Development and Validation of Nomograms for Predicting Delayed Postoperative Radiotherapy Initiation in Head and Neck Squamous Cell Carcinoma.


  • 影响因子:2.03
  • DOI:10.1001/jamaoto.2020.0222
  • 作者列表:"Levy DA","Li H","Sterba KR","Hughes-Halbert C","Warren GW","Nussenbaum B","Alberg AJ","Day TA","Graboyes EM
  • 发表时间:2020-04-02

Importance:The standard of care for initiation of postoperative radiotherapy (PORT) in head and neck squamous cell carcinoma (HNSCC) is within 6 weeks of surgical treatment. Delays in guideline-adherent PORT initiation are common, associated with mortality, and a measure of quality care, but patient-specific tools to estimate the risk of these delays are lacking. Objective:To develop and validate 2 nomograms (that use presurgical and postsurgical data) for predicting delayed PORT initiation. Design, Setting, and Participants:This cohort study obtained patient data from January 1, 2004, to December 31, 2015, from the National Cancer Database. Adults aged 18 years or older with a newly diagnosed HNSCC who underwent surgical treatment and PORT at a Commission on Cancer-accredited facility were included. Data analysis was conducted from June 2, 2019, to January 29, 2020. Exposures:Surgical treatment and PORT. Main Outcomes and Measures:The primary outcome measure was PORT initiation more than 6 weeks after the surgical intervention. Multivariable logistic regression models were created in a random selection of 80% of the sample (derivation cohort) and were internally validated with bootstrapping, assessed for discrimination by calibration plots and the concordance (C) index, and externally validated in the remaining 20% of the sample (validation cohort). Results:The study included 60 766 adults with HNSCC who were grouped into derivation and validation cohorts. The derivation cohort comprised 48 625 patients (mean [SD] age, 59.59 [11.3] years; 36 825 men [75.7%]) selected randomly from the full sample, whereas 12 151 patients (mean [SD] age, 59.63 [11.2] years; 9266 men [76.3%]) composed the validation cohort. The rate of PORT delay was 55.8% (n=27140) in the derivation cohort and 56.7% (n=6900) in the validation cohort. Both nomograms created to predict the risk of PORT initiation delay used variables, including race/ethnicity, insurance type, tumor site, and facility type. The nomogram based on presurgical variables included clinical stage and severity of comorbidity, whereas the nomogram with postsurgical variables included US region, length of stay, and care fragmentation between surgical and radiotherapy facilities. For the presurgical nomogram, the concordance indices were 0.670 (95% CI, 0.664-0.676) in the derivation cohort and 0.674 (95% CI, 0.662-0.685) in the validation cohort. For the nomogram with postsurgical variables, the concordance indices were 0.691 (95% CI, 0.686-0.696) in the derivation cohort and 0.694 (95% CI, 0.685-0.704) in the validation cohort. Conclusions and Relevance:This study found that a nomogram developed with presurgical data to generate personalized estimates of PORT initiation delay may improve pretreatment counseling and the delivery of interventions to patients at high risk for such a delay. A nomogram including postsurgical data can drive institutional quality improvement initiatives and enhance risk-adjusted comparisons of delay rates across facilities.


重要性: 头颈部鳞状细胞癌 (HNSCC) 术后放疗开始的标准护理是在手术治疗 6 周内。遵循指南的端口启动延迟很常见,与死亡率和优质护理措施相关,但缺乏患者特定的工具来估计这些延迟的风险。 目的: 开发并验证 2 个列线图 (使用术前和术后数据) 用于预测端口启动延迟。 设计、设置和参与者: 本队列研究从国家癌症数据库获得了 2004年1月1日至 2015年12月31日的患者数据。包括在癌症委员会认可的机构接受手术治疗和港口的 18 岁或 18 岁以上初诊 HNSCC 的成人。数据分析时间为 2019年6月2日 17 年 2020年1月29日。 暴露: 手术治疗和端口。 主要结局和措施: 主要结局措施是手术干预后超过 6 周的端口启动。在随机选择 80% 的样本 (推导队列) 中创建了多变量逻辑回归模型,并通过自举进行内部验证,通过校准图和一致性 (C) 指数进行区分度评估,并在其余 20% 的样本中进行外部验证 (验证队列)。 结果: 该研究包括 60-766 例成人 HNSCC 患者,分为推导和验证队列。推导队列包括从全样本中随机选择的 48 625 例患者 (平均 [SD] 年龄,59.59 [11.3] 岁; 36 825 例男性 [75.7%]),而 12 151 例患者 (平均 [SD] 年龄,59.63 [11.2] 岁; 9266 例男性 [76.3%]) 组成了验证队列。推导队列中端口延迟率为 55.8% (n = 27140),验证队列中端口延迟率为 56.7% (n = 6900)。为预测港口启动延迟风险而创建的两个列线图都使用了变量,包括种族/民族、保险类型、肿瘤部位和设施类型。基于术前变量的列线图包括临床分期和合并症的严重程度,而具有术后变量的列线图包括 US 地区、住院时间和手术和放疗设施之间的护理碎片化。对于术前列线图,推导队列的一致性指数为 0.670 (95% CI,0.664-0.676),验证队列的一致性指数为 0.674 (95% CI,0.662-0.685)。对于具有术后变量的列线图,推导队列的一致性指数为 0.691 (95% CI,0.686-0.696),验证队列的一致性指数为 0.694 (95% CI,0.685-0.704)。 结论和相关性: 本研究发现,用术前数据开发的列线图来生成口岸启动延迟的个性化估计值,可能会改善预处理咨询和向这种延迟的高风险患者提供干预措施。包括术后数据的列线图可以推动机构质量改进举措,并增强跨机构延迟率的风险调整比较。



