Michalski Jeff M, Winter K, Purdy James A, Perez Carlos A, Ryu Janice K, Parliament Matthew B, Valicenti Richard K, Roach Mack, Sandler Howard M, Markoe Arnold M, Cox James D
Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, USA.
Int J Radiat Oncol Biol Phys. 2004 Mar 1;58(3):735-42. doi: 10.1016/S0360-3016(03)01578-5.
This 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.
A 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.
The 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.
Tolerance 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.
这是关于放射治疗肿瘤学组（RTOG）9406研究中使用IV级剂量（74 Gy）治疗T1 - T2期前列腺腺癌的毒性结果的首次报告。
共有262例患者进入该协作组针对局限性前列腺癌的三维适形放疗I - II期剂量递增试验，给予74 Gy（IV级剂量）；256例患者可进行毒性分析。计划靶体积（PTV）的处方剂量最小为2 Gy/分次。根据Gleason评分和前列腺特异性抗原水平对精囊侵犯风险进行分层。1组患者为临床T1 - T2期肿瘤，精囊侵犯风险<15%。2组患者为临床T1 - T2期肿瘤，精囊侵犯风险≥15%。1组患者的前列腺PTV处方剂量为74 Gy。2组患者的前列腺和精囊（PTV1）处方剂量为54 Gy，随后仅对前列腺（PTV2）进行追加剂量至74 Gy。PTV边界要求在5至10 mm之间。未使用选择性盆腔放疗。将3级或更高级别的晚期效应发生率与RTOG 7506和7706研究中治疗的类似患者组进行比较，并根据治疗完成后的间隔时间对随访时间进行调整。还与206例接受II级剂量（1.8 Gy分次，共73.8 Gy）治疗的患者进行比较，以观察分次剂量是否影响毒性。
治疗完成后，1组和2组发生3级及以上晚期毒性的平均危险月数分别为28.9个月和23.9个月。IV级剂量（74 Gy）的急性毒性非常低，1组仅1%、2组仅3%的患者报告有3级急性效应。未报告4级或5级急性毒性。与RTOG历史对照相比，晚期毒性仍然较低。1组1例患者和2组4例患者发生3级膀胱毒性。2组2例患者发生3级肠道毒性。未报告4级或5级晚期效应。1组和2组2级晚期毒性（任何类型）的发生率分别为23%和16%。1组观察到的3级或更高级别晚期效应发生率（1例）显著低于（p <0.0001）历史对照数据预期的18.5例。2组观察到的发生率（6例）也显著低于（p = 0.0009）预期的21.3例。接受1.8 Gy分次73.8 Gy或2.0 Gy分次74 Gy治疗的患者在急性或晚期毒性发生率上未观察到统计学显著差异。接受2.0 Gy较大分次治疗的患者比接受1.8 Gy分次治疗的患者有更多3级或更高级别毒性（2%对1%，p = 0.09）。对II级剂量进行更长时间随访后的结果表明，随着随访时间延长这些差异可能会增加。
与历史对照相比，2 Gy分次给予74 Gy的三维适形放疗耐受性仍然优于预期。分次剂量的任何影响程度需要进一步随访观察。
