Safety and Tolerability of Online Adaptive High-Field Magnetic Resonance-Guided Radiotherapy.

Importance: In 2018, the first online adaptive magnetic resonance (MR)-guided radiotherapy (MRgRT) system using a 1.5-T MR-equipped linear accelerator (1.5-T MR-Linac) was clinically introduced. This system enables online adaptive radiotherapy, in which the radiation plan is adapted to size and shape changes of targets at each treatment session based on daily MR-visualized anatomy. Objective: To evaluate safety, tolerability, and technical feasibility of treatment with a 1.5-T MR-Linac, specifically focusing on the subset of patients treated with an online adaptive strategy (ie, the adapt-to-shape [ATS] approach). Design, Setting, and Participants: This cohort study included adults with solid tumors treated with a 1.5-T MR-Linac enrolled in Multi Outcome Evaluation for Radiation Therapy Using the MR-Linac (MOMENTUM), a large prospective international study of MRgRT between February 2019 and October 2021. Included were adults with solid tumors treated with a 1.5-T MR-Linac. Data were collected in Canada, Denmark, The Netherlands, United Kingdom, and the US. Data were analyzed in August 2023. Exposure: All patients underwent MRgRT using a 1.5-T MR-Linac. Radiation prescriptions were consistent with institutional standards of care. Main Outcomes and Measures: Patterns of care, tolerability, and technical feasibility (ie, treatment completed as planned). Acute high-grade radiotherapy-related toxic effects (ie, grade 3 or higher toxic effects according to Common Terminology Criteria for Adverse Events version 5.0) occurring within the first 3 months after treatment delivery. Results: In total, 1793 treatment courses (1772 patients) were included (median patient age, 69 years [range, 22-91 years]; 1384 male [77.2%]). Among 41 different treatment sites, common sites were prostate (745 [41.6%]), metastatic lymph nodes (233 [13.0%]), and brain (189 [10.5%]). ATS was used in 1050 courses (58.6%). MRgRT was completed as planned in 1720 treatment courses (95.9%). Patient withdrawal caused 5 patients (0.3%) to discontinue treatment. The incidence of radiotherapy-related grade 3 toxic effects was 1.4% (95% CI, 0.9%-2.0%) in the entire cohort and 0.4% (95% CI, 0.1%-1.0%) in the subset of patients treated with ATS. There were no radiotherapy-related grade 4 or 5 toxic effects. Conclusions and Relevance: In this cohort study of patients treated on a 1.5-T MR-Linac, radiotherapy was safe and well tolerated. Online adaptation of the radiation plan at each treatment session to account for anatomic variations was associated with a low risk of acute grade 3 toxic effects.

Predicting cervical cancer target motion using a multivariate regression model to enable patient selection for adaptive external beam radiotherapy.

Background and purpose: Interfraction motion during cervical cancer radiotherapy is substantial in some patients, minimal in others. Non-adaptive plans may miss the target and/or unnecessarily irradiate normal tissue. Adaptive radiotherapy leads to superior dose-volume metrics but is resource-intensive. The aim of this study was to predict target motion, enabling patient selection and efficient resource allocation. Materials and methods: Forty cervical cancer patients had CT with full-bladder (CT-FB) and empty-bladder (CT-EB) at planning, and daily cone-beam CTs (CBCTs). The low-risk clinical target volume (CTVLR) was contoured. Mean coverage of the daily CTVLR by the CT-FB CTVLR was calculated for each patient. Eighty-three investigated variables included measures of organ geometry, patient, tumour and treatment characteristics. Models were trained on 29 patients (171 fractions). The Two-CT multivariate model could use all available data. The Single-CT multivariate model excluded data from the CT-EB. A univariate model was trained using the distance moved by the uterine fundus tip between CTs, the only method of patient selection found in published cervix plan-of-the-day studies. Models were tested on 11 patients (68 fractions). Accuracy in predicting mean coverage was reported as mean absolute error (MAE), mean squared error (MSE) and R2. Results: The Two-CT model was based upon rectal volume, dice similarity coefficient between CT-FB and CT-EB CTVLR, and uterine thickness. The Single-CT model was based upon rectal volume, uterine thickness and tumour size. Both performed better than the univariate model in predicting mean coverage (MAE 7 %, 7 % and 8 %; MSE 82 %2, 65 %2, 110 %2; R2 0.2, 0.4, -0.1). Conclusion: Uterocervix motion is complex and multifactorial. We present two multivariate models which predicted motion with reasonable accuracy using pre-treatment information, and outperformed the only published method.

