Hospital-based proton therapy implementation during the COVID pandemic: early clinical and research experience in a European academic institution.

INTRODUCTION: A rapid deploy of unexpected early impact of the COVID pandemic in Spain was described in 2020. Oncology practice was revised to facilitate decision-making regarding multimodal therapy for prevalent cancer types amenable to multidisciplinary treatment in which the radiotherapy component searched more efficient options in the setting of the COVID-19 pandemic, minimizing the risks to patients whilst aiming to guarantee cancer outcomes. METHODS: A novel Proton Beam Therapy (PBT), Unit activity was analyzed in the period of March 2020 to March 2021. Institutional urgent, strict and mandatory clinical care standards for early diagnosis and treatment of COVID-19 infection were stablished in the hospital following national health-authorities' recommendations. The temporary trends of patients care and research projects proposals were registered. RESULTS: 3 out of 14 members of the professional staff involved in the PBR intra-hospital process had a positive test for COVID infection. Also, 4 out of 100 patients had positive tests before initiating PBT, and 7 out of 100 developed positive tests along the weekly mandatory special checkup performed during PBT to all patients. An update of clinical performance at the PBT Unit at CUN Madrid in the initial 500 patients treated with PBT in the period from March 2020 to November 2022 registers a distribution of 131 (26%) pediatric patients, 63 (12%) head and neck cancer and central nervous system neoplasms and 123 (24%) re-irradiation indications. In November 2022, the activity reached a plateau in terms of patients under treatment and the impact of COVID pandemic became sporadic and controlled by minor medical actions. At present, the clinical data are consistent with an academic practice prospectively (NCT05151952). Research projects and scientific production was adapted to the pandemic evolution and its influence upon professional time availability. Seven research projects based in public funding were activated in this period and preliminary data on molecular imaging guided proton therapy in brain tumors and post-irradiation patterns of blood biomarkers are reported. CONCLUSIONS: Hospital-based PBT in European academic institutions was impacted by COVID-19 pandemic, although clinical and research activities were developed and sustained. In the post-pandemic era, the benefits of online learning will shape the future of proton therapy education.

The joint use of 99mTc-MAA-SPECT/CT and cone-beam CT optimizes radioembolization planning.

PURPOSE: To determine which imaging method used during radioembolization (RE) work-up: contrast-enhanced computed tomography (CECT), 99mTc-MAA-SPECT/CT or cone beam-CT (CBCT), more accurately predicts the final target volume (TgV) as well as the influence that each modality has in the dosimetric calculation. METHODS: TgVs from 99mTc-MAA-SPECT/CT, CECT and CBCT were consecutively obtained in 24 patients treated with RE and compared with 90Y PET/CT TgV. Using the TgVs estimated by each imaging modality and a fictitious activity of 1 GBq, the corresponding absorbed doses by tumor and non-tumoral parenchyma were calculated for each patient. The absorbed doses for each modality were compared with the ones obtained using 90Y PET/CT TgV. RESULTS: 99mTc-MAA-SPECT/CT predicted 90Y PET/CT TgV better than CBCT or CECT, even for selective or superselective administrations. Likewise, 99mTc-MAA-SPECT/CT showed dosimetric values more similar to those obtained with 90Y PET/CT. Nevertheless, CBCT provided essential information for RE planning, such as ensuring the total coverage of the tumor and, in cases with more than one feeding artery, splitting the activity according to the volume of tumor perfused by each artery. CONCLUSION: The joint use of 99mTc-MAA-SPECT/CT and CBCT optimizes dosimetric planning for RE procedures, enabling a more accurate personalized approach.

Impact of the dosimetry approach on the resulting 90Y radioembolization planned absorbed doses based on 99mTc-MAA SPECT-CT: is there agreement between dosimetry methods?

