Radiotherapy and Oncology

Development and external validation of a multi-task feature fusion network for CTV segmentation in cervical cancer radiotherapy

Accurate segmentation of the clinical target volume (CTV) is essential to deliver an effective radiation dose to tumor tissues in cervical cancer radiotherapy. Also, although automated CTV segmentation can reduce oncologists' workload, challenges persist due to the microscopic spread of tumor cells undetectable in CT imaging, low-intensity contrast between organs, and inter-observer variability. This study aims to develop and validate a multi-task feature fusion network (MTF-Net) that uses distance-based information to enhance CTV segmentation accuracy. We developed a dual-branch, end-to-end MTF-Net designed to address the challenges in cervical cancer CTV segmentation. The MTF-Net architecture consists of a shared encoder and two parallel decoders, one generating a distance location information map (D MTF-Net achieved an average dice score of 84.67% on internal and 77.51% on external testing datasets. Compared with commercial software, MTF-Net demonstrated superior performance across several metrics, including Dice score, positive predictive value, and 95% Hausdorff distance, with the exception of sensitivity. This study indicates that MTF-Net outperforms existing state-of-the-art segmentation methods and commercial software, demonstrating its potential effectiveness for clinical applications in cervical cancer radiotherapy planning.

Can knowledge-based planning models validated on ethnically diverse patients lead to global standardisation of external beam radiation therapy for locally advanced cervix cancer?

Knowledge-based planning (KBP) can consistently and efficiently create high-quality Volumetric Arc Therapy (VMAT) plans for cervix cancer. This study describes the cross-validation of two KBP models on geographically distinct populations and their comparison to manual plans from 67 centers. The purpose was to determine the universal applicability of a generic KBP model. Based on the EMBRACE-II protocol, two KBP models were developed at Tata Memorial Centre, India and Aarhus University Hospital, Denmark using respective patient plans. The KBP models were exchanged between three institutions with different geo-ethnic populations and validated on reference manual plans of 20 node-positive and 20 node-negative patients. Additionally, one patient case was manually planned by 67 centres. These manual treatment plans were compared to the two KBP model plans using a score out of 80, based on 20 DVH parameters. The manual and the KBP plans adhered to the EMBRACE II protocol. OAR sparing in KBP plans was similar or slightly improved as compared to the manual plans. The differences between the medians of manual and either KBP model plans were significant for 8 parameters among node positive patients, and 4 parameters among node negative patients. The comparison between the Tata and Aarhus KBP model plans to manual plans from 67 institutions showed that the two KPBs had superior plan quality in 88-99% of instances. KBP has the potential to generate high-quality plans across institutions and geo-ethnic populations by reducing inter-planner variation, thereby facilitating the global standardisation of radiotherapy for cervical cancer.

Validation and applicability of para-aortic lymph nodal contouring atlas in cervical cancer

CTV delineation guidelines for the para-aortic nodal region for patients with cervical cancer have been proposed (Keenan et al., 2018). The purpose of this study was to validate these guidelines with the use of CT datasets of cervical cancer patients with macroscopic PALN treated with definitive (chemo)radiation (CTRT) at our center. Planning CT datasets of 71 cervical cancer patients with gross PA nodal disease treated with EFRT were used. Two hundred and two PALN were identified based on size and morphology on diagnostic CECT, PET CT, or histologically proven PALN. LN regions were divided into upper, middle, and lower and based on their relation to the aorta and IVC. Macroscopic PALN were contoured, and the CTV for PALN irradiation was generated based on the proposed guidelines on ECLIPSE (Version 13.5). The centre of mass (COM The most common location of PALN was Left para-aortic (105 LN-52%), Aortocaval (55 LN-27.2%), and Precaval (14 LN-6.9%). Lower PALN were the commonest (104 LN-51.5%). Ninety-three were middle PALN (46%), and 5 were upper PALN (2.5%). After excluding upper PALN, COM Our study shows that more than 95% of PALN in this patient cohort were covered using these guidelines with the addition of an extra 5 mm margin laterally on the left.

Dosimetric evaluation of variation in Library of plans selection for cervical cancer radiotherapy

The aim was to determine whether differences in treatment plan selection methods from a Library-of-Plans (LoP) on cone-beam computed tomography (CBCT) leads to significant discrepancies in total accumulated dose. Ten cervical cancer patients were retrospectively analyzed on plan selection and dose distribution. Dose accumulation was performed using two different plan selection methods. 1) The clinical plan selections (i.e. plans as selected during actual treatment) and 2) automatic plan selection, which was based on the largest overlap between LoP clinical target volume (CTV) and (auto-)delineated CTV on CBCT. To evaluate the influence of daily plan selection on the treatment dose, the dose of selected plans was calculated on the daily CBCTs for all fractions and accumulated on the CT. The predefined clinical goals were used to determine if there was a relevant dose difference between the clinical LoP-selection, automatic LoP-selection, and selecting solely the default plan (i.e. full bladder plan with similar margins). Different methods of LoP-plan selection did not result in significant dose differences. However, the default non-LoP plan resulted in significant dose differences compared to LoP-selection methods, with a reduced target coverage (99 % vs 100 %) and higher V40Gy to the rectum (55 % vs 44 %) compared to the clinical selection, respectively. LoP is robust to variations in plan selection and LoP outperforms non-LoP approaches in terms of target coverage and organs-at-risk (OAR) sparing. Therefore, LoP is a safe and efficient alternative to online adaptive replanning, particularly for longer fractionation schemes.

Diffusion weighted imaging for gross tumor volume delineation in primary radiochemotherapy and image guided adaptive brachytherapy for cervical cancer

Accurate gross tumor volume (GTV) delineation is critical for successful radiochemotherapy and image-guided adaptive brachytherapy (BT) in cervical cancer. This study investigated whether diffusion-weighted imaging (DWI) improves GTV delineation accuracy compared to T2-weighted (T2w) MRI alone, across different physician experience levels. Twenty-seven patients with locally advanced cervical carcinoma undergoing primary radiochemotherapy were analyzed. Six physicians (three experts, three residents) delineated GTVs at three time points: diagnosis (init), pre-brachytherapy (preBT), and pre-brachytherapy with applicator in situ (BT). Segmentations were performed using T2w images alone and T2w plus DWI (b=800smm DWI guidance significantly improved inter-observer agreement among experts at init (conformity index: 0.62→ 0.70, p<0.05) and BT (0.33→ 0.39, p<0.05) time points. For residents, DWI guidance enhanced agreement with expert consensus, particularly during BT, with significant improvements in Dice coefficient (median increase 9%, p<0.05) and reduced Hausdorff distance (median decrease 1.3 mm, p<0.05). Tumor volume correlation between preBT and BT time points improved with DWI guidance for both groups. Incorporating DWI into the segmentation workflow reduces inter-observer variability for both expert and resident radiation oncologists. DWI guidance particularly benefits less experienced physicians, enabling them to achieve contours closer to expert consensus standards through additional functional information.

A radiomics approach for predicting acute hematologic toxicity in patients with cervical or endometrial cancer undergoing external-beam radiotherapy

This study is purposed to establish a predictive model for acute severe hematologic toxicity (HT) during radiotherapy in patients with cervical or endometrial cancer and investigate whether the integration of clinical features and computed tomography (CT) radiomics features of the pelvic bone marrow (BM) could define a more precise model. A total of 207 patients with cervical or endometrial cancer from three cohorts were retrospectively included in this study. Forty-one clinical variables and 2226 pelvic BM radiomic features that were extracted from planning CT scans were included in the model construction. Following feature selection, model training was performed on the clinical and radiomics features via machine learning, respectively. The radiomics score, which was the output of the final radiomics model, was integrated with the variables that were selected by the clinical model to construct a combined model. The performance of the models was evaluated using the area under the receiver operating characteristic curve (AUC). The best-performing prediction model comprised two clinical features (FIGO stage and cycles of postoperative chemotherapy) and radiomics score and achieved an AUC of 0.88 (95% CI, 0.81-0.93) in the training set, 0.80 (95% CI, 0.62-0.92) in the internal-test set and 0.85 (95% CI, 0.71-0.94) in the external-test dataset. The proposed model which incorporates radiomics signature and clinical factors outperforms the models based on clinical or radiomics features alone in terms of the AUC. The value of the pelvic BM radiomics in chemoradiotherapy-induced HT is worthy of further investigation.

Are 7.5 Gy×2 fractions more efficient than 6 Gy×3 in exclusive postoperative endometrial cancer brachytherapy? A clinical and dosimetrical analysis

To compare two vaginal brachytherapy (VBT) schedules in postoperative endometrial carcinoma (PEC) patients considering vaginal-cuff relapses (VCR), late toxicities, dosimetry analysis and vaginal dilator use. 110 PEC patients were treated with exclusive high-dose-rate VBT using two schedules. Group-1:44-patients received 6 Gy×3fractions (September-2011-April-2014); Group-2:66-patients were treated with 7.5 Gy×2fractions with a dose limit of equivalent total doses in 2-Gy fr (EQD2 Descriptive analysis, Chi-square, Student's t-tests and Kaplan and Meier method. The median follow-up was 60 months (15.9-60). There were no VCR or late toxicities in bladder or rectum. LVT ≥ G1 appeared in 26/44 (59.1%) in Group-1 and 25/66 (37.9%) in Group-2. The mean EQD2 Considering the lack of vaginal relapses and similar LVT over time, 7.5 Gy×2fractions seem more efficient in terms of patient comfort, workload, and cost. This is the first study using dosimetry parameters to compare effectivity of schedules. Larger series are needed to confirm the present results.

