High-risk Clinical Target Volume Research Articles

External beam radiotherapy followed by image-guided adaptive brachytherapy in locally advanced cervical cancer: a multicenter retrospective analysis.

To evaluate oncological outcomes and toxicities in patients with locally advanced cervical cancer (LACC) treated with concurrent chemoradiotherapy followed by image-guided adaptive brachytherapy at two Italian centres. A retrospective analysis was conducted on 122 patients with LACC treated between 2010 and 2022. Primary endpoints were local control (LC), pelvic control (PC), and nodal control (NC). Secondary endpoints included disease-free survival (DFS), metastasis-free survival (MFS), overall survival (OS), and late toxicity. Correlations between patient characteristics and oncological outcomes were conducted. Brachytherapy planning was CT and MRI-based in 88 (72.1%) and 34 patients (27.9%), respectively. The mean total dose (EQD2) delivered to high-risk clinical target volume was 82Gy. Overall treatment time was ≤ 50days and > 50days in 48 (39.3%) and 74 patients (60.7%), respectively. At a mean follow up of 101months, 3 and 5-year LC rates were 87% and 85%, respectively. Five-year PC and NC rates were 77% and 85.1%. Five-year DFS and OS were 61% and 65.4%, respectively, with significant correlations between these outcomes and FIGO stage and nodal status at diagnosis. Gastrointestinal, genitourinary and vaginal adverse effects were the most reported late toxicities and 8 (6.5%) grade 3-5 events were observed. 32 patients (26.2%) had vaginal stenosis and it was significantly related to 3D imaging used for brachytherapy planning. The study confirmed the efficacy and safety of chemoradiotherapy and IGABT for LACC. Full implementation of MRI treatment planning and interstitial techniques could further enhance personalized treatment and outcomes.

Dual convolution-transformer UNet (DCT-UNet) for organs at risk and clinical target volume segmentation in MRI for cervical cancer brachytherapy

Objective. MRI is the standard imaging modality for high-dose-rate brachytherapy of cervical cancer. Precise contouring of organs at risk (OARs) and high-risk clinical target volume (HR-CTV) from MRI is a crucial step for radiotherapy planning and treatment. However, conventional manual contouring has limitations in terms of accuracy as well as procedural time. To overcome these, we propose a deep learning approach to automatically segment OARs (bladder, rectum, and sigmoid colon) and HR-CTV from female pelvic MRI.Approach. In the proposed pipeline, a coarse multi-organ segmentation model first segments all structures, from which a region of interest is computed for each structure. Then, each organ is segmented using an organ-specific fine segmentation model separately trained for each organ. To account for variable sizes of HR-CTV, a size-adaptive multi-model approach was employed. For coarse and fine segmentations, we designed a dual convolution-transformer UNet (DCT-UNet) which uses dual-path encoder consisting of convolution and transformer blocks. To evaluate our model, OAR segmentations were compared to the clinical contours drawn by the attending radiation oncologist. For HR-CTV, four sets of contours (clinical + three additional sets) were obtained to produce a consensus ground truth as well as for inter/intra-observer variability analysis.Main results. DCT-UNet achieved dice similarity coefficient (mean ± SD) of 0.932 ± 0.032 (bladder), 0.786 ± 0.090 (rectum), 0.663 ± 0.180 (sigmoid colon), and 0.741 ± 0.076 (HR-CTV), outperforming other state-of-the-art models. Notably, the size-adaptive multi-model significantly improved HR-CTV segmentation compared to a single-model. Furthermore, significant inter/intra-observer variability was observed, and our model showed comparable performance to all observers. Computation time for the entire pipeline per subject was 12.59 ± 0.79 s, which is significantly shorter than the typical manual contouring time of >15 min.Significance. These experimental results demonstrate that our model has great utility in cervical cancer brachytherapy by enabling fast and accurate automatic segmentation, and has potential in improving consistency in contouring. DCT-UNet source code is available athttps://github.com/JHU-MICA/DCT-UNet.

Retrospective Evaluation of GEC-ESTRO Constraints for Definitive Radiochemotherapy with Brachytherapy and Correlation with Oncologic Outcome in Cervical Cancer: A Monocenter Study.

This study aims to evaluate patients with locally advanced cervical cancer who underwent definitive radiochemotherapy, including brachytherapy, at the University Hospital of Muenster (UKM), focusing on target volume coverage, oncologic outcome parameters, and organs at risk (OAR) toxicities. Results are compared with the Gyn GEC-ESTRO (GGE) recommendations. Of a cohort of 48 patients, treated between 2013 and 2023, the physical radiation treatment planning with application of CT and MRI and oncologic follow-up data was analyzed. Target volume structures, comprising the high-risk clinical target volume (HR-CTV), intermediate-risk clinical target volume (IR-CTV), Point A, and corresponding EQD2(α/β=10) doses were determined. Endpoints included local tumor control, overall survival (OS), recurrence-free survival (RFS), and progression-free survival (PFS). Total OAR (D2cc) EQD2(α/β=3) doses were correlated with adverse events defined by CTCAE v5.0 and LENT-SOMA criteria. Median follow-up was 58.0 months (95% CI [27.6, 88.4]). FIGO stage I was present in 7 (15%) patients, II in 13 (27%), and III in 28 (58%) patients. A total of 38 (79%) patients showed a complete remission 3 months after treatment. The 5-year event-free rate was 67.4% (95% CI [49.3, 80.3]) for OS, 77.0% (95% CI [56.7, 88.6]) for RFS and 68.1% (95% CI [49.7, 80.9]) for PFS. Incomplete radiation treatment and advanced tumor stages led to worse outcomes. Meeting Point A GGE recommendations increased chances for complete remission and could decrease chances of an event occurring for OS, PFS, and RFS. Compliance with GGE recommendations lowered the chances of OAR toxicity occurring. MRI-based target volume definition for brachytherapy in cervical cancer may improve patients' OS, PFS, and RFS. Time-to-event endpoints are consistent with comparable studies, and adherence to current ESGO/ESTRO/ESP guidelines is endorsed.

