Liver Dose Research Articles

Development of a novel automated algorithm for patient dosimetry in computed tomography: a step towards the facilitation of size-specific dose estimates and organs dosimetry estimations in a busy clinical workflow

Abstract Accurate dosimetry in computed tomography (CT) is essential for patient safety and effective radiation management. This study presents the development of an automated algorithm designed to enhance patient dosimetry by facilitating size-specific dose estimates (SSDE) and organ dose estimations. Utilizing a Python-based script, the proposed method integrates advanced image preprocessing, contour detection, and mathematical calculations to quantify key metrics from CT images. This automated approach addresses the limitations of manual measurement techniques. A retrospective analysis was conducted on CT axial images from examinations acquired with an 80-detector scanner. The algorithm processes DICOM images, converts pixel values to Hounsfield Units, applies Gaussian smoothing, windowing, and thresholding, followed by morphological operations to refine segmentation. It measures the water equivalent diameter (Dw) and estimates both region SSDE and organ doses, incorporating tissue attenuation. Validation was performed using an adult anthropomorphic ATOM phantom, with organ doses measured by optically stimulated luminescence dosimeters. The results demonstrated the algorithm's potential in estimating SSDE and organ doses. Validation of the automated method revealed strong correlations for Dw and SSDE between the proposed method and manual measurements of five expert reviewers ranging from 0.86 to 0.99 for determination coefficient. Comparative analysis of organ doses showed close agreement between results from experimental setup against the proposed algorithm. The automated algorithm estimated brain dose with a mean of 21.8 mGy, while measurements from the ATOM phantom and CT Expo indicated 19.74 mGy and 23.05 mGy, respectively. For lung doses, the automated algorithm estimated 12.5 mGy compared to 11.0 mGy from the ATOM phantom and 13.1 mGy from CT Expo. Liver doses were measured at 12.7 mGy by the automated method, versus 12.1 mGy from the ATOM phantom and 11.1 mGy from CT Expo. This study shows the potential of automated image analysis techniques in enhancing dosimetry accuracy in CT examinations.

Development and validation of an innovative administration system to facilitate controlled holmium-166 microsphere administration during TARE

BackgroundTo develop and validate a novel administration device for holmium-166 transarterial radioembolisation (TARE) with the purpose of facilitating controlled fractional microsphere administration for a more flexible and image-guided TARE procedure.MethodsA Controlled Administration Device (CAD) was developed using MR-conditional materials. The CAD contains a rotating syringe to keep the microspheres in suspension during administration. Different rotational speeds were tested ex vivo to optimise the homogeneity of microsphere fractions administered from the device. The technical performance, accuracy, and safety was validated in three patients in a clinical TARE setting by administering a standard clinical dose in 5 fractions (identifier: NCT05183776). MRI-based dosimetry was used to validate the homogeneity of the given fractions in vivo, and serious adverse device event ((S)A(D)E) reporting was performed to assess safety of the CAD.ResultsA rotational speed of 30 rpm resulted in the most homogeneous microsphere fractions with a relative mean deviation of 1.1% (range: -9.1-8.0%). The first and last fraction showed the largest deviation with a mean of -26% (std. 16%) and 7% (std. 13%). respectively. In the three patient cases the homogeneity of the microsphere fractions was confirmed given that MRI-based dosimetry showed near linear increase of mean absorbed target liver dose over the given fractions with R2 values of 0.98, 0.97 and 0.99. No (S)A(D)E’s could be contributed to the use of the CAD.ConclusionsThe newly developed CAD facilitates safe and accurate fractional microsphere administration during TARE, and can be used for multiple applications in the current and future workflows of TARE.

Treatment Time and Dosimetric Advantage in Cone Beam Computed Tomography-Guided Online Adaptive Radiation Therapy Considering Interfractional and Intrafractional Changes in Patients With Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

Radiation therapy is the standard treatment for localized gastric mucosa-associated lymphoid tissue (MALT) lymphoma. The ETHOS system (Varian Medical System) has enabled us to perform cone beam computed tomography (CBCT)-guided online adaptive radiation therapy (oART). This study presents a retrospective dosimetric analysis for interfractional and intrafractional change and treatment time in oART for gastric MALT lymphoma. We included 3 male patients with gastric MALT lymphoma who underwent exhalation breath-hold fasting oART using the SpiroDynr'X system. Treatment details and plans (3 reference [REF] plans, 51 scheduled [SCH] plans, and adapted [ADP] plans) were retrospectively analyzed. Doses to the clinical target volume in planning CT (CTV_REF), CTV1, and CTV2 (representing the stomach in planning and preirradiation CBCT, respectively) and planning target volume (PTV) in the planning CBCT were estimated. D2%, D98%, D50%, and Dmean for these volumes, along with organ-at-risk doses, were examined across the 3 plans. The PTV dose coverage of CTV2 on preirradiation CBCT was calculated. CBCT-guided oART was completed within the scheduled period, using the ADP plans instead of the SCH plans on each treatment day in all cases. The average treatment time was approximately 45 minutes. CTV1 and CTV2 exhibited intrafractional and interfractional variations, fluctuating above and below CTV_REF. Some ADP plans resulted in incomplete PTV coverage of CTV2, but the unincluded volume was <1% of CTV2. D50%, D98%, and Dmean of CTV1, CTV2, and PTV were significantly improved in the ADP plans than in the SCH plans. Moreover, the Dmean to the liver and kidneys was reduced in the ADP plans. CBCT-guided oART in patients with gastric MALT lymphoma demonstrated that ADP plans improved CTV1, CTV2, and PTV doses and reduced the mean bilateral kidney and liver doses, suggesting that it may offer enhanced treatment precision for gastric MALT lymphoma.

