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Purpose: The purpose of this study was to provide risk estimations for vaginal morbidity with regard to vaginal dilation (summarizing the use of dilators and/or sexual activity) in patients with locally advanced cervical cancer treated with definitive radiochemotherapy and image guided adaptive brachytherapy within the prospective, multi-institutional EMBRACE-I study., Methods and Materials: Physician-assessed vaginal morbidity (National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0), use of vaginal dilators, and patient-reported sexual activity (EORTC-CX24) were prospectively assessed at baseline and during regular follow-ups. Frequency analysis for vaginal dilation was performed in a subcohort of patients with ≥3 follow-ups. Regular dilation was defined if reported in ≥50% of follow-ups, and no/infrequent dilation if reported in <50%. Actuarial estimates were calculated with Kaplan-Meier method; comparisons were evaluated with the log-rank test. Univariate and multivariable Cox proportional hazard regressions were used to evaluate risk factors for vaginal stenosis G≥2., Results: The EMBRACE-I study included a total of 1416 patients (2008-2015); 882 were evaluated in the present report with a median follow-up of 60 months. Of those, 565 (64%) reported regular dilation. This was associated with a significantly lower 5-year risk of vaginal stenosis G≥2 compared with no/infrequent dilation (23% vs 37%, P ≤ .001). This univariate finding was confirmed by multivariable analysis, after adjusting for other risk factors (hazard ratio, 0.630; P = .001). Regular vaginal dilation was also associated with a significantly higher risk for vaginal dryness G≥1 (72% vs 67%, P = .028) and bleeding G≥1 (61% vs 34%, P ≤ .001)., Conclusions: Vaginal stenosis represents irreversible fibrotic changes that can cause pain during gynecologic examination and dyspareunia in locally advanced cervical cancer patients survivors. Regular vaginal dilation (defined as the use of dilators and/or sexual activity) is associated with a significantly lower risk for G≥2 vaginal stenosis, suggesting a potential improvement of vaginal patency. It is also associated with a significantly higher risk for mild G≥1 dryness and bleeding (no higher risk for G≥2), which can be clinically managed., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Major improvements in radiotherapy over the past two decades in the definitive treatment of locally advanced cervical cancer have significantly improved loco-regional control and survival, whereas little progress has been made with chemotherapy since the implementation of concomitant cisplatin 25 years ago. However, the randomized study INTERLACE (A phase III multicenter trial of weekly induction chemotherapy followed by standard chemoradiation versus standard chemoradiation alone in patients with locally advanced cervical cancer) of neoadjuvant chemotherapy presented recently, has shown significant improvement in survival with the use of six cycles of weekly carboplatin and paclitaxel. Although INTERLACE is yet to be published, neoadjuvant chemotherapy is already being advocated as the new standard, and studies are being designed with neoadjuvant chemotherapy followed by chemoradiation and brachytherapy as the standard arm. It is noteworthy that INTERLACE was initiated before the improvements in radiotherapy mentioned above were broadly implemented. The survival rate in the standard arm of INTERLACE was therefore inferior to the results obtained with the latest state-of-the-art external beam radiotherapy and image guided adaptive brachytherapy (EMBRACE, Magnetic Resonance Imaging (MRI)-Guided Brachytherapy in Locally Advanced Cervical Cancer). Moreover, patient selection impedes the comparison of INTERLACE with other studies as the patients included in INTERLACE were younger, had better performance status, and had less advanced disease than in other studies. Notably patients with involved para-aortic nodes were excluded. In this review, we discuss neoadjuvant chemotherapy in the frame of the EMBRACE studies and show how the impact of modern radiotherapy and patient selection affects the interpretation of the results of INTERLACE. This has led us to conclude that neoadjuvant chemotherapy is not needed for the majority of patients with cervical cancer treated with definitive modern radiotherapy, and may cause harm. However, it is possible that short course neoadjuvant chemotherapy may benefit a minor subgroup of patients who need to be identified. Comprehensive understanding, including cost utility analyses, are needed to draw conclusions regarding the potential benefit of neoadjuvant chemotherapy in low and middle income countries with limited access to modern radiotherapy., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Purpose: BIOEMBRACE was designed to study the impact of biomarkers in addition to clinicopathological factors on disease outcomes in patients treated with chemoradiation and magnetic resonance imaging (MRI)-guided brachytherapy (BT) for locally advanced cervical cancer in the EMBRACE study., Methods and Materials: Between 2018 and 2021, 8 EMBRACE-I sites contributed tumor tissue for the immunohistochemistry of p16, PD-L1, and L1CAM. These biomarkers and clinicopathological factors (International Federation of Gynecology and Obstetrics 2009 stage, nodal status, histology, and necrosis on MRI) were analyzed to predict poor response at BT (high-risk clinical target volume [HR-CTV] ≥ 40 cc) at BT) and 5-year local control, pelvic control, and disease-free survival. Interaction between p16, PD-L1, radiation therapy dose (HR-CTV D90), and disease outcomes was investigated. Univariable and multivariable analyses were performed., Results: Two hundred sixty-four patients were included. The median HR-CTV D90 was 89 Gy (86-95). P-16 positive status, PD-L1 > 1%, and L1CAM ≥ 10% was noted in 86.6%, 20.1%, and 17.8% of patients, respectively. P16 negative status (odds ratio, 2.0; 95% CI, 1.0-5.7; P = .04) and necrosis on MRI (odds ratio, 2.1; 95% CI, 1.1-4.3; P < .02) independently predicted for HR-CTV ≥ 40 cc, as did the International Federation of Gynecology and Obstetrics stage and tumor width >5 cm. PD-L1 > 1% was associated with reduced local (82% vs 94%; P = .02) and pelvic control (79% vs 89%; P = .02). HR-CTV D90 < 85 Gy was associated with inferior 5-year local control in p16-positive patients, especially if PD-L1 was coexpressed. On multivariable analysis, PD-L1 > 1% was the only independent factor for 5-year local control (hazard ratio, 3.3; P = .04) and L1CAM ≥ 50% for pelvic control (hazard ratio, 5.5; 95% CI, 1.3-23.3; P = .02)., Conclusions: P16 negative status and tumor necrosis on MRI are independently associated with poor response to chemoradiation, whereas PD-L1 > 1% and L1CAM ≥ 50% have an independent impact on local and pelvic control, suggesting an impact of biomarker expression on outcomes. Further validation is needed., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate oncological outcomes and toxicities in patients with locally advanced cervical cancer (LACC) treated with concurrent chemoradiotherapy followed by image-guided adaptive brachytherapy at two Italian centres., Material and Methods: A retrospective analysis was conducted on 122 patients with LACC treated between 2010 and 2022. Primary endpoints were local control (LC), pelvic control (PC), and nodal control (NC). Secondary endpoints included disease-free survival (DFS), metastasis-free survival (MFS), overall survival (OS), and late toxicity. Correlations between patient characteristics and oncological outcomes were conducted., Results: Brachytherapy planning was CT and MRI-based in 88 (72.1%) and 34 patients (27.9%), respectively. The mean total dose (EQD2) delivered to high-risk clinical target volume was 82 Gy. Overall treatment time was ≤ 50 days and > 50 days in 48 (39.3%) and 74 patients (60.7%), respectively. At a mean follow up of 101 months, 3 and 5-year LC rates were 87% and 85%, respectively. Five-year PC and NC rates were 77% and 85.1%. Five-year DFS and OS were 61% and 65.4%, respectively, with significant correlations between these outcomes and FIGO stage and nodal status at diagnosis. Gastrointestinal, genitourinary and vaginal adverse effects were the most reported late toxicities and 8 (6.5%) grade 3-5 events were observed. 32 patients (26.2%) had vaginal stenosis and it was significantly related to 3D imaging used for brachytherapy planning., Conclusions: The study confirmed the efficacy and safety of chemoradiotherapy and IGABT for LACC. Full implementation of MRI treatment planning and interstitial techniques could further enhance personalized treatment and outcomes., (© 2024. Italian Society of Medical Radiology.)

Purpose: External beam radiotherapy with concurrent chemotherapy combined with brachytherapy has been described as the first treatment choice for locally advanced cervical cancer. This study aimed to systematically review the dose-effect relationship (DER) of target volumes and organs at risk (OARs) in external beam radiotherapy combined with brachytherapy for cervical cancer. Material and methods: Studies reporting DER in radical radiotherapy for cervical cancer were determined by searching PubMed, Web of Science, and Cochrane Library databases till Jan 20, 2023. Dose parameters of DER, endpoint of tumor control or type and grade of side effects of OARs as well as prediction results were analyzed from included studies. Coordinates of DER curves from the included studies were extracted and DER curves were reconstructed in the same coordinate system for comparison. Results: Thirty studies, including eleven dose-response relationships for clinical end-points, and nineteen dose-toxicity relationships for OARs were evaluated in systematic review. The most common dose-response relationship between the same dose parameter and the same clinical end-point was HR-CTV D90 vs. local tumor control, while it was D2cc of rectum versus rectal grade 2-4 side effects for dose-toxicity relationship. Conclusions: In the radical radiotherapy of cervical cancer, there were significant DERs for target volumes and OARs. Considering the interference of these factors, DERs in sub-group patients would provide precise and individualized dose constraints of radiotherapy for cervical cancer in the future. [ABSTRACT FROM AUTHOR]

