Childhood Cancer: Changing the Rules of Engagement for Hope
Recently, I found myself drawn to author Malcolm Gladwell’s works. The latest book that caught my attention is David and Goliath: Underdogs, Misfits and the Art of Battling Giants. In the beginning of the book, Gladwell recounts the epic battle between the seemingly meek shepherd David and the giant Goliath, who was adorned in armor from head to toe, and accompanied by an aide carrying several weapons for use in the battle. Following Gladwell’s description of the battle, which we know was devastatingly and decisively won by David, he then deconstructs this ancient story and shifts the reader’s perspective dramatically. Rather than simply the triumph of an underdog over impossible odds, Gladwell believes that the more important lesson learned is that David created new rules for engagement. Victory it seemed depended upon overcoming insanity. Gladwell argues that Goliath, and all those gathered to observe the giant’s anticipated victory, expected David to engage him at close range with a handheld weapon, thus playing right into the giant’s strengths. Instead, David utilized a destructive weapon with precision, surprise and deadly force and slayed the giant. Accordingly, David’s victory was not at all miraculous; rather it was a result of his understanding that he had to approach the challenge and the problem differently and decisively to gain victory.
On May 25, 2015, CKN published a piece I wrote entitled: The Long Road to Hope for Children with DIPG. In the piece, I struck a hopeful tone for children with DIPG, a tumor that for the past fifty years has had an almost universally fatal prognosis. DIPG, or diffuse intrinsic pontine glioma, is the deadliest pediatric brain tumor with an almost 99% mortality rate two years from diagnosis. Inoperable due to its location, the only treatment that is standard of care is radiation, which remains palliative in nature. To date, over 250 clinical trials have been open for enrollment for children with DIPG. Out of those 250 plus clinical trials there has not been a single drug approved by the Food and Drug Administration (FDA) to be included as standard of care therapy for children with DIPG. When my original piece was published, there was reason to hope as a result of all that took shape since the time of my own daughter’s death from DIPG in January 2011. As I wrote back then, the amount of research funding, foundational support, collaboration and intense interest in DIPG was accelerating and increasing by leaps and bounds. The parents that faced this disease in their children and paid the ultimate price, chose to walk over the crest of the hill with their weapons and take a chance at striking an unlikely blow against the giant. Indeed, the target has been struck on several occasions and those engaged in the battle have learned more about the ultimate target. Despite so much effort, the outcome remains the same. Unfortunately, there are still many who choose to go into battle with conventional thinking, or who are constrained to do so for many reasons, with full knowledge that they will suffer defeat. Extrapolating further from DIPG, for children with cancers that have poor prognoses overall or upon recurrence, there continues to be fear and hesitancy to fight this battle in a way that causes clinical discomfort.
If we learn nothing more from Gladwell’s analysis, it should be this lesson: the time has come to alter the rules and stop fighting against childhood cancer, including DIPG, in a way that is based upon fear or constrained by outdated rules of engagement. As September knocks on our doors and childhood cancer awareness month dawns yet again, I sought to reread that original piece from May 2015 to see whether that hopeful tone endured. I remain hopeful, yet I find that my original hope is not moving down the track like a speeding freight train. Rather, it is slowly crawling along before us, car after car, as we all sit stopped at the crossing gate waiting to move again.
The Hippocratic oath, clinical concern for pain and discomfort of children fighting cancer as a result of treatments and complications, lack of knowledge of more aggressive therapeutic pathways, outdated legislative provisions and on and on all act to restrict the manner in which childhood cancer is treated, researched, understood and discussed. There continues to be a lack of progress in improving overall survival numbers for many forms of childhood cancer. Hope springs eternal, but it also can wither and die on the vine.
History, along with the analysis of David v. Goliath, is rather instructive in an analysis of the state of childhood cancer in general when set upon the backdrop of Gladwell’s book. Unfortunately, it seems some lessons from the past have not taken root and many forms of childhood cancer remain untouched by the weapons used against them. Emil Freireich, MD is perhaps one of the greatest examples of courage in relation to treating children with cancer and overcoming constrained and fearful thinking. Dr. Freireich, along with his colleagues created the drug cocktail that today can be credited with moving childhood leukemia from an almost universally fatal diagnosis to one of the most treatable forms of childhood cancer. Dr. Friereich and his colleagues overcame the clinically uncomfortable nature of their efforts at treating children with leukemia, as well as at times the acerbic characterization of their efforts as “butchers” and engaged the giant differently. The result was hope. Hope borne from moving beyond clinically paternalistic ideals of what was acceptable to put children with cancer through in order to try and save them.
The same audacious mentality has to prevail once again to ensure that many of the cancer giants our children face, including DIPG, will be approached without bowing to false or uninformed fear of harm or clinical myopia. Oftentimes parents seeking to act aggressively in a desperate attempt to save their child are not provided with options that may be more difficult treatment pathways. For children with recurrent or metastatic osteosarcoma, there is still a clinical hesitation to obtain tissue for genetic sequencing. Why? The belief that this act will not help that child or parents will not pay for the procedure and sequencing when insurance fails to provide coverage. It seems more logical that obtaining tissue, if it can be done safely, is critical not only for that child to provide targets to treat, but also the knowledge gained could be the next watershed moment in understanding how to defeat the cancer.
