The Efficacy and Safety of First-line Chemotherapy in Advanced Esophagogastric Cancer: A Network Meta-analysis

Veer, Emil ter; Mohammad, Nadia Haj; Valkenhoef, Gert van; Ngai, Lok Lam; Mali, Rosa M A; Anderegg, Maarten; Oijen, Martijn G.H. van; Laarhoven, Hanneke W. M. van

doi:10.1093/jnci/djw166

Cited by 95 publications

(66 citation statements)

References 86 publications

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“…Results from NMA-2 indicated that oxaliplatin was preferable compared to cisplatin. Findings in advanced esophagogastric cancer support the use of oxaliplatin over cisplatin [66,67,68,69,70,71,72,73,74]. Also, the addition of oxaliplatin to a fluoropyrimidine in a prolonged-adjuvant treatment course conveyed survival benefit compared to fluoropyrimidine-monotherapy although OS results were non-significant due to a lack of power.…”

Section: Discussionmentioning

confidence: 99%

The Efficacy and Safety of (Neo)Adjuvant Therapy for Gastric Cancer: A Network Meta-analysis

Ende

Veer

Machiels

et al. 2019

Cancers

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Background: Alternatives in treatment-strategies exist for resectable gastric cancer. Our aims were: (1) to assess the benefit of perioperative, neoadjuvant and adjuvant treatment-strategies and (2) to determine the optimal adjuvant regimen for gastric cancer treated with curative intent. Methods: PubMed, EMBASE, CENTRAL, and ASCO/ESMO conferences were searched up to August 2017 for randomized-controlled-trials on the curative treatment of resectable gastric cancer. We performed two network-meta-analyses (NMA). NMA-1 compared perioperative, neoadjuvant and adjuvant strategies only if there was a direct comparison. NMA-2 compared different adjuvant chemo(radio)therapy regimens, after curative resection. Overall-survival (OS) and disease-free-survival (DFS) were analyzed using random-effects NMA on the hazard ratio (HR)-scale and calculated as combined HRs and 95% credible intervals (95% CrIs). Results: NMA-1 consisted of 9 direct comparisons between strategies for OS (14 studies, n = 4187 patients). NMA-2 consisted of 16 direct comparisons between adjuvant chemotherapy/chemoradiotherapy regimens for OS (37 studies, n = 10,761) and 14 for DFS (30 studies, n = 9714 patients). Compared to taxane-based-perioperative-chemotherapy, surgery-alone (HR = 0.58, 95% CrI = 0.38–0.91) and perioperative-chemotherapy regimens without a taxane (HR = 0.79, 95% CrI = 0.58–1.15) were inferior in OS. After curative-resection, the doublet oxaliplatin-fluoropyrimidine (for one-year) was the most efficacious adjuvant regimen in OS (HR = 0.47, 95% CrI = 0.28–0.80). Conclusions: For resectable gastric cancer, (1) taxane-based perioperative-chemotherapy was the most promising treatment strategy; and (2) adjuvant oxaliplatin-fluoropyrimidine was the most promising regimen after curative resection. More research is warranted to confirm or reproach these findings.

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Section: Discussionmentioning

confidence: 99%

The Efficacy and Safety of (Neo)Adjuvant Therapy for Gastric Cancer: A Network Meta-analysis

Ende

Veer

Machiels

et al. 2019

Cancers

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“…Globally, gastroesophageal adenocarcinomas are among the most common causes of cancer related deaths [1]. Treatment still largely relies on conventional cytotoxic agents which are only limitedly effective in the majority of patients [2,3]. According to a comprehensive molecular analysis by The Cancer Genome Atlas (TCGA) Network, gastric cancer (including gastroesophageal junction cancer) can be classified into four subgroups based on its molecular characteristics: Epstein-Barr virus (EBV)-infected tumors, microsatellite instable (MSI) tumors, genomically stable (GS) tumors and chromosomally instable (CIN) tumors [4].…”

