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Title: Ki-67 Is an Independent Predictor of Metastasis and Cause-Specific Mortality for Prostate Cancer Patients Treated on Radiation Therapy Oncology Group (RTOG) 94-08

Abstract

Purpose: The association of Ki-67 staining index (Ki67-SI) with overall survival (OS), disease-specific mortality (DSM), distant metastasis (DM), and biochemical failure (BF) was examined in men with favorable- to intermediate-risk prostate cancer receiving radiation therapy (RT) alone or with short-term androgen deprivation (ADT) in Radiation Therapy Oncology Group (RTOG) 94-08. Methods and Materials: 468 patients (23.6%) on RTOG 94-08 had sufficient tissue for Ki67-SI analysis. The median follow-up time was 7.9 years. Ki67-SI was determined by immunohistochemistry and quantified manually and by image analysis. Correlative analysis versus clinical outcome was performed using the third quartile (≥Q3) cutpoint. A proportional hazards multivariable analysis (MVA) dichotomized covariates in accordance with trial stratification and randomization criteria. Results: In MVAs adjusted for all treatment covariates, high Ki67-SI (≥Q3) was correlated with increased DSM (hazard ratio [HR] 2.48, P=.03), DM (HR 3.5, P=.002), and BF (HR 3.55, P<.0001). MVA revealed similar Ki67-associated hazard ratios in each separate treatment arm for DSM, DM, and BF; these reached significance only for DM in the RT-alone arm and for BF in both arms. Ki67-SI was not a significant predictor of intraprostatic recurrence assessed by repeated biopsy 2 years after treatment. Patients with a high or low Ki67-SI seemedmore » to experience a similar relative benefit from the addition of ADT to radiation. Conclusions: High Ki67-SI independently predicts for increased DSM, DM, and protocol BF in primarily intermediate-risk prostate cancer patients treated with RT with or without ADT on RTOG 94-08 but does not predict for local recurrence or for increased relative benefit from ADT. This and prior studies lend support for the use of Ki67-SI as a stratification factor in future trials.« less

Authors:
 [1];  [2];  [1];  [3];  [4];  [5];  [6];  [7];  [8];  [9]
  1. University of Wisconsin Carbone Cancer Center, Madison, Wisconsin (United States)
  2. RTOG Statistical Center, Philadelphia, Pennsylvania (United States)
  3. Case Medical Center, Cleveland, Ohio (United States)
  4. LDS Hospital, Salt Lake City, Utah (United States)
  5. Radiological Associates of Sacramento, Sacramento, California (United States)
  6. Cedars-Sinai Medical Center, Los Angeles, California (United States)
  7. Centre Hospitalier de l'Université de Montréal-Notre Dame, Montreal, Ontario (Canada)
  8. Albert Einstein Medical Center, Philadelphia, Pennsylvania (United States)
  9. University of Miami Miller School of Medicine, Miami, Florida (United States)
Publication Date:
OSTI Identifier:
22224478
Resource Type:
Journal Article
Journal Name:
International Journal of Radiation Oncology, Biology and Physics
Additional Journal Information:
Journal Volume: 86; Journal Issue: 2; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0360-3016
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ANDROGENS; ANIMAL TISSUES; BIOPSY; HEALTH HAZARDS; IMAGE PROCESSING; METASTASES; MORTALITY; NEOPLASMS; PATIENTS; PROSTATE; RADIOTHERAPY

