Magnetic resonance imaging biomarkers in hepatocellular carcinoma: Association with response and circulating biomarkers after sunitinib therapy

Dushyant V. Sahani, Tao Jiang, Koichi Hayano, Dan G. Duda, Onofrio A. Catalano, Marek Ancukiewicz, Rakesh K. Jain, Andrew X. Zhu

Research output: Contribution to journalArticle

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Abstract

Background: To investigate the hypothesis that MRI derived diffusion-weighted imaging (DWI) and perfusion (MRP) parameters are sensitive image biomarkers for monitoring early antiangiogenic effects and predicting progression free survival (PFS) in advanced hepatocellular carcinoma (HCC). Methods. In this phase II clinical trial, 23 of 34 patients were included in the imaging and circulating biomarker study. DWI and MRP were performed at the baseline and at 2-weeks after initiation of sunitinib. The imaging protocol included an axial DWI sequence using b values of 50, 400 and 800 sec/mm 2, and MRP using a series of coronal 3D-VIBE following 20 ml of Gd-DTPA at 2 ml/sec. These parameters were compared with clinical outcome and PFS at 6-months. Correlation between changes in MRI parameters and plasma biomarkers was also evaluated. Results: After 2-week of sunitinib, substantial Ktrans changes in HCC were observed from median baseline value 2.15 min -1 to 0.94 min-1 (P = 0.0001) with increases in median apparent diffusion coefficient (ADC) from 0.88 × 10-3 mm 2/s to 0.98 × 10-3 mm2/s (P = 0.0001). Tumor size remained unchanged by RECIST and mRECIST (both P > 0.05). Patients who showed larger drop in Ktrans and Kep at 2 weeks correlated with favorable clinical outcome, and higher baseline Ktrans and larger drop in EVF correlated with longer PFS (all P <0.05). There was a significant association between a decrease in sVEGFR2 and the drop in Ktrans and Kep (P = 0.044, P = 0.030), and a significant and borderline association between decrease in TNF-α and the drop in Ktrans and Kep, respectively (P = 0.051, P = 0.035). Conclusion: In HCC, MRP may be a more sensitive biomarker in predicting early response and PFS following sunitinib than RECIST and mRECIST. Trial registration. ClinicalTrials.gov: NCT00361309.

Original languageEnglish
Article number51
JournalJournal of Hematology and Oncology
Volume6
Issue number1
DOIs
Publication statusPublished - 2013

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Disease-Free Survival
Hepatocellular Carcinoma
Biomarkers
Magnetic Resonance Imaging
Gadolinium DTPA
Phase II Clinical Trials
Diffusion Magnetic Resonance Imaging
Perfusion Imaging
Therapeutics
sunitinib
Neoplasms
Response Evaluation Criteria in Solid Tumors

Keywords

  • Antiangiogenic treatment
  • Circulating biomarker
  • Diffusion-weighted imaging
  • Dynamic contrast-enhanced MRI
  • Hepatocellular carcinoma
  • Image biomarker

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research
  • Molecular Biology

Cite this

Magnetic resonance imaging biomarkers in hepatocellular carcinoma : Association with response and circulating biomarkers after sunitinib therapy. / Sahani, Dushyant V.; Jiang, Tao; Hayano, Koichi; Duda, Dan G.; Catalano, Onofrio A.; Ancukiewicz, Marek; Jain, Rakesh K.; Zhu, Andrew X.

In: Journal of Hematology and Oncology, Vol. 6, No. 1, 51, 2013.

Research output: Contribution to journalArticle

Sahani, Dushyant V. ; Jiang, Tao ; Hayano, Koichi ; Duda, Dan G. ; Catalano, Onofrio A. ; Ancukiewicz, Marek ; Jain, Rakesh K. ; Zhu, Andrew X. / Magnetic resonance imaging biomarkers in hepatocellular carcinoma : Association with response and circulating biomarkers after sunitinib therapy. In: Journal of Hematology and Oncology. 2013 ; Vol. 6, No. 1.
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abstract = "Background: To investigate the hypothesis that MRI derived diffusion-weighted imaging (DWI) and perfusion (MRP) parameters are sensitive image biomarkers for monitoring early antiangiogenic effects and predicting progression free survival (PFS) in advanced hepatocellular carcinoma (HCC). Methods. In this phase II clinical trial, 23 of 34 patients were included in the imaging and circulating biomarker study. DWI and MRP were performed at the baseline and at 2-weeks after initiation of sunitinib. The imaging protocol included an axial DWI sequence using b values of 50, 400 and 800 sec/mm 2, and MRP using a series of coronal 3D-VIBE following 20 ml of Gd-DTPA at 2 ml/sec. These parameters were compared with clinical outcome and PFS at 6-months. Correlation between changes in MRI parameters and plasma biomarkers was also evaluated. Results: After 2-week of sunitinib, substantial Ktrans changes in HCC were observed from median baseline value 2.15 min -1 to 0.94 min-1 (P = 0.0001) with increases in median apparent diffusion coefficient (ADC) from 0.88 × 10-3 mm 2/s to 0.98 × 10-3 mm2/s (P = 0.0001). Tumor size remained unchanged by RECIST and mRECIST (both P > 0.05). Patients who showed larger drop in Ktrans and Kep at 2 weeks correlated with favorable clinical outcome, and higher baseline Ktrans and larger drop in EVF correlated with longer PFS (all P <0.05). There was a significant association between a decrease in sVEGFR2 and the drop in Ktrans and Kep (P = 0.044, P = 0.030), and a significant and borderline association between decrease in TNF-α and the drop in Ktrans and Kep, respectively (P = 0.051, P = 0.035). Conclusion: In HCC, MRP may be a more sensitive biomarker in predicting early response and PFS following sunitinib than RECIST and mRECIST. Trial registration. ClinicalTrials.gov: NCT00361309.",
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T2 - Association with response and circulating biomarkers after sunitinib therapy

