Sanduleanu Sebastian, Hamming-Vrieze Olga, Wesseling Frederik W R, Even Aniek J G, Hoebers Frank J, Hoeben Ann, Vogel Wouter V, Tesselaar Margot E T, Parvin Daniel, Bartelink Harry, Lambin Philippe
The D-Lab, Dpt of Precision Medicine, GROW - School for Oncology, Maastricht University, The Netherlands.
Department of Radiation Oncology (Netherlands Cancer Institute - Antoni van Leeuwenhoek), Plesmanlaan 121, 1066CX Amsterdam, The Netherlands.
Clin Transl Radiat Oncol. 2020 Apr 18;23:9-15. doi: 10.1016/j.ctro.2020.04.004. eCollection 2020 Jul.
The presence of hypoxia in head-and-neck squamous cell carcinoma is a negative prognostic factor. PET imaging with [18F] HX4 can be used to visualize hypoxia, but it is currently unknown how this correlates with prognosis. We investigated the prognostic value of [18F] HX4 PET imaging in patients treated with definitive radio(chemo)therapy (RTx).
We analyzed 34 patients included in two prospective clinical trials (NCT01347281, NCT01504815). Static [18F] HX4 PET-CT images were collected, both pre-treatment (median 4 days before start RTx, range 1-16), as well as during RTx (median 13 days after start RTx, range 3-17 days). Static uptake at both time points (n = 33 pretreatment, n = 28 during RTx) and measured changes in hypoxic fraction (HF) and hypoxic volume (HV) (n = 27 with 2 time points) were analyzed. Univariate cox analyses were done for local progression free survival (PFS) and overall survival (OS) at both timepoints. Change in uptake was analyzed by comparing outcome with Kaplan-Meier curves and log-rank test between patients with increased and decreased/stable hypoxia, similarly between patients with and without residual hypoxia (rHV = ratio week 2/baseline HV with cutoff 0.2). Voxelwise Spearman correlation coefficients were calculated between normalized [18F] HX4 PET uptake at baseline and week 2.
Analyses of static images showed no prognostic value for [18F] HX4 uptake. Analysis of dynamic changes showed that both OS and local PFS were significantly shorter (log-rank P < 0.05) in patients with an increase in HV during RTx and OS was significantly shorter in patients with rHV, with no correlation to HPV-status. The voxel-based correlation to evaluate spatial distribution yielded a median Spearman correlation coefficient of 0.45 (range 0.11-0.65).
The change of [18F] HX4 uptake measured on [18F] HX4 PET early during treatment can be considered for implementation in predictive models. With these models patients with a worse prognosis can be selected for treatment intensification.
头颈部鳞状细胞癌中缺氧的存在是一个负面预后因素。使用[18F]HX4进行正电子发射断层显像（PET）可用于显示缺氧情况，但目前尚不清楚其与预后的相关性。我们研究了[18F]HX4 PET显像在接受根治性放（化）疗（RTx）患者中的预后价值。
我们分析了纳入两项前瞻性临床试验（NCT01347281、NCT01504815）的34例患者。收集了静态[18F]HX4 PET-CT图像，包括治疗前（RTx开始前中位4天，范围1 - 16天）以及RTx期间（RTx开始后中位13天，范围3 - 17天）。分析了两个时间点的静态摄取情况（治疗前n = 33，RTx期间n = 28）以及测量的缺氧分数（HF）和缺氧体积（HV）的变化（有两个时间点的n = 27）。对两个时间点的局部无进展生存期（PFS）和总生存期（OS）进行单变量cox分析。通过比较缺氧增加和减少/稳定的患者之间以及有和无残留缺氧（rHV = 第2周/基线HV比值，临界值为0.2）的患者之间的Kaplan-Meier曲线和对数秩检验来分析摄取变化。计算基线和第2周时标准化[18F]HX4 PET摄取之间的体素级Spearman相关系数。
静态图像分析显示[18F]HX4摄取无预后价值。动态变化分析表明，RTx期间HV增加的患者OS和局部PFS均显著缩短（对数秩P < 0.05），rHV患者的OS显著缩短，且与HPV状态无关。基于体素的评估空间分布的相关性得出Spearman相关系数中位数为0.45（范围0.11 - 0.65）。
治疗早期在[18F]HX4 PET上测量的[18F]HX4摄取变化可考虑纳入预测模型。通过这些模型，可以选择预后较差的患者进行强化治疗。
