Analysis of CT-verified loco-regional recurrences after definitive IMRT for HNSCC using site of origin estimation methods

Introduction: A significant part of patients with head and neck squamous cell carcinoma (HNSCC) develop recurrent disease after curative radiotherapy. We aimed to analyze loco-regional recurrence pattern by identifying possible points of recurrence origin by three different methods in relation to treatment volumes. Material and methods: A total of 455 patients completed IMRT-based treatment for HNSCC from 2006 to 2012. A total of 159 patients had remaining cancer after IMRT, developed loco-regional recurrence or distant disease during follow-up. Among those, 69 patients with loco-regional recurrences had affirmative CT or PET/CT scan. Possible points of origin (POs) of the recurrences were identified on scans by two independent observers, estimated as center of mass and as maximum surface distance. The recurrence position was analyzed in relation to high-dose treatment volume (CTV1) and 95% of prescription dose. Results: In total, 104 loco-regional recurrences (54 in T-site and 50 in N-site) were identified in 69 patients. Median time to recurrence for the 69 patients was 10 months. No clinically relevant difference was found between the four POs, with standard deviation between POs in x, y and z axes of 3, 3 and 6 mm. For recurrences inside CTV1, 0–5 mm and 5–10 mm outside CTV1 the standard deviation of dose differences between the POs were 1, 1.4 and 1 Gy, respectively. 56% and 25% of T-site and N-site recurrences were inside CTV1, respectively. Coverage by 95% prescription dose to high-dose treatment volume was achieved in 78% of T-site and 39% of N-site recurrences. Conclusions: For recurrences identified by possible points of recurrence origin, no significant difference between observer-based or mathematically estimated methods was found. More than half of T-site recurrences were inside high-dose treatment volume, whereas N-site recurrences were mainly outside.

引言
头颈部鳞状细胞癌（head and neck squamous cell carcinoma, HNSCC）患者中，有相当比例在接受根治性放疗后会出现肿瘤复发。本研究旨在通过三种不同方法，结合治疗靶区特征，明确复发潜在起源位点，进而分析局部区域复发模式。

材料与方法
2006年至2012年间，共计455例头颈部鳞状细胞癌患者接受了基于调强放射治疗（intensity-modulated radiation therapy, IMRT）的方案治疗。其中159例患者在IMRT治疗后存在残留癌，或在随访期间出现局部区域复发、远处转移。在该亚组患者中，69例经CT或PET/CT扫描证实存在局部区域复发的患者被纳入分析。由两名独立观察者在扫描图像上识别复发的潜在起源位点（possible points of origin, POs），并分别通过质心计算与最大表面距离两种方式进行估算。结合高剂量治疗靶区（CTV1）与95%处方剂量覆盖范围，对复发灶位置开展分析。

结果
69例患者中共检出104个局部区域复发灶，其中原发灶部位（T-site）54个，区域淋巴结部位（N-site）50个。69例患者的中位复发时间为10个月。四种潜在起源位点之间未观察到具有临床意义的差异，其在X、Y、Z轴上的标准差分别为3mm、3mm与6mm。针对CTV1内部、CTV1外0~5mm区间以及CTV1外5~10mm区间的复发灶，不同起源位点估算的剂量差异标准差分别为1Gy、1.4Gy与1Gy。原发灶部位复发灶中56%、区域淋巴结部位复发灶中25%位于CTV1内部。78%的原发灶部位复发灶与39%的区域淋巴结部位复发灶处于95%处方剂量覆盖范围内。

结论
针对通过潜在复发起源位点识别的复发灶，基于观察者的估算方法与数学估算方法之间未发现显著差异。超过半数的原发灶部位复发灶位于高剂量治疗靶区内部，而区域淋巴结部位复发灶则主要分布于靶区之外。