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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]

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 aimed to develop an automated Tomotherapy (TOMO) planning method for cervical cancer treatment, and to validate its feasibility and effectiveness. Materials and methods: The study enrolled 30 cervical cancer patients treated with TOMO at our center. Utilizing scripting and Python environment within the RayStation (RaySearch Labs, Sweden) treatment planning system (TPS), we developed automated planning methods for TOMO and volumetric modulated arc therapy (VMAT) techniques. The clinical manual TOMO (M-TOMO) plans for the 30 patients were re-optimized using automated planning scripts for both TOMO and VMAT, creating automated TOMO (A-TOMO) and automated VMAT (A-VMAT) plans. We compared A-TOMO with M-TOMO and A-VMAT plans. The primary evaluated relevant dosimetric parameters and treatment plan efficiency were assessed using the two-sided Wilcoxon signed-rank test for statistical analysis, with a P-value < 0.05 indicating statistical significance. Results: A-TOMO plans maintained similar target dose uniformity compared to M-TOMO plans, with improvements in target conformity and faster dose drop-off outside the target, and demonstrated significant statistical differences (P+ < 0.01). A-TOMO plans also significantly outperformed M-TOMO plans in reducing V50Gy, V40Gy and Dmean for the bladder and rectum, as well as Dmean for the bowel bag, femoral heads, and kidneys (all P+ < 0.05). Additionally, A-TOMO plans demonstrated better consistency in plan quality. Furthermore, the quality of A-TOMO plans was comparable to or superior than A-VMAT plans. In terms of efficiency, A-TOMO significantly reduced the time required for treatment planning to approximately 20 min. Conclusion: We have successfully developed an A-TOMO planning method for cervical cancer. Compared to M-TOMO plans, A-TOMO plans improved target conformity and reduced radiation dose to OARs. Additionally, the quality of A-TOMO plans was on par with or surpasses that of A-VMAT plans. The A-TOMO planning method significantly improved the efficiency of treatment planning. [ABSTRACT FROM AUTHOR]

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

Background The brachytherapy is an indispensable treatment for gynecological tumors, but the quality and efficiency of brachytherapy training for residents is still unclear. Methods An anonymous questionnaire was designed to collect information on gynecological brachytherapy (GBT) training for radiation oncology residents from 28 training bases in China. The questionnaire content was designed based on the principle of competency based medical education (CBME). The Likert scale was employed to evaluate self-reported competence and comprehension regarding GBT. A total of 132 senior residents were included in the final analysis. Results 53.79% (71/132) of senior residents had experience in performing image-guided GBT, whereas 76.52% (101/132) had observed the procedure during their standardized residency training. The proportion of senior residents who reported having the self-reported competence to independently complete the GBT was 78.03% for intracavity GBT, 75.00% for vaginal stump GBT, and 50.03% for interstitial GBT, respectively. The number of successful completion of Interstitial, intracavity and vaginal GBT was correlated with the self- confidence of trainees after standardized training. In particular, the independent completion of interstitial GBT for more than 20 cases was an independent factor for the self-reported competence of senior residents. During the training period, 50.76% and 56.82% of the residents had not participated in the specialized examinations and professional GBT courses. Conclusions The study revealed that the self-confidence of residents to independently complete brachytherapy was relatively high, and the specialized curriculum setting and training process assessment for brachytherapy training still need to be strengthened in the future. [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]

Purpose/objective: Adjuvant whole breast radiotherapy and systemic therapy are part of the current evidence-based treatment protocols for early breast cancer, after breast-conserving surgery. Numerous randomized trials have investigated the therapeutic effects of partial breast irradiation (PBI) compared to whole breast irradiation (WBI), limiting the treated breast tissue. These trials were designed to achieve equal control of the disease with possible reduction in adverse events, improvements in cosmesis and quality of life (QoL). In this meta-analysis, we aimed to investigate the differences between PBI and WBI in side effects and QoL. Material/methods: We performed a systematic literature review searching for randomized trials comparing WBI and PBI in early-stage breast cancer with publication dates after 2009. The meta-analysis was performed using the published event rates and the effect-sizes for available acute and late adverse events. Additionally, we evaluated cosmetic outcomes as well as general and breast-specific QoL using the EORTC QLQ-C30 and QLQ-BR23 questionnaires. Results: Sixteen studies were identified (n = 19,085 patients). PBI was associated with a lower prevalence in any grade 1 + acute toxicity and grade 2 + skin toxicity (OR = 0.12; 95% CI 0.09–0.18; p < 0.001); (OR = 0.16; 95% CI 0.07–0.41; p < 0.001). There was neither a significant difference in late adverse events between the two treatments, nor in any unfavorable cosmetic outcomes, rated by either medical professionals or patients. PBI-technique using EBRT with twice-daily fractionation schedules resulted in worse cosmesis rated by patients (n = 3215; OR = 2.08; 95% CI 1.22–3.54; p = 0.007) compared to WBI. Maximum once-daily EBRT schedules (n = 2071; OR = 0.60; 95% CI 0.45–0.79; p < 0.001) and IORT (p = 0.042) resulted in better cosmetic results grade by medical professionals. Functional- and symptom-based QoL in the C30-scale was not different between PBI and WBI. Breast-specific QoL was superior after PBI in the subdomains of "systemic therapy side effects" as well as "breast-" and "arm symptoms". Conclusion: The analysis of multiple randomized trials demonstrate a superiority of PBI in acute toxicity as well breast-specific quality of life, when compared with WBI. Overall, late toxicities and cosmetic results were similar. PBI-technique with a fractionation of twice-daily schedules resulted in worse cosmesis rated by patients. [ABSTRACT FROM AUTHOR]

Purpose / objective: This study compares the dosimetric plans of three distinct boost modalities in cervical cancer (CC): intracavitary (IC) with tandem/ovoids brachytherapy (BT), IC + interstitial (IS) BT, and Stereotactic-Body-Radiotherapy (SBRT). The aim is to determine the dosimetric impact in terms of target coverage and organ at risk (OAR) doses. Materials and methods: 24 consecutive IC + IS BT boost treatment plans were retrospectively identified. For each plan included, two additional plans were created: IC-BT and SBRT. Importantly, no planning target volume (PTV) or planning (organ at) risk volume (PRV) margins were generated, therefore all structures were identical for any boost modality. Two different normalizations were performed: (1) Normalization to the target: prescription of 7.1 Gy to the D90% (defined as the minimum dose covering 90%) of the high-risk clinical target volume (HR-CTV); (2) Normalization to the OARs. HR-CTV coverage and OARs sparing were compared. The equivalent doses in 2 Gy fractions (EQD2) of EBRT and BT for CTV-HR and OARs were calculated using the linear-quadratic model with α/β of 10 (EQD210) and 3 (EQD23), respectively Results: A total of 72 plans were investigated. In the first normalization, the mean EQD23−D2cc (defined as the minimal dose of the 2 cc) of OAR was significantly higher in the IC-BT plans, and the bladder D2cc hard constraint could not be reached. IC + IS BT leads to a 1 Gy mean absolute decrease of bladder EQD23-D2cc (relative dose: -19%), allowing to reach the hard constraint. SBRT (without PTV) delivers the lowest EQD23-D2cc to the OAR. In the second normalization, IC-BT provides a significantly lower dose to the EQD210-D90% (6.62 Gy) and cannot achieve the coverage goal. SBRT (without PTV) yields the highest dose to the D90% of HR-CTV and a significantly lower EQD210-D50% and D30%. Conclusion: The key dosimetric benefit of BT over SBRT without PTV is a significantly higher D50% and D30% in the HR-CTV, which increases the local and conformal dose to the target. IC + IS BT vs. IC-BT provides significantly better target coverage and a lower dose to the OARs, making it the preferred boost modality in CC. [ABSTRACT FROM AUTHOR]

Background: Segmentation of the Gross Tumor Volume (GTV) is a crucial step in the brachytherapy (BT) treatment planning workflow. Currently, radiation oncologists segment the GTV manually, which is time-consuming. The time pressure is particularly critical for BT because during the segmentation process the patient waits immobilized in bed with the applicator in place. Automatic segmentation algorithms can potentially reduce both the clinical workload and the patient burden. Although deep learning based automatic segmentation algorithms have been extensively developed for organs at risk, automatic segmentation of the targets is less common. The aim of this study was to automatically segment the cervical cancer GTV on BT MRI images using a state-of-the-art automatic segmentation framework and assess its performance. Methods: A cohort of 195 cervical cancer patients treated between August 2012 and December 2021 was retrospectively collected. A total of 524 separate BT fractions were included and the axial T2-weighted (T2w) MRI sequence was used for this project. The 3D nnU-Net was used as the automatic segmentation framework. The automatic segmentations were compared with the manual segmentations used for clinical practice with Sørensen–Dice coefficient (Dice), 95th Hausdorff distance (95th HD) and mean surface distance (MSD). The dosimetric impact was defined as the difference in D98 (ΔD98) and D90 (ΔD90) between the manual segmentations and the automatic segmentations, evaluated using the clinical dose distribution. The performance of the network was also compared separately depending on FIGO stage and on GTV volume. Results: The network achieved a median Dice of 0.73 (interquartile range (IQR) = 0.50–0.80), median 95th HD of 6.8 mm (IQR = 4.2–12.5 mm) and median MSD of 1.4 mm (IQR = 0.90–2.8 mm). The median ΔD90 and ΔD98 were 0.18 Gy (IQR = -1.38–1.19 Gy) and 0.20 Gy (IQR =-1.10–0.95 Gy) respectively. No significant differences in geometric or dosimetric performance were observed between tumors with different FIGO stages, however significantly improved Dice and dosimetric performance was found for larger tumors. Conclusions: The nnU-Net framework achieved state-of-the-art performance in the segmentation of the cervical cancer GTV on BT MRI images. Reasonable median performance was achieved geometrically and dosimetrically but with high variability among patients. [ABSTRACT FROM AUTHOR]

