| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
CLINICAL CASE SEMINAR |
Departments of Nuclear Medicine (M.G.E.H.L., P.P.v.R., J.M.H.d.K.) and Endocrinology (C.J.M.L.) and Clinical Laboratory (E.G.W.M.L.), University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands; Department of Nuclear Medicine (J.M.H.d.K.), Meander Medical Center, Amersfoort, The Netherlands; and Departments of Nuclear Medicine (P.L.J.) and Endocrinology (R.P.F.D.), AZG, Groningen, The Netherlands
Address all correspondence and requests for reprints to: Marnix G. E. H. Lam, M.D., University Medical Center Utrecht, Department of Nuclear Medicine, P.O. Box 85500, 3508 GA Utrecht, The Netherlands. E-mail: M.Lam{at}azu.nl.
 |
Abstract |
|---|
 Top Abstract IntroductionPatients and MethodsResultsDiscussionReferences |
|---|
Setting and Patients: The study took place at University Medical Centers and included two patients (one male, 36 yr of age, and one female, 43 yr of age) with widely spread metastatic pheochromocytoma and bad prognosis because of liver and lung metastases.
Interventions: Instead of a single high dosage, these two patients were treated with multiple intermediate dosages of [131I]MIBG. The first patient received 37 GBq (1 Ci) [131I]MIBG in five sessions [7400 MBq (200 mCi) each; interval range, 2–11 months]; the second patient received 66.6 GBq (1.8 Ci) [131I]MIBG in 12 sessions [5550 MBq (150 mCi) each; interval range, 2–14 months].
Outcome Measures: We measured efficacy, toxicity, and survival.
Results: Both patients had a complete symptomatic response and a partial tumor volume response. The first patient had a partial biochemical response, the second a complete biochemical response. In both cases, toxicity has been confined to nausea during treatment. Hematological toxicity was minimal, and both patients stayed euthyroid. The survival (so far) of these patients was 5 yr (clinical case 1) and 16 yr (clinical case 2) after initial diagnosis.
Conclusions: Repeated intermediate-dosage [131I]MIBG treatment appears to be a reliable and well-tolerated radionuclide therapy and might be a useful adjunct in patients with malignant pheochromocytoma, providing longstanding palliation and prolonged survival.
|
Introduction |
|---|
|
TopAbstractIntroductionPatients and MethodsResultsDiscussionReferences |
|---|
Treatment for pheochromocytoma, and malignant pheochromocytoma in particular, consists primarily of surgery. Preoperatively and during surgery, antihypertensive drugs can block the effect of catecholamines. In the case of irresectable malignant disease, postoperative treatment with 
- and ß-blockade may also be necessary. As well as these antihypertensive drugs that block the effects of catecholamines, -methyltyrosine is also able to block the synthesis of catecholamines (4). However, none of these drugs alter tumor growth. Other approaches such as systemic treatment with radiotherapy or chemotherapy have shown limited success. Although most experience is anecdotal, some reports show the efficacy of chemotherapy (5, 6). Using a neuroblastoma-type chemotherapy protocol, multiple cycles of a combination of cyclophosphamide, vincristine, and dacarbazine produced objective benefits, including one complete remission, in the 14 patients studied (7). In contrast with these other therapies, systemic treatment with radioiodine-labeled metaiodobenzylguanidine (MIBG) had a promising efficacy for various neuroendocrine tumors, including malignant pheochromocytomas (8, 9, 10, 11, 12, 13, 14).
MIBG is a guanethidine analog that resembles norepinephrine and is concentrated similarly by adrenergic tissues. It is mainly sequestered in the storage granules of chromaffin cells in the adrenal medulla. Cellular MIBG uptake is driven both by saturable active type I uptake and by passive diffusion (15). A subsequent active uptake mechanism, different from the transmembrane uptake mechanism, is responsible for the translocation of intracellular MIBG into the storage granules (16).
