Mean Dose Research Articles

Assessing parotid gland function through diffusion weighted MRI during and post-radiotherapy in head and neck cancer patients

ObjectivesThe purpose of this study was to evaluate the usefulness of apparent diffusion coefficient (ADC) variation in irradiated parotid glands during and after 3D conformal radiotherapy (3DCRT). Materials and methodsThis study enrolled 15 head and neck cancer (HNC) patients who were treated with 3DCRT underwent diffusion weighted imaging (DWI) at rest and after gustatory stimulation in three time points as follows: before, during (one day after receiving the mean dose 26 Gy) and 6 months after the end of radiotherapy (RT). Salivary Ejection Fraction (SEF) data was also obtained from salivary gland scintigraphy (SGS) at the same three time points as MRI. Mean ADC at rest and after stimulation (ADCr, ADCs) and SEF were extracted from parotid region for three time points. Finally, SEF and changes of ADC over time at rest and after stimulation and in each time point were compared. ResultsDifference between mean ADCr before RT and during RT was not significant (p = 0.12). The ADCr values were significantly higher after RT than before RT (p = 0.003) and during RT (after dose 26 Gy) (p = 0.001). The difference between ADCr and ADCs in each time point showed that there is significant difference between ADCr and ADCs before RT (p = 0.005). Difference between these parameters after RT was also significant (p = 0.05). Non-significant difference (p = 0.21) between ADCr and ADCs during RT was observed. The result of SEF also was significantly lower after RT than during (p = 0.008) and before RT (p = 0.001). ConclusionMean ADC values could be used as a surrogate marker to characterize the parotid function in different stages of RT.

Low Frequency of Upper Gastrointestinal Bleeding Despite Non-Steroidal Anti-Inflammatory Drugs and Corticosteroids in Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease. It has been identified that non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids can be essential risk factors for developing complications such as upper gastrointestinal bleeding (UGIB). This study aimed to describe the safety profile of drugs used to treat RA focused in UGIB. A cross-sectional study of patients with RA between 2015 and 2021, a description of the population, and an evaluation of the relationship with UGIB through bivariate analysis and logistic regression. Of 405 individuals, 16 presented UGIB (93.8% women, mean age was 65±13.6 years). No statistically significant differences were found regarding UGIB and medication use, except for the mean dose of corticosteroids. In the multivariate analysis, it was found that the presence of anemia in the last three months had an adjusted OR (AOR) of 16.1 (95% CI 2.74- 24.23) and higher HAQ values during the previous three months had an AOR of 6.17 (95% CI 1.79- 21.24). This study found a low frequency of UGIB in patients with RA. More significant disability and anemia in the previous months were independently associated with UGIB. The low frequency of NSAID use in this population is noteworthy. In general, reasonable medication use related to this complication is recommended.

OGC SO08 - Optimising Analgesia in Sub-total Oesophagectomy: A Dose of Success

Abstract Background Sub-total oesophagectomy (STO) is a complex and major surgery with significant associated burdens for our patients. Our centre in North-East England completes 70-80 STOs annually. In the peri-operative period, good analgesia management and delivery is key. Analgesia strategy has evolved across the UK over the past decade, influenced by multi-modal analgesia, progressing surgical approaches towards minimally invasive operations alongside the ongoing drive for enhanced recovery programmes endorsing early mobilisation. Surgical approach in our patient cohort now comprises a combination of Open-Open, combined Open-Minimally invasive and entirely minimally invasive techniques. Our analgesia strategy combines single shot intrathecal diamorphine and regional anaesthesia. Method We engaged our multi-professional (Acute Pain Specialist Nurses, Anaesthesia Consultants and Surgical Consultants) team in a PDSA cycle. A guidance analgesia package was agreed after review of retrospective cases. This package was delivered to our baseline group of 10 patients. We used subjective patient reported abdominal and thorax pain scores on a 0-10 scale, recorded by our pain team each day for post-operative days 1-5. Following analysis, we implemented a single change to Intrathecal diamorphine dosing - changing from uniform delivery of 1000micrograms intrathecal diamorphine to a dose calculated on Ideal Body Weight of 15-20micrograms/kg up to 1500micrograms maximum dose Results Our baseline group of 10 patients all received 1000micrograms of intrathecal diamorphine - mean dose 15.9mcg/kg. Our intervention group of 12 patients received doses based upon their ideal body weight - mean dose 18.9mcg/kg. Overall, there was a trend of reduced pain scores following our intervention. Thoracic reported overall pain scores were significantly lower (p=0.04) following the intervention. No significant difference was demonstrated specifically in the first 24 or 48hours in overall, abdominal or thoracic pain scores. Importantly, there were no reported adverse events related to our higher dosing regime and no recorded side effects such as pruritis or nausea. Conclusion There is little evidence with regards the use of higher dose intrathecal diamorphine in the literature. The sample sizes in our groups are small but overall reduction in patient reported pain scores appear to be associated with use of the higher dose of intrathecal diamorphine, based upon ideal body weight and importantly without any adverse effect. Continued evolution of our analgesia strategies is essential alongside that of surgical techniques. The next iterations of our guidance and PDSA cycle will consider our regional techniques to identify if further advances can be made.