Clinical outcomes and safety of external beam radiotherapy with extensive intrahepatic targets for advanced hepatocellular carcinoma: A single institutional clinical experience.

This study observed the clinical outcome of radiotherapy to extensive intrahepatic targets for advanced hepatocellular carcinoma (HCC) in a single institution. From September 2009 to July 2021, patients who underwent fractionated radiotherapy to a planning target volume (PTV) of over 100 ml with biological effective dose >30 Gy10 for advanced HCC were enrolled. Overall survival (OS) and radiation-induced liver toxicity (RILD) were evaluated. RILD was defined as an increase in Child-Pugh (CP) score ≥2 or liver function tests ≥2.5 times at 3 months after the end of radiotherapy. A total of 136 patients were evaluated. Eighty-nine patients had portal vein tumor thrombus (PVTT), 37 patients were in CP B stage, and the median radiation dose to PTV was 48.8 Gy10. The median OS was 12.3 months. The factors most affecting OS were PVTT (P = 0.001), PTV (>500 ml, P = 0.001), incomplete coverage of the intrahepatic tumor (P = 0.004), and CP B (P = 0.006) in Cox regression. RILD occurred in 22.4% of the patients and was affected by PVTT (P = 0.003), PTV (P = 0.010), pretreatment bilirubin levels (>1.5 mg/ml, P = 0.016), and the mean normal liver dose (MNLD) (≥ EQD2 18 Gy3, P = 0.021) in binary logistic regression. As the PTV was in excess of >500 ml, RILD developed in 30.2% of patients and the prognostic importance of pretreatment bilirubin levels (P = 0.006) and the MNLD (P = 0.014) increased. As PTV is more extensive, the bilirubin level and the MNLD have to be taken into consideration for safe radiotherapy, in addition to the traditional prognostic factors.

A Multicentric study on a dosimetric comparison of extended SSD technique, VMAT-Based and helical tomotherapy (HT) for total body irradiation (TBI)

PurposeIn study, it was aimed to evaluate the dose volume histograms (DVH) of extended SSD technique, VMAT-based, and helical tomotherapy plans dosimetrically in a multi-institutional context to achieve higher plan quality and to harmonize total body irradiation plans. MethodsFour different clinical centers participated in the study. The CT images of ten patients were used in this study. During the first phase, ten patients enrolled for TBI were planned by multiple centers according to a common protocol. During the second phase, all centers shared their plans’ DVHs. Treatment plans were evaluated according to the critical organ dose limits. Statistical analysis was performed in the SPSS (version 22.0) program (p < 0.05). ResultsIn study, the results indicated that there was a statistically significant and considerable difference in the dose coverage of PTV, beam delivery time and MU, lens doses, and kidney doses between the four techniques (p < 0.001). The mean lung doses of the four centers were below 10 Gy. No significant difference in maximum liver doses between plans was obtained. ConclusionIn conclusion, although four treatment techniques were suitable for TBI treatment, more homogeneous dose distribution, and lower critical organ doses were obtained with the tomotherapy technique. However, treatment time, MU, and dose rate for lung were disadvantages of the tomotherapy technique. When it comes to deciding on the TBI treatment method, it need to be reviewed some important points. It is needed to sufficient data on long-term results to be able to standardize TBI techniques between centers.

General toxicity and screening of reproductive and developmental toxicity following bioaccumulation of oral-dosed perfluorooctanoic acid: Loss of the Golgi apparatus

Despite its widespread use as a stabilizer across various industries over the past several decades, the health effects of chronic exposure to PFOA are still unclear. We administered PFOA by oral gavage (0, 12.5, 50, and 200 μg/day/mouse, eight groups) to male and female mice for six months. Body weight gain decreased with dose accompanied by increased liver weight, and PFOA altered liver damage-related-blood biochemical indicators and induced pathological lesions, including hepatocellular hypertrophy, cholangiofibrosis, and centrilobular hepatocellular vacuolation. Loss of the Golgi apparatus, formation of lamellar body-like structures, and lipid accumulation were observed in the liver of PFOA-treated mice. We also cohabited five pairs of male and female mice for the last ten days of administration, dosed PFOA to dam up to 28 days after birth, and investigated effects on reproduction and development. The survival rate of pups and the sex ratio of surviving mice decreased significantly at the highest dose. PFOA tissue concentration increased with the dose in the parent mice's liver and the pups' blood and brain. Taken together, we suggest that PFOA primarily affects the liver and reproduction system and that disturbance in lipid metabolism and Golgi's structural stability may be involved in PFOA-induced toxicity.

