A 71-year-old woman presents to her hematologist-oncologist for follow up after having begun doxorubicin and cyclophosphamide in addition to radiation therapy for the treatment of her stage 3 breast cancer. Her past medical history is significant for preeclampsia, hypertension, polycystic ovarian syndrome, and hypercholesterolemia. She currently smokes 1 pack of cigarettes per day, drinks a glass of wine per day, and denies any illicit drug use. The vital signs include: temperature 36.7°C (98.0°F), blood pressure 126/74 mm Hg, heart rate 111/min, and respiratory rate 23/min. On physical examination, the pulses are strong and irregular, she has a grade 3/6 holosystolic murmur heard best at the left upper sternal border, clear bilateral breath sounds, and erythema over her site of radiation. Which of the following statements regarding doxorubicin is true?

Doxorubicin has a maximum lifetime dose, due to the risk of cardiac toxicity

Doxorubicin has a maximum lifetime dose, due to the risk of pulmonary toxicity

Doxorubicin will increase her risk for deep vein thrombosis (DVT) and pulmonary embolism (PE)

Doxorubicin frequently causes an acneiform rash

Doxorubicin frequently causes cystitis

A 38-year-old female presents to her primary care physician with complaints of several episodes of palpitations accompanied by panic attacks over the last month. She also is concerned about many instances over the past few weeks where food has been getting stuck in her throat and she has had trouble swallowing. She denies any prior medical problems and reports a family history of cancer in her mother and maternal grandfather but cannot recall any details regarding the type of cancer(s) or age of diagnosis. Her vital signs at today's visit are as follows: T 37.6 deg C, HR 106, BP 158/104, RR 16, SpO2 97%. Physical examination is significant for a nodule on the anterior portion of the neck that moves with swallowing, accompanied by mild lymphadenopathy. A preliminary work-up is initiated, which shows hypercalcemia, elevated baseline calcitonin, and an inappropriately elevated PTH level. Diagnostic imaging shows bilateral adrenal lesions on an MRI of the abdomen/pelvis. Which of the following is the most likely diagnosis in this patient?

Multiple endocrine neoplasia (MEN) IIa

Familial medullary thyroid cancer (FMTC)

Multiple endocrine neoplasia (MEN) I

Multiple endocrine neoplasia (MEN) IIb

A 7-year-old girl is brought to the physician because of scant painless bleeding from the vagina 6 hours ago. She has no history of serious illness or trauma. Her older sister had her first period at age 11. The patient is at the 80th percentile for height and 95th percentile for weight and BMI. Examination shows greasy facial skin and sparse axillary hair. Breast development is at Tanner stage 3 and pubic hair development is at Tanner stage 2. The external genitalia appear normal. Serum glucose is 189 mg/dL. Intravenous administration of leuprolide causes an increase in serum luteinizing hormone. Which of the following is the most likely underlying cause of this patient's findings?

Overproduction of adrenal cortisol

A previously healthy 46-year-old woman comes to the physician because of a 3-month history of fatigue and progressive shortness of breath. She does not take any medications. Her pulse is 93/min and blood pressure is 112/80 mm Hg. Examination shows no abnormalities. Her hemoglobin concentration is 8 g/dL, leukocyte count is 22,000/mm3, and platelet count is 80,000/mm3. A peripheral blood smear shows increased numbers of circulating myeloblasts. Bone marrow biopsy confirms the diagnosis of acute myeloid leukemia. ECG, x-ray of the chest, and echocardiogram show no abnormalities. The patient is scheduled to start induction chemotherapy with cytarabine and daunorubicin. This patient is at increased risk for which of the following long-term complications?

Decreased diffusing capacity of the lung for carbon monoxide

An 18-month-old boy is brought to the doctor’s office for evaluation of abdominal pain. The boy looks emaciated and he is now significantly below his growth chart predicted weight. The family history is non-contributory. The vital signs are unremarkable. On physical examination, a non-tender mass is felt in the upper part of the abdomen. A magnetic resonance image (MRI) scan of his abdomen demonstrates a mass in his right adrenal gland. Biopsy of the mass demonstrates an abundance of small round blue cells. With this biopsy result, which 1 of the following findings would confirm the diagnosis?

Elevation of vanillylmandelic acid in the urine

MRI showing the intrarenal origin of the mass

Radiograph of the bone showing the presence of lytic bone lesion with periosteal reaction

A 3-year-old girl is brought to the physician by her parents for complaints of breast development and pubic hair growth for the past 6 months. She has no significant birth or medical history. The temperature is 37.0°C (98.6°F), the pulse is 88/min, and the respirations are 20/min. Physical examination shows enlarged breasts at Tanner stage 3 and pubic hair at stage 2. Height and weight are in the normal range. On GnRH stimulation testing, a luteinizing hormone (LH) response of < 5 IU/L is detected. What is the most appropriate next step in diagnosis?

Measure baseline estradiol levels and perform pelvic ultrasound

Perform leuprolide stimulation test to measure testosterone

Measure FSH levels to evaluate pituitary function

Calculate LH:FSH ratio from previous GnRH test

Repeat GnRH stimulation test to confirm LH response

A 6-year-old girl is brought to the pediatrician by her father for an annual physical examination. The father reports that the patient is a happy and healthy child, but he sometimes worries about her weight. He says that she is a “picky” eater and only wants chicken nuggets and French fries. He also notes some mild acne on her cheeks and forehead but thinks it’s because she “doesn’t like baths.” The father says she has met all her pediatric milestones. She has recently started kindergarten, can tell time, and is beginning to read. Her teacher says she gets along with her classmates well. The patient was born at 38 weeks gestation. She has no chronic medical conditions and takes only a multivitamin. Height and weight are above the 95th percentile. Physical examination reveals scattered comedones on the patient’s forehead and bilateral cheeks. There is palpable breast tissue bilaterally with raised and enlarged areolae. Scant axillary hair and coarse pubic hair are also noted. A radiograph of the left hand shows a bone age of 9 years. Serum follicular stimulating hormone (FSH) level is 9.6 mU/mL (normal range 0.7-5.3 mU/mL) and luteinizing hormone (LH) level is 6.4 mU/mL (normal range < 0.26 mU/mL). Which of the following is the most appropriate diagnostic test?

