Development and validation of a 24-gene predictor of response to postoperative radiotherapy in prostate cancer: a matched, retrospective analysis

Zhao, Shuang G.; Chang, S. Laura; Spratt, Daniel E.; Erho, Nicholas; Yu, Menggang; Ashab, Hussam Al-Deen; Alshalalfa, Mohammed; Speers, Corey; Tomlins, Scott A.; Davicioni, Elai; Dicker, Adam P.; Carroll, Peter R.; Cooperberg, Matthew R.; Freedland, Stephen J.; Karnes, R. Jeffrey; Ross, Ashley E.; Schaeffer, Edward M.; Den, Robert B.; Nguyen, Paul L.; Feng, Felix Y.

doi:10.1016/s1470-2045(16)30491-0

Cited by 190 publications

(127 citation statements)

References 34 publications

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“…However, before this could happen, a prognostic indicator and/ or a measurement output, other than overall survival, to show any differential response of the combination treatment would be required. This could be something similar to the PORTOS score; predictor of response to postoperative radiotherapy in prostate cancer [36] .…”

Section: Discussionmentioning

confidence: 93%

Tumor heterogeneity and therapy resistance - implications for future treatments of prostate cancer

Frame¹,

Noble²,

Klein³

et al. 2017

JCMT

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Aim:To develop new therapies for prostate cancer, disease heterogeneity must be addressed. This includes patient variation, multi-focal disease, cellular heterogeneity, genomic changes and epigenetic modification. This requires more representative models to be used in more innovative ways. Methods: This study used a panel of cell lines and primary prostate epithelial cell cultures derived from patient tissue. Several assays were used; alamar blue, colony forming assays, γH2AX and Ki67 immunofluorescence and comet assays. Ptychographic quantitative phase imaging (QPI), a label-free imaging technique, combined with Cell Analysis Toolbox software, was implemented to carry out real-time analysis of cells and to retrieve morphological, kinetic and population data. Results: A combination of radiation and Vorinostat may be more effective than radiation alone. Primary prostate cancer stem-like cells are more resistant to etoposide than more differentiated cells. Analysis of QPI images showed that cell lines and primary cells differ in their size, motility and proliferation rate. A QPI signature was developed in order to identify two subpopulations of cells within a heterogeneous primary culture. Conclusion: Use of primary prostate epithelial cultures allows assessment of therapies whilst taking into account cellular heterogeneity. Analysis of rare cell populations and embracing novel techniques may ultimately lead to identifying and overcoming treatment resistance.

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Section: Discussionmentioning

confidence: 93%

Tumor heterogeneity and therapy resistance - implications for future treatments of prostate cancer

Frame¹,

Noble²,

Klein³

et al. 2017

JCMT

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“…25–27 Furthermore, genomic markers may distinguish between patients who benefit from adjuvant radiotherapy and those who do not. 28,29 Thus, adjuvant radiotherapy is likely to benefit patients who are identified as being at high risk of biochemical recurrence and metastasis. 30 …”

Section: Discussionmentioning

confidence: 99%

Adjuvant Versus Salvage Radiotherapy for Patients With Adverse Pathological Findings Following Radical Prostatectomy: A Decision Analysis

Wallis

Morton

Jerath

et al. 2017

MDM Policy & Practice

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Background: Patients undergoing surgery for prostate cancer who have adverse pathological findings experience high rates of recurrence. While there are data supporting adjuvant radiotherapy compared to a wait-and-watch strategy to reduce recurrence rates, there are no randomized controlled trials comparing adjuvant radiotherapy with the other standard of care, salvage radiotherapy (radiotherapy administered at the time of recurrence). Methods: We constructed a health state transition (Markov) model employing two-dimensional Monte Carlo simulation using a lifetime horizon to compare the quality-adjusted survival associated with postoperative strategies using adjuvant or salvage radiotherapy. Prior to analysis, we calibrated and validated our model using the results of previous randomized controlled trials. We considered clinically important oncological health states from immediately postoperative to prostate cancer–specific death, commonly described complications from prostate cancer treatment, and other causes of mortality. Transition probabilities and utilities for disease states were derived from a literature search of MEDLINE and expert consensus. Results: Salvage radiotherapy was associated with an increased quality-adjusted life expectancy (QALE) (58.3 months) as compared with adjuvant radiotherapy (53.7 months), a difference of 4.6 months (standard deviation 8.8). Salvage radiotherapy had higher QALE in 53% of hypothetical cohorts. There was a minimal difference in overall life expectancy (-0.1 months). Examining recurrence rates, our model showed validity when compared with available randomized controlled data. Conclusions: A salvage radiotherapy strategy appears to provide improved QALE for patients with adverse pathological findings following radical prostatectomy, compared with adjuvant radiotherapy. As these findings reflect, population averages, specific patient and tumor factors, and patient preferences remain central for individualized management.

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“…In a study published October 12, 2016 in Lancet Oncology, Zhao et al reported a means to address this need. 10 Findings from this study may complement the current treatment paradigm by appropriately triaging patients toward or away from radiation after prostatectomy. Five studies (4 cohort or case-cohort and one case-control) performed at 4 US medical centers from 1987 to 2010 were retrospectively analyzed.…”

mentioning

confidence: 80%

A new predictive tool for postoperative radiotherapy in prostate cancer

Lee

Figg

2017

Cancer Biology & Therapy

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Development and validation of a 24-gene predictor of response to postoperative radiotherapy in prostate cancer: a matched, retrospective analysis

Cited by 190 publications

References 34 publications

Tumor heterogeneity and therapy resistance - implications for future treatments of prostate cancer

Tumor heterogeneity and therapy resistance - implications for future treatments of prostate cancer

Adjuvant Versus Salvage Radiotherapy for Patients With Adverse Pathological Findings Following Radical Prostatectomy: A Decision Analysis

A new predictive tool for postoperative radiotherapy in prostate cancer

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