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CT angiography might be a suitable procedure to avoid arterial puncture in combined intracavitary and interstitial brachytherapy for cervical cancer curatively treated with combined chemoradiation and brachytherapy boost. Data in the literature about this technique are scarce. We introduced this method and collected brachytherapy data from patients treated in our department between May 2021 and April 2024. We analyzed the applicator subtype, needle insertion (planned versus implanted), implanted depth and the role of CT angiography in selecting needle trajectories and insertion depths. None of the patients managed through this protocol experienced atrial puncture and consequent hemorrhage. Needle positions were accurately selected with the aid of CT angiography with proper coverage of brachytherapy targets and avoidance of organs at risk. CT angiography is a promising method for guiding needle insertion during interstitial brachytherapy. [ABSTRACT FROM AUTHOR]

Treatment of recurrent oligometastatic gynecologic malignancy may involve targeted surgery, thermal ablation, or CT-guided high-dose-rate interstitial brachytherapy ablation (CT-HDR-IBTA). The purpose of this study was to describe the safety and efficacy of CT-HDR-IBTA for oligometastatic gynecologic malignancies. With institutional review board approval (IRB) approval and compliance with the Health Insurance Portability and Accountability Act of 1996 (HIPAA) compliance, we searched our database to assemble a single-arm study cohort of all patients with oligometastatic gynecologic cancers who underwent CT-HDR-IBTA from 2012–2022 with follow-up. The electronic record was reviewed to determine relevant clinicopathological variables including patient demographics, prior treatments, clinical course, local control, and local and distant recurrence with follow-up imaging. The study cohort comprised 37 lesions in 34 patients treated with CT-HDR-IBTA for recurrent oligometastatic uterine (n = 17), cervix (n = 1), or ovarian cancer (n = 16) with an average lesion size of 2.5 cm with an average patient age of 61.4 years. Each lesion was treated with an average radiation dose of 23.8 Gy in 1.8 fractions and a median follow-up time of 24.0 months. The primary efficacy of CT HDR ITBA was 73% with a median progression-free survival of 8.0 months (95% CI 3.6–12.8 months) and with 58% of patients still alive at 43 months with median overall survival not reached. The rate of Grade 1 adverse events was 22% without any Grade 2, 3 or 4 events. CT HDR IBTA was safe and effective for treating oligometastatic gynecologic cancers in a heavily pretreated cohort. [ABSTRACT FROM AUTHOR]

Interstitial gynecologic brachytherapy necessitates precise needle placement, requiring time and expertise. We aimed to simplify interstitial procedures and facilitate optimal needle distribution with individualized vaginal templates to guide interstitial needles. We developed the 3D-printed vaginal individualized applicator (VIA), a cylindrical template containing individualized internal channels that guide interstitial needles to cover the tumor extent. Eight patients underwent VIA only interstitial implants (VIA only), and five intact cervical cases were treated using tandem and customized VIA (VIA + T). Procedure length, number of needles utilized and dosimetric measures were evaluated. VIA was successfully designed and used clinically for 24 procedures (8 VIA only, 16 VIA + T). Average procedure needle insertion time reduced from 80.9 min for traditional interstitial to 42.9 min for VIA only, approximately 47% shorter with a similar mean high risk CTV volume (28.3 cc VIA only vs. 32.4 cc) and excellent dosimetry with average CTV V100% (94.3% and 94.4%). VIA + T was particularly useful in patients with small vaginal canals and large tumor size. For the five VIA + T patients average tumor size was 68.0cc (range 26.6–143.5 cc). VIA + T procedures were approximately 20% shorter than hybrid procedures with other applicators with mean length of 20.1 min and an average of 6.8 needles (range 3–12). Our novel 3D-printed VIA facilitates gynecologic interstitial brachytherapy by simplifying needle placement, reducing procedure time, and maintaining excellent dosimetry. VIA can be customized for various clinical scenarios, particularly beneficial for large tumors or small vaginal canals. [ABSTRACT FROM AUTHOR]

Objective: To develop and validate a novel scoring system for predicting the risk of uterine perforation during brachytherapy (BT) in cervical cancer patients and to stratify patients based on this score to guide the use of ultrasound guidance during BT. Methods: Fifty patients with uterine perforation during BT between January 2018 and December 2020 were included. Common reasons for perforation were identified and a scoring system was developed. This was then applied to a cohort of 50 patients without perforation. The 2 cohorts were compared using the χ² test. To validate the scoring system, all newly diagnosed patients who underwent BT in 2021 were scored, and analysed using χ2 test and receiver operator characteristic curves. Results: The mean score in the test cohort was 10.16 (range=7-14) and 5.92 (range=5-8) for patients with and without perforation. In the validation cohort, the mean score was 6.9 (range=5-10) and 9.33 (range=7-11) for those with and without perforation. Patients with a score <8 were classified as low risk, while those with a score =8 were classified as high risk. Among the criteria evaluated for validation, response to external beam radiotherapy, uterine position, cervico-uterine angle (uterine flexion), identification of cervical os at BT assessment, and the total score were significant predictors, while previous history of perforation, uterine length, and additional uterine anomaly were not. Conclusion: The novel scoring system is an effective predictor of perforation risk during BT. Implementing this during BT assessment can optimize the need for ultrasound guidance during the procedure. [ABSTRACT FROM AUTHOR]

Background: Image-guided adaptive brachytherapy (IGABT) demonstrates an excellent local control rate and low toxicity while treating cervical cancer. For intracavitary/interstitial (IC/IS) brachytherapy (BT), several applicators are commercially available. Venezia (Elekta, Sweden), an advanced gynecological applicator, is designed for IC/IS BT for treating locally advanced cervical cancer. There are two types of interstitial needles for the Venezia applicator: the round needle and sharp needle. Generally, a round needle is safer because it has less risk of damaging the organ at risk than a sharp needle. However, there is currently no evidence to suggest that a round needle is better than a sharp needle for the Venezia applicator in IC/IS BT. Herein, we documented our experience of using both round and sharp needles with the Venezia applicator in IC/IS BT for cervical cancer. Case presentation: A 71-year-old woman was diagnosed with clinical stage T2bN0M0 and the International Federation of Gynecology and Obstetrics stage IIB cervical squamous cell carcinoma. Definitive therapy, including a high-dose-rate BT boost, was planned using a round needle with the Venezia applicator in IC/IS BT. After inserting four interstitial round needles during the first and second BT sessions, an unexpectedly large gap (1.5 cm) was detected between the cervix and ovoid. We therefore used a sharp needle with the Venezia applicator for IC/IS BT during the third and fourth BT sessions. Three sharp needles were firmly inserted during the third and fourth BT sessions. Conclusions: The study findings suggest that the interstitial round needle should not be used for cervical cancer patients undergoing IC/IS BT using the Venezia applicator. [ABSTRACT FROM AUTHOR]

Low-dose-rate (LDR) and high-dose-rate (HDR) interstitial brachytherapy are known to be effective in the treatment of lip carcinomas. The aim of this study was to retrospectively compare oncologic and toxicity outcomes between the two techniques. From 2007 to 2018, patients at the Institut de cancérologie de Lorraine (France) who received exclusive or adjuvant interstitial brachytherapy for lip squamous carcinomas were studied. Two groups were defined: the LDR/PDR group, including patients treated with iridium-192 wires, or pulsed-dose rate technique, and the high-dose-rate group, with patients treated by high-dose-rate technique. The dose ranged between 50 Gy and 65 Gy (depending on previous surgery) for low-dose-/pulsed-dose rate treatments, and 39 Gy for high-dose-rate (twice a day). Early, late toxicity events and oncologic control were reported. Among the 61 patients whose data were analyzed retrospectively, 36 received the low-dose-/pulsed-dose rate treatment (59%) and 25 the high-dose-rate brachytherapy (41%). The median follow-up time was 44 months. At 36 months, the local control rates were 96.3% for LDR/PDR group and 100% for HDR (P = 0.180). The regional control rates were 85.9% and 92% without any difference according to the two groups (P = 0.179). The specific overall survival rate was 95.5% with no difference between groups. There were more grade 2 or higher mucositis in the HDR group than in LDR/PDR group (40% versus 16.7%, P = 0.042). One case of grade 3 mucositis was recorded in each group. No grade 3 late complications were recorded. High-dose-rate brachytherapy reduced the length of hospitalization by 2 days (P < 0.001). High-dose- or low-dose-/pulsed-dose rate brachytherapy seemed to be as effective and well tolerated in our experience of 61 patients. [ABSTRACT FROM AUTHOR]

We report an updated analysis of the outcomes and toxicities of MRI-based brachytherapy for locally advanced cervical cancer from a U.S. academic center. A retrospective review was performed on patients treated with MRI-based brachytherapy for cervical cancer. EBRT was standardly 45 Gy in 25 fractions with weekly cisplatin. MRI was performed with the brachytherapy applicator in situ. Dose specification was most commonly 7 Gy for 4 fractions with optimization aim of D90 HR-CTV EQD2 of 85–95 Gy α/β=10 Gy in 2 implants each delivering 2 fractions. Ninety-eight patients were included with median follow up of 24.5 months (IQR 11.9–39.8). Stage IIIA-IVB accounted for 31.6% of cases. Dosimetry results include median GTV D98 of 101.0 Gy (IQR 93.3–118.8) and HR-CTV D90 of 89 Gy (IQR 86.1–90.6). Median D2cc bladder, rectum, sigmoid, and bowel doses were 82.1 Gy (IQR 75.9–88.0), 65.9 Gy (IQR 59.6–71.2), 65.1 Gy (IQR 57.7–69.6), and 55 Gy (IQR 48.9–60.9). Chronic grade 3+ toxicities were seen in the bladder (8.2%), rectosigmoid (4.1%), and vagina (1.0%). Three-year LC, PFS, and OS were estimated to be 84%, 61.7%, and 76.1%, respectively. MRI-based brachytherapy demonstrates excellent local control and acceptable rates of high-grade morbidity. These results are possible in our population with relatively large volume primary tumors and extensive local disease. • Local control, overall survival, and progression-free survival at our institution are similar to larger studies. • Dose planning limits to organs-at-risk were met in a population with a higher proportion of stage IIIA-IVB patients. • Chronic grade 3+ toxicities were seen in 13.3% of patients, mostly in stage IIIB and IVA patients. [ABSTRACT FROM AUTHOR]

