Waldron John, Warde Padraig, Irish Jon, Pintilie Melania, Sellmann Susanna, Bayley Andrew, Cummings Bernard, Kim John, Liu Fei-Fei, Payne David, Ringash Jolie, Brown Dale, Freeman Jeremy, Gilbert Ralph, Gullane Patrick, Witterick Ian, O'Sullivan Brian
Department of Radiation Oncology, Princess Margaret Hospital and the University of Toronto, Canada.
Radiother Oncol. 2008 May;87(2):173-80. doi: 10.1016/j.radonc.2008.02.014. Epub 2008 Mar 14.
To determine toxicity and outcome of radiation dose escalation with hyperfractionated accelerated radiation delivered with neck surgery (HARDWINS) for head and neck cancer.
Patients with stage III and IV squamous cell carcinoma of the oropharynx, hypopharynx or larynx were enrolled. Dose levels of 60, 62 and 64Gy were delivered with twice daily fractionation in 40 fractions over 4 weeks. Involved and at-risk nodal regions received microscopic dose (46.5-48Gy) with neck dissection for node positive patients 8 weeks after radiation.
One hundred and sixty-nine patients were enrolled (60Gy n=22, 62Gy n=26, 64Gy n=121). No grade 4 acute toxicity was observed. Incidence of acute grade 3 toxicity was: skin (2%), larynx (6%), pharynx and esophagus (66%) and mucous membrane (75%). Feeding tube dependence was observed in 14% of patients receiving 64Gy. Overall survival, and relapse free rate at 5 years were 65% and 63%, respectively. Local, nodal and distant relapse free rates at 5 years were 77%, 94% and 81% (median follow-up 3.8 years).
HARDWINS can be delivered without acute grade 4 toxicity but significant grade 3 acute toxicity. A significant proportion of the patients have prolonged swallowing dysfunction. Outcomes suggest this regimen represents an alternative to chemoradiation.
确定头颈部癌采用颈部手术联合超分割加速放疗（HARDWINS）提高放疗剂量后的毒性及疗效。
纳入口咽、下咽或喉III期和IV期鳞状细胞癌患者。在4周内分40次，每天两次分割给予60、62和64Gy的剂量。对于淋巴结阳性患者，在放疗8周后，对受累及有风险的淋巴结区域进行颈部清扫，并给予显微镜下剂量（46.5 - 48Gy）。
共纳入169例患者（60Gy组n = 22，62Gy组n = 26，64Gy组n = 121）。未观察到4级急性毒性反应。3级急性毒性反应的发生率为：皮肤（2%）、喉部（6%）、咽和食管（66%）以及黏膜（75%）。接受64Gy剂量的患者中14%出现饲管依赖。5年总生存率和无复发生存率分别为65%和63%。5年局部、区域和远处无复发生存率分别为77%、94%和81%（中位随访时间3.8年）。
HARDWINS方案可实施且无4级急性毒性反应，但有显著的3级急性毒性反应。相当一部分患者存在吞咽功能障碍延长的情况。结果表明该方案是放化疗的一种替代方案。