Circulating HPV DNA as a Biomarker for Pre-Invasive and Early Invasive Cervical Cancer: A Feasibility Study.

BACKGROUND: High-risk HPV infection is responsible for >99% of cervix cancers (CC). In persistent infections that lead to cancer, the tumour breaches the basement membrane, releasing HPV-DNA into the bloodstream (cHPV-DNA). A next-generation sequencing assay (NGS) for detection of plasma HPV circulating DNA (cHPV-DNA) has demonstrated high sensitivity and specificity in patients with locally advanced cervix cancers. We hypothesised that cHPV-DNA is detectable in early invasive cervical cancers but not in pre-invasive lesions (CIN). METHODS: Blood samples were collected from patients with CIN (n = 52) and FIGO stage 1A-1B CC (n = 12) prior to treatment and at follow-up. DNA extraction from plasma, followed by NGS, was used for the detection of cHPV-DNA. RESULTS: None of the patients with pre-invasive lesions were positive for CHPV-DNA. In invasive tumours, plasma from one patient (10%) reached the threshold of positivity for cHPV-DNA in plasma. CONCLUSION: Low detection of cHPV-DNA in early CC may be explained by small tumour size, poorer access to lymphatics and circulation, and therefore little shedding of cHPV-DNA in plasma at detectable levels. The detection rate of cHPV-DNA in patients with early invasive cervix cancer using even the most sensitive of currently available technologies lacks adequate sensitivity for clinical utility.

Predicting Response to Radical Chemoradiotherapy with Circulating HPV DNA (cHPV-DNA) in Locally Advanced Uterine Cervix Cancer.

BACKGROUND: The majority of locally advanced cervical cancers (LaCC) are causally related to HPV. We sought to investigate the utility of an ultra-sensitive HPV-DNA next generation sequencing (NGS) assay-panHPV-detect-in LaCC treated with chemoradiotherapy, as a marker of treatment response and persistent disease. METHOD: Serial blood samples were collected from 22 patients with LaCC before, during and after chemoradiation. The presence of circulating HPV-DNA was correlated with clinical and radiological outcomes. RESULTS: The panHPV-detect test demonstrated a sensitivity and specificity of 88% (95% CI-70-99%) and 100% (95% CI-30-100%), respectively, and correctly identified the HPV-subtype (16, 18, 45, 58). After a median follow up of 16 months, and three relapses all had detectable cHPV-DNA at 3 months post-CRT despite complete response on imaging. Another four patients with radiological partial or equivocal response and undetectable cHPV-DNA at the 3-month time point did not go on to develop relapse. All patients with radiological CR and undetectable cHPV-DNA at 3-months remained disease free. CONCLUSIONS: These results demonstrate that the panHPV-detect test shows high sensitivity and specificity for detecting cHPV-DNA in plasma. The test has potential applications in assessment of the response to CRT and in monitoring for relapse, and these initial findings warrant validation in a larger cohort.

Carpe Diem: Making the Most of Plan-of-the-Day for Cervical Cancer Radiation Therapy.

PURPOSE: Radiation therapy is the key treatment for locally advanced cervical cancer. Organ motion presents a challenge to accurate targeting of external beam radiation therapy. The plan-of-the-day (PotD) adaptive approach is therefore an attractive option. We present our experience and the procedural steps required to implement PotD for cervix cancer. METHODS AND MATERIALS: We reviewed relevant studies on organ motion and adaptive radiation therapy identified through a literature search and cross referencing. These included 10 dosimetric and 3 quality of life studies directly assessing the PotD approach to radiation therapy in cervix cancer. RESULTS: Studies show improvements in target coverage and reduction of dose received by normal tissues and suggest improved toxicity. Clinical implementation of PotD has been slow because of a number of difficulties and uncertainties, which we discuss with the aim of helping teams to implement PotD at their center. CONCLUSIONS: The PotD approach improves dosimetry and may improve toxicity. We describe a framework to assist with practical implementation.

T-cell receptor determinants of response to chemoradiation in locally-advanced HPV16-driven malignancies.

