British Journal of Radiology 74 (2001),266-269 © 2001 The British Institute of Radiology
Functional imaging as an aid to decision-making in metastatic paraganglioma
J B Bomanji, MBBS, MSc, PhD1,
S W Hyder, MB1,
M N Gaze, MD, FRCR2,
S Gacinovic, MD, MSc1,
D C Costa, MD, PhD, FRCR1,
C Coulter, FRCR2 and
P J Ell, FRCP, FRCR1
1 The Institute of Nuclear Medicine
2 Meyerstein Institute of Oncology, The Middlesex Hospital, Mortimer Street, London W1N 8AA, UK
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Abstract
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Malignant paraganglioma is a rare and slow growing tumour of neuroendocrine origin. At the time of diagnosis, the tumour is usually widespread, with limited therapeutic options. A variety of functional imaging studies are available for staging the disease, guiding therapy and monitoring treatment response. These include 123I-MIBG or 131I-MIBG, 111In-pentetreotide or 111In-lanreotide (somatostatin analogues), and 18F-FDG positron emission tomography. Various radionuclides, including 131I and 90Y, can be targeted to the tumour using MIBG or pentetreotide. Such targeted radionuclide therapy may provide valuable long-term palliation in such patients. We present two cases with metastatic paragangliomas who had widespread soft tissue and bone metastases. One patient was treatment naive and the second had received previous chemotherapy. The functional imaging work-up performed and the targeted radionuclide therapies considered in these patients are described. Both patients were treated with 131I-MIBG. Partial tumour response and complete symptomatic and hormonal response was achieved in one patient; in the second patient there was no change.
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Introduction
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Paragangliomas are rare tumours of neural crest origin. They are thought to arise from chemoreceptor cells, hence the alternative name of chemodectoma. They are also called glomus tumours. Primary sites include the medial aspect of the carotid bulb (carotid body tumour), the vagus nerve ganglion (glomus vagale), the middle ear (glomus tympanicum) and the jugular bulb (glomus jugulare). About 50% of tumours are malignant and develop metastases, usually to lungs, liver, lymph nodes, bone and spleen [1]. Some malignant paragangliomas secrete catecholamines and serotonin. In most cases the disease is sporadic, but a familial form is rarely seen.
Metaiodobenzylguanidine (MIBG) is structurally similar to noradrenaline and is taken into chromaffin cells by an active transport mechanism and concentrated in storage granules. More than 90% of paragangliomas concentrate MIBG, a property that allows these tumours to be imaged with 123I-MIBG [2] and subsequently treated with 131I-MIBG [3–6]. Another feature of these tumours is that they express somatostatin receptors, enabling imaging with radiolabelled somatostatin analogues such as 111In-pentetreotide [7] and subsequent treatment with 90Y-somatostatin analogues (90Y-DOTATOC) [8].
Because of the rarity of malignant paraganglioma, there are only limited data about targeted radionuclide therapy and there is very little guidance about appropriate investigations to guide treatment and to assess response.
Functional imaging was used in the initial assessment and follow-up of two patients with metastatic paragangliomas.
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Case 1
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A 46-year-old man presented in December 1997 with proptosis of the right eye and diplopia. He also gave a history of pain in the left hip for several months. CT showed a lytic lesion in the right lateral orbital wall, with a soft tissue mass extending into the back of the right orbit intracranially and indenting the anterior right temporal lobe (Figure 1
). A metastasis in the left iliac crest and an abdominal mass were also detected on CT. He received urgent palliative radiotherapy to the right eye prior to full investigation. His blood chemistry was unremarkable. Biopsy of the left iliac crest lesion showed a metastatic paraganglioma. The urinary noradrenaline level was 1791 nmol 24 h-1 (normal range 120–590 nmol 24 h-1). A diagnostic 123I-MIBG scan to map the full extent of disease and to assess the possibility of 131I-MIBG therapy showed intense uptake in the right orbital region and the left iliac bone. The scan also showed wide-spread disease involving the skull vault, spine, pelvis and chest region (Figure 2A). Owing to marked avidity for 123I-MIBG, the patient was considered for 131I-MIBG therapy. The initial plan was to give a total of 33.3 GBq (900 mCi) of 131I-MIBG in three cycles at approximately 10 week intervals, assuming there was no significant myelosuppression.
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Figure 1. Case 1. CT showing a destructive soft tissue mass in the back and lateral aspect of the right orbit, displacing the lateral rectus muscle and right globe.
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Figure 2. (A) 123I-MIBG whole body image 24 h post injection, showing multiple foci of increased tracer uptake in the skull vault, spine, ribs and pelvis. (B) 131I-MIBG whole body image 7 days post therapy (12.1 GBq) shows a pattern similar to (A). (C) After approximately 36.8 GBq (993 mCi) of 131I-MIBG therapy given in three cycles, a follow-up 123I-MIBG scan shows minimal residual disease. (D) A second follow-up diagnostic 123I-MIBG scan shows progression of disease. MIBG-avid lesions are noted in the spine, ribs and soft tissues along the paraaortic region.
