High-Specific-Activity-131I-MIBG versus 177Lu-DOTATATE Targeted Radionuclide Therapy for Metastatic Pheochromocytoma and Paraganglioma.

Targeted radionuclide therapies (TRT) using 131I-metaiodobenzylguanidine (131I-MIBG) and peptide receptor radionuclide therapy (177Lu or 90Y) represent several of the therapeutic options in the management of metastatic/inoperable pheochromocytoma/paraganglioma. Recently, high-specific-activity-131I-MIBG therapy was approved by the FDA and both 177Lu-DOTATATE and 131I-MIBG therapy were recommended by the National Comprehensive Cancer Network guidelines for the treatment of metastatic pheochromocytoma/paraganglioma. However, a clinical dilemma often arises in the selection of TRT, especially when a patient can be treated with either type of therapy based on eligibility by MIBG and somatostatin receptor imaging. To address this problem, we assembled a group of international experts, including oncologists, endocrinologists, and nuclear medicine physicians, with substantial experience in treating neuroendocrine tumors with TRTs to develop consensus and provide expert recommendations and perspectives on how to select between these two therapeutic options for metastatic/inoperable pheochromocytoma/paraganglioma. This article aims to summarize the survival outcomes of the available TRTs; discuss personalized treatment strategies based on functional imaging scans; address practical issues, including regulatory approvals; and compare toxicities and risk factors across treatments. Furthermore, it discusses the emerging TRTs.

Phase II study of high-dose [131I]metaiodobenzylguanidine therapy for patients with metastatic pheochromocytoma and paraganglioma.

PURPOSE: To evaluate the safety and efficacy of high-dose [(131)I]metaiodobenzylguanidine ([(131)I]MIBG) in the treatment of malignant pheochromocytoma (PHEO) and paraganglioma (PGL). METHODS: Fifty patients with metastatic PHEO or PGL, age 10 to 64 years, were treated with [(131)I]MIBG doses ranging from 492 to 1,160 mCi (median, 12 mCi/kg). Cumulative [(131)I]MIBG administered ranged from 492 to 3,191 mCi. Autologous hematopoietic stem cells were collected and cryopreserved before treatment with [(131)I]MIBG greater than 12 mCi/kg or with a total dose greater than 500 mCi. Sixty-nine [(131)I]MIBG infusions were given, which included infusions to 35 patients treated once and infusions to 15 patients who received two or three treatments. Response was evaluated by [(123)I]MIBG scans, computed tomography/magnetic resonance imaging, urinary catecholamines/metanephrines, and chromogranin A. RESULTS: The overall complete response (CR) plus partial response (PR) rate in 49 evaluable patients was 22%. Additionally, 35% of patients achieved a CR or PR in at least one measure of response without progressive disease, and 8% of patients maintained stable disease for greater than 12 months. Thirty-five percent of patients experienced progressive disease within 1 year after therapy. The estimated 5-year overall survival rate was 64%. Toxicities included grades 3 to 4 neutropenia (87%) and thrombocytopenia (83%). Grades 3 to 4 nonhematologic toxicity included acute respiratory distress syndrome (n = 2), bronchiolitis obliterans organizing pneumonia (n = 2), pulmonary embolism (n = 1), fever with neutropenia (n = 7), acute hypertension (n = 10), infection (n = 2), myelodysplastic syndrome (n = 2), and hypogonadism (n = 4). CONCLUSION: Although serious toxicity may occur, the survival and response rates achieved with high-dose [(131)I]MIBG suggest its utility in the management of selected patients with metastatic PHEO and PGL.

Malignant pheochromocytoma with hepatic metastasis diagnosed 10 years after a resection of the primary incidentaloma adrenal lesion: report of a case.

A 40-year-old woman developed hepatic tumors 10 years after a resection of pheochromocytoma of the left adrenal gland. Computed tomography showed a round tumor measuring about 35mm in diameter at segment V of the liver (Couinaud's classification), and magnetic resonance imaging showed another tumor measuring about 5mm at segment V-VIII of the liver. The results of the endoscopic examination of her upper gastrointestinal tract and barium enema were normal. Owing to a suspected hepatic metastasis of malignant pheochromocytoma, a right lobectomy of the liver was performed. Postoperatively, [131I]metaiodobenzylguanidine scintigram and computed tomography showed no other residual tumors nor metastasis. The present case suggests that a long-term follow-up only by endocrinological examinations is insufficient to find newly developed metastatic foci, while routine diagnostic imaging at frequent intervals is necessary in cases of pheochromocytoma.

Role of autologous blood transfusion in sacral tumor resection: patient selection and recovery after surgery and blood donation.

