Multiparametric MRI assessment during cisplatin and trastuzumab therapy in esophageal adenocarcinoma xenografts

Connie Siew Poh Yip; Amanda Jayne Weeks; Karen Paula Shaw; Gary John Russell Cook; David Landau; Muhammad Musib Siddique; Vicky Joo-Lin Goh

Multiparametric MRI assessment during cisplatin and trastuzumab therapy in esophageal adenocarcinoma xenografts

Connie Siew Poh Yip, Amanda Jayne Weeks, Karen Paula Shaw, Gary John Russell Cook, David Landau, Muhammad Musib Siddique, Vicky Joo-Lin Goh

Research output: Contribution to journal › Meeting abstract › peer-review

Abstract

Background: Standard CT imaging is limited for determining neoadjuvant treatment response in esophageal cancer but there is increasing interest in assessing multiparametric MRI (mpMRI) in this role.We evaluated changes in mpMRI during Trastuzumab and Cisplatin therapy in a gastroesophageal adenocarcinoma xenograft model (OE19) expressing human epidermal growth factor receptor 2 (HER2). Methods: 3 groups of female severe combined immunodeficient mice (n = 15) were injected subcutaneously with 5x106 OE19 cells. Animals were treated with intraperitoneal (IP) saline twice a week (Control), Cisplatin 4mg/kg once a week (Group C) or Trastuzumab 20mg/kg twice a week (Group T) for a total of 2 weeks. Animals were scanned on a 9.4T MR imaging system (Bruker, Germany) at 3 time points: before (t0), 24 hours after first IP treatment (t1) and on completion of treatment (t2). Contrast-enhanced T1-weighted (T1w), T2-weighted (T2w), diffusion weighted (DW) and T2*-weighted (T2*) sequences were acquired. Early (t1 - t0) and late (t2 - t0) parameter, tumour volume and image heterogeneity changes were compared between the groups using Kruskal-Wallis test. Results: A reduced growth rate was observed in Group T ({Delta}volume = 106%) compared to Control (680%) and Group C (305%) (p = 0.041) between t2-t0. Significant changes in DW and T2* (t2 - t0) were also observed. DW skewness increased in Group T (107%) but decreased in Group C (-28%) and Control (-89%) (p = 0.048). A greater reduction in T2* entropy (Group T -7.1% vs Group C -0.2% vs Control -2.2%, p = 0.032), T2* 50thpercentile (-18% vs 4% vs 15%, p = 0.034) and T2* 75th percentile (-13% vs 0.7% vs 21%, p = 0.024) were observed in Group T. A greater increase in T2* uniformity was found in Group T (48%) compared to Group C (3%) and Control (18%) (p = 0.032). There were no significant differences between groups at early t1-t0 assessment. Conclusions: Significant changes were found in DW and T2* parameters in animals treated with Trastuzumab, Cisplatin and Control, possibly reflecting the different drug mechanisms of action & tumour control, on completion of but not early in treatment. These findings offer potential new clinical imaging biomarkers for response assessment.

Original language	English
Article number	e15108
Journal	Journal of Clinical Oncology
Volume	33
Issue number	15 Supplement
Publication status	Published - 20 May 2015

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Yip, C. S. P., Weeks, A. J., Shaw, K. P., Cook, G. J. R., Landau, D., Siddique, M. M., & Goh, V. J.-L. (2015). Multiparametric MRI assessment during cisplatin and trastuzumab therapy in esophageal adenocarcinoma xenografts. Journal of Clinical Oncology, 33(15 Supplement), Article e15108. http://meeting.ascopubs.org/cgi/content/abstract/33/15_suppl/e15108?sid=1502f12d-8eb8-48a2-ab36-b878aeceaee6