Background: Diffusion-weighted magnetic resonance imaging (DWI) provides a measurement of tumor cellularity. We evaluated the potential of apparent diffusion coefficient (ADC) values obtained from post-external beam radiation therapy (EBRT) DWI and prior to brachytherapy (BT) to predict for complete metabolic response (CMR) in bulky cervical cancer. Methods: Clinical and DWI (b value = 500 s/mm2) data were obtained from patients undergoing interstitial BT with high-risk clinical target volumes (HR-CTVs) > 30 cc. Volumes were contoured on co-registered T2 weighted images and 90th percentile ADC values were calculated. Patients were stratified by CMR (defined by PET-CT at three months post-BT). Relation of CMR with 90th percentile ADC values and other clinical factors (International Federation of Gynecology and Obstetrics (FIGO) stage, histology, tumor and HR-CTV size, pre-treatment hemoglobin, and age) was assessed both in univariate and multivariate logistic regression analyses. Youden's J statistic was used to identify a threshold value. Results: Among 45 patients, twenty-eight (62%) achieved a CMR. On univariate analysis for CMR, only 90th percentile ADC value was significant (p = 0.029) while other imaging and clinical factors were not. Borderline significant factors were HR-CTV size (p = 0.054) and number of chemotherapy cycles (p = 0.078). On multivariate analysis 90th percentile ADC (p < 0.0001) and HR-CTV size (p < 0.003) were highly significant. Patients with 90th percentile ADC values above 2.10 × 10− 3 mm2/s were 5.33 (95% CI, 1.35–24.4) times more likely to achieve CMR. Conclusions: Clinical DWI may serve to risk-stratify patients undergoing interstitial BT for bulky cervical cancer. [ABSTRACT FROM AUTHOR]

Historical gynecologic interstitial brachytherapy templates block direct tumor visualization during needle placement, presenting an opportunity for clinical innovation to develop a novel interstitial template allowing direct tumor visualization during needle insertion. We designed and implemented a novel interstitial template, simple needle attachment post placement interstitial template (SNAPP-IT), that allowed direct visualization of the target vaginal tumor during interstitial needle placement while maintaining the ability to individually secure needles to the template, allow a vaginal cylinder, suture holes for securing to the perineum, MRI compatibility and sterilizable for repeat use. Procedure outcomes including procedure time, needle path lengths, and plan dosimetry were prospectively captured in a patient database. Forty gynecologic interstitial brachytherapy cases were recorded (20 SNAPP-IT, 20 traditional templates). Needle insertion depth was reduced using the SNAPP-IT in comparison with traditional interstitial templates (11.8 cm vs. 3.6 cm, p < 0.0001). The average CTV volume was 25.6 cc for SNAPP-IT and 20.7 cc for traditional; both methods averaged a similar number of needles (15.8, 15.6). Dosimetric constraints were similarly met in both treatment groups. Procedures performed using the SNAPP-IT were shorter compared with those performed with traditional interstitial devices (83.4 minutes vs. 100.7 minutes) and there were no post-operative infections in the SNAPP-IT group. Implementation of a novel gynecologic interstitial brachytherapy template (SNAPP-IT) reduced procedure times, allowed direct tumor visualization, and decreased needle insertion depth. SNAPP-IT provides a useful alternative approach for vaginal interstitial brachytherapy, may increase brachytherapist efficiency with complex procedures and potentially expands access to interstitial brachytherapy. [ABSTRACT FROM AUTHOR]

Cervical cancer is the second most common cancer cause of morbidity and mortality in Filipino women; the age‐standardized annual incidence is 15.2 as of March 2023. The majority are diagnosed at a locally advanced stage and in the reproductive and working age group. This results in important treatment and productivity costs. The importance of image‐guided and interstitial brachytherapy (BRT) in local control and toxicity outcomes has been shown in recent meta‐analyses. We review the status of advanced BRT program training and implementation in the Philippines and important challenges and opportunities to move forward. [ABSTRACT FROM AUTHOR]

Background: Electromagnetic tracking (EMT) has been researched for brachytherapy applications, showing a great potential for automating implant reconstruction, and overcoming image‐based limitations such as contrast and spatial resolution. One of the challenges of this technology is that it does not intrinsically share the same reference frame as the patient's medical imaging. Purpose: To present a novel phantom that can be used for a comprehensive quality assurance (QA) program of brachytherapy EMT systems and use this phantom to validate a novel applicator‐based registration method of EMT and image reference frames for gynecological (GYN) interstitial brachytherapy. Materials and Methods: Eleven 6F‐catheters (20 cm long), one 6F round tip catheter (29.4 cm long) and a tandem and ring gynecological applicator (Elekta, CT/MR 60°, 40 mm long tandem, 30 mm diameter ring) were placed in a rigid custom‐made phantom (Elekta Brachytherapy, Veenendaal, The Netherlands) to reconstruct their geometry using a five‐degree of freedom EMT sensor attached to an afterloader's check cable. All EMT reconstructions were done in three different environments: disturbance free (no metal nearby), computed tomography (CT)‐on‐rails brachytherapy suite and magnetic resonance imaging (MRI) brachytherapy suite. Implants were placed parallel to a magnetic field generatorand were reconstructed using two different acquisition methods: step‐and‐record and continuous motion. In all cases, the acquisition is performed at a rate of approximately 40 Hz. A CT scan of the phantom inside a water cube was obtained. In the treatment planning system (TPS), all catheters in the CT images were manually reconstructed and the applicator reconstruction was achieved by manually placing its solid 3D model, found in the applicator library of the TPS. The Iterative Closest Point and the Coherent Point Drift algorithms were used, initialized with four known points, to register both EMT and CT scan reference frames using corresponding points from the EMT and CT based reconstructions of the phantom, following three approaches: one gynecological applicator, four interstitial catheters inside four calibration plates having an S‐shaped path, and four 5 mm diameter ceramic marbles found in each of the four calibration plates. Once registered, the registration error (perpendicular distance) was computed. Results: The absolute median deviation from the expected value for EMT measurements in the disturbance free environment, CT‐on‐rails brachytherapy suite, and MRI‐brachytherapy suite are 0.41, 0.23, and 0.31 mm, respectively, while for the CT scan it is 0.18 mm. These values significantly lie below the sensor's expected accuracy of 0.70 mm (p < 0.001), suggesting that the environment did not have a significant impact on the measurements, given that care is taken in the immediate surroundings. In all three environments, the two acquisitions and three registration approaches have mean and median registration errors that lie at or below 1 mm, which is lower than the clinical acceptable threshold of 2 mm. Conclusions: The novel phantom allowed to successfully evaluate the accuracy of EMT‐based reconstructions of catheters and a GYN tandem and ring applicator in different clinical environments. A registration method based only on the applicator geometry, reconstructed withan EMT sensor and the TPS solid applicator library, was validated and shows clinically acceptable accuracy, comparable to CT‐based reconstruction but within a few minutes. Since the applicator is also visible in MRI, this method could potentially be used in clinics in an EMT‐MR interstitial GYN brachytherapy workflow. [ABSTRACT FROM AUTHOR]

To demonstrate image-guided preplan workflows for high-dose-rate (HDR) brachytherapy for advanced gynecological malignancies. Two different preplanning scenarios are presented: (1) CT- or MRI-based preplan with partial applicator in place; (2) Preplans generated from prior fractions. The first scenario can be applied to Syed-Neblett template-based implants or hybrid brachytherapy applicators, while the second scenario applies to hybrid applicators. Both scenarios use MRI or CT images acquired with the applicator in place to demonstrate tumor and applicator relative locations and therefore, provide the ability to show optimized suggested needle positions including the implant depths before the actual insertion. The preplanning techniques have demonstrated feasibility and shown five areas of potential improvement: (1) shorter procedure time, (2) decreased number of total needles inserted, (3) shorter physician tumor contour time, (4) shorter planning time, and (5) evaluation of appropriateness for brachytherapy. The use of image-guided brachytherapy preplanning improves clinical efficiency and is recommended for consideration for adaptation into clinical workflows for HDR interstitial and hybrid brachytherapy. [ABSTRACT FROM AUTHOR]

To determine cardiac dose received by patients treated with high dose rate interstitial brachytherapy. Patients with early-stage, node negative breast cancer can be treated using multi-catheter interstitial brachytherapy accelerated partial breast irradiation (MIB-APBI), with the benefit of reduced treatment volumes and favorable toxicity. We conducted a retrospective review of left-sided breast cancer patients treated using MIB-APBI at our institution since 2014. The mean heart dose (MHD) was calculated using the Oncentra 3.2 planning system. The minimum distance between the planning target volume (PTVeval) and heart contour was measured manually. 81 patients were included. The upper outer quadrant was the most common site. The MHD was 97.8 cGy (EQD2a/b=2) (range 22–229 cGy). MHD significantly correlated with the closest distance between PTVeval and heart contour (correlation coefficient -0.823, p <0.001); size of PTVeval (cc) and quadrant location did not. Appropriately selected women with early-stage, low-risk, left-sided breast cancer who received MIB-APBI had acceptable MHD. There was a strong correlation between the distance of PTVeval and MHD. Quadrant breast tumor is in cannot be used as a surrogate for MHD in brachytherapy. Our findings contribute to the growing evidence of the utility and safety of MIB-APBI. [ABSTRACT FROM AUTHOR]

