Radiosurgery for spine tumours: an interview with Dr. Arjun Sahgal
By: Sarasa Tohyama
Dr. Arjun Sahgal is a pioneer in the implementation of stereotactic radiosurgery to treat spine metastases in Canada. He has also played an instrumental role in accelerating the field of spine radiosurgery globally. A staff radiation oncologist at the Sunnybrook Health Sciences Centre and clinician-scientist in the Odette Cancer Research Program at Sunnybrook Research Institute, Dr. Sahgal is also an associate professor in the Department of Radiation Oncology at the University of Toronto. I had the opportunity to sit down with Dr. Sahgal to discover more about his innovative therapeutic strategy.
Can you tell us about your academic trajectory?
I was trained in Toronto as a resident and went on to complete a fellowship in radiosurgery at the University of California San Francisco (UCSF) with Professor David Larson. Traditionally, radiosurgery has been considered a targeted radiation technique used to treat brain metastases. As the technology evolved to deliver highly precise radiation in the body, a few early adopters, including those at UCSF, began to treat spine metastases. The main intent was to maximize local tumour control and prevent malignant spinal cord compression. I had the opportunity to learn the technique–which had yet to be implemented in Canada–and develop it further for mainstream practice, rather than a one-off treatment offered in a few specialized centres.
In San Francisco, I saw firsthand the patient-reported benefits of spine radiosurgery as they achieved complete pain relief, long-term local tumour control, and no damage to the spinal cord. I wanted to make this therapy available for Canadians. However, I realized that many questions remained unanswered regarding its safe practice, and that this therapeutic strategy for spine metastases was an untouched area globally. My goal was to build a robust program for the University of Toronto, as I worked at the time in both the Sunnybrook Odette Cancer Centre and the Princess Margaret Cancer Centre.
How does radiosurgery differ from conventional radiation therapy?
The main difference between the two is the radiation dose and exposure to the surrounding healthy tissues. The dose used in radiosurgery is three to four times greater compared to conventional palliative external beam radiotherapy. As early adopters, we challenged the dogma that dose does not matter for spine metastases. We argued in our publications and at scientific meetings that by escalating the dose, we can achieve both better tumour control and complete pain relief, without damaging the adjacent spinal cord. The bottom line is that we believed dose matters, and we were in the era of applying the technology to allow for high precision spine radiation. It was time to bring this technique to the forefront of global practice.
What has been your most significant finding?
Our biggest accomplishment thus far has been figuring out the optimal dose for spine radiosurgery, which we found to be 24 Gray (Gy: a unit of ionizing radiation) in two-fractions. We established this ideal dose through our observations of treating patients initially with 24 Gy in three-fractions which was common practice, followed by a single fraction of 24 Gy, which we found was too toxic. Ultimately, our observations, understanding of radiobiology, and response assessment led us to develop this new dose for spine radiosurgery. In developing this dose, we also had to find an appropriate spinal cord constraint.
Through an international collaboration, we have published landmark papers on spinal cord tolerance that guided safe practice globally and have been incorporated into clinical trials.1-5 Of particular significance along our trajectory of developing the dose was the observation of radiation induced vertebral compression fracture (VCF). Our data suggested a 10% risk of VCF with our approach, and through collaborations with the MD Anderson and Cleveland Clinic, we determined a complication-dose response relationship. We have since investigated risk factors for VCF with Dr. Cari Whyne’s biomechanics lab. We’ve also developed new approaches to enhance response while performing cement augmentation–a technique used to stabilize VCFs–with Dr. Albert Yee and his photodynamic therapy program for spinal metastases.
It is important to examine the safety profile to its fullest so that everybody understands what to expect of this radiation dose–both in terms of local control and expected side effects, such as fracture, pain, and radiation myelopathy, which is a rare condition where radiation causes damage to the white matter in the spinal cord. Once you establish safe guidelines for practice, you will know how to consent your patients properly. We certainly have achieved this through dedicated research over the last decade.
Where is your research currently going?
Currently, we are testing this 24 Gy two-fractions dose against conventional radiation in a national phase III randomized controlled trial (SC-24) sponsored by the Canadian Clinical Trials Group (CCTG). Our hope is that institutions across Canada can emulate our spine radiosurgery program and use it as a better treatment option compared to standard radiation treatment. This trial is currently more than halfway done. We also contribute our data to the AOSpine EPOSO global spine registry, which is near its first phase of completion and represents a major international initiative to collect high quality outcome data for spinal metastases. Mikki Campbell, as project lead, has been instrumental in the success of this program and is currently helping develop it at other academic programs.
What is one area in your field that future research should focus on?
One of our biggest interests now is to move onto the postoperative patient. Traditionally, we have treated patients postoperatively with a lower dose of radiation to control the tumour, even though they have undergone a massive operation prior. However, there is an incongruence with this philosophy. We are hoping that the postoperative phase will be the focus of the next randomized trial. Specifically, a comparison between postoperative conventional radiation and postoperative radiosurgery. We are surely in need of leaders in the development of postoperative spine radiosurgery.
Lastly, as a clinician-scientist, why do you think it is important to combine both clinical work and research in your field?
The biggest driver is to advance patient care. As a clinician-scientist, you can take your research directly into the clinic and develop something that is geared to improve patient treatment on a local and global scale. If you can do this systematically, you can really make a global impact.
- Thibault I, Whyne CM, Zhou S, et al. Volume of Lytic Vertebral Body Metastatic Disease Quantified Using Computed Tomography-Based Image Segmentation Predicts Fracture Risk After Spine Stereotactic Body Radiation Therapy. Int J Radiat Oncol Biol Phys. 2017 Jan 1;97(1):75-81. doi: 10.1016/j.ijrobp.2016.09.029. Epub 2016 Sep 28.
- Thibault I, Chang EL, Sheehan J, et al. Response assessment after stereotactic body radiotherapy for spinal metastasis: a report from the SPIne response assessment in Neuro-Oncology (SPINO) group. Lancet Oncol. 2015 Dec;16(16):e595-603. doi: 10.1016/S1470-2045(15)00166-7. Review.
- Al-Omair A, Masucci L, Masson-Cote L, et al. Surgical resection of epidural disease improves local control following postoperative spine stereotactic body radiotherapy. Neuro Oncol. 2013 Oct;15(10):1413-9. doi: 10.1093/neuonc/not101.
- Sahgal A, Atenafu EG, Chao S, et al. Vertebral compression fracture after spine stereotactic body radiotherapy: a multi-institutional analysis with a focus on radiation dose and the spinal instability neoplastic score. Clin Oncol. 2013 Sep 20;31(27):3426-31. doi: 10.1200/JCO.2013.50.1411. Epub 2013 Aug 19.
- Sahgal A, Whyne CM, Ma L, Larson DA, Fehlings MG. Vertebral compression fracture after stereotactic body radiotherapy for spinal metastases. Lancet Oncol. 2013 Jul;14(8):e310-20. doi: 10.1016/S1470-2045(13)70101-3. Review