Rhabdomyosarcoma, 71%
Testicular lymphoma, 95%
Wilms tumor, 93%
Cancer survival rates are higher in children than adults because their tumors have different
origins and because clinical trials are more commonly used.
Childhood tumors are typically caused by inherited or constitutional cancer predisposition or
developmental mutations (Kentsis 2020), are not age related and show no “field effects”
(large areas affected by premalignant or malignant change). In contrast, adult tumors are
caused by risk factors acting over decades, including tobacco use and exposure to other
carcinogens, alcohol use, excess weight, Western diet (high fat, few vegetables),
microorganisms and parasites, constant hormonal exposure and immune system
dysfunction. Adult tumors are associated with older age and show prominent field effects.
For example, the average age for lung cancer patients is 70 years and many of these
patients have premalignant and malignant lesions throughout their lungs because cigarette
smoke damages cells throughout the respiratory tract.
There is a strong emphasis on enrolling every child with cancer in a clinical trial to compare
current standard therapy for a particular risk group with a potentially better treatment that
may improve survival or reduce treatment side effects. As a result, children with leukemia are
sorted into different risk categories and treatment plans based on age, gender, weight, race /
ethnicity, central nervous system involvement, testicular involvement, white blood cell count,
characteristics of leukemic cells and genomic alterations (NCI: Childhood Acute
Lymphoblastic Leukemia Treatment (PDQ®)–Health Professional Version, accessed
6Dec20).
Curing childhood tumors requires combining multiple effective treatments with different
mechanisms of action (Mukherjee: The Emperor of All Maladies 2010). Often, “combinations
of combinations” of treatment are needed to kill all tumor cells, even though these tumors
may originate from just one mutation in one cell. Combining treatments is necessary
because biologic pathways are weblike, not linear. This means that treatment directed at
stopping one dangerous pathway may be ineffective because the tumor uses alternative
pathways on the biologic “web” to achieve a similar function (Nollmann 2020).
To cure adult tumors, more combinations may be required than for childhood tumors
because adult tumors originate from many mutations in many cells, due to multiple risk
factors acting over long periods of time. Clinical trials are important because human
physiology follows the principles of self-organized criticality, which indicate that we cannot
easily predict the impact of treatment combinations. This is analogous to the difficulty in
predicting changes in a sandpile as grains of sand are added (Bak, How Nature Works 1999,
Pernick 2017). The only way to effectively test whether treatment combinations are effective
and tolerable in different patient groups is with clinical trials.