惡性嗜鉻細(xì)胞瘤的治療

1、2024/3/7,1,Introduction,rule of 10s for pheochromocytoma (PCC) 10% bilateral 10% extra-adrenal 10% extra-abdomen 10% malignant 10% familial 10% chil

2、dren 10% normal blood pressure,2024/3/7,2,Introduction,The most frequent site of metastases is the skeletonAdditional sites are liver, retroperitoneum with lymph nodes, CNS, pleura, and kidney,2024/3/7,3,Mal

3、ignant vs. Benign,Currently, there is no effective cure for malignant pheochromocytoma.There are also no reliable histopathological methods for distinguishing benign from malignant tumors.Malignancy requires evidence o

4、f metastases at non-chromaffin sites distant from that of the primary tumor.,2024/3/7,4,,Metastatic disease in pheochromocytoma may be present at the time of initial diagnosis or may only became evident after surgical re

5、moval of the primary tumor, usually within 5 years, but sometimes 16 or more years later.,2024/3/7,5,,Due to the rarity of the tumor, clinical studies about pheochromocytoma suffer from a fragmented nature and usually in

6、volve too small a number of cases to reach conclusive results.,2024/3/7,6,,Because there is currently no effective cure for malignant pheochromocytoma, most treatment are palliative, but in some cases may reduce tumor bu

7、rden and prolong survival.Without treatment, the 5-year survival is generally less than 50%.The course, however, can be highly variable with occasional patients living more than 20 years after diagnosis.,2024/3/7,7,,On

8、ce malignancy is diagnosed, therapy is generally directed at controlling blood pressure, but may also include tumor debulking.,2024/3/7,8,Alternative of Current Therapy,SurgeryRadiopharmaceuticalsCombined Chemotherapy

9、Arterial Embolization,2024/3/7,9,Alternative of Current Therapy,SurgeryRadiopharmaceuticalsCombined ChemotherapyArterial Embolization,2024/3/7,10,,Primary surgical resection is the treatment of choice whenever possibl

10、eLimited disease: curative intentionExtended disease: still to be considered in the first place for debulking and as palliative treatment(Mundschenk et al. 1998),2024/3/7,11,Problem,When signs of regional involvement

11、or distant disease are absent, there is currently no reliable preoperative diagnostic test that can differentiate between malignant and benign pheochromocytomas Should pheochromocytoma size influence surgical approach?,

12、2024/3/7,12,,A comparison of 90 malignant and 60 benign pheochromocytomas (Wen T. Shen et al.2004)Comparison of tumor size for benign pheochromocytomas and malignant pheochromocytomas with local disease only Size do

13、es not reliably predict malignancy in pheochromocytomas with local disease only,2024/3/7,13,2024/3/7,14,,Malignant PCCs presenting with only local disease cannot be discriminated from benign PCCs by size alone. When PCC

14、s do not have evidence of invasion or distant metastases and the surgeon acquires an appropriate level of experience, the majority of these tumors can be safely resected laparoscopically.,2024/3/7,15,,Laparoscopic adrena

15、lectomy for pheochromocytoma should be converted to open adrenalectomy for difficult dissection, invasion, adhesions, or surgeon inexperience,2024/3/7,16,Surgical approach,Transabdominal approach is necessaryminimally i

16、nvasive proceduresretroperitoneal approaches should be abandonedto definitely preserve the tumor capsule and perform total lymphadecectomy(Orchard et al. 1993),2024/3/7,17,Secondary Tumors,No experience with adjuvant

17、pre and postoperative radiation existsGenerally are multipleRadical surgical resection is often impossibleOther treatment modalities have to be considered,2024/3/7,18,Alternative of Current Therapy,SurgeryRadiopharma

18、ceuticalsCombined ChemotherapyArterial Embolization,2024/3/7,19,,,2024/3/7,20,,131I-MIBG is the treatment of choice for all unresectable, MIBG positive tumors58 cases of malignant PCC treated by 131I-MIBG—therapeutic

19、results and adverse events(ZHU Ruisen et al. 1999),2024/3/7,21,,Patients were classified into 3 groups according to their tumor size 20 cm3 (26 cases) In group 1, the mean absorption dose per gram of tumor was above

20、1 000 cGy. After treatment ,tumors disappeared or shrinked in all patients,2024/3/7,22,,In group 2 , the absorption dose was similar to that of group 1, but the mean absorption dose per gram was 717.6 cGy , and tumor mas

21、s regression was 36 % ;76 % reduced urinary catecholamine In group 3 , the absorption dose per gram tumor tissue was 277 cGy , and 30 % tumor enlargement , 20 % died ; the remaining 50 % symptomatic improvement without

22、any change in tumor size,2024/3/7,23,,131 I-MIBG is of certain therapeutic effectiveness of symptomatic improvementComplete tumor mass disappearance has only been found in small tumorsTreatment with 131 I-MIBG should b

23、e instituted immediately after surgical resection to eradicate the residual tumor cells and to prevent recurrencesBone marrow suppression is temporary and not dosage related,2024/3/7,24,,In 1997, Loh et al. published a

24、review of the worldwide experience involving 116 patients treated with 131I-MIBG for malignant pheochromocytoma. Overall, there was a symptomatic response in 76%, a hormonal response in 45%, and tumor regression in 30%.

25、 The activity of 131I-MIBG per single dose was 96–300 mCi, and the mean cumulative activity was 490±350 mCi.Only five CRs to 131I-MIBG were reported.,2024/3/7,25,Limitations,Not all patients with multiple metastas

26、es of malignant pheochromocytomas have sufficient uptake of MIBG to allow MIBG therapyMIBG negative lesions coexist with MIBG postive lesions, requiring combined treatment,2024/3/7,26,,As a single agent,131I-MIBG has li

27、mited efficacy in treating malignant pheochromocytoma. Its use in combination with other cytotoxic agents, as is currently being studied in patients with neuroblastoma, may result in additional benefit(Sisson et al. 19

28、99),2024/3/7,27,Alternative of Current Therapy,SurgeryRadiopharmaceuticalsCombined ChemotherapyArterial Embolization,2024/3/7,28,,Only sparse data on chemotherapeutic regimens are available, most of them in reports of

29、 few casesThe most well-established regimen is CVD (Averbuch et al. 1988)CTX 750mg/m2 d1, VCR 1.4mg/m2 d1, Dacarbazine 600mg/m2 d1,2Cycle 21 days,2024/3/7,29,,The CVD regimen was based on the treatment for advanced ne

30、uroblastoma.This regimen has been reported to produce good responses in malignant pheochromocytoma, but the median duration of remission is 21 monthsComplete long-term disease remissions with chemotherapy have not been

31、 reported.,2024/3/7,30,Alternative of Current Therapy,SurgeryRadiopharmaceuticalsCombined ChemotherapyTranscatheter Arterial Embolization,2024/3/7,31,,TAE has been successfully performed in the treatment of malignant

32、PCC with liver metastasesThe therapeutic effects of TAE have been demonstrated to be enhanced by the combination therapy with anticancer chemotherapy,2024/3/7,32,,Mitomycin C has been successfully used in TAE for liver