Standardised Ki-67 proliferation index assessment in early-stage laryngeal squamous cell carcinoma in relation to local control and survival after primary radiotherapy.

Emiel Kop,Geertruida H De Bock,Johannes A Langendijk,Bert Van Der Vegt,Ed Schuuring,Lorian Slagter‐Menkema,Maartje G Noordhuis,Bernard F A M Van Der Laan

doi:10.1111/coa.13449

Abstract

ObjectivesAmbiguous results have been reported on the predictive value of the Ki‐67 proliferation index (Ki‐67 PI) regarding local control (LC) and survival after primary radiotherapy (RT) in early‐stage laryngeal squamous cell cancer (LSCC). Small study size, heterogenic inclusion, variations in immunostaining and cut‐off values are attributing factors. Our aim was to elucidate the predictive value of the Ki‐67 PI for LC and disease‐specific survival (DSS) using a well‐defined series of T1‐T2 LSCC, standardised automatic immunostaining and digital image analysis (DIA).MethodsA consecutive and well‐defined cohort of 208 patients with T1‐T2 LSCC treated with primary RT was selected. The Ki‐67 PI was determined using DIA. Mann‐Whitney U‐tests, logistic and Cox regression analyses were performed to assess associations between Ki‐67 PI, clinicopathological variables, LC and DSS.ResultsIn multivariate Cox regression analysis, poor tumour differentiation (HR 2.20; 95% CI 1.06‐4.59, P = .04) and alcohol use (HR 2.84, 95% CI 1.20‐6.71; P = .02) were independent predictors for LC. Lymph node positivity was an independent predictor for DSS (HR 3.16, 95% CI 1.16‐8.64; P = .03). Ki‐67 PI was not associated with LC (HR 1.59; 95% CI 0.89‐2.81; P = .11) or DSS (HR 0.98; 95% CI 0.57‐1.66; P = .97). In addition, continuous Ki‐67 PI was not associated with LC (HR 2.03; 95% CI 0.37‐11.14, P = .42) or DSS (HR 0.62; 95% CI 0.05‐8.28; P = .72).ConclusionThe Ki‐67 PI was not found to be a predictor for LC or DSS and therefore should not be incorporated in treatment‐related decision‐making for LSCC.

Highlights

Over the years, many studies have been conducted to identify prog‐ nostic and predictive markers for head and neck squamous cell carci‐ noma (HNSCC).[1]
Selection bias may have influenced the outcome of these studies as in one of the studies 36 patients were randomly selected from a larger cohort of 128 patients,[9] another study included only 24 patients with a glottic carcinoma involving the anterior commissure in a 10‐year period
We found a relatively high Ki‐67 Ki‐67 proliferation index (PI) compared with other studies

Summary

Introduction

Many studies have been conducted to identify prog‐ nostic and predictive markers for head and neck squamous cell carci‐ noma (HNSCC).[1] To date, prognostic markers such as age, TNM‐stage and histological type determine decision‐making regarding the most optimal treatment strategy. The results of ear‐ lier studies investigating the relationship between the Ki‐67 PI, local control (LC) and survival after primary RT in laryngeal squamous cell cancer (LSCC) are not unambiguous, as shown in Table 1.4-14 Possible explanations for these differences are variations in patient group fac‐ tors, immunostaining and scoring‐related factors.[15,16,17]

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Conclusion