Interstitial High Dose Rate Research Articles

Radiotherapy as a metastasis directed therapy for liver oligometastases - comparative analysis between CT-guided interstitial HDR brachytherapy and two SBRT modalities performed on double-layer and single layer LINACs

IntroductionSurgical resection is gold standard for treatment of liver metastasis, locally ablative techniques including computer tomography (CT)-guided interstitial high-dose-rate (HDR) brachytherapy (CT-BRT) and stereotactic body radiotherapy (SBRT) have gained prominence as alternatives, offering comparable outcomes in selected patients. We aim to compare CT-BRT and SBRT - based on dosimetric analysis.Material and methodsPatients who underwent CT-BRT for oligometastatic, ≤4cm liver metastases between 2018 and 2024 were eligible. SBRT plans for Halcyon (SBRTh) and TrueBeam (SBRTtb) were prepared virtually. In the CT-BRT group CTV was equal to PTV, for SBRTh and SBRTtb planning, a 5 mm margin was applied to CTV to create PTV. Dose calculation was carried out with the TG-43 algorithm for CT-BRT and Anisotropic Analytical Algorithm for SBRTh and SBRTtb group. Descriptive statistics were used to compare the data. The Wilcoxon pairwise order test was utilized to compare dependent groups.ResultsCT-BRT resulted in a more favorable dose distribution within PTVs for Dmean, D50, and D90, while SBRT showed better results for D98 and V27.5Gy. No significant differences were observed for V25Gy between CT-BRT and SBRTtb, but SBRTh favored over CT-BRT. For OARs, CT-BRT plans showed better values for V5, V10, and V11.6Gy in the uninvolved liver volume. There were no significant differences in dose distribution for the duodenum, bowel, and heart. SBRT modalities performed better in the kidney. CT-BRT had improved dose distribution in the esophagus, great vessels, ribs, skin, spinal cord, and stomach compared to SBRT.ConclusionsCT-BRT could be a viable alternative to SBRT for certain patients with liver malignancies.

Proof-of-concept of real-time electromagnetic guidance for gynecologic interstitial catheters in high dose rate brachytherapy

Background and PurposeThe addition of interstitial needles to intracavitary gynecologic (GYN) high dose rate (HDR) brachytherapy has been shown to improve target coverage and organs-at-risk (OAR) sparing. However, no commercial solution allows real-time guidance of interstitial catheter placement. This phantom study aimed to evaluate the feasibility of an electromagnetic (EM) tracking system guidance workflow for GYN HDR brachytherapy treatment in a magnetic resonance imaging (MRI) and real-time transrectal ultrasound (TRUS) fusion scenario. Materials and MethodsA clinical investigational system combining a treatment planning system and the EM tracking technology was used. The 3D T2 weighted magnetic resonance (MR) image set of a patient treated with intracavitary and interstitial HDR brachytherapy was retrospectively chosen. The MR image set was used to delineate the target and the OARs. A preplan was generated to determine needles positions in advance. The implant was reproduced in a water phantom. A 3D TRUS scan was acquired, and a rigid registration between the MR and the TRUS images was performed. ResultsThe accuracy of the EM tracking system was < 1 mm for both the sagittal and the transverse modes of the TRUS probe. Contours that were delineated on the MRI were propagated on the TRUS images after the rigid registration. Needle insertion was successfully guided in real time with the EM tracking system on the TRUS live image using the MRI contours for guidance. ConclusionBased on this proof-of-concept, real-time EM-guidance of interstitial needle for GYN HDR brachytherapy appears to be feasible.

Total Reference Air Kerma (TRAK) is Associated with Dosimetric Parameters in Template-Based High Dose-Rate (HDR) Interstitial Brachytherapy in Advanced Gynecologic Cancers

To study TRAK and its association with dosimetric parameters in template-based high dose-rate interstitial brachytherapy in advanced gynecologic cancers. Brachytherapy treatment plans of 53 patients treated between 2012 and 2022 at our institution with template-based Iridium-192 HDR brachytherapy, post-external beam RT, for locally advanced cancers of the cervix and vagina were retrospectively reviewed. Brachytherapy dose ranged from 25 to 30-Gy delivered in 4 to 6 fractions. The median number of flexi-guide catheters implanted was 18 (range 10-30). Clinical Target Volume (CTV) values were mean (±SD): 72.2 (±40.4) cm3 (high-risk, HR) and 182.2 (±73.7) cm3 (intermediate-risk, IR) respectively. TRAK per fraction (cGy at 1m), dose-volume information for the implant, target, and organ-at-risk (OAR) were recorded. Indices for dose coverage (CI), homogeneity (DHI), non-uniformity (DNR), overdose volume (ODI) were computed. Regression and correlation tests were used to study the TRAK relationship with various dosimetric parameters. The false discovery rate at a 5% level was corrected using the Benjamini-Hochberg procedure. The average TRAK per fraction was 0.365 (±0.12) cGy. Mean and range values of plan quality indices were - CI 0.92 (0.7- 1.0), DHI 0.57 (0.41 - 0.77), DNR 0.43 (0.23 - 0.59) and ODI 0.22 (0.11 - 0.38), respectively Correlation results for TRAK with various dosimetric indices are presented in Table 1. TRAK showed a weak correlation with the number of flexi-guide catheters implanted (r = 0.35, p = 0.013). TRAK correlated strongly with target volumes (CTV_HR and CTV_IR and CTV_HR V100%) and with isodose volumes at both high (V300, V200, V150), and low dose levels (V90, V85, V50) (p<0.00001). TRAK correlated moderately with OAR 2-cm3 doses (p<0.00001). A weak correlation was observed between TRAK and plan quality indices. TRAK correlates positively with target volume and volumes enclosed by isodoses at various dose levels in interstitial HDR brachytherapy of advanced Gynecologic Cancers. Interestingly, our study observed a comparatively stronger positive correlation between TRAK and Sigmoid 2-cm3 dose, equated to TRAK correlation with bladder, rectum, and small bowel 2-cm3 doses. This finding could interest future studies utilizing TRAK as a surrogate for treatment outcome and toxicity.

