Gross Target Volume Research Articles

3D target definition and initial results from the electroanatomic substrate-guided stereotactic ablative radiotherapy for refractory ventricular tachycardia (ELSTAR-VT)

Abstract Background/introduction Noninvasive stereotactic radiotherapy (STAR) is an emerging transmural ablative therapy for refractory ventricular tachycardia (VT). Delineation of the arrhythmogenic gross target volume (GTV) relies on electrical (exit and isthmus) VT characteristics and anatomical scar detailing. 17-AHA segmental approaches or eyeballing techniques are adopted to transfer the GTV to the treatment planning CT. An individualized 3D GTV delineated with ADAS3D based on the areas of interest of each modality could lead to a smaller GTV compared to 17-AHA segmental approaches. Purpose We investigated whether our workflow using ADAS3D for the delineating of the GTV renders smaller GTV compared to 17-AHA segmental approaches whilst remaining effective for VT treatment during follow-up. Methods We targeted 3D-personalized GTV with STAR in patients with refractory VT in structural heart disease. Electroanatomical detailing was achieved by combining high-resolution invasive and noninvasive (ECG imaging during noninvasive programmed stimulation) mapping, combined with wall thickness analyses by cardiac CT. After coregistration in ADAS3D, a 3D DICOM-radiation therapy file including the delineated target volume was generated and transferred into the free-breathing and respiration-corrected 4D CT scan. Standard STAR using a single-fraction of 20-25 Gy was applied. We compared conventional (17-AHA segmental approaches) versus 3D-based GTV demarcation, and assessed VT burden and procedural safety. Results From January 2023 to February 2024 STAR was successfully performed in three patients (all male, mean age 73±1 years, two ischemic cardiomyopathy, one laminopathy) with persistent VT despite ≥2 catheter-based (endocardial/epicardial) ablation procedures. The 3D-derived GTVs showed a statistical trend towards smaller volumes compared to conventional segmental delineation (11±4 versus 21±3 cm3, p=0.07). VT burden and ICD therapy was reduced by 100% over 9 patients-months (8-week blanking period). No acute or subacute adverse events occurred. One patient died of progressive heart failure. Conclusion 3D-individualized target volume annotation may hold promise for effective and safe STAR employment.ELSTAR workflow

Enhancing stereotactic ablative boost radiotherapy dose prediction for bulky lung cancer: A multi-scale dilated network approach with scale-balanced structure loss.

Partial stereotactic ablative boost radiotherapy (P-SABR) effectively treats bulky lung cancer; however, the planning process for P-SABR requires repeated dose calculations. To improve planning efficiency, we proposed a novel deep learning method that utilizes limited data to accurately predict the three-dimensional (3D) dose distribution of the P-SABR plan for bulky lung cancer. We utilized data on 74 patients diagnosed with bulky lung cancer who received P-SABR treatment. The patient dataset was randomly divided into a training set (51 plans) with augmentation, validation set (7 plans), and testing set (16 plans). We devised a 3D multi-scale dilated network (MD-Net) and integrated a scale-balanced structure loss into the loss function. A comparative analysis with a classical network and other advanced networks with multi-scale analysis capabilities and other loss functions was conducted based on the dose distributions in terms of the axial view, average dose scores (ADSs), and average absolute differences of dosimetric indices (AADDIs). Finally, we analyzed the predicted dosimetric indices against the ground-truth values and compared the predicted dose-volume histogram (DVH) with the ground-truth DVH. Our proposed dose prediction method for P-SABR plans for bulky lung cancer demonstrated strong performance, exhibiting a significant improvement in predicting multiple indicators of regions of interest (ROIs), particularly the gross target volume (GTV). Our network demonstrated increased accuracy in most dosimetric indices and dose scores in different ROIs. The proposed loss function significantly enhanced the predictive performance of the dosimetric indices. The predicted dosimetric indices and DVHs were equivalent to the ground-truth values. Our study presents an effective model based on limited datasets, and it exhibits high accuracy in the dose prediction of P-SABR plans for bulky lung cancer. This method has potential as an automated tool for P-SABR planning and can help optimize treatments and improve planning efficiency.

LatticeOpt: An automatic tool for planning optimisation of spatially fractionated stereotactic body radiotherapy

PurposeLattice radiotherapy (LRT) is a three dimensional (3D) implementation of spatially fractionated radiation therapy, based on regular spatial distribution of high dose spheres (vertices) inside the target. Due to tumour shape heterogeneity, finding the best lattice arrangement is not trivial.The aim of this study was to develop the LatticeOpt tool to generate the best lattice structures on clinical cases for treatment planning. MethodsDeveloped in MATLAB, LatticeOpt finds the 3D-spatial configurations that maximize the number of vertices within the gross target volume (GTV). If organs at risk (OARs) are considered, it chooses the solution that minimizes the overlapping volume histograms (OVH). Otherwise, the lattice structure with the minimum Hausdorff distance between vertices and GTV boundary is chosen to avoid unpopulated regions.Different lattice structures were created for 20 patients, with (OVHopt) and without (OVHunopt) OVH minimization. Imported into TPS (Eclipse, Varian), corresponding plans were generated and evaluated in terms of OAR mean and maximum doses, GTV vertex coverage and dose gradients, as well as pre-clinical plan dosimetry. ResultsPlans based on an optimized lattice structure (OVHopt, OVHunopt) had similar dose distributions in terms of vertex coverage and gradient index score. OAR sparing was observed in all patients, with a 4 % and 9 % difference for mean and max dose (both p-values <0.01), respectively. The best vertices dimensions and their relative distances were patient dependent. ConclusionsLatticeOpt was able to reduce the time-consuming procedures of LRT, as well as to achieve standardized and reproducible results, useful for multicentre studies.

