Tumor and red bone marrow dosimetry

comparison of methods for prospective treatment planning in pretargeted radioimmunotherapy

Wietske Woliner-van der Weg, Rafke Schoffelen, Robert Hobbs, Martin Gotthardt, David M. Goldenberg, Robert M. Sharkey, Cornelis H. Slump, Winette T A van der Graaf, Wim J G Oyen, Otto C. Boerman, George Sgouros, Eric P. Visser

Research output: Contribution to journalArticle

Abstract

Background: Red bone marrow (RBM) toxicity is dose-limiting in (pretargeted) radioimmunotherapy (RIT). Previous blood-based and two-dimensional (2D) image-based methods have failed to show a clear dose-response relationship. We developed a three-dimensional (3D) image-based RBM dosimetry approach using the Monte Carlo-based 3D radiobiological dosimetry (3D-RD) software and determined its additional value for predicting RBM toxicity. Methods: RBM doses were calculated for 13 colorectal cancer patients after pretargeted RIT with the two-step administration of an anti-CEA × anti-HSG bispecific monoclonal antibody and a 177Lu-labeled di-HSG-peptide. 3D-RD RBM dosimetry was based on the lumbar vertebrae, delineated on single photon emission computed tomography (SPECT) scans acquired directly, 3, 24, and 72 h after 177Lu administration. RBM doses were correlated to hematologic effects, according to NCI-CTC v3 and compared with conventional 2D cranium-based and blood-based dosimetry results. Tumor doses were calculated with 3D-RD, which has not been possible with 2D dosimetry. Tumor-to-RBM dose ratios were calculated and compared for 177Lu-based pretargeted RIT and simulated pretargeted RIT with 90Y. Results: 3D-RD RBM doses of all seven patients who developed thrombocytopenia were higher (range 0.43 to 0.97 Gy) than that of the six patients without thrombocytopenia (range 0.12 to 0.39 Gy), except in one patient (0.47 Gy) without thrombocytopenia but with grade 2 leucopenia. Blood and 2D image-based RBM doses for patients with grade 1 to 2 thrombocytopenia were in the same range as in patients without thrombocytopenia (0.14 to 0.29 and 0.11 to 0.26 Gy, respectively). Blood-based RBM doses for two grade 3 to 4 patients were higher (0.66 and 0.51 Gy, respectively) than the others, and the cranium-based dose of only the grade 4 patient was higher (0.34 Gy). Tumor-to-RBM dose ratios would increase by 25% on average when treating with 90Y instead of 177Lu. Conclusions: 3D dosimetry identifies patients at risk of developing any grade of RBM toxicity more accurately than blood- or 2D image-based methods. It has the added value to enable calculation of tumor-to-RBM dose ratios.

Original languageEnglish (US)
Article number5
Pages (from-to)1-14
Number of pages14
JournalEJNMMI Physics
Volume2
Issue number1
DOIs
StatePublished - Dec 1 2015

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Radioimmunotherapy
bone marrow
Dosimetry
dosimeters
planning
Tumors
Bone
tumors
Bone Marrow
Planning
dosage
Neoplasms
blood
grade
Blood
Therapeutics
cranium
toxicity
Toxicity
Thrombocytopenia

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Biomedical Engineering
  • Instrumentation
  • Radiation

Cite this

Woliner-van der Weg, W., Schoffelen, R., Hobbs, R., Gotthardt, M., Goldenberg, D. M., Sharkey, R. M., ... Visser, E. P. (2015). Tumor and red bone marrow dosimetry: comparison of methods for prospective treatment planning in pretargeted radioimmunotherapy. EJNMMI Physics, 2(1), 1-14. [5]. https://doi.org/10.1186/s40658-014-0104-x

Tumor and red bone marrow dosimetry : comparison of methods for prospective treatment planning in pretargeted radioimmunotherapy. / Woliner-van der Weg, Wietske; Schoffelen, Rafke; Hobbs, Robert; Gotthardt, Martin; Goldenberg, David M.; Sharkey, Robert M.; Slump, Cornelis H.; van der Graaf, Winette T A; Oyen, Wim J G; Boerman, Otto C.; Sgouros, George; Visser, Eric P.

In: EJNMMI Physics, Vol. 2, No. 1, 5, 01.12.2015, p. 1-14.

