteristics: multiple NCCN high-risk factors, primary Gleason pattern 5 disease and/or ≥5 biopsy cores with Gleason sums of 8 to 10. Whether these criteria also apply to men undergoing definitive radiation is unclear, as is the optimal treatment regimen in these patients.All men consecutively treated with definitive radiation by a single provider from 1993 to 2006 and who fulfilled criteria for NCCN high-risk disease were identified (n=288), including 99 patients (34%) with VHR disease. Multivariate-adjusted competing risk regression models were constructed to assess associations between the VHR definition and biochemical failure (BF), distant metastasis (DM), and prostate cancer-specific mortality (PCSM). Multivariate-adjusted Cox regression analysis assessed the association of the VHR definition with overall mortality (OM). Cumulative incidences of failure endpoints were compared between VHR men and other NCCN high-risk men.Men with VHR disease compared to other NCCN high-risk men experienced a higher 10-year incidence of BF (54.0% vs 35.4%, respectively, P<.001), DM (34.9% vs 13.4%, respectively, P<.001), PCSM (18.5% vs 5.9%, respectively, P<.001), and OM (36.4% vs 27.0%, respectively, P=.04). VHR men with a detectable prostate-specific antigen (PSA) concentration at the end of radiation (EOR) remained at high risk of 10-year PCSM compared to VHR men with an undetectable EOR PSA (31.0% vs 13.7%, respectively, P=.05).NCCN high-risk prostate cancer patients who meet VHR criteria experience distinctly worse outcomes following definitive radiation and long-term androgen deprivation therapy, particularly if an EOR PSA is detectable. Optimal use of local therapies for VHR patients should be explored further, as should novel agents.
View details for DOI 10.1016/j.ijrobp.2015.10.056
View details for Web of Science ID 000367522000006
View details for PubMedID 26853334
Population-Based Utilities for Upper Extremity Functions in the Setting of Tetraplegia
JOURNAL OF HAND SURGERY-AMERICAN VOLUME
2009; 34A (9): 1674-1681
People with tetraplegia face substantial physical and financial hardships. Although upper extremity reconstruction has been advocated for people with tetraplegia, these procedures are markedly underused in the United States. Population-based preference evaluation of upper extremity reconstruction is important to quantify the value of these reconstructive procedures. This study sought to establish the preferences for 3 health states: tetraplegia, tetraplegia with corrected pinch function, and tetraplegia with corrected elbow extension function.A computer-based, time trade-off survey was administered to a cohort of 81 able-bodied second-year medical students who served as a surrogate for the general public. This survey instrument has undergone pilot testing and has established face validity to evaluate the 3 health states of interest. Utilities were calculated based on an estimated 20 years of remaining life.The mean utility for the tetraplegic health state was low. On average, respondents gave up 10.8 +/- 5.0 out of a hypothetical 20 years for perfect health, for a utility of tetraplegia equal to 0.46. For recovery of pinch function, respondents gave up an average of 6.5 +/- 4.3 years, with a corresponding health utility of 0.68. For recovery of elbow extension function, respondents gave up an average of 7.6 +/- 4.5 years, with a corresponding health utility of 0.74.This study established the preferences for 2 upper extremity surgical interventions: tetraplegia with pinch and tetraplegia with elbow extension. The findings from this study place a high value on upper-limb reconstructive procedures with tetraplegia.
View details for DOI 10.1016/j.jhsa.2009.07.003
View details for Web of Science ID 000271598000013