Delivered Radiation Dose Research Articles

Large-language-model empowered 3D dose prediction for intensity-modulated radiotherapy.

Treatment planning is currently a patient specific, time-consuming, and resource demanding task in radiotherapy. Dose-volume histogram (DVH) prediction plays a critical role in automating this process. The geometric relationship between DVHs in radiotherapy plans and organs-at-risk (OAR) and planning target volume (PTV) has been well established. This study explores the potential of deep learning models for predicting DVHs using images and subsequent human intervention facilitated by a large-language model (LLM) to enhance the planning quality. We propose a pipeline to convert unstructured images to a structured graph consisting of image-patch nodes and dose nodes. A novel Dose Graph Neural Network (DoseGNN) model is developed for predicting DVHs from the structured graph. The proposed DoseGNN is enhanced with the LLM to encode massive knowledge from prescriptions and interactive instructions from clinicians. In this study, we introduced an online human-AI collaboration (OHAC) system as a practical implementation of the concept proposed for the automation of intensity-modulated radiotherapy (IMRT) planning. The proposed DoseGNN model was compared to widely employed DL models used in radiotherapy, including Swin Transformer, 3D U-Net CNN, and vanilla MLP. For PTV, DoseGNN achieved the mean absolute error (MAE) of , , , and between true plans and predicted plans that were 64%, 53%, 64%, 61% of the best baseline model. For the worst case among OARs (left lung, right lung, chest wall, heart, spinal cord), DoseGNN achieved the mean absolute error of , , that were 85%, 91%, 80% of the best baseline model. Moreover, the LLM-empowered DoseGNN model facilitates seamless adjustment to treatment plans through interaction with clinicians using natural language. We developed DoseGNN, a novel deep learning model for predicting delivered radiation doses from medical images, enhanced by LLM to allow adjustment through seamless interaction with clinicians. The preliminary results confirm DoseGNN's superior accuracy in DVH prediction relative to typical DL methods, highlighting its potential to facilitate an online clinician-AI collaboration system for streamlined treatment planning automation.

Дозы на весь организм и их неопределенность при облучении мышей на гамма-радиобиологической установке ИГУР-1М

In the experimental department of the Urals research center for radiation medicine (Chelyabinsk, Russia) the radiobiological studies are carried out with the IGUR-1M gamma installation. In this study, the numerical experiment has been performed to specify the radiation doses in experimental mice and corresponding uncertainties. We evaluate the factors converting the dose in air measured by the ionization chamber to the dose to an organism, which is dependent on the height of the cage with the animals. The relative standard uncertainties of radiation doses for mice under 7 days of age do not exceed 7%. For more active older animals, the uncertainty of the delivered radiation doses can reach 10%.

Absorbed dose rates and biological consequences of discrete alpha-emitting particles embedded in tissue

This study calculates dose rate in Gy y-1 for individual dust, soil, and sediment particles that contain significant amounts of alpha-emitting uranium or thorium. When inhaled or ingested, these particles deliver radiation dose to organs where they embed. The presented method uses X-ray microscopy to measure alpha emitting elements in environmental microparticles, followed by calculation of dose rates delivered to the targeted volume of tissues that surround embedded microparticles. The example calculations use a real-world, 89% uranium house dust particle.

Biocompatibility and radiosensitivity of a fiber optical-based dosimeter: biological applications