Background: The effect of chemoradiation on the anti-cancer immune response is being increasingly acknowledged; however, its clinical implications in treatment responses are yet to be fully understood. Human papillomavirus (HPV)-driven malignancies express viral oncogenic proteins which may serve as tumor-specific antigens and represent ideal candidates for monitoring the peripheral T-cell receptor (TCR) changes secondary to chemoradiotherapy (CRT). Methods: We performed intra-tumoral and pre- and post-treatment peripheral TCR sequencing in a cohort of patients with locally-advanced HPV16-positive cancers treated with CRT. An in silico computational pipeline was used to cluster TCR repertoire based on epitope-specificity and to predict affinity between these clusters and HPV16-derived epitopes. Results: Intra-tumoral repertoire diversity, intra-tumoral and post-treatment peripheral CDR3ß similarity clustering were predictive of response. In responders, CRT triggered an increase peripheral TCR clonality and clonal relatedness. Post-treatment expansion of baseline peripheral dominant TCRs was associated with response. Responders showed more baseline clustered structures of TCRs maintained post-treatment and displayed significantly more maintained clustered structures. When applying clustering by TCR-specificity methods, responders displayed a higher proportion of intra-tumoral TCRs predicted to recognise HPV16 peptides. Conclusions: Baseline TCR characteristics and changes in the peripheral T-cell clones triggered by CRT are associated with treatment outcome. Maintenance and boosting of pre-existing clonotypes are key elements of an effective anti-cancer immune response driven by CRT, supporting a paradigm in which the immune system plays a central role in the success of CRT in current standard-of-care protocols.

Diffusion-weighted MRI to determine response and long-term clinical outcomes in muscle-invasive bladder cancer following neoadjuvant chemotherapy.

Objective: This study aims to determine local treatment response and long-term survival outcomes in patients with localised muscle-invasive bladder cancer (MIBC) patients receiving neoadjuvant chemotherapy (NAC) using diffusion-weighted MRI (DWI) and apparent diffusion coefficient (ADC) analysis. Methods: Patients with T2-T4aN0-3M0 bladder cancer suitable for NAC were recruited prospectively. DWI was performed prior to NAC and was repeated following NAC completion. Conventional response assessment was performed with cystoscopy and tumour site biopsy. Response was dichotomised into response (15.5% was associated with significant improvement in OS (HR, 0.40; 95% CI, 0.19-0.86; p=0.0179), bCSS (HR, 0.26; 95% CI, 0.08-0.82; p=0.0214), PFS (HR, 0.16; 95% CI, 0.05-0.48; p=0.0012), and time to cystectomy (HR, 0.19; 95% CI, 0.07-0.47; p=0.0004). Conclusions: Quantitative ADC analysis can successfully identify NAC response and improved long-term clinical outcomes. Multi-centre validation to assess reproducibility and repeatability is required before testing within clinical trials to inform MIBC treatment decision making. Advances in knowledge: We successfully demonstrated that measured change in DWI can successfully identify NAC response and improved long-term survival outcomes.

The development and validation of a decision aid to facilitate patient choice of surgery versus radiotherapy for high-risk basal cell carcinoma.

Basal cell carcinoma (BCC) is an increasingly common cancer. For high-risk BCCs, there are several treatment options, with similar efficacies. The current best practice in deciding upon a particular treatment is for a patient-centred approach. At present, there are few resources available for patients to assist their choice. This reduces patient autonomy and increases the burden on clinicians within clinic. Patient decision aids (PDAs) have been shown to increase patient autonomy and facilitate shared decision-making. Currently, there is no published PDA designed to facilitate the decision between surgical management or radiotherapy in high-risk BCCs. We developed a novel decision aid designed along the International Patient Decision Aid Standards to fill this clinical need, and evaluated its acceptance by both patients and clinicians. We describe the challenges faced at initial alpha and subsequent beta testing, and go on to validate our PDA with both the Decisional Conflict Scale and the nine-item Shared Decision Making Questionnaire (SDMQ9). We include an example of the PDA and encourage other units to modify the PDA for their own use.

Quantitative analysis of diffusion weighted imaging in rectal cancer during radiotherapy using a magnetic resonance imaging integrated linear accelerator.

