Advertisement

Abdominal Radiology

, Volume 44, Issue 9, pp 3099–3106 | Cite as

5-Fluorouracil induced liver toxicity in patients with colorectal cancer: role of computed tomography texture analysis as a potential biomarker

  • Francesco AlessandrinoEmail author
  • Lei Qin
  • Gisele Cruz
  • Sonia Sahu
  • Michael H. Rosenthal
  • Jeffrey A. Meyerhardt
  • Atul B. Shinagare
Hepatobiliary
  • 71 Downloads

Abstract

Purpose

To assess if CT texture analysis (TA) can serve as a biomarker of liver toxicity in patients with colorectal cancer treated with 5-fluorouracil (5-FU)-based chemotherapy.

Methods

In this IRB-approved, HIPAA-compliant retrospective study, patients with colorectal cancer treated with 5-FU-based regimens during 2008–2010 were identified from institutional electronic database. Total 43 patients (23 women; mean age 56 years) with normal baseline liver function tests (LFTs), availability of baseline (pre-chemotherapy) and first follow-up CT (median 1.7 months, interquartile range (IQR) 1.5–2.5) performed during chemotherapy were included. Two single-slice ROI of right and left liver lobe were obtained on baseline and first follow-up CT for TA. Texture features [mean, entropy, kurtosis, skewness, mean of positive pixel, standard deviation (SD)] were extracted using a commercially available software (TexRAD; Feedback Medical Ltd, Cambridge, UK). Changes in texture parameters between baseline and follow-up CT were evaluated with Wilcoxon signed-rank test for patients with and without LFT elevation during chemotherapy.

Results

Patients with LFT elevation (n = 34; 79%) showed significantly different mean, entropy, skewness, and SD (p values range 0.007–0.047) between baseline and first follow-up CT. No significant changes in features were observed in patients without LFT elevation (n = 9; 21%). In 19 patients (56%), first follow-up CT was performed before elevation of LFTs was observed.

Conclusions

This proof-of-concept study shows that there are early changes in liver texture on first follow-up CT in patients with LFT elevation during 5-FU-based chemotherapy for colorectal cancer. In more than 50% of cases, these changes occur before LFT elevation becomes evident on blood tests.

Keywords

Tomography X-ray computed Chemotherapy Liver Drug-induced liver injury 

Notes

Compliance with ethical standards

Conflict of interest

Francesco Alessandrino, Sonia Sahu, Gisele Cruz, Lei Qin, Michael H. Rosenthal and Jeffrey A. Meyerhardt, no related financial relationships to disclose. Atul B. Shinagare Consultant, Arog Pharmaceuticals; research funding, GTx Inc.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

For this type of study formal consent is not required.