Attention-Gated Deep-Learning–Based Automatic Digitization of Interstitial Needles in High-Dose-Rate Brachytherapy for Cervical Cancer

Deep learning can be used to automatically digitize interstitial needles in high-dose-rate (HDR) brachytherapy for patients with cervical cancer. The aim of this study was to design a novel attention-gated deep-learning model, which may further improve the accuracy of and better differentiate needles. Seventeen patients with cervical cancer with 56 computed tomography-based interstitial HDR brachytherapy plans from the local hospital were retrospectively chosen with the local institutional review board's approval. Among them, 50 plans were randomly selected as the training set and the rest as the validation set. Spatial and channel attention gates (AGs) were added to 3-dimensional convolutional neural networks (CNNs) to highlight needle features and suppress irrelevant regions; this was supposed to facilitate convergence and improve accuracy of automatic needle digitization. Subsequently, the automatically digitized needles were exported to the Oncentra treatment planning system (Elekta Solutions AB, Stockholm, Sweden) for dose evaluation. The geometric and dosimetric accuracy of automatic needle digitization was compared among 3 methods: (1) clinically approved plans with manual needle digitization (ground truth); (2) the conventional deep-learning (CNN) method; and (3) the attention-added deep-learning (CNN+AG) method, in terms of the Dice similarity coefficient (DSC), tip and shaft positioning errors, dose distribution in the high-risk clinical target volume (HR-CTV), organs at risk, and so on. The attention-gated CNN model was superior to CNN without AGs, with a greater DSC (approximately 94% for CNN+AG vs 89% for CNN). The needle tip and shaft errors of the CNN+AG method (1.1 mm and 1.8 mm, respectively) were also much smaller than those of the CNN method (2.0 mm and 3.3 mm, respectively). Finally, the dose difference for the HR-CTV D90 using the CNN+AG method was much more accurate than that using CNN (0.4% and 1.7%, respectively). The attention-added deep-learning model was successfully implemented for automatic needle digitization in HDR brachytherapy, with clinically acceptable geometric and dosimetric accuracy. Compared with conventional deep-learning neural networks, attention-gated deep learning may have superior performance and great clinical potential.

Catheter reconstruction and dosimetric verification of MRI-only treatment planning (MRTP) for interstitial HDR brachytherapy using PETRA sequence

Objective. The feasibility of MRI-only treatment planning (MRTP) for interstitial high-dose rate (HDR) brachytherapy (BT) was investigated for patients diagnosed with gynecologic cancer. Approach. A clinical MRTP workflow utilizing a ‘pointwise encoding time reduction with radial acquisition (PETRA)’ sequence was proposed. This is a clinically available MRI sequence optimized to improve interstitial catheter-tissue contrast. Interstitial needles outside the obturator region were reconstructed using MR images only. For catheters penetrating through the obturator, a library-based reconstruction was proposed. In this work, dwell coordinates from the clinical CT-based reconstruction were used as the surrogate for the library-based approach. For MR-only plan, dwell times were activated and assigned as in the clinical plans. The catheter reconstruction was assessed by comparing dwell position coordinates. The dosimetric comparisons between a clinical plan and MR-only plan were assessed for physical and EQD2 dose and volume parameters for D 90, D 50 and D 98 for clinical target volume (CTV) and D 2cc, D 0.1cc and D 5cc for OARs. Main results. Catheter reconstruction was possible using the optimized PETRA sequence on MR images. An overall reconstruction difference of 1.7 ± 0.5 mm, attributed to registration-based errors, was found compared to the CT-based reconstruction. The MRTP workflow has the potential to generate a treatment plan with an equivalent dosimetric quality compared to the conventional CT/MRI-based approach. For CTV D 90, physical and EQD2 dose and volume parameter differences were 1.5 ± 1.9% and 0.7 ± 1.0 Gy, respectively. For D 2cc OARs, DVH (EQD2) differences were −0.4 ± 1.1% (−0.2 ± 0.5 Gy), 0.5 ± 2.8% (0.2 ± 1.3 Gy) and −0.5 ± 1.4% (−0.2 ± 0.5 Gy) for rectum, bladder, and sigmoid, respectively. Significance. With the proposed MRTP approach, CT imaging may no longer be needed in HDR BT for interstitial gynecologic treatment. A proof-of-concept study was conducted to demonstrated that MRTP using PETRA is feasible, with comparable dosimetric results to the conventional CT/MRI-based approach.

Brachytherapy in the Treatment of Non-Melanoma Skin Peri-Auricular Cancers-A Retrospective Analysis of a Single Institution Experience.