This study introduces a cutting-edge fiber-optic dosimetry (FOD) sensor designed for measuring radiation in biological settings. The accuracy and precision of dosimeters for small animals, particularly prolonged exposure to nonuniform radiation fields, are always challenging. A state-of-the-art in-vivo dosimeter utilizing glass-encapsulated Thermoluminescence cylindrical detector (TLD) was introduced. The FODs are implanted into the rat during a prolonged irradiation scenario involving 137Cs where the rat has the freedom to move within a heterogeneous radiation domain. The implantation surgery was verified with X-ray computed tomography (CT) in addition to biochemical and pathological tests to assess the biocompatibility of FOD in vivo. A versatile FOD is designed for industrial and medical fields, which demand accurate and resilient radiation dosimeters. The dose measurements are associated with precise two-dimensional (2D) radiation distribution imaging. Three cylindrical FODs and three standards TLD_100 for each rat were tested. The measurements of peak irradiation before and after exposure reveal greater stability and superior sensitivity when compared to standard thermo-luminescence detectors in an in-vivo animal test. To the best of our knowledge, FOD testing on live animals is presented for the first time in this paper. Regarding the safety and biocompatibility of FOD, no morphological signs with any kind of inflammation or sensitivity toward the FOD material have been remarked. Moreover, with the current FOD, there is no oedema between the epidermal, dermal, and subdermal sections at the site of implantation. The results also show the stable levels of white blood cells (lymphocytes, granulocytes, MID) as blood inflammatory markers before surgery and at the time of extraction of the implanted dosimeters, thus confirming the biocompatibility for each optical fiber cylinder dosimeter. As a result, the new dosimeters have excellent biocompatibility in living tissues and have 100% accurate reusability intensity of the delivered radiation doses compared to TLD_100 which demonstrated a 45% reduction in its intensity accuracy.

Approaches for Streamlining Performance Control by Monte Carlo Modeling

For decades, cancer has remained a persistent health challenge; this project represents a significant stride towards refining treatment approaches and prognostic insights. Proton beam therapy, a radiation therapy modality employing high-energy protons to target various malignancies while minimizing damage to adjacent healthy tissue, holds immense promise. This study analyzes the relationship between delivered radiation doses and patient outcomes, using various approximation functions and graphical representations for comparison. Statistical analysis is performed through the Monte Carlo method based on repeated sampling to estimate the variables of interest in this analysis, namely, the survival rates, financial implications, and medical effectiveness of proton beam therapy. To this end, open-source data from research centers that publish patient outcomes were utilized. The second study considered the estimation of pay gaps that can have long-lasting effects, leading to differences in retirement savings, wealth accumulation, and overall financial security. After finding a representative sample containing the relevant variables that contribute to pay gaps, such as gender, race, experience, education, and job role, MC modeling is used to simulate a range of possible pay gap estimates. Based on the Monte Carlo results, a sensitivity analysis is performed to identify which variables have the most significant impact on pay gaps.

X-ray-Sensitive Doped CaF2-Based MRI Contrast Agents for Local Radiation Dose Measurement.

Ionizing radiation has become widely used in medicine, with application in diagnostic techniques, such as computed tomography (CT) and radiation therapy (RT), where X-rays are used to diagnose and treat tumors. The X-rays used in CT and, in particular, in RT can have harmful side effects; hence, an accurate determination of the delivered radiation dose is of utmost importance to minimize any damage to healthy tissues. For this, medical specialists mostly rely on theoretical predictions of the delivered dose or external measurements of the dose. To extend the practical use of ionizing radiation-based medical techniques, such as magnetic resonance imaging (MRI)-guided RT, a more precise measurement of the internal radiation dose internally is required. In this work, a novel approach is presented to measure dose in liquids for potential future in vivo applications. The strategy relies on MRI contrast agents (CAs) that provide a dose-sensitive signal. The demonstrated materials are (citrate-capped) CaF2 nanoparticles (NPs) doped with Eu3+ or Fe2+/Fe3+ ions. Free electrons generated by ionizing radiation allow the reduction of Eu3+, which produces a very small contrast in MRI, to Eu2+, which induces a strong contrast. Oxidative species generated by high-energy X-rays can be measured indirectly using Fe2+ because it oxidizes to Fe3+, increasing the contrast in MRI. Notably, in the results, a strong increase in the proton relaxation rates is observed for the Eu3+-doped NPs at 40 kV. At 6 MV, a significant increase in proton relaxation rates is observed using CaF2 NPs doped with Fe2+/Fe3+ after irradiation. The presented concept shows great promise for use in the clinic to measure in vivo local ionizing radiation dose, as these CAs can be intravenously injected in a saline solution.

