Tumor-Absorbed Dose Predicts Progression-Free Survival Following <sup>131</sup>I-Tositumomab Radioimmunotherapy

Dewaraja, Yuni K.; Schipper, Matthew J.; Shen, Jincheng; Smith, Lauren B.; Murgić, Jure; Savas, Hatice; Youssef, Ehab; Regan, Denise; Wilderman, S.J.; Roberson, Peter L.; Kaminski, Mark; Avram, Anca M.

doi:10.2967/jnumed.113.136044

Cited by 46 publications

(44 citation statements)

References 23 publications

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“…For 131 I-tositumomab, the tumor doses have ranged from 102 to 711 cGy (16). In a study that correlated tumor-absorbed dose and progression-free survival for 131 I-tositumomab treatment, a significant difference in progressionfree survival was observed when a dose threshold of 200 cGy was used (11). This 200-cGy threshold is slightly below the estimated median dose delivered to patients in our study.…”

Section: Discussionmentioning

confidence: 54%

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Tumor-Absorbed Dose for Non-Hodgkin Lymphoma Patients Treated with the Anti-CD37 Antibody Radionuclide Conjugate ¹⁷⁷Lu-Lilotomab Satetraxetan

et al. 2016

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177 Lu-lilotomab satetraxetan is a novel antibody radionuclide conjugate currently tested in a phase 1/2a first-in-human dosage escalation trial for patients with relapsed CD371 indolent non-Hodgkin lymphoma. The aim of this work was to develop dosimetric methods and calculate tumor-absorbed radiation doses for patients treated with 177 Lu-lilotomab satetraxetan. Methods: Patients were treated at escalating injected activities (10, 15 and 20 MBq/kg) of 177 Lulilotomab satetraxetan and with different predosing, with or without 40 mg of unlabeled lilotomab. Eight patients were included for the tumor dosimetry study. Tumor radioactivity concentrations were calculated from SPECT acquisitions at multiple time points, and tumor masses were delineated from corresponding CT scans. Tumor-absorbed doses were then calculated using the OLINDA sphere model. To perform voxel dosimetry, the SPECT/CT data and an inhouse-developed MATLAB program were combined to investigate the dose rate homogeneity. Results: Twenty-six tumors in 8 patients were ascribed a mean tumor-absorbed dose. Absorbed doses ranged from 75 to 794 cGy, with a median of 264 cGy across different dosage levels and different predosing. A significant correlation between the dosage level and tumor-absorbed dose was found. Twenty-one tumors were included for voxel dosimetry and parameters describing dose-volume coverage calculated. The investigation of intratumor voxel doses indicates that mean tumor dose is correlated to these parameters. Conclusion: Tumor-absorbed doses for patients treated with 177 Lu-lilotomab satetraxetan are comparable to doses reported for other radioimmunotherapy compounds. Although the intertumor variability was considerable, a correlation between tumor dose and patient dosage level was found. Our results indicate that mean dose may be used as the sole dosimetric parameter on the lesion level.

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Section: Discussionmentioning

confidence: 54%

“…Later, more comprehensive dosimetric models were developed (9), including methods to analyze intratumor dose inhomogeneity. SPECT/CT images from multiple time points were used to obtain a predictive relationship between progression-free survival and mean tumor dose (10,11).…”

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confidence: 99%

Tumor-Absorbed Dose for Non-Hodgkin Lymphoma Patients Treated with the Anti-CD37 Antibody Radionuclide Conjugate ¹⁷⁷Lu-Lilotomab Satetraxetan

et al. 2016

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“…16 In other therapeutic contexts, greater efforts for more sophisticated image corrections in 3D dosimetry gave better correlation results. 59 Patient breathing has been hitherto scarcely considered for dosimetry in TARE, but image correction would be needed, above all for lesions close to liver dome. The breathing is modeled here as a rigid transformation (only translations, no rotation) by a 3D anisotropic kernel with the maximum amplitudes, 50 but the location-specific motion, i.e., larger at the liver dome, and smaller toward the inferior part, can be applied, requiring a combination of rigid and nonrigid transformations.…”

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confidence: 99%

Impact of SPECT corrections on 3D‐dosimetry for liver transarterial radioembolization using the patient relative calibration methodology

et al. 2016

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Purpose: Many centers aim to plan liver transarterial radioembolization (TARE) with dosimetry, even without CT-based attenuation correction (AC), or with unoptimized scatter correction (SC) methods. This work investigates the impact of presence vs absence of such corrections, and limited spatial resolution, on 3D dosimetry for TARE. Methods: Three voxelized phantoms were derived from CT images of real patients with different body sizes. Simulations of 99m Tc-SPECT projections were performed with the SIMIND code, assuming three activity distributions in the liver: uniform, inside a "liver's segment," or distributing multiple uptaking nodules ("nonuniform liver"), with a tumoral liver/healthy parenchyma ratio of 5:1. Projection data were reconstructed by a commercial workstation, with OSEM protocol not specifically optimized for dosimetry (spatial resolution of 12.6 mm), with/without SC (optimized, or with parameters predefined by the manufacturer; dual energy window), and with/without AC. Activity in voxels was calculated by a relative calibration, assuming identical microspheres and 99m Tc-SPECT counts spatial distribution. 3D dose distributions were calculated by convolution with lesions and healthy parenchyma from different reconstructions were compared with those obtained from the reference biodistribution (the "gold standard," GS), assessing differences for D95%, D70%, and D50% (i.e., minimum value of the absorbed dose to a percentage of the irradiated volume). γ tool analysis with tolerance of 3%/13 mm was used to evaluate the agreement between GS and simulated cases. The influence of deep-breathing was studied, blurring the reference biodistributions with a 3D anisotropic gaussian kernel, and performing the simulations once again. Results: Differences of the dosimetric indicators were noticeable in some cases, always negative for lesions and distributed around zero for parenchyma. Application of AC and SC reduced systematically the differences for lesions by 5%-14% for a liver segment, and by 7%-12% for a nonuniform liver. For parenchyma, the data trend was less clear, but the overall range of variability passed from −10%/40% for a liver segment, and −10%/20% for a nonuniform liver, to −13%/6% in both cases. Applying AC, SC with preset parameters gave similar results to optimized SC, as confirmed by γ tool analysis. Moreover, γ analysis confirmed that solely AC and SC are not sufficient to obtain accurate 3D dose distribution. With breathing, the accuracy worsened severely for all dosimetric indicators, above all for lesions: with AC and optimized SC, −38%/−13% in liver's segment, −61%/−40% in the nonuniform liver. For parenchyma, D50% resulted always less sensitive to breathing and sub-optimal correction methods (difference overall range: −7%/13%). Conclusions: Reconstruction protocol optimization, AC, SC, PVE and respiratory motion corrections should be implemented to obtain the best possible dosimetric accuracy. On the other side, thanks to the relative calibration, D50% inaccuracy for the healthy paren...