After the discovery in 1981 that this radiopharmaceutical was able to localize pheochromocytomas, it was recognized in 1984 that it could also be used successfully as a systemic treatment for malignant pheochromocytomas (17, 18). A comprehensive review of 116 reported patients with malignant pheochromocytoma by Loh et al. (11) reported a symptomatic improvement in 76% of patients, tumor responses in 30%, and hormonal responses in 45%. However, only five patients had a complete tumor and hormonal response, lasting from 16–58 months.
Although the efficacy and toxicity of single high-dosage treatment with [131I]MIBG has been studied extensively, little has been published about repeated intermediate-dosage [131I]MIBG treatment. In this report we present two patients who are currently being treated for malignant pheochromocytoma to illustrate the beneficial effect of repeated intermediate-dosage treatment with [131I]MIBG on tumor status, symptoms, and survival.
|
Patients and Methods |
|---|
|
TopAbstractIntroductionPatients and MethodsResultsDiscussionReferences |
|---|
|
Results |
|---|
|
TopAbstractIntroductionPatients and MethodsResultsDiscussionReferences |
|---|
A 36-yr-old white male presented himself with palpitations, hypertension, and profound perspiration. Catecholamine and metabolite levels in 24-h urine were increased. His family history was negative and calcitonin levels were low, making a multiple endocrine neoplasia syndrome type 2 unlikely. Furthermore, there were no signs or symptoms of neurofibromatosis type 1 or Von Hippel-Lindau disease, and therefore most likely a sporadic pheochromocytoma was present. No germline mutations were found by genetic testing. Preoperative computed tomography (CT) of the abdomen showed an enlarged left adrenal with a diameter of 11 cm and small (<1 cm) nonpathological para-aortal lymph nodes. Before and during surgery, the patient was adequately blocked with antihypertensive drugs (- and ß-blockade). An en block resection of the left adrenal, spleen, flexura lienalis of the colon, and the pancreatic tail was performed. In addition to this, the left kidney could not be saved and was also removed. No pathological lymph nodes were discovered. The pathology report mentioned a large pheochromocytoma in the left adrenal (15 x 11 x 8 cm) but no extension into the colon, spleen, or pancreas. In addition, one lymph node (<1 cm) close to the tumor was found to be positive for metastasis with vasoinvasive growth.
Two months after surgery, a diagnostic scintigram with [131I]MIBG [24 h after 2.2 mCi (80 MBq) iv], CT, and ultrasound showed no evidence of recurrent or residual disease. Biochemical studies of urine were first performed 5 months after surgery. Catecholamine and metabolite levels were normal.
Eighteen months after surgery, total metanephrine [12.8 µmol/24 h (maximum, 5 µmol/24 h; 1 µmol = 0.197 µg)] and vanillylmandelic acid [47 µmol/24 h (maximum, 36 µmol/24 h; 1 µmol = 5.05 mg)] levels in urine were increased. A second MIBG scintigram showed a suspicious lesion in the abdomen. Magnetic resonance imaging (MRI) confirmed two lymph nodes of 1 cm left of the aorta in the upper abdominal region. These lesions were considered too small for a renewed surgical intervention.
Repeated scintigraphy and MRI (9 months later) reported clear progression of size and number of the lesions in the upper abdomen, left of the aorta (three lesions between 1 and 2 cm). CT showed, in addition to the known lesions in the abdomen, four lesions in the right lung, one in the left lung, and three in the liver, all less than 1 cm. Free norepinephrine [955 nmol/24 h (maximum, 470 nmol/24 h; 1 nmol = 0.183 µg)], dopamine [3124 nmol/24 h (maximum, 2600 nmol/24 h; 1 nmol = 0.153 µg)], total metanephrine [66.5 µmol/24 h (maximum, 5 µmol/24 h)], and vanillylmandelic acid [194 µmol/24 h (maximum, 36 µmol/24 h)] levels in urine as well as chromogranin A [4242 ng/ml (maximum, 100 ng/ml; 1 ng = 0.02 nmol)] levels in blood had increased progressively, and the patient resumed complaints of palpitations, hypertension, and profound perspiration. The patient was put on -blockade (doxazosine, 8 mg/d) and ß-blockade (metoprololtartrate, 100 mg/d) as well as metyrosine (-methyl-p-tyrosine, 1000 mg/d) (4). Because of the widespread nature of the lesions, surgery was not performed due to of the existence of lung lesions.
