Cancer Survivorship & Late Effects
Learning objectives
- LO 1Describe what long-term follow-up care for childhood cancer survivors aims to do.
- LO 2Name the most common late effects of cancer treatment and the exposures that cause them.
- LO 3Recognize the emotional burden of survivorship and how to support survivors.
- LO 4Identify the survivorship team and explain why communication and relationships keep survivors in care.
MAPFollow the treatment to the organ
LO 1The mission of long-term follow-up
Q1. Why is "cure not enough"?
| Number | Meaning |
|---|---|
| ≈85% | Children with cancer who survive >5 years (most cured) |
| >500,000 | U.S. childhood cancer survivors; ≈1 in 530 adults aged 20–39; >100,000 in college |
| <5% | Survivors actually followed in a survivorship program |
| 15–30 years | When most late effects appear after therapy ends |
| 75% / >40% | Treated 1970s–1990s: 75% develop a chronic disease by 40; >40% a serious problem |
- Late effects come from chemo, radiation, surgery, stem cell transplant and immunotherapy; some appear during treatment, most years later
- Excess early death, in order: (1) second malignancy, (2) cardiovascular, (3) pulmonary disease
- Risk of serious treatment-related disease is still significantly elevated beyond 30 years from diagnosis
In-house exam
When is the risk of serious treatment-related disease highest? It remains significantly elevated beyond 30 years after diagnosis: it doesn't fade.
Analogy — the time bomb
The patient feels well and leaves pediatrics. In their 30s the heart, breast or second-cancer problem goes off, and no one remembers the treatment. Survivorship programs cover that gap.
Q2. What is the Childhood Cancer Survivor Study?
- Largest NIH-funded follow-up study: 17,308 survivors treated 1970–1986 at 26 centers, <21 at diagnosis, survived >5 y
- Compared 10,397 adult survivors with 3,034 siblings → ≈75% had ≥1 chronic condition 30 years after diagnosis
- Tracked growth, organ function, fertility, second cancers, psychosocial issues and early mortality
Q3. What does a survivorship program set out to do?
- Follow survivors carefully for anticipated late effects
- Educate them about their cancer and its treatment
- Educate on risk-taking behaviors, healthy lifestyle, fertility, employment, health insurance
- Transition them to adult programs as they age
- Eligibility: all patients 2 years off therapy
- History: 1960s–mid-1980s, survivors were discharged 5–10 years off therapy and never seen again
- National Academy of Medicine: lifelong, risk-based survivorship care
Memory tool — F-E-E-T
Follow · Educate (cancer) · Educate (life) · Transition. Ticket in = 2 years off therapy.
ApplyLO 1 application question
A1A child finished leukemia therapy 2 years ago and is doing well. Should she enter a long-term follow-up program?
LO 2The most common late effects
Q1. Which late effects do survivors ask about, and which one kills them?
What survivors ask about
- Neurocognitive dysfunction
- Cardiovascular disease
- Infertility and gonadal dysfunction
- Psychosocial problems
What they never ask about
- Second cancer, the leading cause of excess late death
- The physician has to raise it
Q2. What are the neurocognitive and growth effects?
Neurocognitive
- Most at risk: brain tumors and ALL; also after SCT or head/neck radiation
- Cause: cranial radiation, CNS-directed chemo
- Mild deficits → major learning disabilities: reading, spelling, math; attention, memory; processing speed; visual-motor
- Special education needed in 8–50%
Growth
- Cranial radiation → early puberty (early growth-plate fusion)
- Spinal radiation >35 Gy → direct inhibition of vertebral growth → short trunk
- Chemo-related growth slowing is usually temporary
Cranial radiation and growth
- 24 Gy at age 2 → menarche at 10, predicted adult height 147 cm
Step 1
Cranial radiation also causes GH deficiency (most radiation-sensitive pituitary axis); high doses can cause delayed puberty. Check growth velocity and test GH.
Q3. How does treatment damage the heart?
- Anthracyclines (doxorubicin, daunorubicin) → asymptomatic cardiotoxicity → cardiomyopathy, LV dysfunction, CHF
- Mantle (chest) radiation → coronary and carotid artery disease, valve disease
- Risk factors: female sex, younger age at treatment, higher cumulative dose, radiation to the heart
- Cardiovascular disease = 2nd cause of excess late death
Memory tool — YF-BDR
Younger · Female · Big cumulative Dose · Radiation to the heart.
