Dose Falloff Research Articles

Proton therapy in the palliative setting.

Given its sharp dose fall off and ability to spare healthy surrounding tissue, proton beam therapy (PBT) has traditionally been used to treat various types of malignancies in the definitive setting, with strong, empirical data supporting its utility and safety. In the palliative setting, however, photon therapy has generally remained the standard of care in radiation treatment delivery due to lower cost, and greater availability. However, recent data suggest that the use of PBT may provide benefit in terms of symptom management and disease control in patients with locally advanced or recurrent disease who do not qualify for definitive therapy or with metastatic disease. Additionally, due to its unique dosimetric properties, PBT may confer less overall toxicity, thus helping preserve or improve the quality of life in this patient population, especially for those who are nearing end of life. While there is a need for further study, initial data analyzed from both retrospective and prospective single-institution and multi-institution trials are promising. This review aims to explore the efficacy and safety of PBT in the palliative setting among adults and to summarize pertinent studies that support its usage. To the authors' knowledge, this is the first review of the literature pertaining to PBT used in the palliative setting across multiple disease sites.

Towards Biology-Guided Radiotherapy Planning and Delivery on a Novel O-Ring PET-Linac Platform: Extended Beyond Bone and Lung Lesions

Biology-guided radiotherapy (BgRT) with FDG signal collected via an on-board positron emission tomography (PET) system integrated in an O-ring gantry Linac was recently cleared by the FDA for lung and bone lesions. This study aims to determine if BgRT plans, guided via PET signal, are clinically acceptable for FDG-avid lesions in disease sites beyond bone and lung. Ten patients previously treated for lesions in the liver, head and neck (HN), pancreas, renal and pelvic-abdominal lymph nodes were identified. Diagnostic PET/CT images of these treatment sites were first collected and processed/converted to mimic PET images that are acquired on PET-Linac and would be used to guide the delivery. For BgRT planning, the PTV was generated with 5 mm margin from GTV and a Biology Tracking Zone was generated including the anticipated full range of target motion. BgRT plans, guided by the emulated PET signal, were generated with 46Gy in 3 fractions for liver and 40Gy in 5 fractions for all other sites. BgRT plan deliverability was first assessed by evaluating the Activity Concentration (AC) and Normalized Target Signals (NTS) on converted PET images with the goal to meet NTS >2 (hard constraint) and AC >5kBq/ml (goal). BgRT plan quality was then evaluated with institutional guidelines on PTV coverage, OAR doses, conformity index (CI) and Heterogeneity index (HI). BgRT plans were successfully generated for 11 target lesions among ten patients. The average diagnostic PET SUV, derived NTS and AC on converted PET images were 12.62, 9.33 and 12.10 kBq/ml, respectively. All images met the NTS constraints, and 8/11 plans met the AC goal for deliverability. All plans met the OAR hard constraints such as max dose on duodenum, small bowel, large bowel and spinal cord. Five of 11 plans had a limiting GI structure that resulted in an expected reduction in PTV coverage with an average PTV V100% = 77.9%, CI of 1.4, HI of 1.36 and max dose of 133.8%. The other 6 of 11 cases met the PTV V100% = 95%, had an average CI of 1.1, HI of 1.28 and Dmax of 127.67%. The estimated average time for BgRT delivery was 17 mins 25 secs. Although these plan parameters are deemed to be clinically acceptable, heterogeneity was detected inside the target region and suboptimal dose fall off was observed in some cases that may be caused by current implementation. This preliminary study showed that BgRT plans were generated successfully with emulated PET images on 11 treatment sites covering HN, abdominal and pelvic regions. All plans met NTS constraints and 8 out of 11 met AC goals for deliverability. The plan quality of all BgRT plans were clinically acceptable based on institutional constraints. Further investigations are required to test more patients/sites for BgRT plan feasibility. Dosimetric benefit from margin reduction of BgRT target should also be investigated in future study.

Preclinical Intraoperative FLASH Radiotherapy

Intraoperative radiation therapy (IORT) is a method of delivering high radiation doses to an internal target with low dose to adjacent organs. Most organs at risk can often be moved out of the radiation field, so dose is usually limited by in-field vascular and/or nerve structures. It is known that ultra-high (FLASH) dose rate (>40 Gy/s) radiation reduces normal tissue toxicity compared to conventional, while preserving tumor control. We hypothesize that FLASH radiation can increase the dose tolerance of vascular and nerve structures, thus permitting for dose escalation in IORT. Here, we present a novel platform using orthovoltage x-rays to study FLASH effects in preclinical IORT. The experimental setup and dosimetry of the system have been established for FLASH irradiation of the abdominal aorta in rats to investigate dose tolerance. A 150 kVp rotating anode x-ray source with a 75-kW generator was used to deliver FLASH and conventional irradiation. A 3D printed immobilization platform was designed to reproducibly place a surgically exposed rat abdominal aorta at 55mm SSD. A 3-mm thick lead collimator with a 10mm x 10mm aperture was placed into a flange adapter, which docks into the immobilization platform. Phantom and in vivo dosimetry were performed using both calibrated radiographic film and thermoluminescent dosimeters (TLD). Anesthetized 2-month-old Wistar rats underwent laparotomy to expose the abdomen for irradiation. A 10x12x1 mm3 tungsten plate was placed under the aorta to reduce spinal cord dose. Animals were then docked into the irradiator using the immobilization platform. Radiation dose in the range of 20 - 50 Gy were delivered to the abdominal aorta at FLASH and conventional dose-rates. Following treatment, animals undergo MR angiography every two months for 6 months, at which a histological evaluation of aorta wall will be performed. The FLASH dose rate measured at the aorta wall in a rat carcass was 49.7 ± 1.2 Gy/s distal to the collimator. Dose measurements between the films and TLDs showed an agreement within ±3%. Positional uncertainty mainly depends on the visual localization of the aorta on the collimator window, which is verified before irradiation. Vertical uncertainty is less than 1 mm, which is important given the rapid dose fall off of the system. Eight animals went successfully through the procedure, are healthy and currently being follow up with MR angiography. More animals are being treated for meaningful statistical results. MR angiography and IORT are performed on different days to avoid longer times under anesthesia, which initially resulted on mortality. Results of the MR angiography and histological analysis will be presented. The proposed platform has been successfully utilized for precision setup for FLASH IORT in a preclinical laboratory setting. Evaluation of FLASH effects in IORT setup will be an important step in the potential translation of FLASH IORT, where only one high-dose fraction can be delivered.

