Glioblastoma and Cytomegalovirus
Jacob Schor ND, FABNO
October 5, 2013
A paper published last month suggested a possible adjunctive approach that might be useful in treating some patients who have glioblastoma. Writing in the New England Journal of Medicine, Cecilia Söderberg-Nauclér and colleagues from the Karolinska Institute in Stockholm suggest that treating cytomegalovirus (CMV) infections with the antiviral drug Valganciclovir might inhibit growth of this type of brain tumor. They first point out that DNA from this virus is found in several types of human cancer but not in the health tissues that surround the cancer. [1,2] The authors tested 250 glioblastoma patients and found that only one was negative for CMV infection.
CMV is a very common virus. Infection rates are highest in children younger than age 6. The rate of infection in adolescents is about 10–15%, but increase in young adults, up to about 50% by 35 years of age graph of incidence: http://www.atsu.edu/faculty/chamberlain/Website/lectures/lecture/IMAGE/CMVINCID.GIF
By age 60, about 80% of the population is infected. CMV is the most common viral cause of congenital defects in the United States, with 0.2–2% of all newborns infected with CMV. The most common way CMV is passed person to person is through sexual contact, both heterosexual and homosexual. While the virus is common, the frequency of infection found in this Swedish data stands out, greater than 99% of the glioblastoma patient stested were infected.
In an earlier paper looking at a group of 75 glioblastoma patients, the researchers found that survival times varied with the intensity of the CMV infection. Those with low-grade CMV infection survived a median of 33 months while those with high-grade infections survived only a median of 13 months. In other terms the 2-year survival of these two groups of patients was 63.6% and 17.2% respectively.  It appears as it CMV infection affects tumor progression.
In 2011 Baryawno reported that in an animal model of medulloblastoma (another type of brain tumor) treating against CMV reduced tumor growth by 72%. 
Earlier this year, Stragliotto reported the results of a double blind clinical trial in which 42 glioblastoma patients were treated with valganciclovir, an anti-CMV drug. Tumor growth was not significantly less at 3 or 6 months after surgery compared to controls but 2-year survival was more than double for those patients treated (50% vs. 20.6%) and overall survival was nearly doubles 24 months compared to 13.7 months.
In this current Swedish study, the authors present data on 50 glioblastoma patients treated with this same anti-CMV drug. In their words, “The rate of survival of treated patients was remarkably high: at 2 years, 62% were alive, as compared with 18% of contemporary controls ….The median overall survival was 25.0 months, as compared with 13.5 months in the controls … The median survival was higher among 40 patients who received at least 6 months of valganciclovir; their 2-year rate of survival was 70%, and their median overall survival was 30.1 months …. The survival rate was highest among 25 patients who received continuous valganciclovir treatment after the first 6 months, with a 2-year survival rate of 90% and median overall survival of 56.4 months …..”
These results are to quote my colleague Davis Lamson, “Stunning!”
A prudent course of action should now be to test every patient with either glioblastoma or medulloblastoma for CMV infection and to treat the infection if positive. This drug, valganciclovier, is specific for treating CMV. It is routinely used to treat patients who have had an organ transplant to prevent infection. It’s not cheap, four-months of treatment costs about $8500.
Note: my thanks go to Davis Lamson, ND for pointing this research out to me.
1. Taher C, de Boniface J, Mohammad A-A, et al. High prevalence of human cytomegalovirus proteins and nucleic acids in primary breast cancer and metastatic sentinel lymph nodes. PLoS One 2013;8:e56795-e56795
2. Soroceanu L, Cobbs CS. Is HCMV a tumor promoter? Virus Res 2011;157:193-203
3. Rahbar A, Orrego A, Peredo I, et al. Human cytomegalovirus infection levels in glioblastoma multiforme are of prognostic value for survival. J Clin Virol 2013;57:36-42
4. Baryawno N, Rahbar A, Wolmer-Solberg N, et al. Detection of human cytomegalovirus in medulloblastomas reveals a potential therapeutic target. J Clin Invest 2011;121:4043-405
5. Stragliotto G, Rahbar A, Solberg NW, et al. Effects of valganciclovir as an add-on therapy in patients with cytomegalovirus-positive glioblastoma: a randomized, double-blind, proof-of-concept study. Int J Cancer 2013;133:1204-1213
6. Söderberg-Nauclér C, Rahbar A, Stragliotto G. Survival in Patients with Glioblastoma Receiving Valganciclovir. N Engl J Med 2013; 369:985-986September 5, 2013 DOI: 10.1056/NEJMc1302145