Pancreatic cancer

Surgery offers the only chance of curing pancreatic cancer, but most patients present with inoperable disease. Only 20% cases are resectable at presentation, and a proportion of these patients have medical comorbidities that make surgery high risk. Those with metastatic disease are typically offered chemotherapy or best supportive care.

There is however emerging evidence of a dose response relationship, proving that escalated radiation doses are associated with improved local control and overall survival. Therefore, delivering ablative doses of radiation using shorter treatment schedules given the high propensity for metastatic spread minimises the burden of treatment making it very attractive for patients.  

MRI-guided radiation therapy has emerged as a promising modality by which to achieve accurate radiation dose escalation. The benefits of treatment on the ViewRay MRIdian platform derive from its three technological innovations. Firstly, patients undergo reimaging with MRI at each treatment fraction. The soft tissue definition made possible by this step greatly exceeds that which is possible using the cone-beam computed tomography (CBCT) imaging on conventional linear accelerators, giving the treating physician greater precision and therefore confidence in addressing intra and inter-fraction anatomical variability. Secondly, the MRIdian planning system is able to generate, while the patient is in the treatment position, a new radiation plan that accounts for these anatomical variations. Thirdly, the system can detect the movement of the tumour with respiration, gating the radiation beam accordingly. These three elements of so-called adaptive SABR facilitate radiation dose escalation, whilst still respecting the radiation tolerance of normal tissues and surrounding OARs.

Patients will receive 5# SABR to a total dose of 35-40 Gy over two weeks on the GenesisCare MRIdian in Oxford. The protocol is aligned with UK SABR Consortium Guidelines and international best practice at other MRIdian centres.

Patients with medically inoperable, borderline resectable, locally advanced or locally recurrent pancreatic cancer, without any evidence of metastatic disease, constitute the group potentially eligible for the programme.

Patients with operable disease are excluded, as they generally have the option of bridging chemotherapy within the NHS if surgery is not immediately available. It is preferred, but not mandated, that all patients referred have had at least three months of chemotherapy prior to SABR.

A full list of inclusion criteria is available here

A recent retrospective multi-institutional analysis of 44 patients with LAPC treated on the MRIdian platform demonstrated that dose escalated SABR has the potential to improve overall survival compared with standard doses³. All patients were treated on MRIdian, but dose, fractionation and planning approach varied between patients and institutions. Those treated to a BED10>70 Gy were deemed to have received high-dose therapy, whereas those receiving 70 Gy had received standard dose therapy. Of the high dose group, 83% underwent daily treatment adaptation, compared to 15% of the standard group. Importantly, grade 3+ toxicity was 7% in the standard dose/low adaptation group (and was seen in patients receiving concomitant gemcitabine), whereas no grade 3+ toxicity was seen in the high dose/high adaptation group. Median follow up was 17 months. At two years, 49% of the high dose group was alive, compared with 30% of the standard dose group (p=0.03). Local control was not statistically improved. On multi-variate analysis, only radiation dose and duration of induction chemotherapy were correlated with overall survival.

This data led to the prospective phase II study of stereotactic MRI-guided on-table adaptive radiation therapy (SMART) study for patients with borderline or inoperable locally advanced pancreatic cancer, led by the Henry Ford Cancer Institute in Detroit and sponsored by ViewRay (NCT03621644). The primary endpoint of the study is grade 3 or greater toxicity at 90 days when delivering a dose of 50 Gy in 5#. Secondary endpoints are overall survival at two years, distant progression free survival at six months, and changes in patient-reported quality of life at three and 12 months.

The primary purpose of the GenesisCare Foundation Compassionate Access Programme is to make precision radiotherapy available during the COVID-19 pandemic, and its aftermath. Patients are under no obligation whatsoever to participate in the collection of PROMs, and referrers are under no obligation to provide follow up data.

The secondary purpose, however, is to generate a body of data that will inform the development of clinical trials aimed at establishing a definitive role for SABR in the management of pancreatic cancer. We will therefore ask patients to consent to the collection of PROMs via a web-based app, and referring clinicians to report clinical and toxicity outcomes at 3, 6, 12 and 18 months.

Full details of the data we aspire to collect are here

The GenesisCare Foundation is an independent health promotion charity born from the philanthropic vision of GenesisCare. Its mission is to seek out and support life-changing improvements in cancer and cardiac care, in order to create profound impact at scale for both individuals and communities. It does so by investing in research that has the power to radically improve patient outcomes and by enabling access to innovative care. Chaired by Dan Collins, Founder and CEO of GenesisCare, the Board which governs the Foundation is comprised of experts in their fields who share a passion.

Pancreatic Cancer Research Fund is the only national charity dedicated exclusively to funding pancreatic cancer research. With this single-minded focus, its mission is to defeat pancreatic cancer by funding and promoting innovative, world-class research into the disease – research that will lead to the development of more effective detection, diagnosis and treatments and improved survival for patients.

ViewRay is re-envisioning radiation therapy to conquer cancer with the MRIdian® MRI-Guided Radiation Therapy System. MRIdian allows clinicians to see as they treat, adjusting the beam to allow for movement and anatomical changes. The ability to target the tumor while sparing the healthy tissue brings a new level of

control and confidence to stereotactic ablative radiotherapy.   In routine clinical use throughout the world, MRIdian is revolutionising radiation oncology and changing the paradigm in patient care.

Oxford University is renowned for research excellence, innovation, and home to some of the most talented people from across the globe. Its work helps the lives of millions, solving real-world problems through a huge network of partnerships and collaborations. The Oxford Institute for Radiation Oncology is one of the world’s leading centres for radiotherapy-related research and has established a 10-year partnership with GenesisCare, which enables the treatment of NHS patients on the ViewRay MRIdian® as a platform for state-of-the-art treatment and research thanks to a generous donation from the John Black Charitable Foundation.