Spatially Fractionated Radiotherapy with Very High Energy Electron Pencil Beam Scanning.


To evaluate spatially fractionated radiation therapy (SFRT) for very-high-energy electrons (VHEEs) delivered with pencil beam scanning. Radiochromic film was irradiated at the CERN Linear Electron Accelerator for Research (CLEAR) using 194 MeV electrons with a step-and-shoot technique, moving films within a water tank. Peak-to-valley dose ratios (PVDRs), depths of convergence (PVDR≤1.1), peak doses, and valley doses assessed SFRT dose distribution quality. A Monte Carlo (MI) model of the pencil beams was developed using TOPAS and applied to a five-beam VHEE SFRT treatment for a canine glioma patient, compared to a clinical 6 MV VMAT plan. The plans were evaluated based on dose-volume histograms, mean dose, and maximum dose to the planning target volume (PTV) and organs at risk (OARs).
Main Results:
Experimental PVDR values were maximized at 15.5 ± 0.1 at 12 mm depth for 5 mm spot spacing. A depth of convergence of 76.5 mm, 70.7 mm, and 56.6 mm was found for 5 mm, 4 mm, and 3 mm beamlet spacings, respectively. MC simulations and experiments showed good agreement, with maximum relative dose differences of 2% in percentage depth dose curves and less than 3% in beam profiles. Simulated PVDR values reached 180 ± 4, potentially achievable with reduced leakage dose. VHEE SFRT plans for the canine glioma patient showed a decrease in mean dose (>16%) to OARs while increasing the PTV mean dose by up to 15%. Lowering beam energy enhanced PTV dose homogeneity and reduced OAR maximum doses. The presented work demonstrates that pencil beam scanning SFRT with VHEEs could treat deep-seated tumors such as head and neck cancer or lung lesions, though small beam size and leakage dose may limit the achievable PVDR.&#xD.

Impact of deep inspiration breath hold, surface-guided radiotherapy, and daily CBCT on the organs at risk in breast cancer radiotherapy.

The goal of the study was to assess the impact of deep inspiration breath hold technique (DIBH), surface-guided radiotherapy (SGRT), and daily kilovoltage cone-beam computed tomography (kV-CBCT) on the dose to organs at risk (OAR) in left-sided breast cancer radiotherapy. Twenty-six consecutive left-sided breast cancer patients treated using Volumetric Intensity Modulated Arc Therapy (VMAT), DIBH, SGRT, and a hypofractionated regimen were retrospectively evaluated in this study. Dose parameters were extracted from dose-volume histograms (DVH). The Wilcoxon Matched Pairs test was used to test dose parameters obtained in free breathing (FB) and DIBH for statistical significance. Multivariable analysis of variance (ANOVA) and receiver operating characteristics (ROC) analysis were used to identify parameters and cut-off points associated with the reduction of the mean heart dose (MHD) by DIBH. Based on published models, the risk of cardiac and lung toxicity (pneumonitis) using SGRT or daily kV-CBCT was estimated and compared. DIBH substantially reduced the MHD (median, 43.6%; range, 4.2% to 75.1%; P < 0.00001). The risk of cardiac toxicity using SGRT increased by 1%, compared to 3.6% to 20.5% using daily kV-CBCT. No significant difference in the risk of radiation-induced pneumonitis using SGRT versus daily kV-CBCT was detected. The ANOVA revealed the relative increase of the left lung volume by DIBH as the only significant impact factor for the MHD. The ROC analysis of this parameter showed an area under the curve (AUC) of 0.89 (95%CI, 0.71 to 0.98; P < 0.0001). DIBH can substantially reduce the MHD in left-sided breast cancer patients treated with modern radiotherapy techniques and hypofractionation. Patient setup using SGRT compared to daily kV-CBCT may be the preferred option for many patients. In our patient cohort, the relative reduction of the left lung volume by DIBH can be used as a predictor to select patients who benefit from DIBH.