This paper presents the results of a retrospective analysis of 33 patients treated with contact or interstitial high-dose-rate (HDR) brachytherapy for skin cancers of the outer ear, involving the auricle and the skin of the adjacent area. Brachytherapy was used both as a definitive treatment (15 patients-43%) and adjuvant treatment after surgery (18 patients-57%). The basic criterion for adjuvant treatment was a positive or narrow (&lt;1 mm) resection margin. Fraction doses from 3 to 7 Gy per fraction were used at intervals from six hours (interstitial brachytherapy) to a maximum of seven days (contact brachytherapy). The treatment time ranged from 1 to 42 days, and the total dose range was 7 to 49 Gy. The follow-up was 29.75 months (range 2-64). In the group of patients treated with adjuvant therapy, in the patients with post-radiation reaction, the mean time from surgery to the start of brachytherapy was 7.72 ± 3.05 weeks, the median was 8 (6-12) weeks, and in the group without post-radiation reaction, the mean time was 11.13 ± 4.41 weeks, the median time was 11 weeks (8-14). The risk of a post-radiation reaction increased significantly more often in patients with more advanced disease. In the case of contact brachytherapy, the post-radiation reaction occurred significantly more often (14/21 patients-43%) than in the case of interstitial brachytherapy (3/11 patients-9.4%). In patients with post-radiation reactions, a significantly larger volume of the skin receiving a dose of 200% was found, and the volume receiving a dose of 150% was close to statistical significance. The mean volume of the skin receiving a 200% dose in the group with post-radiation reactions was 28.05 ± 16.56 cm3, the median was 24.86 (0.5-52.3) cm3, and the mean volume in the group without post-radiation reaction was 17.98 ± 10.96 cm3, median 14.95 (3.9-44.96) cm3. The result was statistically significant (Z = 2.035, p = 0.041). Interstitial HDR (high-dose-rate) brachytherapy for non-melanoma skin cancers around the ear is highly effective, short, and has a relatively low burden on the patient. The toxicity of the treatment was low. In the case of contact brachytherapy, the toxicity profile is slightly higher but acceptable for patients. This method is preferred in patients in whom interstitial brachytherapy is impossible to perform due to anatomical and logistical reasons. The unquestionable advantage of contact brachytherapy is its ability to be performed on an outpatient basis without the need to stay in the hospital. No severe and late CTCAE ≥III and late RTOG ≥III toxicity was observed. In patients after surgery, in order to minimise the risk of radiation reaction, it is optimal to start treatment at least eight weeks after surgery. In the presence of extensive lesions, the use of interstitial brachytherapy seems to be more advantageous, especially when the expected volume of healthy skin in the dose range of 200% and 150% is above 15 cm3 and 50 cm3, respectively.

Dosimetric evaluation of the feasibility of utilizing a reduced number of interstitial needles in combined intracavitary and interstitial brachytherapy for cervical cancer.

To evaluate the ability of the Venezia advanced multichannel tandem and ring applicator to consistently produce dosimetrically comparable plans utilizing a reduced number of needle channels, to reduce the risk of secondary complications when boosting cervical cancer treatments with high dose rate (HDR) brachytherapy. We evaluated 26 fractions from 13 patients who were treated with HDR brachytherapy using the Venezia (Elekta) applicator. The original plans included a full load of 12-16 needles, including both parallel and 30-degree oblique needles. We replanned each original to nine new configurations, with a reduced number of two, three, four, or six needles. Comparisons included differences in percentage dose coverage to 90% of the high-risk clinical target volume, and percentage dose to 2cm3 of the bladder, rectum, sigmoid, and bowel. We considered new plans "passing" if they remained within our standards (D90>100%; D2cm3 <85% bladder, <65% rectum, sigmoid, bowel) or did not perform worse than original. Removing only the two most anterior or the two most posterior needles from both sides showed 80.8% and 61.5% overall passing rate. Removal of the most anterior and posterior four needles together showed 65.4% overall passing rate. Removing all oblique needles showed 19.2% overall passing rate. Removing only left-sided or only right-sided oblique needles showed 46.2% and 23.1% overall passing, respectively. Removing only right-sided or only left-sided parallel needles separately showed 19.2% and 34.6% overall passing, respectively. Removing all parallel needles showed 11.5% overall passing rate. As only two replans required a full needle load to maintain dosimetric quality and 40 (76.9%), 36 (34.6%), 18 (69.2%), and 10 (19.2%) replans passed with 2, 3, 4, and 6 needles removed respectively, this indicates the potential for using a lesser number of interstitial needles during combined intracavitary and interstitial HDR brachytherapy while maintaining dosimetric quality.

GSOR23 Presentation Time: 12:20 PM: Clinical Outcomes of Interstitial High-Dose Rate Brachytherapy with and without Concurrent Interstitial Hyperthermia for Gynecologic Malignancies

<h3>Purpose</h3> Radiosensitization with external hyperthermia (HT) has demonstrated improved oncologic outcomes for patients with gynecological (GYN) malignancies. However, similar data for multicatheter interstitial HT (IHT) with interstitial high-dose rate (IHDR) brachytherapy is limited. We present a single-institution experience of patients with GYN cancers treated using IHDR with and without concurrent IHT (IHDR-IHT). <h3>Materials and Methods</h3> We retrospectively analyzed 63 patients with locally advanced GYN malignancies treated with IHDR using a Syed-Neblett template (IHDR: 29 and IHDR-IHT: 34 patients). Primary indication for adding IHT was bulky, residual or recurrent disease guided by number, location and geometry of needle placement within HRCTV to allow placement of IHT antennae and thermistors. IHT (target temperature 40-44°C) was performed after IHDR treatment using the same set of interstitial catheters. The median age was 60 yrs (27- 89). Primary sites included cervical (n=40), endometrial (n=9), vaginal (n=10), vulvar (n=3), and non-GYN malignancy with vaginal invasion (n=1). Pelvic radiation therapy was performed prior to IHDR in all but one patient with median dose of 45 Gy (Range, 30.6-55.0 Gy) and 52 patients received concurrent chemotherapy. Median IHDR dose was 23.75 Gy (10-30.0) and number of fractions was 5 (2-5). IHDR and IHDR-IHT groups had similar proportion of reirradiation (p=0.55), stage ≥ III (p=0.11) and HRCTV volume (p=0.65) with marginally higher recurrent cases in the IHDR cohort (p=0.07). Median D90 HRCTV EQD2 was higher in IHDR-IHT (78.2 Gy; 14-105) vs IHDR group (75.9 Gy; range 61-86); p = 0.005. Respective median HRCTV volume were 61.3 cc (25-376) and 48.6 cc (12-175); p = 0.21. Chi -square and Mann-Whitney tests were done to compare variables between the two cohorts. The Kaplan-Meier method with Cox Regression was used to estimate overall survival (OS), local control (LC), locoregional control (LRC) and distant control (DC) and evaluate predictors of LC. <h3>Results</h3> IHDR-IHT and IHDR were well tolerated with no acute procedure-related adverse events. With a median follow up of 12.1 months (<1-59) in IHDR group and 11.0 months (1-76), 1 IHDR-HT patient developed acute CTCAE grade 3+ toxicity (grade 3 urinary obstruction in a patient with horseshoe kidney). Late Grade 3+ toxicity was seen in 9 patients (IHDR: 5, IHDR-IHT: 4 patients); ureteral stricture/incontinence (4), fistula (3) and radiation proctitis (2). Median OS was 31 versus 42 months (p=0.55) in the IHDR and IHDR-IHT groups, respectively. 1 yr LC for IHDR vs IHDR-IHT of 86.9% vs 77.8% (p=0.051). Corresponding, 1-yr LRC and DC were 82.5 vs 74.8% (p=0.056) and 81 vs 77.6% (p=0.84), respectively. On cox regression undergoing IHT (HR 4.7 [95% CI 1.3-16.9] p=0.02) was associated with worse local control. <h3>Conclusions</h3> To our knowledge, this is the largest report describing outcomes from the addition of IHT to IHDR in patients with locally advanced GYN malignancies. Use of IHT had excellent tolerance without any procedural complications. With possible group imbalances, trend to shorter LC and LRC was seen in IHT. Prospective controlled studies will be needed to evaluate clinical benefits.