Background and purpose: Magnetic resonance imaging integrated linear accelerator (MR-Linac) platforms enable acquisition of diffusion weighted imaging (DWI) during treatment providing potential information about treatment response. Obtaining DWI on these platforms is technically different from diagnostic magnetic resonance imaging (MRI) scanners. The aim of this project was to determine feasibility of obtaining DWI and calculating apparent diffusion coefficient (ADC) parameters longitudinally in rectal cancer patients on the MR-Linac. Materials and methods: Nine patients undergoing treatment on MR-Linac had DWI acquired using b-values 0, 30, 150, 500 s/mm2. Gross tumour volume (GTV) and normal tissue was delineated on DWI throughout treatment and median ADC was calculated using an in-house tool (pyOsirix ®). Results: Seven out of nine patients were included in the analysis; all demonstrated downstaging at follow-up. A total of 63 out of 70 DWI were analysed (7 excluded due to poor image quality). An increasing trend of ADC median for GTV (1.15 × 10-3 mm2/s interquartile range (IQ): 1.05-1.17 vs 1.59 × 10-3 mm2/s IQ: 1.37 - 1.64; p = 0.0156), correlating to treatment response. In comparison ADC median for normal tissue remained the same between first and last fraction (1.61 × 10-3 mm2/s IQ: 1.56-1.71 vs 1.67 × 10-3 mm2/s IQ: 1.37-2.00; p = 0.9375). Conclusions: DWI assessment in rectal cancer patients on MR-Linac is feasible. Initial results provide foundations for further studies to determine DWI use for treatment adaptation in rectal cancer.

Interobserver variability in target volume delineation for CT/MRI simulation and MRI-guided adaptive radiotherapy in rectal cancer.

OBJECTIVES: Quantify target volume delineation uncertainty for CT/MRI simulation and MRI-guided adaptive radiotherapy in rectal cancer. Define optimal imaging sequences for target delineation. METHODS: Six experienced radiation oncologists delineated clinical target volumes (CTVs) on CT and 2D and 3D-MRI in three patients with rectal cancer, using consensus contouring guidelines. Tumour GTV (GTVp) was also contoured on MRI acquired week 0 and 3 of radiotherapy. A STAPLE contour was created and volume and interobserver variability metrics were analysed. RESULTS: There were statistically significant differences in volume between observers for CT and 2D-MRI-defined CTVs (p < 0.05). There was no significant difference between observers on 3D-MRI. Significant differences in volume were seen between observers for both 2D and 3D-MRI-defined GTVp at weeks 0 and 3 (p < 0.05). Good interobserver agreement (IOA) was seen for CTVs delineated on all imaging modalities with best IOA on 3D-MRI; median Conformity index (CI) 0.74 for CT, 0.75 for 2D-MRI and 0.77 for 3D-MRI. IOA of MRI-defined GTVp week 0 was better compared to CT; CI 0.58 for CT, 0.62 for 2D-MRI and 0.7 for 3D-MRI. MRI-defined GTVp IOA week three was worse compared to week 0. CONCLUSION: Delineation on MRI results in smaller volumes and better IOA week 0 compared to CT. 3D-MRI provides the best IOA in CTV and GTVp. MRI-defined GTVp on images acquired week 3 showed worse IOA compared to week 0. This highlights the need for consensus guidelines in GTVp delineation on MRI during treatment course in the context of dose escalation MRI-guided rectal boost studies. ADVANCES IN KNOWLEDGE: Optimal MRI sequences for CT/MRI simulation and MRI-guided adaptive radiotherapy in rectal cancer have been defined.

Automatic Segmentation of Pelvic Cancers Using Deep Learning: State-of-the-Art Approaches and Challenges.

The recent rise of deep learning (DL) and its promising capabilities in capturing non-explicit detail from large datasets have attracted substantial research attention in the field of medical image processing. DL provides grounds for technological development of computer-aided diagnosis and segmentation in radiology and radiation oncology. Amongst the anatomical locations where recent auto-segmentation algorithms have been employed, the pelvis remains one of the most challenging due to large intra- and inter-patient soft-tissue variabilities. This review provides a comprehensive, non-systematic and clinically-oriented overview of 74 DL-based segmentation studies, published between January 2016 and December 2020, for bladder, prostate, cervical and rectal cancers on computed tomography (CT) and magnetic resonance imaging (MRI), highlighting the key findings, challenges and limitations.

Online Magnetic Resonance-Guided Radiotherapy (oMRgRT) for Gynecological Cancers.

