Dose Painting Research Articles

From Protons to Picasso: Recreating Famous Paintings Using Proton Beams as a “Paintbrush”

To many, medicine is just as much an artform as it is a science. From the colorful stains used in diagnostic pathology, to the tactile sculpting of surgery, to the dose painting in radiation oncology, there is beauty and art to be found across all disciplines. In pencil-beam-scanning proton therapy, the dose is painted layer-by-layer, spot-by-spot, allowing for significantly more control compared to conventional radiation. This work intends to showcase the immense capability of intensity-modulated proton therapy (IMPT) through the recreation of some of the most renowned artworks throughout history, and has potential applications in patient education, medical/physics education, and quality assurance. Five (5) well-recognized paintings spanning from the Golden Age to the modern era were recreated as treatment plans in the Eclipse (version 16.1) External Beam Planning environment. For each "painting" (treatment plan), clinical protons within the range of 70-250 MeV were used to deposit "paint" (radiation dose) onto a "canvas" (water phantom) to a prescription of 100 Gy. The individual elements of each artwork were first delineated as separate structures. Colors were then assigned to appropriate isodose lines to mimic the corresponding palettes found in the original artworks. For each treatment plan, a single field was used along with inverse optimization to deposit the different doses at a depth of 10 centimeters. The resulting dose distribution was calculated with the proton convolution-superposition algorithm used in clinical practice. The dose distributions of the "paintings" demonstrated a marked semblance to the original artworks with sufficient resolution to elucidate fine details. The "paintings" varied in dimension from 20-30 cm at isocenter and on average took between 5-6 hours to complete. The number of structures used for planning ranged from 6-65 depending on the style and complexity of the original artwork. For a fractional dose of 200 cGy, the number of monitor units ranged from 73,145-269,970. With the advent of IMPT and modern planning techniques, we can now realize increasingly complex treatment plans, allowing for the creation of dose distributions that are highly targeted and specific. This is demonstrated by the capability to create recognizable works of art using proton beams as a "paintbrush".

A Prospective Study Assessing the Efficacy and Toxicity of Stereotactic Body Radiation Therapy for Oligometastatic Bone Metastases

Stereotactic body radiation therapy (SBRT) is a promising treatment for oligometastatic disease in bone due to its delivery of high dose to target tissue and minimal dose to surrounding tissue. The purpose of this study is to assess efficacy and toxicity of this treatment in patients with previously unirradiated oligometastatic bony disease. In this prospective phase II trial, patients with oligometastatic bone disease, defined as ≤3 active sites of disease, were treated with SBRT at one of two academic institutions between December 2016 and May 2019. Local progression-free survival (LPFS), progression-free survival (PFS), prostatic specific antigen (PSA) progression, and overall survival (OS) were reported. Treatment-related toxicity was also reported. A total of 98 patients and 131 lesions arising from various tumor histologies were included in this study. The median age of patients enrolled in the study was 72.8 years (80.6% male, 19.4% female). Median follow-up was 26.7 months. The most common histology was prostate cancer (68.4%, 67/98). The most common dose prescriptions were 27/30 Gy in 3 fractions (26.0%, 34/131), 30 Gy in 5 fractions (19.1%, 25/131), or 30/35 Gy in 5 fractions (16.0%, 21/131). Multiple doses per treatment regimen reflect dose painting employing the lower dose to the clinical target volume (CTV) and higher dose to the gross tumor volume (GTV). Four patients (4.1%, 4/98) experienced local progression at one site for each patient (3.1%, 4/131). Among patients who progressed locally, the median time to local recurrence was 25.8 months (31.0 months among prostate cancer patients, N = 2, and 14.5 months among non-prostate cancer patients, N = 2). Among the entire cohort, 2-year LPFS (including death without local progression) was 85.0%, 2-year PFS (including deaths as well as local, distant, and PSA-based progression) was 47.0%, and 2-year OS was 87.5%. Twenty-seven patients (27.6%, 27/98) developed treatment-related toxicities, and most were Grade 1 (19.4%, 19/98) and 2 (4.1%, 4/98). Four patients (4.1%, 4/98) developed Grade 3 toxicities; there were no Grade 4 toxicities. The most common toxicity was fatigue (10.2%, 10/98). Of 68 treated spine metastases, there were four (5.9%, 4/68) vertebral fractures. Among these four patients, median time to fracture was 23.5 months (range 14.2-39.2 months). Our study supports existing literature in showing that SBRT is effective and tolerable in patients with oligometastatic bone disease. Larger phase III trials are necessary and reasonable to determine long-term efficacy and toxicities.

