Patient Dosimetry Research Articles

The Challenge of Single-Photon Emission Computed Tomography Image Segmentation in the Internal Dosimetry of 177Lu Molecular Therapies.

The aim of this article is to review the single photon emission computed tomography (SPECT) segmentation methods used in patient-specific dosimetry of 177Lu molecular therapy. Notably, 177Lu-labelled radiopharmaceuticals are currently used in molecular therapy of metastatic neuroendocrine tumours (ligands for somatostatin receptors) and metastatic prostate adenocarcinomas (PSMA ligands). The proper segmentation of the organs at risk and tumours in targeted radionuclide therapy is an important part of the optimisation process of internal patient dosimetry in this kind of therapy. Because this is the first step in dosimetry assessments, on which further dose calculations are based, it is important to know the level of uncertainty that is associated with this part of the analysis. However, the robust quantification of SPECT images, which would ensure accurate dosimetry assessments, is very hard to achieve due to the intrinsic features of this device. In this article, papers on this topic were collected and reviewed to weigh up the advantages and disadvantages of the segmentation methods used in clinical practice. Degrading factors of SPECT images were also studied to assess their impact on the quantification of 177Lu therapy images. Our review of the recent literature gives an insight into this important topic. However, based on the PubMed and IEEE databases, only a few papers investigating segmentation methods in 177Lumolecular therapy were found. Although segmentation is an important step in internal dose calculations, this subject has been relatively lightly investigated for SPECT systems. This is mostly due to the inner features of SPECT. What is more, even when studies are conducted, they usually utilise the diagnostic radionuclide 99mTc and not a therapeutic one like 177Lu, which could be of concern regarding SPECT camera performance and its overall outcome on dosimetry.

Radiomics and Artificial Intelligence in Radiotheranostics: A Review of Applications for Radioligands Targeting Somatostatin Receptors and Prostate-Specific Membrane Antigens.

Radiotheranostics refers to the pairing of radioactive imaging biomarkers with radioactive therapeutic compounds that deliver ionizing radiation. Given the introduction of very promising radiopharmaceuticals, the radiotheranostics approach is creating a novel paradigm in personalized, targeted radionuclide therapies (TRTs), also known as radiopharmaceuticals (RPTs). Radiotherapeutic pairs targeting somatostatin receptors (SSTR) and prostate-specific membrane antigens (PSMA) are increasingly being used to diagnose and treat patients with metastatic neuroendocrine tumors (NETs) and prostate cancer. In parallel, radiomics and artificial intelligence (AI), as important areas in quantitative image analysis, are paving the way for significantly enhanced workflows in diagnostic and theranostic fields, from data and image processing to clinical decision support, improving patient selection, personalized treatment strategies, response prediction, and prognostication. Furthermore, AI has the potential for tremendous effectiveness in patient dosimetry which copes with complex and time-consuming tasks in the RPT workflow. The present work provides a comprehensive overview of radiomics and AI application in radiotheranostics, focusing on pairs of SSTR- or PSMA-targeting radioligands, describing the fundamental concepts and specific imaging/treatment features. Our review includes ligands radiolabeled by 68Ga, 18F, 177Lu, 64Cu, 90Y, and 225Ac. Specifically, contributions via radiomics and AI towards improved image acquisition, reconstruction, treatment response, segmentation, restaging, lesion classification, dose prediction, and estimation as well as ongoing developments and future directions are discussed.

First-in-human study of PSMA-targeting agent, [18F]AlF-P16-093: dosimetry and initial evaluation in prostate cancer patients.

This is a first-in-human study to evaluate the radiation dosimetry of a new prostate-specific membrane antigen (PSMA)-targeted radiopharmaceutical, [18F]AlF-P16-093, and also initial investigation of its ability to detect PSMA-positive tumors using PET scans in a cohort of prostate cancer (PCa) patients. The [18F]AlF-P16-093 was automatically synthesized with a GE TRACERlab. A total of 23 patients with histopathologically proven PCa were prospectively enrolled. Dosimetry and biodistribution study investigations were carried out on a subset of six (6) PCa patients, involving multiple time-point scanning. The mean absorbed doses were estimated with PMOD and OLINDA software. [18F]AlF-P16-093 was successfully synthesized, and radiochemical purity was > 95%, and average labeling yield was 36.5 ± 8.3% (decay correction, n = 12). The highest tracer uptake was observed in the kidneys, spleen, and liver, contributing to an effective dose of 16.8 ± 1.3 μSv/MBq, which was ~ 30% lower than that of [68Ga]Ga-P16-093. All subjects tolerated the PET examination well, and no reportable side-effects were observed. The PSMA-positive tumors displayed rapid uptake, and they were all detectable within 10 min, and no additional lesions were observed in the following multi-time points scanning. Each patient had at least one detectable tumor lesion, and a total of 356 tumor lesions were observed, including intraprostatic, lymph node metastases, bone metastases, and other soft tissue metastases. We report herein a streamlined method for high yield synthesis of [18F]AlF-P16-093. Preliminary study in PCa patients has demonstrated its safety and acceptable radiation dosimetry. The initial diagnostic study indicated that [18F]AlF-P16-093 PET/CT is efficacious and potentially useful for a widespread application in the diagnosis of PCa patients.

