Assessing the Clinical Impact of Lutetium-177 DOTATATE Peptide Receptor Radionuclide Therapy (PRRT) on Metastatic Neuroendocrine Tumors: A Multicenter Real-World Data from Türkiye

Caglar Unal¹, Nalan Alan Selcuk², Fatih Selcuk Biricik³, Ozkan Alan³, Cetin Ordu⁴, Oguzhan Selvi⁵, Abdullah Sakin⁵, Nadiye Sever⁶, Zeynep Alaca Topcu⁷, Arif Akyildiz⁸, Eyup Coban⁹, Turkan Evrensel⁹, Erkan Ozcan¹⁰, Bengu Dursun¹¹, Kadriye Bir Yucel¹², Haci Arak¹³, Sercan On¹⁴, Halil Goksel Guzel¹⁵, Derya Kivrak Salim¹⁵, Ziya Kalkan¹⁶, Zeynep Oruc¹⁶, Tomris Duymaz¹⁷, Mustafa Seyyar¹⁸, Gozde Agdas¹⁹, Melike Ozcelik²⁰, Nail Paksoy²¹, Bulent Cetin²², Kanay Yararbas²³, Sezer Saglam⁴

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¹ Division of Medical Oncology, Department of Internal Medicine, Kartal Dr. Lütfi Kırdar City Hospital, İstanbul, Türkiye

² Department of Nuclear Medicine, Faculty of Medicine, Yeditepe University, İstanbul, Türkiye

³ Division of Medical Oncology, Department of Internal Medicine, Koc University Hospital, İstanbul, Türkiye

⁴ Division of Medical Oncology, Department of Internal Medicine, Demiroglu Bilim University, İstanbul, Türkiye

⁵ Division of Medical Oncology, Department of Internal Medicine, Okmeydanı Research and Training Hospital, İstanbul, Türkiye

⁶ Division of Medical Oncology, Department of Internal Medicine, Marmara University Hospital, İstanbul, Türkiye

⁷ Division of Medical Oncology, Department of Internal Medicine, Göztepe Medeniyet University, İstanbul, Türkiye

⁸ Division of Medical Oncology, Department of Internal Medicine, Hacettepe University Institute of Oncology, Ankara, Türkiye

⁹ Division of Medical Oncology, Department of Internal Medicine, Uludağ Medicine Faculty Hospital, Bursa, Türkiye

¹⁰ Division of Medical Oncology, Department of Internal Medicine, Trakya University Medicine Faculy Hospital, Edirne, Türkiye

¹¹ Division of Medical Oncology, Department of Internal Medicine, Ankara University Hospital, Ankara, Türkiye

¹² Division of Medical Oncology, Department of Internal Medicine, Gazi University Medicine Faculty Hospital, Ankara, Türkiye

¹³ Division of Medical Oncology, Department of Internal Medicine, Gaziantep University Medicine Faculty Hospital, Gaziantep, Türkiye

¹⁴ Division of Medical Oncology, Department of Internal Medicine, Ege University Medicine Faculty Hospital, İzmir, Türkiye

¹⁵ Division of Medical Oncology, Department of Internal Medicine, Antalya Research and Training Hospital, Antalya, Türkiye

¹⁶ Division of Medical Oncology, Department of Internal Medicine, Dicle University Hospital, Diyarbakır, Türkiye

¹⁷ Department of Physiotherapy and Rehabilitation, Faculty of Health Sciences, Istanbul Bilgi University, Istanbul, Türkiye

¹⁸ Division of Medical Oncology, Department of Internal Medicine, Kocaeli University Hospital, Kocaeli, Türkiye

¹⁹ Division of Medical Oncology, Department of Internal Medicine, Osmangazi University Hospital, Eskişehir, Türkiye

²⁰ Division of Medical Oncology, Department of Internal Medicine, Ümraniye Research and Training Hospital, İstanbul, Türkiye

²¹ Division of Medical Oncology, Department of Internal Medicine, Tekirdağ City Hospital, Tekirdağ, Türkiye

²² Division of Medical Oncology, Department of Internal Medicine, Ondokuz Mayıs University Medicine Faculty Hospital, Samsun, Türkiye

²³ Department of Medical Genetics, Demiroglu Bilim University, İstanbul, Türkiye

EJMO 2023, 7(3), 232–242; https://doi.org/10.14744/ejmo.2023.48337

Submitted: 10 August 2023 | Revised: 15 September 2023 | Accepted: 17 September 2023 | Published: 6 October 2023

© 2023 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )

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Abstract

Objectives: This study aimed to evaluate the clinical outcomes, including progression-free survival (PFS), overall survival (OS), Objective Response Rate (ORR), and Disease Control Rate (DCR), in patients received Lutetium-177 (Lu-177) DOTATATE Peptide Receptor Radionuclide Therapy (PRRT) for metastatic neuroendocrine tumors. This study further stratified outcomes based on tumor grade, Ki-67 status, primary tumor localization, number of treatment cycles, and associated adverse effects.

Methods: We conducted a multicenter retrospective study analyzing the data of 73 patients with metastatic NETs across 17 different hospitals in various regions of Türkiye. A total of 73 metastatic NET patients underwent Lu-177 DOTATATE PRRT between December 2013 and March 2023.

Results: Over a median follow-up of 52.7 months, patients showed a median PFS of 13.7 months and OS of 51.2 months. The ORR was 29.6%, and the DCR was 66.2%. Grade 1 and 2 tumor patients had superior outcomes (PFS: 16.9 months, OS: 55.5 months) compared to grade 3 tumor patients (PFS: 8.5 months, OS: 29.5 months). Based on their Ki-67 status, those ≤ 20% had prolonged PFS (16.9 months) and OS (55.5 months) than those between 21 and 55% (PFS: 5.9 months, OS: 41.3 months). Regarding primary tumor localization, the PFS values were 13.1, 15.3, 13.7, and 8.6 months for pancreatic, GIS, lung, and unknown origin tumors, respectively. The OS across tumor types fluctuated between 41.1 and 54.1 months. Patients who received more than four cycles demonstrated significantly improved median PFS (22.4 months) and OS (90.3 months) compared to those who received ≤ 4 cycles (median PFS: 9.3 months; median OS: 41.8 months). Grade 3-4 adverse effects were observed in 21.9% of patients.

Conclusion: Our findings affirm that PRRT is a potent and well-tolerated treatment for metastatic NETs. Notably, patients who received more than 4 cycles of PRRT experienced a markedly improved median PFS and OS compared to their counterparts who received ≤4 cycles.

Keywords

Lutetium-177

neuroendocrine tumors

neuroendocrine neoplasm

peptide receptor radionuclide therapy

PRRT

radiolabeled somatostatin analogues

Conflict of interest

None declared.

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