Background: Utero-vaginal brachytherapy (BT) is an irreplaceable care component for the curative treatment of locally advanced cervix cancer (LACC). Magnetic Resonance Imaging (MRI)-image guided adaptive BT (IGABT) using the GYN-GEC-ESTRO EMBRACE guidelines is the international care standard. Usually following chemo–radiation therapy (CRT), IGABT has high proven utility in LACC but requires significant health system resources. Timely access was disrupted by the COVID-19 pandemic which challenged us to re-design our established IGABT care pathway. Methods: From April 2020 consecutive patients with LACC were enrolled after CRT in a single arm exploratory non-inferiority study of a modified IGABT (mIGABT) protocol. This delivered an iso-effective IGABT dose (39.3 Gy: EQD2: α/β10Gy concept) over a 24-h period during a single overnight hospitalisation. Results: Fourteen LACC patients received mIGABT from April 2020 to March 2022. Median age was 62.5 years (37–82 years). LACC histology was primary squamous (9/14) or adeno-carcinoma (5/14). International Federation of Gynaecology and Obstetrics (FIGO) 2018 stages ranged from IB1/2 (N = 3), IIA1/IIB (5), IIIB (2), IIIC1/2 (4) with mean ± standard deviation (SD) gross tumour volume-at-diagnosis (GTV_D) of 37.7 cc ± 71.6 cc. All patients achieved complete metabolic, clinical, and cytologic cancer response with CRT and IGABT. High-risk HPV was cleared by 6-months. Complete MRI-defined cancer response before mIGABT (GTV_Fx1) was seen in 77% of cases (10/13). Only two women developed metastatic disease and one died at 12-months; 13 patients were alive without cancer at mean 20.3 ± 7.2 months follow-up. Actuarial 2-year overall survival was 93%. Compared with our pre-COVID IGABT program, overall mIGABT cost-saving in this cohort was USD 22,866. Prescribed dose covered at least 90% (D90) of the entire cervix and any residual cancer at time of BT (HRCTV_D90: high-risk clinical target volume) with 3-fractions of 8.5 Gy delivered over 24-h (22.8 ± 1.7 h). Total treatment time including CRT was 38 days. The mIGABT schedule was well tolerated and the entire cohort met EMBRACE recommended (EQD2: α/β10Gy) combined HRCTV_D90 coverage of 87.5 ± 3.7 Gy. Similarly, organ-at-risk (OAR) median: interquartile range D2cc constraints (EQD2: α/β3Gy) were EMBRACE compliant: bladder (65.9 Gy: 58.4–72.5 Gy), rectum (59.1 Gy: 55.7–61.8 Gy), and sigmoid colon (54.6 Gy: 50.3–58.9 Gy). ICRU recto-vaginal point dose was significantly higher (75.7 Gy) in our only case of severe (G4) pelvic toxicity. Conclusions: This study demonstrated the utility of mIGABT and VMAT CRT in a small cohort with LACC. Loco-regional control was achieved in all cases with minimal emergent toxicity. Single insertion mIGABT was logistically efficient, cost-saving, and patient-centric during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Recent years have seen both a fresh knowledge of cancer and impressive advancements in its treatment. However, the clinical treatment paradigm of cancer is still difficult to implement in the twenty-first century due to the rise in its prevalence. Radiotherapy (RT) is a crucial component of cancer treatment that is helpful for almost all cancer types. The accuracy of RT dosage delivery is increasing as a result of the quick development of computer and imaging technology. The use of image-guided radiation (IGRT) has improved cancer outcomes and decreased toxicity. Online adaptive radiotherapy will be made possible by magnetic resonance imaging-guided radiotherapy (MRgRT) using a magnetic resonance linear accelerator (MR-Linac), which will enhance the visibility of malignancies. This review's objectives are to examine the benefits of MR-Linac as a treatment approach from the perspective of various cancer patients' prognoses and to suggest prospective development areas for additional study. [ABSTRACT FROM AUTHOR]

Purpose: Integrating magnetic resonance (MR) into radiotherapy planning has several advantages. This report details the clinical implementation of an MR simulation (MR-planning) program for external beam radiotherapy (EBRT) in one of North America's largest radiotherapy programs. Methods and materials: An MR radiotherapy planning program was developed and implemented at Sunnybrook Health Sciences Center in 2016 with two dedicated wide-bore MR platforms (1.5 and 3.0 Tesla). Planning MR was sequentially implemented every 3 months for separate treatment sites, including the central nervous system (CNS), gynecologic (GYN), head and neck (HN), genitourinary (GU), gastrointestinal (GI), breast, and brachial plexus. Essential protocols and processes were detailed in this report, including clinical workflow, optimized MR-image acquisition protocols, MR-adapted patient setup, strategies to overcome risks and challenges, and an MR-planning quality assurance program. This study retrospectively reviewed simulation site data for all MR-planning sessions performed for EBRT over the past 5 years. Results: From July 2016 to December 2021, 8798 MR-planning sessions were carried out, which corresponds to 25% of all computer tomography (CT) simulations (CT-planning) performed during the same period at our institution. There was a progressive rise from 80 MR-planning sessions in 2016 to 1126 in 2017, 1492 in 2018, 1824 in 2019, 2040 in 2020, and 2236 in 2021. As a result, the relative number of planning MR/CT increased from 3% of all planning sessions in 2016 to 36% in 2021. The most common site of MR-planning was CNS (49%), HN (13%), GYN (12%), GU (12%), and others (8%). Conclusion: Detailed clinical processes and protocols of our MR-planning program were presented, which have been improved over more than 5 years of robust experience. Strategies to overcome risks and challenges in the implementation process are highlighted. Our work provides details that can be used by institutions interested in implementing an MR-planning program. [ABSTRACT FROM AUTHOR]

Introduction: The APROVE-trial investigated the tolerability of postoperative proton beam therapy in women with cervical or endometrial cancer. The present analysis evaluated the secondary endpoints of health-related quality of life (HRQOL) and patient-reported symptoms. Methods: 25 patients were included in this prospective phase-II-trial and treated with postoperative radiotherapy using protons alone or in combination with chemotherapy. To attain general and gynecologic-specific HRQOL measures, the EORTC-QLQ-C30 questionnaires combined with -QLQ-CX24 for cervical and -QLQ-EN24 for endometrial cancer were assessed at baseline, at the end of RT and up to 2 years after radiotherapy. The results were compared to an age-matched norm reference population. Symptoms were assessed using Common Terminology Criteria for Adverse Events (CTCAE) and institutional patient-reported symptoms grading. Results: Scores regarding global health status were markedly impaired at baseline (mean: 58.0 ± 20.1) compared to reference population data, but significantly (p = 0.036) improved and evened out to comparable norm values 2 years after proton therapy (mean: 69.9 ± 19.3). Treatment caused acute and long-term worsening of pain (p = 0.048) and gastrointestinal symptoms (p = 0.016) for women with endometrial cancer, but no higher-grade CTCAE ≥ 3° toxicity was observed. Dosimetric evaluation of rectum, sigmoid, large and small bowel showed no correlation with the reported gastrointestinal symptoms. After 2 years, fatigue had significantly improved (p = 0.030), whereas patients with cervical cancer experienced more often lymphedema (p = 0.017). Scores for endometrial cancer pertaining to sexual activity (p = 0.048) and body image (p = 0.022) had improved post treatment; in the latter this effect persisted after 2 years. Conclusion: Proton beam therapy in the adjuvant setting was well tolerated with only low-grade side effects concerning gastrointestinal symptoms, lymphedema and pain. Overall quality of life was impaired at baseline, but patients were able to recover to values comparable to norm population 2 years after proton therapy. Larger studies are needed to confirm whether the benefit of proton therapy translates into a clinical effect. Sexual dysfunction remains an important issue. Trial registration: The trial was registered at https://clinicaltrials.gov (ClinicalTrials.gov Identifier: NCT03184350, 09th June 2017). [ABSTRACT FROM AUTHOR]

Background: To segment the pelvic active bone marrow (PABM) using magnetic resonance (MR) functional imaging and investigate the feasibility and dosimetric characteristics of cervical cancer proton radiotherapy for active bone marrow (ABM) sparing. Methods: We collected CT and MR simulation images of 33 patients with cervical cancer retrospectively. The PBM was contoured on the MRI FatFrac images; the PBM was divided into high-active bone marrow (ABM-high) and low-active bone marrow based on the fat content of the PBM. Four radiotherapy plans were created for each patient, which included intensity-modulated photon therapy (IMRT), bone marrow sparing IMRT (IMRT-BMS), intensity-modulated proton therapy (IMPT), and bone marrow sparing IMPT (IMPT-BMS). The dosimetric differences among the four plans were compared. Results: The ABM-high volume in the enrolled patients accounted for 45.2% of the total ABM volume. The target coverage was similar among the four radiotherapy plans. IMRT-BMS, IMPT, and IMPT-BMS reduced the Dmean of ABM-high by 16.6%, 14.2%, and 44.5%, respectively, compared to the Dmean of IMRT (p < 0.05). IMPT-BMS had the best protective effect on the bone marrow. Compared to IMRT, the volume of ABM-high receiving an irradiation dose of 5–40 Gy decreased by 10.2%, 36.8%, 58.8%, 67.4%, 64.9%, and 44.5%, respectively (p < 0.001). Conclusions: The MR functional imaging technique helped in the grading and segmentation of PABM. MR functional image-guided proton radiotherapy for cervical cancer can achieve optimal BMS. [ABSTRACT FROM AUTHOR]

3. HT ht and HT ht represent steps of different levels of encoding and decoding, respectively, where a larger index i represents a higher level. The Adam solver with high computational efficiency and stability was selected as an optimizer, in which the momentum parameters were set to HT ht 0.5 and HT ht 0.999. Furthermore, HT ht and HT ht , which denote the maximum and average dose respectively, are taken into consideration for OARs. [Extracted from the article]

