Project description:BackgroundThe benefits of neoadjuvant therapy for patients with locally advanced gastric cancer (GC) are increasingly recognized. The 8th edition of the American Joint Committee on Cancer (AJCC) Staging Manual first proposed ypTNM staging, but its accuracy is controversial. This study aims to develop a modified ypTNM staging.Patients and methodsClinicopathological data of 1,791 patients who underwent curative-intent gastrectomy after neoadjuvant therapy in the Surveillance, Epidemiology, and End Results database, as the development cohort, were retrospectively analyzed. Modified ypTNM staging was established based on overall survival (OS). We compared the prognostic performance of the AJCC 8th edition ypTNM staging and the modified staging for patients after neoadjuvant therapy.ResultsIn the development cohort, the 5-year OS for AJCC stages I, II, and III was 58.8%, 39.1%, and 21.6%, respectively, compared with 69.9%, 54.4%, 34.4%, 24.1%, and 13.6% for modified ypTNM stages IA, IB, II, IIIA, and IIIB. The modified staging had better discriminatory ability (C-index: 0.620 vs. 0.589, p < .001), predictive homogeneity (likelihood ratio chi-square: 140.71 vs. 218.66, p < .001), predictive accuracy (mean difference in Bayesian information criterion: 64.94; net reclassification index: 35.54%; integrated discrimination improvement index: 0.032; all p < .001), and model stability (time-dependent receiver operating characteristics curves) over AJCC. Decision curve analysis showed that the modified staging achieved a better net benefit than AJCC. In external validation (n = 266), the modified ypTNM staging had superior prognostic predictive power (all p < .05).ConclusionWe have developed and validated a modified ypTNM staging through multicenter data that is superior to the AJCC 8th edition ypTNM staging, allowing more accurate assessment of the prognosis of patients with GC after neoadjuvant therapy.Implications for practiceThe 8th edition of the American Joint Committee on Cancer (AJCC) Staging Manual first proposed ypTNM staging, but its accuracy is controversial. Based on multi-institutional data, this study developed a modified ypTNM staging, which is superior to the AJCC 8th edition ypTNM staging, allowing more accurate assessment of the prognosis of patients with gastric cancer after neoadjuvant therapy.

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.

Project description:Lauren-classification and human epidermal growth factor receptor 2 (HER2) status are two important pathological features of gastric cancer patients. The prognostic value of HER2 in gastric cancer remains controversial. Intestinal type gastric cancer has better prognosis and higher HER2 positive proportion. What is the interaction between these two factors? We hypothesized that a combination of Lauren-classification and human epidermal growth factor receptor 2 (HER2) status (L-H status) might be more meaningful than either factor alone.We collected 838 gastric cancer patients at all stages who had received treatment in our cancer center. This study was registered in the website of ClinicalTrials.Gov, with the number NCT01927146. We divided the patients into six groups according to their L-H status: Group A, HER2 negative and intestinal type; Group B, HER2 positive and intestinal type; Group C, HER2 negative and diffuse type; Group D, HER2 positive and diffuse type; Group E, HER2 negative and mixed type; and Group F, HER2 positive and mixed type.Diffuse type and intestinal type accounted for 51.0% and 33.9%, respectively. The proportion of HER2 positive patients was 11.2%, 25.4%, 2.1% and 10.2% in the whole patient group, intestinal, diffuse and mixed type, respectively. Median overall survival was 34.0 months, 25.3 months, 27.6 months, 19.2 months, 25.9 months and 26.4 months in the six groups patients, P?=?0.053. There was a significant difference in survival among the first four groups (P?<?0.001). HER2 was an independent prognostic factor in the intestinal type and in stage I?+?II patients, but not in the diffuse type or stage III?+?IV patients. L-H status was an independent prognostic factor in patients at all stages. For the diffuse and intestinal types, the multivariate analysis showed that HER2 was not an independent prognostic factor, while Lauren classification and L-H status were. Moreover, L-H status was a better prognostic factor than the Lauren classification.L-H status is a prognostic factor in diffuse and intestinal type patients, but not in the mixed type. Patients with HER2 negative and intestinal type had the best survival, while patients with HER2 positive status and diffuse type had the worst survival.