Background: High-dose-rate computed tomography (CT)-guided brachytherapy (HDR-BT) has shown promising results in patients with hepatocellular carcinoma (HCC). While growing evidence shows clear limitations of mRECIST, diffusion-weighted imaging (DWI) has relevant potential in improving the response assessment. Purpose: To assess whether DWI allows evaluation of short- and long-term tumor response in patients with HCC after HDR-BT. Material and Methods: A total of 22 patients with 11 non-responding HCCs (NR-HCC; local tumor recurrence within two years) and 24 responding HCCs (R-HCC; follow-up at least two years) were included in this retrospective bi-center study. HCCs were treated with HDR-BT and patients underwent pre- and post-interventional magnetic resonance imaging (MRI). Analyses of DWI were evaluated and compared between pre-interventional MRI, 1.follow-up after 3 months and 2.follow-up at the time of the local tumor recurrence (in NR-HCC) or after 12 months (in R-HCC). Results: ADCmean of R-HCC increased significantly after HDR-BT on the first and second follow-up (ADCmean: 0.87 ± 0.18 × 10−3 mm2/s [pre-interventional]: 1.14 ± 0.23 × 10−3 mm2/s [1. post-interventional]; 1.42 ± 0.32 × 10−3 mm2/s [2. post-interventional]; P < 0.001). ADCmean of NR-HCC did not show a significant increase from pre-intervention to 1. post-interventional MRI (ADCmean: 0.85 ± 0.24 × 10−3 mm2/s and 1.00 ± 0.30 × 10−3 mm2/s, respectively; P = 0.131). ADCmean increase was significant between pre-intervention and 2. follow-up (ADCmean: 1.03 ± 0.19 × 10−3 mm2/s; P = 0.018). There was no significant increase of ADCmean between the first and second follow-up. There was, however, a significant increase of ADCmin after 12 months (ADCmin: 0.87 ± 0.29 × 10−3 mm2/s) compared to pre-interventional MRI and first follow-up (P < 0.005) only in R-HCC. Conclusion: The tumor response after CT-guided HDR-BT was associated with a significantly higher increase in ADCmean and ADCmin in short- and long-term follow-up. [ABSTRACT FROM AUTHOR]

Background: Brachytherapy (BT) is a critical component of radiotherapy for locally advanced cervical cancer (LACC), and it has rapidly developed in recent decades. Since the advent of three-dimensional image-guided adaptive brachytherapy (3D-IGABT), magnetic resonance imaging (MRI) has emerged as the primary modality for image guidance. Meanwhile, other imaging modalities, such as computed tomography, 18F-fluorodeoxyglucose positron emission tomography, ultrasound, and their combinations have also been widely studied. Materials and methods: We reviewed studies on different imaging modalities utilized for target delineation and planning. Emerging techniques in IGABT like real-time image guidance and 3D printing were also included. We summarized research on their feasibility and concentrated on their clinical outcomes. Results: MRI-guided BT was the gold standard, and CT-guided BT was the most widely applied. Other modalities have shown feasibility and promising efficacy in dosimetry studies and preliminary outcomes. The longer-term clinical outcomes associated with these approaches require further elucidation. Conclusions: As 3D-IGABT was validated by promising clinical outcomes, the future of BT for LACC is expected to progress toward the refinement of more effective image-guided procedures. Moreover, achieving operational consensus and driving technological advancements to mitigate the inherent limitations associated with different imaging modes remain essential. [ABSTRACT FROM AUTHOR]

Purpose: Breast brachytherapy (BB) represents an important radiation therapy modality in modern breast cancer treatments. Currently, BB is mainly used for accelerated partial breast irradiation (APBI), local boost after whole breast radiation therapy (WBRT), and as salvage re-irradiation after second lumpectomy (APBrl). Two multi-catheter interstitial brachytherapy (MIB) techniques can be offered: intra-operative (IOB) and post-operative (POB) brachytherapy. The aim of this article was to summarize current available data on these two different brachytherapy approaches for breast cancer. Material and methods: A literature search was performed, and different experiences published by BB expert teams were analyzed and compared. These two different brachytherapy approaches for breast cancer have also been presented and discussed during meetings of the GEC-ESTRO BCWG. In addition, expert recommendations were defined. Results: A comprehensive description and practical comparison of both the techniques, i.e., IOB and POB, considering the latest available published data were presented. Different technical, logistic, and clinical aspects of both the methods were thoroughly examined and analyzed. This detailed comparison of the two breast brachytherapy techniques was supported by scientific data from extensive experience of experts, facilitating an objective analysis that, to our knowledge, has not been previously published. Conclusions: Based on the comprehensive analysis of both the brachytherapy techniques available, this article serves as a valuable resource to guide breast teams in selecting the optimal BB technique (POB or IOB), considering hospital environment, multi-disciplinary collaboration, and patient logistics. [ABSTRACT FROM AUTHOR]

Purpose: Brachytherapy plays a crucial role in the standard of care for locally advanced gynecological malignancies. In this report, we present the experience from a tertiary teaching hospital, which is a referral center for imageguided brachytherapy (IGBT) in the management of locally advanced gynecological malignancies. Material and methods: This was a retrospective study of 130 patients referred to our hospital for IGBT after receiving initial external beam radiotherapy in their primary healthcare facilities, from January 2021 till January 2023. CT-based planning was done to delineate high-risk clinical target volume (HR-CTV). Dose of 6-7.5 Gy in 3-4 fractions was prescribed. Overall treatment time (OTT) was calculated, and patients were assessed for clinical response and toxicity after three months. Results: All patients received IGBT using an intra-cavitary or interstitial technique. The D90 HR-CTV mean EQD2 dose was 28.34 ±2.78 Gy. The mean EQD2 dose to 2 cc of the bladder, rectum, and sigmoid was 18.31 ±5.19 Gy, 14.14 ±5.76 Gy, and 17.43 ±4.75 Gy, respectively. The median interval time between the last fraction of external beam radiation therapy (EBRT) and first evaluation in the hospital was 19 (range, 13-28) days (interquartile range [IQR]). The median time between the completion of chemoradiation and brachytherapy procedure was 25 (range, 19-33) days (IQR). The mean overall treatment time (OTT) was 63.5 ±14.7 days. Conclusions: This study highlights the established advantages of image-guided interstitial brachytherapy and associated challenges. To optimize the overall treatment duration, it is imperative to prioritize and update the referral processes for brachytherapy centers. [ABSTRACT FROM AUTHOR]

Curative-intent radiotherapy for locally advanced and select early stage cervical cancer in the US includes external beam radiotherapy (EBRT) with brachytherapy. Although there are guidelines for brachytherapy dose and fractionation regimens, there are limited data on practice patterns. This study aims to evaluate the contemporary utilization of cervical cancer brachytherapy in the US and its association with patient demographics and facility characteristics. We retrospectively analyzed clinical covariates of cervical cancer patients diagnosed and treated in 2018–2020 with curative-intent radiotherapy from the 2020 National Cancer Database. Associations between patient and institutional factors with the number of brachytherapy fractions were identified with logistic regression. Factors with association (p < 0.10) were then included in a multivariable logistic regression model. All tests were two-sided with significance <0.05 unless specified otherwise. Among the eligible 2517 patients, 97.3% received HDR or LDR and is further analyzed. More patients received HDR than LDR brachytherapy (98.9% vs 1.1%) and intracavitary than interstitial brachytherapy (86.4% vs 13.6%). The most common number of HDR fractions prescribed were 5 (51.0%), 4 (32.9%), and 3 (8.6%). After adjusting for the other variables in the model, ethnicity, private insurance status, overall insurance status, and facility type were the only factors that were significantly associated with the number of brachytherapy factions (p < 0.0001, p = 0.028, p = 0.001, and p < 0.0001, respectively, n = 2184). In the US, various HDR brachytherapy regimens are utilized depending on patient and institutional factors. Future research may optimize cervical cancer brachytherapy by correlating specific dose and fractionation regimens with patient outcomes. • Curative-intent radiotherapy for cervical cancer in the US may include external beam radiotherapy and brachytherapy. • This is the first assessment of physician practice pattern of curative-intent brachytherapy for cervical cancer in the US. • Most patients received HDR intracavitary brachytherapy and completed their radiotherapy as prescribed. • Patient ethnicity, insurance, and facility type are significantly associated with number of HDR brachytherapy fractions. [ABSTRACT FROM AUTHOR]

Purpose: To explore the feasibility and efficacy of interstitial brachytherapy application for nonresectable and chemo-resistant malignant liver and lung lesions. Materials and Methods: Percutaneous high-dose-rate interstitial brachytherapy (HDR ISBT) was applied in nine lesions of seven middle-aged patients with advanced carcinoma (five patients with liver lesion and two patients with lung lesion). All patients were surgically ineligible. All patients had already received systemic chemotherapy. Under computed tomography (CT) guidance (for lung lesion) or ultrasonography (USG) guidance (for liver lesion), a single stainless steel brachytherapy needle was inserted percutaneously in patients with lesion size ≤4 centimeter (cm) and multiple needles were inserted in patients of lesion size >4cm. A single dose of 15 Gy to 20 Gy with HDR ISBT was prescribed at the periphery of the lesion. The needles were removed just after treatment. Patients were kept under observation for 24 h after treatment. Results: The median size of the lesion was 6.5 cm. In all the cases of liver lesion, more than 75% shrinkage of tumor volume in follow-up at 6 mo was observed. It was more than 50% for lung lesion. None of the patients had developed significant complications as on the median follow up period of 15 mo (ranges 3–27 mo). Conclusions: Percutaneous CT-guided high-dose-rate interstitial brachytherapy is a minimally invasive, safe, and feasible treatment option with minimal complication for inoperable, chemo resistant, advanced cancers with encouraging treatment outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To review the evidence for radiotherapy in the management of primary penile cancer, either as brachytherapy or external beam radiation, and the role of external beam radiotherapy in node positive penile cancer. Methods: English language literature was reviewed for the past 3 decades. As penile cancer is uncommon in developed nations, high quality evidence to guide management is limited. Single institution reports often span decades during which time staging systems and treatments have evolved, reducing their relevance to current practice. Successful clinical trials require collaboration not only among disciplines but also among multiple institutions and nations. Results: Radiotherapy is a definitive organ-preserving option for T1-T2 penile cancers. Interstitial brachytherapy is associated with penile preservation in 85% of men at 5 years, maintained in 70% by 10 years. Results of external radiotherapy are not quite as promising but nonetheless 60% of men will have an intact penis at 5 years. Inguino-pelvic external radiotherapy has been reported to increase overall survival when delivered as adjuvant treatment for men with pN3 groin but pN0 pelvic nodes, and improve disease specific survival for those with involved pelvic nodes. InPACT (ECOG-ACRIN_8134) is investigating the role of inguino-pelvic chemo-radiotherapy for men with pN3 inguinal nodes but imaging negative pelvic nodes. Conclusions: Radiotherapy has a well-defined role to play in treatment of squamous cell cancers of other sites, such as vulva, anal canal, uterine cervix and head and neck malignancies. Emerging data support the incorporation of radiotherapy into treatment paradigms for penile cancer. [ABSTRACT FROM AUTHOR]

