Pamela Simon R.N., C.P.N.P, MSN Lucile Packard Children’s Hospital Pediatric Tumors Pamela Simon R.N., C.P.N.P, MSN Lucile Packard Children’s Hospital

Distribution of Childhood Cancer CNS 18% Liver 1% Other 8% Leukemia 33% Retina 3% Germ Cell Bone 5% Wilm's Tumor 6% Hodgkin's NHL NBL Soft Tissue Sarcoma 7% Bone tumors represent 5% of childhood cancers. Sixty percent of these are osteosarcoma resulting in an incidence of 4.8 cases per million patients < 20 years of age in the United States or 400 cases per year. The incidence in black is slightly higher than in whites.

Abdominal masses History Symptoms abdominal discomfort, increased abdominal size or assymptomatic Presence of systemic symptoms bone pain, limping, malaise, fever Other symptoms hematuria

Abdominal masses Physical findings Presence of abdominal mass upper abdomen or lower abdomen Other associated physical findings other masses: orbital bruises hypertension pain

Abdominal Mass Differential diagnosis depends on location Upper abdominal mass Neuroblastoma Wilm’s tumor Hepatoblastoma Rhabdomyosarcoma Germ cell tumor Lymphoma

Abdominal Mass Differential diagnosis (cont) Lower abdominal/pelvic mass Neuroblastoma Rhabdomyosarcoma Germ cell tumor Lymphoma Ewing’s sarcoma

Abdominal Masses Laboratory evaluation Bone marrow aspirate CSF tap neuroblastoma, lymphoma, rhabdomyosarcoma or Ewing’s sarcoma CSF tap if lymphoma is a consideration

Abdominal masses Radiologic work-up Abdominal/pelvic ultrasound useful screening test: helps define location and quality (solid or cystic) not useful to assess for retroperitoneal adenopathy Computed tomography location of mass presence of calcification obstructive signs

Wilm’s Tumor Accounts for 6% childhood malignancies Median age at diagnosis 3 years Metastasizes to lung and lymph nodes 70% patients present with localized disease

Wilm’s Tumor: Signs & Symptoms Most commonly presents as painless abdominal mass Hypertension (20-30%) Pain (20-30%) Hematuria (25%)

Wilm’s Tumor: Staging System Stage Definition I Tumor limited to kidney, completely excised II Tumor extends beyond the kidney, completely resected; no residual tumor beyond resection margins III Residual non-hematogenous tumor confined to abdomen IV Hematogenous metastases V Bilateral renal involvement

Bilateral Wilm’s

Survival by Stage and Histology

Wilms Tumor: Prognosis & Future Directions Prognostic factors: stage and histology Future directions Minimize therapy for favorable histology patients Identify biologic factors predictive of outcome Intensify therapy for patients with unfavorable histology

Osteosarcoma: Distribution by Age and Site Osteosarcoma is extremely rare before the age of 5 and the modal age is 16 years for girls and 18 for boys. Males are affected more frequently than females in most series.

Clinical presentation Pain and swelling usually lasting 3-4 months Duration: sometimes > 6 months Occurs around metaphysis of long bones Most common primary sites: distal femur, proximal tibia and proximal humerus 50-70% around the knee joint Metastases: ~15-20% patients Sites: lung and other bones The clinical presentation for patients with osteosarcoma is fairly non-specific. That is patients typically present with pain and swelling of variable duration, but usually lasting 3-4 months and sometimes > 6 months. The tumor occurs around the metaphysis of long bones and the most common primary sites are the distal femur, proximal tibia and proximal humerus. About 50-70% of the tumors occur around the knee joint. About 15-20% of patients present with clinically detectable metastases most commonly to the lungs.

Most Common Metastatic Sites This slide illustrates the most common metastatic sites for patients with osteosarcoma. On the left panel you see the metastatic sites detected by autopsy, while the right panel shows the metastatic sites detected clinically. As you can see both panels demonstrate the preponderance of lung metastases for these patients followed by bone metastases (clinically), and infrequently at other sites.

