Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Regional Cancer Center West, Western Sweden Healthcare Region, Gothenburg, Sweden.
Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York.
Int J Radiat Oncol Biol Phys. 2018 Dec 1;102(5):1514-1532. doi: 10.1016/j.ijrobp.2018.08.015. Epub 2018 Aug 17.
The aims of this study were to systematically review tolerance doses for late distinct gastrointestinal (GI), genitourinary (GU), and sexual dysfunction (SD) symptoms after external beam radiation therapy (EBRT) alone and treatments involving brachytherapy (BT) for prostate cancer after Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) and ultimately to perform quantitative syntheses of identified dose/volume tolerances represented by dose-volume histogram (DVH) thresholds, that is, statistically significant (P ≤ .05) cutoff points between symptomatic and asymptomatic patients in a certain study.
PubMed was scrutinized for full-text articles in English after QUANTEC (January 1, 2010). The inclusion criteria were randomized controlled trials, case-control studies, or cohort studies with tolerance doses for late distinct symptoms ≥3 months after primary radiation therapy for prostate cancer (N > 30). All DVH thresholds were converted into equivalent doses in 2-Gy fractions (EQD2) and were fitted with a linear or linear-quadratic function (goodness of fit, R). The review was registered on PROSPERO (CRD42016042464).
From 33 identified studies, which included 36 to 746 patients per symptom domain, the majority of dose/volume tolerances were derived for GI toxicity after EBRT alone (GI, 97 thresholds; GU, 8 thresholds; SD, 1 threshold). For 5 symptoms (defecation urgency, diarrhea, fecal incontinence, proctitis, and rectal bleeding), relationships between dose/volume tolerances across studies (R = 0.93 [0.82-1.00]), and across symptoms, leading to a curve for overall GI toxicity (R = 0.98), could be determined. For these symptoms, mainly rectal thresholds were found throughout low and high doses (10 Gy ≤ equivalent dose in 2-Gy fractions using α/β = 3Gy (EQD2) ≤ 50 Gy and 55 Gy ≤ EQD2 ≤ 78 Gy, respectively). For BT with or without EBRT, dose/volume tolerances were also mainly identified for GI toxicity (GI, 14 thresholds; GU, 4 thresholds; SD, 2 thresholds) with the largest number of DVH thresholds concerning rectal bleeding (5 thresholds).
Updated dose/volume tolerances after QUANTEC were found for 17 GI, GU, or SD symptoms. A DVH curve described the relationship between dose/volume tolerances across 5 GI symptoms after EBRT alone. Restricting treatments for EBRT alone using the lower boundaries of this curve is likely to limit overall GI toxicity, but this should be explored prospectively. Dose/volume tolerances for GU and SD toxicity after EBRT alone and after BT with or without EBRT were scarce and support further research including data-sharing initiatives to untangle the dose/volume relationships for these symptoms.
本研究旨在通过系统回顾外照射放疗（EBRT）后及包含近距离放疗（BT）的治疗后晚期明确胃肠道（GI）、泌尿生殖系统（GU）和性功能障碍（SD）症状的耐受剂量，这些治疗均用于前列腺癌。我们的参考标准是临床中正常组织效应的定量分析（QUANTEC）以及最终通过剂量-体积直方图（DVH）阈值进行定量综合，即识别代表症状和无症状患者之间具有统计学意义（P≤.05）的剂量/体积阈值。
在 QUANTEC 后（2010 年 1 月 1 日），我们在 PubMed 上搜索了英文全文文章。纳入标准为随机对照试验、病例对照研究或队列研究，其对前列腺癌根治性放疗后≥3 个月的晚期明确症状的耐受剂量≥30 例。所有 DVH 阈值均转换为等效剂量（2-Gy 分数，EQD2），并拟合线性或线性二次函数（拟合优度，R）。该综述已在 PROSPERO（CRD42016042464）上注册。
从 33 项已识别的研究中，每个症状领域包括 36 至 746 例患者，其中大部分剂量/体积耐受度是基于 EBRT 后单独的 GI 毒性（GI，97 个阈值；GU，8 个阈值；SD，1 个阈值）。对于 5 种症状（排便急迫、腹泻、大便失禁、直肠炎和直肠出血），可以确定各研究之间的剂量/体积耐受度（R=0.93[0.82-1.00]）和各症状之间的关系，从而得到总体 GI 毒性的曲线（R=0.98）。对于这些症状，主要是直肠阈值在低剂量和高剂量时都被发现（10 Gy≤等效剂量（2-Gy 分数，α/β=3Gy（EQD2）≤50 Gy 和 55 Gy≤EQD2≤78 Gy）。对于 BT 加或不加 EBRT，剂量/体积耐受度也主要是针对 GI 毒性（GI，14 个阈值；GU，4 个阈值；SD，2 个阈值），涉及直肠出血的 DVH 阈值最多（5 个阈值）。
在 QUANTEC 之后，我们发现了 17 个 GI、GU 或 SD 症状的更新的剂量/体积耐受度。EBRT 后单独的 5 种 GI 症状的 DVH 曲线描述了剂量/体积耐受度之间的关系。使用该曲线的较低边界来限制 EBRT 单独治疗可能会限制总体 GI 毒性，但这需要前瞻性研究。EBRT 后单独的 GU 和 SD 毒性以及 BT 加或不加 EBRT 的剂量/体积耐受度很少，支持进一步研究，包括数据共享倡议，以厘清这些症状的剂量/体积关系。
