Rectum D2cc Research Articles

Dosimetric evaluation of adaptive planning for five-fraction gynecologic template-based interstitial brachytherapy

Purpose: The purpose of this work was to evaluate whether inter-fraction imaging and replanning enhance treatment delivery adherence to clinical planning objectives in the context of a 5-fraction template-based interstitial brachytherapy (TISB) approach for gynecologic cancer treatment. Methods and Materials: This retrospective study analyzed nineteen patients who underwent five fractions of interstitial brachytherapy over three days using the Syed-Neblett template. A verification CT scan was acquired for applicator assessment and reviewed by a radiation oncologist and medical physicist before each fraction. Eleven patients required replanning at least once during the treatment course. Replanning on the verification CT scan consisted of generating new target and organ-at-risk contours, digitizing catheter positions, and optimizing source dwell times to meet planning objectives. Dwell times and positions from the initial treatment plan were evaluated on the new contours to assess the dose that would have been delivered without replanning (non-adapted). Significance of non-adapted versus adapted dose differences were evaluated using a two-sided Wilcoxon sum rank test. Results: The average (min, max) change in dose (Gy) between the clinically delivered plans and the non-adapted plans were HR-CTV D90%: -6.5 (-0.6, -15.1), HR-CTV D98%: -6.5 (-0.4, -12.6), Bladder D2cc: -0.5 (0.0, -2.8), Bowel D2cc: -0.8 (0.0, -3.2), Rectum D2cc: -1.1 (0.0, -11.5), Sigmoid D2cc: -1.4 (-0.1, -5.4). Dosimetric changes in HR-CTV coverage were significantly improved with replanning while organ-at-risk differences were nonsignificant (p>0.05). Fraction 3 was the most common fraction indicated for replanning. Conclusions: Replanning template-based interstitial brachytherapy can improve target coverage and adherence to planning goals.

169Yb-based high dose rate intensity modulated brachytherapy for focal treatment of prostate cancer

PurposeThis study compares conventional 192Ir-based high dose rate brachytherapy (HDR-BT) with 169Yb-based HDR intensity modulated brachytherapy (IMBT) for focal prostate cancer treatment. Additionally, the study explores the potential to generate less invasive treatment plans with IMBT by reducing the number of catheters needed to achieve acceptable outcomes. Methods and MaterialsA retrospective dosimetric study of ten prostate cancer patients initially treated with conventional 192Ir-based HDR-BT and 5-14 catheters was employed. RapidBrachyMCTPS, a Monte Carlo-based treatment planning system was used to calculate and optimize dose distributions. For 169Yb-based HDR IMBT, a custom 169Yb source combined with 0.8 mm thick platinum shields placed inside 6F catheters was used. Furthermore, dose distributions were investigated when iteratively removing catheters for less invasive treatments. ResultsWith IMBT, the urethra D10 and D0.1cc decreased on average by 15.89 and 15.65 percentage points (pp) and the rectum V75 and D2cc by 1.53 and 11.54 pp, respectively, compared to the conventional clinical plans. Similar trends were observed when the number of catheters decreased. On average, there was an observed increase in PTV V150 from 2.84 pp with IMBT when utilizing all catheters to 8.83 pp when four catheters were removed. PTV V200 increased from 0.42 to 2.96 pp on average. Hotspots in the body were however lower with IMBT compared to conventional clinical plans. Conclusions169Yb-based HDR IMBT for focal treatment of prostate cancer has the potential to successfully deliver clinically acceptable, less invasive treatment with reduced dose to organs at risk.

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.

Preliminary results of adjuvant image-guided vaginal brachytherapy alone for early stage endometrial carcinoma

ObjectiveThis retrospective study evaluated the preliminary outcomes of image-guided vaginal brachytherapy (IG-VBT) in the adjuvant treatment of high intermediate risk endometrial cancer. Materials and MethodsData were collected from 48 patients who underwent adjuvant IG-VBT between 2019 and 2022 at the Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chiang Mai University. The vaginal cuff clinical target volume (CTV-VC) is composed of a 4-mm-thick band around vaginal cylinder at the upper 3 cm of the vaginal cuff. A total dose of 21 Gy in three fractions was delivered to the CTV-VC, and the dose to the bladder and rectum were evaluated. Treatment details, patient characteristics, and outcomes were analyzed. Descriptive statistics were used for analysis, and Kaplan-Meier method was employed for survival analysis. ResultsThe mean age was 62 years, with mainly endometrioid carcinoma pathology (96 %). All patients were at stage I, with 87.5 % receiving complete surgical staging. Mean total treatment time was 10 days with mean D90 of CTV-VC was 29.7 Gy, and D2cc of bladder, rectum, and sigmoid were 24.6 Gy, 21.0 Gy, and 7.7 Gy, respectively. At a median follow-up of 37 months, 3-year local control, disease-free survival, and overall survival rates were 100 %, 100 %, and 97.9 %. respectively. Two patients (4.2 %) experienced grade 1–2 gastrointestinal toxicity, while no genitourinary toxicity or serious adverse events were observed. ConclusionsThe preliminary results of IG-VBT in endometrial cancer demonstrated favorable outcomes in terms of vaginal control and toxicity. Further studies with larger cohorts and longer follow-up durations are warranted.

