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Simple Summary: The research investigates dose distributions to regional lymph-node metastases (RLNMs) in locally advanced cervical cancer (LACC) patients undergoing intracavitary and interstitial hybrid brachytherapy (IC/IS), a subject which has rarely been analyzed. Eleven sequential LACC patients with 38 RLNMs who received 38 IC/IS sessions were analyzed. RLNM dose distributions were assessed based on RLNM positions and ipsilateral interstitial needles, revealing significant differences in RLNM D90 based on whether the position was cranial or caudal of the uterine base and the number of interstitial needles was 0–1 or 2 or more. RLNMs located caudal of the uterine base with two or more ipsilateral interstitial needles received higher brachytherapy doses. The findings suggest that when calculating RLNM dose for external beam boost irradiation, consideration of RLNM position and interstitial needle count is crucial. This research sheds light on optimizing brachytherapy dosage delivery to RLNMs in LACC patients, potentially influencing treatment strategies. Purpose: Analyzing dose distributions to regional lymph-node metastases (RLNMs) in locally advanced cervical cancer (LACC) patients undergoing intracavitary and interstitial hybrid brachytherapy (IC/IS). Methods: Dose distributions of eleven LACC patients with 38 RLNMs, and who received 38 IC/IS sessions were analyzed in EQD2, considering RLNM positions and ipsilateral interstitial needles; these RLNMs, excepting the para-aortic region, were classified into four groups. Results: RLNMs had a median of two ipsilateral interstitial needles per session. Significant differences were observed in total RLNM D90, depending on whether the position was cranial or caudal of the uterine base (85.5 vs. 378.9 cGy, p < 0.0001), and whether the RLNM D90 was associated with a number of ipsilateral interstitial needles between 0–1 or 2 or more (68.4 vs. 112.2 cGy, p = 0.006) per session. At each session, Group 1 RLNMs (cranial of the uterine base, 0–1 ipsilateral interstitial needle) had a mean D90 of 21.1 cGy; Group 2 (cranial, 2 or more), 73.8; Group 3 (caudal, 0–1), 94.7; and Group 4 (caudal, 2 or more), 136.1. Conclusion: RLNMs located caudal of the uterine base associated with two or more ipsilateral interstitial needles in IC/IS had a higher dose contribution, which should be considered when calculating the RLNMs' dose of external beam boost irradiation. [ABSTRACT FROM AUTHOR]

Abstract 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 Purpose This study retrospectively compared the clinical and toxicity outcomes for the cervical cancer of the MRI-guided two adaptive brachytherapy (IGABT) fractions versus one IGABT fraction in one application. Methods One hundred and twenty patients with cervical cancer received external beam radiotherapy combined with or without concurrent chemotherapy, which was followed by the IGABT. The IGABT in 63 patients had one IGABT in each application (Arm 1), while in the other 57 patients, at least one treatment was two continuous IGABT every other day in one application (Arm 2). Clinical outcomes including overall survival (OS), cancer specific survival (CSS), progression free survival (PFS), local control (LC) were analyzed. Brachytherapy-related toxicities were evaluated, which included pain, dizziness, nausea/vomiting, fever/infection, blood loss during the removal of applicator and needles, the deep venous thrombosis, and other acute toxicities. The Common Terminology Criteria for Adverse Events (CTC-AE 5.0) was used to evaluate the incidence and severity of toxicities of the urinary system, lower digestive system, and reproduction system. Kaplan–Meier and the Log-rank test were used to analyze the clinical outcomes. Results The median follow-up time of the patients in Arm 1 and Arm 2 was 23.5 and 12.0 months, respectively. The overall treatment time was significantly shorter in Arm 2 than Arm 1 (60 vs. 64 d; P = 0.017). The OS, CSS, PFS, and LC in Arm1 and Arm 2 was 77.8% vs. 86.0% (P = 0.632), 77.8% vs. 87.7% (P = 0.821), 68.3% vs. 70.2% (P = 0.207), and 92.1% vs. 94.7% (P = 0.583), respectively. The highest NRS of the pain during brachytherapy waiting period (2.22 ± 1.84 vs. 3.02 ± 1.65; P

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]