Evaluating delivered radiation dose in intraoperative radiotherapy for breast cancer using TLD

The extra radiation that it delivers has been questioned by patients, physicians, and the public for early breast cancer patients of intraoperative radiotherapy (IORT). This investigation concerns a left breast Rando phantom with a lumpectomy cavity of 30 cm3 of left breast of Rando phantom made of polymethylmethacrylate (PMMA). Thermoluminescent dosimetry (TLD) was used to evaluate the extra radiation dose or air kerma (kair) rate under IORT from 20 Gy, 50 kV of an Xoft Axxent system. TLDs were first calibrated using 50 kV photons, and then inserted at phantom positions that were close to the positions of the represented organs and tissues. Equivalent doses (DT) delivered to the organ at risks (OAR) were evaluated according to ICRP 103. Entrance surface doses (ESD) or skin doses (Dskin) varied markedly among positions close to the lumpectomy cavity. The dose was 20 Gy at the surface of a balloon applicator and kair varied from 6.40 ± 0.92 Gy down to 1.20 ± 0.30 mGy along the left-right axis of the 17th slice of Rando. These experimental results are compared with those in the literature. The shielding effect of the tungsten-impregnated rubber was also evaluated. This study supports recommendations to patients, relatives, physicians and radiologists concerning IORT.

Possible mechanisms and simulation modeling of FLASH radiotherapy.

FLASH radiotherapy (FLASH-RT) has great potential to improve patient outcomes. It delivers radiation doses at an ultra-high dose rate (UHDR: ≥ 40Gy/s) in a single instant or a few pulses. Much higher irradiation doses can be administered to tumors with FLASH-RT than with conventional dose rate (0.01-0.40Gy/s) radiotherapy. UHDR irradiation can suppress toxicity in normal tissues while sustaining antitumor efficiency, which is referred to as the FLASH effect. However, the mechanisms underlying the effects of the FLASH remain unclear. To clarify these mechanisms, the development of simulation models that can contribute to treatment planning for FLASH-RT is still underway. Previous studies indicated that transient oxygen depletion or augmented reactions between secondary reactive species produced by irradiation may be involved in this process. To discuss the possible mechanisms of the FLASH effect and its clinical potential, we summarized the physicochemical, chemical, and biological perspectives as well as the development of simulation modeling for FLASH-RT.

Veza između nivoa citokina u serumu i razvoja akutne radijacione toksičnosti kod pacijenata sa karcinomom prostate

Radiotherapy plays a significant role in the multidisciplinary approach to treating prostate cancer patients. However, some of these patients may develop severe adverse effects after receiving radiotherapy that negatively affect their quality of life. Radiotoxicity may manifest in the lower gastrointestinal (GI) tract by damaging the rectum or bowel, or genitourinary (GU) tract, causing symptoms due to urethral, bladder or prostate damage. The probability of complications in normal tissue increases as the delivered radiation dose increases. However, there are patients with satisfactory dosimetric parameters who develop radiation toxicity and vice versa. Prediction models that take into account additional parameters to identify patients most susceptible to developing toxicity may serve as essential factors toward personalized radiotherapy. The main objectives are morbidity reduction and life-quality improvement. Changes in the cytokine levels could also be connected with the occurrence of acute gastrointestinal and genitourinary toxicity. Literature data indicate the association of numerous cytokines with the appearance of GI and GU toxicity. There is proof that TGF-b1 stimulates fibroblasts to generate extracellular matrix. According to the literature, IL-6 is regarded as one of the most important immune markers for predicting the radiotherapy-induced toxicity of normal tissues. Increased IL-6 concentrations in the serum during radiotherapy are significantly linked to a higher degree of acute genitourinary toxicity. The goal of this work is to summarize the results of contemporary research in which the connection between the occurrence of acute radiation toxicity and changes in the cytokines levels in the serum during radiotherapy were examined, considering the great future potential of the use of toxicity prediction factors in clinical practice. It can be concluded that radiation therapy, the development of an inflammatory process, and the occurrence of radiation toxicity are all related. However, further research with the aim of adequate stratification of patients for the development of an individualized approach to radiotherapy is required.

