Influence of number of CAG repeats on local control in the RTOG 86-10 protocol

May Abdel-Wahab, Brian A. Berkey, Awtar Krishan, Tom O'Brien, Elizabeth Hammond, Mack Roach, Colleen Lawton, Milijenko Pilepich, Arnold Markoe, Alan Pollack

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

OBJECTIVES: The number of CAG repeats on the androgen receptor (AR) gene is inversely proportional to transcriptional activity. The purpose of this study was to determine if short-term androgen deprivation therapy (RT + HT) can improve outcome in patients with tumors with short CAG repeats (<19). MATERIALS AND METHODS: Prostate cancer patients were randomized to receive either radiotherapy (RT) alone or (RT + HT) in the RTOG 86-10 study. CAG repeats were measured in 94 tumor specimens (21%; test cohort) of the 456 (parent cohort) analyzable cases. AR flow cytometry measurements were done on 13 patients. The effect on local failure (LF), distant metastases (DM), prostate cancer survival (PSS), and overall survival (OS) was studied. RESULTS: Pretreatment characteristics and assigned treatment arm were not significantly different between the parent and test groups except for a significantly higher risk of death (P = 0.049) in the test group. The median CAG repeat was 19. There were no significant differences in stage, or Gleason score between high (19 or greater) and low CAG (<19) patients within each treatment group. Number of CAG repeats alone did not significantly influence LF, DM, PSS, and OS. However, when the CAG repeat outcome was studied in conjunction with androgen deprivation therapy, patients with CAG <19 who received H + RT had improved local control as compared with patients who received RT alone (P = 0.026, 5-year rates 4.6% versus 36.4%) and improved local control over patients with CAG ≥19 that received H + RT (P = 0.028). CONCLUSIONS: Patients with short CAG repeats show a local control benefit with short-term androgen deprivation therapy, but no improvement in survival.

Original languageEnglish
Pages (from-to)14-20
Number of pages7
JournalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
Volume29
Issue number1
DOIs
StatePublished - Feb 1 2006

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Radiotherapy
Survival
Androgens
Prostatic Neoplasms
Androgen Receptors
Neoplasm Metastasis
Therapeutics
Neoplasm Grading
Neoplasms
Flow Cytometry
Genes

Keywords

  • Androgen
  • Prostate cancer
  • Radiation therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Influence of number of CAG repeats on local control in the RTOG 86-10 protocol. / Abdel-Wahab, May; Berkey, Brian A.; Krishan, Awtar; O'Brien, Tom; Hammond, Elizabeth; Roach, Mack; Lawton, Colleen; Pilepich, Milijenko; Markoe, Arnold; Pollack, Alan.

In: American Journal of Clinical Oncology: Cancer Clinical Trials, Vol. 29, No. 1, 01.02.2006, p. 14-20.

Research output: Contribution to journalArticle

Abdel-Wahab, May ; Berkey, Brian A. ; Krishan, Awtar ; O'Brien, Tom ; Hammond, Elizabeth ; Roach, Mack ; Lawton, Colleen ; Pilepich, Milijenko ; Markoe, Arnold ; Pollack, Alan. / Influence of number of CAG repeats on local control in the RTOG 86-10 protocol. In: American Journal of Clinical Oncology: Cancer Clinical Trials. 2006 ; Vol. 29, No. 1. pp. 14-20.
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AU - Abdel-Wahab, May

AU - Berkey, Brian A.

AU - Krishan, Awtar

AU - O'Brien, Tom

AU - Hammond, Elizabeth

AU - Roach, Mack

AU - Lawton, Colleen

AU - Pilepich, Milijenko

AU - Markoe, Arnold

AU - Pollack, Alan

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N2 - OBJECTIVES: The number of CAG repeats on the androgen receptor (AR) gene is inversely proportional to transcriptional activity. The purpose of this study was to determine if short-term androgen deprivation therapy (RT + HT) can improve outcome in patients with tumors with short CAG repeats (<19). MATERIALS AND METHODS: Prostate cancer patients were randomized to receive either radiotherapy (RT) alone or (RT + HT) in the RTOG 86-10 study. CAG repeats were measured in 94 tumor specimens (21%; test cohort) of the 456 (parent cohort) analyzable cases. AR flow cytometry measurements were done on 13 patients. The effect on local failure (LF), distant metastases (DM), prostate cancer survival (PSS), and overall survival (OS) was studied. RESULTS: Pretreatment characteristics and assigned treatment arm were not significantly different between the parent and test groups except for a significantly higher risk of death (P = 0.049) in the test group. The median CAG repeat was 19. There were no significant differences in stage, or Gleason score between high (19 or greater) and low CAG (<19) patients within each treatment group. Number of CAG repeats alone did not significantly influence LF, DM, PSS, and OS. However, when the CAG repeat outcome was studied in conjunction with androgen deprivation therapy, patients with CAG <19 who received H + RT had improved local control as compared with patients who received RT alone (P = 0.026, 5-year rates 4.6% versus 36.4%) and improved local control over patients with CAG ≥19 that received H + RT (P = 0.028). CONCLUSIONS: Patients with short CAG repeats show a local control benefit with short-term androgen deprivation therapy, but no improvement in survival.

AB - OBJECTIVES: The number of CAG repeats on the androgen receptor (AR) gene is inversely proportional to transcriptional activity. The purpose of this study was to determine if short-term androgen deprivation therapy (RT + HT) can improve outcome in patients with tumors with short CAG repeats (<19). MATERIALS AND METHODS: Prostate cancer patients were randomized to receive either radiotherapy (RT) alone or (RT + HT) in the RTOG 86-10 study. CAG repeats were measured in 94 tumor specimens (21%; test cohort) of the 456 (parent cohort) analyzable cases. AR flow cytometry measurements were done on 13 patients. The effect on local failure (LF), distant metastases (DM), prostate cancer survival (PSS), and overall survival (OS) was studied. RESULTS: Pretreatment characteristics and assigned treatment arm were not significantly different between the parent and test groups except for a significantly higher risk of death (P = 0.049) in the test group. The median CAG repeat was 19. There were no significant differences in stage, or Gleason score between high (19 or greater) and low CAG (<19) patients within each treatment group. Number of CAG repeats alone did not significantly influence LF, DM, PSS, and OS. However, when the CAG repeat outcome was studied in conjunction with androgen deprivation therapy, patients with CAG <19 who received H + RT had improved local control as compared with patients who received RT alone (P = 0.026, 5-year rates 4.6% versus 36.4%) and improved local control over patients with CAG ≥19 that received H + RT (P = 0.028). CONCLUSIONS: Patients with short CAG repeats show a local control benefit with short-term androgen deprivation therapy, but no improvement in survival.

KW - Androgen

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