Survey of research attitudes of RTTs working in Scotland: A Scottish radiographer research forum collaboration.

Purpose: Evidence-based practice (EBP) is associated with improved treatment outcomes and survival in cancer patients. Engagement from therapeutic radiographers/radiation therapists (RTTs) in research, has been identified as a challenge. The aim of this survey was to gain an understanding of RTT attitudes to research in Scotland. Methods: This was a prospective study that used a mixed method cross-sectional survey, with an online survey tool (Webropol). The survey was developed with collaborators from all Scottish Radiotherapy Centres (n = 5) and piloted by 6 conveniently sampled RTT and validated by 8 experienced RTTs. The survey comprised 29 items, 7 selection-based demographic questions, and 18 statements with a Likert 5-point metric scale rating (1 = strongly disagree, 2 = disagree, 3 = neutral, 4 = agree, 5 = strongly agree). The validity was measured with the content validity index (CVI) and item-CVI by 8 experienced RTTs. Low scoring I-CVI (<0.78) questions were removed.A total of 314 RTTs working in Scottish Radiotherapy Centres were invited to participate. Approvals were given by each Head of department (HoD), who also confirmed number of RTTs. Results: A total of 102/314 (32.5 %) RTTs responded. The majority of RTTs agreed they were confident they had sufficient research skills to inform EBP (n = 58/102, 56.9 %), felt confident discussing EBP with colleagues (n = 67, 65.7 %) and felt research was important for role development (n = 89, 87.2 %). Low mean scores and standard deviation (SD) were observed for the following: "I know how to get involved in research" 3.2 (1.2), "I have been given the opportunity to get involved in research" 3.2 (1.1), and "I am well informed about current research projects in my department" 3.2 (1.1). 57.8 % (n = 59) of RTTs disagreed they were confident adequate time would be provided to be involved in research. Conclusion: The survey results demonstrated a predominantly positive attitude to research amongst RTTs working in Scottish centres, with most common perceived barriers being access to protected time and staff; training, and support.

The in-silico feasibility of dose escalated, hypofractionated radiotherapy for rectal cancer.

Background and purpose: Short course radiotherapy (SCRT) has a low biological prescription dose. Rectal cancer has a dose response relationship and moderate α/ß ratio (∼5). We hypothesise hypofractionated dose escalation has radiobiological advantages. We assessed in-silico dose escalation to the primary tumour using a simultaneous integrated boost (SIB) technique. Materials and methods: Patients who had received 25 Gy/5# were enrolled. GTV was macroscopic tumour including lumen. CTVA was GTV + 10 mm. CTVB included elective nodes. PTV_Low was created from CTVF (CTVA + CTVB) + 7 mm. PTV_High (SIB) was GTV + 5 mm margin. OAR were as per RTOG guidelines. Each patient had 4 plans created at increasing dose levels (27.5 Gy, 30 Gy, 32.5 Gy and 35 Gy) to PTV_High. PTV_Low was 25 Gy/5#.5 test plans were created for each patient in Eclipse™ v15.5 and consisted of 2 VMAT full arcs (6 MV), Varian Truebeam (2.7). Planning objectives were set in the Photon optimiser (PO) and recalculated using Acuros v15.5. A priori feasibility was defined as 90% of plans achieving the planning objectives at 32.5 Gy dose level (EqD2 53.4 Gy). Results: 20 SCRT patients median age 70, F (n = 5), M (n = 15). Rectum level; low (n = 12), mid (n = 3) and upper (n = 5). 100 plans were analysed. Mean volume of PTV_High was 130 cm3 (SD 81.5) and PTV_Low 769.6 cm3 (SD 241.1). 100% plans complied with mandatory planning dose metrics for each structure at the 25 Gy/5# plan and each dose level. Conclusion: Hypofractionated dose escalation to the primary tumour up to 35 Gy/5# is technically feasible in rectal cancer radiotherapy.

Feasibility of DW-MRI analysis of salivary glands during head and neck radiotherapy.