GPP09 Presentation Time: 10:00 AM: Patient Specific Template-Based Hybrid Brachytherapy for Treatment of Gynecological Cancers

<h3>Purpose</h3> Interstitial vaginal and pelvic brachytherapy (BT) is standard of care in locally advanced vaginal cancers and pelvic recurrence of gynecological malignancies. An in-house automated design and 3D printing workflow for pre-plannable patient-specific cylindrical templates (PSCTs) for IC/IS HDRBT was used for 7 patients treated at BC Cancer - Kelowna. Insertion positions and dosimetry are compared for preplan and final plans, and the practicality of preplanning for IC/IS HDRBT of the vagina is discussed. This work demonstrates that patient-specific treatment techniques for gynecological brachytherapy can be implemented within the clinic at a low cost. <h3>Materials and methods</h3> Seven patients with primary or recurrent vaginal malignancies were treated with IC/IS HDRBT facilitated with a PSCT which guided the position of IC/IS needles. Patients underwent pelvic T2-MRI imaging at least 7 days before their procedure with a dummy cylinder inserted. To satisfy pre-planning goals, virtual needles orientations and dwell times were optimized and adjusted as needed until the final plan is acceptable (Figure 1). Plans were exported and 3D modeled automatically using in-house written software. PSCTs were 3D printed of PEEK, and post-processed to have a smooth final finish, as shown in Figure 1. Each needle was pushed to its final depth under abdominal ultrasound guidance after the cylinder was inserted. Post-insertion CT scans were registered to preplan MRI scans and contoured, and final plans were optimized before treatment using digitized final needle positions. Patient final plan (Figure 1) dosimetry and needle insertion statistics were calculated and compared to pre-insertion plans. <h3>Results</h3> The treated median HRCTV D90, V100, V150, V200, Bladder, Rectum, Sigmoid and Small Bowel D2cm³, were 110.8%, 96.7%, 52.8%, 28.0%, 18.0 Gy, 15.4 Gy, 11.0 Gy, and 12.9 Gy respectively. The median differences of the final treated plan (post-plan) to the preplan were 1.1%, -0.5%, 13.1%, 4.1%, 1.0 Gy, 0.8 Gy, 0.5 Gy, and -0.8 Gy respectively. The median insertion displacement of dwell positions for straight needles, curved needles, and overall was 1.3mm, 4.0mm, and 2.3mm, respectively. <h3>Conclusion</h3> 3D printed patient-specific templates for the guidance of interstitial high dose rate brachytherapy of the vagina can be used to preplan and deliver highly conformal IC/IS Vaginal HDRBT treatments. The PSCT provides a significantly easier IC/IS insertion procedure as compared to using an IC cylinder + grid or freehand needles. Patients whose HRCTV geometry was in one location extending away from the cylinder rather than wrapping around the entire vagina had improved dosimetric indices because the PSCT is geometrically constrained to only be able to fit a maximum number of needles, thus covering a wide range of directions and depths is more difficult as compared to treating a more directed region. It is possible to combine a PSCT with an IS grid template to have the advantages of both techniques. Compared to commercial IC cylinders, the PSCT is preferable, since the preplan allows for patient customization and trade-offs optimization before insertion. Since IS dwell positions are achievable through PSCTs, they achieve preferable dose to target versus OAR trade-offs. Compared to techniques using IS Grid needles, the PSCT facilitates lower interstitial needle lengths, and preferable insertion locations in the vaginal mucosa rather than through the perineum. These templates can facilitate higher quality treatment plans as compared to state of the art techniques, particularly for deep, localized, and top-of-vault lesions, improving target coverage, reducing OAR dose, reducing interstitial needle length and trauma in non-tumor tissue and improving confidence in needle insertion without intraoperative MRI or CT.

