2017 The voice quality after laser surgery versus radiotherapy of T1a glottic carcinoma: systematic review and meta-analysis Tutor：Professor Hongbing Liu Student：Guanjiang Huang

CONTENTS PART 01 Introduction PART 02 Methods PART 03 Results PART 04 Discussion

01 Introduction

Introduction Laryngeal carcinoma is the most common malignant tumors of head and neck,and the majority of laryngeal carcinoma are confined within the glottic area. Nowadays, T1a glottic carcinoma is usually treated by laser therapy (LS) or radiotherapy (RT). Both LS and RT have good oncology and survival outcomes. This systematic review and meta-analysis are conducted to compare voice quality outcomes after LS versus RT of T1a glottic carcinoma.

02 Methods

Methods 01 02 03 04 Data sources Study selection Data extraction PubMed, Web of Science ,Embase, Cochrane Library, Chinese biomedical literature datebase,CNKI and Wanfang digital journals Deadline:October 2016 01 02 Study selection Inclusion criteria Exclusion criteria Data extraction The data of Voice Handicap Index (VHI)、acoustic analysis and GRBAS was extracted from the selected studies by two authors and checked by another author. 03 04 Statistical analysis Review Manager Version 5.3

Index words Glotti*, layn*, vocal Radiation,irradiation, radiotherapy Step 01 Step 02 Step 03 Step 04 Glotti*, layn*, vocal Radiation,irradiation, radiotherapy Surgery, cordectomy, laser Cancer,carcinoma

Study selection Inclusion criteria were: 1) randomized controlled trials, prospective studies or retrospective studies; 2) patients who underwent first treatment for T1a glottic carcinoma; 3) comparing LS with RT on interest outcomes such as Voice Handicap Index (VHI) acoustic analysis and GRBAS. Exclusion criteria were: 1) unable to get the full text of the literature; 2) duplicate reports; 3) information and data are incomplete; 4) patients who underwent non-first treatment for T1a glottic carcinoma;lost of follow-up; and 5) data provided in obvious errors..

Newcastle-Ottawa Scale

03 Results

Results Table 1 Characteristics and demographics of included studies

Table 2　VHI of the 2 treatment groups in the included studies Table 3　Acoustic analysis of the 2 treatment groups in the included studies

Voice Handicap Index (VHI) Figure 1 Forest plots of VHI in patients with T1a glottic carcinoma treated by LS and RT Test for subgroup differences：MD=5.86,95%CI=-5.22 to 16.94], P=0.30), and in VHI(2004-2007) studies subgroup (MD=-5.32,95%CI=-13.77 to 3.14], P=0.22), while in VHI(2008-2016) studies subgroup (MD=16.79,95%CI=14.85 to 18.74, P<0.00001).

Maximal phonation time(MPT) Figure 2 Forest plots of MPT in patients with T1a glottic carcinoma treated by LS and RT RT has increased the maximum time of speech (MPT) (MD=-2.26, 95%CI=-3.94 to -0.59, P=0.008).

Fundamental frequency(F0) Figure 3 Forest plots of F0 in patients with T1a glottic carcinoma treated by LS and RT RT has decreased the fundamental frequency (F0) (MD=14.41, 95%CI=10.64 to 18.19, P<0.00001.

Fundamental frequency(F0) Figure 4 Funnel plots of F0 in patients with T1a glottic carcinoma treated by LS and RT

Jitter Figure 5 Forest plots of Jitter in patients with T1a glottic carcinoma treated by LS and RT There are no statistical significance of Jitter (MD=0.75, 95%CI=-0.28 to 1.79, P= 0.15)

Jitter Figure 6 Funnel plots of Jitter in patients with T1a glottic carcinoma treated by LS and RT

Shimmer Figure 7 Forest plots of Shimmer in patients with T1a glottic carcinoma treated by LS and RT There are no statistical significance of Shimmer (MD=1.07, 95%CI=-0.60 to 2.75, P=0.21)

Shimmer Figure 8 Funnel plots of Shimmer in patients with T1a glottic carcinoma treated by LS and RT

Airflow rate(AFR) Figure 9 Forest plots of AFR in patients with T1a glottic carcinoma treated by LS and RT There are no statistical significance of AFR (MD=21.46, 95%CI=-78.79 to 121.72, P=0.67)

GRBAS GRBAS scale consists of grade (G),roughness (R), breathiness (B), asthenia (A), and strain (S). Ratings of these five aspects of voice quality varied from 0 (normal) to 3 (extremely abnormal). The higher the score, the more dysphonic the voice. Kono et al1 proved that tissue loss because of LS causes incomplete closure, which in turn is related to breathiness. Aaltonen et al2 reported that breathiness improved after RT over the 2-year observation period, whereas no improvement in any of the five voice quality measures of the GRBAS scale occurred in the LS group 1.Kono T, Saito K, Yabe H, et al. Comparative multidimensional assessment of laryngeal function and quality of life after radiotherapy and laser surgery for early glottic cancer.[J]. Head & Neck,2016,38(7):1085-1090. 2.Aaltonen L M, Rautiainen N, Sellman J, et al. Voice quality after treatment of early vocal cord cancer: a randomized trial comparing laser surgery with radiation therapy[J]. Int J Radiat Oncol Biol Phys,2014,90(2):255-260.