Simple Summary: Brachytherapy is a key component of radiation treatment in the curative treatment of locally advanced cervical cancer. To improve the delivery of brachytherapy, recent studies have explored the use of imaging, such as magnetic resonance imaging (MRI), in treatment planning. In this review, we reviewed the current evidence for image-guided brachytherapy and discussed future directions for research. Purpose: The standard of care for patients with locally advanced cervical cancer is definitive chemoradiation followed by a brachytherapy boost. This review describes the current status and future directions of image-guided adaptive brachytherapy for locally advanced cervical cancer. Methods: A systematic search of the PubMed and Clinicaltrials.gov databases was performed, focusing on studies published within the last 10 years. The search queried "cervical cancer [AND] image-guided brachytherapy [OR] magnetic resonance imaging (MRI) [OR] adaptive brachytherapy". Discussion: The retroEMBRACE and EMBRACE-I trials have established the use of MRI as the standard imaging modality for brachytherapy application and planning. Quantitative imaging and radiomics have the potential to improve outcomes, with three ongoing prospective studies examining the use of radiomics to further risk-stratify patients and personalize brachytherapy. Another active area of investigation includes utilizing the superior soft tissue contrast provided by MRI to increase the dose per fraction and decrease the number of fractions needed for brachytherapy, with several retrospective studies demonstrating the safety and feasibility of three-fraction courses. For developing countries with limited access to MRI, trans-rectal ultrasound (TRUS) appears to be an effective alternative, with several retrospective studies demonstrating improved target delineation with the use of TRUS in conjunction with CT guidance. Conclusions: Further investigation is needed to continue improving outcomes for patients with locally advanced cervical cancer treated with image-guided brachytherapy. [ABSTRACT FROM AUTHOR]

(1) Background: External beam radiotherapy (EBRT) and concurrent chemotherapy, followed by brachytherapy (BT), offer a standard of care for patients with locally advanced cervical carcinoma. Conventionally, large safety margins are required to compensate for organ movement, potentially increasing toxicity. Lately, daily high-quality cone beam CT (CBCT)-guided adaptive radiotherapy, aided by artificial intelligence (AI), became clinically available. Thus, online treatment plans can be adapted to the current position of the tumor and the adjacent organs at risk (OAR), while the patient is lying on the treatment couch. We sought to evaluate the potential of this new technology, including a weekly shuttle-based 3T-MRI scan in various treatment positions for tumor evaluation and for decreasing treatment-related side effects. (2) Methods: This is a prospective one-armed phase-II trial consisting of 40 patients with cervical carcinoma (FIGO IB-IIIC1) with an age ≥ 18 years and a Karnofsky performance score ≥ 70%. EBRT (45–50.4 Gy in 25–28 fractions with 55.0–58.8 Gy simultaneous integrated boosts to lymph node metastases) will be accompanied by weekly shuttle-based MRIs. Concurrent platinum-based chemotherapy will be given, followed by 28 Gy of BT (four fractions). The primary endpoint will be the occurrence of overall early bowel and bladder toxicity CTCAE grade 2 or higher (CTCAE v5.0). Secondary outcomes include clinical feasibility, quality of life, and imaging-based response assessment. [ABSTRACT FROM AUTHOR]

Background: Achieving a clinically acceptable dose distribution with commercial vaginal applicators for brachytherapy of recurrent parauterine tumors is challenging. However, the application of three-dimensional (3D) printing technology in brachytherapy has been widely acknowledged and can improve clinical treatment outcomes., Purpose: This study aimed to introduce an individual curved-needle interstitial template (ICIT) created using 3D printing technology for high-dose-rate (HDR) brachytherapy with interstitial treatment to provide a clinically feasible approach to distal parauterine and vaginal cuff tumors. The entire workflow, including the design, optimization, and application, is presented., Methods: Ten patients with pelvic cancer recurrence were examined at our center. The vaginal topography was filled with gauze strips soaked in developer solution, and images were obtained using computed tomography (CT) and magnetic resonance imaging (MRI). Curved needle paths were designed, and ICITs were 3D-printed according to the high-risk clinical target volume (HRCTV) and vaginal filling model. The dose and volume histogram parameters of the HRCTV (V 100 , V 200 , D 90 , and D 98 ) and organs at risk (OARs) (D 2cc ) were recorded., Results: All patients completed interstitial brachytherapy treatment with the 3D-printed ICIT. One patient experienced vaginal cuff tumor recurrence, and nine patients experienced parametrial tumor recurrence (four on the left and five on the right). We used two to five interstitial needles, and the maximum angle of the curved needle was 40°. No source obstruction events occurred during treatment of these 10 patients. The doses delivered to the targets and OARs of all patients were within the dose limits and based on clinical experience at our center., Conclusion: The ICIT is a treatment option for patients with distal parauterine tumor recurrence. This method addresses the limitations of vaginal intracavitary and standard interstitial applicators. The ICIT has the advantages of biocompatibility, personalization, and magnetic resonance imaging compatibility., (© 2024 American Association of Physicists in Medicine.)

Purpose: The present study aimed to analyze the operative duration of image-guided brachytherapy (IGBT) for cervical cancer performed at our institution., Methods: We enrolled cervical cancer patients who had undergone tandem and ovoid-based intracavitary brachytherapy (ICBT) or intracavitary and interstitial brachytherapy (IC/ISBT) between 2020 and 2024. Cone beam computed tomography (CBCT), CT, or CT + MRI were used for IGBT. For each IGBT session, we retrospectively reviewed the following: application time (AT-defined as the duration from entry into the operating room to the initial image acquisition); planning time (PT-defined as the duration from the initial image acquisition to the start of irradiation); and total operation time (TOT- defined as the duration from entry to exit of the operating room)., Results: We analyzed a total of 126 sessions in 36 patients, consisting of 99 ICBT-only sessions and 27 IC/ISBT sessions. The IC/ISBT sessions had a significantly longer mean operative duration than the ICBT-only sessions. The IC/ISBT sessions with three or more interstitial needles had significantly longer AT and TOT. However, the IC/ISBT sessions with one needle showed no significant difference in operative duration compared to ICBT-only sessions. CBCT, CT, and CT + MRI were used in 42, 76, and 8 sessions, respectively. In the ICBT patients, CT + MRI had the longest PT. However, there was no significant differences in TOT among CBCT, CT, and CT + MRI., Conclusions: IC/ISBT sessions with one needle had no significant difference in operative duration compared to ICBT-only sessions. There was no significant difference in TOT between CT + MRI-based IGBT and CT-based IGBT., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

High dose-rate brachytherapy is a treatment technique for gynecologic cancers where intracavitary applicators are placed within the patient's pelvic cavity. To ensure accurate radiation delivery, localization of the applicator at the time of insertion is vital. This study proposes a novel method for acquiring, registering, and fusing three-dimensional (3D) trans-abdominal and 3D trans-rectal ultrasound (US) images for visualization of the pelvic anatomy and applicators during gynecologic brachytherapy. The workflow was validated using custom multi-modal pelvic phantoms and demonstrated during two patient procedures. Experiments were performed for three types of intracavitary applicators: ring-and-tandem, ring-and-tandem with interstitial needles, and tandem-and-ovoids. Fused 3D US images were registered to magnetic resonance (MR) and computed tomography (CT) images for validation. The target registration error (TRE) and fiducial localization error (FLE) were calculated to quantify the accuracy of our fusion technique. For both phantom and patient images, TRE and FLE across all modality registrations (3D US versus MR or CT) resulted in mean ± standard deviation of 4.01 ± 1.01 mm and 0.43 ± 0.24 mm, respectively. This work indicates proof of concept for conducting further clinical studies leveraging 3D US imaging as an accurate, accessible alternative to advanced modalities for localizing brachytherapy applicators., (© 2024. The Author(s).)

