Tissue Dose Research Articles

Impact of administered amount of peptide on tumor dosimetry at the first cycle of peptide receptor radionuclide therapy (PRRT) in relation to total tumor somatostatin receptor expression

BackgroundThe accumulation of 177Lu-DOTATATE might be influenced by the amount of administered peptide in relation to the tumor somatostatin receptor expression. The effect of the administered peptide mass on the resulting absorbed dose in tumors and normal organs has not previously been assessed in relation to the patients’ tumor load.MethodPatients with small intestinal (n = 141) and pancreatic (n = 62) neuroendocrine tumors (NETs) who underwent PRRT were selected for retrospective evaluation. All patients had received 7.4 GBq 177Lu-DOTATATE, and the amount of administered peptide in the preparation varied from 93 to 456 µg. The absorbed dose in tumors and normal tissue at the first PRRT cycle was calculated, based on SPECT-measurements at day 1, 4, and 7 post-infusion. The total tumor somatostatin receptor expression (tTSSTRE) was calculated on SPECT after 24 h by multiplying the functional tumor volume, delineated by 42% cut-off VOIs of the highest activity, with the SUVmean for the respective tumor VOIs. Spearman’s rank correlation analyzed any relationship between the administered amount of peptide and the absorbed dose in tumors and normal organs, in relation to the patients’ tTSSTRE.ResultsThere was no correlation between the amount of peptide and any of the tested parameters in relation to tTSSTRE.ConclusionIn this retrospective analysis, no correlation between the amount of administered peptide in the 177Lu-DOTATATE preparation and the absorbed radiation doses in tumors and normal tissues was demonstrated in relation to the total tumor SSTR expression.

Trimodal Therapy Using an MR–guided Radiation Therapy Partial Bladder Tumor Boost in Muscle Invasive Bladder Cancer

Bladder preservation with trimodal therapy (TMT; maximal tumor resection followed by chemoradiation) is an effective paradigm for select patients with muscle invasive bladder cancer. We report our institutional experience of a TMT protocol using nonadaptive magnetic resonance imaging-guided radiation therapy (MRgRT) for partial bladder boost (PBB). A retrospective analysis was performed on consecutive patients with nonmetastatic muscle invasive bladder cancer who were treated with TMT using MRgRT between 2019 and 2022. Patients underwent intensity modulated RT-based nonadaptive MRgRT PBB contoured on True fast imaging with steady state precession (FISP) images (full bladder) followed sequentially by computed tomography-based RT to the whole empty bladder and pelvic lymph nodes with concurrent chemotherapy. MRgRT treatment time, table shifts, and dosimetric parameters of target coverage and normal tissue exposure were described. Prospectively assessed acute and late genitourinary and gastrointestinal (GI) toxicity were reported. Two-year local control was assessed with Kaplan-Meier methods. Seventeen patients were identified for analysis. PBB planning target volume margins were ≤8 mm in 94% (n=16) of cases. Dosimetric target coverage parameters were favorable and all normal tissue dose constraints were met. For MRgRT PBB fractions, median table shifts were 0.4 cm (range, 0-3.15), 0.45 cm (0-2.65), and 0.75 cm (0-4.8) in the X, Y, and Z planes, respectively. Median treatment time for MRgRT PBB fractions was 9 minutes (range, 6.9-17.4). We identified 32 out of 100 total MRgRT fractions that may have benefitted from online adaptation based on changes in organ position relative to planning target volume, predominantly because of small bowel (13/32, 41%) or rectum (8/32, 25%). Two patients discontinued RT prematurely. The incidence of highest-grade acute genitourinary toxicity was 1 to 2 (69%) and 3 (6%), whereas the incidence of acute GI toxicity was 1 to 2 (81%) and 3 (6%). There were no late grade 3 events; 17.6% had late grade 2 cystitis and none had late GI toxicity. With median follow-up of 18.2 months (95% CI, 12.4-22.5), the local control rate was 92%, and no patient has required salvage cystectomy. Nonadaptive MRgRT PBB is feasible with favorable dosimetry and low resource utilization. Larger studies are needed to evaluate for potential benefits in toxicity and local control associated with this approach in comparison to standard treatment techniques.

Development of a machine learning framework for radiation biomarker discovery and absorbed dose prediction.