Project description:Background: Limited evidence exists on the incidence of gastric cancer (GC), and contradictory results exist for the prognosis of GC based on the Lauren classification. We analyzed the incidence and survival of GC based on the Lauren classification. Methods: The Surveillance, Epidemiology, and End Results (SEER) database from 1975 through 2015 was used to identify all patients with surgically resected, histologically diagnosed intestinal or diffused-type GC. Propensity score matching was used to analyze the association between the Lauren classification type and prognosis. Results: The trend of total GC incidence showed an obvious decrease (APC = -1.51, 95% CI: -2.31 to -1.01) as well as that of the intestinal type (APC = -1.43, 95% CI: -2.01 to -1.12). However, we found that the relative incidence of the diffused type was increased (APC = 0.6, 95% CI: 0.41-0.82). The trend of the total incidence of GC (APC = -1.31, 95% CI: -1.91 to -1.03) and that of the intestinal type (APC = -1.11, 95% CI: -1.53 to -0.98) was decreased in 40-49-year-olds, but that of the diffused type was increased (APC = 1.5, 95% CI: 1.2-1.72). We found that trends in GC incidence exhibited a similar pattern in the regional and distant stages and showed a decrease from 1975 through 2015. However, the incidence rate of the local stage was increased, with an APC of 0.5 (95% CI: 0.3-0.7). We identified 15,989 GC cases from the SEER database, including 13,852 intestinal-type and 2,138 diffused-type cases. The 1,336 intestinal-type cases were matched with 1,336 diffused-type cases using propensity score matching (PSM), and patients with the diffused type had a better prognosis than patients with the intestinal type (HR = 0.56, 95% CI: 0.45-0.78). However, we found that patients with diffused-type GC had worse survival than patients with intestinal-type GC in the cohort from Renji Hospital (P < 0.001). Conclusion: The total incidence of GC and that of the intestinal-type GC decreased, but the incidence of diffused-type GC increased in 40-49-year-olds. Diffused types of GCs may have a different prognosis compared to intestinal-type GCs in different patient cohorts. Nevertheless, these results should be interpreted with caution in assessing the prognosis in combination with other factors.

Project description:Purpose: The primary objective of the current study was to validate biomarkers to identify the 10% to 27% of patients with stage I and 35% of patients with stage IIA squamous cell carcinoma of lung (SC) who are likely to recur following surgical resection, so that these patients may be offered enrollment in clinical trials evaluating directed ACT. A secondary objective was to identify patients with stage IIB SC who are unlikely to develop recurrences and might thereby be spared the potential significant toxicity and expense of ACT. Methods: Two-stage validation used independent core laboratories, objective quality control standards, locked test parameters, and large multi-institutional specimen/data sets. First stage validation confirmed a signature’s ability to stratify patient survival. Second stage validation determined which signature(s) optimally improved risk discrimination when added to baseline clinical predictors. Participants were prospectively enrolled on institutional (Cohort I) or cooperative group (Cohort II) biospecimen/data collection protocols. All cases underwent central review of clinical, pathologic and biospecimen parameters using objective criteria to determine final inclusion (Cohort I: n=249; Cohort II: n=234). Primary selection required that a signature significantly predict 3-years survival after surgery in Cohort I. Signatures meeting this criterion were further tested in Cohort II, comparing risk prediction using baseline risk factors alone versus in combination with the signature. Results: Male sex, advanced age, and higher stage were associated with shorter survival in Cohort I and established a baseline clinical model. Of three signatures validated in Cohort I, one signature was validated in Cohort II and statistically significantly enhanced prognosis relative to the baseline model (C-index difference 0.122; p<0.05). Conclusions: These results represent the first rigorous validation of a test appropriate to direct adjuvant treatment or clinical trials for patients with lung squamous cell carcinoma.

Dataset Information

Superiority of Tumor Location-Modified Lauren Classification System for Gastric Cancer: A Multi-Institutional Validation Analysis.

Background

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Superiority of Tumor Location-Modified Lauren Classification System for Gastric Cancer: A Multi-Institutional Validation Analysis.

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