Neo-adjuvant Chemotherapy-Induced Neutropenia Is Associated with Histological Responses and Outcomes after the Resection of Colorectal Liver Metastases

Chen, Qichen; Wu, Chaorui; Zhao, Hong; Wu, Jianxiong; Zhao, Jianjun; Bi, Xinyu; Li, Zhiyu; Huang, Zhen; Zhang, Yefan; Zhou, Jianguo; Cai, Jianqiang

doi:10.1007/s11605-019-04202-3

Cited by 14 publications

(18 citation statements)

References 40 publications

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“…The mechanisms of this result may be as follows: (I) more NAC cycles would impair immune function and nutritional status (19,20), which is not conducive to the prognosis of patients (21). Some studies have shown that prolonging chemotherapy cycles leads to the occurrence of sarcopenia ( 22) and chemotherapy toxicities (12), and sarcopenia and NAC chemotherapy toxicities are significantly related to poor patient prognosis (13,23). (II) The sensitivity of the tumour to the chemotherapy regimen may decrease as the chemotherapy cycles are extended (24).…”

Section: Discussionmentioning

confidence: 99%

“…The targeted therapy regimens combined with NAC included bevacizumab or cetuximab. The NAC regimens, number of NAC cycles and timing of surgery were determined by a multidisciplinary team (MDT) including surgeons, oncologists, pathologists and imaging physicians, as previously described (13,14). NAC regiments were determined according to the characteristics of these regimens and the specific conditions of patients.…”

Section: Treatmentmentioning

confidence: 99%

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What is the optimal number of neoadjuvant chemotherapy cycles for resectable colorectal liver oligometastases?

Chen¹,

Li²,

Zhao³

et al. 2021

Ann Transl Med

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Background: The optimal number of neoadjuvant chemotherapy (NAC) cycles for resectable colorectal liver oligometastases (CLOM) remains unclear. The aim of this study was to investigate the optimal number of NAC cycles.Methods: One hundred twenty-nine consecutive patients were included in this study. X-tile analysis was implemented to investigate the optimal cut-off point for NAC cycles. Propensity score matching was performed to reduce selection bias. Kaplan-Meier curves and Cox risk regression models were used to analyse progression-free survival (PFS) and overall survival (OS). Results:The optimal cut-off point for NAC cycles was 5. There were no significant differences in R0 resection, pathological response or postoperative complications between the groups with a low number of NAC cycles group (≤5 cycles, n=80) and high number of NAC cycles (>5 cycles, n=49). Patients with a high number of NAC cycles were more likely to have NAC toxicity than those with a low number of cycles (87.8% vs. 65.0%, P=0.004). Multivariate analysis revealed that >5 NAC cycles was an independent predictor of reduced PFS (HR =1.808, 95% CI: 1.205-2.712, P=0.004) and reduced OS (HR =1.723, 95% CI: 1.041-2.851, P=0.034). In the oxaliplatin-based regimen group, patients with a low number of NAC cycles had a better PFS (P<0.001, mPFS: 14.7 vs. 5.4 months) and better OS (P=0.018, mOS: 57.7 months vs. 41.0 months) than those with a high number of cycles. After 1:1 propensity matching (34 cases vs. 34 cases), multivariate analysis revealed that >5 NAC cycles was an independent predictor of reduced PFS (HR =2.265, 95% CI: 1.281-4.007, P=0.005) and reduced OS (HR =2.813, 95% CI: 1.359-5.822, P=0.005). In the oxaliplatin-based regimen group, patients with a low number of NAC cycles had better PFS (P<0.001, mPFS: 17.5 vs. 5.6 months) and better OS (P=0.008, mOS: 59.0 vs. 31.8 months) than those with a high number of cycles. Conclusions: Fewer than 5 NAC cycles was optimal for biologically resectable CLOM patients. Giving more than 5 NAC cycles was unnecessary because a higher number of NAC cycles has more unfavourable survival and higher NAC toxicities, while leading to similar R0 resection rates and pathological responses.