To demonstrate novel clinical implementation of a 3D transvaginal ultrasound (3DTVUS) system for intraoperative needle insertion guidance in perineal template interstitial gynecologic high-dose-rate brachytherapy and assess its impact on implant quality. Interstitial implants began with preimplant 3DTVUS to visualize the tumor and anatomy, with intermittent 3DTVUS to assess the implant and guide needle adjustment. Analysis includes visualization of the implant relative to anatomy, identification of cases where 3DTVUS is beneficial, dosimetry, and a survey distributed to 3DTVUS clinicians. Seven patients treated between November 2021 and October 2022 were included in this study. Twenty needles were inserted under 3DTVUS guidance. The tumor and vaginal wall were well-differentiated in four and all seven patients, respectively. Patients with tumours below the superior aspect of the vagina are suited for 3DTVUS. Four radiation oncologists responded to the survey. There was general agreement that 3DTVUS improves implant and anatomy visualization and is preferred over standard 2D ultrasound guidance techniques. Based on qualitative feedback from primary users and a small preliminary patient cohort, 3DTVUS imaging improves tumor and vaginal wall visualization during gynecologic perineal template interstitial needle implant and is a powerful tool for implant assessment in an intraoperative setting. [ABSTRACT FROM AUTHOR]

Evaluation of the management by first brachytherapy followed by radical hysterectomy (Wertheim type) compared to radical hysterectomy alone (Wertheim type) for the treatment of IB2 cervical cancer. Data from women with histologically proven FIGO stage IB2 cervical cancer treated between April 1996 and December 2016 were retrospectively abstracted from twelve French institutions with prospectively maintained databases. Of the 211 patients with FIGO stage IB2 cervical cancer without lymph node involvement included, 136 had surgical treatment only and 75 had pelvic lymph node staging and brachytherapy followed by surgery. The surgery-only group had significantly more adjuvant treatment (29 vs. 3; p = 0.0002). A complete response was identified in 61 patients (81%) in the brachytherapy group. Postoperative complications were comparable (63,2% vs. 72%, p = 0,19) and consisted mainly of urinary (36 vs. 27) and digestive (31 vs 22) complications and lymphoceles (4 vs. 1). Brachytherapy had no benefit in terms of progression-free survival (p = 0.14) or overall survival (p = 0.59). However, for tumors of between 20 and 30 mm, preoperative brachytherapy improved recurrence-free survival (p = 0.0095) but not overall survival (p = 0.41). This difference was not observed for larger tumors in terms of either recurrence-free survival (p = 0.55) or overall survival (p = 0.95). Our study found that preoperative brachytherapy had no benefit for stage IB2 cervical cancers in terms of recurrence-free survival or overall survival. For tumor sizes between 2 and 3 cm, brachytherapy improves progression-free survival mainly by reducing pelvic recurrences without improving overall survival. [ABSTRACT FROM AUTHOR]

Purpose: To present a new technique for the treatment of vaginal cuff recurrences using 3D-printed vaginal cylindrical template (3D-PVCT) with curved needle channels in brachytherapy. Material and methods: Two patients with vaginal cuff tumor treated with external beam radiotherapy and MRI-guided interstitial brachytherapy were selected for the present study. Prior to treatment, a vaginal cylinder with the same size as 3D-PVCT was inserted into the vagina. Magnetic resonance scan was performed to identify target volumes and organs at risk (OARs). By registration techniques, the implantation angle was determined, appropriate needle channels were selected, and the depth of each needle position was recorded. During the actual treatment, patients were under general anesthesia, and real-time guidance of trans-rectal ultrasound was applied referring to a pre-determined treatment plan. Results: For patient No. 1, 9 needles were inserted into the tumor, with 4 curved needle channels and 5 straight channels. For patient No. 2, 7 needles were inserted into the vaginal cuff tumor, with 6 curved needle channels and 1 straight channel. Doses delivered to volumes of targets and OARs for both patients met the EMBRACE II dose constraints. After follow-up of 15 and 18 months, respectively, both patients showed complete response, with no evidence of tumor recurrence. No significant acute or late toxicities were reported. Conclusions: With careful pre-planning, 3D-PVCT provides good target coverage and sparing of OARs. The results from these two patients indicate that this approach is very promising due to its flexibility and potential widespread application in the future. [ABSTRACT FROM AUTHOR]

Purpose: The addition of interstitial (IS) needles to intra-cavitary (IC) brachytherapy applicators is associated with improved outcomes in locally advanced cervical cancers involving parametrial tumor extensions. The purpose of this work was to validate a clinical workflow involving 3D-printed caps for a commercial IC split ring applicator that enable using IS needle trajectories tailored to each treatment. Material and methods: A dedicated software module was developed in this work allowing users to design patient-specific IS caps without knowledge of computer-aided design (CAD) software. This software module was integrated to 3D Brachy, a commercial software developed by Adaptiiv Medical Technologies Inc. For validation of the workflow, CAD models of ground truth caps with five IS needle trajectories were designed with Fusion 360™, 3D-printed, assembled with a split ring applicator, and CT-scanned with radio-opaque markers. 3D Brachy was then applied to generate a replica based on trajectories reconstructed from the radio-opaque markers. A comparison between ground truth and replicated IS needle trajectories was done using intersection points with planes at the level of the cervix (z = 0 cm) and a representative needle depth (z = 3 cm). Results: Prototypes of interstitial caps 3D-printed in both BioMed Amber and BioMed Clear SLA resins were tested to be functional both pre- and post-sterilization for IS needles with obliquity angles = 45°. Distance-to-agreement at z = 0 cm and 3 cm as well as deviations in pitch and yaw angles of the five IS needle trajectories were found to have mean values of 3.3 ±2.1 mm, 7.3 ±2.0 mm, 2.9° ±2.3°, and 7.0° ±7.0°, respectively. Conclusions: The clinical workflow for image-guided adaptive cervical cancer brachytherapy using the Montreal split ring applicator was validated. [ABSTRACT FROM AUTHOR]

Purpose: Although customized three-dimensional (3D) templates have shown advantages in brachytherapy, widespread application is still full of challenges. The present work proposed the use of a commercial 3D standardized template-guided intracavitary/interstitial brachytherapy (IC/ISBT) that could provide simple and reproducible needles' insertion. Material and methods: 43 patients received external beam radiotherapy (EBRT) with 45-50.4 Gy and subsequent IC/ISBT with 28 Gy in 4 fractions. In terms of IC/ISBT, 24 patients were treated with 3D standardized templates (ST group), and 19 patients were treated using free-hand implantation (FH group). Consistency of implantation for all needles and dosimetric differences for target and organs at risk (OARs) were then compared between two groups. Results: The mean variation of tip position between insertions for needles was 1.41 mm and 2.74 mm in ST group and FH group, respectively (p < 0.001). ST group was superior in terms of dosimetric conformity index (CI) and D90 for high-risk clinical target volume (HR-CTV), significantly improving to 23.21% (p < 0.001) and 3.58% (p = 0.031) compared with FH group. The D2cc of the bladder and sigmoid in the ST group were lower than those in the FH group (p < 0.05). Meanwhile, a strong correlation between the volume of HR-CTV and its CI in the ST group (R = 0.865, p < 0.001) was found with Spearman's correlation analysis. Conclusions: The implementation of 3D standardized template can potentially improve the precision and consistency in the needle insertion procedure that may replace some customized 3D templates, and achieve clinical satisfied dose distribution in IC/ISBT plans for patients with LACC. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study was to evaluate the safety and clinical outcomes of single application multi-fractionated computed tomography (CT)-guided interstitial high-dose-rate brachytherapy given in four fractions in locally advanced cervical cancer. Material and methods: Patients with locally advanced cervical cancer stage IIB-IVA treated definitively with external radiation ± weekly cisplatin, followed by single application multi-fractionated CT-guided interstitial high-dose-rate brachytherapy in four fractions were included. Dosimetry data, clinical response, and toxicity records were reviewed. Results: Between January 2018 and December 2022, twenty-two patients were included. Clinical stage distribution was as follows: IIB - 13.6%, IIIB - 27.3%, IIIC - 22.7%, and IVA - 36.4%. Mean high-risk clinical target volume (HR-CTV) was 66.19 ±32.69 cm3, and HR-CTV D90 dose was 86.8 ±1.7 Gy. 2 cc doses to bladder, rectum, and sigmoid were 84.6 ±2.8 Gy, 71.5 ±2.4 Gy, and 65.6 ±4.0 Gy, respectively. Mean overall treatment time was 66 ±21 days. With a median follow-up of 11.5 months (range, 5-44 months), median survival and local control were not achieved. Oneyear local control rate, one-year progression-free survival, and one-year overall survival were 82%, 66%, and 78%, respectively. Univariate analysis showed overall treatment time to be the only variable associated with all oncologic outcomes. For acute toxicity, grade 3 toxicity in four patients and grade 4 toxicity of infection in one patient were observed. For late toxicity, grade 3 gastrointestinal toxicity was noted in two patients. Conclusions: Initial results suggest that single application multi-fractionated CT-guided interstitial brachytherapy given in four fractions in locally advanced cervical cancer seems to be feasible and safe, but additional evidence is needed to generate more validated conclusions. [ABSTRACT FROM AUTHOR]