@article{e68dd1b55a804478b8f2b077bc8131de,

title = "Multiparametric MRI assessment during cisplatin and trastuzumab therapy in esophageal adenocarcinoma xenografts",

abstract = "Background: Standard CT imaging is limited for determining neoadjuvant treatment response in esophageal cancer but there is increasing interest in assessing multiparametric MRI (mpMRI) in this role.We evaluated changes in mpMRI during Trastuzumab and Cisplatin therapy in a gastroesophageal adenocarcinoma xenograft model (OE19) expressing human epidermal growth factor receptor 2 (HER2). Methods: 3 groups of female severe combined immunodeficient mice (n = 15) were injected subcutaneously with 5x106 OE19 cells. Animals were treated with intraperitoneal (IP) saline twice a week (Control), Cisplatin 4mg/kg once a week (Group C) or Trastuzumab 20mg/kg twice a week (Group T) for a total of 2 weeks. Animals were scanned on a 9.4T MR imaging system (Bruker, Germany) at 3 time points: before (t0), 24 hours after first IP treatment (t1) and on completion of treatment (t2). Contrast-enhanced T1-weighted (T1w), T2-weighted (T2w), diffusion weighted (DW) and T2*-weighted (T2*) sequences were acquired. Early (t1 - t0) and late (t2 - t0) parameter, tumour volume and image heterogeneity changes were compared between the groups using Kruskal-Wallis test. Results: A reduced growth rate was observed in Group T ({Delta}volume = 106%) compared to Control (680%) and Group C (305%) (p = 0.041) between t2-t0. Significant changes in DW and T2* (t2 - t0) were also observed. DW skewness increased in Group T (107%) but decreased in Group C (-28%) and Control (-89%) (p = 0.048). A greater reduction in T2* entropy (Group T -7.1% vs Group C -0.2% vs Control -2.2%, p = 0.032), T2* 50thpercentile (-18% vs 4% vs 15%, p = 0.034) and T2* 75th percentile (-13% vs 0.7% vs 21%, p = 0.024) were observed in Group T. A greater increase in T2* uniformity was found in Group T (48%) compared to Group C (3%) and Control (18%) (p = 0.032). There were no significant differences between groups at early t1-t0 assessment. Conclusions: Significant changes were found in DW and T2* parameters in animals treated with Trastuzumab, Cisplatin and Control, possibly reflecting the different drug mechanisms of action & tumour control, on completion of but not early in treatment. These findings offer potential new clinical imaging biomarkers for response assessment.",

author = "Yip, {Connie Siew Poh} and Weeks, {Amanda Jayne} and Shaw, {Karen Paula} and Cook, {Gary John Russell} and David Landau and Siddique, {Muhammad Musib} and Goh, {Vicky Joo-Lin}",

year = "2015",

month = may,

day = "20",

language = "English",

volume = "33",

journal = "Journal of Clinical Oncology",

issn = "0732-183X",

publisher = "American Society of Clinical Oncology",

number = "15 Supplement",

}

Yip, CSP , Weeks, AJ , Shaw, KP , Cook, GJR , Landau, D , Siddique, MM & Goh, VJ-L 2015, 'Multiparametric MRI assessment during cisplatin and trastuzumab therapy in esophageal adenocarcinoma xenografts', Journal of Clinical Oncology, vol. 33, no. 15 Supplement, e15108. <http://meeting.ascopubs.org/cgi/content/abstract/33/15_suppl/e15108?sid=1502f12d-8eb8-48a2-ab36-b878aeceaee6>

TY - JOUR

T1 - Multiparametric MRI assessment during cisplatin and trastuzumab therapy in esophageal adenocarcinoma xenografts

