Strategy for prevention of cancers of the esophagus

Akiyama, Junichi; Alexandre, Leo; Baruah, Anushka; Buttar, Navtej; Chandra, Ramesh; Clark, Allan; Hart, Andrew; Hawk, Ernest T.; Kandioler, Daniela; Kappel, Sonja; Krishnadath, Sheila; Sharma, Arunima; Singh, Ishtpreet; Straub, Daniëlle; Triadafilopoulos, George; Umar, Asad; Wolf, Brigitte

doi:10.1111/nyas.12529

Cited by 10 publications

(8 citation statements)

References 60 publications

(65 reference statements)

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“…We were also not able to demonstrate that the use of IHC contributed to interstudy heterogeneity in our meta-regression analysis. Nevertheless, with increased knowledge about TP53 mutation variants 60 and more standardised and economical targeted gene sequencing technologies available, 61 our results support the validity of using direct TP53 mutation status as a prognostic biomarker in OAC and raise the possibility that this provides improved prognostic classification than IHC consistent with findings in other cancers. 22 …”

Section: Discussionsupporting

confidence: 74%

The prognostic value of TP53 mutations in oesophageal adenocarcinoma: a systematic review and meta-analysis

Fisher¹,

Lord

Falkenback

et al. 2016

Gut

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ObjectiveTo clarify the prognostic role of tumour protein 53 (TP53) mutations in patients with oesophageal adenocarcinoma (OAC) as there is a need for biomarkers that assist in guiding management for patients with OAC.DesignA systematic review was conducted using MEDLINE, Embase, PubMed and Current Contents Connect to identify studies published between January 1990 and February 2015 of oesophageal cancer populations (with OAC diagnoses >50% of cases) that measured tumoural TP53 status and reported hazard ratios (HR), or adequate data for estimation of HR for survival for TP53-defined subgroups. Risk of bias for HR estimates was assessed using prespecified criteria for the appraisal of relevant domains as defined by the Cochrane Prognosis Methods Group including adherence to Grading of Recommendations, Assessment, Development and Evaluation and REporting recommendations for tumor MARKer prognostic studies guidelines, as well as assay method used (direct TP53 mutation assessment vs immunohistochemistry) and adjustment for standard prognostic factors. A pooled HR and 95% CI were calculated using a random-effects model.ResultsSixteen eligible studies (11 with OAC only and 5 mixed histology cohorts) including 888 patients were identified. TP53 mutations were associated with reduced survival (HR 1.48, 95% CI 1.16 to 1.90, I2=33%). A greater prognostic effect was observed in a sensitivity analysis of those studies that reported survival for OAC-only cohorts and were assessed at low risk of bias (HR 2.11, 95% CI 1.35 to 3.31, I2=0%).ConclusionsPatients with OAC and TP53 gene mutations have reduced overall survival compared with patients without these mutations, and this effect is independent of tumour stage.

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Section: Discussionsupporting

confidence: 74%

The prognostic value of TP53 mutations in oesophageal adenocarcinoma: a systematic review and meta-analysis

Fisher¹,

Lord

Falkenback

et al. 2016

Gut

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“…75 For those who remain in stratum 3, chemopreventatives (e.g., aspirin, statins) might be considered as well as stronger encouragement to modify lifestyle (e.g., smoking cessation, improved diet, weight loss, increased physical activity.) 44,46,76–81 …”

Section: A Different Directionmentioning

confidence: 99%

Precision prevention of oesophageal adenocarcinoma

Vaughan

Fitzgerald

2015

Nat Rev Gastroenterol Hepatol

130

106

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Summary A rapid and continuous rise in incidence of esophageal adenocarcinoma over the past four decades has been well documented in many developed countries across three continents. Among white males, who are in the highest risk demographic, incidence has risen 10-fold in the U.S. since the early 1970s. Incidence among males in the U.K. are among the highest in the world, and 50% higher than in the U.S. Unfortunately, treatments have not kept pace; unless their cancer is identified at a very early stage, most individuals will not survive a year after diagnosis. The beginnings of this widespread problem were first recognized over 25 years ago, yet rates have continued to rise against a backdrop of much improved understanding and management including the introduction of medical and surgical treatments aimed at reducing acid reflux, one of the most important risk factors; the availability of screening and surveillance programs for the precursor lesion Barrett’s metaplasia; and the development of endoscopic therapies for prevention or treatment of early invasive cancer. We estimate that only about 7% of the 10,000 cases of esophageal adenocarcinoma diagnosed annually in the U.S. are identified through current approaches to cancer control, and trace pathways by which the remaining 93% are “lost.” Based on emerging data on etiology and predictive factors coupled with new diagnostic tools, we suggest a five-tier strategy for prevention and control that begins with a wide population base and triages individuals into progressively higher risk strata, each with risk-appropriate prevention, screening and treatment options.

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“…According to Sackett's classification, phase II biomarker studies aim to assess the magnitude of the association between the results of a biomarker and the disease status (Sackett & Haynes, 2002). Phase II biomarker studies are concerned with reproducibility and aim to assess the sensitivity and specificity of the biomarker, together with its ability to "rule out" (high sensitivity) or "rule in" (high specificity) the disease (Sackett & Haynes, 2002;Akiyama et al, 2014).…”

Section: Methodsmentioning

confidence: 99%