Abstract
Purpose
Head and neck paragangliomas (HNPGLs) are rare tumours arising from autonomic nervous system ganglia. Although surgery offers the best chance of complete cure, there is associated morbidity due to the crucial location of these tumours. Radiotherapy arrests tumour growth and provides symptomatic improvement, but has long-term consequences. These tumours express somatostatin receptors (SSTR) and hence peptide receptor radionuclide therapy (PRRT) is now a treatment option. We assessed the molecular, morphological and clinical responses of inoperable HNPGLs to PRRT.
Methods
Nine patients with inoperable HNPGL assessed between June 2006 and June 2014 were included. Four patients had a solitary lesion, four had multifocal involvement and one had distant metastases (bone and lungs). The patients were treated with PRRT using 90Y/177Lu-labelled peptides after positive confirmation of SSTR expression on 68Ga-DOTATOC PET/CT. All patients received two to four courses of PRRT. Subsequent serial imaging with 68Ga-DOTATOC PET/CT was carried out every 6 months to assess response to treatment. Clinical (symptomatic) response was also assessed.
Results
Based on molecular response (EORTC) criteria, four of the nine patients showed a partial molecular response to treatment seen as significant decreases in SUVmax, accompanied by a reduction in tumour size. Five patients showed stable disease on both molecular and morphological criteria. Six out of nine patients were symptomatic at presentation with manifestations of cranial nerve involvement, bone destruction at the primary site and metastatic bone pain. Molecular responses were correlated with symptomatic improvement in four out of these six patients; while two patients showed small reductions in tumour size and SUVmax. The three asymptomatic patients showed no new lesions or symptomatic worsening.
Conclusion
PRRT was effective in all patients, with no disease worsening seen, either in the form of neurological symptoms or distant spread. Though these are preliminary results, PRRT shows promise as a good treatment option for HNPGL, and hence study in a larger patient cohort is essential to establish its place in the management algorithm.
References
Lack EE, Cubilla AL, Woodruff JM. Paragangliomas of the head and neck region. A pathologic study of tumors from 71 patients. Hum Pathol. 1979;10:191–218.
Baysal BE. Hereditary paraganglioma targets diverse paraganglia. J Med Genet. 2002;39:617–22.
Young Jr WF. Paragangliomas: clinical overview. Ann N Y Acad Sci. 2006;1073:21–9.
Jackson CG, Harris PF, Glasscock 3rd ME, Fritsch M, Dimitrov E, Johnson GD, et al. Diagnosis and management of paragangliomas of the skull base. Am J Surg. 1990;159:389–93.
Lightowlers S, Benedict S, Jefferies SJ, Jena R, Harris F, Burton KE, et al. Excellent local control of paraganglioma in the head and neck with fractionated radiotherapy. Clin Oncol (R Coll Radiol). 2010;22:382–9.
Duet M, Guichard JP, Rizzo N, Boudiaf M, Herman P, Tran Ba Huy P. Are somatostatin analogs therapeutic alternatives in the management of head and neck paragangliomas? Laryngoscope. 2005;115:1381–4.
Joshua AM, Ezzat S, Asa SL, Evans A, Broom R, Freeman M, et al. Rationale and evidence for sunitinib in the treatment of malignant paraganglioma/pheochromocytoma. J Clin Endocrinol Metab. 2009;94:5–9.
Hörsch D, Ezziddin S, Haug A, Gratz KF, Dunkelmann S, Krause BJ, et al. Peptide receptor radionuclide therapy for neuroendocrine tumors in Germany: first results of a multi-institutional cancer registry. Recent Results Cancer Res. 2013;194:457–65.
Baum RP, Kulkarni HR, Carreras C. Peptides and receptors in image-guided therapy: theranostics for neuroendocrine neoplasms. Semin Nucl Med. 2012;42:190–207.
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.
Young H, Baum R, Cremerius U, Herholz K, Hoekstra O, Lammertsma AA, et al. Measurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations. European Organization for Research and Treatment of Cancer (EORTC) PET study group. Eur J Cancer. 1999;35:1773–82.
Kollert M, Minovi A, Mangold R, Hendus J, Draf W, Bockmühl U. Paraganglioma of the head and neck – tumor control, functional results and quality of life. Laryngorhinootologie. 2006;85:649–56.
Capatina C, Ntali G, Karavitaki N, Grossman AB. The management of head-and-neck paragangliomas. Endocr Relat Cancer. 2013;20:R291–305.
Sheehan JP, Tanaka S, Link MJ, Pollock BE, Kondziolka D, Mathieu D, et al. Gamma Knife surgery for the management of glomus tumors: a multicenter study. J Neurosurg. 2012;117:246–54.
Baum RP, Kulkarni HR. THERANOSTICS: from molecular imaging using Ga-68 labeled tracers and PET/CT to personalized radionuclide therapy – the Bad Berka experience. Theranostics. 2012;2:437–47.
van Essen M, Krenning EP, Kooij PP, Bakker WH, Feelders RA, de Herder WW, et al. Effects of therapy with [177Lu-DOTA0, Tyr3]octreotate in patients with paraganglioma, meningioma, small cell lung carcinoma, and melanoma. J Nucl Med. 2006;47:1599–606.
Zovato S, Kumanova A, Demattè S, Sansovini M, Bodei L, Di Sarra D, et al. Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE in individuals with neck or mediastinal paraganglioma (PGL). Horm Metab Res. 2012;44:411–4.
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Puranik, A.D., Kulkarni, H.R., Singh, A. et al. Peptide receptor radionuclide therapy with 90Y/177Lu-labelled peptides for inoperable head and neck paragangliomas (glomus tumours). Eur J Nucl Med Mol Imaging 42, 1223–1230 (2015). https://doi.org/10.1007/s00259-015-3029-2
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DOI: https://doi.org/10.1007/s00259-015-3029-2