BACKGROUND: Prior radioembolization, a simulation using 99mTc-macroaggregated albumin as 90Y-microspheres surrogate is performed. Gamma scintigraphy images (planar, SPECT, or SPECT-CT) are acquired to evaluate intrahepatic 90Y-microspheres distribution and detect possible extrahepatic and lung shunting. These images may be used for pre-treatment dosimetry evaluation to calculate the 90Y activity that would get an optimal tumor response while sparing healthy tissues. Several dosimetry methods are available, but there is still no consensus on the best methodology to calculate absorbed doses. The goal of this study was to retrospectively evaluate the impact of using different dosimetry approaches on the resulting 90Y-radioembolization pre-treatment absorbed dose evaluation based on 99mTc-MAA images. METHODS: Absorbed doses within volumes of interest resulting from partition model (PM) and 3D voxel dosimetry methods (3D-VDM) (dose-point kernel convolution and local deposition method) were evaluated. Additionally, a new "Multi-tumor Partition Model" (MTPM) was developed. The differences among dosimetry approaches were evaluated in terms of mean absorbed dose and dose volume histograms within the volumes of interest. RESULTS: Differences in mean absorbed dose among dosimetry methods are higher in tumor volumes than in non-tumoral ones. The differences between MTPM and both 3D-VDM were substantially lower than those observed between PM and any 3D-VDM. A poor correlation and concordance were found between PM and the other studied dosimetry approaches. DVH obtained from either 3D-VDM are pretty similar in both healthy liver and individual tumors. Although no relevant global differences, in terms of absorbed dose in Gy, between both 3D-VDM were found, important voxel-by-voxel differences have been observed. CONCLUSIONS: Significant differences among the studied dosimetry approaches for 90Y-radioembolization treatments exist. Differences do not yield a substantial impact in treatment planning for healthy tissue but they do for tumoral liver. An individual segmentation and evaluation of the tumors is essential. In patients with multiple tumors, the application of PM is not optimal and the 3D-VDM or the new MTPM are suggested instead. If a 3D-VDM method is not available, MTPM is the best option. Furthermore, both 3D-VDM approaches may be indistinctly used.

Significant dose reduction is feasible in FDG PET/CT protocols without compromising diagnostic quality.

PURPOSE: To reduce the radiation dose to patients by optimizing oncological FDG PET/CT protocols. METHODS: The baseline PET/CT protocol in our institution for oncological PET/CT examinations consisted of the administration of 5.18 MBq/kg of FDG and a CT acquisition with a reference current-time product of 120 mAs. In 2016, FDG activity was reduced to 4.44 and 3.70 MBq/kg and reference CT current-time-product was reduced to 100 and 80 mAs. 322 patients scanned with different protocols were retrospectively evaluated. For each patient, effective dose was calculated. The overall image quality was subjectively rated by the referring physician on a 4-point scale (IQ score: 1 excellent, 2 good, 3 poor but interpretable, 4 poor not interpretable). Image quality was quantitatively evaluated measuring noise in the liver. RESULTS: CT Results: Effective dose was progressively reduced from 9.5 ±â€¯2.8 to 8.0 ±â€¯2.3 and 6.2 ±â€¯1.5 mSv (p < 0.001). A mean dose reduction of 34.9% was achieved. There was a significant degradation of IQ score (p < 0.05) and noise (p < 0.001). Nevertheless, the number of poor quality studies (IQ score >2) did not increase. PET Results: Effective dose was gradually reduced from 6.5 ±â€¯1.4 to 5.7 ±â€¯1.3 and 5.0 ±â€¯1.0 mSv (p < 0.001). Average dose reduction was 23.4%. IQ score (p < 0.05) and noise (p < 0.001) significantly degraded for lower activity protocols. However, all images with reduced activity were scored as interpretable (IQ score ≤ 3). CONCLUSIONS: A significant radiation dose reduction of 28.7% was reached. Despite a slight reduction in image quality, the new regime was successfully implemented with readers reporting unchanged clinical confidence.

Is a Technetium-99m Macroaggregated Albumin Scan Essential in the Workup for Selective Internal Radiation Therapy with Yttrium-90? An Analysis of 532 Patients.

