In a recent article in the New England Journal of Medicine I read about a novel possibility for treating cancer that I had not been aware of. The study’s title was “Oncolytic DNX-2401 Virus for Pediatric Diffuse Intrinsic Pontine Glioma”.
It started by saying that pediatric patients with diffuse intrinsic pontine glioma (DIPG) have a poor prognosis, with a median survival of less than 1 year. DNX-2401 is an oncolytic adenovirus that selectively replicates in tumor cells. 12 patients with newly diagnosed DIPG were given a single infusion of the virus through a catheter placed in the cerebellar peduncle, followed by radiotherapy.

Results

Treatment resulted in changes in T-cell activity and a reduction in or stabilization of tumor size in some patients but was associated with adverse events including headache, nausea, vomiting, and fatigue. Hemiparesis and tetraparesis developed in 1 patient each.

The study was done in Spain at the Clínica Universidad de Navarra.

Follow-up

Over a median follow-up of 17.8 months (range, 5.9 to 33.5), a reduction in tumor size, as assessed on magnetic resonance imaging, was reported in 9 patients, a partial response in 3 patients, and stable disease in 8 patients. The median survival was 17.8 months. Two patients were alive at the time of preparation of the report, 1 of whom was free of tumor progression at 38 months.

First impression: Wow!

My first reaction was delight and amazement. I had never imagined that a virus could infect and kill a tumor. That’s welcome knowledge that could potentially have many useful clinical applications. Cutting edge science.

Second impression: What about informed consent?

As I thought more about this, my enthusiasm ebbed. The news from this study is not really so favorable. I reflected that parents of these children would have to give informed consent, and I wondered how many of them would give that consent if they fully understood all the facts.

  • This is an experimental treatment that has only been tried in 12 patients age 3 to 18.
  • The patient has to undergo surgery and brain biopsy. Surgery carries its own risks. The idea of brain biopsy itself is scary; the idea of inserting a cannula deeper into the biopsy tract is even scarier.
  • Deliberately injecting a virus into the brain to cause infection would strike many people as rather barbaric.
  • A 25% reduction in tumor size was seen in 75% of patients. The clinical significance of this was uncertain.
  • At 18 months after treatment, only 50% of the patients were still alive. At 33.5 months after treatment, only 3 of the 12 patients were still alive. Two patients were still alive at the time of preparation of the article, 1 of whom was free of tumor progression at 38 months.
  • Patients were hospitalized for 0.6 to 6.8 days for the procedure and recovery.
  • After treatment, 11 of the 12 patients continued to receive radiation therapy. The parents of 1 patient declined radiotherapy and any further treatment.
  • When there was evidence of tumor progression, other treatments were given at the discretion of the oncologist, including chemotherapy, reirradiation, antiangiogenic therapy, or investigational agents.
  • 75% of the patients had side effects from the treatment.
    • 9 patients each had headache, neurologic deterioration, or vomiting
    • 8 patients had fatigue
    • 6 patients developed a fever
  • Three serious adverse events were reported:
    • One patient had transitory grade 3 hemiparesis which lessened in severity to mild hemiparesis after 12 weeks.
    • One patient had grade 3 neurologic deterioration of increased bilateral oculomotor paresis and tetraparesis, which started after hospital discharge and worsened during radiotherapy.
    • A third patient was hospitalized for abdominal pain; no cause was found

To summarize, this experimental treatment reduced tumor size for some patients but was associated with adverse events. It required hospitalization, surgery, and iatrogenic infection with a virus. Patients continued to receive radiotherapy and other treatments. Due to the small study size, the effect of the treatment on survival could not be calculated.

What to do?

I tried to imagine I was the parent of a child with newly diagnosed DIPG with a median survival of less than a year, especially if they were too young to understand. I would desperately want my child to live, but I hope I would be able to prioritize the best interests of my child over my own feelings. Would I want to subject them to the pain, suffering, and potential side effects of this treatment regimen for such a small chance of benefit? I think I would not. Desperate situations lead to desperate decisions; sometimes those decisions may not be the most rational.

Author

  • Harriet Hall, MD also known as The SkepDoc, is a retired family physician who writes about pseudoscience and questionable medical practices. She received her BA and MD from the University of Washington, did her internship in the Air Force (the second female ever to do so),  and was the first female graduate of the Air Force family practice residency at Eglin Air Force Base. During a long career as an Air Force physician, she held various positions from flight surgeon to DBMS (Director of Base Medical Services) and did everything from delivering babies to taking the controls of a B-52. She retired with the rank of Colonel.  In 2008 she published her memoirs, Women Aren't Supposed to Fly.

Posted by Harriet Hall

Harriet Hall, MD also known as The SkepDoc, is a retired family physician who writes about pseudoscience and questionable medical practices. She received her BA and MD from the University of Washington, did her internship in the Air Force (the second female ever to do so),  and was the first female graduate of the Air Force family practice residency at Eglin Air Force Base. During a long career as an Air Force physician, she held various positions from flight surgeon to DBMS (Director of Base Medical Services) and did everything from delivering babies to taking the controls of a B-52. She retired with the rank of Colonel.  In 2008 she published her memoirs, Women Aren't Supposed to Fly.