Dose-volume relationships of planned versus estimated delivered radiation doses to pelvic organs at risk and side effects in patients treated with salvage radiotherapy for recurrent prostate cancer

PurposeTo investigate estimated delivered dose distributions using weekly cone-beam computed tomography (CBCT) scans for pelvic organs at risk (OARs) in salvage radiotherapy (SRT) after radical prostatectomy. Furthermore, to compare them with the originally planned dose distributions and analyse associations with gastrointestinal (GI) and genitourinary (GU) side effects. MethodsThis study is part of a phase II trial involving SRT for recurrent prostate cancer. Treatment was personalised based on PSA response during SRT, classifying patients as PSA responders or non-responders. Estimated radiation dose distributions were obtained using deformable image registration from weekly CBCT scans. GI and GU toxicities were assessed using the RTOG toxicity scale, while patient-reported symptoms were monitored through self-assessment questionnaires. ResultsThe study included 100 patients, with similar treatment-related side effects observed in both responders and non-responders. Differences in dose-volume metrics between the planned and estimated delivered doses for the examined OARs were mostly modest, although generally statistically significant. We identified statistically significant associations between QUANTEC-recommended dose-volume constraints and acute bowel toxicity, as well as late urinary patient-reported symptoms, for both the estimated delivered and planned dose distributions. ConclusionWe found small but statistically significant differences between estimated delivered and planned doses to OARs. These differences showed trends toward improved associations for estimated delivered dose distributions with side effects. Enhanced registration methods and imaging techniques could potentially further enhance the assessment of truly delivered doses and yield more reliable dose-volume constraints for future therapies.

Determination of acceptable Hounsfield units uncertainties via a sensitivity analysis for an accurate dose calculation in the context of prostate MRI-only radiotherapy

Radiation therapy is moving from CT based to MRI guided planning, particularly for soft tissue anatomy. An important requirement of this new workflow is the generation of synthetic-CT (sCT) from MRI to enable treatment dose calculations. Automatic methods to determine the acceptable range of CT Hounsfield Unit (HU) uncertainties to avoid dose distribution errors is thus a key step toward safe MRI-only radiotherapy. This work has analysed the effects of controlled errors introduced in CT scans on the delivered radiation dose for prostate cancer patients. Spearman correlation coefficient has been computed, and a global sensitivity analysis performed following the Morris screening method. This allows the classification of different error factors according to their impact on the dose at the isocentre. sCT HU estimation errors in the bladder appeared to be the least influential factor, and sCT quality assessment should not only focus on organs surrounding the radiation target, as errors in other soft tissue may significantly impact the dose in the target volume. This methodology links dose and intensity-based metrics, and is the first step to define a threshold of acceptability of HU uncertainties for accurate dose planning.

The Impact of Tumor Location on Cardiac Toxicity in Patients Receiving Partial Breast Irradiation

Accelerated partial breast irradiation (APBI) is an appropriate modality for select women with low-risk breast cancer. While APBI delivers radiation dose to a smaller volume of breast tissue compared to whole breast irradiation, dose to the heart and coronary vessels may be relatively high, depending on the proximity of the tumor bed to these structures. The purpose of this study is to determine if there is a correlation between tumor location and risk of adverse cardiac events in women receiving APBI. This retrospective study included 341 women who received ABPI from 1993 to February 2017 at a single institution. APBI was delivered by catheter-based high-dose-rate (HDR) brachytherapy via single lumen or multi-channel devices (n = 340), or external beam brachytherapy (n = 1). Neither the heart nor cardiac substructures were contoured for patients receiving APBI with HDR brachytherapy. Univariate analysis (UVA) and multivariable analysis (MVA) were conducted to correlate patient age, smoking status, Charlson Comorbidity Index score (CCI), receipt of systemic therapy, and tumor location (right outer, right inner/central, left outer, left inner/central) with subsequent cardiac events. Univariate analyses for patient age, smoking status, CCI, receipt of systemic therapy, and tumor location in correlation to subsequent cardiac events were performed. On UVA, age at diagnosis and CCI score ≥2 were both significant with HR of 1.07 [1.05-1.10] (p<0.001) and HR of 7.02 [3.22-15.3] (p<0.001), respectively. On MVA, age at diagnosis and CCI score ≥2 remained significant with HR of 1.06 [1.03-1.09] (p = <0.001) and HR of 4.56 [2.02-10.40] (p = <0.001), respectively. There was a trend of statistically significant correlation between cardiac events and left inner/central tumor location when compared to right outer tumor location with a HR of 2.06 [1.00,4.24] (p = 0.05). Treatment of tumor beds located in the inner/central portion of the left breast may increase the risk of developing cardiac toxicity in patients receiving APBI. These data support careful contouring and avoidance of cardiac structures during APBI treatment planning, including HDR brachytherapy.

