Personalized dosimetry as a key for optimizing radioligand therapy (RLT) with 177Lu- or 177Lu/90Y-DOTA-TATE in patients with well-differentiated neuroendocrine tumors - an update on the initial results of the DUONEN multicenter study

Marta Opalinska; Grzegorz Kamiński; Marek Dedecjus; Aldona Kowalska; Maciej Kolodziej; Marek Saracyn; Piotr Garnuszek; Wioletta Lenda-Tracz; Danuta Gąsior-Perczak; Anna Borkowska; Joanna Januszkiewicz-Caulier; Joanna Długosińksa; Staszczak Anna Sowa; Anna Budzyńska; Agata Kubik; Krzysztof Kacperski; Wioletta Chalewska; Paulina Cegła; Alicja Hubalewska-Dydejczyk; Renata Mikolajczak

doi:10.1530/endoabs.99.EP601

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Endocrine Abstracts (2024) 99 EP601 | DOI: 10.1530/endoabs.99.EP601

ECE2024 Eposter Presentations Pituitary and Neuroendocrinology (214 abstracts)

Personalized dosimetry as a key for optimizing radioligand therapy (RLT) with 177Lu- or 177Lu/90Y-DOTA-TATE in patients with well-differentiated neuroendocrine tumors – an update on the initial results of the DUONEN multicenter study

Marta Opalinska ¹ , Grzegorz Kamiński ² , Marek Dedecjus ³ , Aldona Kowalska ⁴ , Maciej Kolodziej ² , Marek Saracyn ² , Piotr Garnuszek ⁵ , Wioletta Lenda-Tracz ⁶ , Danuta Gąsior-Perczak ⁴ , Anna Borkowska ⁶ , Joanna Januszkiewicz-Caulier ³ , Joanna Długosińksa ³ , Anna Sowa Staszczak ¹ , Anna Budzyńska ⁷ , Agata Kubik ⁷ , Krzysztof Kacperski ⁷ , Wioletta Chalewska ³ , Paulina Cegła ³ , Alicja Hubalewska-Dydejczyk ¹ & Renata Mikolajczak ⁵

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Author affiliations

¹Jagiellonian University Medical College, Chair and Department of Endocrinology, Krakow;²Military Institute of Medicine - National Research Institute, Department of Endocrinology and Isotope Therapy, Warsaw;³National Institute of Oncology, National Institute of Oncology, Warsaw;⁴Jan Kochanowski University in Kielce, Collegium Medicum, Kielce, Poland;⁵National Centre for Nuclear Research, Radioisotope Center Polatom, Otwock-Swierk;⁶Jagiellonian University Medical College, Faculty of Health Sciences, Kraków, Poland;⁷Military Institute of Medicine - National Research Institute, Department of Nuclear Medicine, Warsaw

Aim/Introduction: Peptide Receptor Radionuclide Therapy (PRRT) is an effective treatment for disseminated neuroendocrine tumors (NETs) expressing somatostatin receptors. Despite many published studies, the consensus on the optimal PRRT treatment algorithm has not been reached yet. The main objective of the DUONEN multicenter, randomized, phase III study (EUDRACT No: 2020-006068-99) is the development of a dosimetry-based personalized PRRT algorithm. The second goal includes the assessment of the efficacy of dosimetry-based personalized therapy with mixed [¹⁷⁷Lu]Lu- and [⁹⁰Y]Y-DOTA-TATE in comparison to [¹⁷⁷Lu]Lu-DOTA-TATE in standard radioactivity doses (7400 MBq). The personalized dosimetry is designed to deliver maximal radiation dose to the tumor tissue while maintaining the safety of critical organs.

Materials and Methods: Adult patients with advanced, unresectable well-differentiated (G1 and G2) NETs, progressing on long-acting somatostatin analogues are randomized into four arms: A - treated with [¹⁷⁷Lu]Lu -DOTA-TATE with constant radioactivity of 7400MBq per cycle B - treated with mixed [¹⁷⁷Lu]Lu-DOTA-TATE and [⁹⁰Y]Y-DOTA-TATE, initially at a ratio of 3700:1850MBq/MBq. The [¹⁷⁷Lu]Lu-DOTATATE radioactivity remains constant in all cycles, and the [⁹⁰Y]Y-DOTA-TATE radioactivity is adjusted in the next cycles, based on bone marrow and kidney dosimetry to the highest radiation dose in the tumor tissue C - analogous to arm B, except that here the radioactivity of [⁹⁰Y]Y-DOTA-TATE remains constant and the radioactivity of [¹⁷⁷Lu]Lu-DOTA-TATE is adjusted depending on the dosimetry results D – first dose analogous to arm A and individualized in the next cycles based on dosimetry results. The treatment efficacy is evaluated on morphological imaging (CT or MR) according to RECIST 1.1 criteria. The safety of PRRT is assessed by the kidney and bone marrow biochemical function.

Results: 35 patients have been enrolled to the study (arm A-9, arm B-9, arm C-9, arm D-8). Six patients discontinued therapy due to disease progression or its side effects. By now 94 cycles of PRRT were administered, including 57 fixed doses (first doses or arm A). Out of the 37 doses adjusted based on personalized dosimetry, the radioactivity dose was increased in 16 and decreased in 21. The first eight patients were evaluated post-PRRT according to RECIST 1.1 criteria achieving stable disease in 3 cases, and partial and complete response in 4 and 1 case, respectively.

Conclusions: Personalized renal and bone marrow dosimetry affects individual PRRT doses in each subsequent treatment cycle. Acknowledgments: The study is funded by the Medical Research Agency (Project number 2019/ABM/01/00077-00).