ESTRO/ESGO/SIOPe guidelines for the management of patients with vaginal cancer

Primary vaginal malignancies are rare, comprising only 2% of all female genital tract malignancies in adults and 4.5% in children. As part of its mission to improve the quality of care for women with gynecological cancers across Europe, the European Society of Gynaecological Oncology (ESGO) jointly with the European Society for Radiotherapy & Oncology (ESTRO) and the European Society of Pediatric Oncology (SIOPe) developed evidence-based guidelines in order to improve the management of patients with vaginal cancer within a multidisciplinary setting. ESTRO/ESGO/SIOPe nominated practicing clinicians who are involved in the management of vaginal cancer patients and have demonstrated leadership through their expertise in clinical care and research, their national and international engagement and profile as well as dedication to the topics addressed to serve on the expert panel (13 experts across Europe comprising the international development group). To ensure that the statements were evidence based, the current literature was reviewed and critically appraised. In the case of absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the international development group. Prior to publication, the guidelines were reviewed by 112 independent international practitionners in cancer care delivery and patient representatives and their comments and input were incorporated and addressed accordingly. These guidelines cover comprehensively the diagnostic pathways as well as the surgical, radiotherapeutical and systemic management and follow-up of adult patients (including those with rare histological subtypes) and pediatric patients (vaginal rhabdomyosarcoma and germ cell tumours) with vaginal tumours.

Results of image guided brachytherapy for stage IB cervical cancer in the RetroEMBRACE study

Multiple treatment options are used in early local-stage cervical cancer, including combinations of surgery with neoadjuvant/adjuvant radiotherapy and chemotherapy. Our aim was to determine the outcome for definitive chemoradiation with image guided brachytherapy (IGBT). FIGO Median age was 48 (23-82) years. FIGO Chemoradiation with IGBT for FIGO

Prospective evaluation of AI-based BiCycle autoplanning for advanced cervical cancer brachytherapy

Rule-based AI BiCycle autoplanning compared favorably with manual planning in retrospective planning studies. In this study, we prospectively evaluated BiCycle's 'real life' impact by running it in parallel to current manual planning. Apart from dosimetric evaluations, treating physicians scored plans, and planning times were recorded. Following clinical routine, in each brachytherapy fraction, an RTT manually generated a plan which was then optionally adjusted by the treating physician, yielding the Man_Adj plan that was delivered. After treatment, a plan was automatically generated using BiCycle, followed by optional adjustment by the treating physician in the clinical TPS (Auto_Adj plan). Man_Adj and Auto_Adj plans were mutually compared and all planning time recorded. Physicians scored plan quality differences. For 28 of 37 evaluated fractions, the treating physician scored a higher quality for the Auto_Adj plan, in 7 fractions there was parity, and for 2 fractions Man_Adj was preferred. With comparable CTV For 95% of fractions, the treatment plan based on autoplanning was either preferred by the involved physician (76% of fractions) or considered similar in quality as the clinical plan (19%). Planning time reduced from 44.1 min for the manual workflow to 9.4 min. The system has recently been clinically introduced, following with the EU Medical Device Regulation.

Late toxicity within a Phase III clinical trial of IG-IMRT in cervix cancer (PARCER): Reanalysis with time weighted adverse event reporting (MOSES)

This post-hoc analysis was performed to report the impact of Image guided intensity modulated radiotherapy (IG-IMRT) and three-dimensional conformal radiotherapy (3D-CRT) across organ system and grades of toxicity within PARCER trial (NCT01279135). Primary endpoint of PARCER focused on grade ≥ 2 late gastrointestinal (GI) toxicity using Common Terminology Criteria for Adverse Events (CTCAE). We now analyze all adverse events using CTCAE and time and severity weighted toxicity reporting method (MOSES). MOSES was calculated separately for GI, genitourinary (GU)/GI, and any late toxicities (GI, GU, lymphedema, fatigue, vaginal stenosis, fibrosis and constitutional symptoms) by imputing proportionate time weightage to CTCAE. Cumulative MOSES (C-MOSES) for multiple system and multiorgan toxicity was determined. Difference in arms was analyzed as time-to-event and intention-to-treat analysis using CTCAE grade ≥ 1 and C-MOSES ≥ 0.70. We observed no difference in the 3-year cumulative incidence of CTCAE grade ≥ 1 GI, GI or GU, or any late toxicity between treatment arms. However, while using C-MOSES, HR of 0.59 (95% CI 0.38-0.92, p = 0.017), 0.68 (95% CI: 0.44-1.05, p = 0.08) and 0.72 (95% CI: 0.52-0.99, p = 0.04) was observed for GI, GI or GU, or any late toxicity within IG-IMRT respectively. This demonstrates superior discrimination of intervention effects using MOSES which demonstrates superiority of IG-IMRT.

Risk of recurrence after chemoradiotherapy identified by multimodal MRI and 18F-FDG-PET/CT in locally advanced cervical cancer

MRI, applying dynamic contrast-enhanced (DCE) and diffusion-weighted (DW) sequences, and 18F-fluorodeoxyglucose (18F-FDG) PET/CT provide information about tumor aggressiveness that is unexploited in treatment of locally advanced cervical cancer (LACC). We investigated the potential of a multimodal combination of imaging parameters for classifying patients according to their risk of recurrence. Eighty-two LACC patients with diagnostic MRI and FDG-PET/CT, treated with chemoradiotherapy, were collected. Thirty-eight patients with MRI only were included for validation of MRI results. Endpoints were survival (disease-free, cancer-specific, overall) and tumor control (local, locoregional, distant). K HF showed a stronger association with outcome than the single modality parameters. This association was confirmed in the validation cohort. Low HF identified low-risk patients with 95% precision. Based on the 50th SUV-percentile (SUV Multimodal combination of MR- and FDG-PET/CT-images improves classification of LACC patients compared to single modality images and clinical factors.

Vaginal 11-point and volumetric dose related to late vaginal complications in patients with cervical cancer treated with external beam radiotherapy and image-guided adaptive brachytherapy

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 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

Evaluation of early regression index as response predictor in cervical cancer: A retrospective study on T2 and DWI MR images

Early Regression Index (ERI A total of 88 patients affected by LACC (FIGO IB2-IVA) and treated with CRT were enrolled. An MRI protocol consisting in two acquisitions (T2-w and DWI) in two times (before treatment and at mid-therapy) was applied. Gross Tumor Volume (GTV) was delineated and ERI ERI This study identified ERI

Dose-effect relationship between vaginal dose points and vaginal stenosis in cervical cancer: An EMBRACE-I sub-study

To evaluate dose-effect relationships between vaginal dose points and vaginal stenosis in patients treated for locally advanced cervical cancer with radio(chemo)therapy and image-guided adaptive brachytherapy. Patients from six centres participating in the EMBRACE-I study were included. Information on doses to different vaginal dose points, including the Posterior-Inferior Border of Symphysis (PIBS) points and recto-vaginal reference (RV-RP) point, were retrieved from the treatment planning system. In addition, the vaginal reference length (VRL) was evaluated. Vaginal stenosis was prospectively assessed according to the CTCAEv3.0 system at baseline and follow-up. Primary endpoint was grade 2 or higher (G ≥ 2) vaginal stenosis. Impact of dose to the vaginal dose points, and impact of VRL, age, vaginal involvement and applicator on vaginal stenosis G ≥ 2 was evaluated with a Cox proportional-hazard regression model. 301 patients were included. Median follow-up was 49 months. During follow-up, the incidence of G0, G1, G2, and G3 vaginal stenosis was 25% (76), 52% (158), 20% (59) and 3% (8), respectively. Median total doses to PIBS+2 cm, PIBS, PIBS-2 cm and the RV-RP were 52.9 (IQR 49.3-64.7), 41.0 (IQR 15.4-49.0), 4.1 (IQR 2.9-7.0) and 64.6 (IQR 60.0-70.6) Gy EQD2 Higher doses to the PIBS+2 cm, PIBS and RV-RP dose points are associated with vaginal stenosis G ≥ 2.