Voxel-Based Dosimetry Predicts Local Tumor Progression Post 90Y Radiation Segmentectomy of Colorectal Liver Metastases

Background Radiation segmentectomy (RS) is an alternative potential local curative treatment for selected colorectal liver metastases (CLMs) not amenable to ablation or limited resection. Purpose The aim of this study was to evaluate the dosimetric response of low volume CLMs to RS in heavily pretreated patients who are not candidates for resection or percutaneous ablation. Patients and Methods This single-center retrospective study evaluated CLMs patients treated with RS (prescribed tumor dose &gt;190 Gy) from 2015 to 2023. RS doses to tumor(s) and margins were calculated from SPECT/CT and PET/CT images. Response and local tumor progression (LTP) were assessed using anatomic (RECIST 1.1) and metabolic (PERCIST) criteria. LTP-free survival (LTPFS) and overall survival were estimated with Kaplan-Meier methodology. Variables were assessed as predictors of LTPFS using the Cox proportional hazards model. Results Thirty-six patients underwent 38 RS procedures to treat 57 tumors. Median time from initial diagnosis to detection of liver metastases and RS were 16.4 (interquartile range: 6.5–32.2) and 26.8 (interquartile range: 12.5–40.0) months, respectively. Median overall survival after RS was 14.3 (95% confidence interval [CI]: 10.8–30.7) months. Predictors of LTPFS included tumor number(s), mean tumor dose (MTD), and margin mean absorbed dose (MMAD). Complete radiographic (hazards ratio [HR]: 1.29e-16, 95% CI: 4.06e–17-4.07e-16, P &lt; 0.001) and metabolic response (HR: 0.38, 95% CI: 0.15–0.95, P = 0.038) correlated with prolonged LTPFS. One-year LTPFS rate was 83.3% for tumors receiving MTD ≥400 Gy and a 5-mm surrounding MMAD ≥350 Gy (P = 0.006). No instances of LTP were observed when tumors received stereotactic irradiation over 300 Gy (at least 95% of the tumor volume received ≥300 Gy). One-year LTPFS rate for tumors receiving MTD ≥400 Gy was 68.6% versus 14.3% for those that did not reach this threshold (P = 0.013). In multivariate analysis, MTD ≥400 Gy and 5-mm MMAD ≥350 Gy were independent predictors of LTPFS (HR: 0.11; 95% CI: 0.01–0.81; P = 0.03). Conclusions MTD ≥400 Gy, MMAD ≥350 Gy, and stereotactic tumor irradiation ≥300 Gy are associated with prolonged LTPFS after RS for CLMs.

Abstract 4137636: Cardiac radiation dose and changes in physical activity and quality of life in patients with locally advanced lung cancer

Background: Physical activity is associated with prognosis in cancer. However, in non-small cell lung cancer (NSCLC), a high cardiovascular (CV) population, the relationships between RT dose, physical activity, and CV patient-reported outcomes remain unclear. We determined the associations between cardiac radiation dose-volume metrics and changes in physical activity and quality-of-life (QoL) in patients treated with definitive chemoradiation. Methods: NSCLC participants treated with chemoradiation were enrolled in a multi-center longitudinal cohort study. Self-reported physical activity via Godin–Shephard Leisure-Time Physical Activity Questionnaire (Godin) and QoL via Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue and Dyspnea Scales were collected at baseline, end of RT, 6, and 12 months post-RT. Changes in Godin and FACIT scores over time were examined using linear mixed-effects models. Multivariable linear regression via generalized estimating equations assessed the associations between: 1) mean heart dose (MHD) and longitudinal changes in physical activity and QoL, and 2) concurrent changes in physical activity and FACIT scores. Results: Across 101 participants, the mean age was 66 years, with 57% male, 66% White, and 25% Black. The median (Q1, Q3) MHD was 10.8 Gy (6.1,16.3). Very low physical activity [9 (0, 25)], high dyspnea [4 (1, 9)], and low fatigue [39 (31,46)] were reported at baseline. With chemoRT, there was a significant worsening of physical activity ( P = 0.03), fatigue ( P &lt; 0.001), and dyspnea ( P &lt; 0.001). Each 1-Gy increase in MHD was associated with a modest decline in physical activity (-0.28; 95% CI -0.53, -0.02, P = 0.03), and higher physical activity was associated with a concurrent decrease in fatigue ( P &lt; 0.001) and dyspnea ( P = 0.007) (Table). Conclusions: In locally advanced NSCLC, physical activity levels prior to RT were very low, and higher cardiac radiation dose was associated with a further decline in physical activity. Increased physical activity was associated with concurrent decreases in fatigue and dyspnea. Strategies to promote physical activity may result in improved QoL in this high CV group.