Impact of the Novel MRI Contrast Agent Gadopiclenol on Radiotherapy Decision Making in Patients With Brain Metastases.

The aim of this study was to assess the effect of gadopiclenol versus gadobenate dimeglumine contrast-enhanced magnetic resonance imaging (MRI) on decision-making between whole-brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS) for treatment of brain metastases (BMs). Patients with BMs underwent 2 separate MRI examinations in a double-blind crossover phase IIb comparative study between the MRI contrast agents gadopiclenol and gadobenate dimeglumine, both administered at 0.1 mmol/kg. The imaging data of a single site using identical MRI scanners and protocols were included in this post hoc analysis. Patients with 1 or more BMs in any of both MRIs were subjected to target volume delineation for treatment planning. Two radiation oncologists contoured all visible lesions and decided upon SRS or WBRT, according to the number of metastases. For each patient, SRS or WBRT treatment plans were calculated for both MRIs, considering the gross target volume (GTV) as the contrast-enhancing aspects of the tumor. Mean GTVs and volume of healthy brain exposed to 12 Gy (V12), as well as Dice similarity coefficient scores, were obtained. The Spearman rank (ρ) correlation was additionally calculated for assessing linear differences. Three different expert radiation oncologists blindly rated the contrast enhancement for contouring purposes. Thirteen adult patients were included. Gadopiclenol depicted additional BM as compared with gadobenate dimeglumine in 7 patients (54%). Of a total of 63 identified metastatic lesions in both MRI sets, 3 subgroups could be defined: A, 48 (24 pairs) detected equal GTVs visible in both modalities; B, 13 GTVs only visible in the gadopiclenol set (mean ± SD, 0.16 ± 0.37 cm3); and C, 2 GTVs only visible in the gadobenate dimeglumine set (mean ± SD, 0.01 ± 0.01). Treatment indication was changed for 2 (15%) patients, 1 from no treatment to SRS and for 1 from SRS to WBRT. The mean GTVs and brain V12 were comparable between both agents (P = 0.694, P = 0.974). The mean Dice similarity coefficient was 0.70 ± 0.14 (ρ = 0.82). According to the readers, target volume definition was improved in 63.9% of cases (23 of 36 evaluations) with gadopiclenol and 22.2% with gadobenate dimeglumine (8 of 36), whereas equivalence was obtained in 13.9% (5 of 36). Gadopiclenol-enhanced MRI improved BM detection and characterization, with a direct impact on radiotherapy treatment decision between WBRT and SRS. Additionally, a more exact target delineation and planning could be performed with gadopiclenol. A prospective evaluation in a larger cohort of patients is required to confirm these findings.

Clinical Implementation and Dosimetric Evaluation of a Robust Proton Lattice Planning Strategy Using Primary and Robust Complementary Beams

Pencil-beam scanning proton therapy has been considered a potential modality for the 3D form of spatially fractionated radiation therapy called lattice therapy. However, few practical solutions have been introduced in the clinic. Existing limitations include degradation in plan quality and robustness when using single-field versus multifield lattice plans, respectively. We propose a practical and robust proton lattice (RPL) planning method using multifield and evaluate its dosimetric characteristics compared to clinically acceptable photon lattice plans. Seven cases previously treated with photon lattice therapy were used to evaluate a novel RPL planning technique using 2-orthogonal beams: a primary beam (PB) and a robust complementary beam (RCB) that deliver 67% and 33%, respectively, of the prescribed dose to vertices inside the gross target volume (GTV). Only RCB is robustly optimized for setup and range uncertainties. The number and volume of vertices, peak-to-valley dose ratios (PVDRs), and volume of low dose to GTV of proton and photon plans were compared. The RPL technique was then used in the treatment of 2 patients and their dosimetric parameters were reported. The RPL strategy was able to achieve the clinical planning goals. Compared to previously treated photon plans, the average number of vertices increased by 30%, the average vertex volume by 49% (18.2 ± 25.9 cc vs 12.2 ± 14.5 cc, P = .21), and higher PVDR (10.5 ± 4.8 vs 2.5 ± 0.9, P < .005) was achieved. In addition, RPL plans show more conformal dose with less low dose to GTV (V30%, 60.9% ± 7.2% vs 81.6% ± 13.9% and V10%, 88.3% ± 4.5% vs 98.6% ± 3.6% [P < .01]). The RPL plan for 2 treated patients showed PVDRs of 4.61 and 14.85 with vertices-to-GTV ratios of 1.52% and 1.30%, respectively. A novel RPL planning strategy using a pair of orthogonal beams was developed and successfully translated to the clinic. The proposed method can generate better quality plans, a higher number of vertices, and higher PVDRs than currently used photon lattice plans.

