Table 1 Summary of prospective clinical trials of personalised RPT studies
From: Use of imaging-based dosimetry for personalising radiopharmaceutical therapy of cancer
Reference | Radiopharmaceutical Therapy | Population | Prescription | Dosimetry | Efficacy* | Toxicity (Grade 3–4 and Serious) |
|---|---|---|---|---|---|---|
Garin et al. [4] Multicentre, France | 90Y glass microspheres radioembolisation | 60 patients with hepatocellular carcinoma, randomised | Personalised arm: 205–250 Gy to the tumour ≤ 120 Gy to the normal liver Standard arm: 120 Gy to the perfused liver Single administration Personalised activity based on pre-treatment dosimetry | Pre-treatment 99mTc-macro-aggregated albumin Planar for lung shunt SPECT/CT for tumour and liver dosimetry | ORR: 71% vs. 36% (p = 0.0074; primary endpoint) PFS: 6.0 vs. 3.4 mo. (p = 0.26). OS: 26.6 vs. 10.7 mo. (p = 0.0096) | Grade ≥ 3: 60% vs. 76% Serious adverse events: 20% vs. 33% |
Fisher et al. [5] Multicentre, United States | 131I-tositumomab radioimmunotherapy | 250 patients with refractory/relapsed non-Hodgkin lymphoma | 0.75 Gy to the whole-body or 0.65 Gy if platelet counts 100-150 × 10− 3/mm3 Single administration Personalised activity based on pre-treatment dosimetry | Pre-treatment with 131I-tositumomab 3-timepoint WB planar Whole-body segmentation | ORR: 56% CR: 30% PFS: 6.4 mo. | From Horning et al. [6]: Hematologic: 50% Thrombopenia: 25% Neutropenia: 43% Anaemia: 10% Non-hematologic: 16% From Bennett et al. [7]: MDS/AML: 2.3% |
Kaminski et al. [8] Ann Harbor, MI, United States | 131I-tositumomab radioimmunotherapy | 76 treatment-naïve patients with stage III/IV follicular lymphoma | 0.75 Gy to the whole-body Single administration Personalised activity based on pre-treatment dosimetry | Pre-treatment with 131I-tositumomab 3-timepoint WB planar Whole-body segmentation | ORR: 95% CR: 75% PFS: 6.1 yr. | Thrombopenia: 17% Neutropenia: 34% Anaemia: 0% Non-hematologic: 21% MDS/AML: 0% |
Wahl et al. [9] Baltimore, MD, and Madison, WI, United States | 90Y-ibritumomab myeloablative radioimmunotherapy | 18 patients with refractory/relapsed non-Hodgkin lymphoma | Dose escalation to the liver, from 18 to 30.5 Gy Single administration Personalised activity based on pre-treatment dosimetry | Pre-treatment with 111In-ibritumomab Hybrid 5-timepoint WB planar and single SPECT/CT Whole liver segmentation | ORR: 89% CR: 72% PFS: > 13 mo. | Myeloablation expected Febrile neutropenia: 22% Hepatic: 0% MDS: 6% |
Cameron et al. [10] Fremantle, Australia | 153Sm-EDTMP RPT | 10 patients with painful bone metastases | 2 Gy to the bone marrow Single administration Personalised activity based on pre-treatment dosimetry | Pre-treatment with 153Sm-EDTMP 2-timepoint WB planar | Pain relief rate (primary): 80% | No grade 3–4 toxicity |
Pryma et al. [11] Multicentre, United States | 131I-MIBG RPT | 68 patients with pheochromocytoma or paraganglioma | Fixed activity of 37 GBq (296 MBq/kg if < 62.5 kg) divided in 2 cycles, personalised (reduced) not to exceed: 12 Gy to bone marrow 16.5 Gy to lungs 18 Gy to kidneys 31 Gy to liver 40 Gy to small intestine | Pre-treatment with 131I-MIBG 3-timepoint WB planar Whole organ segmentation | Anti-hypertensive drugs reduction rate (primary): 25% DCR: 92% ORR: 23% OS: 37 mo. | Hematologic: 72% Thrombopenia: 41% Leucopoenia 41% Neutropenia: 38% Anaemia: 21% MDS/AML/ALL: 7% |
Garske-Román et al. [12] Uppsala, Sweden | 177Lu-DOTATATE PRRT | 200 patients with mixed neuroendocrine tumours | 23 Gy to the kidney Variable number of cycles 7.4 GBq/cycle | Post-treatment 3-timepoint SPECT/CT 4-cc VOI renal sampling | DCR: 97% ORR: 24% PFS: 27 mo. OS: 43 mo. | Hematologic: 15% AML/ALL: 2% Nephrotoxicity: 0.5% |
Sundlöv et al. [13] Lund and Guthenberg, Sweden | 177Lu-DOTATATE PRRT | 96 patients with mixed neuroendocrine tumours | 27 Gy renal BED (up to 40 Gy BED in a subset of patients) Variable number of cycles 7.4 GBq/cycle | Post-treatment Hybrid 5-timepoint planar and one-timepoint SPECT/CT Whole-kidney segmentation | DCR: 82% ORR: 16% PFS: 29 mo. OS: 47 mo. | Thrombopenia: 9% Leucopoenia: 4% Neutropenia: 6% Anaemia: 1% Nephrotoxicity: 0% |
Del Prete et al. [14] Quebec City, Canada | 177Lu-DOTATATE PRRT | 54 patients with mixed neuroendocrine tumours | 23 Gy to the kidney Four cycles Personalised activity at all cycles based on BSA and eGFR at 1st cycle, then post-treatment dosimetry | Post-treatment 3-timepoint SPECT/CT 4-cc VOI renal sampling | DCR: 92% ORR: 23% PFS: 16 mo. OS: not reached | Thrombopenia: 6% Leucopoenia: 6% Neutropenia: 4% Anaemia: 8% Nephrotoxicity: 0% |
Menda et al. [15] Iowa City, IA, United States | 90Y-DOTATOC PRRT | 25 patents with mixed neuroendocrine tumours | 23 Gy to the kidney or 2 Gy to the bone marrow 3 cycles 4.4 GBq at first cycle Personalised activity at cycles 2 and 3 based on post-treatment dosimetry | Post-treatment PET/CT at 5 h and 4-timepoint SPECT/CT Whole kidney segmentation Blood sampling for bone marrow | Not reported | Thrombopenia: 0% Neutropenia: 0% Nephrotoxicity: 0% |
Bushnell et al. [16] Iowa City, IA, United States | Combined 90Y-DOTATOC PRRT and 131I-MIBG RPT | 3 patients with midgut neuroendocrine tumours | 19 Gy to the kidney and 1.5 Gy to the bone marrow 2 cycles Personalised activity based on pre-treatment dosimetry | Pre-treatment with 111In-octreotide and 131I-MIBG 4-timepoint planar and SPECT/CT imaging Whole kidney segmentation Blood sampling for bone marrow | PFS: 0% DCR: 100% | Thrombocytopenia: 33% (1 patient) |