Towards volumetric thresholds in RECIST 1.1: Therapeutic response assessment in hepatic metastases
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To empirically determine thresholds for volumetric assessment of response and progress of liver metastases in line with the unidimensional RECIST thresholds.
Patients with metastatic colorectal cancer initially enrolled in a multicentre clinical phase-III trial were included. In all CT scans, the longest axial diameters and volumes of hepatic lesions were determined semi-automatically. The sum of diameters and volumes of 1, ≤2 and ≤5 metastases were compared to all previous examinations. Volumetric thresholds corresponding to RECIST 1.1 thresholds were predicted with loess-regression. In sensitivity analysis, the concordances of proposed thresholds, weight-maximizing thresholds and thresholds from loess-regression were compared. Classification concordance for measurements of ≤2 metastases was further analyzed.
For measurements of ≤2 metastases, 348 patients with 629 metastases were included, resulting in 4,773 value pairs. Regression analysis yielded volumetric thresholds of -65.3% for a diameter change of -30%, and +64.6% for a diameter change of +20%. When comparing measurements of unidimensional RECIST assessment with volumetric measurements, there was a concordance of significant progress (≥+20% and ≥+65%) in 88.3% and of significant response (≤-30% and ≤-65%) in 85.0%.
In patients with hepatic metastases, volumetric thresholds of +65% and -65% were yielded corresponding to RECIST thresholds of +20% and -30%.
• Volumes and diameters of liver metastases from colorectal cancer were determined.
• Volumetric thresholds of +65%/-65% corresponding to RECIST 1.1 are proposed.
• Comparing both measurements, concordance was 88.3% (significant progress) and 85.0% (significant response).
KeywordsTomography, X-Ray computed Liver Neoplasm metastasis Image interpretation, computer-assisted Response evaluation criteria in solid tumors
Abbreviations and acronyms
Epidermal growth factor receptor
FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as irst-line treatment for patients with metastatic colorectal cancer
Folinic acid, fluorouracil and irinotecan
Vascular endothelial growth factor
The authors would like to thank Merck KGaA Darmstadt, Germany, for providing financial support to perform the current study.
This study has received funding by Merck KGaA Darmstadt, Germany.
Compliance with ethical standards
The scientific guarantor of this publication is Melvin D’Anastasi.
Conflict of interest
The authors of this manuscript declare relationships with the following companies: Merck KGaA Darmstadt, Germany.
Julian Walter Holch served on advisory board for Roche, has received honoraria from Roche and travel support from Novartis
Honoraria: Merck, Amgen, Roche, BMS, MSD, Servier, Sirtex
Travel Support: Amgen, Merck, Roche, Bayer, BMS
Research Grant: Merck, Amgen, Roche
Honoraria for talks and advisory board role from: AMGEN, Bayer, Lilly, Merck KgaA, Roche, Sanofi, Takeda
Honoraria (myself): Merck, Amgen, Roche, Sanofi, SIRTEX, Servier Consulting or Advisory Board (myself): Merck, Amgen, Roche, Sanofi, SIRTEX, BMS; MSD, Novartis, Boehringer Ingelheim, Servier Research funding (my institution): Merck, Amgen, Roche, Sanofi, Pfizer, Boehringer Ingelheim, Sirtex, Bayer Travel accommodation expenses (myself): Merck, Roche, Amgen, SIRTEX, Bayer
Founder Smart Reporting GmbH
Statistics and biometry
One of the authors has significant statistical expertise.
Written informed consent was waived by the Institutional Review Board.
Institutional Review Board approval was obtained.
Study subjects or cohorts overlap
Heinemann V, Fischer von Weikersthal L, Decker T, et al. 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):1065-1075.
Stintzing S, Modest DP, Fischer von Weikersthal L, et al. Independent radiological evaluation of objective response, early tumor shrinkage, and depth of response in FIRE-3 (AIO KRK-0306) in the final RAS evaluable population. Ann Oncol 2014;25(supp 5):v1-v41.
Stintzing S, Modest DP, Rossius L, et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab for metastatic colorectal cancer (FIRE-3): a post-hoc analysis of tumor dynamics in the final RAS wild-type subgroup of this randomised open-label phase 3 trial. Lancet Oncol 2016;17(10):1426-1434.
Stintzing S, Jung A, Rossius L, et al. Mutations within the EGFR signaling pathway: Influence on efficacy in FIRE-3--A randomized phase III study of FOLFIRI plus cetuximab or bevacizumab as first-line treatment for wild-type (WT) KRAS (exon 2) metastatic colorectal cancer (mCRC) patients. J Clin Oncol 2014;32(suppl 3; abstr 445).
Stintzing S, Zhang W, Heinemann V, et al. Polymorphisms in Genes Involved in EGFR Turnover Are Predictive for Cetuximab Efficacy in Colorectal Cancer. Mol Cancer Ther 2015;14(10):2374-2381.
Sebio A, Stintzing S, Heinemann V, et al. A genetic variant in Rassf1a predicts outcome in mCRC patients treated with cetuximab plus chemotherapy: results from FIRE-3 and JACCRO 05 and 06 trials. Pharmacogenomics J 2016.
Modest DP, Ricard I, Heinemann V, et al. 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):1746-1753.
Sunakawa Y, Stintzing S, Cao S, et al. Variations in genes regulating tumor-associated macrophages (TAMs) to predict outcomes of bevacizumab-based treatment in patients with metastatic colorectal cancer: results from TRIBE and FIRE3 trials. Ann Oncol 2015;26(12):2450-2456.
Modest DP, Stintzing S, Fischer von Weikersthal L, et al. Impact of Subsequent Therapies on Outcome of the FIRE-3/AIO KRK0306 Trial: First-Line Therapy With FOLFIRI Plus Cetuximab or Bevacizumab in Patients With KRAS Wild-Type Tumors in Metastatic Colorectal Cancer. J Clin Oncol 2015;33(32):3718-3726.
Michl M, Stintzing S, Fischer von Weikersthal L, et al. CEA response is associated with tumor response and survival in patients with KRAS exon 2 wild-type and extended RAS wildtype metastatic colorectal cancer receiving first-line FOLFIRI plus cetuximab or bevacizumab (FIRE-3 trial). Ann Oncol 2016;27(8):1565-1572.
Tejpar S, Stintzing S, Ciardiello F, et al. Prognostic and Predictive Relevance of Primary Tumor Location in Patients With RAS Wild-Type Metastatic Colorectal Cancer: Retrospective Analyses of the CRYSTAL and FIRE-3 Trials. JAMA Oncol 2016.
“Prognostic value of radiologically enlarged lymph nodes in patients with metastatic colorectal cancer: subgroup findings of the randomized, open-label FIRE-3/AIO KRK0306 trial” (meanwhile published in European Journal of Radiology)
• multicentre study
- 10.Therasse P, Arbuck SG, Eisenhauer EA et al (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92(3):205–216CrossRefGoogle Scholar
- 11.Stintzing S, Modest DP, Rossius L, et al. (2016) FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab for metastatic colorectal cancer (FIRE-3): a post-hoc analysis of tumor dynamics in the final RAS wild-type subgroup of this randomised open-label phase 3 trial. Lancet Oncol. https://doi.org/10.1016/s1470-2045(16)30269-8 CrossRefGoogle Scholar
- 19.Auguie B (2016) gridExtra: Miscellaneous Functions for "Grid" Graphics. Available via https://CRAN.R-project.org/package=gridExtra. Accessed 30 May 2016