1、Therapy of Malignant Pheochromocytoma 恶性嗜铬细胞瘤的治疗,Literature Report,2018/10/22,2,Introduction,rule of 10s for pheochromocytoma (PCC)10% bilateral10% extra-adrenal10% extra-abdomen10% malignant10% familial10% children10% normal blood pressure,2018/10/22,3,Introduction,The most frequent site of metasta
2、ses is the skeleton Additional sites are liver, retroperitoneum with lymph nodes, CNS, pleura, and kidney,2018/10/22,4,Malignant vs. Benign,Currently, there is no effective cure for malignant pheochromocytoma. There are also no reliable histopathological methods for distinguishing benign from malign
3、ant tumors. Malignancy requires evidence of metastases at non-chromaffin sites distant from that of the primary tumor.,2018/10/22,5,Metastatic disease in pheochromocytoma may be present at the time of initial diagnosis or may only became evident after surgical removal of the primary tumor, usually w
4、ithin 5 years, but sometimes 16 or more years later.,2018/10/22,6,Due to the rarity of the tumor, clinical studies about pheochromocytoma suffer from a fragmented nature and usually involve too small a number of cases to reach conclusive results.,2018/10/22,7,Because there is currently no effective
5、cure for malignant pheochromocytoma, most treatment are palliative, but in some cases may reduce tumor burden 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
6、diagnosis.,2018/10/22,8,Once malignancy is diagnosed, therapy is generally directed at controlling blood pressure, but may also include tumor debulking.,2018/10/22,9,Alternative of Current Therapy,Surgery Radiopharmaceuticals Combined Chemotherapy Arterial Embolization,2018/10/22,10,Alternative of C
7、urrent Therapy,Surgery Radiopharmaceuticals Combined Chemotherapy Arterial Embolization,2018/10/22,11,Primary surgical resection is the treatment of choice whenever possible Limited disease: curative intention Extended disease: still to be considered in the first place for debulking and as palliativ
8、e treatment (Mundschenk et al. 1998),2018/10/22,12,Problem,When signs of regional involvement 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 surgic
9、al approach?,2018/10/22,13,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 does not reliably predict malignancy in pheochromocytomas with local dise
10、ase only,2018/10/22,14,2018/10/22,15,Malignant PCCs presenting with only local disease cannot be discriminated from benign PCCs by size alone. When PCCs do not have evidence of invasion or distant metastases and the surgeon acquires an appropriate level of experience, the majority of these tumors ca
11、n be safely resected laparoscopically.,2018/10/22,16,Laparoscopic adrenalectomy for pheochromocytoma should be converted to open adrenalectomy for difficult dissection, invasion, adhesions, or surgeon inexperience,2018/10/22,17,Surgical approach,Transabdominal approach is necessary minimally invasiv
12、e procedures retroperitoneal approaches should be abandoned to definitely preserve the tumor capsule and perform total lymphadecectomy (Orchard et al. 1993),2018/10/22,18,Secondary Tumors,No experience with adjuvant pre and postoperative radiation exists Generally are multiple Radical surgical resec
13、tion is often impossible Other treatment modalities have to be considered,2018/10/22,19,Alternative of Current Therapy,Surgery Radiopharmaceuticals Combined Chemotherapy Arterial Embolization,2018/10/22,20,2018/10/22,21,131I-MIBG is the treatment of choice for all unresectable, MIBG positive tumors
14、58 cases of malignant PCC treated by 131I-MIBGtherapeutic results and adverse events (ZHU Ruisen et al. 1999),2018/10/22,22,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 1 000 cGy. After treatme
15、nt ,tumors disappeared or shrinked in all patients,2018/10/22,23,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 mass regression was 36 % ;76 % reduced urinary catecholamine In group 3 , the absorption dose per gram tum
16、or tissue was 277 cGy , and 30 % tumor enlargement , 20 % died ; the remaining 50 % symptomatic improvement without any change in tumor size,2018/10/22,24,131 I-MIBG is of certain therapeutic effectiveness of symptomatic improvement Complete tumor mass disappearance has only been found in small tumo
17、rs Treatment with 131 I-MIBG should be instituted immediately after surgical resection to eradicate the residual tumor cells and to prevent recurrences Bone marrow suppression is temporary and not dosage related,2018/10/22,25,In 1997, Loh et al. published a review of the worldwide experience involvi
18、ng 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%. The activity of 131I-MIBG per single dose was 96300 mCi, and the mean cumulative activity was 490350 mCi. Only five CRs to
19、 131I-MIBG were reported.,2018/10/22,26,Limitations,Not all patients with multiple metastases of malignant pheochromocytomas have sufficient uptake of MIBG to allow MIBG therapy MIBG negative lesions coexist with MIBG postive lesions, requiring combined treatment,2018/10/22,27,As a single agent,131I
20、-MIBG has limited 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. 1999),2018/10/22,28,Alternative of Current Therapy,Surgery Radiopharmac
21、euticals Combined Chemotherapy Arterial Embolization,2018/10/22,29,Only sparse data on chemotherapeutic regimens are available, most of them in reports of few cases The most well-established regimen is CVD (Averbuch et al. 1988) CTX 750mg/m2 d1, VCR 1.4mg/m2 d1, Dacarbazine 600mg/m2 d1,2 Cycle 21 da
22、ys,2018/10/22,30,The CVD regimen was based on the treatment for advanced neuroblastoma. This regimen has been reported to produce good responses in malignant pheochromocytoma, but the median duration of remission is 21 months Complete long-term disease remissions with chemotherapy have not been repo
23、rted.,2018/10/22,31,Alternative of Current Therapy,Surgery Radiopharmaceuticals Combined Chemotherapy Transcatheter Arterial Embolization,2018/10/22,32,TAE has been successfully performed in the treatment of malignant PCC with liver metastases The therapeutic effects of TAE have been demonstrated to be enhanced by the combination therapy with anticancer chemotherapy,2018/10/22,33,Mitomycin C has been successfully used in TAE for liver metastasis in several cases of malignant PCC.,2018/10/22,34,2018/10/22,35,Malignant pheochromocytoma: past, present and future,
