头颈部恶性肿瘤患者放疗后吞咽困难的危险因素分析及吞咽功能训练的临床应用价值

摘要 目的：分析头颈部恶性肿瘤（HNC）患者放疗后吞咽困难的危险因素,并观察吞咽功能训练的临床应用效果。方法：选择2020年4月~2022年5月期间在华中科技大学同济医学院附属同济医院接受放疗的HNC患者150例。采用自制调查量表获取患者的一般资料,采用单因素和多因素Logistic分析HNC患者放疗后吞咽困难的危险因素,并观察吞咽功能训练的临床应用效果。结果：本研究中150例HNC患者,放疗后出现吞咽困难的有93例,吞咽困难发生率为62.00%。根据放疗后是否出现吞咽困难将患者分为无吞咽困难组（n=57）和吞咽困难组（n=93）。单因素分析显示,HNC患者放疗后吞咽困难与文化程度、婚姻状况、高血压、糖尿病、高脂血症、居住地、体质量指数无关（P>0.05）,而与年龄、性别、吸烟史、饮酒史、肿瘤分期、肿瘤位置、累积放疗剂量有关（P<0.05）。多因素Logistic回归分析,结果显示：年龄偏大、男性、吸烟史、饮酒史、肿瘤分期为III期、肿瘤位置为颈部肿瘤、累积放疗剂量偏高是HNC患者放疗后吞咽困难的危险因素（P<0.05）。HNC患者干预1个月后、干预2个月后安德森吞咽困难量表（MDADI）评分较干预前下降,功能性经口摄食量表（FOIS）评分较干预前升高（P<0.05）。结论：HNC患者放疗后吞咽困难的发生率较高,年龄、性别、吸烟史、饮酒史、肿瘤分期、肿瘤位置、累积放疗剂量等均是其影响因素。HNC患者放疗期间给予吞咽功能训练,可有效改善患者的吞咽状况。     

Age at start of using tobacco on the risk of head and neck cancer: Pooled analysis in the International Head and Neck Cancer Epidemiology Consortium (INHANCE)

BackgroundTobacco use is a well-established risk factor for head and neck cancer (HNC). However, less is known about the potential impact of exposure to tobacco at an early age on HNC risk.MethodsWe analyzed individual-level data on ever tobacco smokers from 27 case-control studies (17,146 HNC cases and 17,449 controls) in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using random-effects logistic regression models.ResultsWithout adjusting for tobacco packyears, we observed that younger age at starting tobacco use was associated with an increased HNC risk for ever smokers (OR_{<10 years vs. ≥30 years}: 1.64, 95% CI: 1.35, 1.97). However, the observed association between age at starting tobacco use and HNC risk became null after adjusting for tobacco packyears (OR_{<10 years vs. ≥30 years}: 0.97, 95% CI: 0.80, 1.19). In the stratified analyses on HNC subsites by tobacco packyears or years since quitting, no difference in the association between age at start and HNC risk was observed.ConclusionsResults from this pooled analysis suggest that increased HNC risks observed with earlier age at starting tobacco smoking are largely due to longer duration and higher cumulative tobacco exposures.     

Llama-derived Single Variable Domains (Nanobodies) Directed against Chemokine Receptor CXCR7 Reduce Head and Neck Cancer Cell Growth in Vivo

The chemokine receptor CXCR7, belonging to the membrane-bound G protein-coupled receptor superfamily, is expressed in several tumor types. Inhibition of CXCR7 with either small molecules or small interference (si)RNA has shown promising therapeutic benefits in several tumor models. With the increased interest and effectiveness of biologicals inhibiting membrane-bound receptors we made use of the “Nanobody platform” to target CXCR7. Previously we showed that Nanobodies, i.e. immunoglobulin single variable domains derived from naturally occurring heavy chain-only camelids antibodies, represent new biological tools to efficiently tackle difficult drug targets such as G protein-coupled receptors. In this study we developed and characterized highly selective and potent Nanobodies against CXCR7. Interestingly, the CXCR7-targeting Nanobodies displayed antagonistic properties in contrast with previously reported CXCR7-targeting agents. Several high affinity CXCR7-specific Nanobodies potently inhibited CXCL12-induced β-arrestin2 recruitment in vitro. A wide variety of tumor biopsies was profiled, showing for the first time high expression of CXCR7 in head and neck cancer. Using a patient-derived CXCR7-expressing head and neck cancer xenograft model in nude mice, tumor growth was inhibited by CXCR7-targeting Nanobody therapy. Mechanistically, CXCR7-targeting Nanobodies did not inhibit cell cycle progression but instead reduced secretion of the angiogenic chemokine CXCL1 from head and neck cancer cells in vitro, thus acting here as inverse agonists, and subsequent angiogenesis in vivo. Hence, with this novel class of CXCR7 inhibitors, we further substantiate the therapeutic relevance of targeting CXCR7 in head and neck cancer.