Optimizing Radiation Therapy for Brain Metastasis Patients: A Comparative Study of Knowledge-Based Treatment Planning with HyperArc

The purpose of this study is to examine the benefits of using a knowledge-based treatment planning (KBP) model in treating brain metastasis patients with HyperArc (HA) automated non-coplanar stereotactic radiosurgery (SRS). Treatment plans of the 113 patients with either single or multiple brain metastases treated with HA were enrolled in the study. The eighty-two treatment plans with 190 metastatic brain lesions were used to construct the training model using the DVH estimation algorithm. The model was then validated on the remaining 31 patients' treatment plans with 56 metastatic brain lesions. Two corresponding HA plans were manually generated for these 31 patients using the two optimization algorithms (SRS NTO and ALDO). The SRS NTO plan generates a rapid dose falloff and prevents dose bridging of adjacent disparate targets, while the ALDO plan can cover the target with the prescribed dose but may create a high inhomogeneous dose within the target. The dosimetric outcomes were compared between the KBP, SRS NTO, and ALDO plans. The KBP, SRS NTO, and ALDO plan consistently showed CTV and PTV coverage levels of over 99%. The KBP plans resulted in similar doses to the organs at risk compared to the SRS NTO plans, but significantly reduced doses to the brainstem and optic apparatus (lens, eyes, optic nerves, and optic chiasma) by 17% to 67% compared to the ALDO plans (P = 0.003 for brainstem and P < 0.001 for optic apparatus). The mean brain dose was not significantly different between the three plans (P = 0.694 for KBP vs. SRS NTO and P = 0.381 for KBP vs. ALDO). However, the ALDO plans showed a statistically better brain V12 Gy than the KBP plans (P = 0.009), with a difference of less than 2 c.c. that was deemed not clinically significant. The ALDO plans also had a significantly better intermediate dose spillage, gradient radius, and conformity index than the KBP plans. The KBP plans showed a significantly faster gradient index and intermediate dose spillage compared to the SRS NTO plans. This study demonstrates the ability of the KBP model (RapidPlan) to generate accurate DVH predictions for use with HA in generating SRS plans that achieve optimal sparing of organs at risk while maintaining dose falloff. The KBP plans showed balanced dosimetric results compared to the SRS NTO and ALDO optimization algorithms.

Central Lung Tumors Eligible for Stereotactic Ablative Radiotherapy (SABR) Trials: Analysis of a Cohort Treated Using MR-Guided SABR

SABR for central and ultracentral lung tumors results in increased toxicity. We implemented MR-guided SABR in patients meeting the IASLC classification for central tumors, namely a Gross Tumor Volume (GTV) ≤2cm from trachea, main bronchi, esophagus, heart, brachial plexus, main mediastinal vessels, phrenic or laryngeal nerves and spinal cord. As patient inclusion criteria for ongoing clinical trials varies, we studied the eligibility of MR-SABR patients for inclusion into 3 clinical trials for central tumors. An Ethics approved institutional database was accessed for details of patients treated using multifractionated lung MR-SABR between 2016 and 2022. GTV and Planning Target Volumes (PTV) had been delineated on a breath-hold planning MRI and CT scans. For each tumor meeting the IASLC classification, patient eligibility for HILUS (NCT04917224), STRICT/STARLUNG (NCT05354596) and SUNSET (NCT03306680) trials were examined. Multifraction MR-SABR was performed in 97 central lung lesions meeting IASLC criteria. Of these, 73 patients (75.3%) fulfilled inclusion criteria for at least 1 trial, but inclusion in all 3 trials was possible in just 18.6% of treated lesions. Inclusion in the HILUS, STRICT/STARLUNG and SUNSET trials were possible in 33.0%, 73.2% and 25.8% of MR-SABR patients, respectively. For HILUS-eligible patients, 11 met the HILUS group A classification (GTV ≤1cm from the trachea and main bronchi), and 21 in group B (GTV >1cm from the trachea and main bronchi but ≤1cm from the intermediate and lobar bronchi). Use of STRICT/STARLUNG trial criteria would have defined 13 tumors as ultracentral (GTV ≤0.5cm from the trachea, main bronchi or intermediary bronchus or esophagus), and 58 as central (GTV 0.5cm-2.5cm from previously described structures or ≤0.5cm from the heart, aorta, spinal cord or lobar bronchi). For the SUNSET study, 25 tumors fulfilled criteria for ultracentral location (PTV touching or overlapping the central bronchial tree, esophagus, pulmonary vein or pulmonary artery). Ongoing clinical trials in central or ultracentral lung SABR enroll considerably different patient populations than those selected using the IASLC definition of central tumors. Due to steep dose-fall off in SABR plans, detailed descriptions of the location of tumor and organs-at-risk, as well as dose-distributions achieved, are necessary in order to allow study results to be uniformly extrapolated to clinical practice.

