Cancer in children and adolescentsCancer in childhood is a rare disease, and the malignancies seen in children differ from the common cancers seen in adults. Currently, cure rates from childhood cancer are high with 8 out of 10 children alive 5 years from diagnosis. Key points In Finland about 150 new cancer cases are diagnosed in children annually, of which approximately 80 in boys and 70 in girls. The most common childhood cancers are leukemia, lymphoma and malignant brain tumors. The relative five-year survival rates of children diagnosed with cancer have improved significantly since the 1970s. At present, the relative survival rate is over 80%. About 7 000 Finns have a history of cancer under the age of 25 years. Two thirds of survivors of childhood cancer suffer from adverse physical or psychosocial effects later in life. Cancer diagnosed before the age of 15 years is classified as childhood cancer. If cancer is detected in adolescence, i.e. from 15 to 19 years of age patients are sometimes treated at the children’s and sometimes on the adult’s oncology departments. According to the international definition, cancer diagnosed at 20-39 years of age is defined as cancer in young adulthood. All children’s cancers are rare, and they differ from the common cancers seen in adults. About 150 cancer cases are diagnosed in children annually, of which 80 cases occur in boys and 70 cases in girls. Common Childhood Cancers The most common childhood malignancies are leukemia, lymphoma and malignant brain tumors (Table 1). Other cancers occurring in children include Wilms’tumor of the kidney, retinoblastoma occurring in the eyes, single soft tissue sarcomas and bone tumors. Today, childhood cancer treatment is often curative. Five years after diagnosis, more than 80% of children are still alive, on average, but survival varies considerably depending on the type of cancer. Leukemia, i.e. blood cancer is the most common cancer in children. About 50 children are diagnosed with it annually, most of them under 5 years of age. The most common leukemia originates from lymphocytes; in which case it is called acute lymphoblastic leukemia or ALL. In some cases, the change occurs in the myeloid cell line in the bone marrow, wherein the term acute myelogenous leukemia, or AML, is used. Brain tumors are the second most common cancers in childhood. A brain tumor can manifest itself as recurrent headaches and vomiting. Presenting symptoms may also include growth disorders, visual disturbances, paralysis, difficulty in walking or seizures. Approximately 45 new brain tumors are diagnosed in Finnish children annually. They appear evenly between ages 0-14. The most common type of cancer in adolescents and young adults, i.e. people aged 15-24 years, is lymphoma. These are malignancies of lymph nodes (lymphocytes), which can cause tumors in lymph nodes, but also elsewhere in the body. Many types of lymphomas are known, including Hodgkin’s lymphoma, which is the most common lymphoma in young adults. The curative treatment is chemotherapy based. Local pain, swelling, warmth and tenderness in the lower limb–or less frequently in the upper limb–may be symptoms of bone cancer. Pain and swelling are commonly associated with limitation of motion. The incidence of bone cancer is highest in adolescence as it is often associated with the pubertal growth spurt. The most common locations for bone cancer are the femur, upper end of the tibia and the upper end of the humerus. Wilms’ tumor is a malignant kidney tumor, which is found mostly in children under 5 years of age. Survival rates are high. Figure 1. Trends in cancer incidence in persons aged under 15 in 1954–2013. Treatments for childhood cancer Developments in the treatments of childhood cancer have led to improved survival rates in this age group. In pediatric patients, the relative five-year survival rates have improved significantly since the 1970s, and in the 2000s, the relative survival rate has reached over 80%.  The change is remarkable, for as late as in the 1960s, most children died shortly after the detection of cancer.  The improvement in survival rates for leukemia began in the 1960s and continued into the 1970-1980s, when the survival rate reached over 70%. Today, nearly 90 percent of children with cancer are alive 5 years from diagnosis. Prognosis is poorest in children diagnosed with a tumor of the brain or central nervous system or a bone tumor. Of these only about 60 percent survive. Of lymphomas, the five-year survival rates are excellent particularly in Hodgkin’s lymphoma. In the 2000s, 97% of patients were alive five years after diagnosis. The survival rates in Non-Hodgkin’s lymphoma are around 89%.  In adolescents and young adults, the 5-year survival rate is 87%. Of the most common malignancies, survival is lowest in leukemia at 73%. Survival figures are over 80% (figure 6). Nearly all patients with thyroid cancer survive, and survival has been 100% since the 1970s. In the other common malignancies survival steadily rose until 2000, with little improvement thereafter. As mortality under the age of 40 years is otherwise low, the relative survival figures represent the true proportion of patients alive 5 years from diagnosis. For all other types of children’s cancers, as well, Finnish survival figures are among the highest on a European and global level . Figure 2. Trends in cancer mortality in persons aged under 15 in 1954–2013. Life after cancer According to estimates currently in Finland there are approximately 7 000 adults who have a history of cancer under the age of 25 years. As more patients become long term survivors, focus has shifted to the potential adverse health effects occurring later in life. Two-thirds of those having suffered from cancer at a young age go on to develop physical or psychosocial adverse effects later in life. Compared with healthy siblings, the risk of adverse health effects in cancer survivors is 2.5-fold and the risk of in mental health problems 1.8-fold . Figure 3. Trends in cancer incidence in persons aged 15–39 in 1954–2013. Starting a family and children’s health The Cancer Registry has long been involved in an international study looking into the health of patients that received treatment for their cancer as a child or young adult, and subsequently the health of the offspring of survivors. Utilizing population-based, nationwide registers covering the entire population allows us to identify all patients and their offspring as well as their adverse health outcomes. Adverse health outcomes of cancer survivors were explored in the comprehensive American Childhood Cancer Survivor Study, which collected data on survivors using a questionnaire design.  