Impact of gadopiclenol on decision making in patients with brain metastases: A post-hoc study.

e14003 Background: Gadopiclenol (Elucirem, Guerbet, France) is a new high relaxivity macrocyclic gadolinium-based contrast agent (GBCA), recently approved by the FDA and EMA at the dose of 0.05 mmol/kg. The aim of this post-hoc analysis was to evaluate the impact of contrast-enhanced MRI with gadopiclenol at 0.1 mmol/kg on decision making and radiotherapy (RT) treatment planning of brain metastases (BM). Methods: This is a post-hoc analysis of data from a phase IIb study where patients underwent two separate MRI examinations, one with gadopiclenol at 0.025, 0.05, 0.1 or 0.2 mmol/kg and one with gadobenate dimeglumine at 0.1 mmol/kg. MR images of patients who received both GBCAs at 0.1 mmol/kg, with ≥1 BM detected in either of the scans, were subjected to a blinded reader analysis and contouring by two radiation oncology experts. For each patient, treatment plans (stereotactic radiosurgery [SRS] or whole-brain radiotherapy [WBRT]) were determined for both MRIs, with the gross target volume (GTV) indicating the contrast-enhancing aspects of the tumor. Mean GTVs and normal tissue volumes receiving 12 Gy (V12), as well as the Dice similarity coefficient (DSC) were obtained for the paired contours. The Spearman´s rank (ρ) correlation was additionally calculated. Furthermore, three experts blindly evaluated the contrast enhancement of each lesion for contouring purposes and subjectively qualified them as “better”, in detriment of the counterpart, or “equal”. Results: In total, images from 13 adult patients were analyzed. MRI with gadopiclenol depicted additional BM as compared with gadobenate dimeglumine in 7 patients (54%). The treatment plan was changed in 2 patients (15%), from no treatment to SRS and from SRS to WBRT. Gadopiclenol depicted additional BM in these 2 patients (from 0 and 10 BM with gadobenate dimeglumine to 1 and 15 BM with gadopiclenol). The mean GTVs and V12 were comparable between gadopiclenol and gadobenate dimeglumine (p=0.694, p=1.974). The mean DSC was 0.70 (SD: 0.14, ρ0.82). From a total of 36 answers, contrast enhancement was qualified as better with gadopiclenol in 21 (58.3%) evaluations, better with gadobenate dimeglumine in 8 (22.2%) evaluations, while no difference was observed in 7 (19.4%) evaluations. Conclusions: Gadopiclenol at 0.1 mmol/kg improved BM detection and contrast enhancement with potential impact on RT treatment decisions.

Advances in gross tumor target volume determination in radiotherapy for patients with hepatocellular carcinoma.

Hepatocellular Carcinoma (HCC) is one of the most common malignant neoplasms. With the advancement of technology, the precision of radiotherapy (RT) for HCC has considerably increased, and it is an indispensable modality in the comprehensive management of HCC. Some RT techniques increase the radiation dose to HCC, which decreases the radiation dose delivered to the surrounding normal liver tissue. This approach significantly improves the efficacy of HCC treatment and reduces the incidence of Radiation-induced Liver Disease (RILD). Clear imaging and precise determination of the Gross Target Volume (GTV) are prerequisites of precise RT of HCC. The main hindrances in determining the HCC GTV include indistinct tumor boundaries on imaging and the impact on respiratory motion. The integration of multimodal imaging, four-dimensional imaging, and artificial intelligence (AI) techniques can help overcome challenges for HCC GTV. In this article, the advancements in medical imaging and precise determination for HCC GTV have been reviewed, providing a framework for the precise RT of HCC.

A novel evaluation model of image registration for cone-beam computed tomography guided lung cancer radiotherapy.

The aim of the study was to establish a weighted comprehensive evaluation model (WCEM) of image registration for cone-beam computed tomography (CBCT) guided lung cancer radiotherapy that considers the geometric accuracy of gross target volume (GTV) and organs at risk (OARs), and assess the registration accuracy of different image registration methods to provide clinical references. The planning CT and CBCT images of 20 lung cancer patients were registered using diverse algorithms (bony and grayscale) and regions of interest (target, ipsilateral, and body). We compared the coverage ratio (CR) of the planning target volume (PTVCT) to GTVCBCT, as well as the dice similarity coefficient (DSC) of the GTV and OARs, considering the treatment position across various registration methods. Furthermore, we developed a mathematical model to assess registration results comprehensively. This model was evaluated and validated using CRFs across four automatic registration methods. The grayscale registration method, coupled with the registration of the ipsilateral structure, exhibited the highest level of automatic registration accuracy, the DSC were 0.87 ± 0.09 (GTV), 0.71 ± 0.09 (esophagus), 0.74 ± 0.09 (spinal cord), and 0.91 ± 0.05 (heart), respectively. Our proposed WCEM proved to be both practical and effective. The results clearly indicated that the grayscale registration method, when applied to the ipsilateral structure, achieved the highest CRF score. The average CRF scores, excellent rates, good rate and qualification rates were 58 ± 26, 40%, 75%, and 85%, respectively. This study successfully developed a clinically relevant weighted evaluation model for CBCT-guided lung cancer radiotherapy. Validation confirmed the grayscale method's optimal performance in ipsilateral structure registration.