RADT-36. FUNCTION-ADAPTED RADIOTHERAPY PLANNING IN THE MANAGEMENT OF HIGH-GRADE GLIOMAS: A COMPARING STUDY FOR DOSE SPARING OF SPEECH-ELOQUENT BRAIN AREAS

Abstract BACKGROUND Radiotherapy (RT) for brain tumors can induce injury of functional white matter tracts. In neurosurgery navigated transcranial magnetic stimulation (nTMS)- and diffusion tensor imaging (DTI)-based fiber tracts (FT) is an established tool to protect functional FT during tumor resection. We investigated it´s applicability in RT planning with the aim of dose reduction of language-associated fiber tracts. METHODS Preoperative, nTMS-generated and DTI-based FT of the functional left hemispheric language network of patients with language-eloquent malignant gliomas (WHO III/IV) were imported into the planning software (ARIA®) according to the DICOM standard and contoured as a risk structure. Brain shift after tumor resection was compensated using elastic fusion (Brainlab®). The treatment plans were optimized or recalculated with the aim of reducing the dose to the fiber tracts outside the planning target volume (PTV). The dosimetric evaluation was performed according to dose volume histogram parameters. RESULTS RT plans of 27 patients were retrospectively evaluated in the study. The mean dose (Dmean) to the fiber tracts was 37.3+/-11.8 Gy, with plan optimization dose was 33.6 +/- 12.2 Gy (-10.9% p&amp;lt;0.01), within the 20 Gy isodose the dose reduction to be achieved was on average - 25.0% (range 0-48.5%). The V54Gy and V20Gy were on average 40.2 +/- 23.7% and 72.3 +/- 21.1% compared to 38.2 +/- 23.5% and 58.1 +/- 23.7% (both p&amp;lt;0.01) with optimization. The Dmean of the PTV did not change (59.8 Gy vs. 59.8 Gy (p=0.5)), nor did the dose homogeneity (HI, (D5-D95)/Dp)(p=0.63)). The dose exposure of the organs at risk was within the specified dose constraints. CONCLUSION This study showed that (nTMS)- and diffusion tensor imaging (DTI)-based fiber tractography could be used in radiotherapy planning to spare language-eloquent brain areas without having to accept dose reductions within the PTV. Whether the concept of tract-based sparing of language function brings clinical benefits to patients needs to be further investigated in prospective studies.

NCOG-04. MEMORY TRACT SPARING USING DIFFUSE TENSOR IMAGING IN RADIATION PLANNING OF PRIMARY BRAIN TUMORS

Abstract INTRODUCTION Radiation therapy (RT) is a critical treatment modality for both primary and metastatic brain tumors, yet approximately 30% of patients experience cognitive decline post-radiotherapy. This cognitive toxicity is linked to low radiation doses affecting neural stem cells in the hippocampal dentate gyrus. Hippocampal Avoidance (HA)-Whole Brain Radiotherapy (WBRT) combined with Memantine has shown promising outcomes in preserving cognitive function and quality of life (QOL) in patients with brain metastases, suggesting it should be the standard of care for those with good performance status and no hippocampal metastases. METHODS We conducted a prospective trial approved by the IRB (SMC0307-23), including patients aged 18 and above with primary brain tumors post-resection or biopsy. Exclusion criteria included multifocal glioma crossing to the other hemisphere. RT was delivered to a total dose of 60Gy in 30 fractions with concomitant TMZ. Diffusion tensor imaging (DTI) was performed to map hippocampal-associated white matter tracts. Memory fiber tracts and hippocampi were contoured and integrated into RT planning using Eclipse treatment planning software. Dosimetric analyses compared two plans: one with memory fiber constraints and one without. RESULTS Twelve patients with low-grade gliomas were included, with successful contouring of memory fibers and hippocampi. VMAT treatment plans met dose constraints for memory fibers, with an average mean dose of 10.1 Gy. The average MoCA score before RT was 27.1 and 26.4 at six months post-treatment, with a p-value of 0.07. Excluding one patient, the scores were 27.1 and 26.6, respectively (p=0.13). CONCLUSION MRI planning using DTI for memory fiber detection and incorporation into RT planning via VMAT techniques enables hippocampal and associated white fiber sparing, potentially preserving cognitive function. Preliminary cognitive data are promising, supporting the need for further validation in a larger cohort.

Multicriteria optimization achieves superior normal tissue sparing in volumetric modulated arc therapy for gastric cancer.

To evaluate the benefits of volumetric modulated arc therapy (VMAT) based on multicriteria optimization (MCO) for gastric cancer patients, particularly the protection of serial organs at risk (OARs) that overlap with the target volume. MCO and single-criterion optimization (SCO) VMAT plans were conducted among 30 gastric cancer patients, with a prescription dose of 50.4Gy delivered in 28 fractions. All treatment plans underwent review, and a comparison was made between the active planning time and different dose-volume parameters. Both the MCO and SCO VMAT plans achieved the target dose coverage, with no significant difference in the conformity index (CI) for the planning target volume (PTV), at median CI values of 0.887 and 0.891, respectively (P = 0.417). The MCO plans showed a slight but significant increase in the homogeneity index of the PTV, with a median increase of 0.029 (P < 0.001). Additionally, the MCO plans resulted in a lower D2% to the small intestine and duodenum, with reductions of 3.43Gy and 0.3Gy, respectively (P < 0.05). Furthermore, the Dmax to the small intestine correlated moderately with the overlapping volume between the small intestine and the target volume (ρ = 0.42, P = 0.023). Except for the mean dose to the liver, the MCO plans performed better in terms of dose indicators for other OARs. Moreover, compared to the SCO plans, the median active planning time in the MCO plans was significantly reduced by 53.2min (P < 0.0001). MCO can effectively help the physicians to quickly select an optimal treatment plan for patients with gastric cancer. It has been shown that MCO VMAT plans can significantly reduce the dose to OARs and shorten the active planning time, with acceptable target coverage. In addition, these plans take less dosimetric time, thereby streamlining the treatment planning process.

