Intratumor heterogeneity could inform the use and type of postoperative adjuvant therapy in patients with head and neck squamous cell carcinoma.
- 作者列表："Mroz EA","Patel KB","Rocco JW
BACKGROUND:After surgery for head and neck squamous cell carcinoma (HNSCC), decisions regarding adjuvant radiotherapy (RT) or chemoradiotherapy (CRT) are based on staging and the presence of high-risk pathology. Because higher mutant allele tumor heterogeneity (MATH; a measure of intratumor genetic heterogeneity) is associated with shorter overall survival (OS) in patients with HNSCC, the authors sought to determine whether MATH analysis might further inform these decisions. METHODS:Adjuvant therapy-associated relationships between MATH and OS were analyzed for 389 patients with HNSCC who were treated surgically. Data were obtained from The Cancer Genome Atlas and analyzed with Cox proportional hazards multiple regression accounting for 7 other patient characteristics. RESULTS:The relationship between MATH and OS differed with adjuvant therapy in a way that could inform therapy decisions. Adjuvant RT alone was found to provide substantial benefit for patients having high-MATH tumors (RT vs no adjuvant therapy: hazard ratio, 0.29 [95% CI, 0.17-0.51]) but no benefit for those having low-MATH tumors. In contrast, adjuvant CRT provided no benefit beyond that of adjuvant RT for patients with high-MATH tumors but substantially improved OS among patients with low-MATH tumors (CRT vs no adjuvant therapy: hazard ratio, 0.34 [95% CI, 0.15-0.78]). CONCLUSIONS:The results of the current analysis suggested that patients with HNSCC with high-MATH tumors who underwent surgical treatment could benefit from adjuvant RT, even when current clinical guidelines indicate otherwise. The addition of adjuvant chemotherapy for patients with high-MATH tumors would not be indicated. Adding chemotherapy might be necessary to radiosensitize low-MATH tumors to adjuvant RT. This potential predictive role of tumor MATH analysis should be evaluated in prospective clinical trials.
背景: 头颈部鳞状细胞癌 (HNSCC) 手术后，关于辅助放疗 (RT) 或放化疗 (CRT) 的决定是基于分期和高危病理的存在。因为较高的突变等位基因肿瘤异质性 (数学; 肿瘤内遗传异质性的测量) 与 HNSCC 患者较短的总生存期 (OS) 相关, 作者试图确定数学分析是否可以进一步为这些决定提供信息。 方法: 对 389 例手术治疗的 HNSCC 患者进行了数学与 OS 的辅助治疗相关关系分析。数据来自癌症基因组图谱，并用 Cox 比例风险多元回归分析占其他 7 个患者特征。 结果: 数学和 OS 之间的关系与辅助治疗不同，可以告知治疗决策。发现单独辅助 RT 对患有高数学肿瘤的患者提供实质性益处 (RT 与无辅助治疗: 风险比，0.29 [95% CI，0.17-0.51]) 但是对那些患有低数学肿瘤的人没有好处。相比之下，辅助 CRT 对高数学肿瘤患者的益处不超过辅助 RT，但对低数学肿瘤患者的 OS 有显著改善 (CRT vs 无辅助治疗: 风险比，0.34 [95% CI，0.15-0.78])。 结论: 目前的分析结果表明，接受手术治疗的高数学肿瘤的 HNSCC 患者可以从辅助 RT 中获益，即使目前的临床指南另有提示。对患有高数学肿瘤的患者添加辅助化疗将不被指示。增加化疗可能是必要的放射增敏低数学肿瘤辅助 RT。肿瘤数学分析的这种潜在预测作用应在前瞻性临床试验中进行评价。
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.
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.
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.