Understanding the Benefit of Magnetic Resonance-guided Adaptive Radiotherapy in Rectal Cancer Patients: a Single-centre Study.

AIMS: Neoadjuvant chemoradiotherapy followed by surgery is the mainstay of treatment for patients with rectal cancer. Standard clinical target volume (CTV) to planning target volume (PTV) margins of 10 mm are used to accommodate inter- and intrafraction motion of target. Treating on magnetic resonance-integrated linear accelerators (MR-linacs) allows for online manual recontouring and adaptation (MRgART) enabling the reduction of PTV margins. The aim of this study was to investigate motion of the primary CTV (CTVA; gross tumour volume and macroscopic nodes with 10 mm expansion to cover microscopic disease) in order to develop a simultaneous integrated boost protocol for use on MR-linacs. MATERIALS AND METHODS: Patients suitable for neoadjuvant chemoradiotherapy were recruited for treatment on MR-linac using a two-phase technique; only the five phase 1 fractions on MR-linac were used for analysis. Intrafraction motion of CTVA was measured between pre-treatment and post-treatment MRI scans. In MRgART, isotropically expanded pre-treatment PTV margins from 1 to 10 mm were rigidly propagated to post-treatment MRI to determine overlap with 95% of CTVA. The PTV margin was considered acceptable if overlap was >95% in 90% of fractions. To understand the benefit of MRgART, the same methodology was repeated using a reference computed tomography planning scan for pre-treatment imaging. RESULTS: In total, nine patients were recruited between January 2018 and December 2020 with T3a-T4, N0-N2, M0 disease. Forty-five fractions were analysed in total. The median motion across all planes was 0 mm, demonstrating minimal intrafraction motion. A PTV margin of 3 and 5mm was found to be acceptable in 96 and 98% of fractions, respectively. When comparing to the computed tomography reference scan, the analysis found that PTV margins to 5 and 10 mm only acceptably covered 51 and 76% of fractions, respectively. CONCLUSION: PTV margins can be reduced to 3-5 mm in MRgART for rectal cancer treatment on MR-linac within an simultaneous integrated boost protocol.

Assessing Bladder Radiotherapy Response With Quantitative Diffusion-Weighted Magnetic Resonance Imaging Analysis.

AIMS: Radiotherapy with radiosensitisation offers opportunity for cure with organ preservation in muscle-invasive bladder cancer (MIBC). Treatment response assessment and follow-up are reliant on regular endoscopic evaluation of the retained bladder. In this study we aim to determine the role of diffusion-weighted magnetic resonance imaging (DWI) and apparent diffusion coefficient (ADC) analysis to assess bladder radiotherapy response. MATERIALS AND METHODS: Patients with T2-T4aN0-3M0 MIBC suitable for radical radiotherapy were recruited prospectively to an ethics approved protocol. Following transurethral resection of the bladder tumour and prior to any treatment, magnetic resonance imaging including DWI was performed on a 1.5T system using b values of 0, 100, 150, 250, 500, 750 s/mm2. DWI was repeated 3 months after completing radiotherapy. Cystoscopy and tumour site biopsy were undertaken following this. The response was dichotomised into response (0.9, P < 0.01). ΔADCall mean of 0.16 × 10-3 mm2/s and ΔADCb100 mean 0.12 × 10-3 mm2/s predicted radiotherapy response with sensitivity/specificity/positive predictive value/negative predictive value of 92.9%/100.0%/100.0%/75.0% and 89.3%/100.0%/100.0%/66.7%, respectively. CONCLUSIONS: Quantitative DWI analysis can successfully provide non-invasive assessment of bladder radiotherapy response. Multicentre validation is required before prospective testing to inform MIBC radiotherapy follow-up schedules and decision making.

Sexual and Psychosexual Consequences of Treatment for Gynaecological Cancers.

Modern multimodality cancer treatment has led to a rise in cancer survivors, and by 2030 the survival rate is estimated to increase by 31.4%. This is an impressive survival statistic on which clinicians and services continue to build. One of the less well-acknowledged consequences of survivorship among health professionals and patients alike is female sexual dysfunction, despite it occurring in more than 60% of women diagnosed with cancer. The systematic assessment and management of late effects from cancer lack integration within current models of oncology follow-up. Although highly prevalent, issues linked to sexual health are often not addressed among survivors. This overview aims to focus on the sexual impact of gynaecological cancer treatment. Clinicians should raise the topic of the sexual consequences of cancer treatment as a legitimate aspect of survivorship and service provision. Increased focus on the sexual consequences of treatment and cancer survivorship may in time lead to greater clinical recognition, service development and, most importantly, increase research focused on the effective management of what remains a neglected aspect of cancer care.

Current Status of Anatomical Magnetic Resonance Imaging in Brachytherapy and External Beam Radiotherapy Planning and Delivery.

