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Multicentre Investigation of Prognostic Factors Incorporating p16 and Tumour Infiltrating Lymphocytes for Anal Cancer After Chemoradiotherapy
Clinical Oncology ( IF 3.2 ) Pub Date : 2021-05-21 , DOI: 10.1016/j.clon.2021.04.015
K Wakeham 1 , L Murray 2 , R Muirhead 3 , M A Hawkins 4 , D Sebag-Montefiore 2 , S Brown 5 , L Murphy 6 , G Thomas 7 , S Bell 8 , M Whibley 9 , C Morgan 9 , K Sleigh 9 , D C Gilbert 6
Affiliation  

Aims

Anal squamous cell carcinomas (ASCC) are strongly associated with human papillomaviruses. Standard of care is chemoradiotherapy at uniform doses with no treatment stratification. Immunohistochemical staining for p16INK4A (p16), a surrogate for human papillomaviruses, is prognostic for outcomes. We investigated this alongside clinical-pathological factors, including tumour infiltrating lymphocyte (TIL) scores.

Materials and methods

Using an independent, multicentre cohort of 257 ASCC treated with chemoradiotherapy, pretreatment biopsies were stained and scored for p16 and TIL. Kaplan–Meier curves were derived for outcomes (disease-free survival [DFS], overall survival and cancer-specific survival), by stage, p16 and TIL scores and Log-rank tests were carried out to investigate prognostic effect. A multivariate analysis was carried out using Cox regression.

Results

Stage, sex, p16 and TILs were independently prognostic. Hazard ratios for death (overall survival) were 2.51 (95% confidence interval 1.36–4.63) for p16 negative versus p16 positive, 2.17 (1.34–3.5) for T3/4 versus T1/2, 2.42 (1.52–3.8) for males versus females and 3.30 (1.52–7.14) for TIL1 versus TIL3 (all P < 0.05).

Conclusions

We have refined prognostic factors in ASCC. p16 adds to stratification by stage with respect to DFS in early disease and overall survival/DFS in locally advanced cancers. Our data support the role of the host immune response in mediating outcomes. These factors will be prospectively evaluated in PLATO (ISRCTN88455282).



中文翻译:

放化疗后肛门癌预后因素的多中心研究,包括 p16 和肿瘤浸润淋巴细胞

目标

肛门鳞状细胞癌 (ASCC) 与人乳头瘤病毒密切相关。护理标准是统一剂量的放化疗,没有治疗分层。p16INK4A (p16)(人乳头瘤病毒的替代物)的免疫组织化学染色可预测预后。我们研究了这一点以及临床病理因素,包括肿瘤浸润淋巴细胞 (TIL) 评分。

材料和方法

使用一个由 257 例接受放化疗治疗的 ASCC 组成的独立多中心队列,对治疗前的活检组织进行染色,并对 p16 和 TIL 进行评分。Kaplan-Meier 曲线得出结果(无病生存期 [DFS]、总生存期和癌症特异性生存期),按阶段、p16 和 TIL 评分以及对数秩检验以研究预后效果。使用 Cox 回归进行多变量分析。

结果

分期、性别、p16 和 TIL 是独立的预后因素。p16 阴性与 p16 阳性的死亡风险比(总生存期)为 2.51(95% 置信区间 1.36-4.63),T3/4 与 T1/2 为 2.17(1.34-3.5),男性与 T1/2 为 2.42(1.52-3.8) TIL1 与 TIL3 的女性和 3.30 (1.52-7.14) (所有P < 0.05)。

结论

我们已经完善了 ASCC 的预后因素。p16 对早期疾病的 DFS 和局部晚期癌症的总生存期/DFS 按阶段进行分层。我们的数据支持宿主免疫反应在调节结果中的作用。这些因素将在 PLATO (ISRCTN88455282) 中进行前瞻性评估。

更新日期:2021-05-21
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