Purpose: This study retrospectively compared the clinical and toxicity outcomes for the cervical cancer of the MRI-guided two adaptive brachytherapy (IGABT) fractions versus one IGABT fraction in one application. Methods: One hundred and twenty patients with cervical cancer received external beam radiotherapy combined with or without concurrent chemotherapy, which was followed by the IGABT. The IGABT in 63 patients had one IGABT in each application (Arm 1), while in the other 57 patients, at least one treatment was two continuous IGABT every other day in one application (Arm 2). Clinical outcomes including overall survival (OS), cancer specific survival (CSS), progression free survival (PFS), local control (LC) were analyzed. Brachytherapy-related toxicities were evaluated, which included pain, dizziness, nausea/vomiting, fever/infection, blood loss during the removal of applicator and needles, the deep venous thrombosis, and other acute toxicities. The Common Terminology Criteria for Adverse Events (CTC-AE 5.0) was used to evaluate the incidence and severity of toxicities of the urinary system, lower digestive system, and reproduction system. Kaplan–Meier and the Log-rank test were used to analyze the clinical outcomes. Results: The median follow-up time of the patients in Arm 1 and Arm 2 was 23.5 and 12.0 months, respectively. The overall treatment time was significantly shorter in Arm 2 than Arm 1 (60 vs. 64 d; P = 0.017). The OS, CSS, PFS, and LC in Arm1 and Arm 2 was 77.8% vs. 86.0% (P = 0.632), 77.8% vs. 87.7% (P = 0.821), 68.3% vs. 70.2% (P = 0.207), and 92.1% vs. 94.7% (P = 0.583), respectively. The highest NRS of the pain during brachytherapy waiting period (2.22 ± 1.84 vs. 3.02 ± 1.65; P < 0.001) and at the time of the removal of the applicator (4.69 ± 1.49 vs. 5.30 ± 1.18; P < 0.001) in the patients who received one hybrid intracavitary and interstitial brachytherapy (IC/ISBT) in one application and two continuous IC/ISBT every other day in one application were significantly different. So far four patients with grade 3 late toxicities have been reported. Conclusions: The findings of this study demonstrated that the two continuous IGABT every other day in one application is a logistically applicable, safe, and effective treatment strategy that could shorten the overall treatment time and reduce the medical cost, comparing with the one IGABT in one application. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the clinical outcome in locally advanced cervical cancer (LACC) after image-guided adaptive brachytherapy (IGABT) with combined intracavitary and interstitial (IC/IS) techniques using the hybrid Venezia applicator (Elekta AB, Sweden). LACC patients (UICC Stage IIB – IVB) treated with radiochemotherapy followed by IGABT with the hybrid IC/IS Venezia applicator at a single institution were retrospectively analyzed. Treatment comprised EBRT of the pelvis with 45 Gy and concomitant weekly cisplatin chemotherapy (40 mg/m2) followed by MRI-based IGABT. Dosimetry, oncological outcome and toxicity were investigated. Forty-six patients underwent a total of 184 fractions of IGABT between 2017 and 2020. Median follow-up was 24 months. Combined IC/IS techniques were used in 40 patients (87%). The median HRCTV volume was 31.2 cm3 and the median HRCTV D 90% was 92.3 Gy (EQD2 10). The median D 2cm 3 was 74.8 Gy for bladder, 57.9 Gy for rectum, 60.0 Gy for sigmoid and 52.2 Gy for bowel (EQD2 3). The 3-yr actuarial rates were 97.6% for local control, 97.6% for pelvic control, 59.9% for distant metastasis-free survival and 81.6% for overall survival. The crude rate for G2 and G3 late toxicity was 21.7% and 4.3%. IGABT with the hybrid Venezia applicator and a pronounced use of a combined IC/IS technique achieved high target doses, while maintaining low doses to organs at risk, leading to excellent local control and overall survival rates with acceptable toxicity. • Combined intracavitary and interstitial brachytherapy achieves high target doses. • This leads to excellent local control. • Toxicity with this combined approach is acceptable. • Distant recurrence is common; improvements in distant control are warranted. [ABSTRACT FROM AUTHOR]

