Comparison of 3 Different Therapeutic Particles in Radioembolization of Locally Advanced Intrahepatic Cholangiocarcinoma.

Our objective was to compare 3 different therapeutic particles used for radioembolization in locally advanced intrahepatic cholangiocarcinoma. Methods: 90Y-glass, 90Y-resin, and 166Ho-labeled poly(l-lactic acid) microsphere prescribed activity was calculated as per manufacturer recommendations. Posttreatment quantitative 90Y PET/CT and quantitative 166Ho SPECT/CT were used to determine tumor-absorbed dose, whole-normal-liver-absorbed dose, treated-normal-liver-absorbed dose, tumor-to-nontumor ratio, lung-absorbed dose, and lung shunt fraction. Response was assessed using RECIST 1.1 and the [18F]FDG PET-based change in total lesion glycolysis. Hepatotoxicity was assessed using the radioembolization-induced liver disease classification. Results: Six 90Y-glass, 8 90Y-resin, and 7 166Ho microsphere patients were included for analysis. The mean administered activity was 2.6 GBq for 90Y-glass, 1.5 GBq for 90Y-resin, and 7.0 GBq for 166Ho microspheres. Tumor-absorbed dose and treated-normal-liver-absorbed dose were significantly higher for 90Y-glass than for 90Y-resin and 166Ho microspheres (mean tumor-absorbed dose, 197 Gy for 90Y-glass vs. 73 Gy for 90Y-resin and 50 Gy for 166Ho; mean treated-normal-liver-absorbed dose, 79 Gy for 90Y-glass vs. 37 Gy for 90Y-resin and 31 Gy for 166Ho). The whole-normal-liver-absorbed dose and tumor-to-nontumor ratio did not significantly differ between the particles. All patients had a lung-absorbed dose under 30 Gy and a lung shunt fraction under 20%. The 3 groups showed similar toxicity and response according to RECIST 1.1 and [18F]FDG PET-based total lesion glycolysis changes. Conclusion: The therapeutic particles used for radioembolization differed from each other and showed significant differences in absorbed dose, whereas toxicity and response were similar for all groups. This finding emphasizes the need for separate dose constraints and dose targets for each particle.

Corrigendum to "Evaluation of image-guided and surface-guided radiotherapy for breast cancer patients treated in deep inspiration breath-hold: A single institution experience" [Tech. Innov. Patient Support Radiat. Oncol. 21 (2022) 51-57].

[This corrects the article DOI: 10.1016/j.tipsro.2022.02.001.].

Evaluation of image-guided and surface-guided radiotherapy for breast cancer patients treated in deep inspiration breath-hold: A single institution experience.

INTRODUCTION: Nowadays, deep inspiratory breath-hold is a common technique to reduce heart dose in left-sided breast radiotherapy. This study evaluates the evolution of the breath-hold technique in our institute, from portal imaging during dose delivery to continuous monitoring with surface-guided radiotherapy (SGRT). MATERIALS AND METHODS: Setup data and portal imaging results were analyzed for 98 patients treated before 2014, and SGRT data for 228 patients treated between 2018 and 2020. For the pre-SGRT group, systematic and random setup errors were calculated for different correction protocols. Residual errors and reproducibility of breath-holds were evaluated for both groups. The benefit of using SGRT for initial positioning was evaluated for another cohort of 47 patients. RESULTS: Online correction reduced the population mean error from 3.9 mm (no corrections) to 1.4 mm. Despite online setup correction, deviations greater than 3 mm were observed in about 10% and 20% of the treatment beams in ventral-dorsal and cranial-caudal directions, respectively. However, these percentages were much smaller than with offline protocols or no corrections. Mean absolute differences between breath-holds within a fraction were smaller in the SGRT-group (1.69 mm) than in the pre-SGRT-group (2.10 mm), and further improved with addition of visual feedback (1.30 mm). SGRT for positioning did not improve setup accuracy, but slightly reduced the time for imaging and setup correction, allowing completion within 3.5 min for 95% of fractions. CONCLUSION: For accurate radiotherapy breast treatments using deep inspiration breath-hold, daily imaging and correction is required. SGRT provides accurate information on patient positioning during treatment and improves patient compliance with visual feedback.

Dose-Response and Dose-Toxicity Relationships for Glass 90Y Radioembolization in Patients with Liver Metastases from Colorectal Cancer.