Dosimetric Evaluation of Targets and Organs at Risk in Dose Escalation Study for Total Marrow and Lymphoid Irradiation

Total marrow and lymphoid irradiation (TMLI) delivers radiation dose to the bone marrow and lymph nodal region while reducing the dose to non-target organs. We conducted a dose-escalation study of TMLI to improve treatment outcomes while reducing OAR doses using intensity-modulated radiation therapy. However, this dose escalation strategy may cause increasing risk of recurrence and adverse events because of dose uniformity compromises of the target. We hypothesized that the homogeneity index (HI) could become worse with increased target's dose while maintaining reduced OAR doses for the nine patients enrolled in the TMLI phase Ⅰ clinical trial. Nine patients treated with TMLI using a treatment delivery system from September 2019 to August 2021 were included. The prescribed doses were 14 Gy/6 fr, 16 Gy/6 fr, and 18 Gy/6 fr twice daily for 3 days, with three patients allocated each prescription. Bone marrow, lymph nodal region, spleen, testis, brain, and liver were designated as targets. The bone marrow was divided into eight parts (see Table); an individual PTV margin was added to each structure. We intended to deliver the D80% prescription dose for PTV. For the brain and liver, the prescribed dose was 12 Gy in consideration of function preservation. Lenses, oral cavity, parotid glands, lungs, heart, esophagus, stomach, kidneys, intestines, and breasts were defined as OAR. Targets were evaluated with HI that was calculated using the formula HI = (D2%-D98%)/D50%, based on ICRU report 83. For OARs, Dmax, D2%, D10%, and mean dose constraint were evaluated. The table lists HI for the PTV_ALL and each target. The HI of PTV_ALL rose with increasing prescription dose and was highest at 18 Gy. The highest HI was 0.632 for PTV_Rib at 18 Gy, and the lowest HI was 0.045 for PTV_testis at 14 Gy. OAR Dose constraints were achieved in all patients. The average OAR doses in all cases for lenses, oral cavity, parotid glands, lungs, heart, esophagus, intestines, kidneys, and breast were 4.7±0.80, 4.4±0.51, 6.7±0.48, 7.6±0.22, 7.8±0.19, 6.7±0.18, 7.4±1.12, 6.9±0.96, and 14.7 Gy, respectively. The Dmax of the lenes, D2% of the esophagus, and D10% of the stomach were 7.2 ± 1.09, 11.5 ± 0.47, and 10.9 ± 0.98 Gy, respectively. In the TMLI phase I clinical trial, we evaluated the dose uniformity to the targets and the OAR dose constraints. Although the HI for PTV_ALL worsened with increasing prescription dose, compliance with OAR dose constraints was achieved in all patients.

Redefining precision radiotherapy through liquid biopsy.

Precision radiotherapy refers to the ability to deliver radiation doses with sub-millimetre accuracy. It does not however consider individual variation in tumour or normal tissue response, failing to maximise tumour control and minimise toxicity. Combining precise delivery with personalised dosing, through analysis of cell-free DNA, would redefine precision in radiotherapy.

