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Open Access 01-12-2021 | Prostate Cancer | Original research

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

Authors: Thomas J. W. Klein Nulent, Robert J. J. van Es, Stefan M. Willems, Arthur. J. A. T. Braat, Lot A. Devriese, Remco de Bree, Bart de Keizer

Published in: EJNMMI Research | Issue 1/2021

Abstract

Background

Advanced 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.

Methods

This 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.

Results

Six 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.

Conclusions

Palliative 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.

Coca-Pelaz A, Rodrigo JP, Bradley PJ, Vander Poorten V, Triantafyllou A, Hunt JL, et al. Adenoid cystic carcinoma of the head and neck—an update. Oral Oncol. 2015;51:652–61. https://doi.org/10.1016/j.oraloncology.2015.04.005.CrossRefPubMed

Bjørndal K, Krogdahl A, Therkildsen MH, Overgaard J, Johansen J, Kristensen CA, et al. Salivary gland carcinoma in Denmark 1990–2005: a national study of incidence, site and histology. Results of the Danish Head and Neck Cancer Group (DAHANCA). Oral Oncol. 2011;47:677–82. https://doi.org/10.1016/j.oraloncology.2011.04.020.CrossRefPubMed

Jang S, Patel PN, Kimple RJ, McCulloch TM. Clinical outcomes and prognostic factors of adenoid cystic carcinoma of the head and neck. Anticancer Res. 2017;37:3045–52. https://doi.org/10.21873/anticanres.11659.CrossRefPubMedPubMedCentral

Spiro RH, Huvos AG, Strong EW. Adenoid cystic carcinoma of salivary origin. A clinicopathologic study of 242 cases. Am J Surg. 1974;128:512–20. https://doi.org/10.1016/0002-9610(74)90265-7.CrossRefPubMed

van Weert S, Reinhard R, Bloemena E, Buter J, Witte BI, Vergeer MR, et al. Differences in patterns of survival in metastatic adenoid cystic carcinoma of the head and neck. Head Neck. 2017;39:456–63. https://doi.org/10.1002/hed.24613.CrossRefPubMed

Ciccolallo L, Licitra L, Cantú G, Gatta G. Survival from salivary glands adenoid cystic carcinoma in European populations. Oral Oncol. 2009;45:669–74. https://doi.org/10.1016/j.oraloncology.2008.10.010.CrossRefPubMed

Laurie SA, Ho AL, Fury MG, Sherman E, Pfister DG. Systemic therapy in the management of metastatic or locally recurrent adenoid cystic carcinoma of the salivary glands: a systematic review. Lancet Oncol. 2011;12:815–24. https://doi.org/10.1016/S1470-2045(10)70245-X.CrossRefPubMed

Alfieri S, Granata R, Bergamini C, Resteghini C, Bossi P, Licitra LF, et al. Systemic therapy in metastatic salivary gland carcinomas: a pathology-driven paradigm? Oral Oncol. 2017;66:58–63. https://doi.org/10.1016/j.oraloncology.2016.12.016.CrossRefPubMed

Afshar-Oromieh A, Avtzi E, Giesel FL, Holland-Letz T, Linhart HG, Eder M, et al. The diagnostic value of PET/CT imaging with the 68Ga-labelled PSMA ligand HBED-CC in the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2015;42:197–209. https://doi.org/10.1007/s00259-014-2949-6.CrossRefPubMed

10.

Klein Nulent TJW, Valstar MH, de Keizer B, Willems SM, Smit LA, Al-Mamgani A, et al. Physiologic distribution of PSMA-ligand in salivary glands and seromucous glands of the head and neck on PET/CT. Oral Surg Oral Med Oral Pathol Oral Radiol. 2018;125:478–86. https://doi.org/10.1016/j.oooo.2018.01.011.CrossRefPubMed

11.

Backhaus P, Noto B, Avramovic N, Grubert LS, Huss S, Bögemann M, et al. Targeting PSMA by radioligands in non-prostate disease—current status and future perspectives. Eur J Nucl Med Mol Imaging. 2018;45:860–77. https://doi.org/10.1007/s00259-017-3922-y.CrossRefPubMed

12.

Klein Nulent TJW, van Es RJJ, Krijger GC, de Bree R, Willems SM, de Keizer B. Prostate-specific membrane antigen PET imaging and immunohistochemistry in adenoid cystic carcinoma-a preliminary analysis. Eur J Nucl Med Mol Imaging. 2017;44:1614–21. https://doi.org/10.1007/s00259-017-3737-x.CrossRefPubMedPubMedCentral

13.

