Guys and St Thomas' NHS Foundation Trust, London, UK.
The London CyberKnife Centre, The Harley Street Clinic, 81 Harley Street, London, W1G 8PP, UK.
Radiat Oncol. 2018 Oct 19;13(1):204. doi: 10.1186/s13014-018-1138-3.
Stereotactic ablative radiotherapy (SABR) offers an alternative treatment for pancreatic cancer, with the potential for improved tumour control and reduced toxicity compared with conventional therapies. However, optimal dose planning and delivery strategies are unelucidated and gastro-intestinal (GI) toxicity remains a key concern.
Patients with inoperable non-metastatic pancreatic cancer who received CyberKnife® SABR (18-36 Gy) in three fractions as primary, adjuvant, consolidation or re-treatment options were studied. Patient individualised planning and delivery variables were collected and their impact on patient outcome examined. Linear-quadratic (LQ) radiobiology modelling methods were applied to assess SABR parameters against a conventional fractionated radiotherapy schedule.
In total 42 patients were included, 37 (88%) of whom had stage T4 disease. SABR was used > 6 months post-primary therapy to re-treat residual disease in 11 (26.2%) patients and relapsed disease in nine (21.4%) patients. SABR was an adjuvant to other primary therapy for 14 (33.3%) patients and was the sole primary therapy for eight (19.0%) patients. The mean (95% CI) planning target volume (PTV), prescription isodose, percentage cover, minimum dose to PTV and biological effective dose (BED) were 76.3(63.8-88.7) cc, 67.3(65.2-69.5)%, 96.6(95.5-97.7)%, 22.3(21.0-23.6) Gy and 50.3(47.7-53.0) Gy, respectively. Only 3/37 (8.1%) patients experienced Grade 3 acute toxicities. Two (4.8%) patients converted to resectable status and median freedom-from-local-progression (FFLP) and overall survival (OS) were 9.8 and 8.4 months, respectively. No late toxicity was experienced in 27/32 (84.4%) patients; however, four (12.5%) patients - of whom two had particularly large PTV, two had sub-optimal number of fiducials and three breached organ-at-risk (OAR) constraints-showed Grade 4 duodenal toxicities. Longer delivery time, extended treatment course and reduced percentage coverage additionally associated with late toxicity, likely reflecting parameters typically applied to riskier patients. Larger PTV size and longer treatment course associated with OS. Comparator regimen LQ modelling analysis indicated 50% of patients received minimum PTV doses less potent than a conventional radiotherapy regimen, indicating scope for dose escalation.
The results demonstrate the value of SABR for a range of indications in pancreatic cancer. Dose escalation to increase BED may improve FFLP and OS in inoperable, non-metastatic disease: however concomitant enhanced stringency for duodenal protection is critical, particularly for patients where SABR is more challenging.
立体定向消融放疗（SABR）为胰腺癌提供了一种替代治疗方法，与传统疗法相比，其具有改善肿瘤控制和降低毒性的潜力。然而，最佳的剂量规划和传递策略尚不清楚，胃肠道（GI）毒性仍然是一个关键问题。
研究了 42 名接受 CyberKnife®SABR（18-36Gy）作为原发性、辅助性、巩固性或再治疗选择的无法手术的非转移性胰腺癌患者。收集了患者个体化的计划和传递变量，并检查了它们对患者结果的影响。应用线性二次（LQ）放射生物学模型方法评估 SABR 参数与常规分割放疗方案的比较。
共有 42 名患者入组，其中 37 名（88%）患者为 T4 期疾病。SABR 用于原发性治疗后>6 个月，以重新治疗 11 名（26.2%）患者的残留疾病和 9 名（21.4%）患者的复发疾病。SABR 是 14 名（33.3%）患者的其他原发性治疗的辅助手段，也是 8 名（19.0%）患者的唯一原发性治疗手段。平均（95%CI）计划靶区（PTV）、处方等剂量、覆盖率、PTV 最小剂量和生物有效剂量（BED）分别为 76.3（63.8-88.7）cc、67.3（65.2-69.5）%、96.6（95.5-97.7）%、22.3（21.0-23.6）Gy 和 50.3（47.7-53.0）Gy。仅 3/37（8.1%）名患者发生 3 级急性毒性。2 名（4.8%）患者转化为可切除状态，中位无局部进展生存期（FFLP）和总生存期（OS）分别为 9.8 和 8.4 个月。27/32（84.4%）名患者无晚期毒性；然而，4 名（12.5%）患者 - 其中 2 名患者 PTV 特别大，2 名患者的基准线数量不足，3 名患者突破了危及器官（OAR）的限制 - 出现了 4 级十二指肠毒性。更长的传递时间、延长的治疗过程和降低的覆盖率与晚期毒性相关，这可能反映了通常应用于风险更高的患者的参数。较大的 PTV 大小和较长的治疗过程与 OS 相关。比较方案的 LQ 模型分析表明，50%的患者接受的 PTV 最小剂量比常规放疗方案的剂量弱，这表明需要增加剂量。
结果表明 SABR 在胰腺癌的多种适应症中具有价值。增加 BED 的剂量升级可能会改善无法手术的非转移性疾病的 FFLP 和 OS：然而，十二指肠保护的严格性需要同时增强，特别是对于 SABR 更具挑战性的患者。