• Vaginal stricture correlated with age, tumor size, and lower vaginal involvement. • PIBS + 2 showed a dose-grade 3 toxicity relationship with ED15 at 57.4 Gy3. • PIBS-2 showed a dose- grade 3 toxicity relationship with ED20 at 7 Gy3. • D + 5 showed a dose- grade 3 toxicity relationship with ED15 at 66.6 Gy3. • The incidence of high grade 3 vaginal stenosis was influenced by local culture. To investigate the vaginal 11 - point and volumetric dose - toxicity relationships in definitive cervical cancer radiotherapy. A retrospective cohort study of patients with cervical cancer with a complete response of at least 12 months was performed. Additional per vaginal examinations and patient - scoring questionnaires on the date of patient enrolment were assessed for vaginal strictures. Retrospective dosimetric analysis of vaginal 11 - point and volumetric doses was performed with descriptive and probit analyses to investigate dose - toxicity relationships. Ninety - seven patients were included in the study, with a 20-month median follow - up. The incidence rate of grade 3 vaginal strictures was 22. 7 %. A comparison between patients with grade 1–3 vaginal strictures revealed significant differences in age, stage, initial tumour size, and vaginal involvement. PIBS + 2, PIBS, PIBS-2, D + 5, and D2cc were all significantly different among grade 1–3 vaginal strictures and showed significant probit coefficients. The lateral dose points were significantly higher in grade 2 strictures, but negative probit coefficients failed to establish causal inferences. Post-estimation analyses yielded effective doses (ED) for 15 % and 20 % probability of grade 3 vaginal strictures (ED15 and ED20) for PIBS + 2 at 57.4 and 111 Gy 3 , respectively. PIBS-2 yielded an ED20 of 7 Gy 3. D + 5 yielded positive ED10, ED15, and ED20 values of 52.2, 66.6, and 78 Gy 3 , respectively. This study showed a significant relationship between age, tumour size, and lower-third vaginal involvement with the incidence of vaginal toxicity. The goal of a cumulative radiotherapy dose of ≤ 55 Gy 3 to PIBS + 2, ≤5 Gy 3 to PIBS-2, and ≤ 65 Gy 3 to D + 5 points may reduce the risk of grade 3 vaginal stenosis to less than 15–20 %. [ABSTRACT FROM AUTHOR]

Purpose: Clinical drawings are integral part of image-guided adaptive brachytherapy (IGABT) of cervical cancer. It was used in EMBRACE study protocol as a useful tool. In our study clinical drawings from EMBRACE study were modified to include scales in all the dimensions for more accurate representation of various tumor related volumes. The aim of the present study was to understand patterns of tumor regression and relationship between gross tumor at diagnosis (GTVD) and high-risk clinical target volume (CTV-THR)/intermediate-risk clinical target volume (CTV-TIR) in brachytherapy (BRT), using modified clinical drawings. Material and methods: 42 cervical cancer patients, staged as FIGO IIB-IIIB according to EMBRACE study, were enrolled. Advanced schematic 3D mapping diagram (3D-MD) in axial, coronal, and sagittal orientations, with a measurement scale (grid with 10 mm distance) for precise assessment and documentation was applied (through MRI at diagnosis and during brachytherapy). Dimensions, including height, width, and thickness as well as volumes (GTVD, CTV-THR and CTV-TIR) were compared both qualitatively and quantitatively. Results and conclusions: We found qualitative and quantitative correlation of the dimensions of final CTV-THR with initial GTVD. Meticulous mapping of tumor volumes can provide useful insights to CTV-THR volume during brachytherapy. [ABSTRACT FROM AUTHOR]

• CT Based Contouring recommendations in IGABT for cervical cancer is a collaborative effort of 13 experts from Indian Brachytherapy Society (IBS), GEC-ESTRO and American Brachytherapy Society (ABS). • The recommendations are comprehensive, providing a pragmatic solution to contour target on CT Imaging at BT in different prevailing clinic-radiological environments which have not been comprehensively addressed. • We expect each institution with no access to MRI at BT to review their working environment and utilize appropriate definitions for defining the target to implement CT based IGABT for cervical cancers. MR Imaging is regarded as the gold standard for Image Gudied Adaptive Brachytherapy (IGABT) for cervical cancer. However, its wide applicability is limited by its availability, logistics and financial implications. Use of alternative imaging like CTand Ultrasound (US) for IGABT has been attempted. In order to arrive at a systematic, uniform and international approach for CT based definition and contouring of target structures, GEC ESTRO, IBS and ABS agreed to jointly develop such recommendations based on the concepts and terms as published in the ICRU Report 89. The minimum requirements are clinical examination & documentation, CT or MR imaging at diagnosis and at a minimum, CT imaging with the applicator in place. The recommendations are based on (i) assessment of the GTV at diagnosis and at brachytherapy, (ii) categorizing the response to external radiation into different clinical remission patterns, (iii) defining various clinico-radiological environments and (iv) definition & delineation of a target on CT imaging at the time of brachytherapy with the applicator in situ. CT based target contouring recommendations based on 4 remission categories within 8 defined environments, aim at improving the contouring accuracy for IGABT using CT, US and MRI as available. For each clinico-radiological environment, there is an attempt to minimize the specific uncertainties in order to arrive at the best possible contouring accuracy. Evaluating feasibility & reproducibility, to achieve a benchmark towards a gold standard MR IGABT and further clinical research including outcomes with CT Based IGABT will become the next steps. [ABSTRACT FROM AUTHOR]