CTNI-03. DECREASED GROWTH VELOCITY IN A PHASE 1 TRIAL (PNOC014) OF TOVORAFENIB IN PATIENTS WITH RECURRENT OR PROGRESSIVE MAPK-ALTERED TUMORS

Abstract BACKGROUND The mechanisms by which MAPK-targeted agents affect children in active phases of neurocognitive and physical development are poorly understood and hence, may place them at risk, particularly for uncommon patient toxicities that may require longer monitoring or larger patient cohorts to understand the long-term implications. Decreased growth velocity was identified in our investigator-initiated phase 1 trial (NCT03429803) of tovorafenib in relapsed MAPK-altered tumors. METHODS Forty-four patients enrolled from February 2018-October 2021. Toxicity was assessed according to CTCAE version 5 term growth suppression (GS). Patients were also evaluated retrospectively based on age-specific growth velocity norms. Post-pubertal patients (n=14), those with pre-existing growth abnormalities (n=3), and those on drug less than 6 months (n=10) were excluded (total n=27; 61%). Growth velocities for each patient were calculated prior to, on, and after discontinuing treatment as available. RESULTS Our safety database included 17 reported events of GS. Sixteen patients experienced grade 3 GS, defined as growth velocity reduction ≥50% ideally measured over a year compared to baseline. One patient experienced grade 2 GS, defined as reduced growth velocity by 30-49% compared to baseline. Separate retrospective analysis using age-specific growth velocity norms further confirmed that all 17 patients (100%) demonstrated decreased growth velocity compared to age-specific norms following start of treatment regardless of dose (3, 5 and 9 patients at 280, 420 and 530 mg/m2/dose, respectively with a mean dose of 507 mg, range: 220-840 mg). Four of 9 patients on 530 mg/m2 were dose reduced for other reasons and hence treated at 420 mg/m2. In 14/15 patients off drug, growth rates recovered at near normal or normal rates within 12 months of discontinuation. CONCLUSIONS Patients on tovorafenib experience decreased growth velocity, which is recoverable off drug. Long-term monitoring of growth and further preclinical investigations to mitigate this toxicity and understand its effect are warranted.

Prescription Patterns of Mycophenolate Mofetil in a Group of Patients from Colombia

Background: Mycophenolate mofetil is used for the prevention of solid organ transplant rejection and for other indications, such as systemic lupus erythematosus (SLE). Objective: To determine the prescription patterns of mycophenolate mofetil in a group of Colombian patients. Methods: This was a cross-sectional study of patients receiving mycophenolate mofetil between 2021 and 2022. The data were obtained from a drug dispensing database. Sociodemographic, clinical (diagnostic), and pharmacological variables were identified. Results: A total of 979 patients who underwent treatment were identified; their mean age was 45.9 ± 17.1 years, and 87.4% were women. The main diagnosis associated with the use of mycophenolate mofetil was SLE (39.1%), followed by other rheumatic diseases (8.5%), nephrotic syndrome (7.5%), and solid organ transplantation (6.4%). The relationship between the mean dose and the defined daily dose was 0.75. Ten percent of patients received mycophenolate alone, whereas 32.9% received mycophenolate in combination therapy with conventional disease-modifying antirheumatic drugs and glucocorticoids. A total of 76.2% had polypharmacy (five or more drugs). Conclusions: Mycophenolate mofetil is used mainly in combination therapy for patients with SLE and other rheumatological diseases and for solid organ transplants at doses lower than those recommended.

Oxygen consumption measurements at ultra-high dose rate over a wide LET range.