Background: Direction Modulated Brachytherapy (DMBT) enables conformal dose distributions. However, clinicians may face challenges in creating viable treatment plans within a fast-paced clinical setting, especially for a novel technology like DMBT, where cumulative clinical experience is limited. Deep learning-based dose prediction methods have emerged as effective tools for enhancing efficiency., Purpose: To develop a voxel-wise dose prediction model using an attention-gating mechanism and a 3D UNET for cervical cancer high-dose-rate (HDR) brachytherapy treatment planning with DMBT six-groove tandems with ovoids or ring applicators., Methods: A multi-institutional cohort of 122 retrospective clinical HDR brachytherapy plans treated to a prescription dose in the range of 4.8-7.0 Gy/fraction was used. A DMBT tandem model was constructed and incorporated onto a research version of BrachyVision Treatment Planning System (BV-TPS) as a 3D solid model applicator and retrospectively re-planned all cases by seasoned experts. Those plans were randomly divided into 64:16:20 as training, validating, and testing cohorts, respectively. Data augmentation was applied to the training and validation sets to increase the size by a factor of 4. An attention-gated 3D UNET architecture model was developed to predict full 3D dose distributions based on high-risk clinical target volume (CTV HR ) and organs at risk (OARs) contour information. The model was trained using the mean absolute error loss function, Adam optimization algorithm, a learning rate of 0.001, 250 epochs, and a batch size of eight. In addition, a baseline UNET model was trained similarly for comparison. The model performance was evaluated on the testing dataset by analyzing the outcomes in terms of mean dose values and derived dose-volume-histogram indices from 3D dose distributions and comparing the generated dose distributions against the ground-truth dose distributions using dose statistics and clinically meaningful dosimetric indices., Results: The proposed attention-gated 3D UNET model showed competitive accuracy in predicting 3D dose distributions that closely resemble the ground-truth dose distributions. The average values of the mean absolute errors were 1.82 ± 29.09 Gy (vs. 6.41 ± 20.16 Gy for a baseline UNET) in CTV HR , 0.89 ± 1.25 Gy (vs. 0.94 ± 3.96 Gy for a baseline UNET) in the bladder, 0.33 ± 0.67 Gy (vs. 0.53 ± 1.66 Gy for a baseline UNET) in the rectum, and 0.55 ± 1.57 Gy (vs. 0.76 ± 2.89 Gy for a baseline UNET) in the sigmoid. The results showed that the mean absolute error (MAE) for the bladder, rectum, and sigmoid were 0.22 ± 1.22 Gy (3.62%) (p = 0.015), 0.21 ± 1.06 Gy (2.20%) (p = 0.172), and -0.03 ± 0.54 Gy (1.13%) (p = 0.774), respectively. The MAE for D 90 , V 100% , and V 150% of the CTV HR were 0.46 ± 2.44 Gy (8.14%) (p = 0.018), 0.57 ± 11.25% (5.23%) (p = 0.283), and -0.43 ± 19.36% (4.62%) (p = 0.190), respectively. The proposed model needs less than 5 s to predict a full 3D dose distribution of 64 × 64 × 64 voxels for any new patient plan, thus making it sufficient for near real-time applications and aiding with decision-making in the clinic., Conclusions: Attention gated 3D-UNET model demonstrated a capability in predicting voxel-wise dose prediction, in comparison to 3D UNET, for DMBT intracavitary brachytherapy planning. The proposed model could be used to obtain dose distributions for near real-time decision-making before DMBT planning and quality assurance. This will guide future automated planning, making the workflow more efficient and clinically viable., (© 2024 The Author(s). Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Introduction: Locally advanced carcinoma cervix (LACC) is a heterogeneous disease with variable combinations of primary tumour extensions with or without nodal involvement. Metabolic information from 18 fluro-deoxyglucose positron emission tomography combined with contrast-enhanced computerized tomography (FDG PET-CT) may potentially augment treatment decision-making for LACC. This study ascertained FDG-PET CT influence on chemoradiation therapy (CTRT) decisions in LACC. We report oncologic and patient-reported outcome measures (PROMs)., Methods: FDG PET-CT scans were reviewed independently by two nuclear medicine specialists and two radiation oncologists. Pelvic CTRT plan digressions were documented and therapy was adapted accordingly. Pelvis radiation (50 Gy/25#/5 weeks) using tomotherapy with weekly cisplatin was used in node-negative disease. Dose-escalated simultaneous integrated boost (SIB) 60 Gy/25#/5 weeks was delivered to involved pelvic nodes. All received brachytherapy. Post-treatment PET-CT scans were at 6 months. Functional assessment of cancer therapy scores were calculated at baseline, treatment completion, 3 months, 1 year and 3 years., Results: Between November 2015 and January 2018, 85 patients were screened, and 77 consented. Extrapelvic disease was seen in 12 (16%) patients (9 para-aortic nodes, 2 distant metastases and 1 synchronous carcinoma breast); 60 patients were included in the final analysis. Decision changes were seen in 10/77 (13%) screened, 8/60 (13%) included and 32 (53.3%) received SIB. Post-treatment, 27 (45%) had grade 2 GI/GU/GYN toxicity, one (2%) had grade 3 GI and five (8.3%) had grade 3 neutropenia. At median follow-up of 54.2 months (95% CI 52.8-58.3), 5-year local failure, pelvic nodal and para-aortic nodal-free survival were 86.8% (95% CI 78.0-96.6), 85.2% (95% CI 76.1-95.3) and 85.2% (95% CI 76.2-95.4). Functional assessment of cancer therapy trial outcome index (FACT TOI) improved by 10.43 at 3 months with no further decline. Grade 3 toxicity was noted for abdominal pain in one (1.7%), cystitis in four (6.7%) and lymphoedema in one (1.7%) at 5 years., Conclusion: PET-CT resulted in major decision changes in 13%. PET-adapted CTRT was associated with acceptable toxicity, encouraging long-term survival and improvement in PROMS., (© 2024 Royal Australian and New Zealand College of Radiologists.)

Objectives: Radiation proctitis is a misunderstanding complication of chemoradiation in locally advanced cervical cancer. The objective of our study is to provide a detailed description and analysis of predictive factors associated with radiation proctitis in a retrospective cohort of patients treated by chemoradiation for locally advanced cervical cancer., Methods: All patients treated by exclusive chemoradiation or chemoradiation followed by brachytherapy for locally advanced cervical cancer from 2011 to 2017 were included in the study. A bivariate analysis was conducted to establish correlations between the occurrence of radiation proctitis and various clinical and technical variables., Results: A total of 128 patients were included in the study. The mean dose (SD) to the planning target volume was 47.1 Gy (6.2). Fifty-nine (46.1%) patients underwent brachytherapy. Sixteen patients (12.5%) developed radiation proctitis, grade 2 or higher in 12 patients (9.3%). In univariate analysis, anticoagulant or antiplatelet treatments ( P =0.039), older age ( P =0.049), rectal volume irradiated at 40 Gy ( P =0.01) and 30 Gy ( P =0.037) were significantly associated with the occurrence of a grade ≥2 radiation proctitis. The delivered dose to 2 cm 3 of rectum (D2cm 3 ) showed a potential association with the occurrence of radiation proctitis of all grades ( P =0.064)., Conclusions: This study highlights clinical and technical factors that should be considered in assessing the risk of radiation proctitis. These results contribute to a better understanding of this complication., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The steep radiation dose gradients in cervical cancer brachytherapy (BT) necessitate a thorough understanding of the behavior of afterloader source cables or needles in the curved channels of (patient-tailored) applicators., Purpose: The purpose of this study is to develop and validate computer models to simulate: (1) BT source positions, and (2) insertion forces of needles in curved applicator channels. The methodology presented can be used to improve the knowledge of instrument behavior in current applicators and aid the development of novel (3D-printed) BT applicators., Methods: For the computer models, BT instruments were discretized in finite elements. Simulations were performed in SPACAR by formulating nodal contact force and motion input models and specifying the instruments' kinematic and dynamic properties. To evaluate the source cable model, simulated source paths in ring applicators were compared with manufacturer-measured source paths. The impact of discrepancies on the dosimetry was estimated for standard plans. To validate needle models, simulated needle insertion forces in curved channels with varying curvature, torsion, and clearance, were compared with force measurements in dedicated 3D-printed templates., Results: Comparison of simulated with manufacturer-measured source positions showed 0.5-1.2 mm median and <2.0 mm maximum differences, in all but one applicator geometry. The resulting maximum relative dose differences at the lateral surface and at 5 mm depth were 5.5% and 4.7%, respectively. Simulated insertion forces for BT needles in curved channels accurately resembled the forces experimentally obtained by including experimental uncertainties in the simulation., Conclusion: The models developed can accurately predict source positions and insertion forces in BT applicators. Insights from these models can aid novel applicator design with improved motion and force transmission of BT instruments, and contribute to the estimation of overall treatment precision. The methodology presented can be extended to study other applicator geometries, flexible instruments, and afterloading systems., (© 2024 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

For locally advanced cervical cancer, the standard therapeutic approach involves concomitant chemoradiation therapy, supplemented by a brachytherapy boost. Moreover, an external beam radiotherapy (RT) boost should be considered for treating gross lymph node (LN) volumes. Two boost approaches exist with Volumetric Intensity Modulated Arc Therapy (VMAT): Sequential (SEQ) and Simultaneous Integrated Boost (SIB). This study undertakes a comprehensive dosimetric and radiobiological comparison between these two boost strategies. The study encompassed ten patients who underwent RT for cervical cancer with node-positive disease. Two sets of treatment plans were generated for each patient: SIB-VMAT and SEQ-VMAT. Dosimetric as well as radiobiological parameters including tumour control probability (TCP) and normal tissue complication probability (NTCP) were compared. Both techniques were analyzed for two different levels of LN involvement - only pelvic LNs and pelvic with para-aortic LNs. Statistical analysis was performed using SPSS software version 25.0. SIB-VMAT exhibited superior target coverage, yielding improved doses to the planning target volume (PTV) and gross tumour volume (GTV). Notably, SIB-VMAT plans displayed markedly superior dose conformity. While SEQ-VMAT displayed favorable organ sparing for femoral heads, SIB-VMAT appeared as the more efficient approach for mitigating bladder and bowel doses. TCP was significantly higher with SIB-VMAT, suggesting a higher likelihood of successful tumour control. Conversely, no statistically significant difference in NTCP was observed between the two techniques. This study's findings underscore the advantages of SIB-VMAT over SEQ-VMAT in terms of improved target coverage, dose conformity, and tumour control probability. In particular, SIB-VMAT demonstrated potential benefits for cases involving para-aortic nodes. It is concluded that SIB-VMAT should be the preferred approach in all cases of locally advanced cervical cancer., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Deep stromal invasion (DSI) is one of the predominant risk factors that determined the types of radical hysterectomy (RH). Thus, the accurate assessment of DSI in cervical adenocarcinoma (AC)/adenosquamous carcinoma (ASC) can facilitate optimal therapy decision., Purpose: To develop a nomogram to identify DSI in cervical AC/ASC., Study Type: Retrospective., Population: Six hundred and fifty patients (mean age of 48.2 years) were collected from center 1 (primary cohort, 536), centers 2 and 3 (external validation cohorts 1 and 2, 62 and 52)., Field Strength/sequence: 5-T, T2-weighted imaging (T2WI, SE/FSE), diffusion-weighted imaging (DWI, EPI), and contrast-enhanced T1-weighted imaging (CE-T1WI, VIBE/LAVA)., Assessment: The DSI was defined as the outer 1/3 stromal invasion on pathology. The region of interest (ROI) contained the tumor and 3 mm peritumoral area. The ROIs of T2WI, DWI, and CE-T1WI were separately imported into Resnet18 to calculate the DL scores (TDS, DDS, and CDS). The clinical characteristics were retrieved from medical records or MRI data assessment. The clinical model and nomogram were constructed by integrating clinical independent risk factors only and further combining DL scores based on primary cohort and were validated in two external validation cohorts., Statistical Tests: Student's t-test, Mann-Whitney U test, or Chi-squared test were used to compare differences in continuous or categorical variables between DSI-positive and DSI-negative groups. DeLong test was used to compare AU-ROC values of DL scores, clinical model, and nomogram., Results: The nomogram integrating menopause, disruption of cervical stromal ring (DCSRMR), DDS, and TDS achieved AU-ROCs of 0.933, 0.807, and 0.817 in evaluating DSI in primary and external validation cohorts. The nomogram had superior diagnostic ability to clinical model and DL scores in primary cohort (all P < 0.0125 [0.05/4]) and CDS (P = 0.009) in external validation cohort 2., Data Conclusion: The nomogram achieved good performance for evaluating DSI in cervical AC/ASC., Level of Evidence: 3 TECHNICAL EFFICACY: Stage 2., (© 2023 International Society for Magnetic Resonance in Medicine.)