Saturday, June 18, 20227:40 AM - 5:00 PMPO22 Presentation Time: 7:40 AM: A Novel Algorithm for Automatic Interstitial Needle Tracking on PETRA MRI for HDR Brachytherapy

<h3>Purpose</h3> Current practice for interstitial high-dose-rate (HDR) brachytherapy treatment planning involves manual tracking of needle positions on CT images. Recently, PETRA MRI showed the potential to detect empty interstitial gynecological brachytherapy needles owing to low needle signal, intermediate tissue contrast and high spatial resolution. We aimed to develop an algorithm for automatic interstitial needle tracking on PETRA images by employing their negative contrast against surrounding tissue. <h3>Materials and Methods</h3> Fourteen ProGuide Sharp Needles 6Fx294mm were implanted in an endometrial adenocarcinoma patient using a Syed-Neblett template. One of the needles lay in the obturator center, and six inside the obturator slots. The patient underwent standard CT imaging with copper-filled needles. After marker removal, 3D PETRA images of the patient's pelvis (TR\TE 3.32\0.07 ms, voxel size 0.9 mm³ isotropic, 416 slices) were acquired on a 3T Siemens Vida MR scanner. PETRA MR images were analyzed for interstitial needle detection using custom code in MATLAB R2022a. A rectangular part of all axial slices where needles may be contained (slices 149-310) was selected. For each slice part, corner points were extracted from the original part and from its sharpened gradient magnitude image by detecting Harris features. Points found within Euclidean distance (ED) of 3 pixels on both images were matched, and the pixel with minimum signal intensity closest to each such point on the original part was selected. Minimum intensity points lying within 2 pixels ED between subsequent slices were considered as possible catheter coordinates. Such points appearing on at least 10 continuous slices were designated as true catheters, and their positions were compared to those visible on CT. <h3>Results</h3> Figure 1a) displays the selected MR image parts for two example slices. Pixels with detected Harris features and their closest signal minima are marked by red and green crosses, respectively, in b). Pixels accepted as needle positions are shown as magenta crosses in c). Matching CT image parts with bright marker-filled needles are displayed in d). Empty interstitial catheters on PETRA images corresponded to local minima of signal intensity, located near Harris features. The assumption of needle position continuity within an allowed distance along subsequent slices helped avoid spurious signal minima, while following needle position variations caused by different deflection angles. Needles guided through the obturator grooves and the central needle were detected only after they became detached from the obturator (ex. figure left). All 14 needles were tracked along their visible length inside tissue (ex. figure right). Visual comparison to CT images confirmed interstitial catheter detection on MRI. Selecting a range of slices and zooming on a part of each slice for analysis reduced computational time and output data size. <h3>Conclusions</h3> Automated detection of interstitial needles is feasible on PETRA MR images and may facilitate MR-only treatment planning in interstitial HDR brachytherapy. The newly developed algorithm was able to track all needles inside tissue based on their signal intensity characteristics, without requiring manual seed position placement.

Effect of 3-Dimensional Interstitial High-Dose-Rate Brachytherapy With Regional Metastatic Lymph Node Intensity-Modulated Radiation Therapy in Locally Advanced Peripheral Non-Small Cell Lung Cancer: 5-Year Follow-up of a Phase 2 Clinical Trial

We aimedto reveal the 5-year clinical outcomes of 3-dimensional (3D) interstitial high-dose-rate (HDR) brachytherapy with regional metastatic lymph node intensity modulated radiation therapy (IMRT) for locally advanced peripheral non-small cell lung cancer (NSCLC), which has been shown to have low toxicity and improved 2-year survival rates in patients with this disease. In this phase 2, single-arm, open-label clinical trial, 83 patients with locally advanced peripheral NSCLC were enrolled (median follow-up [range], 53.7 [4.3-120.4] months). All eligible patients received 3D interstitial HDR brachytherapy with regional metastatic lymph node IMRT. The primary endpoint was overall survival (OS). Secondary endpoints were local recurrence-free survival, regional recurrence-free survival, progression-free survival, distant metastasis-free survival, toxicities, and quality of life. The final analysis included 75 patients (19 [25.3%] females, 56 [74.7%] males; median [range] age, 64 [44-80] years; stage IIIA, 34 [45.3%]; stage IIIB, 41 [54.7%]). At the latest follow-up, 32 (42.7%) patients had survived. The median OS was 38.0 months (5-year OS, 44.5%; 95% confidence interval [CI], 33.8%-58.6%). Local recurrence-free survival, recurrence-free survival, and distant metastasis-free survival at 5 years were 79.2% (95% CI, 68.5%-91.5%), 73.6% (95% CI, 61.5%-88.1%), and 50.3% (95% CI, 38.3%-66.1%), respectively. The dominant failure pattern was distant disease, corresponding to 40% (30 of 75) of patients and 65.2% (30 of 46) of all failures. Two (2.7%) patients developed grade 1 acute pneumonitis. Grade 2 and 3 acute esophagitis occurred in 11 (14.7%) and 4 (5.3%) patients, respectively. No late radiation-related grade ≥2 late adverse events were observed. 3D interstitial HDR brachytherapy with regional metastatic lymph node IMRT for locally advanced peripheral NSCLC shows significant OS and has a low toxicity rate. Additional evaluation in a phase 3 trial is recommended to substantiate these findings.

