Association nationale des etudiants en pharmacie de france (ANEPF)

from EPSA Science!Monthly: The Science of Paediatric Cancer

The Science of Paediatric Cancer

ANEPF is the national association of French pharmacy students, created in 1968. It is a non-profit association, which represents all pharmacy faculties in France, and therefore all pharmacy students in France from the first to the sixth year of study, representing 33 000 students.

Our main goal is to bring the claims of students to several different levels, with the aim of enhancing initial studies while promoting interprofessionalism and the proper care of patients.

We advocate on many issues for students, such as public health, social affairs, academic affairs, environmental transition, European and international affairs and mobility, mentoring, industry, pharmacy, digital health, solidarity, and student representatives, which testify to the deep involvement of the future generation of pharmacists in solidarity commitments, peer support and outreach for our profession.

What it Means To Be Cured: Long-term Side Effects of Childhood Cancer

Cancer is nondiscriminatory and affects people of all races, religions, ethnicities, genders, and ages. More importantly, it affects children across the world. It is estimated that each year 400,000 children aged 0-19 will develop cancer globally1 . The most common childhood cancer is acute lymphoblastic leukaemia, which is estimated to account for 19% of total childhood cancer incidence, followed by nonHodgkin lymphoma (5%), nephroblastoma (5%), Burkitt lymphoma (5%) and retinoblastoma (5%)1. In 2020, 16,000 children were diagnosed with cancer in Europe, and it is estimated that around 10,000 children under the age of 15 in the United States will be diagnosed with cancer in 20232,3. However, with the advances in technology and cancer treatment, 85% of children with cancer now survive 5 years or more2 . According to the National Cancer Institute, a person is considered to be a cancer survivor from the time of diagnosis to until the end of life. Currently, there are between 300,000 and 500,000 childhood cancer survivors in Europe and an estimated 17 million childhood cancer survivors in the United States4

Although remission and cure rates are promising in paediatric cancer patients, the cure often comes with a cost and puts them at a higher risk for other health complications. Ensuring paediatric patients are cared for after treatment will help increase their quality of life and allow them to get back to everyday activities. Longterm survivors of childhood cancer are more likely to have diminished health status and die prematurely5 Exposure to radiation and chemotherapy puts children at a high risk of developing side effects. These complications of childhood cancer treatment can appear months or years after being cured (late effects), while others appear during active treatment and remain for some time after completion (long-term effects)5,6 Approximately two-thirds of childhood cancer survivors experience at least one chronic medical problem5 The most common late side effects of childhood cancer are neurocognitive and psychological, cardiopulmonary, endocrine, musculoskeletal, and secondary malignancies5,6

Neurocognitive

Neurocognitive late effects are prominent in children whose cancer or treatment involves the central nervous system5. Treatment including radiation to the whole brain, systemic chemotherapy with high-dose methotrexate or cytarabine, or intrathecal chemotherapy can lead to neurocognitive side effects6. These late effects are some of the most debilitating and can become apparent within 1-2 years after receiving treatment6 . They may include learning problems, social difficulties, functional deficits, and long-term educational difficulties5 About 50%-60% of childhood cancer survivors will experience neurocognitive impairment resulting from their cancer or its treatment5 Since these long-term effects can be so debilitating, a baseline neuropsychological evaluation is recommended for patients who received treatment that may impact their neurocognitive functioning6. Screening should be repeated as clinically indicated and at key educational transition points to make sure children stay on track with their educational goals6

Psychological/Behavioral

Dealing with the burden of childhood cancer often leads to the development of psychological, social, and spiritual difficulties. Secondary to cancer treatment, patients may worry about the many aspects of survivorship, including the risk of relapses, dying, more treatments, potential problems with sexuality and fertility, body image, school and work performance, and social and family relationships. Risk factors for psychological complications can include CNS-directed therapy, hearing loss, female sex, family history of mental illness, younger age at diagnosis, lower household income, and lower educational achievement6. Despite the risk of dealing with these late side effects, most survivors and their families achieve normal levels of psychological and social functioning5. All childhood cancer survivors should undergo yearly exams focusing on education and/or vocational progress, social withdrawal, and mental health disorders. If needed, school counsellors or social workers can help children navigate their life post-cancer treatment6 .