Objectives: A deep learning (DL) model using image data from pretreatment [ 18 F]fluorodeoxyglucose ([ 18 F] FDG)-PET or computed tomography (CT) augmented with a novel imaging augmentation approach was developed for the early prediction of distant metastases in patients with locally advanced uterine cervical cancer., Methods: This study used baseline [18F]FDG-PET/CT images of newly diagnosed uterine cervical cancer patients. Data from 186 to 25 patients were analyzed for training and validation cohort, respectively. All patients received chemoradiotherapy (CRT) and follow-up. PET and CT images were augmented by using three-dimensional techniques. The proposed model employed DL to predict distant metastases. Receiver operating characteristic (ROC) curve analysis was performed to measure the model's predictive performance., Results: The area under the ROC curves of the training and validation cohorts were 0.818 and 0.830 for predicting distant metastasis, respectively. In the training cohort, the sensitivity, specificity, and accuracy were 80.0%, 78.0%, and 78.5%, whereas, the sensitivity, specificity, and accuracy for distant failure were 73.3%, 75.5%, and 75.2% in the validation cohort, respectively., Conclusion: Through the use of baseline [ 18 F]FDG-PET/CT images, the proposed DL model can predict the development of distant metastases for patients with locally advanced uterine cervical cancer treatment by CRT. External validation must be conducted to determine the model's predictive performance., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The objective of this study was to assess the prognostic value of clinical factors and metabolic parameters measured using fluorodeoxyglucose PET (FDG-PET/CT) in predicting disease recurrence, as well as distant metastasis-free survival (DMFS), local recurrence-free survival (LRFS), and overall survival (OS) in patients with uterine cervical cancer who received definitive chemoradiotherapy., Methods: The clinical data and FDG-PET parameters, including standardized uptake value (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of 194 patients with biopsy-confirmed squamous cell carcinoma of cervical cancer were retrospectively analyzed. Univariate and multivariate analyses were used to ascertain prognostic factors associated with DMFS, LRFS, and OS., Results: With a median follow-up of 12.5 years, 96 patients (49.5%) presented with disease recurrence, at a median of 9.9 months after chemoradiotherapy. Patients who experienced recurrence had significantly higher values for all FDG-PET parameters compared to patients who did not. In multivariate regression analysis, lymph node metastasis, MTV, and SUV mean were significantly correlated with distant metastasis, while local recurrence was only predicted by SUV max . Lymph node metastasis, high MTV, SUV mean , and TLG predicted shorter DMFS, while only the primary tumor SUV max predicted LRFS. Age, regional nodal metastasis, and higher MTV independently predicted shorter OS in multivariate analysis., Conclusion: We found that metabolic parameters derived from FDG-PET/CT could serve as surrogates for disease recurrence in patients with cervical cancer who were treated with definitive chemoradiotherapy. Patients at high risk of distant metastasis could be defined using SUV mean and MTV, and for local recurrence, by using SUV max ., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Complex intracavity and interstitial (IC/IS) applicators, such as the Venezia applicator, can improve the HR-CTV coverage while adequately protecting organs at risk in the treatment of cervical cancer with high-dose-rate (HDR) brachytherapy. Although the Venezia applicator offers more choice for catheter selection, commercially available catheter and dose optimization algorithms are still missing for complex applicators. Moreover, studies on catheter and dose optimization for IC/IS implants in the treatment of cervical cancer are still limited., Purpose: This work aims to combine a GPU-based multi-criteria optimization (gMCO) algorithm with a sparse catheter (SC) optimization algorithm for the Venezia applicator., Methods: Fifty-eight cervical cancer patients who received 28 Gy in 4 fx of HDR brachytherapy with the Venezia applicator (combination to external beam radiation therapy) are retrospectively revisited. The modelization of the applicator is done by virtually reconstructing all the IS catheters passing through the ring. Template catheters are reconstructed using an in-house python script. To perform simultaneous MCO and SC optimization (SC+MCO), the objective function includes aggregated dose objectives in a weighted sum and a group sparsity term that individually penalizes the contribution of IS catheters. Plans generated with the SC+MCO algorithm are compared with plans generated with MCO using clinical catheters (CC+MCO) and the clinical plans (CP). The EMBRACE II soft constraints (planning aims) and hard constraints (limits for prescribed dose) are used as plan evaluation criteria., Results: CC+MCO gives the most important gain with an increase up to 20.7% in meeting all EMBRACE II soft constraints compared with CP. The SC+MCO algorithm (adding catheter optimization to MCO) provides a second order increase (up to 12.1% with total acceptance rate of 60.3% or 35/58) in the acceptance rate versus CC+MCO (total increase of 32.8% vs. CP). Acceptance rate in EMBRACE II hard constraints is 98.3% (57/58) for both CC+MCO and SC+MCO versus 91.4% (53/58) for CP. The median SC+MCO optimization time is 11 s to generate a total of 5000 Pareto-optimal plans with different catheter configurations (position and number) for each fraction., Conclusions: Simultaneous catheter and MCO optimization is clinically feasible for HDR cervical cancer brachytherapy using the Venezia applicator. Clinical catheter configurations could be improved and/or the catheter number could be reduced without decreasing plan quality using SC+MCO compared with the CP., (© 2023 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Background: Cervical cancer survivors can experience vaginal length shortening, vaginal stenosis, vaginal elasticity deterioration, sexual frequency reduction and sexual dysfunction. This prospective, uncontrolled, monocentric clinical interventional study aimed to evaluate the effect of vaginal dilation therapy on vaginal condition and sexual function of cervical cancer survivors who had not received timely vaginal dilation. Methods: A total of 139 patients completed the study. They received 6 months of vaginal dilation therapy. We evaluated their vaginal elasticity, vaginal diameter, vaginal length and sexual function before and after vaginal dilation therapy. Their vaginal conditions were evaluated by customised vaginal moulds, and the sexual function was assessed by female sexual function index. The SPSS 25 software was used to analyse all the data. Results: Age, vaginal diameter and sexual intercourse frequency before diagnosis were significantly associated with female sexual dysfunction of the patients after cancer treatment. Vaginal dilation therapy improved vaginal stenosis, vaginal length and sexual function in all the patients; however, the vaginal elasticity and incidence of sexual dysfunction did not improve significantly. Sexual intercourse frequency before diagnosis, vaginal elasticity, time interval from last treatment and treatment modalities were significantly associated with the change in female sexual function index score before and after vaginal dilation therapy. Patients with a time interval from the last treatment less than 24 months or those who had moderate or good vaginal elasticity, benefitted more from vaginal dilatation therapy. Conclusions: cervical cancer survivors who had not received timely vaginal dilation still benefitted from vaginal dilation therapy, irrespective of the treatment methods they received. Moreover, vaginal dilation therapy should be performed as early as possible after cervical cancer treatment. [ABSTRACT FROM AUTHOR]

Cervical cancer (CC) is the fourth most common neoplasia in women worldwide. Although early-stage CC is often curable, 40 to 50% of patients are diagnosed at a locally advanced stage. Metastatic disease accounts for the principal cause of death. Lymph node (LN) status is a major factor impacting treatment options and prognosis. Historically, CC was staged based only on clinical findings. However, in 2018, imaging modalities and/or pathological findings were included in the International Federation of Gynecology and Obstetrics (FIGO) staging classification. In the last decades, LN status assessment has evolved considerably. Full pelvic lymphadenectomy used to be the only way to determine LN status. Currently, several options exist: surgery with full lymphadenectomy, sentinel lymph node (SLN) biopsy or imaging modalities such as computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET). Regarding surgery, the SLN biopsy technique has become a standard procedure in cases of CC, with indocyanine green (ICG) being the preferred dye. Pelvic MRI is a valuable imaging technique modality for the evaluation of pelvic LNs. In locally advanced or in early-stage disease with suspicious LNs on CT scans or MRI, PET/CT is recommended for assessment of nodal and distant status. The best strategy for LN assessment remains a highly controversial topic in the literature. In this article, we aim to review and compare the advantages and limitations of each modality, i.e. imaging or surgical (lymphadenectomy or SLN biopsy) approaches. [ABSTRACT FROM AUTHOR]

Background: Over the past decade, the adoption of screening programs, digital mammography, and magnetic resonance imaging (MRI) has increased early-stage breast cancer diagnosis rates. Mortality rates have decreased due to early detection and improved treatments, including personalized therapies. Accelerated partial-breast irradiation (APBI) is emerging as a convenient and effective treatment for some patients, with studies exploring its preoperative use. Preoperative APBI, especially with MRI guidance, offers improved tumor targeting and potentially reduced side effects. Magnetic Resonance Imaging-Guided Single-Fraction Pre-Operative Radiotherapy for Early-Stage Breast Cancer (RICE trial) aims to assess the feasibility and efficacy of MRI-guided single-dose radiotherapy (RT) for early-stage breast cancer. Methods: The RICE study is a prospective, single-arm study evaluating single-fraction preoperative, APBI treatment for patients with early-stage breast cancer using a magnetic resonance imaging linear accelerator (MRI linac). Eligible patients enrolled in this study will have a core biopsy to confirm estrogen receptor-positive and HER2-negative sub-type. RT planning will use a planning computed tomography (CT) co-registered with a MRI with the patient in either the supine or prone position. For the diagnostic workup, [18F] fluorodeoxyglucose positron emission tomography/CT ([18F] FDG PET/CT) and [18F] fluoroestradiol positron emission tomography/CT ([18F] FES PET/CT) will be performed prior to treatment. Thirty patients will receive a single ablative RT dose of 21 Gray to the tumor. Pre-treatment and post-treatment MRI scans will be acquired at baseline and 5 weeks post-RT respectively. Breast-conserving surgery will be scheduled for 6 weeks after APBI treatment using the MRI linac. The primary study endpoint is the successful administration of a single fraction of preoperative breast RT under the guidance of an MRI linac. Secondary endpoints include evaluating the utility of MRI, [18F] FDG PET/CT, and [18F] FES PET/CT as a non-invasive method for assessing treatment response in patients undergoing single-fraction preoperative APBI. Conclusion: The RICE trial represents a significant step in breast cancer treatment, offering insights that could lead to treatment protocols with minimized RT appointments and enhanced patient outcomes. Trial registration: This trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR). Registered 31st of May 2021. Registration number: ACTRN12621000659808. [ABSTRACT FROM AUTHOR]

