1 / 23

R. D. Issels, L.Lindner, Munich, Germany P. Hohenberger, Berlin/Mannheim, Germany

13th Annual CTOS Meeting. EARLY PROGRESSION IN PATIENTS WITH HIGH-RISK SOFT TISSUE SARCOMAS AN ANALYSIS FROM A PHASE III RANDOMIZED PROSPECTIVE TRIAL (EORTC 62961/ESHO) OF NEOADJUVANT CHEMOTHERAPY WITH OR WITHOUT REGIONAL HYPERTHERMIA (RHT).

Download Presentation

R. D. Issels, L.Lindner, Munich, Germany P. Hohenberger, Berlin/Mannheim, Germany

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. 13th Annual CTOS Meeting EARLY PROGRESSION IN PATIENTS WITH HIGH-RISK SOFT TISSUE SARCOMASAN ANALYSIS FROMA PHASE III RANDOMIZED PROSPECTIVE TRIAL (EORTC 62961/ESHO) OF NEOADJUVANT CHEMOTHERAPY WITH OR WITHOUT REGIONAL HYPERTHERMIA (RHT) R. D. Issels, L.Lindner, Munich, GermanyP. Hohenberger, Berlin/Mannheim, Germany

  2. Treatment options for locally advanced sarcoma High grade: multimodal therapy • Chemotherapy (systemic) • TNF limb perfusion • Preop. Radio-(+C) therapy • Chemotherapy + RHTdeep-wave hyperthermia

  3. Application of EIA with RHT Etoposide 125 [mg/m²] Ifosfamide 1500 [mg/m²] Adriamycin 50 [mg/m²] Hyperthermia (RHT) 60 min [40°C-43°C] Day 1 2 3 4

  4. S S U U R R G G E E R R Y Y Study design S1 = primary tumor ≥5 cm, G2/G3 S2 = local recurrence of S1 tumor S3 = inadequate surgery of S1 or S2 tumor Risk groups R R RHT RHT A A Arm A Arm A D D EIA EIA I I R R A A T T I I EIA EIA Arm B Arm B O O N N Stratification: Center, Risk Group, Extremity, Non-Extremity

  5. Regional Hyperthermia (RHT) Technology Courtesy of BSD Medical Corporation model BSD 2000 3D ESHO quality assurance guidelines for regional hyperthermia Lagendijk et al. Int J Hyperthermia 1998

  6. b a

  7. b a

  8. Study objectives Primary Endpoint • Local Progression Free Survival (LPFS) Secondary Endpoints • Tumor response (WHO) • Disease Free Survival (DFS) • Overall Survival

  9. Patient characteristics (1)

  10. Patient characteristics (2)

  11. Patient characteristics (3)

  12. Preoperative chemotherapy

  13. Local treatment after chemotherapy

  14. WHO objective response evaluation (96% response review) * p<0.001 • 117 pts notevaluable for response (61 pts with EIA+ RHT / 56 pts with EIA)

  15. N=341 50.4% 49.6% 16.2 29.9 Median Treatment Arm n=172 n=169 88 110 Events EIA+RHT EIA 120 0 0 months 108 2 1 96 4 3 84 13 7 Disease Free Survival (All Progressions or Death) EORTC 62961/ESHO RHT 95-Study 72 13 17 rhtsur2.sas IBE 20SEP2007:12:11:53 60 24 20 Log-Rank: p=0.0034 48 27 34 36 35 44 24 50 68 12 88 114 Patients at Risk 0 172 169 0 10 90 80 70 60 50 40 30 20 100 Fig. 1 % Disease Free Survival (Any Progression or Death) After 3 months: 94.0% vs. 83.2%Diff. 10.8%, CI95=4.1-17.5%, p=0.002 After 6 months: 87.9% vs. 74.1% Diff. 13.8%, CI95=5.5-22.1%, p<0.001 Cox hazard ratio = 0.66 CI95 = 0.50-0.88, p = 0.004

  16. N=341 50.4% 49.6% 26.2 37.7 Median Treatment Arm n=172 n=169 95 79 Events EIA+RHT EIA 120 0 0 months 108 2 1 96 4 4 84 14 8 Local Progression Free Survival (Local Progression or Death) EORTC 62961/ESHO RHT 95-Study 72 17 20 rhtsur2.sas IBE 20SEP2007:12:11:53 60 29 24 Log-Rank: p=0.0226 48 34 41 36 45 54 24 63 82 12 99 125 Patients at Risk 0 172 169 0 10 90 80 70 60 50 40 30 20 100 Fig. 2 % Local Progression Free Survival (Local Progression or Death) After 3 months: 94.6% vs. 86.2%Diff. 8.4%, CI95=2.2-14.7%, p=0.008 After 6 months: 91.6% vs. 78.2% Diff. 13.4%, CI95=5.7-20.9%, p<0.001 Cox hazard ratio = 0.68 CI95 = 0.50-0.93, p=0.014

  17. Early Progression* S1 = primary tumor ≥5 cm, GII/GIII S2 = local recurrence of S1 tumor S3 = inadequate surgery of S1 or S2 tumor * local progression or death of any reason

  18. N=199 51.3% 48.7% 19.5 29.3 Median Treatment Arm n=102 57 55 n=97 Events EIA+RHT EIA 120 0 0 months 108 1 1 96 2 2 84 4 9 Subgroup S1/S2 Local Progression Free Survival (Local Progression or Death) EORTC 62961/ESHO RHT 95-Study 72 9 9 rhtsur2.sas IBE 20SEP2007:12:11:53 60 17 10 Log-Rank: p=0.4333 48 20 19 36 26 28 24 34 42 12 57 69 Patients at Risk 0 97 102 0 10 90 80 70 60 50 40 30 20 100 Fig. 4 % Local Progression Free Survival (Local Progression or Death) S1 + S2 - Subgroup After 3 months: 90.6% vs. 81.5%Diff. 9.1%, CI95=0.5-18.7%, p=0.065 After 6 months: 85.4% vs. 74.2% Diff. 11.3%, CI95=0,0-22.5%, p=0.049

  19. N=142 49.3% 50.7% 30.0 Median - Treatment Arm 38 24 n=70 n=72 Events EIA+RHT EIA 120 0 months 108 1 0 96 2 2 84 4 5 Subgroup S3 Local Progression Free Survival (Local Progression or Death) EORTC 62961/ESHO RHT 95-Study 72 11 8 rhtsur2.sas IBE 20SEP2007:12:11:53 60 12 14 Log-Rank: p=0.0053 48 14 22 36 19 26 24 29 40 12 42 56 Patients at Risk 0 70 72 0 10 90 80 70 60 50 40 30 20 100 Fig. 5 % Local Progression Free Survival (Local Progression or Death) S3-Subgroup After 3 months: 100% vs. 92.8%Diff. 7.2%, CI95=1.1-13.4% After 6 months: 100% vs. 84.0% Diff. 16.0%, CI95=7.3-24.6%

  20. Cumulative Incidence Analysis EIA Distant Progression NS EIA + RHT EIA Local Progression P=0.03 EIA+RHT NS EIA + RHT Death EIA

  21. Influence on Progression* (Cox model) *local progression or death

  22. ESHO National Research Center for Environment and Health Conclusions For patients with locally advanced high-grade STSregional hyperthermia + chemotherapy leads to a statistically significant improvement in: • Tumor response rate • Disease-free survival (DFS) • Local progression-free survival (LPFS) • Chemotherapy combined with hyperthermia lowers the risk of early PD for all patients - irrespective of the time point of surgery • Patients receiving chemotherapy + hyperthermia after inadequate surgery seem to profit most

More Related