Cardiopulmonary

Children with a history of childhood cancer can have long-term cardiopulmonary effects due to the various chemotherapy regimens their bodies were exposed to. 5year childhood cancer survivors have an 8.8-fold increased risk of mortality related to pulmonary complications6. There is an elevated risk when children receive bleomycin and alkylating agents such as cyclophosphamide and melphalan5,6. It is recommended that children who received these medications have an annual pulmonary exam along with pulmonary function tests to diagnose any problems as soon as possible6

Along with pulmonary complications, patients who were treated with anthracyclines and thoracic radiation are at risk for long-term cardiotoxic effects5. An estimated 60% of all childhood cancer survivors have a history of previous anthracycline exposure and/or radiation to the chest area6. Cardiotoxic side effects can include cardiomyopathy, congestive heart failure, ischemia, valvular disease, arrhythmias, and pericarditis6. It is recommended that children receive an annual comprehensive cardiac exam as well as an echocardiogram every 1-5 years depending on patientspecific factors6 .

Endocrine Function

Late side effects of the endocrine system can include thyroid dysfunction (hypo and hyperthyroidism), growth hormone deficiency, delayed puberty, and hypopituitarism5 . Approximately, 20-50% of childhood survivors experience some sort of endocrine complication5. Treatment with radiation and chemotherapy can also affect fertility and reproduction in these patients5. Depending on the age and intended treatment, fertility preservation should be offered if possible5

Screening for endocrine abnormalities is vital in childhood cancer survivors. Female survivors should have an annual exam focused on puberty, menstruation, pregnancy, and sexual function. Lab tests such as follicle-stimulating hormone, luteinizing hormone, and estradiol should be evaluated at age 13 and beyond as clinically indicated. Male survivors should have an annual exam focusing on puberty and sexual function. Measurement of testicular volume and semen analysis are two ways for patients to ensure proper development has occurred following cancer treatment. Testosterone levels can also be drawn if clinically indicated6

Musculoskeletal

Growing children are subject to the effects of chemotherapy and radiation on their bones5. Osteoporosis/osteopenia, avascular necrosis, scoliosis, and bone atrophy or hypoplasia are some of the skeletal side effects that can occur after cancer treatment6 Radiation effects on the bone might not be able to be seen during treatment but are more prominent as children continue to grow, especially during puberty5 Chemotherapy agents such as methotrexate can affect bone growth directly and indirectly by disrupting hormone systems. This is also the case for some ancillary (or supportive care) medications, such as corticosteroids5. Long-term survivors should have their bone density evaluated at baseline and then repeated as necessary6. An annual exam should also include a history of joint pain, swelling, immobility, and limited range of motion6. Children who are receiving treatment before they go through puberty should also have an annual spine exam for scoliosis and kyphosis until their growth is complete6

Secondary Malignancies

Childhood cancer survivors are at an increased risk of developing secondary malignancies6. The cumulative risk of secondary malignancies 20 years following primary treatment for childhood cancer is between 3%-10% and is 5 to 20 times greater than that expected in the general population5. Secondary malignancies are defined as a new (or different) type of cancer that develops at least 2 months after finishing treatment for the primary malignancy6. Radiation therapy has been linked with the development of thyroid cancer, breast cancer, melanoma, brain tumours, and bone and soft tissue sarcomas. Certain types of chemotherapy, such as alkylating agents and topoisomerase II inhibitors, are associated with the development of leukemia5. Eliminating radiation or reducing doses, along with altering chemotherapy schedules, can help reduce the risk of secondary malignancies5. Children who received radiation or chemotherapeutic agents with known carcinogenic effects should be informed of their risk and should be seen regularly by a healthcare provider familiar with their treatment and risks who can evaluate early signs and symptoms appropriately5

Survivors that received alkylating agents and anthracyclines should undergo yearly exams, for up to 10 years after exposure to the agent, focusing on fatigue, bleeding, and easy bruising. They should be counselled to report fatigue, pallor, or bone pain and should have a complete blood count and bone marrow examination as clinically indicated6 . Children who received radiation therapy should undergo yearly physical exams as well. Physicals should focus on the inspection of the skin and soft tissues in the irradiated field(s)6. It is important that childhood cancer survivors know about the proper screening to help reduce the risk of secondary malignancies.

New technology and advances in childhood cancer treatment have helped children diagnosed with cancer reach remission and cure and continue on with life. However, the long-term effects of cancer treatment can cause lingering physical and mental stress throughout the life of the child and into adulthood. It is important as healthcare professionals to be aware of these side effects and how to help survivors when needed. Furthermore, connecting the paediatric survivor (including necessary caregivers) to proper follow-up care for monitoring and survivorship programs to promote continued overall wellness is essential to allow survivors to continue a healthy way of life.

Author: Yarelis Diaz-Rohena, PharmD | Oncology, Advocacy, Health Policy, and Equity Fellow | NCODA