From the completion of neoadjuvant chemotherapy to surgery for colorectal cancer liver metastasis: What is the optimal timing?

Abstract

Background Neoadjuvant chemotherapy (NAC) has been widely performed in the treatment of colorectal cancer liver metastasis (CRLM) patients, but the optimal timing of surgery after NAC is unclear. The aim of this study was to investigate the optimal timing of surgery. Methods From December 2010 to May 2018, 101 consecutive patients who received NAC followed by liver resection for CRLM were included in this study. The main outcome parameters were pathological response, progression‐free survival (PFS), and overall survival (OS). The effect of time to surgery (TTS) on patient outcomes, defined as a high TTS and a low TTS according to an X‐tile analysis, was investigated. To adjust for potential selection bias, propensity score matching at 1:2 was performed with two high TTS patients matched to one low TTS patient. Kaplan‐Meier curves, logistic regression analyses, and Cox regression models were used for the data analysis. Results The optimal cut‐off value for the TTS was 5 weeks by X‐tile analysis. The patients in this study were divided into low (≤5 weeks, n = 27) and high (>5 weeks, n = 74) TTS groups. Patients with a high TTS were more likely to have an unfavorable pathological response (75.7% vs 48.1%, P = .008). In multivariate analysis, a low TTS significantly predicted a better pathological response (OR = 3.397, 95% CI: 1.116‐10.344, P = .031). Compared to patients with a high TTS, patients with a low TTS had significantly better PFS (P < .001, mPFS: 16 months vs 7 months) and better OS (P = .037, mOS: not reached vs 36 months). Multivariate analysis revealed that a TTS > 5 weeks was an independent predictor of decreased PFS (HR = 2.041, 95% CI: 1.152‐3.616, P = .014) but not OS. After propensity matching, the patients with a low TTS had significantly better PFS (P < .001, mPFS: 18.2 months vs 10 months) and an equivalent OS (P = .115, mOS: not reached vs 41 months). Multivariate analysis revealed that a TTS > 5 weeks was an independent predictor of decreased PFS (HR = 3.031, 95% CI: 1.494‐6.149, P = .002) but not OS. Conclusion The longer TTS after the completion of NAC may be disadvantageous for a favorable pathological response and long‐term PFS. These results should be validated prospectively in a randomized trial.

Predictive value of red blood cell distribution width level on histological response and prognosis in colorectal liver metastases

“…Thus, a primary tumour in the right colon with a favorable pathological response is reasonable. In addition, a significant correlation between the radiological response and the pathological response was identified, consistent with a previous study (11). This Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the noncommercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license).…”

“…Accumulating evidence unequivocally demonstrates that NAC can significantly prolong the survival of CRLM patients who undergo liver resection (7)(8)(9). Pathological response is an important factor in the evaluation of chemotherapy efficacy and the prediction of outcomes in patients treated with NAC followed by liver resection (10,11). A favorable pathological response, which has been recognized as a predictor of improved postoperative survival, was observed in 45-57% of these patients (12,13).…”

“…In addition, there is no study focusing on the predictive value of RDW level in CRLM patients. Pre-NAC testing markers and the fluctuation in testing markers during NAC have a potentially predictive value for pathological response and survival in CRLM patients (6,11,12). Consequently, we sought to comprehensively determine the value of RDW in CRLM patients by evaluating the predictive value of the pre-neoadjuvant chemotherapy (pre-NAC) RDW level, the preoperative RDW level and the fluctuation between the pre-NAC RDW level and the preoperative RDW level.…”

Recent Developments in Inonotus obliquus (Chaga mushroom) Polysaccharides: Isolation, Structural Characteristics, Biological Activities and Application

“…The anticancer mechanism of IOPS mainly includes: Decreasing the expression of MMP-2, MMP-7, and MMP-9, increasing the expression of tissue metallopeptidase inhibitor 2 (TIMP-2), and decreasing the expression of NF-κB in cancer cells [2,3,8,9,[84][85][86][87][88][89][90][91].…”

2-4 weeks is the optimal time to operate on colorectal liver metastasis after neoadjuvant chemotherapy

“…Adam et al (29) found that disease progressed in about 25% of patients during the interval between NAC and surgery. Another study found that the cohort of patients who underwent resection more than 5 weeks after NAC, compared to the group that underwent less than 5 weeks after, had a worse pathological reaction and worse RFS (30). Thomas et al (13) concluded that surgery within 2 months of NAC improved long-term outcomes.…”