PURPOSE: To determine if baseline patient, tumor, and pretreatment evaluation characteristics could help identify patients who require technetium-99m (99mTc) macroaggregated albumin (99mTc MAA) imaging before selective internal radiation therapy (SIRT). MATERIALS AND METHODS: In this retrospective analysis, 532 consecutive patients with primary (n = 248) or metastatic (n = 284) liver tumors were evaluated between 2006 and 2015. Variables were compared between patients in whom 99mTc MAA imaging results contraindicated/modified SIRT administration with yttrium-90 (90Y) resin microspheres and those who were treated as initially planned. The 99mTc MAA findings that contraindicated/modified SIRT were a lung shunt fraction (LSF) > 20%, gastrointestinal 99mTc MAA uptake, or a mismatch between 99mTc MAA uptake and intrahepatic tumor distribution. RESULTS: LSF > 20% and gastrointestinal MAA uptake were observed in 7.5% and 3.9% of patients, respectively, and 11% presented a mismatch. Presence of a single lesion (odds ratio [OR] = 2.4) and vascular invasion (OR = 5.5) predicted LSF > 20%, and GI MAA uptake was predicted by the presence of liver metastases (OR = 3.7) and 99mTc MAA injection through the common/proper hepatic artery (OR = 4.7). Vascular invasion (OR = 4.1) was the only predictor of LSF > 20% and/or GI MAA uptake (sensitivity = 49.2%, specificity = 80.3%, negative predictive value = 92.4%). Previous antiangiogenic treatment (OR = 2.4) and presence of a single lesion (OR = 2.6) predicted mismatch. CONCLUSIONS: Imaging with 99mTc MAA is essential in SIRT workup because baseline characteristics may not adequately predict 99mTc MAA results. Nevertheless, the absence of vascular invasion potentially identifies a group of patients at low risk of SIRT contraindication/modification in whom performing SIRT in a single session (ie, pretreatment evaluation and SIRT on the same day) should be explored.

Commissioning of small field size radiosurgery cones in a 6-MV flattening filter-free beam.

This study aimed to describe the commissioning of small field size radiosurgery cones in a 6-MV flattening filter free (FFF) beam and report our measured values. Four radiosurgery cones of diameters 5, 10, 12.5, and 15 mm supplied by Elekta Medical were commissioned in a 6-MV FFF beam from an Elekta Versa linear accelerator. The extraction of a reference signal for measuring small fields in scanning mode is challenging. A transmission chamber was attached to the lower part of the collimators and used for percentage depth dose (PDD) and profile measurements in scanning mode with a stereotactic diode. Tissue-maximum ratios (TMR) and output factors (OF) for all collimators were measured with a stereotactic diode (IBA). TMR and the OF for the largest collimator were also acquired on a polystyrene phantom with a microionization chamber of 0.016 cm3 volume (PTW Freiburg PinPoint 3D). Measured TMR with diode and PinPoint microionization chamber agreed very well with differences smaller than 1% for depths below 20 cm, except for the smaller collimator, for which differences were always smaller than 2%. Calculated TMR were significantly different (up to 7%) from measured TMR. OF measured with diode and chamber showed a difference of 3.5%. The use of a transmission chamber allowed the measurement of the small-field dosimetric properties with a simple setup. The commissioning of radiosurgery cones in FFF beams has been performed with essentially the same procedures and recommended detectors used with flattened beams. Good agreement was found between TMR measurements acquired with the IBA stereotactic diode and the PinPoint 3D microionization chamber. The transmission chamber overcomes the problem of extracting a reference signal and is of great help for small-field commissioning.

Effective dose estimation for oncological and neurological PET/CT procedures.