A randomized trial evaluating a novel hydrogel packing system compared to standard packing during image-guided high-dose rate brachytherapy boost for cervical cancer

INTRODUCTIONThe purpose of this prospective randomized trial was to compare the use of a novel vaginal hydrogel packing system (BrachyGel) to standard vaginal packing (VP) during high dose rate (HDR) brachytherapy (BT) for locally advanced cervical cancer (LACC). METHODSThis cross-over study included LACC patients receiving HDR BT boost (intracavitary +/- interstitial). All patients received alternating gauze or BrachyGel VP on Arms A and B. Patients, physicians, and physicists evaluated BT characteristics via a 4-point Likert scale. Adverse events (AEs) were prospectively collected and scored per CTCAE. RESULTSThe 20 patients enrolled. The mean bladder D2cc difference between gauze and BrachyGel in Arm A was 0.117 Gray (Gy) and in Arm B 0.013 Gy. The mean difference in rectum D2cc in Arm A and Arm B was -0.189 Gy and -0.191 Gy, respectively. The mean dose to 90% of the high-risk clinical target volume (HR-CTV) for gauze compared to BrachyGel was -0.032 Gy (95% CI: 0.472, 0.409). Patient-reported discomfort was similar with BrachyGel and gauze (“mild/moderate” 70.0% vs 74.0%, respectively). The clarity of VP was similar between BrachyGel and gauze (86.8% vs 89.7%, respectively). The completeness of VP was more frequently “excellent/good” with BrachyGel (79.0%) compared to gauze (56.4%). The ease of packing was more frequently “extremely easy” with BrachyGel (21.2% vs 0%). No serious AEs were reported. CONCLUSIONThis randomized trial found no clinically significant difference in OAR or HR-CTV dosimetry between BrachyGel and standard VP. BrachyGel performed well compared to gauze for the patient and physician use experience.

Radiochemotherapy and interstitial brachytherapy for cervical cancer: clinical results and patient-reported outcome measures

ObjectiveTo evaluate clinical results and long-term patient-reported outcome measures (PROMs) on quality of life in cervical cancer patients following radiochemotherapy (RCT) and brachytherapy (BT) as definitive treatment.Materials and methodsBetween 2003 and 2023, a total of 132 patients with advanced cervical cancer were evaluated for possible treatment. Patients treated by postoperative RCT, palliative radiotherapy, and those treated for recurrent disease were excluded. Thus, 46 patients receiving standard RCT and BT as their curative treatment were included in this study. PROMs were assessed prospectively by patients’ self-completion of the EORTC-QLQ-C30 and EORTC-QLQ-CX24 questionnaires.ResultsFive-year overall survival (OS), distant metastases-free survival (DMFS), and pelvic tumor-free survival rates (PTFS) were 53%, 54%, and 83%, respectively. A significant impact on OS was seen for FIGO (International Federation of Gynecologic Oncology) stage (IIB–IIIA: 79% vs. IIIB–IVA: 33%, p = 0.015), for overall treatment time (OTT; 50–65 d: 64% vs. > 65 d: 38%, p = 0.004), and for rectal D2cc (≤ 73 Gy: 50% vs. > 73 Gy: 38%, p = 0.046). The identical parameters were significantly associated with DMFS (FIGO stage: p = 0.012, OTT: p = 0.008, D2cc: p = 0.024). No parameters with a significant influence on PTFS were seen. In multivariate analysis, an impact of FIGO stage on OS (p = 0.05) and DMFS (p = 0.014) was detected, and of rectal D2cc on DMFS (p = 0.031). The overall QoL score was 63/100. Cognitive function was the least impaired (84/100), while role functioning was the worst (67/100). On the symptom scale, insomnia (46/100), fatigue (41/100), dyspnea (32/100), pain (26/100), and financial difficulties (25/100) were scored the worst. According to EORTC-QLQ-CX24, peripheral neuropathy (36/100) and lymphedema (32/100) occurred most frequently. Impaired sexual/vaginal functioning (32/100) and body image (22/100) were also frequently recorded.ConclusionIn patients with advanced cervical cancer, a combination of RCT and BT remains an excellent treatment option. In terms of patient-reported long-term quality of life, specific support is needed to alleviate symptoms including lymphedema, peripheral neuropathy, and impaired sexual activity.

Outcome and toxicity of chemoradiation using volumetric modulated arc therapy followed by 3D image-guided brachytherapy for cervical cancer: Vietnam National Cancer Hospital experience.