Efficient bone marrow irradiation and low uptake by non-haematological organs with an yttrium-90-anti-CD66 antibody prior to haematopoietic stem cell transplantation

We report the results of a Phase I radiation dose escalation study using an yttrium-90 (90Y) labelled anti-CD66 monoclonal antibody given with standard conditioning regimen for patients receiving haematopoietic stem cell transplants for myeloid leukaemia or myeloma. The 90Y-labelled anti-CD66 was infused prior to standard conditioning. In total, 30 patients entered the trial and 29 received 90Y-labelled mAb, at infused radiation activity levels of 5, 10, 25, or 37.5 megaBequerel (MBq)/kg lean body weight. A prerequisite for receiving the 90Y-labelled mAb was favourable dosimetry determined by single-photon emission computerised tomography (SPECT) dosimetry following administration of indium-111 (111In) anti-CD66. Estimated absorbed radiation doses delivered to the red marrow demonstrated a linear relationship with the infused activity of 90Y-labelled mAb. At the highest activity level of 37.5 MBq/kg, mean estimated radiation doses for red marrow, liver, spleen, kidneys and lungs were 24.6 ± 5.6 Gy, 5.8 ± 2.7 Gy, 19.1 ± 8.0 Gy, 2.1 ± 1.1 and 2.2 ± 0.9, respectively. All patients engrafted, treatment-related mortality 1-year post-transplant was zero. Toxicities were no greater than those anticipated for similar conditioning regimens without targeted radiation. The ability to substantially intensify conditioning prior to haematopoietic stem cell transplantation without increasing toxicity warrants further testing to determine efficacy. clinicaltrials.gov identifier: NCT01521611.

Resin-Based 90 Y Tumor Dose as a Predictor of Duration of Response and Survival in Patients With Surgically Unresectable Hepatocellular Carcinoma : A Prospective Single-Arm Study.

Personalized dosimetry improves overall survival (OS) in patients with hepatocellular carcinoma (HCC) treated with glass 90 Y radioembolization. This study evaluated personalized tumor dose (TD) as a predictor of OS, progression-free survival (PFS), and local duration of response (DOR) in patients with surgically unresectable HCC treated with resin 90 Y radioembolization. This prospective, single-center, single-arm clinical trial (NCT04172714) evaluated the efficacy of scout activity of resin 90 Y versus 99m Tc-MAA for treatment planning. A secondary aim of this study was to evaluate personalized dosimetry as a predictor of OS, PFS, and DOR. Partition dosimetry model was utilized for nonsegmental therapies with targeted TD >200 Gy and nontumoral liver dose <70 Gy. Single compartment dose of 200 Gy was used for segmentectomies. OS, PFS, and local DOR from 90 Y was estimated using Kaplan-Meier estimation with log-rank analysis used to determine predictors of prolonged survival. Thirty patients with treatment-naive HCC and 33 tumors (19 segmental and 14 nonsegmental) were included. Overall, 18 patients underwent segmental Y90-RE and 12 underwent non-segmental/lobar therapies. The mean 90 Y TD was 493 Gy. The median follow-up since enrollment into the study was 37 months. The mean OS was 32.2 months for the entire cohort. A total of 5 patients underwent orthotopic liver transplantation post 90 Y and were excluded from further survival analysis. The mean OS for the remainder of the cohort was 30.1 months (median not reached). The mean TD >250 Gy resulted in prolonged mean OS and PFS. The median local DOR was 32.7 months with mean TD 330 Gy predicting prolonged DOR. For patients with surgically unresectable HCC treated with resin 90 Y, there is mean TD threshold predicting prolonged OS, PFS, and local DOR. Therefore, there should be further emphasis on personalized dosimetry for optimization of patient outcomes.

Hypofractionated Radiotherapy-Related Lymphopenia Is Associated With Worse Survival in Unresectable Intrahepatic Cholangiocarcinoma.

The aim of this study was to evaluate the incidence of radiotherapy (RT)-related lymphopenia, its predictors, and association with survival in unresectable intrahepatic cholangiocarcinoma (ICC) treated with hypofractionated-RT (HF-RT). Retrospective analysis of 96 patients with unresectable ICC who underwent HF-RT (median 58.05 Gy in 15 fractions) between 2009 and 2022 was performed. Absolute lymphocyte count (ALC) nadir within 12 weeks of RT was analyzed. Primary variable of interest was severe lymphopenia, defined as Grade 3+ (ALC <0.5 k/μL) per CTCAE v5.0. Primary outcome of interest was overall survival (OS) from RT. Median follow-up was 16 months. Fifty-two percent of patients had chemotherapy pre-RT, 23% during RT, and 40% post-RT. Pre-RT, median ALC was 1.1 k/μL and 5% had severe lymphopenia. Post-RT, 68% developed RT-related severe lymphopenia. Patients who developed severe lymphopenia had a significantly lower pre-RT ALC (median 1.1 vs. 1.5k/μL, P =0.01) and larger target tumor volume (median 125 vs. 62 cm 3 , P =0.02). In our multivariable Cox model, severe lymphopenia was associated with a 1.7-fold increased risk of death ( P =0.04); 1-year OS rates were 63% vs 77% ( P =0.03). Receipt of photon versus proton-based RT (OR=3.50, P =0.02), higher mean liver dose (OR=1.19, P <0.01), and longer RT duration (OR=1.49, P =0.02) predicted severe lymphopenia. HF-RT-related lymphopenia is an independent prognostic factor for survival in patients with unresectable ICC. Patients with lower baseline ALC and larger tumor volume may be at increased risk, and use of proton therapy, minimizing mean liver dose, and avoiding treatment breaks may reduce RT-related lymphopenia.

