Use of Neoadjuvant Chemotherapy Plus Molecular Targeted Therapy in Colorectal Liver Metastases: A Systematic Review and Meta-analysis

Sabanathan, Dhanusha; Eslick, Guy D.; Shannon, Jenny

doi:10.1016/j.clcc.2016.03.007

Cited by 31 publications

(19 citation statements)

References 22 publications

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“…Current guidelines suggest oxaliplatin-based doublet chemotherapy (FOLFOX/ XELOX) as the neoadjuvant treatment-of-choice for resectable CRLM, while FOLFIRI or FOLFOXIRI are alternatives[9,10]. A meta-analysis showed the addition of molecular targeted therapy conferred a higher overall response rate than chemotherapy alone (68% vs 43%), but did not improve survival[56]. A lack of PFS benefit was also observed in the New EPOC trial, which studied the effect of combining EGFR-inhibitor (cetuximab) to perioperative systemic chemotherapy; patients who received cetuximab actually experienced worse PFS (14.1 vs 20.5 months in control)[57].…”

Section: Neoadjuvant Treatmentmentioning

confidence: 99%

Colorectal liver metastases: An update on multidisciplinary approach

Chow¹,

Chok²

2019

WJH

190

148

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Liver metastasis is the commonest form of distant metastasis in colorectal cancer. Selection criteria for surgery and liver-directed therapies have recently been extended. However, resectability remains poorly defined. Tumour biology is increasingly recognized as an important prognostic factor; hence molecular profiling has a growing role in risk stratification and management planning. Surgical resection is the only treatment modality for curative intent. The most appropriate surgical approach is yet to be established. The primary cancer and the hepatic metastasis can be removed simultaneously or in a two-step approach; these two strategies have comparable long-term outcomes. For patients with a limited future liver remnant, portal vein embolization, combined ablation and resection, and associating liver partition and portal vein ligation for staged hepatectomy have been advocated, and each has their pros and cons. The role of neoadjuvant and adjuvant chemotherapy is still debated. Targeted biological agents and loco-regional therapies (thermal ablation, intra-arterial chemo- or radio-embolization, and stereotactic radiotherapy) further improve the already favourable results. The recent debate about offering liver transplantation to highly selected patients needs validation from large clinical trials. Evidence-based protocols are missing, and therefore optimal management of hepatic metastasis should be personalized and determined by a multi-disciplinary team.

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Section: Neoadjuvant Treatmentmentioning

confidence: 99%

Colorectal liver metastases: An update on multidisciplinary approach

Chow¹,

Chok²

2019

WJH

190

148

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“…These recommendations are based on the results of Phase II and III trials that demonstrated improved median OS and progression-free survival (PFS) with combination therapy versus 5-FU and LV alone. A recent meta-analysis found however, that the response rates in these trials averaged only 68% (16). First line regimens may also include the combination of FOLFOX or FOLFIRI with: 1) Bevacizumab; 2) Cetuximab; or 3) Panitumumab.…”

Section: A Backgroundmentioning

confidence: 99%

Molecular Pathways: Targeting the Microenvironment of Liver Metastases

Milette

Sicklick

Lowy

et al. 2017

Clinical Cancer Research

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Curative treatment for metastatic solid cancers remains elusive. The liver, which is nourished by a rich blood supply from both the arterial and portal venous systems is the most common site of visceral metastases, particularly from cancers arising in the gastrointestinal (GI) tract, with colorectal cancer (CRC) being the predominant primary site in Western countries. A mounting body of evidence suggests that the liver microenvironment (LME) provides autocrine and paracrine signals originating from both parenchymal and non-parenchymal cells, that collectively create both pre-and pro-metastatic niches for the development of hepatic metastases. These resident cells and their molecular mediators represent potential therapeutic targets for the prevention and/or treatment of liver metastases (LM). This review summarizes: 1) the current therapeutic options for treating LM with a particular focus on CRC LM (CRCLM); 2) the role of the LME in LM at each of its phases 3) potential targets in the LME identified through pre-clinical and clinical investigations and 4) potential therapeutic approaches for targeting elements of the LME before and/or after the onset of LM, as the basis for future clinical trials.