Five months later, 3 yr after the diagnosis was made, treatment with 200 mCi (7400 MBq) [131I]MIBG was started. Eight days after therapy, a posttreatment scintigram showed clear uptake of the radiopharmaceutical in the lesions in the abdomen and in two lesions in the right lung and one in the supraclavicular area on the left side (Fig. 1A
). Chest x-ray confirmed the lesions in the right lung and showed one in the left lung. The second treatment with 200 mCi (7400 MBq) [131I]MIBG was scheduled 3 months later. Posttreatment scintigraphy showed decreased uptake in the lesions in the lung and unchanged uptake in the abdomen and neck.
|
), but total metanephrine [94.9 µmol/24 h (maximum, 5 µmol/24 h)] (Fig. 3) and dopamine [5098 nmol/24 h (maximum, 2600 nmol/24 h)] (Fig. 4) levels in urine and chromogranin A [7575 ng/ml (maximum, 100 ng/ml)] levels in blood had considerably increased. Because of side effects, especially extreme fatigue, additional - and ß-blockade was difficult to tolerate, and because more complications from the tumor were expected, this led to a preference for surgical reexploration of the abdomen for palliative treatment. Another reason for surgical debulking was our expectation that additional [131I]MIBG therapy would be more effective for smaller lesions. During reexploration of the abdomen, the surgeon removed the tumor on the left side of the aorta together with several pathological lymph nodes on the left and right. A biopsy of the liver was also taken, because of morphological (and CT) suspicion of liver metastasis. The pathologist confirmed malignancy with extranodal invasion and vasoinvasive growth in all removed samples (14 lymph nodes, all >0.5 cm in diameter, the largest 6 x 1.5 x 8 cm). Resection proved not to be complete, based on the pathology report.
|
|
|
). As expected, the degree of abnormal uptake in the abdomen had decreased, as a result of surgery. The lesion in the left neck coincided with a palpable lesion in the low supraclavicular region on the left side. Ultrasound on the neck revealed a pathological lymph node (2.5 x 2.5 x 1.5 cm) in the left supraclavicular region that was surgically removed from the area dorsal of the left musculus sternocleidomastoideus. Malignancy was proven histologically. The fourth treatment with 200 mCi (7400 MBq) [131I]MIBG was given 4 months later. Although a pathological lymph node had been removed from the neck, we could still see pathological uptake of the radiopharmaceutical on the left side of the neck on posttreatment scintigraphy; however, all residual lesions (lung, abdomen) showed a further decline in activity. Chest x-ray showed no additional lesions in the lung. Ultrasound of the neck showed again a pathological lymph node on the left side. Because the patient complained of extreme fatigue caused by the medication, a successful attempt was made to stop all medical treatment. No rise in blood pressure and/or recurrent symptoms were encountered.
The fifth and last treatment with 200 mCi (7400 MBq) [131I]MIBG so far (cumulative dosage of 1000 mCi, or 37 GBq) was given 11 months later. Posttreatment scintigraphy now showed a complete scintigraphic remission of all lesions (neck, lung, and abdomen). Chest x-ray had already shown complete remission of lung lesions, but unfortunately radiological imaging has been insufficient to prove objective tumor volume response (World Health Organization response criteria) (19). In addition, free norepinephrine (Fig. 2) and dopamine levels (Fig. 4) in urine had normalized. Chromogranin A levels in blood had decreased by more than 50% but remained elevated [3461 ng/ml (maximum, 100 ng/ml)]. Catecholamine metabolite (normetanephrine) levels, however, had continued to increase [91.2 µmol/24 h (maximum, 3.3 µmol/24 h)] (Fig. 3). More than 5 yr after diagnosis, the patient has no complaints, is without medication, and has no morphological evidence of disease.