Brain magnetic resonance imaging (MRI)

Dehydroepiandrosterone sulfate levels

Long-term survivor follow-up for USMLE Step 3: High-Yield Pediatrics Lessons

Survivor Follow-up - The Long Game

Goal: Lifelong, risk-based monitoring for "late effects" of cancer therapy to improve quality of life & survival.
Key Principle: The specific chemo agents and radiation fields dictate the long-term follow-up (LTFU) plan.
Common Late Effects & Screening:
- Cardiotoxicity: Anthracyclines (e.g., Doxorubicin >250 mg/m²). Requires regular ECHO/ECG.
- Secondary Malignancy: Alkylating agents (AML/MDS); Radiation (solid tumors like sarcoma, breast, thyroid).
- Pulmonary Fibrosis: Bleomycin, chest RT.
- Endocrinopathies: Cranial/neck RT (GH deficiency, hypothyroidism). Monitor growth, annual TSH.
- Infertility: Alkylating agents (Cyclophosphamide), gonadal RT.

⭐ Anthracycline-induced cardiotoxicity is a critical late effect. It is dose-dependent and can manifest as cardiomyopathy years after treatment completion.

Late effects of pediatric cancer therapy by organ system

Cardiopulmonary & Renal - Systems Under Siege

Cardiac Toxicity: Primarily from Anthracyclines (Doxorubicin, Daunorubicin) & chest radiation.
- Risk ↑ with cumulative Doxorubicin dose > 250 mg/m².
- Manifests as: Dilated Cardiomyopathy (DCM), arrhythmias, pericarditis.
- Monitoring: Baseline & serial ECG, Echocardiography.
- 💡 Cardioprotection with Dexrazoxane.
Pulmonary Toxicity:
- Key drugs: Bleomycin, Busulfan.
- Leads to: Pulmonary fibrosis, pneumonitis (especially post-radiation).
- Monitoring: Pulmonary Function Tests (PFTs).
Renal & Bladder Toxicity:
- Cisplatin: Ototoxicity & Nephrotoxicity (tubular damage, ↓ GFR).
- Ifosfamide: Proximal tubulopathy (Fanconi Syndrome) & Hemorrhagic Cystitis.
⭐ Hemorrhagic cystitis from Ifosfamide/Cyclophosphamide is preventable with vigorous hydration and co-administration of MESNA.

Endocrine & Musculoskeletal - Growth & Strength

Growth Failure & Monitoring:
- Most common cause: Growth Hormone (GH) deficiency, especially after cranial irradiation >18-24 Gy.
- Other culprits: Total Body Irradiation (TBI), high-dose methotrexate, hypothyroidism.
- Action: Monitor height, weight, and growth velocity annually. Assess bone age if growth falters.
Puberty & Bone Health:
- Precocious Puberty: Can occur with cranial irradiation >18 Gy.
- Delayed Puberty/Hypogonadism: Risk from gonadal irradiation and alkylating agents.
- ↓ Bone Mineral Density: Due to steroids, methotrexate, radiation. Screen with DEXA in high-risk cases.
- Avascular Necrosis (AVN): Strongly associated with high-dose steroid use.

⭐ High-Yield: The most frequent endocrine complication following cancer therapy is GH deficiency, particularly after cranial irradiation for brain tumors or leukemia prophylaxis.

Second Malignancies - The Unwanted Sequel

A leading cause of mortality in long-term survivors. The risk is cumulative and lifelong, significantly influenced by the original cancer treatment.
Primary Risk Factors:
- Radiotherapy (RT): The most potent factor. Tumors (sarcomas, breast, thyroid) arise within or at the edge of the radiation field.
- Chemotherapy:
  - Alkylating agents (e.g., cyclophosphamide) → AML/MDS.
  - Topoisomerase II inhibitors (e.g., etoposide) → AML.
- Genetic Predisposition: e.g., RB1 gene, Li-Fraumeni syndrome.
Timeline:
- Solid tumors: Latency of >10 years.
- Therapy-related AML/MDS: Peaks 2-10 years post-therapy.

⭐ The most common second malignancies are solid tumors, particularly after radiotherapy. Chemotherapy-induced leukemias (AML/MDS) typically have a much shorter latency period.

Cumulative risk of solid cancer after Hodgkin lymphoma

High-Yield Points - ⚡ Biggest Takeaways

Anthracyclines (e.g., doxorubicin) cause dose-dependent cardiotoxicity, mandating lifelong cardiac follow-up.

Cyclophosphamide carries risks of hemorrhagic cystitis, infertility, and later bladder cancer.

Bleomycin is associated with pulmonary fibrosis; requires pulmonary function tests.

Cisplatin is known for ototoxicity and nephrotoxicity.

Vincristine commonly results in cumulative peripheral neuropathy.

Cranial radiation can lead to neurocognitive defects, endocrinopathies, and secondary CNS tumors.

Etoposide is linked to therapy-related leukemia (t-AML).

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