Molecular radiation biomarkers are an emerging tool in radiation research with applications for cancer radiotherapy, radiation risk assessment, and even human space travel. However, biomarker screening in genome-wide expression datasets using conventional tools is time-consuming and underlies analyst (human) bias. Machine Learning (ML) methods can improve the sensitivity and specificity of biomarker identification, increase analytical speed, and avoid multicollinearity and human bias. To develop a resource-efficient ML framework for radiation biomarker discovery using gene expression data from irradiated normal tissues. Further, to identify biomarker panels predicting radiation dose with tissue specificity. A strategic search in the Gene Expression Omnibus database identified a transcriptomic dataset (GSE44762) for normal tissues radiation responses (murine kidney cortex and medulla) suited for biomarker discovery using an ML approach. The dataset was pre-processed in R and separated into train and test data subsets. High computational cost of Genetic Algorithm/k-Nearest Neighbor (GA/KNN) mandated optimization and 13 ML models were tested using the caret package in R. Biomarker performance was evaluated and visualized via Principal Component Analysis (PCA) and dose regression. The novelty of ML-identified biomarker panels was evaluated by literature search. Caret-based feature selection and ML methods vastly improved processing time over the GA approach. The KNN method yielded overall best performance values on train and test data and was implemented into the framework. The top-ranking genes were Cdkn1a, Gria3, Mdm2 and Plk2 in cortex, and Brf2, Ccng1, Cdkn1a, Ddit4l, and Gria3 in medulla. These candidates successfully categorized dose groups and tissues in PCA. Regression analysis showed that correlation between predicted and true dose was high with R2 of 0.97 and 0.99 for cortex and medulla, respectively. The caret framework is a powerful tool for radiation biomarker discovery optimizing performance with resource-efficiency for broad implementation in the field. The KNN-based approach identified Brf2, Ddit4l, and Gria3 mRNA as novel candidates that have been uncharacterized as radiation biomarkers to date. The biomarker panel showed good performance in dose and tissue separation and dose regression. Further training with larger cohorts is warranted to improve accuracy, especially for lower doses.

Radiation Dosimetry, Artificial Intelligence and Digital Twins: Old Dog, New Tricks.

Developments in artificial intelligence, particularly convolutional neural networks and deep learning, have the potential for problem solving that has previously confounded human intelligence. Accurate prediction of radiation dosimetry pre-treatment with scope to adjust dosing for optimal target and non-target tissue doses is consistent with striving for improved the outcomes of precision medicine. The combination of artificial intelligence and production of digital twins could provide an avenue for an individualised therapy doses and enhanced outcomes in theranostics. While there are barriers to overcome, the maturity of individual technologies (i.e. radiation dosimetry, artificial intelligence, theranostics and digital twins) places these approaches within reach.

Dosimetric evaluation in brachytherapy and teletherapy for prostate cancer using Monte Carlo simulation and anatomically realistic virtual anthropomorphic phantom

The benefits that radiotherapy provides to the patient are unquestionable. However, there is growing concern about the increased risk of radiation-induced secondary cancer and the late damage to organs and tissues associated with the treatment. In this sense, the main objective of this study was to determine the radiation doses in the organs and tissues of the prostate cancer patient for two radiotherapy options, using the Monte Carlo code MCNP×2.7.0. The patient was represented by the ICRP 110 reference virtual anthropomorphic phantom and underwent brachytherapy with a192Ir source, Nucletron Microselectron V2 model, and alternatively, conventional 3D-CRT radiotherapy with an 18 MV X-ray beam from a Varian 2100c medical linear accelerator with 4-field planning (anteroposterior, 0°; posteroanterior, 180°; left lateral, 90°; and right lateral, 270°). A set of conversion factors (CF) for equivalent and effective dose were determined. The obtained results showed that in the more distant organs related to the prostate, such as the lung, brain, and salivary glands, the contribution of scattered radiation decreases, especially when brachytherapy is used. Comparing the two treatment modalities, the CF for effective dose per therapeutic dose was 42% lower when 192Ir was chosen as the main form of treatment. The CF values for photon equivalent doses calculated in 3D-CRT 4-fields are among one and two orders of magnitude higher than 192Ir therapy. These differences are even higher when the neutron equivalent dose in 3D-CRT is considered. In this way, the tools and methodology presented significantly improve the previously used to accurately estimate the equivalent doses in organs and tissues, which is the best quantity to assess the risk of inducing secondary cancer of healthy organs and tissues of patients undergoing treatment with radiotherapy.