Toxicity was confined to nausea during treatment. During surgery and additional MIBG treatments, blood pressure did not rise significantly. No other elevations of sympathetic autonomic function were encountered. Clinically relevant myelosuppression after MIBG treatment was not encountered. Hemoglobin, platelet, and leukocyte levels remained normal throughout (monthly measurements), without any transient falls. By administering potassium iodate, 170 mgd for 10 d starting 2 d in advance, an attempt was made to reduce free 131I uptake in the thyroid gland. Every posttherapy scintigram showed free 131I uptake in the thyroid, but the patient stayed clinically euthyroid, without increases in TSH level.
Clinical case 2
A 43-yr-old woman was diagnosed with a pheochromocytoma (9 cm in diameter), localized in the right adrenal. She had hypertension and complained of palpitations and profound perspiration. Catecholamines and metabolites in 24-h urine were elevated. Sporadic disease was most likely the case. Genetic testing for germline mutations was not performed at the time. After surgery, the disease was in remission for approximately 5 yr.
She then developed complaints consistent with recurrent disease: pain in the right groin, fatigue, and frequent attacks of trembling, anxiety, dizziness, and headache (no palpitations, normal blood pressure). Recurrent pheochromocytoma was confirmed by biochemical analysis in 24-h urine [metanephrines, 3880 µmol/mmol creatinine (maximum, 99 µmol/mmol creatinine; 1 µmol = 0.197 mg); normetanephrines, 2080 µmol/mmol creatinine (maximum, 260 µmol/mmol creatinine; 1 µmol = 0.183 mg); and 3-m-tyramine (metabolite of dopamine), 4260 µmol/mmol creatinine (maximum, 197 µmol/mmol creatinine; 1 µmol = 0.166 mg)], CT/MRI, and [123I]MIBG scintigraphy [24 h after 5 mCi (185 MBq) iv]. Disease had spread to the liver (three lesions) and retroperitoneum (several lesions in the adrenal region on the right side). Under medical treatment with -blockade (phenoxybenzamine) and ß-blockade (propranolol), reoperation was performed including hemihepatectomy (three malignant lesions), right nephrectomy, cholecystectomy, and resection of several 1- to 2-cm retroperitoneal lesions (multiple lymph node metastases). After surgery, she improved clinically and her catecholamine metabolite levels and [123I]MIBG scintigraphy [24 h after 5 mCi (185 MBq) iv] normalized. All medication was discontinued. No rise in blood pressure and/or recurrent symptoms were encountered.
Two years later, however, she developed the same complaints as previously as well as palpitations and chest pains. Catecholamine metabolite levels in urine had risen above normal levels [metanephrines, 285 µmol/mmol creatinine (maximum, 99 µmol/mmol creatinine); normetanephrines, 270 µmol/mmol creatinine (maximum, 260 µmol/mmol creatinine); and 3-m-tyramine, 270 µmol/mmol creatinine (maximum, 197 µmol/mmol creatinine)] (Fig. 5). Renewed recurrent disease in the abdomen was confirmed by [123I]MIBG scintigraphy, which showed lesions in the left and right adrenal region, two lesions under the liver, on the right side in the abdomen, and one lesion in the left lower abdomen. Repeated CT and MRI were, however, not able to confirm the evident lesions visualized by scintigraphy. It was decided to start therapy with [131I]MIBG as well as -blockade (phenoxybenzamine) and a short period of ß-blockade (propranolol).
|
). All lesions had avid uptake of the radiopharmaceutical.