Использование явления термостимулированной радиационно- обусловленной люминесценции микрокристаллов морской соли для внутриполостной «ин виво» дозиметрии при брахитерапии рака предстательной железы источником Ir192: оценка потенциала

Aim of the study – use of the phenomenon of thermo stimulated luminescence in natural microcrystals of sea salt (NaCl) in the range of therapeutic doses in order to develop a method for off line intracavitary «in vivo» dosimetry of patients at high dose-rate brachytherapy of prostate cancer with a 192Ir source. Samples of aliquots with natural microcrystals (a fraction with a size of about 100 m) of sea salt were used in the study. Measurements were carried out using a Harshaw 3500 device, which is a thermoluminescent reader. Irradiation of samples to construct the calibration dependences was carried out by a standard 90Sr/90Y source providing the dose rate of 2.99 mGy/s. It was established, that: (1) there is a linear dose dependence of luminescence intensity from studied microcrystals in the range of therapeutic absorbed doses from 1 to 20 Gy with an error in measuring the luminescence intensity of the studied microcrystal samples of less than 5%; (2) it was revealed that fading (decrease in microdosimeter readings over time) does not exceed 5% 5 days after irradiation; (3) clinical testing of «in vivo» dosimetry method using sea salt microcrystals for high dose-rate brachytherapy of prostate cancer shows that the results of measurements of absorbed doses in the organ at risk (rectum) using studied natural NaCl crystals are consistent, within the limits of error, with the results of measurements by synthetic LiF:Mg,Ti crystals (with intracavitary placement in the organ at risk and simultaneous irradiation both assemblies of these microcrystals). It was concluded that the use of the studied sea salt microcrystals is promising for «in vivo» dosimetry in application to 192Ir high dose-rate brachytherapy of prostate cancer.

Implication of ICRP pediatric reference voxel phantoms on dose assessment of patients in radioiodine therapy

To investigate the impact of the recently released pediatric reference voxel phantoms (0-, 1-, 5-, 10-, 15-year-old males and females) of the International Commission on Radiological Protection (ICRP) on organ dose estimates for radioactive iodine (RAI) treatment in pediatric patients, we calculated and analyzed pediatric-specific iodine-131 S values (rT ← thyroid) for the 30 radiosensitive organs by conducting Monte Carlo simulations using the Geant4. The gender dependency in the S values was frequently seen for the 15-year-old phantoms with higher S values of female than male. In addition, the age dependency in the S values was observed for most target organs; that is, the S values tend to decrease for older ages (e.g., ∼120 times for the gonads between the adult and newborn) due mainly to the inter-organ distances generally longer for older ages. Moreover, we observed that the iodine-131 S values tend to be significantly greater by up to ∼145.5 times than those of the stylized phantoms that have been widely used for organ dose estimates of pediatric RAI patients. We believe that the pediatric-specific iodine-131 S values (rT ← thyroid) of the ICRP pediatric reference voxel phantoms should be beneficial to improve the dosimetry of pediatric RAI patients.

Dose escalation with simultaneous integrated boost for un-methylated multiple glioblastoma.

Simultaneous involvement of multiple distinct brain regions occurs in 2-5% of all high-grade gliomas (HGG) and is associated with poor prognosis. Whereas radiotherapy (RT) is an important and well-established treatment for high-grade glioma, the role of dose-escalated radiotherapy has yet to be established. In this case series, we report upon the dosimetry, adverse effects, and response in patients with multiple un-methylated high-grade gliomas receiving dose-escalated radiation. We reviewed charts of patients with multifocal high grade glioma treated at our institution since January 2022. All patients had stereotactic biopsies after an magnetic resonance imaging (MRI) contrast-enhanced with T1, T2, FLAIR sequences and were discussed in a multidisciplinary oncology team. MGMT-positive patients received either TMZ alone or RT with TMZ and were excluded from this analysis. Un-methylated patients received dose-escalated RT without temezolamide (TMZ). Following computed tomography (CT) and MR simulation, the gros tumor volume (GTV) was delineated and prescribed 52.5 Gy in 15 fractions within the standard 40.05 Gy planning treatment volume (PTV). Treatment planning was volumetric modulated arc therapy. A total of 20 patients with multiple un-methylated MGMT glioblastoma multiforme were treated with dose-escalated radiation therapy between January 2022 and June 2023. All patients completed dose escalated radiotherapy without acute adverse effects. Progression-free survival at six months was 85%, as defined by the RANO criteria. In this case series, we showed that un-methylated multiple high-grade glioma could be safely treated with dose escalation. Results of progression-free survival should be validated in a larger prospective clinical trial.

