Previously, a synchrotron-based horizontal proton beamline (87.2 MeV) was successfully commissioned to deliver radiation doses in FLASH and conventional dose rate modes to small fields and volumes. In this study, we developed a strategy to increase the effective radiation field size using a custom robotic motion platform to automatically shift the positions of biological samples. The beam was first broadened with a thin tungsten scatterer and shaped by customized brass collimators for irradiating cell/organoid cultures in 96-well plates (a 7-mm-diameter circle) or for irradiatingmice (1-cm2 square). Motion patterns of the robotic platform were written in G-code, with 9-mm spot spacing used for the 96-well plates and 10.6-mm spacing for the mice. The accuracy of target positioning was verified with a self-leveling laser system. The dose delivered in the experimental conditions was validated with EBT-XD film attached to the 96-well plate or the back of the mouse. Our film-measured dose profiles matched Monte Carlo calculations well (1D gamma pass rate >95% with the criteria of 2%/1 mm/2% dose threshold). The FLASH dose rates were 113.7 Gy/s for cell/organoid irradiation and 191.3 Gy/s for mouse irradiation. These promising results indicate that this robotic platform can be used to effectively increase the field size for preclinical experiments with proton FLASH.
Purpose: We aim to perform image-guided, dose-escalated, well-controlled liverirradiated animal studies and subsequently evaluate radiation induced liver injury (RILI) using longitudinal CT.
Methods: Eighteen 6–8 weeks mice were divided into three groups: control, 15Gy and 30Gy irradiated groups. The animal protocol was approved by the animal care ethics committee of our institution. Precision radiotherapy started with CT simulation, followed by treatment planning using volumetric modulated arc therapy (VMAT), image guidance with cone beam CT (CBCT) and radiation delivery on a medical linear accelerator. Weekly CT was conducted on the same CT simulator using same scanning parameters. At the end of fifth week, all mice were sacrificed, and histological staining was performed. Body weight, liver volume, HUvalues and histogramdistributions were analyzed.
Results: Body weight of irradiation groups was significantly reduced compared to that of the control group (p<0.05). Liver volume in irradiated groups was reduced too. The average liver HU was significantly reduced in irradiated groups (HU mean = 62±3, 48±6, and 36±8 for the control, 15Gy and 30Gy respectively; p control vs. 15Gy < 0.05, p control vs. 30Gy < 0.05). A linear relationship between liver HU and radiation dose was found. Furthermore, HU histogram changes with time and dose showed not only density but also structure might be affected by radiation. HE and Masson Trichrome staining confirmed histological change and increased collagen deposition in irradiated liver.
Conclusion: Longitudinal unenhanced CT is a useful imaging tool to evaluate the severity and progression of radiation induced liver injury.
Beam-matched linear accelerators (linacs) enable flexible patient scheduling and efficient treatment delivery in the event of unexpected machine downtime. The purpose of this study was to test the feasibility of 3D gamma index as an additional metric beyond standard measurement-based comparisons for more efficient evaluation of treatment plans between linacs with nominally matched beam models to ensure safe patient transfer. Seventeen 3D conformal radiotherapy (3DCRT) plans and thirty-six volumetric-modulated radiation therapy (VMAT) plans for different disease sites were selected from the original linac. An in-house script was used to automatically create new plans for the target linac and calculate dose using parameters of the original plans. 3D gamma analysis was performed to compare plan dose distributions between the target and original linacs using PyMedPhys. The 2%/2 mm gamma pass (γ≤1) rate was >99.99% for all 3DCRT plans. The median 1%/1 mm pass rate was 99.86% but two cases failed (< 90%). For VMAT plans, the median and minimum 2%/2mmgamma pass rateswere 99.43% and 93.81%. For 1%/1mm, the median pass rate was 92.02% but ten cases failed. The results indicated using 3D gamma index can enhance the confidence and add an extra layer for safe patient transfer.
Radiation-induced heart disease (RIHD) is a serious complication but difficult to assess in patients undergoing thoracic radiotherapy (RT). We aim to analyze RIHD using heart ultrasound and elastic modulus, exploring relationships between functional, anatomical or biomechanical changes of the heart and radiation dose.
Twenty BALB/c mice were divided into four groups (control, 10 Gy, 20 Gy and 25 Gy) with a single fraction of image-guided volumetric modulated arc radiotherapy (VMAT) to murine heart on a linear accelerator. Transthoracic echocardiography (TTE) was performed on a small-animal ultrasound imaging system with a handheld microscan transducer. E-wave/A-wave ratio (E/A) and myocardial performance index (MPI) for diastolic performancewere noninvasively evaluatedweekly, aswell as ejection fraction (EF%), fractional shortening (FS%), left ventricle (LV) mass and heart wall thickening for systolic performance. At the end of the fifth week, all mice were sacrificed for elastic modulus measurement on a dynamic mechanical analyzer (DMA) and for histopathological staining. All experiments were conducted in accordance with the local institution’s animal research committee guideline.
