Organ Doses Research Articles

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

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

Organ-based tube current modulation versus spectral shaping via tin prefiltration: What does bismuth breast shielding add in low-dose lung CT?

PurposeSince organ-based tube current modulation (OBTCM) and tin prefiltration are limited on their own in lowering the dose of lung CT examinations, this experimental study was designed to investigate whether combinations with anterior patient shielding can increase the dose reduction potential. Material and methodsThree pairs of scan protocols without/with breast shield (P1/P2: standard 120kVp, P3/P4: OBTCM at 100 kVp, P5/P6: Sn 100 kVp) were employed for radiation exposure and image quality comparisons on an anthropomorphic Alderson-Rando phantom. Equivalent doses were measured in eleven sites via thermoluminescent dosimetry and the effective dose was obtained by summation of the weighted organ doses. Dose-weighted contrast-to-noise ratios (CNRD) were calculated and four radiologists independently assessed the quality of images generated with each protocol. ResultsWhile no significant difference was determined between standard and OBTCM protocols regardless of breast shield (p ≥ 0.068), equivalent doses with spectral shaping were substantially lower (p ≤ 0.003). The highest effective dose was ascertained for standard scans (P1/P2: 7.3/6.8 mSv) with a dose reduction of 8.0 % via breast shielding. The use of a bismuth shield was more beneficial in OBTCM (P3/P4: 6.6/5.3 mSv) and spectral shaping (P5/P6: 0.7/0.6 mSv), reducing the effective dose by 19.8 % and 13.9 %, respectively. Subjective assessment favoured standard protocol P1 over tin prefiltration low-dose scans (p ≤ 0.032), however, no scan protocol entailed diagnostically insufficient image quality. ConclusionsWhereas breast shielding is particularly beneficial in combination with OBTCM, spectral shaping via tin prefiltration facilitates the most pronounced dose reduction in lung CT imaging with acceptable image quality.

Third mortality follow-up of the Mallinckrodt uranium processing workers, 1942–2019

Introduction Mallinckrodt Chemical Works was a uranium processing facility during the Manhattan Project from 1942 to 1966. Thousands of workers were exposed to low-dose-rates of ionizing radiation from external and internal sources. This third follow-up of 2514 White male employees updates cancer and noncancer mortality potentially associated with radiation and silica dust. Materials and methods Individual, annualized organ doses were estimated from film badge records (n monitored = 2514), occupational chest x-rays (n = 2514), uranium urinalysis (n = 1868), radium intake through radon breath measurements (n = 487), and radon ambient measurements (n = 1356). Silica dust exposure from pitchblende processing was estimated (n = 1317). Vital status and cause of death determination through 2019 relied upon the National Death Index and Social Security Administration Epidemiological Vital Status Service. The analysis included standardized mortality ratios (SMRs), Cox proportional hazards, and Poisson regression models. Results Vital status was confirmed for 99.4% of workers (84.0% deceased). For a dose weighting factor of 1 for intakes of uranium, radium, and radon decay products, the mean and median lung doses were 65.6 and 29.9 mGy, respectively. SMRs indicated a difference in health outcomes between salaried and hourly workers, and more brain cancer deaths than expected [SMR: 1.79; 95% confidence interval (CI): 1.14, 2.70]. No association was seen between radiation and lung cancer [hazard ratio (HR) at 100 mGy: 0.93; 95%CI: 0.78, 1.11]. The relationship between radiation and kidney cancer observed in the previous follow-up was maintained (HR at 100 mGy: 2.07; 95%CI: 1.12, 3.79). Cardiovascular disease (CVD) also increased significantly with heart dose (HR at 100 mGy: 1.11; 95%CI: 1.02, 1.21). Exposures to dust ≥23.6 mg/m3-year were associated with nonmalignant kidney disease (NMKD) (HR: 3.02; 95%CI: 1.12, 8.16) and kidney cancer combined with NMKD (HR: 2.46; 95%CI: 1.04, 5.81), though without evidence of a dose-response per 100 mg/m3-year. Conclusions This third follow-up of Mallinckrodt uranium processors reinforced the results of the previous studies. There was an excess of brain cancers compared with the US population, although no radiation dose-response was detected. The association between radiation and kidney cancer remained, though potentially due to few cases at higher doses. The association between levels of silica dust ≥23.6 mg/m3-year and NMKD also remained. No association was observed between radiation and lung cancer. A positive dose-response was observed between radiation and CVD; however, this association may be confounded by smoking, which was unmeasured. Future work will pool these data with other uranium processing worker cohorts within the Million Person Study.

