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NCI Researchers Discuss Prospects and Challenges of Treating Glioblastoma


Amidst news of Senator John McCain’s glioblastoma diagnosis, a recent discussion between 2 neuro-oncology researchers explored the reasons why this aggressive brain tumor is so difficult to manage, and outlined the ongoing investigations into possible therapies.

Amidst news of Senator John McCain’s glioblastoma diagnosis, a recent discussion between 2 neuro-oncology researchers explored the reasons why this aggressive brain tumor is so difficult to manage and outlined the ongoing investigations into possible therapies.

Mark Gilbert, MD, senior investigator and chief of the Neuro-Oncology Branch (NOB) of the National Cancer Institute (NCI), and Terri Armstrong, PhD, senior investigator in the NOB Patient Outcomes Program, participated in a question and answer session published by NCI. They discussed the prognosis, current treatments, and potential new therapies for patients with glioblastoma.

The grade IV cancer grows quickly in the brain, they explained, leading to generally poor prognoses and a current median survival time of 15 to 18 months. Treatment options include brain surgery to remove the tumor followed by radiation and chemotherapy to slow the tumor’s growth. The most commonly used chemotherapy drug is temozolomide.

According to Armstrong, “the standard of care for glioblastoma patients aged 70 and above has been less standardized than that for younger patients.” However, older patients like Senator McCain, who will turn 81 later this month, may be encouraged by the results of a Canadian trial that found patients with glioblastoma aged 65 and older tolerated a regimen of radiation and temozolomide well and demonstrated improved survival.

Glioblastoma presents a number of challenges that make it difficult to treat effectively, the experts said. First, these tumors are fast-growing and heterogeneous, which can make them resistant to traditional cancer treatments. Their location in the brain further complicates matters: the blood-brain barrier prevents many drugs from reaching the tumors, surgery must be performed conservatively to avoid cognitive or neurological damage, and the swelling that often accompanies cancer treatments is more dangerous inside the hard skull.

Still, some of the qualities that make glioblastoma difficult to manage may provide clues to opportunities for improvement. “The immune response to brain tumors is generally weak,” said Gilbert, but researchers are optimistic that with more research into the brain’s immune system, it will someday be possible to treat glioblastoma with immunotherapy.

That goal appeared to be set back in April with the news that a trial of nivolumab in patients with recurrent glioblastoma failed to meet the primary endpoint of improved survival compared with the standard of care treatment.

However, other promising avenues involving immunotherapy remain. A case study published in December 2016 demonstrated that a course of 10 chimeric antigen receptor-T cell infusions administered to a single patient with glioblastoma was associated with reductions in the size of all intracranial and spinal tumors.

An active phase II trial aims to test the efficacy of radiation, temozolomide, and pembrolizumab with or without vitespen in patients with newly diagnosed glioblastoma. Vitespen, a vaccine made from the patient’s tumor cells, “may help the body build an effective immune response to kill tumor cells that express gp96 heat shock proteins,” according to the NCI’s description of the trial.

In the discussion, the researchers emphasized that while glioblastoma may be a daunting diagnosis, patients can help advance current knowledge by participating in clinical trials.

“Although the improvements in outcomes have been small and slow, we are optimistic that with continued research efforts, we will discover better, less-toxic treatments and make progress against this disease,” Gilbert concluded.

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