Radiation therapy (RT) is increasingly being used in gynecological cancer management. RT delivered with curative or palliative intent can be administered alone or combined with chemotherapy or surgery. Advanced treatment planning and delivery techniques such as intensity-modulated radiation therapy, including volumetric modulated arc therapy, and image-guided adaptive brachytherapy allow for highly conformal radiation dose delivery leading to improved tumor control rates and less treatment toxicity. Quality on-board imaging that provides accurate visualization of target and surrounding organs at risk is a critical feature of these advanced techniques. As soft tissue contrast resolution is superior with magnetic resonance imaging (MRI) compared to other imaging modalities, MRI has been used increasingly to delineate tumor from adjacent soft tissues and organs at risk from initial diagnosis to tumor response evaluation. Gynecological cancers often have poor contrast resolution compared to the surrounding tissues on computed tomography scan, and consequently the benefit of MRI is high. One example is in management of locally advanced cervix cancer where adaptive MRI guidance has been broadly implemented for adaptive brachytherapy. The role of MRI for external beam RT is also steadily increasing. MRI information is being used for treatment planning, predicting, and monitoring position shifts and accounting for tissue deformation and target regression during treatment. The recent clinical introduction of online MRI-guided radiation therapy (oMRgRT) could be the next step in high-precision RT. This technology provides a tool to take full advantage of MRI not only at the time of initial treatment planning but as well as for daily position verification and online plan adaptation. Cervical, endometrial, vaginal, and oligometastatic ovarian cancers are being treated on MRI linear accelerator systems throughout the world. This review summarizes the current state, early experience, ongoing trials, and future directions of oMRgRT in the management of gynecological cancers.

CT-Based Pelvic T1-Weighted MR Image Synthesis Using UNet, UNet++ and Cycle-Consistent Generative Adversarial Network (Cycle-GAN).

BACKGROUND: Computed tomography (CT) and magnetic resonance imaging (MRI) are the mainstay imaging modalities in radiotherapy planning. In MR-Linac treatment, manual annotation of organs-at-risk (OARs) and clinical volumes requires a significant clinician interaction and is a major challenge. Currently, there is a lack of available pre-annotated MRI data for training supervised segmentation algorithms. This study aimed to develop a deep learning (DL)-based framework to synthesize pelvic T1-weighted MRI from a pre-existing repository of clinical planning CTs. METHODS: MRI synthesis was performed using UNet++ and cycle-consistent generative adversarial network (Cycle-GAN), and the predictions were compared qualitatively and quantitatively against a baseline UNet model using pixel-wise and perceptual loss functions. Additionally, the Cycle-GAN predictions were evaluated through qualitative expert testing (4 radiologists), and a pelvic bone segmentation routine based on a UNet architecture was trained on synthetic MRI using CT-propagated contours and subsequently tested on real pelvic T1 weighted MRI scans. RESULTS: In our experiments, Cycle-GAN generated sharp images for all pelvic slices whilst UNet and UNet++ predictions suffered from poorer spatial resolution within deformable soft-tissues (e.g. bladder, bowel). Qualitative radiologist assessment showed inter-expert variabilities in the test scores; each of the four radiologists correctly identified images as acquired/synthetic with 67%, 100%, 86% and 94% accuracy. Unsupervised segmentation of pelvic bone on T1-weighted images was successful in a number of test cases. CONCLUSION: Pelvic MRI synthesis is a challenging task due to the absence of soft-tissue contrast on CT. Our study showed the potential of deep learning models for synthesizing realistic MR images from CT, and transferring cross-domain knowledge which may help to expand training datasets for 21 development of MR-only segmentation models.

Patterns of Care, Tolerability, and Safety of the First Cohort of Patients Treated on a Novel High-Field MR-Linac Within the MOMENTUM Study: Initial Results From a Prospective Multi-Institutional Registry.

PURPOSE: High-field magnetic resonance-linear accelerators (MR-Linacs), linear accelerators combined with a diagnostic magnetic resonance imaging (MRI) scanner and online adaptive workflow, potentially give rise to novel online anatomic and response adaptive radiation therapy paradigms. The first high-field (1.5T) MR-Linac received regulatory approval in late 2018, and little is known about clinical use, patient tolerability of daily high-field MRI, and toxicity of treatments. Herein we report the initial experience within the MOMENTUM Study (NCT04075305), a prospective international registry of the MR-Linac Consortium. METHODS AND MATERIALS: Patients were included between February 2019 and October 2020 at 7 institutions in 4 countries. We used descriptive statistics to describe the patterns of care, tolerability (the percentage of patients discontinuing their course early), and safety (grade 3-5 Common Terminology Criteria for Adverse Events v.5 acute toxicity within 3 months after the end of treatment). RESULTS: A total 943 patients participated in the MOMENTUM Study, 702 of whom had complete baseline data at the time of this analysis. Patients were primarily male (79%) with a median age of 68 years (range, 22-93) and were treated for 39 different indications. The most frequent indications were prostate (40%), oligometastatic lymph node (17%), brain (12%), and rectal (10%) cancers. The median number of fractions was 5 (range, 1-35). Six patients discontinued MR-Linac treatments, but none due to an inability to tolerate repeated high-field MRI. Of the 415 patients with complete data on acute toxicity at 3-month follow-up, 18 (4%) patients experienced grade 3 acute toxicity related to radiation. No grade 4 or 5 acute toxicity related to radiation was observed. CONCLUSIONS: In the first 21 months of our study, patterns of care were diverse with respect to clinical utilization, body sites, and radiation prescriptions. No patient discontinued treatment due to inability to tolerate daily high-field MRI scans, and the acute radiation toxicity experience was encouraging.