Valuation of advanced Dosimetry in Transarterial Radioembolization of Hepatocellular Carcinoma with 90Y microspheres

Objective : The aim of our study was to analyze the relationships between tumor (T) and normal tissue (N) absorbed dose in relation to the clinical outcomes in hepatocellular carcinoma (HCC) patients treated with 90Y microspheres. Materials and methods : After transarterial radioembolization of HCC with 90Y microspheres, 62 patients (10 females: 52 males, mean age 68.2±8.2 years) were imaged using a four-ring, time-of-flight (TOF), PET/CT system. Low dose, non-diagnostic CT images from PET/CT were utilized for localization of the 90Y microspheres and attenuation correction of PET images. Response assessment was conducted using mRECIST criteria on MRI one month post treatment and subsequently every three months after 90Y treatment. Results : Among 62 patients, mean liver, tumor, and normal tissue doses (mean ± SD) were 51.38±23.32 Gy, 682.60±785.19 Gy and 45.54±21.19 Gy, respectively. Out of these patients, 39 exhibited complete response (CR), 11 showed partial response (PR), 2 had stable disease (SD), and 10 showed progression of the disease (PD). For CR+PR patients the mean T was 824.63±833.10 Gy, whereas for PD patients, the mean T was significantly lower at 205.70±183.22 Gy. The mean liver and normal tissue doses were comparable; for CR+PR patients had liver and normal tissue doses of 51.01±22.55 Gy and 45.18±20.68 Gy, respectively, and for PD patients, these values were 54.34±26.73 Gy and 49.10±22.97 Gy, respectively. Conclusion : Despite not considering the partial volume effect and having a limited number of PD cases, our data indicates a statistically significant lower (P = 0.0001) tumor dose in patients with disease progression compared to those with complete and partial response. These results suggest that post-therapy personalized, and image-based dosimetry provides promising predictive outcomes in 90Y microsphere radiation therapy for liver cancers.

Managing hepatocellular carcinoma across the stages: efficacy and outcomes of stereotactic body radiotherapy

PurposeHepatocellular carcinoma (HCC) poses a unique challenge due to its predilection for developing on compromised livers, often limiting surgical options. Stereotactic body radiotherapy (SBRT) has emerged as a promising local treatment modality for HCC. This study aims to assess the effectiveness of SBRT in HCC patients not suitable for surgery, focusing on local control, optimal radiation dosing, and prognostic factors.MethodsIn this retrospective analysis, 52 HCC patients treated with SBRT were examined. The study assessed local control, progression-free survival (PFS), and overall survival (OS) while conducting dosimetric analyses. The relationship between mean liver dose and Child–Pugh score (CPS) progression was also explored.ResultsSBRT demonstrated 93.4% freedom from local progression (FFLP) at 12 months. Notably, a near minimum dose (D98%) below 61 Gy as an equivalent dose in 2‑Gy fractions with α/β 10 Gy (EQD2α/β10) was associated with reduced FFLP (p-value 0.034). Logistic regression analysis revealed a dose–response relationship for FFLP and D98% with 95% and 98% probability of FFLP at a dose of 56.9 and 73.1 Gy, respectively. The study observed OS rates of 63.7% at 1 year and 34.3% at 3 years. Patients with portal vein tumor thrombus (PVTT) and larger tumors (≥ 37 cm3) experienced decreased PFS and OS. Multivariate analysis identified PVTT, larger tumor volume, and performance status as independent predictors of reduced OS. Notably, classical radiation-induced disease (cRILD) was absent, but nonclassical (nc) RILD occurred in 7.7% of patients. Regression analysis linked a mean EQD2α/β3–8 dose to the liver (12.8–12.6) with a 10% likelihood of ncRILD.ConclusionSBRT offers a compelling option for achieving high local control and promising survival outcomes in HCC. The study supports a radiation dose range of 61–73.1 Gy, coupled with a mean liver dose under 12.6–12.8 Gy as EQD2, to achieve favorable FFLP rates, with acceptable toxicity rates.

REPeated mAgnetic resonance Image-guided stereotactic body Radiotherapy (MRIg-reSBRT) for oligometastatic patients: REPAIR, a mono-institutional retrospective study

BackgroundOligo-progression or further recurrence is an open issue in the multi-integrated management of oligometastatic disease (OMD). Re-irradiation with stereotactic body radiotherapy (re-SBRT) technique could represent a valuable treatment option to improve OMD clinical outcomes. MRI-guided allows real-time visualization of the target volumes and online adaptive radiotherapy (oART). The aim of this retrospective study is to evaluate the efficacy and toxicity profile of MRI-guided repeated SBRT (MRIg-reSBRT) in the OMD setting and propose a re-SBRT classification.MethodsWe retrospectively analyzed patients (pts) with recurrent liver metastases or abdominal metastatic lesions between 1 and 5 centimeters from liver candidate to MRIg-reSBRT showing geometric overlap between the different SBRT courses and assessing whether they were in field (type 1) or not (type 2).ResultsEighteen pts completed MRIg-reSBRT course for 25 metastatic hepatic/perihepatic lesions from July 2019 to January 2020. A total of 20 SBRT courses: 15 Type 1 re-SBRT (75%) and 5 Type 2 re-SBRT (25%) was delivered. Mean interval between the first SBRT and MRIg-reSBRT was 8,6 months. Mean prescribed dose for the first treatment was 43 Gy (range 24–50 Gy, mean BEDα/β10=93), while 41 Gy (range 16–50 Gy, mean BEDα/β10=92) for MRIg-reSBRT. Average liver dose was 3,9 Gy (range 1–10 Gy) and 3,7 Gy (range 1,6–8 Gy) for the first SBRT and MRIg-reSBRT, respectively. No acute or late toxicities were reported at a median follow-up of 10,7 months. The 1-year OS and PFS was 73,08% and 50%, respectively. Overall Clinical Benefit was 54%.ConclusionsMRIg-reSBRT could be considered an effective and safe option in the multi-integrated treatment of OMD.