A Prospective Study of Machine Learning-Assisted Radiotherapy Planning for Patients Receiving 54 Gy to the Brain

Radiotherapy (RT) planning is presently a semi-manual, iterative, labor-intensive process which may result in unnecessary variation in plan quality. To improve treatment plan quality and decrease RT planning time, we conducted a prospective, blinded study to compare machine learning-assisted planning with conventional manual planning for patients receiving 54 Gy in 30 fractions for a primary brain tumor. From January 31, 2022 to January 10, 2023, 40 patients receiving 54 Gy for primary CNS tumors were prospectively enrolled (median age 50 years, range 4-78 years). Patients underwent standard CT/MR simulation and target/OAR delineation by the treating radiation oncologist. Each patient had one ML plan and 1-2 manual RT plans created by different planners. The reviewing oncologist was blinded to planning method by removing optimization and IMRT/VMAT beam arrangement details from all plans, which were then rated based on clinical acceptability, target coverage, OAR sparing, conformity, and dose-fall off. One preferred plan was chosen and used for clinical treatment. A total of 115 plans for 40 patients were evaluated: 40 ML plans (35% of all plans), and 75 manual plans (65% of all plans; 5 and 35 patients had 1 and 2 manual plans created, respectively). ML plans required a mean planning time of 65 min as compared to 107 min for manual plans, with a mean time savings of 41 min per patient (paired t-test p = 0.002). 97% of ML plans (95% confidence interval [CI] 85-100) and 96% of manual plans (95% CI 87-99) were designated clinically acceptable by the treating radiation oncologist. While ML-assisted plans represented 35% of plans evaluated, they were chosen as preferred for clinical treatment in 43% of cases (17/40, 95% CI 29-58, p = 0.32). Median doses to the brain (10.8 Gy vs. 11.3 Gy, Wilcoxon rank-sum p = 0.012) and brain minus PTV (9.2 Gy vs 10.0 Gy, Wilcoxon rank-sum p = 0.009) were lower with ML planning versus manual planning, respectively. Doses to other structures, including hippocampi, cochlea, pituitary and hypothalamus were not statistically different. In this prospective study with blinded oncologist evaluation, ML-assisted RT planning for primary CNS tumors was faster than manual planning, and produced a very high rate of acceptable plans with similar or superior OAR sparing. Future work will be undertaken to iteratively refine the ML model using the preferred cases from this study.

Zinc-Doped Iron Oxide Nanoparticles as a Proton-Activatable Agent for Dose Range Verification in Proton Therapy.

Proton therapy allows the treatment of specific areas and avoids the surrounding tissues. However, this technique has uncertainties in terms of the distal dose fall-off. A promising approach to studying the proton range is the use of nanoparticles as proton-activatable agents that produce detectable signals. For this, we developed an iron oxide nanoparticle doped with Zn (IONP@Zn-cit) with a hydrodynamic size of 10 nm and stability in serum. Cytotoxicity, defined as half of the surveillance, was 100 μg Zn/mL in the U251 cell line. The effect on clonogenic cell death was tested after X-ray irradiation, which suggested a radioprotective effect of these nanoparticles at low concentrations (1-10 μg Zn/mL). To evaluate the production of positron emitters and prompt-gamma signals, IONP@Zn-cit was irradiated with protons, obtaining prompt-gamma signals at the lowest measured concentration (10 mg Zn/mL). Finally, 67Ga-IONP@Zn-cit showed accumulation in the liver and spleen and an accumulation in the tumor tissue of 0.95% ID/g in a mouse model of U251 cells. These results suggest the possibility of using Zn nanoparticles as proton-activatable agents to verify the range by prompt gamma detection and face the challenges of prompt gamma detection in a specific biological situation, opening different avenues to go forward in this field.