Background Despite lack of clinical therapy in acute kidney injury (AKI) or its progression to chronic kidney disease (CKD), administration of growth factors shows great potential in the treatment of renal repair and further fibrosis. At an early phase of AKI, administration of exogenous fibroblast growth factor 2 (FGF2) protects against renal injury by inhibition of mitochondrial damage and inflammatory response. Here, we investigated whether this treatment attenuates the long-term renal interstitial fibrosis induced by ischemia–reperfusion (I/R) injury. Methods Unilateral renal I/R with contralateral nephrectomy was utilized as an in vivo model for AKI and subsequent CKD. Rats were randomly divided into four groups: Sham-operation group, I/R group, I/R-FGF2 group and FGF2-3D group. These groups were monitored for up to 2 months. Serum creatinine, inflammatory response and renal histopathology changes were detected to evaluate the role of FGF2 in AKI and followed renal interstitial fibrosis. Moreover, the expression of vimentin, α-SMA, CD31 and CD34 were examined. Results Two months after I/R injury, the severity of renal interstitial fibrosis was significantly attenuated in both of I/R-FGF2 group and FGF2-3D group, compared with the I/R group. The protective effects of FGF2 administration were associated with the reduction of high-mobility group box 1 (HMGB1)-mediated inflammatory response, the inhibition of transforming growth factor beta (TGF-β1)/Smads signaling–induced epithelial–mesenchymal transition and the maintenance of peritubular capillary structure. Conclusions A single dose of exogenous FGF2 administration 1 h or 3 days after reperfusion inhibited renal fibrogenesis and thus blocked the transition of AKI to CKD. Our findings provided novel insight into the role of FGF signaling in AKI-to-CKD progression and underscored the potential of FGF-based therapy for this devastating disease. [ABSTRACT FROM AUTHOR]

This article discusses the case of a 19-month-old boy diagnosed with an embryonal tumor with multilayered rosettes (ETMR) located in the brainstem. ETMR is a rare malignant tumor that primarily affects infants. The recommended treatment approach for ETMR includes surgical resection, radiation therapy, and high-dose chemotherapy with stem-cell transplantation. However, the prognosis for brainstem ETMR remains poor, with a median overall survival of 10-12 months. In this case, the boy underwent multimodal treatment, including surgical resection, chemotherapy, stereotactic interstitial brachytherapy, and stem-cell transplantation. The treatment resulted in a significant reduction in tumor volume and a favorable outcome for the patient. The authors suggest that combining conventional therapies with interstitial brachytherapy may improve the outcomes for patients with ETMR. [Extracted from the article]

We developed a 3-dimensionally (3D) printed tandem anchored radially guiding interstitial template (TARGIT) to increase the simplicity of intracavitary/interstitial technique for tandem-and-ovoid (T&O) procedures in cervical cancer brachytherapy. This study compared dosimetry and procedure logistics between T&O implants using the original TARGIT versus the next-generation TARGIT-Flexible-eXtended (TARGIT-FX) 3D-printed template designed for practice-changing ease-of-use with further simplified needle insertion and increased flexibility in needle placement. This single-institution retrospective cohort study included patients undergoing T&O brachytherapy as part of definitive cervical cancer treatment. Procedures used the original TARGIT from November 2019 through February 2022 and the TARGIT-FX from March 2022 through November 2022. The FX design features full extension to the vaginal introitus with 9 needle channels and allows for needle additions or depth adjustments intraprocedure and after computed tomography/magnetic resonance imaging. A total of 148 implants were performed, 68 (46%) with TARGIT and 80 (54%) with TARGIT-FX, across 41 patients. Across implants, the TARGIT-FX achieved higher mean V100% (+2.8%, P =.0019), and across patients, the TARGIT-FX achieved higher D90 (+2.0 Gy, P =.037) and higher D98 (+2.7 Gy, P =.016) compared with the original TARGIT. Doses to organs at risk were overall similar between templates. Procedure times for TARGIT-FX implants were 30% shorter on average than for those using the original TARGIT (P <.0001), and 28% shorter on average for the subset of implants with high-risk clinical target volume ≥30 cc (P =.013). All residents (100%, N = 6) surveyed regarding the TARGIT-FX indicated ease-of-use for needle insertion and interest in applying the technique in future practice. The TARGIT-FX achieved shorter procedure times with increased tumor coverage and similar normal tissue sparing compared with the previously applied TARGIT and illustrates the potential of 3D printing to enhance efficiency and shorten the learning curve for intracavitary/interstitial procedure technique in cervical cancer brachytherapy. [ABSTRACT FROM AUTHOR]

Purpose: To explore the feasibility and efficacy of interstitial brachytherapy application for nonresectable and chemo-resistant malignant liver and lung lesions. Materials and Methods: Percutaneous high-dose-rate interstitial brachytherapy (HDR ISBT) was applied in nine lesions of seven middle-aged patients with advanced carcinoma (five patients with liver lesion and two patients with lung lesion). All patients were surgically ineligible. All patients had already received systemic chemotherapy. Under computed tomography (CT) guidance (for lung lesion) or ultrasonography (USG) guidance (for liver lesion), a single stainless steel brachytherapy needle was inserted percutaneously in patients with lesion size =4 centimeter (cm) and multiple needles were inserted in patients of lesion size >4cm. A single dose of 15 Gy to 20 Gy with HDR ISBT was prescribed at the periphery of the lesion. The needles were removed just after treatment. Patients were kept under observation for 24 h after treatment. Results: The median size of the lesion was 6.5 cm. In all the cases of liver lesion, more than 75% shrinkage of tumor volume in follow-up at 6 mo was observed. It was more than 50% for lung lesion. None of the patients had developed significant complications as on the median follow up period of 15 mo (ranges 3-27 mo). Conclusions: Percutaneous CT-guided high-dose-rate interstitial brachytherapy is a minimally invasive, safe, and feasible treatment option with minimal complication for inoperable, chemo resistant, advanced cancers with encouraging treatment outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Biomarkers are essential to implement personalized therapies in cancer treatment options. As primary liver tumors are increasing and treatment is coupled to liver function and activation of systemic cells of the immune system, we investigated blood-based cells for their ability to predict response to local ablative therapy. Methods: We analyzed peripheral blood cells in 20 patients with primary liver cancer at baseline and following brachytherapy. In addition to platelets, leukocytes, lymphocytes, monocytes, neutrophils and most common ratios PLR, LMR, NMR and NLR, we investigated T cell and NKT cell populations of 11 responders and 9 non-responders using flow cytometry. Results: We have found a peripheral blood cell signature that differed significantly between responders and non-responders treated with interstitial brachytherapy (IBT). At baseline, non-responders featured higher numbers of platelets, monocytes and neutrophils, a higher platelet-to-lymphocyte ratio and an increase in the NKT cell population with a concurrent reduction in CD16 + NKT cells. Simultaneously, a lower percentage of CD4 + T cells was present in non-responders, as also reflected in a lower CD4/8 ratio. CD45RO + memory cells were lower in both, CD4 + and CD8 + T cell populations whereas PD-1 + T cells were only present in the CD4 + T cell population. Conclusion: Baseline blood-based cell signature may function as a biomarker to predict response following brachytherapy in primary liver cancer. [ABSTRACT FROM AUTHOR]

In select cases of locally advanced cervical cancer, a hybrid brachytherapy (HBT) approach consisting of a combined intracavitary (IC)/insterstitial (IS) implant can yield improved target coverage and/or decreased organ at risk dose compared to IC techniques while limiting invasiveness compared to IS techniques. The technique involves placement of transvaginal and/or perineal needles in addition to the tandem and ring/ovoids using either a specialized applicator or free-hand placement. Following applicator and needle placement, brachytherapy may then be planned using principles similar to IC or IS techniques. During treatment planning, it can be helpful to obtain both MRI and CT imaging, as plastic MRI-compatible needles do not show up well on MRI. In patients where acceptable target coverage cannot be achieved using IC alone or doses to nearby OAR are too high, HBT should be evaluated. HBT can improve both dose to target and OAR while sparing patients the morbidity of perineal template-based interstitial brachytherapy. Specific scenarios where HBT may be preferred include bulky residual primary tumor especially with poor response to EBRT, extension into the lateral parametrium, vaginal extension of tumor, and an asymmetric target. Use of HBT can typically permit extension of dose coverage by an additional 1–2 cm beyond what can be achieved with an IC alone technique. HBT allows for improved therapeutic ratio by improving target volume coverage and/or lowering doses to OARs. Brachytherapists should be trained on the practical aspects of administering HBT to be able to offer a less invasive and impactful treatment option when appropriate. [ABSTRACT FROM AUTHOR]

Brachytherapy irradiation carries risks of both bleeding and venous thromboembolism (VTE). No screening or management recommendations for VTE in this setting have been developed. Our study aims to understand the incidence of VTE, compile published anticoagulation guidelines, and call for future guidelines to address thromboprophylaxis in this population. A retrospective, single institution study of patients undergoing brachytherapy irradiation between 2012 and 2022 was undertaken. We analyzed 2 cohorts: 87 patients undergoing brachytherapy with an inpatient admission, and 66 patients assessed for risk of VTE or bleeding after discharge from an inpatient admission for brachytherapy. Caprini risk scores were calculated for each patient, and statistical analyses were performed. Eighty-seven patients were included, and 25% had a VTE diagnosis. Forty-seven (54%) of patients included underwent brachytherapy as definitive treatment of cervical cancer, and 16 (18%) received brachytherapy irradiation to treat recurrent endometrial cancer. In the cohort of 66 patients assessed for risk of VTE or bleeding after brachytherapy discharge, 23 (34.8%) were discharged with thromboprophylaxis, and 43 (65.2%) were discharged without thromboprophylaxis. None of the patients discharged on thromboprophylaxis were diagnosed with a VTE within 90 days of discharge after brachytherapy, whereas 3 of 43 (7%) discharged without thromboprophylaxis were diagnosed with a VTE, OR and 95% CI: 0.25 (0.01–5.29), p = 0.37. Of the 23 patients discharged on thromboprophylaxis, 1 was readmitted for bleeding OR and 95% CI: 5.8 (0.22–155.18), p = 0.29. The median Caprini score was 11. VTE is a common occurrence in patients undergoing brachytherapy. Patients undergoing brachytherapy irradiation who require inpatient admission represent a unique population, and specialty organizations should develop consensus recommendations to address these clinical challenges. [ABSTRACT FROM AUTHOR]