Co-relation of Portal Vein Tumour Thrombus Response With Survival Function Following Robotic Radiosurgery in Vascular Invasive Hepatocellular Carcinoma

Purpose or ObjectiveProspective evaluation of stereotactic body radiotherapy (SBRT) with Robotic Radiosurgery in hepatocellular carcinoma patients with macrovascular invasion (HCC-PVT). Materials and MethodsPatients with inoperable HCC-PVT, good performance score (PS0-1) and preserved liver function (up to Child Pugh B7) were accrued after ethical and scientific committee approval [CTRI: 2022/01/050234] for treatment on Robotic Radiosurgery (M6) and planned with Multiplan (iDMS V2.0). Triple-phase contrast computed tomography (CT) scan was done for contouring and gross tumor volume (GTV) included contrast enhancing mass within main portal vein and adjacent parenchymal disease. Dose prescription was as per risk stratification protocol (22- 50Gy in 5 fractions) while achieving the constraints of mean liver dose <15Gy, 800 cc liver <8Gy and the duodenum max of <24 Gy). Response assessment done at 2 months follow up for recanalization. Patient and treatment related factors evaluated for influence in survival function. ResultsBetween Jan 2017 till May 2022, 317 consecutive HCC with PVT patients were screened and 219 patients were accrued [male 92%, CP score 5-7 90%, mean age 63 years (38-85yrs), CLIP <3: 84 (40%), 3-6 117 (56%), infective etiology 9.5%, Performance status (PS) 0-37%; 1-56%]. Among 209 consecutive patients after accrual SBRT treatment done (10 patients were excluded after accrual due to ascites and decompensation), 139 were evaluable for response assessment (>2 mo follow up). At mean follow up of 10.2 months (SD 8.43), 88 (63%) patients expired and 51 (36%) were alive. 82 (59%) patients had recanalization of PVT (response), 57 (41%) pts did not recanalize, 28 (17%) had progressive disease had progressive/metastatic disease prior to response evaluation (<2 months). Mean overall survival in responders and non-responders were 18.4 (SE 2.52) and 9.34 month (SE 0.81) respectively (p<0.001). Mean survival in patients with PS0, PS1 and PS2 were 17, 11.7 and 9.7 months (p- 0.019) respectively. Overall survival (OS) in partial recanalization, bland thrombus and complete recanalization was 12.4, 14.1, 30.3 months respectively (p-0.002). Adjuvant sorafenib, Barcelona Clinic Liver Classification (BCLC) stage, gender, age, RT dose did not influence response to treatment. Recanalization rate was higher in good PS patients (p-0.019). OS in patients with response to treatment, no response to treatment, fit but not accrued and not suitable patients were 18.4, 9.34, 5.9, 2.6 months respectively (p-<0.001). 36/139 patients (24%) had RILD [10 (7.2%) had Classic Radiation induced liver disease (RILD) & 26 (19%) had non-classic RILD]. Derangement in Child Pugh Score (CP score change) by more than 2 was seen in 30 (24%) within 2-month period after Robotic Radiosurgery. 18 (13%) had unplanned admissions, two patients required embolization due to fiducial related bleeding, 20 (14%) had ascites of which 9 (6%) patients required abdominocentesis. ConclusionPVT response or recanalization after SBRT is a statistically significant prognostic factor for survival function in HCC-PVT.

Linear Boltzmann equation solver for voxel-level dosimetry in radiopharmaceutical therapy: Comparison with Monte Carlo and kernel convolution.