Background: This paper attempts to conduct a systematic review and meta-analysis of deep learning (DLs) models for cervical cancer CT image segmentation.Methods: Relevant studies were systematically searched in PubMed, Embase, The Cochrane Library, and Web of science. The literature on DLs for cervical cancer CT image segmentation were included, a meta-analysis was performed on the dice similarity coefficient (DSC) of the segmentation results of the included DLs models. We also did subgroup analyses according to the size of the sample, type of segmentation (i.e., two dimensions and three dimensions), and three organs at risk (i.e., bladder, rectum, and femur). This study was registered in PROSPERO prior to initiation (CRD42022307071).Results: A total of 1893 articles were retrieved and 14 articles were included in the meta-analysis. The pooled effect of DSC score of clinical target volume (CTV), bladder, rectum, femoral head were 0.86(95%CI 0.84 to 0.87), 0.91(95%CI 0.89 to 0.93), 0.83(95%CI 0.79 to 0.88), and 0.92(95%CI 0.91to 0.94), respectively. For the performance of segmented CTV by two dimensions (2D) and three dimensions (3D) model, the DSC score value for 2D model was 0.87 (95%CI 0.85 to 0.90), while the DSC score for 3D model was 0.85 (95%CI 0.82 to 0.87). As for the effect of the capacity of sample on segmentation performance, no matter whether the sample size is divided into two groups: greater than 100 and less than 100, or greater than 150 and less than 150, the results show no difference (P > 0.05). Four papers reported the time for segmentation from 15 s to 2 min.Conclusion: DLs have good accuracy in automatic segmentation of CT images of cervical cancer with a less time consuming and have good prospects for future radiotherapy applications, but still need public high-quality databases and large-scale research verification. [ABSTRACT FROM AUTHOR]

Background and Purpose: Dose escalation for positive node maybe improve the regional control of patients with node-positive cervical cancer, but the optimal dose for nodes of different sizes remains controversial. The purpose of this study was to explore the individualized dose escalation for lymph nodes (LNs) with different sizes in the definitive radiotherapy of cervical cancer.Methods: A total of 1002 cervical cancer patients with the International Federation of Gynecology and Obstetrics (FIGO 2009) stage IB1-IVA, who were treated by definitively radiotherapy between September 2013 and December 2016 were enrolled. All LNs identified by computed tomography/magnetic resonance imaging (CT/MRI) were assigned into three groups according to the short diameters of < 1 cm, 1-2 cm or ≥ 2 cm at pretreatment.Results: In total, 580 patients with 1310 LNs were detected. The nodal control rate in groups of LNs < 1 cm, 1-2 cm and ≥ 2 cm was 99.4%, 96%, and 75.9%, respectively (P = 0.000). Among LNs < 1 cm, the control, overall survival (OS) and progression-free survival (PFS) rates did not significantly differ among three dose-based groups (≤ 50.4 Gy, 50.4-60 Gy, > 60 Gy) (control rate, 99.4% vs. 99.3% vs. 100%, P = 0.647) (5-year OS, 76.2% vs. 79% vs. 81.6%, P = 0.682) (5-year PFS, 74.1% vs. 73.9% vs. 78.9% P = 0.713). Among LNs of 1-2 cm, the control and PFS rates were significantly higher in the group of dose ≥ 55 Gy than the group of dose < 55 Gy (control rate, 98% vs. 93.6%, P = 0.028) (5-year PFS, 69.6% vs. 56.7%, P = 0.025). However, this did not cause a significant difference for 5-year OS rate (72.6% vs. 68.3%, P = 0.5). Among LNs ≥ 2 cm, the control, OS, and PFS rates were higher in the group of dose ≥ 55 Gy than the group of dose < 55 Gy, while no significant difference was found (control rate, 82.1% vs. 63.2%, P = 0.107) (5-year OS, 60.6% vs. 37.5%, P = 0.141) (5-year PFS, 51.5% vs.37.5%, P = 0.232).Conclusions: Radiation dose escalation is not necessary for LNs < 1 cm, and dose escalation of 55 Gy is enough for LNs of 1-2 cm. [ABSTRACT FROM AUTHOR]

Purpose: Fast and accurate outlining of the organs at risk (OARs) and high-risk clinical tumor volume (HRCTV) is especially important in high-dose-rate brachytherapy due to the highly time-intensive online treatment planning process and the high dose gradient around the HRCTV. This study aims to apply a self-configured ensemble method for fast and reproducible auto-segmentation of OARs and HRCTVs in gynecological cancer.Materials and Methods: We applied nnU-Net (no new U-Net), an automatically adapted deep convolutional neural network based on U-Net, to segment the bladder, rectum and HRCTV on CT images in gynecological cancer. In nnU-Net, three architectures, including 2D U-Net, 3D U-Net and 3D-Cascade U-Net, were trained and finally ensembled. 207 cases were randomly chosen for training, and 30 for testing. Quantitative evaluation used well-established image segmentation metrics, including dice similarity coefficient (DSC), 95% Hausdorff distance (HD95%), and average surface distance (ASD). Qualitative analysis of automated segmentation results was performed visually by two radiation oncologists. The dosimetric evaluation was performed by comparing the dose-volume parameters of both predicted segmentation and human contouring.Results: nnU-Net obtained high qualitative and quantitative segmentation accuracy on the test dataset and performed better than previously reported methods in bladder and rectum segmentation. In quantitative evaluation, 3D-Cascade achieved the best performance in the bladder (DSC: 0.936 ± 0.051, HD95%: 3.503 ± 1.956, ASD: 0.944 ± 0.503), rectum (DSC: 0.831 ± 0.074, HD95%: 7.579 ± 5.857, ASD: 3.6 ± 3.485), and HRCTV (DSC: 0.836 ± 0.07, HD95%: 7.42 ± 5.023, ASD: 2.094 ± 1.311). According to the qualitative evaluation, over 76% of the test data set had no or minor visually detectable errors in segmentation.Conclusion: This work showed nnU-Net's superiority in segmenting OARs and HRCTV in gynecological brachytherapy cases in our center, among which 3D-Cascade shows the highest accuracy in segmentation across different applicators and patient anatomy. [ABSTRACT FROM AUTHOR]

Background The purpose of the study was to evaluate the feasibility of deformable image registration (DIR) in assessing cumulative dose distributions of the combination of external beam radiotherapy (EBRT) and fractionated intracavitary brachytherapy (ICBT) for cervical cancer. Materials and methods Three-dimensional image data sets of five consecutive patients were used. The treatment plan consisted of whole pelvic EBRT (total dose: 45 Gy in 25 fractions) combined with computed tomography (CT)-based high-dose rate ICBT (≥24 Gy in 4 fractions to the high risk clinical target volume (HR-CTV)). Organs at risk and HR-CTV were contoured on each CT images and dose-volume parameters were acquired. Pre-imaging preparations were performed prior to each ICBT to minimize the uncertainty of the organ position. Physical doses of each treatment were converted to biologically equivalent doses in 2 Gy daily fractions by the linear quadratic model. Three-dimensional dose distributions of each treatment were accumulated on CT images of the first ICBT using DIR with commercially available image registration software (MIM Maestro®). To compare with DIR, 3D dose distributions were fused by rigid registration based on bony structure matching. To evaluate the accuracy of DIR, the Dice similarity coefficient (DSC) was measured between deformed contours and initial contours. Results The cumulative dose distributions were successfully illustrated on the CT images using DIR. Mean DSCs of the HR-CTV, rectum, and bladder were 0.46, 0.62 and 0.69, respectively, with rigid registration; and 0.78, 0.76, and 0.87, respectively, with DIR (p <0.05). The mean DSCs derived from our DIR procedure were comparable to those of previous reports describing the quality of DIR algorithms in the pelvic region. DVH parameters derived from the 2 methods showed no significant difference. Conclusions Our results suggest that DIR-based dose accumulation may be acceptable for assessing cumulative dose distributions to assess doses to the tumor and organs at risk in combined radiotherapy for cervical cancer under pre-imaging preparations. [ABSTRACT FROM AUTHOR]

Background Interstitial brachytherapy (ISBT) is an optional treatment for locally advanced gynecological tumours for which conventional intracavitary brachytherapy (ICBT) would result in suboptimal dose coverage. However, ISBT with Martinez Universal Perineal Interstitial Template (MUPIT), in which ~10-20 needles are usually applied, is more time-consuming and labor-intensive than ICBT alone, making it a burden on both practitioners and patients. Therefore, here we investigated the applicability of a combined intracavitary/interstitial (IC/IS) approach in image-guided adaptive brachytherapy for bulky and/or irregularly shaped gynecological tumours for which interstitial brachytherapy (ISBT) was performed. Methods Twenty-one consecutive patients with gynecological malignancies treated with computed tomography-guided ISBT using MUPIT were analyzed as cases for this dosimetric study. For each patient, the IC/IS plan using a tandem and 1 or 2 interstitial needles, which was modeled after the combined IC/IS approach, was generated and compared with the IS plan based on the clinical ISBT plan, while the IC plan using only the tandem was applied as a simplified control. Maximal dose was prescribed to the high-risk clinical target volume (HR-CTV) while keeping the dose constraints of D2cc bladder < 7.0 Gy and D2cc rectum < 6.0 Gy. The plan with D90 HR-CTV exceeding 6.0 Gy was considered acceptable. Results The average D90 HR-CTV was 77%, 118% and 140% in the IC, IC/IS and IS plans, respectively, where 6 Gy corresponds to 100%. The average of the ratio of D90 HR-CTV to D2cc rectum (gain factor (GF) rectum) in the IC, IC/IS and IS plans was 0.8, 1.3 and 1.5 respectively, while GFbladder was 0.9, 1.4 and 1.6, respectively. In the IC/IS plan, D90 HRCTV, GFrectum and GFbladder exceeded 100%, 1.0 and 1.0, respectively, in all patients. Conclusions These data demonstrated that the combined IC/IS approach could be a viable alternative to ISBT for gynecological malignancies with bulky and/or irregularly shaped tumours. [ABSTRACT FROM AUTHOR]