Radioembolization based on personalized treatment planning requires established dose-response and dose-toxicity relationships. The aim of this study was to investigate dose-response and dose-toxicity relationships in patients with colorectal liver metastases (CRLMs) treated with glass 90Y-microspheres. Methods: All CRLM patients treated with glass 90Y-microspheres in our institution were retrospectively analyzed. The tumor-absorbed dose was calculated for each measurable metastasis (i.e.,18F-FDG-positive and more than a 5-cm3 tumor volume) on posttreatment 90Y PET. Metabolic tumor response was determined on 18F-FDG PET/CT by measuring the total lesion glycolysis at baseline and at 3 mo after treatment. The relationship between tumor-absorbed dose and metabolic response was determined on a per-lesion and per-patient basis using a linear mixed-effects regression model. Clinical toxicity and laboratory toxicity were correlated with healthy liver-absorbed dose. Results: Thirty-one patients were included. The median tumor-absorbed dose of 85 measurable metastases was 133 Gy (range, 20-1001 Gy). Per response category, this was 196 Gy for complete response (CR), 177 Gy for partial response (PR), 72 Gy for stable disease, and 95 Gy for progressive disease (PD). A significant dose-response relationship was found on a tumor level, with a significantly higher tumor-absorbed dose in metastases with CR (+94%) and PR (+74%) than in metastases with PD (P < 0.001). A similar relationship was found on a patient level, with PR having a higher tumor-absorbed dose than did PD (+58%, P = 0.044). A tumor-absorbed dose of more than 139 Gy predicted a 3-mo metabolic response with the greatest accuracy (89% specificity and 77% sensitivity), whereas a tumor-absorbed dose of more than 189 Gy predicted response with 97% specificity and 45% sensitivity. The median healthy liver-absorbed dose was 63 Gy (range, 24-113 Gy). Toxicity was limited mostly to grades 1 and 2, with 1 case of radioembolization-induced liver disease in a patient who received the highest healthy liver-absorbed dose. A positive trend was seen for most laboratory parameters in our dose-toxicity analysis. Conclusion: A significant relationship was observed between dose and response in CRLM patients treated with glass 90Y radioembolization.

Comparison of the Biograph Vision and Biograph mCT for quantitative 90Y PET/CT imaging for radioembolisation.

BACKGROUND: New digital PET scanners with improved time of flight timing and extended axial field of view such as the Siemens Biograph Vision have come on the market and are expected to replace current generation photomultiplier tube (PMT)-based systems such as the Siemens Biograph mCT. These replacements warrant a direct comparison between the systems, so that a smooth transition in clinical practice and research is guaranteed, especially when quantitative values are used for dosimetry-based treatment guidance. The new generation digital PET scanners offer increased sensitivity. This could particularly benefit 90Y imaging, which tends to be very noisy owing to the small positron branching ratio and high random fraction of 90Y. This study aims to determine the ideal reconstruction settings for the digital Vision for quantitative 90Y imaging and to evaluate the image quality and quantification of the digital Vision in comparison with its predecessor, the PMT-based mCT, for 90Y imaging in radioembolisation procedures. METHODS: The NEMA image quality phantom was scanned to determine the ideal reconstruction settings for the Vision. In addition, an anthropomorphic phantom was scanned with both the Vision and the mCT, mimicking a radioembolisation patient with lung, liver, tumour, and extrahepatic deposition inserts. Image quantification of the anthropomorphic phantom was assessed by the lung shunt fraction, the tumour to non-tumour ratio, the parenchymal dose, and the contrast to noise ratio of extrahepatic depositions. RESULTS: For the Vision, a reconstruction with 3 iterations, 5 subsets, and no post-reconstruction filter is recommended for quantitative 90Y imaging, based on the convergence of the recovery coefficient. Comparing both systems showed that the noise level of the Vision is significantly lower than that of the mCT (background variability of 14% for the Vision and 25% for the mCT at 2.5·103 MBq for the 37 mm sphere size). For quantitative 90Y measures, such as needed in radioembolisation, both systems perform similarly. CONCLUSIONS: We recommend to reconstruct 90Y images acquired on the Vision with 3 iterations, 5 subsets, and no post-reconstruction filter for quantitative imaging. The Vision provides a reduced noise level, but similar quantitative accuracy as compared with its predecessor the mCT.

Adaptive scan duration in SPECT: Evaluation for radioembolization.