Correlation of chemokines and growth factors with radiation-induced liver injury after interstitial high dose rate (HDR) brachytherapy of liver metastases

BackgroundLocoregional therapies, as imaging-guided tumor-directed procedures, are emerging treatment strategies in the management of primary and secondary liver malignancies such as e.g. colorectal cancer liver metastases. As one of those, irradiation-based interstitial high dose rate brachytherapy (iBT) of liver metastases bears a risk of developing focal radiation-induced liver injury (fRILI). Since little is known about biological factors involved in hepatic dysfunction after irradiation, the aim of this study was to identify factors, that may play a role in the underlying mechanism of fRILI, and that potentially may serve as biomarkers for post-therapeutic fRILI to improve specific management and treatment of patients.MethodsTwenty-two patients with hepatic malignancies (tumor patients, TP) underwent iBT with total ablative doses of radiation to the target volume ranging from e.g. 15 to 25 Gy. Hepatobiliary magnetic resonance imaging (MRI) was performed 6 weeks after iBT to quanitify fRILI. Blood samples were taken before (pre) and 6 weeks after (post) iBT from TP, and from ten healthy volunteers (HV controls) for the analyses of humoral mediators: monocyte chemoattractant protein-1 (MCP-1), chemokine (C-X3-C motif) ligand 1 (CX3CL1), vascular endothelial growth factor (VEGF) and beta-nerve growth factor (beta-NGF) using the Multi-Analyte Flow Assay via flow cytometry. Correlation analyses between the humoral mediators (pre and post iBT) with the tumor volume and fRILI were performed.ResultsWhile MCP-1 and CX3CL1 tended to decrease in TP vs. HV, VEGF was significantly decreased in TP vs. HV pre and post iBT (p < 0.05). Beta-NGF levels were significantly increased in TP vs. HV pre and post iBT (p < 0.05). Baseline circulating levels of MCP-1, VEGF and beta-NGF have shown significant positive correlations with the hepatic tumor volume (p < 0.05). Circulating levels of humoral mediators before treatment did not correlate with fRILI, while CX3CL1 and VEGF after iBT have shown significant positive correlations with fRILI (p < 0.05).ConclusionTumor volume and threshold dose of irradiation damage correlated positively with MCP-1 and VEGF as well as NGF and CX3CL, respectively. Thus, investigation of biological mediators in blood samples from tumor patients may provide an appropriate tool to predict fRILI after interstitial HDR brachytherapy of liver metastases.

Determination of variation in dosimetric parameters of treatment planning with Co-60 and Ir-192 sources in high dose rate brachytherapy of cervical carcinoma

AimTo determine the differences in dosimetric parameters in patients of intracavitary brachytherapy and interstitial HDR brachytherapy using Co-60 and Ir-192 sources. Materials and methodsComputed tomography (CT) based treatment plans of 20 cervical carcinoma patients treated with intracavitary and interstitial high dose rate brachytherapy were retrospectively studied. Patients were planned using Co-60 and Ir-192 sources, keeping the same dwell positions and dose objectives. The dosimetric parameters such as V100, D90, homogeneity index (HI) and conformal index (CI) for target and D2cc, D1cc and D0.1cc for organs at risk (OAR) were compared for both sources. ResultsFor interstitial brachytherapy plans, HR-CTV mean V100 values for Co-60 and Ir-192-based plans were 97.03 ± 1.93% and 96.42 ± 2.18%, respectively. There was no significant difference found in target coverage (p = 0.370). Ir-192 based plans were more homogeneous (HI = 0.68 ± 0.09) than the Co-60 plans (HI = 0.59 ± 0.10). However, the conformity was similar with both the sources. No significant difference was found between D2cc, D1cc, and D0.1cc values of bladder and rectum. In intracavitary brachytherapy plans, we did not find any significant difference in the dosimetric parameters such as point A values, D90, V100, and OAR doses on comparing plans from both sources. ConclusionThere are no significant differences in dosimetric parameters and no clinical advantage of using Co-60 over Ir-192-based brachytherapy. However, when it comes to cost management, Co-60 has a longer half-life, which reduces the cost of frequent source replacement and disposal.

First pointwise encoding time reduction with radial acquisition (PETRA) implementation for catheter detection in interstitial high-dose-rate (HDR) brachytherapy

PURPOSEA pointwise encoding time reduction with radial acquisition (PETRA) sequence was optimized to detect empty catheters in interstitial (HDR) brachytherapy with clinically acceptable spatial accuracy for the first time. Image quality and catheter detectability were assessed in phantoms, and the feasibility of PETRA's clinical implementation was assessed on a gynecological cancer patient. METHODS AND RESULTSEmpty catheters embedded in a gelatin phantom displayed positive signal on PETRA and more accurate cross-sections than on clinically employed T2-weighted sequences, differing by 0.4 mm on average from their nominal 2 mm diameter. PETRA presented minimal susceptibility differences and a symmetric metal artifact, contrary to the clinical sequences. The PETRA-CT catheter tip position differences assessed by a treatment planning system (TPS) were < 1 mm. PETRA also detected an interstitial template with empty catheters penetrating a poultry phantom and fused very well with CT. Interstitial catheter positional difference between PETRA and CT images was < 1 mm on average, increasing with distance from isocenter. All interstitial catheters and the employed interstitial template were detected on PETRA images of an endometrial adenocarcinoma patient. Empty needles were traceable using a TPS, with higher spatial resolution and more favorable contrast than on T2-weighted images used for contouring. A treatment plan could be produced by combining information from PETRA for catheter detection and from T2-weighted images for tumor and organs delineation. CONCLUSIONSPETRA detected successfully and accurately interstitial catheters in phantoms. Its first clinical implementation shows a potential for MR-only treatment planning in interstitial HDR brachytherapy.

TNF-α Indicates Radiation-induced Liver Injury After Interstitial High Dose-rate Brachytherapy.