A feasibility study of dose-band prediction in radiation therapy: Predicting a spectrum of plan dose

The current deep learning-based dose prediction methods only predict one dose distribution. If the predicted dose is inaccurate, no additional options can be selected. To overcome this limitation, we propose a novel dose prediction method called "dose-band prediction," which provides a spectrum of predicted dose distributions for planning and quality assurance (QA) purposes. We utilized Upper/Lower-band losses in 3D neural networks to establish the Upper/Lower-band models (UBM/LBM). The maximum/minimum rational dose predicted in UBM/LBM defined the ideal dose spectrum for each voxel. We enrolled 104 nasopharyngeal carcinoma cases with tomotherapy (dataset 1), 54 cervical carcinoma cases with IMRT (dataset 2), and 37 cervical carcinoma cases with VMAT (dataset 3) in the study. Moreover, a dose band-based auto planning (Auto-plan The UBM/LBM doses tend to be higher/lower than the clinical dose, forming a predicted dose spectrum. The Middle-line dose represents the average of the Upper/Lower-band, which was consistent with the clinical dose. The mean differences of the planning target volumes (PTVs) and organs at risk (OARs) for the Upper-band, Middle-line, and Lower-band in Dataset 1 were 3.66 %, -0.40 %, and -4.48 % in Dataset 2, they were 2.40 %, -1.62 %, and -5.57 %; in Dataset 3, they were 2.18 %, -0.59 %, and -3.31 %. When PTVs meet prescription, the mean difference between Auto-plan The dose-band prediction successfully predicted a spectrum of doses, making auto-planning and QA flexible and high quality.

A T2-weighted MRI-based radiomic signature for disease-free survival in locally advanced cervical cancer following chemoradiation: An international, multicentre study

To develop and validate a T2-weighted magnetic resonance imaging (MRI)-based radiomic signature associated with disease-free survival (DFS) in locally advanced cervical cancer. The study comprised a training dataset of 132 patients (93 Norwegian; 39 The Cancer Imaging Archive (TCIA) and an independent validation Canadian dataset of 199 patients with FIGO stage IB-IVA cervical cancer treated with chemoradiation. Radiomic features were extracted using PyRadiomics. A radiomic signature was developed based on a multivariable radiomic prognostic model for DFS built using the training dataset, with minimal redundancy maximum relevancy feature selection method. Univariate and multivariable Cox regression analyses were then conducted to examine the association of the derived radiomic signature with DFS. A radiomic signature was prognostic for DFS in the training cohort (Norwegian hazard ratio [HR] 5.54, p = 0.002; TCIA HR 3.59, p = 0.04). The radiomic signature remained independently associated with DFS (HR 3.70, p = 0.004) when adjusted for stage and tumor volume. The radiomic signature was also prognostic for DFS in the validation cohort, both on univariate analysis (HR 2.22, p = 0.003), and multivariable analysis adjusted for stage and tumor volume (HR 1.84, p = 0.04). The 4-year DFS rates of patients with radiomic signature score > 0 vs ≤ 0 were 48.2 % vs 87.9 %, and 56.4 % vs 80.8 % for training and validation cohorts respectively. An MRI-based radiomic signature can be used as a prognostic biomarker for DFS in patients with locally advanced cervical cancer undergoing chemoradiation.

Management of oligo-metastatic and oligo-recurrent cervical cancer: A pattern of care survey within the EMBRACE research network

In the metastatic or recurrent cervical cancer, systemic chemotherapy constitutes the main treatment. Though there is an increasing use of high dose external radiation and brachytherapy in the metastatic setting, no consensus exists. A 17-item survey was designed with additional case-based questions to explore present management of oligo-metastatic and oligo-recurrent cervix cancer within EMBRACE research group participating sites. The questions were designed to elicit prevailing practices in the management of de-novo oligo-metastasis and oligo-recurrent setting after completing the primary treatment of cervix cancer. The survey was sent electronically with two rounds of email reminders to respond over a 2-week survey period. The online survey was designed such that it was mandatory to complete all questions. The responses were recorded and results were summarized as proportions and summary statistics were generated. Twenty-two centers responded to this survey. A majority (90%) of respondents reported a low incidence of de-novo oligo-metastatic cervical cancer in their practice (<5%), with a higher proportion of patients with oligo-recurrence after completing primary treatment (5-10%). All responding sites preferred to treat pelvic disease in the de-novo oligo-metastatic setting albeit with different fractionation regimens. While 68.2% of respondents recommended chemo-radiation and brachytherapy, 31.8% considered additional systemic therapy. Overall 77.3% centers recommended the use of stereotactic ablative radiation therapy to oligo-metastasis. For out-of-field nodal recurrences, 63.7% of respondents considered treating with curative intent, while 59% preferred treating in-field recurrence with palliative intent. A vast majority of the participating centers (90%) have stereotactic radiation therapy capacity and would consider a clinical trial addressing oligo-metastatic and oligo-recurrent cervical cancer. Although contemporary practice is variable, a substantial proportion of EMBRACE centers consider high dose radiation in de-novo metastatic and oligo-recurrence settings. However, there is clear need for a joint clinical protocol and prospective studies to address the role of high dose radiation within oligo-recurrent and oligo-metastatic scenarios.

Recommendations from gynaecological (GYN) GEC-ESTRO working group – ACROP: Target concept for image guided adaptive brachytherapy in primary vaginal cancer

External beam radiotherapy (EBRT) combined with brachytherapy has an essential role in the curative treatment of primary vaginal cancer. EBRT is associated with significant tumour shrinkage, making primary vaginal cancer suitable for image guided adaptive brachytherapy (IGABT). The aim of these recommendations is to introduce an adaptive target volume concept for IGABT of primary vaginal cancer. In December 2013, a task group was initiated within GYN GEC-ESTRO with the purpose to introduce an IGABT target concept for primary vaginal cancer. All participants have broad experience in IGABT and vaginal cancer brachytherapy. The target concept was elaborated as consensus agreement based on an iterative process including target delineation and dose planning comparison, retrospective analysis of clinical data and expert opinions. Gynaecological examination and MR imaging are the modalities of choice for local tumour assessment. A specific template for standardised documentation with clinical drawings for vaginal cancer was developed. The adaptive target volume concept comprises different response-related target volumes. For EBRT these are related to the primary tumour and the lymph nodes, while for IGABT these are related to the primary tumour and are consisting of the residual gross tumour volume (GTV-T This target concept for IGABT of primary vaginal cancer defines adaptive target volumes for volumetric dose prescription and should improve comparability of different radiotherapy schedules of this rare disease. A prospective evaluation of the target volume concept within a multicentre study is planned.

Importance of the ICRU bladder point dose on incidence and persistence of urinary frequency and incontinence in locally advanced cervical cancer: An EMBRACE analysis

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 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.

Early alteration in apparent diffusion coefficient and tumor volume in cervical cancer treated with chemoradiotherapy or radiotherapy: Incremental prognostic value over pretreatment assessments

Our study aimed to evaluate a prognostic value of early changes in apparent diffusion coefficients (ADC) and tumor volume during treatment in patients with cervical cancer treated with chemoradiotherapy or radiotherapy, and to assess whether the early changes provided an incremental value to pre-treatment ADC and tumor volume in predicting disease recurrences. A total of 103 patients with stage IB-IVA cervical cancer including 76 (74%) patients with stage ≥IIIA who underwent magnetic resonance imaging before and during (25 ± 4.6 days after start) the treatment were enrolled. Eighty-one patients received chemoradiotherapy and the remaining 22 had radiotherapy. Both a volumetric ADC and volume of a tumor before and during treatment were measured. %ADC increase and %Volume reduction were defined as changes in the ADCs and tumor volume before and during treatment, respectively. During a median follow-up of 2.7 years, 42 (41%) patients had disease recurrences. Univariate Cox regression analysis revealed that pre-treatment ADC (Hazard ratio [HR] = 2.8; p = 0.002), %ADC increase (HR = 6.8; p < 0.001), and %Volume reduction (HR = 2.7; p = 0.003) were significant predictors for disease recurrences. On multivariate analysis, %ADC increase was the only independent predictor (adjusted HR = 5.2; p < 0.001) for disease recurrences when adjusted for %Volume reduction and pre-treatment ADC. Global chi-square analysis demonstrated that %ADC increase and %Volume reduction had an additional prognostic value over pre-treatment ADC and tumor volume (p < 0.05). Kaplan-Meier curve analysis showed that both smaller %ADC increase and %Volume reduction were associated with worse prognosis in disease-free survival (log-rank, p < 0.001 and p = 0.002, respectively). Among patients with cervical cancer treated with chemoradiotherapy or radiotherapy, early changes in tumor ADCs and tumor volume during treatment are associated with better prognosis. %ADC increase and %Volume reduction during the treatment have an additional prognostic value for predicting tumor recurrence to pre-treatment ADC and tumor volume.

Dihydroouabain, a novel radiosensitizer for cervical cancer identified by automated high-throughput screening

Radiotherapy plays a crucial role in the treatment of cervical cancer, but existing radiosensitizers have limited efficacy in clinical applications. The aims of this study were to establish and verify an efficient method for identifying new radiosensitizers, to use this to identify candidate radiosensitizers for cervical cancer, and to investigate the specific mechanisms of these when used in combination with radiotherapy. An automated platform for identifying radiosensitizers for cervical cancer was created based on high-throughput screening technology. The radiosensitizing effects of candidate compounds from the LOPAC1280 chemical library were evaluated in radiosensitive and radioresistant cervical cancer cells using a clonogenic survival assay, with cell cycle analyses, and western blot analyses performed for both cell lines. The automated high-throughput screening approach identified four hit compounds. One of the most potent candidates was dihydroouabain (DHO), an inhibitor of Na DHO is a novel radiosensitizer for the treatment of cervical cancer. The automated high-throughput screening platform developed in this study proved to be powerful and effective, with the potential to be widely used in the future identification of radiosensitizers.