INTRODUCTION: With no effective treatment for xerostomia, there remains an unmet need to reduce radiation induced toxicity. Measuring physiological changes during RT in salivary glands using DW-MRI may predict which patients are most at risk of severe toxicity. This study evaluated the feasibility of measuring apparent diffusion coefficient (ADC) in the major salivary glands and describes the observed changes in volume and ADC during RT. METHODS: Scans were acquired at baseline (MR_base) and after 10 fractions (MR_rpt). Sequences included T1 post contrast fat saturated (T1PCFS) and DW-MRI (5b values, 0-1000 s/mm2). Ipsilateral and contralateral parotid (iPG/cPG), submandibular (iSMG/cSMG) and sublingual glands (iSLG/cSLG) were delineated on T1PCFS, modified on b0 and copied to the ADC map. RESULTS: 31 patients with intermediate/high risk squamous cell carcinoma (SCC) of the oropharynx were evaluated. On 124 scans, SMG and SLG delineations were successful on all; parotids were fully contoured in 90.7%. Baseline mean ADC were significantly different between each gland type (p < 0.0001). IPG and cPG volume decreased during treatment by 6.7% and 11.2%. ISMG, cSMG, iSLG and cSLG volume increased by 6.9, 0.9, 60.8 and 60.3% respectively. All structures showed an increase in mean_ADC values. For each gland the increase in ADC was statistically significant p < 0.0001. A smaller mean percentage increase in ADC was observed in the group experiencing a higher grade (2 or > ) of toxicity. CONCLUSION: It is feasible to measure volume and ADC of the salivary glands prior to and during RT for HNC. Early data suggests a lower rise in ADC during treatment is associated with more severe late xerostomia.

Durvalumab (MEDI 4736) in combination with extended neoadjuvant regimens in rectal cancer: a study protocol of a randomised phase II trial (PRIME-RT).

BACKGROUND: Advances in multi-modality treatment of locally advanced rectal cancer (LARC) have resulted in low local recurrence rates, but around 30% of patients will still die from distant metastatic disease. In parallel, there is increasing recognition that with radiotherapy and systemic treatment, some patients achieve a complete response and may avoid surgical resection, including in many cases, the need for a permanent stoma. Extended neoadjuvant regimes have emerged to address these concerns. The inclusion of immunotherapy in the neoadjuvant setting has the potential to further enhance this strategy by priming the local immune microenvironment and engaging the systemic immune response. METHODS: PRIME-RT is a multi-centre, open label, phase II, randomised trial for patients with newly diagnosed LARC. Eligible patients will be randomised to receive either: short course radiotherapy (25 Gray in 5 fractions over one week) with concomitant durvalumab (1500 mg administered intravenously every 4 weeks), followed by FOLFOX (85 mg/m2 oxaliplatin, 350 mg folinic acid and 400 mg/m2 bolus 5-fluorouracil (5-FU) given on day 1 followed by 2400 mg/m2 5-FU infusion over 46-48 h, all administered intravenously every 2 weeks), and durvalumab, or long course chemoradiotherapy (50 Gray to primary tumour in 25 fractions over 5 weeks with concomitant oral capecitabine 825 mg/m2 twice per day on days of radiotherapy) with durvalumab followed by FOLFOX and durvalumab. The primary endpoint is complete response rate in each arm. Secondary endpoints include treatment compliance, toxicity, safety, overall recurrence, proportion of patients with a permanent stoma, and survival. The study is translationally rich with collection of bio-specimens prior to, during, and following treatment in order to understand the molecular and immunological factors underpinning treatment response. The trial opened and the first patient was recruited in January 2021. The main trial will recruit up to 42 patients with LARC and commence after completion of a safety run-in that will recruit at least six patients with LARC or metastatic disease. DISCUSSION: PRIME-RT will explore if adding immunotherapy to neoadjuvant radiotherapy and chemotherapy for patients with LARC can prime the tumour microenvironment to improve complete response rates and stoma free survival. Sequential biopsies are a key component within the trial design that will provide new knowledge on how the tumour microenvironment changes at different time-points in response to multi-modality treatment. This expectation is that the trial will provide information to test this treatment within a large phase clinical trial. Trial registration Clinicaltrials.gov NCT04621370 (Registered 9th Nov 2020) EudraCT number 2019-001471-36 (Registered 6th Nov 2020).

Dosimetric impact of organ at risk daily variation during prostate stereotactic ablative radiotherapy.

