The use of neo-adjuvant chemotherapy in patients with resectable colorectal liver metastases: Clinical risk score as possible discriminator

Ayez, Ninos; Stok, Eric P. van der; Grünhagen, Dirk J.; Rothbarth, Joost; Meerten, Esther van; Eggermont, Alexander; Verhoef, Cornelis

doi:10.1016/j.ejso.2015.04.012

Cited by 70 publications

(53 citation statements)

References 37 publications

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“…The pooled HR for 5-year OS of NEO calculated using a random-effects model was 0.69 (95% CI: 0.55-0.87; p = 0.000; I 2 = 0.0%, p = 0.48) (Supplementary Figure 3a). The same four studies identified factors contributing to a low risk of recurrence and compared the 5-year OS rate of NEO and SG [13, 14, 24, 28]. The pooled HR for 5-year OS of NEO calculated using a random-effects model was 1.10 (95% CI: 0.79-1.54; p = 0.58; I 2 = 34.8%, p = 0.20) (Supplementary Figure 3b).…”

Section: Resultsmentioning

confidence: 99%

“…Nine studies presented data on the R1 rate after hepatic resection in NEO and SG [11, 13, 14, 16, 17, 19, 22, 25, 26]. The pooled overall OR for NEO resection was 0.98 (95% CI: 0.95-1.00; p = 0.10; I 2 = 0.0%, p = 0.76), indicating that neoadjuvant chemotherapy didn not increase R1 rate after hepatic resection, as compared to SG (Supplementary Figure 5).…”

Section: Resultsmentioning

confidence: 99%

“…The most widely used and validated clinical risk scores were described by Fong et al and Nordlinger et al [33, 34]. Based on these scores, four studies identified factors associated with a high risk of recurrence [13, 14, 24, 28]. However, the prognostic significance of the majority of these factors was determined at a time when effective cytotoxic agents were not available.…”

Section: Discussionmentioning

confidence: 99%

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The role of neoadjuvant chemotherapy for resectable colorectal liver metastases: a systematic review and meta-analysis

et al. 2016

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Neoadjuvant chemotherapy is being increasingly accepted as an effective treatment of resectable colorectal liver metastases (CRLM), but it may also damage the hepatic parenchyma. We performed a meta-analysis to compare the outcomes of patients who received neoadjuvant chemotherapy (NEO) prior to hepatic resection with hepatic resection without neoadjuvant chemotherapy (SG). Eligible trials were identified from Embase, PubMed, the Web of Science and the Cochrane library. Hazard ratios (HRs) with a 95% confidence intervals (CIs) were used to measure the pooled effect using a random-effects model. Statistical heterogeneity was detected by I2 test. Sensitivity analyses and publication bias were also assessed. The study outcomes included 3-year, 5-year disease-free and overall survival rate, respectively. Eighteen studies involving 6,254 patients were included. The pooled HRs for 5-year DFS and 5-year OS for NEO in the included studies calculated using the random-effects model were 1.38 (95 % CI; 1.26-1.51, p=0.00; I2=9.6%, p=0.36) and 1.19 (95% CI: 1.02-1.38; p=0.03; I2=49.2%, p=0.03), respectively. For CRLM patients with factors indicating a high risk of recurrence, the pooled HR for 5-year OS of NEO in the included studies calculated using the random-effects model was 0.69 (95% CI: 0.55-0.87; p=0.00; I2=0.0%, p=0.48). These results suggest neoadjuvant chemotherapy improved survival of patients with initially resectable CRLM and a high risk of disease recurrence.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The role of neoadjuvant chemotherapy for resectable colorectal liver metastases: a systematic review and meta-analysis

et al. 2016

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“…Identification of patients for neo‐adjuvant (preoperative) therapy is certainly possible since prognostic gene expression profiles may be detected in liquid biopsies before surgery (Mostert et al., 2013, 2015). Currently the clinical risk scores do not impact clinical management, although some retrospective reports have suggested they may be effective (Ayez et al., 2015a; Rahbari et al., 2014) (this is prospectively investigated at present in the CHARISMA trial (Ayez et al., 2015b)). There may be a synergistic effect between the clinical risk score and the molecular score of the current study.…”

