The impact of targeted molecular therapies on the level of renal cell carcinoma vena caval tumor thrombus

Nicholas G. Cost, Scott E. Delacroix, Joshua P. Sleeper, Paul J. Smith, Ramy F. Youssef, Brian F. Chapin, Jose A. Karam, Stephen Culp, E. Jason Abel, James B Brugarolas, Ganesh Raj, Arthur I Sagalowsky, Christopher G. Wood, Vitaly Margulis

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Abstract

Background: Targeted molecular therapies (TMTs) previously have demonstrated oncologic activity in renal cell carcinoma (RCC) by reducing the size of primary tumors and metastases. Objective: To assess the cytoreductive effect of TMTs on inferior vena cava tumor thrombi. Design, setting, and participants: A multi-institutional database of patients treated with TMTs for RCC was reviewed. The subset with in situ level II or higher caval thrombi (above renal vein) was assessed for radiographic response in thrombus size and level. Pre- and posttreatment characteristics of this population were assessed for predictors of response in height, diameter, and level of the tumor thrombi. Measurements: The main outcome measured was a change in the clinical level of tumor thrombus following TMT. We also measured radiographic responses in thrombus size and location before and after TMT. Results and limitations: Twenty-five patients met the inclusion criteria. Before TMT, thrombus level was II in 18 patients (72%), III in 5 patients (20%), and IV in 2 patients (8%). The first-line therapy was sunitinib in 12 cases; alternative TMTs were administered in 13. The median duration of therapy was two cycles (range: one to six cycles). Following TMT, 7 patients (28%) had a measurable increase in thrombus height, 7 (28%) had no change, and 11 (44%) had a decrease. One patient (4%) had an increase in thrombus-level classification, 21 (84%) had stable thrombi, and in 3 (12%) the thrombus level decreased. There was only one case (4%) where the surgical approach was potentially affected by tumor thrombus regression (level IV to III). No statistically significant predictors of tumor thrombus response to TMTs were found. Limitations include the descriptive and retrospective study design. Because TMTs were initiated according to physician and/or patient preferences, and not all patients were treated in anticipation of surgery, no conclusions could be drawn regarding selection and duration of therapy. Thus it may not be appropriate to extrapolate our experience to all patients with locally advanced RCC. Although this is the largest reported experience with in situ caval tumor thrombi treated with TMT, this series lacks sufficient statistical power to assess the usefulness of TMTs adequately in tumor thrombus cytoreduction. Conclusions: TMT had a minimal clinical effect on RCC tumor thrombi. Only patients treated with sunitinib had clinical thrombus regression; however, the clinical magnitude and relevance of this effect is not clear and should be investigated prospectively.

Original languageEnglish (US)
Pages (from-to)912-918
Number of pages7
JournalEuropean Urology
Volume59
Issue number6
DOIs
StatePublished - Jun 2011

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Molecular Targeted Therapy
Venae Cavae
Renal Cell Carcinoma
Thrombosis
Neoplasms
Renal Veins

Keywords

  • Renal cell carcinoma
  • Targeted molecular therapies
  • Tumor thrombus

ASJC Scopus subject areas

  • Urology

Cite this

The impact of targeted molecular therapies on the level of renal cell carcinoma vena caval tumor thrombus. / Cost, Nicholas G.; Delacroix, Scott E.; Sleeper, Joshua P.; Smith, Paul J.; Youssef, Ramy F.; Chapin, Brian F.; Karam, Jose A.; Culp, Stephen; Abel, E. Jason; Brugarolas, James B; Raj, Ganesh; Sagalowsky, Arthur I; Wood, Christopher G.; Margulis, Vitaly.

In: European Urology, Vol. 59, No. 6, 06.2011, p. 912-918.

Research output: Contribution to journalArticle

Cost, NG, Delacroix, SE, Sleeper, JP, Smith, PJ, Youssef, RF, Chapin, BF, Karam, JA, Culp, S, Abel, EJ, Brugarolas, JB, Raj, G, Sagalowsky, AI, Wood, CG & Margulis, V 2011, 'The impact of targeted molecular therapies on the level of renal cell carcinoma vena caval tumor thrombus', European Urology, vol. 59, no. 6, pp. 912-918. https://doi.org/10.1016/j.eururo.2011.02.032
Cost, Nicholas G. ; Delacroix, Scott E. ; Sleeper, Joshua P. ; Smith, Paul J. ; Youssef, Ramy F. ; Chapin, Brian F. ; Karam, Jose A. ; Culp, Stephen ; Abel, E. Jason ; Brugarolas, James B ; Raj, Ganesh ; Sagalowsky, Arthur I ; Wood, Christopher G. ; Margulis, Vitaly. / The impact of targeted molecular therapies on the level of renal cell carcinoma vena caval tumor thrombus. In: European Urology. 2011 ; Vol. 59, No. 6. pp. 912-918.
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T1 - The impact of targeted molecular therapies on the level of renal cell carcinoma vena caval tumor thrombus

AU - Cost, Nicholas G.