OBJECTIVE: Prostate stereotactic ablative radiotherapy (SABR) delivers large doses using a fast dose rate. This amplifies the effect geometric uncertainties have on normal tissue dose. The aim of this study was to determine whether the treatment dose-volume histogram (DVH) agrees with the planned dose to organs at risk (OAR). METHODS: 41 low-intermediate risk prostate cancer patients were treated with SABR using a linac based technique. Dose prescribed was 35 Gy in five fractions delivered on alternate days, planned using volumetric modulated arc therapy (VMAT) with 10X flattening filter free (FFF). On treatment, prostate was matched to fiducial markers on cone beam CT (CBCT). OAR were retrospectively delineated on 205 pre-treatment CBCT images. Daily CBCT contours were overlaid on the planning CT for dosimetric analysis. Verification plan used to evaluate the daily DVH for each structure. The daily doses received by OAR were recorded using the D%. RESULTS: The median rectum and bladder volumes at planning were 67.1 cm3 (interquartile range 56.4-78.2) and 164.4 cm3 (interquartile range 120.3-213.4) respectively. There was no statistically significant difference in median rectal volume at each of the five treatment scans compared to the planning scan (p = 0.99). This was also the case for median bladder volume (p = 0.79). The median dose received by rectum and bladder at each fraction was higher than planned, at the majority of dose levels. For rectum the increase ranged from 0.78-1.64Gy and for bladder 0.14-1.07Gy. The percentage of patients failing for rectum D35% < 18 Gy (p = 0.016), D10% < 28 Gy (p = 0.004), D5% < 32 Gy (p = 0.0001), D1% < 35 Gy (p = 0.0001) and bladder D1% < 35 Gy (p = 0.001) at treatment were all statistically significant. CONCLUSION: In this cohort of prostate SABR patients, we estimate the OAR treatment DVH was higher than planned. This was due to rectal and bladder organ variation. ADVANCES IN KNOWLEDGE: OAR variation in prostate SABR using a FFF technique, may cause the treatment DVH to be higher than planned.

Safety and feasibility of prostate stereotactic ablative radiotherapy using multimodality imaging and flattening filter free.

OBJECTIVE: To investigate feasibility and safety of stereotactic ablative radiotherapy in the management of prostate cancer while employing MR/CT fusion for delineation, fiducial marker seeds for positioning and Varian RapidArc with flattening filter free (FFF) delivery. METHODS: 41 patients were treated for low-intermediate risk prostate cancer with initial prostate-specific antigen of ≤20 ng ml-1, Gleason score 6-7. Patients had MR/CT fusion for delineation of prostate ±seminal vesicles. CT/MR fusion images were used for delineation and planned using flattening filter free modality. Verification on treatment was cone beam CT imaging with fiducial markers for matching. Patients had Radiation Therapy Oncology Group scoring for genitourinary and gastointestinal symptoms at baseline, week 4, 10 and 18. RESULTS: Clinically acceptable plans were achieved for all patients, all plans achieved the objective clinical target volume D99% ≥ 95%, and for planning target volume D95% ≥ 95%. Rectum dose constraints were met for 95.1% for V18 Gy ≤ 35%, 80% V28 Gy ≤ 10%. A total of 32 (78.0%) plans achieved all rectum dose constraints. Grade 1 acute genitourinary symptoms were 53.7% of patients at baseline, 90.2% [95% CI (76.8-97.3%)] (p = 0.0005) at treatment 5, falling to 78.0% (62.4-89.4%) at week 4, and 75.0% (58.8-87.3%) by week 10 and 52.5% (36.1-68.5%) (p = 1.00) at week 18. Acute gastrointestinal symptoms were 5% at baseline, 46.3% [95% CI (30.7-62.6%)] at treatment 5, week 4 43.9% [95% CI (28.5-60.3%)], week 10 25.0% (11.1-42.3%), and declined slightly by week 18 [-20.095% CI (12.7-41.2)] p = 0.039. Overall 75.6% (31/41) of patients experienced Grade 1-2 toxicity during or after treatment. CONCLUSION: This planning and delivery technique is feasible, safe and efficient. A homogeneous dose can be delivered to prostate with confidence, whilst limiting high dose to nearby structures. The use of this technology can be applied safely within further randomized study protocols. Advances in knowledge: Multimodality imaging for delineation and linac-based image-guided RT with FFF for the treatment of prostate stereotactic ablative radiotherapy.