The MOMENTUM Study: An International Registry for the Evidence-Based Introduction of MR-Guided Adaptive Therapy.

Purpose: MR-guided Radiation Therapy (MRgRT) allows for high-precision radiotherapy under real-time MR visualization. This enables margin reduction and subsequent dose escalation which may lead to higher tumor control and less toxicity. The Unity MR-linac (Elekta AB, Stockholm, Sweden) integrates a linear accelerator with a 1.5T diagnostic quality MRI and an online adaptive workflow. A prospective international registry was established to facilitate the evidence-based implementation of the Unity MR-linac into clinical practice, to systemically evaluate long-term outcomes, and to aid further technical development of MR-linac-based MRgRT. Methods and Results: In February 2019, the Multi-OutcoMe EvaluatioN of radiation Therapy Using the MR-linac study (MOMENTUM) started within the MR-linac Consortium. The MOMENTUM study is an international academic-industrial partnership between several hospitals and industry partner Elekta. All patients treated on the MR-linac are eligible for inclusion in MOMENTUM. For participants, we collect clinical patient data (e.g., patient, tumor, and treatment characteristics) and technical patient data which is defined as information generated on the MR-linac during treatment. The data are captured, pseudonymized, and stored in an international registry at set time intervals up to two years after treatment. Patients can choose to provide patient-reported outcomes and consent to additional MRI scans acquired on the MR-linac. This registry will serve as a data platform that supports multicenter research investigating the MR-linac. Rules and regulations on data sharing, data access, and intellectual property rights are summarized in an academic-industrial collaboration agreement. Data access rules ensure secure data handling and research integrity for investigators and institutions. Separate data access rules exist for academic and industry partners. This study is registered at ClinicalTrials.gov with ID: NCT04075305 (https://clinicaltrials.gov/ct2/show/NCT04075305). Conclusion: The multi-institutional MOMENTUM study has been set up to collect clinical and technical patient data to advance technical development, and facilitate evidenced-based implementation of MR-linac technology with the ultimate purpose to improve tumor control, survival, and quality of life of patients with cancer.

Ano-uro-genital mucosal melanoma UK national guidelines.

Ano-uro-genital (AUG) mucosal melanomas are rare cancers associated with poor outcomes and limited evidence-based management. The United Kingdom AUG mucosal melanoma guideline development group used an evidence-based systematic approach to make recommendations regarding the diagnosis, treatment and surveillance of patients diagnosed with AUG mucosal melanomas. The guidelines were sent for international peer review, and are accredited by The National Institute for Health and Clinical Excellence (NICE). A summary of the key recommendations is presented. The full documents are available on the Melanoma Focus website.

The Stacked-Ellipse Algorithm: An Ultrasound-Based 3-D Uterine Segmentation Tool for Enabling Adaptive Radiotherapy for Uterine Cervix Cancer.

The stacked-ellipse (SE) algorithm was developed to rapidly segment the uterus on 3-D ultrasound (US) for the purpose of enabling US-guided adaptive radiotherapy (RT) for uterine cervix cancer patients. The algorithm was initialised manually on a single sagittal slice to provide a series of elliptical initialisation contours in semi-axial planes along the uterus. The elliptical initialisation contours were deformed according to US features such that they conformed to the uterine boundary. The uterus of 15 patients was scanned with 3-D US using the Clarity System (Elekta Ltd.) at multiple days during RT and manually contoured (n = 49 images and corresponding contours). The median (interquartile range) Dice similarity coefficient and mean surface-to-surface-distance between the SE algorithm and manual contours were 0.80 (0.03) and 3.3 (0.2) mm, respectively, which are within the ranges of reported inter-observer contouring variabilities. The SE algorithm could be implemented in adaptive RT to precisely segment the uterus on 3-D US.