Application of a Contralateral Esophageal-Sparing Technique to Reduce Radiation Esophagitis in Limited-Stage Small Cell Lung Cancer Treated with Twice-Daily Radiotherapy and Concurrent Chemotherapy

Acute esophagitis (AE) is a common radiation-related toxicity after concurrent twice-daily hyperfractionated radiotherapy and chemotherapy in limited-stage small cell lung cancer (LS-SCLC) patients, which could limit dose-escalation of the target and make treatment postponed to decrease local tumor control. More esophageal protective techniques should be proposed to reduce radiation severe esophagitis of LS-SCLC patients. We retrospectively applied a contralateral esophagus sparing technique (CEST) in 20 unresectable LS-SCLC patients, who had gross tumor within 1 cm of the esophagus and received a total dose of 45 Gy of concurrent twice-daily radiation and standard chemotherapy regimen. The contralateral esophagus (CE) was contoured as an avoidance structure, and the feasibility of CEST on promoting a steep dose falloff beyond the target volume near esophagus was analyzed. The appropriate dose constraints of CE were also investigated. The AE events were recorded according to the RTOG acute toxicity grading system. We performed CEST in 20 LS-SCLC consecutive patients, among whom three patients experienced severe AE after concurrent chemoradiotherapy. Each treatment plan of eligible patients assured high radiation doses delivering, with the planning and gross tumor volume covered by 95% and 100% of the prescription dose. Among these patients, the median maximum esophagus dose declined from 47.9 Gy (range, 46.6-49.7 Gy) to 41.3 Gy (range, 35.9-48.2 Gy), as well as V30 and V36 of esophagus decreased from 9.22 Gy (range, 0.42-17.71 Gy) and 7.39 Gy (range, 0-16.19 Gy) to 2.40 Gy (range, 0-5.68 Gy) and 0.53 Gy (range, 0 -2.69 Gy) after CEST applying, respectively (all p<0.001). The CE's median maximum dose, V30, and V36 were 41.3 Gy, 2.13 cc, and 0.24 cc, respectively. By using proposed CE dose constraints of Dmax≤42 Gy, V30 ≤3.5 cc and V36 ≤0.5 cc, we confirmed the feasibility and efficacy of CEST to avoid exposing the esophagus cross-section to high prescription doses in LS-SCLC patients receiving twice-daily hyperfractionated IMRT and concurrent chemotherapy. These findings support the clinical practice of CEST in LS-SCLC patients, while more prospective and large-scale studies are warranted.

Mitigation of Dosimetric Uncertainty in MRI-Based Proton Planning Using Spot-Scanning Proton Arc (SPArc) Technique

MRI-based synthetic CT (SCT) images created using generative adversarial network (GAN) have been demonstrated to be feasible for intensity-modulated proton therapy (IMPT) planning. However, dose calculation accuracy can be uncertain in some regions within/near the target of head and neck patients due to the local CT number estimation error or sharp dose fall-off. This study investigated the feasibility of using the SPArc technique to mitigate such dosimetric uncertainty. A GAN using a 3D U-net as the generator and a 6-layer 3D convolutional neural network as the discriminator was trained with T1-weighted MR-CT image pairs from 162 nasopharyngeal carcinoma patients (14 for validation). The generator was used to generate SCT images from MR images for 7 test patients. For each test patient, the CT image was used to create a SPArc plan and an IMPT plan with the same clinical objectives. The SPArc plans (control point frequency sampling, arc trajectory, etc.) were optimized using a previously developed iterative approach. The dose distributions of both SPArc plans and IMPT plans were re-calculated on the SCT images and compared to the one calculated on the CT images. The dosimetric uncertainty was quantified using the gamma index. The 2%/2mm and 3%/3mm passing rates for SPArc plans were (96.9¡À2.7) % and (98.6¡À1.5) %, while the passing rates for IMPT plans were (94.0¡À3.9) % and (96.4+2.9) %. A significant reduction in dosimetric uncertainty was identified for SPArc plans (p ¡Ü0.021). Table 1 shows the passing rates for the 7 test individuals. SPArc can mitigate the uncertainty of dose calculation in MRI-based proton planning. Further research needs to validate these findings on a larger patient cohort. The study paves the road map for using MRI for SPArc planning.

Robust mixed electron-photon radiation therapy planning for soft tissue sarcoma.

Mixed electron-photon beam radiation therapy (MBRT) is an emerging technique in which external electron and photon beams are simultaneously optimized into a single treatment plan. MBRT exploits the steep dose falloff and high surface dose of electrons while maintaining target conformity by leveraging the sharp penumbra ofphotons. This study investigates the dosimetric benefits of MBRT for soft tissue sarcoma (STS)patients. A retrospective cohort of 22 STS of the lower extremity treated with conventional photon-based Volumetric Modulated Arc Therapy (VMAT) were replanned with MBRT. Both VMAT and MBRT treatments were planned on the Varian TrueBeam linac using the Millenium multi-leaf collimator. No electron applicator, cutout or additional collimating devices were used for electron beams of MBRT plans. MBRT plans were optimized to use a combination of 6 MV photons and five electron energies (6, 9, 12, 16, 20 MeV) by a robust column generation algorithm. Electron beams in this study were planned at standard 100 cm source-axis distance (SAD). The dose to the clinical target volume (CTV), bone, normal tissue strip and other organs-at-risk (OARs) were compared using a Wilcoxon signed-ranktest. As part of the original VMAT treatment, tissue-equivalent bolus was required in 10 of the 22 patients. MBRT plans did not require bolus by virtue of the higher electron entrance dose. CTV coverage by the prescription dose was found to be clinically equivalent between plans of either modality: (MBRT) = 97.9 ± 0.2% versus (VMAT) = 98.1 ± 0.6% (p=0.34). Evaluating the absolute paired difference between doses to OARs in MBRT and VMAT plans, we observed lower to normal tissue in MBRT plans by 14.9 ± 3.2% ( ). Similarly, to bone was found to be decreased by 8.2 ± 4.0% ( ) of the bonevolume. For STS with subcutaneous involvement, MBRT offers statistically significant sparing of OARs without sacrificing target coverage when compared to VMAT. MBRT plans are deliverable on conventional linacs without the use of electron applicators, shortened source-to-surface distance (SSD) or bolus. This study shows that MBRT is a logistically feasible technique with clear dosimetricbenefits.

