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Curing cancer - Adult versus childhood cancer

Originally posted at Nat Pernick's Curing Cancer Blog on 15 December 2020, revised 29 April 2022.

This paper compares cancer in adults to cancer in children (ages 0-14) and adolescents (ages 15-19). The main differences discussed here are numbers of deaths, clinical (microscopic) types, survival rates, etiology (how they arise) and curative treatment. All statistics are from Cancer Facts & Figures 2022 unless otherwise indicated.

Cancer deaths overall
In the US, cancer remains the second leading cause of death after heart disease with 609,360 projected deaths for all ages in 2022; yet over 99% of these deaths will occur in adults. In 2020, cancer caused 17.8% of actual (not projected) US deaths from all causes, and, in all age groups, there were 602,350 US cancer deaths and 3,383,729 US deaths from all causes (CDC-Mortality in the United States, 2020, data table for figure 4, accessed 18Apr22).

Cancer deaths in children
US cancer deaths in children are uncommon, with only 1,050 deaths projected for children and 550 deaths projected for adolescents for 2022. However, this still represents the second to fourth leading cause of childhood death (ages 1-4 years: not a leading cause; ages 5-9; second leading cause after accidents; ages 10-12: third leading cause after accidents and suicide; ages 12-19: fourth leading cause after accidents, homicide and suicide, see CDC-Child Health, accessed 15Apr22, CDC-Mortality Among Teenagers, accessed 15Apr22).

Top 10 causes of US cancer death
The top 10 causes of death from cancer in the US, as projected for 2022 (for all ages, which almost exclusively involves adults) are listed below; these include the projected number of deaths and survival rates. The 5 year relative survival rate is calculated as the number of cancer patients alive 5 years after diagnosis (with or without disease), divided by the number of people of a similar age expected to be alive who do not have cancer, based on a normal life expectancy. Note that 5 year survival is not necessarily a cure - some patients may have a late relapse.

#1 Lung cancer, 130,180 deaths, 5 year survival 22%

#2 Colon cancer, 52,580 deaths, 5 year survival 65%

#3 Pancreatic cancer, 49,830 deaths, 5 year survival 11%

#4 Breast cancer, 43,780 deaths, 5 year survival 90%

#5 Prostate cancer, 34,500 deaths, 5 year survival 98%

#6 Liver cancer, 30,520 deaths, 5 year survival 20%

#7 Non Hodgkin lymphoma, 20,250 deaths, 5 year survival 73%

#8 Central nervous system (brain) cancer, 18,280 deaths, 5 year survival 33%

#9 Bladder cancer, 17,100 deaths, 5 year survival 77%

#10 Esophageal cancer, 16,410 deaths, 5 year survival 20%

These top 10 cancers are projected to cause 413,430 deaths or 67.8% of the total projected 609,360 US cancer deaths in 2022.

Cancer in children and adolescents
Children and adolescents have completely different types of cancer compared to adults and the 5 year survival tends to be much higher. The 5 year survival rates for common cancers during 2011-2017 for both children and adolescents are listed below (note: survival statistics also from American Cancer Society, accessed 15Apr22, which uses slightly different age parameters):

Central nervous system cancer, 74%, 76%

Ewing sarcoma, 76%, 59%

Hodgkin lymphoma, 99%, 97%

Leukemia, 87%, 75%

Neuroblastoma, 82%, 54%

Non Hodgkin lymphoma, 91%, 88%

Osteosarcoma, 68%, 68%

Retinoblastoma, 96%, does not occur in adolescents

Rhabdomyosarcoma, 70%, 51%

Wilms tumor (nephroblastoma), 93%, 72%

These higher survival rates in children have been attributed to higher enrollment in clinical trials, improvements in treatment and having types of cancers that have more successful treatments.

Causes of cancer in adults versus children
The causes of cancer also differ in adults, versus children and adolescents. Adult cancers are typically 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 hormone exposure and immune system dysfunction. Adult cancers that are due to "random chronic stress" or unknown causes are common in the pancreas and lung (Pernick 2021). Adult cancers are associated with older age and show prominent field effects (large areas affected by premalignant or malignant change). For example, the average age of patients with lung cancer is 70 years (American Cancer Society-Lung Cancer, accessed 15Apr22). Many of these patients have premalignant and malignant lesions throughout their lungs because cigarette smoke damages cells throughout the respiratory tract.

In contrast, although childhood and adolescent cancers may be associated with inherited or constitutional cancer predisposition or developmental mutations (Kentsis 2020), in most cases, no cause is identified (Gargallo 2021) and they show no field effects.

Curing childhood cancers
Curing childhood cancers requires the combination of multiple effective treatments with different mechanisms of action (Mukherjee: The Emperor of All Maladies 2010), even though these cancers may originate from a single mutation in one cell. Combining treatments is necessary because biologic pathways are weblike, not linear. This means that the cancer cells use alternative pathways in the biologic "web" to achieve similar functions so a treatment directed at stopping just one dangerous pathway may be ineffective (Pernick: Strategic Plan for Curing Cancer, step 1b).

Curing adult cancers
To cure adult cancers, we suggest more extensive and diverse combinations ("combinations of combinations") than may be required for childhood cancers; this is because adult cancers originate from more mutations in many cells and are due to multiple risk factors acting over long periods of time. We propose that these combinations should involve diverse treatments that affect the main cancer site, as well as its microenvironment (neighboring tissue that nurtures the cancer cells), and systemic changes that accompany, or enable, the development of the cancer (chronic inflammation, immune system dysfunction, hormonal effects, germline changes [genetic predisposition]).

The importance of clinical trials
Less than 5% of adult cancer patients enroll in cancer clinical trials (Unger 2016). In contrast, more than 60% of children with cancer are enrolled (Children’s Oncology Group, accessed 15Apr22). There is a strong emphasis on enrolling every child with cancer into a clinical trial; this allows for the comparison of the current standard therapy for a particular risk group with a potentially better treatment that may improve survival or reduce treatment side effects. Clinical trials and treatment plans may be quite sophisticated; for example, children with acute lymphoblastic 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 15Apr22).

The recently proposed "Reignited Cancer Moonshot" aims to increase adult participation in clinical trials (The White House, 17Mar22). To achieve high cure rates for adult cancers, clinical trials are important because human physiology tends to follow 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 know whether treatment combinations will be effective and tolerable in different patient groups is to test them with clinical trials.
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