Volumetric modulated arc therapy (VMAT) and 3D image-guided brachytherapy (3D-IGBT) have recently been introduced in Vietnam for the treatment of locally advanced cervical cancer. This study aims to assess the outcomes and toxicities of chemoradiation using VMAT followed by 3D-IGBT in Vietnamese cervical cancer patients. A prospective interventional study on 72 patients with 2018 International Federation of Gynecology and Obstetrics (FIGO) stage IB3-IIIC2 disease who underwent concurrent chemoradiation using VMAT, followed by 3D-IGBT according to EMBRACE-II protocol. Primary endpoints were locoregional control; secondary endpoints were systemic control and toxicity. Median body volume received 43 Gy was 1589.1 cm3 (range 1214.8-2574.8). Median high-risk clinical target volume (CTV-HR) was 18.8 cm3 (range 8.6-61.2) with a median dose to 90% (D90) of CTV-HR of 90.6 Gy (range 86.8-99.6). Mean doses to 2cc (D2cc) of bladder, rectum, and sigmoid were 75.8, 55.2, and 62.1 Gy, respectively. At median 19-month follow-up (range 12-25), locoregional control and systemic control were 95.8% and 81.9%, respectively. Systemic control was the lowest in N2 disease (54.5%). Grade ≥ 3 acute toxicities were less than 10%, except neutropenia (31.9%). Extended-field radiation increased significantly nausea, fatigue, and thrombocytopenia. No grade ≥ 3 proctitis or cystitis; 8.3% had grade 3 vaginal stenosis. VMAT-based chemoradiation therapy followed by 3D-IGBT achieved high locoregional control with manageable toxicities in locally advanced cervical cancer. Systemic control correlated with disease stage.

Fletcher suit or ring: A comparison of Fletcher suit and ring applicators for retroverted uteri.

Approximately 20% of women worldwide have a retroverted uterus. A retroverted uterus is closer to the rectum and may cause toxicity during brachytherapy. Upon manipulation, a small percentage turn anteverted. Conventional brachytherapy applicators are designed for an anteverted uterus and can pose issues during insertion. Modified Fletcher suit and ring applicators have major differences in their geometry to achieve similar target coverage, and were analyzed in this study with respect to immediate adverse events and dosimetry. Three hundred seventy-four consecutive applications performed over a 20-month period were studied retrospectively to identify intra-cavitary applications (ICAs) in retroverted uteri. Cases were divided into 2 groups: modified Fletcher suit applicator with hemi-ovoids (group A) and ring applicator (group B). D2cc for bladder and rectum were noted, and acute adverse events were recorded. Seventy-five applications were identified, out of which 47 cases used Fletcher suit applicator, and 28 cases used ring applicator. The median bladder D2cc for group A and B were 5.98 Gy and 6.3 Gy, respectively, and the median rectum D2cc was 5.27 Gy and 3.68 Gy, respectively; the median dose prescribed to point A was 6 Gy (range, 5.5-9.0 Gy). All patients had a point A coverage between 97% and 102%. Eighteen cases in both groups complained of pain requiring analgesics. Twenty-five cases (53.2%) and 20 cases (71.4%) in group A and B, respectively, required dose optimization, which was statistically insignificant (p > 0.11). A significant difference was identified (p < 0.00001) in rectal doses. A higher reported pain was noted in ring applicator group (p < 0.03). No patient experienced a profuse bleeding. In most parameters, the two applicators demonstrated comparable results. The control of rectal dosage is superior in the ring applicator at the cost of higher pain incidence. Patient's comfort and rectal dose in EBRT should be taken into consideration, with preference given to the ring applicator.

A unified strategy to focal brachytherapy incorporating transperineal biopsy, image fusion, and real-time implantation with and without rectal spacer simulated in prostate phantoms.

To develop an approach to the diagnosis and treatment of prostate cancer using one platform for fusion biopsy, followed by focal gland ablation utilizing permanent prostate brachytherapy with and without a rectal spacer. Prostate phantoms containing multiparametric magnetic resonance imaging (mpMRI) regions of interest (ROI) underwent fusion biopsy, followed by image co-registration of positive sites to a treatment planning brachytherapy program. A partial hemi-ablation and both posterior lobes using a Mick applicator and linked stranded seeds were simulated. Dummy sources were modeled as iodine-125 (125I) with a prescribed dose of at least 210 Gy to gross tumor (GTV) and clinical target volume (CTV), as defined by mpMRI visible ROI and surrounding negative biopsy sites. Computer tomograms (CT) were performed post-implant prior to and after rectal spacer insertion. Different prostate and rectal constraints were compared with and without the spacer. The intra-operative focal volumes of CTV ranged from 6.2 to 14.9 cc (mean, 11.3 cc), and the ratio of focal volume/whole prostate volume ranged between 0.19 and 0.42 (mean, 0.31). The intra- and post-operative mean focal D90 of GTV, CTV, and for the entire prostate gland was 265 Gy and 235 Gy, 214 Gy and 213 Gy, and 66.1 Gy and 57 Gy, respectively. On average, 13 mm separation was achieved between the prostate and the rectum (range, 12-14 mm) on post-operative CT. The mean doses in Gy to 2 cc of the rectum (D2cc) without spacer vs. with spacer were 39.8 Gy vs. 32.6 Gy, respectively. Doses above 200 Gy and the implantation of seeds in clinically significant region for focal therapy in phantoms are feasible. All rectal dosimetric parameters improved for the spacer implants, as compared with the non-spacer implants. Further validation of this concept is warranted in clinical trials.