References

  1. 1.
    American Cancer Society. Key statistics for Colorectal Cancer. https://www.cancer.org/cancer/colon-rectal-cancer/about/key-statistics.html Page created Feb 21, 2018, accessed October 24, 2018.
  2. 2.
    Benson AB 3rd, Venook AP, Cederquist L, et al (2017) Colon Cancer, Version 1.2017, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 15(3):370–398.Google Scholar
  3. 3.
    Robinson SM, Wilson CH, Burt AD, Manas DM, White SA (2012) Chemotherapy-associated liver injury in patients with colorectal liver metastases: a systematic review and meta-analysis. Ann Surg Oncol 19:4287–4299.CrossRefGoogle Scholar
  4. 4.
    Vauthey JN, Pawlik TM, Ribero D, et al (2006) Chemotherapy regimen predicts steatohepatitis and an increase in 90-day mortality after surgery for hepatic colorectal metastases. J Clin Oncol 24(13):2065-2072.CrossRefGoogle Scholar
  5. 5.
    Han NY, Park BJ, Kim MJ, Sung DJ, Cho SB (2015) Hepatic Parenchymal Heterogeneity on Contrast-enhanced CT Scans Following Oxaliplatin-based Chemotherapy: Natural History and Association with Clinical Evidence of Sinusoidal Obstruction Syndrome. Radiology 276(3):766–774.CrossRefGoogle Scholar
  6. 6.
    Rubbia-Brandt L, Lauwers GY, Wang H, et al (2010) Sinusoidal obstruction syndrome and nodular regenerative hyperplasia are frequent oxaliplatin-associated liver lesions and partially prevented by bevacizumab in patients with hepatic colorectal metastasis. Histopathology 56(4):430–439.CrossRefGoogle Scholar
  7. 7.
    Klinger M, Eipeldauer S, Hacker S, et al (2009) Bevacizumab protects against sinusoidal obstruction syndrome and does not increase response rate in neoadjuvant XELOX/FOLFOX therapy of colorectal cancer liver metastases. Eur J Surg Oncol 35(5):515–520.CrossRefGoogle Scholar
  8. 8.
    Imai K, Emi Y, Iyama K-I, et al (2014) Splenic volume may be a useful indicator of the protective effect of bevacizumab against oxaliplatin-induced hepatic sinusoidal obstruction syndrome. Eur J Surg Oncol 40(5):559–566.CrossRefGoogle Scholar
  9. 9.
    Volk AM, Fritzmann J, Reissfelder C, Weber GF, Weitz J, Rahbari NN (2016) Impact of Bevacizumab on parenchymal damage and functional recovery of the liver in patients with colorectal liver metastases. BMC Cancer 16:84.CrossRefGoogle Scholar
  10. 10.
    Cleary JM, Tanabe KT, Lauwers GY, Zhu AX (2009) Hepatic toxicities associated with the use of preoperative systemic therapy in patients with metastatic colorectal adenocarcinoma to the liver. Oncologist 14(11):1095-1105.CrossRefGoogle Scholar
  11. 11.
    McWhirter D, Kitteringham N, Jones RP, Malik H, Park K, Palmer D (2013) Chemotherapy induced hepatotoxicity in metastatic colorectal cancer: a review of mechanisms and outcomes. Crit Rev Oncol Hematol 88(2):404-415.CrossRefGoogle Scholar
  12. 12.
    Rubbia-Brandt L, Audard V, Sartoretti P, et al (2004) Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer. Ann Oncol 15(3):460–466.CrossRefGoogle Scholar
  13. 13.
    Zorzi D, Laurent A, Pawlik TM, Lauwers GY, Vauthey JN, Abdalla EK (2007) Chemotherapy-associated hepatotoxicity and surgery for colorectal liver metastases. Br J Surg 94(3):274–286.CrossRefGoogle Scholar
  14. 14.
    Hubert C, Sempoux C, Humblet Y, et al (2013) Sinusoidal obstruction syndrome (SOS) related to chemotherapy for colorectal liver metastases: factors predictive of severe SOS lesions and protective effect of bevacizumab. HPB 15(11):858–864.CrossRefGoogle Scholar
  15. 15.
    Overman MJ, Maru DM, Charnsangavej C, et al (2010) Oxaliplatin-Mediated Increase in Spleen Size As a Biomarker for the Development of Hepatic Sinusoidal Injury. J Clin Oncol 28(15):2549–2555.CrossRefGoogle Scholar
  16. 16.
    Wai C (2003) A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology 38(2):518–526.CrossRefGoogle Scholar
  17. 17.
