Ewings Tumor

Epidemiology

  • 2nd most common bone primary bone tumor of children (osteosarcoma #1)
  • 3% of all pediatric tumors. (200 cases/yr)
  • Peak incidence in 12-16 years old
  • More boys than girls (1.5-2:1)
  • Rare in African Americans and Asians

Pathology

  • Small round blue cells with hyperchromatic nuclei, slight cytoplasm and noncleft nuclear margins from primitive neuroectodermal tissue.
  • Other SRC tumors include PNET, rhabdomyosarcoma, lymphoma, osteosarcoma
  • PAS and vimentin positive and enolase negative.
  • Genetic: t (11; 22) found in 90% of the tumors and remainder have t(21; 22) and also c-myc.

Presentation

  • Radiosensitive bone tumor that typically occurs in the metaphyseal/diaphyseal region of the long or flat bones.
  • 75-80% present with localized dz. 40% are extremity lesions.Pain, swelling or mass, decreased mobility, fever.
  • 53% of Ewing’s sarcoma has primary site in an extremity and 47% have central primaries.
  • Distant metastasis
  • 21-23% at presentation
  • 25-30% for pelvic lesions and 10% for extremity lesions
  • Common site of metastasis include: lung 40% or bones 40%.

Figure 33.3 Primary tumor sites in Ewing sarcoma family of tumors. Data based on 1,426 patients from European Intergroup Cooperative Ewing Sarcoma Studies (EI-CESS) trials. (Pizzo)

Diagnosis

  • H/P
  • Labs: CBC, CHEM 20 with LDH (related to tumor volume), ESR
  • Radiological studies: CT or MRI for local tumor extent, Chest CT, bone scan, BM biopsy, plain x-ray of the bone which often shows a destructive lytic lesion in the metaphyseal or diaphysis that grows outward with periosteal elevations characteristic of an onion ring appearance.
  • Pathology: biopsy with immunohistochemistry and cytogenetics

Staging and Prognosis

No Official Staging System

  • High Risk: 100 cc (~8cm tumor) +DM, as documented by St. Jude’s and UF.
  • Standard risk: <100cc, no DM

Prognosis

Risk 5-yr LC 5-yr OS
Low Risk 85-90% 50%
High Risk 65% (DFS)
present with DM 20%

Findings and Prognostic factors

Patient-related

  • Gender (females is worse)
  • Age: younger is better
  • Symptom duration

Tumor-related

  • Metastatic disease
  • Location (pelvis/ central = worse)
  • Primary tumor size (> 8 cm or 500 cm3), worse

Radiographic findings

  • "Honeycombing" seen on plain films
  • Lab findings
  • Elevated LDH correlates to tumor burden and thus is a poor prognostic factor.
  • elevated ESR, moderate anemia, or leukocytosis are non-specific findings

Treatment-related

  • Chemotherapy – 6 drug regimen better than 4 drugs
  • Response to chemotherapy
  • Complete surgical resection

Treatment

Summary

  • Local Therapy: surgery, radiation OR surgery and radiation with LC rates from 53%-93%
  • Surgery alone needs wide
  • There are no randomized trials that have directly compared RT to surgery for LC of Ewing’s
  • Systemic therapy has improved cure rates from 20% to

Surgery:

  • Surgery is the standard for easily resectable small lesions in dispensable bones such as fibula, ribs, clavicle and hands or very young children in whom late effects are a consideration.

MSK (Rosen)

  • compared RT + chemotherapy (LC was 81%) to surgery + chemotherapy (LC 100%).

CEES-81 (German Cooperative Group Study)

  • showed benefit for surgery but there was inadequate RT
  • 5-year RFS was 54% for surgery and 43% for radiation alone.

**CEES-86 **

  • compared RT alone (60Gy) versus surgery +RT versus surgery + chemotherapy.
  • No difference in either group with comparable survivals in each group at about 62-67%.

Chemotherapy:

  • VAC with alternating IE is the standard chemotherapy regiment

IESS-1

  • randomized patients to 3 forms of adjuvant chemotherapy
  • 1) VACA, 2) VAC, 3) VAC + bilateral lung RT.
  • The survival was better for VACA > VAC + WL > VAC.

IESS-2

  • compared high-dose intermittent VACA and moderate-dose continuous VACA
  • high-dose intermittent regimen better.

IESS-3

  • randomized pts with localized or metastatic dz to VDC vs VDCA alternating with VP-16/ifosfamide.
  • local tx given at wk 9-15 with RT, surgery, or both.
  • Adding VP-16/ifosfamide improved 5 yr OS (61  72%) for localized disease, NOT for metastatic dz(25%).

CCG 7881/POG 8850

  • evaluated VACA +/- IFO and VP16
  • showed improved survival with 6 drugs alternating rather than 4 in local disease (80% versus 56%).

Radiation Therapy:

Dose

  • 5580 cGy
    • gross/residual tumor
    • pre-treatment boney portion of the tumor regardless of response
  • 5040 cGy (SJCRH)
    • 1 cm post chemotherapy volume with CR
    • microscopic tumor
  • 4500 cGy (COG)
    • 1.5 cm pre-treatment soft-tissue volume
  • 3600 cGy
    • Chest wall primary with pleural based secondary tumor
    • pre-treatment tumor
  • 1500 cGy in 10 fractions
    • to Hemithorax in chest wall primary with either positive pleural fluid or secondary tumor in pleura.

Timing

  • RT is given __after induction chemotherapy __VACA.

POG 8346

  • compared whole bone versus tailored fields and no difference in survival.

Metastatic Disease

  • IE was not significantly better for metastatic patients
  • Some early enthusiasm for TBI with BMT had good 3-yr EFS of 43% but 5-yr EFS was disappointing 27%.

Complications

  • Complications: second malignancies incidence is 6% after 15 years.
  • Secondary malignancy: 2% for dose <60Gy, 10% for dose > 60Gy.
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