title: Association of rectal toxicity with thermal dose parameters in treatment of locally advanced prostate cancer with radiation and hyperthermia.
abstract: OBJECTIVE
  Although hyperthermia has been used for more than two decades in the treatment of pelvic tumors, little is known about the potential impact of heat on rectal toxicity when combined with other treatment modalities. Because rectal toxicity is a concern with radiation and may be exacerbated by hyperthermia, definition of the association of thermal dose parameters with rectal toxicity is important. In this report, we correlate rectal toxicity with thermal dose parameters for patients treated with hyperthermia and radiation for prostate cancer.
  
  
  METHODS
  Thirty patients with T2b-T3b disease (1992 American Joint Committee On Cancer criteria) enrolled in a Phase II study of external beam radiation +/- androgen-suppressive therapy with two transrectal ultrasound hyperthermia treatments were assessed for rectal toxicity. Prostatic and anterior rectal wall temperatures were monitored for all treatments. Rectal wall temperatures were limited to 40 degrees C in 19 patients, 41 degrees C in 3 patients, and 42 degrees C in 8 patients. Logistic regression was used to estimate the log hazard of developing National Cancer Institute Common Toxicity Criteria Grade 2 toxicity based on temperature parameters. The following were calculated: hazard ratios, 95% confidence intervals, p values for statistical significance of each parameter, and proportion of variability explained for each parameter.
  
  
  RESULTS
  Gastrointestinal toxicity was limited to Grade 2. The rate of acute Grade 2 proctitis was greater for patients with an allowable rectal wall temperature of >40 degrees C. In this group, 7 of 11 patients experienced acute Grade 2 proctitis, as opposed to 3 of 19 patients in the group with rectal wall temperatures limited to 40 degrees C (p = 0.004). Preliminary assessment of long-term toxicity revealed no differences in toxicity. Hazard ratios for acute Grade 2 proctitis for allowable rectal wall temperature, average rectal wall Tmax, and average prostate Tmax were 9.33 (p = 0.01), 3.66 (p = 0.03), and 2.29 (p = 0.08), respectively. A model combining these three parameters explained 48.6% of the variability among groups.
  
  
  CONCLUSIONS
  Rectal toxicity correlates with maximum allowable rectal wall temperature, average rectal wall Tmax, and average prostate Tmax for patients undergoing transrectal ultrasound hyperthermia combined with radiation for treatment of advanced clinically localized prostate cancer. Further definition of this association of thermal dose parameters with rectal toxicity in treatment of pelvic malignancies with hyperthermia should advance the goal of delivering thermal therapy in an effective yet safe manner.
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. mhurwitz@lroc.harvard.edu
authors.forename: Mark D
authors.initials: MD
authors.lastname: Hurwitz
authors.forename: Irving D
authors.initials: ID
authors.lastname: Kaplan
authors.forename: Jorgen L
authors.initials: JL
authors.lastname: Hansen
authors.forename: Savina
authors.initials: S
authors.lastname: Prokopios-Davos
authors.forename: George P
authors.initials: GP
authors.lastname: Topulos
authors.forename: Kenneth
authors.initials: K
authors.lastname: Wishnow
authors.forename: Judith
authors.initials: J
authors.lastname: Manola
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Bornstein
authors.forename: Kullervo
authors.initials: K
authors.lastname: Hynynen
mesh_terms: D004064:Digestive System / Q000473:pathology / Q000528:radiation effects; D006801:Humans; D006979:Hyperthermia, Induced; D008297:Male; D011471:Prostatic Neoplasms / Q000532:radiotherapy* / Q000628:therapy*; D011522:Protons; D020266:Radiotherapy, Conformal; D012007:Rectum / Q000473:pathology* / Q000528:radiation effects*; D013696:Temperature; D013997:Time Factors
chemical_list: D011522:Protons