Significant difference was observed in E/A ratio between the control and 25 Gy irradiated groups (1.8±0.5 and 0.7±0.9, respectively; p<0.05), indicating reduced diastolic performance and increased stiffness in left ventricle after high-dose heart radiation. Diastolic dysfunction in irradiated groups was also observed with significantly increased MPI. In contrast, posterior wall thickness, aortic peak velocity, heart rate, EF and FS were not significantly different after RT. Heart elasticity was reduced substantially with the increased radiation dose. HE and Masson Trichrome staining confirmed more fibrosis deposition in irradiated hearts.
RIHD evaluation with ultrasound imaging noninvasively and biomechanical modulus measurement invasively in the image guided, precision dose-escalated murine heart irradiation is feasible. Increased myocardial stiffness, abnormal diastolic relaxation, more collagen deposition, and reduced tissue elasticity are observed in irradiated heart tissue. This study may facilitate our understanding of RIHD and facilitate improving patients’ quality of life in the future.
Purpose: Lattice radiotherapy can potentially deliver high doses to the tumor core, while conventional doses to the periphery resulting in improved response rates in large tumors (> 5 cm).We assessed the feasibility of planning lattice radiotherapy and dosimetrically compared it with conventional radiotherapy.
Methods: This retrospective dosimetric study evaluated 10 patients with large tumors (>5 cm) treated with palliative intent with a dose of 20Gy in five fractions. High-dose lattice pointswere created at doses of 50Gy in non-hepatic tumors and 35Gy in hepatic tumors. Lattice plans were compared with treatment plans regarding dose coverage and organ-at-risk dosimetry.
Results: Treated sites included soft tissue metastases to the neck, lungs, abdomen, pelvis, and liver. The mean lesion volume was 1103 cc (352–3173 cc). The maximum tumor size was 16 cm. The target volume coverage was > 95% in all but one case (88% to achieve organ constraints). Dosimetry and organ-at-risk doses were similar in both palliative treatment and simulated lattice plans.
Conclusion: Lattice radiotherapy is feasible in large tumors using volumetricmodulated arc therapy and achieves good coverage while meeting organ constraints. However, a prospective clinical evaluation is required to confirm its efficacy.
Purpose: This study aimed to examine the individualized neoadjuvant therapies for operable esophageal cancer.
Methods and Materials: Data of 95,444 patients diagnosed with esophageal cancer between 2010 and 2017 were collected from the Surveillance, Epidemiology, and End Results database. The effectiveness of neoadjuvant chemoradiotherapy (nCRT), neoadjuvant chemotherapy (nCT), and surgery alone was compared in patients with stage II esophageal cancer. Patients with stage III diseasewere divided into “local invasive type” group (type I, T3N1M0, T4N0-1M0) and “regional metastatic type” group (type II, T1-2N2-3M0) according to the tumor invasion pattern. The effectiveness of nCRT and nCT in different patterns was compared.
Results: In 2,706 patients with stage II disease, a statistical difference was observed in the overall survival (OS) between nCRT (85.1%), nCT (3.0%), and surgery alone (11.9%, P<0.001, median OS (mOS): 54 vs 41 vs 24 months). Meanwhile, 3,303 patients with stage III disease who received nCRT were included in the propensity score matching. A statistical difference was observed in the OS between “Type I” (n = 217) and “Type II” (n = 217, P = 0.023, mOS: 45 VS 28 months). Among 93 patients with stage III receiving nCT, those with “Type II” (23.7%) showed a greater potential benefit from nCT than those with “Type I” (76.3%, P = 0.686, mOS: 51 vs 40 months).
Conclusions: nCRT is recommended for stage II esophageal cancer. In patients with stage III, those with “local invasive type” may greatly benefit from nCRT, while those with “regionalmetastatic type” may greatly benefit from nCT.
A 47-year-old woman underwent [18F]-FDG and [18F]-NOTA-FAPI-04 PET/CT to assess the staging of suspected axillary lymph node enlargement following breastconserving surgery. The imaging with these two PET agents revealed starkly contrasting results. Significant [18F]-FDG uptake in the right axillary fossa, intrathoracic muscles, and clavicle lymph nodes led nuclear medicine physicians to suspect metastasis. However, no uptake of [18F]-NOTA-FAPI-04 was observed. Subsequently, the patient underwent an ultrasound-guided biopsy of the enlarged axillary lymph nodes, which pathologically confirmed the diagnosis as inflammation. After a multidisciplinary discussion, the patient received radiotherapy for the right breast and 2.15Gy/F×28F for the tumor bed. She was discharged following the completion of her radiotherapy. Accurate diagnosis and staging are pivotal in selecting the optimal clinical treatment for breast cancer patients. Notably, [18F]-NOTA-FAPI-04 PET/CT downgraded this patient’s staging, significantly influencing the treatment strategy.