PEDIATRIC SOLID TUMORS

1. PEDIATRIC SOLID TUMORS Radiation Oncology II 4412

3. Despite its rarity, cancer is the chief cause of death by disease in children between the ages of 1 and 14. • The leading cause of death in children is accidents. • About 1/3 of cancer deaths are from leukemia. • Mortality rates have declined 50% since 1973.

4. Early detection: • Cancers in children are hard to recognize. • Children should have regular check-ups

5. Parents should be alert to the following: • unusual mass or swelling • unexplained paleness and loss of energy • sudden tendency to bruise • a persistent, localized pain or limping • prolonged, unexplained fever or illness • frequent headaches, often with vomiting • sudden eye or vision changes • excessive, rapid weight loss

6. Childhood cancers include: • Leukemia which accounts for about 30% of cases in children ages 0-14. • Osteosarcoma (2.7%) a bone cancer which may cause no pain at first; swelling in the area of the tumor is often the first sign. • Ewing’s sarcoma (1.8%) bone cancer

7. Neuroblastoma (7.3%) a cancer of the sympathetic nervous system which can appear anywhere but usually occurs in the abdomen as a swelling. • Rhabdomyosarcoma (3.4%) the most common soft tissue sarcoma, can occur in the head and neck area, genitourinary area, trunk, and extremities.

8. Brain and intraspinal cancers (21%) which in early stages may cause headaches, nausea, vomiting; blurred or double vision, dizziness, and difficulty in walking or handling objects.

9. Non-Hodgkin’s lymphomas (4.0%) and Hodgkin’s disease (4.4%), cancers that involve the lymph nodes, but also may invade bone marrow and other organs. They may cause swelling of lymph nodes in the neck, armpit, or groin. Other symptoms may include general weakness and fever.

10. Retinoblastoma (2.8%) an eye cancer, usually occurs in children under the age of 4. When detected early, cure is possible with appropriate treatment. • Wilm’s tumor (5.9%), a kidney cancer, may be recognized by a swelling or lump in the abdomen.

11. Childhood cancers tend to respond better to chemotherapy • Children tolerate chemotherapy better than adults • Children will have to be followed the rest of their lives due to the long term side effects of chemotherapy

12. Since the 1960’s most children and adolescents have been treated at specialized centers • Pediatric oncologists, pathologists, surgeons, radiation oncologists, pediatric oncology nurses and nurse practitioners • Psychologists, social workers, child life specialists, nutritionists, rehabilitation, physical therapists, educators

13. Most children in the US will be treated at a center that is a member of the Children’s Oncology Group (COG) • All are associated with a university or children’s hospital

14. Leukemia • A malignant disease of bone marrow. • Acute lymphocytic leukemia is a disorder of stem cells and results from an overgrowth of immature lymphoid and myeloid cells called blasts which replace bone marrow cells

15. Leukemia cont’d • Chemotherapy is the treatment of choice. • TBI may be used when performing a bone marrow transplant. • Radiation therapy is used for CNS prophylaxis, CNS relapse, or testicular relapse. • CNS and testicles are “sanctuary sites” at risk for harboring disease.

16. Leukemia cont’d • Radiation therapy- • Cranial irradiation combined with intrathecal methotrexate is standard treatment to prevent relapse in high risk patients. • Target volume • entire subarachnoid space and optic nerves • Proper attention to anatomical landmarks is imperative

17. Superior margin- junction of inferior border of the cranial port • Inferior- below S2 • Lateral- the width should cover the entire vertebral bodies in the cervical, thoracic and lumbar areas

19. CNS disease or CNS relapse require craniospinal portals. • Patient is treated in the prone position to match the junction of the portals. • Forehead is placed on head rest to align cervical and thoracic spine. • Maximum chin extension so radiation doesn’t exit through the mandible.

20. Collimator for lateral head fields should be angled to match the divergence of the spinal field. • Treatment couch is angled to eliminate overlap from the divergence of the lateral head ports. • The junction between the cranial and spinal ports should be shifted at least once during treatment to prevent under or over dosage at the junction site.

21. The entire width of the vertebral bodies is covered to treat width of spinal cord & CSF • Testicular fields may be treated with photons or electrons with a single anterior field including both testicles and the scrotal skin. • Doses: • CNS prophylaxis 1800 cGy • Craniospinal 2400 cGy head • 1200 cGy spine • Testiculomegaly 2400 cGy 300 cGy testes

22. NEUROBLASTOMAS • Neuroblastoma is a form of cancer that starts in certain types of very primitive nerve cells found in an embryo or fetus. • They begin in early nerve cells of the sympathetic nervous system (sympathetic neuroblasts) • They can be found anywhere along this system

23. Most common cancer in infants • Accounts for about 7% of all cancers in children • Neuroblastoma is the second most common solid tumor (after brain tumors). • Average age at the time of diagnosis is about 1-2 years

24. In rare cases, can be detected by sonography before birth • Rare over the age of 10 years • 2 out of 3 cases, the disease has already metastasized at diagnosis

25. Neuroblastoma cont’d • Majority of neuroblastomas occur in the abdomen, with the origin in the adrenal gland or paraspinal ganglia. • A lethargic, ill-appearing child less than 2 years of age with an abdominal mass is common.

