By Annette M. Boyle
ATLANTA — Because of unique challenges faced by many veterans treated at VA, their median survival rate with Stage IV glioblastoma multiforme is half that reported by the National Cancer Institute’s Surveillancel Epidemiology and End Results (SEER) statistics.
That’s according to a presentation by David Cory Adamson, MD, of the Durham, NC, VAMC at the recent Association of Veterans Administration Hematologists and Oncologists (AVAHO) meeting in Atlanta.
“Clearly, veterans are not doing well in terms of getting therapies they might benefit from,” Adamson told U.S. Medicine.
Median survival for veterans are 6.5 months, while one, two and five year survival rates are 26.8, 5.4, and 0.5%, respectively, according to a study published last year in the Journal of Neuro-Oncology.1
“The tumor biology for veterans is not different than for everyone else, but the patients have different issues,” he said. “The longer survival rate seen in SEER probably results from complex therapy that is very challenging for veterans to receive — surgery, followed by radiation, followed by chemotherapy.”
Economic and logistic issues likely compound physical complications for veterans, Adamson pointed out.
“Because we’ve concentrated neurosurgery services in a few centers, many veterans travel a great distance to see us,” he said. “Veterans have more comorbidities that simply make it more difficult to progress through complex therapy for malignant gliomas. For patients with economic and other challenges, the treatment required to achieve the longer survival rate is likely too complex.”
Even for patients who are able to undertake the complex course of therapy, the median survival rate is only one year, fairly comparable to civilian survival but much lower than most cancers. Glioblastoma (GBM) is the most common and lethal of malignant primary brain tumors. A Grade IV astrocytoma, a tumor originating in the star-shaped glial cells or astrocytes that make up the supportive tissue of the brain, GBM accounts for about 17% of all brain tumors.
Treatment of Grade II astrocytoma, which may progress to glioblastoma, starts with surgery. Even at this stage, Adamson cautions that the tumors are difficult to surgically remove because of the difficulty distinguishing tumor from brain tissue and the tentacle-like projections common to their structure. “Ideally, a patient should have a complete resection upfront. The surgery is difficult, and sending a patient to someone comfortable doing it may be best,” he noted.
Adamson does not recommend radiation following surgery for all patients at this stage. “It depends on the individual patient, their age and how good the resection was. My preference for Grade II is to delay if possible. These might transform into malignant tumors, and it will be important then to treat them with everything you can.”
He particularly advises delaying radiation in a young patient with a good prognosis. “If you have a patient in their 20s, you would hate for them to develop cognitive problems from radiation in their 30s and still have many years to live.”
Grade III tumors are a different matter. “They are considered a malignant glioma like Grade IV; the biology and patients are similar. The outcomes are significantly different, however, with Grade III patients surviving a median of two to four years compared with less than a year for Grade IV,” he said.
While the treatment is similar, Adamson noted that clinical trials that lump Grade III and IV tumors together “skew results in clinical studies. They may suggest that Grade IVs will do better, when really you’re seeing the longer survival rate of Grade IIIs.”
For Grade IV GBM, a good resection increases survival close to 100%. A partial resection, however, can be highly problematic with the residual tumor often swelling quickly and hemorrhaging. “In this situation, it’s debatable if you have a positive impact on patient survival,” Adamson suggested. “I don’t recommend surgery unless you can get a very good resection. In many European countries, surgery isn’t even offered as a treatment at this stage.”
Radiation and chemotherapy increase survival rates a bit. Bevacizumab appears to boost survival somewhat more and the results of two recent clinical trials indicate that the therapy does not significantly increase hemorrhaging, something Adamson noted had concerned many surgeons.
While existing treatments have improved median survival incrementally, Adamson said that a few new strategies may change the course of treatment in the next decade.
GBM has four distinct genetic subtypes, and research in the past decade has concentrated on their mutations, signaling pathways and protein expression as opportunities for treatment. “Therapy now is very nonspecific, but researchers are trying to find agents that target specific tumor characteristics on a patient-by-patient basis,” Adamson said.
Efforts during the past few years have not been successful, “but we’re hoping that with all the momentum something will turn up. Some therapies have worked in small clinical trials and many studies are currently in process,” he added.
Of the therapies currently in development, Adamson said he considers amino therapies and vaccines especially promising. “GBM is a diffuse brain problem, and we need a therapy that’s global. If we could develop a vaccine against a particular type of tumor, it would excite the immune system to go after the tumor and kill it. These are new strategies that make very, very good sense, but it may still be many years until we see anything very effective.”
1. Arrigo RT, Boakye M, Skirboll SL. Patterns of care and survival for glioblastoma patients in the Veterans population. J Neurooncol. 2012 Feb;106(3):627-35. doi: 10.1007/s11060-011-0702-6. Epub 2011 Sep 1. PubMed PMID: 21881877.