• Urinary morbidity after treatment of locally advanced cervical cancer is prevalent. • Bladder dose constraints based on a high level clinical evidence are not available. • EMBRACE I provides prospective morbidity data for analysis in a large cohort. • Individual physician and patient reported urinary endpoints were analysed in EMBRACE I. • Bladder fistula, bleeding and cystitis showed dose–effect with bladder D 2cm3. To identify patient- and treatment-related risk factors for fistula, bleeding, cystitis, pain and difficulty in voiding in locally advanced cervical cancer patients treated with radio(chemo)therapy and image-guided adaptive brachytherapy (IGABT). Morbidity within the EMBRACE-I study was prospectively reported for physician-assessed (CTCAE) fistula, bleeding and cystitis and patient-reported (EORTC) pain and difficulty in voiding. Analysis of risk factors was performed in patients without bladder infiltration. Risk factors were tested with Cox regression for grade (G) ≥ 3 cystitis, for G ≥ 2 fistula, bleeding and cystitis, and for EORTC "very much" and "quite a bit" or worse. Of 1416 patients enrolled, 1153 and 884 patients without bladder infiltration were evaluable for the analysis of CTCAE and EORTC items, respectively. Median follow-up was 48[3–120] months. Crude incidence rates for G ≥ 2 fistula, bleeding and cystitis were 0.7%, 2.7% and 8.8%, respectively, and 16% and 14% for "quite a bit" or worse pain and difficulty in voiding, respectively. Baseline urinary morbidity and overweight/obesity were significant risk factors for most endpoints. Bladder D 2cm3 correlated with G ≥ 2 fistula, bleeding and cystitis, while ICRU bladder point dose correlated with EORTC pain "quite a bit" or worse. An increase from 75 Gy to 80 Gy in bladder D 2cm3 resulted in an increase from 8% to 13% for 4-year actuarial estimate of G ≥ 2 cystitis. Clinical and treatment-related risk factors for bladder fistula, bleeding and cystitis were identified within a prospective and multi-institutional setting. A dose–effect was established with bladder D 2cm3 , reinforcing the importance of continued optimization during individualized IGABT planning. [ABSTRACT FROM AUTHOR]

• Urinary side effects after radiotherapy can rely on different bladder substructures. • EMBRACE I provides prospective morbidity data to study individual urinary symptoms. • Frequency and incontinence are frequent side effects in cervix cancer radiotherapy. • Limited clinical evidence supports the predictive value of ICRU Bladder point dose. • This analysis showed correlation of ICRU Bladder point dose with incontinence. To identify patient- and treatment-related risk factors and dose-effects for urinary frequency and incontinence in locally advanced cervical cancer (LACC) treated with radio(chemo)therapy and image-guided adaptive brachytherapy (IGABT). Physician-assessed (CTCAE) and patient-reported (EORTC) frequency and incontinence recorded in the EMBRACE-I study were analysed. Risk factors analysis was performed in patients without bladder infiltration and with baseline morbidity available. Cox regression was used for CTCAE grade (G) ≥ 3 and G ≥ 2 and for EORTC "very much" and "quite a bit" or worse. Logistic regression was used for late persistent morbidity defined when CTCAE G ≥ 1 or EORTC ≥ "quite a bit" were scored in at least half of follow-ups. Longitudinal data on 1153 and 884 patients were available for CTCAE and EORTC analysis, respectively. Median follow-up was 48[3-120] months. Crude incidence rates of G≥2 were 13% and 11% for frequency and incontinence, respectively. Baseline morbidity and overweight-obesity were risk factors for both symptoms. Elderly patients were at higher risk for incontinence. Patients receiving conformal-radiotherapy were at higher risk for frequency. ICRU bladder point (ICRU-BP) dose was a stronger predictor for incontinence than bladder D 2cm3. The 5-year actuarial estimate of G ≥ 2 incontinence increased from 11% to 20% with ICRU-BP doses > 75 Gy compared to ≤ 65 Gy. Frequency showed weaker associations with dose. ICRU-BP dose, in addition to clinical parameters, is a risk factor for urinary incontinence and shows a dose–effect after radio(chemo)therapy and IGABT. ICRU-BP dose should be monitored during treatment planning alongside volumetric parameters. Frequency seems associated with larger irradiated volumes. [ABSTRACT FROM AUTHOR]