The role of radiolytic oxygen consumption for the in-vitro "Ultra-High Dose Rate" (UHDR) sparing and in-vivo FLASH effect is subject to active debate, but data on key dependencies such as the radiation quality are lacking. The influence of "dose-averaged Linear Energy Transfer" (LETd) and dose rate on radiolytic oxygen consumption was investigated by monitoring the oxygen concentration during irradiation with electrons, protons, helium, carbon, and oxygen ions at UHDR and "Standard Dose Rates" (SDR). Sealed "Bovine Serum Albumin" (BSA) 5% samples were exposed to 15Gy of electrons and protons, and for the first time helium, carbon, and oxygen ions with LETd values of 1, 5.4, 14.4, 65, and 100.3keV/µm, respectively, delivered at mean dose rates of either 0.3-0.4Gy/s for SDR or approximately 100Gy/s for UHDR. The Oxylite (Oxford Optronics) system allowed measurements of the oxygen concentration before and after irradiation to calculate the oxygen consumption rate. The oxygen consumption rate was found to decrease with increasing LETd from 0.351mmHg/Gy for low LET electrons to 0.1796mmHg/Gy for high LET oxygen ions at SDR and for UHDR from 0.317 to 0.1556mmHg/Gy, respectively. A higher consumption rate for SDR irradiation compared to the corresponding UHDR irradiation persisted for all particle types. The measured consumption rates demonstrate a distinct LETd dependence. The obtained dataset, encompassing a wide range of LETd values, could serve as a benchmark for Monte Carlo simulations, which may aid in enhancing our comprehension of oxygen-related mechanisms after irradiations. Ultimately, they could help assess the viability of different hypotheses regarding UHDR sparing mechanisms and the FLASH effect. The found LETd dependence underscores the potential of heavy ion therapy, wherein elevated consumption rates in adjacent normal tissue offer protective benefits, while leaving tumor regions with generally higher "Linear Energy Transfer" (LET) vulnerable.

Monte Carlo modeling of a commercial machine and experimental setup for FLASH‐minibeam irradiations with electrons

BackgroundUltra‐high dose rate (UHDR/FLASH) irradiations, along with particle minibeam therapy (PMBT) are both emerging as promising alternatives to current radiotherapy techniques thanks to their improved healthy tissue sparing and similar tumor control.PurposeMonte Carlo (MC) modeling of a commercial machine delivering 5–7 MeV electrons at UHDR. This model was used afterward to compare measurements against simulations for an experimental setup combining both FLASH and PMBT modalities.MethodsWe modeled the main accelerator elements with TOPAS3.8/Geant4.10.07.p03, optimized the electron source parameters, and subsequently benchmarked this geometry against measurements. Minibeam experiments were performed by delivering 7 MeV electrons at UHDR on three different 65‐mm thick brass collimators as manufactured for protons with a 400‐µm slit width: single slit, 5 slits with a center‐to‐center (CTC) distance of 4 mm and 9 slits with CTC of 2 mm. Finally, complementary simulations were run by changing critical PMBT collimator parameters to assess their specific impact on peak‐to‐valley dose ratio (PVDR) as well as on the Bremsstrahlung photon contribution to the total dose.ResultsPercentage depth dose (PDD) distributions and lateral dose profiles showed a good agreement between simulations and measurements, with a maximum discrepancy of less than 4%. With the PMBT collimators in place, discrepancies between simulated and measured dose profiles, lateral and in‐depth in peaks and valleys, were within 3%. High PVDR between 5 and 26 were observed until 4 mm in the phantom. During the experiments, a mean dose rate of 167 Gy/s and an instantaneous dose rate of 1.2 × 105 Gy/s were obtained for the FLASH‐minibeam setup. PMBT collimator parameters need to be optimized to maximize PVDR while limiting Bremsstrahlung photon contribution to the total dose.ConclusionsThe validation of the MC model and the configuration of an electron FLASH‐minibeam setup were successfully completed, paving the way for future radiobiological investigations.

Evaluation of dose and anatomy variability for nasopharyngeal carcinoma radiotherapy with a new fully integrated CT-linac

The goal of this study was to investigate the variability of target volume and parotid gland dose distribution for nasopharyngeal carcinoma (NPC), and to explore the shifting patterns of parotid gland centroid and neck radius during radiotherapy. Twenty patients with NPC were enrolled. The target volume dose difference between planning dose and recalculated dose on weekly CT was analyzed. The recalculated doses on every weekly CT were cumulated to assess the difference between delivered dose and planning dose. The relationship of parotid gland centroid deviation with dose was studied, and the shrinking distances of neck radius were calculated for cervical vertebra 1, 2, 3 levels (C1, C2, C3). The ratio of GTVs and CTVs doses on weekly CTs to the doses on planning CT was all above 0.98; the dose of PTVs on weekly CT tended to decrease compared with planning. RMD was defined as the ratio of the mean dose of the left and right parotid glands (L-PG, R-PG) to the planning mean dose. The fitted relationships of RMD and the deviation of centroid (D) for L-PG and R-PG were: RMD=0.37*D+0.98 (R2 = 0.62, p < 0.001) and RMD = 0.33*D+0.97 (R2 = 0.72, p < 0.001), respectively. The order of neck radius shrinking distance at different levels was C1>C2=C3. In this study, we quantitatively analyzed the dosimetric variabilities of target volumes, and established linear models of parotid gland dose and its centroid deviation, which provides fractional and full-course dose evaluation during radiotherapy for NPC.