A proposed tailored investigational algorithm for women treated for gynaecological cancer with long-term gastrointestinal consequences.

BACKGROUND AND AIM: Long-term changes in gastrointestinal function impacting quality of life after treatment for cancer are common. Peer reviewed guidance to investigate and manage GI dysfunction following cancer treatment has been published. This study reviewed gastrointestinal symptoms of women previously treated for gynaecological cancer and considered whether suggested algorithms could be amended to optimise management for this cohort. METHODS: Demographic and clinical data recorded for patients attending a specialist consequences of cancer treatment gastroenterology service prospectively are reported using median and range. The Wilcoxon signed rank test analysed changes in symptoms between initial assessment to discharge from the service. RESULTS: Between April 2013 and March 2016, 220 women, with a median age of 57 years (range 24-83 years), treated for gynaecological cancer (cervical (50%)), endometrial (28%), ovarian (15%), vaginal or vulval (7%) attended. Twelve gastrointestinal symptoms were statistically significantly reduced by time of discharge from the specialist gastroenterology clinic including bowel frequency ≥ 4/day (88%), type 6 or 7 stool consistency (36%), urgency (31%) and incontinence (21%). General quality of life improved from a median score of 4 at first assessment to a median of 6 at discharge (p < 0.001). A median of four (range, 1-9) diagnoses were made. CONCLUSION: Women with gastrointestinal symptoms after cancer treatment benefit from a systematic management approach. After excluding disease recurrence, a proposed investigational algorithm and the oncology team includes FBC, U&Es, LFTs, thyroid function test, vitamin B12, vitamin D, a hydrogen methane breath test and a SeHCAT scan. If rectal bleeding is present, iron studies, flexible sigmoidoscopy or colonoscopy should be performed. Patients with normal investigations or symptoms not responding to treatment require gastroenterology input.

Realizing the potential of magnetic resonance image guided radiotherapy in gynaecological and rectal cancer.

CT-based radiotherapy workflow is limited by poor soft tissue definition in the pelvis and reliance on rigid registration methods. Current image-guided radiotherapy and adaptive radiotherapy models therefore have limited ability to improve clinical outcomes. The advent of MRI-guided radiotherapy solutions provides the opportunity to overcome these limitations with the potential to deliver online real-time MRI-based plan adaptation on a daily basis, a true "plan of the day." This review describes the application of MRI guided radiotherapy in two pelvic tumour sites likely to benefit from this approach.

Combined Ultrasound and Cone Beam CT Improves Target Segmentation for Image Guided Radiation Therapy in Uterine Cervix Cancer.

PURPOSE: Adaptive radiation therapy strategies could account for interfractional uterine motion observed in patients with cervix cancer, but the current cone beam computed tomography (CBCT)-based treatment workflow is limited by poor soft-tissue contrast. The goal of the present study was to determine if ultrasound (US) could be used to improve visualization of the uterus, either as a single modality or in combination with CBCT. METHODS AND MATERIALS: Interobserver uterine contour agreement and confidence were compared on 40 corresponding CBCT, US, and CBCT-US-fused images from 11 patients with cervix cancer. Contour agreement was measured using the Dice similarity coefficient (DSC) and mean contour-to-contour distance (MCCD). Observers rated their contour confidence on a scale from 1 to 10. Pairwise Wilcoxon signed-rank tests were used to measure differences in contour agreement and confidence. RESULTS: CBCT-US fused images had significantly better contour agreement and confidence than either individual modality (P < .05), with median (interquartile range [IQR]) values of 0.84 (0.11), 1.26 (0.23) mm, and 7 (2) for the DSC, MCCD, and observer confidence ratings, respectively. Contour agreement was similar between US and CBCT, with median (IQR) DSCs of 0.81 (0.17) and 0.82 (0.14) and MCCDs of 1.75 (1.15) mm and 1.62 (0.74) mm. Observers were significantly more confident in their US-based contours than in their CBCT-based contours (P < .05), with median (IQR) confidence ratings of 7 (2.75) versus 5 (4). CONCLUSIONS: CBCT and US are complementary and improve uterine segmentation precision when combined. Observers could localize the uterus with a similar precision on independent US and CBCT images.