With recent interest in patient-specific dosimetry for radiopharmaceutical therapy (RPT) and selective internal radiation therapy (SIRT), an increasing number of voxel-based algorithms are being evaluated. Monte Carlo (MC) radiation transport, generally considered to be the most accurate among different methods for voxel-level absorbed dose estimation, can be computationally inefficient for routine clinical use. This work demonstrates a recently implemented grid-based linear Boltzmann transport equation (LBTE) solver for fast and accurate voxel-based dosimetry in RPT and SIRT and benchmarks it against MC. A deterministic LBTE solver (Acuros MRT) was implemented within a commercial RPT dosimetry package (Velocity 4.1). The LBTE is directly discretized using an adaptive mesh refined grid and then the coupled photon-electron radiation transport is iteratively solved inside specified volumes to estimate radiation doses from both photons and charged particles in heterogeneous media. To evaluate the performance of the LBTE solver for RPT and SIRT applications, 177Lu SPECT/CT, 90Y PET/CT, and 131I SPECT/CT images of phantoms and patients were used. Multiple lesions (2-1052mL) and normal organs were delineated for each study. Voxel dosimetry was performed with the LBTE solver, dose voxel kernel (DVK) convolution with density correction, and a validated in-house MC code using the same time-integrated activity and density maps as input to the different dose engines. The resulting dose maps, difference maps, and dose-volume-histogram (DVH) metrics were compared, to assess the voxel-level agreement. Evaluation of mean absorbed dose included comparison with structure-level estimates from OLINDA. In the phantom inserts/compartments, the LBTE solver versus MC and DVK convolution demonstrated good agreement with mean absorbed dose and DVH metrics agreeing to within 5% except for the D90 and D70 metrics of a very low activity concentration insert of 90Y where the agreement was within 15%. In the patient studies (five patients imaged after 177Lu DOTATATE RPT, five after 90Y SIRT, and two after 131I radioimmunotherapy), in general, there was better agreement between the LBTE solver and MC than between LBTE solver and DVK convolution for mean absorbed dose and voxel-level evaluations. Across all patients for all three radionuclides, for soft tissue structures (kidney, liver, lesions), the mean absorbed dose estimates from the LBTE solver were in good agreement with those from MC (median difference<1%, maximum 9%) and those from DVK (median difference<5%, maximum 9%). The LBTE and OLINDA estimates for mean absorbed dose in kidneys and liver agreed to within 10%, but differences for lesions were larger with a maximum 14% for 177Lu, 23% for 90Y, and 26% for 131I. For bone regions, the agreement in mean absorbed doses between LBTE and both MC and DVK were similar (median<11%, max 11%) while for lung the agreement between LBTE and MC (median<1%, max 8%) was substantially better than between LBTE and DVK (median<16%, max 33%). Voxel level estimates for soft tissue structures also showed good agreement between the LBTE solver and both MC and DVK with a median difference<5% (maximum<13%) for the DVH metrics with all three radionuclides. The largest difference in DVH metrics was for the D90 and D70 metric in lung and bone where the uptake was low. Here, the difference between LBTE and MC had a median value<14% (maximum 23%) for bone and<4% (maximum 37%) for lung, while the corresponding differences between LBTE and DVK were<23% (maximum 31%) and<67% (maximum 313%), respectively. For a typical patient with a matrix size of 166×166×129 (voxel size 3×3×3 mm3), voxel dosimetry using the LBTE solver was as fast as ∼2 min on a desktop computer. Having established good agreement between the LBTE solver and MC for RPT and SIRT applications, the LBTE solver is a viable option for voxel dosimetry that can be faster than MC. Further analysis is being performed to encompass the broad range of radionuclides and conditions encountered clinically.

90Y post-radioembolization clinical assessment with whole-body Biograph Vision Quadra PET/CT: image quality, tumor, liver and lung dosimetry

PurposeEvaluation of 90Y liver radioembolization post-treatment clinical data using a whole-body Biograph Vision Quadra PET/CT to investigate the potential of protocol optimization in terms of scan time and dosimetry.Methods17 patients with hepatocellular carcinoma with median (IQR) injected activity 2393 (1348–3298) MBq were included. Pre-treatment dosimetry plan was based on 99mTc-MAA SPECT/CT with Simplicit90Y™ and post-treatment validation with Quadra using Simplicit90Y™ and HERMIA independently. Regarding the image analysis, mean and peak SNR, the coefficient of variation (COV) and lesion-to-background ratio (LBR) were evaluated. For the post-treatment dosimetry validation, the mean tumor, whole liver and lung absorbed dose evaluation was performed using Simplicit90Y and HERMES. Images were reconstructed with 20-, 15-, 10-, 5- and 1- min sinograms with 2, 4, 6 and 8 iterations. Wilcoxon signed rank test was used to show statistical significance (p < 0.05).ResultsThere was no difference of statistical significance between 20- and 5- min reconstructed times for the peak SNR, COV and LBR. In addition, there was no difference of statistical significance between 20- and 1- min reconstructed times for all dosimetry metrics. Lung dosimetry showed consistently lower values than the expected. Tumor absorbed dose based on Simplicit90Y™ was similar to the expected while HERMES consistently underestimated significantly the measured tumor absorbed dose. Finally, there was no difference of statistical significance between expected and measured tumor, whole liver and lung dose for all reconstruction times.ConclusionIn this study we evaluated, in terms of image quality and dosimetry, whole-body PET clinical images of patients after having been treated with 90Y microspheres radioembolization for liver cancer. Compared to the 20-min standard scan, the simulated 5-min reconstructed images provided equal image peak SNR and noise behavior, while performing also similarly for post-treatment dosimetry of tumor, whole liver and lung absorbed doses.

Clinical Internal Dosimetry and Biodistribution of 177 Lu-DOTA-Trastuzumab in HER2-Positive Metastatic and Locally Advanced Breast Carcinoma.

