A genetically determined dose-volume histogram predicts for rectal bleeding among patients treated with prostate brachytherapy.

Abstract

PURPOSE:

To examine whether possession of genetic alterations in the ATM (ataxia telangiectasia) gene is associated with rectal bleeding in a dose-dependent and volume-dependent manner.

METHODS AND MATERIALS:

One hundred eight prostate cancer patients who underwent brachytherapy using either an (125)I implant, a (103)Pd implant, or the combination of external beam radiotherapy with a (103)Pd implant and had a minimum of 1 year follow-up were screened for DNA sequence variations in the 62 coding exons of the ATM gene using denaturing high-performance liquid chromatography. Rectal dose was reported as the volume (in cubic centimeters) of rectum receiving the brachytherapy prescription dose. The two-sided Fisher exact test was used to compare differences in proportions.

RESULTS:

A significant correlation between the presence of any ATM sequence alteration and Grade 1 to 2 proctitis was obtained when the radiation dose to rectal tissue was quantified. Rectal bleeding occurred in 4 of 13 patients (31%) with a variant versus 1 of 23 (4%) without a genetic alteration for patients who had <0.7 cm(3) of rectal tissue receiving the implant prescription dose (p = 0.05). Of patients in whom 0.7-1.4 cm(3) of the rectum received the implant prescription, 4 of 11 (36%) with an ATM alteration exhibited Grade 1 to 2 proctitis, whereas 1 of 21 (5%) without a variant (p = 0.04) developed this radiation-induced late effect.

CONCLUSIONS:

The possession of genetic variants in the ATM gene is associated with the development of radiation-induced proctitis after prostate cancer radiotherapy for patients who receive the full prescription dose to either a low or a moderate volume of rectal tissue.

• Authors: Jamie A Cesaretti, Richard G Stock, David P Atencio, Sheila A Peters, Christopher A Peters, Ryan J Burri, Nelson N Stone, Barry S Rosenstein
• Journal: International journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 68 Issue 5 Pg. 1410-6 (Aug 01 2007) ISSN: 0360-3016 [Print] United States
• PMID: 17490827 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Cell Cycle Proteins
• DNA-Binding Proteins
• Iodine Radioisotopes
• Radioisotopes
• Tumor Suppressor Proteins
• Palladium
• ATM protein, human
• Ataxia Telangiectasia Mutated Proteins
• Protein Serine-Threonine Kinases

Topics

• Aged
• Analysis of Variance
• Ataxia Telangiectasia Mutated Proteins
• Brachytherapy (adverse effects)
• Cell Cycle Proteins (genetics)
• DNA-Binding Proteins (genetics)
• Dose-Response Relationship, Radiation
• Erectile Dysfunction (genetics)
• Gastrointestinal Hemorrhage (genetics)
• Humans
• Iodine Radioisotopes (therapeutic use)
• Male
• Middle Aged
• Mutation, Missense (genetics)
• Palladium (therapeutic use)
• Proctitis (genetics)
• Prostatic Neoplasms (radiotherapy)
• Protein Serine-Threonine Kinases (genetics)
• Radioisotopes (therapeutic use)
• Rectal Diseases (genetics)
• Rectum (radiation effects)
• Tumor Suppressor Proteins (genetics)