Implementing an online radiotherapy quality assurance programme with supporting continuous medical education – report from the EMBRACE-II evaluation of cervix cancer IMRT contouring

EMBRACE-II is an international prospective study of IMRT and MRI-guided adaptive brachytherapy (IGABT) in locally advanced cervix cancer. An online radiotherapy quality assurance (RTQA) programme with minimal data transfer and supporting continuing medical education (CME) was implemented for IMRT contouring. Participant contours for six volumes-of-interest (VOIs) on one benchmark case were scored (2 = excellent, 1 = fair, 0 = revision required) against a consensus reference contour. For contours receiving a 0 or 1 score, additional qualitative comments were provided. The Jaccard conformity index (JCI) was retrospectively calculated. User interaction with CME content (pre-accreditation questionnaire, contouring atlas, practice cases, quizzes, internal target volume (ITV-T) guide) was analysed. 78 clinicians submitted contours for evaluation. 41% passed at the first attempt, 44% after one revision and 6% after two or more revisions. 9% did not re-submit after failing. The lowest mean scores were for the elective nodal CTV (CTV-E) (1.01/2) and ITV-T (1.06/2). 60 different errors across the six VOIs were identified; five potentially had high impact on loco-regional control. A JCI cut-off of 0.7 would have identified 87% contours that failed expert assessment, but also excluded 54% of passing contours. 39 clinicians responded to the pre-accreditation questionnaire - 36% anticipated difficulties with the ITV-T and 13% with the CTV-E. 35% clinicians contoured on the practice cases, 17% answered a quiz, 96% used the atlas and 38% the ITV-T guide. Expert evaluation with qualitative feedback improved contouring compliance. The JCI is not a reliable alternative to expert assessment. Moderate uptake of optional CME content limited evaluation.

Image registration, contour propagation and dose accumulation of external beam and brachytherapy in gynecological radiotherapy

This review provides an overview of the current status of image registration for image guided gynaecological brachytherapy including combination with external beam radiotherapy. Contour propagation between individual fractions and dose accumulation can be useful for cervix cancer radiotherapy. Contour mapping and applicator reconstruction with rigid registration based on the applicator geometry provide good accuracy. However, deformable image registration is particularly challenging in the pelvic region, due to the large and complex deformations caused by tumor shrinkage, bladder and rectum filling, insertion of a brachytherapy applicator and presence of packing material. This causes substantial limitations and uncertainties when using it in the clinical workflow so that the current generation of deformable image registration algorithms is not yet robust enough to handle complexities involving the dose accumulation of external beam and brachytherapy. The direct addition of doses provides a reasonable estimate of the total absorbed dose. However, in case of significant dose gradients from external beam boosts or midline-shielding adding dose contributions from the different radiotherapy modalities and fractions remains subject to large uncertainties.

Deep learning-based auto-segmentation of organs at risk in high-dose rate brachytherapy of cervical cancer

Delineation of organs at risk (OARs), such as the bladder, rectum and sigmoid, plays an important role in the delivery of optimal absorbed dose to the target owing to the steep gradient in high-dose rate brachytherapy (HDR-BT). In this work, we propose a deep convolutional neural network-based approach for fast and reproducible auto-contouring of OARs in HDR-BT. Images of 113 patients with locally-advanced cervical cancer were utilized in this study. We used ResU-Net deep convolutional neural network architecture, which uses long and short skip connections to improve the feature extraction procedure and the accuracy of segmentation. Seventy-three patients chosen randomly were used for training, 10 patients for validation, and 30 patients for testing. Well established quantitative metrics, such as Dice similarity coefficient (DSC), Hausdorff distance (HD), and average symmetric surface distance (ASSD), were used for evaluation. The DSC values for the test dataset were 95.7 ± 3.7%, 96.6 ± 1.5% and 92.2 ± 3.3% for the bladder, rectum, and sigmoid, respectively. The HD values (mm) were 4.05 ± 5.17, 1.96 ± 2.19 and 3.15 ± 2.03 for the bladder, rectum, and sigmoid, respectively. The ASSDs were 1.04 ± 0.97, 0.45 ± 0.09 and 0.79 ± 0.25 for the bladder, rectum, and sigmoid, respectively. The proposed deep convolutional neural network model achieved a good agreement between the predicted and manually defined contours of OARs, thus improving the reproducibility of contouring in brachytherapy workflow.

In regard to Spampinato et al

Response to Yuce Sari et al.

Risk factors and dose-effects for bladder fistula, bleeding and cystitis after radiotherapy with imaged-guided adaptive brachytherapy for cervical cancer: An EMBRACE analysis

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 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

Multicenter deep learning–based automatic delineation of CTV and PTV in uterine malignancy CT imaging

Accurate delineation of the clinical target volume (CTV) and planning target volume (PTV) is essential for effective radiotherapy in uterine malignancies. Manual contouring is laborious, time-consuming, and subjective, and current automatic methods often focus on a single cancer type with limited external validation. To address this, we developed a deep-learning model capable of accurately delineating both CTV and PTV across multiple uterine malignancies using CT imaging. We retrospectively collected 602 contrast-enhanced CT scans, comprising 302 cases (cervical and endometrial cancers) from our institution and an additional 300 cervical cancer scans from external centers. Expert radiation oncologists manually delineated the CTV and PTV on each image. Among the 302 internal cancer cases, 177 cervical cancer cases were used for model training with five-fold cross-validation. Additionally, 41 cervical cancer cases were reserved as an internal testing cohort, while 84 endometrial cancer cases constituted the first external testing cohort to assess the model's generalizability across cancer types. The remaining 300 cervical cancer scans from external centers formed a second external testing cohort to assess model robustness across institutions. We evaluated three segmentation architectures-2D, full-resolution 3D, and cascaded 3D networks-and measured their performance using three standard metrics: Dice Similarity Coefficient (DSC), 95% Hausdorff Distance (HD95), and Average Surface Distance (ASD). The model-generated segmentations demonstrated strong concordance with the expert contours. In the internal testing cohort with the same cancer type, performance metrics (DSC, HD95, ASD) were consistently high. Similarly, the external testing cohort with different cancer types showed robust performance, indicating effective generalizability. On the internal testing cohort, the model demonstrated strong performance, achieving mean DSCs of 83.42% for PTV and 81.23% for CTV, with low spatial errors (PTV: ASD 2.01 mm, HD95 5.71 mm; CTV: ASD 1.35 mm, HD95 4.75 mm). In the endometrial cancer cohort, PTV segmentation achieved a DSC of 82.88%, while CTV segmentation yielded an HD95 of 5.85  mm and an ASD of 1.34  mm. Additionally, clinical evaluation revealed that approximately 90% of the model-generated contours required no or only minor revision. We present a multicenter-validated deep-learning based framework for automatic CTV and PTV delineation across diverse uterine malignancies on CT. Our model offers a scalable, generalized solution with the potential to reduce the workload in radiation oncology, improve consistency, and streamline clinical workflows.

Pain control and opioid use as a function of workflow in MRI-guided interstitial cervix brachytherapy

/Objective(s): Pain management during brachytherapy for cervix cancer is challenging. Institutional practice for brachytherapy delivery and pain management varies. Here we retrospectively assessed pain control and opioid use requirements during different MRI-guided interstitial cervix brachytherapy workflows. /Methods: In this retrospective study, data was collected on ninety-one patients receiving MR-guided interstitial brachytherapy for cervix cancer between June 2022 and June 2024. Abstracted data included: demographics, disease characteristics, pain scores, opioid use, and brachytherapy workflow. Patients were either treated as in-patients or out-patients. In-patients remained overnight to receive a second fraction the following day. Out-patients received a single fraction and were discharged the same day. Out-patients were further divided into intra-operative versus post-operative treatment. For intra-operative treatment the entire procedure was performed under general anesthesia (GA). For post-operative treatment only applicator insertion was under GA. Multivariable linear regression modelling was used for analysis of opioid dose and pain scores. Ninety-one patients were eligible for inclusion, corresponding to 201 separate insertions. Median age was 51. Majority (69 %) had cT2b disease. Mean CTV In-patient treatment was associated with worse pain control, despite increased opioid use. Within those treated as out-patients, intra-operative treatment further improved pain management.

