Limits...
Magnetic resonance imaging biomarkers in hepatocellular carcinoma: association with response and circulating biomarkers after sunitinib therapy.

Sahani DV, Jiang T, Hayano K, Duda DG, Catalano OA, Ancukiewicz M, Jain RK, Zhu AX - J Hematol Oncol (2013)

Bottom Line: These parameters were compared with clinical outcome and PFS at 6-months.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).In HCC, MRP may be a more sensitive biomarker in predicting early response and PFS following sunitinib than RECIST and mRECIST.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Abdominal Imaging and Intervention, Harvard Medical School and Massachusetts General Hospital, 55 Fruit Street, White 270, Boston, MA 02114, USA. dsahani@partners.org

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/mm2, 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 mm²/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.

Show MeSH

Related in: MedlinePlus

MR diffusion weighted images during sunitinib therapy. Transverse enhanced MR T1-weighted images (A, B) and MR diffusion weighted images (DWIs) for estimated apparent diffusion coefficient (ADC) (C, D) at baseline and after 2-week of sunitinib therapy in the same 47-year-old man with HCC (arrows). After two weeks of treatment with sunitinib, there was an increase in ADC value from 0.86 × 10-3 mm2/s to 0.94 × 10-3 mm2/s.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3722053&req=5

Figure 2: MR diffusion weighted images during sunitinib therapy. Transverse enhanced MR T1-weighted images (A, B) and MR diffusion weighted images (DWIs) for estimated apparent diffusion coefficient (ADC) (C, D) at baseline and after 2-week of sunitinib therapy in the same 47-year-old man with HCC (arrows). After two weeks of treatment with sunitinib, there was an increase in ADC value from 0.86 × 10-3 mm2/s to 0.94 × 10-3 mm2/s.

Mentions: The tumor parameters at baseline and 2-week post- sunitinib therapy are shown in Table 1. There was minimal change in median tumor burden based on RECIST (from 10.00 cm to 11.10 cm, P = 0.197) and mRECIST (from 9.94 cm to 10.11 cm, P = 0.96) and median tumor thrombus diameter (from 28.67 mm to 29.81 mm, P = 0.365). There was an increase in median tumor ADC value from 0.88 × 10-3 mm2/s to 0.98 × 10-3 mm2/s (P < 0.0001) and in median tumor thrombus ADC value from 0.89 × 10-3 mm2/s to 1.02 × 10-3 mm2/s (P = 0.035). The Ktrans change of HCC in MRP was more substantial with a decrease from median baseline value of 2.15 min−1 to 2-week post-treatment value of 0.94 min−1 (P < 0.0001). The HCC also showed relatively higher median Kep at baseline (4.15 min−1) and a significant decrease compared with post-treatment value (1.44 min−1) (P < 0.0001). The tumor thrombus displayed similar diffusion and perfusion features as their primary HCC at baseline and after treatment. The examples of Ktrans and ADC changes in an indexed HCC lesion after sunitinib administration are illustrated in Figures 1 and 2.


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

Sahani DV, Jiang T, Hayano K, Duda DG, Catalano OA, Ancukiewicz M, Jain RK, Zhu AX - J Hematol Oncol (2013)

MR diffusion weighted images during sunitinib therapy. Transverse enhanced MR T1-weighted images (A, B) and MR diffusion weighted images (DWIs) for estimated apparent diffusion coefficient (ADC) (C, D) at baseline and after 2-week of sunitinib therapy in the same 47-year-old man with HCC (arrows). After two weeks of treatment with sunitinib, there was an increase in ADC value from 0.86 × 10-3 mm2/s to 0.94 × 10-3 mm2/s.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3722053&req=5

Figure 2: MR diffusion weighted images during sunitinib therapy. Transverse enhanced MR T1-weighted images (A, B) and MR diffusion weighted images (DWIs) for estimated apparent diffusion coefficient (ADC) (C, D) at baseline and after 2-week of sunitinib therapy in the same 47-year-old man with HCC (arrows). After two weeks of treatment with sunitinib, there was an increase in ADC value from 0.86 × 10-3 mm2/s to 0.94 × 10-3 mm2/s.
Mentions: The tumor parameters at baseline and 2-week post- sunitinib therapy are shown in Table 1. There was minimal change in median tumor burden based on RECIST (from 10.00 cm to 11.10 cm, P = 0.197) and mRECIST (from 9.94 cm to 10.11 cm, P = 0.96) and median tumor thrombus diameter (from 28.67 mm to 29.81 mm, P = 0.365). There was an increase in median tumor ADC value from 0.88 × 10-3 mm2/s to 0.98 × 10-3 mm2/s (P < 0.0001) and in median tumor thrombus ADC value from 0.89 × 10-3 mm2/s to 1.02 × 10-3 mm2/s (P = 0.035). The Ktrans change of HCC in MRP was more substantial with a decrease from median baseline value of 2.15 min−1 to 2-week post-treatment value of 0.94 min−1 (P < 0.0001). The HCC also showed relatively higher median Kep at baseline (4.15 min−1) and a significant decrease compared with post-treatment value (1.44 min−1) (P < 0.0001). The tumor thrombus displayed similar diffusion and perfusion features as their primary HCC at baseline and after treatment. The examples of Ktrans and ADC changes in an indexed HCC lesion after sunitinib administration are illustrated in Figures 1 and 2.

Bottom Line: These parameters were compared with clinical outcome and PFS at 6-months.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).In HCC, MRP may be a more sensitive biomarker in predicting early response and PFS following sunitinib than RECIST and mRECIST.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Abdominal Imaging and Intervention, Harvard Medical School and Massachusetts General Hospital, 55 Fruit Street, White 270, Boston, MA 02114, USA. dsahani@partners.org

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/mm2, 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 mm²/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.

Show MeSH
Related in: MedlinePlus