• Jeff M Michalski, K Winter, James A Purdy, Carlos A Perez, Janice K Ryu, Matthew B Parliament, Richard K Valicenti, Mack Roach, Howard M Sandler, Arnold M Markoe, and James D Cox.
• Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, USA. michalski@radonc.wustl.edu
• Int. J. Radiat. Oncol. Biol. Phys. 2004 Mar 1; 58 (3): 735-42.

PurposeThis is the first report of the toxicity outcomes using dose level IV (74 Gy) on Radiation Therapy Oncology Group (RTOG) study 9406 for Stage T1-T2 prostate adenocarcinoma.Methods And MaterialsA total of 262 patients were entered in this cooperative group, Phase I-II, dose-escalation trial of three-dimensional conformal radiotherapy for localized prostate carcinoma treated to a dose of 74 Gy (Level IV); 256 patients were analyzable for toxicity. A minimal dose of 2 Gy/fraction was prescribed to the planning target volume (PTV). Patients were stratified according to the risk of seminal vesicle invasion on the basis of the Gleason score and presenting prostate-specific antigen level. Group 1 patients had clinical Stage T1-T2 tumors with a seminal vesicle invasion risk of <15%. Group 2 patients had clinical Stage T1-T2 tumors with a seminal vesicle invasion risk of >/=15%. Patients in Group 1 were prescribed 74 Gy to a prostate PTV. Patients in Group 2 were prescribed 54 Gy to the prostate and seminal vesicles (PTV1) followed by a boost to the prostate only (PTV2) to 74 Gy. PTV margins between 5 and 10 mm were required. Elective pelvic radiotherapy was not used. The frequency of late effects of Grade 3 or greater was compared with that for a similar group of patients treated in RTOG studies 7506 and 7706, with length of follow-up adjustments made for the interval from therapy completion. A second comparison was made with 206 patients treated to dose level II (73.8 Gy in 1.8-Gy fractions) to see whether the fraction size affected toxicity.ResultsThe average months at risk for late Grade 3+ toxicity after therapy completion were 28.9 and 23.9 months for Group 1 and 2, respectively. Acute toxicity at dose level IV (74 Gy) was remarkably low, with Grade 3 acute effects reported in only 1% of Group 1 and 3% of Group 2 patients. No Grade 4 or 5 acute toxicities were reported. Late toxicity continued to be low compared with RTOG historical controls. One patient in Group 1 and 4 patients in Group 2 experienced Grade 3 bladder toxicity. Two patients in Group 2 experienced Grade 3 bowel toxicity. No Grade 4 or 5 late effects were reported. The rate of late Grade 2 toxicity (any type) was 23% and 16% in Group 1 and 2, respectively. The observed rate of Grade 3 or greater late effects for Group 1 (1 case) was significantly lower (p <0.0001) than the 18.5 cases that would have been expected from the historical control data. The observed rate for Group 2 (6 cases) was also significantly lower (p = 0.0009) than the 21.3 cases expected. No statistically significant difference was noted in the rate of acute or late toxicity in patients who were treated to 73.8 Gy at 1.8 Gy/fraction or 74 Gy at 2.0 Gy/fraction. Patients treated with the larger 2.0-Gy fractions tended to have more Grade 3 or greater toxicity than patients treated with 1.8-Gy fractions (2% vs. 1%, p = 0.09). The results after the longer follow-up with dose level II suggest these differences may increase with additional follow-up.ConclusionTolerance to three-dimensional conformal radiotherapy with 74 Gy in 2-Gy fractions remains better than expected compared with historical controls. The magnitude of any effect from fraction size requires additional follow-up.

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