Objectives: To quantify the pelvic bone marrow (PBM) fat content changes receiving different radiation doses of concurrent chemoradiotherapy for cervical cancer and to determine association with peripheral blood cell counts.Methods: The data of 54 patients were prospectively collected. Patients underwent MRI iterative decomposition of water and fat with echo asymmetrical and least squares estimation (IDEAL IQ) scanning at RT-Pre, RT mid-point, RT end, and six months. The changes in proton density fat fraction (PDFF%) at 5-10 Gy, 10-15 Gy, 15-20 Gy, 20-30 Gy, 30-40 Gy, 40-50 Gy, and > 50 Gy doses were analyzed. Spearman's rank correlations were performed between peripheral blood cell counts versus the differences in PDFF% at different dose gradients before and after treatment.Results: The lymphocytes (ALC) nadirs appeared at the midpoint of radiotherapy, which was only 27.6% of RT-Pre; the white blood cells (WBC), neutrophils (ANC), and platelets (PLT) nadirs appeared at the end of radiotherapy which was 52.4%, 65.1%, and 69.3% of RT-Pre, respectively. At RT mid-point and RT-end, PDFF% increased by 46.8% and 58.5%, respectively. Six months after radiotherapy, PDFF% decreased by 4.71% under 5-30 Gy compared to RT-end, while it still increased by 55.95% compared to RT-Pre. There was a significant positive correlation between PDFF% and ANC nadirs at 5-10 Gy (r = 0.62, P = 0.006), and correlation was observed between PDFF% and ALC nadirs at 5-10 Gy (r = 0.554, P = 0.017).Conclusion: MRI IDEAL IQ imaging is a non-invasive approach to evaluate and track the changes of PBM fat content with concurrent chemoradiotherapy for cervical cancer. The limitation of low-dose bone marrow irradiation volume in cervical cancer concurrent chemoradiotherapy should be paid more attention to. [ABSTRACT FROM AUTHOR]

Background To establish a generalized equivalent uniform dose (gEUD) -based prescription method for Image Guided Brachytherapy (IGBT) that reproduces the Gyn GEC-ESTRO WG (GGE) prescription for cervix carcinoma patients on CT images with limited soft tissue resolution. Methods The equivalence of two IGBT planning approaches was investigated in 20 patients who received external beam radiotherapy (EBT) and 5 concomitant high dose rate IGBT treatments. The GGE planning strategy based on dose to the most exposed 2 cm³ (D2cc) was used to derive criteria for the gEUD-based planning of the bladder and rectum. The safety of gEUD constraints in terms of GGE criteria was tested by maximizing dose to the gEUD constraints for individual fractions. Results The gEUD constraints of 3.55 Gy for the rectum and 5.19 Gy for the bladder were derived. Rectum and bladder gEUD-maximized plans resulted in D2cc averages very similar to the initial GGE criteria. Average D2ccs and EUDs from the full treatment course were comparable for the two techniques within both sets of normal tissue constraints. The same was found for the tumor doses. Conclusions The derived gEUD criteria for normal organs result in GGE-equivalent IGBT treatment plans. The gEUD-based planning considers the entire dose distribution of organs in contrast to a single dose-volume-histogram point. [ABSTRACT FROM AUTHOR]

Background and Purpose: Chemoradiotherapy (CRT) followed by a brachytherapy (BT) boost is the standard of care for patients with locally advanced or recurrent gynecological cancer (LARGC). However, not every patient is suitable for BT. Therefore, we investigated the feasibility of an MR-guided SBRT boost (MRg-SBRT boost) following CRT of the pelvis.Material and Methods: Ten patients with LARGC were analyzed retrospectively. The patients were not suitable for BT due to extensive infiltration of the pelvic wall (10%), other adjacent organs (30%), or both (50%), or ineligibility for anesthesia (10%). Online-adaptive treatment planning was performed to control for interfractional anatomical changes. Treatment parameters and toxicity were evaluated to assess the feasibility of MRg-SBRT boost.Results: MRg-SBRT boost was delivered to a median total dose of 21.0 Gy in 4 fractions. The median optimized PTV (PTVopt) size was 43.5ccm. The median cumulative dose of 73.6Gy10 was delivered to PTVopt. The cumulative median D2ccm of the rectum was 63.7 Gy; bladder 72.2 Gy; sigmoid 65.8 Gy; bowel 59.9 Gy (EQD23). The median overall treatment time/fraction was 77 min, including the adaptive workflow in 100% of fractions. The median duration of the entire treatment was 50 days. After a median follow-up of 9 months, we observed no CTCAE ≥ °II toxicities.Conclusion: These early results report the feasibility of an MRg-SBRT boost approach in patients with LARGC, who were not candidates for BT. When classical BT-OAR constraints are followed, the therapy was well tolerated. Long-term follow-up is needed to validate the results. [ABSTRACT FROM AUTHOR]

Purpose: Cardiac effects after breast cancer radiation therapy potentially affect more patients as survival improves. The heart's heterogeneous radiation exposure and composition of functional structures call for establishing individual relationships between structure dose and specific late effects. However, valid dosimetry requires reliable contouring which is challenging for small volumes based on older, lower-quality computed tomography imaging. We developed a heart atlas for robust heart contouring in retrospective epidemiologic studies.Methods and Materials: The atlas defined the complete heart and geometric surrogate volumes for six cardiac structures: aortic valve, pulmonary valve, all deeper structures combined, myocardium, left anterior myocardium, and right anterior myocardium. We collected treatment planning records from 16 patients from 4 hospitals including dose calculations for 3D conformal tangential field radiation therapy for left-sided breast cancer. Six observers each contoured all patients. We assessed spatial contouring agreement and corresponding dosimetric variability.Results: Contouring agreement for the complete heart was high with a mean Jaccard similarity coefficient (JSC) of 89%, a volume coefficient of variation (CV) of 5.2%, and a mean dose CV of 4.2%. The left (right) anterior myocardium had acceptable agreement with 63% (58%) JSC, 9.8% (11.5%) volume CV, and 11.9% (8.0%) mean dose CV. Dosimetric agreement for the deep structures and aortic valve was good despite higher spatial variation. Low spatial agreement for the pulmonary valve translated to poor dosimetric agreement.Conclusions: For the purpose of retrospective dosimetry based on older imaging, geometric surrogate volumes for cardiac organs at risk can yield better contouring agreement than anatomical definitions, but retain limitations for small structures like the pulmonary valve. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): The purpose of the study was to assess the uterus motions and bladder volume changes of fractional movements in cervical sites throughout the external beam radiotherapy (EBRT) treatment. Materials/methods: A prospective online MR imaging tracking study was conducted in EBRT 43 patients with at least 4 scans during each treatment (before: ultrasound scan, MRI scan, CBCT scan, after: MRI scan) were included. In order to improve the treatment repeatability, each patient was instructed to empty the bladder and drink 500 ml water 1 h before CT simulation and each treatment. If the ultrasound scan result reached the CT simulation volume of bladder, the treatment began. Bladder was outlined on the T2 weighted axial sequence and CBCT image by the two observers to avoid the influence of contouring. The data of bladder volume and scanning time were accurately recorded. The bladder volumes, filling rates and uterus motion were retrospectively analyzed by MIM software. Results: Inter-fraction variation of the bladder volume was significant (p < 0.0001). Intra-fraction mean increase of the bladder volume was modest (30 cc) but significant (p < 0.001). Both inter- and intra-fraction of the uterus motion were significant. The average time between the pre-and post-fraction MRI scans was 27.82 ± 7.12 min (range 10–55 min) for IMRT plans and 24.14 ± 5.86 min (range7-38 min) for VMAT plan. Average bladder filling rate was 3.43 ml/min. The bladder filling rate did not change significantly with the course of treatment, but the bladder was more intolerant. Conclusion: This is the most detailed assessment of intra-fraction and inter-fraction motion during EBRT for cervical cancer. Finally, this study will inform appropriate treatment margins for online adaptive radiotherapy. We suggest that at least one image scan is needed before the EBRT. The portable US scanner provides a quick but unreliable measurement of the bladder volume. There is a significant statistical difference between the results of ultrasonic scanning and that of image scanning. [ABSTRACT FROM AUTHOR]

Introduction: Lymph node metastases presenting with locally advanced cervical cancer are poor prognostic features. Modern radiotherapy approaches enable dose escalation to radiologically abnormal nodes. This study reports the results of a policy of a simultaneous integrated boost (SIB) in terms of treatment outcomes. Materials and methods: Patients treated with radical chemoradiation with weekly cisplatin for locally advanced cervical cancer including an SIB to radiologically abnormal lymph nodes were analysed. All patients received a dose of 45 Gy in 25 fractions and a SIB dose of 60 Gy in 25 fractions using intensity modulated radiotherapy/volumetric modulated arc therapy, followed by high dose rate brachytherapy of 28 Gy in 4 fractions. A control cohort with radiologically negative lymph nodes was used to compare impact of the SIB in node positive patients. Treatment outcomes were measured by overall survival (OS), post treatment tumour response and toxicities. The tumour response was based on cross sectional imaging at 3 and 12 months and recorded as local recurrence free survival (LRFS), regional recurrence free survival (RRFS) and distant recurrence free survival (DRFS). Results: In between January 2015 and June 2017, a total of 69 patients with a median follow up of 30.9 months (23 SIB patients and 46 control patients) were identified. The complete response rate at 3 months was 100% in the primary tumour and 83% in the nodal volume receiving SIB. The OS, LRFS, RRFS and DRFS at 3 years of the SIB cohort were 69%, 91%, 79% and 77% respectively. High doses can be delivered to regional pelvic lymph nodes using SIB without excessive toxicity. Conclusion: Using a SIB, a total dose of 60 Gy in 25 fractions chemoradiation can be delivered to radiologically abnormal pelvic nodes with no increase in toxicity compared to node negative patients. The adverse impact of positive nodal status may be negated by high dose deposition using SIB, but larger prospective studies are required to confirm this observation. [ABSTRACT FROM AUTHOR]