Dose optimization of 2D X-ray image acquisition protocols in image-guided radiotherapy

PurposeIn contemporary radiotherapy, patient positioning accuracy relies on kV imaging. This study aims at optimizing planar kV image acquisition protocols regarding patient dose without degrading image quality. Materials and methodsAn image quality test-object was placed in-between PMMA plates, suitably arranged to model head or pelvis. Constructed phantoms were imaged using default protocols, the resultant image quality was assessed and the corresponding radiation dose was measured. The process was repeated using numerous kV/mAs combinations to identify those acquisition settings providing images at lower dose than the default protocols but without deterioration in image quality. Default and dose-optimized protocols were then tested on an anthropomorphic phantom and on 51 patients during two successive treatment sessions. Image quality was independently assessed by two readers. Organ and effective doses were estimated using a Monte Carlo simulation software. ResultsLow-contrast detectability exhibited a stronger dependence on kV/mAs settings, compared to high-contrast resolution. Dose-optimized protocols resulted in significant dose reductions (anteroposterior-head 48.0 %, lateral-head 30.0 %, anteroposterior-pelvis 28.4 %, lateral-pelvis 27.0 %) compared to the default ones, without compromising image quality. Optimized protocols decreased effective doses by 54 % and 29.6 % in head and pelvic acquisitions, respectively. Regarding image quality, anthropomorphic and patient images acquired using the dose-optimized protocols were subjectively evaluated equivalent to those obtained with the corresponding default settings, indicating that the proposed protocols may be routinely used. ConclusionsGiven the potentially large number of radiotherapy fractions and the pertinent image acquisitions, dose-optimized protocols could significantly reduce patient dose associated with planar imaging without compromising positioning accuracy.

Pilot Study of a Novel Ring Gantry-Based PET/CT Linear Accelerator in Patients with Prostate Cancer Receiving [18F]-DCFPyL for PSMA PET Imaging.

The RefleXion X1® system is a hybrid PET imaging-radiotherapy system that uses real-time positron emissions from a PET tracer to deliver biologically guided radiotherapy (BgRT). This study (NCT05470699) evaluated the hypothesis that the X1 PET imaging subsystem would be able to detect [18F]-DCFPyL PSMA PET signal sufficient to generate a deliverable BgRT plan in patients with prostate cancer. Patients with prostate cancer scheduled for a diagnostic [18F]-DCFPyL PSMA PET scan as part of standard of care were eligible. Upon completion of the diagnostic PSMA PET scan, images were transferred to the radiotherapy planning system for target identification and contouring. If at least one PET avid tumor lesion was identified, the patient was then scanned on the X1 unit. BgRT planning was performed on each X1 scanned patient. The target lesion volume, activity concentration (AC) and normalized target signal (NTS) were acquired. Successful and deliverable BgRT plans required that the target AC was ≥ 5 kBq/ml and NTS ≥ 2.7. Twenty-six patients underwent [18F]-DCFPyL PET scans (13 with rising PSA after surgery or radiotherapy, 6 with known metastases and 7 with newly diagnosed high-risk prostate cancer). Median (range) PSA was 3.40 (0.04-122). In 16 patients a PET avid tumor was identified and contoured for planning (4 lymph nodes, 5 bone, 6 prostate gland, and 1 prostate bed). In 13 patients the target lesion was visualized on the X1 PET scan, while in 3 patients the target lesion was too close to the bladder to be clearly visualized. BgRT planning was feasible and met standard of care published SBRT organ dose constraints in 8 patients (3 prostate gland, 3 bone, 2 lymph nodes). BgRT planning was not feasible in 8 patients due to insufficient AC, low NTS or proximity of the target lesion to the PET avid bladder. The accompanying table compares median (range) target volume, AC and NTS for feasible versus not feasible plans. This is the first study to investigate the feasibility of using [18F]-DCFPyL PET imaging for BgRT plan generation on the X1 system in patients with prostate cancer. Lesions that are relevant to radiotherapy of prostate cancer can be visualized including lymph node and bone metastases. A dedicated BgRT workflow with PSMA PET imaging on the X1 at 60 minutes post injection will result in higher target AC and will optimize BgRT planning. PET avid lesions < 1 cm or close to the bladder may make BgRT planning challenging. [18F]-DCFPyL-guided BgRT is technically feasible using the RefleXion X1. BgRT using targeted PET radiopharmaceuticals to biologically guide external beam radiotherapy represents a promising new dimension in radiation oncology and warrants further investigation.

Estimation of Lifetime Attributable Risk (LAR) of Cancer Associated with Chest Computed Tomography Procedures in Children

Purpose: The danger of radiation at low doses continues linearly, and without a threshold, investigations concluded that although the risk of cancer from Computed Tomography (CT) scans is low, it is not zero.&#x0D; This study aims to determine the patient's radiation dose and estimate the Lifetime Attributable Risk (LAR) of cancer incidence for a single chest CT scan in children.&#x0D; Materials and Methods: We divided 1,105 children into four age groups: 0 years, 5 years, 10 years, and 15 years. Dosimetric data of chest CT scan were plugged in VirtualDoseCT software, and organ dose and effective dose were calculated. The cancer risk based on organ dose is estimated according to the BEIR VII report.&#x0D; Results: The highest dose in boys was related to lung (5.13 - 6.8 mSv) and heart (5.27-5.97 mSv), and in girls, lung (4.98 - 5.91 mSv), breast (4.24 - 5.21 mSv), and heart (4.9 - 5.71 mSv) had the highest dose. The highest LAR (per 100,000) was obtained for the breast in the age group of 0 years (61.01), followed by the breast for the age group of 5 years (46.16) and lung in the age group of 0 years (43.32) in girls.&#x0D; Conclusion: This study shows a better concept of radiation dose in the chest CT scan in children and how much effective dose and organ dose values increase the cancer risk.

