Evaluating the repeatability and set-up sensitivity of a large field of view distortion phantom and software for magnetic resonance-only radiotherapy

Background and purpose: Magnetic Resonance (MR)-only radiotherapy requires geometrically accurate MR images over the full scanner Field of View (FoV). This study aimed to investigate the repeatability of distortion measurements made using a commercial large FoV phantom and analysis software and the sensitivity of these measurements to small set-up errors. Materials and methods: Geometric distortion was measured using a commercial phantom and software with 2D and 3D acquisition sequences on three different MR scanners. Two sets of repeatability measurements were made: three scans acquired without moving the phantom between scans (single set-up) and five scans acquired with the phantom re-set up in between each scan (repeated set-up). The set-up sensitivity was assessed by scanning the phantom with an intentional 1 mm lateral offset and independently an intentional 1° rotation. Results: The mean standard deviation of distortion for all phantom markers for the repeated set-up scans was for all scanners and sequences. For the lateral offset scan of the markers agreed within two standard deviations of the mean of the repeated set-up scan (median of all scanners and sequences, range 78%–93%). For the 1° rotation scan, 80% of markers agreed within two standard deviations of the mean (range 69%–93%). Conclusions: Geometric distortion measurements using a commercial phantom and associated software appear repeatable, although with some sensitivity to set-up errors. This suggests the phantom and software are appropriate for commissioning a MR-only radiotherapy workflow

Caution is required in the implementation of 90-day mortality indicators for radiotherapy in a curative setting: A retrospective population-based analysis of over 16,000 episodes

Background: 90-day mortality (90DM) has been proposed as a clinical indicator in radiotherapy delivered in a curative setting. No large scale assessment has been made. Its value in allowing robust comparisons between centres and facilitating service improvement is unknown. Methods: All radiotherapy treatments delivered in a curative setting over seven years were extracted from the local electronic health record and linked to cancer registry data. 90DM rates were assessed and factors associated with this outcome were investigated using logistic regression. Cause of death was identified retrospectively further characterising the cause of 90DM. Results: Overall 90DM was 1.25%. Levels varied widely with diagnosis (0.20%-5.45%). Age (OR 1.066, 1.043-1.073), year of treatment (OR 0.900, 0.841-0.969) and diagnosis were significantly associated with 90DM on multi-variable logistic regression. Cause of death varied with diagnosis; 50.0% post-operative in rectal cancer, 40.4% treatment-related in head and neck cancer, 59.4% disease progression in lung cancer. Conclusion: Despite the drive to report centre level comparative outcomes, this study demonstrates that 90DM cannot be adopted routinely as a clinical indicator due to significant population heterogeneity and low event rates. Further national investigation is needed to develop a meaningful robust indicator that delivers appropriate comparisons and drive improvements in care

Superiority of deformable image co-registration in the integration of diagnostic positron emission tomography-computed tomography to the radiotherapy treatment planning pathway for oesophageal carcinoma

Aims To investigate the use of image co-registration in incorporating diagnostic positron emission tomography-computed tomography (PET-CT) directly into the radiotherapy treatment planning pathway, and to describe the pattern of local recurrence relative to the PET-avid volume. Materials and methods Fourteen patients were retrospectively identified, six of whom had local recurrence. The accuracy of deformable image registration (DIR) and rigid registration of the diagnostic PET-CT and recurrence CT, to the planning CT, were quantitatively assessed by comparing co-registration of oesophagus, trachea and aorta contours. DIR was used to examine the correlation between PET-avid volumes, dosimetry and site of recurrence. Results Positional metrics including the dice similarity coefficient (DSC) and conformity index (CI), showed DIR to be superior to rigid registration in the co-registration of diagnostic and recurrence imaging to the planning CT. For diagnostic PET-CT, DIR was superior to rigid registration in the transfer of oesophagus (DSC = 0.75 versus 0.65, P < 0.009 and CI = 0.59 versus 0.48, P < 0.003), trachea (DSC = 0.88 versus 0.65, P < 0.004 and CI = 0.78 versus 0.51, P < 0.0001) and aorta structures (DSC = 0.93 versus 0.86, P < 0.006 and CI = 0.86 versus 0.76, P < 0.006). For recurrence imaging, DIR was superior to rigid registration in the transfer of trachea (DSC = 0.91 versus 0.66, P < 0.03 and CI = 0.83 versus 0.51, P < 0.02) and oesophagus structures (DSC = 0.74 versus 0.51, P < 0.004 and CI = 0.61 versus 0.37, P < 0.006) with a non-significant trend for the aorta (DSC = 0.91 versus 0.75, P < 0.08 and CI = 0.83 versus 0.63, P < 0.06) structure. A mean inclusivity index of 0.93 (range 0.79–1) showed that the relapse volume was within the planning target volume (PTVPET-CT); all relapses occurred within the high dose region. Conclusion DIR is superior to rigid registration in the co-registration of PET-CT and recurrence CT to the planning CT, and can be considered in the direct integration of PET-CT to the treatment planning process. Local recurrences occur within the PTVPET-CT, suggesting that this is a suitable target for dose-escalation strategies