Innovative approaches to enhance high-LETd tumor targeting in carbon ion radiotherapy

PurposeTo present novel approaches in particle therapy that could result in an improvement of patient outcome.MethodsTechnological/planning and biological innovations could bring particle therapy into a new area of precision medicine. However, several hurdles have to be overcome in order to transform these R&D opportunities into clinical advantages. In this contribution, we summarize the potential advantages of novel tumor targeting, through high-LETd boosting strategies with carbon ions, over standard IMPT: LETd-optimization for IMPT plan, IMPTLET, and spot-scanning hadron arc (SHArc) therapy. Two patient cases are presented to showcase the benefit: a pancreatic cancer patient (PATA) and a recurrent glioblastoma patient (PATB).ResultsFor both patients, the prescription dose and target/organs at risk (OARs) optimization goals were reached for the three techniques. In standard IMPT, the maximum LETd is placed outside of the target volume and extends into normal tissues. For the gross target volume (GTV), mean LETd values were, on average, around ∼40–60 keV/µm. IMPTLET allowed an increase in the GTV minimum LETd from 38.4 keV/µm to 48.6 keV/µm, and from 55.1 to 87.1 keV/µm, for PATA and PATB, respectively. SHArc led to an enhancement of the maximum LETd in the GTV up to at least 125 keV/µm, while the minimum GTV LETd were 47.2 keV/µm and 46.1 keV/µm, respectively. For PATA, SHArc lowers the maximum LETd in the gastrointestinal tract to 47.5 keV/µm compared to 88.0 keV/µm and 83.0 keV/µm found for the IMPT and IMPTLET plans, respectively.ConclusionsMany technological and biological innovations could enhance our current clinical approach. Following the current success of the IMPTLET introduction in clinic, SHARc will represent an interesting clinical option in carbon ion therapy.

Evaluating contouring accuracy and dosimetry impact of current MRI-guided adaptive radiation therapy for brain metastases: a retrospective study

BackgroundMagnetic resonance imaging (MRI) guided adaptive radiotherapy (MRgART) has gained increasing attention, showing clinical advantages over conventional radiotherapy. However, there are concerns regarding online target delineation and modification accuracy. In our study, we aimed to investigate the accuracy of brain metastases (BMs) contouring and its impact on dosimetry in 1.5 T MRI-guided online adaptive fractionated stereotactic radiotherapy (FSRT).MethodsEighteen patients with 64 BMs were retrospectively evaluated. Pre-treatment 3.0 T MRI scans (gadolinium contrast-enhanced T1w, T1c) and initial 1.5 T MR-Linac scans (non-enhanced online-T1, T2, and FLAIR) were used for gross target volume (GTV) contouring. Five radiation oncologists independently contoured GTVs on pre-treatment T1c and initial online-T1, T2, and FLAIR images. We assessed intra-observer and inter-observer variations and analysed the dosimetry impact through treatment planning based on GTVs generated by online MRI, simulating the current online adaptive radiotherapy practice.ResultsThe average Dice Similarity Coefficient (DSC) for inter-observer comparison were 0.79, 0.54, 0.59, and 0.64 for pre-treatment T1c, online-T1, T2, and FLAIR, respectively. Inter-observer variations were significantly smaller for the 3.0 T pre-treatment T1c than for the contrast-free online 1.5 T MR scans (P < 0.001). Compared to the T1c contours, the average DSC index of intra-observer contouring was 0.52‒0.55 for online MRIs. For BMs larger than 3 cm3, visible on all image sets, the average DSC indices were 0.69, 0.71 and 0.64 for online-T1, T2, and FLAIR, respectively, compared to the pre-treatment T1c contour. For BMs < 3 cm3, the average visibility rates were 22.3%, 41.3%, and 51.8% for online-T1, T2, and FLAIR, respectively. Simulated adaptive planning showed an average prescription dose coverage of 63.4‒66.9% when evaluated by ground truth planning target volumes (PTVs) generated on pre-treatment T1c, reducing it from over 99% coverage by PTVs generated on online MRIs.ConclusionsThe accuracy of online target contouring was unsatisfactory for the current MRI-guided online adaptive FSRT. Small lesions had poor visibility on 1.5 T non-contrast-enhanced MR-Linac images. Contour inaccuracies caused a one-third drop in prescription dose coverage for the target volume. Future studies should explore the feasibility of contrast agent administration during daily treatment in MRI-guided online adaptive FSRT procedures.

Comparison of different target volume delineation strategies based on recurrence patterns in adjuvant radiotherapy for glioblastoma.

Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) recommendations are commonly used guidelines for adjuvant radiotherapy in glioblastoma. In our institutional protocol, we delineate T2-FLAIR alterations as gross target volume (GTV) with reduced clinical target volume (CTV) margins. We aimed to present our oncologic outcomes and compare the recurrence patterns and planning parameters with EORTC and RTOG delineation strategies. Eighty-one patients who received CRT between 2014 and 2021 were evaluated retrospectively. EORTC and RTOG delineations performed on the simulation computed tomography and recurrence patterns and planning parameters were compared between delineation strategies. Statistical Package for the Social Sciences (SPSS) version 23.0 (IBM, Armonk, NY, USA) was utilized for statistical analyses. Median overall survival and progression-free survival were 21 months and 11 months, respectively. At a median 18 month follow-up, of the 48 patients for whom recurrence pattern analysis was performed, recurrence was encompassed by only our institutional protocol's CTV in 13 (27%) of them. For the remaining 35 (73%) patients, recurrence was encompassed by all separate CTVs. In addition to the 100% rate of in-field recurrence, the smallest CTV and lower OAR doses were obtained by our protocol. The current study provides promising results for including the T2-FLAIR alterations to the GTV with smaller CTV margins with impressive survival outcomes without any marginal recurrence. The fact that our protocol did not result in larger irradiated brain volume is further encouraging in terms of toxicity.

Chronomodulated chemotherapy for locoregionally advanced nasopharyngeal carcinoma: A phase II randomized controlled trial

ObjectiveTo validate the safety and efficacy of chronochemotherapy for locoregionally advanced nasopharyngeal carcinoma (NPC). MethodsParticipants for this phase II randomized controlled trial were recruited from the Department of Head and Neck Oncology at the Affiliated Cancer Hospital of Guizhou Medical University. Patients enrolled (128 in total, 112 in the final analysis) between April 1, 2017, and February 28, 2018, were randomly divided into the chronochemotherapy and conventional chemotherapy groups. In the chronochemotherapy group, docetaxel was intravenously administered between 3:30 a.m. and 4:30 a.m. on day 1, followed by intravenous administration of cisplatin between 10:00 a.m. and 10:00 p.m. from day 1to day 5. In addition, 5-fluorouracil was administered through a continuous intravenous pump between 10:00 p.m. and 10:00 a.m. (2nd day) from day 1 to day 5. In the conventional chemotherapy group, docetaxel (on day 1), cisplatin (on day 2), and 5-fluorouracil (from day 1 to day 5, 120 ​h in total) were administered without time-specific constraints. Both groups underwent intensity-modulated radiation therapy with 6-MV X-rays. The gross target volume (GTV) comprised the nasopharyngeal GTV and cervical lymph node GTV. The primary endpoint was immune function, quantified by measuring dendritic cell and lymphocyte subsets, whereas the secondary endpoints were therapeutic efficacy and incidence of adverse events. Pearson Chi-square test was applied to compare total events between the groups, Mann-Whitney U test was used to compare the DC subsets and toxicities, and Wilcoxon signed-rank test ​was used to compare the continuous variables between the two groups. ResultsChronochemotherapy preserved immune function, as evidenced by elevated levels of myeloid dendritic cells (P ​= ​0.394) and higher CD4/CD8 ratio (P ​= ​0.781). No significant difference in overall response rate, measured as the sum of complete and partial response rates, was observed between the groups (P ​= ​0.711). A reduction in the incidence of vomiting (P ​= ​0.002), stomatitis (P ​= ​0.028), and mucositis (P ​= ​0.028) was observed in the chronochemotherapy group. Leukopenia incidence rate was 83.3 ​% and 92.3 ​% in the chronochemotherapy and conventional chemotherapy groups, respectively (P ​= ​0.232). ConclusionsIn patients with locoregionally advanced NPC, the overall response rate of chronochemotherapy is comparable to that of conventional chemotherapy; however, chronochemotherapy shows fewer adverse events.

Rethinking automatic segmentation of gross target volume from a decoupling perspective

Accurate and reliable segmentation of Gross Target Volume (GTV) is critical in cancer Radiation Therapy (RT) planning, but manual delineation is time-consuming and subject to inter-observer variations. Recently, deep learning methods have achieved remarkable success in medical image segmentation. However, due to the low image contrast and extreme pixel imbalance between GTV and adjacent tissues, most existing methods usually obtained limited performance on automatic GTV segmentation. In this paper, we propose a Heterogeneous Cascade Framework (HCF) from a decoupling perspective, which decomposes the GTV segmentation into independent recognition and segmentation subtasks. The former aims to screen out the abnormal slices containing GTV, while the latter performs pixel-wise segmentation of these slices. With the decoupled two-stage framework, we can efficiently filter normal slices to reduce false positives. To further improve the segmentation performance, we design a multi-level Spatial Alignment Network (SANet) based on the feature pyramid structure, which introduces a spatial alignment module into the decoder to compensate for the information loss caused by downsampling. Moreover, we propose a Combined Regularization (CR) loss and Balance-Sampling Strategy (BSS) to alleviate the pixel imbalance problem and improve network convergence. Extensive experiments on two public datasets of StructSeg2019 challenge demonstrate that our method outperforms state-of-the-art methods, especially with significant advantages in reducing false positives and accurately segmenting small objects. The code is available at https://github.com/shijun18/GTV_AutoSeg.

Impact of clinical target volume margin reduction in glioblastoma patients treated with concurrent chemoradiation.