AU - Yip, Connie Siew Poh

AU - Weeks, Amanda Jayne

AU - Shaw, Karen Paula

AU - Cook, Gary John Russell

AU - Landau, David

AU - Siddique, Muhammad Musib

AU - Goh, Vicky Joo-Lin

PY - 2015/5/20

Y1 - 2015/5/20

N2 - Background: Standard CT imaging is limited for determining neoadjuvant treatment response in esophageal cancer but there is increasing interest in assessing multiparametric MRI (mpMRI) in this role.We evaluated changes in mpMRI during Trastuzumab and Cisplatin therapy in a gastroesophageal adenocarcinoma xenograft model (OE19) expressing human epidermal growth factor receptor 2 (HER2). Methods: 3 groups of female severe combined immunodeficient mice (n = 15) were injected subcutaneously with 5x106 OE19 cells. Animals were treated with intraperitoneal (IP) saline twice a week (Control), Cisplatin 4mg/kg once a week (Group C) or Trastuzumab 20mg/kg twice a week (Group T) for a total of 2 weeks. Animals were scanned on a 9.4T MR imaging system (Bruker, Germany) at 3 time points: before (t0), 24 hours after first IP treatment (t1) and on completion of treatment (t2). Contrast-enhanced T1-weighted (T1w), T2-weighted (T2w), diffusion weighted (DW) and T2*-weighted (T2*) sequences were acquired. Early (t1 - t0) and late (t2 - t0) parameter, tumour volume and image heterogeneity changes were compared between the groups using Kruskal-Wallis test. Results: A reduced growth rate was observed in Group T ({Delta}volume = 106%) compared to Control (680%) and Group C (305%) (p = 0.041) between t2-t0. Significant changes in DW and T2* (t2 - t0) were also observed. DW skewness increased in Group T (107%) but decreased in Group C (-28%) and Control (-89%) (p = 0.048). A greater reduction in T2* entropy (Group T -7.1% vs Group C -0.2% vs Control -2.2%, p = 0.032), T2* 50thpercentile (-18% vs 4% vs 15%, p = 0.034) and T2* 75th percentile (-13% vs 0.7% vs 21%, p = 0.024) were observed in Group T. A greater increase in T2* uniformity was found in Group T (48%) compared to Group C (3%) and Control (18%) (p = 0.032). There were no significant differences between groups at early t1-t0 assessment. Conclusions: Significant changes were found in DW and T2* parameters in animals treated with Trastuzumab, Cisplatin and Control, possibly reflecting the different drug mechanisms of action & tumour control, on completion of but not early in treatment. These findings offer potential new clinical imaging biomarkers for response assessment.

AB - Background: Standard CT imaging is limited for determining neoadjuvant treatment response in esophageal cancer but there is increasing interest in assessing multiparametric MRI (mpMRI) in this role.We evaluated changes in mpMRI during Trastuzumab and Cisplatin therapy in a gastroesophageal adenocarcinoma xenograft model (OE19) expressing human epidermal growth factor receptor 2 (HER2). Methods: 3 groups of female severe combined immunodeficient mice (n = 15) were injected subcutaneously with 5x106 OE19 cells. Animals were treated with intraperitoneal (IP) saline twice a week (Control), Cisplatin 4mg/kg once a week (Group C) or Trastuzumab 20mg/kg twice a week (Group T) for a total of 2 weeks. Animals were scanned on a 9.4T MR imaging system (Bruker, Germany) at 3 time points: before (t0), 24 hours after first IP treatment (t1) and on completion of treatment (t2). Contrast-enhanced T1-weighted (T1w), T2-weighted (T2w), diffusion weighted (DW) and T2*-weighted (T2*) sequences were acquired. Early (t1 - t0) and late (t2 - t0) parameter, tumour volume and image heterogeneity changes were compared between the groups using Kruskal-Wallis test. Results: A reduced growth rate was observed in Group T ({Delta}volume = 106%) compared to Control (680%) and Group C (305%) (p = 0.041) between t2-t0. Significant changes in DW and T2* (t2 - t0) were also observed. DW skewness increased in Group T (107%) but decreased in Group C (-28%) and Control (-89%) (p = 0.048). A greater reduction in T2* entropy (Group T -7.1% vs Group C -0.2% vs Control -2.2%, p = 0.032), T2* 50thpercentile (-18% vs 4% vs 15%, p = 0.034) and T2* 75th percentile (-13% vs 0.7% vs 21%, p = 0.024) were observed in Group T. A greater increase in T2* uniformity was found in Group T (48%) compared to Group C (3%) and Control (18%) (p = 0.032). There were no significant differences between groups at early t1-t0 assessment. Conclusions: Significant changes were found in DW and T2* parameters in animals treated with Trastuzumab, Cisplatin and Control, possibly reflecting the different drug mechanisms of action & tumour control, on completion of but not early in treatment. These findings offer potential new clinical imaging biomarkers for response assessment.

M3 - Meeting abstract

SN - 0732-183X

VL - 33

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

IS - 15 Supplement

M1 - e15108

ER -

Multiparametric MRI assessment during cisplatin and trastuzumab therapy in esophageal adenocarcinoma xenografts

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