D91. Effect of Pre-pectoral Versus Sub-pectoral Implant Placement in Breast Reconstruction on the Delivery of Post-mastectomy Radiation

PURPOSE: The placement of breast implants in a pre-pectoral compared to sub-pectoral plane has become increasingly popular in breast reconstruction, though data are limited on how this affects radiation delivery for locoregional disease control in women with breast cancer. This study aims to assess the dosimetric implications of implant location in women undergoing post-mastectomy radiation therapy (PMRT) after immediate breast reconstruction. METHODS: Patients with breast cancer treated with mastectomy, implant breast reconstruction, and PMRT between 2014-2022 at a single center were included. All patients received either intensity-modulated or 3-D conformal radiation therapy over an average of 5 weeks. Demographic, clinical and treatment data were collected through chart review. Patients were matched 1:1 on cancer sidedness, use of boost, fractionation and extent of radiation fields. Groups were compared using Mann-Whitney U or t-tests for continuous variables, and chi-square or Fisher’s Exact tests for categorical variables, as appropriate. RESULTS: Twenty-seven patients with pre-pectoral and 26 patients with sub-pectoral implants were included. Patients with pre-pectoral reconstruction had lower average implant volumes (452cc vs 503cc) prior to radiation. There was no difference in chest wall coverage (p=0.107), internal mammary node coverage (p=0.215), heart dose (p=0.627) or lung V20Gy (p=0.774). CONCLUSION: In this assessment of radiotherapeutic dosimetry in patients undergoing immediate breast reconstruction, we found no significant difference in target coverage or normal tissue dose based on pre- versus sub-pectoral implant location. This suggests that implant placement can be selected to optimize reconstructive outcomes, without concern for compromise to the oncologic quality of PMRT.

Exploring the Potential of Zirconium-89 in Diagnostic Radiopharmaceutical Applications: An Analytical Investigation

This study highlights the use of 89Zr-oxalate in diagnostic applications with the help of WinAct and IDAC2.1 software. It presents the biodistribution of the drug in various organs and tissues, including bone, blood, muscle, liver, lung, spleen, kidneys, inflammations, and tumors, and analyzes the maximum amount of nuclear transformation per Bq intake for each organ. The retention time of the maximum nuclear transformation and the absorbed doses of the drug in various organs and tissues are also examined. Data from clinical and laboratory studies on radiopharmaceuticals are used to estimate the coefficients of transition. The accumulation and excretion of the radiopharmaceutical in the organs is assumed to follow an exponential law. The coefficients of transition from the organs to the blood and vice versa are estimated using a combination of statistical programs and digitized data from the literature. WinAct and IDAC 2.1 software are used to calculate the distribution of the radiopharmaceutical in the human body and to estimate the absorbed doses in organs and tissues. The results of this study can provide valuable information for the biokinetic modeling of wide-spectrum diagnostic radiopharmaceuticals. The results show that 89Zr-oxalate has a high affinity for bones and a relatively low impact on healthy organs, making it helpful in targeting bone metastases. This study provides valuable information for further research on the development of this drug for potential clinical applications.

A treatment plan optimization method with direct minimization of number of energy jumps for proton arc therapy

Objective. The optimization of energy layer distributions is crucial to proton arc therapy: on one hand, a sufficient number of energy layers is needed to ensure the plan quality; on the other hand, an excess number of energy jumps (NEJ) can substantially slow down the treatment delivery. This work will develop a new treatment plan optimization method with direct minimization of (NEJ), which will be shown to outperform state-of-the-art methods in both plan quality and delivery efficiency. Approach. The proposed method jointly optimizes the plan quality and minimizes the NEJ. To minimize NEJ, (1) the proton spots x is summed per energy layer to form the energy vector y; (2) y is binarized via sigmoid transform into y 1 ; (3) y 1 is multiplied with a predefined energy order vector via dot product into y 2; (4) y 2 is filtered through the finite-differencing kernel into y 3 in order to identify NEJ; (5) only the NEJ of y 3 is penalized, while x is optimized for plan quality. The solution algorithm to this new method is based on iterative convex relaxation. Main results. The new method is validated in comparison with state-of-the-art methods called energy sequencing (ES) method and energy matrix (EM) method. In terms of delivery efficiency, the new method had fewer NEJ, less energy switching time, and generally less total delivery time. In terms of plan quality, the new method had smaller optimization objective values, lower normal tissue dose, and generally better target coverage. Significance. We have developed a new treatment plan optimization method with direct minimization of NEJ, and demonstrated that this new method outperformed state-of-the-art methods (ES and EM) in both plan quality and delivery efficiency.