Dosimetric Study of Total Marrow and Lymphoid Irradiation on a Ring Gantry-Based Medical Linac with a Two-Layer Multi-Leaf Collimator

In this study, we aimed to evaluate dosimetric quality of total marrow and lymphoid irradiation (TMLI) plans for a ring gantry-based medical Linac with a two-layer multi-leaf collimator. We retrospectively retrieved treatment planning CT images, structure sets, and plan dose for four adult patients, two male and two female, who previously received TMLI treatments on helical tomotherapy (HT) at our institution. TMLI plans were optimized for a ring gantry-based medical Linac with a two-layer multi-leaf collimator (Halcyon, Varian Medical Systems, Inc., Palo Alto, CA). A prescription dose of 12 Gy in 8 fractions was prescribed to the skeletal bones from the skull to mid-thigh, spleen, spinal canal, and lymphoid volume. Five or six isocenters were placed with equal spacing along the patient's longitudinal direction in each TMLI plan with two 6-MV flattening filter-free volumetric modulated arc therapy (VMAT) fields at each isocenter. Isocenter separation ranged from 15 cm to 16.5 cm. Each VMAT field has a field size of 28 cm to 28 cm with the collimator at 90° and a full gantry rotation. The nominal dose rate was 800 MU/minute, and the maximum gantry rotation speed was 24°/sec. Institutional dosimetric constraints were used for optimization including a mean lung dose limit of less than 8 Gy. All the plans were normalized so that 85% the primary planning target volume received the prescription dose. The average mean doses to the target volumes ranged from 12.2 to 12.6 Gy in the Halcyon TMLI plans, while they ranged from 12.1 to 12.5 Gy in the HT TMLI plans. Relative to the prescription dose, the average mean dose for normal organs ranged from 21.3% to 56.6% in the Halcyon TMLI plans, while it ranged from 10.1% to 68.4% in the clinical HT plans. The difference in the average mean dose to normal organs was less than 0.5 Gy except two organs between the Halcyon and HT TMLI plans. The average median dose for normal organs ranged from 18.2% to 48.8% relative to the prescription dose in the Halcyon TMLI plans. The mean lung dose (MLD) in the Halcyon TMLI plans met the institutional limit with an average dose of 6.75±0.42 Gy (range: 6.44 - 7.36 Gy), while the average MLD was 6.54±0.77 Gy (range: 6.24 - 7.22 Gy) in the HT plans (p-value = 0.71 in the paired t-test). The average total monitor unit in the Halcyon TMLI plans was 4,425±906 MU (range: 3,470 - 5,575 MU) with an average beam-on time of 5.1±1.3 minutes (range: 4.1 - 7.0 minutes), which excludes isocenter setup time, while the average beam-on time was 22.2±3.2 minutes (range: 19.6 - 26.1 minutes) with the HT plans. Halcyon TMLI plans met our institutional dosimetric constraints with adequate normal organ sparing and target dose coverage. The beam-on time with the Halcyon plans was significantly shorter than that with the HT plans, which could lead to shorter treatment time and increased patient comfort. This study showed the feasibility of TMLI treatments on the Halcyon machine. The same method could be used for total body irradiation on Halcyon.

Plan Comparison of Left Breast Postmastectomy Radiotherapy: Halcyon IMRT and VMAT Plan vs. Truebeam Fixed-Jaws Plan

The purpose of this work is to provide a Varian Halcyon planning solution for left breast postmastectomy radiotherapy by comparing the plan quality of Varian Truebeam plan with Halcyon plan. Ten patients who previously received left breast postmastectomy intensity-modulated radiotherapy (IMRT) on Truebeam were retrospectively selected and replanned using Halcyon. The planning target volume (PTV) included chest wall and supraclavicular region, and the prescribed dose was 50 Gy in 25 fractions (2 Gy/F). In addition to the original Truebeam fixed-jaws IMRT (IMRT_T), a Halcyon IMRT (IMRT_H) plan and a Halcyon volumetric-modulated arc therapy (VMAT_H) plan were designed for each patient. The conformity index (CI) and homogeneity index (HI) of the PTVs, and the dose of organs at risk were calculated and compared. Statistical significance was performed using the LSD-t test or Wilcoxon signed-rank test with a significance level of 0.05. The V20 and V30 of ipsilateral lung, the V20, V30 and Dmean of heart, and CI of target area in IMRT_H plan were significantly lower than those in IMRT_T plan (P<0.05). No significant difference was found in the V5, V10 and Dmean of ipsilateral lung, the V5 and Dmean of contralateral lung, the V5 and Dmean of contralateral breast, HI of PTV (P>0.05), but the Dmean of left humeral head in IMRT_H plan was significantly higher than that of IMRT_T plan (P<0.05). All the metrics mentioned above showed higher level in VMAT_H plan than the IMRT_T plan and IMRT_H plan (P<0.05), except for HI (P>0.05) and Dmean of left humeral head (P>0.05 when compared to IMRT_H plan). The IMRT_H plan acts better in OAR sparing and PTV conformity than the IMRT_T plan, while the VMAT-H plan can only parallel the other two techniques in HI. The IMRT_H plan is promising in treating left breast postmastectomy patients with dosimetric improvements.

