A tissue biomarker -based model that identi fies patients with a high risk of distant metastasis and differential survival by length of androgen deprivation therapy in RTOG protocol 92-02

Alan Pollack, James J. Dignam, Dayssy A. Diaz, Qian Wu, Radka Stoyanova, Kyounghwa Bae, Adam P. Dicker, Howard Sler, Gerald E. Hanks, Felix Y. Feng

Research output: Contribution to journalArticle

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Abstract

Purpose: To examine the relationship between the expression of 7 promising apoptotic/cell proliferation proteins (Ki-67, p53, MDM2, bcl-2, bax, p16, and Cox-2) and risk of distant metastasis. Experimental Design: RTOG 92-02 compared external beam radiotherapy (EBRT) to approximately 70 Gy + short-term androgen deprivation therapy (STADT) with EBRT - long-term ADT (LTADT). Immunohistochemical analysis was available for >4 biomarkers in 616 of 1,521 assessable cases. Biomarkers were evaluated individually and jointly via multivariable modeling of distant metastasis using competing risks hazards regression, adjusting for age, prostate-specific antigen, Gleason score, T stage, and treatment.

Results: Modeling identified four biomarkers (Ki-67,MDM2,p16 and Cox-2) that were jointly associated with distant metastasis. The c-index was 0.77 for the full model and 0.70 for the model without the biomarkers; a relative improvement of about 10% (likelihood ratio P < 0.001). Subdivision of the patients into quartiles based on predicted distant metastasis risk identified a high-risk group with 10-year distant metastasis risk of 52.5% after EBRT - STADT and 31% with EBRT - LTADT; associated 10-year prostate cancer-specific mortality (PCSM) risks were 45.9% and 14.5% with STADT and LTADT.

Conclusion: Four biomarkers were found to contribute significantly to a model that predicted distant metastasis and identified a subgroup of patients at a particularly high risk of both distant metastasis and PCSM when EBRT + STADT was used. LTADT resulted in significant reductions in distant metastasis and improvements in PCSM, and there was a suggestion of greater importance in the very high risk subgroup.

Original languageEnglish
Pages (from-to)6379-6388
Number of pages10
JournalClinical Cancer Research
Volume20
Issue number24
DOIs
StatePublished - Dec 15 2014

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Androgens
Biomarkers
Neoplasm Metastasis
Survival
Radiotherapy
Prostatic Neoplasms
Therapeutics
Mortality
Neoplasm Grading
Prostate-Specific Antigen
Research Design
Cell Proliferation
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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A tissue biomarker -based model that identi fies patients with a high risk of distant metastasis and differential survival by length of androgen deprivation therapy in RTOG protocol 92-02. / Pollack, Alan; Dignam, James J.; Diaz, Dayssy A.; Wu, Qian; Stoyanova, Radka; Bae, Kyounghwa; Dicker, Adam P.; Sler, Howard; Hanks, Gerald E.; Feng, Felix Y.

In: Clinical Cancer Research, Vol. 20, No. 24, 15.12.2014, p. 6379-6388.

Research output: Contribution to journalArticle

Pollack, Alan ; Dignam, James J. ; Diaz, Dayssy A. ; Wu, Qian ; Stoyanova, Radka ; Bae, Kyounghwa ; Dicker, Adam P. ; Sler, Howard ; Hanks, Gerald E. ; Feng, Felix Y. / A tissue biomarker -based model that identi fies patients with a high risk of distant metastasis and differential survival by length of androgen deprivation therapy in RTOG protocol 92-02. In: Clinical Cancer Research. 2014 ; Vol. 20, No. 24. pp. 6379-6388.
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abstract = "Purpose: To examine the relationship between the expression of 7 promising apoptotic/cell proliferation proteins (Ki-67, p53, MDM2, bcl-2, bax, p16, and Cox-2) and risk of distant metastasis. Experimental Design: RTOG 92-02 compared external beam radiotherapy (EBRT) to approximately 70 Gy + short-term androgen deprivation therapy (STADT) with EBRT - long-term ADT (LTADT). Immunohistochemical analysis was available for >4 biomarkers in 616 of 1,521 assessable cases. Biomarkers were evaluated individually and jointly via multivariable modeling of distant metastasis using competing risks hazards regression, adjusting for age, prostate-specific antigen, Gleason score, T stage, and treatment.Results: Modeling identified four biomarkers (Ki-67,MDM2,p16 and Cox-2) that were jointly associated with distant metastasis. The c-index was 0.77 for the full model and 0.70 for the model without the biomarkers; a relative improvement of about 10{\%} (likelihood ratio P < 0.001). Subdivision of the patients into quartiles based on predicted distant metastasis risk identified a high-risk group with 10-year distant metastasis risk of 52.5{\%} after EBRT - STADT and 31{\%} with EBRT - LTADT; associated 10-year prostate cancer-specific mortality (PCSM) risks were 45.9{\%} and 14.5{\%} with STADT and LTADT.Conclusion: Four biomarkers were found to contribute significantly to a model that predicted distant metastasis and identified a subgroup of patients at a particularly high risk of both distant metastasis and PCSM when EBRT + STADT was used. LTADT resulted in significant reductions in distant metastasis and improvements in PCSM, and there was a suggestion of greater importance in the very high risk subgroup.",
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T1 - A tissue biomarker -based model that identi fies patients with a high risk of distant metastasis and differential survival by length of androgen deprivation therapy in RTOG protocol 92-02