|
), intervals were prolonged after six treatments to intervals of 6 months. No new lesions were visualized, and catecholamine metabolite levels had normalized [free catecholamine metabolites in 24-h urine (Fig. 5)]. Repeated x-ray, CT, and MRI were not able to confirm the lesions, but scintigraphy visualized persistent lesions, with partial reduction in size and function after each therapy, including the last. After 10 treatments, intervals increased to 1 yr and more, the last treatment being given 14 months after the previous one. She discontinued medication (phenoxybenzamine) after six treatments with [131I]MIBG, more than 7 yr ago (after catecholamine and metabolite levels had normalized), without any complaints of high blood pressure or any other elevations of sympathetic autonomic function.
Toxicity was confined to nausea during treatment. No transient falls in hemoglobin, platelet or leukocyte levels, or any other hematological toxicities were encountered (monthly measurements). Blood pressure remained normal during surgery (with - and ß-blockade) and during MIBG treatment (with and without blockade). Lugol droplets (potassium iodine) for a period of 14 d, starting 3 d in advance, were administered to block free 131I uptake in the thyroid. Although on every posttherapy scintigram a fair amount of free 131I uptake in the thyroid was visualized, thyroid function remained normal, both clinically and biochemically.
|
Discussion |
|---|
|
TopAbstractIntroductionPatients and MethodsResultsDiscussionReferences |
|---|
With regard to survival, the first and second patient currently survive for 5 and 16 yr after initial diagnosis. Both patients initially had liver metastases, and the first patient has lung metastases. The prognosis of metastases in vital organs such as the liver and lung is worse (21, 22). This, compared with the fact that both patients proved to have progressive disease before the start of treatment, strongly suggests beneficial therapeutic effect. However, there have been occasional reports of prolonged survival despite extensive metastatic disease (2, 3). The evaluation of survival benefit is therefore complicated in these rare tumors. For this purpose, it is thought to be important to install databases on a national or international level.
Although both patients received very high cumulative dosages [37 GBq (1 Ci) and 66.6 GBq (1.8 Ci)], toxicity during and after treatment has been low. The only side effect was a transient nausea shortly after the administration of [131I]MIBG, but blood pressure stayed normal without extra - and ß-blockade. Hematological toxicity was not encountered with normal hemoglobin, platelet, and leukocyte counts. Blood counts were measured on a monthly basis, which showed no transient falls. To prevent hypothyroidism, an attempt was made to block the thyroid by giving oral potassium iodate, 170 mg/d for 10 d, starting 2 d in advance (clinical case 1), or giving Lugol droplets (potassium iodine) for a period of 14 d, starting 3 d in advance (clinical case 2). Despite this pretreatment, there was still considerable uptake of 131I in the thyroid. During the fifth treatment of the first patient, 100 mg potassium iodine was given instead of 170 mg potassium iodate, for 14 d, starting 2 d in advance, combined with 500 mg potassium perchlorate twice daily for 8 d, starting 2 d in advance. With this more stringent policy, there was still some uptake in the thyroid that, although reduced, could be visualized. Pharmacologically, there does not seem to be one favorable method for use in blocking the thyroid. We favored potassium iodate because of its prolonged expiration date and ease of use. In all cases, however, considerable uptake in the thyroid is still seen. An alternative approach might therefore be a thiourea derivate (thiamazol), combined with levothyroxine, blocking the thyroid completely. Most important, however, is that both patients remained clinically and biochemically euthyroid over all the years of treatment and with a follow-up of 8 months (clinical case 1) and 3.5 yr (clinical case 2) after the last treatment. Radiation dosimetry was not performed.