Analysis of on-trial quality assurance for the SPARC clinical trial using novel peer-review methodology

Pre-trial radiotherapy quality assurance (RTQA) for the SPARC trial of preoperative pancreas SBRT highlighted overgenerous target contouring. We aimed to assess for improvement following a training workshop and appraise the effectiveness of a novel web-conferencing format for on-trial RTQA

High hospital research participation and improved colorectal cancer survival outcomes: a population-based study

Objective: In 2001, the National Institute for Health Research (NIHR) Cancer Research Network (NCRN) was established, leading to a rapid increase in clinical research activity across the English NHS. Using colorectal cancer (CRC) as an example, we test the hypothesis that high, sustained hospital-level participation in interventional clinical trials improves outcomes for all CRC patients managed in those research-intensive hospitals. Design: Data for patients diagnosed with CRC in England in 2001-2008 (n=209,968) were linked with data on accrual to NCRN CRC studies (n=30,998). Hospital Trusts were categorised by the proportion of patients accrued to interventional studies annually. Multivariable models investigated the relationship between 30-day post-operative mortality and five-year survival and the level and duration of study participation. Results: Most of the Trusts achieving high participation were district general hospitals and the effects were not limited to cancer “centres of excellence”, although such centres do make substantial contributions. Patients treated in Trusts with high research participation (≥16%) in their year of diagnosis had lower post-operative mortality (p<0.001) and improved survival (p<0.001) after adjustment for casemix and hospital-level variables. The effects increased with sustained research participation, with a reduction in post-operative mortality of 1.5% (6.5% to 5%, p<2.2*10-6) and an improvement in survival (p<10 19; 5-year difference: 3.8% (41.0% to 44.8%)) comparing high participation for ≥4 years with 0 years. Conclusion: There is a strong independent association between survival and participation in interventional clinical studies for all CRC patients treated in the hospital, not only study participants. Improvement precedes and increases with the level and years of sustained participation

A Systematic Review of the Clinical Implementation of Pelvic Magnetic Resonance Imaging (MR)-Only Planning for External Beam Radiation Therapy

The use of magnetic resonance imaging (MRI) scans alone for radiotherapy treatment planning (MR-only planning) has been highlighted as one method of improving patient outcomes. Recent technological advances have meant that introducing MR-only planning to the clinic is now becoming a reality, with several specialist radiotherapy clinics treating patients with this technique. As such, substantial efforts are being made to introduce this technique into wide-spread clinical implementation. A systematic review of publications investigating the clinical implementation of pelvic MR-only radiotherapy treatment planning was undertaken following the PRISMA guidelines. The Medline, Embase, Scopus, Science Direct, CINAHL and Web of Science databases were searched (timespan: all years to 2nd January 2019). Twenty six articles met the inclusion criteria. The studies were grouped into the following categories: 1. MR acquisition and synthetic-CT generation verification, 2. MR distortion quantification and phantom development, 3. Clinical validation of patient treatment positioning in an MR-only workflow and 4. MR-only commissioning processes. Key conclusions from this review are: i) MR-only planning has been clinically implemented for prostate cancer treatments; ii) A substantial amount of work remains to translate MR-only planning into wide spread clinical implementation for all pelvic sites; iii) MR scanner distortions are no longer a barrier to MR-only planning; however they must be managed appropriately; iv) MR-only based patient positioning verification shows promise, however limited evidence is reported in the literature and further investigation is required; and v) a number of MR-only commissioning processes have been reported which can aid centres as they undertake local commissioning, however this needs to be formalised in guidance from national bodies

Clinical development of new drug-radiotherapy combinations.