First-in-Human Phase I Trial Combining Biologically Guided Radioimmunotherapy (RIT) Using a 90Y-Anti-CD25 Monoclonal Antibody (Mab) with CT-guided Total Marrow and Lymphoid Irradiation (TMLI) in Relapsed and Refractory (R/R) Acute Leukemia

Patients with R/R acute leukemia after allogeneic hematopoietic cell transplant (alloHCT) have a dismal prognosis with 3-year survival rates of < 20%. To improve outcomes, innovative targeted forms of organ sparing radiotherapy, such as tumor-specific RIT and TMLI, are needed to dose escalate with acceptable toxicities, especially in patients ≥ age 60 years who cannot tolerate total body irradiation (TBI) / myeloablative regimens and who have a poor prognosis. CD25 is an ideal RIT target given its expression in acute leukemias, association with poor prognosis, and expression by leukemia stem cells. In this phase I trial (NCT05139004) we hypothesized that combining dose escalated 90Y-anti-CD25 RIT with fixed dose TMLI 12 Gy, fludarabine (flu), and melphalan (mel) in patients with R/R disease is safe and associated with acceptable toxicities. The primary objective of this trial is to determine the maximum tolerated dose and recommended phase 2 dose of 90Y-anti-CD25 Mab (Day -15) with 12 Gy TMLI (1.5 Gy twice a day, days -8 to -5), flu (30 mg/m2/d days -5 to -2), and mel (100 mg/m2, day -2) in patients ≥ 60 years old or with a HCT-comorbidity index ≥ 2 and with R/R AML, ALL or myelodysplastic syndrome (MDS) scheduled to undergo alloHCT from a matched donor. TMLI mean organ dose constraints for kidney, lung and liver were 4 Gy. Planned dose levels of 90Y-anti-CD25 were 0.3, 0.4, and 0.5 mCi/kg. 111In-anti-CD25 (5 mCi) was co-infused followed by serial nuclear scans to assess dosimetry and biodistribution. To date 5 patients (ages 31-74) with R/R AML have been treated. Marrow and circulating blasts ranged from 10-36% and 9-44%, respectively. For the 3 patients at 0.3 mCi/kg, follow-up ranged from 89-191+ days. 90Y/111In-anti-CD25 nuclear scans demonstrated persistent uptake in bone out to 144 hours, which was associated with a decline in circulating blasts. After combined RIT and TMLI, mean doses (Gy) to lungs ranged from 5.7-6.5, to kidneys from 7.5-8.2 and to liver from 7.2-11.6. No dose-limiting toxicities (DLT) were observed. All 3 patients achieved CR on day +30 bone marrow biopsies and 2 remained in CR on day +90 biopsies. Two patients have recently been treated at the 0.4 mCi/kg dose level. The results of patients treated at the higher dose levels will be provided. Dose escalation by adding 90Y-anti-CD25 RIT at 0.3 mCi/kg to 12 Gy TMLI was safe, including in older patients, with no dose-limiting toxicities, mean critical organ doses lower than conventional myeloablative TBI, and encouraging response rates. The toxicity profile and dose estimates at 0.3 mCi/kg predict that the planned higher dose levels will also be feasible with acceptable toxicities. RIT and TMLI are complementary and when combined address the limitations of each modality. Combining these targeted therapies may be a superior strategy to intensify dose to leukemia compared to dose escalation of either modality alone.

VMAT TBI Technique Using Autoplanning Scripts

Evident by the Children's Oncology Group (COG) survey of pediatric total body irradiation (TBI) practice, 100% of physicians were open to refining the conventional TBI technique to lower the lung dose and 75% of respondents were interested in implementing VMAT or a 3-D CRT and IMRT system TBI. Unfortunately, only a handful of COG institutions have implemented VMAT or Tomo TBI. We created the autoplanning scripts and shared them with the public to make the VMAT TBI more wide-spread. Here, we report on our initial experience of treating Stanford VMAT TBI technique using the scripts. From October 2019 to February 2023, 75 patients were treated with VMAT TBI at our institution. Organ sparing depended on the regimen: myeloablative (lungs, kidneys, and lenses); non-myeloablative (lungs, kidneys, lenses, gonads, brain, and thyroid). Treatment planning was performed using Eclipse Scripting Application Programming Interface (ESAPI) auto-planning scripts. Data on patient, treatment details, and dosimetric indices were collected. Treatment was delivered using IGRT for every isocenter and every fraction. In-vivo measurements were performed on the matchline between the VMAT and AP/PA fields and on the testes for the first fraction. Median patient age was 13 years (range, 1 - 64). The patient height and width range were 83.6-197.3 cm and 24.9-60.3 cm, respectively. Forty-eight percent of patients were treated using myeloablative and 52% nonmyeloablative regimens. For all patients the lungs, lungs-1cm, and kidneys Dmean were consistently spared to 59.8±4.7%, 43.0±6.5%, and 70.9±7.7% of the prescription dose, respectively. Gonadal sparing (Dmean = 31.5±5.9%) was achieved for all patients with benign disease. In addition, brain and thyroid was spared for these patients. For nine patients, VMAT TBI offered additional organ sparing (liver, heart, and previously irradiated areas) and possibility to perform the simultaneously integrated boost. The average PTV D1cc was 120.3±6.6% for all patients. PTV D1cc correlated with patient height and width (R2 = 0.62 and 0.53). Sixteen patients (21.3%) with height <116cm were treated with 3-isocenter VMAT only plans, 59 patients (78.6%) were treated with 3-4 isocenter VMAT plans in head-first-supine position and 1-3 AP/PA plan in feet-first-supine position. Rotational platform was used to change the patient orientation. The average matchline dose measurement indicated patient setup was reproducible (96.1±4.5% relative to planned dose). For the first 35 patients, treatment time, including patient setup and beam-on, was 47.5±9.5 min. VMAT TBI is a modern alternative to conventional 2D TBI treatment offering the possibility of organ sparing, dose painting, and accurate treatment using IGRT. The automated scripts enable streamline planning with consistent plan quality.