Hypoxia dose painting in SBRT – the virtual clinical trial approach

Background Treating hypoxic tumours remains a challenge in radiotherapy as hypoxia leads to enhanced tumour aggressiveness and resistance to radiation. As escalating the doses is rarely feasible within the healthy tissue constraints, dose-painting strategies have been explored. Consensus about the best of care for hypoxic tumours has however not been reached because, among other reasons, the limits of current functional in-vivo imaging systems in resolving the details and dynamics of oxygen transport in tissue. Computational modelling of the tumour microenvironment enables the design and conduction of virtual clinical trials by providing relationships between biological features and treatment outcomes. This study presents a framework for assessing the therapeutic influence of the individual characteristics of the vasculature and the resulting oxygenation of hypoxic tumours in a virtual clinical trial on dose painting in stereotactic body radiotherapy (SBRT) circumventing the limitations of the imaging systems. Material and methods The homogeneous doses required to overcome hypoxia in simulated SBRT treatments of 1, 3 or 5 fractions were calculated for tumours with heterogeneous oxygenation derived from virtual vascular networks. The tumour control probability (TCP) was calculated for different scenarios for oxygenation dynamics resulting on cellular reoxygenation. Results A three-fractions SBRT treatment delivering 41.9 Gy (SD 2.8) and 26.5 Gy (SD 0.1) achieved only 21% (SD 12) and 48% (SD 17) control in the hypoxic and normoxic subvolumes, respectively whereas fast reoxygenation improved the control by 30% to 50%. TCP values for the individual tumours with similar characteristics, however, might differ substantially, highlighting the crucial role of the magnitude and time evolution of hypoxia at the microscale. Conclusion The results show that local microvascular heterogeneities may affect the predicted outcome in the hypoxic core despite escalated doses, emphasizing the role of theoretical modelling in understanding of and accounting for the dominant factors of the tumour microenvironment.

P18.07.A CLINICAL OUTCOMES OF PATIENTS TREATED WITH FRACTIONATED PHOTON RADIOTHERAPY FOR INTERMEDIATE AND HIGH-RISK MENINGIOMAS AT THE CHRISTIE HOSPITAL

Abstract BACKGROUND Radiotherapy is often used as a postoperative treatment for WHO Grade 2 (G2) and Grade 3 (G3) meningioma. However, there is limited data on the long-term outcomes following radiotherapy for these patients. The present study aims to evaluate the outcomes of intermediate and high-risk meningioma patients treated with radiotherapy. MATERIAL AND METHODS A retrospective analysis was conducted on all G2 and G3 meningioma patients treated at our centre with fractionated radiotherapy from 2012 to 2021. Clinical status at follow up was updated to 20 March 2023. Those who received stereotactic radiosurgery or were re-irradiated were excluded. Univariate Cox Regression modelling was conducted to assess association of progression, progression-free survival (PFS) and overall survival (OS) with clinical variables. RESULTS Forty-three patients were included in the analysis, 25 (58.2%) female. 39 patients had G2 and 4 G3 meningioma. Median age was 60 (range 11-80) years. Median follow-up was 72 months. At the time of radiotherapy, most (n= 34) had an ECOG performance status (PS) of 0-1. The dose fractionation was 50.4Gy (n=2), 54Gy (n=20) or 59.4Gy(n=1) in 1.8Gy fractions, or 60Gy(n=20) in 2Gy fractions. The PFS was 76.7% (95%CI:64.1,89.4) at 3 years and 64.3% (95%CI:49.8,78.9) at 5 years. OS was 79.1% (95% CI:66.9,91.2) at 3 years and 74.0% (95% CI:60.8,87.3) at 5 years. For the lower dose subgroup (50.4/54Gy), 3 and 5-year PFS rates were 86.4% (95% CI: 72.0,100) and 72.7% (95% CI:54.1,91.3), while 3 and 5-year OS rates were both 86.4% (95% CI:72.0,100). For the higher dose subgroup (59.4/60Gy), 3 and 5-year PFS rates were 66.7% (95% CI:46.5,86.8) and 55.0% (95% CI: 32.8,77.2), while 3 and 5 year OS were 71.4% (95% CI: 52.1,90.8) and 59.9% (95% CI: 38.1,81.8). All survival times were calculated from radiotherapy end date. Effect of dose (low vs high), age (either continuous or categorical as <60 vs ≥60), gender, WHO grade and PS were examined in univariate Cox regression for relationship to each of progression free status at last assessment, PFS and OS. No factor was statistically significant for progression free status or PFS. For OS, we found a significant association of worse OS with higher doses (59.4/60Gy), Hazard ratio (HR) 3.749 (95%CI: 1.18,11.9), p=0.025, and a borderline significance for age ≥60, HR 3.056 (95%CI:0.995,9.39), p=0.051. At the end of follow-up, 18 patients were alive without progression (16 G2, 2 G3), 8 were alive with progression (all G2), 10 had died with progression (9 G2, 1 G3) and 7 had died without progression (6 G2, 1 G3). CONCLUSION The worse OS in the higher dose group likely relates to clinical risk factors beyond WHO grade. There is a need for clinical trials to improve outcomes for intermediate and high risk meningioma. This may require better risk stratification by use of molecular markers, dose escalation or dose painting of high risk sub volumes and when possible targeted agents.

From coarse to fine: a deep 3D probability volume contours framework for tumour segmentation and dose painting in PET images.