For children with DIPG, from the first moment the physician advises their parent or caregiver about the diagnosis the clock begins ticking and not in a positive direction. Parents are often only guided towards radiation or advised about clinical trials at their “home” institution or several other institutions. Many clinical trials are comprised of single drugs or sometimes multiple drug combinations. All clinical trials for DIPG to date have failed to create improvement in overall survival and thus, hope cannot be rested in this pathway in a vacuum.
DIPG has several aggressive new weapons being developed and perfected for the fight. Medically and scientifically logical and reasonable, there are researchers and clinicians desperate to carry them over the hill and engage aggressively. Convection enhanced delivery (insertion of catheters directly into the brain to dose the tumor thus bypassing the blood brain barrier), immunotherapy, intra-arterial drug delivery with multiple agents sequenced over time, new technologies for passing drugs through the blood brain barrier; the weapons are being gathered in the arsenal and readied for battle. These modalities, therapies and treatments employed in a vacuum though continue to fail. The long road to hope sometimes must travel upon uncomfortable paths. Discomfort that is borne not from a laissez faire attitude of nonchalantly throwing everything at the cancer, but rather as an outgrowth of an understanding that it is not palatable to accept death for these children because of ingrained conventional beliefs and fear. In the case of this long path or road for children with DIPG or other forms of childhood cancer, true hope will exist when we think more like David.
Unfortunately, for so many reasons that are beyond the scope of this piece, parents are generally not provided with the entire collection of these weapons. Clinicians unfamiliar with the multitude of therapy modalities or therapeutic options may not be able to, or willing to for that matter, counsel parents about options outside of their purview, personal bias or comfort. In many cases the message sent to parents is there is nothing more to be done for their child and David falls. To the contrary, the message should be nothing short of an unequivocal statement to parents and caregivers that every means and method available, regardless of location and cost, will be considered, discussed and arranged if that is the path they desire.
It should be noted of course that protections must remain in place to ensure that clinics and clinicians do not purposely harm or deceive desperate parents. Indeed there are too many stories that abound of parents being promised a cure by clinicians who, without naming names, should have their license revoked. This is a difficult balance to achieve. The negative and injurious examples of clinics and clinicians acting in unscrupulous manners often have the unfortunate effect of creating greater clinical concern for aggressive treatment approaches or therapies that are not within current clinical trials or are not part of the peer reviewed literature. In the end, I do not believe in the removal of safeguards or oversight for treating children with cancer to provide unfettered access to treatments or therapies.
What must happen is a major shift in the mentality behind what price families are paying as a result of fear, bias and clinical paternalism in some cases. In the instance of DIPG, the price is almost universal death without clinical availability of all weapons aggressively combined and available. In the case of childhood cancer in general, lessons from the past must guide our actions of today and the future to overcome limiting hurdles. The long road to hope for children with cancer, including those with DIPG, is a path that all those who involuntarily and voluntarily walk need do so together without hesitation and fear. Those in positions of control or who act as gatekeepers for access must maintain oversight but should never let their lack of understanding – absence of first-hand experience with childhood cancer – or personal discomfort stand in the way of hope. Hope is and can be painful. Since I wrote the piece about the long road to hope I truly believe that one day, given the people that stand shoulder to shoulder in the childhood cancer community, we will all walk over the hill and engage the giant swiftly and unequivocally without fear.
Jonathan Eric Agin, JD, is the Executive Director for the Max Cure Foundation and the Institutional Official, Development Liaison for the Children’s Cancer Therapy Development Institute, a non-profit childhood cancer research biotech located in Beaverton, OR. He is also the Cancer Knowledge Network (Canadian Oncology Journal) Childhood Cancer Awareness and Advocacy Section Co-Editor and frequent contributor to the Huffington Post. Jonathan is an attorney by training and a former trial lawyer from Washington, DC. He is one of the most recognized names in the childhood cancer community. He has testified before the United States Congress on issues of identity theft impacting the childhood cancer community, which ultimately led to the introduction of bipartisan legislation named after his daughter Alexis (HR 2720, The Alexis Agin Identity Theft Protection Act of 2013). This legislation was later enacted into law as part of the overall budget deal of 2013. Jonathan’s legislative advocacy has proven effective in the passage of several bills in a climate of congressional stagnation and he continues to work closely with members of the community and beyond on legislative initiatives impacting the rare disease community. He has provided public comment before the FDA pedODAC Committee on the topic of biopsy in children with DIPG (an inoperable and almost universally fatal pediatric brain tumor). Jonathan became involved in the childhood cancer community following the diagnosis of his daughter Alexis at the age of two with DIPG in April 2008. Alexis battled heroically for thirty-three months until January 14, 2011. Jonathan frequently interacts with members of Congress and their staff, the White House, as well as various regulatory agencies and other cancer organizations in an effort to improve the plight of children with cancer. He is an original founding steering council member of the DIPG Collaborative. Jonathan resides in Falls Church, Virginia and has four children, Alexis (1-31-06 to 1-14-11), Gabriel age 7, Trevor age 4 and Kylie 2 years. Jonathan maintains his own website for his advocacy activities: www.jonathanagin.com and can be followed on Twitter @jonathanagin. In his spare time he also competes in endurance events like running marathons and triathlons.