Cicchetti A, Rancati T, Ebert M, Fiorino C, Palorini F, Kennedy A, Joseph D J, Denham J W, Vavassori V, Fellin G, Avuzzi B, Stucchi C, Valdagni R
Prostate Cancer Program, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Prostate Cancer Program, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Phys Med. 2016 Dec;32(12):1690-1697. doi: 10.1016/j.ejmp.2016.09.018. Epub 2016 Oct 6.
To investigate late gastrointestinal toxicity in a large pooled population of prostate cancer patients treated with radical radiotherapy. Normal tissue complication probability models were developed for late stool frequency and late rectal pain.
Population included 1336 patients, 3-year minimum follow-up, treated with 66-80Gy. Toxicity was scored with LENT-SOMA-scale. Two toxicity endpoints were considered: grade ⩾2 rectal pain and mean grade (average score during follow-up) in stool frequency >1. DVHs of anorectum were reduced to equivalent uniform dose (EUD). The best-value of the volume parameter n was determined through numerical optimization. Association between EUD/clinical factors and the endpoints was investigated by logistic analyses. Likelihood, Brier-score and calibration were used to evaluate models. External calibration was also carried out.
4% of patients (45/1122) reported mean stool frequency grade >1; grade ⩾2 rectal pain was present in the TROG 03.04 RADAR population only (21/677, 3.1%): for this endpoint, the analysis was limited to this population. Analysis of DVHs highlighted the importance of mid-range doses (30-50Gy) for both endpoints. EUDs calculated with n=1 (OR=1.04) and n=0.35 (OR=1.06) were the most suitable dosimetric descriptors for stool frequency and rectal pain respectively. The final models included EUD and cardiovascular diseases (OR=1.78) for stool frequency and EUD and presence of acute gastrointestinal toxicity (OR=4.2) for rectal pain.
Best predictors of stool frequency and rectal pain are consistent with findings previously reported for late faecal incontinence, indicating an important role in optimization of mid-range dose region to minimize these symptoms highly impacting the quality-of-life of long surviving patients.
在接受根治性放疗的大量前列腺癌患者汇总群体中研究晚期胃肠道毒性。针对晚期排便频率和晚期直肠疼痛建立正常组织并发症概率模型。
研究群体包括1336例患者，接受66 - 80Gy照射，最短随访3年。毒性采用LENT - SOMA量表评分。考虑两个毒性终点：≥2级直肠疼痛和排便频率平均分级（随访期间平均得分）>1。将直肠肛门的剂量体积直方图（DVH）换算为等效均匀剂量（EUD）。通过数值优化确定体积参数n的最佳值。通过逻辑分析研究EUD/临床因素与终点之间的关联。使用似然度、Brier评分和校准来评估模型。还进行了外部校准。
4%的患者（45/1122）报告排便频率平均分级>1；仅在TROG 03.04 RADAR群体中出现≥2级直肠疼痛（21/677，3.1%）：对于该终点，分析仅限于该群体。DVH分析突出了中等剂量范围（30 - 50Gy）对两个终点的重要性。分别用n = 1（OR = 1.04）和n = 0.35（OR = 1.06）计算的EUD是排便频率和直肠疼痛最合适的剂量学描述指标。最终模型包括排便频率的EUD和心血管疾病（OR = 1.78）以及直肠疼痛的EUD和急性胃肠道毒性的存在（OR = 4.2）。
排便频率和直肠疼痛的最佳预测因素与先前报道的晚期大便失禁的结果一致，表明在优化中等剂量区域以尽量减少这些对长期存活患者生活质量有高度影响的症状方面具有重要作用。