AU - Pollack, Alan

AU - Dignam, James J.

AU - Diaz, Dayssy A.

AU - Wu, Qian

AU - Stoyanova, Radka

AU - Bae, Kyounghwa

AU - Dicker, Adam P.

AU - Sler, Howard

AU - Hanks, Gerald E.

AU - Feng, Felix Y.

PY - 2014/12/15

Y1 - 2014/12/15

N2 - Purpose: To examine the relationship between the expression of 7 promising apoptotic/cell proliferation proteins (Ki-67, p53, MDM2, bcl-2, bax, p16, and Cox-2) and risk of distant metastasis. Experimental Design: RTOG 92-02 compared external beam radiotherapy (EBRT) to approximately 70 Gy + short-term androgen deprivation therapy (STADT) with EBRT - long-term ADT (LTADT). Immunohistochemical analysis was available for >4 biomarkers in 616 of 1,521 assessable cases. Biomarkers were evaluated individually and jointly via multivariable modeling of distant metastasis using competing risks hazards regression, adjusting for age, prostate-specific antigen, Gleason score, T stage, and treatment.Results: Modeling identified four biomarkers (Ki-67,MDM2,p16 and Cox-2) that were jointly associated with distant metastasis. The c-index was 0.77 for the full model and 0.70 for the model without the biomarkers; a relative improvement of about 10% (likelihood ratio P < 0.001). Subdivision of the patients into quartiles based on predicted distant metastasis risk identified a high-risk group with 10-year distant metastasis risk of 52.5% after EBRT - STADT and 31% with EBRT - LTADT; associated 10-year prostate cancer-specific mortality (PCSM) risks were 45.9% and 14.5% with STADT and LTADT.Conclusion: Four biomarkers were found to contribute significantly to a model that predicted distant metastasis and identified a subgroup of patients at a particularly high risk of both distant metastasis and PCSM when EBRT + STADT was used. LTADT resulted in significant reductions in distant metastasis and improvements in PCSM, and there was a suggestion of greater importance in the very high risk subgroup.

AB - Purpose: To examine the relationship between the expression of 7 promising apoptotic/cell proliferation proteins (Ki-67, p53, MDM2, bcl-2, bax, p16, and Cox-2) and risk of distant metastasis. Experimental Design: RTOG 92-02 compared external beam radiotherapy (EBRT) to approximately 70 Gy + short-term androgen deprivation therapy (STADT) with EBRT - long-term ADT (LTADT). Immunohistochemical analysis was available for >4 biomarkers in 616 of 1,521 assessable cases. Biomarkers were evaluated individually and jointly via multivariable modeling of distant metastasis using competing risks hazards regression, adjusting for age, prostate-specific antigen, Gleason score, T stage, and treatment.Results: Modeling identified four biomarkers (Ki-67,MDM2,p16 and Cox-2) that were jointly associated with distant metastasis. The c-index was 0.77 for the full model and 0.70 for the model without the biomarkers; a relative improvement of about 10% (likelihood ratio P < 0.001). Subdivision of the patients into quartiles based on predicted distant metastasis risk identified a high-risk group with 10-year distant metastasis risk of 52.5% after EBRT - STADT and 31% with EBRT - LTADT; associated 10-year prostate cancer-specific mortality (PCSM) risks were 45.9% and 14.5% with STADT and LTADT.Conclusion: Four biomarkers were found to contribute significantly to a model that predicted distant metastasis and identified a subgroup of patients at a particularly high risk of both distant metastasis and PCSM when EBRT + STADT was used. LTADT resulted in significant reductions in distant metastasis and improvements in PCSM, and there was a suggestion of greater importance in the very high risk subgroup.

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