Schultheiss T E, Hanks G E, Hunt M A, Lee W R
Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Int J Radiat Oncol Biol Phys. 1995 Jun 15;32(3):643-9. doi: 10.1016/0360-3016(95)00149-s.
The fundament hypothesis of conformal radiation therapy is that tumor control can be increased by using conformal treatment techniques that allow a higher tumor dose while maintaining an acceptable level of complications. To test this hypothesis, it is necessary first to estimate the incidence of morbidity for both standard and conformal fields. In this study, we examine factors that influence the incidence of late Grade 3 and 4 morbidity in patients treated with conformal and standard radiation treatment for prostate cancer.
Six hundred sixteen consecutive patients treated with conformal or standard techniques between 1986 and 1994 to doses greater than 65 Gy and with more than 3 months follow-up were analyzed. No patients treated with prostatectomies were included in the analysis. The conformal technique includes special immobilization by a cast, careful identification of the target volume in three dimensions, localization of the inferior border of the prostate using a retrograde urethrogram, and individually shaped portals that conform to the Planning Target Volume (PTV). Multivariate analysis using a proportional hazards model compares differences in the incidence of Radiation Therapy Oncology Group/European Organization for Research and Center Treatment (RTOG/EORTC) Grade 3 and 4 late gastrointestinal (GI) and genitourinary (GU) morbidity by technique, T-stage, grade, age, hormonal treatment, irradiated volume, dose, and comorbid conditions. Grade 3 rectal bleeding was defined as requiring three or more cautery procedures.
The overall actuarial incidence of genitourinary (GU) toxicities at 5 years was 3.4%, with the crude incidence being six cases in 616 patients satisfying the selection criteria; for gastrointestinal (GI) toxicities, the overall actuarial incidence was 2.7%, with the crude incidence being 13 cases out of 616 patients. The average time to complication for our patients was 12.8 months for GI toxicity and 32.9 months for GU toxicity (p < 0.001). No factors were found that were predictive for GU morbidity. The only factors significantly related to incidence of late GI morbidity on multivariate analysis of our data were dose and age. The central axis dose was a more significant variable than the dose prescribed to the Treated Volume. Age was negatively correlated with late GI morbidity, with older patients having a reduced incidence of toxicity. The median tolerance dose for GI complications was estimated to be 92.8 Gy, and the dose for 10% incidence was estimated to be 80.2 Gy. Treating the pelvis to 45 Gy did not increase the incidence of late morbidity. Late GI and GU toxicities were not correlated.
The conformal technique has been associated with fewer acute Grade 2 toxicities (6). The use of conformal fields did not decrease the incidence of late GI morbidity; however, patients with this technique invariably had higher doses. Because of the dose response for this complication and the correlation between the dose and the use of conformal fields, one would not expect to demonstrate an advantage to conformal fields in this data set. On the other hand, no dose effect was observed for late GU morbidity. In this case, there appears to be an advantage for conformal treatment that has not reached statistical significance because the follow-up time is shorter than for the patients treated with conventional fields and the latency for GU morbidity is long.
适形放射治疗的基本假设是，通过使用适形治疗技术可提高肿瘤控制率，该技术能在维持可接受并发症水平的同时给予更高的肿瘤剂量。为验证这一假设，首先有必要估算标准照射野和适形照射野的发病几率。在本研究中，我们考察了接受适形和标准放射治疗的前列腺癌患者中影响3级和4级晚期并发症发生率的因素。
分析了1986年至1994年间连续接受适形或标准技术治疗、剂量大于65 Gy且随访超过3个月的616例患者。接受前列腺切除术的患者未纳入分析。适形技术包括通过模具进行特殊固定、在三维空间中仔细确定靶区体积、使用逆行尿道造影定位前列腺下缘以及与计划靶区（PTV）相符的个体化照射野形状。使用比例风险模型进行多因素分析，比较按技术、T分期、分级、年龄、激素治疗、照射体积、剂量和合并症划分的放射治疗肿瘤学组/欧洲癌症研究与治疗组织（RTOG/EORTC）3级和4级晚期胃肠道（GI）和泌尿生殖系统（GU）并发症发生率的差异。3级直肠出血定义为需要三次或更多次烧灼治疗。
5年时泌尿生殖系统（GU）毒性的总体精算发生率为3.4%，在满足入选标准的616例患者中粗发生率为6例；对于胃肠道（GI）毒性，总体精算发生率为2.7%，616例患者中粗发生率为13例。我们的患者发生GI毒性的平均并发症时间为12.8个月，发生GU毒性的平均并发症时间为32.9个月（p < 0.001）。未发现可预测GU并发症的因素。在对我们的数据进行多因素分析时，与晚期GI并发症发生率显著相关的唯一因素是剂量和年龄。中心轴剂量比给予治疗体积的处方剂量是更显著的变量。年龄与晚期GI并发症呈负相关，老年患者毒性发生率降低。GI并发症的中位耐受剂量估计为92.8 Gy，10%发生率的剂量估计为80.2 Gy。盆腔照射至45 Gy未增加晚期并发症发生率。晚期GI和GU毒性不相关。
适形技术与较少的2级急性毒性相关（6）。使用适形照射野并未降低晚期GI并发症的发生率；然而，采用该技术的患者剂量总是更高。由于该并发症的剂量反应以及剂量与适形照射野使用之间的相关性，在该数据集中预计不会显示适形照射野的优势。另一方面，未观察到晚期GU并发症的剂量效应。在这种情况下，适形治疗似乎存在优势，但未达到统计学意义，因为随访时间短于接受传统照射野治疗的患者，且GU并发症的潜伏期长。