Diagnostic workup Imaging Work-up: Plain X ray, MRI of primary Metastatic workup Chest CT Bone scan PET scan Biopsy Work-up includes a plain film, and MR of the primary site and a metastatic work up including a chest CT, bone scan and most recently PET scans appear to be useful for determining response to chemotherapy pre-operatively. The diagnosis is usually established via a biopsy. We usually prefer open biopsies so that we can obtain adequate tissue for ancillary studies.

Imaging Evaluation This is an example of the imaging evaluation for osteosarcoma. On the left panel you see a plain film illustrating the sunburst sign (pretty characteristic for osteosarcoma) with periosteal reaction. On the right panel, the presence of a large soft tissue mass is evident as well as marrow signal abnormality.

Metastatic Work-Up: Chest X-Ray This illustrates the presence of a large lung metastatic lesion on chest radiograph. We have gradually shifted towards using computed tomography of the chest to detect the presence of metastases.

Metastatic Work-Up: Chest CT Computed tomography of the same patient illustrated previously. The CT demonstrates a larger number of lesions that those seen by chest radiograph.

Metastatic Work-Up: Bone Scan Bone scintigraphy illustrating increased uptake in the whole femur for a patient with osteosarcoma. It is important when evaluating these patients to perform whole bone magnetic resonance imaging to detect skip lesions if present since all sites of disease have to be surgically removed to achieve long term survival.

Pathology Intramedullary high-grade sarcoma Malignant mesenchymal cells producing osteoid The World Health Organization (WHO) recognizes three major subtypes: based on matrix: Osteoblastic Chondroblastic fibroblastic Pathologically, osteosarcoma is a high-grade intramedullary high grade sarcoma characterized by malignant mesenchymal cells producing osteoid. The WHO recognizes three major sub-types of osteosarcoma based on the matrix. These include osteoblastic, chondroblastic and fibroblastic osteosarcoma.

Osteosarcoma: Pathology This panel illustrates the three major sub-types of osteosarcoma as defined by the WHO.

Osteosarcoma: Therapy Historically, 2-year survival < 20% for patients treated with surgery and/or radiotherapy Uncontrolled trials of adjuvant chemotherapy resulted in EFS of 45-60% suggesting chemotherapy improved outcome What about treatment? Historically, the outcome for patients with osteosarcoma was poor before the introduction of chemotherapy with 2-year survivals of about 20% with the use of surgery and/or radiotherapy. At that time, uncontrolled trials of adjuvant chemotherapy suggested improved outcome.

Multi-Institutional Osteosarcoma Study: Design R A N D O M I Z E Adjuvant Chemotherapy B I O P S Y S U R G E R Y The multi-institutional osteosarcoma study (ran by Dr. Michael Link) was designed to determine whether chemotherapy improved the outcome for patients with extremity non-metastatic osteosarcoma. No Adjuvant Chemotherapy

Osteosarcoma: Treatment Current therapy: multi-agent chemotherapy usually including cisplatin, doxorubicin and methotrexate. Complete surgical resection for local control. Based on the results of the MIOS the standard of care has become the use of multi-agent chemotherapy along with complete surgical resection for local control. The survival curve on this slide illustrates the impact of inadequate surgery on outcome. Therefore, it is essential to perform complete resection to achieve cure.

Osteosarcoma Treatment Types of surgical techniques Amputation Rotationplasty “growing’ prosthesis Total knee titanium replacement

Amputation

Rotationplasty

Rotationplasty

Total knee titanium replacement (endoprosthesis)

Prognostic Factors: Metastases The most important prognostic factor for patients with newly diagnosed osteosarcoma remains the presence of clinically detectable metastases. As illustrated here, the outcome for patients with metastatic disease remains poor.