Predicting Prostate VMAT 3D Radiation Doses of Continuously Varying Organ Dose Trade-Offs Using a Conditional Variational Autoencoder

Predicting 3D radiation doses from planning structures is a promising method of knowledge-based treatment planning. However, most models are designed to predict only one 3D dose distribution per patient, based on historical organ dose trade-offs. To allow customizable plan generation, in this study, we aim to show the feasibility of dose prediction in which the degrees of organ dose trade-off could be explicitly specified. Specifically, the bladder vs. rectum dose trade-off in prostate cancer was investigated. In an IRB-approved study, we obtained imaging and structure contours for 167 patients with prostate cancer who received definitive radiotherapy. Training data was generated by automatically creating 3 different plans for each patient: while keeping target dose patterns constant, 1 base plan was generated with optimization objectives directly based on the output of a custom RapidPlan model prediction (S = 0), 1 plan with the goal to significantly lower bladder dose relative to the rectum (S = -1), and 1 plan with the goal to significantly lower rectum dose relative to the bladder (S = 1). This process was achieved by adjusting priority values during optimization. S is a scalar indicating the degree of bladder vs. rectum dose trade-off (higher S = higher dose to the bladder relative to the rectum). A conditional variational autoencoder (cVAE) was constructed as the generative model. Training, validation, and testing sets consist of 124, 10, and 33 patients, respectively. During training, the inputs to the model were 3D structure masks with voxel values modified based on S, and the output was the corresponding 3D dose. For model testing, we selected 7 equispaced values of S in the range [-1, +1] for each of the 33 test patients, generated the 3D doses for each S value (normalized to D2% = 110%), and calculated the differences of key dosimetric parameters (for S levels other than 0) compared to the predicted base plan (S = 0). The mean and standard deviations for these differences were reported. The cVAE model converged after training for 800 epochs. As the value of S increased from -1 to +1, the target coverage remained similar, while the doses to the bladder and rectum increased and decreased, respectively, as expected (Table 1). This pattern was also confirmed by qualitative examination of dose-volume histograms for additional S values. We demonstrated the feasibility of predicting 3D radiation dose distributions for prostate cancer where the degrees of organ dose trade-off could be explicitly specified.

Knowledge Based Planning for Lung SBRT: Model Transferability between Treatment Systems and Calculation Algorithms

Knowledge based planning (KBP) is known to be effective and clinically feasible in achieving high quality treatment plans with less variability between planners and reduced planning time. A KBP model is highly dependent on characteristics of the training data. Our institution developed and validated a lung SBRT KBP model from plans treated with a C-arm linear accelerator (Linac). This study aims to evaluate the quality of lung SBRT plans with a KBP model when this model is used for an O-ring Linac with different MLC design, beam quality, and calculation algorithm. Two academic hospitals in the same healthcare network were included in this study. One hospital trained a KBP model for five-fraction lung SBRT using 43 plans calculated using the Eclipse AcurosXB v15.6 algorithm for a C-arm Linac. The model was developed to prioritize dose gradient outside the PTV while satisfying institutional critical organ limits and validated using an additional set of 12 plans. A cohort of 10 patients (11 plans) previously treated with lung SBRT using the O-ring Linac at the second hospital was selected. These plans were calculated using the Eclipse AAA v15.6 algorithm with prescription doses of 30-50 Gy in five fractions. Each plan was re-optimized using the KBP model, without manual adjustment of the optimization objectives, using the same beam geometry as in the clinical plans. KBP plans were normalized to achieve the same PTV coverage as the clinical plans. Clinical and KBP plans were evaluated for ITV D98%, PTV conformity index (CI), R50 and maximum dose at 2 cm from the PTV (D2cm). All clinical and KBP plans met critical organ dose constraints. The range of CI was 1-1.13 vs. 0.96-1.05 for clinical plans and KBP plans, respectively. R50 and D2cm were lower with KBP plans (p = 0.007 and p = 0.05, respectively). ITV D98% range was 105-120% vs. 117-122% of the PTV prescription dose for clinical plans and KBP plans, respectively, and higher with KBP plans (p<0.001). For plans where the PTV overlaps the chest wall (n = 7), the maximum chest wall doses (D0.03cc) from KBP plans were higher than the clinical plans (p = 0.16), with an absolute chest wall D0.03cc difference of 9 Gy (54 Gy vs 63 Gy). The KBP model includes an ITV SIB of 120% of the PTV prescription, whereas the clinical plans reduced the ITV SIB when the PTV overlapped the chest wall, highlighting a difference in clinical practice between the two hospitals in this study. This study supports that a lung SBRT KBP model trained using plans for one Linac system and the AcurosXB algorithm can be used to generate clinically acceptable plans without manual planner intervention for a different Linac system and the AAA calculation algorithm, indicating the potential of a KBP model use for centralized planning process across different Linac systems and calculation algorithms.