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Section: Discussionmentioning

confidence: 99%

Section: Treatmentmentioning

confidence: 99%

What is the optimal number of neoadjuvant chemotherapy cycles for resectable colorectal liver oligometastases?

Chen¹,

Li²,

Zhao³

et al. 2021

Ann Transl Med

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“…The treatment strategies for CRLM were determined by a multidisciplinary team as described previously 5,15 . A flowchart about the treatment strategy of CRLM patients in this study is shown in Figure 2.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2020

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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.

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“…Liver resection of colorectal liver metastasis (CRLM) offers the best chance for a cure and long-term survival, as it has a five-year survival of up to 47-60%. Recurrences occur in 40-75% of patients with CRLM (2,4) and the incidence of postoperative complications is approximately 38-54% (5,6). Therefore, effective prediction of the survival of patients with CRLM in this specific clinical scenario is urgently needed.…”

Section: Introductionmentioning

confidence: 99%

Nomograms incorporating preoperative RDW level for the prediction of postoperative complications and survival in colorectal liver metastases after resection

et al. 2021

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Background: This study aimed to investigate the predictive significance of preoperative red cell volume distribution width (RDW) level for prognosis and to establish nomograms incorporating preoperative blood markers to predict postoperative complications and survival in patients with colorectal liver metastases (CRLM).Methods: This retrospective study included 380 enrolled CRLM patients who underwent hepatic resection.Predictors of postoperative complications were explored using binary logistic regression analysis. Covariates associated with overall survival (OS) and progression-free survival (PFS) were evaluated through univariate and multivariate Cox regression analyses. Only variables that reached statistical significance at P<0.1 in the univariate analysis were allowed to enter the multivariate analyses. The independent predictors that retained in the final multivariate model were incorporated into nomograms. Results:The optimal cut-off point of preoperative RDW-CV was 16%, and elevated RDW-CV was significantly associated with better prognosis (mPFS: 5.0 vs. 8.9 months, P=0.007; mOS: 59.0 vs. 42.0 months, P=0.041). The optimal cut-off point of preoperative RDW-SD was 43.9 fl, and elevated RDW-SD was significantly associated with worse prognosis (mPFS: 8.0 vs. 13.0 months, P<0.001; mOS:36.8 vs. 70.2 months, P=0.001). A nomogram predicting postoperative complications was constructed based on preoperative gamma-glutamyl transpeptidase (GGT) ≥34.5 U/L, preoperative RDW-CV ≥14.1%, and intraoperative blood loss ≥200.0 mL, with AUROC of 0.658. The calibration curves and Hosmer-Lemeshow test revealed desirable model calibration (chi-square: 3.99, P=0.91). A nomogram predicting PFS was constructed based on preoperative GGT ≥31.0 U/L, preoperative D-dimer ≥0.251 mg/L, preoperative RDW-CV <16.0%, preoperative RDW-SD ≥43.9 fl, positive lymph node metastasis, bilobar liver distribution, and R0 resection with good discrimination (C-index: 0.676±0.016) and calibration. A nomogram for the prediction of OS was constructed with favorable discrimination (C-index: 0.700±0.021) and calibration. Significant differences in PFS and OS were shown among patients stratified into three different risk groups (P<0.001) based on the nomograms. Conclusions: This study first revealed the relationship between preoperative RDW-SD, RDW-CV, and prognosis in patients with CRLM. It also established nomograms especially considering preoperative blood markers to predict postoperative complications, PFS, and OS, which facilitated physicians to determine the optimal clinical management strategies.

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Neo-adjuvant Chemotherapy-Induced Neutropenia Is Associated with Histological Responses and Outcomes after the Resection of Colorectal Liver Metastases

Cited by 14 publications

References 40 publications

What is the optimal number of neoadjuvant chemotherapy cycles for resectable colorectal liver oligometastases?

What is the optimal number of neoadjuvant chemotherapy cycles for resectable colorectal liver oligometastases?

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

Nomograms incorporating preoperative RDW level for the prediction of postoperative complications and survival in colorectal liver metastases after resection

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