Glioblastoma (GBM) is widely treated using large radiotherapy margins, resulting in substantial irradiation of the surrounding cerebral structures. In this context, the question arises whether these margins could be safely reduced. In 2018, clinical target volume (CTV) expansion was reduced in our institution from 20 to 15 mm around the gross target volume (GTV) (ie, the contrast-enhancing tumor/cavity). We sought to retrospectively analyze the impact of this reduction. All adult patients with GBM treated between January 2015 and December 2020 with concurrent chemoradiation (60Gy/2Gy or 59.4Gy/1.8Gy) were analyzed. Patients treated using a 20 (CTV20, n = 57) or 15 mm (CTV15, n = 56) CTV margin were compared for target volumes, dose parameters to the surrounding organs, pattern of recurrence, and survival outcome. Mean GTV was similar in both groups (ie, CTV20: 39.7cm3; CTV15: 37.8cm3; P = .71). Mean CTV and PTV were reduced from 238.9cm3 to 176.7cm3 (P = .001) and from 292.6cm3 to 217.0cm3 (P < .001), for CTV20 and CTV15, respectively. As a result, average brain mean dose (Dmean) was reduced from 25.2Gy to 21.0Gy (P = .002). Significantly lower values were also observed for left hippocampus Dmean, brainstem D0.03cc, cochleas Dmean, and pituitary Dmean. Pattern of recurrence was similar, as well as patient outcome, ie, median progression-free survival was 8.0 and 7.0 months (P = .80), and median overall survival was 11.0 and 14.0 months (P = .61) for CTV20 and CTV15, respectively. In GBM patients treated with chemoradiation, reducing the CTV margin from 20 to 15 mm appears to be safe and offers the potential for less treatment toxicity.

Development and Validation of a Deep Learning-Based Auto-Delineation of Target Volume and Organs at Risk in Pancreatic Cancer Radiotherapy.

The delineation of the clinical target volume (CTV), gross target volume (GTV) and organs at risk (OARs) is a crucial and laborious in pancreatic cancer radiotherapy. In this work, we propose and evaluate a three-dimensional (3D) novel convolutional neural network (CNN) for automatic and accurate CTV, GTV and OARs in pancreatic cancer. A total of 120 computed tomography (CT) scans patients with pancreatic cancer were collected. A novel 3D CNN network, called ResUNet3D, was developed to achieve auto-delineation. 96 patients chosen randomly were used for training, 12 patients for validation, and 12 patients for testing. Meanwhile, the Dice similarity coefficient (DSC) and 95th percentile Hausdorff distance (HD95%) were used to assess the performance. The DSC values for the test data were 80.9±8.6%, 77.5±5.6%, 94.5±1.3%, 66.2±13.4%, 73.6±7.6%, 79.0±8.7%, 94.1±1.9%, 94.6±1.4%, 87.3±5.8% for CTV, GTV, liver, duodenum, spinal cord, bowel, kidney left, kidney right, stomach. The corresponding HD95% values were 10.7±6.9mm, 7.8±5.7mm, 11.6±5.6mm, 18.6±5.6mm, 2.7±0.7mm, 17.7±8.6mm, 3.9±1.4mm, 3.7±1.9mm, 13.4±5.7mm, respectively. The average delineation time for one patient's CT images was within 5 seconds. The experimental results demonstrate that the CTV, GTV and OARs delineated for pancreatic cancer by ResUNet3D achieved a close agreement with the ground truth. ResUNet3D could significantly reduce the radiation oncologists' contouring time.

Objective Boundary Generation for Gross Target Volume and Organs at Risk Using 3D Multi-Modal Medical Images.

Accurate delineation of Gross Target Volume (GTV) and Organs at Risk (OARs) in medical images is an essential but challenging step in radiotherapy. Deep-learning based automated delineation methods, which learn from manual annotations, are currently prevalent in academic research. However, the limited resolution of medical images and the fuzzy boundaries of lesions and organs present a challenge to the precision of manual annotations. By leveraging the complementary information from multi-modal medical images, this study proposed a novel method to generate objective boundaries of GTV and OARs. We present a novel method of objective boundary generation, inspired by image matting primarily used for 2D RGB natural images, to process 3D grayscale medical images. The proposed method has the following advantages. 1) It allows for flexible input modalities and assigns weights to each modality according to their relative significance when computing information flows in the matting algorithm. 2) It computes 3D spatial information flow among voxels, which has more advantages over its 2D counterpart. 3) It has a closed-form solution that generates deterministic results. To evaluate the characteristics of the generated boundaries, patients with stage I nasopharyngeal carcinoma (NPC) were studied, with CT images and multi-modal MR images (T1, T1C, T2) aligned using deformable registration. Region of Interests (ROIs), i.e., GTV and parotid gland, were used, with a rough trimap marking extremely few foreground voxels, many background voxels, and a large unknown region. The proposed algorithm leverages the connection between each voxel and its nearest neighbors in the feature space, to propagate the opacity information. We evaluated the results by employing both qualitative and quantitative methods. Using qualitative evaluation, experienced clinicians confirmed that the results were in agreement with the input data, especially for areas where borders were visible in most modalities (e.g., between air and tumor). For more challenging regions, where boundaries were unclear in the images, the results displayed fine-grained opacity transitions indicating the confidence of each voxel belonging to the ROI. When compared to the delineations made by clinicians, we found our results are usually more compact. We define a precision metric that evaluates the ratio of the matted foreground inside clinicians' delineations versus the entire matted foreground. Using a threshold of 0.4, our binarized result scored 0.95 for GTV and 0.92 for parotid gland. The proposed method demonstrated satisfactory results on challenging ROIs. The objective boundaries generated by this method have advantages in many aspects, including improvement of delineation protocols, enhancement of manual annotation consistency, and increase of deep-learning based automated delineation accuracy.

