Pediatric Oncology.pdf

Pediatric Oncology Zhour Barnawi, MBBS Pediatric Core Lectures King Abdulaziz University- Faculty of Medicine (Rabigh) Monday, Sep 16th, 2024 Objectives By the end of this lecture, the student should be able to: Recognize the risk factors to develop...

Pediatric Oncology Zhour Barnawi, MBBS Pediatric Core Lectures King Abdulaziz University- Faculty of Medicine (Rabigh) Monday, Sep 16th, 2024 Objectives By the end of this lecture, the student should be able to: Recognize the risk factors to develop cancer in general. Identify the most encountered types in children. Be familiar with leukemia and lymphoma: List the types Recognize the clinical presentations Discuss the investigations and main treatment principles Recognize the common types of brain tumor in children. Discuss Wilm’s tumor. Discuss Neuroblastoma. Identify the general principles of treatments of pediatric cancer. What is Cancer? Cancer is a group of diseases characterized by uncontrolled cell division. Carcinogenesis occurs when the cellular regulatory mechanisms are disrupted. Hallmarks of cancer cells: Sustained proliferative signaling Evasion of growth suppressors Resistance to apoptosis? Invasion and metastasis Pathogenesis: Mutations in oncogenes, tumor suppressor genes, and DNA repair genes lead to abnormal cell behavior. Epidemiology of Pediatric Cancer Childhood cancers are rare Cancer is the 2nd leading cause of death in children, after accidents. Most common pediatric cancers: Leukemia (30%) Brain and CNS tumors (26%) Lymphomas (8%) Epidemiology of Pediatric Cancer in Saudi, 2020 Childhood cancers accounted for 5.4% of all cancer among Saudis. The leading cancer among Saudi children: Leukemia (30.8%) Brain CNS (16.7%) Hodgkin’s lymphoma (16.3 %) Bone tumor (6.8%) Epidemiology of Pediatric Cancer Age Differences: Leukemias are more common in young children (ages 1-4) Lymphomas are more prevalent in adolescents (ages 15-19). Racial/Ethnic Variations: Higher leukemia rates in Hispanic and American Indian/Alaska Native children Higher brain/CNS tumor rates in White and American Indian/Alaska Native populations. Differences Between Adult & Pediatric Cancers Feature Pediatric Cancers Adult Cancers Primarily hematologic (leukemia, Primarily carcinomas (e.g., lung, Type of Cancer lymphoma) and embryonal tumors breast, colon) (e.g., neuroblastoma, Wilms' tumor) Environmental factors (e.g., smoking) Genetic Mutations Developmental genetic mutations Accumulated DNA damage More responsive to chemotherapy More likely to develop chemotherapy Response to Treatment with higher cure rates resistance and higher relapse risk More favorable, better response due Often worse prognosis due to age- Prognosis to lack of comorbidities related comorbidities Long-term side effects (e.g. growth Short-term toxicities are more Treatment Toxicity issues, secondary cancers, prominent neurodevelopmental issues) Cancer Risk Factors in Pediatrics Genetic Predisposition: Familial syndromes that increase cancer risk Environmental Factors: Limited role in pediatric cancers compared to adults Radiation exposure (e.g., from prior cancer treatment) → leukemia, brain tumor, osteosarcoma, thyroid cancer Most Common Genetic Syndromes Associated with Childhood Cancer Syndrome/Mutation Associated Cancers Down Syndrome (Trisomy 21) Acute Myeloid Leukemia (AML)* , Acute Lymphoblastic Leukemia (ALL) Li-Fraumeni Syndrome (TP53 mutation) Multiple cancers: Sarcomas, breast cancer, brain tumors, leukemia Beckwith-Wiedemann Syndrome Wilms' tumor, hepatoblastoma Optic gliomas (NF1), bilateral vestibular schwannoma (NF2), CNS Neurofibromatosis tumors Retinoblastoma (RB1 mutation) Retinoblastoma, osteosarcoma Fanconi Anemia Leukemia, solid tumors Ataxia-Telangiectasia Leukemia, lymphoma WAGR Syndrome Wilms' tumor, Aniridia, Genitourinary abnormalities, Retardation Trisomy 21 Beckwith-Wiedemann Syndrome Retinoblastoma (Leukocoria) Neurofibromatosis Key points for cancer treatment Staging and grading; depend on the cancer type Concept of risk stratification Types of cancer treatment Surgical resection Chemotherapy Radiation Immunotherapy; targeted therapy Bone marrow transplantation Principle and goal for cancer treatment Curative vs palliative Response to therapy; complete response, partial response, treatment failure, Survivor; event-free survivor, 5-year