Radio-Immune Response of Spatially Fractionated Radiotherapy for VMAT Lattice Plans

To evaluate radio-immune response of spatially fractionated radiotherapy (SFRT) for large tumors using VMAT Lattice technique in terms of tumor volume under irradiation and dose fractionation schemes after SFRT. Eleven patients treated with SFRT from a single institution were retrospectively replanned to deliver 15Gy in single fraction using Lattice technique. High dose regions are defined by multiple spheres with the diameter of 1.25 to 1.5cm and their vertex space of 3.0 to 4.0cm inside of GTV. VMAT plans with multiple arcs were developed for SFRT. Four palliative fractionation regimens of 200cGy x 12 (EQD2 = 24Gy with a/b of 10Gy), 400cGy x 5 (23.3Gy), 600cGy x 3 (24Gy) and 800cGy x2 (24Gy) and four definitive regimens of 200cGy x 24 (EQD2 = 48Gy), 400cGy x 10 (46.7Gy), 600cGy x 6 (48Gy) and 800cGy x 4 (48Gy) were considered for radiotherapy to follow SFRT. Linear quadratic (LQ) model is compared with radio-immune (RI) response model in which the activation of cytotoxic T lymphocytes, tumor immune suppression capability and immunotherapy drugs can be considered. Tumor regrowth time (TRT, time to tumor regrowth to the original volume after treatment) from each model was compared as a measure of benefit achieved from the application of SFRT. The average volume of GTVs in this study was 776cc (range 58-2944cc). Three different SFRT plans (2D GRID technique with conventional collimator, 2D GRID with step & shoot IMRT, and 3D Lattice) were developed for each patient but only Lattice plans were considered in this study since they produced comparable dose modulation inside the tumor but only Lattice significantly reduced skin and critical organ dose. Radio-immune response model always expects longer TRT than LQ model. For palliative regimens, TRT of RI model is longer than that of LQ model by 14.5±9.9, 15.1±10.6, 17.2±12.4, 17.5±12.8 days for each fractionation scheme. When Lattice plan of 15Gy is delivered before the palliative treatment, the difference becomes 25.9±15.3, 31.5±23.3, 36.7±27.6, 37.5±28.5 days. The benefit of SFRT from RI response is only about 10-20 days. Interestingly, RI response is inversely proportional to tumor volume. When curative dose is considered, the difference of TRT is drastically changed from 25.9±9.8, 460.7±285.8, 1180.8±985.7, 1512.0±1327.5 days to 20.7±4.4, 449.0±411.7, 1725.4±2171.0, 3517.7±4531.7 days. The benefit of SFRT from RI response appears larger for large tumor with hypo-fractionation in definitive regimens. The benefit of SFRT is significant for large tumors with hypo fractionation in the definitive regimens when radio-immune response model is considered which is not apparent in LQ model. Radio-immune response model may help to guide the development of successful treatment scheme large tumor volumes.

Dose Constraints and Planning Considerations for Thoracic Radiation Therapy: Delphi Consensus from a National Survey of Experts

Many physicians refer to trial protocols or published guidelines (NCCN, QUANTEC, HyTEC) for dose-volume histogram (DVH) metrics. However, there may be variation in implementing these metrics during plan optimization. Some studies have suggested better outcomes for patients treated at high-volume, high-expertise centers. These differences may in part be due to greater standardization or center-specific treatment planning processes. We surveyed radiation oncologists with stated thoracic-specific expertise using the Delphi method to formulate consensus DVH metrics that would be considered ideal for high-quality radiation treatment plans. Thoracic radiation oncology experts were identified using departmental websites of ACGME-accredited radiation oncology programs. After confirming their expertise, panelists were invited to submit their institutional templates and complete three rounds of questions related to normal organ dose constraints, target coverage metrics, prescribing practices, and other planning considerations. Queried radiation schemes included conventional fractionation, twice-daily fractionation, and stereotactic body radiation therapy (3 and 5 fractions). Preliminary consensus statements were generated using median values for DVH metrics and were iteratively refined in subsequent surveys. Consensus was pre-defined as ≥75% agreement among panelists. A total of 194 experts were invited, and 100 agreed to participate. The panel was 28% female and included experts from 29 states with a median of 11 years of clinical experience (IQR 6-19). 89% specialized in 1-2 disease sites. Response rates for the Demographics, round 1, 2, and 3 surveys were 83%, 78%, 57%, and 55%, respectively. 93% of panelists believed that DVH metrics should provide thresholds for both optimal and acceptable criteria for treatment planning. 49 of the 96 proposed normal tissue dose constraint statements were iterated to consensus (Table 1), and 5 of 7 proposed target coverage metric statements achieved consensus. This study highlights the heterogeneity in metrics used by thoracic radiation oncologists and provides levels of consensus on ideal and acceptable dose constraints as guidance for treatment planning. Future directions include using these statements to develop prescription templates and acceptance criteria for treatment planning systems for widespread use as well as extending this Delphi approach to additional disease sites.

