Some Considerations in Treating Malignant Head and Neck Paragangliomas

To the Editor As academic physicians with an interest in pheochromocytoma/paraganglioma, we read with great interest the article by McCrary et al¹ characterizing malignant head and neck paragangliomas (HNPGLs). The authors used the paraganglioma cohort from an academic tertiary cancer center diagnosed between 1963 and 2018. They found that the prevalence of malignant HNPGLs was 6 of 70 (9%), with 5 of 6 patients carrying the succinate dehydrogenase subunit B (SDHB) mutation. They suggested that patients with paragangliomas should undergo genetic testing, and owing to the difficulty in diagnosing malignant HNPGL prior to surgery, selective neck dissection should be performed during an initial resection. The data presented here are informative, and we congratulate the authors on this effort, yet we have a few concerns.

Recently, the advent of precision medicine has resulted in the development of a theranostic pair that targets somatostatin receptors, overexpressed in paragangliomas, for both diagnosis and therapy. Use of ⁶⁸Ga-DOTA(0)-Tyr(3)-octreotate (⁶⁸Ga-DOTATATE, a somatostatin receptor analog) positron emission tomography-computed tomography (PET/CT) on 20 patients with HNPGLs (9 patients with an SDHB mutation and 16 patients with metastatic disease) had a perlesion detection rate of 38 of 38 (100%).² Further, ⁶⁸Ga-DOTATATE diagnosed metastatic disease in 16 of 16 (100%) patients and 30 of 30 (100%) distant metastatic sites including bones, liver, lungs, mediastinum, and abdomen.² Use of ⁶⁸Ga-DOTATATE PET/CT not only helps in diagnosis, but could also determine patients’ eligibility for peptide receptor radionuclide therapy (PRRT), where DOTATATE is labeled with therapeutic β emitters such as ¹⁷⁷Lu and ⁹⁰Y. In a prospective study, 9 patients with inoperable HNPGLs, including 1 patient with metastatic HNPGL, were treated with 2 to 4 cycles of ⁹⁰Y/¹⁷⁷Lu-DOTATATE, with all the patients demonstrating stable disease on RECIST 1.1.³ Symptomatic improvement was observed in all 6 patients who were symptomatic at presentation. Therefore, in the case of somatostatin receptor–avid malignant HNPGLs requiring systematic therapy, PRRT should be considered.

Optimal therapy for HNPGLs has generated considerable debate and has ranged from surgery to radiotherapy. However, surgery can present with complications ranging from bleeding, stroke, cranial nerve deficits, and even death.⁴ Further, not all lesions in patients with malignant HNPGLs, especially those with distant metastases, can be surgically resected. Similarly, radiotherapy cannot target all the lesions in malignant HNPGLs. The results of standard chemotherapy have been modest, and exposing these patients with slow-growing tumors to toxic chemotherapy seems unwarranted.⁴ Hence, in the setting of SDHB-related HNPGL, a patient should undergo ⁶⁸Ga-DOTATATE PET/CT for localization, and if found to be inoperable or metastatic, PRRT should always be considered.