Which Glioblastoma Multiforme Patient will Become a Long-Term Survivor?
Which Glioblastoma Multiforme Patient will Become a Long-Term Survivor?
abstract & commentary
Source: Scott JN, et al. Which glioblastoma multiforme patient will become a long-term survivor? A population-based study. Ann Neurol 1999;46:183-188.
Glioblastoma is the most deadly of all prima-ry brain tumors, with a median survival of 12 months following diagnosis. Long-living (LL) exceptions are thought to exist, however, and Scott and associates provide a well-written description of one relatively tiny group with a prolonged course, a low incidence of the tumor, an unusually slow evolution of symptoms, and, possibly, a favorable reaction to chemotherapy.
Patients were selected from the Alberta Cancer Registry, which, by statute, has required the registration of all cancer patients in that Canadian province since 1941. Patients selected in the present report included all diagnosed glioblastoma multiforme (GBM) cases in the province (n = 689) between 1975 and 1991. Time of onset was taken from that of the first histopathologic diagnosis and subsequent lengths of patients’ survivals Scott et al reexamined all previous charts and pathological histology. From those findings, they identified 15 persons (2.2%) from the total who have lived three years or longer from the initial clinical diagnosis. Mean survival times of the LL group amounted to 78.4 ± 13.4 months (range, 38-189 months) compared to the 97.8% remaining of 11.8 ± 1.3 months (range, 0-35 months). The biologic qualities expressed by the long-term GBM survivors [LTGBMSs] were then compared against similar qualities in three short-term control GBM patients of average age, sex, and years following time of diagnosis. The mean age of the LTGBMSs at onset averaged about 10 years younger than their sicker classic GBM confreres (i.e., 43.5 ± 3.3 yrs vs 53 ± yrs of age). They also had higher Karnowski Scale Performance scores when first diagnosed and they were capable of enduring larger brain resections than the classic GBM controls. Surgically increased post-operative neurological dysfunction is not described.
Table-Items Expressed by LTGBMSs Compared to GBM Controls | ||
LTGBMSs | GBMCs | |
n = 15 | n = 43 | |
Karnofsky Performance Status* | 86 | 76.7 |
Duration of symptoms until histology (wks)* | 31 ± 10.2 | 11.1 ± 3.7 |
Age at onset (yrs)* | 43.5 ± 3.3 | 53 ± 0.55 |
Mean survival time (months)* | 78.4 ± 13.4 | 11.8 ± 1.8 |
Range of survival time (months)* | 38-189 | 0-35 |
Presenting with seizures | 10/15 | 10/43 |
Headache, motor signs, mental status change, mood, vision | No difference | |
Gross, total’ resection | 6/15 | 6/43 |
Treated with radiation, mean cGY 6221 | Both | |
Treated with chemotherapy (n=) | 7/15 | 0/43 |
*statistically determined difference |
The histological material from the long-term survivors showed mild, but important, differences from the pathological histology found from most glioblastoma patients whose median survival time is about 12 months. Only after the blinded evaluations of all biopsy samples were passed and identified as GBMs did Scott et al’s pathologist go back to reevaluate the earlier obtained histological brain tissue of the LTGBMS. Notably, the tissues revealed fewer mitotic figures than the usual GBM, a lower number of Ki-67-positive nuclei (including slower mitoses and reduced proliferations), and, in some cells, a three-fold increase in lymphocytic infiltration compared to the number of lymphocytes invading short-lived tumors.
Commentary
Scott et al cite several things that might have lengthened survival in these patients. The LL cohort was younger by a decade from the classic GBM sufferers. They also appear to have been in better neurological health than most patients with classic GBMs when they underwent aggressive surgery. In addition, they also had a longer convalescent time to complete postoperative chemotherapy than was biologically possible for the classic GBM group. However, one-third of the long-term survivors eventually developed radiation dementia and three of the six who lived to an average of at least six years after radiotherapy suffered that complication. Whether chemotherapy applied after surgical and/or radiation therapy influenced the ultimate longevity of these patients can only be guessed at. This report emphasizes the histological variances that were identified as glioblastomas in this particular group. Even before the biopsy and after it as well, however, their early and late progression of symptoms and signs differed from the usual GBM. Why such a difference between groups? It’s hard to believe that anything but a different set of nepotistic genes expressed the more favorable course that extended these less stricken lives. —fp
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