Target and organ delineation during prostate high-dose-rate (HDR) brachytherapy treatment planning can be improved by acquiring both a postimplant CT and MRI. However, this leads to a longer treatment delivery workflow and may introduce uncertainties due to anatomical motion between scans. We investigated the dosimetric and workflow impact of MRI synthesized from CT for prostate HDR brachytherapy. Seventy-eight CT and T2-weighted MRI datasets from patients treated with prostate HDR brachytherapy at our institution were retrospectively collected to train and validate our deep-learning-based image-synthesis method. Synthetic MRI was assessed against real MRI using the dice similarity coefficient (DSC) between prostate contours drawn using both image sets. The DSC between the same observer's synthetic and real MRI prostate contours was compared with the DSC between two different observers' real MRI prostate contours. New treatment plans were generated targeting the synthetic MRI-defined prostate and compared with the clinically delivered plans using target coverage and dose to critical organs. Variability between the same observer's prostate contours from synthetic and real MRI was not significantly different from the variability between different observer's prostate contours on real MRI. Synthetic MRI-planned target coverage was not significantly different from that of the clinically delivered plans. There were no increases above organ institutional dose constraints in the synthetic MRI plans. We developed and validated a method for synthesizing MRI from CT for prostate HDR brachytherapy treatment planning. Synthetic MRI use may lead to a workflow advantage and removal of CT-to-MRI registration uncertainty without loss of information needed for target delineation and treatment planning. [ABSTRACT FROM AUTHOR]

To study the effect of various dose-volume parameters on the severity of vaginal stricture (VS) and the correlation of the latter with the posterior-inferior border of symphysis (PIBS) points in locally advanced cervical cancer patients treated with concurrent chemoradiation and brachytherapy. A prospective study was done on 45 histologically proven locally advanced cervical cancer patients between January 2020 and March 2021. All of them were treated with concurrent chemoradiation with 6 MV photon linear accelerator to a dose of 45 Gy/25 fractions in 5 weeks. Twenty-three patients were treated with intracavitary brachytherapy with a dose of 7 Gy/fraction/week for three fractions. Twenty-two patients were treated with interstitial brachytherapy, with 6 Gy/fraction for four fractions, each fraction 6 h apart. Grading of VS was done as per Common Terminology Criteria for Adverse Events version 5. The median followup was 21.5 months. About 37.8% of patients had VS with a median duration of 8.0 months (4.0–12 months). About 22.2% had Grade 1, 6.7% had Grade 2, and 8.9% had Grade 3 toxicity. Doses at PIBS and PIBS−2 points had no correlation with vaginal toxicity, however, the dose at PIBS+2 was significantly associated with VS (p = 0.004). The treated length of the vagina at the time of brachytherapy (p = 0.001), initial tumor volume (p = 0.009), and vaginal involvement after completion of external beam radiotherapy (EBRT) (p = 0.01) were also statistically significant with the development of VS of Grade 2 or more. Dose at PIBS + 2, treated length of the vagina with brachytherapy, initial tumor volume, and post-EBRT vaginal involvement are strong predictors for the severity of VS. [ABSTRACT FROM AUTHOR]

Ongoing advances in precision cancer therapy have increased the number of molecularly targeted and immuno-oncology agents for a variety of cancers, many of which have been associated with a risk of pulmonary complications, among the most concerning being drug-induced interstitial lung disease/pneumonitis (DI-ILD). As the number of patients undergoing treatment with novel anticancer agents continues to grow, DI-ILD is expected to become an increasingly significant clinical challenge. Trastuzumab deruxtecan (T-DXd) is an antibody–drug conjugate targeting human epidermal growth factor receptor 2 that is gaining widespread use in the metastatic breast cancer setting and is undergoing exploration for other oncologic indications. ILD/pneumonitis is an adverse event of special interest associated with T-DXd, which has potentially fatal consequences if left untreated and allowed to progress. When identified in the asymptomatic stage (grade 1), T-DXd-related ILD can be monitored and treated effectively with the possibility of treatment continuation. Delayed diagnosis and/or treatment, however, results in progression to grade 2 or higher toxicity and necessitates immediate and permanent discontinuation of this active agent. Strategies are, therefore, needed to optimize careful monitoring during treatment to ensure patient safety and optimize outcomes. Several guidance documents have been developed regarding strategies for the early identification and management of T-DXd-related ILD, although none have been within the context of the Canadian health care environment. A Canadian multidisciplinary steering committee was, therefore, convened to evaluate existing recommendations and adapt them for application in Canada. A multidisciplinary approach involving collaboration among medical oncologists, radiologists, respirologists, and allied health care professionals is needed to ensure the proactive identification and management of T-DXd-related ILD and DI-ILD associated with other agents with a similar toxicity profile. [ABSTRACT FROM AUTHOR]

Aim: To investigate the impact of pentoxifylline (PTX, 3 × 400 mg per day) and ursodeoxycholic acid (UDCA, 3 × 250 mg per day) administered for 12 weeks on radiation-induced liver toxicity. Materials and methods: Inclusion criteria were liver metastases of extrahepatic malignancies undergoing HDR-BT. 36 patients were prospectively randomized to the medication (N = 18) or control arm (N = 18) and follow-up by hepatobiliary magnetic resonance imaging (MRI) was scheduled 6 and 12 weeks after local ablation by HDR-BT. We determined the threshold doses of fRILI by image fusion of MRI with the dosimetry data. Results: 32 patients completed the study schedule. Per-protocol treatment was limited to 8 patients in the medication group and 16 patients in the control group. 22 adverse events of any grade likely or certainly related to PTX were recorded in 12 patients leading to the discontinuation of the study medication in 7 patients and to a dose reduction of PTX in 2 patients. In the per-protocol population, statistical analysis failed to prove a reduction of fRILI 6 and 12 weeks after HDR-BT. The incidence of adverse effects attributed to PTX (70.6%) was well above the data found in the literature for its approved indication. Conclusion: The study endpoint was not met mainly attributed to the low statistical power of the small per-protocol cohort. Independently, PTX cannot be recommended for the reduction of radiation-induced liver toxicity in oncologic patients undergoing HDR-BT of liver metastases. Further studies might focus on a combination of UDCA with other potential drugs to help establish a preventive and tolerable regimen. [ABSTRACT FROM AUTHOR]

Purpose: To explore differences in dosimetry and planning parameters between intra-cavitary/interstitial interpolation (IC + ISBT) three-dimensional (3D)-printed template-based (3D-printed) and simple intra-cavity (ICBT) radiation techniques using a fixed Rotterdam three-tube applicator (TT) for computed tomography-guided high-dose-rate brachytherapy in locally advanced cervical cancer. Material and methods: This retrospective study included 100 patients (n = 50 each in 3D-printed and Rotterdam three-tube applicator treatment groups) with FIGO stages IIB-IVB cervical cancer from May 2019 to May 2022. Using high-risk clinical target volume, 377 of 400 plans categorized at intervals of 10 cm3 into 20-30, 30-40, 40-50, 50-60, 60-70, and 70-80 cm3; 23 plans with < 20 and > 80 cm³ volume were excluded. Dosimetry parameters (D90 and D98 of high-risk clinical target volume, and D2cc of organs at risk, including bladder, rectum, sigmoid, and bowel) and planning parameters (homogeneity index [HI], conformation number [CN], and organ at risk sparing factor) were compared between the two groups separately for six high-risk clinical target volume plan categories. Results: For the 3D-printing group, target coverage, organs at risk protection, and plan conformity and uniformity were better than those for the Rotterdam three-tube group. Particularly, in high-risk clinical target volume plans between 50-60 cm³, the mean D90 and D98 of high-risk clinical target volume were approximately 0.35 and 0.3 Gy higher, while the average D2cc of the bladder, rectum, sigmoid, and bowel were approximately 1.3, 0.9, 0.9, and 0.8 Gy significantly lower than those of the Rotterdam three-tube group, respectively (p < 0.05). The above-mentioned planning parameters differed significantly between the groups (p < 0.05). Conclusions: For the 3D-printing group, IC/ISBT reduced the dose for organs at risk while ensuring target coverage and conformation. This was especially noticeable for plans with high-risk clinical target volume of 50-60 cm³. [ABSTRACT FROM AUTHOR]

Background: Electromagnetic tracking (EMT) systems have been shown to provide valuable information on the geometry of catheter implants in breast cancer patients undergoing interstitial brachytherapy (iBT). In the context of an extended patient‐specific, pre‐treatment verification, EMT can play a key role in determining the potential need and, if applicable, the appropriate time for treatment adaptation. To detect dosimetric shortcomings the relative position between catheters, and target volume and critical structures must be known. Since EMT cannot provide the anatomical context and standard imaging techniques such as cone‐beam CT are not yet available in most brachytherapy suites, it is not possible to detect anatomic changes on a daily or fraction basis, so the need for adaptive planning cannot be identified. Purpose: The aim of this feasibility study is to develop and evaluate a technique capable of estimating follow‐up CTs at any time based on the initial treatment planning CT (PCT) and surrogate information about changes of the implant geometry from an EMT system. Methods: A deformation vector field is calculated from two different implant reconstructions acquired in treatment position through EMT, the first immediately after the PCT and the second at another time point during the course of treatment. The calculation is based on discrete displacement vectors of pairs of control and target points. These are extrapolated by means of different radial basis functions in order to cover the entire CT volume. The adequate parameters for the calculation of the deformation field were identified. By warping the PCT according to the deformation field, one obtains an estimated CT (ECT) that reflects the geometric changes. For the proof of concept, ECTs were computed for the time point of the clinical follow‐up CT (FCT) that is embedded in the treatment workflow after the fourth fraction. Results: ECT and clinical FCTs of 20 patients were compared to each other quantitatively in terms of absolute Hounsfield unit differences in the planning target volume (PTV) and in a convex hull (CH) enclosing the catheters. The median differences were 31.2 and 29.5 HU for the CH and the PTV, respectively. Conclusion: The proposed ECT approach was able to approximate the "anatomy of the day" and therefore, in principle, allows a dosimetric appraisal of the treatment plan quality before each fraction. In this way, it can contribute to a more detailed patient‐specific quality assurance in iBT of the breast and help to identify the timing for a potential treatment adaptation. [ABSTRACT FROM AUTHOR]