Safe dose escalation and reduction of the fraction number of uterine cervical brachytherapy using a gel spacer in the rectovaginal and vesicouterine septum: A planning study

PURPOSETo evaluate the possibility of dose escalation and reduction of fraction number in cervical brachytherapy using a gel spacer. MATERIAL AND METHODSTwenty patients with uterine cervical cancer treated with image-guided adaptive brachytherapy (IGABT) were selected. Hyaluronic acid gel injection (HGI) was performed in the rectovaginal and vesicouterine septum for 10 patients. The other ten patients were not with HGI. Both groups were treated with IGABT involving tandem/ovoid or cylindrical applicators along with additional interstitial needles. Dose distributions approved by radiation oncologists were retrospectively analyzed, and a dose summation of 45 Gy/25 of external beam radiation therapy and IGABT was performed. Dose constraints for D2cc of bladder, rectum, and sigmoid were 80, 70, and 70 Gy, respectively. Equivalent dose in 2-Gy fractions calculations used α/β = 10 Gy for high-risk clinical target volume (CTVHR) D90 and α/β = 3 Gy for organs at risks (OARs). As a planning study, dose distribution rescaling was conducted to deliver as much dose to CTVHR D90 as possible within the dose constraint limitation for OARs when IGABT was performed for four, three, and two fractions in both groups. RESULTSThe median CTVHR D90 was >80 Gy in the non-HGI group and >85 Gy in the HGI group for virtual two and three fractions. Rectum D2cc was significantly lower in the HGI group for three fractions (p < 0.01). CONCLUSIONSIn the HGI group, adequate dose delivery to CTVHR could be achieved with a reduced IGABT fraction number while meeting the dose constraints of OARs.

Vaginal Dose Reduction by Changing the Ovoid Loading Pattern in Image Guided Intracavitary Brachytherapy of Cervix.

Locally advanced cervical cancer is frequently treated using a combination of external beam radiotherapy and brachytherapy. Radiotherapy often leads to vaginal morbidity, which poses a significant problem. This study aims to analyze the impact of reducing ovoid loading on dosimetry. We analyzed forty-five CT-based intracavitary brachytherapy plans from fifteen patients. Three plan sets were created for the 45 applications: a standard loading plan (A), a plan with reduced ovoid loading (B), and a tandem-only loading plan (C). We generated Dose-Volume Histograms and recorded dose volume parameters for the three plan sets. The D90 for the Clinical Target Volume (CTV) did not show significant differences among the three plan sets (p = 0.20). The average D90 values for plans A, B, and C were 8.15Gy, 8.16Gy, and 7.4Gy, respectively. No statistically significant differences were observed in D2cc bladder (p = 0.09) (average values: 6.8Gy, 6.5Gy, and 5.9Gy for plans A, B, and C, respectively) and D2cc sigmoid (p = 0.43) (average values: 2.8Gy, 2.6Gy, and 2.4Gy, respectively) among the three plan sets. However, there was a statistically significant difference in D2cc rectum (p < 0.001) (average values: 4Gy, 3.3Gy, and 1.8Gy, respectively), as well as in vaginal dose points (p < 0.001). Reducing ovoid loading significantly decreased the doses to vaginal dose points and the rectum without compromising the dose to the Clinical Target Volume (CTV). Therefore, in carefully selected cases, the adoption of tandem-only loading or reduced ovoid loading could be considered to minimize vaginal morbidity following high dose rate intracavitary brachytherapy.

Dosimetric Investigation of Interstitial Versus Combined Interstitial with Intracavitary High Dose Rate Brachytherapy for Cervical Cancer

The purpose of the study was to evaluate clinical target (HR-CTV) coverage and OAR doses of ISBT and IS-ICBT brachytherapy techniques for cervix cancer. As this is a retrospective study, 11 patients treated from 2018 to 2022 were identified, ISBT (n=4) and IC-ISBT (n=7). Dose-volume histogram (DVH) from Oncentra Treatment Planning System and dosimetric parameters were analyzed and evaluated.The results showed the mean EQD2 of HR-CTV for both techniques were 89.1 ± 11.71 Gy while the mean EQD2 of D2cc for bladder, rectum and sigmoid were 88.9 ± 16.71 Gy, 81.2 ± 12.63 Gy, and 70.1 ± 15.95 Gy, respectively. For IC-ISBT technique, the mean EQD2 of HR-CTV was 91.5 ± 8.4 Gy which was slightly exceeds the dose constraints of 80 to 90 Gy based on ABS recommendation. HR-CTV volume that ranged from 34.93 - 168.33 cm3. The mean of CI was 0.90 and the mean of DHI for this technique was 0.36 ± 0.06. Meanwhile for ISBT technique, the mean HR-CTV volume range from 26.95 - 82.82 cm3. The mean EQD2 of HR-CTV was at 85.1 ± 16.75. The mean CI and DHI were at 0.85 ± 0.16 and 0.37 ± 0.1, respectively. As a conclusion, the mean EQD2 doses to the rectum (81.2 Gy) in both techniques slightly exceeded the limit from ABS recommendation. The mean DHI value was not quite significant different in both techniques. However, the IS-ICBT technique was more superior in conforming dose to HR-CTV based on higher CI value compared to ISBT alone.

Dosimetric Parameters Predictive of Treatment-Related Toxicity in High Dose-Rate Brachytherapy as Monotherapy for Prostate Cancer.