With the increasing integration of functional imaging techniques like Positron Emission Tomography (PET) into radiotherapy (RT) practices, a paradigm shift in cancer treatment methodologies is underway. A fundamental step in RT planning is the accurate segmentation of tumours based on clinical diagnosis. Furthermore, novel tumour control methods, such as intensity modulated radiation therapy (IMRT) dose painting, demand the precise delineation of multiple intensity value contours to ensure optimal tumour dose distribution. Recently, convolutional neural networks (CNNs) have made significant strides in 3D image segmentation tasks, most of which present the output map at a voxel-wise level. However, because of information loss in subsequent downsampling layers, they frequently fail to precisely identify precise object boundaries. Moreover, in the context of dose painting strategies, there is an imperative need for reliable and precise image segmentation techniques to delineate high recurrence-risk contours. To address these challenges, we introduce a 3D coarse-to-fine framework, integrating a CNN with a kernel smoothing-based probability volume contour approach (KsPC). This integrated approach generates contour-based segmentation volumes, mimicking expert-level precision and providing accurate probability contours crucial for optimizing dose painting/IMRT strategies. Our final model, named KsPC-Net, leverages a CNN backbone to automatically learn parameters in the kernel smoothing process, thereby obviating the need for user-supplied tuning parameters. The 3D KsPC-Net exploits the strength of KsPC to simultaneously identify object boundaries and generate corresponding probability volume contours, which can be trained within an end-to-end framework. The proposed model has demonstrated promising performance, surpassing state-of-the-art models when tested against the MICCAI 2021 challenge dataset (HECKTOR).

Plan Assessment Metrics for Dose Painting in Stereotactic Radiosurgery

As radiation therapy treatment precision increases with advancements in imaging and radiation delivery, dose painting treatment becomes increasingly feasible, where targets receive a nonuniform radiation dose. The high precision of stereotactic radiosurgery (SRS) makes it a good candidate for dose painting treatments, but no suitable metrics to assess dose painting SRS plans exist. Existing dose painting assessment metrics weigh target overdose and underdose equally but are unsuited for SRS plans, which typically avoid target underdose more. Current SRS metrics also prioritize reducing healthy tissue dose through selectivity and dose fall-off, and these metrics assume single prescriptions. We propose a set of metrics for dose painting SRS that would meet clinical needs and are calculated with nonuniform dose painting prescriptions. Sample dose painting SRS prescriptions are first created from Gamma Knife SRS cases, apparent diffusion coefficient magnetic resonance images, and various image-to-prescription functions. Treatment plans are found through semi-infinite linear programming optimization and using clinically determined isocenters, then assessed with existing and proposed metrics. Modified versions of SRS metrics are proposed, including coverage, selectivity, conformity, efficiency, and gradient indices. Quality factor, a current dose painting metric, is applied both without changes and with modifications. A new metric, integral dose ratio, is proposed as a measure of target overdose. The merits of existing and modified metrics are demonstrated and discussed. A modified conformity index using mean or minimum prescription dose would be suitable for dose painting SRS with integral or maximum boost methods, respectively. Either modified efficiency index is a suitable replacement for the existing gradient index. The proposed modified SRS metrics are appropriate measures of plan quality for dose painting SRS plans and have the advantage of giving equal values as the original SRS metrics when applied to single-prescription plans.

MO-0956 Time evolved hypoxia guided proton therapy dose painting in HNSCC patients

MO-0956 Time evolved hypoxia guided proton therapy dose painting in HNSCC patients

PO-1181 Clinical outcomes after re-irradiation with dose painting of head and neck cancer

PO-1181 Clinical outcomes after re-irradiation with dose painting of head and neck cancer

On the correction of respiratory motion-induced image reconstruction errors in positron-emission tomography-guided radiation therapy

Free breathing (FB) positron emission tomography (PET) images are routinely used in radiotherapy for lung cancer patients. Respiration-induced artifacts in these images compromise treatment response assessment and obstruct clinical implementation of dose painting and PET-guided radiotherapy. The purpose of this study is to develop a blurry image decomposition (BID) method to correct motion-induced image-reconstruction errors in FB-PETs. Assuming a blurry PET is represented as an average of multi-phase PETs. A four-dimensional computed-tomography image is deformably registered from the end-inhalation (EI) phase to other phases. With the registration-derived deformation maps, PETs at other phases can be deformed from a PET at the EI phase. To reconstruct the EI-PET, the difference between the blurry PET and the average of the deformed EI-PETs is minimized using a maximum-likelihood expectation-maximization algorithm. The developed method was evaluated with computational and physical phantoms as well as PET/CT images acquired from three patients. The BID method increased the signal-to-noise ratio from 1.88±1.05 to 10.5±3.3 and universal-quality index from 0.72±0.11 to 1.0 for the computational phantoms, and reduced the motion-induced error from 69.9% to 10.9% in the maximum of activity concentration and from 317.5% to 8.7% in the full width at half maximum of the physical PET-phantom. The BID-based corrections increased the maximum standardized-uptake values by 17.7±15.4% and reduced tumor volumes by 12.5±10.4% on average for the three patients. The proposed image-decomposition method reduces respiration-induced errors in PET images and holds potential to improve the quality of radiotherapy for thoracic and abdominal cancer patients.