Effects of tissue heterogeneity and comparisons of collapsed cone and Monte Carlo fast neutron patient dosimetry using the University of Washington clinical neutron therapy system (CNTS)

Fast neutron therapy is a high linear energy transfer (LET) radiation treatment modality offering advantages over low LET radiations. Multileaf collimator technology reduces normal-tissue dose (toxicity) and makes neutron therapy more comparable to MV x-ray treatments. Published clinical-trial and other experiences with fast neutron therapy are reported. Early comparative studies failed to consider differences in target-dose spatial conformality between x-ray and neutron treatments, which is especially important for organs-at-risk close to tumor targets. Treatments planning systems (TPS) for high-energy neutrons lag behind TPS tools for MV x-rays, creating challenges for comparative studies of clinical outcomes. A previously published Monte Carlo model of the University of Washington (UW) Clinical Neutron Therapy System (CNTS) is refined and integrated with the RayStation TPS as an external dose planning/verification tool. The collapsed cone (CC) dose calculations in the TPS are based on measured dose profiles and output factors in water, with the absolute dose determined using a tissue-equivalent ionization chamber. For comparison, independent (external) Monte Carlo simulation computes dose on a voxel-by-voxel basis using an atlas that maps Hounsfield Unit (HU) numbers to elemental composition and density. Although the CC algorithm in the TPS accurately computes neutron dose to water compared to Monte Carlo calculations, calculated dose to water differs from bone or tissue depending largely on hydrogen content. Therefore, the elemental composition of tissue and bone, rather than the material or electron density, affects fast neutron dose. While the CC algorithm suffices for reproducible patient dosimetry in fast neutron therapy, adopting methods that consider tissue heterogeneity would enhance patient-specific neutron dose accuracy relative to national standards for other types of ionizing radiation. Corrections for tissue composition have a significant impact on absolute dose and the relative biological effectiveness (RBE) of neutron treatments compared to other radiation types (MV x-rays, protons, and carbon ions).

Phase I/IIa trial of 18F-prostate specific membrane antigen (PSMA) 1007 PET/CT in healthy volunteers and prostate cancer patients.

18F-PSMA 1007 is a promising PET tracer for prostate cancer. We aimed to examine the safety, biodistribution, radiation dosimetry, and clinical effectiveness in Japanese healthy volunteers and patients with prostate cancer. Part A evaluated the pharmacokinetics and exposure doses in three healthy volunteers. Part B evaluated the diagnostic accuracy in patients with untreated preoperative prostate cancer (Cohort 1, n=7) and patients with biochemical recurrence (Cohort 2, n=3). All subjects received a single dose of 3.7MBq/kg 18F-PSMA 1007. Results: 18F-PSMA 1007 was found to be safe and well tolerated in all subjects. No serous AEs or drug-related AEs were identified during the present study. The average blood radioactivity concentration reached a maximum of 47.87±1.05 (percentage of injected dose [%ID]/ml) at 5min and then decreased to 1.60±0.78 in 6h. The systemic radioactivity reached a maximum of 211.05±6.77 (%ID$\times$103) at 5min and decreased to 7.18±3.91 in 6h. The sensitivity and positive predictive value were 100% and 100% based on both pathologic and imaging confirmation as gold standard. In Cohort 1, 15 primary foci (11.9%) were >5mm in the largest diameter and identified in 39 of 126 segments (30.1%). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for 60min uptake time acquisition were 80.0, 96.5, 91.4, 91.2 and 91.3%, respectively. Our study revealed that 18F-PSMA 1007 was safe, well tolerated and showed high accuracy in the diagnosis of prostate cancer.

Beam delivery characteristics of the Hitachi carbon ion scanning system at Osaka Heavy Ion Medical Accelerator in Kansai (HIMAK).

Using the pencil beam raster scanning method employed at most carbon beam treatment facilities, spots can be moved without interrupting the beam, allowing for the delivery of a dose between spots (move dose). This technique is also known as Dose-Driven-Continuous-Scanning (DDCS). To minimize its impact on HIMAK patient dosimetry, there's an upper limit to the move dose. Spots within a layer are grouped into sets, or "break points," allowing continuous irradiation. The beam is turned off when transitioning between sets or at the end of a treatment layer or spill. The control system beam-off is accomplished by turning off the RF Knockout (RFKO) extraction and after a brief delay the High Speed Steering Magnet (HSST) redirects the beam transport away from isocenter to a beam dump. The influence of the move dose and beam on/off control on the dose distribution and irradiation time was evaluated by measurements never before reported and modelled for Hitachi Carbon DDCS. We conducted fixed-point and scanning irradiation experiments at three different energies, both with and without breakpoints. For fixed-point irradiation, we utilized a 2D array detector and an oscilloscope to measure beam intensity over time. The oscilloscope data enabled us to confirm beam-off and beam-on timing due to breakpoints, as well as the relative timing of the RFKO signal, HSST signal, and dose monitor (DM) signals. From these measurements, we analyzed and modelled the temporal characteristics of the beam intensity. We also developed a model for the spot shape and amplitude at isocenter occurring after the beam-off signal which we called flap dose and its dependence on beam intensity. In the case of scanning irradiation, we measured move doses using the 2D array detector and compared these measurements with our model. We observed that the most dominant time variation of the beam intensity was at 1 kHz and its harmonic frequencies. Our findings revealed that the derived beam intensity cannot reach the preset beam intensity when each spot belongs to different breakpoints. The beam-off time due to breakpoints was approximately 100 ms, while the beam rise time and fall time (tdecay ) were remarkably fast, about 10 ms and 0.2 ms, respectively. Moreover, we measured the time lag (tdelay ) of approximately 0.2 ms between the RFKO and HSST signals. Since tdelay ≈ tdecay at HIMAK then the HSST is activated after the residual beam intensity, resulting in essentially zero flap dose at isocenter from the HSST. Our measurements of the move dose demonstrated excellent agreement with the modelled move dose. We conducted the first move dose measurement for a Hitachi Carbon synchrotron, and our findings, considering beam on/off control details, indicate that Hitachi's carbon synchrotron provides a stable beam at HIMAK. Our work suggests that measuring both move dose and flap dose should be part of the commissioning process and possibly using our model in the Treatment Planning System (TPS) for new facilities with treatment delivery control systems with higher beam intensities and faster beam-off control.