Defining the potential for sexual structures-sparing for prostate cancer external beam radiotherapy: A dosimetric study

PurposeThe purpose of the study was to evaluate the dosimetric impact of sexual-sparing radiotherapy for prostate cancer, with magnetic resonance-only treatment planning. Material and methodsFifteen consecutive patients receiving prostate cancer radiotherapy were selected. A synthetic CT was generated with a deep learning method from each T2-weighted MRI performed at the time of treatment planning. For each patient, two plans were performed: standard treatment planning and sexual-structures sparing treatment planning. The treatment plan was designed to deliver a dose of 78Gy to the prostate and 50Gy to the seminal vesicles in 2Gy daily fractions, using volumetric arc therapy. Dose–volume histograms were computed to compare treatment plans. ResultsAll plans fulfilled dosimetric objectives and were equivalent regarding planning target volume coverage. The doses delivered to both rectum, bladder, and femoral heads were similar between plans (P=0.20). Sexual-sparing plans enabled to decrease all dosimetric parameters on sexual organs-at-risk. The mean penile bulb dose in sexual-sparing plans was significantly reduced (21.1Gy±20.7 versus 13.4Gy±14.0, P<0.01), however with large variability observed between individuals. The mean dose delivered to the corpora cavernosa was also significantly reduced within sexual-sparing plans (13.1Gy±16.7 versus 8.6Gy±10.4, P<0.01). A significant reduction was also observed in the highest doses delivered to internal pudendal arteries (D10%: 48.4Gy±8.3 versus 33.1Gy±4.6, P<0.05; D5%: 52.0Gy±8.7 versus 36.8Gy±5.5, P<0.05). ConclusionSparing of sexual structures appears feasible, without compromising neither planning target volume coverage nor doses delivered to non-sexual organs at risk. The clinical significance of this dose-reduction requires prospective evaluation.

Exploring the Relationship Between Radiation-Induced Moya Moya Syndrome and Radiation Dose for Pediatric Patients Treated with Proton Radiation Therapy: Moya Moya in Peds Patients After Proton RT.

The incidence and risk factors associated with radiation-induced Moya-Moya Syndrome (RIMMS) in pediatric brain tumor patients treated with proton radiotherapy (PRT) remain poorly understood. The objective of this study was to determine the incidence of RIMMS in the setting of CNS proton radiotherapy (PRT) in a pediatric cohort and assess its relationship with dose to the Circle of Willis (COW) or optic chiasm (OC). We performed a retrospective review of pediatric brain tumor patient treated with intracranial PRT (1995-2021). The exposure of interest was mean dose to the optic chiasm due to close proximity to the COW vasculature. Wilcoxon rank-sum test was used to determine the association between OC dose and RIMMS. Univariable logistic regression modeling was used to determine the odds of developing RIMMS based on a cutpoint of 52Gy. Of 676 patients, 14 developed RIMMS, with a median onset of 1.9 years. The cumulative incidence of RIMMS at 8 years was 2.4%. Patients with RIMMS had higher mean OC dose than those without (51.5 Gy vs 23.7 Gy, p<0.0001). Univariable logistic regression showed patients with an OC dose > 52 Gy had increased RIMMS risk compared to those with dose < 52 Gy (OR = 9.9, p<0.001). The incidence of RIMMS remains low in our primarily proton-treated pediatric cohort with a cumulative incidence of 2.4% over 8 years and is similar to photon-treated cohorts. Development of RIMMS was associated with higher doses to the COW and OC.

Comparison of the effectiveness of prepubertal growth hormone treatment on height and predicted adult height in children with short stature born small for gestational age vs. with a growth hormone deficiency.

We compared the effects of growth hormone (GH) treatment on height and predicted adult height in children with short stature born small for gestational age (SGA-SS) vs. with a growth hormone deficiency (GHD). This retrospective study analyzed the background and clinical characteristics of children who presented to Tanaka Growth Clinic for short stature and were diagnosed with either SGA-SS or GHD and underwent treatment with GH. We compared differences in height, height velocity, GHdose increases, insulin-like growth factor-1 levels, and bone-age/chronological-age ratio between the two groups. Out of these children, 33 SGA-SS and 54 GHD children started GH treatment before the age of 8 years, witha mean dose of 0.25 mg/kg/week and 0.20 mg/kg/week, respectively. At treatment initiation, the age and height standard deviation scores (SDS) of the SGA-SS group were significantly lower than those of the GHD group. The height velocity was significantly greater in the SGA-SS group for 3 years owing to higher GH doses and younger age. No notable differences in puberty onset height or predicted adult height were observed between the two groups for boys or girls. The increase in height SDS from the start of GH treatment until the onset of puberty was substantially greater in the SGA-SS group than in the GHD group for both sexes. Adult height of patients with SGA-SS is expected to resemble that of patients with GHD but may notreach the-1.0 SD achieved with GH treatment of those patients in Western countries.