Introduction: tumors of the uterine cervix are among the most common carcinomas in women. Intracervical brachytherapy is an indispensable part of curative treatment. Although the tumor is significantly more recognizable in MRI than in CT, the practical application of MRI in brachytherapy planning is still difficult. The present study examines the technical possibilities of merging CT and MRI. Materials and Methods: the treatment files and imaging of all 53 patients who had been irradiated by image-guided adaptive brachytherapy (IGABT) between January 2019 and August 2021 at the Department of Radiotherapy of the Hannover Medical School were evaluated, retrospectively. Patients were treated first with an external beam radiotherapy (EBRT) combined with simultaneous chemotherapy. After an average of 4.2 weeks, the preparation for IGABT began. The clinical target volume (CTV) for brachytherapy was contoured first in an MRI acquired before starting EBRT (MRI 1) and once more in a second MRI just before starting IGABT (MRI 2). Then, after inserting the intravaginal applicator, a CT-scan was acquired, and the CTV was contoured in the CT. Finally, the recordings of MRI 1, MRI 2, and the CT were merged, and the congruence of CTVs was quantitatively evaluated. Results: the CTV delineated in MRI 2 was, on average, 28% smaller than that in MRI 1 after an average applied radiation dose of 42 Gy. The CTV delineated in the CT covered an average of no more than 80.8% of the CTV delineated in MRI 2. The congruence of CTVs was not superior in patients with a smit sleeve in the cervical channel, with a 3D-volumetric MRI or with a contrast-enhanced sequence for MRI. Conclusion: the anatomical shape and position of the uterus is significantly changed by introducing a vaginal applicator. Despite the superior delimitability of the tumor in MRI, brachytherapy cannot be reliably planned by the image fusion of an MRI without a vaginal applicator.

To evaluate the difference between GTVBT (Gross Tumor Volume at Brachytherapy) and HR CTV (High Risk Clinical Tumor Volume) delineated with DWI and T2W MRI. To evaluate doses to organs at risk and targets from plans generated using T2W and DWI. Functional imaging with DWI can improve cervical tumor distinction as it is more sensitive than T2W MRI even in detecting parametrial invasion. This study does a dosimetric comparison between a T2W and DWI based plan. Fifty carcinoma cervix patients were subjected to MRI based brachytherapy. T2W and a diffusion weighted sequence were acquired. Target delineation and brachytherapy planning was done on both T2W and DWI. Standard DVH parameters were recorded and the treatment was given using the plan generated from T2W images. GTVBT and HRCTV contours on DWI were different when compared with T2W. Mean GTVBT volume on T2W and DWI was 5.25 and 5.23, respectively (p value 0.8). Mean HRCTV on T2W and DWI was 28.3 and 27 cc, respectively (p value 0.003). Planning on the above volumes resulted in a superior coverage in terms of HRCTV D90 and D100 for DWI based plan, HRCTV D90 — 735.1 and 741 cGy for T2W and DWI, respectively (p value 0.006), HRCTV D100 — 441.05 and 444.5 for T2W and DWI plans, respectively (p value = 0.006). Doses to the OAR were not significantly increased. GEC ESTRO based contouring guidelines cover all the functionally abnormal areas on DWI. DWI should only be used as a supplement to T2W for contouring target volumes. [ABSTRACT FROM AUTHOR]