The aim of this study was to assess the biodistribution and dosimetry of 177 Lu-DOTA-trastuzumab in patients with HER2-positive breast carcinoma using whole-body (WB) planar imaging at multiple time points. This study was a prospective evaluation of HER2-positive metastatic/locally advanced breast carcinoma patients who underwent gamma camera imaging for dosimetry and biodistribution studies by using 177 Lu-DOTA-trastuzumab. The standard diagnostic dosimetry protocol was followed, which included cold trastuzumab injection followed by in-house produced 177 Lu-DOTA-trastuzumab. Serial WB planar images (anterior and posterior) were obtained on gamma camera after the infusion of 177 Lu-DOTA-trastuzumab at multiple time points. Whole-body and organ regions of interest were drawn, and the numbers of disintegrations were obtained. The mean absorbed doses for the liver, spleen, kidneys, heart, red marrow, and tumor were obtained from OLINDA EXM v2.1.1 and ORIGIN software. The study included a cohort of 21 female breast carcinoma patients. Tracer activity ( 177 Lu-DOTA-trastuzumab) was noted in the physiological organs such as the liver, spleen, kidneys, heart, as well as in the tumors. On visual analysis of 177 Lu-DOTA-trastuzumab biodistribution, the liver activity showed gradual clearance over time, and although spleen was comparatively faintly visualized than liver and similarly, kidneys were faintly visualized suggestive of the alternate route of tracer excretion. The maximum number of patients (n = 12) showed 2 components of clearance, namely, fast and slow. The average effective half-life of all the patients (including single and 2 components of clearance) was 106.25 ± 22.14 hours (84.11-128.39 hours). The mean absorbed dose for the liver, spleen, kidneys, heart, whole body, and red marrow was 1.0702 ± 0.731, 1.4114 ± 0.462, 1.4232 ± 0.364, 1.4719 ± 0.602, 0.2412 ± 0.0295, and 0.1485 ± 0.0213 mGy/MBq, respectively, by OLINDA EXM and 0.5741 ± 0.333, 0.8096 ± 0.224, 0.7943 ± 0.235, 1.8971 ± 0.713, and 0.09619 ± 0.0144 for liver, spleen, kidneys, heart and whole body respectively by ORIGIN. The absorbed radiation dose for tumor was 1.94E+2 by OLINDA EXM software and 1.78E+2 by ORIGIN software. In this study, during and after infusion of 177 Lu-DOTA-trastuzumab, no major adverse effects were noted in any patient except 1 patient who had grade 1 nausea and managed conservatively by antiemetic drug. The results of our study demonstrated expected and favorable biodistribution and dosimetry with 177 Lu-DOTA-trastuzumab in HER2-positive breast carcinoma patients. We noticed the mean absorbed dose to the normal organs within the limits of maximum tolerable dose, and also tumor dose was higher than the normal liver dose. Therefore, we conclude that 177 Lu-DOTA-trastuzumab radioimmunotherapy is feasible and a safe treatment option for treating HER2-positive breast carcinoma patients.

Deep inspirational breast hold (DIBH) for right breast irradiation: Improved sparing of liver and lung tissue

ObjectiveTo reduce liver and lung dose during right breast irradiation while maintaining optimal dose to the target volume. This dose reduction has the potential to decrease acute side effects and long-term toxicity. Materials and Methods16 patients treated with radiation therapy for localized carcinoma of the right breast were included retrospectively. For the planning CT, each patient was immobilised on an indexed board with the arms placed above the head. CT scans were acquired in free-breathing (FB) as well as with deep inspiration breath hold (DIBH). Both scans were acquired with the same length. Planning target volumes (PTV's) were created with a 5 mm margin from the respective clinical target volumes (CTV's) on both CT datasets. The liver was outlined as scanned. Dose metrics evaluated were as follows: differences in PTV coverage, dose to the liver (max, mean, V90%, V50%, V30%), dose to lung (mean, V20Gy, relative electron density) and dose to heart (Dmax). The p-values were calculated using Wilcoxon signed-rank tests. A p-value was significant when <0.05. ResultsDifferences in PTV coverage between plans using FB and DIBH were less than 2 %. Maximum liver dose was significantly less using DIBH: 17.5 Gy versus FB: 40.3 Gy (p < 0.001). The volume of the liver receiving 10 % of the dose was significantly less using DIBH with 1.88 cm3 versus 72.2 cm3 under FB (p < 0.001). The absolute volume receiving 20 Gy in the right lung was larger using DIBH: 291 cm3 versus 230 cm3 under FB (p < 0.001) and the relative volume of lung receiving dose greater than 20 Gy was smaller with DIBH: 11.5 % versus 14 % in FB (p = 0.007). The relative electron density of lung was significantly less with DIBH: 0.59 versus 0.62 with FB, (p < 0.001). This suggests that the lung receives less dose due to its lower density when using DIBH. ConclusionRadiation of the right breast using DIBH spares liver and lung tissue significantly and thus carries the potential of best practice for right sided breast cancer.

Liver toxicity following reirradiation and multiple-target SBRT for primary hepatocellular carcinoma.