SURVIVAL OF PATIENTS WITH LOCALIZED OSTEOSARCOMA 100 1980’s- combination chemo 2004 - chemo regimens multiple intensified 1960’s – single agent chemo 80 % survival 60 40 This slide illustrates the progress we have made over the last 30 years in the treatment of osteosarcoma and as you can see it appears that we have reached a plauteau in survival. 20 pre-chemo 1 2 3 4 5 years

Osteosarcoma: Outcome Modern Trials This slide illustrates the survival for osteosarcoma patients in 4 different cooperative groups (European Osteosarcoma Intergroup, Children’s Oncology Group, COSS and Scandinavia Sarcoma Group). Based on these results investigators agree that we have to find creative ways to try to continue improving outcome.

Osteosarcoma: Outcome Reached a plateau in outcome for osteosarcoma patients Further improvement will require large cooperative studies: International collaboration EURAMOS: North American Children’s Oncology Group (COG) German Austrian Swiss Cooperative Osteosarcoma Study Group (COSS) European Osteosarcoma Intergroup (EOI) Scandinavian Sarcoma Group (SSG) We all agree that further improvements will require large number of patients and likely international collaboration. Therefore, the COG, COSS, EOT, SSG have agreed to embark on a cooperative trial involving a relatively simple question.

Osteosarcoma: Conclusions We have made significant progress in the treatment of osteosarcoma Therapy has reached a plateau and further improvements will require large number of patients International collaboration: significant barriers but offers the best chance of increasing the number of patients available Biologic studies: essential for continued progress

CNS TUMORS

CNS TUMORS Most common solid tumors in children 2nd most frequent (16.6% of all childhood malignancies) Incidence has increased over the past 2 decades Males > females, white> African American

CNS TUMORS Signs & Symptoms (related to the location, histologic grade of tumor & age of child) General -Headache -Seizures -Mental status changes -Increased intracranial Pressure (ICP)

CNS TUMORS Signs & Symptoms-Posterior Fossa -Cerebellum- -nausea, vomiting, headache, papilledema, clumsy walk, double vision, dizzyness -Brainstem- -vomiting, cranial nerve palsies, headache, head tilt, personality changes, hearing loss

CNS TUMORS S&S-Cerebral Hemisphere Frontal lobe-one-sided paralysis, memory loss, mental changes, urinary changes Occipital lobe-visual changes, seizures Parietal lobe-Language disturbances, seizures, loss of reading, math Temporal lobe-seizures, unable to recognize sounds, visual impairments

CNS TUMORS S&S-Midline Tumors Headache, nausea/vomiting, papilledema, visual loss or abnormal eye movements, precocious puberty, diabetes insipidus (impairment of hypothalmic/pituitary fx)

CNS TUMORS S&S- Spinal Cord-depends on location Thoracic-chest pain Cervical or lumbar-neck, arm, back, leg weakness, muscle spasms & wasting, altered bowel, bladder function Progression of symptoms can result in paralysis

CNS TUMORS Age & developmental stage are important factors in re: to symptoms -infants-delay or loss of dev. Milestones -school age-personality changes, decline in school performance, change in handwriting

CNS TUMORS Diagnostic Evaluation MRI head-preferred CT head Add spine if required CT head Lumbar puncture Lab work for “tumor markers” for germ cell tumors-AFP & B-hCG Pet Scan

CNS TUMORS TREATMENT Surgery Most extensive resection feasible --Radiation Therapy --Chemotherapy

CNS TUMORS Prognosis Varies greatly depending on type of tumor, resectability,

CNS TUMORS Astrocytoma Occur at any age & various areas of brain Graded according to anaplasia Low grade cerebellar-pilocytic-85-95 % 5 year survival rate Low grade cerebral-90% 5 year survival rate -High grade astrocytoma-29% for anaplastic astrocytoma & 18% -glioblastoma multiforme

CNS TUMORS Medulloblastoma (PNET) 20-25%of all brain tumors Small, round blue cell tumor-fast growing 30% metastasis Surgery, radiation & chemotherapy 5 yr survival rates 80%