Retrospective assessment of HDR brachytherapy dose calculation methods in locally advanced cervical cancer patients: AcurosBV vs. AAPM TG43 formalism.

This retrospective analysis was completed to investigate the use of a model-based dose calculation algorithm (MBDCA) AcurosBV, for use in HDR BT treatments for locally advanced cervical cancer treated with tandem and ovoid applicators with interstitial needles. A cohort of 32 patients receiving post-EBRT HDR brachytherapy boost with a prescription dose of 5.5Gy × 5 fractions to the high-risk clinical target volume (CTVHR) were selected for this study. For standard TG43 dose calculation, applicators were manually digitized on the planning images, while for AcurosBV calculations, solid renderings of Titanium Fletcher Suite Delclos (FSD) applicators included in BrachyVision were matched to those used clinically and Ti needles were manually digitized. The dose was recalculated using Varian's AcurosBV 13.5 and dose-to-medium-in-medium (Dm,m) was reported. EQD2 values for targets and organs at risk were compared between dose calculation formalisms. D90% and D98% values were reported for the high and intermediate-risk CTVs, and values were reported for OARs including bladder, rectum, sigmoid, bowel, and vagina. Due to variability within the patient cohort, the dosimetric impact of AcurosBV was investigated corresponding to planning image modality (CT vs. CBCT), presence of Ti needles, and contrast within vaginal balloons used to stabilize implants. AcurosBV showed lower dosimetric values for all plans compared to TG43. The average±standard deviation of dosimetric reduction in D90% was 4.33±0.09% for CTVHR and 4.12±0.09% for CTVIR. The reduction to OARs was: 4.99±0.15% for bladder, 7.87±0.16% for rectum, 5.79±0.17% for sigmoid, 6.91±0.14% for bowel, and 4.55±0.14% for vagina. AcurosBV should be utilized for HDR BT GYN cases, treated with tandem and ovoid applicators, with high degrees of heterogeneity and calculated in tandem with TG43.

Deep learning-based segmentation for high-dose-rate brachytherapy in cervical cancer using 3D Prompt-ResUNet

Objective.To develop and evaluate a 3D Prompt-ResUNet module that utilized the prompt-based model combined with 3D nnUNet for rapid and consistent autosegmentation of high-risk clinical target volume (HRCTV) and organ at risk (OAR) in high-dose-rate brachytherapy for cervical cancer patients.Approach.We used 73 computed tomography scans and 62 magnetic resonance imaging scans from 135 (103 for training, 16 for validation, and 16 for testing) cervical cancer patients across two hospitals for HRCTV and OAR segmentation. A novel comparison of the deep learning neural networks 3D Prompt-ResUNet, nnUNet, and segment anything model-Med3D was applied for the segmentation. Evaluation was conducted in two parts: geometric and clinical assessments. Quantitative metrics included the Dice similarity coefficient (DSC), 95th percentile Hausdorff distance (HD95%), Jaccard index (JI), and Matthews correlation coefficient (MCC). Clinical evaluation involved interobserver comparison, 4-grade expert scoring, and a double-blinded Turing test.Main results.The Prompt-ResUNet model performed most similarly to experienced radiation oncologists, outperforming less experienced ones. During testing, the DSC, HD95% (mm), JI, and MCC value (mean ± SD) for HRCTV were 0.92 ± 0.03, 2.91 ± 0.69, 0.85 ± 0.04, and 0.92 ± 0.02, respectively. For the bladder, these values were 0.93 ± 0.05, 3.07 ± 1.05, 0.87 ± 0.08, and 0.93 ± 0.05, respectively. For the rectum, they were 0.87 ± 0.03, 3.54 ± 1.46, 0.78 ± 0.05, and 0.87 ± 0.03, respectively. For the sigmoid, they were 0.76 ± 0.11, 7.54 ± 5.54, 0.63 ± 0.14, and 0.78 ± 0.09, respectively. The Prompt-ResUNet achieved a clinical viability score of at least 2 in all evaluation cases (100%) for both HRCTV and bladder and exceeded the 30% positive rate benchmark for all evaluated structures in the Turing test.Significance.The Prompt-ResUNet architecture demonstrated high consistency with ground truth in autosegmentation of HRCTV and OARs, reducing interobserver variability and shortening treatment times.

Individual curved-needle interstitial template created using three-dimensional printing for brachytherapy for distal parauterine tumor recurrence.