Purpose : Intra-fractional organs at risk (OARs) deformations can lead to dose variation during image-guided adaptive brachytherapy (IGABT). The aim of this study was to modify the final accepted brachytherapy treatment plan to dosimetrically compensate for these intra-fractional organs-applicators position variations and, at the same time, fulfilling the dosimetric criteria. Material and methods : Thirty patients with locally advanced cervical cancer, after external beam radiotherapy (EBRT) of 45-50 Gy over five to six weeks with concomitant weekly chemotherapy, and qualified for intracavitary high-dose-rate (HDR) brachytherapy with tandem-ovoid applicators were selected for this study. Second computed tomography scan was done for each patient after finishing brachytherapy treatment with applicators in situ. Artificial neural networks (ANNs) based models were used to predict intra-fractional OARs dose-volume histogram parameters variations and propose a new final plan. Results : A model was developed to estimate the intra-fractional organs dose variations during gynaecological intracavitary brachytherapy. Also, ANNs were used to modify the final brachytherapy treatment plan to compensate dosimetrically for changes in ‘organs-applicators’, while maintaining target dose at the original level. Conclusions : There are semi-automatic and fast responding models that can be used in the routine clinical workflow to reduce individually IGABT uncertainties. These models can be more validated by more patients’ plans to be able to serve as a clinical tool.

Purpose: To develop a novel decision-support system for radiation oncology that incorporates clinical, treatment and outcome data, as well as outcome models from a large clinical trial on magnetic resonance image-guided adaptive brachytherapy (MR-IGABT) for locally advanced cervical cancer (LACC)., Methods: A system, called EviGUIDE, was developed that combines dosimetric information from the treatment planning system, patient and treatment characteristics, and established tumor control probability (TCP), and normal tissue complication probability (NTCP) models, to predict clinical outcome of radiotherapy treatment of LACC. Six Cox Proportional Hazards models based on data from 1341 patients of the EMBRACE-I study have been integrated. One TCP model for local tumor control, and five NTCP models for OAR morbidities., Results: EviGUIDE incorporates TCP-NTCP graphs to help users visualize the clinical impact of different treatment plans and provides feedback on achievable doses based on a large reference population. It enables holistic assessment of the interplay between multiple clinical endpoints and tumour and treatment variables. Retrospective analysis of 45 patients treated with MR-IGABT showed that there exists a sub-cohort of patients (20%) with increased risk factors, that could greatly benefit from the quantitative and visual feedback., Conclusion: A novel digital concept was developed that can enhance clinical decision- making and facilitate personalized treatment. It serves as a proof of concept for a new generation of decision support systems in radiation oncology, which incorporate outcome models and high-quality reference data, and aids the dissemination of evidence-based knowledge about optimal treatment and serve as a blueprint for other sites in radiation oncology., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Intra-fractional organs at risk (OARs) deformations can lead to dose variation during image-guided adaptive brachytherapy (IGABT). The aim of this study was to modify the final accepted brachytherapy treatment plan to dosimetrically compensate for these intra-fractional organs-applicators position variations and, at the same time, fulfilling the dosimetric criteria. Material and methods: Thirty patients with locally advanced cervical cancer, after external beam radiotherapy (EBRT) of 45-50 Gy over five to six weeks with concomitant weekly chemotherapy, and qualified for intracavitary high-dose-rate (HDR) brachytherapy with tandem-ovoid applicators were selected for this study. Second computed tomography scan was done for each patient after finishing brachytherapy treatment with applicators in situ. Artificial neural networks (ANNs) based models were used to predict intra-fractional OARs dose-volume histogram parameters variations and propose a new final plan. Results: A model was developed to estimate the intra-fractional organs dose variations during gynaecological intracavitary brachytherapy. Also, ANNs were used to modify the final brachytherapy treatment plan to compensate dosimetrically for changes in 'organs-applicators', while maintaining target dose at the original level. Conclusions: There are semi-automatic and fast responding models that can be used in the routine clinical work- flow to reduce individually IGABT uncertainties. These models can be more validated by more patients' plans to be able to serve as a clinical tool. [ABSTRACT FROM AUTHOR]