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“…Hepatic steatosis can be used as an independent predictor of postoperative complications. Other studies have shown that moderate or more severe SOS will increase the risk of postoperative complications, mainly infection and bleeding [35,36]. Therefore, it is important to determine the timing, mode, and prognosis of surgery by observing the state of the liver as a whole, using intuitive imaging methods, performing a non-invasive quantitative evaluation before surgery [37].…”

Section: Discussionmentioning

confidence: 99%

“…And the efficiency of some imaging biomarkers like CT value only reflect the part, not the whole. Although several novel imaging approaches have been studied, no single modality, currently, can roundly and accurately assess and grade liver injury with NC [ 35 – 37 ].…”

Section: Discussionmentioning

confidence: 99%

“…These pathological changes in our study are consistent with the reported expert consensus [ 23 ], and might cause a reduction in effective blood perfusion and an increase in fat content within liver parenchyma [ 24 ]. Previous studies using IVIM-DWI demonstrated the change of effective blood volume before and after chemotherapy and liver fibrosis [ 14 , 17 ], and using PDFF and 25OH-VitD3 demonstrated an increase in fat content of patients with NAFLD [ 33 – 35 , 38 ]. Hence, the quantification of blood perfusion and fat content within liver parenchyma might help to diagnose and grade liver damage related NC in patients with CRCLM.…”

Section: Discussionmentioning

confidence: 99%

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Quantified MRI and 25OH-VitD3 can be used as effective biomarkers for patients with neoadjuvant chemotherapy-induced liver injury in CRCLM?

Wang

et al. 2020

BMC Cancer

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Background: To evaluate proton-density fat-fraction (PDFF) and intravoxel incoherent motion (IVIM) techniques, and human 25-hydroxyvitamin D3 (25OH-VitD3) levels, as potential biomarkers in patients with colorectal cancer with liver metastasis (CRCLM). Changes were compared with those related to chemotherapy-associated steatohepatitis (CASH) and sinusoidal obstruction syndrome (SOS). Methods: 63 patients with pathologically confirmed colorectal adenocarcinoma received 4-6 courses of NC before liver resection and underwent magnetic resonance imaging (MRI) with iterative decomposition of water and fat with echo asymmetry and least-squares estimation quantification and IVIM sequences. Blood samples were analyzed using CTCAE. Pathological changes of liver tissues outside the metastases were assessed as the gold standard, and receiver operating characteristic (ROC) curves were analyzed. Results: 16 cases had CASH liver injury, 14 cases had SOS changes, and 4 cases had CASH and SOS, and 7 showed no significant changes. Consistency between biochemical indices and pathological findings was poor (kappa = 0.246, p = 0.005). The areas under the ROC curve (AUCs) of ALT, AST, ALP, GGT, and TBIL were 0.571-0.691. AUCs of D, FF, and 25OH-VitD3 exceeded 0.8; when considering these markers together, sensitivity was 85.29% and specificity was 93.13%. ANOVA showed statistically significant differences among D, FF, and 25OH-VitD3 for different grades of liver injury (F = 4.64-26.5, p = 0.000-0.016). Conclusions: D, FF, and 25OH-VitD3 are biomarkers for accurate prediction of NC-induced liver injury in patients with CRCLM, while FF and 25OH-VitD3 might be beneficial to distinguish liver injury grades. Trial registration: Current Trials was retrospectively registered as ChiCTR1800015242 at Chinese Clinical Trial Registry on March 16, 2018.

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Use of Neoadjuvant Chemotherapy Plus Molecular Targeted Therapy in Colorectal Liver Metastases: A Systematic Review and Meta-analysis

Cited by 31 publications

References 22 publications

Colorectal liver metastases: An update on multidisciplinary approach

Colorectal liver metastases: An update on multidisciplinary approach

Molecular Pathways: Targeting the Microenvironment of Liver Metastases

Quantified MRI and 25OH-VitD3 can be used as effective biomarkers for patients with neoadjuvant chemotherapy-induced liver injury in CRCLM?

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