04 Discussion

Discussion Patients who had undergone RT have increased MPT and decreased F0 in comparison with LS. No statistical difference was observed between the two groups in terms of VHI, Jitter, Shimmer, AFR and GRBAS.

Both strategies present benefits and drawbacks Discussion Both strategies present benefits and drawbacks LS is precise,quick,inexpensive, and has the advantage of being repeatable or followed by RT in the event of recurrence. RT has the advantage of avoiding general anesthesia. RT is a longer treatment and may lead to lesions in tissue adjacent to the tumor with occasional sequelae such as mucosal edema, fibrosis and laryngeal chondronecrosis. However, it requires surgical expertise and the feasibility of surgical removal will depend on patient anatomy.

Discussion Radiotherapy can achieve similar therapeutic effects of laser surgery for patients of T1a glottic carcinoma. MPT offers favorable outcomes, whereas the other parameters lead to unfavorable outcomes. Compare with conventional radiotherapy, modern radiotherapy technology tends to be more targeted accurately,which can be accurately applied to the tumor location, and reduce the damage to normal cells. There is a mild tendency in all parameters that favors radiotherapy. However, we still have some limitations for this meta-analysis.

Discussion The sample number of the analysis is relatively less, and selection bias could not be excluded. The studies included lacked detail information on the radiation dose for RT and different types of the laser equipment for LS. The proportion of RCT and prospective study is relatively small，most of them are retrospective studies. The follow-up time was also inconsistent.

Conclusion In conclusion, radiotherapy may be a better choice in the aspect of voice quality for T1a glottic carcinoma treatment. To confirm our findings, more large, multi-center and randomized-controlled trials are urgently needed.

Research achievements 05 Research achievements 攻读学位期间的研究成果

List 1. 1篇SCI Guanjiang Huang, Mengsi Luo, Jingxuan Zhang, Hongbing Liu.The voice quality after laser surgery versus radiotherapy of T1a glottic carcinoma: Systematic review and meta-analysis[J]. OncoTargets and Therapy, 2017(已录用). 影响因子:2.2分. 2. 8篇北大中文核心 [1]黄冠江,张靖萱,罗梦思,朱财明,刘建国,刘红兵. 复发性头颈鳞状细胞癌的挽救性手术的研究进展[J]. 临床耳鼻咽喉头颈外科杂志,2016,(20):1659-1663. [2]黄冠江,刘红兵,张靖萱,罗梦思,朱财明. 经口机器人手术在喉癌外科治疗中的应用进展[J]. 临床耳鼻咽喉头颈外科杂志,2016,(21):1744-1746. [3]黄冠江,罗梦思,张靖萱,朱财明,刘月辉,刘红兵. 经口机器人手术在口咽癌外科治疗中的研究进展[J]. 临床耳鼻咽喉头颈外科杂志,2017,(02):159-161. [4]黄冠江,罗梦思,张靖萱,朱财明,刘月辉,刘红兵. 激光治疗早期喉癌术后对声带不同功能特征影响的网状Meta分析[J]. 临床耳鼻咽喉头颈外科杂志,2017,(05):382-387. [5]黄冠江,罗梦思,张靖萱,朱财明,刘月辉,刘红兵. T1a声门型喉癌经激光手术和放射治疗的Meta分析[J]. 临床耳鼻咽喉头颈外科杂志,2017,(07):534-540. [6]黄冠江,罗梦思,张靖萱,朱财明,刘红兵. 鼻内镜双径路切除上颌窦骨化性纤维瘤囊性变1例[J]. 临床耳鼻咽喉头颈外科杂志,2017,(08):641-642. [7]黄冠江,罗梦思,张靖萱,朱财明,刘建国,刘红兵.T1a声门型喉癌经激光和放射治疗后嗓音功能评估的meta分析[J]. 听力学及言语疾病杂志, 2017,(09): 725-728. [8]黄冠江,罗梦思,张靖萱,刘红兵.T1a期声门型喉癌的外科治疗进展[J]. 临床耳鼻咽喉头颈外科杂志, 2017（已录用）.

06 Acknowledgement 致谢

Acknowledgement 首先衷心感谢我的导师刘红兵教授，在攻读硕士研究生期间给予我学业和生活上的鼓励和帮助。 01 02 感谢耳鼻咽喉头颈外科的刘月辉教授、其他老师们三年来对我的真诚关切和帮助，以及临床实践上的细心指导。 03 衷心感谢答辩委员会的各位老师们，在百忙之中抽出时间来审阅论文，为我指点迷津。 04 衷心感谢我的家人和朋友，默默地支持和包容我。

谢谢欣赏