1 / 14

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.

Download Presentation

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

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  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.

More Related