survivor, relapse/recurrence Leukemias Acute* ALL BLL Chronic CLL CML: Philadelphia chromosome t(9:22) Bone Marrow Peripheral Blood Leukemia- Acute Lymphoblastic Leukemia (ALL) ALL is the most common leukemia Clinical presentation: 75-80% of all pediatric leukemias 5% of children might be Subtypes: B-cell, T-cell, other asymptotic Risk factors for ALL: Non-specific findings are more Exposure to ionizing radiation or common chemotherapy Fatigue, pallor, fever, bone pain Monozygotic twin of affected (refusal to walk), bruising, siblings (100% if 25% blasts (MOST IMPORTANT TEST), cytogenetic testing Lumber puncture (why?) Testicular US (why?) Chest X-ray, CT Treatment: Based on risk stratifications (high risk, low risk, intermediate risk) Chemotherapy (induction, consolidation, Interim Maintenance , delayed intensification, maintenance) New treatments modalities: immunotherapy, CAR-T, bone marrow transplant Bone Marrow Biopsy Lymphoblast Lymphocyte vs Lymphoblast Phases of Acute Leukemia Treatment Phase Goal Induction Achieve complete remission Consolidation Eliminate residual leukemia cells You need to give intrathecal chemotherapy (IT) Interim Maintenance Allow bone marrow recovery while treating throughout the treatment period of leukemia (why?) Delayed Intensification Intensify treatment to target remaining cells Maintenance Sustain remission and prevent relapse Leukemia- Acute Myeloid Leukemia (AML) Less common than ALL but more aggressive Down syndrome has higher incidence Clinical Presentation: Similar to ALL More association with bleeding symptoms Anemia, thrombocytopenia, and neutropenia (pancytopenia) Diagnosis: Auer rod crystal Similar to ALL. Tissue biopsy (BM), Flowcytometry +, immunohistochemistry, cytogenetics Coagulation: PT/INR/PTT, Fibrinogen Treatment: Chemotherapy, bone marrow transplant Brain Tumors Most common solid tumors in children 2nd most common childhood cancer, after leukemia Primary vs secondary Incidence higher in male 1.2:1 Overall, 5-year survival is ~70-75% Types: Medulloblastoma (most common malignant tumor) Astrocytoma (most common overall) Ependymoma, craniopharyngioma, meningioma, glioma, lymphoma Familial Predisposition of Brain Tumor Neurofibromatosis Type I Low grade glioma (optic pathway & brainstem) Neurofibromatosis Type 2 Bilateral acoustic schwannomas, meningiomas, ependymomas Li Fraumeni Malignant glioma Retinoblastoma (germline) Trilateral retinoblastoma (unilateral/bilateral retinoblastoma, pineoblastoma) Brain Tumors Clinical presentation: Generalized symptoms: irritability, fatigue, poor school performance, developmental delay, behavioral changes. Localized symptoms: ataxia, vision changes, seizure, cranial neuropathies, motor or sensory deficit Symptoms of increased ICP: headaches, persistent or morning vomiting, bulging fontanel, papilledema Endocrine symptoms: DI, hypothyroid, precocious puberty Diagnosis: MRI, biopsy Treatment: Surgery, radiation, chemotherapy High-grade Glioma Medulloblastoma Lymphoma 3rd common pediatric cancer Malignant cells of lymphoid origin B-cell (e.g., Burkitt lymphoma) vs T-cell types Types: Hodgkin Lymphoma: Painless lymphadenopathy, Reed-Sternberg cells on biopsy Non-Hodgkin Lymphoma: Rapidly growing masses (mediastinal, abdominal) Diagnosis: CT, positron emission tomography (PET), excisional biopsy Treatment: Chemotherapy, radiation for localized disease Hodgkin vs Non-Hodgkin Lymphoma Hodgkin Lymphoma Non-Hodgkin Lymphoma Feature (Burkitt, DLCBL, ALCL) More common in younger Incidence Peaks in adolescence children Histopathology Reed-Sternberg cells No Reed-Sternberg cells Rapidly growing masses Painless lymphadenopathy, Presentation (mediastinal, abdominal→ usually cervical intussusception), SVS B symptoms: Fever >38°C, night B symptoms may or may not be Systemic symptoms sweats, weight loss >10% in 6m present Often extra nodal, Spread Predictable, contiguous spread hepatosplenomegaly Common Sites of Abdomen, mediastinum, CNS, Cervical, mediastinal nodes Involvement bone marrow Varies; aggressive forms (e.g., Prognosis Excellent with treatment Burkitt lymphoma) but often curable Chemotherapy, radiation for Primarily chemotherapy, less Treatment localized disease use of radiation Lymphoma Neuroblastoma Originates in neural crest tissue: sympathetic ganglia and adrenal gland Most common solid tumor in infants Key features: Abdominal mass, Horner's syndrome, opsoclonus- myoclonus syndrome Diagnosis: Imaging: CT,MRI, MIBG scans Biopsy Elevated urine catecholamines; Homovanillic acid (HVA) and vanillylmandelic acid (VMA) Treatment: Surgery, chemotherapy, radiation, bone marrow transplantation Neuroblastoma Asymptomatic mass Systemic symptoms neck weight loss thorax irritability abdomen fever pelvis hypertension Horner’s Syndrome intractable diarrhea (VIP) Ptosis, miosis, anhidrosis opsoclonus/myoclonus Spinal Cord Compression Bone pain (medical emergency) limp back pain refusal to walk neurologic deficits Pallor “Racoon eyes” Skin lesions preorbital ecchymoses proptosis Hepatomegaly Neuroblastoma- opsoclonus/myoclonus https://www.youtube.com/wat https://www.youtube.com/shor ch?v=OatItXWkWUE ts/Kh7fpBRn4gU Dancing Eyes Atxia Wilms' Tumor (Nephroblastoma) Most common kidney tumor in children Peak age: 3-4 years Presentation: painless abdominal mass, hematuria, anemia?, hypertension Associated with genetic syndromes: WAGR Beckwith-Wiedemann Diagnosis: AUS, CT, MRI Treatment: Surgery (nephrectomy), chemotherapy, radiation Oncological Emergencies Oncological Emergencies Tumor lysis syndrome Superior vena cava syndrome Acute Spinal Cord Compression Febrile neutropenia: requires immediate antibiotics to prevent sepsis Tumor Lysis Syndrome (TLS) Rapid destruction of tumor cells leading to electrolyte imbalances→ depositions → renal failure Risk factors: High tumor burden Rapidly dividing cells (e.g., leukemia, lymphoma) First few days after starting chemotherapy Laboratory findings: Hyperkalemia, hyperphosphatemia, hyperuricemia, hypocalcemia Prevention and treatment: Aggressive hydration Allopurinol? Rasburicase? Acute Spinal Cord Compression Causes: mass originate from solid tumors such as neuroblastoma, lymphoma compressing spinal cord Presentation: Back pain, weakness, sensory deficits, loss of bowel/bladder control Diagnosis: MRI Treatment: High-dose steroids (why?), surgery, radiation Multidisciplinary approach Mediastinal Mass / SVC Syndrome Common in T-cell lymphoma, Hodgkin lymphoma, germ cell tumors Presentation: Cough, dyspnea, superior vena cava syndrome (facial/upper extremity swelling) Imaging: Chest X-ray, CT scan to assess the extent of mass Oncologic emergency: Risk of airway compression Management: Steroids (to reduce tumor size) Avoid anesthesia/sedation if possible due to airway compromise risk Chemotherapy or radiation therapy for urgent reduction of mass size Chemotherapy Toxicities Myelosuppression: Neutropenia, anemia, thrombocytopenia → Increased risk of infection, bleeding Gastrointestinal: Mucositis, nausea, vomiting, diarrhea Cardiotoxicity: Anthracyclines (e.g., doxorubicin) Nephrotoxicity: Cisplatin, ifosfamide, cyclophosphamide → Acute kidney injury Hemorrhagic cystitis: cyclophosphamide Neurotoxicity: Vincristine → Peripheral neuropathy Hepatotoxicity: Methotrexate, mercaptopurine → Liver damage Ototoxicity: Cisplatin → Hearing loss Prevention: Monitoring and use of protective agents (e.g., dexrazoxane for cardioprotection) Chemo Man ☺ Venous Access for Chemotherapy PICC line Long-Term Complications Cancer survivors need long-term follow up and monitoring: Secondary malignancies due to radiation/chemotherapy Growth and endocrine disorders Neurocognitive effects (especially in brain tumor survivors) Fertility preservation before treatment in pubescent patients Psychosocial Aspects Impact on family dynamics and mental health School reintegration for survivors Importance of supportive care: Psychosocial support, pain management, palliative care Special Considerations for Cancer Patients Nutritional support Immunocompromised status: Risk of infection hence treat fevers aggressively Avoid checking temperature rectally (why?) Avoid live vaccinations (which?) while receiving active chemotherapy Questions Question 1 Which of following trisomy has a higher incidence of developing hematological malignancies: A. Trisomy 13 B. Trisomy 18 C. Trisomy 21 D. Trisomy 17 Question 2 A newly diagnosed patient with acute myeloblastic leukemia (AML) on day 3 of induction chemotherapy. The initial WBC was 150,000 with 90% blasts. A chemistry panel is drawn. Which of the following lab results are consistent with tumor lysis syndrome? A. Hypophosphatemia B. Hypoglycemia C. Hyperkalemia D. Hypercalcemia Questions Comments