CBCT-based deformable dose accumulation of external beam radiotherapy in cervical cancer

Background: Delivered radiotherapy doses do not exactly match those planned for a course of treatment, largely due to inter-fraction changes in anatomy. In this study, accumulated delivered dose was calculated for a sample of cervical cancer patients, by deformably registering daily cone beam computed tomography (CBCT) images to the planning computed tomography (CT) scan. Planned and accumulated doses were compared for the clinical target volume (CTV), bladder, and rectum. Material and Methods: For 10 patients receiving 45 Gy in 25 fractions of external beam radiotherapy, daily dose distributions were calculated on CBCT. These images were deformed onto the planning CT and the dose was accumulated using Velocity 4.1 (Varian Medical Systems, Palo Alto, USA). The quality of deformable image registration was evaluated visually and by calculating Dice similarity coefficients and mean distance to agreement. Results: V95%>99% was achieved for the primary CTV in 9/10 patients for the planned dose distribution and 7/10 patients for the accumulated dose distribution. Primary CTV coverage by 95% of the prescription dose was reduced in one patient, due to an increase in anterior-posterior separation. Comparison of planned and accumulated dose volume histograms (DVHs) for the bladder and rectum found agreement within 5% at low and intermediate doses, but differences exceeded 20% at higher doses. Direct addition of CBCT DVHs was seen to be a poor estimate for the accumulated DVH at higher doses. Conclusion: Computation of delivered radiotherapy dose that accounts for inter-fraction anatomical changes is important for establishing dose-effect relationships. Updating delivered dose distributions after each fraction would support informed clinical decision making on any potential treatment interventions.

Difference between planned and delivered radiotherapy dose to the internal mammary nodes in high-risk breast cancer patients.

Chest wall movement during radiotherapy can impact the delivered dose to the internal mammary nodes (IMN) in high-risk breast cancer patients. Using portal imaging and dose reconstruction we aimed to examine the delivered IMN dose coverage. Cine MV images were recorded for 39 breast cancer patients treated with daily image-guided radiotherapy (IGRT) in deep-inspiration breath-hold (DIBH). On the final frame of each cine MV recording the chest wall was matched with the Digitally Reconstructed Radiograph (DRR) from the treatment plan. The geometrical chest wall error was determined in the imager-plane perpendicular to the cranio-caudal direction, rounded to integer millimeters, and binned. For each 1mm bin, an isocenter-shifted treatment plan was recalculated assuming that the projected error observed in the cine MV image was caused by anterior-posterior chest wall movement in the IMN region. A weighted plan sum yielded the IMN clinical target volume receiving at least 90% dose (V90_CTVn_IMN). The mean number of cine MV observations per patient was 36 (range 26-55). Most patients (67%) had on average a posterior chest wall position at treatment compared to planned. This translated into a change in the delivered median V90_CTVn_IMN of -0.7% (range, -11.9-2.9%; p<0.001). The V90_CTVn_IMN reduction wasgreater than9% in three patients. No clinically relevant differences were found for the mean lung dose or mean heart dose. Using cine MV images, we found that the delivered V90_CTVn_IMN was significantly lower than planned. In 8% of the patients, the V90_CTVn_IMN reduction exceeded 9%.

177Lu-PSMA radioligand therapy for patients with recurrent/metastatic (R/M) salivary gland cancer (SGC): A phase II pilot study.