The aim of the present study was to determine whether the early systemic markers of inflammation, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), respond to high dose-rate (HDR) brachytherapy, and their possible correlation with radiation-induced liver injury of patients with liver metastases. This prospective study included 20 tumor patients (TP) undergoing irradiation-based interstitial HDR brachytherapy (iBT) of liver metastases, who received total radiation ablative doses to the planning target volume ranging from 15 to 25 Gy, depending on the tumor entity. Hepatobiliary magnetic resonance imaging (MRI) was performed 6 weeks after iBT to assess the maximum extent of focal radiation-induced liver injury (fRILI). Furthermore, blood samples for the pro-inflammatory cytokine response were taken one day prior to and 6 weeks after irradiation. IL-6 and TNF-α were measured by flow cytometry. Ten healthy volunteers (HV) were used as control group. Compared to HV, TNF-α was significantly enhanced in TP before and after therapy (p<0.05 for both comparisons), while IL-6 increase at baseline was not statistically significant. HDR brachytherapy significantly reduced IL-6 levels after 6 weeks in TP (p<0.05). IL-6 levels after 6 weeks have shown a significant negative correlation with the tumor volume (r=-0.5606; p=0.0261), while no significant correlation was observed between baseline IL-6 or follow-up IL-6 levels with the fRILI. Baseline TNF-α levels positively correlated with the tumor volume (r=0.4342; p=0.0492), and post treatment TNF-α levels showed a significant correlation with the fRILI (r=0.7404; p=0.0022). TNF-α was correlated with both tumor volume and radiation-induced liver injury; thus, representing a promising biomarker for focal radiation-induced liver injury.

Interstitial high dose rate brachytherapy boost in early-stage breast cancer: deformable image registration for defining target volume

Purpose: optimization of the technique of additional irradiation of the removed tumor bed using high-dose brachytherapy for breast cancer. Material and Methods: the results of treatment of 28 patients diagnosed with breast cancer were analyzed. After surgical treatment and a course of external radiation therapy, all patients underwent additional irradiation of the removed tumor bed using high-dose brachytherapy. The assessment of the operation protocols, the data of the pathomorphological conclusion was carried out, and on the basis of pre- and postoperative CT images, the formation of irradiation fields for high-dose brachytherapy was carried out. Results: After deformable (nonrigid) registration of pre- and postoperative CT images of 28 patients, it was revealed that in 18 women (64.3% of cases) the location of interstitial markers and the primary tumor focus does not match topographically, which can cause incorrect formation of borders irradiation. In 35.7% of cases, radiopaque markers were located on the chest wall (on the pectoralis major muscle) when the primary tumor was located in the breast tissue. In 25% of cases, the markers were located cranial or caudal to the topography of the primary tumor focus. Label migration occurred in 3.6% of cases. In 35.7% of cases, the topography of the primary tumor node and marks completely coincided. Conclusions: The use of deformable (non-rigid) registration of pre- and postoperative CT images is a simpler method to determine the topography of the removed tumor bed, which subsequently leads to a more accurate formation of the clinical volume of irradiation.

The 3-Year Outcome of 3D High-Dose-Rate Brachytherapy in Combination With Regional Metastatic Lymph Nodes Intensity-Modulated Radiotherapy in Peripheral Locally Advanced Non-Small Cell Lung Cancer: A Phase I/II Clinical Trial

To determine the safety, late toxicities and locoregional control of three-dimensional(3D) high-dose-rate (HDR) brachytherapy in combination with regional metastatic lymph nodes intensity-modulated radiotherapy (IMRT) in patients with peripheral locally advanced non-small cell lung cancer (LA-NSCLC).Eligible patients with LA-NSCLC were recruited to this prospective, phase I/II clinical study. The primary lung tumors were treated with the CT-guided interstitial HDR brachytherapy, DT:30Gy/F. The IMRT was applied to the regional positive lymph nodes, DT: 60-70Gy/30-33F/ 6-7W. The concurrent chemotherapy regimens include used Etoposide and cisplatin, the sequential chemotherapy consisted of paclitaxel/pemetrexed + cisplatin/carboplatin. The safety analysis included operational complications and toxicity related to radiotherapy and chemotherapy. Clinical evaluation includes short-term efficacy, survival, and quality of life scores.A total of 83 patients were enrolled in this study. There were 56 males and 27 females, with a median age of 65 years (45-80 years). The median follow-up time was 55 months (32-114 months) up to November 2020. The operational complications included mild pneumothorax (16.8%) and minor hemorrhage around the needle (19.3%). The major toxicity was myelosuppression and gastrointestinal reaction during the concurrent chemoradiotherapy and sequential chemotherapy. The clinical symptoms alleviated after symptomatic supportive treatment. The radiotherapy was completed successfully without grade 4 or more serious acute toxicity. Grade 1 late radiation pneumonitis was found by in 5 patients (6.1%), and only showed imaging changes after radiotherapy. There were 61 patients achieved complete remission, 20 patients achieved partial remission, and 2 patients were in stable disease in the primary tumor, the total response rate was 97.6%. There were 55 patients achieved complete remission, 22 patients achieved partial remission, 5 patients were in stable disease and 1 patient with progressive disease in the positive lymph nodes, the total response rate was 92.8%. The 1-,2-,3-year overall survival rates were 90.6%, 70.6% and 62.4%. The 1-,2-,3-year local control rates were 90.0%,81.0% and 54.5%. The 1-,2-,3-year disease-free survival rates were 68.3%,42.2% and 23.9%. The 1-,2-,3-year metastasis-free survival rates were 73.3%, 50.9% and 39.5%. The patient who treated with 3D interstitial high dose rate brachytherapy has a higher life quality score than the baseline level.3D interstitial high dose rate brachytherapy combined with regional positive lymph node intensity-modulated radiotherapy is safe and feasible for the locally advanced peripheral non-small cell lung cancer, with low adverse reactions, increased the survival, and improved the life quality. But it still needs a phase III randomized controlled trial to investigate its clinical utility and promotion, compared to IMRT.