A dosimetric and robustness analysis of proton arc therapy with early energy layer and spot assignment for lung cancer versus conventional intensity modulated proton therapy.

Intensity Modulated Proton Therapy (IMPT) faces challenges in lung cancer treatment, like maintaining plan robustness for moving tumors against setup, range errors, and interplay effects. Proton Arc Therapy (PAT) is an alternative to maintain target coverage, potentially improving organ at risk (OAR) sparing, reducing beam delivery time (BDT), and enhancing patient experience. We aim to perform a systematic plan comparison study between IMPT and energy layer (EL) and spot assignment algorithm - Proton Arc Therapy (ELSA-PAT) to assess its potential for lung cancer treatment. A total of 14 Lung ELSA-PAT plans were compared retrospectively with IMPT plans. 4D worst-case minimax robust optimization was performed, including 84 scenarios (3%, 3 mm). Dosimetry assessment included target (clinical tumor volume [CTV]) and important OARs, on nominal and worst-case scenarios. Most relevant normal tissue complication probabilities (NTCP), target coverage robustness against interplay effect, and BDT were evaluated. CTV D95% and D98% showed no significant difference in comparison. PAT demonstrated better conformality by 66% (p = 0.00012) but delivered a higher heart mean dose (HMD, 23%). There was a 2% increase in NTCP 2-year mortality risk with PAT. Total BDT was comparable among techniques. IMPT was more robust than PAT against interplay effect, considering both D1% (1.0 ± 0.8 Gy vs 1.1 ± 1.4 Gy) and D98% bandwidths (0.9 ± 0.9 Gy vs 1.1 ± 1.3 Gy). Both techniques provide a similar level of dose coverage to the target volume. Although PAT improved dose conformality, higher HMD translated into increased heart toxicity, presumably due to chosen planning methodology and OAR proximity to target. Increased ELs and spots raised PAT BDT, although it could improve daily treatment workflow.

New onset of left ventricular dysfunction and diastolic dysfunction are uncommon in patients with her2+ breast cancer after completion of cancer therapy

Abstract Background Cardiotoxicity from anthracyclines and trastuzumab is common among patients with breast cancer during therapy. However, there are limited data on new onset of cardiotoxicity (systolic or diastolic dysfunction) after completion of therapy. This knowledge has implications to guide long-term follow-up. Purpose The aim of this study was to evaluate the incidence of cancer therapy related cardiac systolic dysfunction (CTRCD) and diastolic dysfunction (DD) in women with HER2+ breast cancer after completion of cancer therapy and compare to incidence during cancer therapy. Methods We conducted a prospective cohort study of women with HER2+ breast cancer who were treated with sequential anthracycline and trastuzumab therapy, with or without radiation therapy (The EMBRACE-MRI trial, NCT02306538). Comprehensive surveillance echocardiograms were performed at baseline and every 3 months during treatment, early post-trastuzumab, then at years 1, 2, and 3 post trastuzumab completion. CTRCD was defined as a reduction in 3D-left ventricular ejection fraction (LVEF) by ≥ 10% from baseline to &amp;lt; 55%. Diastolic dysfunction was defined as per the American Society of Echocardiography guidelines. Results A total of 136 female patients, with a mean age of 51.1 ± 9.2 years were recruited. Among them, 15.4% had hypertension, 3.7% had diabetes mellitus, and 10.3% had dyslipidemia. The mean cumulative doxorubicin equivalent dose was 203.9 ± 12.5 mg/m2, 120 patients received radiation therapy with the mean heart dose of 170.8 ± 75.9 cGy. During cancer treatment, 27 out of 136 patients (19.9%) developed CTRCD. In long-term follow-up, due to death or interruption due to the COVID-19 pandemic, follow-up was available in 128 patients at 1 year, 117 at 2 years and 111 at 3 years. 5 of the 27 patients still had persistent LV dysfunction (3 at 1 year, 1 at 2 year and 1 at 3 year), however, there were no new diagnosis of CTRCD post completion of therapy. Of 129 patients with baseline normal or indeterminate diastolic function, new DD was identified in 25/129 patients (19.4%) during cancer treatment (17 grade I, 2 grade II, 6 unable to grade). After completion of cancer therapy, 5 patients had persistent DD. In patients with no DD during therapy and completed 3 year follow-up, 5 patients developed new DD after therapy (2 grade I, 3 unable to grade). Figure 1 illustrates the percentage of patients with new CTRCD or new diastolic dysfunction at each timepoint. None of the patients developed clinical heart failure. Conclusion Although both CTRCD and diastolic dysfunction are common during sequential therapy with anthracyclines and trastuzumab in women with HER2+ breast cancer, new onset after treatment completion is rare during a careful follow-up. These findings have implications for long-term surveillance.