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“…This is often the case in SPECT and PET studies (He et al 2009, Dewaraja et al 2014, Palmedo et al 2014). However, in some applications, the optimal reconstruction parameters or method could be different for different organs (Cheng et al 2013, 2014), and advanced imaging procedures could incorporate this feature.…”

Section: Discussionmentioning

confidence: 91%

A no-gold-standard technique for objective assessment of quantitative nuclear-medicine imaging methods

2016

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The objective optimization and evaluation of nuclear-medicine quantitative imaging methods using patient data is highly desirable but often hindered by the lack of a gold standard. Previously, a regression-without-truth (RWT) approach has been proposed for evaluating quantitative imaging methods in the absence of a gold standard, but this approach implicitly assumes that bounds on the distribution of true values are known. Several quantitative imaging methods in nuclear-medicine imaging measure parameters where these bounds are not known, such as the activity concentration in an organ or the volume of a tumor. We extended upon the RWT approach to develop a no-gold-standard (NGS) technique for objectively evaluating such quantitative nuclear-medicine imaging methods with patient data in the absence of any ground truth. Using the parameters estimated with the NGS technique, a figure of merit, the noise-to-slope ratio (NSR), can be computed, which can rank the methods on the basis of precision. An issue with NGS evaluation techniques is the requirement of a large number of patient studies. To reduce this requirement, the proposed method explored the use of multiple quantitative measurements from the same patient, such as the activity concentration values from different organs in the same patient. The proposed technique was evaluated using rigorous numerical experiments and using data from realistic simulation studies. The numerical experiments demonstrated that the NSR was estimated accurately using the proposed NGS technique when the bounds on the distribution of true values were not precisely known, thus serving as a very reliable metric for ranking the methods on the basis of precision. In the realistic simulation study, the NGS technique was used to rank reconstruction methods for quantitative single-photon emission computed tomography (SPECT) based on their performance on the task of estimating the mean activity concentration within a known volume of interest. Results showed that the proposed technique provided accurate ranking of the reconstruction methods for 97.5% of the 50 noise realizations. Further, the technique was robust to the choice of evaluated reconstruction methods. The simulation study pointed to possible violations of the assumptions made in the NGS technique under clinical scenarios. However, numerical experiments indicated that the NGS technique was robust in ranking methods even when there was some degree of such violation.

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Tumor-Absorbed Dose Predicts Progression-Free Survival Following ¹³¹I-Tositumomab Radioimmunotherapy

Cited by 46 publications

References 23 publications

Tumor-Absorbed Dose for Non-Hodgkin Lymphoma Patients Treated with the Anti-CD37 Antibody Radionuclide Conjugate ¹⁷⁷Lu-Lilotomab Satetraxetan

Tumor-Absorbed Dose for Non-Hodgkin Lymphoma Patients Treated with the Anti-CD37 Antibody Radionuclide Conjugate ¹⁷⁷Lu-Lilotomab Satetraxetan

Impact of SPECT corrections on 3D‐dosimetry for liver transarterial radioembolization using the patient relative calibration methodology

A no-gold-standard technique for objective assessment of quantitative nuclear-medicine imaging methods

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Tumor-Absorbed Dose Predicts Progression-Free Survival Following 131I-Tositumomab Radioimmunotherapy

Cited by 46 publications

References 23 publications

Tumor-Absorbed Dose for Non-Hodgkin Lymphoma Patients Treated with the Anti-CD37 Antibody Radionuclide Conjugate 177Lu-Lilotomab Satetraxetan

Tumor-Absorbed Dose for Non-Hodgkin Lymphoma Patients Treated with the Anti-CD37 Antibody Radionuclide Conjugate 177Lu-Lilotomab Satetraxetan

Impact of SPECT corrections on 3D‐dosimetry for liver transarterial radioembolization using the patient relative calibration methodology

A no-gold-standard technique for objective assessment of quantitative nuclear-medicine imaging methods

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Tumor-Absorbed Dose Predicts Progression-Free Survival Following ¹³¹I-Tositumomab Radioimmunotherapy

Tumor-Absorbed Dose for Non-Hodgkin Lymphoma Patients Treated with the Anti-CD37 Antibody Radionuclide Conjugate ¹⁷⁷Lu-Lilotomab Satetraxetan

Tumor-Absorbed Dose for Non-Hodgkin Lymphoma Patients Treated with the Anti-CD37 Antibody Radionuclide Conjugate ¹⁷⁷Lu-Lilotomab Satetraxetan