Early response evaluation during preoperative chemotherapy for colorectal liver metastases: Combined size and morphology-based criteria predict pathological response and survival after resection.

Florian Primavesi,Eva Gassner,Eva Braunwarth,Dietmar Öfner,Nikolaus Fadinger,Georg Göbel,Simon Biggel,Stefan Stättner,Susanne Sprung,Elisabeth Gasser

doi:10.1002/jso.25796

Abstract

BackgroundShort treatment‐duration with early restaging is crucial to avoid liver injury after preoperative chemotherapy (preopCTX) for colorectal liver metastases (CRLM). Response evaluation according to response evaluation criteria in solid tumors (RECIST) criteria implies several limitations. Early tumor shrinkage (ETS; ≥20% size reduction <6‐12 weeks) or morphological criteria (MC) may better predict oncological outcome.MethodsIn patients undergoing resection after preopCTX between 2003–2017 pathological and radiological response was reassessed according to Blazer classification, ETS, MC, and RECIST within 90 days and correlated with survival.ResultsSeventy‐two patients were included, with a median of two (1‐10) liver lesions, 53% bilobar involvement, and 7% extrahepatic disease. PreopCTX was applied for 3 months in median (1‐6). During restaging after a median of 62 days, presence of ETS was associated with improved median overall survival (OS; 57.1 vs 33.7 months; P = .010) and disease‐free survival (16 vs 7.2 months; P = .025). MC significantly correlated with major pathological response (P = .021). When combining ETS with optimal MC, presence of one or both factors was associated with pathological response (61.5% and 92.3%; P = .044) and OS in log‐rank (P = .011), and multivariable analysis (hazard ratio [HR] 0.41; 95% confidence interval [CI], 0.19‐0.90 and HR 0.32; 95%CI, 0.11‐0.97).ConclusionResponse‐grading by combined ETS/MC criteria less than 90 days after preopCTX initiation predicts pathological response and postoperative survival in CRLM.

Highlights

The liver represents the most frequent site of metastases in colorectal cancer (CRC), affecting about 15% to 20% of newly diagnosed CRC cases simultaneously,[1,2] and 20% to 50% of patients in the further course of the disease.[3]
While our cohort represents typical western world colorectal liver metastases (CRLM) patients, notable the majority had synchronous disease with advanced, multiple liver metastases up to 10.5 cm, preoperatively treated mostly with oxaliplatin‐based chemotherapy and additional biologicals. 90‐day‐morbidity occurred in 23 patients (31.9%), whereby 9 (12.5%) experienced severe complications (≥3b Dindo‐ Clavien) and one patient (1.4%) deceased
Early tumor shrinkage (ETS) defined by ≥20% tumor shrinkage was present in 70.8%, suboptimal or optimal morphological criteria (MC) response in 19.4% and 26.4%, respectively

Summary

| INTRODUCTION

The liver represents the most frequent site of metastases in colorectal cancer (CRC), affecting about 15% to 20% of newly diagnosed CRC cases simultaneously,[1,2] and 20% to 50% of patients in the further course of the disease.[3]. A previous single center study showed, that response assessment according to morphological criteria (MC) with evaluation of changes in radiological CRLM appearance (tumor density, tumor‐liver border) better predicts histological viability and prognosis after liver resection than size‐based criteria like RECIST.[26,27]. The present study aims to investigate the prognostic value of early response assessment by ETS and MC within 90 days after preopCTX initiation in CRLM patients undergoing liver resection. Two radiologists with >30 years combined clinical experience blinded for treatment and outcome of patients reviewed baseline and first restaging CT images for response according to three previously reported criteria: (a) RECIST 1.1.18; (b) ETS (≥20% shrinkage within 90 days after CTX start)[19]; (c) MC26 (3 groups; Figure 2A,B). Calculations were performed with SPSS Version 21 (IBM Inc, Armonk, NY), a two‐tailed P value of

| RESULTS

| DISCUSSION

| CONCLUSIONS