来源期刊:BMJ open
作者列表:["Wendland EM","Kops NL","Comerlato J","Horvath JDC","Bessel M","Sperb D","Pimenta C","de Souza FMA","Mendes Pereira GF","Falcetta FS"]

METHODS:INTRODUCTION:Human papillomavirus (HPV) is the most common sexually transmitted infection and is associated with several types of cancer. The number of cases of HPV-associated head and neck squamous cell carcinomas (HNSCCs), especially oropharyngeal carcinomas, has increased significantly in recent years despite decreased tobacco smoking rates. Currently, no data concerning the risk factors and prevalence of HPV in HNSCC patients in all regions of Brazil are available, making it difficult to promote advances in this field of public health. Therefore, our goal is to determine the impact of infection by HPV, including HPVs with different genotypes, on head and neck cancer and the risk factors associated with the development of head and neck cancer in all regions of Brazil. METHODS AND ANALYSIS:This is a case-control study that will include 622 patients and 622 controls from all regions of Brazil. A questionnaire will be applied to gather information on sociodemographic, behavioural and health factors. Oral, cervical or penile/scrotal, and anal specimens and serum samples will be collected from all participants. Formalin-fixed paraffin-embedded tissue from tumour biopsies will be analysed only in the case group. Molecular and serological analyses will be performed to evaluate the presence and role of HPV in the development of head and neck cancer. ETHICS AND DISSEMINATION:This project was approved by the research ethical committee of the proposing institution (Hospital Moinhos de Vento, number 2.852.060). Ethical approval from the collaborators is currently under evaluation and is not yet complete. The results of this study will be presented at meetings with the Brazilian Ministry of Health through technical reports and to the scientific community at national and international events, with subsequent publication of scientific articles.

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来源期刊:Head & neck
作者列表:["Soldera EB","Ortigara GB","Bonzanini LIL","Schulz RE","Danesi CC","Antoniazzi RP","Linhares Ferrazzo K"]

METHODS:BACKGROUND:Factors related to head and neck cancer and the treatment of the disease can affect quality of life. The aim of this study was to determine factors associated with the severity of impact on oral health-related quality of life (OHRQoL) in survivors of head and neck cancer using a multivariate analysis. METHODS:This cross-sectional study evaluated 90 volunteers who had completed radiotherapy at least 3 months earlier. OHRQoL was assessed using oral health impact profile (OHIP-14) and the data were analyzed using robust variance poisson regression models. RESULTS:The mean total OHIP-14 score was 23.98 ± 12.55. Patients with hyposalivation had 56% higher (worse) mean OHIP-14 total scores (CI:1.11-2.18) and patients with advanced stage tumors had 31% higher mean OHIP-14 total scores (CI:1.03-1.66) in multivariate analyses. CONCLUSION:OHRQoL of survivors of head and neck cancer experienced a negative impact following radiotherapy. The impact was associated with hyposalivation and advanced stage tumors.

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作者列表:["Ramos-Vega V","Venegas Rojas B","Donoso Torres W"]

METHODS:BACKGROUND:To immunohistochemically evaluate the association between the presence of cancer-associated fibroblasts (CAFs) and the tumour expression of podoplanin (PDPN) in head and neck squamous cell carcinoma (HNSCC) and their association with clinicopathological variables. MATERIAL AND METHODS:A tissue microarray (TMA) with biopsy sections from patients diagnosed with HNSCC was stained with antibodies against the CAFs marker, α-smooth muscle actin (α-SMA), and PDPN. We subsequently evaluated their expression to determine the association between them and with clinicopathological variables including age, primary tumour site, TNM stage, and tumour differentiation grade. RESULTS:Positive reaction to α-SMA was observed in the tumour stroma, revealing spindle-shaped cells compatible with CAFs, which showed a high expression in 62% of cases and a significant association with laryngeal carcinomas, advanced clinical stages, and lower tumour differentiation (P ≤ 0.05). PDPN staining on tumour cells showed low expression in 72% of cases, and it was not associated with any clinicopathological variable or with the presence of CAFs. CONCLUSIONS:The presence of CAFs in the tumour stroma is related to an aggressive phenotype and could increase as the disease progresses, although based on our findings, it would have no relationship, at least directly, with the expression of PDPN.

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