Evaluation of brachytherapy applicators and their association with morbidity and local control in cervix cancer: An EMBRACE I analysis

To investigate the effects of brachytherapy (BT) applicator and implant type on morbidity and local control (LC) in locally advanced cervix cancer patients. 1071 patients treated with radiochemotherapy including MRI-guided BT using tandem&ring (T&R) or tandem&ovoids (T&O) from 19 EMBRACE-I centers were analyzed. Intracavitary (IC) or intracavitary/interstitial (IC/IS) implants were used. Centers came from different brachytherapy traditions and followed their institutional dose aims and planning strategies. LC and physician-assessed morbidity (median follow-up 48 months) was compared between applicator/implant types using Cox proportional hazard model adjusting for patient characteristics and treatment-related potential confounders. Moderate-to-severe (G ≥ 2) genito-urinary (cystitis/frequency/incontinence), gastro-intestinal (proctitis/bleeding/diarrhea) and vaginal (stenosis/mucositis) symptoms were analysed individually. Severe events (G ≥ 3) were pooled per organ. The T&O (n = 346) compared to T&R (n = 725) had a higher risk of morbidity, with HRs > 1.3 in 14/16 individual G ≥ 2 symptoms and in 3/4 G ≥ 3 pooled organ symptoms. Patients treated with IC/IS (n = 512) compared to IC (n = 559) were not at higher risk of G ≥ 2 symptoms, with HRs < 1 in 6/8 MVAs. Crude incidence of local failure was 7.3 % (25/343) for T&O and 6.6 % (47/712) for T&R. In this patient cohort, treated between 2008-2015, T&R and T&O demonstrated comparable LC. However, a higher risk of morbidity is reported for T&O. This increased risk was partly explained by hotspot doses, with factors such as irradiated volumes and organ irradiation length also contributing. Additionally, implant quality, dose planning aims and strategies, and morbidity reporting may have impacted the observed differences in morbidity. IC/IS applicators did not increase morbidity risk compared to IC applicators.

Dose-volume constraints for severe acute gastrointestinal toxicity in cervical cancer patients receiving extended-field intensity-modulated radiotherapy and concurrent chemotherapy

Extended-field intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy may lead to severe toxicity. This study aims to investigate the incidence and dosimetric predictors of acute gastrointestinal toxicity in cervical cancer patients. Dosimetric data of the duodenum and small bowel loop from 273 eligible patients were analyzed. Logistic regression and Pearson's pairwise correlation were used to identify the best predictors. Receiver operating characteristic curves were used to determine the optimal cutoff values. Logistic models were established to predict the normal tissue complication probability. Twenty-six patients experienced grades ≥ 3 (G3 Limiting V

Less than whole uterus irradiation for patients with locally advanced cervical cancer

Current consensus guidelines for definitive cervical cancer intensity modulated radiation therapy (IMRT) recommend inclusion of the entire uterus within the clinical target volume, however this is debated. We aimed to evaluate outcomes of patients with cervical cancer who were treated with less than whole uterus irradiation. We identified 109 patients with FIGO Stage IB-IVA cervical cancer treated definitively with concurrent chemoradiation, including IMRT and brachytherapy, from 2010 to 2022 at a single institution where the practice was to include the gross cervix tumor with an internal target volume with differences in bladder filing accounted for, plus additional 5 mm planning target volume (PTV) margin. Local, regional, and distant recurrences were analyzed using competing risk methods, and a Wilcoxon rank sum test was performed to assess differences in dose to organs at risk based on the proportion of the uterus included in the PTV, with the median proportion of the uterus included (75 %) used as the cut-point. The median follow-up time was 65 months (range 3-352 months). The 2-year cumulative incidence of LR for the entire cohort was 4.2 % (95 % confidence interval [CI] 1.3-9.7). Compared with patients who had ≥ 75 % of the uterus included in the PTV, patients who had < 75 % of the uterus included in the PTV had significantly lower bowel D200cc (p = 0.02). The cumulative incidence of local failure (LR) was not significantly different between the two groups. Including less than the whole uterus for definitive cervix cancer IMRT does not seem to compromise local control. Less than whole uterus irradiation could be considered for carefully selected cervix cancer patients to decrease bowel dose and possible treatment-related toxicity.

Impact of primary radiotherapy on the psychosocial well-being of patients with locally advanced cervical cancer (IMPRaCC study)

Treatment for locally advanced cervical cancer (LACC), and especially brachytherapy, can be physically and psychologically demanding for patients. The IMPRaCC study (Impact of primary Radiotherapy on the psychosocial well-being of patients with LACC) aimed to investigate risk factors, peak moments of distress, and unmet needs. Analyses of EORTC-C30 questionnaires in a cohort of LACC patients (2019-2024) were combined with semi-structured interviews 4-16 weeks post-treatment. Questionnaires were collected at baseline, during treatment, and regularly throughout follow-up up to two years. Linear-mixed models evaluated changes in scores from baseline. Scores were also compared to a healthy reference population. Logistic regression identified factors associated with deteriorations in emotional (EF) and social functioning (SF) and fatigue during treatment and follow-ups. Interviews were evaluated using thematic analyses. Among 142 LACC patients, baseline EF and SF during treatment were impaired compared to the reference population, but improved in follow-up. Deteriorations in EF, SF and fatigue were more frequent during treatment (18.6%, 48.8%, 62.8%) than follow-up (10.4%, 25%, 34.4%). Psychiatric history was associated with worse SF during treatment, while being in a relationship and psychological support were protective factors. Brachytherapy delivered in four vs. three fractions seemed to be associated with worse EF, SF and fatigue. Interviews with 13 patients revealed emotional distress, especially before brachytherapy, and need for clear and consistent communication across multiple healthcare professionals. Psychiatric history assessments, psychological support, and consistent communication support tailored care for LACC patients. Brachytherapy regimens of three fractions may further reduce psychosocial distress.

Limitations and future directions in identifying risk factors for radiotherapy related pelvic insufficiency fractures in gynecological cancers: A scoping review

A systematic search of PubMed and EMBASE was conducted using terms such as "pelvic insufficiency fractures", "radiotherapy" and "gynecological cancers". Citations of relevant studies were also screened. Eligible studies included gynecolgical patients treated with pelvic RT, and reporting risk factors for RRIFs. Key data, including study characteristics, incidence rates, fracture definitions, imaging and dosimetry methods and statistical approaches were extracted. The Transparent Reporting of a multivariable prediction modelfor Individual Prognosis Or Diagnosis (TRIPOD) checklist was used to assess the methodological quality of the included studies. 28 studies met the inclusion criteria. RRIF incidence ranged from 1.7% to 37.4%. Commonly reported risk factors included advanced age, postmenopausal status, higher RT doses, low body weight, pre-existing osteoporosis, and concurrent chemotherapy. Imaging protocols, fracture definitions, and timing of detection varied widely. Statistical limitations, including reliance on univariable analyses, small sample sizes, and inconsistent baseline assessments, were common and limit reliable interpretation of risk factors. Anatomical targets for dose evaluation varied, with few studies correcting for biologically effective dose. Only one study developed a predictive model for RRIFs, which demonstrated moderate performance but lacked validation. Bone health assessments were inconsistently performed. Interdisciplinary approaches to improve fracture risk prediction, reduce treatment-related toxicity, and guide clinical decision-making.

Patient-reported acute GI symptoms in locally advanced cervical cancer patients correlate with rectal dose

To investigate relationships between patient-reported acute gastro-intestinal symptoms in a locally advanced cervical cancer (LACC) prospective cohort and clinical and dosimetric parameters, while also taking spatial dose into account. A total of 103 patients was included, receiving radiotherapy based on a plan-library-based plan-of-the-day protocol, combined either with concurrent chemotherapy or with neo-adjuvant chemotherapy and concomitant hyperthermia. Toxicity endpoints were extracted from questionnaires sent out weekly during treatment and regularly in the acute phase after treatment. Endpoints were defined for symptoms concerning obstipation, diarrhea, fecal leakage, bowel cramps and rectal bleeding. Dose surface maps were constructed for the rectum. Clinical parameters and dosimetric parameters of the bowel bag and rectum were collected for all patients. The use of concomitant chemotherapy and an increase in Planning Target Volume (PTV) resulted in a significant increase in reported diarrhea. The dose-volume parameters V The significance of results for patients reporting diarrhea symptoms found for PTV volume indicates a potential benefit for a plan-of-the-day protocol. Additionally, the results suggest that a reduction of inferior rectum dose could decrease patient-reported diarrhea symptoms, while the administration of concomitant chemotherapy appears to lead to radiosensitizing effects that increase these symptoms.

IBS-GEC ESTRO-ABS recommendations for CT based contouring in image guided adaptive brachytherapy for cervical cancer

MR Imaging is regarded asthe gold standardfor 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.