BACKGROUND: The aim of this study was to retrospectively evaluate the patient effective dose (ED) for different PET/CT procedures performed with a variety of PET radiopharmaceutical compounds. PET/CT studies of 210 patients were reviewed including Torso (n = 123), Whole body (WB) (n = 36), Head and Neck Tumor (HNT) (n = 10), and Brain (n = 41) protocols with 18FDG (n = 170), 11C-CHOL (n = 10), 18FDOPA (n = 10), 11C-MET (n = 10), and 18F-florbetapir (n = 10). ED was calculated using conversion factors applied to the radiotracer activity and to the CT dose-length product. RESULTS: Total ED (mean ± SD) for Torso-11C-CHOL, Torso-18FDG, WB-18FDG, and HNT-18FDG protocols were 13.5 ± 2.2, 16.5 ± 4.5, 20.0 ± 5.6, and 15.4 ± 2.8 mSv, respectively, where CT represented 77, 62, 69, and 63% of the protocol ED, respectively. For 18FDG, 18FDOPA, 11C-MET, and 18F-florbetapir brain PET/CT studies, ED values (mean ± SD) were 6.4 ± 0.6, 4.6 ± 0.4, 5.2 ± 0.5, and 9.1 ± 0.4 mSv, respectively, and the corresponding CT contributions were 11, 14, 23, and 26%, respectively. In 18FDG PET/CT, variations in scan length and arm position produced significant differences in CT ED (p < 0.01). For dual-time-point imaging, the CT ED (mean ± SD) for the delayed scan was 3.8 ± 1.5 mSv. CONCLUSIONS: The mean ED for body and brain PET/CT protocols with different radiopharmaceuticals ranged between 4.6 and 20.0 mSv. The major contributor to total ED for body protocols is CT, whereas for brain studies, it is the PET radiopharmaceutical.

Brain PET imaging optimization with time of flight and point spread function modelling.

PURPOSE: To assess the influence of reconstruction algorithms and parameters on the PET image quality of brain phantoms in order to optimize reconstruction for clinical PET brain studies in a new generation PET/CT. METHODS: The 3D Hoffman phantom that simulates (18)F-fluorodeoxyglucose (FDG) distribution was imaged in a Siemens Biograph mCT TrueV PET/CT with Time of Flight (TOF) and Point Spread Function (PSF) modelling. Contrast-to-Noise Ratio (CNR), contrast and noise were studied for different reconstruction models: OSEM, OSEM + TOF, OSEM + PSF and OSEM + PSF + TOF. The 2D multi-compartment Hoffman phantom was filled to simulate 4 different tracers' spatial distribution: FDG, (11)C-flumazenil (FMZ), (11)C-Methionine (MET) and 6-(18)F-fluoro-l-dopa (FDOPA). The best algorithm for each tracer was selected by visual inspection. The maximization of CNR determined the optimal parameters for each reconstruction. RESULTS: In the 3D Hoffman phantom, both noise and contrast increased with increasing number of iterations and decreased with increasing FWHM. OSEM + PSF + TOF reconstruction was generally superior to other reconstruction models. Visual analysis of the 2D Hoffman brain phantom suggested that OSEM + PSF + TOF is the optimum algorithm for tracers with focal uptake, such as MET or FDOPA, and OSEM + TOF for tracers with diffuse cortical uptake (i.e. FDG and FMZ). Optimization of CNR demonstrated that OSEM + TOF reconstruction must be performed with 2 iterations and a filter FWHM of 3 mm, and OSEM + PSF + TOF reconstruction with 4 iterations and 1 mm FWHM filter. CONCLUSIONS: Optimization of reconstruction algorithm and parameters has been performed to take particular advantage of the last generation PET scanner, recommending specific settings for different brain PET radiotracers.

Fabry kidney disease.

Fabry disease (FD), the second most common type of lysosomal storage disease (LSD), is one of 41 disorders characterized by accumulation of substances normally degraded within lysosomes. It is an X-linked recessive disorder characterized by a deficiency of lysosomal alpha-galactosidase A (alpha-Gal A). The locus for human alpha-Gal A is located on the Xq22 chromosome. Most FD mutations are confined to a single family. Although FD is an X-linked disorder, up to one third of female carriers develop clinical manifestations of the disease. It typically presents during infancy or adolescence with crisis of neuropathic pain (acroparesthesia), angiokeratomas, and asymptomatic corneal lesions. As Gb3 deposition progresses, clinical manifestations occur in other organs. Patients typically die in the fourth or fifth decade of life due to cardiac, renal or cerebrovascular complications. Usually, there is diffuse deposition of glycosphingolipid in the renal glomeruli, tubules, interstitium, and vasculature. Clinically, the renal disease manifests with hypertension, microscopic hematuria (rare), moderate proteinuria, which can be in the nephrotic range, and lipiduria. End-stage renal disease can be treated with either dialysis or transplantation. Thegene for (x-Gal A was cloned and sequenced, which eventually led to production of enzyme for therapeutic use by either recombinant DNA technology or gene activation.