Background: To assess the intra-fractional dosimetric variations of image-guided brachytherapy of cervical cancer.Methods: A total of 38 fractions (9 patients) undergoing brachytherapy for cervical cancer underwent a CT scanning for treatment planning (planning CT) and a Cone-beam CT (CBCT) scanning immediately prior to delivery (pre-delivery CBCT). The variations of volumes as well as the dosimetric impact from treatment planning to delivery (intra-application) were evaluated. The dose volume histogram parameters including volume, D90 of high-risk clinical target volume (HRCTV) and D2cc of organs at risk (OARs) were recorded.Results: The relative differences (mean ± 1SD) of the volume and D90 HRCTV across the two scans were - 2.0 ± 3.3% and - 1.2 ± 4.5%, respectively. The variations of D2cc for bladder, rectum, sigmoid and small intestine are - 0.6 ± 17.1%, 9.3 ± 14.6%, 7.2% ± 20.5% and 1.5 ± 12.6%, respectively. Most of them are statistically nonsignificant except the D2cc for rectum, which showed a significant increase (P = 0.001). Using 5% and 10% uncertainty of physical dose for HRCTV at a 6 Gy × 5 high-dose-rate schedule, the possibility of total equivalent doses in 2 Gy fractions (EQD2) lower than 85 Gy is close to 0% and 3%, respectively. Performing similar simulation at 15% and 20% uncertainty of a 4 Gy physical dose for OARs, the possibility of total EQD2 dose exceeding 75 Gy is about 70%. Less than 1% of the total EQD2 of OARs would exceed 80 Gy.Conclusions: Average intra-fractional dosimetric variation of HRCTV was small in an interval of less than 1 h, and the possibility of total EQD2 exceeding 85 Gy is higher than 97%. The intra-fractional dosimetric variations of OARs might result in an overdose for OARs in a single fraction or the whole treatment. It is necessary to detect unfavorable anatomical changes by re-imaging and take interventions to minimize applied doses and reduce the risk of complications. [ABSTRACT FROM AUTHOR]

Introduction: Lymph node metastases presenting with locally advanced cervical cancer are poor prognostic features. Modern radiotherapy approaches enable dose escalation to radiologically abnormal nodes. This study reports the results of a policy of a simultaneous integrated boost (SIB) in terms of treatment outcomes.Materials and Methods: Patients treated with radical chemoradiation with weekly cisplatin for locally advanced cervical cancer including an SIB to radiologically abnormal lymph nodes were analysed. All patients received a dose of 45 Gy in 25 fractions and a SIB dose of 60 Gy in 25 fractions using intensity modulated radiotherapy/volumetric modulated arc therapy, followed by high dose rate brachytherapy of 28 Gy in 4 fractions. A control cohort with radiologically negative lymph nodes was used to compare impact of the SIB in node positive patients. Treatment outcomes were measured by overall survival (OS), post treatment tumour response and toxicities. The tumour response was based on cross sectional imaging at 3 and 12 months and recorded as local recurrence free survival (LRFS), regional recurrence free survival (RRFS) and distant recurrence free survival (DRFS).Results: In between January 2015 and June 2017, a total of 69 patients with a median follow up of 30.9 months (23 SIB patients and 46 control patients) were identified. The complete response rate at 3 months was 100% in the primary tumour and 83% in the nodal volume receiving SIB. The OS, LRFS, RRFS and DRFS at 3 years of the SIB cohort were 69%, 91%, 79% and 77% respectively. High doses can be delivered to regional pelvic lymph nodes using SIB without excessive toxicity.Conclusion: Using a SIB, a total dose of 60 Gy in 25 fractions chemoradiation can be delivered to radiologically abnormal pelvic nodes with no increase in toxicity compared to node negative patients. The adverse impact of positive nodal status may be negated by high dose deposition using SIB, but larger prospective studies are required to confirm this observation. [ABSTRACT FROM AUTHOR]

Background: Primary cardiac tumors are an extremely rare disease with limited prognosis. The treatment of choice is surgery. Other treatment options include chemotherapy and radiation therapy, which historically represented a palliative approach in patients who were not eligible for surgery. The development of hybrid MR-guided radiation therapy makes it possible to better visualize cardiac lesions and to apply high doses per fraction in sensible organs such as the heart.Case Presentation: Patients affected by inoperable primary cardiac sarcomas and treated at two different institutions were considered for this analysis and retrospectively analyzed. All patients were treated using a 0.35 T hybrid MR Linac system (MRIdian, ViewRay Inc., Mountain View, CA). In the present study we investigated the feasibility, early outcome and toxicity of MR-guided RT in primary cardiac sarcomas. Four consecutive non-metastasized patients who were treated between 05-09/2020 were analyzed. The cardiac sarcomas were mostly located in the right atrium (50%) and one patient presented with 3 epicardial lesions. All patients received MRgRT as a salvage treatment for recurrent cardiac sarcoma after initial surgery, after a mean interval of 12 months (range 1-29 months). Regarding the treatment characteristics, the mean GTV size was 22.9 cc (range 2.5-56.9 cc) and patients were treated with a mean GTV dose of 38.9 Gy (range 30.1-41.1 Gy) in 5 fractions. Regarding feasibility, all treatments were completed as planned and all patients tolerated the treatment very well and showed only mild grade 1 or 2 symptoms like fatigue, dyspnea or mild chest pain at early follow-up.Conclusion: To the best of our knowledge, in this retrospective analysis we present the first and largest series of patients presenting with primary cardiac sarcomas treated with online adaptive MRgRT. However, further studies are needed to evaluate the impact of this new methodology on the outcome of this very rare disease. [ABSTRACT FROM AUTHOR]

Future radiation oncology encompasses a broad spectrum of topics ranging from modern clinical trial design to treatment and imaging technology and biology. In more detail, the application of hybrid MRI devices in modern image-guided radiotherapy; the emerging field of radiomics; the role of molecular imaging using positron emission tomography and its integration into clinical routine; radiation biology with its future perspectives, the role of molecular signatures in prognostic modelling; as well as special treatment modalities such as brachytherapy or proton beam therapy are areas of rapid development. More clinically, radiation oncology will certainly find an important role in the management of oligometastasis. The treatment spectrum will also be widened by the rational integration of modern systemic targeted or immune therapies into multimodal treatment strategies. All these developments will require a concise rethinking of clinical trial design. This article reviews the current status and the potential developments in the field of radiation oncology as discussed by a panel of European and international experts sharing their vision during the "X-Change" symposium, held in July 2019 in Munich (Germany). [ABSTRACT FROM AUTHOR]

Background: Fatigue is one of the most common and distressing side-effects of breast cancer radiotherapy. According to current guidelines, accelerated partial breast irradiation (APBI) may be considered as an alternative treatment option for women with early-stage low-risk breast cancer. One method for APBI is single-dose intraoperative radiotherapy (IORT) applied directly to the tumor bed during breast conserving surgery (BCS). The COSMOPOLITAN trial therefore aims to analyze the intensity of fatigue following single-shot IORT with electrons (IOERT) compared to conventional hypofractionated whole breast irradiation (WBI) in low risk early breast cancer patients.Methods: This trial is conducted as a multicenter, prospective, randomized, two-arm phase II study comparing the intensity of fatigue in early-stage breast cancer (cT1cN0cM0, tumor size < 2,5 cm, ER pos. Her2neu neg., age > 50 years) treated either with WBI or APBI after BCS. Secondary outcomes investigated are tumor control, overall survival (OS), disease-free survival (DFS), acute and chronic toxicity, quality of life (QoL) and cosmesis. A total of 202 patients will be randomized into two arms: Patients in arm A will receive WBI (40.05 Gy, 15 fractions) after surgical resection, while patients in arm B will receive IOERT (21 Gy to the 90%-isodose) during BCS. Fatigue will be assessed 12 weeks post surgery with the help of the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale.Discussion: The present trial aims to evaluate treatment response to compare single-shot intraoperative electron APBI to conventional WBI following BCS in early-stage low risk breast cancer patients. Fatigue is selected as the primary, patient-reported endpoint due its major clinical relevance.Trial Registration: The study is prospectively registered on February 12th, 2019: Clinicaltrials.gov, NCT03838419. "Intraoperative Electron Radiotherapy for Low-risk Early Breast Cancer (COSMOPOLITAN)".Study Status: Ongoing study. Start of recruitment was December 2019. [ABSTRACT FROM AUTHOR]

Purpose: To compare CTVHR and OAR dimensions and inter-rater agreement between magnetic resonance (MR) and trans-rectal ultrasound (TRUS) images in IB cervical cancer patients.Methods: IB cervical cancer patients treated with (chemo)radiotherapy plus MR-guided brachytherapy (BT) were prospectively enrolled in this study. Radiation oncologists contoured CTVHR and OARs in pre-BT MR images (MRI) and intra-operative TRUS images. These contours were subsequently compared in regard to volume and dimension. Contour inter-rater agreement analysis was also investigated using kappa index (KI). Stata 15.0 was used for statistical analysis and a p-value < 0.05 was considered statistically significant.Results: TRUS CTVHR volumes were statistically smaller than the respective MRI contoured volumes. TRUS CTVHR thickness was found to be consistently smaller than MRI contours in all patients. No statistical difference was seen in width and height between the two different imaging modalities. MRI contours had a median KI of 0.66 (range: 0.56-0.77) while TRUS-based contours had a median KI of 0.64 (range: 0.47-0.77). Bladder and rectum had very satisfactory KI in both imaging modalities. Vaginal contours had moderate agreement in MR (0.52) and in TRUS images (0.58).Conclusion: TRUS images allow good visualization of CTVHR and OARs in IB cervical cancer patients. Inter-rater contour variability was comparable between TRUS and MR images. TRUS is a promising modality on its own for image-guided BT. [ABSTRACT FROM AUTHOR]

Purpose: To compare treatment plans for interstitial high dose rate (HDR) liver brachytherapy with 192Ir calculated according to current-standard TG-43U1 protocol with model-based dose calculation following TG-186 protocol.Methods: We retrospectively evaluated dose volume histogram (DVH) parameters for liver, organs at risk (OARs) and clinical target volumes (CTVs) of 20 patient cases diagnosed with hepatocellular carcinoma (HCC) or metastatic colorectal cancer (mCRC). Dose calculations on a homogeneous water geometry (TG-43U1 surrogate) and on a computed tomography (CT) based geometry (TG-186) were performed using Monte Carlo (MC) simulations. The CTs were segmented based on a combination of assigning TG-186 recommended tissues to fixed Hounsfield Unit (HU) ranges and using organ contours delineated by physicians. For the liver, V5Gy and V10Gy were analysed, and for OARs the dose to 1 cubic centimeter (D1cc). Target coverage was assessed by calculating V150, V100, V95 and V90 as well as D95 and D90. For every DVH parameter, median, minimum and maximum values of the deviations of TG-186 from TG-43U1 were analysed.Results: TG-186-calculated dose was found to be on average lower than dose calculated with TG-43U1. The deviation of highest magnitude for liver parameters was -6.2% of the total liver volume. For OARs, the deviations were all smaller than or equal to -0.5 Gy. Target coverage deviations were as high as -1.5% of the total CTV volume and -3.5% of the prescribed dose.Conclusions: In this study we found that TG-43U1 overestimates dose to liver tissue compared to TG-186. This finding may be of clinical importance for cases where dose to the whole liver is the limiting factor. [ABSTRACT FROM AUTHOR]