Dosimetric impact of bone marrow sparing for robustly optimized IMPT for locally advanced cervical cancer

To investigate the trade-off between bone marrow sparing (BMS) and dose to organs at risk (OARs) for intensity modulated proton therapy (IMPT) for women with locally advanced cervical cancer (LACC). Twenty LACC patients were retrospectively included. IMPT plans were created for each patient using automated treatment planning. These plans progressively reduced bone marrow mean doses by steps of 1 GyRBE, while constraining target coverage and conformality. The relation between bone marrow dose and bladder, small bowel, rectum, and sigmoid doses was evaluated. A total of 140 IMPT plans were created. Plans without BMS had an average [range] bone marrow mean dose of 17.3 [14.7-21.6] Gy Achieving 1 Gy

ESGO/ESTRO quality indicators for radiation therapy of cervical cancer

The European Society of Gynaecological Oncology (ESGO) has previously defined and established a list of quality indicators for the surgical treatment of cervical cancer. As a continuation of this effort to improve overall quality of care for cervical cancer patients across all aspects, ESGO and the European SocieTy for Radiotherapy and Oncology (ESTRO) initiated the development of quality indicators for radiation therapy of cervical cancer. To develop a list of quality indicators for radiation therapy of cervical cancer that can be used to audit and improve clinical practice by giving to practitioners and administrators a quantitative basis to improve care and organizational processes, notably for recognition of the increased complexity of modern external radiotherapy and brachytherapy techniques. Quality indicators were based on scientific evidence and/or expert consensus. The development process included a systematic literature search for identification of potential quality indicators and documentation of scientific evidence, consensus meetings of a group of international experts, an internal validation process, and external review by a large international panel of clinicians (n = 99). Using a structured format, each quality indicator has a description specifying what the indicator is measuring. Measurability specifications are detailed to define how the quality indicators will be measured in practice. Targets were also defined for specifying the level which each unit or center should be aiming to achieve. Nineteen structural, process, and outcome indicators were defined. Quality indicators 1-6 are general requirements related to pretreatment workup, time to treatment, upfront radiation therapy, and overall management, including active participation in clinical research and the decision making process within a structured multidisciplinary team. Quality indicators 7-17 are related to treatment indicators. Quality indicators 18 and 19 are related to patient outcomes. This set of quality indicators is a major instrument to standardize the quality of radiation therapy in cervical cancer. A scoring system combining surgical and radiotherapeutic quality indicators will be developed within an envisaged future ESGO accreditation process for the overall management of cervical cancer, in an effort to support institutional and governmental quality assurance programs.

ESGO/ESTRO/ESP Guidelines for the management of patients with cervical cancer – Update 2023

In 2018, the European Society of Gynecological Oncology (ESGO) jointly with the European Society for Radiotherapy and Oncology (ESTRO) and the European Society of Pathology (ESP) published evidence-based guidelines for the management of patients with cervical cancer. Given the large body of new evidence addressing the management of cervical cancer, the three sister societies jointly decided to update these evidence-based guidelines. The update includes new topics to provide comprehensive guidelines on all relevant issues of diagnosis and treatment in cervical cancer. To serve on the expert panel (27 experts across Europe) ESGO/ESTRO/ESP nominated practicing clinicians who are involved in managing patients with cervical cancer and have demonstrated leadership through their expertise in clinical care and research, national and international engagement, profile, and dedication to the topics addressed. To ensure the statements were evidence based, new data identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the international development group. Before publication, the guidelines were reviewed by 155 independent international practitioners in cancer care delivery and patient representatives. These updated guidelines are comprehensive and cover staging, management, follow-up, long-term survivorship, quality of life and palliative care. Management includes fertility sparing treatment, early and locally advanced cervical cancer, invasive cervical cancer diagnosed on a simple hysterectomy specimen, cervical cancer in pregnancy, rare tumors, recurrent and metastatic diseases. The management algorithms and the principles of radiotherapy and pathological evaluation are also defined.

EviGUIDE - a tool for evidence-based decision making in image-guided adaptive brachytherapy for cervical cancer

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). 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. 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. 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.

Impact of the Common Terminology Criteria for Adverse Events (CTCAE) evolution on toxicity scoring in gynaecological radiotherapy

The Common Terminology Criteria for Adverse Events (CTCAE) is the established toxicity scoring system that assigns severity grades (G1 = mild to G5 = death) to Adverse Events (AEs). Compared to CTCAE v3.0 (2006), updated versions introduced changes in severity grade definitions. This study evaluated changes between v3.0 and v5.0 (2017) for AEs in gynaecological radiotherapy. After selecting AEs relevant for gynaecological radiotherapy in v3.0, changes in severity grades were identified using CTCAE v3.0-to-v5.0 mapping tables. Six radiation oncologists (ROs) evaluated severity grade definitions for changes in: clinical interpretation, subjective (patient-reported symptoms) and objective (details on medication/intervention) information, and expected severe (≥G3) events. Agreement was based on at least five (≥5)ROs. Gastrointestinal, urinary, reproductive, general and injury/musculoskeletal AEs were selected (n = 118). G4 definitions in v5.0 were removed in 22 % of AEs. ≥5ROs agreed on changes affecting clinical interpretation especially for G2 (31 %) and G3 (30 %). For subjective information, 18 % of G2 and 15 % of G3 were judged relying more on patient-reported symptoms. Less objective information was found in 51 % of G3 definitions. Variability in agreement was observed especially for subjective information in G3 and expected ≥G3 events. This analysis revealed that severity grade definitions in v3.0 and v5.0 for AEs in gynaecological radiotherapy present changes with potential impact on scoring in clinical studies. Notably, 22 % of AEs in v5.0 no longer have G4 defined, and G3 definitions often include fewer details on medication/intervention. Variability in ROs' interpretations is frequently observed, highlighting the need for education to standardise toxicity scoring.

Point-A vs. volume-based brachytherapy for the treatment of cervix cancer: A meta-analysis

To report disease-free survival (DFS) for volume-based and point-A based brachytherapy (BT) in locally advanced cervical cancer. We conducted a meta-analysis of studies assessing the effects of point-A and volume-based brachytherapy on 3-year DFS. Studies including stage I-IVA cervical cancer patients were included if standard treatment of concomitant chemo-radiotherapy and high-dose- or pulsed dose rate BT was delivered. The primary outcome was 3-year DFS, and secondary outcomes were 3-year local control (LC), 3-year overall survival (OS) and late toxicity. A random-effects subgroup meta-analysis was done. In total, 5499 studies were screened, of which 24 studies with 5488 patients were eligible. There was significant heterogeneity among point-A studies (1538 patients) (I Volume-based BT results in superior 3-year DFS and 3-year LC. In the absence of randomized trials, this meta-analysis provides the best evidence regarding transition to 3D planning.

Multi-center analysis of machine-learning predicted dose parameters in brachytherapy for cervical cancer

Image-guided adaptive brachytherapy (IGABT) is a key component in the treatment of cervical cancer, but the nature of the clinical workflow makes it vulnerable to suboptimal plans, as the theoretical optimal plan depends heavily on organ configuration. Patient anatomy-based quality-assurance (QA) with overlap volume histograms (OVHs) is a promising tool to detect such suboptimal plans, and in this analysis its suitability as a multi-institutional clinical QA tool is investigated. A total of 223 plans of 145 patients treated in accordance with the current state-of-the-art IGABT protocols from UMC Utrecht (UMCU) and Erasmus MC (EMC) were included. Machine-learning models were trained to predict dose D Intra-validation of UMCU data demonstrated OVH model robustness to needle use and applicator type. The model trained on UMCU data was found to be robust within the same protocol on EMC data, for all investigated OARs. Mean squared error between planned and predicted D OVH-based models can provide a solid basis for multi-institutional QA when trained on a sufficiently strict protocol. Further research will quantify the model's impact as a QA tool.

Use of patient-derived tumor organoids from head and neck squamous cell carcinoma for the evaluation of the differential effect of carbon ions over X-rays

Changes in bone marrow fat fraction and immune cell counts in women with cervical cancer treated with primary chemoradiotherapy

Hematologic toxicity (HT) is a common effect of chemoradiotherapy in primary locally advanced cervical cancer (LACC) and related to bone marrow (BM) fat increase. However, longitudinal effects and dose-relationships are unknown. In this study, pre- and post-treatment BM fat fraction and blood immune cell counts were evaluated in women with primary LACC undergoing BM sparing chemoradiotherapy. Water-fat MRI scans and blood samples were obtained at baseline, during, and at 3 and 12 months (post-)treatment. The mean proton density fat fraction (PDFF) [%] was calculated for each vertebra, categorized into a no (5 Gy) dose group, and the pelvic bones. Associations between PDFF and dose, immune cells, and patient characteristics were assessed with linear mixed models. Eighteen women were included. Vertebral PDFF in the no dose group remained unchanged, whereas the low and high dose group showed an increase of 24-35 PDFF% during treatment. PDFF in the low dose group recovered slightly but remained elevated up to 12 months post-treatment. Mean dose to pelvic subregions was ≥ 18.8 Gy and PDFF increase was 12-29 PDFF%. Only the lower pelvic PDFF recovered to baseline. Blood immune cell decline lasted up to 12 months post-treatment and was correlated with higher mean vertebral PDFF. Vertebral fat fraction increased during treatment for dose > 1 Gy, without post-treatment recovery for dose > 5 Gy. Immunosuppression persisted up to 12 months post-treatment and was related to a higher mean vertebral PDFF. 5 Gy might be relevant for BM damage, but this threshold should be validated.

MRI-guided dynamic risk assessment in cervical cancer based on tumor hypoxia at diagnosis and volume response at brachytherapy

Improvements in treatment outcome for patients with locally advanced cervical cancer (LACC) require a better classification of patients according to their risk of recurrence. We investigated whether an imaging-based approach, combining pretreatment hypoxia and tumor response during therapy, could improve risk classification. Ninety-three LACC patients with T2-weigthed (T2W)-, dynamic contrast enhanced (DCE)- and diffusion weighted (DW)-magnetic resonance (MR) images acquired before treatment, and T2W- and, for 64 patients, DW-MR images, acquired at brachytherapy, were collected. Pretreatment hypoxic fraction (HF HF The combination of pretreatment hypoxia and volume regression at brachytherapy improved patient risk classification. Integration of ADC with volume regression showed promise as a new tumor response parameter.

ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma

A European consensus conference on endometrial carcinoma was held in 2014 to produce multidisciplinary evidence-based guidelines on selected questions. Given the large body of literature on the management of endometrial carcinoma published since 2014, the European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy & Oncology (ESTRO) and the European Society of Pathology (ESP) jointly decided to update these evidence-based guidelines and to cover new topics in order to improve the quality of care for women with endometrial carcinoma across Europe and worldwide. ESGO/ESTRO/ESP nominated an international multidisciplinary development group consisting of practicing clinicians and researchers who have demonstrated leadership and expertise in the care and research of endometrial carcinoma (27 experts across Europe). To ensure that the guidelines are evidence-based, the literature published since 2014, identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 191 independent international practitioners in cancer care delivery and patient representatives. The guidelines comprehensively cover endometrial carcinoma staging, definition of prognostic risk groups integrating molecular markers, pre- and intra-operative work-up, fertility preservation, management for early, advanced, metastatic, and recurrent disease and palliative treatment. Principles of radiotherapy and pathological evaluation are also defined.

Development of an age- and comorbidity- adjusted optimal radiotherapy utilisation rate for lung, rectal, prostate and cervical cancers

Optimal radiotherapy utilisation (RTU) modelling estimates the proportion of people with cancer who would benefit from radiotherapy. Assessment of comorbidities is an important component of the assessment of suitability for radiotherapy in addition to chronological age and life expectancy. Comorbidities have not been considered in previous optimal RTU models. We aimed to develop an age- and comorbidity- adjusted optimal RTU model for patients with lung, rectal, prostate, and cervical cancer, and compare them to actual RTU rates, with a particular focus on those aged 80+ years, METHODS: New South Wales (NSW) Cancer Registry data (2010-2014) linked to radiotherapy data (2010-2015) and hospitalisation data (2008-2015) were used to determine the number of patients diagnosed with lung, rectal, prostate and cervical cancer. The Cancer Specific C3 'all sites' comorbidity index was calculated from hospital diagnosis data for each patient to determine suitability for radiotherapy. The index was then incorporated into a tumour site-specific decision tree model. The actual RTU was also calculated using the linked datasets. 14,696 patients were diagnosed with non-small cell lung cancer (NSCLC), 1839 with small cell lung cancer (SCLC), 5551 with rectal cancer, 30,935 with prostate cancer and 1216 with cervical cancer in New South Wales from 2010-2014. The proportion of patients aged 80+ years at cancer diagnosis was 25% (3603 patients), 15% (279 patients), 17% (943 patients), 12% (3745 patients), and 7% (88 patients) respectively. The age- and comorbidity- adjusted optimal RTU rates for patients aged 80+ years using the C3 index were 49% (NSCLC), 49% (SCLC), 43% (rectal), 51% (prostate) and 40% (cervical). The corresponding actual RTU rates for patients aged 80+ years were 25%, 32%, 27%, 16%, and 56%. Even after adjusting for age and comorbidities, the actual radiotherapy utilisation rates were lower than optimal radiotherapy utilisation rates in patients aged 80+ years except for patients with cervical cancer. This warrants further assessment and research into reasons and solutions.

MRI radiomics nomogram integrating postoperative adjuvant treatments in recurrence risk prediction for patients with early-stage cervical cancer

Adjuvant treatments are valuable to decrease the recurrence rate and improve survival for early-stage cervical cancer patients (ESCC), Therefore, recurrence risk evaluation is critical for the choice of postoperative treatment. A magnetic resonance imaging (MRI) based radiomics nomogram integrating postoperative adjuvant treatments was constructed and validated externally to improve the recurrence risk prediction for ESCC. 212 ESCC patients underwent surgery and adjuvant treatments from three centers were enrolled and divided into the training, internal validation, and external validation cohorts. Their clinical data, pretreatment T2-weighted images (T2WI) were retrieved and analyzed. Radiomics models were constructed using machine learning methods with features extracted and screen from sagittal and axial T2WI. A nomogram for recurrence prediction was build and evaluated using multivariable logistic regression analysis integrating radiomic signature and adjuvant treatments. A total of 8 radiomic features were screened out of 1020 extracted features. The extreme gradient boosting (XGboost) model based on MRI radiomic features performed best in recurrence prediction with an area under curve (AUC) of 0.833, 0.822 in the internal and external validation cohorts, respectively. The nomogram integrating radiomic signature and clinical factors achieved an AUC of 0.806, 0.718 in the internal and external validation cohorts, respectively, for recurrence risk prediction for ESCC. In this study, the nomogram integrating T2WI radiomic signature and clinical factors is valuable to predict the recurrence risk, thereby allowing timely planning for effective treatments for ESCC with high risk of recurrence.

Radiation- versus surgery-based treatment for patients with resectable IIIC1 cervical adenocarcinoma

To describe the utilization trend of radiation-based and surgery-based treatment in patients with resectable IIIC1 cervical adenocarcinoma and explore the optimal treatment strategy for these patients. Patients with resectable IIIC1 cervical adenocarcinoma in 2005-2022 from Surveillance, Epidemiology, and End Results program (SEER) were analyzed. Trends over time in the utilization of radiation- and surgery-based treatment were plotted and estimated using Mantel-Haenszel test. Logistic regression analysis was performed to identify factors associated with the utilization of treatment. Survival outcomes were assessed and compared using Kaplan-Meire method and log-rank test, respectively. Inverse probability of treatment weighting (IPTW) was performed for adjustment of baseline characteristics. Sensitivity analysis was conducted using a cohort of cervical adenocarcinoma patients from our institution. The utilization of radiation-based treatment has grown steadily from 2005 to 2022 while the trend for surgery-based treatment showed opposite way (P = 0.002). Age, year of diagnosed, tumor size and T stage impacted the utilization of radiation-based treatment (All P < 0.05). Surgery-based treatment demonstrated superior overall survival (HR = 0.55, 95%CI:0.44-0.69; P < 0.001) and cancer specific survival (HR = 0.58, 95%CI:0.45-0.75; P < 0.001) to radiation-based treatment before adjustment of IPTW. However, no significant differences were observed in overall survival (HR = 0.77, 95%CI:0.56-1.05; P = 0.1) and cancer specific survival (HR = 0.86, 95%CI:0.60-1.23; P = 0.4) after baseline characteristics were balanced. Besides, the cohort from our institution further verified that similar survival outcomes were observed between two treatment strategies. The utilization of radiation-based treatment has increased over time and showed non-inferior efficacy for patients with resectable IIIC1 cervical adenocarcinoma when compared to surgery-based treatment.

Development and validation of a deep learning algorithm for auto-delineation of clinical target volume and organs at risk in cervical cancer radiotherapy

The delineation of the clinical target volume (CTV) is a crucial, laborious and subjective step in cervical cancer radiotherapy. The aim of this study was to propose and evaluate a novel end-to-end convolutional neural network (CNN) for fully automatic and accurate CTV in cervical cancer. A total of 237 computed tomography (CT) scans of patients with locally advanced cervical cancer were collected and evaluated. A novel 2.5D CNN network, called DpnUNet, was developed for CTV delineation and further applied for CTV and organ-at-risk (OAR) delineation simultaneously. Comprehensive comparisons and experiments were performed. The mean Dice similarity coefficient (DSC), 95th percentile Hausdorff distance (95HD) and subjective evaluation were used to assess the performance of this method. The mean DSC and 95HD values were 0.86 and 5.34 mm for the delineated CTVs. The clinical experts' subjective assessments showed that 90% of the predicted contours were acceptable for clinical usage. The mean DSC and 95HD values were 0.91 and 4.05 mm for bladder, 0.85 and 2.16 mm for bone marrow, 0.90 and 1.27 mm for left femoral head, 0.90 and 1.51 mm for right femoral head, 0.82 and 4.29 mm for rectum, 0.85 and 4.35 mm for bowel bag, 0.82 and 4.96 mm for spinal cord respectively. The average delineation time for one patient's CT images was within 15 seconds. The experimental results demonstrate that the CTV and OARs delineated for cervical cancer by DpnUNet was in close agreement with the ground truth. DpnUNet could significantly reduce the radiation oncologists' contouring time.

Nine years of plan of the day for cervical cancer: Plan library remains effective compared to fully online-adaptive techniques

Since 2011, our center has been using a library-based Plan-of-the-Day (PotD) strategy for external beam radiotherapy of cervical cancer patients to reduce normal tissue dose while maintaining adequate target coverage. With the advent of fully online-adaptive techniques such as daily online-adaptive replanning, further dose reduction may be possible. However, it is unknown how this reduction relates to plan library approaches, and how the most recent PotD strategies relate to no adaptation. In this study we compare the performance of our current PotD strategy with non-adaptive and fully online-adaptive techniques in terms of target volume size and normal tissue sparing. Treatment data of 376 patients treated with the PotD protocol between June 2011 and April 2020 were included. The size of the Planning Target Volumes (PTVs) was reconstructed for different strategies: full online adaptation, no adaptation, and the latest clinical version of the PotD protocol. Normal tissue sparing was estimated by the difference in margin volume to construct the PTV and the volume overlap of the PTV with bladder and rectum. The current version of our PotD approach reduced the PTV margin volume by a median of 250 cm The current version of the PotD protocol is an effective technique to improve normal tissue sparing compared to no adaptation. Further sparing can be achieved using fully online-adaptive techniques, but at the cost of a more complex workflow and with a potentially limited impact. PotD-type protocols can therefore be considered as a suitable alternative to fully online-adaptive approaches.

