By Anastasia Alenova
Childhood cancers are less common than adult cancers. Although it might sound as reassuring news, this difference can lead to worse management of disease in children. While causes for adult cancers are better defined, especially the impact of lifestyle choices such as smoking, causes for paediatric cancers are less well-defined. A hypothesis leans towards genetic causes, but this only lies at the root of few paediatric cancers. Furthermore, types of cancers differ between age groups, with the most common childhood cancers being leukaemias, lymphomas and brain tumours, while adult cancers occur most likely occur in the lung, colon and breast (Woods, 2017). However, the drivers of these discrepancies between adult and paediatric cancers are still unclear.
Better understanding the biological causes underlying adult and paediatric cancer differences is essential. For instance, childhood sarcoma, a rare connective tissue tumour, has very little connection to adult sarcoma activity. This has a severe impact on prognosis, as 60.5% of children have a 5-year survival rate, compared to 26.6% in adults (Van der Graf et al., 2017). This may be explained by the increased chemosensitivity of paediatric sarcomas and the tendency of children to present symptoms earlier than young adults, allowing earlier detection. With age, tolerance to chemotherapy may also change unfavourably (Thomas et al., 2006). There is also a possible increased genomic complexity with age, with chromosomal complexity possibly harbouring a strong association with metastatic outcomes. It is extremely important to assess differences in survival between children and young adults and its underlying genetic complexity, as it can impact patient management such as care organisation and trial availability (Van der Graf et al., 2017).
Another striking example of discrepancies between adult and paediatric cancers, are the genetic abnormalities found in gliomas. Glioma encompasses tumours which arise from the glioma lineage, such as astrocytes, and can occur at any age. However, low grade gliomas are more frequent in children while adults mostly suffer from high grade gliomas. However, for the sake of comparison, paediatric high-grade gliomas, due to the distribution of histological grade, site of presentation and rate of malignant transformations, differ from their adult counterparts. As mentioned previously, the tumour location differs in children and adults. For the former, it is mostly located in the infratentorial regions, such as the brainstem and cerebellum. For adults, tumours mostly occur in the supratentorial region of the brain (Jones et al., 2012).
Other than location, there are many biological distinctions as well. However, it is important to note that the scarcity of paediatric samples limits certain conclusions from being made. The amount of DNA copy number changes, such as chromosome 7 gain, is lower on average for childhood high-grade gliomas compared to histologically similar tumours in adults. Furthermore, certain genetic amplifications or deletions occur at different rates in adults and children, such as EGFR amplification, which occurs in 60% of high-grade adult gliomas versus only 10% in paediatric ones. Such differences may be due to differential expression of developmentally restricted genes between the age groups. Outcomes for adults and children with high-grade glioma is poor. However, children have strikingly higher survival. This may be due to the distinct tumour biology, as well as the desire of avoiding deleterious effects of radiotherapy on the developing brain in children, which has led to the study of specific cytotoxic drugs (Jones et al., 2012). This underlines the importance of properly understanding how adult and paediatric cancers differ for more patient-specific research.
Another major difference between adult and childhood cancers is the psychological aspect. Adolescents suffering from cancer in particular face stagnation in personal development when confronted with the personal growth of their peers, which can impact adherence to treatment (Van der Graf et al., 2017). This, added to the unique educational needs and complex interaction with the health-care system, leads to worse cancer outcomes in young people. To overcome this hurdle, there is a need for schools to promote engagement in education despite treatment to avoid isolation (Thomas et al., 2006).
Due to location and biological discrepancies between paediatric and adult cancers, there is a need to develop different treatments and an appropriate model system for each age group. Despite a seemingly close relation of paediatric and adult cancers, there is a distinct molecular heterogeneity between different ages (Jones et al., 2012). In light of novel immune strategies and targeted therapies, there is a need to progress age-specific clinical trials, to better respond to child and adult needs (Van der Graf et al., 2017). However, tumour discrepancies have only been evaluated for few cancers, and, in addition to dealing with patient management issues, there is a requirement to better understand what differences underly different types of paediatric and adult cancers.
Woods, M. (2017) How Childhood Cancers Differ from Adult Cancers, Beth Israel Lahey Health, Winchester Hospital, [Accessed on 12 June 2021], Available from: https://www.winchesterhospital.org/health-library/article?id=30409
Van der Graaf, W. T. A., Orbach, D., Judson, I. R., Ferrari, A. (2017) Soft tissue sarcomas in adolescents and young adults: a comparison with their paediatric and adult counterparts. The Lancet Oncology. 18 (3), e166-e175. Available from: https://www.clinicalkey.es/playcontent/1-s2.0-S1470204517300992. Available from: doi: 10.1016/S1470-2045(17)30099-2
Thomas, D. M., Seymour, J. F., O’Brien, T., Sawyer, S. M. & Ashley, D. M. (2006) Adolescent and young adult cancer: a revolution in evolution? Internal Medicine Journal. 36 (5), 302-307. Available from: https://api.istex.fr/ark:/67375/WNG-X1GHLGQ8-0/fulltext.pdf. Available from: doi: 10.1111/j.1445-5994.2006.01062.x.
Jones, C., Perryman, L. & Hargrave, D. (2012) Paediatric and adult malignant glioma: close relatives or distant cousins? Nature Reviews. Clinical Oncology. 9 (7), 400-413. Available from: https://www.ncbi.nlm.nih.gov/pubmed/22641364. Available from: doi: 10.1038/nrclinonc.2012.87