Experimental validation of an innovative approach in biokinetics study for personalised dosimetry of molecular radiation therapy treatments

One of today’s main challenges in molecular radiation therapy is to assess an individual dosimetry that allows treatment to be tailored to the specific patient, in accordance with the current paradigm of ‘personalized medicine’. The evaluation of the absorbed doses for tumor and organs at risk in molecular radiotherapy is typically based on MIRD schema acquiring few experimental points for the assessement of biokinetic parameters. WIDMApp, the wearable individual dose monitoring apparatus, is an innovative approach for internal dosimetry based on a wearable radiation detecting system for individual biokinetics sampling, a Monte Carlo simulation for particle interaction, and an unfolding algorithm for data analysis and integrated activity determination at organ level. A prototype of a WIDMApp detector element was used to record the photon emissions in a body phantom containing 3 spheres with liquid sources (18F, 64Cu and 99m Tc) to simulate organs having different washout. Modelling the phantom geometry on the basis of a CT scan imaging, the Monte Carlo simulation computed the contribution of each emitting sphere to the signal detected in 3 positions on the phantoms surface. Combining the simulated results with the data acquired for 120 h, the unfolding algorithm deconvolved the detected signal and assessed the decay half-life (T 1/2) and initial activity values (A(0)) that best reproduces the observed exponential decays. A 3%–18% level of agreement is found between the actual A(0) and T 1/2 values and those obtained by means of the minimization procedure based on the Monte Carlo simulation. That resulted in an estimation of the cumulated activity <15%. Moreover, WIDMApp data redundancy has been used to mitigate some experimental occurrences that happened during data taking. A first experimental test of the WIDMApp approach to internal radiation dosimetry is presented. Studies with patients are foreseen to validate the technique in a real environment.

Reduksi Dosis Serap Mata dengan Implementasi Software Organ Dose Modulation (ODM) pada Protokol CT Scan Sinus Paranasal

Background: CT Scan examination of the paranasal sinuses includes organs that are sensitive to radiation exposure, one of which is the lens of the eye whose damage can be known after radiation exposure of about 500 mGy. Currently found an alternative to reduce the dose received by patients is with Organ Dose Modulation (ODM) software This ODM serves to reduce radiation dose in the eye -18.9%, Brain -10.1%, Breast -31.3%, Lung -20.7% and Liver -24%. The purpose of this study is to determine the role of ODM software in dose reduction on CT Scan SPN, determine the amount of absorption dose profile with the implementation of ODM software, differences in anatomical image information with the implementation of ODM software and without ODM on CT Scan SPN.Methods: This type of research is quantitative with experimental studies, comparing the use of software with and without ODM to absorption dose reduction and anatomical image information of SPN. Samples using phantom performed Paranasal Sinus CT Scan procedure. Respondents consisted of 3 radiologists to assess the anatomical image of the maxillaris bone, bilateral maxillar sinus, and rice septum. Data analysis was carried out by statistical tests using SPSS Software to find the value of significance differences.Results: The use of ODM software on CT scans of the paranasal sinuses plays an important role in reducing the absorbed dose of the eye. Statistical test results showed a significant reduction in eye absorption dose (p-value 0.05). The dose profile resulting from the use of the ODM software is a decrease in the absorbed dose by the eye by 9.75%. The value of differences in SPN anatomical information using and without ODM resulted in a p-value of 1.00 (p-value 0.05).Conclusion: The value of the absorbed dose of eye radiation is significantly different with and without the use of ODM. However, there is no significant difference in the SPN anatomical image information. From the implementation of the ODM software, it can reduce the absorbed dose in the eye without reducing the anatomical image information.

The application of 3D-printed oral stents in intensity-modulated radiotherapy for oropharyngeal cancer and their dosimetric effect on organs at risk

BackgroundThis study investigates the accuracy of 3D-printed dental stents in intensity-modulated radiotherapy (IMRT) for oropharyngeal cancer (OPC) and their dosimetric effects on normal tissues.MethodsWe selected 60 patients with OPC who underwent IMRT in the Department of Oncology, Special Medical Center of Army Medical University. These patients were randomly assigned into 3D-printed oral stent, simple glass bottle, and nonstent groups (20 patients/group). The positioning error was analyzed with the onboard imaging system once a week after 5 fractions of IMRT. The conformity index (CI), homogeneity index (HI), radiation dose of organs at risk (OARs), and oral mucosal reaction were compared among the three groups.ResultsNo significant difference was observed in the conformity and uniformity of the target dose and the dose received by the spinal cord, larynx, and bilateral parotid glands among the three groups (P > 0.05). Meanwhile, the dose received by the upper cheek, hard palate, and soft palate of patients was significantly lower in the 3D-printed oral stent group than in the nonstent group (P < 0.05) but insignificantly different between the 3D-printed oral stent and simple glass bottle groups (P > 0.05). When compared with the nonstent group, the simple glass bottle group showed a markedly lower dose received by the upper cheek (P < 0.05) and an insignificantly different dose received by the hard palate and soft palate (P > 0.05). According to Common Terminology Criteria for Adverse Events v.5.0, the adverse response rate of the hard palate mucosa was lower in the 3D-printed oral stent group than in the simple glass bottle and nonstent groups (P < 0.05).ConclusionsFor OPC patients undergoing IMRT, the application of 3D-printed oral stents can significantly reduce the exposure dose of the upper cheek and hard palate and decrease the occurrence of adverse events such as oral mucositis although it cannot affect the positioning error.

Tumor-Targeted Interleukin 2 Boosts the Anticancer Activity of FAP-Directed Radioligand Therapeutics.

