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Distinct molecular subtypes of gastric cancer: from Lauren to molecular pathology.

ABSTRACT: In Western countries the majority of gastric cancers (GC) are usually diagnosed in advanced stages reporting a 5-year survival rate of only 26%. The Laurén classification of GC was most widely used in clinical practice since it reflects GC morphology, epidemiology, tumor biology, clinical management and outcome. Despite the initial promise of individualizing antitumor treatment, the management of GC still remains relatively broad and general. Apart from clinical staging, molecular profiling enables targeting of the identified underlying alterations, rather than histology. In contrast to breast carcinoma, molecular classification of GC does not yet imply treatment modality. Molecular classifications of GC and their therapeutic implications are therefore extensively studied. The current proposed molecular divisions of GC come from three different parts of the world where different standard treatment modalities for advanced GC are recommended. Wider use of GC molecular subtyping may solve problems, such as susceptibility to novel systemic therapy regimens or selection of patients for aggressive surgery and targeted adjuvant/conversion therapy. In any case, the rapid entry of novel molecular targeted therapies into routine oncology practice clearly underscores the urgent need for clinicians to be aware of these new possibilities.

SUBMITTER: Cislo M

PROVIDER: S-EPMC5922408 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Distinct molecular subtypes of gastric cancer: from Laurén to molecular pathology.

Cisło Magdalena M Filip Agata Anna AA Arnold Offerhaus George Johan GJ Ciseł Bogumiła B Rawicz-Pruszyński Karol K Skierucha Małgorzata M Polkowski Wojciech Piotr WP

Oncotarget 20180410 27

In Western countries the majority of gastric cancers (GC) are usually diagnosed in advanced stages reporting a 5-year survival rate of only 26%. The Laurén classification of GC was most widely used in clinical practice since it reflects GC morphology, epidemiology, tumor biology, clinical management and outcome. Despite the initial promise of individualizing antitumor treatment, the management of GC still remains relatively broad and general. Apart from clinical staging, molecular profiling enab ...[more]

PMID: 29721214

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Project description:BackgroundThe choice of chemotherapy in HER2-negative gastric cancer is based on centre's preferences and adverse effects profile. No schedule is currently accepted as standard, nor are there any factors to predict response, other than HER2 status. We seek to evaluate whether Lauren type influences the efficacy of various chemotherapies and on patient overall survival (OS).MethodsWe have conducted a multicenter study in 31 hospitals. The eligibility criteria include diagnosis of stomach or gastroesophageal junction adenocarcinoma, HER2 negativity, and chemotherapy containing 2-3 drugs. Cox proportional hazards regression adjusted for confounding factors, with tests of 'treatment-by-histology' interaction, was used to estimate treatment effect.ResultsOur registry contains 1303 tumours analysable for OS end points and 730 evaluable for overall response rate (ORR). A decrease in ORR was detected in the presence of a diffuse component: odds ratio 0.719 (95% confidence interval (CI), 0.525-0.987), P=0.039. Anthracycline- or docetaxel-containing schedules increased ORR only in the intestinal type. The diffuse type displayed increased mortality with hazard ratio (HR) of 1.201 (95% CI, 1.054-1.368), P=0.0056. Patients receiving chemotherapy with docetaxel exhibited increased OS limited to the intestinal type: HR 0.65 (95% CI, 0.49-0.87), P=0.024, with no increment in OS for the subset having a diffuse component. With respect to progression-free survival (PFS), a significant interaction was seen in the effect of docetaxel-containing schedules, with better PFS limited to the intestinal type subgroup, in the comparison against any other schedule: HR 0.65 (95% CI, 0.50-0.85), P=0.015, and against anthracycline-based regimens: HR 0.64 (95% CI, 0.46-0.88), P=0.046.ConclusionsAs a conclusion, in this registry, Lauren classification tumour subtypes predicted survival and responded differently to chemotherapy. Future clinical trials should stratify effect estimations based on histology.

Project description:BACKGROUND:Preoperative prediction of the Lauren classification in gastric cancer (GC) is very important to the choice of therapy, the evaluation of prognosis, and the improvement of quality of life. However, there is not yet radiomics analysis concerning the prediction of Lauren classification straightly. In this study, a radiomic nomogram was developed to preoperatively differentiate Lauren diffuse type from intestinal type in GC. METHODS:A total of 539 GC patients were enrolled in this study and later randomly allocated to two cohorts at a 7:3 ratio for training and validation. Two sets of radiomic features were derived from tumor regions and peritumor regions on venous phase computed tomography (CT) images, respectively. With the least absolute shrinkage and selection operator logistic regression, a combined radiomic signature was constructed. Also, a tumor-based model and a peripheral ring-based model were built for comparison. Afterwards, a radiomic nomogram integrating the combined radiomic signature and clinical characteristics was developed. All the models were evaluated regarding classification ability and clinical usefulness. RESULTS:The combined radiomic signature achieved an area under receiver operating characteristic curve (AUC) of 0.715 (95% confidence interval [CI], 0.663-0.767) in the training cohort and 0.714 (95% CI, 0.636-0.792) in the validation cohort. The radiomic nomogram incorporating the combined radiomic signature, age, CT T stage, and CT N stage outperformed the other models with a training AUC of 0.745 (95% CI, 0.696-0.795) and a validation AUC of 0.758 (95% CI, 0.685-0.831). The significantly improved sensitivity of radiomic nomogram (0.765 and 0.793) indicated better identification of diffuse type GC patients. Further, calibration curves and decision curves demonstrated its great model fitness and clinical usefulness. CONCLUSIONS:The radiomic nomogram involving the combined radiomic signature and clinical characteristics holds potential in differentiating Lauren diffuse type from intestinal type for reasonable clinical treatment strategy.

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Distinct molecular subtypes of gastric cancer: from Lauren to molecular pathology.

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Distinct molecular subtypes of gastric cancer: from Laurén to molecular pathology.

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