Background: Electromagnetic tracking (EMT) is a promising technology that holds great potential to advance patient‐specific pre‐treatment verification in interstitial brachytherapy (iBT). It allows easy determination of the implant geometry without line‐of‐sight restrictions and without dose exposure to the patient. What it cannot provide, however, is a link to anatomical landmarks, such as the exit points of catheters or needles on the skin surface. These landmarks are required for the registration of EMT data with other imaging modalities and for the detection of treatment errors such as incorrect indexer lengths, and catheter or needle shifts. Purpose: To develop an easily applicable method to detect reference points in the positional data of the trajectory of an EMT sensor, specifically the exit points of catheters in breast iBT, and to apply the approach to pre‐treatment error detection. Methods: Small metal objects were attached to catheter fixation buttons that rest against the breast surface to intentionally induce a local, spatially limited perturbation of the magnetic field on which the working principle of EMT relies. This perturbation can be sensed by the EMT sensor as it passes by, allowing it to localize the metal object and thus the catheter exit point. For the proof‐of‐concept, different small metal objects (magnets, washers, and bushes) and EMT sensor drive speeds were used to find the optimal parameters. The approach was then applied to treatment error detection and validated in‐vitro on a phantom. Lastly, the in‐vivo feasibility of the approach was tested on a patient cohort of four patients to assess the impact on the clinical workflow. Results: All investigated metal objects were able to measurably perturb the magnetic field, which resulted in missing sensor readings, that is two data gaps, one for the sensor moving towards the tip end and one when retracting from there. The size of the resulting data gaps varied depending on the choice of gap points used for calculation of the gap size; it was found that the start points of the gaps in both directions showed the smallest variability. The median size of data gaps was ⩽8 mm for all tested materials and sensor drive speeds. The variability of the determined object position was ⩽0.5 mm at a speed of 1.0 cm/s and ⩽0.7 mm at 2.5 cm/s, with an increase up to 2.3 mm at 5.0 cm/s. The in‐vitro validation of the error detection yielded a 100% detection rate for catheter shifts of ≥2.2 mm. All simulated wrong indexer lengths were correctly identified. The in‐vivo feasibility assessment showed that the metal objects did not interfere with the routine clinical workflow. Conclusions: The developed approach was able to successfully detect reference points in EMT data, which can be used for registration to other imaging modalities, but also for treatment error detection. It can thus advance the automation of patient‐specific, pre‐treatment quality assurance in iBT. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between serum tumor markers and pathological features of cervical cancer and the prediction of postoperative recurrence. Methods: 82 patients with cervical cancer who came to our hospital from January 2015 to December 2017 were selected as the observation group, and 50 healthy women who came to our hospital for physical examination during the same period were selected. The serum levels of CA125, CA153, CA199 and CEA in both groups were detected by electrochemical luminescence immunoassay. Patients in the observation group were followed up until December 2022. The serum CA125, CA153, CA199, CEA levels of the two groups were compared, and the relationship between the serum CA125, CA153, CA199, CEA levels and clinicopathological characteristics of the observation group was analyzed. The recurrence of patients in the observation group was analyzed after the postoperative follow-up, and the univariate and multivariate Cox regression results of the recurrence of patients after radical resection of cervical cancer were analyzed. Prognostic value of serum CA125, CA153, CA199 and CEA levels for recurrence of cervical cancer after radical resection. Results: The levels of serum CA125, CA153, CA199 and CEA in observation group were significantly higher than those in control group (P<0.05). The levels of serum CA125, CA153, CA199 and CEA among patients with cervical cancer at different FIGO stages, depth of interstitial invasion and presence of lymph node metastasis were statistically significant (P<0.05). The follow-up time of 82 patients was 13-60 months, and the median survival time was 39 months. By the end of December 2022, 18 of 82 patients (21.95%) had relapse after surgery. Univariate and multivariate Cox regression analysis showed that FIGO stage in stage Ⅱ A, interstitial infiltration depth ≥ 1/2, lymph node metastasis, CA125 ≥ 307.41U/mL, CA153 ≥ 185.89U/mL, CA199 ≥ 153.23U/mL, CEA≥ 30.15ng/mL are independent risk factors for postoperative recurrence of cervical cancer.ROC curve showed that the AUC value of CA125+CA153+CA199+CEA in predicting postoperative recurrence of cervical cancer was significantly higher than that of CA125, CA153, CA199 and CEA alone (P<0.05). Conclusion: Serum CA125, CA153, CA199 and CEA are highly expressed in patients with cervical cancer, which is related to the depth of interstitial infiltration, FIGO stage, lymph node metastasis and postoperative recurrence. The combination of the four can be used as a predictor of postoperative recurrence of cervical cancer. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the treatment results with focus on local control (LC) by computed tomography (CT)-guided intracavity brachytherapy and interstitial brachytherapy (ICBT/ISBT) for locally advanced cervical cancer (LACC). Patients with LACC undergoing ICBT/ISBT at least once in our institution between January 2017 and June 2019 were analyzed retrospectively. The primary endpoint was local control (LC), and the secondary endpoints were progression-free survival (PFS), overall survival (OS), and late toxicities. Differences between patient subgroups for prognostic factors in LC, PFS, and OS were analyzed using the log-rank test. The recurrence patterns of LC were also investigated. Forty-four patients were included in the present study. The median high-risk clinical target volume (HR-CTV) at the initial brachytherapy was 48.2 cc. The median total dose of HR-CTV D90 (EQD2) was 70.7 Gy. The median followup period was 39.4 months. The 3-year LC, PFS and OS rates in all patients were 88.2%, 56.6%, and 65.4% (95% CI 50.3–78.0%), respectively. Corpus invasion and large HR-CTV (70 cc or more) were significant prognostic factors in LC, PFS, and OS. Marginal recurrences at the fundus of the uterus were detected in 3 of 5 patients in whom local recurrence was observed. Late toxicities of Grade 3 or higher were detected in 3 patients (6.8%). Favorable LC was achieved by performing CT-guided ICBT/ISBT for LACC. The brachytherapy strategy for patients with corpus invasion or large HR-CTV may need to be reconsidered. [ABSTRACT FROM AUTHOR]

Brachytherapy (BT) is integral in treatment of gynecological malignancies and is also an option for many other cancers. Data on training and proficiency levels of early career oncologists is limited. Like other continents a survey was conducted for early career oncologists in India. An online survey was conducted from November 2019 to February 2020, through Association of Radiation Oncologists of India (AROI) for early career radiation oncologists expected to be within 6 years of training. The survey used a 22 item questionnaire that was also used for European survey. Responses to individual statements were recorded on a 1–5 Likert-type scale. Descriptive statistics were used to describe proportions. One-hundred twenty-four (17%) of 700 recipients responded to the survey. Majority of the respondents (88%) stated that being able to perform BT at the end of their training was important. Two-thirds of the respondents (81/124) had performed >10 intracavitary procedure and 22.5% had performed >10 intracavitary-interstitial implants. Many respondents had not performed nongynecological procedure- breast (64%), prostate(82%), gastro-intestinal (47%). Respondents predicted that in next 10 years, the role of BT is likely to increase. Lack of dedicated curriculum and training was perceived as the greatest barriers to achieving independence in BT (58%). Respondents suggested that BT training should be prioritized during conferences (73%) and online teaching modules (56%), along with development of BT skills labs (65%). This survey identified a lack of proficiency in gynecological intracavitary-interstitial brachytherapy and non-gynecological brachytherapy, despite BT training being regarded as highly important. Dedicated programs, including standardized curriculum and assessment need to be developed for training early- career radiation oncologists in BT. [ABSTRACT FROM AUTHOR]

To analyze clinical outcomes of high-dose-rate (HDR) interstitial brachytherapy boost (ISBT) after external beam radiation therapy (EBRT) or chemoradiotherapy (CRT) for the treatment of anal canal cancers (ACC). A total of 78 patients with ACC were treated at our institution by ISBT. Local Control (LC), disease-free survival (DFS), overall survival (OS), colostomy-free survival (CFS) and toxicity rates were analyzed. With a median followup (FU) of 59.8 months (95% CI [55.8–64.2]), six (7.7%) local recurrences with 2 patients (2.6%) having persistent disease at 3 months were observed. The 5-year rate of LC for the entire population was 92% [83–96%]. The 5-year DFS rate was 86% [76–93%]. The 5-year OS was 96% [88–99%]. In the univariate analysis, chemotherapy was significantly associated with morbidity grade ≥2. Late digestive toxicity grade ≥3 was reported in 8.9% patients, 1 patient underwent colostomy due to toxicity. The 5-year CFS rate was 88% [79–94%]. HDR interstitial brachytherapy boost provide excellent rates of tumor control and colostomy-free survival with a favorable profile of GI toxicity. Continence in anal cancer survivors is a challenge and the boost technique must be discussed in a multidisciplinary approach as part of de-escalation treatments. [ABSTRACT FROM AUTHOR]

