CPHON Late Effects of Childhood Cancer Treatment 2 — Questions and Answers

Question 1: Which late effect is associated with bleomycin chemotherapy used in treatment of Hodgkin lymphoma?

Pulmonary fibrosis (Correct answer)
Renal tubular dysfunction
Hepatic veno-occlusive disease
Peripheral neuropathy

Correct answer: Pulmonary fibrosis

Bleomycin causes inflammation and progressive fibrosis of the pulmonary parenchyma. Pulmonary fibrosis is the major dose-limiting late toxicity, potentially resulting in chronic restrictive lung disease.

Bleomycin causes oxidative damage to pulmonary endothelial cells, triggering an inflammatory cascade that leads to fibrosis of the lung parenchyma. Late pulmonary toxicity manifests as reduced diffusion capacity (DLCO), restrictive lung pattern, and exertional dyspnea. Risk is increased by cumulative dose, concurrent oxygen therapy, and thoracic radiation. Pulmonary function tests (PFTs) should be monitored in all survivors who received bleomycin.

Question 2: A 10-year-old who received high-dose methotrexate during ALL treatment now has difficulty with math and reading comprehension. Which pathologic mechanism best explains this?

Leukoencephalopathy from methotrexate-induced white matter damage (Correct answer)
Direct neurotoxicity from corticosteroids
Vascular steal syndrome from L-asparaginase
CNS relapse causing tumor infiltration

Correct answer: Leukoencephalopathy from methotrexate-induced white matter damage

High-dose methotrexate can cause leukoencephalopathy—demyelination and white matter injury—leading to cognitive deficits in attention, processing speed, and academic skills.

Methotrexate, especially at high doses or given intrathecally, can cause leukoencephalopathy—a condition characterized by demyelination and white matter necrosis. This is seen on MRI as white matter signal abnormalities. Clinically it presents with neurocognitive deficits including impaired memory, processing speed, attention, and academic difficulties. The combination of high-dose IV methotrexate plus intrathecal methotrexate plus cranial radiation further increases risk. Neuropsychological evaluation is recommended.

Question 3: Which late effect monitoring test is most important for a childhood cancer survivor who received high-dose cisplatin?

Audiogram for sensorineural hearing loss (Correct answer)
Ophthalmologic exam for cataracts
Dental panorex for root foreshortening
Bone density scan for osteoporosis

Correct answer: Audiogram for sensorineural hearing loss

Cisplatin is ototoxic, causing permanent sensorineural hearing loss—particularly in high frequencies. Regular audiologic monitoring is essential for survivors who received cisplatin.

Cisplatin-induced ototoxicity results from damage to the outer hair cells of the cochlea, particularly in the basal turn, which processes high-frequency sounds. Hearing loss is typically bilateral, permanent, and sensorineural. Children are especially vulnerable because high-frequency hearing is critical for speech and language development. Risk increases with cumulative dose, younger age at treatment, concurrent cranial radiation, and co-administration of other ototoxic drugs (e.g., aminoglycosides). Baseline and serial audiograms are mandatory in survivorship care.

Question 4: A male survivor of childhood cancer who received testicular radiation or alkylating agents should be counseled about which reproductive late effect?

Azoospermia and infertility (Correct answer)
Testicular torsion
Erectile dysfunction
Retrograde ejaculation

Correct answer: Azoospermia and infertility

Testicular radiation and alkylating agents destroy spermatogonia, leading to azoospermia and potential permanent infertility. Testosterone production may or may not be affected depending on Leydig cell damage.

Spermatogonial stem cells are among the most radiosensitive cells in the body; even low doses of gonadal radiation can cause azoospermia. Alkylating agents, especially cyclophosphamide and busulfan at high cumulative doses, similarly destroy spermatogonia. Azoospermia may be permanent. Leydig cells producing testosterone are more radioresistant, so testosterone production is often preserved unless very high doses are used. Sperm banking before gonadotoxic therapy is strongly recommended for post-pubertal males.

Question 5: Which late effect is associated with corticosteroid use during childhood cancer treatment?

Avascular necrosis of bone (Correct answer)
Secondary leukemia
Pulmonary fibrosis
Renal tubular necrosis

Correct answer: Avascular necrosis of bone

Prolonged high-dose corticosteroid use impairs blood supply to bone, most commonly affecting the femoral head and causing avascular necrosis (osteonecrosis), which can lead to joint collapse and chronic pain.

Avascular necrosis (osteonecrosis) is a recognized late effect of prolonged corticosteroid therapy used in protocols for ALL, lymphoma, and transplant conditioning. Steroids disrupt lipid metabolism and increase intraosseous pressure, compromising microvascular blood supply to bone. The femoral head is most commonly affected, but the humeral head, knees, and ankles can also be involved. Adolescents and those receiving dexamethasone are at higher risk. MRI is the gold standard for diagnosis. Orthopedic consultation and weight-bearing restrictions are key management strategies.

Question 6: A long-term survivor of childhood Hodgkin lymphoma who received mantle field radiation is at significantly elevated risk for which secondary malignancy?

Breast cancer (Correct answer)
Colon cancer
Brain tumor
Thyroid cancer only

Correct answer: Breast cancer

Females who received mantle field radiation involving the chest are at markedly elevated lifetime risk for breast cancer, often presenting at a younger age than in the general population.

Mantle field radiation, historically used for Hodgkin lymphoma, covers the mediastinum, axilla, and neck, directly exposing developing breast tissue to radiation. Female survivors have a significantly elevated risk of breast cancer, with risk increasing beginning about 8 years post-radiation and continuing to rise lifelong. Annual breast MRI starting at age 25 (or 8 years post-radiation, whichever is later) is recommended by survivorship guidelines. The risk is dose-dependent and attenuated somewhat by oophorectomy or chemotherapy-induced ovarian suppression.

CPHON Late Effects of Childhood Cancer Treatment 2

Which late effect is associated with bleomycin chemotherapy used in treatment of Hodgkin lymphoma?