Treatment Outcomes and Toxicity Profile of MRI-Guided Gated-Real Time Online Adaptive Stereotactic Body Radiotherapy to Patients with Pancreatic Tumors

Stereotactic body radiation therapy (SBRT) to patients with inoperable pancreas cancer has shown promising outcomes. Dose escalation is challenging given the associated risks to nearby organs at risk and requires treatment plan adaptation and motion management. This study reports the treatment related adverse events and treatment outcomes of MRI-guided SBRT utilizing gated-real time online adaptive radiotherapy to patients with pancreatic tumors. This is a single institution retrospective IRB approved study and included patients with pancreatic tumors who were treated with MRI-guided SBRT utilizing gated-real time online adaptive radiotherapy, consecutively between 2019 and 2022. All patients were treated with 0.35T MRI linear accelerator. All patients' charts and radiation plans were reviewed for this study. The study included 25 patients treated consecutively to 125 radiation fractions with MRI-guided SBRT. The study included 15 females and 10 males, 19 white, 2 Asians, 1 Latin American and 2 African Americans. The median age was 74, and all patients had pancreatic adenocarcinoma (92%) except two patients who had biopsy proven renal cell carcinoma metastatic to the pancreas without evidence of disease elsewhere. Most patients (68%) received chemotherapy (FOLFIRINOX or Gemcitabine / Protein-bound paclitaxel) prior to SBRT. The median dose to gross target volume (GTV) was 50 Gy, and to planning target volume (PTV) was 35 Gy. All patients were treated in 5 radiation fractions. Thirteen patients (52%) received elective nodal irradiation (ENI). All patients had at least a single real-time online adaptive replanning (median 3 fractions, range 1-5 fractions). All treatment fractions were gated (100%) with MRI guidance. The 1-, 2-, & 3- year local-regional control (LRC) were 81%, 57%, & 57% respectively (Median 16 months). The 1-, 2-, & 3- year Distant Control (DC) were 81%, 74%, & 56% respectively (Median 14 months). The 1-, 2-, 3-year overall survival (OS) were 77%, 35%, & 24% (Median 21 months). Planning Target Volume (PTV) dose ≥40Gy was significantly associated with improved local-regional control (p = 0.02). Gross Target Volume (GTV) dose <50Gy was significantly associated with lower DC (p = 0.03). ENI showed a trend towards improved local-regional control but was not statistically significant (p = 0.1). None of the patients experienced ≥ grade 3 toxicities. Most common adverse event were grades 1 or 2 fatigue (24%), nausea (16%), and abdominal discomfort (12%). In this cohort, MRI-guided SBRT utilizing gated-real time online adaptive radiotherapy was a safe and effective approach for patients with pancreatic tumors who are not surgical candidates. In this study, dose escalation was significantly associated with improved local-regional (PTV ≥40 Gy) and distant control (GTV ≥50Gy). None of the patients experienced grade ≥3 radiation induced adverse events.

Toward Global Consensus for MR-Guided Treatment Planning for Pancreatic Tumors on a 1.5 T MR-Linac

MR-guided SBRT with a 1.5 T MR-Linac is a relatively new therapy for pancreatic tumors with varying expertise levels. Moreover, treatment planning in the upper abdomen can be challenging as target coverage is often compromised by dosimetric constraints of abutting bowel structures. This may lead to large differences between centers in protocols, practices. To increase harmonization a worldwide consortium was founded among 1.5 T MR-Linac users. In this work we report on the outcome of the first phase within this collaboration, which is the assessment of the baseline variation between the treatment planning protocols and subsequent dose distributions. Twelve centers across three continents (North America, Europe, and Australia) participated in this consortium. Each center was sent the same two anonymized data sets reflecting two cases of locally advanced pancreatic cancer of different complexity levels. The data sets included a CT scan, a predefined structure set containing the gross target volume (GTV) and the OARs, a brief medical history, tumor motion characteristics, and auxiliary CT and MR imaging. Centers were asked to create an MRgRT treatment plan according to their clinical five-fraction SBRT protocol, using their institutional margin structures, beam setup, target prescriptions, and OAR constraints. Key DVH parameters that were evaluated are D99%, D90%, D50%, D1% for the GTV and D0.5cc for the duodenum, small bowel, and stomach. In general, large variations were observed in planning objectives and machine settings yielding widely varying inhomogeneous dose distributions to both the tumor and organs at risk (Table 1). This was especially manifest for case 2 where the tumor abutted with both the duodenum and small bowel over a trajectory of multiple centimeters. Not only were different trade-offs between target coverage and OAR sparing observed, but also different strategies for optimizing the integral dose to the tumor. These results indicate a large variety in the treatment planning strategies that could well translate to differences in outcome. Based on this first evaluation, the consortium will work towards a collective consensus protocol with a second evaluation round after internal discussions.