6099 Background: New treatments are warranted due to limited systemic treatment options for SGC patients (pts). Gallium [68Ga]Ga prostate-specific membrane antigen (PSMA) PET imaging results in SGC pts have demonstrated PSMA expression of SGC and thus indicated that PSMA radionuclide therapy may be a useful option, especially in the case of adenoid cystic carcinoma (AdCC) and salivary duct carcinoma (SDC) subtypes. Therefore, this study (EudraCT number 2019-003857-27) evaluated the safety and efficacy of PSMA-targeted radionuclide therapy in AdCC and SDC pts. Methods: This was a single-center, single-arm, phase II pilot study. R/M AdCC (n = 10) and SDC (n = 5) pts with sufficient PSMA tracer uptake on [68Ga]Ga-PSMA PET imaging, i.e., ≥1 lesion ≥1.5cm with PSMA expression above mean liver level, were treated with 2-4 cycles of 7.4 GBq [177Lu]Lu-PSMA-I&amp;T, with an interval of 6±1 weeks. Baseline imaging was repeated for evaluation 4 weeks after cycle 2; in case of progressive disease (PD) per RECIST 1.1 the treatment was discontinued; otherwise, pts received the full treatment (4 cycles). All pts received whole body post-therapeutic imaging after 1, 24, 48, 72 h and 7d after each cycle. The primary endpoint was safety. Secondary endpoints include the objective response rate, progression-free survival (PFS), and overall survival (OS). Results: Between 6-2020 and 2-2023, 15 AdCC pts and 10 SDC pts were screened for eligibility. Five AdCC pts and 8 SDC pts were screen failures due to insufficient PSMA expression in 11 pts (AdCC n = 4; SDC n = 7) or due to brain metastases in 2 pts (AdCC n = 1; SDC n = 1). Ten AdCC and 2 SDC pts received at least one cycle of 7.4 GBq [177Lu]Lu-PSMA-I&amp;T. The most observed adverse events (grade 1-2) included: nausea (75%), dry mouth (75%), fatigue (67%), and anemia (58%). Two pts (17%) developed grade 3 toxicity; lymphocytopenia (n = 1) and hyponatremia (n = 1). No grade 4-5 toxicities were observed. Two pts (AdCC n = 1; SDC n = 1) received only 1 treatment cycle due to early PD. The interim-treatment evaluation resulted in the discontinuation of treatment after 2 cycles in an additional 3 AdCC and the second SDC pts due to PD. Six AdCC pts received the full treatment (4 cycles); no responses were observed; 3 pts (75%) showed stable disease of more than 3 months after treatment completion (5, 15 and 21 months); 3 pts showed PD at 3 months after treatment completion. Median PFS in 10 AdCC pts was 6.7 months (95%CI: 0.0-15.1); OS was not reached after a median follow-up of 11.9 months. Conclusions: [177Lu]Lu-PSMA-I&amp;T treatment in SGC pts is well-tolerated. The efficacy in AdCC was limited; only stable disease was achieved in 3 out of 10 pts. In most screened SDC pts, PSMA expression was insufficient to undergo [177Lu]Lu-PSMA-I&amp;T treatment; the 2 SDC pts included showed early PD. Dosimetry analyses will be performed to calculate the delivered radiation doses to organs at risk as well as tumor lesions. Clinical trial information: EUCTR2019-003857-27.

Location of Recurrences after Trimodality Treatment for Glioblastoma with Respect to the Delivered Radiation Dose Distribution and Its Influence on Prognosis.

While prognosis of glioblastoma after trimodality treatment is well examined, recurrence pattern with respect to the delivered dose distribution is less well described. Therefore, here we examine the gain of additional margins around the resection cavity and gross-residual-tumor. All recurrent glioblastomas initially treated with radiochemotherapy after neurosurgery were included. The percentage overlap of the recurrence with the gross tumor volume (GTV) expanded by varying margins (10 mm to 20 mm) and with the 95% and 90% isodose was measured. Competing-risks analysis was performed in dependence on recurrence pattern. Expanding the margins from 10 mm to 15 mm, to 20 mm, to the 95%- and 90% isodose of the delivered dose distribution with a median margin of 27 mm did moderately increase the proportion of relative in-field recurrence volume from 64% to 68%, 70%, 88% and 88% (p < 0.0001). Overall survival of patients with in-and out-field recurrence was similar (p = 0.7053). The only prognostic factor significantly associated with out-field recurrence was multifocality of recurrence (p = 0.0037). Cumulative incidences of in-field recurrences at 24 months were 60%, 22% and 11% for recurrences located within a 10 mm margin, outside a 10 mm margin but within the 95% isodose, or outside the 95% isodose (p < 0.0001). Survival from recurrence was improved after complete resection (p = 0.0069). Integrating these data into a concurrent-risk model shows that extending margins beyond 10 mm has only small effects on survival hardly detectable by clinical trials. Two-thirds of recurrences were observed within a 10 mm margin around the GTV. Smaller margins reduce normal brain radiation exposure allowing for more extensive salvage radiation therapy options in case of recurrence. Prospective trials using margins smaller than 20 mm around the GTV are warranted.

Towards quantitative in vivo dosimetry using x-ray acoustic computed tomography.