High dose-rate (HDR) brachytherapy as monotherapy is an effective treatment for patients with low- and intermediate-risk prostate cancer and is increasingly being offered as a 2-fraction protocol. There is a lack of consensus on the optimal dosimetric planning parameters to use, or whether there is any benefit summating dosimetric parameters from more than one implant. Our goal is to determine planning parameters associated with disease control, toxicity and health-related quality of life (HRQOL). Data were collected on 83 patients with low- and intermediate-risk prostate cancer who received 2 fractions of 13.5 Gy HDR brachytherapy without androgen-deprivation therapy as part of a randomized phase II clinical trial. An in-house deformable, registration algorithm was used to co-register and dose-summate the plans from both implants for each patient. Acute and late GU and GI toxicities were measured using CTCAE 4.0 and HRQOL was measured in urinary, bowel, sexual and hormonal domains using the EPIC scores. Treatment efficacy was assessed through PSA measurement and imaging with or without biopsy where indicated. Covariates included baseline clinical factors, disease characteristics and treatment dosimetric parameters. Cox proportional hazards was performed to evaluate covariates impact on treatment toxicity and efficacy, and logistic regression analysis evaluated covariates impact on HRQOL. Among the 83 patients, median prostate volume was 46.7cm3. Median summated planning target volume receiving 100% prescription dose (PTV V100%) was 97.4%, median PTV V150% 42.4% and median PTV V200% 15.5%. Median highest dose to the 1cm3 rectum (D1cc) was 66.9% of the prescription dose and median rectum V80% was 0.008cm3. Median urethral D1cc was 99.0% of the prescription dose, median urethral Dmax 121.7% and median urethral D10% 116.2%. Grade ≥2 GI toxicity was uncommon (3.7% acute and 8.5% late), but grade ≥2 GU toxicity was reported in 73.2% (acute) and 46.3% (late) patients. Rectum D1cc and V80% were found to be significantly associated with grade 2 or higher acute GI toxicity, while use of a-blocker at baseline was associated with grade ≥2 acute GU toxicity. Similarly, use of a-blocker was associated with late grade ≥2 GU toxicity, but with no dosimetric associations. No other variables were associated with treatment-related toxicities. Only rectum D1cc was significantly associated with changes in bowel EPIC scores. Estimated 5-year biochemical disease-free survival was 93.9% and 5-year cumulative incidence of local failure was 3.8%. HDR monotherapy with 27 Gy delivered in 2 fractions in treatment of prostate cancer is well tolerated with high rates of disease control and minimal toxicity. Dose summation between 2 fractions of HDR brachytherapy is feasible, with rectal dose predicting acute GI toxicity. The lack of association between dose metrics and urinary toxicity raises the potential for further dose escalation.

Assessing Displacement of Plastic Interstitial Catheters in Image-Guided Gynecological HDR Brachytherapy

Interstitial HDR brachytherapy involves precise, localized delivery to targets with high dose gradients, sparing adjacent organs at risk. Due to the proximity of the rectum and bladder to the target, deviations in the catheters with respect to patient anatomy can change dose to those structures. While utilizing plastic interstitial catheters allows the patient to receive hyperthermia therapy during their course of interstitial treatment, the plastic catheters were observed to show significant deflection when the metal stylets are removed for treatment. The hyperthermia electrodes and the HDR source cable are both wires of approximately the same thickness. The purpose of this study is to assess the magnitude and deflection of the plastic catheters for gynecologic interstitial plans and determine whether using flexible wires for visualization on pre-treatment imaging is suitable for reconstructing the actual treatment received. Pre-treatment CT images where the stylets were utilized for catheter visualization were registered to a subsequent CT scan with the metal stylets removed. The original treatment dwell positions were adjusted to the second CT to evaluate 3D catheter displacement and dose distributions calculated for the bladder, rectum, and target. The plans were subsequently reconstructed on a pre-planning CT with flexible 20-gauge wires instead of metal stylets to determine their suitability as a surrogate for stylets. Absolute 3D displacement for all patients was 3.5 ± 5.4 mm (n = 3433 catheter dwell positions, mean ± SD, p < 0.001) comparing plans with the stylet in versus out. Absolute catheter deflection for interstitial treatments increased with the removal of the metal stylets with a difference of 0.75 ± 0.49° (n = 313 catheters, mean ± SD, p < 0.01). The plans utilizing flexible wire instead of stylets are observed to correlate with the plans with no stylets with absolute 3D displacement and angular deflection of 1.1 ± 0.6 mm and 0.35° ± 0.3° respectively (n = 39 catheters, mean ± SD, p > 0.2). While the average target EQD2 D90 reduced by 5% ± 5% by planning without the stylets, four patients would have experienced a deviation from the prescription by >10%. There was an overall decrease in bladder D2cc and overall increase in rectal D2cc in the plans with the stylets utilized vs removed. Bladder D2cc, rectal D2cc, and target coverage showed no appreciable difference between utilizing flexible wires and the plans without. The difference in HU between the metal stylets and flexible wires was negligible. Catheter reconstruction in interstitial gynecological treatments with CT imaging revealed significant changes in catheter positioning with respect to the target volume once the stylets are removed for treatment. Using flexible wires of similar thickness to the source cable allow for more accurate tracking during planning without distorting the patient's anatomy or the treatment images, preserving the integrity of the treatment plan.

