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‘Out-of-the-Box’ Approaches Needed for Glioblastoma

More “out-of-the-box” approaches are being called for in the treatment of glioblastoma, because long-term survival remains unchanged and grim despite recent concentrated efforts to improve outcomes for these patients, a retrospective analysis shows.

“I expected the 5-year survival [outcomes] to be poor because the median survival for these patients is only about 1 year,” senior author Daniel Trifiletti, MD, Mayo Clinic, Jacksonville, Florida, told Medscape Medical News.

“But what is remarkable to me is not so much that the 5-year survival is so poor but that there hasn’t been any improvement in it,” he said.

“So we need to imagine more novel, more radical, more ‘out-of-the-box’ approaches to treat this tumor if we are going to achieve anything other than incremental, short-term benefits,” he added.

The study was published online June 20 in the Mayo Clinic Proceedings.

Observational Cohort

For their study, the authors took an observational cohort from the National Cancer Database, which accounts for about 70% of patients in the United States who have been treated for cancer.

Only patients diagnosed between January 2004 and December 2009 were included in the analysis in order to reflect current clinical practice in the treatment of glioblastoma.

Of 48,652 patients who had received a pathologic diagnosis of glioblastoma during the study interval, only 4.6% survived to 5 years.

For the overall cohort, median survival was 8.1 months, although median survival rates varied greatly, depending on whether patients survived 5 years or not, the investigators note.

Twelve months after being diagnosed, 38% of patients were still alive, as were 16% at 24 months, 9% at 36 months, and 6% at 48 months, the researchers add.

These survival rates are probably lower than median survival rates reported from clinical trials, Trifiletti commented. Only patients with a better performance status are enrolled in clinical trials, whereas patients with poorer performance status are rarely selected.

Among patients who survived to 5 years, the median age at diagnosis was 52 years, which is younger than the median age of 64 years among those who did not survive to 5 years, the investigators write.

For those who survived to 5 years, median survival was 88 months, vs a median of 7 months among patients who did not live to 5 years, the investigators add.

Longer-term survivors had a number of favorable characteristics; 85% of these patients had a Charlson/Deyo score of 0, “signifying no recorded comorbid medical condition,” the researchers observe.

The use of radiotherapy was more frequent among the 5-year survivors, at 82%, compared to 68% for those who did not survive 5 years.

So, too, was the use of chemotherapy; 46% of patients who survived 5 years received chemotherapy, compared with 35% of those who did not survive to 5 years.

On multivariable analysis, patients who received radiotherapy were 64% more likely to survive to 5 years than patients who did not (odds ratio [OR], 1.64; P < .001).

Similarly, patients in the highest median income quartile were 52% more likely to survive to 5 years compared to those in the lowest median income quartile (OR, 1.52; P < .001).

Other favorable prognostic features associated with an increased likelihood of achieving longer-term survivorship include the following:

  • Nonwhite race: 50% more likely to live 5 years vs white patients (OR, 1.50; P = .04)

  • Female sex: 40% more likely to live 5 years vs male sex (OR, 1.40; P < .001)

  • Residing farther than 100 miles from the treatment center: 27% more likely to live 5 years compared with residing less distance from the treatment center (OR, 1.27; P = .04)

  • Left-sided tumors: 16% more likely to live 5 years compared to having tumors located elsewhere (OR, 1.16; P = .02)

Age at diagnosis negatively affected survival odds, with each 1-year increase in age decreasing 5-year survival odds by 5% (OR, 0.95; < . 001).

Patients whose tumors were located in the brainstem were 60% less likely to survive 5 years than patients whose tumors were located elsewhere (OR, 0.40; P < .001).

However, in contrast to other reports, tumor size did not significantly alter the likelihood of patients achieving long-term survivorship, the investigators note.

“To me, what these findings mean is that increasing the radiation dose or offering more cycles of chemotherapy will not impact the long-term outcome of this disease,” Trifiletti said.

“So we need to find new pathways of inhibition, new types of surgery, new types of radiation. We need to change the way we think about the typical management of this disease, which to me would have more of an impact on long-term survival than any change in radiation dose of chemotherapy,” he added.

The investigators recommend that patients with glioblastoma be offered a chance to participate in any available clinical trial. They hope that the new approaches to the treatment of cancer overall — which include immunotherapy, checkpoint inhibitors, and chimeric antigen–receptor (CAR) T-cell and stem-cell therapies — may lead to a breakthrough in the treatment of this deadly malignancy.

Trifiletti has received research grants from NovoCure. One coauthor serves on the data and safety monitoring board of Novella. The other authors have disclosed no relevant financial relationships.

Mayo Clin Proc. Published online June 20, 2019. Full text

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