Radiation injuries, particularly those resulting from therapeutic or accidental exposure, present complex challenges for medical management. These injuries can manifest localized skin damage or extend to deeper tissues, presenting as various clinical entities that require treatment strategies, ranging from conservative management to complex surgical interventions. Radiation treatment constitutes a fundamental component of neoplastic management, with nearly two out of three oncological instances undergoing it as an element of their therapeutic strategy. The therapeutic approach to radiation injury consists of expanding prophylactic measures while maintaining the efficacy of treatment, such as conservative treatment or local debridement followed by reconstruction. The armamentarium of reconstructive methods available for plastic surgeons, from secondary healing to free tissue transfer, can be successfully applied to radiation injuries. However, the unique pathophysiological changes induced by radiation necessitate a careful and specialized approach for their application, considering the altered tissue characteristics and healing dynamics. The therapeutic strategy is guided by both the severity and progression of the injury, with the primary aim of restoring functionality and aesthetic aspects while simultaneously minimizing the risk of complications. This paper explores the various conditions encompassed by the term "radiation injury," reviews both non-surgical and surgical therapeutic strategies for managing these injuries, and highlights the unique challenges associated with treating irradiated tissues within specific oncological contexts. [ABSTRACT FROM AUTHOR]

The trace element zinc influences a number of biological reactions, including cell growth, apoptosis, and DNA damage, which affect tumor therapy. The natural compound betulinic acid (BA) and its derivatives are known for their antiviral, antibacterial, and antitumor effects. Previous studies show that BA and 3-acetyl-28-sulfamoyloxybetulin (CAI3) have high cytotoxicity and induce radiosensitization in breast cancer cells. This study investigates the effects of zinc supplementation on treatment with BA or CAI3 and radiotherapy of breast cancer cell lines MDA-MB-231 and HS578T. Expression analysis shows that BA and CAI3 lead to altered expression of genes involved in zinc metabolism. Zinc supplementation affects cell survival and cell death alone and in combination with BA or CAI3 in both breast cancer cell lines. In MDA-MB-231 cells, zinc excess protects against ROS formation by BA or CAI3 and exhibits radioprotective effects compared to the single agent treatment. In contrast, in HS578T cells, zinc induces ROS formation but does not affect radiosensitivity. The variable effects of zinc on radiosensitivity highlight the importance of individualized treatment approaches. Although zinc has cytotoxic, pro-apoptotic, and anti-clonogenic effects, it seems worthwhile to consider its radioprotective properties when making treatment decisions in the case of adjuvant radiotherapy of breast cancer. [ABSTRACT FROM AUTHOR]

Background/Aim: We hypothesized that adding bevacizumab to platinum-based neoadjuvant chemotherapy -- whose efficacy for patients with recurrent or metastatic cervical cancer has already been proven -- could optimize the therapy regimen, leading to improved response rates and survival outcomes. Patients and Methods: Forty patients with histologically confirmed cervical cancer with FIGO stage IB3- IVA who received platinum-based neoadjuvant treatment between March 2008 and January 2019 in the Department of Obstetrics and Gynecology of University Hospital Cologne were analyzed. Twenty patients were treated with additional bevacizumab. The comparative cohort consisted of 18 patients treated with neoadjuvant chemotherapy alone. The response rates and clinical outcomes, including progression-free survival and overall survival, were evaluated. Results: Neoadjuvant chemotherapy combined with bevacizumab significantly improved the response rate (p=0.046). The survival analysis showed that patients treated without bevacizumab had better progression-free survival up to FIGO stage IVA than patients treated with bevacizumab. However, overall survival was similar for both cohorts. For patients with advanced tumor stage, including FIGO IVB, progressionfree survival and overall survival improved with the addition of bevacizumab. Pathological complete remission was a statistically significant prognostic factor for progression-free survival (p=0.039) but did not significantly affect overall survival (p=0.098). Conclusion: While bevacizumab did not demonstrate a significant improvement in overall survival rates, it was associated with a notable reduction in tumor size and showed a trend towards improved clinical response rates. These findings suggest that bevacizumab may have potential in optimizing the neoadjuvant treatment approach. [ABSTRACT FROM AUTHOR]

Background/Aim: This study aimed to compare the use of a rotating gantry in liver tumor carbon-ion radiotherapy using of a fixed-port for treatment planning. Materials and Methods: Thirty patients with liver tumors were analyzed. Three treatment plans were developed for each case: one with a rotating gantry with a 360° angle, one with fixed ports of 0° and 90° with a ±20° couch rolling setting, and one with fixed ports of 45° and 90° with a ±20° couch rolling setting. The dose--volume histogram parameters of the clinical target volume (CTV) and organs at risk (OARs) for each treatment plan were compared. Results: Significant differences in the volume of the liver-gross tumor volume (GTV) of normal liver irradiated with 5 Gy to 15 Gy were found between the gantry treatment plans and fixed-port treatment plans. There were no significant differences in the OARs, except for the CTV and liver GTV, between the gantry and fixed-port treatment plans. Conclusion: The study results support the potential of using a rotating gantry to reduce liver doses, especially in the low-to-medium dose range, while maintaining target and OAR doses except for the liver. A rotating gantry could be especially useful in cases in which the relationship between the tumor and OAR is complicated by location. [ABSTRACT FROM AUTHOR]

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Simple Summary: Ureteral stricture disease is a rare but fearsome complication after radiation therapy for pelvic malignancies. Several minimally-invasive managements have been proposed: however, the optimal strategy is still a matter of debate, and available literature on this topic is rather heterogeneous. This multi-institutional retrospective analysis showed that an endourological attempt is reliable in case of a short, mid-proximal stricture, while robot-assisted reconstructive surgery seems to best fit with the remaining cases. Up to 15% of recurrences develops within 6 months. Regardless of treatment strategy, a significant improvement in eGFR was found during follow-up. Stricture length and concomitant chemotherapy at the time of radiation therapy were identified as predictors of recurrence. An adequate preoperative strategy is paramount, since stricture's features and oncologic anamnesis could be potential predictors of surgical failure. Objectives. A radiation-induced ureteral stricture (RIUS) is a challenging condition in urologic surgery, and the optimal surgical strategy is still a matter of debate. The aim of this study was to report post-operative outcomes of minimally invasive management of this condition from a multi-institutional cohort. Methods. Data of patients with diagnoses of RIUS at five referral robotic centers between January 2017 and December 2022 were retrospectively analyzed. Pre-, intra- and post-operative variables were collected. Recurrence was defined as the presence of flank pain combined with imaging findings for obstruction, and requiring further management. Univariate and multivariate logistic regression models were built to identify predictors of ureteral stricture recurrence. Results. Fifty-three patients with a diagnosis of an RIUS were included. Primary pelvic malignancy was mostly cervical (42%). In 72% of cases (mostly mid-proximal and short strictures) endourological management was attempted, which was deemed successful in 74% of patients at stent removal. The endourology success rate at a median follow-up of 12 months was 59%. Twenty-five patients (47%) were scheduled for robotic surgery. The reconstructive techniques most often performed were end-to-end anastomosis (44%) and ureteral reimplantation (52%). Three low-grade Clavien-Dindo post-operative complications (12%) occurred. Robotic surgery was successful in all cases except one. Considering the entire cohort, eight patients (15%) developed recurrence at a median follow-up of 5 months. All patients with recurrence were managed by permanent drainage. A statistically significant improvement in eGFR with respect to baseline was found at a median follow-up of 12 months (p = 0.007). The univariate logistic regression model identified ureteral stricture length >2 cm (OR 6.4, 95% C.I. 1.1–36.9, p = 0.04) and concomitant chemotherapy (OR 8.9, 95% C.I. 1.6–49.9, p = 0.01) as predictors of recurrence. At multivariate analysis concomitant chemotherapy was confirmed as an independent predictor of recurrence (OR 7.8, 95% C.I. 1.3–49.0, p = 0.03). Conclusions. Endourological management of an RIUS is reasonable for short and mid-proximal ureteral strictures, while robotics is required in almost all the remaining cases. Up to 15% of recurrence develops within 6 months. Re-do reconstructive surgery is rarely performed, even in referral centers. [ABSTRACT FROM AUTHOR]

Objective: This study aims to evaluate the efficacy and safety of 3D printing technology in brachytherapy for cervical cancer, comparing its outcomes with conventional free hand implantation brachytherapy. Methods: A total of 50 cervical cancer patients treated at the First Affiliated Hospital of Gannan Medical College from January 2019 to July 2023 were included in this study. Patients were divided into two groups: 25 patients received intensity-modulated radiotherapy (IMRT) combined with 3D-printed brachytherapy, and 25 patients underwent IMRT combined with free hand brachytherapy implantation. Key indicators analyzed included short-term therapeutic effects, survival outcomes, operation times, the number of CT scans, the number of needles inserted, dosimetric parameters, and complications. Results: The use of 3D-printed brachytherapy significantly improved the safety of radiation therapy operations, especially for large tumors (≥ 30 mm), by providing more precise dose distribution and reducing the radiation doses received by critical organs such as the bladder and rectum. Compared to the artificial implant group (88% prevalence), the 3D-printed brachytherapy group showed a significantly lower incidence of radiation enteritis (29.2% prevalence, p < 0.001). There were no significant differences in other complications between the two groups. For instance, the incidence of radiation cystitis was relatively high in the 3D-printed brachytherapy group (79.2% prevalence) compared to the artificial implant group (64% prevalence, p = 0.240). The median follow-up period in this study was 22.5 months [IQR 18–29]. Among the 49 patients included, 43 had cervical squamous carcinoma and 6 had cervical adenocarcinoma. Short-term therapeutic response rates were comparable, with no significant difference in overall survival observed between the two groups. Conclusion: 3D-printed brachytherapy offers a more effective and safer therapeutic option for patients with cervical cancer, particularly for those with large tumors or complex anatomical structures. [ABSTRACT FROM AUTHOR]

