Magnetic resonance image guided radiotherapy, or MRIgRT, is the most exciting development in advanced radiotherapy for years. By combining a linear accelerator with a high definition MR scanner, MRIdian allows clinicians to see as they treat – adjusting the beam to allow for movements and anatomical changes. It provides a step-change in accurate stereotactic ablative radiotherapy (SABR), bringing a new level of control and confidence with tumour targeting and sparing of normal tissue. MRIdian makes truly adaptive SABR possible for the first time.
GenesisCare is the first to introduce MRIdian technology to the UK at our Oxford centre – the first member of an emerging MRIgRT network that will put us at the forefront of exploring the possibilities of this innovative approach.
MRIdian 50/5 – our experience so far
The MRIdian MR linac is one of the most advanced forms of radiation therapy, demanding a high level of clinician input, a skilled team, a robust workflow and a completely new way of working. MRIdian 50/5 chronicles our experience of how we overcame these challenges and we were able to set up a service in six months and treat our first 50 patients during the next five. In that time, the benefits to patients have been even greater than any of us imagined. We want to share what we’ve learned so that other centres can replicate this service with the same efficiency and positive outcome. MRI-guided radiotherapy will play a major role in cancer care in the next five to ten years and will be adopted by many more healthcare organisations.
Inoperable pancreatic cancer is a new indication for high-dose SABR – it’s only possible because of MR linacDr James Good, Clinical Director of Stereotactic Radiotherapy, GenesisCare UK
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MRIdian specialists at GenesisCare
Patient care on the MRIdian is delivered by a team of specially trained consultant oncologists, selected on the basis of their clinical expertise. Collectively the team provide a comprehensive infrastructure for patient selection, peer review, and clinical governance for all referrals, and the credentialing of new clinicians in MRI-guided radiotherapy. We are excited to be partnering with the University of Oxford to build a body of evidence that will impact the lives of many patients.
Real-time on-table adaptive radiotherapy brings a new level of confidence to SABR delivery.
MRI-guided radiotherapy improves on conventional image-guided radiotherapy (IGRT) by providing enhanced soft tissue definition without additional radiation exposure through high-quality MR images.
By capturing MR images of the target many times a second, the MRIdian provides real-time moving images that capture the anatomical positional changes that occur naturally within the body. Uniquely, the MRIdian allows tracking of the target position in real time, coupled with a gating facility that prevents beam delivery when the target is outside the treatment boundaries. This level of accuracy means that uncertainty is reduced, eliminating the need for large margins around the target.
The MRIdian has opened up new avenues of treatment, particularly tumours that move and are within close proximity of organs at risk (OAR) such as tumours of the liver and pancreas, where high doses are achievable while keeping the doses to OARs within tolerance.
Image: Mittauer, Cureus
The MRIdian allows clinicians to provide true online adaptive radiotherapy. The treatment planning system is clear and intuitive, making daily re-contouring of tumour and normal tissues straightforward. The updated plans are rapidly re-optimised providing a personalised radiation treatment on every patient, every fraction.
The MRIdian uses a patented split-magnet MR design, so that the radiation beam is not distorted by the magnetic field and is at the optimum distance for exceptionally sharp, high dose-rate SABR
The MR set-up captures multiple high-definition, high-quality images many times a second, seeing even the tiniest movement of the tumour and surrounding organs
The MRIdian performs real-time on-table plan adjustments to reflect both inter- and intra-fraction anatomical changes or movements
When the gating target moves outside the pre-specified gating boundary, the radiation beam automatically stops until the target returns back inside the gating boundary
The gating target and gating boundary are visualised on the display and some patients benefit from being able to view this while inside the MRIdian – enabling them to take an active role in gated delivery with adjustments to their breathing
Coupled with the unique target tracking and gating system is a precise stereotactic radiation beam, giving the clinician greater control and confidence in delivering maximal dose to the tumour target while preserving critical structures
The evidence base suggests that the MRIdian makes it possible to achieve ablative doses without reaching prohibitive levels of toxicity, particularly in the abdomen. The offers the prospect of improving clinical outcomes for previously hard-to-treat cancers such as locally advanced or recurrent pancreatic cancer and inoperable liver tumours.
Compassionate Access Programme
For eligible NHS patients with localised pancreatic cancer, the GenesisCare Foundation Compassionate Access Programme is making available MR-guided stereotactic ablative radiotherapy (SABR) on the ViewRay MRIdian platform, without cost.
With 10,000 patients treated to date worldwide, MRIdian has been widely used for gastrointestinal, lung and prostate cancer, and is increasingly recognised as a possible platform for partial breast treatments and safer re-irradiation. The possibility of incorporating on-table functional MRI into treatment pathways is just around the corner.
