MEXICO CITY— Image Guided Cancer Specialist Medical doctor, board-certified radiologist and researcher Jason Williams, MD, has a new solution to the spiraling costs of cancer treatments: Inject the immunotherapy drugs directly into the cancerous tumor after using image-guided cryoablation.
Approved immunotherapy drugs (such as Yervoy, Keytruda and Optdivo) are proving highly effective at manipulating the body’s immune system to fight cancer. When cancer develops, the tumor’s cells put a brake on the immune system, stopping normal immune reactions to protect the invading cancer cells. The current class of immunotherapy drugs flips the switch back, so that the immune system can function normally.Cryoablation Immunotherapy
However, these drugs are also extremely expensive. The average cost for using these drugs in combination at a standard dose is about $300,000 per year. And the higher doses being used in the current research mean that figure could climb to $1 million annually. At the American Society of Clinical Oncology Annual Meeting last year,Leonard Saltz, MD, from Memorial Sloan Kettering Cancer Center in New York, said the total cost to treat all metastatic cancer patients in the United States would be an “unsustainable” $174 billion per year. Other issues are that these drugs can potentially provoke an autoimmune disease response; by taking off the brake, the immune system can go into overdrive and begin attacking normal cells.
That’s because they are administered intravenously and, therefore, throughout the body. Dr. Williams wants to take the benefits of immunotherapy drugs and enhance them with better precision. Indeed, injection of immunotherapy is very promising (see “Further reading”). Animal research has shown that combining injection of immunotherapy drugs with cryoablation of the tumor improves survival rates by more than 80%. The ablation process kills the tumor inside the body, releasing tumor antigens to stimulate an anti-cancer immune response. However, this immune stimulation is rarely strong enough on its own to generate a curative response — until you add immune checkpoint-inhibitor drugs.
“Biologically, the idea makes sense, because intentionally leaving dead tissue for the body to dispose of naturally is a way to potentially immunize against cancer cells,” says tumor immunology and immunotherapy researcher Alex Y. Huang, MD, PhD, associate professor of the department of pediatrics at Case Western Reserve University School of Medicine, and clinical fellowship director of the division of pediatric hematology/oncology at University Hospitals Case Medical Center/Rainbow Babies & Children’s Hospital. “Cryoablation uses cold temperature to induce necrotic cell death, which is a signal for the immune system to wake up. The dead tumor proteins will be seen as foreign by the immune system, which will attack the cancer.”
Dr. Williams’s model is novel because after freezing and killing those cells, he then uses image guidance technology to put probes into the remaining tumor. Then, instead of surgically removing the cancerous growth, he injects the immunotherapy drugs directly into the problematic tissue.
“This has the double benefit of activating the local immune system against cancer in other locations, without globally activating the immune system against the patient’s healthy tissue,” says Dr. Huang. “The risk of hitting the wrong tissue is low and, we know these drugs are safe at much higher systemic rather than smaller, targeted doses. The potential for systemic toxicity is lower and, because the drugs are given only locally, the cost is vastly reduced.”
Animal-model studies have shown that one-eighth the typical IV dose is required when using local injections. If the current therapy costs $300,000 per year, the same clinical effectiveness could be achieved for $37,500worth of drug.
80 humans treated
Dr. Williams has already used this therapy in approximately 80 human patients, including one patient with advanced breast cancer who had more than 30 tumors in the lungs, bones and brain.
“A single treatment ablated two lung tumors and, using combination immunotherapy, she had complete resolution of the tumors in the body and 50% reduction in size and number of the brain tumors,” says Dr. Williams. In many patients, we have seen complete resolution of their cancer, even in remote sites not directly treated. We have treated enough patients now to know that these results are not a fluke, but I look forward to testing this therapy in an official clinical trial.”
Dr. Huang notes that clinical trials are needed to prove the technique, and further research would be needed to develop protocols for patient selection and reproducibly safe, effective use of the combined cryoablation/immunotherapy-injection technique. Dr. Williams hopes to get funding and approval for further trials, so that he can prove his results in a controlled setting.
“The combination offers equal effectiveness, reduced cost and lower toxicity — it’s a win all the way around,” says Dr. Williams. “I think with a little tweaking of the therapy, and we could be truly talking about a ‘cure,’ in a very high percentage of patients,” says Dr. Williams.