Background: Ultrasound (US) imaging has been proved as an excellent diagnostic tool in gynecology and, due to its wide availability and limited cost, is under intense investigation as base for dose adaptation in cervical cancer brachytherapy. Purpose of this work is to test inter/intra-observer uncertainties between magnetic resonance (MR) and trans-rectal ultrasound (TRUS) imaging in defining maximum tumor width before first brachytherapy (BT) application in a prospective cohort of cervical cancer patients undergoing image-guided adaptive brachytherapy (IGABT).Methods: One hundred ten consecutive cervical cancer patients treated between 2013 and 2016 were included. Before the first BT implant patients underwent MR and TRUS scan with no applicator in place. Images were independently analyzed by three examiners, blinded to the other's results. With clinical information at hand, maximum tumor width was measured on preBT TRUS and MR. Quantitative agreement analysis was undertaken. Intra-class correlation coefficient (ICC), Passing-Bablok and Bland Altman plots were used to evaluate the intra/inter-observers measurement agreement.Results: Average difference between tumor width measured on MR (HRCTVMR) and TRUS (HRCTVTRUS) was 1.3 ± 3.2 mm (p <  0.001); 1.1 ± 4.6 mm (p = 0.01) and 0.7 ± 3 mm (p = 0.01). The error was less than 3 mm in 79, 82 and 80% of the measurements for the three observers, respectively. Intra-observer ICC was 0.96 (CI95% 0.94-0.97), 0.93 (CI95% 0.9-0.95) and 0.96 (CI95% 0.95-0.98) respectively. Inter-observer ICC for HRCTVMR width measures was 0.92 (CI95% 0.89-0.94) with no difference among FIGO stages. Inter-observer ICC for HRCTVTRUS was 0.86 (CI95% 0.81-0.9). For FIGO stage I and II tumors, ICC HRCTVTRUS values were comparable to respective HRCTVMR ICC values. For larger tumors HRCTVTRUS inter-observer ICC values were lower than respective HRCTVMR although remaining acceptable.Conclusions: Our results suggest that TRUS is equivalent to MR in assessing preBT tumor maximum width in cervical cancer FIGO stage I/II. In more advanced stages TRUS seems to be slightly inferior to MR although maintaining a good agreement to gold standard imaging. [ABSTRACT FROM AUTHOR]

Background: To update the clinical outcome of an elderly women cohort with early breast cancer who underwent accelerated partial breast irradiation (APBI) based on a post-operative single fraction of multicatheter interstitial high dose-rate brachytherapy (MIB).Material and Methods: A single institution retrospective cohort study was performed focusing on elderly patients (≥ 65 years old) presenting a low-risk breast carcinoma treated by lumpectomy plus axillary evaluation followed by MIB APBI. A single fraction of 16 Gy was prescribed on the 100% isodose. Clinical outcome at 5 years was reported based on local relapse free survival (LRFS), specific survival (SS) and overall survival (OS). Late toxicity was evaluated. Cosmetic results were evaluated clinically by the physician.Results: Between January 2012 and August 2015, 48 women (51 lesions) were treated. Median age was 77.7 years (range: 65-92) with a median tumor size of 12 mm (range: 3-32). Five patients (pts) presented an axillary lymph node involvement (4 Nmic, 1 N1). Invasive ductal carcinoma was the most frequent histology type (86.3%). With a median follow-up of 64 months (range: 56-71), no local relapse occurred while 1 pt. developed an axillary relapse (2.1%). No Grade 3 or higher late toxicity was observed while 16 late toxicities occurred (G1: 14 events [87.5%) mainly G1 breast fibrosis). The rate of excellent cosmetic outcome was 76.4%.Conclusion: We confirmed the safety of the process and remained encouraging clinical outcome of a post-operative single fraction of MIB ABPI in the elderly. This approach leads to consider a very APBI as an attractive alternative to intra-operative radiation therapy while all the patients will be good candidates for APBI in regards to the post-operative pathological report. [ABSTRACT FROM AUTHOR]

Purpose: To determine the best method to contour the planning organ at risk volume (PRV) for the urethra, this study aimed to investigate the displacement of a Foley catheter in the urethra with a soft and thin guide-wire.Methods: For each patient, the study used two sets of computed tomography (CT) images for radiation treatment planning (RT-CT): (1) set with a Foley urethral catheter (4.0 mm diameter) plus a guide-wire (0.46 mm diameter) in the first RT-CT and (2) set with a guide-wire alone in the second CT recorded 2 min after the first RT-CT. Using three fiducial markers in the prostate for image fusion, the displacement between the catheter and the guide-wire in the prostatic urethra was calculated. In 155 consecutive patients treated between 2011 and 2017, 5531 slices of RT-CT were evaluated.Results: Assuming that ≥3.0 mm of difference between the catheter and the guide-wire position was a significant displacement, the urethra with the catheter was displaced significantly from the urethra with the guide-wire alone in > 20% of the RT-CT slices in 23.2% (36/155) of the patients. The number of patients who showed ≥3.0 mm anterior displacement with the catheter in ≥20% RT-CT slices was significantly larger at the superior segment (38/155) than at the middle (14/155) and inferior segments (18/155) of the prostatic urethra (p < 0.0167).Conclusions: The urethral position with a Foley catheter is different from the urethral position with a thin and soft guide-wire in a significant proportion of the patients. This should be taken into account for the PRV of the urethra to ensure precise radiotherapy such as in urethra-sparing radiotherapy. [ABSTRACT FROM AUTHOR]

Background: The clinical efficacy of definitive pelvic radiotherapy for primary tumors in patients with newly diagnosed organ metastatic cervical cancer is unclear. Therefore, we conducted a retrospective study to evaluate the efficacy of definitive pelvic radiotherapy combined with systemic chemotherapy in patients with organ metastatic cervical cancer.Methods: We retrospectively analysed medical records from patients with newly diagnosed organ metastatic cervical cancer, all treated with chemotherapy at the Zhejiang Cancer Hospital between October 2006 and December 2016. Survival times were compared using the Kaplan-Meier method. The univariate log-rank method and multivariate Cox proportional hazard models were used to identify associated variables with survival.Results: A total of 48 patients were identified from 11,982 primary cervical cancer patients and divided into two groups according to treatment mode: 36 patients received chemotherapy combined with definitive pelvic radiotherapy (group A), 12 patients underwent chemotherapy with/without palliative pelvic radiotherapy (group B). Median follow-up was 14.4 months (range, 4.6-114.7 months). Median overall survival (OS) for group A and group B was 17.3 and 10 months, respectively. Using the univariate analysis, group A was found to have a better OS than group B (p = 0.002). In multivariate analysis, group A (hazard ratio [HR], 0.32; 95% confidence interval [CI], 0.15-0.67, p = 0.003) was associated with lower risk of death compared with group B. The main reason for treatment failure was found to be due to the progression of distant metastatic lesions in 36 patients (75%) from the whole cohort.Conclusion: In this cohort of organ metastatic cervical cancer patients in good performance status, chemotherapy combined with definitive pelvic radiotherapy was associated with improved survival outcomes when compared with chemotherapy with/without palliative pelvic radiotherapy. Prospective trials evaluating definitive pelvic radiotherapy for newly diagnosed organ metastatic cervical cancer, therefore, are warranted. [ABSTRACT FROM AUTHOR]

Background: Carbon ion radiotherapy (CIRT) has been delivered to more than 20,000 patients worldwide. International trials have been recommended in order to emphasize the actual benefits. The ULICE program (Union of Light Ion Centers in Europe) addressed the need for harmonization of CIRT practices. A comparative knowledge of the sources and magnitudes of uncertainties altering dose distribution and clinical effects during the whole CIRT procedure is required in that aim.Methods: As part of ULICE WP2 task group, we sent a centrally reviewed questionnaire exploring candidate sources of uncertainties in dose deposition to the ten CIRT facilities in operation by February 2017. We aimed to explore native beam characterization, immobilization, anatomic data acquisition, target volumes and organs at risks delineation, treatment planning, dose delivery, quality assurance prior and during treatment. The responders had to consider the clinical case of a clival chordoma eligible for postoperative CIRT according to their clinical practice. With the results, our task group discussed ways to harmonize CIRT practices.Results: We received 5 surveys from facilities that have treated 77% of the patients worldwide per November 2017. We pointed out the singularity of the facilities and beam delivery systems, a divergent definition of target volumes, the multiplicity of TPS and equieffective dose calculation approximations.Conclusion: Multiple uncertainties affect equieffective dose definition, deposition and calculation in CIRT. Although it is not possible to harmonize all the steps of the CIRT planning between the centers, our working group proposed counter-measures addressing the improvable limitations. [ABSTRACT FROM AUTHOR]

Background: Local recurrences after breast conserving treatment are mainly close to the original tumor site, and as such shorter fractionation strategies focused on and nearest mammary gland, i.e. accelerated partial breast irradiation (APBI), have been developed. Stereotactic APBI has been attempted, although there is little experience using CyberKnife (CK) for early breast cancer.Methods: This pilot study was designed to assess the feasibility of CK-APBI on 20 evaluable patients of 29 eligible, followed for 2 years. The primary endpoint was acute/sub-acute toxicity; secondary endpoints were late toxicity and the cosmetic result.Results: Mean pathological tumor size was 10.5 mm (±4.3, range 3-18), 8 of these patients were classified as LumA-like, 11 as LumB-like, and 1 as LumB-HER2-enriched. Using CK-APBI with Iris, the treatment time was approximately 60 min (range~ 35 to ~ 120). All patients received 30 Gy in five fractions delivered to the PTV. The median number of beams was 180 (IQR 107-213; range:56-325) with a median PTV isodose prescription of 86.0% (IQR 85.0-88.5; range:82-94). The median PTV was 88.1 cm3 (IQR 63.8-108.6; range:32.3-238.8). The median breast V100 and V50 was 0.6 (IQR 0.1-1.5; range:0-13) and 18.6 (IQR 13.1-21.7; range:7.5-37), respectively. The median PTV minimum dose was 26.2 Gy (IQR 24.7-27.6; range 22.3-29.3). Mild side effects were recorded during the period of observation. Cosmetic evaluations were performed by three observers from the start of radiotherapy up to 2 years. Patients' evaluation progressively increase from 60% to 85% of excellent rating; this trend was similar to that of external observer.Conclusions: These preliminary results showed the safe feasibility of CK-APBI in early breast cancer, with mild acute and late toxicity and very good cosmetic results.Trial Registration: The present study is registered at Clinicaltrial.gov ( NCT02896322 ). Retrospectively egistered August 4, 2016. [ABSTRACT FROM AUTHOR]