Purpose In image-guided adaptive brachytherapy (IGABT), dose distributions are optimized for each fraction. Optimum fractional dose can be constant or adapted to previous fractions and a conjecture about the future ones. We evaluate the efficacy of different fraction size schemes, derived from total IGABT dose constraints, against constant per-fraction constraints. Methods and Materials This retrospective planning study included 20 IGABT patients where four different fractionation schedules were compared based on modern planning recommendations. A total high-risk–clinical target volume D 90 (minimum dose in 90% of the volume) dose aim of 90.0 Gy with constant per-fraction organs at risk (OARs) dose constraint planning (CONST) was compared with conservative and aggressive fractionation compensation (COMP) techniques. COMP allows variations in the per-fraction dose constraints. Dose accumulation was performed through dose summation at a given volume and equivalent uniform dose (EUD) worst-case dose estimates. Results No significant differences were identifiable between dose metrics of CONST and COMP in the total patient population. However, a subgroup of patients with alternating dose-limiting OARs had significant benefit from COMP. Median high-risk–clinical target volume dose escalation ranged from 5% to 12%, whereas OAR dose increases were lower and ranged from 3% to 8%. EUD-based planning delivered similar tumor doses, although slightly lower OAR doses. By distributing the treatment aim over an increased number of treatment fractions, median tumor dose could be increased by a further 8% per additional treatment fraction at the same OAR dose levels for both CONST and COMP. Conclusions COMP is effective in patients with alternating dose-limiting OARs and is enhanced using more treatment fractions and EUD constraints. [ABSTRACT FROM AUTHOR]

• Development of a comprehensive data dashboard for radiation oncology. • Tested within an international multi-center study. • Centers can compare their treatment approach with reference population. • Automatically detect implausibilities in patient, treatment, and outcome data. • Overview of the most common pitfalls and uncertainties in current radiotherapy for cervical cancer. To develop and implement a software that enables centers, treating patients with state-of-the-art radiation oncology, to compare their patient, treatment, and outcome data to a reference cohort, and to assess the quality of their treatment approach. A comprehensive data dashboard was designed, which al- lowed holistic assessment of institutional treatment approaches. The software was tested in the ongoing EMBRACE-II study for locally advanced cervical cancer. The tool created individualized dashboards and automatic analysis scripts, verified pro- tocol compliance and checked data for inconsistencies. Identified quality assurance (QA) events were analysed. A survey among users was conducted to assess usability. The survey indicated favourable feedback to the prototype and highlighted its value for internal monitoring. Overall, 2302 QA events were identified (0.4% of all collected data). 54% were due to missing or incomplete data, and 46% originated from other causes. At least one QA event was found in 519/1001 (52%) of patients. QA events related to primary study endpoints were found in 16% of patients. Sta- tistical methods demonstrated good performance in detecting anomalies, with precisions ranging from 71% to 100%. Most frequent QA event categories were Treatment Technique (27%), Patient Characteristics (22%), Dose Reporting (17%), Outcome 156 (15%), Outliers (12%), and RT Structures (8%). A software tool was developed and tested within a clinical trial in radia- tion oncology. It enabled the quantitative and qualitative comparison of institutional patient and treatment parameters with a large multi-center reference cohort. We demonstrated the value of using statistical methods to automatically detect implau- sible data points and highlighted common pitfalls and uncertainties in radiotherapy for cervical cancer. [ABSTRACT FROM AUTHOR]

Purpose To demonstrate the utility of “3D Slicer” for easy treatment verification by comparing dose-volume histograms (DVHs) calculated on pretreatment and posttreatment images. Methods and materials Thirty cervical cancer patients were CT scanned twice: first for treatment planning and a second time after the dose delivery. The initial plan was manually duplicated on the posttreatment image set in Flexiplan treatment planning system, and DVH parameters were calculated. Pretreatment and posttreatment images, organ structures, and plan data were exported from the treatment planning system to 3D Slicer to validate DVH parameter calculation with 3D Slicer. The gamma analysis was used to compare Flexiplan and 3D Slicer DVHs. Posttreatment images were rigidly fused on the initial CT to automatically transfer the data of the pretreatment plan onto the posttreatment images. DVH parameters were calculated in 3D Slicer for both image sets, and their relative variations were compared. Results In calculating DVH parameter variations, no significant differences were observed between Flexiplan and 3D Slicer. Where the registration accuracy was better than 0.03, they returned similar results for D 2 cm 3 of bladder, rectum, and sigmoid. Mean and standard deviation of DVH parameters were calculated on pretreatment and posttreatment images for several organs; both the manually duplicated plan and the automatically registered plan in SlicerRT returned comparable relative variations of these parameters. For 88% of the organs, more than 95% of the DVH dose bins passed the gamma analysis. Conclusions We tested an automated DVH assessment method with an imaging freeware, 3D Slicer, for use in image-guided adaptive brachytherapy. SlicerRT is a viable verification tool to report and detect DVH variations between different contoured images series. [ABSTRACT FROM AUTHOR]