Over the last few years, radiation therapy (RT) techniques have evolved very rapidly, with the aim of conforming high-dose volume tightly to a target. Although to date CT is still considered the imaging modality for target delineation, it has some known limited capabilities in properly identifying pathologic processes occurring, for instance, in soft tissues. This limitation, along with other advantages such as dose reduction, can be overcome using magnetic resonance imaging (MRI), which is increasingly being recognized as a useful tool in RT clinical practice. This review has a two-fold aim of providing a basic introduction to the physics of MRI in a narrative way and illustrating the current knowledge on its application "from head to toe" (i.e., different body sites), in order to highlight the numerous advantages in using MRI to ensure the best therapeutic response. We provided a basic introduction for residents and non-radiologist on the physics of MR and reported evidence of the advantages and future improvements of MRI in planning a tailored radiotherapy treatment "from head to toe". Critical relevance statement: This review aims to help understand how MRI has become indispensable, not only to better characterize and evaluate lesions, but also to predict the evolution of the disease and, consequently, to ensure the best therapeutic response. Key Points: MRI is increasingly gaining interest and applications in RT planning. MRI provides high soft tissue contrast resolution and accurate delineation of the target volume. MRI will increasingly become indispensable for characterizing and evaluating lesions, and to predict the evolution of disease. [ABSTRACT FROM AUTHOR]

Introduction: Randomised evidence supports the use of partial breast irradiation (PBI) with targeted intraoperative radiotherapy (TARGIT-IORT) for early stage breast cancer, but prospective data from real-world adoption of this technique is also important. The aim of this study was to determine if the outcome reported in TARGIT-A trial could be replicated in large cohort of early stage breast cancer treated with TARGIT-IORT. Methods: This prospective observational study analysed all patients treated with TARGIT-IORT between 2004 and 2021 in a single national cancer institute. TARGIT-IORT during lumpectomy was performed according to the riskadapted TARGIT-A protocol using the Intrabeam® device. We analysed the completeness of follow up, 5-year in-breast-tumour-recurrence (IBTR), long term local recurrence free survival, distant disease-free survival, overall survival and breast-cancer-related survival, using the Kaplan-Meier method. A covariate analysis was performed to investigate risk factors for IBTR. We also analysed high grade toxicity events. Results: The study included 814 patients and the a median follow up was 72 months. The majority of patients (60.3%) received TARGIT-IORT as PBI modality ("exclusive IORT" group); 39.7% received additional EBRT. There was no significant difference between the 5 years IBTR for the whole study population and the "exclusive IORT" cohort (1.6% (95%CI=1.1-2.1%) and 2.5% (95%CI=1.7%- 3.3%) respectively). 5 years overall survival and tumour related survival were >95%. In 21% of patients with recurrence, breast was preserved. Radiotherapy toxicity (CTCAE Grade>2) was very rare (0.9%). Conclusions: This large single institute study found that breast cancer control and survival outcomes with TARGIT-IORT were consistent with TARGIT-A trial results. This "real world" experience confirmed that the randomised evidence showing the value of TARGIT-IORT as partial breast irradiation modality that can be replicated in routine clinical practice. [ABSTRACT FROM AUTHOR]

Simple Summary: Definitive radiochemotherapy represents a well-established and proven treatment option for locally advanced cervical cancer. The Gyn GEC-ESTRO (GGE) provides a protocol for the method and administration of the associated brachytherapy, in which restrictions for target volumes and organs at risk are established through several studies. This study aims to validate the results of the internal treatment protocol and compare them with the GGE recommendations. A sample of 48 patients with locally advanced cervical cancer treated from 2013 to 2023 was retrospectively analyzed. The GGE target volumes were contoured, evaluated, and then compared with patients' oncologic outcome, as well as bladder and rectal toxicities. The use of MRI during brachytherapy was observed to have a positive effect on survival times in this study. Adherence to the GGE recommendations may also improve local tumor control and time-to-event endpoints, which were comparable to those of other studies. A realistic representation of patient treatment in a radiation oncology center without constant access to MRI for brachytherapy planning was obtained. Background: This study aims to evaluate patients with locally advanced cervical cancer who underwent definitive radiochemotherapy, including brachytherapy, at the University Hospital of Muenster (UKM), focusing on target volume coverage, oncologic outcome parameters, and organs at risk (OAR) toxicities. Results are compared with the Gyn GEC-ESTRO (GGE) recommendations. Methods: Of a cohort of 48 patients, treated between 2013 and 2023, the physical radiation treatment planning with application of CT and MRI and oncologic follow-up data was analyzed. Target volume structures, comprising the high-risk clinical target volume (HR-CTV), intermediate-risk clinical target volume (IR-CTV), Point A, and corresponding EQD2(α/β=10) doses were determined. Endpoints included local tumor control, overall survival (OS), recurrence-free survival (RFS), and progression-free survival (PFS). Total OAR (D2cc) EQD2(α/β=3) doses were correlated with adverse events defined by CTCAE v5.0 and LENT-SOMA criteria. Results: Median follow-up was 58.0 months (95% CI [27.6, 88.4]). FIGO stage I was present in 7 (15%) patients, II in 13 (27%), and III in 28 (58%) patients. A total of 38 (79%) patients showed a complete remission 3 months after treatment. The 5-year event-free rate was 67.4% (95% CI [49.3, 80.3]) for OS, 77.0% (95% CI [56.7, 88.6]) for RFS and 68.1% (95% CI [49.7, 80.9]) for PFS. Incomplete radiation treatment and advanced tumor stages led to worse outcomes. Meeting Point A GGE recommendations increased chances for complete remission and could decrease chances of an event occurring for OS, PFS, and RFS. Compliance with GGE recommendations lowered the chances of OAR toxicity occurring. Conclusions: MRI-based target volume definition for brachytherapy in cervical cancer may improve patients' OS, PFS, and RFS. Time-to-event endpoints are consistent with comparable studies, and adherence to current ESGO/ESTRO/ESP guidelines is endorsed. [ABSTRACT FROM AUTHOR]

Background: Dose escalation with brachytherapy after pelvic irradiation is standard for treating cervical cancer. Its application can be impossible for some patients. Dose escalation with SBRT is widely used with high local control and acceptable toxicity rates in different body parts. The study enrolled patients who underwent SBRT treatment for dose escalation in the cervix. Methods: Patients who were pathologically diagnosed and treated with cervical SBRT after definitive CRT were included in the study. A total of 30 Gy in 5 fractions for the high-risk volume was prescribed. The first response evaluation was performed three months after the completion of treatment. Treatment toxicity was documented according to the RTOG-EORTC scale. Oncological outcomes and toxicity were assessed. Results: Between 02.2019 and 05.2023, 40 patients were treated with an SBRT boost after pelvic irradiation. The median follow-up time was 16 months (7–44 months). The median HR CTV was 47 cc (8,3-168,2 cc). There were 39 patients who achieved a complete response and one who achieved a partial response in the third month after treatment. There were two local or two regional recurrences. The 1-year metastasis-free survival was 88%, and the 1-year progression-free survival was 88%. During the follow-up period, one grade 3 gastrointestinal side effect was observed. Conclusions: SBRT which has low toxicity and reasonable locoregional control rates in a short follow-up period, may be an option for dose escalation in brachytherapy-ineligible cervical cancer patients. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer (CC) is a serious public health concern, being the fourth most common cancer among women and a leading cause of cancer mortality. In Brazil, many women are diagnosed late, and in Mato Grosso, with its geographical diversity, there are specific challenges. This study analyzed hospital survival and its predictors using data from the Hospital Information System (SIH) of the Unified Health System (SUS) in Mato Grosso from 2011 to 2023. Methods: Cox regression and Kaplan-Meier models were applied to determine survival time and identify mortality predictors. The adjusted Hazard Ratio (AHR) with a 95% Confidence Interval (CI) was used to measure the association between the factors analyzed. Results: The hospital mortality rate was 9.88%. The median duration of hospitalization was 33 days (interquartile range [IQR]: 12–36), with a median survival of 43.7%. Patients were followed up for up to 70 days. In the multivariable Cox model, after adjusting for potential confounders, the risk of death during hospitalization was higher in patients aged 40–59 years (AHR = 1.39, p = 0.027) and 60–74 years (AHR = 1.54, p = 0.007), in the absence of surgical procedures (AHR = 4.48, p < 0.001), in patients with medium service complexity (AHR = 2.40, p = 0.037), and in the use of ICU (AHR = 4.97, p < 0.001). On the other hand, patients with hospital expenses above the median (152.971 USD) showed a reduced risk of death (AHR = 0.21, p < 0.001). Conclusion: This study highlights that hospitalized CC patients have reduced survival, underscoring the need for interventions to improve care, including strategies for early diagnosis and expanded access to adequately resourced health services. [ABSTRACT FROM AUTHOR]