Step 1
Anthracycline = dose-dependent, irreversible dilated cardiomyopathy (free radicals, iron). Dexrazoxane (iron chelator) protects; monitor with echo. Trastuzumab = reversible, not dose-dependent.
Q4. How does treatment affect fertility in boys vs girls?
| Males | Females | |
|---|---|---|
| Sensitivity | Testes very sensitive | Ovaries relatively resistant to chemo, sensitive to radiation |
| Damaging exposure | ≈10 g cyclophosphamide; low-dose radiation 200–300 cGy | Abdominal/pelvic radiation (22–30 Gy), high-dose alkylators, cranial RT, TBI |
| Result | Sterility (azoospermia); testosterone usually kept | Pubertal delay, premature ovarian failure → osteoporosis, early CAD |
| Age | — | Older girls (13–19, fewer follicles) at higher risk |
| Prevent | Sperm banking | Oocyte / ovarian tissue freezing |
- TBI before BMT = highest risk: premature ovarian failure in 100% of girls >10 y, 50% <10 y
- Why osteoporosis and early CAD? Loss of estrogen, which protects bone and vessels
Memory tool
"Testes break easily; ovaries fear radiation."
In-house exam
Know the numbers: 10 g cyclophosphamide or 200–300 cGy sterilizes boys; TBI is the top risk for ovarian failure.
Q5. What other organ effects matter?
| Exposure | Late effect | Screen |
|---|---|---|
| Neck / mantle radiation | Hypo- and hyperthyroidism, thyroid cancer | Yearly TSH, neck exam |
| Glucocorticoids | Osteonecrosis, osteoporosis, cataracts | Bone density |
| Hormone loss, radiation | Osteoporosis/osteopenia, metabolic syndrome | Lipids, glucose |
| Bleomycin, busulfan | Pulmonary fibrosis (3rd cause of excess death) | PFTs; no smoking |
| Cisplatin | Nephrotoxicity, hearing loss | Audiology |
| Vincristine | Peripheral neuropathy | Neuro exam |
| Cyclophosphamide | Hemorrhagic cystitis, bladder cancer | Mesna (prevention) |
Step 1
Drug → toxicity pairs: doxorubicin → heart · bleomycin/busulfan → lung · cisplatin → ear, kidney · vincristine → nerves · cyclophosphamide → bladder (mesna).
Q6. What second cancers occur?
| Second cancer | Cause | Timing / clue |
|---|---|---|
| AML / MDS | Alkylators | 5–10 y; del 5q / −7 |
| AML | Topoisomerase II inhibitors (etoposide) | 1–3 y; 11q23 (KMT2A) |
| Breast cancer | Chest radiation in teens (Hodgkin) | 20s–40s |
| Skin cancer | Radiation | Basal + squamous cell |
| Brain tumors | Cranial radiation | Malignant and benign |
| In-field cancers | Any radiation field | Soft-tissue sarcoma, SCC, osteosarcoma; thyroid cancer after neck RT |
Therapy-related AML
- Blasts years after chemo
High yield
Therapy-related MDS/AML has a worse prognosis than primary disease. Pancytopenia, ringed sideroblasts and del(5q) 7 years after lymphoma chemo → t-MDS.
Step 1
After chest radiation, start breast screening (MRI + mammogram) at age 25 or 8 years after radiation, whichever is later.
ApplyLO 2 application questions
A1A 28-year-old who received doxorubicin at age 8 now has dyspnea, an S3 and an ejection fraction of 30%. Cause?
A2A 17-year-old who had 40 Gy of spinal radiation for medulloblastoma is much shorter than his family, with a short trunk. Why?
A3A 30-year-old treated with leg radiation for Ewing sarcoma develops a new mass in the same field. Most likely?
LO 3The emotional burden of survivorship
Q1. What psychological problems do survivors face?
- More likely to have mental health disorders (anxiety, depression), chronic pain, fatigue, sleep disorders
- PTSD in ≈1 in 5; can emerge months to years after treatment
- Parents get PTSD too
- Social burden: employment, health insurance, fertility worries, risk-taking
In-house exam
PTSD affects about one fifth of survivors (and their parents) and may appear years after treatment.
Step 1
PTSD: intrusion, avoidance, negative mood, hyperarousal for >1 month. Treat with trauma-focused CBT ± SSRI.