Van Boxtel W, Lütje S, Van Engen-Van Grunsven ICH, Verhaegh GW, Schalken JA, Jonker MA, et al. 68Ga-PSMA-HBED-CC PET/CT imaging for adenoid cystic carcinoma and salivary duct carcinoma: a phase 2 imaging study. Theranostics. 2020;10:2273–83. https://doi.org/10.7150/thno.38501.CrossRefPubMedPubMedCentral

14.

Hofman MS, Violet J, Hicks RJ, Ferdinandus J, Ping Thang S, Akhurst T, et al. [177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. Lancet Oncol. 2018;19:825–33. https://doi.org/10.1016/S1470-2045(18)30198-0.CrossRefPubMed

15.

Sartor O, de Bono J, Chi K, Fizazi K, Herrmann K, Rahbar K, et al. Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med. 2021. https://doi.org/10.1056/NEJMOA2107322.CrossRefPubMed

16.

Boellaard R, Delgado-Bolton R, Oyen WJG, Giammarile F, Tatsch K, Eschner W, et al. FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0. Eur J Nucl Med Mol Imaging. 2015;42:328–54. https://doi.org/10.1007/s00259-014-2961-x.CrossRefPubMed

17.

Yadav MP, Ballal S, Sahoo RK, Dwivedi SN, Bal C. Radioligand therapy with 177Lu-PSMA for metastatic castration-resistant prostate cancer: A systematic review and meta-analysis. Am J Roentgenol. 2019;213:275–85. https://doi.org/10.2214/AJR.18.20845.CrossRef

18.

Fendler WP, Reinhardt S, Ilhan H, Delker A, Böning G, Gildehaus FJ, et al. Preliminary experience with dosimetry, response and patient reported outcome after 177Lu-PSMA-617 therapy for metastatic castration-resistant prostate cancer. Oncotarget. 2017;8:3581–90. https://doi.org/10.18632/oncotarget.12240.CrossRefPubMed

19.

Uijen MJM, Derks YHW, Merkx RIJ, Schilham MGM, Roosen J, Privé BM, et al. PSMA radioligand therapy for solid tumors other than prostate cancer: background, opportunities, challenges, and first clinical reports. Eur J Nucl Med Mol Imaging. 2021. https://doi.org/10.1007/s00259-021-05433-w.CrossRefPubMedPubMedCentral

20.

Kratochwil C, Bruchertseifer F, Rathke H, Bronzel M, Apostolidis C, Weichert W, et al. Targeted alpha therapy of mCRPC with (225)Actinium-PSMA-617: dosimetry estimate and empirical dose finding. J Nucl Med. 2017;58:1624–31. https://doi.org/10.2967/jnumed.117.191395.CrossRefPubMed

21.

Klein Nulent TJW, Valstar MH, Smit LA, Smeele LE, Zuithoff NPA, de Keizer B, et al. Prostate-specific membrane antigen (PSMA) expression in adenoid cystic carcinoma of the head and neck. BMC Cancer. 2020;20:519. https://doi.org/10.1186/s12885-020-06847-9.CrossRefPubMedPubMedCentral

22.

Has Simsek D, Kuyumcu S, Agaoglu FY, Unal SN. Radionuclide therapy with 177Lu-PSMA in a case of metastatic adenoid cystic carcinoma of the parotid. Clin Nucl Med. 2019;44:764–6. https://doi.org/10.1097/rlu.0000000000002645.CrossRefPubMed

23.

WHO Fact Sheet Palliative Care, World Health Organization 2020. https://www.who.int/news-room/fact-sheets/detail/palliative-care. Accessed 19 Mar 2021.

Title: First experiences with 177Lu-PSMA-617 therapy for recurrent or metastatic salivary gland cancer
Authors: Thomas J. W. Klein Nulent
Robert J. J. van Es
Stefan M. Willems
Arthur. J. A. T. Braat
Lot A. Devriese
Remco de Bree
Bart de Keizer
Publication date: 01-12-2021
Publisher: Springer Berlin Heidelberg
Keywords: Prostate Cancer
Salivary Gland Cancer
Prostate Cancer
Radiotherapy
Salivary Gland Cancer
Radionuclide Therapy
Fatigue
Published in: EJNMMI Research / Issue 1/2021
Electronic ISSN: 2191-219X
DOI: https://doi.org/10.1186/s13550-021-00866-8

At a glance: The STEP trials

Springer Medicine

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

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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