Prognostic Value of Sarcopenia in Metastatic Colorectal Cancer Patients Treated with Trifluridine/Tipiracil

Abstract

Sarcopenia is common in metastatic colorectal cancer (mCRC), increases the risk of treatment-related toxicity and reduces survival. Trifluridine/tipiracil (TT) chemotherapy significantly improved survival in refractory mCRC patients, but the prognostic and predictive role of pretherapeutic sarcopenia and variation in the skeletal muscle index (SMI) during this treatment has not been investigated so far. In this retrospective, observational study, clinical data on mCRC patients treated with TT at six cancer centres in Poland were collected. Computed tomography (CT) scans acquired at the time of initiation of TT (CT1) and on the first restaging (CT2), were evaluated. SMI was assessed based on the skeletal muscle area (SMA) at the level of the third lumbar vertebra. Progression-free survival (PFS) and overall survival (OS) were calculated from the treatment start. Neither initial sarcopenia nor ≥5% skeletal mass loss (SML) between CT1 and CT2 had a significant effect on PFS in treated patients (p = 0.5526 and p = 0.1092, respectively). In the multivariate analysis, reduced OS was found in patients with ≥5% SML (HR: 2.03 (1.11-3.72), p = 0.0039). We describe the prognostic role of sarcopenia beyond second line treatment and analyze other factors, such as performance status, tumor histological differentiation or carcinoembryonic antigen level that could predict TT treatment response.

Keywords: cancer cachexia; metastatic colorectal cancer; sarcopenia; trifluridine/tipiracil.

Figure 1

(A) Example of contrast-enhanced computed tomography scan of the third lumbar vertebra (L3) region in the venous phase (contains psoas, paraspinal and abdominal wall muscles); (B) image processed by Data Analysis Facilitation Suite ver. 2.0.5 by Voronoi Health Analytics, Vancouver, Canada with the Automatic Body composition Analyzer using Computed tomography image Segmentation module provided by Voronoi Health Analytics, Canada (2020); non-optimal segmentations were re-edited using open-source software 3D Slicer ver. 4.11 by 3D Slicer, Boston, MA, USA; skeletal muscles (pink) are separated from intra-abdominal fat (yellow) and subcutaneous fatty tissue (blue).

Figure 2

Kaplan–Meier curves showing (A) progression-free survival under trifluridine/tipiracil; (B) overall survival under trifluridine/tipiracil.

Figure 3

(A,B): Kaplan–Meier curves (KMC) showing progression-free survival under trifluridine/tipiracil. (A): KMC adjusted to baseline sarcopenia (yes or no); (B): KMC adjusted to carcinoembryonic antigen (normal or elevated); (C): KMC showing overall survival under trifluridine/tipiracil adjusted to SMI significant decrease on treatment (yes or no).