853P - Prediction of response of primary tumors to neoadjuvant sunitinib using perfusion (DCE) computed tomography (CT) in metastatic renal cell carcinoma...

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Renal Cell Cancer
Imaging, Diagnosis and Staging
Presenter Mehdi Bouaboula
Citation Annals of Oncology (2014) 25 (suppl_4): iv280-iv304. 10.1093/annonc/mdu337
Authors M. Bouaboula1, L. Fournier1, Y. Vano2, H. Pereira3, L. Albiges4, L. Salomon5, S. Taieb6, E. Anglade7, S. Abadie-Lacourtoisie8, A. Scherrer9, C. Theodore10, C. De Bazelaire11, S. Culine12, L.M. Caquot13, J. Eymard13, C. Le Rest2, G. Chatellier3, A. Mejean14, C.A. Cuenod1, S. Oudard2
  • 1Radiology Department, Georges Pompidou European hospital, FR-75015 - Paris/FR
  • 2Oncology Department, Georges Pompidou European hospital, FR-75015 - Paris/FR
  • 3Clinical Research Department, Georges Pompidou European hospital, FR-75015 - Paris/FR
  • 4Dept. Of Medicine, Institut de Cancérologie Gustave Roussy, 94805 - Villejuif/FR
  • 5Urology, Henri Mondor hospital, Paris/FR
  • 6Medical Imaging, Centre Oscar Lambret, 59000 - Lille/FR
  • 7Radiology Department, Centre Paul Papin, Angers/FR
  • 8Oncology Department, Centre Paul Papin, Angers/FR
  • 9Radiology Department, Foch Hospital, Suresnes/FR
  • 10Medical Oncology, HÔPITAL FOCH, 92151 - Suresnes/FR
  • 11Radiology Department, Saint Louis Hospital, Paris/FR
  • 12Oncology, Hôpital Saint-Louis, 75010 - Paris/FR
  • 13Oncology Department, Institut Jean Godinot, FR-51056 - Reims CEDEX/FR
  • 14Urology Department, Georges Pompidou European hospital, FR-75015 - Paris/FR

Abstract

Aim

Sunitinib is approved in 1st line for mRCC patients, but the prognosis remains poor with a median PFS of 11 months and an overall survival of 2-3 years. Determination of predictive biomarkers of response to sunitinib is urgently needed. The PREINSUT trial was conducted to determine biological, pathological and imaging markers for a neoadjuvant sunitinib in mRCC patients prior to nephrectomy. The perfusion imaging sub-analysis is presented here.

Methods

Thirty-three patients were included to assess the efficacy of 2 cycles of neoadjuvant sunitinib (50mg, 4weeks/6) before nephrectomy. DCE scans were performed at baseline and at the end of the 4 weeks of the 1st cycle of sunitinib. The following perfusion parameters were calculated in the primary renal tumor and correlated to the response in size at the end of the neoadjuvant therapy: tissue blood flow (Ft), tissue blood volume (Vt), permeability surface coefficient (PS), area under the enhancement curve at 60s (AUC). Patients were considered responders if there was a decrease ≥ 10 % of the renal tumor size. Perfusion parameters were compared between responders and non-responders using a Mann-Whitney test and correlated to changes in size using the Spearman correlation (r).

Results

Nineteen patients were eligible for the DCE imaging analysis. Mean baseline values of Ft, Vt, PS and AUC were 212 ± 136 mL/min/100mL, 29 ± 13%, 8.3 ± 4.2 mL/min/100mL, and 0.4 ± 0.2, respectively. There was a negative correlation between baseline values of Ft and the response in size (r = -0.54, p = 0.04), PS (r = -0.53, p = 0.04). Responders (N = 7) had a larger decrease in AUC between baseline and 4 weeks than non-responders (N = 12) (-39.2% vs 6.0%, p = 0.04). There was a positive correlation between size response and both PS (r = 0.62, p = 0.02), and AUC changes (r = 0.65, p = 0.02). Blood volume was negatively correlated, moderately but significantly, to plasmatic VEGF levels (r = -0.36, p = 0.01).

Conclusions

Perfusion CT parameters measured on baseline and early changes (4 weeks) after neoadjuvant sunitinib therapy were predictive of the final 3-months response of the renal tumor. We demonstrate in this study that the higher the tumor perfusion and permeability, the greater the reduction in size of the primary renal tumor.

Disclosure

Y. Vano: Honoraria from: Pfizer, Novartis, GSK, Sanofi, Astellas, Sandoz, Teva; S. Oudard: Consultant or Advisory Role: Sanofi, Novartis, Roche, Bayer, Keocyt, Amgen, Honoraria: Sanofi, Novartis, Roche, Bayer, Keocyt, Amgen, Pfizer. All other authors have declared no conflicts of interest.