European Society for radiotherapy and oncology (ESTRO) committee The ESTRO Radiation Therapist committee (RTTC) is made up of 14 representatives (including 2 elected members of the RTT alliance) working as radiation therapists (RTTs) in clinical departments and academic institutes. The role of the RTT in Europe has been described in previous ESTRO documents, with clear guidelines and definitions as to the educational standards required of an undergraduate practitioner (level 6) [1] and advanced/specialist practitioner (7&8) [2]. From here on, this paper will refer to our profession as RTT.
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.
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.
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)
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