514 Background: Stereotactic body radiation therapy (SBRT) is increasingly used to treat hepatocellular carcinoma (HCC), but its safety in the treatment of multiple synchronous or recurrent lesions is underreported. We aim to better characterize SBRT-related hepatic toxicity in this population. Methods: We conducted a retrospective analysis of patients with primary HCC who underwent SBRT for 2 or more synchronous or recurrent liver lesions. We collected patient characteristics and dosimetric data (mean liver dose, cumulative effective volume [Veff], cumulative volume of liver receiving 15Gy [V15Gy], and cumulative planning target volume [PTV]) along with liver-related toxicity (measured by albumin-bilirubin [ALBI] and Child-Pugh [CP] scores). We employed a linear mixed-effects model to assess the effect of multi-target SBRT on changes in ALBI. Results: There were 25 patients and 56 lesions with median follow-up of 29 months. Eleven patients had synchronous lesions and 14 had recurrent lesions treated with separate SBRT courses. Eight local failures occurred at a median of 8 months (range: 4 – 25 months) after SBRT. Among those receiving multiple SBRT courses, there were 7 lesions with overlap of V15Gy (median V15Gy overlap: 35mL, range: 0.5 – 388mL). There was no association between cumulative Veff, V15Gy, or PTV and change in ALBI. Four of 25 patients an increase of Child-Pugh (CP) score by ≥ 2 points, within 3 to 6 months after SBRT. Neither increase in CP nor ALBI were associated with cumulative Veff, V15Gy, and PTV. Comparing the groups that received SBRT in a single course versus multiple courses revealed no statistically significant differences in liver toxicity. Conclusions: LiverSBRT for multiple lesions in a single or in separate courses results in worsening of CP scores or ALBI in a small percentage of patients, suggesting a low risk of RILD. Prospective studies with a larger cohort are needed to better characterize safety in this population.

Modeling the effect of daughter migration on dosimetry estimates for unlabeled actinium-225.

Actinium-225 (225Ac) is an alpha emitting radionuclide which has demonstrated promising results in Targeted Alpha Therapy (TAT). A concern with 225Ac is that the decay energy can break the bond to the targeting vehicle, resulting in the release of free alpha-emitting daughter radionuclides in the body. The aim of this work is to develop a compartment model to describe the movement of unlabeled 225Ac in a human where the daughter isotopes of 225Ac have unique biokinetics. The ICRP Occupational Intake of Radionuclides reports were used to construct a compartment model for the 225Ac decay chain where the daughter isotopes of 225Ac are assigned their own unique transfer coefficients (TCs) between compartments. Computer simulations were performed for unlabeled 225Ac uniformly placed in the plasma and only the dose from alpha particles was considered. Absorbed doses to normal organs were determined for the liver, kidneys, bone, soft tissue, active marrow, and blood. Simulations were performed for the case when: (1) the daughters have unique biokinetics and (2) the daughters decay at the site of 225Ac. When the daughters have unique biokinetics, the organs that receive the highest absorbed dose are the liver (male: 1466.6 mGy/MBq, female: 1885.7 mGy/MBq), bone (male: 293.6 mGy/MBq, female: 403.6 mGy/MBq) and kidneys (male: 260.8 mGy/MBq, female: 294.0 mGy/MBq). These doses were compared to the case when the daughters of 225Ac decay at the site of 225Ac. There was a 13.5% increase in kidney dose, a 0.8% decrease in liver dose, and <0.1% decrease in bone dose calculations when the daughters have unique biokinetics compared to assuming the daughters decay at the site of 225Ac. The kidneys received a large dose estimate (260-295 mGy/MBq) as well as a considerable change in dose of +13.5% when the daughters have unique biokinetics compared to assuming the daughters decay at the site of 225Ac. Therefore, to accurately determine the kidney dose from unlabeled 225Ac in a human, the biokinetics of the daughter isotopes should be considered.

Combined Stereotactic Body Radiation Therapy and Immune Checkpoint Inhibition for Liver Metastases: Safety and Outcomes in a Pooled Analysis of 3 Phase 1 Trials

PurposeStereotactic body radiotherapy (SBRT) safely and effectively controls liver metastases, but its safety and efficacy when combined with immune checkpoint inhibitors (ICIs) are not well characterized. This analysis of three phase I trials of combination SBRT and ICI evaluates whether liver metastasis SBRT (LM-SBRT) increases the risk for hepatotoxicity when combined with ICI and explores efficacy endpoints. MethodsData were analyzed from three phase I trials of combination SBRT and ICI for patients with metastatic solid tumors conducted between 2016 and 2020. ICI was administered per trial protocol with LM-SBRT delivered to 45 Gy in 3 fractions with mean liver dose <16 Gy and ≥700cc of normal liver spared 17.1 Gy. Hepatic adverse events (HAEs) were defined as hepatic failure; autoimmune hepatitis; or elevation of AST, ALT, bilirubin or alkaline phosphatase using CTCAE 4.0. Cumulative incidence of HAE and local failure were modeled with death as a competing risk. Competing risks regression was performed using Fine-Gray modeling. Survival was estimated by the Kaplan-Meier method. Results200 patients were analyzed, including 81 patients with liver metastases, 57 of whom received LM-SBRT. The 12-month rate of any grade ≥2 HAE was 11% and 10% in LM-SBRT and non-LM-SBRT patients, respectively (NS). Radiographic evidence for liver disease and dual-agent ICI were significantly associated with HAEs on univariable and multivariable analysis while liver dose metrics were not. Patients with liver metastases had significantly worse progression-free and overall survival compared to those without and local failure of treated liver metastases was significantly higher than for treated extrahepatic metastases (28% vs 4% at 12 months, p < 0.001). ConclusionsCombination LM-SBRT and ICI did not significantly increase the risk for HAE compared to ICI without LM-SBRT, suggesting hepatotoxicity is largely driven by factors other than liver RT such as choice of ICI. Liver metastasis is associated with worse overall survival and local control outcomes.