Quantitative 177Lu SPECT/CT imaging for personalized dosimetry using a ring-shaped CZT-based camera

BackgroundDosimetry after radiopharmaceutical therapy with 177Lu (177Lu-RPT) relies on quantitative SPECT/CT imaging, for which suitable reconstruction protocols are required. In this study, we characterized for the first time the quantitative performance of a ring-shaped CZT-based camera using two different reconstruction algorithms: an ordered subset expectation maximization (OSEM) and a block sequential regularized expectation maximization (BSREM) combined with noise reduction regularization. This study lays the foundations for the definition of a reconstruction protocol enabling accurate dosimetry for patients treated with 177Lu-RPT.MethodsA series of 177Lu-filled phantoms were acquired on a StarGuide™ (GE HealthCare), with energy and scatter windows centred at 208 (± 6%) keV and 185 (± 5%) keV, respectively. Images were reconstructed with the manufacturer implementations of OSEM (GE-OSEM) and BSREM (Q.Clear) algorithms, and various combinations of iterations and subsets. Additionally, the manufacturer-recommended Q.Clear-based reconstruction protocol was evaluated. Quantification accuracy, measured as the difference between the SPECT-based and the radionuclide calibrator-based activity, and noise were evaluated in a large cylinder. Recovery coefficients (RCs) and spatial resolution were assessed in a NEMA IEC phantom with sphere inserts. The reconstruction protocols considered suitable for clinical applications were tested on a cohort of patients treated with [177Lu]Lu-PSMA-I&T.ResultsThe accuracy of the activity from the cylinder, although affected by septal penetration, was < 10% for all reconstructions. Both algorithms featured improved spatial resolution and higher RCs with increasing updates at the cost of noise build-up, but Q.Clear outperformed GE-OSEM in reducing noise accumulation. When the reconstruction parameters were carefully selected, similar values for noise (~0.15), spatial resolution (~1 cm) and RCs were found, irrespective of the reconstruction algorithm. Analogue results were found in patients.ConclusionsAccurate activity quantification is possible when imaging 177Lu with StarGuide™. However, the impact of septal penetration requires further investigations. GE-OSEM is a valid alternative to the recommended Q.Clear reconstruction algorithm, featuring comparable performances assessed on phantoms and patients.

Assessment and comparison of radiation dose and cancer risk in thoracic diagnostic and radiotherapy treatment planning CT scans

PurposeThis study intends to compare the radiation doses and cancer induction risks from thoracic diagnostic CT (DG-CT) and radiotherapy treatment planning CT (RP-CT) scans. Material and methodsA cross-sectional study on two groups of patients who underwent thoracic CT scans with RP-CT (n = 100) and DG-CT (n = 100) was conducted. The characteristics of the two groups, including age, weight, height, and body mass index were almost similar. To calculate organ and effective doses in a standard 70 kg phantom, the volume CT Dose Index (CTDIv) and dose-length product (DLP) were recorded and utilized with the ImPACT CT Patient Dosimetry Calculator. Patient-specific organ and effective doses were acquired by applying a weight-based correction factor. The lifetime attribute risk (LAR) of cancers was estimated according to the method proposed in Biological Effects of Ionizing Radiation (BEIR VII) which considers age and sex differences. ResultsThe mean ± standard deviation values of CTDIv, DLP, and effective dose were 12.19 ± 3.49 mGy, 568.68 ± 109.42 mGy cm, and 11.46 ± 2.07 mSv for RP-CT, respectively. For DG-CT, these values were 12.33 ± 3.37 mGy, 372.46 ± 99.57 mGy cm, and 7.65 ± 2.07 mSv, respectively. In males, the mean ± SD of cancer incidence risk of all cancers, all solid, and leukemia were 34.57 ± 18.91, 28.79 ± 16.74, 5.77 ± 2.28 per 100,000 individuals, respectively, for DG-CT. These values were 50.77 ± 14.53, 42.37 ± 12.81, and 9.09 ± 1.67 per 100,000 individuals, respectively, for RP-CT. In the female patients, the mean ± SD of cancer incidence risk of all cancers, all solid, and leukemia were 55.04 ± 31.64, 50.77 ± 14.53, 4.32 ± 1.26 per 100,000 individuals, respectively, for DG-CT. These values for RP-CT were 85.46 ± 30.10, 73.49 ± 26.12, and 6.97 ± 1.69 cancers per 100,000 individuals, respectively. ConclusionCancer incidence and mortality risks for RP-CT were higher than for DG-CT scans, highlighting the need for greater optimization of exposure parameters. For individuals, particularly young female patients, the advantages of CT imaging must be balanced against the risks of radiation.