High single-dosage treatment with [131I]MIBG instead of repeated intermediate dosages used in our cases has proven efficacy (9, 10). As already mentioned briefly, Loh et al. (11) reported a symptomatic improvement in 76% of patients, tumor responses in 30%, and hormonal responses in 45% (115 cases with malignant pheochromocytoma). Matthay et al. (14) reported a dose escalation study of [131I]MIBG to define dose-limiting toxicity with and without autologous bone marrow support, in 30 patients with relapsed neuroblastoma. They used escalating dosages of 3–18 mCi/kg (111–666 MBq/kg).A higher response rate was found with increasing [131I]MIBG activity. However, grade 4 hematological toxicity occurred in greater then 80% of the patients treated with dosages of 5–18 mCi/kg (555–666 MBq/kg). Stem cell harvest before such therapy is therefore mandatory. Other investigators (9, 10) also found higher response rates by using higher dosages of [131I]MIBG with a median single treatment dosage as high as 29.6 GBq (800 mCi) (9). However, the biggest disadvantage of a single high-dosage treatment is considerable myelotoxicity.
Although the efficacy and toxicity of single high-dosage treatment has been studied extensively, little has been published about repeated intermediate-dosage treatment, especially more than three treatments (11, 23). By administering repeated intermediate dosages of [131I]MIBG it is possible to keep toxicity low while creating a high cumulative tumor radiation dose. Hematological toxicity is increased by bone marrow involvement of tumor cells. This is not always appreciated pretreatment, because of the lack of sensitivity of diagnostic modalities for detection of small lesions or diffuse lesions in the bone marrow. Mirallie et al. (24) recently used three different diagnostic modalities (bone scintigraphy, MRI, and post-radioimmunotherapy-immunoscintigraphy) in a phase I/II study group, consisting of patients with medullary thyroid carcinoma, treated with radioimmunotherapy. They reported a much higher bone marrow involvement of medullary thyroid carcinoma than previously reported, explaining high toxicity in their treatment group, administering relatively small dosages of radioactivity. Bone MRI was recommended in the postsurgical workup of such patients to choose the best therapeutic intervention. Bone marrow involvement in malignant pheochromocytoma might also be much higher than reported, thus explaining high and predominant myelotoxicity administering high-dosage [131I]MIBG. Intermediate repeated dosages of [131I]MIBG are very effective for small and diffuse bone marrow metastases, keeping toxicity low. For bigger lesions, repeated dosages could result in a further decline in tumor size and function after each treatment, but one should always keep surgery in mind for tumor debulking of the biggest lesions. In the first case, repeated intermediate-dosage [131I]MIBG therapy is probably capable of attacking residual disease more efficiently as a result of surgical debulking of tumor load and providing a better response on residual smaller lesions. In addition to these advantages of repeated intermediate-dosage treatments, a possible disadvantage may be faster dedifferentiation of tumor lesions by radiation-induced mutations in the pheochromocytoma cells, which might impair their ability to take up and retain the radiopharmaceutical. Second, tumor cells might survive intermediate-dosage treatments, creating survival selection, further stimulating dedifferentiation of the tumor. In our cases, however, considerable uptake of the radiopharmaceutical was seen with a good response and a clear arrest of progression.
As an alternative to a single high dosage or intermediate repeated dosages, high repeated dosages might lead to an even better response, optimizing the peeling off effect, with maximum efficacy. Toxicity, however, would increase and stem cell harvest would probably be mandatory. Another approach could be the combination of [131I]MIBG treatment with chemotherapy. The chemosensitizing effect might lead to increased efficacy, but again toxicity poses a problem (6). For patients with malignant pheochromocytoma with a limited prognosis, quality of life is very important. A balance between optimal efficacy and toxicity must be found, keeping quality of life in mind but aiming for an increase in survival time. In this regard, repeated intermediate-dosage [131I]MIBG therapy appears to have a high efficacy with tolerable toxicity. In addition to a good response to repeated intermediate-dosage [131I]MIBG therapy, both cases also illustrate some interesting issues on the detection of residual disease.
