A quantitative evaluation of the determinant proteins for S-1 responsiveness in a biopsy specimen assists in patient selection to neoadjuvant therapy in cases of advanced gastric cancer

56 Background: The biopsy specimen by endoscopy can only show the surface of its gene profiles. We hypothesis whether the biopsy specimen can reflect all part of gene profile or not. We tested how 5-FU related genes and angiogenesis gene expressed in the invasion depth in the primary tumor of the Stage II or III advanced gastric cancer. Methods: Twenty-five patients with stage II or III advanced gastric cancer who underwent gastrectomy were analyzed.Formalin-fixed, paraffin-embedded tumor tissues were dissected from the surface section (mainly mucosa), the middle section (mainly submucossa) and the deep section (the part invaded most deeply) of the primary tumor and the normal gastric mucosa tissue by the laser-captured microdissection technique and were analyzed for target gene expressions using a quantitative real-time polymerase chain reaction.We analyzed for target genes as TS, TP, DPD, ERCC1, EGFR, VEGF and HIF1α. Results: In the primary tumor, TP and HIF1α gene expression in the surface section was significantly higher than in the deep section (p=0.021, p=0.012). These gene expression and the depth of the primary tumor had a correlation coefficient (TP; r=0.29, HIF1α; r=0.33). There was no significantly difference between surface and deep section in the primary tumor in TS, DPD, ERCC1, VEGF, EGFR except TP and HIF1α. There was no significantly difference between surface and middle section in the primary tumor in all gene expression. There was no significantly difference between middle and deep section in the primary tumor in all gene expression. Conclusions: Only TP and HIF1α had tendency that these gene expression became higher as invaded from the surface section to the deep section of primary tumor. These data suggested that biopsy specimens could be predicted gene expression profile from the surface of gastric cancer. But as you know, gastric cancer has a heterogeneity gene profile. We need at least few samples to say whole gene expression of its tumors. This is preliminary data, it will need further study to proof these result.

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Apatinib combined with SOX neoadjuvant therapy for locally advanced gastric cancer: A multicenter, single-armed, prospective study.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.367 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 367-367

Author(s):

Jian-Xian Lin ◽

Changming Huang

Keyword(s):

Gastric Cancer ◽

Prospective Study ◽

Neoadjuvant Therapy ◽

Advanced Gastric Cancer ◽

Locally Advanced ◽

Gastric Surgery ◽

R0 Resection ◽

Resection Rate ◽

Locally Advanced Gastric Cancer ◽

Tumor Response Evaluation

367 Background: Molecular targeted therapy has made great progress in the treatment of gastric cancer. In some previous studies, apatinib, an oral small molecular of VEGFR-2 TKI, had been confirmed can improve OS and PFS with an acceptable safety profile in patients with advanced gastric cancer refractory to two or more lines of prior chemotherapy. However, there is limited evidence about the safety and feasibility of apatinib combined with SOX regimen as neoadjuvant therapy for locally advanced gastric cancer (AGC). Methods: This is a multicenter, single-armed, prospective study. Patients with AGC (cT2-4N+M0) without prior anti-cancer strategies were included. Patients were received 2 to 5 cycles (21 days a cycle) of neoadjuvant therapy using S-1 (po, 40-60 mg bid, day1-day14), oxaliplatin (iv, 130 mg/m2, day1), and apatinib (po, 500 mg qd). Apatinib was prohibited in the last cycle. The operation should be performed 2 to 4 weeks later of the neoadjuvant therapy. The primary endpoint was R0 resection rate. The secondary endpoint included safety, ORR, and DCR. Results: A total of 56 patients from 10 centers in China were recruited. There were 43 males and 13 females. The median age was 63.04 years (range 41-75 years). There were 43 patients with tumor response evaluation, 29 patients (67.4%) had partial response (PR), 12 patients (27.9%) had stable disease (SD), and 2 patient (4.6%) had progressive disease (PD). The ORR and DCR were 67.4% (29/43) and 95.3% (41/43), respectively. 36 patients received gastric surgery, the R0 resection rate was 97.2%, 3 patients had postoperative complication: one had intestinal obstruction and 2 had pneumonia (all Clavien-Dindo classification less than grade II). 46 patients were included for safety analysis. The incidence of adverse events (AEs) and grade 3/4 AEs were 84.8% (39/46) and 17.4% (8/46), respectively. The most common AEs were neutropenia (40%), low platelet count (40%), leucopenia (32.6%), vomit (13%). Conclusions: This prospective study shows that neoadjuvant therapy using apatinib plus SOX brings clinical benefit to AGC with a high disease control rate and tolerable adverse reactions. Clinical trial information: NCT 03192735.

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Application of Circulating Tumor Cells and Circulating Free DNA from Peripheral Blood in the Prognosis of Advanced Gastric Cancer

Journal of Oncology ◽

10.1155/2022/9635218 ◽

2022 ◽

Vol 2022 ◽

pp. 1-9

Author(s):

Pengjie Yu ◽

Shengmao Zhu ◽

Yushuang Luo ◽

Ganggang Li ◽

Yongqiang Pu ◽

...

Keyword(s):

Gastric Cancer ◽

Neoadjuvant Chemotherapy ◽

Neoadjuvant Therapy ◽

Advanced Gastric Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Peripheral Blood ◽

Circulating Free Dna ◽

Free Dna ◽

N Stage

Objective. To explore the application value of circulating tumor cells (CTCs) and circulating free DNA (cfDNA) from peripheral blood in the prognosis of advanced gastric cancer (AGC). Here, we measured CTCs and cfDNA quantity for predicting the outcome of patients. Patients and Methods. Forty-five patients with advanced gastric cancer who underwent neoadjuvant chemotherapy and surgical treatment were enrolled in this study. All patients received neoadjuvant chemotherapy with paclitaxel + S-1 + oxaliplatin (PSOX) regimen, and CTCs and cfDNA of the peripheral blood were detected before and after neoadjuvant therapy. Relationships between the number/type of CTC or cfDNA and the efficacy of neoadjuvant chemotherapy were analyzed. Results. Among 45 patients, 43 (95.6%) were positive, and the positive rate of mesenchymal CTC was increased with the increase in the T stage. The proportion of mesenchymal CTC was positively correlated with the N stage ( P < 0.05 ), and the larger N stage will have the higher proportion of mesenchymal CTC. Patients with a small number of mesenchymal CTC before neoadjuvant chemotherapy were more likely to achieve partial response (PR) with neoadjuvant therapy. Patients with positive CA-199 were more likely to achieve PR with neoadjuvant therapy ( P < 0.05 ). Patients in the PR group were more likely to have decreased/unchanged cfDNA concentration after neoadjuvant therapy ( P = 0.119 ). After neoadjuvant therapy (before surgery), the cfDNA concentration was higher and the efficacy of neoadjuvant therapy (SD or PD) was lower ( P = 0.045 ). Conclusions. Peripheral blood CTC, especially interstitial CTC and cfDNA, has a certain value in predicting the efficacy and prognosis of neoadjuvant chemotherapy in advanced gastric cancer.

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