Fiorino Claudio, Vavassori Vittorio, Sanguineti Giuseppe, Bianchi Carla, Cattaneo Giovanni Mauro, Piazzolla Anna, Cozzarini Cesare
Servizio di Fisica Sanitaria e Radiochemioterapia, H. San Raffaele, Via Olgettina 60, 20132 Milan, Italy.
Radiother Oncol. 2002 Jun;63(3):249-55. doi: 10.1016/s0167-8140(01)00469-8.
Recent investigations showed some correlation between three-dimensional (3D) treatment planning dose-volume data (dose-volume histograms: DVH, dose statistics) and rectal toxicity for patients treated for prostate cancer. However, no data are available about the possible impact of inter-institute variability in contouring the rectum, so that the possibility of reliably using information from single-centre studies remains doubtful.
Within a retrospective three-institutes study on correlation between dose-volume treatment planning data and rectum bleeding in patients treated for prostate cancer, an investigation about the impact of inter- and intra-observer variability in contouring the rectum was performed.
Ten patients were considered for a dummy run exercise and three observers (one per Institute) contoured the rectum (including filling). An anatomically based definition of rectum extension was previously accepted by the three observers. Six of the ten patients were randomly chosen in the subgroup of patients (large spacing, LS) with a distance between computed tomography (CT) slices (outside the prostate region) equal to 10 mm; for the remaining four patients the distance between CT slices was 5 mm over the whole rectum volume (small spacing, SS). The original 3D treatment planning was recovered on the Cadplan treatment planning system for each patient and rectum dose statistics (mean, median and maximum rectum dose), volume, DVH and NTCP values were calculated for each observer. For DVH analysis, the values of V(50), V(55), V(60), V(65) and V(70) (defined as the % of rectum volume receiving at least 50, 55, 60, 65, 70 Gy) were considered. Normal tissue complication probabilities (NTCPs) were calculated for the original ICRU dose and for a 75.6 Gy ICRU dose (NTCP and NTCP(75.6), respectively). Intra-observer variability was investigated by asking the observers to redraw the same rectum contours 6 months later and comparing the two contouring sessions.
In general, a good agreement was found for most patients and, in particular, for all SS patients. The impact of inter-observer variability was quite significant on dose statistics and DVH in two of six LS patients. Looking at the patient population, some systematic deviations, even if quite small, were demonstrated between institute B and institute C (volume, P = 0.02) and between institute A and institute B (mean/median dose, V(50)-V(65), NTCP(75.6); P < 0.05). Four of six LS patients (0/4 in the SS group) presented a maximum difference among observers at the cranial and/or caudal limit of the rectum equal to 1 cm. For these patients, inter-observer variability was significantly higher than for the others (P < 0.03). When inter-observer variability was expressed in terms of standard deviations (SD), values around 2-3 Gy and 0.5 Gy for LS and SS patients, respectively, were found for mean/median dose; values around 3-4% and 0.5-2% for LS and SS patients, respectively, were found for V(50)-V(70). The average SD for NTCP and NTCP(75.6) were 0.4 and 0.6%, respectively (0.5 and 0.9% for LS patients; 0.2 and 0.3% for SS patients). Intra-observer variability was found to be lower than inter-observer variability even if the impact on dose statistics and DVH was visible.
Once a robust definition of rectum is assessed, inter- and intra-institute variability in contouring the rectum appear relatively modest. However, the results suggest that the number of LS patients in DVH correlation studies should be as low as possible; the low number of these patients in the multi-centric trial involving our institutions should not have significant impact on the results of the study.
近期研究表明,前列腺癌患者的三维(3D)治疗计划剂量 - 体积数据(剂量 - 体积直方图:DVH,剂量统计)与直肠毒性之间存在一定相关性。然而,目前尚无关于直肠轮廓勾画中机构间差异可能影响的相关数据,因此,能否可靠地使用单中心研究信息仍存疑问。
在一项关于前列腺癌患者剂量 - 体积治疗计划数据与直肠出血相关性的回顾性三机构研究中,对直肠轮廓勾画中观察者间及观察者内差异的影响进行了调查。
选取10例患者进行模拟操作练习,由三名观察者(每个机构一名)对直肠进行轮廓勾画(包括充盈情况)。三名观察者事先已接受基于解剖学的直肠延伸定义。在患者亚组中,随机选择10例患者中的6例(大间距,LS),其计算机断层扫描(CT)切片(前列腺区域外)之间的距离为10 mm;其余4例患者在整个直肠体积上CT切片之间的距离为5 mm(小间距,SS)。针对每位患者,在Cadplan治疗计划系统上恢复原始的3D治疗计划,并计算每位观察者的直肠剂量统计数据(平均、中位数和最大直肠剂量)、体积、DVH和NTCP值。对于DVH分析,考虑V(50)、V(55)、V(60)、V(65)和V(70)的值(定义为接受至少50、55、60、65、70 Gy的直肠体积百分比)。计算原始ICRU剂量和75.6 Gy ICRU剂量下的正常组织并发症概率(分别为NTCP和NTCP(75.6))。通过要求观察者在6个月后重新绘制相同的直肠轮廓并比较两次轮廓勾画过程,研究观察者内差异。
总体而言,大多数患者,尤其是所有SS患者,轮廓勾画结果一致性良好。在6例LS患者中的2例中,观察者间差异对剂量统计和DVH的影响相当显著。从患者群体来看,机构B与机构C之间(体积,P = 0.02)以及机构A与机构B之间(平均/中位数剂量、V(50) - V(65)、NTCP(75.6);P < 0.05)存在一些系统性偏差,尽管偏差较小。6例LS患者中有4例(SS组为0/4)在直肠的头侧和/或尾侧边界处观察者间的最大差异等于1 cm。对于这些患者,观察者间差异显著高于其他患者(P < 0.03)。当以标准差(SD)表示观察者间差异时,LS患者和SS患者的平均/中位数剂量的标准差分别约为2 - 3 Gy和0.5 Gy;V(50) - V(70)的标准差分别约为3 - 4%和0.5 - 2%。NTCP和NTCP(75.6)的平均标准差分别为0.4%和0.6%(LS患者为0.5%和0.9%;SS患者为0.2%和0.3%)。发现观察者内差异低于观察者间差异,尽管对剂量统计和DVH的影响仍可见。
一旦确定了稳健的直肠定义,直肠轮廓勾画中的机构间及机构内差异相对较小。然而,结果表明DVH相关性研究中LS患者的数量应尽可能少;在涉及我们机构的多中心试验中,这些患者数量较少对研究结果不应有显著影响。