Radiation dosimetry is essential for radiation therapy (RT) to ensure that radiation dose is accurately delivered to the tumor. Despite its wide use in clinical intervention, the delivered radiation dose can only be planned and verified via simulation. This makes precision radiotherapy challenging while in-line verification of the delivered dose is still absent in the clinic. X-ray-induced acoustic computed tomography (XACT) has recently been proposed as an imaging tool for in vivo dosimetry. Most of the XACT studies focus on localizing the radiation beam. However, it has not been studied for its potential for quantitative dosimetry. The aim of this study was to investigate the feasibility of using XACT for quantitative in vivo dose reconstruction during radiotherapy. Varian Eclipse system was used to generate simulated uniform and wedged 3D radiation field with a size of 4 cm 4 cm. In order to use XACT for quantitative dosimetry measurements, we have deconvoluted the effects of both the x-ray pulse shape and the finite frequency response of the ultrasound detector. We developed a model-based image reconstruction algorithm to quantify radiation dose in vivo using XACT imaging, and universal back-projection (UBP) reconstruction is used as comparison. The reconstructed dose was calibrated before comparing it to the percent depth dose (PDD) profile. Structural similarity index matrix (SSIM) and root mean squared error (RMSE) are used for numeric evaluation. Experimental signals were acquired from 4 cm 4 cm radiation field created by Linear Accelerator (LINAC) at depths of 6, 8, and 10 cm beneath the water surface. The acquired signals were processed before reconstruction to achieve accurate results. Applying model-based reconstruction algorithm with non-negative constraints successfully reconstructed accurate radiation dose in 3D simulation study. The reconstructed dose matches well with the PDD profile after calibration in experiments. The SSIMs between the model-based reconstructions and initial doses are over 85%, and the RMSEs of model-based reconstructions are eight times lower than the UBP reconstructions. We have also shown that XACT images can be displayed as pseudo-color maps of acoustic intensity, which correspond to different radiation doses in the clinic. Our results show that the XACT imaging by model-based reconstruction algorithm is considerably more accurate than the dose reconstructed by UBP algorithm. With proper calibration, XACT is potentially applicable to the clinic for quantitative in vivo dosimetry across a wide range of radiation modalities. In addition, XACT's capability of real-time, volumetric dose imaging seems well-suited for the emerging field of ultrahigh dose rate "FLASH" radiotherapy.

Radioembolization with Yttrium-90 Glass Microspheres as a First-Line Treatment for Unresectable Intrahepatic Cholangiocarcinoma—A Prospective Feasibility Study

PurposeTo evaluate the safety and effectiveness of yttrium-90 (90Y) radioembolization as first-line treatment for unresectable intrahepatic cholangiocarcinoma (ICC). Materials and MethodsThis prospective study enrolled patients who had never received chemotherapy, liver embolization, and radiation therapy. The tumors were solitary in 16 patients, multiple in 8 patients, unilobar in 14 patients, and bilobar in 10 patients. Patients underwent transarterial radioembolization with 90Y-labeled glass microspheres. The primary end point was hepatic progression-free survival (HPFS). Secondary end points were overall survival (OS), tumor response, and toxicity. ResultsTwenty-four patients (age, 72.3 years ± 9.3; 12 women) were included in the study. The median delivered radiation dose was 135.5 Gy (interquartile range, 77.6 Gy). The median HPFS was 5.5 months (95% CI, 3.9–7.0 months). Analysis failed to identify any prognostic factor associated with HPFS. Imaging response at 3 months showed 56% disease control, and the best radiographic response was 71% disease control. The median OS from the radioembolization treatment was 19.4 months (95% CI, 5.0–33.7). Patients with solitary ICC had significantly longer median OS than patients with multifocal ICC: 25.9 months (95% CI, 20.8–31.0 months) versus 10.7 months (95% CI, 8.0–13.4 months) (P = .02). Patients with progression on the 3-month imaging follow-up had significantly shorter median OS than patients who had stable disease at 3 months: 10.7 months (95% CI, 0.7–20.7 months) versus 37.3 months (95% CI, 16.5–58.1 months) (P = .003). Two (8%) Grade 3 toxicities were reported. ConclusionsFirst-line treatment of ICC with radioembolization showed promising OS and minimal toxicity, especially in patients with solitary tumor. Radioembolization may be considered as a first-line treatment option for unresectable ICC.