卵巢癌的诊断和治疗医大讲.ppt

1、Diagnosis and Treatment of Ovarian Cancer,Shen Keng Department of OB/GYN Peking Union Medical College Hospital,Epidemiology and Genetic Factors,Ovarian cancer is the second most common gynecological malignancy, but the commonest malignancy of the female genital tract to result in death Incidence: In

2、 general population lifetime risk for ovarian cancer in a women is roughly 1/70 or 1.4%.,Epidemiology and Genetic Factors,The incidence in Asia, Africa and Latin America is lower than in Western countries. The most common tumor type is epithelial (85%).,卵巢癌的危险因素,年龄,危险因素,与子宫内膜、结肠、乳腺癌的关系,家庭史,生产史和激素水平,

3、Epidemiology and Genetic Factors,High risk factors: 1. More than 40yrs. 2. Caucasian race (white) 3. Late menopause. 4. Infertility 5. Positive family history of CA ovary 6. BRCA gene,Epidemiology and Genetic Factors,Family history is the strongest risk factor for ovarian cancer Women with one affec

4、ted first class relative: risk rate for ovarian cancer is 5% Women with two affected first class relative: risk rate for ovarian cancer is 7% A member of HOCS: risk rate for ovarian cancer is 20%-50% BRCA1 conservative resection preserve fertility in bilateral borderline tumours adjuvant therapy unp

5、roven Unfavourable type poorly differentiated clear cell tumours capsule penetration ruptured capsule positive washings stage II: standard operation + adjuvant therapy,早期卵巢癌的化疗,FIGO I，II期卵巢癌 “预后好”的患者90%以上可长期无瘤存活，而且不需要辅助化疗。 有高危因素的患者，30%-40%有复发的危险，25%-30%在首次手术后5年内死亡。 与复发有关的高危因素： （1）包膜破裂 （2）肿瘤表面生长 （3）低

6、分化（G3）（4）与周围组织粘连 （5）透明细胞癌 （6）腹腔冲洗液阳性 （7）卵巢癌外转移,Management of Ovarian Cancer,Advanced stage disease Stage III/IV Primary cytoreductive surgery / interval debulking Obtained optimal debulkung (residual tumor 6 months)-secondary debunking following chemotherapy Palliative treatment (Radiotherapy, immun

7、otherapy) unproven,Chemotherapy in ovarian cancer,First line chemotherapy for epithelial ovarian cancer CHexUP and Thio-Tepa protocol ( 1982-1985) PAC or PC (1986-1990) DDP, 5-FU, Ara-c, Bleomycin, CTX. IP & IV Combination (1991-1994) Taxol, DDP/Carpa (1995-2000) Weekly taxol /Carpa(2000-),Combinati

8、on Chemotherapy,Cisplatin acts by binding to DNA and producing cross-links and DNA adducts. Cisplatin is a very effective drug for ovarian cancer. Important side effects include severe nausea and vomiting, dose-related nephrotoxicity, ototoxicity, peripheral nerutoxicity and myelosuppresion,Combinat

9、ion Chemotherapy,The mechanism of action of carboplatin is the same as that of cisplatin, the side effects, however, differ greatly. The most important side effect is thrombocytopenia. Leukopenia and anemia also occur but are less severe. Neurotoxicity and nephrotoxicity are less severe with carbopl

10、atin than with cisplatin Other important side effect include alopecia and mucositis.,Combination Chemotherapy,Paclitaxel acts as a mitotic spindle poison. Paclitaxel is also a very effective drug for ovarian cancer at the present time Some patients exhibit hypersensitivity to paclitaxel. Other side

11、effect include myelosuppression , nerotoxicity, mucositis, diarrhea, alopcia nausea and vomiting,卵巢上皮癌的化疗,铂基础治疗方案通常联合: 紫杉醇 环磷酰胺 阿霉素 通常需要间隔3- 4周至少6个周期的治疗,晚期卵巢癌的化疗,一线治疗 国内 顺铂+环磷酰胺(PC) 顺铂+阿霉素+环磷酰胺(PAC) 国外 泰素顺铂 泰素卡铂 泰素每周疗法,Combination Chemotherapy,Combination chemotherapy most often is used as postopera

12、tive treatment for advanced epithelial ovarian cancer. Combination chemotherapy with six courses of cisplatin or carboplatin plus paclitaxel is the treatment of choice for patients with advanced disease. Courses are given every 3 to 4 weeks with monitoring of tumor status by physical examination. CA

13、125 levels ,and imaging studies if appropriate,卵巢癌病人化疗存活率,McGuire WP et al. N Engl J Med. 1996,Post-Therapy Surveillance,Follow-up after therapy in ovarian cancer is poorly defined. At the present time there is no definitive test for detecting the presence of microscopic recurrent epithelial ovarian

14、 cancer For this reason there remains significant controversy as to what constitutes optimal posttherapy surveillance.,Post-Therapy Surveillance,Screening modalities: 1. Pelvic Examination 2. CA 125 (44% sensitivity, 96% specificity, 65% accuracy) 3. Ultrasound (20%-89% sensitivity, 75%-100% specifi

