Childhood cancer

It seems impossible to imagine a more absurd phrase. What are these - mistakes of nature or the price of civilization - The New Times found out

According to data from January 2015, the incidence of cancer in Russian children under the age of 15 is 120 cases per 1 million people per year. Although the figure has increased over the past 15 years, this, according to Vladimir Polyakov, the chief pediatric oncologist of Russia, does not reflect an increase in the number of diseases, but an improvement in detection: parents began to see doctors earlier, and, most importantly, diagnosis has improved

* * ** See the interview dated May 25, 2015 here . In developed countries, childhood cancer rates range from 110 cases per 1 million in Japan to 165 per 1 million in the USA. In most developed countries, pediatric oncology ranks second among the causes of child mortality (injuries and accidents usually take first place).

Childhood cancer is a very heterogeneous group of diseases, and the spectrum of diseases in children differs sharply from adult oncology. Approximately 30% of childhood cancers are a blood disease, acute lymphoblastic leukemia (ALL), which usually appears between the ages of one and two years. Another third are diseases of the nervous system: astrocytomas (brain tumors) and neuroblastomas (tumors of the peripheral nerves). This is followed in terms of prevalence by another disease of the hematopoietic system—acute myeloid leukemia (15–20%)—and a number of rarer diseases.

Defective genes Approximately 5–10% of childhood cancers are associated with several known susceptibility genes. For example, 3% of sick children in the United States suffer from retinoblastoma, a rare eye disease that is caused by a single defective gene (in Russia there is no complete statistics on such patients). Some children inherit this gene from their parents, while in others it mutates during fetal development. This mutation affects one or both eyes, and with timely diagnosis, an almost 100 percent cure is achieved, although vision cannot always be preserved.

Another relatively common genetic risk factor is Down syndrome, which significantly increases the likelihood of all malignant diseases, including childhood ones. In particular, the likelihood of ALL increases 50-fold before the age of 5 years and 10-fold in the next 10 years. But due to the relative rarity of Down syndrome, such children account for only 2–3% of all childhood leukemia.

The traditional method of studying the contribution of genetic factors to the development of certain diseases is to determine their occurrence in pairs of identical twins. The likelihood of both twins having the disease varies between studies, but usually does not exceed 40%. In other close relatives of sick children, the probability of cancer differs little from the average: say, in siblings it is increased no more than 2-3 times.

Another approach to studying the role of genetic factors and the contribution of heredity is to compare incidence in different ethnic groups. For example, in the United States, with an average overall incidence of 165 cases per year per million, there are marked differences between ethnic groups: 120 among African Americans and 173 among whites.

Modern technologies for deciphering the genome and exome (i.e., the totality of working genes) will certainly help in the search for new susceptibility genes to childhood cancer. For now, we can say that in most childhood cancers, genetic predisposition has a very limited effect.

Civilization risks There are few scientifically proven factors of negative environmental impact. The main well-established risk factor is maternal radiation exposure during pregnancy (X-rays)

* Stewart A., Kneale GW Radiation dose effects in relation to obstetric x-rays and childhood cancers. Lancet. 1970; 1(7658):1185-8. . However, now the radiation doses used in conventional X-rays are one to two orders of magnitude lower than they were in 1943–1965, when the study was done, and do not pose such a danger. Computed tomography is much more dangerous: it requires doses 10–20 times higher than for x-rays in 1970, and its use during pregnancy is practically excluded.

The Chernobyl disaster of 1986 made it possible to collect extensive statistical data on the impact of radioactive contamination on the incidence of malignant diseases, including in children. The main consequence of pollution was an increase in the incidence of thyroid cancer (up to 30–100 times) due to the accumulation of the radioactive isotope of iodine in it

* Williams D. Cancer after nuclear fallout: lessons from the Chernobyl accident. Nat. Rev. Cancer. 2002; 2(7):543-9. . The incidence of other cancers in children remained within the normal statistical fluctuations.

The question of other environmental factors that increase the risk of childhood malignancies is controversial - the results, as a rule, are on the verge of statistical significance. For example, maternal exposure to pesticides before and during pregnancy slightly increases the child's chance of lymphoma but has no effect on other cancers. Herbicides and diesel exhaust may affect the overall incidence of cancer in children, but there are no confirmed results yet. But a number of studies unexpectedly revealed that another risk factor for the occurrence of cancer in children may be both insufficient and overweight newborns. In particular, the risk of acute lymphoblastic leukemia, central nervous system tumors, and other neoplasms increases with newborn weight. One possible explanation for this finding is that these children are exposed to growth hormone for longer. On the other hand, the risk of liver tumors increases markedly as the newborn's weight decreases. But these observations require a convincing explanation to become the basis for preventive measures.

Another risk factor is the general weakening of the immune system of mother and child. Against this background, infection occurs with carcinogenic viruses HHV-8 (one of the herpes viruses), hepatitis B, Kaposi's sarcoma, and Burkitt's lymphoma. Some of these viruses are widespread in completely healthy people and cause cancer only if the immune system is weakened.

