CT Attenuation of Liver Metastases Before Targeted Therapy is a Prognostic Factor of Overall Survival in Colorectal Cancer Patients. Results from the Randomised, Open-label FIRE-3/AIO KRK0306 Trial

Overview

Journal Eur Radiol

Specialty Radiology

Date 2018 Jun 9

PMID 29882070

Citations 10

Authors

Matthias F Froelich

Volker Heinemann

Wieland H Sommer

Julian W Holch

Franziska Schoeppe

Nina Hesse

Alena B Baumann

Wolfgang G Kunz

Maximilian F Reiser

Jens Ricke

Melvin DAnastasi

Sebastian Stintzing

Dominik P Modest

Philipp M Kazmierczak

Felix O Hofmann

Affiliations

Soon will be listed here.

Abstract

Objectives: To assess the prognostic value of pre-therapeutic computed tomography (CT) attenuation of liver metastases for overall survival (OS) in metastatic colorectal cancer (mCRC).

Methods: In the open-label, randomised, prospective phase-III FIRE-3 trial, patients with histologically confirmed mCRC received fluorouracil (5-FU), leucovorin and irinotecan (FOLFIRI) with either cetuximab or bevacizumab. Participating patients gave written informed consent prior to study entry. In CT at baseline (portal venous phase, slice thickness ≤5 mm), mean attenuation [Hounsfield units (HU)] of liver metastases was retrospectively assessed by semi-automated volumetry. Its prognostic influence on OS was analysed in Kaplan-Meier-analysis and Cox proportional hazard regression and an optimal threshold was determined.

Results: In FIRE-3, 592 patients were enrolled between 2007 and 2012. Among the 347 patients eligible for liver volumetry, median baseline CT attenuation of liver metastases was 59.67 HU [interquartile range (IQR), 49.13, 68.85]. Increased attenuation was associated with longer OS {per 10 HU: hazard ratio (HR), 0.85 [95% confidence interval (CI), 0.78, 0.93], p < 0.001}. The optimised threshold (≥61.62 HU) was a strong predictor for increased OS [median, 21.3 vs 30.6 months; HR, 0.61 (95% CI, 0.47, 0.80), p < 0.001]. Multivariate regression controlling for correlated and further prognostic factors confirmed this [HR, 0.60 (95% CI, 0.45, 0.81), p = 0.001]. Furthermore, mean attenuation ≥61.62 HU was significantly associated with increased early tumour shrinkage (p = 0.002) and increased depth of response (p = 0.012).

Conclusions: Increased mean baseline CT attenuation of liver metastases may identify mCRC patients with prolonged OS and better tumour response.

Key Points: • In colorectal cancer, increased attenuation of liver metastases in baseline computed tomography is a prognostic factor for prolonged OS (p < 0.001). • A threshold of ≥61.62 HU was determined as optimal cut-off to identify patients with prolonged OS (p < 0.001), early tumour shrinkage (p = 0.002) and increased depth of response (p = 0.012).

Citing Articles

Photon-counting computed tomography versus energy-integrating computed tomography for detection of small liver lesions: comparison using a virtual framework imaging.

Felice N, Wildman-Tobriner B, Segars W, Bashir M, Marin D, Samei E J Med Imaging (Bellingham). 2024; 11(5):053502.

PMID: 39430123 PMC: 11486217. DOI: 10.1117/1.JMI.11.5.053502.

Predictive Value of Quantitative Parameters of F-FDG PET/CT in Patients with Liposarcoma.

Martiniova L, Kamel S, Kairemo K, Benjamin R, Somaiah N, Ravizzini G Diagnostics (Basel). 2024; 14(18).

PMID: 39335700 PMC: 11431839. DOI: 10.3390/diagnostics14182021.

Radiomics analysis of baseline computed tomography to predict oncological outcomes in patients treated for resectable colorectal cancer liver metastasis.

Montagnon E, Cerny M, Hamilton V, Derennes T, Ilinca A, Elforaici M PLoS One. 2024; 19(9):e0307815.

PMID: 39259736 PMC: 11389941. DOI: 10.1371/journal.pone.0307815.

Textural heterogeneity of liver lesions in CT imaging - comparison of colorectal and pancreatic metastases.

Pietsch F, Haag F, Ayx I, Grawe F, Vellala A, Schoenberg S Abdom Radiol (NY). 2024; 49(12):4295-4306.

PMID: 39115682 PMC: 11522118. DOI: 10.1007/s00261-024-04511-5.

Prognostic value of the tumor-to-liver density ratio in patients with metastatic colorectal cancer treated with bevacizumab-based chemotherapy. A post-hoc study of the STIC-AVASTIN trial.

Mazard T, Mollevi C, Loyer E, Leger J, Chautard R, Bouche O Cancer Imaging. 2024; 24(1):77.

PMID: 38886836 PMC: 11181627. DOI: 10.1186/s40644-024-00722-7.