Radiotherapy planning and delivery have dramatically improved in recent times. Imaging is key to a successful three-dimensional and increasingly four-dimensional based pathway with computed tomography embedded as the backbone modality. Computed tomography has significant limitations for many tumour sites where soft-tissue discrimination is suboptimal, and where magnetic resonance imaging (MRI) has largely superseded in the diagnostic arena. MRI is increasingly used together with computed tomography in the radiotherapy planning pathway and is now established as a prerequisite for several tumours. With the advent of combined MRI and linear accelerator (MR-linac) systems, a transition to MRI-based radiotherapy planning is becoming reality, with increasing experience and research involving these new platforms. In this overview, we aim to highlight how magnetic resonance-guided imaging has improved radiotherapy, using gynaecological malignancies to illustrate, in both external beam radiotherapy and image-guided brachytherapy, and will assess the early evidence for magnetic resonance-guided radiotherapy using combined MR-linac systems.

RTT-led IGRT for cervix cancer; training, implementation and validation.

INTRODUCTION: IGRT in cervical cancer treatment delivery is complex due to significant target and organs at risk (OAR) motion. Implementing image assessment of soft-tissue target and OAR position to improve accuracy is recommended. We report the development and refinement of a training and competency programme (TCP), leading to on-line Radiation Therapist (RTT) led soft-tissue assessment, evaluated by a prospective audit. METHODS AND MATERIALS: The TCP comprised didactic lectures and practical sessions, supported by a comprehensive workbook. The content was decided by a team comprised of Clinical Oncologists, RTTs, and Physicists. On completion of training, RTT soft-tissue review proficiency (after bony anatomy registration) was assessed against a clinician gold-standard from a database of 20 cervical cancer CBCT images. Reviews were graded pass or fail based on PTV coverage assessment and decision taken in concordance with the gold-standard. Parity was set at ≥80% agreement.The initial TCP (stage one) focussed on offline verification and decision making. Sixteen RTTs completed this stage, four achieved ≥80%. This was not sufficient to support clinical implementation.The TCP was redesigned, more stringent review guidelines and greater anatomy teaching was added. TCP stage two focussed on online verification and decision making supported by a decision flowchart. Twenty-one RTTs completed this TCP, all achieved ≥80%. This supported clinical implementation of RTT-led soft-tissue review under prospective audit conditions.The prospective audit was conducted between March 2017 and August 2017. Daily online review was performed by two trained RTTs. Online review and decision making proficiency was evaluated by a clinician. RESULTS: Thirteen patients were included in the audit. Daily online RTT-led IGRT was achieved for all 343 fractions. Two-hundred CBCT images were reviewed offline by the clinician; the mean number of reviews per patient was 15. 192/200 (96%) RTT image reviews were in agreement with clinician review, presenting excellent concordance. DISCUSSION AND CONCLUSION: Multidisciplinary involvement in training development, redesign of the TCP and inclusion of summative competency assessment were important factors to support RTT skill development. Consequently, RTT-led cervical cancer soft-tissue IGRT was clinically implemented in the hospital.

The Impact of Systemic Therapy Beyond First-line Treatment for Advanced Cervical Cancer.

AIMS: Despite recent advances in the primary and secondary prevention of cervical cancer, a significant number of women present with or develop metastatic disease. There is currently no consensus on the standard of care for second-line systemic treatment of recurrent/metastatic cervical cancer. The purpose of this study was to evaluate the second-line systemic therapy used and the associated outcomes in a single cancer centre. MATERIALS AND METHODS: A retrospective review of patients with cervical cancer who received one or more lines of treatment for recurrent or metastatic cervical cancer at the Royal Marsden Hospital between 2004 and 2014 was carried out. The primary objective was to establish the types of second-line systemic treatment used. Secondary end points included objective response rate, progression-free survival and overall survival after second-line therapy. RESULTS: In total, 75 patients were included in the study; 53 patients (70.7%) received second-line therapy for recurrent/metastatic disease. The most common second-line therapy was weekly paclitaxel (28.3%). Carboplatin-based chemotherapy (24.5%), targeted agent monotherapy within clinical trials (22.6%), docetaxel-based chemotherapy (13.2%), topotecan (9.4%) and gemcitabine (1.9%) were also used. The objective response rate to second-line therapy was 13.2%, which included three partial responses to carboplatin and paclitaxel, two partial responses to docetaxel-based chemotherapy, one partial response to weekly paclitaxel and one partial response to cediranib. Twenty-two patients (41.5%) achieved stable disease at 4 months. The median progression-free survival for women treated with second-line therapy was 3.2 months (95% confidence interval 2.1-4.3) and median overall survival was 9.3 months (95% confidence interval 6.4-12.5). Thirty-nine per cent of patients received third-line therapy. CONCLUSION: Seventy per cent of patients treated with first-line systemic therapy for recurrent/metastatic cervical cancer subsequently received second-line treatment but response rates were poor. There remains no standard of care for second-line systemic therapy for advanced cervical cancer. Patients should be considered for clinical trials whenever feasible, including novel targeted agents and immunotherapy.

Initial UK Experience of Stereotactic Body Radiotherapy for Extracranial Oligometastases: Can We Change the Therapeutic Paradigm?