Section: Discussionmentioning

confidence: 99%

mRNA expression profiles of colorectal liver metastases as a novel biomarker for early recurrence after partial hepatectomy

et al. 2016

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SurgeryBiomarker mRNA Prognostic value A B S T R A C TBackground: Identification of specific risk groups for recurrence after surgery for isolated colorectal liver metastases (CRLM) remains challenging due to the heterogeneity of the disease. Classical clinicopathologic parameters have limited prognostic value. The aim of this study was to identify a gene expression signature measured in CRLM discriminating early from late recurrence after partial hepatectomy. Methods: CRLM from two patient groups were collected: I) with recurrent disease 12 months after surgery (N ¼ 33), and II) without recurrences and disease free for !36 months (N ¼ 30). The patients were clinically homogeneous; all had a low clinical risk score (0e2) and did not receive (neo-) adjuvant chemotherapy. Total RNA was hybridised to Illumina arrays, and processed for analysis. A leave-one-out cross validation (LOOCV) analysis was performed to identify a prognostic gene expression signature. Results: LOOCV yielded an 11-gene profile with prognostic value in relation to recurrent disease 12 months after partial hepatectomy. This signature had a sensitivity of 81.8%, with a specificity of 66.7% for predicting recurrences ( 12 months) versus no recurrences for at least 36 months after surgery (X 2 P < 0.0001). Conclusion:The current study yielded an 11-gene signature at mRNA level in CRLM discriminating early from late or no relapse after partial hepatectomy.

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“…In the high CRS (3-5) group, there was a significant difference in OS between patients with and without CHT (46 months vs. 33 month, p value = 0.004). The authors concluded that patients with a high CRS benefit from neo-adjuvant CHT, while in patients with a low risk profile, neo-adjuvant CHT might not be beneficial (81).…”

Section: B Long Term Outcomesmentioning

confidence: 99%

Surgical Options in Synchronous Liver Metastases from Colorectal Cancer

Alexandrescu¹,

Diaconescu²,

Popescu³

2017

JTMR

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Currently, the treatment of liver metastases of colorectal cancer (CRC) requires a multidisciplinary approach and should be individualized for each patient. Liver resection provides 5 years survival rates ranging between 30 and 58% in patients with liver metastases of CRC. The optimal timing of liver resection, resection of the primary tumor and neoadjuvant chemotherapy has not been fully established, yet, neither for initially resectable synchronous liver metastases, nor for those initially unresectable which could be converted to resectability. Advocates of simultaneous resection and those of staged resection (delayed liver resection or "liver first approach"), both presented theoretical arguments in favor of each of these therapeutic strategies. Progresses in liver surgery, anesthesia, intensive care and oncology caused a paradigm shift regarding the approach of synchronous colorectal liver metastases, with simultaneous resection (SR) becoming a safer procedure in the last decade. As well, the oncologic outcomes of SR are similar to those achieved by staged resection. In this review we present the literature data concerning the results achieved by each of the currently available therapeutic approaches. Abbreviations: CLMs -colorectal liver metastases, SCLMs -synchronous colorectal liver metastases, CRC -colorectal cancer, PVL-portal vein ligation, PVE -portal vein embolization, SR -simultaneous resection, DR -delayed liver resection, SgR -staged resections, FLR -future liver remnant, CHT -chemotherapy, OS -overall survival, DFS -disease-free survival, ETS -early tumor shrinkage

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The use of neo-adjuvant chemotherapy in patients with resectable colorectal liver metastases: Clinical risk score as possible discriminator

Cited by 70 publications

References 37 publications

The role of neoadjuvant chemotherapy for resectable colorectal liver metastases: a systematic review and meta-analysis

The role of neoadjuvant chemotherapy for resectable colorectal liver metastases: a systematic review and meta-analysis

mRNA expression profiles of colorectal liver metastases as a novel biomarker for early recurrence after partial hepatectomy

Surgical Options in Synchronous Liver Metastases from Colorectal Cancer

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