Feasibility of Using a Single Planning MRI for Two-Insertion Intracavitary Brachytherapy for Cervical Cancer

MRI is an essential tool in treatment planning for cervical cancer patients undergoing definitive chemoradiation involving brachytherapy. However, due access to MRI for many patients may be limited. We sought to examine the feasibility and quality of treatment planning for organs at risk (OAR) and target volumes of a single treatment planning MRI for a planned two-insertion HDR intracavitary cervical brachytherapy. Eighteen patients with cervical cancer who underwent MRI-based treatment planning for intracavitary brachytherapy were selected for analysis. Patients underwent two intracavitary applicator insertions using a tandem and ring applicator (TnR_1 and TnR_2) with both CT (for digitization only) and MRI following each insertion and two fractions delivered with each insertion (total 7 Gy x 4fx). MRI-based TnR_2 plans were retrospectively replanned with the following procedure: 1) register MRI from TnR_1 to TnR_2 CT, 2) transfer cervix contour (Cx_simul) and plan from TnR_1 to TnR_2 CT, simulating blinding from TnR_2 MRI, 3) crop Cx_simul from TnR_2 OARs, 4) adjust plan only to meet OAR constraints or clinical doses if clinical plan (TnR_2 original MRI plan summed with TnR_1 and EBRT doses) violates constraints. Coverage changes (∆_D90%) in actual MRI defined TnR_2 cervix (Cx_real) was compared to clinical plans and evaluated against our clinical target goal: >85 Gy EQD2 (EBRT+BT). Differences between Cx_simul and Cx_real contours were evaluated with Dice Similarity Coefficient (DSC). Changes in bladder, rectum, rectosigmoid, and bowel D2cc was evaluated. Procedure time was recorded to determine time added by MRI (time between CT and final MRI timestamps; n = 29). Plan modification to meet OAR constraints was required for 5/18 plans. Cx_real target coverage from clinical to simulated plans decreased in 7/18 plans (∆_D90% = 1.7±6%). Composite EQD2 was <85 Gy in 2/18 cases, with ∆_D90% of -1.3% (clinical EQD2<85 Gy for this case also) and -7.3%, which was due to inconsistent cervix shape between insertions 1 and 2. Cervix DSC values between Cx_simul and Cx_real ranged from 0.68-0.88 (mean = 0.78 ± 0.06). Bladder, rectum, rectosigmoid, and bowel D2cc increased on average 4 ± 12%, 3 ± 9%, 5 ± 10%, and 5 ± 17%, respectively. Including planning MRI increased procedure time by 41.8 ± 10.4 min. The proposed method of utilizing TnR_1 MRI contours for TnR_2 CT planning reduces procedure time and provides reasonable target coverage for most cases. OAR assessment varies between imaging modality which likely represents variability in OAR position rather than treatment planning modality. Next steps are to increase patients studied, and implement this technique prospectively while waiting for TnR_2 MRI completion and compare the clinical TnR_2 MRI plan with the TnR_2 CT plan created with Cx_simul. This will provide further confidence in validity of the approach and ensure plan quality is maintained prior to full implementation.

Can Volume-Based MRI-Guided Planning for Interstitial Gynecologic Brachytherapy Overcome Clinicopathologic Risk Factors for Fistula Formation?

Tumor and patient factors requiring an interstitial (IS) approach for gynecologic tract brachytherapy (BT) may be associated with high morbidity despite the conformality maximizing effect of ISBT. We reviewed outcomes from a diverse, high-volume center to evaluate the association of clinical features and planning parameters with toxicity, with the hypothesis that MRI-guided volume-based planning mitigates clinicopathologic risk factors associated with treatment related fistula (TRF) after ISBT. We retrospectively reviewed patients treated with Syed-based ISBT at a single institution from 2014-2019. Fisher's exact was used for group comparison with p<0.05. Kaplan-Meier method was used to estimate local control (LC), overall survival (OS), and fistula-free survival (FFS). Cox regression was used for univariate (UVA) and multivariate analysis (MVA) to estimate hazard ratios (HR). Collinearity was assessed using variable inflation factor and Pearson's correlation. A total of 54 patients (median age 58 [IQR 46-67], 54% Caucasian, 39% African American, 15% Hispanic) treated with ISBT (89% MRI-guided) with median follow-up 32 months had initial (89%) or recurrent (11%) disease from cervical (70%), vaginal (15%), urethral (6%), and other cancers. At presentation 5.5% had clinically evident fistula. There was radiographic rectal and bladder involvement in 22.0% and 19.2%, respectively. 89% received concurrent chemotherapy and 98% received EBRT prior to ISBT with a cumulative median high-risk CTV (HRCTV) dose 80.8 Gy (IQR 76.8-84.3), bladder D2cc 84.3 Gy (IQR 75.8-89.0), and rectal D2cc 73.8 Gy (IQR 67.7-80.0 Gy). All 7 patients who developed a TRF (rectovaginal in 6/7 and vesicovaginal in 5/7) were former or current smokers, had primary cervical cancer, and received chemotherapy. Management included surgical intervention in 6 (85.7%). LC, OS, and FFS at 2-years was 89.3% (95% CI 75.9-95.4%), 87.8% (95% CI 66.9-89.8%), and 85.2% (95% CI 69.9-93.1%), respectively. On UVA, current smoking (HR 4.60, 95% CI 1.02-20.74), BT bladder D2cc (HR 1.63, 95% CI 1.07-2.47) and BT rectal Dmax (HR 1.30, 95% CI 1.07-1.58) predicted for increased risk of TRF. Most factors were non-significant including Charlson Comorbidity Index, age, BMI, surgical history, extent of vaginal involvement, race, HRCTV volume and number of needles used. No patients with radiographic bladder or rectal invasion developed TRF. On MVA, only smoking status (HR 14.05, 95% CI 1.48-133.1) remained significant. 0% of never (0/26), 20% of former (3/15) and 31% of current (4/13) smokers developed fistulas from toxicities (p<0.05). In patients with locally advanced cancers of the gynecologic tract treated with MRI-guided volume-based ISBT, smoking was the only factor predictive of TRF formation, occurring primarily in cervical cancer patients. This highlights the importance of smoking cessation during treatment and appropriately counseling patients at high risk for this morbidity.

