First experiences with 177Lu-PSMA-617 therapy for recurrent or metastatic salivary gland cancer

Stefan M Willems,Thomas J W Klein Nulent,Robert J J Van Es,Lot A Devriese,Bart De Keizer,Arthur J A T Braat,Remco De Bree

doi:10.1186/s13550-021-00866-8

Stefan M Willems, Thomas J W Klein Nulent + Show 5 more

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https://doi.org/10.1186/s13550-021-00866-8

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Abstract

BackgroundAdvanced salivary gland cancers become difficult to treat when they are technically irresectable and radiotherapy limits are exceeded. There is also an unmet need to improve palliative systemic therapy. Salivary glands depict the Prostate-Specific Membrane Antigen (PSMA) on 68Ga-PSMA-PET/CT, a transmembrane protein that is targeted for diagnosis and treatment of advanced prostate cancer. Some salivary gland carcinomas also express PSMA.MethodsThis study aimed to retrospectively evaluate the effectiveness of 177Lu-PSMA-617 therapy for recurrent or metastatic salivary gland cancers, as a last resort treatment. Patients with serious tumour-related discomfort for whom no regular option was available were selected and critically re-assessed by the tumour board. Radionuclide therapy eligibility was confirmed when tumour targeting was greater than liver SUVmax on 68Ga-PSMA-PET/CT. The protocol aimed at four cycles of 6.0–7.4 GBq 177Lu-PSMA-617 every 6–8 weeks. Clinical response was evaluated by questionnaires and radiological response by 68Ga-PSMA-PET/CT.ResultsSix patients were treated with 177Lu-PSMA: four adenoid cystic carcinomas, one adenocarcinoma NOS and one acinic cell carcinoma. In two patients, radiological response was observed, showing either stable disease or a partial response, and four patients reported immediate relief of tumour-related symptoms. Most reported side effects were grade 1–2 fatigue, nausea, bone pain and xerostomia. Four patients prematurely discontinued therapy: three due to disease progression and one due to demotivating (grade 1) side-effects.ConclusionsPalliative 177Lu-PSMA therapy for salivary gland cancer may lead to rapid relief of tumour-associated discomfort and may even induce disease stabilization. It is safe, relatively well tolerated and can be considered when regular treatment options fail.

Highlights

Salivary gland cancer is a rare malignant head and neck tumour
Six patients were treated with 177Lu-Prostate-Specific Membrane Antigen (PSMA) of which four were diagnosed with Adenoid cystic carcinoma (AdCC), one with salivary gland adenocarcinoma and one with acinic cell carcinoma
This study describes our first experiences with 177LuPSMA as palliative radionuclide treatment for recurrent and/or metastatic salivary gland malignancies of the head and neck

Summary

Introduction

Salivary gland cancer is a rare malignant head and neck tumour. They account for 3–10% of all head and neck malignancies and exhibit a diverse clinical and biological behaviour. Diseasespecific survival (DSS) is moderate with 5- and 10-year survival rates of 68–78% and 54–65%, respectively [5, 6]. The effectiveness of both systemic chemotherapy and targeted immunotherapy is limited for symptomatic recurrent or distant disease and might only be beneficial to a small group of patients [7, 8]. Research revealed tracer accumulation on 68Ga-PSMA-PET/CT in normal salivary and lacrimal glands, and in areas of adenomas and adenocarcinomas such as AdCC, and more recently in salivary duct carcinoma (SDC). Salivary glands depict the Prostate-Specific Membrane Antigen (PSMA) on 68Ga-PSMA-PET/CT, a transmembrane protein that is targeted for diagnosis and treatment of advanced prostate cancer.

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