Dose painting to reduce surgical wound complications after preoperative radiotherapy for soft tissue sarcomas: a double-blinded randomized phase 2 clinical trial

Dose painting to reduce surgical wound complications after preoperative radiotherapy for soft tissue sarcomas: a double-blinded randomized phase 2 clinical trial

A novel approach for dose painting radiotherapy of brain metastases guided by mr perfusion images.

To investigate the feasibility and dosimetric index features of dose painting guided by perfusion heterogeneity for brain metastasis (BMs) patients. A total of 50 patients with single BMs were selected for this study. CT and MR simulation images were obtained, including contrast-enhanced T1-weighted images (T1WI+C) and cerebral blood flow (CBF) maps from 3D-arterial spin labeling (ASL). The gross tumor volume (GTV) was determined by fusion of CT and T1WI+C images. Hypoperfused subvolumes (GTVH) with less than 25% of the maximum CBF value were defined as the dose escalation region. The planning target volume (PTV) and PTVH were calculated from GTV and GTVH respectively. The PTVN was obtained by subtracting PTVH from PTV, and conventional dose was given. Three kinds of radiotherapy plans were designed based on the CBF values. Plan 1 was defined as the conventional plan with an arbitrary prescription dose of 60 Gy for PTV. For dose painting, Plan 2 and Plan 3 escalated the prescription dose for PTVH to 72 Gy based on Plan 1, but Plan 3 removed the maximum dose constraint. Dosimetric indices were compared among the three plans. The mean GTV volume was 34.5 (8.4-118.0) cm3, and mean GTVH volume was 17.0 (4.5-58.3) cm3, accounting for 49.3% of GTV. Both conventional plan and dose painting plans achieved 98% target coverage. The conformity index of PTVH were 0.44 (Plan1), 0.64 and 0.72 (Plan 2 and Plan 3, P<0.05). Compared to Plan 1, the D2%, D98% and Dmean values of the PTVH escalated by 20.50%, 19.32%, and 19.60% in Plan 2 and by 24.88%, 17.22% and 19.22% in Plan 3 respectively (P<0.05). In the three plans, the index of achievement value for PTVH was between 1.01 and 1.03 (P<0.05). The dose increment rates of Plan 2 and Plan 3 for each organs at risk (OARs) was controlled at 2.19% - 5.61% compared with Plan 1. The doses received by OARs did not significantly differ among the three plans (P >0.05). BMs are associated with significant heterogeneity, and effective escalation of the dose delivered to target subvolumes can be achieved with dose painting guided by 3D-ASL without extra doses to OARs.

Introducing new plan evaluation indices for prostate dose painting IMRT plans based on apparent diffusion coefficient images

BackgroundDose painting planning would be more complicated due to different levels of prescribed doses and more complex evaluation with conventional plan quality indices considering uniform dose prescription. Therefore, we tried to introduce new indices for evaluating the dose distribution conformity and homogeneity of treatment volumes based on the tumoral cell density and relative volumes of each lesion in prostate IMRT.MethodsCT and MRI scans of 20 male patients having local prostate cancer were used for IMRT DP planning. Apparent diffusion coefficient (ADC) images were imported to a MATLAB program to identify lesion regions based on ADC values automatically. Regions with ADC values lower than 750 mm2/s and regions with ADC values higher than 750 and less than 1500 mm2/s were considered CTV70Gy (clinical tumor volume with 70 Gy prescribed dose), and CTV60Gy, respectively. Other regions of the prostate were considered as CTV53Gy. New plan evaluation indices based on evaluating the homogeneity (IOE(H)), and conformity (IOE(C)) were introduced, considering the relative volume of each lesion and cellular density obtained from ADC images. These indices were compared with conventional homogeneity and conformity indices and IOEs without considering cellular density. Furthermore, tumor control probability (TCP) was calculated for each patient, and the relationship of the assessed indices were evaluated with TCP values.ResultsIOE (H) and IOE (C) with considering cellular density had significantly lower values compared to conventional indices and IOEs without considering cellular density. (P < 0.05). TCP values had a stronger relationship with IOE(H) considering cell density (R2 = -0.415), and IOE(C) without considering cell density (R2 = 0.624).ConclusionIOE plan evaluation indices proposed in this study can be used for evaluating prostate IMRT dose painting plans. We suggested to consider cell densities in the IOE(H) calculation formula and it’s appropriate to calculate IOE(C) without considering cell density values.