Q2. Why do survivors drop out of follow-up?
| Barrier | Strategy to bring them back |
|---|---|
| Relied on parents to track appointments | Education near the end of treatment for survivors and parents |
| Too young to know treatment details | Treatment summary; Passport for Care |
| Want normalcy, "done with cancer" | Theme: focus on wellness |
| Lost after high school | Remote yearly check-ups via telehealth |
| Not interested in lifestyle education | Support groups; survivorship conferences on specific late effects |
| Adult doctors unfamiliar with late effects | Simplified COG guidelines; educate primary care providers |
Trap
A survivor with nightmares who misses visits isn't just "noncompliant": avoidance is a PTSD symptom. Respond with empathy and a psychology referral.
ApplyLO 3 application question
A1A 19-year-old says: "I'm done with cancer. I'm not going back to the children's hospital." Best response?
LO 4The survivorship team and communication
Q1. Who is on the team, and what are the core components of care?
Team
- MD
- Nurse practitioner
- Social worker
- Psychologist
- Nutritionist
- + the primary care physician as an integral partner
Core components
- Cancer treatment summary and plan (drugs, cumulative doses, radiation fields)
- COG Long-Term Follow-Up Guidelines
- Delivery of risk-based care
Shared care model
- Pediatrician ↔ oncologist ↔ PCP, joined by communication
Memory tool
Team = "My Nurse Says Please Nourish": MD · NP · Social worker · Psychologist · Nutritionist.
Q2. How does transition to adult care work?
- Move from the sheltered pediatric environment to the independent adult one
- Challenge: an effective handoff between pediatric- and adult-centered providers
- Optimal care: longitudinal, survivor-focused care into young adulthood so screening and psychosocial support continue
- Models: pediatric oncology center, adult oncology center, primary care, formal transition programs (e.g., STAR), or a combination
Trap — communication questions
The best answer is rarely "insist they come" or "talk to the parents instead." Choose the patient-centered option: explore concerns, frame follow-up around wellness, give anticipatory guidance, speak to the survivor directly (an adult at 18), and partner with the PCP.
High yield — lecture summary
Late effects are frequent and serious · proactive, risk-based care reduces morbidity · the PCP is an integral partner · education of survivors, families and PCPs is essential.
ApplyLO 4 application question
A1A 20-year-old college student had Wilms tumor at 6, doesn't know his treatment and hasn't seen an oncologist in 8 years. First step?
IDExposure drill: name the late effect
Doxorubicin at age 8
Mantle radiation for Hodgkin at 15 (girl)
Cranial radiation for ALL at 4
Spinal radiation 40 Gy
10 g cyclophosphamide (boy)
TBI before BMT (girl, 14)
Etoposide 2 years ago
Bleomycin + chest radiation
MCQExam-style questions
1For childhood cancer survivors, the risk of serious treatment-related disease is best described as:
2Which is the leading cause of excess late death in childhood cancer survivors?
3A 9-year-old finished ALL therapy 2 years ago. Which describes his eligibility for a long-term follow-up program?
4Which patient has the highest risk of anthracycline cardiotoxicity?
5A 32-year-old woman had mantle radiation for Hodgkin lymphoma at 15. She now has a breast mass. Most likely explanation?
6A 12-year-old treated with cranial radiation for ALL at 4 is failing math and has trouble paying attention. Best next step?
7A boy receives about 10 g of cyclophosphamide for sarcoma. Which late effect is most expected?
8Which exposure carries the highest risk of premature ovarian failure?
9A 26-year-old woman had whole-abdominal radiation at 14. She now has amenorrhea, hot flashes and low bone density. Why is she also at risk for early coronary disease?
10A 50-year-old man treated with chemotherapy for DLBCL 7 years ago now has infections, pancytopenia, ringed sideroblasts and del(5q). Diagnosis?
11About what fraction of childhood cancer survivors develop PTSD?
12A 24-year-old leukemia survivor asks only about heart disease and fertility at her visit. What should the physician add?
13Which is NOT one of the three core components of survivor care?
!Source notes
| Item | Lecture | Step 1 / standard references |
|---|---|---|
| Cranial radiation | Early puberty | Also GH deficiency; delayed puberty at high doses |
| Male sterility dose | ≈10 g cyclophosphamide | COG flags risk from cyclophosphamide-equivalent doses ≥4 g/m² |
| Breast screening after chest RT | — | Age 25 or 8 years after radiation, whichever is later |
| Late effect prevention | Not covered | Dexrazoxane (heart), mesna (bladder), fertility preservation before therapy |