A radiomics-based model for predicting prognosis of locally advanced gastric cancer in the preoperative setting

AbstractThis study aims to evaluate the performance of a radiomic signature-based model for predicting recurrence-free survival (RFS) of locally advanced gastric cancer (LAGC) using preoperative contrast-enhanced CT. This retrospective study included a training cohort (349 patients) and an external validation cohort (61 patients) who underwent curative resection for LAGC in 2010 without neoadjuvant therapies. Available preoperative clinical factors, including conventional CT staging and endoscopic data, and 438 radiomic features from the preoperative CT were obtained. To predict RFS, a radiomic model was developed using penalized Cox regression with the least absolute shrinkage and selection operator with ten-fold cross-validation. Internal and external validations were performed using a bootstrapping method. With the final 410 patients (58.2 ± 13.0 years-old; 268 female), the radiomic model consisted of seven selected features. In both of the internal and the external validation, the integrated area under the receiver operating characteristic curve values of both the radiomic model (0.714, P < 0.001 [internal validation]; 0.652, P = 0.010 [external validation]) and the merged model (0.719, P < 0.001; 0.651, P = 0.014) were significantly higher than those of the clinical model (0.616; 0.594). The radiomics-based model on preoperative CT images may improve RFS prediction and high-risk stratification in the preoperative setting of LAGC.

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Duration of Perioperative Chemotherapy in Locally Advanced Gastric Cancer: A “Less Is More” Question When ypN0 Is Achieved

Frontiers in Oncology ◽

10.3389/fonc.2021.775166 ◽

2021 ◽

Vol 11 ◽

Author(s):

Zining Liu ◽

Yinkui Wang ◽

Fei Shan ◽

Xiangji Ying ◽

Yan Zhang ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Cox Regression ◽

Locally Advanced ◽

R0 Resection ◽

Perioperative Chemotherapy ◽

Tree Model ◽

Less Is More ◽

Locally Advanced Gastric Cancer ◽

Significant Difference

BackgroundsPerioperative chemotherapy (PEC) and neoadjuvant chemotherapy (NAC) have become a vital part of locally advanced gastric cancer (LAGC) treatment, but the optimal duration of PEC has not been studied. The aim of this study was to demonstrate the possibility of duration reduction in PEC in the adjuvant chemotherapy (AC) phase for ypN0 patients.MethodsWe included LAGC patients who achieved ypN0 after NAC in our institution from 2005 to 2018. The risk/benefit of AC and other covariates were majorly measured by overall survival (OS) and progression-free survival (PFS). We developed a survival-tree-based model to determine the optimal PEC duration for ypN0 patients in different classes.ResultsA total of 267 R0 resection patients were included. There were 55 patients who did not receive AC. The 5-year OS was 74.34% in the non-AC group and 83.64% in the AC group with a significant difference (p = 0.012). Multivariate Cox regression revealed that both AC (AC vs. non-AC: HR, 0.49; 95%CI, 0.27–0.88; p = 0.018) and ypT stages (ypT3-4 vs. ypT0-2: HR, 2.00; 95%CI, 1.11–3.59; p = 0.021) were significant protective/risk factors on patients OS and PFS. A decision tree model for OS indicated an optimal four to six cycles of PEC, which was recommended for ypT0-2N0 patients, while a minimum of five PEC cycles was recommended for ypT3-4N0 patients.ConclusionAC treatment is still necessary for ypN0. The duration reduction could be applied for the ypT0-2N0 stage patients but may not be suitable for higher ypT stages and beyond. A multicenter-based study is required.

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Clinical outcomes of patients with gastric cancer according to pre and post-neoadjuvant chemotherapy PD-L1 immunohistochemistry (IHC) expression.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e16569 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e16569-e16569

Author(s):

Heber Salvador de Castro Ribeiro ◽

Wilson Luiz da Costa ◽

Maria Dirlei de Souza Begnami ◽

Celso Abdon Lopes Mello ◽

Tatiane Neotti ◽

...

Keyword(s):

Gastric Cancer ◽

Neoadjuvant Chemotherapy ◽

Advanced Gastric Cancer ◽

Cox Regression ◽

Locally Advanced ◽

Neoadjuvant Treatment ◽

Cancer Center ◽

Survival Outcomes ◽

Surgical Specimen ◽

Locally Advanced Gastric Cancer

e16569 Background: The incidence, prognostic and predictive impacts of PD-L1 expression in locally advanced gastric cancer is unknown. We aimed to determine the expression of PD-L1 by CPS in the pre-treatment biopsy and surgical specimens of patients (pts) with gastric cancer who received neoadjuvant therapy and its association with pathological response and survival outcomes. Methods: Retrospective cohort of pts treated at a cancer center from 2007 to 2017. Pts with confirmed gastric or GEJ adenocarcinoma who received neoadjuvant treatment and curative-intent D2 surgery were included. Gastric stump tumors and those who had a total esophagectomy were excluded. Clinical data were obtained from medical charts. Biopsy samples and a tissue microarray with the most representative areas of the surgical specimen were used to detect PD-L1 IHC expression with 22C3 phamDx antibody. Results were analyzed using the CPS score. Overall and DFS survival included the Kaplan-Meier product-limit estimator in an ITT analysis and a Cox regression was used to obtain crude and adjusted HR for prognostic factors. Results: 270 pts were included: median age was 58.9 years, most (51.5%) had cT3-T4N+ stages, 45% had diffuse histology and 87.8% completed the preoperative regimen. 13% had a pCR, while 53% had minimal tumor regression. With a median follow-up of 60.3 months (CI 95% 54.7 – 65.8), the median OS and DFS were not reached. 11.4% of biopsies and 18.6% of surgical specimens had positive CPS, with a median score of 3 (IQR 2,0 – 7,5) and 9 (IQR 5.0 – 20.0) respectively. In 18.9% of paired samples the PD-L1 expression was found to be negative in the biopsy sample and positive in the surgical specimen. PD-L1 expression was neither associated with pathologic response after neoadjuvant chemotherapy, nor with survival outcomes. Conclusions: PD-L1 expression on the setting of locally advanced gastric cancer was low and it was different when biopsy and surgical specimens were compared. No impact on survival results could be detected. [Table: see text]