Imaging doses for different CBCT protocols on the Halcyon 3.0 linear accelerator – TLD measurements in an anthropomorphic phantom

IntroductionImage guided radiotherapy allows for particularly conformal tumour irradiation through precise patient positioning. Becoming the standard for radiotherapy, this increases imaging doses to the patient. The Halcyon 3.0 linear accelerator (Varian Medical Systems, Palo Alto, CA) requires daily imaging due to its geometry. For this reason, the accelerator is equipped with on-line kV and MV imaging. However, daily CBCT images required for irradiation apply additional radiation, which increases the dose to normal tissue and therefore can affect the patient's secondary cancer risk. In this study, actual organ doses were measured for the kV system, and a comparison of normal tissue doses for all available kV CBCT protocols was presented to demonstrate differences in imaging doses across entities and protocols. In addition, effective dose and secondary cancer risk from imaging are evaluated. Material and methodsMeasurements were performed with thermoluminescent dosimeters in an anthropomorphic phantom positioned according to each entity (brain, head and neck, breast, lung, pelvis). CBCT images were obtained, using all available pre-set protocols without further adjustment of the parameters. Measured doses for each position and each protocol were then compared and secondary cancer risk of relevant and specifically radiosensitive organs was calculated. ResultsIt was found that imaging doses for protocols such as Pelvis and Head could be reduced by up to half using the corresponding Fast and Low Dose modes, respectively. On the other hand, larger field sizes or the Large mode yielded higher doses than their initial protocols. Image Gently was found to spare normal tissue best, however it is not suitable for certain entities due to low image quality or insufficient projection data. DiscussionBy using appropriate kV-CBCT protocols, it is possible to reduce imaging doses to a significant extent and therefore spare healthy tissue. Combined with studies of image quality, the results of this study could lead to adjustments in workflow regarding the choice of protocols used in daily routine. This could prevent unnecessary radiation exposure and reduce secondary cancer risk.

Dose Planning Evaluation of Intensity-Modulated Proton Therapy (IMPT) Technique Based on In-House Dynamic Thorax Phantom

One of the drawbacks of the Intensity Modulated Radiation Therapy (IMRT) technique is that the absorbed dose in healthy tissue is relatively high. Proton beam has characteristics that can compensate for these drawbacks. The Bragg peak characteristic of a proton beam allows the administration of high radiation doses to the target organ only. Non-Small Cell Lung Cancer (NSCLC) cases are located in the vicinity of many vital organs, so radiation doses that exceed a certain limit will have a significant impact on these organs. Proton is a heavy particle that exhibits interaction patterns with tissue heterogeneity that differ from that of photon. This study aims to determine the distribution of proton beam planning doses in the NSCLC cases with the Intensity Modulated Proton Therapy (IMPT) technique and compare its effectiveness with the IMRT technique. Treatment planning was done by using TPS Eclipse on the water phantom and on the in-house thorax dynamic phantom. The water phantom planning parameters used are one field at 0° and three fields at 45°, 135°, and 225°. In this study, a single, sum, and multiple field techniques on the in-house thorax dynamic phantom were used. The evaluation was performed by calculating Conformity Index (CI), Homogeneity Index (HI), and Gradient Index (GI) parameters for each treatment planning. As a result, a bit of difference in the CI the HI values are shown between IMPT and IMRT planning. The GI values of IMPT planning are in the range between 4.15-4.53, while the GI value of IMRT is 7.89. The histogram results of the planar dose distribution show that the IMPT treatment planning provides fewer off-target organ doses than the IMRT planning. Evaluation was also carried out on the IMPT treatment planning of target organs in five areas of interest and four OAR positions. The evaluation results were then compared with the IMRT measurement data. As a result, the value of the point doses at the target organ did not differ significantly. However, the absorbed dose with the IMPT technique at four OAR positions is nearly zero, which had a large difference compared to the IMRT technique.

