The Prognostic Significance of Metabolic Response Heterogeneity in Metastatic Colorectal Cancer

Abstract

BackgroundTumoral heterogeneity is a major determinant of resistance in solid tumors. FDG-PET/CT can identify early during chemotherapy non-responsive lesions within the whole body tumor load. This prospective multicentric proof-of-concept study explores intra-individual metabolic response (mR) heterogeneity as a treatment efficacy biomarker in chemorefractory metastatic colorectal cancer (mCRC).MethodsStandardized FDG-PET/CT was performed at baseline and after the first cycle of combined sorafenib (600mg/day for 21 days, then 800mg/day) and capecitabine (1700 mg/m²/day administered D1-14 every 21 days). MR assessment was categorized according to the proportion of metabolically non-responding (non-mR) lesions (stable FDG uptake with SUVmax decrease <15%) among all measurable lesions.ResultsNinety-two patients were included. The median overall survival (OS) and progression-free survival (PFS) were 8.2 months (95% CI: 6.8–10.5) and 4.2 months (95% CI: 3.4–4.8) respectively. In the 79 assessable patients, early PET-CT showed no metabolically refractory lesion in 47%, a heterogeneous mR with at least one non-mR lesion in 32%, and a consistent non-mR or early disease progression in 21%. On exploratory analysis, patients without any non-mR lesion showed a significantly longer PFS (HR 0.34; 95% CI: 0.21–0.56, P-value <0.001) and OS (HR 0.58; 95% CI: 0.36–0.92, P-value 0.02) compared to the other patients. The proportion of non-mR lesions within the tumor load did not impact PFS/OS.ConclusionThe presence of at least one metabolically refractory lesion is associated with a poorer outcome in advanced mCRC patients treated with combined sorafenib-capecitabine. Early detection of treatment-induced mR heterogeneity may represent an important predictive efficacy biomarker in mCRC.Trial RegistrationClinicalTrials.gov NCT01290926

Heterogeneous radiological response to neoadjuvant therapy is associated with poor prognosis after resection of colorectal liver metastases

“…One-third of our patients received EGFR and/or VEGF inhibitors, but the number of patients with CT before and after treatment was too low to perform meaningful analyses of morphological response. Chemotherapy-induced metabolic changes of metastases can be demonstrated with PET/CT [36], and most studies show a correlation with pathological response and survival [37e41], also for heterogeneous response [42], but the method is not in routine use in resectable CRLM.…”

The metabolic clinical risk score as a new prognostic model for surgical decision‐making in patients with colorectal liver metastases

“…Finally, other metabolic parameters, such as the heterogeneity of the tumor metabolism, could also be considered to improve the performance of such metabolic clinical scores. [33][34][35]…”

Is early response by 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography a predictor of long-term outcome in patients with metastatic colorectal cancer?

“…Other confounding factor is the heterogeneity of metabolic response within body tumor load. In a recent trial, in metastatic CRC patients treated with capecitabine and sorafenib, a PET-CT performed after the first cycle of therapy with at least one metabolically refractory lesion is associated with poor outcome (40). An interesting result in the present study is the unplanned analysis of the patients had not submitted to metastases resection.…”