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 »
- Authors:
-
- University of Wisconsin Carbone Cancer Center, Madison, Wisconsin (United States)
- RTOG Statistical Center, Philadelphia, Pennsylvania (United States)
- Case Medical Center, Cleveland, Ohio (United States)
- LDS Hospital, Salt Lake City, Utah (United States)
- Radiological Associates of Sacramento, Sacramento, California (United States)
- Cedars-Sinai Medical Center, Los Angeles, California (United States)
- Centre Hospitalier de l'Université de Montréal-Notre Dame, Montreal, Ontario (Canada)
- Albert Einstein Medical Center, Philadelphia, Pennsylvania (United States)
- 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}
}