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Neoadjuvant Chemotherapy in Limb Soft Tissue Sarcoma: The significance of ErbB-4 Expression .

Neoadjuvant Chemotherapy in Limb Soft Tissue Sarcoma: The significance of ErbB-4 Expression. O. Merimsky, J. Issakov, V. Soyfer, I. Schwartz, Y. Kollender, J. Bickels, I. Meller, M. Inbar The Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel. ErbB-4.

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Neoadjuvant Chemotherapy in Limb Soft Tissue Sarcoma: The significance of ErbB-4 Expression .

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  1. Neoadjuvant Chemotherapy in Limb Soft Tissue Sarcoma: The significance of ErbB-4 Expression. O. Merimsky, J. Issakov, V. Soyfer, I. Schwartz, Y. Kollender, J. Bickels, I. Meller, M. Inbar The Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.

  2. ErbB-4 • A recently described member of the epidermal growth factor receptor (EGFR) family. • A possible role of erbB-4 expression product as a tissue marker for STS, and its correlation with the response to ChT were assessed.

  3. Patients • Biopsy proven G2-G3 STS of an extremity • AJCC stage IIB, IIIA or IIIB • Age < 60 years • Good PS and organ reserve

  4. Treatment Protocol • Pre-Op: 3 ADR-based courses (w/o IFX, CDDP) • Limb Sparing Surgery - LSS • Post-Op: 3 ADR-based courses (w/o IFX, CDDP) • RT: 1.8 Gy/#, x 5/W, MPD 63 Gy (70 Gy in case of marginal excision. • Follow-up: history, physical examination, CBC, LDH and radiological chest studies q3mo.

  5. Pathology • The extent of tumor necrosis was evaluated histologically • >90% necrosis = good response • 60-90% necrosis = partial response • <60% necrosis = no response • Immunohistochemical stains for were performed on paraffin sections using the avidin-biotin-peroxidase method.

  6. Pathology • Immunopositivity was subjectively graded according to staining intensity and recorded as negative (-), weak (+), moderate (++), or strong (+++). • For statistical analysis all patients were divided in 2 groups: a) “negative”: negative or weak staining, Vs. b) “positive”: moderate or strong positive staining.

  7. Response to Preoperative ChT • Clinical Response Rate: CR 7%; PR 28%; MR 24%; SD 24%; PD 17% • Resection Rate: wide 42%; marginal 48%; amputation: 7%; no surgery: 3% • Tumor Necrosis: > 90% in 31%; 60-90% in 41%; < 60% in 24%

  8. ErbB-4 expression • The change in expression of ErbB-4 was assessed in view of the clinical response • An increase in ErbB-4 expression was more common in cases with no response to chemotherapy • No change or decrease in ErbB-4 was more common in responsive tumors (p=0.004).

  9. ErbB-4 expression • No correlation could be found between the change in level of expression of erbB-4 and: • the degree of necrosis • the type of the chemotherapeutic regimen • the type of STS • the disease-free survival

  10. Conclusions • The change in intensity of erbB-4 staining was related to outcome of induction chemotherapy. • It is assumed that post chemotherapy new expression of the erbB-4 represents tumor aggressiveness. • The same may be true when chemotherapy fails to down-regulate the expression of the erbB-4.

  11. Conclusions • A Molecular Response could be defined as reduction or no change in expression of erbB4 following induction chemotherapy • Molecular Response as an end-point?

  12. Conclusions • The Molecular Response rate was 33% (9/27), molecular no-change 37% (10/27), and molecular progression 30%. • Clinical PD was associated with molecular failure or no change, while molecular response was more common in clinical PR or MR. • It remained unclear why in some cases clinical PR was associated with 95% necrosis (as expected) but with molecular progression.

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