A Comparison of Two Plan Optimization Methods in Three-Dimensional Brachytherapy for Cervical Cancer

To compare dose distributions created by using two Inverse Planning Simulated Annealing (IPSA) and Hybrid Inverse Planning Optimization (HIPO) in three-dimensional (with CT image guidance) brachytherapy planning for cervical cancer. Brachytherapy plans for thirty patients with cervical cancer were created using the IPSA and HIPO algorithms (The IPSA algorithm is calculated based on the anatomical structure, and the simulated annealing algorithm is used to optimize the residence time, and the HIPO algorithm is the optimization and replacement for the IPSA). To obtain a HIPO plan, a manually optimized post-loading treatment plan was applied to these 30 patients, and then the treatment plan was reoptimized using the HIPO algorithm based on the original image information. Individual patients will consider interpolation therapy according to the needs of their condition. The types of plans were compared based on a variety of dose volume parameters, including the mean dose covering 90% of high-risk clinical target volume (D90 for HR-CTV), the mean dose to 2 cm3 volume (D2cc) for bladder, rectum, intestine and sigmoid, and average treatment time were compared and analyzed. Compared with the two groups of plans, mean value of HR-CTV D90 for the HIPO plans was (585 cGy), which was significantly higher than that for the IPSA plans (567 cGy. This difference is statistically significant (P<0.05). The HIPO plans had mean D2cc 422±47 cGy for bladder, 403±38 cGy for rectum, which were lower than those from the SA plans, i.e., 446±42 cGy for bladder and 427±31 cGy for rectum; These differences were statistically significant (t = 5.125, 4.729, P <0.05). There was no statistically significant difference in the sigmoid D2cc doses between the two algorithms. The treatment times for delivering the two types of plans were not significant different. Depending on patient's condition, whether conventional brachytherapy therapy or interpolation therapy is used, the use of the HIPO algorithm to design the treatment regimen without additional treatment time can provide a higher target dose than the manually optimized brachytherapy regimen. Meanwhile, the bladder and rectum doses can be reduced to a certain extent under the premise of ensuring that the target dose met the treatment requirements. There is some increasement for the intestine dose with HIPO planning group, but the dose limits required by the guidelines are still met clinical requirement.

Clinical Outcomes of Sidewall/Parametrial Simultaneous Integrated Boost for Patients with Cervical Cancer

In the treatment of cervical cancer, simultaneous integrated boost (SIB) is a common technique to deliver increased dose to gross disease in the para-aortic and pelvic nodal basins. However, SIB to the pelvic sidewall/parametria is not well characterized in the literature. We hypothesized that sidewall simultaneous integrated boost (SIB) in the treatment of cervical cancer is associated with acceptable levels of toxicity. From 1/2009-12/2018, patients who received concurrent chemoradiation with external beam radiation therapy, utilizing a sidewall SIB technique, followed by low dose rate or high dose rate brachytherapy treatment were retrospectively identified. Sidewall SIB was defined as treatment at 2.1-2.4Gy/fraction to the parametria-usually performed for those with disease width >4cm at time of treatment start. Acute and late toxicity grading was defined by the Common Terminology Criteria for Adverse Events Version 5.0. Overall survival (OS), local control, progression-free survival (PFS), and toxicity were analyzed utilizing the Kaplan Meier method. Potential associations between cumulative D2cc for bladder and rectum and time to toxicity were investigated using Cox regression. Fifty-six patients with IB2-IVB cervical cancer treated with sidewall SIB were identified, with a median follow up of 7.0 years (95% CI: 6.3, 8.3). Patients had a median age of 43 years (range: 26-68); 2 (3.6%) had FIGO stage I, 7 (12.5%) stage II, 46 (82.1%) stage III, and 1 (1.8%) stage IV disease. A majority had squamous cell histology (83.9%). Nearly all patients (96.4%) received concurrent cisplatin chemotherapy. Rates of acute grade ≥3 gastrointestinal (GI), genitourinary (GU), vaginal, and hematologic toxicity were 1.8%, 1.8%, 0%, and 15.9% respectively. Rates of late grade ≥3 GI, GU, and vaginal toxicity were 11.3%, 18.5%, and 11.1% respectively. OS and local control rates at five years were 0.61 (95% CI: 0.46, 0.73) and 0.95 (95% CI: 0.84, 0.98), respectively. Median PFS was 7.8 years (95% CI: 2.4, Not reached). Cumulative D2cc bladder was not significantly associated with time to Grade 2 or greater (HR 1.04, p = 0.33) or Grade 3 or greater (HR 1.02; p = 0.64) GU toxicity. Cumulative D2cc rectum was not significantly associated with time to Grade 2 or greater (HR 1.06, p = 0.06) or Grade 3 or greater (HR 1.08; p = 0.09) GI toxicity. Sidewall SIB is a feasible technique for dose escalation in the treatment of cervical cancer with rates of acute and late toxicity consistent with other reports.