Achieving a clinically acceptable dose distribution with commercial vaginal applicators for brachytherapy of recurrent parauterine tumors is challenging. However, the application of three-dimensional (3D) printing technology in brachytherapy has been widely acknowledged and can improve clinical treatment outcomes. This study aimed to introduce an individual curved-needle interstitial template (ICIT) created using 3D printing technology for high-dose-rate (HDR) brachytherapy with interstitial treatment to provide a clinically feasible approach to distal parauterine and vaginal cuff tumors. The entire workflow, including the design, optimization, and application, is presented. Ten patients with pelvic cancer recurrence were examined at our center. The vaginal topography was filled with gauze strips soaked in developer solution, and images were obtained using computed tomography (CT) and magnetic resonance imaging (MRI). Curved needle paths were designed, and ICITs were 3D-printed according to the high-risk clinical target volume (HRCTV) and vaginal filling model. The dose and volume histogram parameters of the HRCTV (V100, V200, D90, and D98) and organs at risk (OARs) (D2cc) were recorded. All patients completed interstitial brachytherapy treatment with the 3D-printed ICIT. One patient experienced vaginal cuff tumor recurrence, and nine patients experienced parametrial tumor recurrence (four on the left and five on the right). We used two to five interstitial needles, and the maximum angle of the curved needle was 40°. No source obstruction events occurred during treatment of these 10 patients. The doses delivered to the targets and OARs of all patients were within the dose limits and based on clinical experience at our center. The ICIT is a treatment option for patients with distal parauterine tumor recurrence. This method addresses the limitations of vaginal intracavitary and standard interstitial applicators. The ICIT has the advantages of biocompatibility, personalization, and magnetic resonance imaging compatibility.

Potential anatomical triggers for plan adaptation of cervical cancer external beam radiotherapy.

This study aimed to identify potential anatomical variation triggers using magnetic resonance imaging for plan adaption of cervical cancer patients to ensure dose requirements were met over an external beam radiotherapy course. Magnetic resonance images (MRIs) acquired before and during treatment were rigidly registered to a pre-treatment computerised tomography (CT) image for 11 retrospective cervix cancer datasets. Target volumes (TVs) and organs at risk (OARs) were delineated on both MRIs and propagated onto the CT. Treatment plans were generated based on the pre-treatment contours and applied to the mid-treatment contours. Anatomical and dosimetric changes between each timepoint were assessed. The anatomical changes included the change in centroid position and volume size. Dosimetric changes included the V30Gy and V40Gy for the OARs, and V95%, V100%, D95% and D98% for the TVs. Correlation with dosimetric and anatomical changes were assessed to determine potential replan triggers. Changes in the bowel volume and position in the superior-inferior direction, and the high-risk CTV anterior posterior position were highly correlated with a change in dose to the bowel and target, respectively. Hence changes in bowel and high-risk CTV could be used as a potential replan triggers.

Inversion-recovery ultrashort-echo-time (IR-UTE) MRI-based detection of radiation dose heterogeneity in gynecologic cancer patients treated with HDR brachytherapy

PurposeTo evaluate the relationship between delivered radiation (RT) and post-RT inversion-recovery ultrashort-echo-time (IR-UTE) MRI signal-intensity (SI) in gynecologic cancer patients treated with high-dose-rate (HDR) brachytherapy (BT).MethodsSeven patients underwent whole-pelvis RT (WPRT) followed by BT to the high-risk clinical target volume (HR-CTV). MR images were acquired at three time-points; pre-RT, post-WPRT/pre-BT, and 3–6 months post-BT. Diffuse-fibrosis (FDiffuse) was imaged with a non-contrast dual-echo IR (inversion time [TI] = 60 ms) UTE research application, with image-subtraction of the later echo, only retaining the ultrashort-echo SI. Dense-fibrosis (FDense) imaging utilized single-echo Late-Gadolinium-Enhanced IR-UTE, acquired ∼ 15 min post-Gadavist injection. Resulting FDiffuse and FDense SI were normalized to the corresponding gluteal-muscle SI. Images were deformably registered between time-points based on normal tissue anatomy. The remnant tumor at both time-points was segmented using multi-parametric MRI. Contours corresponding to the 50%, 100%, 150%, and 200% isodose lines (IDLs) of the prescription BT-dose were created. Mean FDiffuse and FDense SI within (i) each IDL contour and (ii) the remnant tumor were calculated. Post-BT FDiffuse and FDense SI were correlated with prescribed BT-dose. To determine the relationship between BT-dose and IR-UTE SI, the differences in the post-BT FDense across IDLs was determined using paired t-tests with Bonferroni correction.ResultsFDense was higher in regions of higher dose for 6/7 patients, with mean ± SD values of 357 ± 103% and 331 ± 97% (p = .03) in the 100% and 50% IDL, respectively. FDense was higher in regions of higher dose in the responsive regions with mean ± SD values of 380 ± 122% and 356 ± 135% (p = .03) in the 150% and 50% IDL, respectively. Within the segmented remnant tumor, an increase in prescribed dose correlated with an increase in FDense post-BT (n = 5, r = .89, p = .04). Post-BT FDiffuse inversely correlated (n = 7, r = -.83, p = .02) with prescribed BT-dose within the 100% IDL.ConclusionsResults suggest that FDense SI 3–6 months post-BT is a sensitive measure of tissue response to heterogeneous BT radiation-dose. Future studies will validate whether FDiffuse and FDense are accurate biomarkers of fibrotic radiation response.

