Space Coast Cancer Center, Titusville, FL, USA.
Radiat Oncol. 2013 Nov 20;8:273. doi: 10.1186/1748-717X-8-273.
Flattening filter-free (FFF) linear accelerators (linacs) are capable of delivering dose rates more than 4-times higher than conventional linacs during SBRT treatments, causing some to speculate whether the higher dose rate leads to increased toxicity owing to radiobiological dose rate effects. Despite wide clinical use of this emerging technology, clinical toxicity data for FFF SBRT are lacking. In this retrospective study, we report the acute and late toxicities observed in our lung radiosurgery experience using a FFF linac operating at 2400 MU/min.
We reviewed all flattening filter-free (FFF) lung SBRT cases treated at our institution from August 2010 through July 2012. Patients were eligible for inclusion if they had at least one clinical assessment at least 30 days following SBRT. Pulmonary, cardiac, dermatologic, neurologic, and gastrointestinal treatment related toxicities were scored according to CTCAE version 4.0. Toxicity observed within 90 days of SBRT was categorized as acute, whereas toxicity observed more than 90 days from SBRT was categorized as late. Factors thought to influence risk of toxicity were examined to assess relationship to grade > =2 toxicity.
Sixty-four patients with >30 day follow up were eligible for inclusion. All patients were treated using 10 MV unflattened photons beams with intensity modulated radiation therapy (IMRT) inverse planning. Median SBRT dose was 48 Gy in 4 fractions (range: 30-60 Gy in 3-5 fractions). Six patients (9%) experienced > = grade 2 acute pulmonary toxicity; no non-pulmonary acute toxicities were observed. In a subset of 49 patients with greater than 90 day follow up (median 11.5 months), 11 pulmonary and three nerve related grade > =2 late toxicities were recorded. Pulmonary toxicities comprised six grade 2, three grade 3, and one each grade 4 and 5 events. Nerve related events were rare and included two cases of grade 2 chest wall pain and one grade 3 brachial plexopathy which spontaneously resolved. No grade > =2 late gastrointestinal, skin, or cardiac toxicities were observed. Tumor size, biologically effective dose (BED10, assuming α/β of 10), and tumor location (central vs peripheral) were not significantly associated with grade > =2 toxicity.
In this early clinical experience, lung SBRT using a FFF linac operating at 2400 MU/min yields minimal acute toxicity. Preliminary results of late treatment related toxicity suggest reasonable rates of grade > =2 toxicities. Further assessment of late effects and confirmation of the clinical efficacy of FFF SBRT is warranted.
在立体定向体部放射治疗（SBRT）中，使用不带准直器滤过的（FFF）线性加速器（linacs）能够提供比传统 linacs 高出 4 倍以上的剂量率，这使得一些人推测较高的剂量率是否会因放射生物学剂量率效应而导致毒性增加。尽管这项新兴技术得到了广泛的临床应用，但目前还缺乏 FFF SBRT 的临床毒性数据。在这项回顾性研究中，我们报告了在使用以 2400 MU/min 运行的 FFF 直线加速器进行肺部放射外科手术时观察到的急性和晚期毒性。如果患者在 SBRT 后至少有 30 天的临床评估，他们有资格被纳入研究。根据 CTCAE 第 4.0 版对肺、心脏、皮肤、神经和胃肠道相关的治疗毒性进行评分。在 SBRT 后 90 天内观察到的毒性被归类为急性，而在 SBRT 后超过 90 天观察到的毒性被归类为晚期。检查了被认为会影响毒性风险的因素，以评估与≥2 级毒性的关系。
64 名有≥30 天随访的患者符合纳入标准。所有患者均采用 10MV 未准直光子束和调强放疗（IMRT）逆向计划进行治疗。SBRT 剂量中位数为 48Gy，分 4 次（范围：30-60Gy，分 3-5 次）。6 名患者（9%）发生了≥2 级急性肺部毒性；未观察到非肺部急性毒性。在 49 名随访时间超过 90 天（中位时间 11.5 个月）的患者亚组中，记录了 11 例肺部和 3 例神经相关的≥2 级晚期毒性。肺部毒性包括 6 例 2 级、3 例 3 级和 1 例 4 级和 5 级事件。神经相关事件较为罕见，包括 2 例 2 级胸壁疼痛和 1 例 3 级臂丛神经病，均自行缓解。未观察到≥2 级晚期胃肠道、皮肤或心脏毒性。肿瘤大小、生物有效剂量（BED10，假设 α/β 为 10）和肿瘤位置（中央与外周）与≥2 级毒性无显著相关性。
在这项早期临床经验中，使用以 2400 MU/min 运行的 FFF 直线加速器进行肺部 SBRT 产生的急性毒性最小。晚期治疗相关毒性的初步结果表明，≥2 级毒性的发生率合理。需要进一步评估晚期效应并确认 FFF SBRT 的临床疗效。