26. Causes • Not completely known • A failure of neuroblasts to mature and to stop growing due to abnormal DNA in the neuroblasts • Inherited DNA mutations

27. Neuroblastoma cont’d • Most common- unusual lump or mass found in the abdomen causing swelling • Pressure on the superior vena cava • Drooping eyelids, small pupils • Pressure on nerves near spine • Weakness and anemia from bone marrow invasion • painful bony metastases

28. blue skin lesions • massive liver involvement, may occur even with a small primary tumor • Frequent infections, excessive bleeding • Neuroblastoma is one of the few cancers in children that release hormones that can cause paraneoplastic syndromes • Fever, constant diarrhea, high blood pressure, rapid heartbeat, reddening of the skin, sweating

29. Work up • Blood, urine tests • CBC, liver and kidney function • Diagnostic x-ray • CT, MRI • Ultrasound • PET • Bone Scan • Biopsy

30. MIBG scan- uses a form of the chemical meta-iodobenzylguanidine(MIBG) that contains a small amount of radioactive iodine. • Injected and attaches to neuroblastoma cells anywhere in the body • Body is scanned • Preferred as a standard exam to evaluate children with neuroblastoma

31. Staging • International Neuroblastoma Staging System • Stage 1, 2A, 2B, 3, 4, 4S and recurrent disease

32. Treatment • Surgery • Chemotherapy • Retinoid therapy- related to Vitamin A • Retinoid called 13-cis-retinoic acid • Radiation therapy • High dose chemotherapy/radiation therapy and stem cell transplant • Immunotherapy

33. Radiation Therapy- • Acute treatment of infants- 500 cGy • Older children- 2100 cGy • Chemotherapy has taken the place of radiation therapy • Radiation therapy can be used for residual disease after surgery and chemotherapy • Used for palliation

34. RHABDOMYOSARCOMA • Most common soft tissue sarcoma of childhood • peak age 2-5 years old • second peak 15-19 years old • Have been associated with: • various syndromes (neurofibromatosis, Li-Fraumeni syndrome) • environmental factors • Anomalies • 2/3 of patients will be long term survivors

35. Rhabdomyosarcomas • Malignant neoplasms from embryonic mesenchymal cells • May occur anywhere in the body • 60% are embryonal subtype • usually found in the younger age group • usually found in head and neck • genitourinary areas • Orbit is the most common site in the head/neck

36. Rhabdomyosarcomas cont’d • In older children the alveolar subtype is found in the extremities and perineal sites. • Alveolar subtype metastasizes through lymphatics • Has a poor prognosis

37. Spread • local extension • blood stream • lymphatics • Common sites are lung, bone, bone marrow, lymph nodes

38. Treatment • Surgery • Tumor excision is preferred • Chemotherapy • All patients receive multiagent chemotherapy after surgical staging

39. Radiation Therapy • Conventional radiation therapy can be given • depending on site and extension of disease • Treat the extent of the primary tumor and an adequate margin (2cm) to cover tumor and suspected areas of involvement • Lymph node chain draining the area is included if involved at time of diagnosis

40. Dose- depends on site and extent of disease • 40 Gy- microscopic residual tumor • 50 Gy (or above) if there is still visible residual disease

41. BRAIN STEM GLIOMA • Occur in all ages- most often found in children • Low grade astrocytomas to high grade glioblastoma multiform • 38% will be high grade • Symptoms are gait disturbance (most common),headache, hemiparesis, strabismus, cranial nerve dysfunction

42. Brain Stem Glioma cont’d • 50% will arise in the pons • These tumors involve cranial nerves VI and VII. • Spread is by local infiltration- midbrain, pons, medulla, brachium ports or cerebellum.

43. Treatment • Usually treated with radiation therapy • Due to location and infiltration, usually are not surgically resected. • Dose- 50-55 Gy, 1.8 Gy per fraction • 5 year survival 15-20% • Research- hyperfractionation trials using • 70.2-78Gy, 1Gy 2x day

44. MEDULLOBLASTOMA • Is a posterior fossa malignancy • tumor usually arises in the midline of the cerebellum • can invade the 4th ventricle and brain stem • can spread throughout the cerebrospinal fluid • Makes up 20-25% of all childhood brain tumors • Affects 2-12 year olds, peaks at age 5 • Rarely occurs in adults

45. Medulloblastoma cont’d • Symptoms will occur over a period of weeks to a few months. • Hydrocephalus will occur due to invasion and compression of the 4th ventricle. • Headaches, early-morning vomiting. • Ataxia and cranial nerve abnormalities from invasion of the brain stem.

46. It is one CNS tumor that can develop distant mets- usually will travel through CSF to the bone. • Infiltrate locally and disseminate throughout the neuroaxis • About 45% have spread beyond the posterior fossa at diagnosis

47. Treatment • Surgery is used for maximum tumor removal. (diagnosis, tumor debulking and decompression) • Post-op craniospinal irradiation is recommended for all patients due to spread through CSF • Children <5 yrs old chemotherapy is used to delay radiation therapy

48. Medulloblastoma cont’d • Adjuvant chemotherapy is used for serious disease (recurrent, brain stem invasion, disseminated disease, advanced primary tumors) • Post-op craniospinal irradiation • complete coverage of subarachnoid space • two lateral head ports • one post. Spine port (just like ALL)

49. RETINOBLASTOMA • Neuroectodermal tumor of the retina • Most common intraocular tumor in children • Occur in children 6 months to 4 years • Well documented hereditary autosomal-dominant pattern (25-35%) • Cases without hereditary factors- 65%

50. Retinoblastoma cont’d • Diagnosis • Usually discovered as a result of an abnormal retinal light reflex (camera flash) • shows white instead of red • Ophthalmologist exam • CT or ultrasound of the orbit