Letter to the editor by The Philadelphia Inquirer’s James Neff
We see far too many patients with glioblastoma (GBM), an aggressive and almost always fatal malignant brain tumor.
Initial conversations with patients and families faced with this devastating diagnosis typically center on optimal treatment plans, including both standard-of-care therapy (surgical resection, radiation therapy, and multiple courses of temozolomide), and experimental options available through clinical trials.
Further discussions often focus on goals of care and how best to extend survival while maximizing health-related quality of life, but many patients eventually ask a question that lacks a satisfactory response:
“Why did I get this tumor?”
With the exception of ionizing radiation, which accounts for less than 1% of GBM diagnoses, no modifiable environmental or behavioral factors have been convincingly linked with GBM causation. In this regard, GBM is unusual among cancers as even canonical risk factors, like cigarette smoking, have not been shown to modify GBM risk.1
Within the neuro-oncology community there is a sense that the GBM patient population may even be enriched for high-achieving and health-conscious individuals. This clinical observation is increasingly supported by emerging research, including prospective cohort data observing that healthier diets are associated with an elevated risk of GBM, and genomic studies linking GBM risk to biomarkers of healthier aging and improved baseline cognitive function.2-4
Although an ongoing area of study, decades of epidemiologic research has reached an expert consensus that the causes of GBM are multifactorial, genetically influenced, modified by sex and age, and that the effects of any alleged environmental toxicants are most likely modest or nonexistent.
Two misleading stories appearing in The Philadelphia Inquirer5-6 have given voice to the unfounded belief that six Philadelphia Phillies players developed GBM as a result of exposure to chemicals used in the manufacture of artificial turf.
We do not begrudge The Inquirer for its interest in understanding the causes of GBM, as we have devoted our careers to addressing this very issue. However, by focusing on a sensational and exceedingly speculative exposure, these articles misrepresent the state of the science and do a disservice to the brain tumor community. We hope to remedy that here.
The occurrence of six GBM diagnoses among the more than 500 players on the Phillies roster over a span of several decades reflects an approximately 3-fold higher rate than expected. However, it also reflects a very small dataset, even by the standards used in analysis of “cancer clusters,” which themselves have a long history of over-interpretation.
We also note that GBM incidence is highest in men, in non-Hispanic white individuals, and in those ages 50-75, which is to say that ballplayers from the latter half of the twentieth century exemplify the key GBM demographic. We discussed this potential GBM cluster with the Phillies front office more than two years ago, after a cable news commentator suggested radar speed guns could be responsible.
By focusing on a sensational and exceedingly speculative exposure, these articles misrepresent the state of the science and do a disservice to the brain tumor community.
While three of the six Phillies players diagnosed with GBM were pitchers, radar guns operate in the same electromagnetic band as motion detectors, with frequencies below the visible spectrum and well below that of ionizing radiation (e.g., X-rays).
One of us (KMW) also had multiple conversations with a reporter from The Inquirer regarding the notion that per- and polyfluoroalkyl substances (PFAS) that they detected in souvenir sections of the old AstroTurf (purchased on eBay) could be a cause of GBM.
While noting that environmental health concerns around PFAS exposure are based on valid scientific research, we also cited research showing that compounds like PFAS have poor penetrance across the blood-brain barrier and reach the brain at levels 1,000-fold lower than other organs.
Thus, there is little biologic plausibility for a connection between these compounds and GBM, particularly compared to more credible malignancies (e.g., renal or hepatic cancer). While some of this information was included in the first Inquirer article, that article was five pages of newsprint and titled “Field of Dread.”
This may garner clicks and sell papers, but it does not represent a balanced presentation of an investigation rife with caveats.
One of us (HSF) was privileged to be the physician for Tug McGraw, who died from a GBM in 2004 at the age of 59.
As Tug’s neuro-oncologist, he is personally aware of the distress and emotional turmoil that this exploitative piece has inflicted on Tug’s wonderful family.
Families who have lost loved ones to GBM should not have their shared tragedies propagandized in articles that are light on scientific facts and heavy on alarmism.
We wholeheartedly agree that more research into GBM causation is desperately needed in order to intercept these tumors early in their clinical course or, ideally, to prevent them from ever forming. The brain tumor research community is actively engaged in this undertaking, and that work is informed by decades of dedicated effort and well-designed studies that lay a foundation for future discoveries.
There is nothing inherently wrong with evaluating the chemicals referenced in The Inquirer article for a possible role in GBM causation. However, given the state of the science, this would represent an injudicious use of the finite financial, personnel, and tissue resources available.
These resources should be allocated to the most cogent and impactful research if we seek to transform GBM prevention and care.
References
- Ostrom, Q.T., et al. The epidemiology of glioma in adults: a “state of the science” review. Neuro-oncology 16, 896-913 (2014).
- Walsh, K., et al. Shared genomic architecture of glioma and neuro-cognitive and neuro-psychiatric traits revealed by LD-score regression. Neuro Oncol 21, vi78 (2019).
- Walsh, K.M. & Claus, E.B. Diet and risk of glioma: targets for prevention remain elusive. Neuro Oncol 21, 832-833 (2019).
- Walsh, K.M., et al. Longer genotypically-estimated leukocyte telomere length is associated with increased adult glioma risk. Oncotarget 6, 42468-42477 (2015).
- Field of Dread
- What to know about ‘forever chemicals’, artificial turf, Phillies cancer deaths, and our story
