Prognostic factors and survival unique to surgically treated p16+ oropharyngeal cancer
Prognostic factors and survival unique to surgically treated p16+ oropharyngeal cancer
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DOI：
10.1002/lary.23493
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发表时间：
2012-09-01
期刊：
影响因子：
2.6
通讯作者：
Sinha, Parul
中科院分区：
文献类型：
--
作者：
Haughey, Bruce H.;Sinha, Parul
目的/假设：目前头颈部流行病学研究表明，p16+人乳头瘤病毒相关性口咽鳞状细胞癌(OPSCC)的发病率呈稳步上升趋势。这种独特的肿瘤亚型与更好的生存结果相关。越来越多的人认识到需要确定考虑到这些癌症的固有病理生物学属性并以最低发病率提供最佳肿瘤学控制的管理方案。通过对预测p16+OPSCC患者疾病结局的预后变量的清楚了解，这一点得到了促进。为了提供预后评估，病理分期和组织病理学参数通常优于临床分期。然而，对病理预测因素的了解很少，主要是因为通常采用的非手术治疗策略采用了放化疗。口咽部微创手术，特别是经口腔激光显微手术(TLM)，是公认的口咽癌有效的主要治疗方法。从这样的序列中，根据原发灶和颈部的手术标本的病理信息进行详细的评估是可行的，以建立p16+口咽癌患者特有的预后指标。研究设计：收集1996-2010年间接受TLM+/-颈淋巴清扫术+/-辅助治疗的口咽癌患者的前瞻性数据库，回顾分析其生存和复发情况。方法：基本的纳入标准是：1)先前未经治疗的经活检证实的OPSCC接受了初次TLM+/-颈淋巴清扫术，2)手术标本中弥漫性的p16阳性，3)辅助治疗的可用性，以及4)至少12个月的随访或死亡。COX比例风险回归分析用于确定对无病生存期(DFS)、研究的主要终点以及疾病特异性生存期(DSS)和总生存期有预测作用的变量。Kaplan-Meier生存估计和疾病复发模式也被评估。我们还探讨了临床(CT，CN)和病理(CT，PT)评估T分期和N分期的一致性。结果：在TLM数据库中的211名患者中，171名符合所有资格标准。中位随访期为47个月。3年和5年Kaplan-Meier对DFS的估计分别为91%和88%，而DSS分别为95.5%和94.4%。共有12例(7%)复发：2例局部复发，4例区域性复发，6例远处复发。在所有T分期分类中，PT4肿瘤是较差的DFS的最强预测因子。CT4扁桃体原发灶、吸烟状况、3个或更多转移结节、pN2b+分期和放疗辅助治疗是DFS的其他预后因素。血管侵犯和T3-T4肿瘤是DSS降低的预后因素，尽管吸烟参数不是。包膜外扩散、N分期和切缘是非预测因素。递归分割分析定义了高风险和低风险的预后因素分组。应用病理分类可观察到31%的肿瘤临床T分期降低。结论：我们记录了一组明确的预后变量，在预后良好的p16+OPSCC队列中，这些变量可以特异性和准确地识别预后降低的风险个体。基于这些预测因子，可以更准确地做出适当的患者咨询、辅助治疗建议和试验分层。我们还观察到TLM为更准确的临床和病理T分期提供了额外的优势。
Objectives/Hypothesis: Current head and neck epidemiology demonstrates a steadily increasing incidence of p16+ human papillomavirus-related oropharynx squamous cell cancer (OPSCC). This distinct tumor subtype is associated with better survival outcomes. There is a growing recognition of the need to define management regimens that take into account the inherent patho-biological attributes of these cancers and provide optimum oncological control with minimum morbidity. This is facilitated by a clear understanding of the prognostic variables that predict disease outcome in patients with p16+ OPSCC. To provide prognostic estimates, pathological staging and histopathological parameters are usually superior to clinical staging. However, knowledge of pathological predictors is sparse, mainly because of commonly employed nonsurgical management policies utilizing chemoradiotherapy. Minimally invasive approaches to the oropharynx, particularly transoral laser microsurgery (TLM), are well-reported effective primary treatments for oropharynx cancers. From such series, it is feasible to conduct a detailed appraisal based on pathologic information from surgical specimens of both the primary and neck, to establish prognosticators unique to p16+ oropharynx cancer patients. Study Design: A prospectively assembled database of oropharynx cancer patients treated with primary TLM +/- neck dissection +/- adjuvant therapy from 1996 to 2010, analyzed retrospectively for survival and recurrence. Methods: The fundamental inclusion criteria were: 1) previously untreated biopsy-proven OPSCC treated with primary TLM +/- neck dissection, 2) diffuse p16 positivity in the surgical specimen, 3) availability for adjuvant therapy, if indicated, and 4), minimum follow-up of 12 months or to death. Cox proportional hazard regression analyses were used to identify variables that were prognostic for disease-free survival (DFS), the primary end point of the study, as well as disease-specific survival (DSS) and overall survival. Kaplan-Meier survival estimates and patterns of disease recurrence were also assessed. We also explored concordance for T and N staging, when assessed by clinical (cT, cN) and pathological (cT, pT) measures. Results: Of 211 patients in the TLM database, 171 met all the eligibility criteria. The median follow-up was 47 months. The 3- and 5-year Kaplan-Meier estimates for DFS were 91% and 88%, respectively, whereas for DSS they were 95.5% and 94.4%, respectively. A total of 12 (7%) recurrences occurred: two local, four regional, and six distant. Of all T-stage categories, pT4 tumors were strongest predictors of poorer DFS. cT4 tonsil primaries, ever smoking status, three or more metastatic nodes, pN2b+ stage, and radiation-based adjuvant therapy were other prognosticators for DFS. Angioinvasion and T3-T4 tumors were prognostic for reduced DSS, although smoking parameters were not. Extracapsular spread, N stage, and margins were nonprognosticators. Recursive partitioning analysis defined high- and low-risk groupings of prognosticators. Downstaging of clinical T stage was observed for 31% of tumors on application of pathological classification. Conclusions: We document a well-delineated set of prognostic variables that specifically and accurately identify individuals at risk of reduced outcomes in an otherwise good prognosis p16+ OPSCC cohort. Based on these prognosticators, appropriate patient counseling, adjuvant treatment recommendations, and stratification for trials can more accurately be made.We also observed an additional edge conferred by TLM toward more accurate clinical as well as pathological T staging.