Shoulder Muscle Dosimetry and Post-Treatment Rehabilitation Utilization for Early-Stage Breast Cancer Patients

Rehabilitation services for recovery of impaired physical function following breast cancer treatments are largely underutilized. We previously found that breast cancer survivors treated with radiation who received higher radiation doses to the pectoralis major are more likely to self-report shoulder pain and disability. This study aims to address whether radiation dose delivered to the pectoralis major (Pmaj) and pectoralis minor (Pmin) are correlated with referrals for rehabilitation services post-treatment. A retrospective 1:1 matched case-control study was conducted for breast cancer patients who were and were not referred for breast or shoulder rehabilitation services between 2014-2019 at a single academic institution. Patients were included if they had a lumpectomy and adjuvant radiation without regional nodal irradiation. Cohorts were matched based on age, axillary surgery (none vs. sentinel lymph node biopsy (SLNB)), and use of radiation boost. We used non-parametric Mann-Whitney U tests to determine whether Pmaj or Pmin doses (mean, V50Gy, V45Gy, V40Gy, V35Gy, V30Gy, V20Gy) were different between the two groups. Muscle doses were converted to EQD2 assuming an α/β ratio of 2.5. In our study of 30 patients of a median age 57 years (IQR 12.75), 20 (66.67%) patients underwent SLNB in addition to lumpectomy. Median tumor size was 1.1cm (range 0.16 - 7.30cm). Stage was 0 for 11 patients (36.67%), I for 14 patients (46.67%), and II for 5 patients (16.67%). 3D conformal radiation was delivered to the whole breast with a moderately hypofractionated (n = 17) or conventionally fractionated regimen (n = 13). The most common rehabilitation diagnoses were lymphedema (n = 8), scar management (n = 7) and shoulder pain (n = 5). Mean dose to both the Pmaj (20.8Gy vs. 18.6Gy; p = 0.02) and Pmin (30.6Gy vs. 24.6Gy; p = 0.01) were significantly higher in patients who received post-treatment rehabilitation compared to those without. The V40Gy, V35Gy, V30Gy and V20Gy (all p<0.02) for the Pmin and V35Gy, V30Gy and V20Gy for the Pmaj (all p<0.04) were also significantly higher in those who underwent rehabilitation. In this cohort of patients with early-stage breast cancer, increased mean doses to the pectoralis muscles were correlated with increased use of rehabilitation services after radiation. Physicians might consider using these dosimetric data to complement clinical symptoms in the decision-making process for referrals for rehabilitation services. This may help facilitate earlier referral to rehabilitation interventions, which is important since early intervention is correlated with improved shoulder morbidity.

Pectoralis Muscle Dosimetry and Posttreatment Rehabilitation Utilization for Patients With Early-Stage Breast Cancer

Up to 50% of women treated for localized breast cancer will experience some degree of arm or shoulder morbidity. Although radiation is thought to contribute to this morbidity, the mechanism remains unclear. Prior studies have shown biologic and radiographic changes in the pectoralis muscles after radiation. This study thus aimed to investigate the relationship between radiation to the pectoralis muscles and referrals for rehabilitation services posttreatment for arm and shoulder morbidity. A retrospective 1:1 matched case-control study was conducted for patients with breast cancer who were and were not referred for breast or shoulder rehabilitation services between 2014 and 2019 at a single academic institution. Patients were included if they had a lumpectomy and adjuvant radiation. Patients who underwent an axillary lymph node dissection were excluded. Cohorts were matched based on age, axillary surgery, and use of radiation boost. Muscle doses were converted to equivalent dose in 2 Gy fractions assuming an α:β ratio of 2.5 and were compared between the 2 groups. In our cohort of 50 patients of a median age 60 years (interquartile range, 53-68 years), 36 patients (72%) underwent a sentinel lymph node biopsy in addition to a lumpectomy. Although pectoralis muscle doses were generally higher in those receiving rehabilitation services, this was not statistically significant. Pectoralis major V20-40 Gy reached borderline significance, as did pectoralis major mean dose (17.69 vs 20.89 Gy; P=.06). In this limited cohort of patients, we could not definitively conclude a relationship between pectoralis muscle doses and use of rehabilitation services. Given the borderline significant findings, this should be further investigated in a larger cohort.

Lesion Dosimetry for [177Lu]Lu-PSMA-617 Radiopharmaceutical Therapy Combined with Stereotactic Body Radiotherapy in Patients with Oligometastatic Castration-Sensitive Prostate Cancer.