Three-dimensional arterial spin labeling-guided dose painting radiotherapy for non-enhancing low-grade gliomas

PurposeTo investigate the feasibility and dosimetric characteristics of dose painting for non-enhancing low-grade gliomas (NE-LGGs) guided by three-dimensional arterial spin labeling (3D-ASL).Materials and methodsEighteen patients with NE-LGGs were enrolled. 3D-ASL, T2 fluid-attenuated inversion recovery (T2 Flair) and contrast-enhanced T1-weighted magnetic resonance images were obtained. The gross tumor volume (GTV) was delineated on the T2 Flair. The hyper-perfusion region of the GTV (GTV-ASL) was determined by 3D-ASL, and the GTV-SUB was obtained by subtracting the GTV-ASL from the GTV. The clinical target volume (CTV) was created by iso-tropically expanding the GTV by 1 cm. The planning target volume (PTV), PTV-ASL were obtained by expanding the external margins of the CTV, GTV-ASL, respectively. PTV-SUB was generated by subtracting PTV-ASL from PTV. Three plans were generated for each patient: a conventional plan (plan 1) without dose escalation delivering 95–110% of 45–60 Gy in 1.8–2 Gy fractions to the PTV and two dose-painting plans (plan 2 and plan 3) with dose escalating by 10–20% (range, 50–72 Gy) to the PTV-ASL based on plan 1. The plan 3 was obtained from plan 2 without the maximum dose constraint. The dosimetric differences among the three plans were compared.ResultsThe volume ratio of the PTV-ASL to the PTV was (23.49 ± 11.94)% (Z = − 3.724, P = 0.000). Compared with plan 1, D2%, D98% and Dmean of PTV-ASL increased by 14.67%,16.17% and 14.31% in plan2 and 19.84%,15.52% and 14.27% in plan3, respectively (P < 0.05); the D2% of the PTV and PTV-SUB increased by 11.89% and 8.34% in plan 2, 15.89% and 8.49% in plan 3, respectively (P < 0.05). The PTV coverages were comparable among the three plans (P > 0.05). In plan 2 and plan 3, the conformity indexes decreased by 18.60% and 12.79%; while the homogeneity index increased by 1.43 and 2 times (P < 0.05). Compared with plan 1, the D0.1 cc of brain stem and Dmax of optic chiasma were slightly increased in plan 2 and plan 3, and the absolute doses met the dose constraint. The doses of the other organs at risk (OARs) were similar among the three plans (P > 0.05).ConclusionThe dose delivered to hyper-perfusion volume derived from 3D-ASL can increased by 10–20% while respecting the constraints to the OARs for NE-LGGs, which provides a basis for future individualized and precise radiotherapy, especially if the contrast agent cannot be injected or when contrast enhancement is uncertain.

Acute Toxicity in ARTFORCE: A Randomized Phase III Dose-Painting Trial in Head and Neck Cancer

<h3>Purpose/Objective(s)</h3> Local recurrences of squamous cell carcinomas of the head and neck are often located within the primary tumor volume, suggesting radio-resistance. Targeting dose escalation to radio-resistant sub-volumes within the primary tumor might increase tumor control as well as toxicity risks. Adaptive radiotherapy could limit these risks by improving dose painting precision. This hypothesis was tested in the Adaptive Radiation Treatment for Head and Neck Cancer (ARTFORCE) trial (NCT01504815); a multicenter randomized phase III trial evaluating a 18F-FDG PET/CT-guided dose painting and a scheduled adaptation strategy in locally advanced squamous cell carcinomas of the head and neck (LAHNSCC). Here, the first acute toxicity analysis will be presented. <h3>Materials/Methods</h3> A total of 222 patients with LAHNSCC scheduled for chemoradiotherapy were randomized: 109 patients in the experimental arm (A) and 113 in the standard arm (B). In arm A, a boost (min 70Gy, max 84Gy, mean 77Gy) was targeted at the PTV-PET: a 3mm expansion of the sub-volume within the primary tumor with PET-SUV ≥ SUV50%. Irradiation was performed in 35 fractions by simultaneous integrated boost technique. In this arm, two strategies were used to contain toxicity risks. First, the PTV surrounding PTV-PET received a slightly lower dose with a mean of 67Gy (min 64Gy, max 70Gy). Secondly, delineations were adjusted at the 10^th fraction for obvious anatomical changes. Patients in arm B were treated by conventional radiation treatment with a homogenous dose of 70Gy in 35 fractions. The doses to the pathological lymph nodes and nodal volumes were identical for both arms; 70Gy and 54.25Gy, respectively. Acute toxicities were scored according to the CTCAE v4.0 and defined as toxicities occurring during treatment until 90 days after treatment or until 110 days after treatment if these immediately subsided after 110 days. For statistical analysis, maximum CTCAE grades were dichotomized three times: ≥ grade 2, ≥ grade 3 and ≥ grade 4. Fisher's exact test was then used to detect statistical differences between the two study arms using a level of significance of 0.05. <h3>Results</h3> No statistically significant differences (p ≥ 0.11) in acute toxicity rates between both study arms were observed. Most common reported grade ≥3 toxicities were mucositis (62% in arm A versus 57% in arm B, p = 0.41), dysphagia (53% versus 54%, p = 1), hematologic toxicities (21% versus 26%, p = 0.43) and radiation dermatitis (18% versus 16%, p = 0.72). Half of the reported grade 4 toxicities were due to hematologic toxicities (6% versus 7%, p = 1). Grade 4 mucositis presented twice in both arms. One patient in arm A and two patients in arm B developed grade 4 dysphagia. One patient in arm A died due to aspiration pneumonia. No other grade 5 toxicities were reported. <h3>Conclusion</h3> The results of this analysis suggest that this dose painting and adaptive radiotherapy strategy preserves acute toxicity rates while increasing dose to radio-resistant sub-volumes.