An experimental setup for proton irradiation of a murine leg model for radiobiological studies

Background The purpose of this study was to introduce an experimental radiobiological setup used for in vivo irradiation of a mouse leg target in multiple positions along a proton beam path to investigate normal tissue- and tumor models with varying linear energy transfer (LET). We describe the dosimetric characterizations and an acute- and late-effect assay for normal tissue damage. Methods The experimental setup consists of a water phantom that allows the right hind leg of three to five mice to be irradiated at the same time. Absolute dosimetry using a thimble (Semiflex) and a plane parallel (Advanced Markus) ionization chamber and Monte Carlo simulations using Geant4 and SHIELD-HIT12A were applied for dosimetric validation of positioning along the spread-out Bragg peak (SOBP) and at the distal edge and dose fall-off. The mice were irradiated in the center of the SOBP delivered by a pencil beam scanning system. The SOBP was 2.8 cm wide, centered at 6.9 cm depth, with planned physical single doses from 22 to 46 Gy. The biological endpoint was acute skin damage and radiation-induced late damage (RILD) assessed in the mouse leg. Results The dose–response curves illustrate the percentage of mice exhibiting acute skin damage, and at a later point, RILD as a function of physical doses (Gy). Each dose–response curve represents a specific severity score of each assay, demonstrating a higher ED50 (50% responders) as the score increases. Moreover, the results reveal the reversible nature of acute skin damage as a function of time and the irreversible nature of RILD as time progresses. Conclusions We want to encourage researchers to report all experimental details of their radiobiological setups, including experimental protocols and model descriptions, to facilitate transparency and reproducibility. Based on this study, more experiments are being performed to explore all possibilities this radiobiological experimental setup permits.

Comparing biological and physical cost functions in VMAT planning for pediatric nasopharyngeal cancer

BackgroundVolumetric Modulated Arc Therapy (VMAT) is an option for the delivery of Radiotherapy treatment technique for pediatric nasopharyngeal cancer, VMAT is the most common treatment technique for pediatric nasopharyngeal cancer. The use of a combination of both biological and physical parameters in VMAT planning optimization may produce better target coverage and sparing of critical organs. This work was to compare Biological Cost Functions (BCFs) and Physical Cost Functions (PCFs) in the VMAT of pediatric nasopharyngeal cancer patients. MethodVMAT plans for 20 nasopharyngeal pediatric cancer patients were created using Monaco 5.11® treatment planning system (TPS). Three VMAT plans were retrospectively generated for each patient using BCFs, PCFs and mixed plan with a total dose of 61.2 Gy in 34 fractions to planning target volume (PTV). All plans were adjusted to deliver 95% of the prescribed dose to 95% of the PTV. The calculated plans were qualitatively and quantitatively evaluated using the dose-volume histogram (DVH). ResultsThe coverage of the target and the maximum dose for the three plans were nearly the same, and better sparing was achieved in the serial organs (spinal cord and brain stem) with PCFs. On the contrary, more dose spring was observed using the BCFs in the organs at risk (OARs) that were not involved in the dose optimization, such as the optic nerve maximum dose, with a significant p-value (0.035 and 0.0001) respectively. Using the PCFs, both parotids received a lower mean dose, but not for the oral cavity, which had a lower mean dose using BCFs (p=<0.0001). The same values of tumor control probability (TCP) were found for both cost functions in PTVs and normal tissue complications probability (NTCP) (99%). The values reported were as follows: spinal cord = 0.5%, brain stem = 19.1%, and brain = 90.7% for BCFs, compared to spinal cord = 0.3%, brain stem = 14.9%, and brain = 90.7% for PCFs. The delivery time was found to be less in BCFs (p=0.005). ConclusionThe BCFs are superior to the PCFs in conformity index and time of radiation delivery. However, PCFs were better at dose sparing for the serial organs and achieving a sharper falloff dose around the involved volumes. A patient-specific clinical compromise is recommended to gain the best plan that meets the clinical goals.

Tackling range uncertainty in proton therapy: Development and evaluation of a new multi-slit prompt-gamma camera (MSPGC) system

In theory, the sharp dose falloff at the distal end of a proton beam allows for high conformal dose to the target. However, conformity has not been fully achieved in practice, primarily due to beam range uncertainty, which is approximately 4% and varies slightly across institutions. To address this issue, we developed a new range verification system prototype: a multi-slit prompt-gamma camera (MSPGC). This system features high prompt-gamma detection sensitivity, an advanced range estimation algorithm, and a precise camera positioning system. We evaluated the range measurement precision of the prototype for single spot beams with varying energies, proton quantities, and positions, as well as for spot-scanning proton beams in a simulated SSPT treatment using a phantom. Our results demonstrated high accuracy (<0.4 mm) in range measurement for the tested beam energies and positions. Measurement precision increased significantly with the number of protons, achieving 1% precision with 5 × 108 protons. For spot-scanning proton beams, the prototype ensured more than 5 × 108 protons per spot with a 7 mm or larger spot aggregation, achieving 1% range measurement precision. Based on these findings, we anticipate that the clinical application of the new prototype will reduce range uncertainty (currently approximately 4%) to 1% or less.

