A genetically determined dose-volume histogram predicts for rectal bleeding among patients treated with prostate brachytherapy.
OBJECTIVE
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
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.
Cesaretti
Jamie A
JA
Department of Radiation Oncology, Mount Sinai School of Medicine, New York, NY 10029, USA. jamie.cesaretti@msnyu.health.org
Stock
Richard G
RG
Atencio
David P
DP
Peters
Sheila A
SA
Peters
Christopher A
CA
Burri
Ryan J
RJ
Stone
Nelson N
NN
Rosenstein
Barry S
BS
D000368:Aged; D000704:Analysis of Variance; D064007:Ataxia Telangiectasia Mutated Proteins; D001918:Brachytherapy / Q000009:adverse effects*; D018797:Cell Cycle Proteins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D004307:Dose-Response Relationship, Radiation; D007172:Erectile Dysfunction / Q000235:genetics; D006471:Gastrointestinal Hemorrhage / Q000235:genetics*; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D010165:Palladium / Q000627:therapeutic use; D011349:Proctitis / Q000235:genetics; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011868:Radioisotopes / Q000627:therapeutic use; D012002:Rectal Diseases / Q000235:genetics*; D012007:Rectum / Q000528:radiation effects; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D007457:Iodine Radioisotopes; D011868:Radioisotopes; D025521:Tumor Suppressor Proteins; D010165:Palladium; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases