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For many neurosurgeons, years of training and technical refinement culminate in safely removing a patient’s brain tumor. We dedicate our careers to shepherding people past this inflection point, but the patient journey does not end there. For those with malignant tumors, our surgical heroics are quickly unraveled by tumor recurrence. Theoretically, adjuvant medical therapy should firewall patients against this reality; however, as we all know, no drug today provides much security to brain tumor patients. Our specialty is uniquely positioned to do something about this. Drug development is no longer the sole domain of oncologists, and some of the most impactful drug studies live in our operating rooms.

Conventional clinical trials are exercises in tremendous faith: an educated guess matches a patient to a new drug, followed by months of therapy (and side effects), ending with an MRI that provides, at best, an indirect measure of putative drug effect. For neurosurgical oncologists, Phase 0 and window-of-opportunity clinical trial paradigms offer a different take: brief, presurgical exposure to the experimental therapy, followed by a tumor resection that allows for direct measurement of drug penetration and target modulation in the patient’s own tissue. If the drug proves its worth in the patient’s tumor, the patient can remain on the drug long-term. In other words, safe and rapid quantification of drug effects in the end-user without sacrificing the one commodity all malignant brain tumor patients have in short supply — time.

It was nearly 20 years ago that the Food and Drug Administration last approved a new drug capable of extending high-grade brain tumor patients’ lives. Let that sink in for a moment, and allow yourself to question everything about it. This 20-year losing streak we are all living through is not happening for lack of effort or expertise. We are all aware of the unique challenges facing brain tumor drug development:

  • Poorly-predictive animal models;
  • Unclear tumor driver mutations;
  • Poorly brain-penetrant drugs;
  • Insufficient translational science funding;
  • Small market size; and
  • Patient risks from aggressive treatment.

These realities, and our accompanying track record, suggest that current systems governing oncology drug development should make way for a new paradigm — accelerated early-phase clinical trialing that quickly identifies and prioritizes drugs that deliver on their promise and, with equal analytical ruthlessness, eliminates those that do not.

Understanding the varied dimensions of drug development is a tall order for any specialty. But decades ago, ours made a concerted effort to expand the neurosurgeon-neuroscientist footprint. Today, an entire generation of us are as fluent in the laboratory as in the operating room. Drug development is our next frontier. For neurosurgeons like myself who are engaging in it, each patient’s operation has become a beginning instead of an end.

Editor’s Note: We hope you will share what you learn from our posts. We invite you to join the conversation on Twitter by following @Neurosurgery and @NSTumorSection and using the hashtag #TumorSeries.

Nader Sanai, MD, FAANS

Phoenix, Ariz.

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