A single-institution prospective pilot clinical trial was performed to demonstrate the feasibility of combining [177Lu]Lu-PSMA-617 radiopharmaceutical therapy (RPT) with stereotactic body radiotherapy (SBRT) for the treatment of oligometastatic castration-sensitive prostate cancer. Methods: Six patients with 9 prostate-specific membrane antigen (PSMA)-positive oligometastases received 2 cycles of [177Lu]Lu-PSMA-617 RPT followed by SBRT. After the first intravenous infusion of [177Lu]Lu-PSMA-617 (7.46 ± 0.15 GBq), patients underwent SPECT/CT at 3.2 ± 0.5, 23.9 ± 0.4, and 87.4 ± 12.0 h. Voxel-based dosimetry was performed with calibration factors (11.7 counts per second/MBq) and recovery coefficients derived from in-house phantom experiments. Lesions were segmented on baseline PSMA PET/CT (50% SUVmax). After a second cycle of [177Lu]Lu-PSMA-617 (44 ± 3 d; 7.50 ± 0.10 GBq) and an interim PSMA PET/CT scan, SBRT (27 Gy in 3 fractions) was delivered to all PSMA-avid oligometastatic sites, followed by post-PSMA PET/CT. RPT and SBRT voxelwise dose maps were scaled (α/β = 3 Gy; repair half-time, 1.5 h) to calculate the biologically effective dose (BED). Results: All patients completed the combination therapy without complications. No grade 3+ toxicities were noted. The median of the lesion SUVmax as measured on PSMA PET was 16.8 (interquartile range [IQR], 11.6) (baseline), 6.2 (IQR, 2.7) (interim), and 2.9 (IQR, 1.4) (post). PET-derived lesion volumes were 0.4-1.7 cm3 The median lesion-absorbed dose (AD) from the first cycle of [177Lu]Lu-PSMA-617 RPT (ADRPT) was 27.7 Gy (range, 8.3-58.2 Gy; corresponding to 3.7 Gy/GBq, range, 1.1-7.7 Gy/GBq), whereas the median lesion AD from SBRT was 28.1 Gy (range, 26.7-28.8 Gy). Spearman rank correlation, ρ, was 0.90 between the baseline lesion PET SUVmax and SPECT SUVmax (P = 0.005), 0.74 (P = 0.046) between the baseline PET SUVmax and the lesion ADRPT, and -0.81 (P = 0.022) between the lesion ADRPT and the percent change in PET SUVmax (baseline to interim). The median for the lesion BED from RPT and SBRT was 159 Gy (range, 124-219 Gy). ρ between the BED from RPT and SBRT and the percent change in PET SUVmax (baseline to post) was -0.88 (P = 0.007). Two cycles of [177Lu]Lu-PSMA-617 RPT contributed approximately 40% to the maximum BED from RPT and SBRT. Conclusion: Lesional dosimetry in patients with oligometastatic castration-sensitive prostate cancer undergoing [177Lu]Lu-PSMA-617 RPT followed by SBRT is feasible. Combined RPT and SBRT may provide an efficient method to maximize the delivery of meaningful doses to oligometastatic disease while addressing potential microscopic disease reservoirs and limiting the dose exposure to normal tissues.

Infrastructure tools to support an effective Radiation Oncology Learning Health System.

Radiation Oncology Learning Health System (RO-LHS) is a promising approach to improve the quality of care by integrating clinical, dosimetry, treatment delivery, research data in real-time. This paper describes a novel set of tools to support the development of a RO-LHS and the current challenges they can address. We present a knowledge graph-based approach to map radiotherapy data from clinical databases to an ontology-based data repository using FAIR concepts. This strategy ensures that the data are easily discoverable, accessible, and can be used by other clinical decision support systems. It allows for visualization, presentation, and data analyses of valuable information to identify trends and patterns in patient outcomes. We designed a search engine that utilizes ontology-based keyword searching, synonym-based term matching that leverages the hierarchical nature of ontologies to retrieve patient records based on parent and children classes, connects to the Bioportal database for relevant clinical attributes retrieval. To identify similar patients, a method involving text corpus creation and vector embedding models (Word2Vec, Doc2Vec, GloVe, and FastText) are employed, using cosine similarity and distance metrics. The data pipeline and tool were tested with 1660 patient clinical and dosimetry records resulting in 504180 RDF (Resource Description Framework) tuples and visualized data relationships using graph-based representations. Patient similarity analysis using embedding models showed that the Word2Vec model had the highest mean cosine similarity, while the GloVe model exhibited more compact embeddings with lower Euclidean and Manhattan distances. The framework and tools described support the development of a RO-LHS. By integrating diverse data sources and facilitating data discovery and analysis, they contribute to continuous learning and improvement in patient care. The tools enhance the quality of care by enabling the identification of cohorts, clinical decision support, and the development of clinical studies and machine learning programs in radiation oncology.