We carried out sacral en-bloc resection in six patients (three with chordoma; one with pheochromocytoma; one with malignant schwannoma; and one with giant cell tumor) using preoperatively collected autologous blood, to avoid homologous blood transfusion. An average of 3200 ml was collected preoperatively, with patients receiving recombinant human erythropoietin (r-HuEPO), at a total dose of 130 000 units on average. In four patients, we were able to accomplish the surgery without homologous blood transfusion. Postoperatively, the hemoglobin level in these four patients recovered to the pre-collective level in 4.5 weeks, on average. These clinical results indicate that en-bloc sacrectomy, which requires a large volume of blood transfusion, can be accomplished with preoperatively collected autologous blood alone.

[Monitored anesthesia care for a patient with malignant pheochromocytoma].

Monitored anesthesia care (MAC) is being increasingly used in the 1990s for a wide variety of diagnostic and therapeutic procedures. The primary objective in providing MAC is to ensure patients' comfort and safety, whether in the operating room or in other places. We experienced MAC for a patient with pheochromocytoma. A 63-year-old man with hepatic metastasis of malignant pheochromocytoma, received transcatheter arterial embolization (TAE) in the angiographic room. Hypertension and ventricular arrhythmia occurred during the hepatic arterial embolization. However, we successfully controlled the hemodynamic changes using phentolamine and propranolol under the close monitoring. He showed an uneventful recovery during postoperative period except for mild hypotension on the third day which needed temporary norepinephrine infusion.

Giant hepatic biloma following transcatheter oily chemoembolization in a patient with hepatic metastases from malignant pheochromocytoma.

A 48-year-old woman developed hepatic metastases from malignant pheochromocytoma resected 8 years previously. Angiography revealed multiple tumor stains in the liver. Transcatheter oily chemoembolization using styrenomaleic acid neocarzinostatin and iodized oil was performed. The patient complained of severe right upper quadrant pain immediately following the transcatheter oily chemoembolization. Necrotizing cholecystitis developed on the 4th day post-transcatheter oily chemoembolization, hepatic infarction on the 12th day, and a biloma on the 19th day. Despite the administration of antibiotics and percutaneous transhepatic drainage, neither the volume of drainage nor the size of the biloma decreased. Biliary reconstruction was performed using a metallic stent, which decreased the size of the biloma.

The current status of radioiodinated metaiodobenzylguanidine therapy of neuro-endocrine tumors.

The avidity of many metastatic pheochromocytomas and neuroblastomas for metaiodobenzylguanidine (MIBG) observed at diagnostic scintigraphy has led to attempts to treat these lesions with large doses of MIBG. We and others have achieved therapeutic responses with 131I-MIBG (usually partial) in about a third of malignant pheochromocytomas. A small but important subgroup of advanced, poor prognosis neuroblastomas which have been resistant to all other therapies have also shown responses including occasional long-term survival (> 5 years) and apparent complete responses to 131I-MIBG. Because the physical properties of 131I are suboptimal for the delivery of therapeutic radiation to bone marrow micrometastases, a frequent problem in neuroblastoma, we have performed preliminary studies in poor prognosis Stage III and VI neuroblastoma using 125I-MIBG which has more satisfactory emissions. This has led to prolonged tumor stabilization and survival (> 19 to > 52 months) in 5 of 10 patients. MIBG radiopharmaceutical treatment of neuroendocrine tumor patients must still be considered an experimental but nevertheless promising treatment modality.

Scintigraphic localization of a disseminated malignant pheochromocytoma with the use of 131I-meta-iodobenzylguanidine.

Preliminary clinical studies with 131I-meta-iodobenzylguanidine, a newly synthesized radiopharmaceutical and guanethidine analog capable of imaging the adrenal medulla, have led to the identification of a case of disseminated malignant pheochromocytoma with the localization of brain and bone metastases. The result is of particular interest as the symptomatology in this case appeared rather equivocal and various investigations had led to a completely different diagnosis. This new scintigraphic technique has proved to be safe, specific and noninvasive, and it may have a clinical application as a complementary or alternative technique to conventional diagnostic tests.

Complementary roles of CT and 131I-MIBG scintigraphy in diagnosing pheochromocytoma.

Recently 131I-MIBG (metaiodobenzylguanidine), an adrenergic tissue-localizing radiopharmaceutical, has been used for diagnosis of pheochromocytoma. In a retrospective study of 32 patients with pathologically proved primary, metastatic, or recurrent pheochromocytoma, the roles of 131I-MIBG scintigraphy and computed tomography (CT) in pheochromocytoma detection were compared. The two methods were equally accurate in the identification of primary and recurrent pheochromocytoma. 131I-MIBG scanning was more accurate as the initial examination in patients with extraadrenal tumors. In patients with metastatic disease, scintigraphy was preferable to CT because of its nontomographic nature, which permitted imaging of the entire body. Although a positive MIBG scan is diagnostic of pheochromocytoma, CT of extraadrenal tumors (particularly in the chest) has been very useful in planning appropriate surgical intervention. Furthermore, the roles of 131I-MIBG scintigraphy and CT in the detection of pheochromocytoma are complementary because each method has certain limitations.