Childhood Cancer Late Effects: Questions for Follow-Up

Late effects are health problems that show up months or years after cancer treatment ends. NCI describes them across nearly every body system, from the heart and lungs to hearing, bones, hormones, thinking, and second cancers.

But no survivor is at risk for all of them. Risk follows exposure. The useful question at a follow-up visit is not "what cancer did I have," it is "what did I receive, how much, and where."

The Children's Oncology Group builds its Long-Term Follow-Up Guidelines on exactly that logic. Version 6 is organized by exposure. You look up the drugs and radiation fields a survivor actually received, and the guideline gives the screening that goes with them. Passport for Care, a COG tool, does that lookup and prints the screening list.

So bring the treatment summary to the visit. Then work through the exposures below one at a time.

Anthracyclines are a family of chemotherapy drugs. St. Jude names doxorubicin, daunorubicin, idarubicin, mitoxantrone, and epirubicin. They can weaken heart muscle, and the damage can appear long after treatment ends.

Risk tracks the cumulative dose, meaning the total added up across the whole treatment. It is measured in milligrams per square meter of body surface area, written mg/m². St. Jude puts a total under 100 mg/m² in the lower-risk group and 250 mg/m² or more in the high-risk group.

Chest radiation adds to this. St. Jude sorts chest radiation risk as low under 15 Gy, moderate from 15 to under 30 Gy, and high at 30 Gy or more. A gray, abbreviated Gy, is the unit of radiation dose.

The screening test is an echocardiogram, an ultrasound of the heart. St. Jude calls it an easy, non-invasive way to find heart disease before symptoms start.

Questions worth asking out loud:

• What was my total anthracycline dose in mg/m²?
• Did radiation reach my heart, and at what dose in Gy?
• How often should I have an echocardiogram, and who orders it?

Report severe fatigue or new swelling to the clinic. Chest pain, an irregular heartbeat or a faint need emergency care instead, not a message left with the office.

This is the late effect most often missed, because the survivor is usually far too young for routine screening.

St. Jude reports that survivors who had chest radiation carry a breast cancer risk comparable to women with a BRCA gene change, and that 10 Gy or more raises risk. The risk starts climbing about 8 years after radiation, or at age 25, whichever comes later. Second breast cancers in this group typically appear between ages 30 and 40, rather than after 50.

The recommended surveillance is more intensive than standard screening:

• A yearly mammogram and a yearly breast MRI, beginning at age 25 or 8 years after radiation, whichever comes last.
• A clinical breast exam yearly from puberty to age 25, then every 6 months.
• Monthly self-exams from puberty on.

St. Jude also notes that anthracycline doses of 250 mg/m² or more are linked to higher breast cancer risk.

A 27-year-old asking for a breast MRI will often be told she is too young. Bring the guideline printout.

Alkylating agents are the drug group most linked to gonadal damage, meaning injury to the ovaries or testes. St. Jude names busulfan, carmustine, chlorambucil, cyclophosphamide, ifosfamide, lomustine, mechlorethamine, melphalan, and procarbazine. Cisplatin and carboplatin also count. Radiation to the pelvis and total body irradiation before a transplant add more.

Monitoring is simple to ask for. For young men, St. Jude recommends yearly checkups with growth and puberty tracked, plus blood tests for testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH). A semen analysis answers the fertility question directly once a man is sexually mature. For young women, tests include FSH and anti-Mullerian hormone (AMH), which reflects how many eggs remain.

Ask two separate questions. Can I have children? And are my hormone levels normal? Those can have different answers, and low hormones need treatment on their own.

The pituitary gland sits at the base of the brain and directs growth, puberty, thyroid function, and stress hormones. St. Jude notes that radiation to the head or brain, total body irradiation, and surgery near the pituitary can all damage it.

Growth hormone deficiency is the most common of these. The warning sign is growth velocity, not height. St. Jude flags a child growing fewer than 2 inches per year as growing more slowly than expected. Diagnosis uses a growth hormone stimulation test, in which medicine prompts the pituitary and levels are measured over time. Blood tests for IGF-1 and IGFBP-3, plus a bone age x-ray, support the picture. Treatment is manufactured growth hormone, given as a daily or weekly injection into the fat under the skin.

Keep plotting height and weight on a growth chart at every visit through the teen years. The trend is the test.

St. Jude links cognitive late effects to radiation of the head, neck, upper spine, or whole body, to high-dose intravenous methotrexate, to cytarabine, to chemotherapy given into the spinal fluid, to brain surgery, and to corticosteroids. Risk is higher in children treated young and in girls who had cranial radiation.

The effects hit memory, attention, processing speed, planning and organizing, handwriting, reading, spelling, and math. They may appear months or years after treatment, so a child who did fine at age 8 can struggle at 12.

Ask for neuropsychological testing, which measures attention, memory, processing speed, language, motor skills, and academic achievement. Ask for it before a school problem becomes a school failure, and bring the report to the school team.

NCI adds several exposures worth naming at every visit:

• Cisplatin, high-dose carboplatin, and high-dose brain radiation can cause hearing loss or ringing in the ears months to years later. NCI advises at least one visit with an audiologist after treatment.
• Radiation to the head or neck can damage the thyroid and cause dry mouth, cavities, or jaw problems. NCI advises dental visits every 1 to 2 months for at least 6 months after radiation to the mouth area.
• Chemotherapy, steroids, hormone therapy, and radiation can thin bones.
• Chemotherapy and chest radiation can cause lung damage years later, and having both raises risk further.
• Any cancer treatment can lead to a different, new cancer many years later.

Call a doctor, and say you are a childhood cancer survivor in the first sentence:

• Shortness of breath climbing stairs, or swelling of the ankles or abdomen.
• A new lump anywhere, especially inside a radiation field.
• Growth that stalls in a child or teen.
• Periods that stop for three months or more.
• New hearing loss or ringing in the ears.
• Any change in the body lasting longer than a few weeks.

Call 911 or go to an emergency department for chest pain, sudden severe breathlessness, a faint or blackout, or a heartbeat that races or thumps out of rhythm. After anthracyclines or chest radiation the heart is the organ most likely to be behind those, and they are not worth a wait for a clinic slot.

See Late Effects of Childhood Cancer Treatment for the overview and What to Expect at a Survivorship Visit for the appointment itself. Also useful: Childhood Cancer Survivorship, School 504 Plans During Childhood Cancer, and Questions to Ask About Childhood Cancer Treatment.

• Late Effects of Treatment for Childhood Cancer (PDQ), National Cancer Institute
• Late Effects of Cancer Treatment, National Cancer Institute
• Survivorship and Long-Term Follow-Up Guidelines, Children's Oncology Group
• COG Long-Term Follow-Up Guidelines, Version 6 (PDF)
• Passport for Care, Children's Oncology Group
• Cardiac (Heart) Late Effects in Childhood Cancer Survivors, Together by St. Jude
• Breast Cancer Risk in Childhood Cancer Survivors, Together by St. Jude
• Growth Hormone Deficiency, Together by St. Jude
• Endocrine Late Effects of Childhood Cancer Treatment, Together by St. Jude
• Male Reproductive Issues in Childhood Cancer Survivors, Together by St. Jude
• Cognitive Effects of Childhood Cancer and Stem Cell Transplant, Together by St. Jude