After perusing the newly minted New England Journal of Medicine (NEJM) article, "Anti-GD2 Antibody with GM-CSF, Interleukin-2, and Isotretinoin for Neuroblastoma," I was reminded of my fascination (okay, obsession) with neuroblastoma prognostic factors. The article had an interesting discussion on the most recent revelations concerning the prognostic factors for children with high risk neuroblastoma and I once again found my mind wondering. What matters?
Throughout Sydney's treatment I had a morbid fascination with the statistics and an intense need to know everything about the factors that affected Sydney's prognosis. There were several occasions when medical experts commented on my obsession. "Why does it matter? You are already high risk? It wouldn't change anything therapeutically." But, would it? Even though I have great respect for the oncologists and researchers that gave me that response, I totally disagreed then and I still do today.
In one sense they were right. We were already on a high risk trial and whether or not she was NMYC amplified or diploid did not matter therapeutically. What they never considered was my willingness to jump ship on any trial at any moment if I believed another trial or treatment would be in her best interest. For example, today if Sydney was diagnosed with neuroblastoma and she had some significantly poor prognostic factors I might be more inclined to participate in a trial which included tandem transplants or offered the ability to move on to MIBG therapy if she was less than responsive. However, if she was high risk but had good prognostic factors, all things being considered, I might be more inclined to favor a trial aimed at reducing toxicity such as the one that includes Sodium Thiosulfate.
Later in Sydney's therapy it did turn out that Sydney's prognostic factors actually did impact treatment. We were far more aggressive with her relapse treatment and her prognosis played a large part of my personal decision. And the phase 1 vaccine trial that we participated in Houston, well, that decision was absolutely influenced by prognostic factors. We were more aggressive because of what we knew about Sydney's disease.
The fact is that prognostic factors can influence decisions and should. It is all risk. If the risk of death is higher then we are willing to take more risk to reverse that reality. You need to know what your risks are.
Prognostic factors matter!
So, with all of that being said. What did I learn about prognostic factors in the NEJM article. As expected, we found that the event-free survival was worse in patients with disease of INSS stage 4 than in patients with disease of INSS stage 2, 3, or 4S (P = 0.003). Interestingly, especially to me, diploidy, representing normal tumor-cell DNA index, was predictive of worse overall survival than hyperdiploidy (P = 0.007). Finally, a complete or very good partial response, as compared with a partial response, before autologous stem-cell transplantation was predictive of improved event-free survival (P = 0.04) and overall survival (P=0.02). Surprisingly, no other prognostic factors studied were predictive of outcome. Yes, even age, MCYN amplification, and tumor histology were not found to be statistically significant when comparing high risk patients. Although it is probably still worth pointing out that even though the results were not statistically significant the 2 year event free and overall survival statistics were higher for younger patients, non NMYC amplified patients and patients with favorable histology. I would bet money (in my non professional and non medically degreed opinion) that a higher number of patients and randomization based on the stratification of patients would have probably given this more power and shown these to be factors to be statistically significant.
So, are all of these rules hard and fast. Absolutely, not! But I have to argue that they can be an important influence in decision making. While I certainly would not let one of these factors influence my decision to accept anything less than the standard of care for high risk neuroblastoma, I would be lying if I did not say that they might influence my decision to do more.
Purpose can and should be influenced.