PURPOSE: It may be challenging to select the optimal scan duration for single-photon emission computed tomography (SPECT) protocols because the activity distribution characteristics can differ in every scan. Using simulations and experiments, we investigated whether the scan duration can be optimized for every scan separately by evaluating the activity distribution during scanning. We refer to this as adaptive scanning. METHODS: The feasibility of adaptive scanning was evaluated for the detection of extrahepatic depositions in the pretreatment procedure of radioembolization, in which 99m Tc-labeled macroaggregated albumin (99m Tc-MAA) is injected into the liver. We simulated fast 1-min detector rotations and updated the reconstruction with the newly collected counts after every rotation. The scan was terminated when one of the two criteria was met: (a) when the mask difference of the detected extrahepatic deposition between two consecutive rotations was lower than 5%; or (b) when the reconstructed extrahepatic activity was negligible with respect to the total reconstructed activity (<0.075%). The performance of adaptive scanning was evaluated using a digital phantom with various activity distributions, a physical phantom experiment, and simulations based on 129 patient activity distributions. RESULTS: The digital phantom data showed that the scan termination times substantially depended on the activity distribution characteristics. The experimental phantom data showed the feasibility of adaptive scanning with physical scanner measurements and illustrated that fast detector motion was not limiting the adaptive scanning performance. The patient data showed a large spread in the scan terminations times. By adaptive scanning, the mean scan duration of the patient distributions was shortened from 20 min (current clinical protocol) to 4.8 ± 0.2 min. The detection accuracy of extrahepatic depositions was unaffected and the mean difference in the extrahepatic deposition masks (compared with the 20-min scan) was only 7.0 ± 1.0%. CONCLUSION: Our study suggests that the SPECT scan duration can be personalized by assessing the activity distribution characteristics during scanning for the detection of extrahepatic depositions in the pretreatment procedure of radioembolization. The adaptive scanning approach might also be of benefit for other SPECT protocols, as long as a measure of interest is available for optimization.

Feasibility of imaging 90 Y microspheres at diagnostic activity levels for hepatic radioembolization treatment planning.

PURPOSE: Prior to 90 Y hepatic radioembolization, a dosage of 99m Tc-macroaggregated albumin (99m Tc-MAA) is administered to simulate the distribution of the 90 Y-loaded microspheres. This pretreatment procedure enables lung shunt estimation, detection of potential extrahepatic depositions, and estimation of the intrahepatic dose distribution. However, the predictive accuracy of the MAA particle distribution is often limited. Ideally, 90 Y microspheres would also be used for the pretreatment procedure. Based on previous research, the pretreatment activity should be limited to the estimated safety threshold of 100 MBq, making imaging challenging. The purpose of this study was to evaluate the quality of intra- and extrahepatic imaging of 90 Y-based pretreatment positron emission tomography/computed tomography (PET/CT) and quantitative single photon emission computed tomography (SPECT)/CT scans, by means of phantom experiments and a patient study. METHODS: An anthropomorphic phantom with three extrahepatic depositions was filled with 90 Y chloride to simulate a lung shunt fraction (LSF) of 5.3% and a tumor to nontumor ratio (T/N) of 7.9. PET /CT (Siemens Biograph mCT) and Bremsstrahlung SPECT/CT (Siemens Symbia T16) images were acquired at activities ranging from 1999 MBq down to 24 MBq, representing post- and pretreatment activities. PET/CT images were reconstructed with the clinical protocol and SPECT/CT images were reconstructed with a quantitative Monte Carlo-based reconstruction protocol. Estimated LSF, T/N, contrast to noise ratio of all extrahepatic depositions, and liver parenchymal and tumor dose were compared with the phantom ground truth. A clinically reconstructed SPECT/CT of 150 MBq 99m Tc represented the current clinical standard. In addition, a 90 Y pretreatment scan was simulated for a patient by acquiring posttreatment PET/CT and SPECT/CT data with shortened acquisition times. RESULTS: At an activity of 100 MBq 90 Y, PET/CT overestimated LSF [+10 percentage point (pp)], underestimated liver parenchymal dose (-3 Gy/GBq), and could not detect the extrahepatic depositions. SPECT/CT more accurately estimated LSF (-0.7 pp), parenchymal dose (-0.3 Gy/GBq) and could detect all three extrahepatic depositions. 99m Tc SPECT/CT showed similar accuracy as 90 Y SPECT/CT (LSF: +0.2 pp, parenchymal dose: +0.4 Gy/GBq, all extrahepatic depositions visible), although the noise level in the liver compartment was considerably lower for 99m Tc SPECT/CT compared to 90 Y SPECT/CT. The patient's SPECT/CT simulating a pretreatment 90 Y procedure accurately represented the posttreatment 90 Y microsphere distribution. CONCLUSIONS: Quantitative SPECT/CT of 100 MBq 90 Y could accurately estimate LSF, T/N, parenchymal and tumor dose, and visualize extrahepatic depositions.

Performance of a dual-layer scanner for hybrid SPECT/CBCT.