Background: The effectiveness of metallic stents in treating ureteral strictures following surgery and radiotherapy for gynecological tumors is currently uncertain. We aimed to investigate the efficacy and safety of thermo-expandable metallic stent (Memokath) in the treatment of ureteral stricture after radiotherapy for gynecological tumors. Methods: In this descriptive cross-sectional study, 27 patients with ureteral stricture were treated with Memokath stent after gynecological tumor radiotherapy with or without chemotherapy that was admitted to our hospital from August 2021 to August 2023. Clinical data on efficacy, safety, and complications during stent insertion and indwelling were analyzed. Results: The successful insertion of thirty-three stents in twenty-seven patients studied. The stenosis length was 10.14 ± 6.76 cm, and the hospitalization was 4.43 ± 1.83 days. One patient has died from the primary disease carrying a patency stent. The Kaplan-Meier graph showed that the cumilative patency rate of patients with thermo-expandable metallic stent were 92.4% (SD = 5.2%) in eight months, 77.4% (9.1%) in 12 months and 67.7% (SD = 12%) in 29 months, while the cumilative survival rate was 87.5% (SD = 11.5%) in 29 months. The stent patency was 81.48% and later complications of stent indwelling were 5/27, including refractory urinary tract infection (UTI) in three cases, stent migration, and stent intolerance respectively. The creatinine levels, hydronephrosis degree, and glomerular filtration rate improved after the operation, and the first two indicators were statistically significant. Conclusion: Memokath stent is a safe and effective treatment for ureteral stricture after surgery and radiotherapy with or without chemotherapy for gynecological tumors. [ABSTRACT FROM AUTHOR]

Objectives: This study evaluates the efficacy and toxicity of image-guided brachytherapy combined with or without external beam radiotherapy (IGBT ± EBRT) as definitive treatment for patients with inoperable endometrial cancer (IOEC), in addition to establishing a risk classification to predict prognosis. Methods: Fifty-one IOEC patients who underwent IGBT ± EBRT at Peking Union Medical College Hospital from January 2012 to December 2021 were retrospectively analyzed, of which 42 patients (82.4%) were treated with IGBT + EBRT and 9 patients (17.6%) with IGBT alone. Establishing risk classification based on FIGO 2009 staging and biopsy pathology, stage III/IV, non-endometrioid, or Grade 3 endometrioid cancer were included in the high-risk group (n = 25), and stage I/II with Grade 1–2 endometrioid cancer was included in the low-risk group (n = 26). Results: The median follow-up time was 58.0 months (IQR, 37.0–69.0). Clinical complete remission (CR) was achieved in 92.2% of patients after radiotherapy (n = 47). The cumulative incidences of locoregional and distant failure were 19.6% (n = 10) and 7.8% (n = 4), respectively. A total of 20 patients died (39.2%), including 10 cancer-related deaths (19.6%) and 10 comorbidity-related deaths (19.6%). The 5-year locoregional control (LRC), time to progression (TTP), overall survival (OS), and cancer-specific survival (CSS) were 76.9%, 71.2%, 59.4%, and 77.0%, respectively. No Grade 3 or above acute or late toxicities were reported. In univariate analysis, LRC, TTP, and CSS were significantly higher in the low-risk group than in the high-risk group (P < 0.05). After adjusting for age, number of comorbidities, radiotherapy modality, and chemotherapy, the low-risk group was still significantly better than the high-risk group in terms of LRC (HR = 6.10, 95% CI: 1.18–31.45, P = 0.031), TTP (HR = 8.07, 95% CI: 1.64–39.68, P = 0.010) and CSS (HR = 6.29, 95% CI: 1.19–33.10, P = 0.030). Conclusions: IGBT ± EBRT is safe and effective as definitive treatment for IOEC patients, achieving satisfactory locoregional control, favorable survival outcomes, and low toxicity. Risk classification based on FIGO 2009 staging and biopsy pathology is an independent prognostic factor for LRC, TTP, and CSS. [ABSTRACT FROM AUTHOR]

Simple Summary: Brachytherapy is a form of internal radiation therapy where radioactive sources are placed directly in or near tumors. This paper shows how brachytherapy can be personalized using new technologies like 3D-printed applicators, advanced imaging techniques, and artificial intelligence to make treatment more precise and effective. The authors also explore the role of genetic tests and biomarkers for choosing the best treatments for each patient, as well as future approaches such as combining brachytherapy with immunotherapy and developing new ways to shape radiation doses using shielding. By tailoring treatments to individual patients, personalized brachytherapy aims to effectively treat cancer while reducing treatment-related side effects. Brachytherapy offers a highly conformal and adaptive approach to radiation therapy for various oncologic conditions. This review explores the rationale, applications, technological advances, and future directions of personalized brachytherapy. Integration of advanced imaging techniques, 3D-printed applicators, and artificial intelligence are rapidly enhancing brachytherapy delivery and efficiency, while genomic tests and molecular biomarkers are refining patient and dose selection. Emerging research on combining brachytherapy with immunotherapy offers unique synergistic potential, and technologies such as intensity-modulated and shielded brachytherapy applicators present novel opportunities to further optimize dose distributions. Despite these promising advances, the field faces challenges including a need to train more practitioners and develop new approaches to treating a broader range of malignancies. As personalized medicine evolves, brachytherapy's ability to deliver highly targeted, individualized treatments positions it as a critical component in future cancer care. [ABSTRACT FROM AUTHOR]

Simple Summary: Since no randomized clinical trial has compared surgery to chemoradiotherapy (CTRT) in FIGO stage IB3 cervical cancer patients, the optimal management remains controversial. In our study, nerve-sparing laparoscopic radical hysterectomy (nsLRH) proved to be safe and effective. The encouraging results on toxicity and survival, when compared to CTRT, warrant further investigation and reinforce the idea that surgery is a valid option for these patients. (1) Background: In 2018 FIGO reclassified tumors confined to the cervix larger than 4 cm as stage IB3. Although concurrent CTRT has been the standard of care and surgery the alternative, optimal management remains controversial due to the lack of direct comparison between surgery and CTRT. (2) Methods: This prospective observational study investigated the efficacy, safety and oncologic outcomes of nerve-sparing laparoscopic radical hysterectomy (nsLRH) for FIGO stage IB3 cervical cancer patients (IB3). From 2009 to 2023, IB3 patients underwent laparoscopic pelvic lymphadenectomies with frozen section analysis, followed by a nsLRH if the lymph nodes were tumor-free. No uterine manipulator was used and the vaginal cuff was sealed before retrieving the specimen. Intermediate-risk patients were under close observation without adjuvant therapy. Outcomes were monitored until 2023. (3) Results: During the study period, 74 IB3 patients were treated. Sixty-eight (91.9%) underwent a nsLRH. A complete resection with negative margins was achieved in all cases. At a median of 68 months of follow-up, the disease-free survival (DFS) rate was 89.7% and the overall survival (OS) rate was 93.1%. The overall complication rate was 23.5% and there were no grade 4–5 complications. (4) Conclusions: In patients with IB3 cervical cancer, a nsLRH is safe and effective. While awaiting the results from ongoing randomized trials, these findings support nsLRH as a viable treatment. [ABSTRACT FROM AUTHOR]

In this comprehensive review supported by clinical examples, the authors explore the topic of cervical cancer in pregnancy, with emphasis on potential pre-cancer progression, the possibility of coexisting preinvasive and invasive disease, and neoadjuvant chemotherapy. This manuscript addresses the challenges of managing cervical cancer in pregnant women with a pregnancy-preserving approach, including the importance of screening, the timing of surgery, and the impact of pregnancy on the course of the disease. The first case study illustrates the potential for a benign cervical lesion to transform into a malignant one during pregnancy and the possible coexistence of preinvasive lesions together with early-stage cervical cancer. It also questions the rationale behind the non-treatment of pregnant patients initially diagnosed with CIN 2/3 during pregnancy. The second presented clinical example shows the histologically confirmed response to neoadjuvant chemotherapy, resulting in a radiologically diagnosed FIGO stage IIA1 being downgraded to adenocarcinoma in situ in the histology report after surgery performed six weeks postpartum. The treatment of cervical cancer, which is becoming increasingly prevalent among pregnant women, and the necessity for an individualized diagnostic and therapeutic approach represent significant challenges for contemporary medicine. Discrepancies in therapeutic options proposed among centers within the same region lead to the conclusion that there is a need for centralization and unification of evidence-based management in referral centers with both high-level oncological and perinatal care. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to introduce modified fixed field volumetric modulated arc therapy (MF‐VMAT) which manually opened the field size by fixing the jaws and comparing it to the typical planning technique, auto field volumetric modulated arc therapy (AF‐VMAT) in cervical cancer treatment planning. Methods and materials: Previously treated twenty‐eight cervical cancer plans were retrospectively randomly selected and replanned in this study using two different planning techniques: AF‐VMAT and MF‐VMAT, resulting in a total of fifty‐six treatment plans. In this study, we compared both planning techniques in three parts: (1) Organ at Risk (OARs) and whole‐body dose, (2) Treatment plan efficiency, and (3) Treatment plan accuracy. Results: For OARs dose, bowel bag (p‐value = 0.001), rectum (p‐value = 0.002), and left femoral head (p‐value = 0.001) and whole‐body (p‐value = 0.000) received a statistically significant dose reduction when using the MF‐VMAT plan. Regarding plan efficiency, MF‐VMAT exhibited a statistically significant increase in both number of monitor units (MUs) and control points (p‐values = 0.000), while beam‐on time, maximum leaf travel, average maximum leaf travel, and maximum leaf travel per gantry rotation were statistically significant decreased (p‐values = 0.000). In terms of plan accuracy, the average gamma passing rate was higher in the MF‐VMAT plan for both absolute dose (AD) (p‐value = 0.001, 0.004) and relative dose (RD) (p‐value = 0.000, 0.000) for 3%/3 and 3%/2 mm gamma criteria, respectively. Conclusion: The MF‐VMAT planning technique significantly reduces OAR doses and decreases the spread of low doses to normal tissues in cervical cancer patients. Additionally, this planning approach demonstrates efficient plans with lower beam‐on time and reduced maximum leaf travel. Furthermore, it indicates higher plan accuracy through an increase in the average gamma passing rate compared to the AF‐VMAT plan. Consequently, MF‐VMAT offers an effective treatment planning technique for cervical cancer patients. [ABSTRACT FROM AUTHOR]