Delivering highly conformal treatment plans for high-dose rate vaginal brachytherapy using commercially available applicators can be challenging. A partially automated workflow is presented for the in-house modeling and 3D printing of patient-specific cylindrical templates (PSCTs), which facilitate placement of flexible intracavitary and interstitial needles. To demonstrate feasibility, we compare PSCT treatment plans to retrospective interstitial brachytherapy plans delivered at our center. PSCTs derived from these plans were 3D printed to test the validity of the auto-design process. To facilitate clinical implementation, we validated the steam sterilization compatibility of PSCTs printed using polyetheretherketone (PEEK). Plans for ten patients treated using a combination of vaginal cylinder and interstitial needles were compared to PSCT-based plans created for the same patient. DVH parameters for the HRCTV (V100, V150, V200, D90) and OARs (D2 cm3) were evaluated, as well as the number of needles used and the total interstitial length. Each planned PSCT was printed and compared to the intended needle geometry. 3D printed models were sterilization validated by an independent contractor for an autoclave protocol. PSCT plans demonstrated advantages over template based perineal BT in reducing the total interstitial needle length required while preserving or improving HRCTV and OAR dosimetry. All printed PSCTs matched planned geometry. PSCTs stand to be an alternative to current HDR-BT templates/applicators for patients with vaginal and locally recurrent endometrial cancers. Clinically equivalent or improved treatment plans can be created and devices to deliver these plans can be accurately printed and sterilized. [ABSTRACT FROM AUTHOR]

To provide a systematic review of the applications of 3D printing in gynecological brachytherapy. Peer-reviewed articles relating to additive manufacturing (3D printing) from the 34 million plus biomedical citations in National Center for Biotechnology Information (NCBI/PubMed), and 53 million records in Web of Science (Clarivate) were queried for 3D printing applications. The results were narrowed sequentially to, (1) all literature in 3D printing with final publications prior to July 2022 (in English, and excluding books, proceedings, and reviews), and then to applications in, (2) radiotherapy, (3) brachytherapy, (4) gynecological brachytherapy. Brachytherapy applications were reviewed and grouped by disease site, with gynecological applications additionally grouped by study type, methodology, delivery modality, and device type. From 47,541 3D printing citations, 96 publications met the inclusion criteria for brachytherapy, with gynecological clinical applications compromising the highest percentage (32%), followed by skin and surface (19%), and head and neck (9%). The distribution of delivery modalities was 58% for HDR (Ir-192), 35% for LDR (I-125), and 7% for other modalities. In gynecological brachytherapy, studies included design of patient specific applicators and templates, novel applicator designs, applicator additions, quality assurance and dosimetry devices, anthropomorphic gynecological applicators, and in-human clinical trials. Plots of year-to-year growth demonstrate a rapid nonlinear trend since 2014 due to the improving accessibility of low-cost 3D printers. Based on these publications, considerations for clinical use are provided. 3D printing has emerged as an important clinical technology enabling customized applicator and template designs, representing a major advancement in the methodology for implantation and delivery in gynecological brachytherapy. [ABSTRACT FROM AUTHOR]

Locoregionally recurrent head and neck cancer is a complex clinical scenario that often requires multimodality treatment. These patients have often previously received definitive treatment with a combination of surgery, radiation therapy, and systemic therapy, which can make further management difficult. A second isolated locoregional failure is rare and clinicians are faced with a challenge to optimize disease control while minimizing treatment-related toxicity. In this report, we present the diagnosis, management, and outcomes of a patient with an isolated locoregional recurrence who was previously treated with two courses of radiation. The patient was treated with a second course of reirradiation using interstitial brachytherapy as well as a discussion regarding patient selection and optimal management for recurrent head and neck cancer. Repeat reirradiation using interstitial HDR-brachytherapy with the use of an alloderm spacer was successfully delivered to the patient for an in-field right neck nodal recurrence. He received a total EQD2/BED dose of 127.70/153.24 Gy. At 1-year followup, the patient was without evidence of recurrent disease or new significant side effects. Recurrent head and neck cancer should be managed with a multidisciplinary approach given the complex clinical scenario. Reirradiation is a commonly used salvage measure for recurrent head and neck cancer that requires careful planning and patient selection due to prior treatment-related effects and dose constraints. We reported a case of a second course of reirradiation using interstitial HDR-brachytherapy for locoregionally recurrent head and neck cancer and showed no recurrence of disease or worsening long term side effects at 1 year. [ABSTRACT FROM AUTHOR]

Introduction: The role of mitochondria in post coronavirus disease 2019 (post-COVID-19) complications is unclear, especially in the long-term pulmonary complications. This study aims to investigate the association between post-COVID-19 pulmonary complications and mitochondrial regulatory proteins in the context of oxidative stress. Methodology: Patients who had recovered from COVID-19 were enrolled. According to the evidence of persistent interstitial lung lesions on computed tomography (CT), patients were divided into a long-term pulmonary complications group (P(+)) and a control group without long-term pulmonary complications (P(−)). We randomly selected 80 patients for investigation (40 subjects for each group). Biomarkers levels were determined by enzyme-linked immunosorbent assay (ELISA). Results: The serum concentrations of mitochondrial regulatory proteins were significantly higher in the P(+) group, including PTEN-induced kinase 1 (PINK1): 1.62 [1.02–2.29] ng/mL vs. 1.34 [0.94–1.74] ng/mL (p = 0.046); Dynamin-1-like protein (DNM1L): 1.6 [0.9–2.4] ng/mL IQR vs. 0.9 [0.5–1.6] ng/mL (p = 0.004); and Mitofusin-2 (MFN2): 0.3 [0.2–0.5] ng/mL vs. 0.2 [0.1–0.3] ng/mL IQR (p = 0.001). Patients from the P(+) group also had higher serum levels of chemokine ligand 18 (PARC, CCL18), IL-6, and tumour necrosis factor-alpha (TNF-α) cytokines than the P(−) group. The concentration of interferon alpha (IFN-α) was decreased in the P(+) group. Furthermore, we observed statistically significant correlations between the advanced glycation end product (sRAGE) and TNF-α (Pearson's factor R = 0.637; p < 0.001) and between serum levels of DNM1L and IFN-α (Pearson's factor R = 0.501; p = 0.002) in P(+) patients. Conclusions: Elevated concentrations of mitochondrial biomarkers in post-COVID-19 patients with long-term pulmonary complications indicate their possible role in the pathobiology of COVID-19 pulmonary sequelae. Oxidative stress is associated with the immune response and inflammation after COVID-19. TNF-α could be a promising biomarker for predicting pulmonary complications and may be a potential target for therapeutic intervention in patients with post-COVID-19 complications. [ABSTRACT FROM AUTHOR]

Purpose: Interstitial brachytherapy (ISBT) is indicated for intact cervical carcinoma (IN-CC) if intracavitary brachytherapy (ICRT) is not feasible and also in vault carcinoma (VA-C). We aimed to evaluate the doses to pelvic lymph node regions in IN-CC and VA-C treated with ISBT. Material and methods: Ten patients (6 IN-CC, 4 VA-C) were chosen for this dosimetric study. IN-CC had a central tandem in addition to the needles. External iliac (EI-N), internal iliac (II-N), obturator (OB-N) and sacral (SA-N) groups of lymph nodes were delineated. A dose of 10 grays (Gy) and 8 Gy each x 2 fractions was prescribed to the target in IN-CC and VA-C respectively. Doses received by 100%, 90% and 50% volume (D100, D90, D50) and D2cc, D1cc, D0.1cc were evaluated. Doses to lymph nodal groups in IN-CC vs. VA-C were compared using Student's t-test. Results: For 20 implants, the median number of needles was 18 (range, 16-20). Mean D90 and D2cc of the combined bilateral OB-N, II-N, EI-N and SA-N groups were 33.62 ±3.46% and 102.94 ±10.71%, 6.98 ±0.65% and 39.69 ±3.64%, 5.1 ±0.51% and 15.4 ±0.8%, 7.76 ±0.95% and 15.36 ±1.09% of the prescribed doses respectively. Patients with a central tandem (IN-CC) received significantly higher doses to external, internal iliac and sacral group of lymph nodes (p < 0.001) as compared to VA-C. Conclusions: In patients with cervical carcinoma treated with ISBT, pelvic lymph node groups received significant doses. The dose contribution to pelvic lymph nodes is higher in patients with intact cervical cancer where a central tandem is used as compared to post-operative patients. [ABSTRACT FROM AUTHOR]

Purpose: To report outcomes of using image-guided hybrid intra-cavitary/interstitial applicators under moderate sedation for locally advanced cervical cancer patients in our institution. Material and methods: A total of 69 fractions of brachytherapy with hybrid applicators were performed in 33 patients from January 2017 to April 2021. All patients underwent MRI pelvis 1 week pre-brachytherapy to determine suitability for interstitial brachytherapy and pre-plan needle placement. All insertion of applicators were performed under moderate sedation with midazolam and/or fentanyl. Fifty-eight (84.1%) fractions were planned with CT alone. Clinical outcomes, dose volume parameters, and toxicities were analyzed. Results: The median follow-up was 28 months. A total of 320 needles (median, 5 needles per fraction) were implanted, with a median insertion depth of 3 cm (range, 1.5-4 cm). The median high-risk clinical target volume (HR-CTV) during initial brachytherapy was 34.5 cc (range, 17.8-74.7 cc). The median total EQD2 D2cc of the rectum, bladder, sigmoid, and small intestine colon was 71.8 Gy, 81.5 Gy, 69 Gy, and 58.3 Gy, respectively. The 2-year local control and overall survival were 80.7% and 77.7%, respectively. Larger volume HR-CTV was significantly associated with worse local control (HR = 1.08, p = 0.005) and overall survival (HR = 1.04, p = 0.015). None of the patients required in-patient admission or blood transfusion post-procedure. Late grade 3 gastrointestinal and genitourinary toxicities were observed in 4 patients (12.2%). Conclusions: Hybrid applicators inserted under moderate sedation are feasible and safe. Image-guided interstitial brachytherapy with CT planning aided by MRI performed 1 week pre-brachytherapy is associated with favorable outcomes and modest toxicities. [ABSTRACT FROM AUTHOR]