What the numbers show In the past, statistics have shown that childhood cancers are on the rise, but this has been driven by radical improvements in diagnostics: for example, in the late 1980s, the use of MRI (magnetic resonance imaging) dramatically increased the detection rate of brain tumors. Currently, breakthroughs in diagnostic methods are rare, and statistics on childhood cancer in developed countries rather reflect the real state of affairs.

One of the important works on the dynamics of cancer incidence among children was carried out in the UK. It clearly shows that every increase in incidence between 1966 and 2005 was due to new diagnostic methods and improved registration of sick children, including universal compulsory registration introduced in the country in 1993

* M. E. Kroll, L. M., Carpenter, M. F. G. Murphy, C. A. Stiller. Effects of changes in diagnosis and registration on time trends in recorded childhood cancer incidence in Great Britain. BJ Cancer. 2012 Sep 25; 107(7): 1159–1162. . Another study examined the incidence in the United States over the past 20 years: the incidence rate increased by 0.7% per year, but the result did not reach statistical significance. In Japan, the incidence has decreased slightly since the 1990s. At the same time, for unknown reasons, the spectrum of childhood malignant diseases is changing: in the USA the proportion of diseases of the hematopoietic system is growing and the proportion of diseases of the nervous system is falling, in Japan it is the other way around

* Limin Yang and Junichiro Fujimoto. Childhood cancer mortality in Japan, 1980–2013. BMC Cancer 2015:15:446. . Be that as it may, there is no reliable data indicating an increase in childhood cancer in countries with a reliable accounting system.

Unfortunately, morbidity statistics in Russia seem to be insufficiently complete. In particular, children with ALL often die from concomitant infections, and as a result, their primary diagnosis is not recorded anywhere. The unreliability of Russian statistics is evidenced, in particular, by the significant dispersion of data across regions

* Statistics of malignant neoplasms in Russia and the CIS countries in 2012. Ed. M.I. Davydov and E.M. Axel. Publishing group RONC, 2014. .

Budget to the Rescue Oncological diseases in children develop much faster and more aggressively than in adults; the main condition for successful treatment is early diagnosis. Unfortunately, in Russia in 2012, 77% of children were admitted to specialized centers in the late stages of the disease. In most cases, this is the result of unpreparedness of local doctors: a general pediatrician often does not even ask the question why the child is “sick all the time” and does not sound the alarm.

Treatment of childhood cancers includes complex protocols of chemotherapy, radiation, the use of supportive medications, sometimes requiring a bone marrow transplant, and in the case of tumors, surgery. This is a very expensive area of ​​medicine. The situation is unlikely to have improved after the closure of the Federal National Oncology Program last year and a 30% reduction in budget spending on health care

* Daria Burlakova. The state program to combat oncology will not be continued. November 14, 2014 . But in Russia in 2012 (the last year for which statistics are available), only 1,283 children were treated for cancer! The standard criterion for assessing the effectiveness of cancer treatment is 5-year survival. In Germany, Japan, and the USA, the overall survival rate reaches 82–83%. Of course, this indicator varies greatly for different cancers: the highest survival rate is for thyroid tumors, blood cancer, liver tumors, kidney tumors, the lowest is for lesions of the nervous system and soft tissue sarcomas.

If you believe Russian specialized journals, in Russia, childhood mortality from cancer in 1989-2012 decreased by almost half

* Men T.Kh., Polyakov V.G., Aliev M.D. Epidemiology of malignant neoplasms in children in Russia. Oncopediatrics, 2014, No. 1, 7–12. . Nevertheless, it remains high, and it is not possible to calculate it accurately enough. The same article states that “the undercount of sick children in Russia is currently at least 20%” and that “the mortality rate of children from leukemia and tumors of the central nervous system (which together make up half of all malignant diseases of children in Russia. - A.K. .) in our country is more than 50% higher than the mortality rate in developed countries... and the mortality rate from soft tissue tumors (this is about 12% of all cancer diseases. - A.K.) is more than 2 times higher than similar indicators (in the countries of the North Europe)".

Unfortunately, surviving for 5 years does not mean that the child will be completely healthy in the more distant future. Firstly, the return of the primary disease cannot be ruled out due to incomplete destruction of malignant cells. Secondly, the main methods of treatment - radiotherapy and especially chemotherapy - are themselves carcinogenic, and some chemotherapeutic agents damage the cardiovascular system. In total, a quarter of all patients who survive for 5 years experience serious and even life-threatening complications in the future. These complications can disrupt the functions of almost any organ, affecting the quality and length of life, but they belong to another area of ​​medicine.

Yet the progress made over the past 40–50 years in saving children with cancer cannot be overestimated.

* The author is a molecular biologist, candidate of biological sciences, formerly an employee of the Institute of Molecular Biology named after. V.A. Engelhardt. After moving to the United States in 1991, he worked at the medical school of the University of Illinois in Chicago.

Photo: Donat Sorokin/ITAR-TASS