Brachytherapy Dose Prediction Based on Monte Carlo Simulations Using Artificial Neural Networks

The current brachytherapy dose calculation is still based on the oversimplified water kernel superposition algorithm recommended by AAPM TG43. Monte Carlo (MC) method provides high accuracy in dose calculation. However, the MC simulation is computationally intensive and too slow to use in the time-sensitive clinical workflow. This study aims to develop a fast neural network (SK-UNet) to predict 3D brachytherapy dose distribution calculated by the MC simulations. We hypothesize that the tracks of Ir-192 inside applicators are essential in dose map prediction and the Selective Kernel Networks (SK) can be employed to emphasize the contribution of the applicator in training. We then included SK in UNet to select appropriate receptive field sizes as needed. The network inputs were CT images of patient anatomy, binary masks of HRCTV, bladder, rectum, and source tracks, and the output was the predicted dose map. Totally, 120 cases were used for training and 30 for testing. All clinically common applicators (e.g., vaginal, tandem and ovoid, multi-channel applicator, free needles, etc.) were involved in the study. Model performance was evaluated by the mean absolute error (MAE) of DVH dosimetric metrics and dose distribution metrics between ground truth (GT) and prediction. A smaller MAE indicated a more accurate dose prediction. Dose distribution metrics include the overdose volume index (ODI), target conformity (TC), dose homogeneity index (DHI), and conformal index (COIN). GT was dose calculated by MC simulations. 3D Gamma analysis was also involved. As shown in Table 1, compared with GT, SK-Net showed comparable DVH dosimetric metrics with 0.28±0.19 deviation for HRCTV D90%, 0.21±0.16 deviation for bladder D2cc, and 0.25±0.22 deviation for rectum D2cc. In dose distribution metrics, the deviations between GT and prediction were TC = 0.04±0.02, ODI = 0.03±0.03, DHI = 0.02±0.02, and COIN = 0.02±0.03. The gamma passing rate was 93%±6%. The 3D dose map prediction for each patient takes about 6s on average in an NVIDIA GeForce RTX 3060 GPU compared to hours with MC simulations. SK-Net demonstrated comparable performance to the MC simulation but with a significantly shorter execution time, taking only 6 seconds on average. It offered a solution to the trade-off between accuracy and speed and has the potential to serve as an alternative to the time-consuming MC simulation in brachytherapy. The developed technique is believed to have the potential for future application with other types of radiation sources and cancers.

Per-fraction planning to enhance optimization degrees of freedom compared to the conventional single-plan approach.

&#xD;In conventional radiotherapy, a single treatment plan is generated pre-treatment, and delivered in daily fractions. In this study, we propose to generate different treatment plans for all fractions ('Per-fraction' planning) to reduce cumulative OAR doses. Per-fraction planning was compared to the 'Conventional' single-plan approach for non-coplanar 4x9.5 Gy prostate SBRT.&#xD;&#xD;Approach:&#xD;An in-house application for fully automated, non-coplanar multi-criterial treatment planning with integrated beam angle and fluence optimization was used for plan generations. For the Conventional approach, a single 12-beam non-coplanar IMRT plan with individualized beam angles was generated for each of the 20 included patients. In Per-fraction planning, four fraction plans were generated for each patient. For each fraction, a different set of patient-specific 12-beam configurations could be automatically selected. Per-fraction plans were sequentially generated by adding dose to already generated fraction plan(s). For each fraction, the cumulative- and fraction dose were simultaneously optimized, allowing some minor constraint violations in fraction doses, but not in cumulative.&#xD;&#xD;Main results:&#xD;In the Per-fraction approach, on average 32.9 ± 3.1 [29;39] unique beams per patient were used. PTV doses in the separate Per-fraction plans were acceptable and highly similar to those in Conventional plans, while also fulfilling all OAR hard constraints. When comparing total cumulative doses, Per-fraction planning showed improved bladder sparing for all patients with reductions in Dmean of 22.6% (p=0.0001) and in D1cc of 2.0% (p=0.0001), reductions in patient volumes receiving 30% and 50% of the prescribed dose of 54.7% and 6.3%, respectively, and a 3.1% lower rectum Dmean (p=0.007). Rectum D1cc was 4.1 % higher (p=0.0001) and Urethra dose was similar. &#xD;&#xD;Significance:&#xD;In this proof-of-concept paper, Per-fraction planning resulted in several dose improvements in healthy tissues compared to the Conventional single-plan approach, for similar PTV dose. By keeping the number of beams per fraction the same as in Conventional planning, reported dosimetric improvements could be obtained without increase in fraction durations. Further research is needed to explore the full potential of the Per-fraction planning approach.&#xD.