Abstract 105: Communicating the Gynecologic Brachytherapy Experience (CoGBE): Clinician Perceived Benefits of a Graphic Narrative Patient Education Tool

Abstract Purpose: Radiotherapy patient education materials fail to meet readability standards, impairing access for patients with low educational attainment, disabilities, or limited-English proficiency. Design professionals and physicians developed graphic narrative discussion guides, Communication of the Gynecologic Brachytherapy Experience (CoGBE), for cylinder, intracavitary, and interstitial high-dose rate (HDR) gynecologic brachytherapy. This study assesses perceived clinical benefits, usability, and anxiety-reduction of CoGBE. Methods: An electronic survey was sent to members of the American Brachytherapy Society. Participants were assigned to assess one of the three modality-specific CoGBE guides using a modified Systems Usability Scale (mSUS), modified state-trait anxiety index (mSTAI), and Likert-type questions. Free response data was analyzed using modified grounded theory. Results: Median mSUS score was 76.3 (interquartile range [IQR], 71.3-82.5) and there were no significant differences between guide types. Median mSTAI was 40 (IQR, 40-43.3) for all guides collectively. The cylinder guide had a significantly higher median mSTAI than the intracavitary and interstitial guides (41.6 vs 40.0 and 40.0; p=0.04) suggesting the cylinder guide may have less impact on reducing anxiety. 72.7% rated CoGBE as “quite” or “extremely” helpful compared to a text-only pamphlet. When compared to their current education practices, 77.3% reported patients would understand “more” or “a lot more” after initial consultation and 81.8% reported CoGBE would be at least moderately helpful in making initial consultations more memorable for patients. Lastly, 79.5% reported at least a moderate likelihood of using CoGBE. Qualitative analysis themes included personalization, relatability, and graphic narrative (positive domains); generalizability and character affect (negative domains). Conclusion: Clinicians rate CoGBE as usable with potential to reduce patient anxiety, especially with more invasive treatment modalities including intracavitary or interstitial HDR. The CoGBE guides (including multilingual versions) have global applicability, in low resource settings with high cervical cancer burdens and patient populations that may benefit from the graphic narrative format. Citation Format: Santiago Avila, María J. Ruiz, Ritu Arya, Brian Callender, Yasmin Hasan, Josephine S. Kim, Nita Lee, Anne McCall, Christina H. Son, Kate Stack, Sabah Asif, Tyler Besecker, Arushi Juneja, Zhongyang Li, Pinakee Naik, Tanvi Ranka, Prachi Saxena, Brian Siegfried, Tomoko Ichikawa, Daniel W. Golden. Communicating the Gynecologic Brachytherapy Experience (CoGBE): Clinician Perceived Benefits of a Graphic Narrative Patient Education Tool [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 105.

Interstitial multi-catheter breast brachytherapy: Technical aspects and experience feedback in a comprehensive cancer center

PurposeTo focus on technical aspects of the implementation of interstitial high dose rate brachytherapy, with a step-by-step approach. Materials and methodsPatients were selected during multidisciplinary tumor boards, according to inclusion criteria adapted from GEC-ESTRO guidelines. A CT scan was performed a few days before implantation. On pre-implant CT, using surgical scar and clips, surgical and pathological reports, and preoperative images, we delineated the tumor bed to be included in the Clinical Target Volume (CTV), according to GEC ESTRO Recommendations. A 3D virtual implant simulation of the best catheter positions was performed in order to cover the target volume. Implantation was then carried out under local anaesthetic using 3D projections of the catheter inlets and outlets. Dosimetry was performed on post-implantation CT scan. A dose of 34Gy was delivered in 10 fractions. Acute and late side effects, and local control were evaluated 2 and 8 months after treatment. ResultsBetween July 2017 and January 2020, 20 patients were treated with accelerated partial breast irradiation. Dose constraints regarding target volume coverage, overdose, dose homogeneity, conformation index and organs at risk were met in 94.7%, 100%, 63.2%, 0% and 89.5% of the treatment plans, respectively. Grade 1-2 acute adverse events were observed in 21% of patients, with no grade 3-4 events. ConclusionThe first dosimetric results and early clinical tolerance and efficacy achieved by the implementation of breast interstitial multicatheter brachytherapy in routine clinical practice are very encouraging, and confirm the interest of extending this practice.

Quality of life and Comprehensive Geriatric Assessment (CGA) in older adults receiving Accelerated Partial Breast Irradiation (APBI) using a single fraction of Multi-Catheter Interstitial High-Dose Rate Brachytherapy (MIB). The SiFEBI phase I/II trial

ObjectivesThe SiFEBI trial demonstrated that a post-operative Multicatheter Interstitial Brachytherapy (MIB) appears feasible and with acceptable toxicity in older adults aged 70 years and older presenting with low-risk breast cancer. The aim of the present ancillary study was to analyze the quality of life and Comprehensive Geriatric Assessment (CGA) domains within 6 months in older adults receiving Accelerated Partial Breast Irradiation (APBI) using a single fraction of MIB. Materials and MethodsFrom 11/2012 to 09/2014, 37 patients were included and 26 were evaluable. Patients (pts) aged 70 years and older with a Balducci score of 1 or 2 and presenting with low-risk breast cancer were prospectively enrolled in this phase I/II trial (NCT01727011). After lumpectomy, intra-operative catheter implantation was performed for post-operative APBI after pathological findings. Quality of life (QoL) evaluation and CGA were scheduled at baseline and 1, 3, and 6 months after APBI. Autonomy decline was defined as a 1-point decrease in Activities of Daily Living (ADL). ResultsMean age was 77 years. Within the first 6 months of follow-up, no autonomy decline was observed in ADL, 3 patients had an autonomy decline in Instrumental Activities of Daily Living (IADL) and 2 patients had a slower gait speed but no changes in cognitive function, nutritional status, and depression screening. Global QoL was quite similar at baseline compared to 1, 3, and 6 months. No differences were observed for functional items. ConclusionAPBI based on a single fraction of MIB in older adults with low-risk breast cancer appears to be feasible with a minimal loss of autonomy regarding IADL, no loss of autonomy in ADL, an acceptable decrease in other CGA domains, and with no impact on global quality of life.