15、city) 4. Second-look laparotomy 5. CT scan (44% sensitivity, 86% specificity, 63% accuracy) 6. MIR imaging. 6. Position emission tomography (PET) (83% sensitivity, 80% specificity, 82% accuracy),卵巢癌复发的诊断和治疗,首次的规范化治疗(理想的肿瘤细胞减灭术加上以足够疗程的铂类和/或紫杉醇为基础的联合化疗) 70%-80%的患者可获得临床完全缓解. 60%-70%的患者最终还会复发. 对卵巢癌复发的诊断

16、和治疗是卵巢癌治疗中最为棘手的问题. 怎样合理处理复发性卵巢癌意见尚不统一,卵巢癌的复发类型 (1),化疗敏感型卵巢癌: 定义为对初期以铂类药物为基础的治疗有明确反应,且已经达到临床缓解,停用化疗6个月以上,病灶复发.,卵巢癌的复发类型 (2),化疗耐药型卵巢癌: 定义为患者对初期的化疗有反应,但在完成化疗相对短的时间内证实复发,一般认为,完成化疗后6个月内的复发,应考虑为铂类药物耐药,卵巢癌的复发类型(3),顽固性卵巢癌: 是指在初期化疗时对化疗有反应或明显反应的患者中发现有残余病灶,例如:“二探”阳性者.,卵巢癌的复发类型 (4),难治性卵巢癌: 是指对化疗没有产生最小有效反应的患者,包括

17、在初始化疗期间,肿瘤稳定或肿瘤进展者,大约发生于20%的患者. 这类患者对二线化疗的有效反应率最低.,卵巢癌复发的治疗,治疗前的准备: 详细复习病史包括: (1)手术分期. (2)组织学类型和分级. (3)手术的彻底性. (4)和残余瘤的大小及部位. (5)术后化疗的方案,途径,疗程,疗效. (6)停用化疗的时间. (7)出现复发的时间等. 对复发性卵巢癌进行定性、分型、定位分析 对患者的生活状态(PS)进行评分,对患者重要器官的功能进行评估.,目前观点认为: 对于复发性卵巢癌的治疗目的一般是趋于保守性的, 因此在选择复发性卵巢癌治疗方案时,对所选择方案的预期毒性作用及其对整个生活质量的影响都

18、应该加以重点考虑.,复发性卵巢癌的手术治疗,手术对复发性卵巢癌的治疗价值尚未确定, 手术的指征和时机还存在一些争论. 复发性卵巢癌的手术治疗主要用于三个方面: 1.解除肠梗阻 2.12个月复发灶的减灭. 3.切除孤立的复发灶. 对晚期复发卵巢癌是先手术还是先化疗仍有争议.,Chemotherapy in Ovarian Cancer,Second line chemotherapy for epithelial ovarian cancer Patients with persistent or recurrent diseases should be treated with second

19、line chemotherapy. Unfortunately, response rates for second line chemotherapy are only 10% to 30%. Regarding of the approach, second line chemotherapy for persistent or recurrent ovarian cancer is not curative.,Second line chemotherapy for epithelial ovarian cancer Depending on the initial chemother

20、apy, second line chemotherapy may include: Topotecan Paclitaxel Platinum Ifosfamide Taxotere Hexamethylmelamine,Combination Chemotherapy,对复发卵巢癌有效的新药,Survival,Early-stage disease Five year survival rate for patients with stage I or stage II disease are 80% to 100, depending on the tumor grade Advance

21、d disease Five year survival rate for patients with stage IIIa is 30% to 40% Five year survival rate for patients with stage IIIb is 20% Five year survival rate for patients with stage IIIc or IV is 5% Recurrent disease Five year survival rate for patients with negative SLL is 50% Five year survival

22、 rate for patients with microscopic disease is 35% Five year survival rate for patients with macroscopic disease is 5%,Malignant Germ Cell Tumor of the Ovary,Twenty percent to 25% of all malignant tumor of the ovary are of germ cell origin. In the first decades of life, 70% of ovarian tumors are of

23、germ cell origin and one third are malignant Germ cell tumors are quite rare after the third decades of life.,1.Malignant germ cell tumor of the ovary is very sensitive to the chemotherapy. Chemotherapy has been a very important treatment for this kind ovarian tumor. 2.Chemotherapy has improved the

24、survival of patients with Malignant germ cell tumor of the ovary dramatically. Survival rate has been increased from 10% to 90% 3.Reproductive function can be preserved for any stage patients with malignant germ cell tumor of the ovary,Malignant Germ Cell Tumor of the Ovary,Management of malignant g

25、erm cell tumor of the ovary,Primary treatment is surgical. Unilateral oophorectomy with preserved reproductive function is considered. PVB and PEB chemotherapy are the treatment of choice for patients with MGCT postoperatively Courses of chemotherapy are depending on the high risk factors of the tum

26、or and tumor maker levels,Sex cord stromal tumors,Ovarian sex cord-stromal tumor account for less than 5%. It may occur at any age, although the age of peak incidence for granular cell tumors is in the postmenopausal years. No standard therapy exists. Lower malignant potential and late recurrence,Sex cord stromal tumors,Surgery remains cornerstone of treatment for patients with ovarian sex c