In countries with the best cancer outcomes, approximately 60% of patients receive radiotherapy as part of their treatment, which is one of the most cost-effective cancer treatments. Notably, around 40% of cancer cures include the use of radiotherapy, either as a single modality or combined with other treatments. Radiotherapy can provide enormous benefit to patients with cancer. In the past decade, significant technical advances, such as image-guided radiotherapy, intensity-modulated radiotherapy, stereotactic radiotherapy, and proton therapy enable higher doses of radiotherapy to be delivered to the tumour with significantly lower doses to normal surrounding tissues. However, apart from the combination of traditional cytotoxic chemotherapy with radiotherapy, little progress has been made in identifying and defining optimal targeted therapy and radiotherapy combinations to improve the efficacy of cancer treatment. The National Cancer Research Institute Clinical and Translational Radiotherapy Research Working Group (CTRad) formed a Joint Working Group with representatives from academia, industry, patient groups and regulatory bodies to address this lack of progress and to publish recommendations for future clinical research. Herein, we highlight the Working Group's consensus recommendations to increase the number of novel drugs being successfully registered in combination with radiotherapy to improve clinical outcomes for patients with cancer

Preoperative radiotherapy combined with 5 days per week capecitabine chemotherapy in locally advanced rectal cancer

There is increasing evidence supporting the use of preoperative chemoradiotherapy in patients with locally advanced rectal cancer in an attempt to facilitate complete surgical resection with clear margins. We describe our experience of using a 5-day per week regime of preoperative capecitabine chemoradiotherapy. Between November 2004 and September 2006, 70 patients with MRI-defined locally advanced rectal cancer were selected for treatment. Capecitabine was given at a dose of 900 mg m−2 for 5 days per week combined with 45 Gy of radiotherapy in 25 doses. This regime was well tolerated with 89% of our patients receiving the full dose of chemotherapy and 96% receiving the full dose of radiotherapy. Ninety-three per cent proceeded to macroscopically complete surgical resection. The pathological complete response rate was 9.2% with a node-negative rate of 66%. A negative circumferential margin was achieved by 79% of the patients who underwent resection. Compared to studies using a 7-day per week capecitabine schedule, our results show increased compliance and less dose reductions with comparable pathological outcome

Preoperative chemoradiation with capecitabine, irinotecan and cetuximab in rectal cancer: significance of pre-treatment and post-resection RAS mutations

Background: The influence of EGFR pathway mutations on cetuximab-containing rectal cancer preoperative chemoradiation (CRT) is uncertain. Methods: In a prospective phase II trial (EXCITE), patients with magnetic resonance imaging (MRI)-defined non-metastatic rectal adenocarinoma threatening/involving the surgical resection plane received pelvic radiotherapy with concurrent capecitabine, irinotecan and cetuximab. Resection was recommended 8 weeks later. The primary endpoint was histopathologically clear (R0) resection margin. Pre-planned retrospective DNA pyrosequencing (PS) and next generation sequencing (NGS) of KRAS, NRAS, PIK3CA and BRAF was performed on the pre-treatment biopsy and resected specimen. Results: Eighty-two patients were recruited and 76 underwent surgery, with R0 resection in 67 (82%, 90%CI: 73–88%) (four patients with clinical complete response declined surgery). Twenty–four patients (30%) had an excellent clinical or pathological response (ECPR). Using NGS 24 (46%) of 52 matched biopsies/resections were discrepant: ten patients (19%) gained 13 new resection mutations compared to biopsy (12 KRAS, one PIK3CA) and 18 (35%) lost 22 mutations (15 KRAS, 7 PIK3CA). Tumours only ever testing RAS wild-type had significantly greater ECPR than tumours with either biopsy or resection RAS mutations (14/29 [48%] vs 10/51 [20%], P=0.008), with a trend towards increased overall survival (HR 0.23, 95% CI 0.05–1.03, P=0.055). Conclusions: This regimen was feasible and the primary study endpoint was met. For the first time using pre-operative rectal CRT, emergence of clinically important new resection mutations is described, likely reflecting intratumoural heterogeneity manifesting either as treatment-driven selective clonal expansion or a geographical biopsy sampling miss