A retrospective study of adjuvant proton radiotherapy for breast cancer after lumpectomy: a comparison of conventional-dose and hypofractionated dose

PurposeThis study aimed to compare the adverse reactions of conventional-dose and hypofractionated dose of proton therapy for breast cancer.Materials and methodsBreast cancer patients treated with proton radiotherapy in conventional-dose or hypofractionated dose were studied retrospectively.ResultFrom January 2017 to December 2019, our center treated 50 patients following lumpectomy with proton radiotherapy. According to the AJCC 8th Edition standard, there were stage I in 26 patients, stage II in 22 patients, and stage III in 2 patients. A total of 14 patients received intensity-modulated proton therapy at a dose of 50 Gy in 25 fractions, followed by a 10 Gy 4 fractionated boost to the lumpectomy cavity, while 36 received 40.05 Gy in 15 fractions, simultaneous integrated boost (SIB) 48 Gy to the lumpectomy cavity. Median follow-up time for 40.05 Gy group was 35.6 months (15–43 months). Median follow-up time for 50 Gy group was 46.8 months (36–68 months). For acute toxicity, the grade 1 and 2 radiodermatitis in conventional-dose group were 35.7% and 57.1%, respectively. In hypofractionated dose group, the grade 1 and 2 radiodermatitis were 91.7% and 8.3%, respectively. The radiodermatitis is hypofractionneted dose better than conventional-dose significantly. Grade 1 radiation-induced esophagitis in conventional-dose group and hypofractionated dose group were 85.71% and 60%, respectively. For late toxicity, no patients developed radiation-induced pneumonitis and rib fracture in conventional-dose group. Three patients presented grade 1 pneumonitis; one patient presented graded 2 pneumonitides and two patients presented rib fracture in hypofractionated dose group. One presented hypothyroidism in hypofractionated dose group. All patients were satisfied with breast shape. The one- and two-year OS and DFS for conventional-dose group were 100 and 100; 100 and 92.9%, respectively. The one- and two-year OS and DFS for hypofractionated dose group were 100 and 100; 100 and 100%, respectively.ConclusionProton radiation therapy can significantly reduce the normal tissue dose in breast cancer patients' hearts, lungs, and other organs. Hypofractionated proton therapy shortens the treatment course with mild radiation-related adverse effects, and has a better effect on addressing the acute adverse reactions than conventional proton radiotherapy.

Yttrium-90 Radiation Segmentectomy of Hepatocellular Carcinoma: A Comparative Study of the Effectiveness, Safety, and Dosimetry of Glass-Based versus Resin-Based Microspheres

PurposeTo evaluate the differences in safety, effectiveness, and dosimetry between glass-based and resin-based ablative yttrium-90 (90Y) transarterial radioembolization (TARE) of hepatocellular carcinoma (HCC). Materials and MethodsUsing the modified Response Evaluation Criteria in Solid Tumors and Common Terminology Criteria for Adverse Events, both tumor response and adverse events (AEs) were assessed at 3 months after 90Y-TARE. Post procedure 90Y-bremsstrahlung single-photon emission computed tomography/computed tomography voxel-based dosimetry analysis was used to create tumor dose (TD) and normal tissue dose (NTD) volume histograms, and to calculate tumor particle loading and specific activity. The TD and NTD receiver operating characteristic curves evaluated the dose threshold able to predict objective (partial or complete) and complete tumor responses in addition to any-grade and grade ≥3 AE incidences. The chi-square test and Student t-test were used to assess variable differences where appropriate. ResultsBetween 2019 and 2020, 81 patients with HCC (20 in the resin-based cohort and 61 in the glass-based cohort) underwent ablative 90Y-TARE. The resin-based cohort had more males (89% vs 65%, P = .03), lower tumor-to-normal ratio (1.81 ± 0.39 vs 2.22 ± 0.94, P = .03), higher tumor particle loading (40,172 particles/mL ± 28,039 vs 17,081 particles/mL ± 12,555, P = .0001), lower specific activity (158 Bq/particle ± 3 vs 1,058 Bq/particle ± 331, P = .001), and lower mean TD (308 Gy ± 210 vs 794 Gy ± 523, P = .0002) than the glass-based cohort. No significant differences in baseline characteristics or posttreatment AEs were noted. The overall objective and complete response rates were 85% (95% resin-based vs 82% glass-based; P = .1) and 65% (95% resin-based vs 56% glass-based; P = .003), respectively. The mean TD thresholds able to predict the objective and complete responses were 176 Gy and 247 Gy for resin-based radioembolization and 290 Gy and 481 Gy for glass-based radioembolization, respectively. A maximum NTD of 999 Gy predicted any-grade AEs in glass-based ablative 90Y-TARE. ConclusionsCompared with glass-based ablative 90Y-TARE, resin-based ablative 90Y-TARE can offer comparable safety and effectiveness profiles for patients with HCC. The impact of the significantly different tumor particle loading, particle specific activities, and delivered TDs on tumor response outcomes merits further investigation.