References

Riihimaki M, Hemminki A, Sundquist J, Hemminki K . Patterns of metastasis in colon and rectal cancer. Sci Rep. 2016; 6:29765. PMC: 4945942. DOI: 10.1038/srep29765. View

Goh V, Padhani A, Rasheed S . Functional imaging of colorectal cancer angiogenesis. Lancet Oncol. 2007; 8(3):245-55. DOI: 10.1016/S1470-2045(07)70075-X. View

Modest D, Ricard I, Heinemann V, Hegewisch-Becker S, Schmiegel W, Porschen R . Outcome according to KRAS-, NRAS- and BRAF-mutation as well as KRAS mutation variants: pooled analysis of five randomized trials in metastatic colorectal cancer by the AIO colorectal cancer study group. Ann Oncol. 2016; 27(9):1746-53. PMC: 4999563. DOI: 10.1093/annonc/mdw261. View

Huellner M, Hennedige T, Winterhalder R, Zander T, Venkatesh S, Yong W . Prognostic value of different CT measurements in early therapy response evaluation in patients with metastatic colorectal cancer. Cancer Imaging. 2012; 12:212-24. PMC: 3392781. DOI: 10.1102/1470-7330.2012.0021. View

Sorich M, Wiese M, Rowland A, Kichenadasse G, McKinnon R, Karapetis C . Extended RAS mutations and anti-EGFR monoclonal antibody survival benefit in metastatic colorectal cancer: a meta-analysis of randomized, controlled trials. Ann Oncol. 2014; 26(1):13-21. DOI: 10.1093/annonc/mdu378. View

Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh J, Comber H . Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer. 2013; 49(6):1374-403. DOI: 10.1016/j.ejca.2012.12.027. View

Auer R, White R, Kemeny N, Schwartz L, Shia J, Blumgart L . Predictors of a true complete response among disappearing liver metastases from colorectal cancer after chemotherapy. Cancer. 2010; 116(6):1502-9. DOI: 10.1002/cncr.24912. View

Kohne C, Cunningham D, Di Costanzo F, Glimelius B, Blijham G, Aranda E . Clinical determinants of survival in patients with 5-fluorouracil-based treatment for metastatic colorectal cancer: results of a multivariate analysis of 3825 patients. Ann Oncol. 2002; 13(2):308-17. DOI: 10.1093/annonc/mdf034. View

Lencioni R, Llovet J . Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 2010; 30(1):52-60. DOI: 10.1055/s-0030-1247132. View

10.

Aschoff A, Catalano C, Kirchin M, Krix M, Albrecht T . Low radiation dose in computed tomography: the role of iodine. Br J Radiol. 2017; 90(1076):20170079. PMC: 5603952. DOI: 10.1259/bjr.20170079. View

11.

Wu B, Yao Y, Zhang K, Ma X . RAS testing and cetuximab treatment for metastatic colorectal cancer: a cost-effectiveness analysis in a setting with limited health resources. Oncotarget. 2017; 8(41):71164-71172. PMC: 5642627. DOI: 10.18632/oncotarget.17029. View

12.

Heinemann V, Fischer von Weikersthal L, Decker T, Kiani A, Vehling-Kaiser U, Al-Batran S . FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014; 15(10):1065-75. DOI: 10.1016/S1470-2045(14)70330-4. View

13.

Van Cutsem E, Cervantes A, Nordlinger B, Arnold D . Metastatic colorectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014; 25 Suppl 3:iii1-9. DOI: 10.1093/annonc/mdu260. View

14.

Brufau B, Cerqueda C, Villalba L, Salvador Izquierdo R, Mellado Gonzalez B, Nicolau Molina C . Metastatic renal cell carcinoma: radiologic findings and assessment of response to targeted antiangiogenic therapy by using multidetector CT. Radiographics. 2013; 33(6):1691-716. DOI: 10.1148/rg.336125110. View

15.

Eisenhauer E, Therasse P, Bogaerts J, Schwartz L, Sargent D, Ford R . New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2008; 45(2):228-47. DOI: 10.1016/j.ejca.2008.10.026. View

16.

Giessen C, Graeven U, Laubender R, Modest D, Schulz C, Porschen R . Prognostic factors for 60-day mortality in first-line treatment of metastatic colorectal cancer (mCRC): individual patient analysis of four randomised, controlled trials by the AIO colorectal cancer study group. Ann Oncol. 2013; 24(12):3051-5. DOI: 10.1093/annonc/mdt402. View

17.

Douillard J, Oliner K, Siena S, Tabernero J, Burkes R, Barugel M . Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med. 2013; 369(11):1023-34. DOI: 10.1056/NEJMoa1305275. View

18.

Siegel R, Miller K, Jemal A . Cancer statistics, 2015. CA Cancer J Clin. 2015; 65(1):5-29. DOI: 10.3322/caac.21254. View

19.

Choi H . Response evaluation of gastrointestinal stromal tumors. Oncologist. 2008; 13 Suppl 2:4-7. DOI: 10.1634/theoncologist.13-S2-4. View

20.

Chun Y, Vauthey J, Boonsirikamchai P, Maru D, Kopetz S, Palavecino M . Association of computed tomography morphologic criteria with pathologic response and survival in patients treated with bevacizumab for colorectal liver metastases. JAMA. 2009; 302(21):2338-44. PMC: 4139149. DOI: 10.1001/jama.2009.1755. View