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The first therapy dose of 131I-MIBG was given in March 1998 (Figure 2B
). The thyroid gland was blocked with oral potassium iodide 60 mg given twice daily, which was started 2 days prior to treatment and continued for 17 days after the infusion. 12.1 GBq (327 mCi) of 131I-MIBG was infused intravenously over 30 min. A complete blood count was done weekly to monitor any myelosuppression. No immediate adverse effect was observed, apart from nausea 8 h post infusion. Mild thrombocytopaenia was noted by the third week, but this recovered within 1 week. The patient reported marked improvement in leg pain 2 months after treatment. A second dose of 12.2 GBq (329 mCi) of 131I-MIBG was given in May 1998. The third dose of 12.5 GBq (337 mCi) was given in September 1998. The patient tolerated these doses well and only after the third dose did he develop a significant haematological nadir. His haemoglobin (7.6 g dl-1) and platelets count (22x109 l-1) dropped and three units of blood were transfused. He made an uneventful recovery and remained well and asymptomatic without further treatment. His 123I-MIBG scan in February 1999 showed partial remission of disease (Figure 2C). He remained asymptomatic and returned to work. His most recent scan in November 1999 showed progression of disease (Figure 2D). A 99Tcm-methylene diphosphonate (MDP) bone scan showed uptake in only the iliac crest (Figure 3A) and an 111In-pentetreotide study was negative (Figure 3B). 18F-fluorodeoxyglucose (FDG) positron emission tomography showed glucose-avid metastases with a similar distribution to the 123I-MIBG scan (Figures 3C,D). The disease continued its progress and the patient died in October 2000.
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Figure 3. Case 1. (A) 99Tcm-MDP bone scan (posterior whole body image) shows some distortion of the left iliac crest outline. (B) 111In-pentetreotide whole body scan 24 h post injection shows no abnormality (C,D) 18F-FDG positron emission tomography (coronal sections) show multiple glucose-avid lesions predominantly in the paraaortic region extending above and below the diaphragm. There is minimal involvement of the spine compared with the 123I-MIBG scan (Figure 2D).
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Case 2
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A 28-year-old male presented in 1993 with a carotid body tumour and pulmonary metastases. A diagnosis of metastatic paraganglioma was made. The carotid body mass was surgically resected and he received chemotherapy in 1995, with no response. In March 1999 he re-presented with weight loss, haemoptysis and excessive sweating. CT showed progression of the lung metastases. An 123I-MIBG scan in April 1999 showed mild tracer uptake in the hilar region, thoracic and lumber spine, and left sacroiliac region (Figure 4A), and a lesion in the left orbital area. 111In-pentetreotide scan showed poor uptake in the lung metastases, normal but pronounced uptake in the kidneys and faint marrow activity. The orbital lesion was not visualized (Figure 4B). A similar pattern was observed with 111In-lanreotide.
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Figure 4. Case 2. (A) 123I-MIBG posterior whole body view 24 h post injection showing abnormal focal but faint uptake in the lung fields, spine and right sacroiliac region. (B) 111In-pentetreotide posterior whole body scan 24 h post injection shows minimal asymmetry in the left sacroiliac joint. (C) 99Tcm-MDP bone scan (posterior whole body view) shows multiple focal areas of increased tracer uptake in the spine, right scapula, some ribs and sacroiliac joints. (D,E) 18F-FDG positron emission tomography (coronal sections) shows multiple glucose-avid lesions predominantly involving lung soft tissues and the spine.
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A 99Tcm-MDP bone scan showed the characteristic appearance of multiple and widespread bony metastasis involving the skull and spine, the right coracoid process, several ribs and both iliac bones (Figure 4C). 18F-FDG position emission tomography delineated multiple foci of increased uptake in the hilar lymph nodes, both lung fields and virtually the whole spine (Figures 4D,E).
In spite of the poor 123I-MIBG uptake observed on the diagnostic scan, it was decided to give a single therapy dose of 131I-MIBG. This judgement was based on past experience when we have occasionally observed relatively higher uptake and longer duration of activity in metastatic sites. In this case, post-therapy scans on Days 2 and 7 showed a similar distribution pattern to the diagnostic study, but the biological half-life of the therapeutic dose was less than the time expected from the diagnostic test. No further active anticancer treatment was given. The patient died in September 2000.
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Discussion
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These two cases show the nature of the disease in its treated and naive form. Radiolabelled MIBG has a sensitivity of over 90% for detecting metastatic paragangliomas. Uptake by the metastases is high and this provides an ideal opportunity to carry out targeted radionuclide therapy with 131I-MIBG. In Case 1 there was no prior systemic treatment and the tumour showed marked avidity for 131I-MIBG. The proptosis was treated successfully by a combination of external beam radiotherapy and targeted radionuclide therapy. While only a partial response was achieved in terms of tumour mass, a complete hormonal response was obtained. The patient was able to continue his employment and enjoy a normal quality of life until December 1999.