Predicting the Achievable Ablative Radiation Dose Coverage to Gross Tumor Volumes in Pancreatic Cancer Patients

<h3>Purpose/Objective(s)</h3> Ablative radiation therapy (RT) in pancreas cancer is associated with durable control of the primary tumor leading to favorable survival outcomes. A key planning goal is to achieve ablative dose (> 100 Gy BED) to the gross tumor volume (GTV), while still respecting organ-at-risk (OAR) dose constraints. However, the GTVs are typically located near radiosensitive OARs such as small bowel, large bowel, and stomach. This makes predicting V100 coverage to the GTV difficult to assess a priori. Each patient's GTV and OAR location, shape, and volume vary significantly and introduces uncertainty to the achievable GTV V100. Currently, achievable GTV V100 coverage is determined through trial and error as the planner explores tradeoffs between OAR sparing and prescription dose coverage. Iterative planning is time and labor intensive. In this study, we present a customized patient anatomy dependent prediction formula that can be used to guide the planning goals and improve planning speed and quality. <h3>Materials/Methods</h3> The minimum GTV coverage prediction formula was empirically derived as below Gf=fGTV - [fs × (1-fGTV)/3] + [(1-fs) × (1-fGTV)/20] ± 4% Gf: GTV V100 prediction value OARs=Small bowel + Large bowel + Stomach+ Duodenum OARs_5.5mm: OARs with 5.5mm 3D expansion fGTV: VGTV- OARs_5.5mm / VGTV fs: SOAR / SGTV VGTV: GTV volume VGTV- OARs_5.5mm: GTV volume subtract OARs with 5.5mm 3D margin SGTV: total number CT slices with GTV SOAR: total number CT slices with OARs within 3cm from the GTV Using this formula, 30 patients were randomly selected for testing efficacy. Patient plans were prescribed with dose painting to 3750cGy and 6750cGy in 15 fractions with GTVs intending to receive 6750cGy. Plans were generated using 2 or 3 6X VMAT full arcs with jaw tracking. If the original GTV coverage differed by 4% below the predicted GTV coverage, it was replanned with same treatment field geometry to verify the reliability of the prediction value. <h3>Results</h3> For the 30 patients, the GTV size ranged from 10.8 cc to 183.9cc. The fGTV and fs factor ranged from 0.61 -1 and 0 - 1. The GTV coverage for 17 out of the 30 patients was within the predicted GTV coverage range. The remaining patients had GTV coverage more than 4% below the predicted value with differences ranging from 5.1% to 22.3%. For these 13 patients, the GTV coverage improved to within the predicting formula range by adding a high priority minimum GTV coverage dose constraint to the optimization parameters. <h3>Conclusion</h3> The presented formula can sufficiently predict achievable GTV coverage while accommodating patient-specific anatomy and GTV volume sizes. The prediction formula is a stable tool to assist planners during the optimization process while maintaining plan quality. Future developments will include adjusting the formula to accommodate different prescription doses.

Implementation of an Automated Radiation Oncology Prescription Checking System, Revealing a Baseline Prescription Error Rate of at Least 0.2%

<h3>Purpose/Objective(s)</h3> Radiation dose prescriptions serve as the radiation oncologist's (RO) treatment intent, containing vital information such as treatment technique, total dose, dose per fraction, and number of fractions. Despite serving as a critical communication tool, prescriptions are entered manually and prone to various forms of error. Human systems and traditional safety checks may not catch these, due to assumption of RO intent and deference to ROs. This can lead to significant wasted treatment planning resources and, if not ultimately caught, can lead to misadministration. In response to the potential for erroneous prescription entry, an automated prescription checking system was designed and implemented. <h3>Materials/Methods</h3> Rules defining clinically appropriate prescriptions were generated, examining specific types of errors: 1) Approved dose per fraction. This was based on review of 14,487 prescriptions written in 2019-2020, divided into 17 disease sites, and manually curated by disease site experts for approved doses per fraction per site. 2) Dose per fraction too large for non-stereotactic treatment technique. 3) Dose per fraction too low (in dose painting prescriptions). With a goal of catching errors as far upstream as possible to minimize their propagation, a report was created and run every 30 minutes, checking all newly written prescriptions against the above rules. When prescriptions did not fall within the bounds of the rules, an automated email was sent to the prescriber alerting them of the atypical prescription and prompting them to check if it was written as intended. The rules were continuously analyzed in an attempt at balancing error detection against false positive alerts. <h3>Results</h3> From June-December 2021, 9,577 prescriptions were checked, and 70 email alerts were triggered, for an average alert rate of 0.7%. Of the 70 alerts, 60 (85.7%) were unapproved doses per fraction, 8 (11.4%) were doses too large for non-stereotactic treatment technique, and 2 (2.9%) were doses that were too low. The alert rate was 1.1% in June and trended down to 0.6% in December. Of the 70 alerts, 23 (32.9%) prescriptions were subsequently amended suggesting that the rate of erroneous prescription entry was 0.2% (23/9,577). <h3>Conclusion</h3> A baseline error rate of radiation oncology prescription entry has not been previously reported. This data suggests that the rate of erroneous prescription entry is at least 0.2%. Given the significant consequences of erroneous prescription entry, ranging from wasted resources and treatment delays (should these errors be caught prior to treatment), to potentially serious misadministration, there is significant value in implementing automated prescription checking systems in radiation oncology clinics.