    Vincenzi B, Imperatori M, Picardi A, et al (2015) Liver toxicity in colorectal cancer patients treated with first-line FOLFIRI-containing regimen: a single institution experience. Expert Rev Anticancer Ther 15(8):971-976.CrossRefGoogle Scholar
  18. 18.
    Ganeshan B, Miles KA (2013) Quantifying tumour heterogeneity with CT. Cancer Imaging 13:140–149.CrossRefGoogle Scholar
  19. 19.
    Lubner MG, Malecki K, Kloke J, Ganeshan B, Pickhardt PJ (2017) Texture analysis of the liver at MDCT for assessing hepatic fibrosis. Abdom Radiol (NY) 42(8):2069-2078.CrossRefGoogle Scholar
  20. 20.
    Daginawala N, Li B, Buch K, et al (2016) Using texture analyses of contrast enhanced CT to assess hepatic fibrosis. Eur J Radiol 85(3):511–517.CrossRefGoogle Scholar
  21. 21.
    Ahn SJ, Kim JH, Park SJ, Han JK (2016) Prediction of the therapeutic response after FOLFOX and FOLFIRI treatment for patients with liver metastasis from colorectal cancer using computerized CT texture analysis. Eur J Radiol 85(10):1867–1874.CrossRefGoogle Scholar
  22. 22.
    Miles KA, Ganeshan B, Griffiths MR, Young RC, Chatwin CR (2009) Colorectal cancer: texture analysis of portal phase hepatic CT images as a potential marker of survival. Radiology 250(2):444–452.CrossRefGoogle Scholar
  23. 23.
    Simpson AL, Adams LB, Allen PJ, et al (2015) Texture analysis of preoperative CT images for prediction of postoperative hepatic insufficiency: a preliminary study. J Am Coll Surg 220(3):339–346.CrossRefGoogle Scholar
  24. 24.
    Lubner MG, Smith AD, Sandrasegaran K, Sahani DV, Pickhardt P (2017) CT Texture Analysis: Definitions, Applications, Biologic Correlates, and Challenges. RadioGraphics 37:5:1483-1503.CrossRefGoogle Scholar
  25. 25.
    Miles KA, Ganeshan B, Hayball MP (2013) CT texture analysis using the filtration-histogram method: what do the measurements mean? Cancer Imaging 13(3):400-406.CrossRefGoogle Scholar
  26. 26.
    Senior JR (2009) Monitoring for hepatotoxicity: what is the predictive value of liver "function" tests? Clin Pharmacol Ther 85(3):331-334.CrossRefGoogle Scholar
  27. 27.
    Pereyra D, Rumpf B, Ammann M, et al (2019) The Combination of APRI and ALBI Facilitates Preoperative Risk Stratification for Patients Undergoing Liver Surgery After Neoadjuvant Chemotherapy. Ann Surg Oncol.  https://doi.org/10.1245/s10434-018-07125-6.
  28. 28.
    Park S, Kim HY, Kim H, et al (2016) Changes in Noninvasive Liver Fibrosis Indices and Spleen Size During Chemotherapy: Potential Markers for Oxaliplatin-Induced Sinusoidal Obstruction Syndrome. Medicine 95(2):e2454.CrossRefGoogle Scholar
  29. 29.
    Han NY, Park BJ, Yang KS, et al (2017) Hepatic Parenchymal Heterogeneity as a Marker for Oxaliplatin-Induced Sinusoidal Obstruction Syndrome: Correlation With Treatment Response of Colorectal Cancer Liver Metastases. Am J Roentgenol 209(5):1039-1045.CrossRefGoogle Scholar
  30. 30.
    Weiss GJ, Ganeshan B, Miles KA, et al (2014) Noninvasive Image Texture Analysis Differentiates K-ras Mutation from Pan-Wildtype NSCLC and Is Prognostic. de Mello RA, ed. PLoS ONE 9(7):e100244.Google Scholar
  31. 31.
    Lubner MG, Stabo N, Abel EJ, Del Rio AM, Pickhardt PJ (2016) CT Textural Analysis of Large Primary Renal Cell Carcinomas: Pretreatment Tumor Heterogeneity Correlates With Histologic Findings and Clinical Outcomes. Am J Roentgenol 207(1):96-105.CrossRefGoogle Scholar
  32. 32.
    Lee SJ, Zea R, Kim DH, Lubner MG, Deming DA, Pickhardt PJ (2018) CT texture features of liver parenchyma for predicting development of metastatic disease and overall survival in patients with colorectal cancer. Eur Radiol 28(4):1520-1528.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Imaging, Dana Farber Cancer InstituteHarvard Medical SchoolBostonUSA
  2. 2.Department of Radiology, Brigham and Women’s HospitalHarvard Medical SchoolBostonUSA
  3. 3.Gastrointestinal Cancer Treatment Center, Dana Farber Cancer InstituteHarvard Medical SchoolBostonUSA

Personalised recommendations