Comparison of 3D-printed multichannel non–co-planar vaginal applicators and single-channel vaginal applicators for brachytherapy with positive or close surgical margins in cervical cancer

OBJECTIVEThis study was conducted to compare the differences between 3D-printed multichannel non-coplanar vaginal applicators and single-channel vaginal applicators in cervical cancer patients with positive or close surgical margins. METHODSBetween January 2015 and June 2023, 104 cervical cancer patients who underwent radical surgery with positive or close surgical margins were enrolled to receive concurrent intensity-modulated chemoradiotherapy combined with 3D-printed multichannel non-coplanar vaginal applicators (3D-printed group, 41 patients) or single-channel vaginal applicators (single-channel group, 63 patients) guided brachytherapy. The dosimetric parameters, 5-year local control (LC), progression-free survival (PFS), overall survival (OS) of two groups were retrospectively analyzed. RESULTSThe high-risk clinical target volume (D90, D100) and high-dose volume fraction (V150) in 3D-printed group were significantly higher than those in single-channel group (p<0.05), and the homogeneity index (HI) and conformal index (COIN) were equally better in 3D-printed group. In 3D-printed group, the D2cc, D1cc, and D0.1cc of the bladder and rectum were significantly lower than those of the single-channel group (p<0.05). The 3D-printed group had significantly superior 5-year LC (70.0% vs. 51.3%, P=0.041) and PFS (63.0% vs. 44.2%, P=0.045), but OS were not significantly different between treatment groups (75.4% vs. 59.7%, P=0.112). The incidence of radiation enteritis and cystitis was lower in the 3D-printed group than in the single-channel group, but no statistical difference was noted. CONCLUSIONSThe 3D-printed multichannel non-coplanar vaginal insertion applicators shows the advantage of target dose, improve the LC and PFS in patients with positive or close surgical margins after cervical cancer surgery. Thus, the popularization of this method and its application may be of value.

Neural network dose prediction for cervical brachytherapy: Overcoming data scarcity for applicator-specific models.

3D neural network dose predictions are useful for automating brachytherapy (BT) treatment planning for cervical cancer. Cervical BT can be delivered with numerous applicators, which necessitates developing models that generalize to multiple applicator types. The variability and scarcity of data for any given applicator type poses challenges for deep learning. The goal of this work was to compare three methods of neural network training-a single model trained on all applicator data, fine-tuning the combined model to each applicator, and individual (IDV) applicator models-to determine the optimal method for dose prediction. Models were produced for four applicator types-tandem-and-ovoid (T&O), T&O with 1-7 needles (T&ON), tandem-and-ring (T&R) and T&R with 1-4 needles (T&RN). First, the combined model was trained on 859 treatment plans from 266 cervical cancer patients treated from 2010 onwards. The train/validation/test split was 70%/16%/14%, with approximately 49%/10%/19%/22% T&O/T&ON/T&R/T&RN in each dataset. Inputs included four channels for anatomical masks (high-risk clinical target volume [HRCTV], bladder, rectum, and sigmoid), a mask indicating dwell position locations, and applicator channels for each applicator component. Applicator channels were created by mapping the 3D dose for a single dwell position to each dwell position and summing over each applicator component with uniform dwell time weighting. A 3D Cascade U-Net, which consists of two U-Nets in sequence, and mean squared error loss function were used. The combined model was then fine-tuned to produce four applicator-specific models by freezing the first U-Net and encoding layers of the second and resuming training on applicator-specific data. Finally, four IDV models were trained using only data from each applicator type. Performance of these three model types was compared using the following metrics for the test set: mean error (ME, representing model bias) and mean absolute error (MAE) over all dose voxels and ME of clinical metrics (HRCTV D90% and D2cc of bladder, rectum, and sigmoid), averaged over all patients. A positive ME indicates the clinical dose was higher than predicted. 3D global gamma analysis with the prescription dose as reference value was performed. Dice similarity coefficients (DSC) were computed for each isodose volume. Fine-tuned and combined models showed better performance than IDV applicator training. Fine-tuning resulted in modest improvements in about half the metrics, compared to the combined model, while the remainder were mostly unchanged. Fine-tuned MAE=3.98%/2.69%/5.36%/3.80% for T&O/T&R/T&ON/T&RN, and ME over all voxels=-0.08%/-0.89%/-0.59%/1.42%. ME D2cc were bladder=-0.77%/1.00%/-0.66%/-1.53%, rectum=1.11%/-0.22%/-0.29%/-3.37%, sigmoid=-0.47%/-0.06%/-2.37%/-1.40%, and ME D90=2.6%/-4.4%/4.8%/0.0%. Gamma pass rates (3%/3mm) were 86%/91%/83%/89%. Mean DSCs were 0.92%/0.92%/0.88%/0.91% for isodoses ≤150% of prescription. 3D BT dose was accurately predicted for all applicator types, as indicated by the low MAE and MEs, high gamma scores and high DSCs. Training on all treatment data overcomes challenges with data scarcity in each applicator type, resulting in superior performance than can be achieved by training on IDV applicators alone. This could presumably be explained by the fact that the larger, more diverse dataset allows the neural network to learn underlying trends and characteristics in dose that are common to all treatment applicators. Accurate, applicator-specific dose predictions could enable automated, knowledge-based planning for any cervical brachytherapy treatment.

