Overview

Definition:
-Late effects of childhood cancer refer to adverse health conditions that arise as a consequence of cancer treatment (chemotherapy, radiation, surgery) or the cancer itself, occurring months or years after diagnosis and completion of therapy
-These effects can impact virtually any organ system and may range from mild, asymptomatic conditions to severe, life-threatening sequelae.
Epidemiology:
-With cure rates for childhood cancers exceeding 80% in many high-income countries, a large population of survivors now exists
-Approximately two-thirds of childhood cancer survivors experience at least one late effect, and one-third report severe or life-threatening late effects
-The cumulative incidence of any late effect increases with time since diagnosis, reaching over 70% by 30 years post-diagnosis
-Risk is influenced by the type of cancer, treatment intensity, age at diagnosis, and specific treatment modalities used.
Clinical Significance:
-Effective surveillance for late effects is critical to detect, manage, and potentially prevent serious health problems in childhood cancer survivors
-Early identification and intervention can improve quality of life, reduce morbidity and mortality from treatment-related sequelae, and prevent secondary malignancies
-These guidelines are essential for pediatricians, oncologists, and other healthcare professionals involved in the long-term care of these patients, and are a key area tested in DNB and NEET SS examinations.

Surveillance Principles

Risk Stratification:
-Survivors are stratified into risk groups based on their original diagnosis, treatment modalities received (type, dose, duration of chemotherapy and radiation, surgical interventions), and age at diagnosis
-Specific treatment protocols (e.g., PTCOG, COG, NOPHO protocols) provide detailed risk-stratified recommendations.
Multidisciplinary Approach:
-Surveillance requires a multidisciplinary team including pediatric oncologists, primary care physicians, specialists in cardiology, pulmonology, endocrinology, neurology, audiology, ophthalmology, and reproductive health
-Regular communication between the survivor, family, and healthcare providers is crucial.
Age Appropriate Screening:
-Screening strategies evolve with the survivor's age, moving from childhood-specific concerns to adult-onset conditions
-General health maintenance, including immunizations and screenings for common adult diseases, is integrated alongside cancer-specific surveillance.
Patient Education And Empowerment:
-Survivors and their families must be educated about potential late effects and the importance of ongoing surveillance
-Empowering survivors to actively participate in their healthcare promotes adherence to follow-up recommendations and early symptom recognition.

Common Late Effects And Screening

Cardiac Toxicity:
-Risk factors include anthracyclines, chest radiation
-Screening: Echocardiogram (baseline, periodic based on risk), ECG, clinical assessment for dyspnea, palpitations, chest pain
-Specific recommendations vary by cumulative dose of anthracyclines and radiation fields.
Pulmonary Toxicity:
-Risk factors include bleomycin, lung radiation
-Screening: Pulmonary function tests (PFTs) (spirometry, DLCO), chest X-ray, clinical assessment for dyspnea and cough
-Periodic monitoring starting 2-5 years post-treatment, depending on exposure.
Endocrine Dysfunction:
-Risk factors include cranial/neck radiation, high-dose chemotherapy, surgery of endocrine glands
-Screening: Growth monitoring, thyroid function tests (TSH, fT4), evaluation for diabetes mellitus (HbA1c, fasting glucose), assessment of gonadal function (hormonal assays, fertility counseling), bone mineral density scans (DEXA) for osteopenia/osteoporosis
-Regular checks from childhood through adulthood.
Neurological Sequelae:
-Risk factors include cranial radiation, intrathecal chemotherapy, neurotoxic agents
-Screening: Neuropsychological evaluations (cognitive function, learning disabilities), assessment for endocrine dysfunction (pituitary), cranial nerve deficits, seizures, peripheral neuropathy
-Early and ongoing assessment is vital.
Ototoxicity And Vision Impairment:
-Risk factors include platinum agents (cisplatin, carboplatin), cranial radiation
-Screening: Audiometry (baseline, annual or biannual based on risk), ophthalmological examination (visual acuity, visual fields, slit-lamp examination for cataracts, fundus examination for retinopathy) recommended annually or biannually.
Musculoskeletal Issues:
-Risk factors include radiation to bone, corticosteroid therapy, surgery affecting growth plates
-Screening: Monitoring of growth, skeletal surveys, assessment for scoliosis, joint stiffness, limb length discrepancies, and risk of fractures
-DEXA scans for bone density.
Secondary Malignancies:
-Risk factors include alkylating agents, radiation
-Screening: Comprehensive physical examination, age-appropriate cancer screening guidelines (e.g., mammography for female survivors of chest radiation, colonoscopy), and prompt investigation of any suspicious symptoms
-Surveillance typically continues lifelong.

Surveillance Guidelines By Age Group

Childhood And Adolescence:
-Focus on immediate post-treatment effects: growth, endocrine function, neurocognitive development, ototoxicity, cardiac function
-Regular physical exams, growth charts, basic lab tests (CBC, LFTs, RFTs), audiometry, ophthalmology, PFTs for high-risk individuals
-Education on sun protection and healthy lifestyle.
Young Adulthood:
-Transition to adult care
-Continued monitoring of major organ systems (cardiac, pulmonary, endocrine)
-Introduction of age-appropriate cancer screening
-Fertility counseling and management of reproductive health issues
-Psychological support and management of psychosocial adjustments
-Emphasis on lifestyle modifications.
Adult Survivorship:
-Lifelong surveillance for chronic conditions and secondary malignancies
-Regular specialist consultations as needed based on identified risks
-Management of age-related comorbidities alongside cancer-related late effects
-Continued patient education for self-advocacy.

Key Points

Exam Focus:
-Understand the specific treatment modalities (chemotherapy agents, radiation fields) that predispose to particular late effects
-Know the recommended screening tests and their frequency for common late effects like cardiac, pulmonary, and endocrine dysfunction
-Recognize the importance of risk stratification for personalized surveillance plans.
Clinical Pearls:
-Always maintain a high index of suspicion for late effects in childhood cancer survivors presenting with vague symptoms
-Integrate general health maintenance with cancer-specific surveillance
-Empower survivors with knowledge about their treatment history and follow-up needs
-Facilitate smooth transitions to adult care.
Common Mistakes:
-Underestimating the cumulative toxicity of combined treatment modalities
-Inadequate risk stratification leading to under- or over-screening
-Lack of coordinated care between primary care and specialists
-Failing to educate survivors about their long-term risks and the importance of adherence to surveillance
-Not considering psychosocial aspects of survivorship.