In the first clinical case, the last posttherapy scintigraphy showed no further uptake of the radiopharmaceutical, with normalization of catecholamine levels. However, increasing levels of normetanephrine suggest residual disease. This may be caused by tumor catecholamine production that is already metabolized before actually leaving the tumor, thus creating increased metabolite levels without increased catecholamine levels. Eisenhofer et al. (25) postulated that the membrane-bound form of the enzyme catechol-o-methyltransferase is responsible for intratumor metabolism of catecholamines. It is abundant in the same tumor cells in which catecholamines are synthesized and stored, producing high intratumor and extratumor metanephrine levels. It is concluded that, because some tumors are quiescent or nonfunctional and do not readily or continually secrete catecholamines because of intratumor metabolism, measurements of free metanephrines (in plasma) provide a more reliable marker for the presence of a pheochromocytoma than do the parent amines (25). The normalization of posttherapy scintigraphy may be because the lesions have decreased in size and activity, or it may indeed be residual disease, with the possibility of dedifferentiation of the tumor lesions, losing the capability to store catecholamines. To rule out any residual disease activity, one could consider performing positron emission tomography using [18F]fluorodopamine or [18F]dihydroxyphenylalanine (26, 27). In our case, however, where dedifferentiation is suspected, [18F]fluoro-2-deoxy-D-glucose positron emission tomography or radiolabeled somatostatin may be required as the next step of the imaging algorithm (27, 28, 29). In the case of persistent or recurrent disease, detected by positive somatostatin receptor imaging, additional treatment with somatostatin analogs instead of MIBG might be considered.
In the second case, catecholamine metabolite levels had normalized and residual disease was never detected by CT or MRI, whereas[131I]MIBG scintigraphy showed multiple persistent lesions in the abdomen. This can be explained by the difficulty of localizing small pathological lesions in abdominal sites, where repeated operations took place (30, 31, 32). During the treatment period, posttherapy scintigraphy showed a gradual decline in size and activity of all abdominal lesions after each treatment (Fig. 6).
By the use of repeated intermediate-dosage treatment in our cases, a very high cumulative dosage was administered with negligible toxicity. Both patients responded very well on repeated intermediate-dosage [131I]MIBG therapy over a long treatment period. They have had a long symptom-free and overall survival and did not experience any significant toxicity. In these patients, repeated intermediate-dosage treatment seems favorable to single high-dosage treatment.
Conclusion
Malignant pheochromocytoma is a rare but potentially lethal disease. Surgery is the first choice of treatment for initial therapy and for curative reoperation or palliative debulking of tumor mass. In the two cases reported, repeated intermediate-dosage [131I]MIBG therapy as an additive treatment after surgery proves to be an efficient therapy, with minor toxicity. It provides longstanding palliation and possibly even prolonged survival. Because of the low prevalence of this disease, national or even international cooperation is needed to further investigate these important issues.
|
Footnotes |
|---|
Abbreviations: CT, Computed tomography; MIBG, metaiodobenzylguanidine; MRI, magnetic resonance imaging.
Received November 24, 2004.
Accepted July 18, 2005.
|
References |
|---|
|
TopAbstractIntroductionPatients and MethodsResultsDiscussionReferences |
|---|
This article has been cited by other articles:
 |
|
 |
|
  A. Chrisoulidou, G. Kaltsas, I. Ilias, and A. B Grossman The diagnosis and management of malignant phaeochromocytoma and paraganglioma Endocr. Relat. Cancer, September 1, 2007; 14(3): 569 - 585. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Scholz, G. Eisenhofer, K. Pacak, H. Dralle, and H. Lehnert Current Treatment of Malignant Pheochromocytoma J. Clin. Endocrinol. Metab., April 1, 2007; 92(4): 1217 - 1225. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W. B. de Groot, T. P. Links, J. T. M. Plukker, C. J. M. Lips, and R. M. W. Hofstra RET as a Diagnostic and Therapeutic Target in Sporadic and Hereditary Endocrine Tumors Endocr. Rev., August 1, 2006; 27(5): 535 - 560. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