Estimation of the risk of secondary cancer in rectum and bladder after radiation therapy for prostate cancer using a feasibility dose-volume histogram.

We investigated the risk of secondary cancers in rectum and bladder for prostate cancer radiotherapy using a feasibility assessment tool. We calculated the risk of secondary cancer by generating a dose-volume histogram based on an ideal dose falloff function (f-value). This study found a smaller f-value was associated with a lower secondary cancer risk in the rectum but a higher risk in the bladder. The study suggests setting the f-value at 0-0.1 as the optimization goal for the rectum and 0.4 for the bladder is reasonable and feasible for reducing the risk of secondary cancer and other adverse events.

A pilot curriculum to transition from 2D to 3D image-guided brachytherapy: A preliminary needs assessment.

11039 Background: Gynecologic cancers are one of the leading causes of death globally with a disproportionate burden of disease found in low to middle income countries (LMIC). Brachytherapy is often a necessary component in treatment management as it can deliver a high dose of radiation to the tumor while employing a steep dose fall off that spares the adjacent organs at risk. With 3D image guided brachytherapy (3D-IGBT), treatment planning utilizes volumetric images with the target volume and organs at risk contoured, reducing toxicity and improving outcomes when compared to 2D planar imaging. Despite this advantage, only a limited number of LMIC centers perform 3D-IGBT. Transitioning to 3D-IGBT requires considerable planning, resources, and training. The development of a multidisciplinary, computer-based training program to facilitate the transition to 3D-IGBT was identified as a priority of multiple Radiation Oncology departments in Nigeria. The aim of this preliminary needs assessment was to identify the necessary resources and anticipated barriers to development of a pilot training curriculum for the transition to 3D-IGBT. Methods: An anonymous, 16-question online survey was distributed to clinicians, physicists, radiation therapists, and staff within a Radiation Oncology department of a teaching hospital in Lagos, Nigeria. Results: In January 2023, 53 respondents completed the survey. Of the respondents, 36.5% were female and 63.5% were male. The average age was 37.5 (SD = 7.8). Clinical experience ranged from &lt; 5 years (52.6%), 6-10 years (9.4%), to &gt; 10 years (30.2%). Respondents included radiation therapists (28.8%), clinicians (27%), nurses (23.1%), and physicists (15.4%). Multiple barriers to implementation of 3D-IGBT were identified including lack of training (79.2%) or experience (58.5%), lack of financial investment (50.9%), and anticipated repair/replacement of equipment (41.5%). A majority of respondents identified staff training/education (66%) as critical to delivering 3D-IGBT. When asked about the curriculum components needed, most respondents believed that it should include plan review (96.2%), contour review (94.3%), and peer review of clinical cases (92.5%). Conclusions: Various areas of potential need were identified through this preliminary needs assessment, most notably, staff training. These findings suggest that there is an unmet need to further develop and implement a structured didactic and skills-based curriculum to transition from 2D to 3D-IGBT at these institutions. Identified focus areas including contour, peer, and plan review will help guide the refinement of this curriculum. These findings are an important first step in delivery of safe and efficacious 3D-IGBT in an LMIC.

Application of a contralateral esophageal-sparing technique to reduce radiation esophagitis in limited-stage small cell lung cancer treated with twice-daily radiotherapy and concurrent chemotherapy.

e20644 Background: Acute esophagitis (AE) is a common radiation-related toxicity after concurrent twice-daily hyperfractionated radiotherapy and chemotherapy in limited-stage small cell lung cancer (LS-SCLC) patients, which could limit dose-escalation of the target and make treatment postponed to decrease local tumor control. More esophageal protective techniques should be proposed to reduce radiation severe esophagitis of LS-SCLC patients. Methods: We retrospectively applied a contralateral esophagus sparing technique (CEST) in 20 unresectable LS-SCLC patients, who had gross tumor within 1 cm of the esophagus and received a total dose of 45 Gy of concurrent twice-daily radiation and standard chemotherapy regimen. The contralateral esophagus (CE) was contoured as an avoidance structure, and the feasibility of CEST on promoting a steep dose falloff beyond the target volume near esophagus was analyzed. The appropriate dose constraints of CE were also investigated. The AE events were recorded according to the RTOG acute toxicity grading system. Results: We performed CEST in 20 LS-SCLC consecutive patients, among whom three patients experienced severe AE after concurrent chemoradiotherapy. Each treatment plan of eligible patients assured high radiation doses delivering, with the planning and gross tumor volume covered by 95% and 100% of the prescription dose. Among these patients, the median maximum esophagus dose declined from 47.9 Gy (range, 46.6-49.7 Gy) to 41.3 Gy (range, 35.9-48.2 Gy), as well as V30 and V36 of esophagus decreased from 9.22 Gy (range, 0.42-17.71 Gy) and 7.39 Gy (range, 0-16.19 Gy) to 2.40 Gy (range, 0-5.68 Gy) and 0.53 Gy (range, 0 -2.69 Gy) after CEST applying, respectively (all p &lt; 0.001). The CE’s median maximum dose, V30, and V36 were 41.3 Gy, 2.13 cc, and 0.24 cc, respectively. Conclusions: By using proposed CE dose constraints of Dmax≤42 Gy, V30 ≤3.5 cc and V36 ≤0.5 cc, we confirmed the feasibility and efficacy of CEST to avoid exposing the esophagus cross-section to high prescription doses in LS-SCLC patients receiving twice-daily hyperfractionated IMRT and concurrent chemotherapy. These findings support the clinical practice of CEST in LS-SCLC patients, while more prospective and large-scale studies are warranted.