The impact of organ motion and the appliance of mitigation strategies on the effectiveness of hypoxia-guided proton therapy for non-small cell lung cancer

Background and PurposeTo investigate the impact of organ motion on hypoxia-guided proton therapy treatments for non-small cell lung cancer (NSCLC) patients. Materials and MethodsHypoxia PET and 4D imaging data of six NSCLC patients were used to simulate hypoxia-guided proton therapy with different motion mitigation strategies including rescanning, breath-hold, respiratory gating and tumour tracking. Motion-induced dose degradation was estimated for treatment plans with dose painting of hypoxic tumour sub-volumes at escalated dose levels. Tumour control probability (TCP) and dosimetry indices were assessed to weigh the clinical benefit of dose escalation and motion mitigation. In addition, the difference in normal tissue complication probability (NTCP) between escalated proton and photon VMAT treatments has been assessed. ResultsMotion-induced dose degradation was found for target coverage (CTV V95% up to −4%) and quality of the dose-escalation-by-contour (QRMS up to 6%) as a function of motion amplitude and amount of dose escalation. The TCP benefit coming from dose escalation (+4–13%) outweighs the motion-induced losses (<2%). Significant average NTCP reductions of dose-escalated proton plans were found for lungs (−14%), oesophagus (−10%) and heart (−16%) compared to conventional VMAT plans. The best plan dosimetry was obtained with breath hold and respiratory gating with rescanning. ConclusionNSCLC affected by hypoxia appears to be a prime target for proton therapy which, by dose-escalation, allows to mitigate hypoxia-induced radio-resistance despite the sensitivity to organ motion. Furthermore, substantial reduction in normal tissue toxicity can be expected compared to conventional VMAT. Accessibility and standardization of hypoxia imaging and clinical trials are necessary to confirm these findings in a clinical setting.

Adaptive dose painting for prostate cancer.

PurposeDose painting (DP) is a radiation therapy (RT) strategy for patients with heterogeneous tumors delivering higher dose to radiation resistant regions and less to sensitive ones, thus aiming to maximize tumor control with limited side effects. The success of DP treatments is influenced by the spatial accuracy in dose delivery. Adaptive RT (ART) workflows can reduce the overall geometric dose delivery uncertainty. The purpose of this study is to dosimetrically compare ART and non-adaptive conventional RT workflows for delivery of DP prescriptions in the treatment of prostate cancer (PCa).Materials and methodsWe performed a planning and treatment simulation study of four study arms. Adaptive and conventional workflows were tested in combination with DP and Homogeneous dose. We used image data from 5 PCa patients that had been treated on the Elekta Unity MR linac; the patients had been imaged in treatment position before each treatment fraction (7 in total). The local radiation sensitivity from apparent diffusion coefficient maps of 15 high-risk PCa patients was modelled in a previous study. these maps were used as input for optimization of DP plans aiming for maximization of tumor control probability (TCP) under rectum dose constraints. A range of prostate doses were planned for the homogeneous arms. Adaptive plans were replanned based on the anatomy-of-the-day, whereas conventional plans were planned using a pre-treatment image and subsequently recalculated on the anatomy-of-the-day. The dose from 7 fractions was accumulated using dose mapping. The endpoints studied were the TCP and dose-volume histogram metrics for organs at risk.ResultsAccumulated DP doses (adaptive and conventional) resulted in high TCP, between 96-99%. The largest difference between adaptive and conventional DP was 2.6 percentage points (in favor of adaptive DP). An analysis of the dose per fraction revealed substantial target misses for one patient in the conventional workflow that—if systematic—could jeopardize the TCP. Compared to homogeneous prescriptions with equal mean prostate dose, DP resulted in slightly higher TCP.ConclusionCompared to homogeneous dose, DP maintains or marginally increases the TCP. Adaptive DP workflows could avoid target misses compared to conventional workflows.

Safety of Inhomogeneous Dose Distribution IMRT for High-Grade Glioma Reirradiation: A Prospective Phase I/II Trial (GLIORAD TRIAL).

