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研究生:蔡晶玫
研究生(外文):Ching-Mei Tsai
論文名稱:合併放射線治療在犬中至高分級惡性肥大細胞瘤之療效
論文名稱(外文):The Efficacy of Adjuvant Radiation Therapy in Treating Canine Intermediate to High Grade Mast Cell Tumor
指導教授:李繼忠李繼忠引用關係
口試委員:李雅珍林辰栖廖泰慶王尚麟
口試日期:2019-07-05
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:臨床動物醫學研究所
學門:獸醫學門
學類:獸醫學類
論文種類:學術論文
論文出版年:2019
畢業學年度:107
語文別:英文
論文頁數:113
中文關鍵詞:犬肥大細胞瘤低分次放射線治療
DOI:10.6342/NTU201901771
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肥大細胞瘤(Mast cell tumor, MCT)為犬體表最常見腫瘤,占所有犬體表腫瘤之16-21%。肥大細胞瘤之臨床表現受到許多因子影響,其中組織病理分級為最重要的因子之一。根據Patnaik組織分級系統,第二級以及第三級的肥大細胞瘤,由於單純手術切除後有較高局部復發以及遠端轉移機率,因此治療建議為手術切除加上合併輔助治療。
此研究收集國立台灣大學生物資源暨農學院附設動物醫院動物腫瘤治療中心從西元2009年至西元2019年診斷為第二級以及第三級肥大細胞瘤的病例,進行回溯性方法分析與研究。共有42例犬隻符合收案條件而納入,並進一步就合併低分次放射線治療在此類病患中的治療效力進行分析。依據是否有接受手術後放射線治療進行分組,10隻犬隻進行外科手術、低分次放射線治療及內科治療而歸類為放療組,另外32隻進行外科手術及內科治療而歸類為非放療組。
結果顯示放療組相較於非放療組有較長的無疾病進展時間(Progression-free interval, PFI)、總體存活時間(Overall survival time, OST)以及較低的局部腫瘤復發率。兩組的中位無疾病進展時間為230 以及119 天(P = 0.029),總體存活時間為533 以及224 天(P = 0.021), 以及局部復發率為40% 以及75 % (P = 0.012)。
在多變數分析不同因子分別與無疾病進展時間以及總體存活時間的關係時,接受放射線治療對於無疾病進展時間有顯著差異 (P = 0.041, 危害比 2.876),以及對於總體存活時間也有顯著差異 (P = 0.021, 危害比 2.549)。腫瘤組織分級對於無疾病進展時間 (P = 0.035, hazard ratio 3.169)以及總體存活時間 (P = 0.016,危害比 2.803)有顯著影響。臨床分期對於總體存活時間有顯著影響(P = 0.025, 危害比2.643)但是對於無疾病進展時間並無顯著影響(P = 0.064)。
此篇研究之結果顯示,罹患臨床表現較惡性之肥大細胞瘤之犬隻,接受積極局部控制包括手術以及手術後低分次放射線治療,加上合併內科治療,相較於進行手術以及單純內科治療有較好之預後。
Mast cell tumor (MCT) is the most common skin tumor in dogs, representing for 16% to 21% of all canine cutaneous neoplasms. The clinical behavior of the MCT is highly variable due to many factors, with the histologic grade being the most important one. For grade II and grade III (according to the Patnaik classification) MCTs, adjuvant therapy is generally recommended because of the high incidence of local recurrence and distant metastasis after surgical excision alone.
The medical records of the dogs diagnosed with intermediate to high grade mast cell tumor from 2009 to 2019 at National Taiwan University Veterinary Hospital were reviewed and analyzed retrospectively. Forty-two client-owned dogs met the inclusion criteria, receiving surgery and post-operative systemic treatment with or without hypofractionated radiation therapy (RT) were analyzed in the study, 10 cases were receiving adjuvant RT treatment and designated as RT group and 32 cases were not. The efficacy of aggressive local tumor control by adjuvant radiation therapy and the prognostic factors of these patients were evaluated in this study.
The result revealed the dogs treated with adjuvant hypofractionated RT had the clinical benefit on progression-free interval (PFI), overall survival time (OST) and local recurrence rate compared to the non-RT group. The median PFI was 230 and 119 days (P = 0.029), the median OST was 533 and 224 days (P = 0.021), the local recurrence rate was 40% and 75% (P = 0.012).
In the multivariate analysis of the association of several factors with PFI and OST, the dogs that received adjuvant radiation therapy had statistically significant influence on PFI (P = 0.041, hazard ratio 2.876) and OST (P = 0.021, hazard ratio 2.549). Tumor grade also had statistically significant influence on PFI (P = 0.035, hazard ratio 3.169) and OST (P = 0.016, hazard ratio 2.803). The clinical stage had statistically significant influence on OST (P = 0.025, hazard ratio 2.643) but not for PFI (P = 0.064).
The result from the present study indicates that the aggressive local control including surgery excision and hypofractionated radiation therapy combined with systemic treatment can improve the outcome for the dogs with histologic grade II to grade III MCT compared to surgical excision and systemic treatment alone.
口試委員審定書 i
誌謝 ii
List of abbreviations iii
中文摘要 iv
ABSTRACT vi
CONTENTS viii
LIST OF TABLES xi
LIST OF FIGURES xii
Chapter 1 Literature review 14
1.1 Canine mast cell tumor 14
1.2 Local control 15
1.3 Systemic treatment 18
1.3.1 Corticosteroid 18
1.3.2 Chemotherapy 19
1.3.3 Target therapy 19
1.4 Prognostic factors 20
Chapter 2 Introduction 23
Chapter 3 Material and methods 24
3.1 Patient selection 24
3.2 Data collection 24
3.3 Clinical stage 25
3.4 Tumor grade 26
3.5 Surgery 26
3.6 Systemic treatment 26
3.6.1 Medication 26
3.6.2 Monitor 27
3.7 Radiation therapy 27
3.8 Treatment response 28
3.9 Treatment toxicity 29
3.10 Statistical analysis 29
Chapter 4 Results 32
4.1 Demographic 32
4.2 Adjuvant hypofractionated radiation therapy group 33
4.2.1 Radiation therapy 35
4.2.2 Medical treatment and outcome 36
4.2.3 Outcome 38
4.3 Non-radiation therapy group 39
4.3.1 Post-operative first-line medical treatment and outcome 41
4.3.2 Outcome 45
4.4 Statistical analysis 46
4.4.1 Compare two study groups 46
4.4.2 Kaplan-Meier curve of PFI in RT and non-RT group 46
4.4.3 Kaplan-Meier curve of ST in RT and non-RT group 47
4.4.4 Prognostic factors of the RT group 47
4.4.5 Prognostic factors analysis for the progression-free interval (PFI) 48
4.4.6 Prognostic factors analysis for overall survival time (OST) 49
Chapter 5 Discussion 51
5.1 Demographic 51
5.2 Treatment efficacy 52
5.3 Influential factors evaluation 55
5.4 Limitations of this study 60
Chapter 6 Conclusion 61
Appendix 62
Appendix 1. Treatment timeline of the RT and non-RT group 62
Appendix 2. Diagnostic and treatment algorithms for MCT 63
Tables 65
Figures 83
REFERENCE 105
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