Berwouts Dieter, Madani Indira, Duprez Frédéric, Olteanu AnaMaria Luiza, Vercauteren Tom, Boterberg Tom, Deron Philippe, Bonte Katrien, Huvenne Wouter, De Neve Wilfried, Goethals Ingeborg
Department of Radiotherapy and Experimental Cancer Research, Ghent University Hospital, Ghent, Belgium.
Department of Nuclear Medicine, Ghent University Hospital, Ghent, Belgium.
Head Neck. 2017 Nov;39(11):2264-2275. doi: 10.1002/hed.24892. Epub 2017 Aug 21.
The purpose of this study was to report the long-term outcome of F-fluorodeoxyglucose-positron emission tomography ( F-FDG-PET)-guided dose painting for head and neck cancer in comparison to conventional intensity-modulated radiotherapy (IMRT) in a matched case-control study.
Seventy-two patients with nonmetastatic head and neck cancer treated with dose painting were compared with 72 control patients matched on tumor site and T classification. Either F-FDG-PET-guided dose painting by contour (DPBC) or voxel intensity-based dose painting by number (DPBN) was performed; control patients underwent standard IMRT. A total median dose to the dose-painted target was 70.2-85.9 Gy/30-32 fractions versus 69.1 Gy/32 fractions with conventional IMRT. In 31 patients, dose painting was adapted to per-treatment changes in the tumor and organs-at-risk (OAR).
Median follow-up in living dose-painting and control patients was 87.7 months (range 56.1-119.3) and 64.8 months (range 46.3-83.4), respectively. Five-year local control rates in the dose-painting patients were 82.3% against 73.6% in the control (P = .36); in patients treated to normalized isoeffective doses >91 Gy (NID2Gy) local control reached 85.7% at 5 years against 73.6% in the control group (P =.39). There was no difference in regional (P = .82) and distant control (P = .78). Five-year overall and disease-specific survival rates were 36.3% versus 38.1% (P = .50) and 56.5% versus 51.7% (P = .72), respectively. A half of the dose-painting patients developed acute grade ≥3 dysphagia (P = .004). Late grade 4 mucosal ulcers at the site of dose escalation in 9 of 72 patients was the most common severe toxicity with dose painting versus 3 of 72 patients with conventional IMRT (P = .11). Patients in the dose-painting group had increased rates of acute and late dysphagia (P = .004 and P = .005).
Dose-painting strategies can be used to increase dose to specific tumor subvolumes. Five-year local, regional, and distant control rates are comparable with patients treated with conventional IMRT. Volume and intensity of dose escalation should be further tailored, given the possible increase in severe acute and chronic toxicity. Adapting treatment and decreasing dose to the swallowing structures might contribute to lower toxicity rates when applied in smaller tumor volumes. Whether adaptive DPBN can significantly improve outcomes is currently being investigated in a novel clinical trial.
本研究旨在通过一项匹配病例对照研究，报告氟脱氧葡萄糖正电子发射断层扫描（F-FDG-PET）引导的剂量调强放疗用于头颈癌的长期疗效，并与传统调强放疗（IMRT）进行比较。
72例接受剂量调强放疗的非转移性头颈癌患者与72例在肿瘤部位和T分期相匹配的对照患者进行比较。采用F-FDG-PET引导的轮廓剂量调强放疗（DPBC）或基于体素强度的数字剂量调强放疗（DPBN）；对照患者接受标准IMRT。剂量调强放疗靶区的总中位剂量为70.2 - 85.9 Gy/30 - 32次分割，而传统IMRT为69.1 Gy/32次分割。31例患者的剂量调强放疗根据每次治疗时肿瘤和危及器官（OAR）的变化进行调整。
接受剂量调强放疗的患者和对照患者的中位随访时间分别为87.7个月（范围56.1 - 119.3个月）和64.8个月（范围46.3 - 83.4个月）。剂量调强放疗患者的5年局部控制率为82.3%，对照患者为73.6%（P = 0.36）；接受归一化等效剂量>91 Gy（NID2Gy）治疗的患者5年局部控制率达到85.7%，对照组为73.6%（P = 0.39）。区域控制（P = 0.82）和远处控制（P = 0.78）无差异。5年总生存率和疾病特异性生存率分别为36.3%对38.1%（P = 0.50）和56.5%对51.7%（P = 0.72）。一半的剂量调强放疗患者发生急性3级及以上吞咽困难（P = 0.004）。72例患者中有9例在剂量增加部位出现晚期4级黏膜溃疡，这是剂量调强放疗最常见的严重毒性反应，而72例接受传统IMRT的患者中有3例出现（P = 0.11）。剂量调强放疗组患者的急性和晚期吞咽困难发生率增加（P = 0.004和P = 0.005）。
剂量调强放疗策略可用于增加特定肿瘤亚体积的剂量。5年局部、区域和远处控制率与接受传统IMRT治疗的患者相当。考虑到严重急性和慢性毒性可能增加，应进一步调整剂量增加的体积和强度。当应用于较小肿瘤体积时，调整治疗方案并减少对吞咽结构的剂量可能有助于降低毒性发生率。目前正在一项新的临床试验中研究自适应DPBN是否能显著改善疗效。