Cleaning the dose falloff with low modulation in SBRT lung plans

Purpose. This dosimetric study is intended to lower the modulation factor in lung SBRT plans generated in the Eclipse TPS that could replace highly modulated plans that are prone to the interplay effect. Materials and methods. Twenty clinical lung SBRT plans with high modulation factors (≥4) were replanned in Varian Eclipse TPS version 15.5 utilizing 2 mm craniocaudal and 1 mm axial block margins followed by light optimization in order to reduce modulation. A unique plan optimization methodology, which utilizes a novel shell structure (OptiForR50) for R50% optimization in addition to five consecutive concentric 5 mm shells, was utilized to control dose falloff according to RTOG 0813 and 0915 recommendations. The prescription varied from 34–54 Gy in 1–4 fractions, and the dose objectives were PTV D95% = Rx, PTV Dmax < 140% of Rx, and minimizing the modulation factor. Plan evaluation metrics included modulation factor, CIRTOG, homogeneity index (HI), R50%, D2cm, V105%, and lung V8–12.8Gy (Timmerman Constraint). A random-intercept linear mixed effects model was used with a p ≤ 0.05 threshold to test for statistical significance. Results. The retrospectively generated plans had significantly lower modulation factors (3.65 ± 0.35 versus 4.59 ± 0.54; p < 0.001), lower CIRTOG (0.97 ± 0.02 versus 1.02 ± 0.06; p = 0.001), higher HI (1.35 ± 0.06 versus 1.14 ± 0.04; p < 0.001), lower R50% (4.09 ± 0.45 versus 4.56 ± 0.56; p < 0.001), and lower lungs V8–12.8Gy (Timmerman) (4.61% ± 3.18% versus 4.92% ± 3.37%; p < 0.001). The high dose spillage V105% was borderline significantly lower (0.44% ± 0.49% versus 1.10% ± 1.64%; p = 0.051). The D2cm was not statistically different (46.06% ± 4.01% versus 46.19% ± 2.80%; p = 0.835). Conclusion. Lung SBRT plans with significantly lower modulation factors can be generated that meet the RTOG constraints, using our planning strategy.

Multi-isocenter VMAT craniospinal irradiation using feasibility dose-volume histogram-guided auto-planning technique.

This study aims to propose a novel treatment planning methodology for multi-isocenter volumetric modulated arc therapy (VMAT) craniospinal irradiation (CSI) using the special feasibility dose-volume histogram (FDVH)-guided auto-planning (AP) technique. Three different multi-isocenter VMAT -CSI plans were created, including manually based plans (MUPs), conventional AP plans (CAPs) and FDVH-guided AP plans (FAPs). The CAPs and FAPs were specially designed by combining multi-isocenter VMAT and AP techniques in the Pinnacle treatment planning system. Specially, the personalized optimization parameters for FAPs were generated using the FDVH function implemented in PlanIQ software, which provides the ideal organs at risk (OARs) sparing for the specific anatomical geometry based on the valuable assumption of the dose fall-off. Compared to MUPs, CAPs and FAPs significantly reduced the dose for most of the OARs. FAPs achieved the best homogeneity index (0.092 ± 0.013) and conformity index (0.980 ± 0.011), while CAPs were slightly inferior to the FAPs but superior to the MUPs. As opposed to MUPs, FAPs delivered a lower dose to OARs, whereas the difference between FAPs and CAPs was not statistically significant except for the optic chiasm and inner ear_L. The two AP approaches had similar MUs, which were significantly lower than the MUPs. The planning time of FAPs (145.00 ± 10.25min) was slightly lower than that of CAPs (149.83 ± 14.37min) and was substantially lower than that of MUPs (157.92 ± 16.11min) with P < 0.0167. Overall, introducing the multi-isocenter AP technique into VMAT-CSI yielded positive outcomes and may play an important role in clinical CSI planning in the future.

The effects of different photon beam energies in stereotactic radiosurgery with cones.

