Michalski J M, Purdy J A, Winter K, Roach M, Vijayakumar S, Sandler H M, Markoe A M, Ritter M A, Russell K J, Sailer S, Harms W B, Perez C A, Wilder R B, Hanks G E, Cox J D
Mallinckrodt Institute of Radiology, St. Louis, MO 63110, USA.
Int J Radiat Oncol Biol Phys. 2000 Jan 15;46(2):391-402. doi: 10.1016/s0360-3016(99)00443-5.
A prospective Phase I dose escalation study was conducted to determine the maximally-tolerated radiation dose in men treated with three-dimensional conformal radiation therapy (3D CRT) for localized prostate cancer. This is a preliminary report of toxicity encountered on the 3DOG/RTOG 9406 study.
Each participating institution was required to implement data exchange with the RTOG 3D quality assurance (QA) center at Washington University in St. Louis. 3D CRT capabilities were strictly defined within the study protocol. Patients were registered according to three stratification groups: Group 1 patients had clinically organ-confined disease (T1,2) with a calculated risk of seminal vesicle invasion of < 15%. Group 2 patients had clinical T1,2 disease with risk of SV invasion > or = 15%. Group 3 (G3) patients had clinical local extension of tumor beyond the prostate capsule (T3). All patients were treated with 3D techniques with minimum doses prescribed to the planning target volume (PTV). The PTV margins were 5-10 mm around the prostate for patients in Group 1 and 5-10 mm around the prostate and SV for Group 2. After 55.8 Gy, the PTV was reduced in Group 2 patients to 5-10 mm around the prostate only. Minimum prescription dose began at 68.4 Gy (level I) and was escalated to 73.8 Gy (level II) and subsequently to 79.2 Gy (level III). This report describes the acute and late toxicity encountered in Group 1 and 2 patients treated to the first two study dose levels. Data from RTOG 7506 and 7706 allowed calculation of the expected probability of observing a > or = grade 3 late effect more than 120 days after the start of treatment. RTOG toxicity scores were used.
Between August 23, 1994 and July 2, 1997, 304 Group 1 and 2 cases were registered; 288 cases were analyzable for toxicity. Acute toxicity was low, with 53-54% of Group 1 patients having either no or grade 1 toxicity at dose levels I and II, respectively. Sixty-two percent of Group 2 patients had either none or grade 1 toxicity at either dose level. Few patients (0-3%) experienced a grade 3 acute bowel or bladder toxicity, and there were no grade 4 or 5 toxicities. Late toxicity was very low in all patient groups. The majority (81-85%) had either no or mild grade 1 late toxicity at dose level I and II, respectively. A single late grade 3 bladder toxicity in a Group 2 patient treated to dose level II was recorded. There were no grade 4 or 5 late effects in any patient. Compared to historical RTOG controls (studies 7506, 7706) at dose level I, no grade 3 or greater late effects were observed in Group 1 and Group 2 patients when 9.1 and 4.8 events were expected (p = 0.003 and p = 0.028), respectively. At dose level II, there were no grade 3 or greater toxicities in Group 1 patients and a single grade 3 toxicity in a Group 2 patient when 12.1 and 13.0 were expected (p = 0.0005 and p = 0.0003), respectively. Multivariate analysis demonstrated that the relative risk of developing acute bladder toxicity was 2.13 if the percentage of the bladder receiving > or = 65 Gy was more than 30% (p = 0.013) and 2.01 if patients received neoadjuvant hormonal therapy (p = 0.018). The relative risk of developing late bladder complications also increased as the percentage of the bladder receiving > or = 65 Gy increased (p = 0.026). Unexpectedly, there was a lower risk of late bladder complications as the mean dose to the bladder and prescription dose level increased. This probably reflects improvement in conformal techniques as the study matured. There was a 2.1 relative risk of developing a late bowel complication if the total rectal volume on the planning CT scan exceeded 100 cc (p = 0.019).
Tolerance to high-dose 3D CRT has been better than expected in this dose escalation trial for Stage T1,2 prostate cancer compared to low-dose RTOG historical experience. With strict quality assurance standards and review, 3D CRT can be safely studied in a co
开展一项前瞻性I期剂量递增研究，以确定接受三维适形放疗（3D CRT）治疗局限性前列腺癌的男性患者的最大耐受辐射剂量。这是3DOG/RTOG 9406研究中所遇毒性的初步报告。
要求各参与机构与圣路易斯华盛顿大学的RTOG 3D质量保证（QA）中心进行数据交换。研究方案中严格定义了3D CRT的能力。患者根据三个分层组进行登记：第1组患者患有临床器官局限性疾病（T1,2），精囊侵犯计算风险<15%。第2组患者患有临床T1,2疾病，精囊侵犯风险≥15%。第3组（G3）患者肿瘤临床局部扩展超出前列腺包膜（T3）。所有患者均采用3D技术治疗，对计划靶体积（PTV）规定最小剂量。第1组患者前列腺周围的PTV边界为5 - 10 mm，第2组患者前列腺和精囊周围的PTV边界为5 - 10 mm。55.8 Gy之后，第2组患者的PTV仅缩小至前列腺周围5 - 10 mm。最小处方剂量从68.4 Gy（I级）开始，递增至73.8 Gy（II级），随后递增至79.2 Gy（III级）。本报告描述了接受前两个研究剂量水平治疗的第1组和第2组患者所遇到的急性和晚期毒性。来自RTOG 7506和7706的数据用于计算治疗开始后超过120天观察到≥3级晚期效应的预期概率。使用RTOG毒性评分。
1994年8月23日至1997年7月2日期间，登记了304例第1组和第2组病例；288例可分析毒性情况。急性毒性较低，第1组患者在I级和II级剂量水平时分别有53 - 54%无毒性或为1级毒性。第2组患者在任一剂量水平时62%无毒性或为1级毒性。很少有患者（0 - 3%）经历3级急性肠道或膀胱毒性，无4级或5级毒性。所有患者组的晚期毒性都非常低。大多数（分别为81 - 85%）在I级和II级剂量水平时无晚期毒性或为轻度1级晚期毒性。记录到1例接受II级剂量水平治疗的第2组患者出现1级晚期膀胱毒性。任何患者均无4级或5级晚期效应。与历史RTOG对照（7506、7706研究）在I级剂量水平相比，第1组和第2组患者预期出现9.1次和4.8次≥3级晚期效应时，未观察到≥3级晚期效应（p = 0.003和p = 0.028）。在II级剂量水平时，第1组患者无≥3级毒性，第2组1例患者出现1级毒性，预期分别为12.1次和13.0次（p = 0.0005和p = 0.0003）。多因素分析表明，如果接受≥65 Gy照射的膀胱百分比超过30%，发生急性膀胱毒性的相对风险为2.13（p = 0.013），如果患者接受新辅助激素治疗，相对风险为2.01（p = 0.018）。随着接受≥65 Gy照射的膀胱百分比增加，发生晚期膀胱并发症的相对风险也增加（p = 0.026）。出乎意料的是，随着膀胱平均剂量和处方剂量水平增加，晚期膀胱并发症风险降低。这可能反映了随着研究成熟，适形技术有所改进。如果计划CT扫描上直肠总体积超过100 cc，发生晚期肠道并发症的相对风险为2.1（p = 0.019）。
与RTOG低剂量历史经验相比，在这项T1,2期前列腺癌剂量递增试验中，对高剂量3D CRT的耐受性优于预期。通过严格的质量保证标准和审查，3D CRT可在联合……中安全研究
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