Background: Despite screening campaigns, cervical cancers remain among the most prevalent malignancies and carry significant mortality, especially in developing countries. Most studies report outcomes of patients receiving the usual standard of care. It is possible that these selected patients may not correctly represent patients in a real-world setting, which may be a limitation in interpreting outcomes. This study was undertaken to identify prognostic factors, management strategies and outcomes of locally advanced cervical cancers (LACC) treated in daily clinical practice.Methods: Medical files of all consecutive patients treated with curative intent for LACC in a French Cancer Care Center between 2004 and 2014 were reviewed retrospectively.Results: Ninety-four patients were identified. Performance status was ≥ 2 in 10.6%. Median age at diagnosis was 63.0. Based on the International Federation of Gynecology and Obstetrics classification, tumours were classified as follows: 10.6% IB2, 22.3% IIA, 51.0% IIB, 4.3% IIIA and 11.7% IIIB. Pelvic lymph nodes were involved in 34.0% of cases. Radiotherapy was delivered for all patients. Radiotherapy technique was intensity modulated radiation therapy or volumetric modulated arc therapy in 39.4% of cases. A concurrent cisplatin chemotherapy was delivered in 68.1% of patients. Brachytherapy was performed in 77.7% of cases. The recommended standard care (concurrent chemoradiotherapy with at least five chemotherapy cycles during radiotherapy, followed by brachytherapy) was delivered in 43.6%. The median overall treatment time was 56 days. Complete tumour sterilisation was achieved in 55.2% of cases. Mean follow-up was 54.3 months. Local recurrence rate was 18.1%. Five-year overall survival was 61.9% (95% Confident Interval (CI) = 52.3-73.2) and five-year disease-specific survival was 68.5% (95% CI = 59.2-79.2). Poor performance status, lymph nodes metastasis and absence of concurrent chemotherapy were identified as poor prognostic factors in multivariate analysis.Conclusions: Less than 50% of patients received the standard care. Because LACC patients and disease are heterogeneous, treatment tailoring appears to be common in current clinical practice. However, guidelines for tailoring management are not currently available. More data about real-world settings are required in order to to optimise clinical trials' aims and designs, and make them translatable in daily clinical practice.Trial Registration: retrospectively registered. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the present study was to compare the dose distribution generated from photon volumetric modulated arc therapy (VMAT), intensity modulated proton therapy (IMPT), and intensity modulated carbon ion therapy (IMCIT) in the delivery of hypo-fractionated thoracic radiotherapy.Methods and Materials: Ten selected patients who underwent thoracic particle therapy between 2015 and 2016 were re-planned to receive a relative biological effectiveness (RBE) weighted dose of 60 Gy (i.e., GyE) in 15 fractions delivered with VMAT, IMPT, or IMCIT with the same optimization criteria. Treatment plans were then compared.Results: There were no significant differences in target volume dose coverage or dose conformity, except improved D95 was found with IMCIT compared with VMAT (p = 0.01), and IMCIT was significantly better than IMPT in all target volume dose parameters. Particle therapy led to more prominent lung sparing at low doses, and this result was most prominent with IMCIT (p < 0.05). Improved sparing of other thoracic organs at risk (OARs) was observed with particle therapy, and IMCIT further lowered the D1cc and D5cc for major blood vessels, as compared with IMPT (p = 0.01).Conclusion: Although it was comparable to VMAT, IMCIT led to significantly better tumor target dose coverage and conformity than did IMPT. Particle therapy, compared with VMAT, improved thoracic OAR sparing. IMCIT, compared with IMPT, may further improve normal lung and major blood vessel sparing under limited respiratory motion. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study is to investigate the dosimetric advantages of volumetric modulated arc therapy (VMAT) in the treatment of intraocular cancer by comparing it directly with three-dimensional conformal radiotherapy (CRT) and intensity-modulated radiotherapy (IMRT).Methods: CRT plan, 7f-IMRT plan, and one-arc VMAT plan were generated for 14 intraocular cancer patients. Dosimetric and biological quality indices for target volume and organs at risks (OARs) were evaluated and compared.Results: The target coverage presented by V95 for CRT, IMRT and VMAT were 95.02% ± 0.67%, 95.51% ± 2.25%, and 95.92% ± 3.05%, respectively. The homogeneity index (HI) for CRT, IMRT and VMAT were 0.15 ± 0.05, 0.23 ± 0.05, and 0.23 ± 0.06, respectively. IMRT and VMAT greatly decreased the dose to ipsilateral lens compared with CRT with a D1 of 2972.66 ± 1407.12 cGy, 3317.82 ± 915.28 cGy and 4809.54 ± 524.60 cGy for IMRT, VMAT and CRT, respectively. Similar results were observed for ipsilateral eyeballs. IMRT and VMAT also spared better on brainstem, optical nerves and optical chiasm compared CRT. However, CRT achieved lower dose to the eyeballs compared with IMRT and VMAT. VMAT and IMRT showed mixed results on target coverage and OAR sparing. The average MUs and delivery time of IMRT and VMAT were 531.25 ± 81.21 vs. 400.99 ± 61.49 and 5.05 ± 0.53 vs.1.71 ± 0.69 min, respectively.Conclusions: Although no clear distinction on PTV coverage among CRT, IMRT and VMAT plans was observed in the treatment of intraocular cancer, VMAT and IMRT achieved better homogeneity and conformity for target volume, and delivered fewer doses to ipsilateral lens and eyeballs compared with CRT. However, VMAT and IMRT increased the low dose volume to the contralateral OARs. Although VMAT and IMRT showed mixed results on target coverage and OAR sparing, VMAT decreased MU and delivery time significantly compared with IMRT. VMAT is a promising and feasible external beam radiotherapy technique in the treatment of intraocular cancer patients. [ABSTRACT FROM AUTHOR]

Background: Derivation of dose-volume correlated with toxicity for multi-modal treatments can be difficult due to the perceived need for voxel-by-voxel dose accumulation. With data available for a single-institution cohort with long follow-up, an investigation was undertaken into rectal dose-volume effects for gastrointestinal toxicities after deformably-registering each phase of a combined external beam radiotherapy (EBRT)/high-dose-rate (HDR) brachytherapy prostate treatment. Methods: One hundred and eighteen patients received EBRT in 23 fractions of 2 Gy and HDR (TG43 algorithm) in 3 fractions of 6.5 Gy. Results for the Late Effects of Normal Tissues - Subjective, Objective, Management and Analytic toxicity assessments were available with a median follow-up of 72 months. The HDR CT was deformably-registered to the EBRT CT. Doses were corrected for dose fractionation. Rectum dose-volume histogram (DVH) parameters were calculated in two ways. (1) Distribution-adding: parameters were calculated after the EBRT dose distribution was 3D-summed with the registered HDR dose distribution. (2) Parameter-adding: the EBRT DVH parameters were added to HDR DVH parameters. Logistic regressions and Mann-Whitney U-tests were used to correlate parameters with late peak toxicity (dichotomised at grade 1 or 2). Results: The 48-80, 40-63 and 49-55 Gy dose regions from distribution-adding were significantly correlated with rectal bleeding, urgency/tenesmus and stool frequency respectively. Additionally, urgency/tenesmus and anorectal pain were associated with the 25-26 Gy and 44-48 Gy dose regions from distribution-adding respectively. Parameteradding also indicated the low-mid dose region was significantly correlated with stool frequency and proctitis. Conclusions: This study confirms significant dose-histogram effects for gastrointestinal toxicities after including deformable registration to combine phases of EBRT/HDR prostate cancer treatment. The findings from distributionadding were in most cases consistent with those from parameter-adding. The mid-high dose range and near maximum doses were important for rectal bleeding. The distribution-adding mid-high dose range was also important for stool frequency and urgency/tenesmus. We encourage additional studies in a variety of institutions using a variety of dose accumulation methods with appropriate inter-fraction motion management. [ABSTRACT FROM AUTHOR]

Background: Deformable image registration (DIR) is a key component in many radiotherapy applications. However, often resulting deformations are not satisfying, since varying deformation properties of different anatomical regions are not considered. To improve the plausibility of DIR in adaptive radiotherapy in the male pelvic area, this work integrates a local rigidity deformation model into a DIR algorithm.Methods: A DIR framework is extended by constraints, enforcing locally rigid deformation behavior for arbitrary delineated structures. The approach restricts those structures to rigid deformations, while surrounding tissue is still allowed to deform elastically. The algorithm is tested on ten CT/CBCT male pelvis datasets with active rigidity constraints on bones and prostate and compared to the Varian SmartAdapt deformable registration (VSA) on delineations of bladder, prostate and bones.Results: The approach with no rigid structures (REG0) obtains an average dice similarity coefficient (DSC) of 0.87 ± 0.06 and a Hausdorff-Distance (HD) of 8.74 ± 5.95 mm. The new approach with rigid bones (REG1) yields a DSC of 0.87 ± 0.07, HD 8.91 ± 5.89 mm. Rigid deformation of bones and prostate (REG2) obtains 0.87 ± 0.06, HD 8.73 ± 6.01 mm, while VSA yields a DSC of 0.86 ± 0.07, HD 10.22 ± 6.62 mm. No deformation grid foldings are observed for REG0 and REG1 in 7 of 10 cases; for REG2 in 8 of 10 cases, with no grid foldings in prostate, an average of 0.08 % in bladder (REG2: no foldings) and 0.01 % inside the body contour. VSA exhibits grid foldings in each case, with an average percentage of 1.81 % for prostate, 1.74 % for bladder and 0.12 % for the body contour. While REG1 and REG2 keep bones rigid, elastic bone deformations are observed with REG0 and VSA. An average runtime of 26.2 s was achieved with REG1; 31.1 s with REG2, compared to 10.5 s with REG0 and 10.7 s with VMS.Conclusions: With accuracy in the range of VSA, the new approach with constraints delivers physically more plausible deformations in the pelvic area with guaranteed rigidity of arbitrary structures. Although the algorithm uses an advanced deformation model, clinically feasible runtimes are achieved. [ABSTRACT FROM AUTHOR]

