前瞻性研究评估诱导化疗和反应适应性治疗局部区域病毒相关口咽癌中游离 HPV DNA 的动态变化。
Prospective study evaluating dynamic changes of cell-free HPV DNA in locoregional viral-associated oropharyngeal cancer treated with induction chemotherapy and response-adaptive treatment.
机构信息
Department of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA.
Section of Otolaryngology-Head and Neck Surgery, University of Chicago, Chicago, IL, USA.
出版信息
BMC Cancer. 2022 Jan 3;22(1):17. doi: 10.1186/s12885-021-09146-z.
BACKGROUND
Human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) has a favorable prognosis which has led to efforts to de-intensify treatment. Response-adaptive de-escalated treatment is promising, however improved biomarkers are needed. Quantitative cell-free HPV-DNA (cfHPV-DNA) in plasma represents an attractive non-invasive biomarker for grading treatment response and post-treatment surveillance. This prospective study evaluates dynamic changes in cfHPV-DNA during induction therapy, definitive (chemo)radiotherapy, and post-treatment surveillance in the context of risk and response-adaptive treatment for HPV + OPC.
METHODS
Patients with locoregional HPV + OPC are stratified into two cohorts: High risk (HR) (T4, N3, [Formula: see text] 20 pack-year smoking history (PYH), or non-HPV16 subtype); Low risk (LR) (all other patients). All patients receive induction chemotherapy with three cycles of carboplatin and paclitaxel. LR with ≥ 50% response receive treatment on the single-modality arm (minimally-invasive surgery or radiation alone to 50 Gy). HR with ≥ 50% response or LR with ≥ 30% and < 50% response receive treatment on the intermediate de-escalation arm (chemoradiation to 50 Gy with cisplatin). All other patients receive treatment on the regular dose arm with chemoradiation to 70 Gy with concurrent cisplatin. Plasma cfHPV-DNA is assessed during induction, (chemo)radiation, and post-treatment surveillance. The primary endpoint is correlation of quantitative cfHPV-DNA with radiographic response.
DISCUSSION
A de-escalation treatment paradigm that reduces toxicity without compromising survival outcomes is urgently needed for HPV + OPC. Response to induction chemotherapy is predictive and prognostic and can select candidates for de-escalated definitive therapy. Assessment of quantitative cfHPV-DNA in the context of response-adaptive treatment of represents a promising reliable and convenient biomarker-driven strategy to guide personalized treatment in HPV + OPC.
TRIAL REGISTRATION
This trial is registered with ClinicalTrials.gov on October 1, 2020 with Identifier: NCT04572100 .
背景
人乳头瘤病毒（HPV）相关口咽癌（OPC）的预后良好，这促使人们努力减少治疗强度。反应适应性降级治疗具有广阔前景，但需要更好的生物标志物。血浆中游离 HPV-DNA（cfHPV-DNA）的定量检测是一种有吸引力的非侵入性生物标志物，可用于评估治疗反应和治疗后监测。本前瞻性研究评估了在 HPV 阳性 OPC 患者中，诱导治疗、根治性（放化疗）和治疗后监测期间 cfHPV-DNA 的动态变化，这些患者的治疗方案为风险和反应适应性治疗。
方法
局部晚期 HPV 阳性 OPC 患者分为两个队列：高危（HR）（T4、N3、[Formula: see text]20 包年吸烟史（PYH），或非 HPV16 亚型）；低危（LR）（其他所有患者）。所有患者均接受三周期卡铂和紫杉醇诱导化疗。LR 患者中 ≥ 50%有反应者接受单模态治疗（微创手术或单独放疗至 50Gy）。HR 患者中 ≥ 50%有反应者或 LR 患者中 ≥ 30%但 < 50%有反应者接受中间降级治疗（放疗至 50Gy 加顺铂）。其余所有患者均接受标准剂量治疗，放化疗至 70Gy 并同步顺铂。在诱导、（放化疗）期间和治疗后监测期间评估血浆 cfHPV-DNA。主要终点是定量 cfHPV-DNA 与放射学反应的相关性。
讨论
HPV 阳性 OPC 患者迫切需要一种降低毒性而不影响生存结果的降级治疗方案。诱导化疗反应具有预测性和预后性，可以选择适合降级确定性治疗的候选者。在反应适应性治疗背景下评估定量 cfHPV-DNA 是一种很有前途的可靠且方便的基于生物标志物的策略，可以指导 HPV 阳性 OPC 的个体化治疗。
试验注册
本试验于 2020 年 10 月 1 日在 ClinicalTrials.gov 注册，标识符为 NCT04572100。
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