Stereotactic radiosurgery (SRS) relies on small fields to ablate lesions. Currently, linac based treatment is delivered via circular cones using a 6 MV beam. There is interest in both lower energy photon beams, which can offer steeper dose fall off as well as higher energy photon beams, which have higher dose rates, thus reducing radiation delivery times. Of interest in this study is the 2.5 MV beam developed for imaging applications and both the 6 and 10 MV flattening-filter-free (FFF) beams, which can achieve dose rates up to 2400 cGy/min. This study aims to assess the benefit and feasibility among different energy beams ranging from 2.5 to 10 MV beams by evaluating the dosimetric effects of each beam and comparing the dose to organs-at-risk (OARs) for two separate patient plans. One based on a typical real patient tremor utilizing a 4mm cone and the other a typical brain metastasis delivered with a 10mm cone. The Monte Carlo codes BEAMnrc/DOSXYZnrc were used to generate beams of 2.5 MV, 6 MV-FFF, 6 MV-SRS, 6 MV, 10 MV-FFF, and 10 MV from a Varian TrueBeam except 6 MV-SRS, which is taken from a Varian TX model linear accelerator. Each beam's energy spectrum, mean energy, %dd curve, and dose profile were obtained by analyzing the simulated beams. Calculated patient dose distributions were compared among six different energy beam configurations based on a realistic treatment plan for thalamotomy and a conventional brain metastasis plan. Dose to OARs were evaluated using dose-volume histograms for the same target dose coverage. The mean energies of photons within the primary beam projected area were insensitive to cone sizes and the values of percentage depth-dose curves (%dd) at d=5cm and SSD=95cm for a 4mm (10mm) cone ranges from 62.6 (64.4) to 82.2 (85.7) for beam energy ranging from 2.5 to 10 MV beams, respectively. Doses to OARs were evaluated among these beams based on real treatment plans delivering 15000 and 2200cGy to the target with a 4 and 10mm cone, respectively. The maximum doses to the brainstem, which is 10mm away from the isocenter, was found to be 434 (300), 632 (352), 691 (362), 733 (375), 822 (403), and 975 (441)cGy for 2.5 MV, 6 MV-FFF, 6 MV-SRS, 6 MV, 10 MV-FFF, and 10 MV beams delivering 15000 (2200) cGy target dose, respectively. Using the 6 MV-SRS as reference, changes of the maximum dose (691 cGy) to the brain stem are -37%, -9%, +6%, +19%, and 41% for 2.5 MV, 6 MV-FFF, 6 MV, 10 MV-FFF, and 10 MV beams, respectively, based on the thalamotomy plan, where the "-" or "+" signs indicate the percentage decrease or increase. Changes of the maximum dose (362 cGy) to brain stem, based on the brain metastasis plan are much less for respective beam energies. The sum of 21 arcs beam-on time was 39 min on our 6 MV-SRS beam with 1000 cGy/min for thalamotomy. The beam-on time can be reduced to 16 min with 10 MV-FFF.

A novel dose fall-off index and preliminary application in brain and lung stereotactic radiotherapy.

Stereotactic radiotherapy (SRT) has been widely used for the treatment of brain metastases and early stage non-small-cell lung cancer (NSCLC). Excellent SRT plans are characterized by steep dose fall-off, making it critical to accurately and comprehensively predict and evaluate dose fall-off. A novel dose fall-off index was proposed to ensure high-quality SRT planning. The novel gradient index (NGI) had two different modes: NGIx V for three-dimensions and NGIx r for one-dimension. NGIx V and NGIx r were defined as the ratios of the decreased percentage dose (x%) to the corresponding isodose volume and equivalent sphere radii, respectively. A total of 243 SRT plans at our institution between April 2020 and March 2022 were enrolled, including 126 brain and 117 lung SRT plans. Measurement-based verifications were performed using SRS MapCHECK. Ten plan complexity indexes were calculated. Dosimetric parameters related to radiation injuries were also extracted, including the normal brain volume exposed to 12 Gy (V12 ) and 18 Gy (V18 ) during single-fraction SRT (SF-SRT) and multi-fraction SRT (MF-SRT), respectively and the normal lung volume exposed to 12 Gy (V12 ). The performance of NGI and other common dose fall-off indexes, gradient index (GI), R50% and D2cm were evaluated using Spearman correlation analysis to explore their correlations with the PTV size, gamma passing rate (GPR), plan complexity indexes and dosimetric parameters. There were statistically significant correlations between NGI and PTV size (r = -0.98, p < 0.01 for NGI50 V and r = -0.93, p < 0.01 for NGI50 r), which were the strongest correlations compared with GI (r = 0.11, p = 0.13), R50% (r = -0.08, p = 0.19) and D2cm (r = 0.84, p < 0.01). The fitted formulas of NGI50 V = 23.86V-1.00 and NGI50 r = 113.5r-1.05 were established. The GPRs of enrolled SRT plans were 98.6 ± 1.7%, 94.2 ± 4.7% and 97.1 ± 3.1% using the criteria of 3%/2 mm, 3%/1 mm and 2%/2 mm, respectively. NGI50 V achieved the strongest correlations with various plan complexity indexes (|r| ranged from 0.67 to 0.91, p < 0.01). NGI50 V also showed the highest r values with V12 (r = -0.93, p < 0.01) and V18 (r = -0.96, p < 0.01) of the normal brain during SF-SRT and MF-SRT, respectively and V12 (r = -0.86, p < 0.01) of the normal lung during lung SRT. Compared with GI, R50% and D2cm , the proposed dose fall-off index, NGI, had the strongest correlations with the PTV size, plan complexity and V12 /V18 of the normal tissues. These correlations established on NGI are more helpful and reliable for SRT planning, quality control and reducing the risk of radiation injuries. This article is protected by copyright. All rights reserved.