Dosimetric intra-fraction uncertainties in MRI-guided brachytherapy were analysed for HR-CTV and OARs. While dose differences were generally small, individual outliers occurred. In contrast to HDR, patients treated with PDR show increased mean rectal dose over time. Re-imaging prior to dose delivery helps to detect unfavorable anatomical changes, and allows for intervention. [ABSTRACT FROM AUTHOR]

Cervical cancer, IGABT, Urinary morbidity, Risk factors, Dose-effect relationship, Clinical study. [Extracted from the article]

Simple Summary: Primary vaginal cancer is a rare disease and, consequently, evidence about the outcome of treatment is scarce. The aim of our retrospective, observational multicenter study was to assess the oncological outcome of the nowadays standing treatment for vaginal cancer, namely radio(chemo)therapy, followed by image-guided adaptive brachytherapy (IGABT). Our study confirms the results of the earlier published small monocentric IGABT studies, showing a high local control with acceptable morbidity. Notably, patients with large (T3/T4) tumors especially seem to benefit from volumetric (3D) image-guided brachytherapy, as compared to two-dimensional-based radiotherapy. In addition, although interpreted with caution, as for cervical cancer, a higher dose seems to lead to better local control. These results should, however, be further investigated in a prospective trial. Purpose: This study assessed outcomes following the nowadays standing treatment for primary vaginal cancer with radio(chemo)therapy and image-guided adaptive brachytherapy (IGABT) in a multicenter patient cohort. Methods: Patients treated with computer tomography (CT)–MRI-assisted-based IGABT were included. Retrospective data collection included patient, tumor and treatment characteristics. Late morbidity was assessed by using the CTCAE 3.0 scale. Results: Five European centers included 148 consecutive patients, with a median age of 63 years. At a median follow-up of 29 months (IQR 25–57), two- and five-year local control were 86% and 83%; disease-free survival (DFS) was 73% and 66%, and overall survival (OS) was 79% and 68%, respectively. Crude incidences of ≥ grade-three urogenital, gastro-intestinal and vaginal morbidity was 8%, 3% and 8%, respectively. Lymph node metastasis was an independent prognostic factor for disease-free survival (DFS). Univariate analysis showed improved local control in patients with T2–T4 tumors if >80 Gy EQD2α/β10 was delivered to the clinical target volume (CTV) at the time of brachytherapy. Conclusions: In this large retrospective multicenter study, IGABT for primary vaginal cancer resulted in a high local control with acceptable morbidity. These results compared favorably with two-dimensional (2D) radiograph-based brachytherapy and illustrate that IGABT plays an important role in the treatment of vaginal cancer. [ABSTRACT FROM AUTHOR]

Purpose: New technologies were integrated into a novel treatment platform combining electromagnetically (EM) tracked catheters, a 3D ultrasound (3DUS) imaging device, and a new treatment planning system to provide a real-time prostate high-dose-rate (HDR) brachytherapy treatment system. This work defines workflows for offline CT and online 3DUS planning scenarios and preclinical end-to-end validation of the platform., Methods and Materials: The platform is composed of an EM-tracked stylet, a EM-tracked 3DUS probe, and an EM-tracked template guide, all used with the NDI Aurora field generator (NDI, Ontario, Canada). The treatment planning system performs continuous position and angular readings from all three EM sensors into a streamlined environment that allows for (1) contouring; (2) planning; (3) catheter insertion guidance and reconstruction; (4) QA of catheter path and tip position; and (5) exporting to an afterloader. Data were gathered on the times required for the various key steps of the 3DUS-based workflow., Results: The complete 3DUS-based workflow on 16-catheter implant phantoms took approximately 15 min. This time is expected to increase for actual patients. Plan generation is fast (7.6 ± 2.5s) and the initial catheter reconstruction with updated dose distribution is obtained at no (time) cost as part of the insertion process. Subsequent catheter reconstruction takes on average 10.5 ± 3.1s per catheter, representing less than 3 min for a 16-catheter implant., Conclusions: This preclinical study suggests that EM technology could help to significantly streamline real-time US-based high-dose-rate prostate brachytherapy., (Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)