It was not surprising that we were unable to eradicate MIBG-avid disease completely. Our past experience, and that of other groups [3–6], indicates that approximately 73% of patients show at least partial tumour response, hormonal response or symptomatic improvement. Complete remission is rare. Tumour shrinkage is achieved in metastatic disease, and small lesions tend to resolve while larger ones usually persist. Our reluctance to pursue tumour eradication further should be viewed against a background of having already given 36.7 GBq (993 mCi) of 131I-MIBG over a period of 6 months, by which time myelosuppression developed. Other therapeutic options include surgical debulking and chemotherapy. In this case surgery was not a viable option and we opted for a "wait and see" approach. This may permit marrow recovery and allow the possibility of further treatment with 131I-MIBG if the patient relapses and becomes symptomatic or a hormone secretor. Chemotherapy could also be considered if escape from 131I-MIBG therapy occurs [9].
The extent of radiopharmaceutical avidity by relapsed disease is poorly understood and the progress of disease may be variable. Our second patient was a case in point. His presentation 4 years after initial chemotherapy suggests that the progress of disease was slow. However, the spread was extensive at presentation. Most of the radionuclide diagnostic tests were initiated in this patient with a view to palliative radionuclide therapy. It was clear that his treated disease showed poor avidity for 123I-MIBG and 131I-MIBG. Furthermore, there was no uptake of 111In-pentetreotide and 111In-lanreotide, excluding the possibility of treatment with 90Y-pentetreotide/lanreotide. No histological evidence of somatostatin receptors was sought to explain this lack of uptake. It can only be speculated that tumour dedifferentiation may have led to these findings. Painful bone metastases may be treated with rhenium-186-HEDP. However, this treatment was not carried out as pain was not the major complaint and the risk of serious myelosuppression would have been high. In addition, the extensive soft tissue metastases would have escaped treatment. Despite these findings, we decided to give a trial of 131I-MIBG therapy in the hope that some palliation may be achieved in spite of weak uptake of MIBG. Unfortunately, this was not the case and the patient died in September 2000.
It is concluded that, in view of the aggressive nature of the disease and the poor response to other treatments, 131I-MIBG may be a useful therapeutic modality for patients with metastatic paraganglioma.
Received for publication September 18, 2000.
Accepted for publication October 16, 2000.
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References
|
|---|
-
Razakaboay M, Maillefect JF, Wendling D, Juvin R, Toussirot E, Tavernier C, et al. Bone metastases from a paraganglioma. A review of five cases. Rev Rhum Engl Ed 1999;66:86–91.[Medline]
-
Sission JC, Frager MS, Valek TW, Gross MD, Swanson DP, Wieland DM, et al. Scintigraphic localization of pheochromocytoma. N Engl J Med 1981;305:12–7.[Abstract]
-
Loh KC, Fitzgerald PA, Matthay KK, Yeo PP, Price DC, et al. The treatment of malignant pheochromocytoma with iodine-131 metaiodobenzylguanidine (131I-MIBG): a comprehensive review of 116 reported patients. J Endocrinol Invest 1997;20:648–58.[Medline]
-
Shapiro B, Sisson JC, Wieland DM, Mangner TJ, Zempel SM, Mudgett E, et al. Radiopharmaceutical therapy of malignant pheochromocytoma with [131-I] metaiodobenzylguanidine: results from ten years of experience. J Nucl Biol Med 1991;35:269–76.
-
Troncone L, Rufini V, Daidone MS, DeSantis M, Luizi S. [131-I] metaiodobenzylguanidine treatment of malignant pheochromocytoma: experience of Rome group. J Nucl Biol Med 1991;35:295–9.
-
Bomanji J, Britton KE, Ur E, Hawkins L, Grossman A, Besser GM. Treatment of malignant pheochromocytoma, paraganglioma and carcinoid tumours with 131I-metaiodobenzylguanidine. Nucl Med Commun 1993;14:856–61.[Medline]
-
Krenning EP, Kwekkeboom DJ, Bakker WH, Breeman WAP, Kooij PPM, Oei HY, et al. Somatostatin receptor scintigraphy with [111In-DTPA-D-Phel]- and [123I-Tyr3]-octreotide: the Rotterdam experience with more than 1000 patients. Eur J Nucl Med 1993;20:716–31.[Medline]
-
Otte A, Herrmann R, Heppeler A, Behe M, Jermann E, Powell P, et al. Yttrium-90 DOTATOC: first clinical results. Eur J Nucl Med 1999;26:1439–47.[Medline]
-
Kimura S, Iwai M, Fukuda T, Akamatsu T, Ochi F, Masugi J, et al. Combination chemotherapy for malignant paraganglioma. Intern Med 1997;36:35–9.[Medline]
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Abstract
Introduction