Citation Formats

Verhoven, Bret, Yan, Yan, Ritter, Mark, Khor, Li-Yan, Hammond, Elizabeth, Jones, Christopher, Amin, Mahul, Bahary, Jean-Paul, Zeitzer, Kenneth, and Pollack, Alan. Ki-67 Is an Independent Predictor of Metastasis and Cause-Specific Mortality for Prostate Cancer Patients Treated on Radiation Therapy Oncology Group (RTOG) 94-08. United States: N. p., 2013. Web. doi:10.1016/J.IJROBP.2013.01.016.
Verhoven, Bret, Yan, Yan, Ritter, Mark, Khor, Li-Yan, Hammond, Elizabeth, Jones, Christopher, Amin, Mahul, Bahary, Jean-Paul, Zeitzer, Kenneth, & Pollack, Alan. Ki-67 Is an Independent Predictor of Metastasis and Cause-Specific Mortality for Prostate Cancer Patients Treated on Radiation Therapy Oncology Group (RTOG) 94-08. United States. https://doi.org/10.1016/J.IJROBP.2013.01.016
Verhoven, Bret, Yan, Yan, Ritter, Mark, Khor, Li-Yan, Hammond, Elizabeth, Jones, Christopher, Amin, Mahul, Bahary, Jean-Paul, Zeitzer, Kenneth, and Pollack, Alan. 2013. "Ki-67 Is an Independent Predictor of Metastasis and Cause-Specific Mortality for Prostate Cancer Patients Treated on Radiation Therapy Oncology Group (RTOG) 94-08". United States. https://doi.org/10.1016/J.IJROBP.2013.01.016.
@article{osti_22224478,
title = {Ki-67 Is an Independent Predictor of Metastasis and Cause-Specific Mortality for Prostate Cancer Patients Treated on Radiation Therapy Oncology Group (RTOG) 94-08},
author = {Verhoven, Bret and Yan, Yan and Ritter, Mark and Khor, Li-Yan and Hammond, Elizabeth and Jones, Christopher and Amin, Mahul and Bahary, Jean-Paul and Zeitzer, Kenneth and Pollack, Alan},
abstractNote = {Purpose: The association of Ki-67 staining index (Ki67-SI) with overall survival (OS), disease-specific mortality (DSM), distant metastasis (DM), and biochemical failure (BF) was examined in men with favorable- to intermediate-risk prostate cancer receiving radiation therapy (RT) alone or with short-term androgen deprivation (ADT) in Radiation Therapy Oncology Group (RTOG) 94-08. Methods and Materials: 468 patients (23.6%) on RTOG 94-08 had sufficient tissue for Ki67-SI analysis. The median follow-up time was 7.9 years. Ki67-SI was determined by immunohistochemistry and quantified manually and by image analysis. Correlative analysis versus clinical outcome was performed using the third quartile (≥Q3) cutpoint. A proportional hazards multivariable analysis (MVA) dichotomized covariates in accordance with trial stratification and randomization criteria. Results: In MVAs adjusted for all treatment covariates, high Ki67-SI (≥Q3) was correlated with increased DSM (hazard ratio [HR] 2.48, P=.03), DM (HR 3.5, P=.002), and BF (HR 3.55, P<.0001). MVA revealed similar Ki67-associated hazard ratios in each separate treatment arm for DSM, DM, and BF; these reached significance only for DM in the RT-alone arm and for BF in both arms. Ki67-SI was not a significant predictor of intraprostatic recurrence assessed by repeated biopsy 2 years after treatment. Patients with a high or low Ki67-SI seemed to experience a similar relative benefit from the addition of ADT to radiation. Conclusions: High Ki67-SI independently predicts for increased DSM, DM, and protocol BF in primarily intermediate-risk prostate cancer patients treated with RT with or without ADT on RTOG 94-08 but does not predict for local recurrence or for increased relative benefit from ADT. This and prior studies lend support for the use of Ki67-SI as a stratification factor in future trials.},
doi = {10.1016/J.IJROBP.2013.01.016},
url = {https://www.osti.gov/biblio/22224478}, journal = {International Journal of Radiation Oncology, Biology and Physics},
issn = {0360-3016},
number = 2,
volume = 86,
place = {United States},
year = {Sat Jun 01 00:00:00 EDT 2013},
month = {Sat Jun 01 00:00:00 EDT 2013}
}