Background: To evaluate the current status of prospective interventional clinical trials that includes brachytherapy (BT) procedures.Methods: The records of 175,538 (100 %) clinical trials registered at ClinicalTrials.gov were downloaded on September 2014 and a database was established. Trials using BT as an intervention were identified for further analyses. The selected trials were manually categorized according to indication(s), BT source, applied dose rate, primary sponsor type, location, protocol initiator and funding source. We analyzed trials across 8 available trial protocol elements registered within the database.Results: In total 245 clinical trials were identified, 147 with BT as primary investigated treatment modality and 98 that included BT as an optional treatment component or as part of the standard treatment. Academic centers were the most frequent protocol initiators in trials where BT was the primary investigational treatment modality (p < 0.01). High dose rate (HDR) BT was the most frequently investigated type of BT dose rate (46.3 %) followed by low dose rate (LDR) (42.0 %). Prostate was the most frequently investigated tumor entity in trials with BT as the primary treatment modality (40.1 %) followed by breast cancer (17.0 %). BT was rarely the primary investigated treatment modality for cervical cancer (6.8 %).Conclusion: Most clinical trials using BT are predominantly in early phases, investigator-initiated and with low accrual numbers. Current investigational activities that include BT mainly focus on prostate and breast cancers. Important questions concerning the optimal usage of BT will not be answered in the near future. [ABSTRACT FROM AUTHOR]

Background: Locoregional hyperthermia combined with radiotherapy significantly improves locoregional control and overall survival for cervical tumors compared to radiotherapy alone. In this study biological modelling is applied to quantify the effect of radiosensitization for three cervical cancer patients to evaluate the improvement in equivalent dose for the combination treatment with radiotherapy and hyperthermia.Methods: The Linear-Quadratic (LQ) model extended with temperature-dependent LQ-parameters α and β was used to model radiosensitization by hyperthermia and to calculate the conventional radiation dose that is equivalent in biological effect to the combined radiotherapy and hyperthermia treatment. External beam radiotherapy planning was performed based on a prescription dose of 46Gy in 23 fractions of 2Gy. Hyperthermia treatment using the AMC-4 system was simulated based on the actual optimized system settings used during treatment.Results: The simulated hyperthermia treatments for the 3 patients yielded a T50 of 40.1 °C, 40.5 °C, 41.1 °C and a T90 of 39.2 °C, 39.7 °C, 40.4 °C, respectively. The combined radiotherapy and hyperthermia treatment resulted in a D95 of 52.5Gy, 55.5Gy, 56.9Gy in the GTV, a dose escalation of 7.3-11.9Gy compared to radiotherapy alone (D95 = 45.0-45.5Gy).Conclusions: This study applied biological modelling to evaluate radiosensitization by hyperthermia as a radiation-dose escalation for cervical cancer patients. This model is very useful to compare the effectiveness of different treatment schedules for combined radiotherapy and hyperthermia treatments and to guide the design of clinical studies on dose escalation using hyperthermia in a multi-modality setting. [ABSTRACT FROM AUTHOR]

Background: Accelerated partial breast irradiation (APBI) is an option for adjuvant radiotherapy according to ASTRO and ESTRO recommendations. Among the available techniques, volumetric-modulated arc therapy (VMAT) is attractive but has not been extensively studied for APBI. This study assessed its feasibility, tolerance and early oncological outcomes.Methods: We analysed the data of nine patients (median age 74 years) with ten lesions (one bilateral cancer) treated from May 2011 to July 2012 with APBI using VMAT. The radiation oncologist delineated the surgical tumour bed, and added an 18 mm isotropic margin to obtain the planning target volume (PTV). The dose was 40 Gy prescribed in 4 Gy fractions given twice a day over five days. Patients were regularly followed for toxicities and oncological outcomes.Results: Mean PTV was 100.0 cm(3) and 95 % of the PTV received a mean dose of 99.7 % of the prescribed dose. Hot spots represented 0.3 % of the PTV. 6.2 %, 1.6 % and 0.3 % of the ipsilateral lung volume received 5 Gy (V5Gy), 10 Gy (V10Gy) and 20 Gy (V20Gy), respectively. Regarding the contralateral lung, V5Gy was 0.3 %, and V10Gy and V20Gy were nil. V5Gy accounted for 3.1 % of the heart. An average 580 monitor units were delivered. No acute or late grade ≥ 2 toxicities were observed. With a median follow-up of 26 months, no relapses occurred.Conclusion: In our study, VMAT allowed optimal dosimetry with consequential high therapeutic ratio in elderly and frail patients. [ABSTRACT FROM AUTHOR]

Background: Whole breast irradiation after conserving surgery for breast cancer requires precise definition of the target volume. The standard approach uses computed tomography (CT) images. However, since fatty breast and non-breast tissues have similar electronic densities, difficulties in differentiating between them hamper breast volume delineation. To overcome this limitation the breast contour is defined by palpation and then radio-opaque wire is put around it before the CT scan. To optimize assessment of breast margins in the cranial, caudal, medial, lateral and posterior directions, the present study evaluated palpation and CT and determined whether ultrasound (US) provided any added value. Methods: Twenty consecutive patients were enrolled after they had provided informed consent to participating in this prospective study which was approved by the Regional Public Health Ethics Committee. Palpation and US defined breast margins and each contour was marked and outlined with a fine plastic wire. Breasts were then contoured on axial CT images using the breast window width (WW) and window level (WL) (401 and 750 Hounsfield Units -HU- respectively), at which setting the plastic wires were invisible. Then, the lung window function (WW 1601 HU; WL -300 HU) was inserted to visualize the plastic wires which were used as guidelines to contour the palpable and US breast volumes. As each wire had a different diameter, both volumes were easily defined on CT slices. Results were analyzed using descriptive statistics, percentage overlap and reproducibility measures (agreement and reliability). Results: Volumes: US gave the largest and palpation the smallest. Agreement was best between palpation and CT. Reliability was almost perfect in all correlations. Extensions: Cranial and posterior were highest with US and smallest with palpation. Agreement was best between palpation and CT in all extensions except the cranial. Since strong to almost perfect agreement emerged for all comparisons, reliability was high. Conclusions: US may be useful in defining the cranial and posterior extensions, mainly when tumours are localized there. This study demonstrates that the now standard radio-opaque wires around the palpable breast may not be needed in breast contouring. [ABSTRACT FROM AUTHOR]

Background: In Japan, breast-conserving surgery with closed cavity has generally been performed for breast cancer patients, and accelerated partial breast irradiation (APBI) is considered difficult because Asian females generally have smaller breast sizes than Western females. Therefore, common identification of target and treatment plan method in APBI is required. A prospective multicenter study was conducted in Japan to determine institutional compliance with APBI using high-dose-rate interstitial brachytherapy (ISBT) designed for Japanese female patients. Methods: For this study, 46 patients were recruited at eight institutions from January 2009 to December 2011. The reproducibility of the ISBT-APBI plan was evaluated using three criteria: (1) minimum clinical target volume dose with a clip dose ≥ 6 Gy/fraction, (2) irradiated volume constraint of 40-150 cm3, and (3) uniformity of dose distribution, expressed as the dose non-uniformity ratio (DNR, V150/V100) < 0.35. The ISBT-APBI plan for each patient was considered reproducible when all three criteria were met. When the number of non-reproducible patients was ≤ 4 at study completion, APBI at this institution was considered statistically reproducible. Results: Half of the patients (52 %) had a small bra size (A/B cup). The mean values of the dose-constrained parameters were as follows: Vref, 117 cm3 (range, 40-282), DNR, 0.30 (range, 0.22-0.51), and clip dose, 784 cGy (range, 469-3146). A total of 43/46 treatment plans were judged to be compliant and ISBT-APBI was concluded to be reproducible. Conclusions: This study showed that multi-institutional ISBT-APBI treatment plan was reproducible for small breast patient with closed cavity. [ABSTRACT FROM AUTHOR]

Purpose: We are reporting the five-year biochemical control, toxicity profile and dosimetric parameters using iodine-125 low dose rate brachytherapy (BT) as monotherapy for early stage prostate cancer at a single institution. Material and methods: Between April 2006 and December 2010, 169 men with early stage prostate cancer were treated with BT. Biochemical failure was defined using the Phoenix definition (nadir + 2 ng/mL). Treatment-related morbidities, including urinary, rectal and sexual function, were measured, applying the International Prostate Symptom Score (IPSS), the 7-grade Quality of Life Scale (QoL) and medical status, the International Consultation on Incontinence Modular Questionnaire (ICIQ), the International Index of Erectile Function (IIEF-5) and the Common Terminology Criteria for Adverse Events (CTCAE v4.03). Seed migration and loss, dosimetric parameters and learning effects were also analyzed. Results: Medium follow-up time was 50 months (range, 1-85 months). The five-year biochemical failure rate was 7%. Acute proctitis rates were 19% (grade 1) and 1% (grade 2), respectively. The overall incidence of incontinence was 19% (mild), 16% (moderate) and < 1% (severe). An increase in IPSS ⩾ 5 points was detected in 59% of patients, with 38% regaining their baseline. Seed dislocation was found in 24% of patients and correlated with D90 and V100. A learning curve was found for seed migration, D90 and V100. QoL correlated with the general health condition of patient, incontinence symptoms and IPSS. Conclusions: BT for early stage prostate cancer offers excellent five-year biochemical control with low toxicities. QoL aspects are favorable. A learning curve was detected for procedural aspects but its impact on patient relevant endpoints remains inconclusive. [ABSTRACT FROM AUTHOR]