Fluoroscopic procedures involving radionuclides would benefit from interventional nuclear imaging by obtaining real-time feedback on the activity distribution. We have previously proposed a dual-layer detector that offers such procedural guidance by simultaneous fluoroscopic and nuclear planar imaging. Acquisition of single photon computed tomography (SPECT) and cone beam computed tomography (CBCT) could provide additional information on the activity distribution. This study investigates the feasibility and the image quality of simultaneous SPECT/CBCT, by means of phantom experiments and simulations. Simulations were performed to study the obtained reconstruction quality for (i) clinical SPECT/CT, (ii) a dual-layer scanner configured with optimized hardware, and (iii) our (non-optimized) dual-layer prototype. Experiments on an image quality phantom and an anthropomorphic phantom (including extrahepatic depositions with volumes and activities close to the median values encountered in hepatic radioembolization) were performed with a clinical SPECT/CT scanner and with our dual-layer prototype. Nuclear images were visually and quantitatively evaluated by measuring the tumor/non-tumor (T/N) ratio and contrast-to-noise ratio (CNR). The simulations showed that the maximum obtained CNR was 38.8 ± 0.8 for the clinical scanner, 30.2 ± 0.9 for the optimized dual-layer scanner, and 20.8 ± 0.4 for the prototype scanner. T/N ratio showed a similar decline. The phantom experiments showed that performing simultaneous SPECT/CBCT is feasible. The CNR obtained from the SPECT reconstruction of largest sphere in the image quality phantom was 43.1 for the clinical scanner and 28.6 for the developed prototype scanner. The anthropomorphic phantom showed that the extrahepatic depositions were detected with both scanners. A dual-layer detector is able to simultaneously acquire SPECT and CBCT. Both CNR and T/N ratio are worse than that of a clinical system, but the phantom experiments showed that extrahepatic depositions with volumes and activities close to the median values encountered in hepatic radioembolization could be distinguished.

The physics of radioembolization.

Radioembolization is an established treatment for chemoresistant and unresectable liver cancers. Currently, treatment planning is often based on semi-empirical methods, which yield acceptable toxicity profiles and have enabled the large-scale application in a palliative setting. However, recently, five large randomized controlled trials using resin microspheres failed to demonstrate a significant improvement in either progression-free survival or overall survival in both hepatocellular carcinoma and metastatic colorectal cancer. One reason for this might be that the activity prescription methods used in these studies are suboptimal for many patients.In this review, the current dosimetric methods and their caveats are evaluated. Furthermore, the current state-of-the-art of image-guided dosimetry and advanced radiobiological modeling is reviewed from a physics' perspective. The current literature is explored for the observation of robust dose-response relationships followed by an overview of recent advancements in quantitative image reconstruction in relation to image-guided dosimetry.This review is concluded with a discussion on areas where further research is necessary in order to arrive at a personalized treatment method that provides optimal tumor control and is clinically feasible.

Technical Advances in Image Guidance of Radionuclide Therapy.

Internal radiation therapy with radionuclides (i.e., radionuclide therapy) owes its success to the many advantages over other, more conventional, treatment options. One distinct advantage of radionuclide therapies is the potential to use (part of) the emitted radiation for imaging of the radionuclide distribution. The combination of diagnostic and therapeutic properties in a set of matched radiopharmaceuticals (sometimes combined in a single radiopharmaceutical) is often referred to as theranostics and allows accurate diagnostic imaging before therapy. The use of imaging benefits treatment planning, dosimetry, and assessment of treatment response. This paper focuses on a selection of advances in imaging technology relevant for image guidance of radionuclide therapy. This involves developments in nuclear imaging modalities, as well as other anatomic and functional imaging modalities. The quality and quantitative accuracy of images used for guidance of radionuclide therapy is continuously being improved, which in turn may improve the therapeutic outcome and efficiency of radionuclide therapies.

Application of circularly polarized light for non-invasive diagnosis of cancerous tissues and turbid tissue-like scattering media.

Polarization-based optical techniques have become increasingly popular in the field of biomedical diagnosis. In the current report we exploit the directional awareness of circularly and/or elliptically polarized light backscattered from turbid tissue-like scattering media. We apply circularly and elliptically polarized laser light which illuminates the samples of interest, and a standard optical polarimeter is used to observe the polarization state of light backscattered a few millimeters away from the point of incidence. We demonstrate that the Stokes vector of backscattered light depicted on a Poincaré sphere can be used to assess a turbid tissue-like scattering medium. By tracking the Stokes vector of the detected light on the Poincaré sphere, we investigate the utility of this approach for characterization of cancerous and non-cancerous tissue samples in vitro. The obtained results are discussed in the framework of a phenomenological model and the results of a polarization tracking Monte Carlo model, developed in house. Schematic illustration of the experimental approach utilizing circularly and elliptically polarized light for probing turbid tissue-like scattering media.