P03.14.A DUMMY RUN QUALITY ASSURANCE STUDY IN THE ONGOING PHASE 3 RANDOMIZED PRO-GLIO TRIAL

Abstract BACKGROUND PRO-GLIO is an ongoing multicenter phase 3 randomized controlled trial in Norway and Sweden. In this trial, 224 adult patients with isocitrate dehydrogenase (IDH) -mutated diffuse gliomas grade 2-3, astrocytomas and oligodendrogliomas are randomized 1:1 between proton and photon radiotherapy. Study inclusion commenced in Oslo University Hospital (OUH) in January 2022, with other study-centers following. A number of outcomes will be assessed, including several survival, quality of life, and cognition parameters. For patients with diffuse gliomas delineation of target volumes when planning radiotherapy may be inherently difficult, not least due to the diffuse infiltrative growth pattern. There are also interobserver variability in delineation of organs at risk (OAR) and treatment planning. These factors may influence the planned and delivered treatment and thereby potentially affect clinical outcome. As part of the PRO-GLIO trial, all participating study-centers must undergo a qualifying radiotherapy dummy run procedure prior to initiation of patient inclusion to minimize the variations of these factors and to ensure protocol adherence. MATERIAL AND METHODS In the dummy run procedure, all centers delineate target volumes and OAR on a given case, and thereafter perform dose planning based on a consensus structure set for the same case. Swedish centers prepare photon and proton therapy plans, whereas Norwegian centers prepare photon plans only. Delineations are evaluated based on pre-defined quantitative and qualitative parameters. For all volumes - gross target volume (GTV), clinical target volume (CTV), and OARs - a Dice similarity coefficient (DSC) is calculated. RESULTS References values were made from consensus delineations among five radiation oncologists from OUH and Sahlgrenska University Hospital. For each of the target volumes and OARs, the DSC was cross calculated for the five experts, and the lowest value was used as a reference during the evaluation of submitted contours. Initial analysis has been performed based on data from the 6 centers which have completed the procedure. Mean DSC for GTV is 0.78, for CTV 0.87, for optic chiasm 0.42, for brain stem surface 0.92, and for right and left hippocampus 0.61 and 0.59, respectively. An inherent weakness of the DSC is that it is sensitive to the volume of the organ. This is seen in our data with the highest value for the largest volume (CTV) and a lower value for the optic chiasm. Thus, a qualitative evaluation was also performed. All submitted contours were approved. CONCLUSION The dummy run procedure revealed differences in OAR and target volume definition between centers and experts. Nonetheless, a DSC of 0.87 for CTV is re-assuring and prove a high coherence between participating centers. A dummy run procedure seems to be a valuable tool to ensure protocol adherence and draw attention to OAR and target volume delineation.

Feasibility of quantitative diffusion-weighted imaging during intra-procedural MRI-guided brachytherapy of locally advanced cervical and vaginal cancers

PurposeTo determine the feasibility of quantitative apparent diffusion coefficient (ADC) acquisition during magnetic resonance imaging-guided brachytherapy (MRgBT) using reduced field-of-view (rFOV) diffusion-weighted imaging (DWI). Methods and MaterialsT2-weighted (T2w) MR and full-FOV single-shot echo planar (ssEPI) DWI were acquired in 7 patients with cervical or vaginal malignancy at baseline and prior to brachytherapy, while rFOV-DWI was acquired during MRgBT following brachytherapy applicator placement. The gross target volume (GTV) was contoured on the T2w images and registered to the ADC map. Voxels at the GTV's maximum Maurer distance comprised a central sub-volume (GTVcenter). Contour ADC mean and standard deviation were compared between timepoints using repeated measures ANOVA. ResultsssEPI-DWI mean ADC increased between baseline and prebrachytherapy from 1.03 ± 0.18 10−3 mm2/s to 1.34 ± 0.28 10−3 mm2/s for the GTV (p = 0.06) and from 0.84 ± 0.13 10−3 mm2/s to 1.26 ± 0.25 10−3 mm2/s at the level of the GTVcenter (p = 0.03), consistent with early treatment response. rFOV-DWI during MRgBT demonstrated mean ADC values of 1.28 ± 0.14 10−3 mm2/s and 1.28 ± 0.19 10−3 mm2/s for the GTV and GTVcenter, respectively (p = 0.02 and p = 0.03 relative to baseline). No significant differences were observed between ssEPI-DWI and rFOV-DWI ADC measurements. ConclusionsQuantitative ADC measurement in the setting of MRI guided brachytherapy implant placement for cervical and vaginal cancers is feasible using rFOV-DWI, with comparable mean ADC comparable to prebrachytherapy ssEPI-DWI, and may enable MRI-guided radiotherapy targeting of low ADC, radiation resistant sub-volumes of tumor.