Effects of ionizing radiation exposure during pregnancy.

To review the effects of ionizing radiation to the conceptus and the relationship to the timing of the exposure during pregnancy. To consider strategies that would mitigate potential harms associated with exposure to ionizing radiation during pregnancy. Data reported in the peer-reviewed literature on entrance KERMA received from specific radiological examinations were combined with published results from experiment or Monte Carlo modeling of tissue and organ doses per entrance KERMA to estimate total doses that could be received from specific procedures. Data reported in the peer-reviewed literature on dose mitigation strategies, best practices for shielding, consent, counseling and emerging technologies were reviewed. For procedures utilizing ionizing radiation for which the conceptus is not included in the primary radiation beam, typical doses are well below the threshold for causing tissue reactions and the risk of induction of childhood cancer is low. For procedures that include the conceptus in the primary radiation field, longer fluoroscopic interventional procedures or multiphase/multiple exposures potentially could approach or exceed thresholds for tissue reactions and the risk of cancer induction must be weighed against the expected risk/benefit of performing (or not) the imaging examination. Gonadal shielding is no longer considered best practice. Emerging technologies such as whole-body DWI/MRI, dual-energy CT and ultralow dose studies are gaining importance for overall dose reduction strategies. The ALARA principle, considering potential benefits and risks should be followed with respect to the use of ionizing radiation. Nevertheless, as Wieseler et al. (2010) state, "no examination should be withheld when an important clinical diagnosis is under consideration." Best practices require updates on current available technologies and guidelines.

Difference in the occurrence of capsular contracture according to the characteristics of the tissue in an irradiated rat model.

In this study, it was hypothesized that the capsule formation varies according to the radiation dose in the muscle tissues; chest wall tissues, including the ribs; and acellular dermal matrices (ADM) that are in contact with the silicone implant. This study consisted of 20 SD rats that underwent submuscular plane implant reconstruction using ADM. They were divided into four groups: Group 1 as the un-radiated control (n = 5), Group 2 with non-fractionated radiation at a dose of 10 Gy (n = 5), Group 3 with non-fractionated radiation at a dose of 20 Gy (n = 5), and Group 4 with fractionated radiation at a dose of 35 Gy (n = 5). Three months after surgery, hardness was measured. Moreover, the histology and immunochemistry of the capsule tissues of the ADM, muscle tissues, and chest wall tissues were analyzed. As the radiation dose increased, the silicone implant became harder. But no significant difference in capsule thickness according to the radiation dose was observed. Based on the tissue in contact with the silicone implant, ADM has a thinner capsule thickness than the muscle tissues and less inflammation as well as less neovascularization compared with the other tissues. This study described a new rat model of clinically relevant implant-based breast reconstruction using a submuscular plane and ADM with irradiation. Therefore, it was confirmed that the ADM in contact with the silicone implant, even after irradiation, was protected from radiation compared with the other tissues.

(Potential) Mishaps of High-Dose-Rate Vaginal Cuff Brachytherapy

Considering how commonly vaginal cuff brachytherapy is used, there is relatively little literature regarding the potential, albeit low, risk for complications. We present 3 potentially serious mishaps involving cylinder misplacement, dehiscence, and excessive normal tissue irradiation due to unique anatomy. Three patients with potentially serious treatment errors were encountered in the authors’ usual clinical practice. Each patient's records were reviewed for this report. For patient 1, computed tomography (CT) simulation revealed grossly inadequate cylinder insertion, which was most obvious on the sagittal view. For patient 2, CT simulation revealed that the cylinder extended beyond the perforated vaginal cuff and was surrounded by bowel. For patient 3, CT images were used only to verify cylinder depth. A standard library plan based on cylinder diameter and active length was used. In retrospect, the images revealed an unusually thin rectovaginal septum, with the lateral and posterior vaginal wall thickness estimated to be <2 mm. This patient's fractional normal tissue doses were calculated for this report, revealing a rectal maximum dose (per fraction) of 10.8 Gy, maximum dose that 2 cc of the organ receives of 7.4 Gy, and volume of the organ that receives the prescription dose or higher of 2.8 cc. All doses were far in excess of those anticipated for a minimal 0.5-cm vaginal wall depth. Vaginal cuff high-dose-rate brachytherapy is a high-volume, routine procedure. Even in experienced hands, however, it carries a risk of improper cylinder placement, cuff dehiscence, and excessive normal tissue dose, all of which could seriously affect outcomes. These potential mishaps would be better appreciated and avoided with more extensive use of CT-based quality assurance measures.