AU - Delacroix, Scott E.

AU - Sleeper, Joshua P.

AU - Smith, Paul J.

AU - Youssef, Ramy F.

AU - Chapin, Brian F.

AU - Karam, Jose A.

AU - Culp, Stephen

AU - Abel, E. Jason

AU - Brugarolas, James B

AU - Raj, Ganesh

AU - Sagalowsky, Arthur I

AU - Wood, Christopher G.

AU - Margulis, Vitaly

PY - 2011/6

Y1 - 2011/6

N2 - Background: Targeted molecular therapies (TMTs) previously have demonstrated oncologic activity in renal cell carcinoma (RCC) by reducing the size of primary tumors and metastases. Objective: To assess the cytoreductive effect of TMTs on inferior vena cava tumor thrombi. Design, setting, and participants: A multi-institutional database of patients treated with TMTs for RCC was reviewed. The subset with in situ level II or higher caval thrombi (above renal vein) was assessed for radiographic response in thrombus size and level. Pre- and posttreatment characteristics of this population were assessed for predictors of response in height, diameter, and level of the tumor thrombi. Measurements: The main outcome measured was a change in the clinical level of tumor thrombus following TMT. We also measured radiographic responses in thrombus size and location before and after TMT. Results and limitations: Twenty-five patients met the inclusion criteria. Before TMT, thrombus level was II in 18 patients (72%), III in 5 patients (20%), and IV in 2 patients (8%). The first-line therapy was sunitinib in 12 cases; alternative TMTs were administered in 13. The median duration of therapy was two cycles (range: one to six cycles). Following TMT, 7 patients (28%) had a measurable increase in thrombus height, 7 (28%) had no change, and 11 (44%) had a decrease. One patient (4%) had an increase in thrombus-level classification, 21 (84%) had stable thrombi, and in 3 (12%) the thrombus level decreased. There was only one case (4%) where the surgical approach was potentially affected by tumor thrombus regression (level IV to III). No statistically significant predictors of tumor thrombus response to TMTs were found. Limitations include the descriptive and retrospective study design. Because TMTs were initiated according to physician and/or patient preferences, and not all patients were treated in anticipation of surgery, no conclusions could be drawn regarding selection and duration of therapy. Thus it may not be appropriate to extrapolate our experience to all patients with locally advanced RCC. Although this is the largest reported experience with in situ caval tumor thrombi treated with TMT, this series lacks sufficient statistical power to assess the usefulness of TMTs adequately in tumor thrombus cytoreduction. Conclusions: TMT had a minimal clinical effect on RCC tumor thrombi. Only patients treated with sunitinib had clinical thrombus regression; however, the clinical magnitude and relevance of this effect is not clear and should be investigated prospectively.

AB - Background: Targeted molecular therapies (TMTs) previously have demonstrated oncologic activity in renal cell carcinoma (RCC) by reducing the size of primary tumors and metastases. Objective: To assess the cytoreductive effect of TMTs on inferior vena cava tumor thrombi. Design, setting, and participants: A multi-institutional database of patients treated with TMTs for RCC was reviewed. The subset with in situ level II or higher caval thrombi (above renal vein) was assessed for radiographic response in thrombus size and level. Pre- and posttreatment characteristics of this population were assessed for predictors of response in height, diameter, and level of the tumor thrombi. Measurements: The main outcome measured was a change in the clinical level of tumor thrombus following TMT. We also measured radiographic responses in thrombus size and location before and after TMT. Results and limitations: Twenty-five patients met the inclusion criteria. Before TMT, thrombus level was II in 18 patients (72%), III in 5 patients (20%), and IV in 2 patients (8%). The first-line therapy was sunitinib in 12 cases; alternative TMTs were administered in 13. The median duration of therapy was two cycles (range: one to six cycles). Following TMT, 7 patients (28%) had a measurable increase in thrombus height, 7 (28%) had no change, and 11 (44%) had a decrease. One patient (4%) had an increase in thrombus-level classification, 21 (84%) had stable thrombi, and in 3 (12%) the thrombus level decreased. There was only one case (4%) where the surgical approach was potentially affected by tumor thrombus regression (level IV to III). No statistically significant predictors of tumor thrombus response to TMTs were found. Limitations include the descriptive and retrospective study design. Because TMTs were initiated according to physician and/or patient preferences, and not all patients were treated in anticipation of surgery, no conclusions could be drawn regarding selection and duration of therapy. Thus it may not be appropriate to extrapolate our experience to all patients with locally advanced RCC. Although this is the largest reported experience with in situ caval tumor thrombi treated with TMT, this series lacks sufficient statistical power to assess the usefulness of TMTs adequately in tumor thrombus cytoreduction. Conclusions: TMT had a minimal clinical effect on RCC tumor thrombi. Only patients treated with sunitinib had clinical thrombus regression; however, the clinical magnitude and relevance of this effect is not clear and should be investigated prospectively.

KW - Renal cell carcinoma

KW - Targeted molecular therapies

KW - Tumor thrombus

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