Biomarker Expression and Clinical Outcomes in International Study of Chemoradiation and Magnetic Resonance Imaging-Based Image-Guided Brachytherapy for Locally Advanced Cervical Cancer: BIOEMBRACE

PurposeBIOEMBRACE-I was designed to study the impact of biomarkers in addition to clinic-pathological factors on disease outcomes in patients treated with chemoradiation and MRI-guided brachytherapy (BT) for locally advanced cervical cancer in EMBRACE study. Patient and MethodsBetween 2018-2021, eight EMBRACE-I sites contributed tumour tissue for immunohistochemistry of p16, PD-L1 and L1CAM. These biomarkers and clinicopathological factors (FIGO 2009 stage, nodal status, histology, necrosis on MRI) were analysed to predict poor response at brachytherapy (BT) (high-risk clinical target volume [HR-CTV] ≥40cc) at BT), and 5-year local control, pelvic control and disease-free survival (DFS). Interaction between p16, PD-L1, radiotherapy dose (HR-CTV D90) and disease outcomes was investigated. Univariable and multivariable analysis were performed. ResultsTwo-hundred sixty-four patients were included. The median HR-CTV D90 was 89 (86-95) Gy. p16 positive (pos), PD-L1>1% and L1CAM ≥ 10% was noted in 86.6%, 20.1% and 17.8% respectively. P16 negative (neg) status (OR 2.0 (1.0-5.7), p=0.04), necrosis on MRI (OR 2.1 (1.1-4.3), p<0.02) independently predicted for HR-CTV≥40cc, as did FIGO stage and tumour width >5cm. PDL1>1% was associated with reduced local (82% vs. 94%, p=0.02) and pelvic control (79% vs. 89%, p=0.02). HR-CTV D90 <85Gy was associated with inferior 5-year local control in p16+ patients especially if PD-L1 was co-expressed. On multivariable analysis, PD-L1>1% was the only independent factor for 5-year local control (HR 3.3, p=0.04) and L1CAM ≥50% for pelvic control (HR 5.5 (1.3-23.3), p =0.02). ConclusionsP16 neg status and tumor necrosis on MRI are independently associated with poor response to chemoradiation, whereas PD-L1>1% and L1CAM≥50% have an independent impact on local and pelvic control suggesting impact of biomarker expression on outcomes. Further validation is needed.

Impact of Dosimetric Compromises on Early Outcomes of Chordomas and Chondrosarcomas Treated With Image-guided Pencil Beam Scanning Proton Beam Therapy

PurposeTo critically review the clinical factors, dosimetry, and their correlation with early outcomes in patients with chordomas and chondrosarcomas treated with pencil beam scanning proton beam therapy (PBS-PBT). MethodsConsecutive 64 patients diagnosed with chordoma, or chondrosarcoma treated at our centre were studied. Patient, tumor and treatment-related factors including dosimetry were captured. Early and late toxicities and early outcomes were evaluated and correlated with clinical and dosimetric factors using standard statistical tools. ResultsThe median age of patients was 39(4-74 years) and most common site was skullbase (47%) followed by sacrum(31%) and mobile spine(22%). The median prescription dose to the high-risk CTV for chordoma and chondrosarcoma was 70.4CGE(Cobalt Gray equivalent) and 66CGE at 2.2CGE per fraction respectively. At presentation to our centre, 55% presented after a recurrence/progression of which 17% received prior radiation and 32% had a significant neural compression. At the time of PBT, 25% of patients had suboptimal neural separation. Three-fourths of patients had at least an acceptable target coverage. While 11% had a tier-1 compromise (GTVD98<90%), 14% had a tier-2 compromise (GTVD98<59CGE). With a median follow-up of 27.5 months, 2-year local control and PFS was 86.7% and 81.8% for chordomas and 87.5% and 77.1% for chondrosarcomas respectively. Residual GTV>25cc and a tier-2 compromise were associated with inferior local control (HR-0.19,p=0.019; HR-0.061,p=0.022 respectively) and progression-free survival (HR-0.128,p=0.014; HR-0.194,p=0.025 respectively) on multivariate analysis. Despite multiple surgeries, a majority with recurrent disease and prior radiations, grade-3 acute and late toxicities were limited and comparable to others in the literature. ConclusionDespite multiple surgeries, adequate neural separation was challenging to achieve. Severe dosimetric compromise(GTVD98<59CGE) led to inferior early outcomes. Adequate neural separation is key to avoiding dosimetric compromise and achieving optimal local control.

The safety and efficacy of volumetric modulated Arc therapy combined with computer tomography-guided adaptive brachytherapy for locally advanced cervical cancer: a single institution experience