Simple SummaryGlioblastoma multiforme (GBM) is the most frequent primary malignant brain tumor, and despite advances in imaging techniques and treatment options, the outcome remains poor and recurrence is inevitable. Salvage therapy presents a challenge, and re-irradiation can be a therapeutic option in recurrent GBM. The decision-making process for re-irradiation is a challenge for radiation oncologists due to the expected toxicity of a second course of radiotherapy and the limited radiation tolerance of normal tissue; nevertheless, it is being increasingly used, as several studies have demonstrated its feasibility. The current study aimed to investigate the safety of moderate–high-voxel-based dose escalation radiotherapy in recurrent GBM patients after conventional concurrent chemoradiation. Twelve patients were enrolled in this prospective single-center study. Retreatment consisted of re-irradiation with a total dose range of 30–50 Gy over 5 days using the IMRT (arc VMAT) technique using dose painting planning. The treatment was well tolerated. No toxicities greater than 3 were recorded; only one patient had severe G3 acute toxicity, characterized by muscle weakness and fatigue. Median overall survival (OS2) and progression-free survival (PFS2) from the time of re-irradiation were 10.4 months and 5.7 months, respectively. Our phase I study demonstrated an acceptable tolerance profile of this approach, and the future prospective phase II study will analyze the efficacy in terms of PFS and OS.Glioblastoma multiforme (GBM) is the most aggressive astrocytic primary brain tumor, and concurrent temozolomide (TMZ) and radiotherapy (RT) followed by maintenance of adjuvant TMZ is the current standard of care. Despite advances in imaging techniques and multi-modal treatment options, the median overall survival (OS) remains poor. As an alternative to surgery, re-irradiation (re-RT) can be a therapeutic option in recurrent GBM. Re-irradiation for brain tumors is increasingly used today, and several studies have demonstrated its feasibility. Besides differing techniques, the published data include a wide range of doses, emphasizing that no standard approach exists. The current study aimed to investigate the safety of moderate–high-voxel-based dose escalation in recurrent GBM. From 2016 to 2019, 12 patients met the inclusion criteria and were enrolled in this prospective single-center study. Retreatment consisted of re-irradiation with a total dose of 30 Gy (up to 50 Gy) over 5 days using the IMRT (arc VMAT) technique. A dose painting by numbers (DPBN)/dose escalation plan were performed, and a continuous relation between the voxel intensity of the functional image set and the risk of recurrence in that voxel were used to define target and dose distribution. Re-irradiation was well tolerated in all treated patients. No toxicities greater than G3 were recorded; only one patient had severe G3 acute toxicity, characterized by muscle weakness and fatigue. Median overall survival (OS2) and progression-free survival (PFS2) from the time of re-irradiation were 10.4 months and 5.7 months, respectively; 3-, 6-, and 12-month OS2 were 92%, 75%, and 42%, respectively; and 3-, 6-, and 12-month PFS2 were 83%, 42%, and 8%, respectively. Our work demonstrated a tolerable tolerance profile of this approach, and the future prospective phase II study will analyze the efficacy in terms of PFS and OS.

A Brief Report on the Role of SPECT/TC in the Optimization of Radiotherapy Treatment with Radical Intent for Unresectable Stage III NSCLC

Background: The standard treatment for locally advanced non-small cell lung cancer (LA-NSCLC) is represented by concomitant chemo-radiotherapy followed by consolidation with durvalumab that ensures a 5-year survival of 46%. However, the risk of radiotherapy-induced pneumonia (RIP) is almost 10–15%. Complete cardiological examination is also usually performed during the cardiopulmonary pre-treatment evaluation and pulmonary function testing is one of the most used tool to predict the risk of RIP development. Aim: The aim of this study is to investigate the impact of Tc-99 macroaggregated albumin (MAA) lung perfusion scan with single photon emission-computed tomography/computed tomography (SPECT/CT) in the preliminary assessment of lung functions and its potential role for the optimization of the radiotherapy treatment planning. Methods: Descriptive and statistical analysis were performed on eight patients affected by unresectable stage III LA-NSCLC treated with chemo-radiotherapy. Before starting radiotherapy, patients underwent lung perfusion SPECT/CT. The SPECT/CT images were firstly co-registered with the simulation CT scan ones, then a specific region of interest (ROI) of lung volumes was created to represent the areas with a perfusion of at least 20% 40%, 60% and 80% of maximum perfusion, respectively. Finally, optimization of the standard treatment plan was performed with the aim of preserving the better perfused lung volumes. The dosimetric correlations of both plans were made comparing pulmonary V20 and V5, mean pulmonary, esophagus and heart dose. Results: From the DVH comparative analysis of the two treatment plans (standard one versus SPECT optimized one) obtained for each patient, the data confirmed an equal coverage of the target volume while respecting all lungs, heart and esophagus dose constraints. At the same time, SPECT-optimized plans allowed to reduce the average dose to the better perfused lung volumes. Conclusions: Lung perfusion scintigraphy could be considered a preliminary assessment tool to explore lung functions and stratify the risk of RIP development. SPECT/TC may also be proposed as a dose painting tool to optimize radiotherapy treatment plans. Only prospective analysis will be enable us to confirm the real reduction of RIP risk in lung areas with an optimal perfusion.