Dose Estimation for Extravasation of 177Lu, 99mTc, and 18F.

Extravasation is the situation in which a nuclear medicine injection deposits some fraction of its radioactivity into the soft tissue rather than the bloodstream and may result in a large local radiation dose to tissue. An understanding of localized radiation dose from such unexpected events can be an important aspect of clinical radiation protection. The aim of this study was to estimate and assess absorbed radiation dose to localized soft tissue for hypothetical scenarios of radiopharmaceutical extravasation. Specifically, the goal was to understand whether a radiopharmaceutical extravasation could exceed the US Nuclear Regulatory Commission's medical event reporting limit of 0.5 Sv dose equivalent to tissue or levels at which tissue damage would be anticipated (1.0 Sv dose equivalent). We used the GATE Monte Carlo simulation software to calculate self-dose to spherical volumes containing uniformly distributed amounts of common radiopharmaceutical isotopes. Simulated volumes, radioactivity levels, and effective half-lives represented real-world nuclear medicine procedures. Chosen scenarios consisted of 50 mCi and 100 mCi 177Lu within 20 cm3 and 40 cm3 tissue volumes and a 60 min biological clearance half-time (59.6 min effective half-life), 6 mCi and 12 mCi 99mTc within 1 cm3 and 5 cm3 tissue volumes and a 120 min biological clearance half-time (90 min effective half-life), and 3 mCi and 6 mCi 18F within 1 cm3 and 5 cm3 tissue volumes with a 30 min biological clearance half-time (23.6 min effective half-life). We calculated absorbed doses to be between 5.5 Gy and 23.5 Gy for 177Lu, between 0.9 Gy and 12.4 Gy for 99mTc, and between 1.5 Gy and 16.2 Gy for 18F. Radiopharmaceutical extravasations can result in tissue doses that surpass both medical event reporting limits and levels at which deterministic effects are expected. Radiation safety programs should include identification, mitigation, dosimetry, and documentation of significant extravasation events.

Dependence of the Translocation Frequency in Blood Lymphocytes on the Dose and Age at the Onset of Exposure in Residents of the Techa Riverside Settlements

Evaluation of age effect on the frequency of radiation-induced translocations, registered using FISH in circulating T-lymphocytes in the long-term period after exposure, is both of theoretical and practical interest for the purposes of biodosimetry. The objective of our study was to analyze the dose dependence of the translocation frequency in the peripheral blood T-lymphocytes in donors of different age who were exposed in the Techa Riverside settlements (n = 197). In cytogenetic studies, whole chromosome painting probes were used to stain three pairs of chromosomes. A total of 104,721 genome equivalents (GE) were calculated and 2,540 translocations were found. For each donor, the individual absorbed doses in organs and tissues at the time of blood sampling were calculated using the Techa River Dosimetry System. In addition, doses to T-lymphocytes and their progenitors were calculated using the innovative modelling approach with due account of age related-dynamics of T-lymphocytes. The age dependence of the translocation frequency was associated particularly with these doses. The main sources of donor exposure were 89,90Sr, accumulating in bones and irradiating the bone marrow almost locally. To assess the parameters of the dose-effect relationship, linear regression model was used. After taking into account background values, the lowest frequency of translocations per 1000 GE per Gy was found in donors aged 0–5 years at the time of exposure (9.3 ± 1.3), which is statistically significantly lower than in children aged 6–18 years (15.3 ± 1.5), but not in adults (11.9 ± 2.9). The value for adults (18 years) was characterized by the maximum scatter, but was close to the values obtained in an international study of nuclear enterprise personnel after external exposure (11.6 ± 1.6). The values of the background translocation frequencies registered in various age groups correspond to the published data obtained in a joint international study on unexposed donors. We have also confirmed the absence of sex-effect on the frequency of translocations.

