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

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 > or =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.

Tissue micro-array: a cost and time-effective method for correlative studies by regional and national cancer study groups.

Tissue micro-arrays have been used for molecular and immunohistochemical studies. We sought to evaluate whether such arrays could substitute for whole sections in correlative studies performed by the Radiation Therapy Oncology Group. Four multitumor 150-sample arrays were built using formalin-fixed, paraffin-embedded, archival prostate, brain, and head/neck tumor blocks from RTOG tissue bank. p53 immunostaining of arrays and whole sections was done. Blind evaluation of each slide was made, and agreement rates between the two techniques were determined in various scenarios. Cost was also evaluated. Results demonstrate excellent agreement for p53 between slides and arrays. Agreement improved when three or four replicate arrays were used. Findings based on one to four arrays agree well with those obtained from analysis of the whole tissue samples. Minimal tissue damage, improved tissue salvage, cost reduction, ease of interpretation, and significant time savings were realized by using the arrays. Tissue micro array technique is a valuable tool for evaluation of patient materials associated with clinical trials.