Ten fraction hypofractionated stereotactic body radiotherapy for the management of ultracentral lung tumors: a retrospective analysis of dosimetry, outcomes, and toxicity

BackgroundThe management of ultracentral thoracic tumors with ablative dose of radiotherapy remains challenging given proximity to critical central structures. We report patient outcomes, toxicity, and dosimetry for ultracentrally located tumors with hypofractionated stereotactic body radiotherapy (hfSBRT).MethodsSeventy-eight individuals (50 initial radiotherapy, 28 re-irradiation) undergoing 10 fraction hfSBRT for ultracentrally located thoracic tumors treated between 2009 and 2020 at a single institution were retrospectively reviewed. Overall survival (OS), progression free survival (PFS), and local control (LC) were calculated. Incidence and grade of treatment related toxicity were evaluated. Dosimetric analysis of treatment plans and critical adjacent OARs was performed.ResultsAt a median follow up time of 13 months, 1- and 3-year OS, PFS, and LC were 89%/63%, 37%/18%, and 84%/65%, respectively. Median dose was 65 Gy (BED10 = 107.25 Gy). Median primary bronchial tree maximum dose (Dmax) was 60 Gy (V50 = 0.96 cc). Median esophageal Dmax was 38 Gy (V40 = 0 cc). Median great vessel Dmax was 68 Gy (V50 = 3.53 cc). The most common ≥ grade 2 adverse event was pneumonitis, in 15 individuals (20%). Grade 3 or higher toxicity was observed in 9 individuals (12%): three cases of grade 3 pneumonitis (two re-irradiation, one initial radiotherapy), one grade 3 esophageal stricture following re-irradiation, two grade 3 endobronchial obstructions both following initial radiotherapy, and three grade 5 hemoptysis events (two re-irradiation, one initial radiotherapy). One hemoptysis event was categorized as “possibly” related to treatment, while the remaining two events were categorized as “unlikely” related to treatment in patients with clear evidence of disease progression.ConclusionshfSBRT to ultracentral lung tumors delivered over 10 fractions is a safe and effective treatment option, with acceptable rates of toxicity and good rates of tumor control.Trial registration: IRB registration number 12573.

Predictive Value of [99mTc]-MAA-Based Dosimetry in Hepatocellular Carcinoma Patients Treated with [90Y]-TARE: A Single-Center Experience.

Transarterial radioembolization is a well-established method for the treatment of hepatocellular carcinoma. The tolerability and incidence of hepatic decompensation are related to the doses delivered to the tumor and healthy liver. This retrospective study was performed at our center to evaluate whether tumor- and healthy-liver-absorbed dose levels in TARE are predictive of tumor response according to the mRECIST 1.1 criteria and overall survival. One hundred and six patients with hepatocellular carcinoma were treated with [90Y]-loaded resin microspheres and completed the follow-up. The dose delivered to each compartment was calculated using a compartmental model. The model was based on [99mTc]-labelled albumin aggregate images obtained before the start of therapy. Tumor response was assessed after three months of treatment. Kaplan-Meier analysis was used to assess survival. The mean age of our population was 66 ± 13 years with a majority being BCLC B tumors. Forty-two patients presented with portal vein thrombosis. The response rate was 57% in the overall population and 59% in patients with thrombosis. Target-to-background (TBR) values measured on initial [99mTc]MAA-SPECT-imaging and tumor model dosimetric values were associated with tumor response (p < 0.001 and p = 0.009, respectively). A dosimetric threshold of 136.5 Gy was predictive of tumor response with a sensitivity of 84.2% and specificity of 89.4%. Overall survival was 24.1 months [IQR 13.1-36.4] for patients who responded to treatment compared to 10.4 months [IQR 6.3-15.9] for the remaining patients (p = 0.022). In this cohort, the initial [99mTc]MAA imaging is predictive of response and survival. The dosimetry prior to the application of TARE can be used for treatment planning and our results also suggest that the therapy is well-tolerated. In particular, hepatic decompensation can be predicted even in the presence of PVT.

Full Dose SBRT in Combination With Mediastinal Chemoradiation for Locally Advanced, Non-Small Cell Lung Cancer: A Practical Guide for Planning, Dosimetric Results From a Phase 2 Study, and a Treatment Planning Guide for the Phase 3 NRG Oncology LU-008 Trial