Research output: Contribution to journalArticle

Woliner-van der Weg, W, Schoffelen, R, Hobbs, R, Gotthardt, M, Goldenberg, DM, Sharkey, RM, Slump, CH, van der Graaf, WTA, Oyen, WJG, Boerman, OC, Sgouros, G & Visser, EP 2015, 'Tumor and red bone marrow dosimetry: comparison of methods for prospective treatment planning in pretargeted radioimmunotherapy', EJNMMI Physics, vol. 2, no. 1, 5, pp. 1-14. https://doi.org/10.1186/s40658-014-0104-x
Woliner-van der Weg, Wietske ; Schoffelen, Rafke ; Hobbs, Robert ; Gotthardt, Martin ; Goldenberg, David M. ; Sharkey, Robert M. ; Slump, Cornelis H. ; van der Graaf, Winette T A ; Oyen, Wim J G ; Boerman, Otto C. ; Sgouros, George ; Visser, Eric P. / Tumor and red bone marrow dosimetry : comparison of methods for prospective treatment planning in pretargeted radioimmunotherapy. In: EJNMMI Physics. 2015 ; Vol. 2, No. 1. pp. 1-14.
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abstract = "Background: Red bone marrow (RBM) toxicity is dose-limiting in (pretargeted) radioimmunotherapy (RIT). Previous blood-based and two-dimensional (2D) image-based methods have failed to show a clear dose-response relationship. We developed a three-dimensional (3D) image-based RBM dosimetry approach using the Monte Carlo-based 3D radiobiological dosimetry (3D-RD) software and determined its additional value for predicting RBM toxicity. Methods: RBM doses were calculated for 13 colorectal cancer patients after pretargeted RIT with the two-step administration of an anti-CEA × anti-HSG bispecific monoclonal antibody and a 177Lu-labeled di-HSG-peptide. 3D-RD RBM dosimetry was based on the lumbar vertebrae, delineated on single photon emission computed tomography (SPECT) scans acquired directly, 3, 24, and 72 h after 177Lu administration. RBM doses were correlated to hematologic effects, according to NCI-CTC v3 and compared with conventional 2D cranium-based and blood-based dosimetry results. Tumor doses were calculated with 3D-RD, which has not been possible with 2D dosimetry. Tumor-to-RBM dose ratios were calculated and compared for 177Lu-based pretargeted RIT and simulated pretargeted RIT with 90Y. Results: 3D-RD RBM doses of all seven patients who developed thrombocytopenia were higher (range 0.43 to 0.97 Gy) than that of the six patients without thrombocytopenia (range 0.12 to 0.39 Gy), except in one patient (0.47 Gy) without thrombocytopenia but with grade 2 leucopenia. Blood and 2D image-based RBM doses for patients with grade 1 to 2 thrombocytopenia were in the same range as in patients without thrombocytopenia (0.14 to 0.29 and 0.11 to 0.26 Gy, respectively). Blood-based RBM doses for two grade 3 to 4 patients were higher (0.66 and 0.51 Gy, respectively) than the others, and the cranium-based dose of only the grade 4 patient was higher (0.34 Gy). Tumor-to-RBM dose ratios would increase by 25{\%} on average when treating with 90Y instead of 177Lu. Conclusions: 3D dosimetry identifies patients at risk of developing any grade of RBM toxicity more accurately than blood- or 2D image-based methods. It has the added value to enable calculation of tumor-to-RBM dose ratios.",
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T1 - Tumor and red bone marrow dosimetry

T2 - comparison of methods for prospective treatment planning in pretargeted radioimmunotherapy

AU - Woliner-van der Weg, Wietske

AU - Schoffelen, Rafke

AU - Hobbs, Robert

AU - Gotthardt, Martin

AU - Goldenberg, David M.

AU - Sharkey, Robert M.

AU - Slump, Cornelis H.

AU - van der Graaf, Winette T A

AU - Oyen, Wim J G

AU - Boerman, Otto C.

AU - Sgouros, George

AU - Visser, Eric P.

PY - 2015/12/1

Y1 - 2015/12/1

N2 - Background: Red bone marrow (RBM) toxicity is dose-limiting in (pretargeted) radioimmunotherapy (RIT). Previous blood-based and two-dimensional (2D) image-based methods have failed to show a clear dose-response relationship. We developed a three-dimensional (3D) image-based RBM dosimetry approach using the Monte Carlo-based 3D radiobiological dosimetry (3D-RD) software and determined its additional value for predicting RBM toxicity. Methods: RBM doses were calculated for 13 colorectal cancer patients after pretargeted RIT with the two-step administration of an anti-CEA × anti-HSG bispecific monoclonal antibody and a 177Lu-labeled di-HSG-peptide. 3D-RD RBM dosimetry was based on the lumbar vertebrae, delineated on single photon emission computed tomography (SPECT) scans acquired directly, 3, 24, and 72 h after 177Lu administration. RBM doses were correlated to hematologic effects, according to NCI-CTC v3 and compared with conventional 2D cranium-based and blood-based dosimetry results. Tumor doses were calculated with 3D-RD, which has not been possible with 2D dosimetry. Tumor-to-RBM dose ratios were calculated and compared for 177Lu-based pretargeted RIT and simulated pretargeted RIT with 90Y. Results: 3D-RD RBM doses of all seven patients who developed thrombocytopenia were higher (range 0.43 to 0.97 Gy) than that of the six patients without thrombocytopenia (range 0.12 to 0.39 Gy), except in one patient (0.47 Gy) without thrombocytopenia but with grade 2 leucopenia. Blood and 2D image-based RBM doses for patients with grade 1 to 2 thrombocytopenia were in the same range as in patients without thrombocytopenia (0.14 to 0.29 and 0.11 to 0.26 Gy, respectively). Blood-based RBM doses for two grade 3 to 4 patients were higher (0.66 and 0.51 Gy, respectively) than the others, and the cranium-based dose of only the grade 4 patient was higher (0.34 Gy). Tumor-to-RBM dose ratios would increase by 25% on average when treating with 90Y instead of 177Lu. Conclusions: 3D dosimetry identifies patients at risk of developing any grade of RBM toxicity more accurately than blood- or 2D image-based methods. It has the added value to enable calculation of tumor-to-RBM dose ratios.

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