Cagney D N, Thirion P G, Dunne M T, Fleming C, Fitzpatrick D, O'Shea C M, Finn M A, O'Sullivan S, Booth C, Collins C D, Buckney S J, Shannon A, Armstrong J G
St Luke's Radiation Oncology Network, Dublin, Ireland.
St Luke's Radiation Oncology Network, Dublin, Ireland.
Clin Oncol (R Coll Radiol). 2018 Jan;30(1):30-38. doi: 10.1016/j.clon.2017.10.010. Epub 2017 Oct 31.
The objective of this phase II clinical trial was to prospectively evaluate the safety and efficacy of accelerated hypofractionated three-dimensional conformal radiation therapy (3DCRT) in localised non-resectable/non-operable non-small cell lung cancer (NSCLC).
Sixty patients with stage I-III NSCLC were enrolled in a prospective single-arm All Ireland Co-operative Oncology Research Group (ICORG 99-09) toxicity end point phase II trial. The protocol allocated patients between three radiation schedule dose levels (60, 66 or 72 Gy, in 20, 22 and 24 fractions, respectively, 3 Gy daily, five fractions per week) according to combined lung V (V ≤ 30%) with built-in early stopping toxicity rules. The primary end point was toxicity with evaluation of dose-limiting toxicity. The secondary objectives included radiological tumour response rate at 3 months after the completion of radiation therapy and the thoracic progression-free survival time.
Sixty patients were recruited from August 1999 to June 2009. Forty-nine patients were included in the primary per-protocol analysis. Eleven patients were not evaluable. In the first 30 evaluable patient cohort, severe oesophageal toxicity was reported in two patients (2/49; 4% experiencing grade 5 oesophageal late toxicity, related to the 97% oesophageal length). The trial was temporarily closed and was then reopened to validate an oesophageal dose volume constraint (DVC) of limiting the length of oesophagus fully encompassed by the 97% isodose to less than 1 cm (applied to 21 patients). The trial prospectively showed the safety of the oesophageal DVC, with no oesophageal toxicity above grade 3 thereafter. Thirty-nine per cent of patients had disease progression at 3-4 months after radiotherapy, 22% had stable disease, 20% had a complete response and 14% had a partial response. The median overall survival was 13.6 months (95% confidence interval 10.5-16.7) and overall survival at 1 and 3 years was 57% and 29%, respectively.
A strategy using accelerated hypofractionated 3DCRT is feasible and reasonably safe for patients with inoperable NSCLC. It is safe to deliver for centrally located tumours if DVCs are applied to the oesophagus, which is the primary dose-limiting toxicity. Further studies are required to assess the efficacy of hypofractionated regimens for centrally located tumours using an oesophageal DVC and monitoring for oesophageal toxicity.
本II期临床试验的目的是前瞻性评估加速分割三维适形放射治疗（3DCRT）在局部不可切除/无法手术的非小细胞肺癌（NSCLC）中的安全性和疗效。
60例I - III期NSCLC患者参加了一项前瞻性单臂全爱尔兰合作肿瘤学研究组（ICORG 99 - 09）毒性终点II期试验。该方案根据肺V体积（V≤30%）并结合内置的早期停止毒性规则，将患者分配到三个放射治疗计划剂量水平（分别为60、66或72 Gy，分20、22和24次分割，每日3 Gy，每周5次分割）。主要终点是毒性，并评估剂量限制毒性。次要目标包括放疗完成后3个月时的放射学肿瘤反应率和无胸内进展生存期。
1999年8月至2009年6月共招募了60例患者。49例患者纳入主要符合方案分析。11例患者无法评估。在最初可评估的30例患者队列中，有2例患者报告了严重的食管毒性（2/49；4%发生5级食管晚期毒性，与97%食管长度相关）。试验暂时关闭，随后重新开放以验证食管剂量体积限制（DVC），即将97%等剂量线完全覆盖的食管长度限制在小于1 cm（应用于21例患者）。试验前瞻性地显示了食管DVC的安全性，此后无3级以上食管毒性。39%的患者在放疗后3 - 4个月疾病进展，22%疾病稳定，20%完全缓解，14%部分缓解。中位总生存期为13.6个月（95%置信区间10.5 - 16.7），1年和3年总生存率分别为57%和29%。
对于无法手术的NSCLC患者，采用加速分割3DCRT的策略是可行且相当安全的。如果对食管应用DVC，对于中心型肿瘤进行放疗是安全的，食管是主要的剂量限制毒性部位。需要进一步研究来评估使用食管DVC并监测食管毒性的分割方案对中心型肿瘤的疗效。