Gynaecological reirradiation with image-guided radiotherapy: Tumour Control Probability and Normal Tissue Complication Probability in pre-immunotherapy era

Management of recurrent gynaecological cancers after previous pelvic radiation is challenging. This institutional cohort describes clinical outcomes with image-guided radiotherapy techniques. From 2020 to 2023, patients with recurrent or second primary gynaecological malignancies previously treated with radiotherapy were included. Reirradiation was delivered using image-guided volumetric arc therapy (IG-VMAT), stereotactic body radiotherapy (SBRT), and/or image-guided brachytherapy (IGBT) as clinically appropriate. Infield control, progression-free survival (PFS), and overall survival (OS) were estimated using the Kaplan-Meier method. Prognostic factors for infield control were assessed with uni- and multivariate analyses. Adverse events were reported (CTCAE version 5.0). The dose-response effect for tumour control and late effects were estimated. Seventy patients underwent reirradiation. Of these 62 (88.5 %), 6 (8.5 %), and 2 (2.8 %) had cervical cancer, endometrial cancer, and vulvovaginal cancer, respectively. The majority of patients had squamous cell histology (81.4 %). Fifty-nine patients (84.2 %) were treated for local and/ or nodal recurrence, and 11 patients were treated (15.8 %) for second primary cancer. The median reirradiation dose was 50 Gy (IQR 42.2-64.2 Gy). In this cohort, 34/70 (48.6 %) patients received systemic chemotherapy, and no Bevacizumab or Immunotherapy. With a median follow-up of 37 months, the 3-year infield control, PFS, and OS were 63.5 %, 62.4 %, and 68 %, respectively. Reirradiation dose ≥50 Gy and disease-free interval ≥24 months were independently associated with improved infield control (p = 0.04, 0.004). Grade ≥3 gastrointestinal/genitourinary toxicity occurred in 18.5 % patients. Cumulative EQD2 ≥130 Gy Image-guided radiotherapy techniques for reirradiation achieve excellent local control with acceptable toxicity in patients with recurrent gynaecological cancers.

Should we embrace hypofractionated radiotherapy for cervical cancer? A technical note on management during the COVID-19 pandemic

Cervical cancer is a deadly disease and the COVID-19 pandemic has the potential to further impact its lethality. Hypofractionated radiotherapy could mitigate this impact, however robust data in cervical cancer setting still is lacking. Information provided here could help institutions in reducing radiotherapy fractions for cervical cancer patients.

Sensitivity of radiomic features to inter-observer variability and image pre-processing in Apparent Diffusion Coefficient (ADC) maps of cervix cancer patients

The aims of this study are to evaluate the stability of radiomic features from Apparent Diffusion Coefficient (ADC) maps of cervical cancer with respect to: (1) reproducibility in inter-observer delineation, and (2) image pre-processing (normalization/quantization) prior to feature extraction. Two observers manually delineated the tumor on ADC maps derived from pre-treatment diffusion-weighted Magnetic Resonance imaging of 81 patients with FIGO stage IB-IVA cervical cancer. First-order, shape, and texture features were extracted from the original and filtered images considering 5 different normalizations (four taken from the available literature, and one based on urine ADC) and two different quantization techniques (fixed-bin widths from 0.05 to 25, and fixed-bin count). Stability of radiomic features was assessed using intraclass correlation coefficient (ICC): poor (ICC < 0.75); good (0.75 ≤ ICC ≤ 0.89), and excellent (ICC ≥ 0.90). Dependencies of the features with tumor volume were assessed using Spearman's correlation coefficient (ρ). The approach using urine-normalized values together with a smaller bin width (0.05) was the most reproducible (428/552, 78% features with ICC ≥ 0.75); the fixed-bin count approach was the least (215/552, 39% with ICC ≥ 0.75). Without normalization, using a fixed bin width of 25, 348/552 (63%) of features had an ICC ≥ 0.75. Overall, 26% (range 25-30%) of the features were volume-dependent (ρ ≥ 0.6). None of the volume-independent shape features were found to be reproducible. Applying normalization prior to features extraction increases the reproducibility of ADC-based radiomics features. When normalization is applied, a fixed-bin width approach with smaller widths is suggested.

MRI-based contouring of functional sub-structures of the lower urinary tract in gynaecological radiotherapy

Research in radiation-induced urinary morbidity is limited by lack of guidelines for contouring and dose assessment of the lower urinary tract. Based on literature regarding anatomy, physiology and imaging of the lower urinary tract, this study aimed to provide advice on contouring of relevant sub-structures, reference points and reference dimensions for gynaecological radiotherapy. 210 MRIs for Image-Guided Adaptive Brachytherapy (IGABT) were analysed in 105 locally advanced cervical cancer patients treated with radio(chemo)therapy. Sub-structures (trigone, bladder neck and urethra) were contoured and trigone height (TH) and width (TW) were measured. Internal urethral ostium (IUO) and Posterior inferior border of pubic symphysis-urethra (PIBS-U) points were used to identify proximal and middle/low urethra, respectively. Urethra reference length (URL) was defined as IUO and PIBS-U distance. TH, TW and URL were also quantified on 54 MRIs acquired for External Beam Radiotherapy (EBRT). Median absolute differences in volumes and dimensions between first and second IGABT fraction were 0.7 cm This study proposed relevant urinary sub-structures and dose points and showed that standardized contouring is reproducible. Trigone reference dimensions are robust despite different bladder filling and treatment conditions. Standardized contouring and reference points may improve understanding of urinary morbidity.

Trials and tribulations of bone marrow sparing radiotherapy for cervical cancer. Re: Zhou et al. Radiother Oncol. 2021;165:103–118

Correlations between bone marrow radiation dose and hematologic toxicity in locally advanced cervical cancer patients receiving chemoradiation with cisplatin: a systematic review

Patients with locally advanced cervical cancer (LACC) treated with chemoradiation often experience hematologic toxicity (HT), as chemoradiation can induce bone marrow (BM) suppression. Studies on the relationship between BM dosimetric parameters and clinically significant HT might provide relevant indices for developing BM sparing (BMS) radiotherapy techniques. This systematic review studied the relationship between BM dose and HT in patients with LACC treated with primary cisplatin-based chemoradiation. A systematic search was conducted in Embase, Medline, and Web of Science. Eligibility criteria were treatment of LACC-patients with cisplatin-based chemoradiation and report of HT or complete blood cell count (CBC). The search identified 1346 papers, which were screened on title and abstract before two reviewers independently evaluated the full-text. 17 articles were included and scored according to a selection of the TRIPOD criteria. The mean TRIPOD score was 12.1 out of 29. Fourteen studies defining BM as the whole pelvic bone contour (PB) detected significant associations with V10 (3/14), V20 (6/14), and V40 (4/11). Recommended cut-off values were V10 > 95-75%, V20 > 80-65%, and V40 > 37-28%. The studies using lower density marrow spaces (PBM) or active bone marrow (ABM) as a proxy for BM only found limited associations with HT. Our study was the first literature review providing an overview of articles evaluating the correlation between BM and HT for patients with LACC undergoing cisplatin-based chemoradiation. There is a scarcity of studies independently validating developed prediction models between BM dose and HT. Future studies may use PB contouring to develop normal tissue complication probability models.

Brachytherapy for locally advanced cervical cancer: A survey of UK provision of care and support

Gynaecological brachytherapy can cause anxiety, distress and discomfort. It is not known how variation in delivery impacts women's experiences. To inform future research an online survey was carried out to identify variations in brachytherapy and support available to women receiving treatment for locally advanced cervical cancer (LACC). An online survey was sent to 44 UK brachytherapy centres using the Qualtrics® survey platform. It included questions about brachytherapy scheduling, inpatient/day case treatment, anaesthetic/analgesia, non-pharmacological support and health professionals' opinions regarding holistic care. A mixture of closed questions with pre-specified options and open questions were employed. Descriptive statistics were generated to identify variance in UK practice. Free text responses were analysed using inductive content analysis. Responses were received from 39/43 eligible centres (91% response rate). Brachytherapy was predominantly given on an inpatient basis at 65% and day case at 35% of centres. Eleven scheduling regimes were reported with typical duration of brachytherapy ranging from three to 52 h. The main categories identified in response to what worked well were: 'consistency of staff'; 'good information provision' and 'experienced/skilled/senior staff'. The main categories identified as needing improvement were: 'training of different staff groups' and 'follow up and support' with many suggestions for service improvements. The survey provided a comprehensive overview of brachytherapy services for LACC demonstrating wide variability in scheduling regimes, duration of treatment and holistic care. The findings support the need to explore women's experiences with a range of treatment regimes and anaesthesia and analgesia techniques to inform improvements to future clinical care.