I truly believe we’re at the beginning of something great in terms of fundamentally changing how we approach pancreatic cancer, the third leading cause of cancer death in the United States. With a mortality rate of roughly 80 percent, it’s been referred to as a medical emergency, yet minimal progress has been made in its treatment over the past few decades.
In the world of radiation oncology, published literature has shown that delivering ablative – or destructive – doses of radiation offers the best outcomes in terms of local control of the tumor and survival; however, doing so requires the utmost precision to ensure the cancer-killing dose is hitting the tumor, with careful attention to ensuring surrounding healthy tissues and critical organs are spared.
As you can imagine, this is especially challenging in the treatment of pancreatic cancer, where the nearby bowel and stomach are intolerant of high doses of radiation, and exposure can cause significant issues, including death.
Often these pancreatic tumors have entangled themselves into surrounding blood vessels and tissue in the abdomen, leaving many patients inoperable and further contributing to the deadly nature of the disease. In fact, at diagnosis, only about 20 percent of pancreatic cancer patients are eligible for surgery, and their prognosis is especially poor.
The current standard of care in pancreatic cancer includes CT-guided radiation therapy; however, a shortcoming of CT guidance is the lack of a clear definition of normal organs and the tumor leaving clinicians to essentially guess the whereabouts of the tumor and nearby healthy tissue. This results in the addition of buffers, known as margins, to account for this uncertainty and the need to constrain the delivered dose to a non-ablative one. Studies have shown the median survival for inoperable pancreatic patients receiving this standard form of radiation therapy and chemotherapy to be only about 12 to 15 months.
This leaves us with an unmet need that could be filled by ablative therapy, but in order to deliver such a high dose in pancreatic cancer, we need to be able to see what is happening inside the body. I’d equate it to achieving outcomes that may be similar to surgery – without the scalpel — and a surgeon would never operate blindfolded, so the same principles apply here.
Fortunately, the past decade has brought us advances in image guidance, including the introduction of MR-guided radiation therapy, which uses real-time MRI imaging to continuously track the tumor throughout treatment. This soft-tissue visualization lets us see what’s happening inside the body and thereby control the radiation beam so that it can be delivered with pinpoint accuracy.
This has enabled a new form of treatment known as SMART, which stands for “stereotactic MR-guided adaptive radiation therapy.” With SMART, modifications can be made throughout treatment in response to changes in the tumor and nearby internal anatomy, enabling a more precise, personalized treatment and allowing for the safe delivery of ablative doses. SMART treatments do not require anesthesia, are completely non-invasive, and are done as an outpatient typically in five treatment sessions, which is an added patient convenience when compared to the (approximately) 30 sessions required for standard radiation therapy. This novel treatment results in little to no downtime for patients, who are typically able to carry out their day-to-day activities without limitations.
I recently had the opportunity to present recent data on SMART for inoperable pancreatic cancer during the annual meeting of the American Society for Radiation Oncology (ASTRO). Using the Radiosurgery SocietyRSSearch Registry, my coinvestigators and I pooled data from my institution – Miami Cancer Institute – and two other centers to create what I believe is the largest analysis of ablative radiation therapy for pancreatic cancer (both CT-guided and MR-guided).
The findings from 148 inoperable pancreatic cancer patients treated with ablative doses using SMART, showed longer median survival of 26 months compared to 12-15 months typically seen in patients receiving chemotherapy and standard radiation therapy. Most impressive was the 2-year overall survival, which was 52.7 percent — more than double the expected two-year survival rate of 20 percent with lower dose radiation. Importantly these outcomes were achieved with low rates of major adverse events, no higher than those reported with standard radiation therapy.
The data are remarkable and promising, though beyond the numbers is a bigger picture. Each data point represents a life – a mother, uncle, grandparent, loved one, friend. Technological advances in image guidance and therapeutic delivery are allowing us to extend life – and quality of life – for patients who previously thought they were facing sudden death. Seeing these patients celebrate another birthday, travel somewhere new, and achieve major milestones is humbling and what drives my work every day.
I believe these improved survival findings are just the tip of the iceberg. With MRI-guided radiation therapy, we’re changing the paradigm in the treatment of pancreatic cancer, and I venture to guess that through continued awareness, research and innovation, I may be fortunate enough to present findings that rival even these someday soon.
Michael Chuong is a radiation oncologist.
Image credit: Shutterstock.com
