A response prediction model for taxane, cisplatin, and 5-fluorouracil chemotherapy in hypopharyngeal carcinoma

Qi Zhong,Yixiang Zhang,Junhui Ye,Qing Zhang,Yifan Yang,Jugao Fang,Yejun Wang,Yingduan Cheng,Xinjie Hui,Zhigang Huang,Ying Ying,Honggang Liu,Meng Lian

doi:10.1038/s41598-018-31027-y

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. The five-year survival rate of HNSCC has not improved even with major technological advancements in surgery and chemotherapy. Currently, docetaxel, cisplatin, and 5-fluoruracil (TPF) treatment has been the most popular chemotherapy method for HNSCC; but only a small percentage of HNSCC patients exhibit a good response to TPF treatment. Unfortunately, at present, no reasonably effective prediction model exists to assist clinicians with patient treatment. For this reason, patients have no other alternative but to risk neoadjuvant chemotherapy in order to determine their response to TPF. In this study, we analyzed the gene expression profile in TPF-sensitive and non-sensitive patient samples. We identified a gene expression signature between these two groups. We further chose 10 genes and trained a support vector machine (SVM) model. This model has 88.3% sensitivity and 88.9% specificity to predict the response to TPF treatment in our patients. In addition, four more TPF responsive and four more TPF non-sensitive patient samples were used for further validation. This SVM model has been proven to achieve approximately 75.0% sensitivity and 100% specificity to predict TPF response in new patients. This suggests that our 10-genes SVM prediction model has the potential to assist clinicians to personalize treatment for HNSCC patients.

Highlights

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide[1]
This breast cancer model constitutes a good example of personalized medicine, and has saved at least USD 300 million of unnecessary chemotherapy costs in the U.S Here, we used microarray-based gene expression profiles to identify the gene signature that related to TPF response
If tumor volume decreased approximately 70% after chemotherapy, we considered it as a chemotherapy-sensitive one

Summary

Introduction

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide[1]. In order to improve the quality of life of HNSCC patients, especially for laryngeal, oro- and hypopharyngeal cancer, preserving a functional organ constitutes a focus for surgeons and oncologists[5] With this aim, efficient chemotherapy treatment has become even more critical. With the increase of relevant clinical studies, TPF treatment has been more widely utilized with patients, since TPF has better survival and organ preservation rates compared to PF therapy in locally advanced laryngeal, oro- and hypopharyngeal cancer[15,16]. Our study provides a set of potential biomarkers to predict patient response to TPF treatment, as well as the possible benefits of: 1) avoiding toxic effects of ineffective chemotherapy; 2) avoiding delays for other therapeutic options; and 3) minimizing the cost of treatment[18]

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Conclusion