Stereotactic body radiation therapy (SBRT) has been utilized with high effectiveness in early stage NSCLC but has not been studied extensively in locally advanced NSCLC. We conducted a phase II study delivering SBRT to the primary tumor followed by conventionally fractionated chemoradiation to the involved lymph nodes for patients with node positive locally advanced NSCLC. This manuscript serves as both a guide to planning techniques utilized on this trial and the subsequent phase III study, NRG Oncology LU-008, and to report patient dosimetry and toxicity results. We initiated a phase II multi-center single arm study evaluating SBRT to the primary tumor (50-54 Gy in 3-5 fractions) followed by conventionally fractionated chemoradiation to 60 Gy in 2 Gy fractions with doublet chemotherapy to the involved lymph nodes for patients with stage III or unresectable stage II NSCLC. Patients eligible for adjuvant immunotherapy received up to 12 months of durvalumab. We report a detailed guide for the entire treatment process from CT simulation through treatment planning and delivery. The dosimetric outcomes from the 60 patients who completed therapy on study are reported both for target coverage and normal structure doses. We also report correlation between radiation related toxicities and dosimetric parameters. 60 patients were enrolled between 2017-2022. Planning techniques utilized were primarily VMAT for both SBRT to the primary tumor and conventionally fractionated radiation to the involved nodes, with a minority of cases utilizing dynamic conformal arcs technique or static DMLC IMRT. Grade 2 or higher pneumonitis was associated with lung dose V5Gy >70 % and grade 2 or higher pulmonary toxicity was associated with lung dose V10Gy>50%. Only 3 patients (5%) experienced grade 3 or higher pneumonitis. Grade 2 or higher esophagitis was associated with esophageal doses, including mean dose >20Gy, V60Gy >7%, and D1cc >55Gy. Only one patient (1.7%) experienced grade 3 esophagitis. SBRT to the primary tumor followed by conventionally fractionated chemoradiation to the involved lymph nodes is feasible with planning techniques as described. Radiation related toxicity on this phase II study was low. This manuscript serves as a guideline for the recently activated NRG Oncology LU-008 phase III trial evaluating this experimental regimen.

A dosimetric analysis of rectal hydrogel spacer use in patients with recurrent prostate cancer undergoing salvage high-dose-rate brachytherapy

We hypothesize rectal hydrogel spacer (RHS) improves rectal dosimetry in patients undergoing salvage high-dose-rate brachytherapy (HDR-BT) for intact, recurrent prostate cancer (PC). A prospectively collected institutional database was queried for recurrent PC patients treated with salvage HDR-BT from September 2015 to November 2021. Patients were offered RHS beginning June 2019. Dosimetric variables were compared between RHS and no-RHS groups for the average of two fractions using Wilcoxon rank-sum tests. Primary outcomes were rectal volume receiving 75% of prescription dose (V75%) and prostate volume receiving 100% of prescription dose (V100%). Generalized estimating equation (GEE) model was used to evaluate the association between other planning variables and rectal V75%. Forty-one PC patients received salvage HDR-BT, of whom 20 had RHS. All patients received 2400cGy in 2 fractions. Median RHS volume was 6.2cm3 (Standard deviation [SD]: ± 3.5cm3). Median follow-up was 4 months and 17 months in the RHS and no-RHS groups, respectively. Median rectal V75% with and without RHS were 0.0cm3 (IQR: 0.0-0.0cm3) and 0.06cm3 (IQR: 0.0-0.14cm3), respectively (p<0.001). Median prostate V100% with and without RHS were 98.55% (IQR: 97.86-99.22%) and 97.78% (IQR: 97.50-98.18%), respectively (p = 0.007). RHS, rectum, and prostate volumes did not significantly affect rectal V75% per GEE modeling. There was 10% G1-2 and 5% G3 rectal toxicity in RHS group. There was 9.5% G1-2 and no G3+ rectal toxicities in the no-RHS group. Absolute improvement in rectal V75% and prostate V100% was significant with RHS in PC patients undergoing salvage HDR-BT, but clinical benefit is marginal.

Multicenter, dual fractionation scheme, single core lab comparison of rectal volume dose reduction following injection of two biodegradable perirectal spacers.

A multicenter, double-arm, central core lab, retrospective study was performed to compare the rectal dosimetry of patients implanted with two injectable, biodegradable perirectal spacers, in conventional fractionation (CF), as well as ultrahypofractionation (UH) treatment plans. Fifty-nine patients were enrolled into the study in five centers: two centers in Europe, which implanted a biodegradable balloon spacer in a total of 24 subjects and three centers in the US, which implanted the SpaceOAR in 35 subjects. Anonymized CTs (pre and post-implantation) were reviewed by the central core lab. For VMAT CF plans rectal V50, V60, V70, and V80 were calculated. For UH plans, a corresponding rectal V22.6, V27.1, V31.37, and V36.25 were established representing 62.5%, 75%, 87.5%, and 100% of the 36.25Gy prescribed dose. For CF VMAT, a comparison between the balloon spacer and the SpaceOAR revealed a significant difference of 33.4% decrease in mean rectal V50 (71.9%vs. 38.5%, p<0.001), 27.7% in mean rectal V60 (79.6%vs. 51.9%, p<0.001), 17.1% difference in mean rectal V70 (84.1%vs. 67.0%, p=0.001), and a significant difference of 3.0% (p=0.019) in mean rectal V80 (87.2%vs. 84.2%). With UH analysis, the mean rectal dose reduction for the balloon spacer compared to the SpaceOAR was 79.2% and 53.3% for V27.1 (p<0.001), 84.1% and 68.1% for V31.71 (p=0.001), and 89.7% and 84.8% for V36.25 (p=0.012), respectively. Rectal dosimetry is more favorable for treatment with the balloon spacer compared with SpaceOAR. Further research, particularly in the context of a prospective randomized clinical trial design, is needed to assess the acute and late toxicity experience as well as physician satisfaction with achieving symmetrical implantation, and ease of use in light of increasing clinical use.