AU - Sahani, Dushyant V.

AU - Jiang, Tao

AU - Hayano, Koichi

AU - Duda, Dan G.

AU - Catalano, Onofrio A.

AU - Ancukiewicz, Marek

AU - Jain, Rakesh K.

AU - Zhu, Andrew X.

PY - 2013

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N2 - Background: To investigate the hypothesis that MRI derived diffusion-weighted imaging (DWI) and perfusion (MRP) parameters are sensitive image biomarkers for monitoring early antiangiogenic effects and predicting progression free survival (PFS) in advanced hepatocellular carcinoma (HCC). Methods. In this phase II clinical trial, 23 of 34 patients were included in the imaging and circulating biomarker study. DWI and MRP were performed at the baseline and at 2-weeks after initiation of sunitinib. The imaging protocol included an axial DWI sequence using b values of 50, 400 and 800 sec/mm 2, and MRP using a series of coronal 3D-VIBE following 20 ml of Gd-DTPA at 2 ml/sec. These parameters were compared with clinical outcome and PFS at 6-months. Correlation between changes in MRI parameters and plasma biomarkers was also evaluated. Results: After 2-week of sunitinib, substantial Ktrans changes in HCC were observed from median baseline value 2.15 min -1 to 0.94 min-1 (P = 0.0001) with increases in median apparent diffusion coefficient (ADC) from 0.88 × 10-3 mm 2/s to 0.98 × 10-3 mm2/s (P = 0.0001). Tumor size remained unchanged by RECIST and mRECIST (both P > 0.05). Patients who showed larger drop in Ktrans and Kep at 2 weeks correlated with favorable clinical outcome, and higher baseline Ktrans and larger drop in EVF correlated with longer PFS (all P <0.05). There was a significant association between a decrease in sVEGFR2 and the drop in Ktrans and Kep (P = 0.044, P = 0.030), and a significant and borderline association between decrease in TNF-α and the drop in Ktrans and Kep, respectively (P = 0.051, P = 0.035). Conclusion: In HCC, MRP may be a more sensitive biomarker in predicting early response and PFS following sunitinib than RECIST and mRECIST. Trial registration. ClinicalTrials.gov: NCT00361309.

AB - Background: To investigate the hypothesis that MRI derived diffusion-weighted imaging (DWI) and perfusion (MRP) parameters are sensitive image biomarkers for monitoring early antiangiogenic effects and predicting progression free survival (PFS) in advanced hepatocellular carcinoma (HCC). Methods. In this phase II clinical trial, 23 of 34 patients were included in the imaging and circulating biomarker study. DWI and MRP were performed at the baseline and at 2-weeks after initiation of sunitinib. The imaging protocol included an axial DWI sequence using b values of 50, 400 and 800 sec/mm 2, and MRP using a series of coronal 3D-VIBE following 20 ml of Gd-DTPA at 2 ml/sec. These parameters were compared with clinical outcome and PFS at 6-months. Correlation between changes in MRI parameters and plasma biomarkers was also evaluated. Results: After 2-week of sunitinib, substantial Ktrans changes in HCC were observed from median baseline value 2.15 min -1 to 0.94 min-1 (P = 0.0001) with increases in median apparent diffusion coefficient (ADC) from 0.88 × 10-3 mm 2/s to 0.98 × 10-3 mm2/s (P = 0.0001). Tumor size remained unchanged by RECIST and mRECIST (both P > 0.05). Patients who showed larger drop in Ktrans and Kep at 2 weeks correlated with favorable clinical outcome, and higher baseline Ktrans and larger drop in EVF correlated with longer PFS (all P <0.05). There was a significant association between a decrease in sVEGFR2 and the drop in Ktrans and Kep (P = 0.044, P = 0.030), and a significant and borderline association between decrease in TNF-α and the drop in Ktrans and Kep, respectively (P = 0.051, P = 0.035). Conclusion: In HCC, MRP may be a more sensitive biomarker in predicting early response and PFS following sunitinib than RECIST and mRECIST. Trial registration. ClinicalTrials.gov: NCT00361309.

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