Cooke Saskia A, de Ruysscher Dirk, Reymen Bart, Lambrecht Maarten, Fredberg Persson Gitte, Faivre-Finn Corinne, Dieleman Edith M T, Lewensohn Rolf, van Diessen Judi N A, Sikorska Karolina, Lalezari Ferry, Vogel Wouter, van Elmpt Wouter, Damen Eugène M F, Sonke Jan-Jakob, Belderbos José S A
Department of Radiation Oncology, Netherlands Cancer Institute (NKI-AVL), Amsterdam, the Netherlands.
Department of Radiation Oncology (MAASTRO Clinic), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, the Netherlands.
Radiother Oncol. 2023 Apr;181:109492. doi: 10.1016/j.radonc.2023.109492. Epub 2023 Jan 24.
We aimed to assess if radiation dose escalation to either the whole primary tumour, or to an F-FDG-PET defined subvolume within the primary tumour known to be at high risk of local relapse, could improve local control in patients with locally advanced non-small-cell lung cancer.
Patients with inoperable, stage II-III NSCLC were randomised (1:1) to receive dose-escalated radiotherapy to the whole primary tumour or a PET-defined subvolume, in 24 fractions. The primary endpoint was freedom from local failure (FFLF), assessed by central review of CT-imaging. A phase II 'pick-the-winner' design (alpha = 0.05; beta = 0.80) was applied to detect a 15 % increase in FFLF at 1-year.
gov:NCT01024829.
150 patients were enrolled. 54 patients were randomised to the whole tumour group and 53 to the PET-subvolume group. The trial was closed early due to slow accrual. Median dose/fraction to the boosted volume was 3.30 Gy in the whole tumour group, and 3.50 Gy in the PET-subvolume group. The 1-year FFLF rate was 97 % (95 %CI 91-100) in whole tumour group, and 91 % (95 %CI 82-100) in the PET-subvolume group. Acute grade ≥ 3 adverse events occurred in 23 (43 %) and 20 (38 %) patients, and late grade ≥ 3 in 12 (22 %) and 17 (32 %), respectively. Grade 5 events occurred in 19 (18 %) patients in total, of which before disease progression in 4 (7 %) in the whole tumour group, and 5 (9 %) in the PET-subvolume group.
Both strategies met the primary objective to improve local control with 1-year rates. However, both strategies led to unexpected high rates of grade 5 toxicity. Dose differentiation, improved patient selection and better sparing of central structures are proposed to improve dose-escalation strategies.
我们旨在评估对整个原发肿瘤或对原发肿瘤内已知局部复发风险高的F-FDG-PET定义子体积进行剂量递增放疗，是否能改善局部晚期非小细胞肺癌患者的局部控制。
无法手术的II-III期非小细胞肺癌患者被随机（1:1）分配接受对整个原发肿瘤或PET定义子体积的剂量递增放疗，分24次进行。主要终点是无局部失败（FFLF），通过CT成像的中心审查进行评估。采用II期“选出胜者”设计（α = 0.05；β = 0.80）来检测1年时FFLF增加15%。
gov:NCT01024829。
共入组150例患者。54例患者被随机分配至全肿瘤组，53例至PET子体积组。由于入组缓慢，试验提前结束。全肿瘤组增强体积的中位分次剂量为3.30 Gy，PET子体积组为3.50 Gy。全肿瘤组1年FFLF率为97%（95%CI 91 - 100），PET子体积组为91%（95%CI 82 - 100）。急性≥3级不良事件分别发生在23例（43%）和20例（38%）患者中，晚期≥3级分别发生在12例（22%）和17例（32%）患者中。5级事件共发生在19例（18%）患者中，其中全肿瘤组4例（7%）在疾病进展前发生，PET子体积组5例（9%）。
两种策略均达到了提高1年局部控制率的主要目标。然而，两种策略均导致了意外的高5级毒性发生率。建议进行剂量区分、改进患者选择并更好地保护中心结构，以改善剂量递增策略。
