PEDIATRIC SOLID TUMORS

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PEDIATRIC SOLID TUMORS

• Radiation Oncology II
• 4412

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• 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.

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

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• 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

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• 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.
• Ewings sarcoma (1.8) bone cancer

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• 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.

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• 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.

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• Non-Hodgkins lymphomas (4.0) and Hodgkins
  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.

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

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• 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

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• Since the 1960s 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

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

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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

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Leukemia contd

• 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.

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Leukemia contd

• 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

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• 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

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• 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 doesnt exit
  through the mandible.

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• 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.

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• 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

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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

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• 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

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• 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

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Neuroblastoma contd

• 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.

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Causes

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

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Neuroblastoma contd

• 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

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• 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

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Work up

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

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• 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

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Staging

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

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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

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• 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

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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

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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

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Rhabdomyosarcomas contd

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

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

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Treatment

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

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• 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

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

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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

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Brain Stem Glioma contd

• 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.

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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

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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

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Medulloblastoma contd

• 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.

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• 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

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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 lt5 yrs old chemotherapy is used to delay
  radiation therapy

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Medulloblastoma contd

• 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)

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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

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Retinoblastoma contd

• 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

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Treatment

• Treatment
• radiation therapy for bilateral or inoperable
  unilateral disease
• external beam to the entire retina and spare the
  cornea and lens
• Good response with chemotherapy
• although it is not a curable disease

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EPENDYMOMA

• Occurs in all age groups, but are most common in
  children
• Arise from the ependymal lining of the
  ventricular system and spinal canal
• They spread locally filling the 4th ventricle or
  invading the cerebellum
• Can spread through the CSF

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Ependymoma

• These tumors are sensitive to chemotherapy, but
  with no benefit
• Surgery is the treatment of choice
• Radiation therapy is used for post-op

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WILMS TUMOR or Nephroblastoma

• Named after Max Wilms, German doctor, wrote an
  article in 1899
• Malignant embryonal tumor of the kidney
• Most common malignant lesion of the genitourinary
  tract in children. 9/10 children will have kidney
  tumors
• In 5 of cases the cancer is bilateral, most are
  unilateral

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Wilms tumor contd

• Associated with congenital conditions, although
  no definite cause
• WAGR syndrome- deletion of part of chromosome 11
• W Wilms tumor
• A Aniridia, complete or partial lack of the iris
  of the eyes
• G Genitourinary tract abnormalities
• R Mental retardation

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• Familial- 1-3 of children with Wilms will have
  one or more relatives with the same cancer
• Experts think the cancer comes from cells that
  were in the fetus but failed to develop into
  mature kidney cells

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• Affects children less than 6 years of age.
• Average age- 3 years
• Uncommon over age of 6
• More common in African Americans and girls
• Most tumors become very large before being
  noticed
• The average weight being 1 pound

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Types of Wilms Tumor

• Favorable Histology
• 9 out of 10 Wilms tumors have a favorable
  histology
• There is some differentiation
• Unfavorable Histology
• Anaplastic- loss of functional and structural
  differentiation
• Harder to cure

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Signs and Symptoms

• Hard to find- tumors can grow large without
  symptoms
• Swelling or hard mass in the abdomen, found by
  parents bathing or dressing child
• Not painful
• Fever, nausea, loss of appetite, constipation,
  blood in urine

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Work-up

• Sonography- first exam done
• CT- look at mass and spread
• MRI- inferior vena cava in the abdomen
• Chest xray
• Bone scan
• Lab tests- urinalysis
• Kidney biopsy

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Staging

• National Wilms tumor Study Group (NWTSG)
• Stage I- 40-45 of all Wilms tumors
• Tumor contained in one kidney, completely removed
  by surgery
• Stage II- 20-25
• Tumor grew beyond kidney, completely removed

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• Stage III- 20-25-
• Not completely removed, remaining cancer is
  limited to the abdomen, has spread to local lymph
  nodes, invasion of nearby structures, Cancer
  spill during surgery
• Stage IV- 10
• Cancer has spread through blood to organs
• Stage V- 5
• Tumors in both kidneys

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Survival

• Varies by Staging
• Tumor Stage I, favorable histology, 99
• Tumor Stage I, unfavorable histology, 83
• Tumor Stage V, favorable histology, 87
• Tumor Stage V, unfavorable histology, 55
• Overall, 9 out of 10 children will be cured

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• Spread
• by local invasion
• lymphatic
• or hematogenous routes
• will metastasize to lungs and liver

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Treatment

• Surgery is the initial definitive treatment
  followed by chemotherapy or radiation therapy
• Radical nephrectomy- removes cancer and whole
  kidney, fatty tissue around kidney, ureter,
  adrenal gland
• Partial nephrectomy- usually done when cancer is
  in both kidneys
• If both kidneys are removed, child will have
  dialysis, followed by kidney transplant

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• Chemotherapy- usually given after surgery
• Different drugs depending on stage and type of
  cancer
• Once a week for several months
• Long term side effects- heart damage, risk of
  developing another cancer (leukemia)

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• Radiation therapy is usually given for more
  advanced Wilms tumors (III,IV,V), unfavorable
  histology
• Whole abdomen radiation therapy may be used if
  there is peritoneal metastasis
• Or if diffuse spillage at surgery or pre-op
  intra-peritoneal rupture is present.
• 3D-Conformal Radiation Therapy, IMRT

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• With
• Tanner Onder at Colorado concert, 2008
• Make a Wish Foundation