BackgroundVolumetric modulated arc therapy (VMAT) is a novel form of IMRT, which can deliver more accurate dose distribution and shorten treatment time. Compared to MRI-guided adaptive brachytherapy, which is recommended as gold standard imaging for cervical cancer contours, CT-guided adaptive brachytherapy (CTGAB) is more available, more widespread, and more affordable in many centers. This study aims to retrospectively analyze the efficacy and the safety of VMAT combined with CTGAB for patients with locally advanced cervical cancer.Methods and materialsThis study retrospectively analyzed 102 patients with locally advanced cervical cancer who underwent VMAT and CTGAB. Clinical outcomes including local control (LC), overall survival (OS) and progression-free survival (PFS), tumor response to treatment evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1), and toxicities including gastrointestinal toxicity, urinary toxicity and hematologic toxicity evaluated by the Common Terminology Criteria for Adverse Events (CTCAE) (version 5.0) were analyzed. The Kaplan-Meier method was used to calculate LC, OS, and PFS.ResultsMedian follow-up time was 19 months. Complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) occurred in 68 (66.7%), 24 (23.5%), 4 (3.92%), and 6 (5.88%), respectively. The 2-year and 3-year OS were 89.6% and 83%, respectively. The 2-year and 3-year PFS were 84.2% and 74.3%, respectively. The 2-year and 3-year LC were 90.1% and 79.3%, respectively. The average cumulative D2cm3 in the rectum, the bladder, the colon, and the small intestine were 78.07 (SD: 0.46) Gy, 93.20 (SD: 0.63) Gy, 63.55 (SD: 1.03) Gy and 61.07 (SD: 0.75) Gy, respectively. The average cumulative D90% of the high-risk clinical target volume (HR-CTV) was 92.26 (SD: 0.35) Gy. Grade ≥ 3 gastrointestinal and urinary toxicities occurred in 4.9% and 0.98%, respectively. 1.96% of patients were observed grade ≥ 4 gastrointestinal toxicities and none of the patients observed grade ≥ 4 urinary toxicities.ConclusionVMAT combined with CTGAB for locally advanced cervical cancer was an effective and safe treatment method, which showed satisfactory LC, OS, PFS, and acceptable toxicities.

Dosimetric evaluation and treatment planning considerations for GammaTile permanent brain implants - a pilot, institutional experience.

GammaTile® (GT) is a brachytherapy platform that received Federal Drug Administration (FDA) approval as brain tumor therapy in late 2018. Here, we reviewed our institutional experience with GT as treatment for recurrent glioblastomas and characterized dosimetric parameter and associated clinical outcome. A total of 20 consecutive patients with 21 (n = 21) diagnosis of recurrent glioblastoma underwent resection followed by intraoperative GT implant between 01/2019 and 12/2020. Data on gross tumor volume (GTV), number of GT units implanted, dose coverage for the high-risk clinical target volume (HR-CTV), measured by D90 or dose received by 90% of the HR-CTV, dose to organs at risk, and six months local control were collected. The median D90 to HR-CTV was 56.0Gy (31.7-98.7Gy). The brainstem, optic chiasm, ipsilateral optic nerve, and ipsilateral hippocampus median Dmax were 11.2, 5.4, 6.4, and 10.0Gy, respectively. None of the patients in this study cohort suffered from radiation necrosis or adverse events attributable to the GT. Correlation was found between pre-op GTV, the volume of the resection cavity, and the number of GT units implanted. Of the resection cavities, 7/21 (33%) of the cavity experienced shrinkage, 3/21 (14%) remained stable, and 11/21 (52%) of the cavities expanded on the 3-months post-resection/GT implant MRIs. D90 to HR-CTV was found to be associated with local recurrence at 6-month post GT implant, suggesting a dose response relationship (p = 0.026). The median local recurrence-free survival was 366.5days (64-1,098days), and a trend towards improved local recurrence-free survival was seen in patients with D90 to HR-CTV ≥ 56Gy (p = 0.048). Our pilot, institutional experience provides clinical outcome, dosimetric considerations, and offer technical guidance in the clinical implementation of GT brachytherapy.

The current state and future perspectives of radiotherapy for cervical cancer.

Radiotherapy is an effective treatment method for cervical cancer and is typically administered as external beam radiotherapy followed by intracavitary brachytherapy. In Japan, center shielding is used in external beam radiotherapy to shorten treatment time and reduce the doses delivered to the rectum or bladder. However, it has several challenges, such as uncertainties in calculating the cumulative dose. Recently, external beam radiotherapy has been increasingly performed with intensity-modulated radiotherapy, which reduces doses to the rectum or bladder without center shielding. In highly conformal radiotherapy, uncertainties in treatment delivery, such as inter-fractional anatomical structure movements, affect treatment outcomes; therefore, image-guided radiotherapy is essential for appropriate and safe performance. Regarding intracavitary brachytherapy, the use of magnetic resonance imaging-based image-guided adaptive brachytherapy is becoming increasingly widespread because it allows dose escalation to the tumor and accurately evaluates the dose delivered to the surrounding normal organs. According to current evidence, a minimal dose of D90% of the high-risk clinical target volume is significantly relevant to local control. Further improvements in target coverage have been achieved with combined interstitial and intracavity brachytherapy for massive tumors with extensive parametrical involvement. Introducing artificial intelligence will enable faster and more accurate generation of brachytherapy plans. Charged-particle therapies have biological and dosimetric advantages, and current evidence has proven their effectiveness and safety in cervical cancer treatment. Recently, radiotherapy-related technologies have advanced dramatically. This review provides an overview of technological innovations and future perspectives in radiotherapy for cervical cancer.

The partial adaptation strategy for online-adaptive proton therapy: A proof of concept study in head and neck cancer patients.

