Sir
In his review of molecular mechanisms of glioma invasiveness, Rao1 addresses the mean survival time of glioblastoma (GBM) patients. According to the author, survival ranges from 17 weeks without treatment to 30 weeks after surgery and radiotherapy (S+RT) and goes up to 50 weeks after additional chemotherapy (S+RT+ChT). These figures need some clarification.
Although the prognosis of GBM patients is still very poor, the 30 weeks after S+RT are fewer than today's average. On the other hand, the 20-week — or 67% — difference between S+RT and S+RT+ChT is also not typical. Taken together, the data seem to indicate a significant impact of additional chemotherapy, which is not the case. Chemotherapy might have its merits for a subset of patients, but its influence on the median of survival, in particular, has been limited for a large number of drugs tested2,3,4.
As source for his survival data, Rao cites a review article by Avgeropoulos and Batchelor5, but these authors mention 14 weeks for conservative treatment of grade IV gliomas, 36 weeks after S+RT and 40–50 weeks for S+RT+ChT. Unfortunately, these figures are also not supported by the publications that they quote. For example, one of their references is a meta-analysis that compares S+RT versus S+RT+ChT of 16 studies, most of which comprise mixed histologies6. The two sole GBM trials yield 8.7 and 14 months for S+RT and 8, 9 and 12 months for the additional ChT arms, respectively7,8. A second reference compares historical data from the1970s and earlier9. But these S+RT results are better (40 weeks) and those for additional ChT worse (44 weeks) than those cited by Rao.
Today, radiotherapy must still be considered the main life-prolonging treatment for GBMs. Standard conventional irradiation (approximately 60 Gy high-voltage X-rays, localized in 2 Gy-fractions, 5 days per week) offers at least an additional 6 months survival compared with surgery alone9,10,11. Chemotherapeutics, if responsive at all, might change this figure by another 10–20%7,9,12.
The absolute and relative differences between the values given by Rao and those mentioned here might seem minor. However, for a rapidly developing deadly disease such as GBM, a difference in median survival of 10–20 weeks is important.
There are two other points in Rao's review that I would like to comment on. When referring to oligodendrogliomas (ODGs), he states that their prognosis worsens with the size of the necrotic areas. To my knowledge, this is not generally agreed on among pathologists. For example, Ellsworth Alvord has shown that there is marked overlap in survival rates for patients with ODGs with or without necrosis13.
According to Rao, oligodendrocytes and astrocytes are derived from the same glial progenitor cells. As was described in a recent Nature Reviews Cancer article14, this perception has been challenged. Oligodendrocytes might share the same progenitor with motor neurons, but not with astrocytes15 (Table 1).
References
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Linz, U. Aspects on the survival of patients with glioblastoma and the origin and histology of oligodendrogliomas. Nat Rev Cancer 3, 77–82 (2003). https://doi.org/10.1038/nrc1121-c1
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DOI: https://doi.org/10.1038/nrc1121-c1