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A Predictive Signature for Oxaliplatin and 5-fluorouracil Based Chemotherapy Inlocally Advanced Gastric Cancer

10.21203/rs.3.rs-34678/v1 ◽

2020 ◽

Author(s):

Qinchuan Wang ◽

Xiyong Liu ◽

Chen Chen ◽

Jida Chen ◽

Beisi Xu ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Risk Model ◽

Cox Regression ◽

Cox Model ◽

Locally Advanced ◽

Discovery Cohort ◽

Cox Models ◽

Locally Advanced Gastric Cancer ◽

Ic50 Value

Abstract Background: Adjuvantchemotherapy(AC)plays a substantial role in the treatment of locally advanced gastric cancer (LAGC), but the response remains poor. Weaims to improve its efficacy in LAGC. Methods: We identified the expression of eight genes closely associated with platinum and fluorouracil metabolism (RRM1, RRM2, RRM2B, POLH, DUT, TYMS, TYMP, MKI67) in the discovery cohort (N=291). And we further validated the findings in TCGA (N=279) and GEO. Overall survival (OS) was used as an endpoint. Univariate and multivariate Cox models were applied. A multivariate Cox regression model was simulated to predict theOS. Results: In the discovery cohort,the univariate Coxmodelindicated that AC was beneficial to high-RRM1, high-DUT, low-RRM2, low-RRM2B, low-POLH, low-KI67, low-TYMS or low-TYMP patients, the results were validated in the TCGA cohort. The multivariate Cox model showed consistent results. Cumulative analysis indicated that patients with low C-Score respond poorly to the AC, whereas thehigh and mediumC-Score patients significantly benefit from AC. A risk model based on the above variables successfully predicted the OS in both cohorts (AUC=0.75 and 0.67, respectively). Further validation in a panel of gastric cancer cell (GC) lines (N=37) indicated that C-Score is significantly associated with IC50 value to fluorouracil. Mutation profiling showed that C-Score was associated with the number and types of mutations. Conclusion: In this study, we successfully simulated a predictive signature for the efficacy of AC in LAGC patients and further explored the potential mechanisms. Our findings could promote precision medicine and improve the prognosis of LAGC patients.

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Perioperative chemotherapy in locally advanced gastric cancer in Chile: From evidence to daily practice.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.4_suppl.92 ◽

2016 ◽

Vol 34 (4_suppl) ◽

pp. 92-92

Author(s):

Bettina G. MÃ¼ller ◽

Carlos Garcia ◽

Jose Antonio Sola ◽

Carlos Benavides ◽

Patrick Werner ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Performance Status ◽

Locally Advanced ◽

Public Hospitals ◽

R0 Resection ◽

Perioperative Chemotherapy ◽

Locally Advanced Gastric Cancer ◽

Informed Consent Form ◽

Preoperative Ct

92 Background: Gastric cancer is the leading cause of cancer death in Chile, with mortality rate of 26.7/100.000 in men, placing the country among the highest mortality rates worldwide. For locally advanced gastric cancer, a multimodality treatment is recommended, but in Chile, the treatment covered by the public health insurance, which assists more than 70% of the patients, is surgery alone. We conducted an observational study to assess efficacy and toxicity of perioperative chemotherapy (CT) in public hospitals in Chile (NCT01633203). Methods: Patients with locally advanced, operable gastric carcinoma, defined as presence of invasion of serosa or beyond (cT > 3 AJCC 2002) and/or lymph node metastasis (cN+) without distant metastasis (M0), were offered to receive preoperative CT with Epirubicin+Cisplatin+Capecitabine (ECX) regimen for 3 cycles followed by curative surgery with D2 lymphadenectomy. Staging abdominal CT scan was mandatory, laparoscopy was recommended. Patients with gastric retention, severe dysphagia or contraindications for CT were excluded. All patients signed the IRB approved informed consent form prior to enrolment. Data were collected using the OpenClinica platform. Results: Between August 2010 and March 2013, 110 patients were screened and 61 enrolled. Median age was 62 years (23-76 years) and most patients had good performance status at baseline (ECOG 0: 42, ECOG 1: 19). Tumor site was proximal in 24 (39%), medial in 16 (26%) and distal in 10 patients (16%). All but 4 patients (n = 57, 93%) completed three cycles of preoperative CT as planned. Fifty-five patients were operated and 54 (89%) had curative R0 resection. Of these, 36 (67%) had pT0-2, and 15 (28%) had pN0 tumors. A complete pathological response was found in 2 patients. Two patients were not operated for other reasons (one patient refused surgery and one patient presented a cerebrovascular accident during preoperative CT and died), and 5 patients (8%) progressed. As of September 1, 2015, 32 patients died. Three-year survival rate was 49%. Conclusions: Perioperative CT is feasible in public hospitals in Chile and should be offered as an alternative to primary surgery for patients with locally advanced gastric cancer.

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