The evidence base for SABR is growing and there is currently a range of clinical scenarios into which it can be integrated. At GenesisCare, we currently offer SABR in the following situations:
Localised prostate cancer, where hypofractionated treatment offers an alternative to conventional radiotherapy
Early stage lung cancer
Pelvic reirradiation
Hepatobiliary cancer, including primary liver cancers and inoperable/recurrent pancreatic cancer
Selected cases of oligo-metastatic and oligo-progressive cancers
Renal cell carcinoma where surgery is not possible or not preferrable, and other treatments are not advisable (e.g. for larger tumours where risk of damage to surrounding organs is greater, or central kidney tumours where surgery is not possible and SABR would preserve greater renal function)
We have defined SABR referral criteria based on the experience of our SABR clinical expert team, published clinical studies and international best practice. All SABR referrals will be assessed for a possible benefit of treatment on MRIdian. For example:
Tumours where there is significant movement, e.g. in the upper abdomen and lung
Tumours that are in close proximity to organs at risk (OAR), e.g. in the prostate, upper abdomen and central lung
Pivotal studies
Our strategy for the introduction of MRIgRT is to align with international best practice based on evidence-based protocols. There is an increasing international evidence base for MR linac and notably the MRIdian system. Through our academic collaboration with Oxford University, we will build on this body of evidence with an ongoing programme of clinical evaluation in the UK. Here are some of the pivotal studies that have informed our approach.
Prostate
SABR is increasingly used for treatment of localised prostate cancer. However, with any hypofractionated approach, concerns remain about early and late gastrointestinal (GI) and genitourinary (GU) toxicity. MRIdian offers the potential to deliver SABR with reduced uncertainty margins and daily, real-time adaptive planning to reduce toxicity. A phase 2 study of 101 patients treated with MRIgRT for clinical stage T1‑3b N0 M0 prostate cancer showed a low incidence of early GI and GU toxicity, as recorded both in clinician and patient-reported outcome measurement. Although radiotherapy can be safely given over five days without MRIgRT, MRIdian gives peace of mind to clinician and patient that the target is hit every time with minimum damage to surrounding tissues. Bruynzeel et al, 2019
Pancreas
A study of 44 patients with inoperable pancreatic cancer evaluated the overall survival outcomes of adaptive, high-dose MRIgRT compared with the lower SABR doses deliverable of conventional radiotherapy machines. SABR for pancreatic cancer has traditionally been constrained by the tolerance of the duodenum to radiation therapy – but the soft-tissue visualisation, beam gating, and adaptive approach made possible by MRIdian are changing the landscape. High-dose MRIgRT patients (n = 24) had a statistically significant improvement in 2-year overall survival (OS) (49% vs 30%, P = 0.03) and trended towards significance for 2-year freedom from local failure (FFLF) (77% vs 57%, P = 0.15) compared to standard-dose patients (n = 20, 45%). This improved OS was achieved without any increased toxicity in the high dose group. Whilst not randomised, this data is hugely encouraging. With MRIdian, for the first time, radiation therapy could impact survival in pancreatic cancer by facilitating safe dose-escalation. Rudra et al, 2019
Kidney
Treatment on the MRIdian MR Linac allows for a reduction in radiation dose to the surrounding normal tissues, such as the small bowel, spinal cord, large bowel and second kidney[3], reducing the risk of possible toxicity which may otherwise be caused. It also offers a reduced risk of diminished renal function when compared to other interventions. In a study of 95 patients with larger (T1b, >4 cm) renal cell carcinoma, where 77.6% were defined as inoperable by the referring urologist. 38 patients (40%) had a grade 1 to 2 toxicity and no grade 3 to 5 toxicities were reported. Cancer-specific survival, overall survival, and progression-free survival were 96.1%, 83.7%, and 81.0% at two years and 91.4%, 69.2%, 64.9% at four years, respectively.[4] Read more about MRIdian for kidney cancer
Patient Reported Outcomes (PROMs)
MRIgRT requires the patient to remain within the MR bore for up to 90 minutes. In a study of 150 patients that measured patient reported outcomes only 5% reported ‘considerable anxiety’. Participation in the video feedback and breath-hold delivery was well appreciated by most patients.
Bruynzeel, A et al. A Prospective Single-Arm Phase 2 Study of Stereotactic Magnetic Resonance Guided Adaptive Radiation Therapy for Prostate Cancer: Early Toxicity Results International Journal of Radiation Oncology, Biology, Physics.
Rudra, S. et al. Using adaptive magnetic resonance image-guided radiation therapy for treatment of inoperable pancreatic cancer. Cancer Med. 8, 2123–2132 (2019).
Siva S, Correa R, Warner A, Staehler M, Ellis R, Ponsky L et al. Stereotactic Ablative Radiotherapy for ≥T1b Primary Renal Cell Carcinoma: A Report From the International Radiosurgery Oncology Consortium for Kidney (IROCK). Int. J. Radiat. Oncol. Biol. Phys. 2020;108(4):941-949.
