METHODS: The administered activity of 177 Lu-DOTATATE was 7.99 ± 0.36 GBq. SPECT/CT images were acquired 0.5, 4, 24, and 48 h after injection in Sunway Medical Centre. For the multiple VSV method, VSV kernels of 177 Lu in media with various densities were generated by Geant4 Application for Emission Tomography (GATE) simulation first. The second step involved the convolution of the time-integrated activity map with each kernel to produce medium-specific dose maps. Third, each medium-specific dose map was masked using binary medium masks, which were generated from CT-based density maps. Finally, all masked dose maps were summed to generate the final dose map. VSV methods with four different VSV sets (1, 4, 10, and 20 VSVs) were compared. Voxel-wise density correction for the single VSV method was also performed. The absorbed doses in the kidneys, bone marrow, and tumors were analyzed, and the relative errors between the VSV and Monte Carlo simulation approaches were estimated. Organ-based dosimetry using Organ Level INternal Dose Assessment/EXponential Modeling (OLINDA/EXM) was also compared.
RESULTS: The accuracy of the multiple VSV approach increased with the number of dose kernels. The average dose estimation errors of a single VSV with density correction and 20 VSVs were less than 6% in most cases, although organ-based dosimetry using OLINDA/EXM yielded an error of up to 123%. The advantages of the single VSV method with density correction and the 20 VSVs over organ-based dosimetry were most evident in bone marrow and bone-metastatic tumors with heterogeneous medium properties.
CONCLUSION: The single VSV method with density correction and multiple VSV method with 20 dose kernels enabled fast and accurate radiation dose estimation. Accordingly, voxel-based dosimetry methods can be useful for managing administration activity and for investigating tumor dose responses to further increase the therapeutic efficacy of 177 Lu-DOTATATE.
Methods: We performed a multinational, multicenter, prospective registry of adult patients with PTCLs that was named as the International Cooperative non-Hodgkin T-cell lymphoma prospective registry study where thirty-two institutes from six Asian countries and territories (Korea, China, Taiwan, Singapore, Malaysia, and Indonesia) participated.
Findings: A total of 486 patients were registered between April 2016 and February 2019, and more than a half of patients (57%) had stage III or IV. Extranodal natural killer (NK)/T- cell lymphoma was the most common subtype (n = 139,28.6%), followed by angioimmunoblastic T-cell lymphoma (AITL, n = 120,24.7%), PTCL-not otherwise specified (PTCL-NOS, n = 101,20.8%), ALK-positive anaplastic large cell lymphoma (ALCL, n = 34,6.9%), and ALK-negative ALCL (n = 30,6.2%). The median progression-free survival (PFS) and overall survival (OS) were 21.1 months (95% CI,10.6-31.6) and 83.6 months (95% CI, 56.7-110.5), respectively. Upfront use of combined treatment with chemotherapy and radiotherapy showed better PFS than chemotherapy alone in localized ENKTL whereas consolidation with upfront autologous stem cell transplantation (SCT) provided longer PFS in advance stage ENKTL. In patients with PTCLs other than ENKTL, anthracycline-containing chemotherapies were widely used, but the outcome of those regimens was not satisfactory, and upfront autologous SCT was not significantly associated with survival benefit, either. The treatment outcome of salvage chemotherapy was disappointing, and none of the salvage strategies showed superiority to one another.
Interpretation: This multinational, multicenter study identified the relative frequency of each subtype of PTCLs across Asian countries, and the survival outcomes according to the therapeutic strategies currently used.
Funding: Samsung Biomedical Research Institute.