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Independent validation of tumour volume, cancer stem cell markers and hypoxia-associated gene expressions for HNSCC after primary radiochemotherapy.

ABSTRACT: Objective:To independently validate the impact of tumour volume, p16 status, cancer stem cell (CSC) marker expression and hypoxia-associated gene signatures as potential prognostic biomarkers for patients with locally advanced head and neck squamous cell carcinoma (HNSCC), who underwent primary radiotherapy or radiochemotherapy (RCTx). These markers have previously been reported in a study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG) (Linge et al., 2016). Materials and methods:In this retrospective monocentric study, 92 patients with locally advanced HNSCC were included. Univariable and multivariable logistic regressions and Cox models presented in the study of the DKTK-ROG were validated using the area under the curve (AUC) and the concordance index (ci), respectively. The primary endpoint of this study was loco-regional tumour control (LRC) after primary RCTx. Results:Although both cohorts significantly differed in the proportion of the tumour subsites, the parameters tumour volume, p16 status and N stage could be validated regarding LRC and overall survival (OS) using multivariable Cox regression (LRC ci: 0.59, OS ci: 0.63). These models were slightly improved by combination with the putative CSC marker CD44 (LRC ci: 0.61, OS ci: 0.69). The logistic regression model for 2-year LRC based on tumour volume, p16 status and CD44 protein was validated with an AUC of 0.64. The patient stratification based on hypoxia-associated gene signatures status was similar to the original study but without significant differences in LRC and OS. Conclusions:In this validation study, the inclusion of the putative CSC marker CD44 slightly improved the prognostic performance of the baseline parameters tumour volume, p16 status and N stage. No improvement was observed when including expressions of the hypoxia-associated gene signatures. Prospective validation on a larger cohort is warranted to assess the clinical relevance of these markers.

SUBMITTER: Linge A

PROVIDER: S-EPMC6449705 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Independent validation of tumour volume, cancer stem cell markers and hypoxia-associated gene expressions for HNSCC after primary radiochemotherapy.

Linge Annett A Schmidt Stefan S Lohaus Fabian F Krenn Constanze C Bandurska-Luque Anna A Platzek Ivan I von Neubeck Cläre C Appold Steffen S Nowak Alexander A Gudziol Volker V Buchholz Frank F Baretton Gustavo B GB Baumann Michael M Löck Steffen S Krause Mechthild M

Clinical and translational radiation oncology 20190318

<h4>Objective</h4>To independently validate the impact of tumour volume, p16 status, cancer stem cell (CSC) marker expression and hypoxia-associated gene signatures as potential prognostic biomarkers for patients with locally advanced head and neck squamous cell carcinoma (HNSCC), who underwent primary radiotherapy or radiochemotherapy (RCTx). These markers have previously been reported in a study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG) (Linge et al., 2016).<h4>Materi ...[more]

PMID: 30993218

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Project description:BackgroundPreoperative PSA, ISUP grade group (GG), prostate examination and multiparametric MRI (mpMRI) form the basis of prostate cancer staging. Unlike other solid organ tumours, tumour volume (TV) is not routinely used aside from crude estimates such as maximum cancer core length. The aim of this study is to assess the role of TV as a marker for oncological outcomes in high-risk non-metastatic prostate cancer.MethodsA prospectively maintained database of patients undergoing minimally invasive (laparoscopic or robot-assisted laparoscopic) radical prostatectomy at a UK centre between 2007 and 2019 were analysed. A total of 251 patients with NCCN high or very high-risk prostate cancer were identified. Primary outcome measure was time to biochemical recurrence (BCR) and the secondary outcome was time to treatment failure (TTF). TV was measured on the pathological specimen using the stacking method. Multivariable cox regression analysis was used to identify factors predicting BCR and TFF. TV as a predictor of BCR and TFF was further analysed through time-dependent receiver operating characteristic (ROC) curves. Kaplan-Meier survival estimates were used to evaluate TV cut-off scores.ResultsMedian follow up was 4.50 years. Four factors were associated with BCR and TFF on multivariable analysis (TV, pathological GG, pathological T stage, positive margin >3 mm). Area under the Curve (AUC) for TV as a predictor of BCR and TTF at 5 years was 0.71 and 0.75, respectively. Including all 4 variables in the model increased AUC to 0.84 and 0.85 for BCR and TFF. A 2.50 cm TV cut off demonstrated a significance difference in time to BCR, p < 0.001.ConclusionsPathological tumour volume is an independent predictor of oncological outcomes in high risk prostate cancer but does not add significant prognostic value when combined with established variables. However, the option of accurate TV measurement on mpMRI raises the possibility of using TV as useful marker for preoperative risk stratification.

Dataset Information

Independent validation of tumour volume, cancer stem cell markers and hypoxia-associated gene expressions for HNSCC after primary radiochemotherapy.

Publications

Independent validation of tumour volume, cancer stem cell markers and hypoxia-associated gene expressions for HNSCC after primary radiochemotherapy.

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