The challenge in these surveys was that patients recalled their medical history in a different way than healthy siblings or reference persons. In Finland, every hospitalization is recorded in the Hospital Discharge Register, and therefore the data in the registry allows us to reliably evaluate the disease burden of survivors. Furthermore, we can be sure that data on the cancer patients and their siblings’ diseases are equally reliable. One of the main focuses of our research has been to explore the extent to which radiation therapy and cytotoxic chemotherapies have influenced the risk of cancer in survivors and their offspring, congenital anomalies, and neonatal mortality in the offspring, as well as the fertility of patients and morbidity at a later age. According to our results, patients who recovered from cancer were 50% less likely to parent a child than their siblings.  However, parenting a second child was almost as common as among siblings. Parenthood was least likely among women who had had cancer in young adulthood, particularly among survivors of breast cancer. The small number of children of leukemia survivors, in turn, is explained by infertility induced by chemotherapy. Figure 4. Trends in cancer mortality in persons aged 15–39 in 1954–2013. Men that had had cancer in their childhood were least likely to parent children. The connection can be explained partly by the fact that sperm cryopreservation is not possible until adolescence. Also, the time period when the illness occurred had an impact on parenthood rates in young adults. Before the 1980s, not having children was significantly more prevalent amongst young adults who had suffered from cancer. This phenomenon might reflect the development of cancer therapies, but also the change in psychological atmosphere and fertility treatments. The pregnancies of women who have had and recovered from cancer as children or young adults seem to end more frequently in preterm delivery.  Radiation therapy to the abdomen and pelvic area was statistically significantly associated with premature delivery. Also women receiving chemotherapy alone had a higher than average risk of delivering prematurely. In our material, the risk of infant mortality (during the first year of life), and stillbirth did not differ statistically significantly from the risk of siblings’ offspring.  However, the new-born children of those who had suffered from cancer in the past were under enhanced monitoring and supervision compared to the children of their siblings. The cancer risk of offspring was about the same as the children of healthy siblings, when the identified, hereditary cancer predisposing syndromes were removed from the material.  Gender, cancer type or radiation therapy had no effect on offspring’s risk of cancer, either. The results indicate that offspring of people who have had cancer at a young age have the same risk of cancer as the children of their healthy siblings and the population in general, unless there was a predisposing hereditary cancer syndrome. Based on the results, the treatment of cancer does not seem to have an impact on the cancer risk in offspring. Figure 5. Trends in relative five-year survival ratio for cancer patients diagnosed at 0–14 years of age in 1954–2013. Cancer and psychosocial health The Finnish Cancer Registry is involved in a joint Nordic project: Adult Life on Childhood Cancer in Scandinavia (ALiCCS): Socioeconomic Consequences of long-term survival. The purpose of the project is to examine the socio-economic impact of the history of cancer at a young age. In addition, the aim is to identify groups of patients who later face challenges. The study results will help in the design of follow-up for those who have suffered from cancer in childhood or adolescence. Based on this information, neurocognitive and social support can be provided to those in need, to secure education and employment possibilities for cancer survivors. Figure 6. Trends in relative five-year survival ratio for cancer patients diagnosed at 15–39 years of age in 1954–2013. Literature  Madanat-Harjuoja LM, Pokhrel A, Kivivuori SM, Saarinen-Pihkala UM. Childhood cancer survival in Finland (1953-2010): A nationwide population-based study. Int J Cancer 2014; 135(9): 2129–34.  Gatta G, Zigon G, Capocaccia R et al. Survival of European children and young adults with cancer diagnosed 1995-2002. Eur J Cancer 2009; 45: 992–1005.  Hudson MM, Mertens AC, Yasui Y et al. Health status of adult long-term survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. JAMA 2003; 290: 1583–92.  Madanat LM, Malila N, Dyba T, Hakulinen T, Sankila R, Boice JD Jr, Lähteenmäki PM. Probability of parenthood after early onset cancer: A population-based study. Int J Cancer 2008; 123(12): 2891–8.  Madanat-Harjuoja LM, Malila N, Lähteenmäki PM, Boice JD Jr, Gissler M, Dyba T. Preterm delivery among female survivors of childhood, adolescent and young adulthood cancer. Int J Cancer 2010; 127(7): 1669–79.  Madanat-Harjuoja LM, Lähteenmäki PM, Dyba T, Gissler M, Boice JD Jr, Malila N. Early death, stillbirth and neonatal morbidity among offspring of female cancer survivors. Acta Oncol 2013; 52(6): 1152–9.  Madanat-Harjuoja LM, Malila N, Lähteenmäki PM et al. Risk of cancer among children of cancer patients. A nationwide study in Finland. Int J Cancer 2010; 126(5): 1196–205. Table 1. The average numbers of new cancer cases of children of different ages in 2009-2013.