1. 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

2. 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.

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

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

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

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

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

8. 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

9. 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

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

11. 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

12. Bilateral Wilm’s

13. Survival by Stage and Histology

14. 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

15. 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.

16. 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.

17. 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.

18. 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.

19. 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.

20. 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.

21. 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.

22. 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.

23. 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.

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

25. 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.

26. 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

27. 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.

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

29. Amputation

30. Rotationplasty

31. Rotationplasty

32. Total knee titanium replacement
(endoprosthesis)

33. 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.

34. 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

35. 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.

36. 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.

37. 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

38. CNS TUMORS

39. 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

40. 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)

41. 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

42. 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

43. 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)

44. 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

45. 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

46. 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

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

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

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

50. 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%