The accuracy of intensity-modulated proton therapy (IMPT) is greatly affected by anatomy variations that might occur during the treatment course. Online plan adaptations have been proposed as a solution to intervene promptly during a treatment session once the anatomy changes are detected. The implementation of online-adaptive proton therapy (OAPT) is still hindered by time-consuming tasks in the workflow. The study introduces the novel concept of partial adaptation and aims at investigating its feasibility as a potential solution to parallelize tasks during an OAPT workflow for saving valuable in-room time. The proof-of-principle simulation study includes datasets from six head and neck cancer (HNC) patients, each consisting of one planning CT (pCT) and three contoured control CTs (cCTs). Robust 3-field normo-fractionated initial IMPT plans were generated on the pCTs with a standardized field configuration, delivering 66 Gy and 54Gy to the high-risk and low-risk clinical target volume (CTVHigh and CTVLow), respectively.For each cCT, a dose-mimicking-based partial adaptation was applied: two fields were adapted on the current anatomy taking into account the background dose of the first non-adapted field supposedly delivered in the meantime. Fraction doses on the cCTs resulting from partially adapted plans with different first (non-adapted) field assignments were compared against those from non-adapted and fully adapted plans regarding target coverage and organs at risk (OARs) sparing. The robustness of partially adapted plans was also evaluated. Partially adapted plans showed comparable results to fully adapted plans and were superior to non-adapted plans for both target coverage and OAR sparing. Target coverage degradation in the non-adapted plans (median D98%: 95.9% and 97.5% for CTVLow and CTVHigh, respectively) was recovered by both partial (98.0% and 98.5%) and full adaptation (98.2% and 98.7%) in comparison to the initial plans (98.7% and 98.8%). The initial hotspot dose for the CTVHigh (median D2%: 101.8%) increased in the non-adapted plans (102.9%) and was recovered by the adaptive strategies (partial: 102.5%, full: 101.9%). The near-maximum dose (D0.01cc) to brainstem and spinal cord was within clinical constraints for all investigated dose distributions, but clearly increased for no adaptation and improved in the (both partially and fully) adapted plans with respect to the non-adapted ones. The parotids' median doses (D50) were mainly patient-specific depending on the proximity to the target region, but anyway lower for the partially and fully adapted plans compared to the non-adapted ones. OAR sparing was furthermore improved for the partially adapted plans in comparison to full adaptation. Robustness of the target dose metrics was preserved in all evaluated scenarios. For OAPT of HNC patients, partial adaptation is able to generate plans of superior conformity to non-adapted plans and of comparable conformity as fully adapted plans, while having the potential to speed up the online-adaptive workflows. Thus, partial adaptation represents an intermediate approach until fast online adaptation workflows become available. Furthermore, it can be applied in workflows where online treatment verification stops the delivery and triggers an online adaptation for the remaining fraction.

Attention 3D U-NET for dose distribution prediction of high-dose-rate brachytherapy of cervical cancer: Direction modulated brachytherapy tandem applicator.

Direction Modulated Brachytherapy (DMBT) enables conformal dose distributions. However, clinicians may face challenges in creating viable treatment plans within a fast-paced clinical setting, especially for a novel technology like DMBT, where cumulative clinical experience is limited. Deep learning-based dose prediction methods have emerged as effective tools for enhancing efficiency. To develop a voxel-wise dose prediction model using an attention-gating mechanism and a 3D UNET for cervical cancer high-dose-rate (HDR) brachytherapy treatment planning with DMBT six-groove tandems with ovoids or ring applicators. A multi-institutional cohort of 122 retrospective clinical HDR brachytherapy plans treated to a prescription dose in the range of 4.8-7.0Gy/fraction was used. A DMBT tandem model was constructed and incorporated onto a research version of BrachyVision Treatment Planning System (BV-TPS) as a 3D solid model applicator and retrospectively re-planned all cases by seasoned experts. Those plans were randomly divided into 64:16:20 as training, validating, and testing cohorts, respectively. Data augmentation was applied to the training and validation sets to increase the size by a factor of 4. An attention-gated 3D UNET architecture model was developed to predict full 3D dose distributions based on high-risk clinical target volume (CTVHR) and organs at risk (OARs) contour information. The model was trained using the mean absolute error loss function, Adam optimization algorithm, a learning rate of 0.001, 250 epochs, and a batch size of eight. In addition, a baseline UNET model was trained similarly for comparison. The model performance was evaluated on the testing dataset by analyzing the outcomes in terms of mean dose values and derived dose-volume-histogram indices from 3D dose distributions and comparing the generated dose distributions against the ground-truth dose distributions using dose statistics and clinically meaningful dosimetric indices. The proposed attention-gated 3D UNET model showed competitive accuracy in predicting 3D dose distributions that closely resemble the ground-truth dose distributions. The average values of the mean absolute errors were 1.82±29.09Gy (vs. 6.41±20.16Gy for a baseline UNET) in CTVHR, 0.89±1.25Gy (vs. 0.94±3.96Gy for a baseline UNET) in the bladder, 0.33±0.67Gy (vs. 0.53±1.66Gy for a baseline UNET) in the rectum, and 0.55±1.57Gy (vs. 0.76±2.89Gy for a baseline UNET) in the sigmoid. The results showed that the mean absolute error (MAE) for the bladder, rectum, and sigmoid were 0.22±1.22Gy (3.62%) (p=0.015), 0.21±1.06Gy (2.20%) (p=0.172), and -0.03±0.54Gy (1.13%) (p=0.774), respectively. The MAE for D90, V100%, and V150% of the CTVHR were 0.46±2.44Gy (8.14%) (p=0.018), 0.57±11.25% (5.23%) (p=0.283), and -0.43±19.36% (4.62%) (p=0.190), respectively. The proposed model needs less than 5 s to predict a full 3D dose distribution of 64×64×64 voxels for any new patient plan, thus making it sufficient for near real-time applications and aiding with decision-making in the clinic. Attention gated 3D-UNET model demonstrated a capability in predicting voxel-wise dose prediction, in comparison to 3D UNET, for DMBT intracavitary brachytherapy planning. The proposed model could be used to obtain dose distributions for near real-time decision-making before DMBT planning and quality assurance. This will guide future automated planning, making the workflow more efficient and clinically viable.

