PATHOS: a phase II/III trial of risk-stratified, reduced intensity adjuvant treatment in patients undergoing transoral surgery for Human papillomavirus (HPV) positive oropharyngeal cancer
PATHOS: a phase II/III trial of risk-stratified, reduced intensity adjuvant treatment in patients undergoing transoral surgery for Human papillomavirus (HPV) positive oropharyngeal cancer
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DOI：
10.1186/s12885-015-1598-x
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发表时间：
2015-08-27
期刊：
影响因子：
3.8
通讯作者：
Evans, Mererid
中科院分区：
文献类型：
--
作者：
Owadally, Waheeda;Hurt, Chris;Evans, Mererid
背景：人乳头瘤病毒阳性的口咽鳞状细胞癌在世界范围内的发病率正在上升。目前的治疗与高存活率相关，但通常会导致显著的长期毒性。特别是，长期吞咽困难对患者的生活质量和健康有负面影响。PATHOS的目的是确定在这种预后良好的疾病中，降低微创经口手术后辅助治疗的强度是否会导致更好的长期吞咽功能，同时保持良好的疾病特异性生存结局。方法/设计：该研究是一项多中心II/III期随机对照试验，针对活检证实的T1-T4期人乳头瘤病毒阳性口咽鳞状细胞癌患者。T3 N 0-N2 b，原发性肿瘤可通过经口途径切除。在经口手术和颈淋巴清扫术后，根据复发的病理风险因素将患者分为三组。低风险病理组的患者将不接受辅助治疗，如标准实践。中危病理组患者将随机接受标准剂量术后放疗（对照）或降低剂量放疗。高危病理组患者将随机接受术后放化疗（对照）或单纯放疗。II期研究的主要结局是治疗后12个月使用MD安德森吞咽困难量表评分测量的患者报告的吞咽功能。如果第二阶段的研究是成功的，PATHOS将进行第三阶段的非劣效性试验，总生存率作为主要终点。讨论：PATHOS是一个前瞻性的，随机试验人乳头瘤病毒阳性口咽癌，这是一个不同的疾病实体相比，其他头部和颈部癌症。该试验旨在证明可以通过降低辅助治疗的强度来减轻长期吞咽困难，而不会对临床结局产生负面影响。这项研究将在英国推广经口手术和术后调强放疗方案，并开发一个金标准吞咽评估小组。一个相关的计划转化研究计划，以肿瘤标本和作为PATHOS一部分收集的连续血液为基础，将促进对这种新疾病及其对治疗反应的进一步经验性理解。
Background: Human papillomavirus-positive oropharyngeal squamous cell carcinoma is increasing in incidence worldwide. Current treatments are associated with high survival rates but often result in significant long-term toxicities. In particular, long-term dysphagia has a negative impact on patient quality of life and health. The aim of PATHOS is to determine whether reducing the intensity of adjuvant treatment after minimally invasive transoral surgery in this favourable prognosis disease will result in better long-term swallowing function whilst maintaining excellent disease-specific survival outcomes.Methods/Design: The study is a multicentre phase II/III randomised controlled trial for patients with biopsy-proven Human papillomavirus-positive oropharyngeal squamous cell cancer staged T1-T3 N0-N2b with a primary tumour that is resectable via a transoral approach. Following transoral surgery and neck dissection, patients are allocated into three groups based on pathological risk factors for recurrence. Patients in the low-risk pathology group will receive no adjuvant treatment, as in standard practice. Patients in the intermediate-risk pathology group will be randomised to receive either standard dose post-operative radiotherapy (control) or reduced dose radiotherapy. Patients in the high-risk pathology group will be randomised to receive either post-operative chemoradiotherapy (control) or radiotherapy alone. The primary outcome of the phase II study is patient reported swallowing function measured using the MD Anderson Dysphagia Inventory score at 12 months post-treatment. If the phase II study is successful, PATHOS will proceed to a phase III non-inferiority trial with overall survival as the primary endpoint.Discussion: PATHOS is a prospective, randomised trial for Human papillomavirus-positive oropharyngeal cancer, which represents a different disease entity compared with other head and neck cancers. The trial aims to demonstrate that long-term dysphagia can be lessened by reducing the intensity of adjuvant treatment without having a negative impact on clinical outcome. The study will standardise transoral surgery and post-operative intensity-modulated radiotherapy protocols in the UK and develop a gold-standard swallowing assessment panel. An associated planned translational research programme, underpinned by tumour specimens and sequential blood collected as part of PATHOS, will facilitate further empirical understanding of this new disease and its response to treatment.