Section: Introductionmentioning

confidence: 99%

MSI as a predictive factor for treatment outcome of gastroesophageal adenocarcinoma

Velzen

Derks

Grieken

et al. 2020

Cancer Treatment Reviews

114

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Gastroesophageal cancers are a major cause of death worldwide and treatment outcomes remain poor. Adequate predictive biomarkers have not been identified. Microsatellite instability (MSI) as a result of mismatch repair deficiency is present in four to twenty percent of gastroesophageal cancers and has been associated with favorable survival outcomes compared to microsatellite stable tumors. This prognostic advantage may be related to immunosurveillance, which may also explain the favorable response to immune checkpoint inhibition observed in MSI high (MSI-H) tumors. The value of conventional cytotoxic treatment in MSI-H tumors is unclear and results on its efficacy range from detrimental to beneficial effects. Here the recent data on MSI as a predictive factor for outcome of gastroesophageal cancer treatment is reviewed.

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“…Although EGC are two distinct entities, patients with metastatic adenocarcinoma of the esophagus and stomach are often studied collectively, because the dysregulation of oncogenic pathways and standard treatment often overlap [ 5 ]. Currently, chemotherapy with a combination of capecitabine and oxaliplatin (CAPOX) is the standard treatment for metastatic EGC in many centers [ 6 , 7 ]. Although some patients with metastatic disease do benefit substantially from this palliative systemic treatment, others do not while still experiencing adverse effects [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Feasibility of CT radiomics to predict treatment response of individual liver metastases in esophagogastric cancer patients

et al. 2018

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In this study we investigate a CT radiomics approach to predict response to chemotherapy of individual liver metastases in patients with esophagogastric cancer (EGC). In eighteen patients with metastatic EGC treated with chemotherapy, all liver metastases were manually delineated in 3D on the pre-treatment and evaluation CT. From the pre-treatment CT scans 370 radiomics features were extracted per lesion. Random forest (RF) models were generated to discriminate partial responding (PR, >65% volume decrease, including 100% volume decrease), and complete remission (CR, only 100% volume decrease) lesions from other lesions. RF-models were build using a leave one out strategy where all lesions of a single patient were removed from the dataset and used as validation set for a model trained on the lesions of the remaining patients. This process was repeated for all patients, resulting in 18 trained models and one validation set for both the PR and CR datasets. Model performance was evaluated by receiver operating characteristics with corresponding area under the curve (AUC). In total 196 liver metastases were delineated on the pre-treatment CT, of which 99 (51%) lesions showed a decrease in size of more than 65% (PR). From the PR set a total of 47 (47% of RL, 24% of initial) lesions were no longer detected in CT scan 2 (CR). The RF-model for PR lesions showed an average training AUC of 0.79 (range: 0.74–0.83) and 0.65 (95% ci: 0.57–0.73) for the combined validation set. The RF-model for CR lesions had an average training AUC of 0.87 (range: 0.83–0.90) and 0.79 (95% ci 0.72–0.87) for the validation set. Our findings show that individual response of liver metastases varies greatly within and between patients. A CT radiomics approach shows potential in discriminating responding from non-responding liver metastases based on the pre-treatment CT scan, although further validation in an independent patient cohort is needed to validate these findings.

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The Efficacy and Safety of First-line Chemotherapy in Advanced Esophagogastric Cancer: A Network Meta-analysis

Abstract: Based on efficacy and toxicity, F-doublets FOx, FI, and FT are preferred as first-line treatment for AEGC compared with C-doublets, A-triplets, and TCF. FOxT is the most promising triplet.

Cited by 95 publications

References 86 publications

The Efficacy and Safety of (Neo)Adjuvant Therapy for Gastric Cancer: A Network Meta-analysis

The Efficacy and Safety of (Neo)Adjuvant Therapy for Gastric Cancer: A Network Meta-analysis

MSI as a predictive factor for treatment outcome of gastroesophageal adenocarcinoma

Feasibility of CT radiomics to predict treatment response of individual liver metastases in esophagogastric cancer patients

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