We studied the antitumor efficacy of a combination of 177Lu-labeled radioligand therapeutics targeting the fibroblast activation protein (FAP) (OncoFAP and BiOncoFAP) with the antibody-cytokine fusion protein L19-interleukin 2 (L19-IL2) providing targeted delivery of interleukin 2 to tumors. Methods: The biodistribution of 177Lu-OncoFAP and 177Lu-BiOncoFAP at different molar amounts (3 vs. 250 nmol/kg) of injected ligand was studied via SPECT/CT in mice bearing subcutaneous HT-1080.hFAP tumors, and self-absorbed tumor and organ doses were calculated. The invivo anticancer effect of 5 MBq of the radiolabeled preparations was evaluated as monotherapy or in combination with L19-IL2 in subcutaneously implanted HT-1080.hFAP and SK-RC-52.hFAP tumors. Tumor samples from animals treated with 177Lu-BiOncoFAP, L19-IL2, or both were analyzed by mass spectrometry-based proteomics to identify therapeutic signatures on cellular and stromal markers of cancer and on immunomodulatory targets. Results: 177Lu-BiOncoFAP led to a significantly higher self-absorbed dose in FAP-positive tumors (0.293 ± 0.123 Gy/MBq) than did 177Lu-OncoFAP (0.157 ± 0.047 Gy/MBq, P = 0.01) and demonstrated favorable tumor-to-organ ratios at high molar amounts of injected ligand. Administration of L19-IL2 or 177Lu-BiOncoFAP as single agents led to cancer cures in only a limited number of treated animals. In 177Lu-BiOncoFAP-plus-L19-IL2 combination therapy, complete remissions were observed in all injected mice (7/7 complete remissions for the HT-1080.hFAP model, and 4/4 complete remissions for the SK-RC-52.hFAP model), suggesting therapeutic synergy. Proteomic studies revealed a mechanism of action based on the activation of natural killer cells, with a significant enhancement of the expression of granzymes and perforin 1 in the tumor microenvironment after combination treatment. Conclusion: The combination of OncoFAP-based radioligand therapeutics with concurrent targeting of interleukin 2 shows synergistic anticancer effects in the treatment of FAP-positive tumors. This experimental finding should be corroborated by future clinical studies.

Complete patient exposure during paediatric brain cancer treatment for photon and proton therapy techniques including imaging procedures.

In radiotherapy, especially when treating children, minimising exposure of healthy tissue can prevent the development of adverse outcomes, including second cancers. In this study we propose a validated Monte Carlo framework to evaluate the complete patient exposure during paediatric brain cancer treatment. Organ doses were calculated for treatment of a diffuse midline glioma (50.4 Gy with 1.8 Gy per fraction) on a 5-year-old anthropomorphic phantom with 3D-conformal radiotherapy, intensity modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT) and intensity modulated pencil beam scanning (PBS) proton therapy. Doses from computed tomography (CT) for planning and on-board imaging for positioning (kV-cone beam CT and X-ray imaging) accounted for the estimate of the exposure of the patient including imaging therapeutic dose. For dose calculations we used validated Monte Carlo-based tools (PRIMO, TOPAS, PENELOPE), while lifetime attributable risk (LAR) was estimated from dose-response relationships for cancer induction, proposed by Schneider etal. Out-of-field organ dose equivalent data of proton therapy are lower, with doses between 0.6 mSv (testes) and 120 mSv (thyroid), when compared to photon therapy revealing the highest out-of-field doses for IMRT ranging between 43 mSv (testes) and 575 mSv (thyroid). Dose delivered by CT ranged between 0.01 mSv (testes) and 72 mSv (scapula) while a single imaging positioning ranged between 2 μSv (testes) and 1.3 mSv (thyroid) for CBCT and 0.03 μSv (testes) and 48 μSv (scapula) for X-ray. Adding imaging dose from CT and daily CBCT to the therapeutic demonstrated an important contribution of imaging to the overall radiation burden in the course of treatment, which is subsequently used to predict the LAR, for selected organs. The complete patient exposure during paediatric brain cancer treatment was estimated by combining the results from different Monte Carlo-based dosimetry tools, showing that proton therapy allows significant reduction of the out-of-field doses and secondary cancer risk in selected organs.

Radiation dose evaluation to organs in neonatal patients by field size during potable X-ray examination in incubators: A Monte Carlo simulation study.

Neonatal patients located in incubators are exposed to as many as 159 radiographs until discharge. To reduce the dose exposed to the patient, factors that may cause unnecessary exposure to the patient were judged. When conducting portable X-rays of neonatal patients located in an incubator, it is not easy to determine the exact field size because collimation light is exposed on the acrylic plate, an incubator canopy, and the resulting shadow is reflected on the patient's body. This study aims to measure the organ dose exposed to the patient according to the field size when a portable radiograph is given to a neonatal patient in a neonatal intensive care unit (NICU) incubator. To identify the absorbed organ dose depending on the radiation field size during portable X-ray examination of neonatal patient, a Monte Carlo N-Particle (MCNP) simulation, a SpeckCalc program, and a neonatal phantom from the ICRP 89 are applied for the calculation. According to the minimal field size (MinFS) standards of the European Commission (EC), the smaller field size is intended to measure tightly from the top of the lung apices to the bottom of the genitals; a larger field size is also calculated by adding 6 cm in width and length. Compared to the hospital C condition from the previous study, the larger and smaller field sizes are decreased by an average of 45% and 67%, respectively. Study results also show a 42% reduction in smaller field size compared to the larger field size. When taking chest and abdomen radiographic images of neonatal patients in incubators, appropriate field sizes are required to prevent inappropriate dose absorption for non-thoracic organs.