Liver SBRT dose accumulation to assess the impact of anatomic variations on normal tissue doses and toxicity in patients treated with concurrent sorafenib

Background and PurposeUnexpected liver volume reductions occurred during trials of liver SBRT and concurrent sorafenib. The aims were to accumulate liver SBRT doses to assess the impact of these anatomic variations on normal tissue dose parameters and toxicity. Materials and MethodsThirty-two patients with hepatocellular carcinoma (HCC) or metastases treated on trials of liver SBRT (30–57 Gy, 6 fractions) and concurrent sorafenib were analyzed. SBRT doses were accumulated using biomechanical deformable registration of daily cone-beam CT. Dose deviations (accumulated-planned) for normal tissues were compared for patients with liver volume reductions > 100 cc versus stable volumes, and accumulated doses were reported for three patients with grade 3–5 luminal gastrointestinal toxicities. ResultsPatients with reduced (N = 12) liver volumes had larger mean deviations of 0.4–1.3 Gy in normal tissues, versus −0.2–0.4 Gy for stable cases (N = 20), P > 0.05. Deviations > 5% of the prescribed dose occurred in both groups. Two HCC patients with toxicities to small and large bowel had liver volume reductions and deviations to the maximum dose of 4% (accumulated 36.9 Gy) and 3% (accumulated 33.4 Gy) to these organs respectively. Another HCC patient with a toxicity of unknown location plus tumor rupture, had stable liver volumes and deviations to luminal organs of −6% to 4.5% (accumulated < 30.5 Gy). ConclusionLiver volume reductions during SBRT and concurrent sorafenib were associated with larger increases in accumulated dose to normal tissues versus stable liver volumes. These dosimetric changes may have further contributed to toxicities in HCC patients who have higher baseline risks.

Evaluation and modelling of the lithium fluoride based thermoluminescent detector response at the CERN-EU high-energy reference field (CERF)

Lithium fluoride (LiF) thermoluminescent detectors (TLDs) are commonly used for measurements in mixed high energy radiation fields such as space, hadron radiotherapy and other high energy accelerator facilities. However, the results of these measurements are often challenging to interpret since the radiation field compositions are not known a priori. The goal of this work was to model and understand the LiF TLD response in the CERN-EU high-energy Reference Field (CERF).Six different LiF TLD types, namely MTS (LiF:Mg,Ti) and MCP (LiF:Mg,Cu,P) TLDs with different Li abundances, were irradiated at CERF. For the modelling of their response, CERF reference fluence energy spectra from FLUKA simulations and TLD relative luminescence efficiencies according to the Microdosimetric d(z) Model were collected from previous works and supplemented with new relative luminescence efficiency calculations for neutrons with energies above 0.01 MeV. Dedicated MCNP6.2 simulations were performed to obtain the required fluence to absorbed dose conversion factors.Results demonstrated that the response of LiF detectors can be well predicted even for complicated, mixed radiation fields. The modelling allowed to assess the dose contributions from different radiation types in mixed fields. Based on the results of this work, a methodology was proposed to perform LiF TLD measurements in well-characterized mixed fields in terms of absorbed dose in water or tissue. In unknown mixed radiation fields MTS-7 TLDs are recommended to assess the non-neutron component of the absorbed dose in water or tissue. Assessing the dose from neutrons requires dedicated neutron detectors.

PBPK modeling to evaluate maximum tolerated doses: A case study with 3-chloroallyl alcohol.

Introduction: A physiologically based pharmacokinetic (PBPK) model for 3-chloroallyl alcohol (3-CAA) was developed and used to evaluate the design of assays for the in vivo genotoxicity of 3-CAA. Methods: Model development was supported by read across from a published PBPK model for ethanol. Read across was motivated by the expectation that 3-CAA, which like ethanol is a primary alcohol, is metabolized largely by hepatic alcohol dehydrogenases. The PBPK model was used to evaluate how two metrics of tissue dosimetry, maximum blood concentration (Cmax; mg/L) and area under the curve (AUC; mg-hr/L) vary with dose of 3-CAA and with dose route (oral gavage, drinking water). Results: The model predicted that oral gavage results in a 6-fold higher Cmax than the same dose administered in drinking water, but in similar AUCs. Predicted Cmax provided the best correlation with severe toxicity (e.g., lethality) from 3-CAA, consistent with the production of a reactive metabolite. Therefore, drinking water administration can achieve higher sustained concentration without severe toxicity in vivo. Discussion: This evaluation is significant because cytotoxicity is a potential confounder of mutagenicity testing. The PBPK model can be used to ensure that studies meet OECD and USEPA test guidelines and that the highest dose used is not associated with severe toxicity. In addition, PBPK modeling provides assurance of target tissue (e.g., bone marrow) exposure even in the absence of laboratory data, by defining the relationship between applied dose and target tissue dose based on accepted principles of pharmacokinetics, relevant physiology and biochemistry of the dosed animals, and chemical-specific information.