Role of the gel spacer in safely delivering whole pelvic radiation therapy without central shielding in computed tomography-based image-guided adaptive brachytherapy for uterine cervical cancer patients

BackgroundTo protect the rectum and bladder from high dose exposure, the Japanese guidelines for managing uterine cervical carcinoma recommend pelvic irradiation with central shielding (CS). Conversely, the European Society for Radiotherapy and Oncology (ESTRO) and the American Brachytherapy Society (ABS) guidelines recommend delivering ≥ 85 Gy to high-risk clinical target volume D90 (CTVHR D90%). In this study, we investigated whether a gel spacer can enable the safe delivery of the ESTRO/ABS-recommended doses to the target while observing dose constraints for the OARs without using CS in external beam radiation therapy (EBRT). Materials and MethodsTwenty patients who received definitive radiation therapy without CS and were treated by brachytherapy with a gel spacer between April 2017 and May 2022 were retrospectively reviewed. The cumulative doses of EBRT and brachytherapy expressed in the form of the equivalent dose in 2 Gy fractions (EQD2) were calculated. Treatment outcomes and incidence of adverse events were also examined. ResultsThe median cumulative CTVHR D90%, rectum D2cm3, and bladder D2cm3 were 86.6 Gy (range, 69.8–103.7), 62.9 Gy (range, 55.3–72.5), and 72.0 Gy (range, 62.9–84.1), respectively. The median follow-up was 35.9 months (range, 10.9–70.3). The 2-year local control rate was 95% (95% CI: [69–99%]). There were no CTCAE ≥Grade 3 late gastrointestinal or genitourinary adverse events. ConclusionsThe use of gel spacer can enable ESTRO/ABS-recommended dose constraints even without using CS in EBRT, with favorable outcomes and low adverse event rates.

Effective timing of hyaluronate gel injection in image-guided adaptive brachytherapy for uterine cervical cancer: a proposal of the 'adjusted dose score'.

Hyaluronate gel injection (HGI) in the rectovaginal septum and vesicovaginal septum is effective in the setting of high-dose-rate image-guided adaptive brachytherapy (IGABT) for cervical cancer. We aimed to retrospectively investigate optimal conditions for HGI to achieve optimal dose distribution with a minimum number of HGI. We classified 50 IGABT plans of 13 patients with cervical cancer who received IGABT both with and without HGI in the rectovaginal septum and vesicovaginal septum into the following two groups: plan with (number of plans = 32) and plan without (number of plans = 18) HGI. The irradiation dose parameters of high-risk clinical target volume (CTVHR) and organs at risk per fraction were compared between these groups. We also developed the adjusted dose score (ADS), reflecting the overall irradiation dose status for four organs at risk and CTVHR in one IGABT plan and investigated its utility in determining the application of HGI. HGI reduced the maximum dose to the most exposed 2.0cm3 (D2.0 cm3) of the bladder while increasing the minimum dose covering 90% of CTVHR and the percentage of CTVHR receiving 100% of the prescription dose in one IGABT plan without causing any associated complications. An ADS of ≥2.60 was the optimum cut-off value to decide whether to perform HGI. In conclusion, HGI is a useful procedure for improving target dose distribution while reducing D2.0 cm3 in the bladder in a single IGABT plan. The ADS can serve as a useful indicator for the implementation of HGI.

Dosimetric Analysis of Computed Tomography-Based Brachytherapy Planning in Carcinoma Cervix

Background The standard of care for locally advanced cervical cancer is concurrent chemoradiation followed by intracavitary brachytherapy (BT). BT forms an integral part of management as it improves local control and overall survival. In recent times, image-guided BT (IGBT) has been recommended as the standard of care. Computed tomography (CT) scan-based BT is a cost-effective and easily available modality for IGBT. The aim of the study was to do a dosimetric analysis of CT scan-based BT for patients with cervical cancer. Methods This was a retrospective study and included patients with cervical cancer treated with radical chemoradiation followed by BT. CT scan was done before every fraction after applicator placement, and CT-based planning was done for all fractions. Clinical details were abstracted from the case records, and dosimetric details were collected from the treatment planning systems. Total equivalent dose in 2 Gy per fraction (EQD2) was calculated for external beam radiation therapy and BT target volumes and organs at risk (OARs). Results This study included 50 patients. The mean age was 45 years. The majority of the cases were stage III. The mean high-risk clinical target volume (HRCTV) for the 1st, 2nd, and 3rd fraction was 53.1, 52.1, and 51.3 mL, respectively. Mean D90 HRCTV (dose received by 90% of the HRCTV) dose was 81.4 Gy (EQD2 10 Gy) and D2cc was 75.8 Gy (EQD2 3 Gy) for the rectum and sigmoid and 86.2 Gy (EQD2 3 Gy) for the bladder. Conclusion CT-based BT is a reasonable option in high-volume and low-resource settings where the availability of magnetic resonance imaging is limited. CT-based BT at every fraction can ensure proper applicator placement and aid in optimizing the dose to the target volumes and OARs.