AIMS: To retrospectively review the toxicity and early outcome data from patients who have received stereotactic body radiotherapy (SBRT) for extracranial oligometastases at a single UK institution. MATERIALS AND METHODS: Eligible patients had ≤3 extracranial metastases and performance status ≤2. Prior systemic therapy and radical treatment of oligometastastic relapse with any standard treatment modality was permitted. Patients with synchronous metastatic disease were excluded unless they had evidence of controlled primary disease after radical therapy. Follow-up consisted of clinical examination, biochemical and radiological assessments in accordance with standard clinical care. Progression events were defined using RECIST. Toxicity was evaluated using CTCAE v4.0. Local control, progression-free survival (PFS), freedom from widespread distant metastasis (defined as disease not amenable to further radical salvage therapy) and overall survival were calculated. RESULTS: Between July 2011 and April 2014, 73 patients with 87 metastases received SBRT (range 1-3 per patient). The median follow-up was 14.5 months (range 0-26.4). The median PFS was 14.5 months (1 year PFS 57%, 2 year 28%); 1 year overall survival 96%, 2 year 79.8%; 2 year local control 88%. At 2 years, 46% of patients were free from widespread distant metastases. No ≥ grade 3 acute or late toxicity was observed. CONCLUSION: At this time point, observed toxicity is minimal with excellent local control rates. This promising treatment paradigm requires further investigation in the context of a randomised controlled trial to establish if the addition of SBRT to standard care improves survival outcomes.

Radiographer-led plan selection for bladder cancer radiotherapy: initiating a training programme and maintaining competency.

OBJECTIVE: The implementation of plan of the day selection for patients receiving radiotherapy (RT) for bladder cancer requires efficient and confident decision-making. This article describes the development of a training programme and maintenance of competency. METHODS: Cone beam CT (CBCT) images acquired on patients receiving RT for bladder cancer were assessed to establish baseline competency and training needs. A training programme was implemented, and observers were asked to select planning target volumes (PTVs) on two groups of 20 patients' images. After clinical implementation, the PTVs chosen were reviewed offline, and an audit performed after 3 years. RESULTS: A mean of 73% (range, 53-93%) concordance rate was achieved prior to training. Subsequent to training, the mean score decreased to 66% (Round 1), then increased to 76% (Round 2). Six radiographers and two clinicians successfully completed the training programme. An independent observer reviewed the images offline after clinical implementation, and a 91% (126/139) concordance rate was achieved. During the audit, 125 CBCT images from 13 patients were reviewed by a single observer and concordance was 92%. CONCLUSION: Radiographer-led selection of plan of the day was implemented successfully with the use of a training programme and continual assessment. Quality has been maintained over a period of 3 years. ADVANCES IN KNOWLEDGE: The training programme was successful in achieving and maintaining competency for a plan of the day technique.

Clinical implementation of adaptive hypofractionated bladder radiotherapy for improvement in normal tissue irradiation.

AIMS: Adaptive bladder radiotherapy, with plan of the day selection and plan library development based on individual filling patterns, has been previously modelled in patients receiving weekly hypofractionated treatment and improved geometric accuracy has been shown. The aim of this study was to assess the clinical implementation of the technique. MATERIALS AND METHODS: Conformal plans (with small, intermediate and large planning target volumes) were developed for 25 patients. After pre-treatment cone-beam computed tomography, the optimal plan of the day was selected and delivered by two trained observers. Independent off-line plan selection was also carried out. Concordance between the on-line and off-line selections, frequency of plan usage, target coverage and normal tissue sparing were assessed. RESULTS: Plan selection concordance was 91%. Fifty-five per cent of fractions were delivered using small or large plans. The mean coverage of the clinical target volume by the 95% isodose was 99%. The mean reduction in the volume of normal tissue treated to 95% of the prescription dose was 219 cm(3) compared with the previous institutional standard approach. CONCLUSIONS: Good concordance in plan selection is shown with clinical implementation of the adaptive strategy. Adequate target coverage was achieved with reduction in the volume of normal tissue irradiated to a high dose compared with the previous standard approach.

Investigating the relationship between virtual cystoscopy image quality and CT slice thickness.

OBJECTIVE: To investigate the effect of reconstruction slice thickness on image quality at CT virtual cystoscopy (VC). METHODS: Pelvic CT examinations in bladder cancer patients were reconstructed at different slice thicknesses (0.6-5 mm) and intervals, and resulting VC images assessed. Quality indicators were ridging, holes, floaters and dimpling artefacts, tumour definition, and an overall score, ranked 1 (best) to 7 (worst). CT number and standard deviation (SD) for bladder contents and bladder wall were recorded. The mean SD was used as a measure of noise, and the contrast-to-noise ratio (CNR) was calculated as the CT number difference between them divided by the average image noise. The mean CNR across the three levels was used for analysis. Each qualitative image quality measure was compared with CT number, noise and CNR measurements. RESULTS: Dimpling artefacts increased with thinner slice reconstruction and correlated with increased noise, often resulting in poor tumour definition. The best overall image quality score was seen for VC images reconstructed at 1.2 mm slice thickness, probably because of the competing effects of spatial resolution and CNR. CONCLUSION: A slice thickness reconstruction <1.2 mm does not provide for better image quality at VC owing to the presence of increased noise.