Introduction: The utilization of metal shields in intensity-modulated brachytherapy (IMBT) enables the modulation of the dose, resulting in improved conformance to the tumor while simultaneously reducing the doses to organs at risk (OARs). Utilizing higher-energy sources like 60Co in IMBT for cervical and vaginal cancers has consistently posed challenges. This study evaluates the dosimetric aspects of modified applicators designed for IMBT using 60Co and 192Ir sources. Materials and Methods: GATE, a Geant4-based simulation code, was utilized to model and simulate four distinct applicators. The clinical applicators were redesigned to place the structure of the source tube and the shield while keeping the general characteristics unchanged. These shields were evaluated by calculating transmission factors (TFs) and the dose homogeneities were also determined. Result: Transmission factors for the IMBT technique in redesigned intrauterine applicators and tungsten shields for iridium and cobalt sources were at least 12.8 and 65.4%, and these values were obtained for the intravaginal applicator at 0.2 and 7.0%, respectively. The dose homogeneities for all combinations of radionuclide-shield were within a 15% range of the non-IMBT applicators. Conclusion: This study has quantitatively evaluated the dosimetric effect of tungsten shields in the IMBT technique for cervical and vaginal cancer using cobalt sources. 192Ir compared to 60Co resulted in higher effectiveness for the designed intrauterine and intravaginal shields. while implementing tungsten shields in the redesigned applicators against the 60Co source may not offer complete protection, it does show promising results in reducing the dose to organs at risk. [ABSTRACT FROM AUTHOR]

Background: Postoperative neurogenic bladder (PONB) frequently occurs as a complication after rectal cancer surgery. This study aimed to analyze risk factors for developing PONB after rectal cancer surgery, particularly the association between pelvic anatomy and visceral fat mass. Methods: We included 138 patients who underwent rectal resection for lower rectal cancer in our department between 2017 and 2021. PONB was defined as the need for urethral catheter reinsertion or oral medication administration for urinary retention after catheter removal with severe NB that required treatment for ≥ 60 days. We obtained visceral fat area (VFA) at the umbilical level based on a CT scan and measured five pelvic dimensions. Results: Of the 138 patients, 19 developed PONB, with 16 being severe cases. PONB more frequently occurs in patients with a height of < 158 cm, age ≥ 70 years, surgery lasting ≥ 8 h, intraoperative bleeding volume ≥ 150 mL, lateral lymph node dissection, and narrower pelvis. It was more prevalent in cases with low VFA. Conversely, gender, body mass index (BMI), and medical history showed no significant correlations. Multivariate analysis revealed older age, prolonged surgery, and low VFA as independent risk factors for PONB. Independent risk factors for severe PONB included low VFA, older age, prolonged surgery, and deep pelvis. Conclusion: Lower VFA, older age, and prolonged surgery are independent risk factors for developing PONB. Additionally, a deep pelvis is an independent risk factor for severe PONB. Delicate surgical techniques should consider the risk of nerve injury in cases with low VFA and deep pelvis. [ABSTRACT FROM AUTHOR]

Objective: Vulvar carcinoma exhibits a robust correlation alongside HPV infection; however, the impact of HPV rank on the prognostic outcomes of radiation therapy within vulvar malignancies stays ambiguous. In the present study, we performed a comprehensive examination as well as meta-analysis to assess the influence of infection with HPV upon the long-term outlook as well as sensitivity of individuals with vulvar cancer undergoing radiation therapy. Methods: A meticulous examination of the existing research was conducted in accordance with the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A thorough search was conducted in the PubMed, Embase, Web of Science, as well as Cochrane Library databases, covering the entire available literature till April 1, 2023. The studies that met the inclusion criteria contained data about HPV infection and oncological outcomes in patients with vulvar cancer who received radiation therapy. This study was registered in PROSPERO (CRD42023417957). Results: We identified 12 retrospective studies meeting our inclusion criteria, which included a total of 3967 patients. Patients with HPV-associated vulvar cancer achieved a better overall survival rate after radiotherapy (HR=0.71, 95%CI: 0.54-0.93, P=0.01), and showed a significant improvement in disease-free survival (HR=0.75, 95%CI: 0.58-0.97, P=0.09) and progression-free survival (HR=0.31, 95%CI: 0.22-0.45, P,<0.01). Meanwhile, the complete remission rate after radiotherapy was higher for HPV-associated vulvar cancer patients (MH= 4.02, 95% CI: 1.87-8.61, P=0.0003), and the local control rate was better (HR=1.90, 95% CI: 1.15-3.15, P=0.01), exhibiting a reduced incidence of relapse within the field of study (HR=0.21, 95% CI: 0.10-0.42, P<0.001). Conclusion: In comparison to HPV-independent vulvar squamous cell carcinoma, patients with HPV-associated vulvar cancer exhibit higher sensitivity to radiotherapy, with a significant difference in prognosis. Further research should investigate the mechanisms underlying this high sensitivity to radiotherapy caused by HPV, and should be evaluated using high-quality randomized controlled trials. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy (RT) is effective for cervical cancer but causes late side effects (SE) to nearby organs. These late SE occur more than 3 months after RT and are rated by clinical findings to determine their severity. While imaging studies describe late gastrointestinal (GI) SE, none demonstrate the correlation between the findings and the toxicity grading. In this study, we demonstrated the late GI toxicity prevalence, CT findings, and their correlation. Methods: We retrospectively studied uterine cervical cancer patients treated with RT between 2015 and 2018. Patient characteristics and treatment(s) were obtained from the hospital's databases. Late RTOG/EORTC GI SE and CT images were obtained during the follow-up. Post-RT GI changes were reviewed from CT images using pre-defined criteria. Risk ratios (RR) were calculated for CT findings, and multivariable log binomial regression determined adjusted RRs. Results: This study included 153 patients, with a median age of 57 years (IQR 49–65). The prevalence of ≥ grade 2 RTOG/EORTC late GI SE was 33 (27.5%). CT findings showed 91 patients (59.48%) with enhanced bowel wall (BW) thickening, 3 (1.96%) with bowel obstruction, 7 (4.58%) with bowel perforation, 6 (3.92%) with fistula, 0 (0%) with bowel ischemia, and 0 (0%) with GI bleeding. Adjusted RRs showed that enhanced BW thickening (RR 9.77, 95% CI 2.64–36.07, p = 0.001), bowel obstruction (RR 5.05, 95% CI 2.30–11.09, p < 0.001), and bowel perforation (RR 3.82, 95% CI 1.96–7.44, p < 0.001) associated with higher late GI toxicity grades. Conclusions: Our study shows CT findings correlate with grade 2–4 late GI toxicity. Future research should validate and refine these findings with different imaging and toxicity grading systems to assess their potential predictive value. [ABSTRACT FROM AUTHOR]

Background: A predictive assay for late radiation toxicity would allow more personalized treatment planning, reducing the burden of toxicity for the more sensitive minority, and improving the therapeutic index for the majority. In a previous study in prostate cancer patients, the γ-H2AX foci decay ratio (γ-FDR) was the strongest predictor of late radiation toxicity. The current study aimed to validate this finding in a more varied group of patients with pelvic cancer. Additionally, the potential correlation between the γ-FDR and patient-reported outcomes was investigated. Methods: Prostate and gynecological cancer patients with ≥ 24 months of follow-up were included in the current analysis. Toxicity was evaluated by physician (CTCAE version 4) and patient (EORTC questionnaires). γ-FDRs were determined in ex vivo irradiated lymphocytes. Correlation between γ-FDR and toxicity was assessed using both linear and logistic regression analyses. The highest toxicity grade recorded during follow-up was used. The association between global quality of life and γ-FDR was tested by comparing the change in quality of life over time in patients with γ-FDR < or ≥ 3.41, a previously established threshold. Results: Eighty-eight patients were included. Physician-assessed and patient-reported cumulative grade ≥ 2 toxicity was 25% and 29%, respectively; which is much lower than in the previous cohort (i.e., 51% CTCAE grade ≥ 2). Patients with toxicity exhibited less favorable dose-volume parameters. In men, these parameters showed significant improvement compared to the previous cohort. The proportion of patients with a low γ-FDR increased with severity of toxicity, but this trend was not statistically significant. In addition, a γ-FDR < 3.41 was not correlated with the development of moderate to severe toxicity. Post-treatment decline in global quality of life was minimal, and similar for patients with γ-FDR < or ≥ 3.41. Conclusions: In the present study, the γ-H2AX foci decay ratio could not be validated as a predictor of late radiation toxicity in patients with pelvic cancer. Improved radiotherapy techniques with smaller irradiated bladder and bowel volumes have probably resulted in less toxicities. Future studies on genetic markers of toxicity should be powered on these lower incidences. We further recommend taking persistency, next to severity, into consideration. [ABSTRACT FROM AUTHOR]

Purpose: This study provides a comprehensive overview of the progress in hadron therapy within Europe, particularly highlighting the critical roles of the Proton Ion Medical Machine Study (PIMMS) and the European Network for Light Ion Hadron Therapy (ENLIGHT). Methods: Our approach includes a retrospective analysis of the advances in hadron therapy facilities, facilitated by a synthesis of interdisciplinary collaboration data gathered from ENLIGHT's annual meetings since 2002, and an assessment of European-funded projects and networks' contributions to the field. Results: The results showcase significant advancements in cancer treatment due to collective efforts in hadron therapy, underscored by ENLIGHT's pivotal role in fostering interdisciplinary cooperation and the harmonization of treatment protocols across Europe. Conclusion: The evolution of hadron therapy, from its inception to its current impact on patient care, demonstrates the successful realization of complex medical technologies through sustained collaboration and standardized practices across European institutions and projects. [ABSTRACT FROM AUTHOR]