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Despite ‘incremental’ progress, long-term survival rates ‘have not budged’ in glioblastoma
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Although median and short-term OS rates have improved for glioblastoma, still only a small proportion of patients achieve 5-year survival, according to study results published in Mayo Clinic Proceedings.
“This was a very practical study that looked at patients treated with this type of brain tumor over the years described,” Daniel M. Trifiletti, MD, radiation oncologist and researcher at Mayo Clinic in Jacksonville, Florida, said in an interview with HemOnc Today. “Over that time, we’ve been using more chemotherapy and there have been other advancements in the care of patients with brain tumors, but the long-term survival rates for the disease have not budged.”
Glioblastoma is the most common primary brain cancer in adults, accounting for approximately 75% of malignant brain tumors.
In the retrospective, observational cohort study, Trifiletti and colleagues searched the National Cancer Database for all cases of histopathologically confirmed glioblastoma between 2004 and 2009. Researchers used multivariable logistic regression models to characterize factors independently linked to survival beyond 5 years after diagnosis.
Among 48,652 patients eligible for study inclusion, 2,249 (4.6%; 95% CI, 4.5-4.7) attained 5-year OS (median, 88 months vs. 7 months for ≤ 5-year OS). Survival rates after diagnosis were 38% at 1 year, 16% at 2 years, 9% at 3 years and 6% at 4 years.
Multivariable analysis revealed several factors significantly associated with higher odds of 5-year OS, including younger median age at diagnosis (5-year OS cohort, 52 years vs. ≤ 5-year OS cohort, 64 years), female sex (45.4% vs. 42.7%), fewer medical comorbidities (Charlson/Deyo score of zero, 85.1% vs. 72.3%), nonwhite race (18.8% vs. 12%), median income above $63,000 (40.5% vs. 32.3%), left-sided tumors (51% vs. 47.4%) and treatment with radiotherapy (82.4% vs. 68.1%; P < .05 for all).
Median survival among all patients during the 6-year study period was 8.1 months (95% CI, 8-8.2).
“The 1-year survival rates improved over that time, but the 5-year survival rates did not,” Trifiletti said. “These were not patients who were necessarily enrolled in clinical trials; and they were patients treated at a variety of medical centers, both academic and community.”
‘The rule is that they recur’
Trifiletti spoke with HemOnc Today about the challenges of treating glioblastoma.
“One issue is that it’s in the brain, so surgery is always going to be somewhat limited,” he said. “In the same way, chemotherapy is limited in its access to the brain; it has difficulty getting in the brain. The tumor cells have also been known to infiltrate the brain beyond what we can see, so even if the surgeon could cut everything out, they can’t necessarily see everything that needs to be cut out.”
Additionally, Trifiletti said, glioblastoma tumor cells quickly become resistant to current chemotherapies and radiation techniques.
“Essentially, the rule is that they recur with the current treatments that we have,” he said.
Although improvements in median and short-term survival are encouraging, they suggest only modest success in controlling this difficult-to-treat cancer, Trifiletti said.
“It wasn’t that surprising that 1-year survival improved over the time period,” he told HemOnc Today. “As a whole, it suggests that although we’re making improvements, they’re really incremental and it could be delaying things more than solving them.”
‘Swing hard for the fences’
Trifiletti said new research being conducted in glioblastoma could improve the outlook for patients.
“It’s not just more radiation, more chemotherapy or bigger surgeries,” he said. “It’s using targeted therapies that have never been used in humans before. It’s all very early, but things like immunotherapy represent different cancer therapy domains, and a new way of thinking about systemic therapy.”
Trifiletti noted that researchers are exploring cellular therapies to target cancers and bioengineering nanoparticles to treat brain tumors. In these approaches, researchers create a de novo virus in a laboratory that can be delivered to the patient’s tumor to affect and alter its DNA. He said compelling work is being done with the polio and measles viruses, and his lab is using a virus to infect stem cells, modify their DNA and, in turn, trigger the stem cells to attack the cancer.
“I think these approaches are going to redefine the treatment of cancer beyond traditional chemotherapies, which were validated in the 1950s; radiotherapy, which was validated in the early 1900s; and surgery, which we’ve been doing for a thousand years,” Trifiletti told HemOnc Today. “Not all of these new approaches are going to work. It’s going to be dangerous, but it’s my belief that we need to be exploring these areas and pushing the envelope. We need to think bigger than small studies with incremental, short-term benefits and really swing hard for the fences.” - by Jennifer Byrne
For more information:
Daniel M. Trifiletti, MD, can be reached at 4500 San Pablo Road, Jacksonville, FL 32224; email: trifiletti.daniel@mayo.edu.
Disclosures: Trifiletti reports institutional funding from Novocure and publishing fees from Springer Inc. Please see the study for all other authors’ relevant financial disclosures.
Perspective
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John Suh, MD
Glioblastoma is the most common primary malignant brain tumor among adults, with an estimated 12,000 cases annually in the United States. Public awareness of this tumor increased following the deaths of U.S. Sens. John McCain and Ted Kennedy. In their honor, the Senate designated July 17, 2019, as Glioblastoma Awareness Day.
Despite advances in surgery, radiation therapy, imaging and chemotherapy, median survival for patients with glioblastoma remains dismal. It is a devastating cancer that deserves better therapeutic approaches and translational research.
The study from Cantrell and colleagues is the largest to evaluate factors associated with long-term survival for patients with glioblastoma. The researchers analyzed numerous factors to determine which group of patients achieved long-term survival, which was defined as 5 years or more. Not surprisingly, multivariate analysis revealed the use of radiation therapy, fewer medical comorbidities, higher median income quartile, nonbrainstem tumor location and younger age were associated with better outcomes. Median OS was 8.1 months and the 5-year survival rate was 4.6%. Unfortunately, despite treatment advances, this study demonstrated that 5-year survival rates were unchanged over the 6-year study period.
Limitations of this retrospective study included the unknown status of tumor biomarkers such as isocitrate dehydrogenase 1 (IDH-1) and O⁶-methylguanine-DNA methyltransferase (MGMT), the potential impact of newer therapeutic approaches such as bevacizumab (Avastin, Genentech) and tumor-treating fields, and our current understanding of patient stratification based on tumor biology and genetics.
This study underscores that the likelihood for long-term survival for patients with glioblastoma remains elusive despite the efforts of many dedicated physicians and scientists. Given the current outcomes, the importance of innovative multidisciplinary approaches and clinical trials remains paramount for a disease that clearly has an unmet clinical need.
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