Unresectable Gastric Cancer Patients Research Articles

Stomach-partitioning versus conventional gastrojejunostomy for unresectable gastric cancer with gastric outlet obstruction: A propensity score matched cohort study

BackgroundStomach partitioning gastrojejunostomy (SPGJ) was introduced to deal with delayed gastric emptying (DGE). This study aimed to compare the short- and long-term outcomes of SPGJ versus conventional gastrojejunostomy (CGJ). MethodThis cohort study analyzed 108 patients who underwent gastrojejunostomy for unresectable gastric cancer: 70 patients underwent SPGJ, and 38 patients underwent CGJ between 2018 and 2022. Propensity score-matched (PSM) analysis was used to balance the baseline characteristics. ResultsAfter PSM, there were 26 patients in each group. SPGJ group had significantly lower incidence of DGE (3.8% vs. 34.6%), vomiting (3.8% vs. 42.3%), and prokinetics requirement (11.5% vs. 46.2%). SPGJ group had significantly shorter time to solid diet tolerance (4.1 days vs. 5.7 days) and postoperative hospital stay (7.7 days vs. 9.3 days). There was no significant difference in relapse reinterventions, gastric outlet obstruction (GOO) recurrence, conversion surgery, and survival outcomes. ConclusionsSGPJ was associated with lower rate of DGE, prokinetics requirement, and shorter time of solid diet tolerance compared to CGJ in the treatment of unresectable gastric cancer patients with GOO.

Clinical outcomes of capecitabine-based versus S-1-based regimens as first-line chemotherapy in patients with unresectable or metastatic gastric cancer: a propensity score matched single-center comparison

Fluoropyrimidine-based regimens are the cornerstone of first-line chemotherapy for metastatic gastric cancer (GC). Capecitabine or S-1 might be used as an alternative to infusional 5-fluorouracil, especially in pan-Asian. This study aimed to compare the clinical outcomes of capecitabine-based and S-1-based regimens as first-line chemotherapy in Chinese patients with unresectable or metastatic GC. We conducted a retrospective study including unresectable or metastatic GC patients treated with the capecitabine-based or S-1-based regimen as first-line chemotherapy at the First Hospital of China Medical University. Propensity score matching (PSM) analysis was performed to reduce selection bias. Overall survival (OS) outcomes were compared using the Kaplan-Meier method and log-rank test. Prognostic significance was determined using multivariate Cox regression analysis. In addition, subgroup analyses were conducted to determine the effectiveness of capecitabine-based and S-1-based regimens in clinically relevant patient subsets. The clinical data of 469 patients included between October 2005 and September 2018. PSM analysis identified 187 patients receiving capecitabine-based or S-1-based regimen. No significant difference in OS (10.7 vs. 11.1 months, P=0.523) was detected between the two groups after PSM. In the subgroup analysis, the median OS (12.2 vs. 9.3 months, P=0.013) was longer for patients with peritoneum metastasis who received the capecitabine-based regimen compared to those who received the S-1-based regimen. No significant difference in clinical outcomes was observed between the capecitabine and S-1-based regimen as first-line chemotherapy for metastatic or unresectable GC patients in China. The capecitabine-based regimen should be considered in the treatment of the GC patients with peritoneum metastasis.

Abstract 2288: Cell-surface vimentin as a novel biomarker for detecting circulating tumor cells from advanced gastric cancer patients

Abstract Background: Aberrant activation of epithelial-mesenchymal transition (EMT) is closely associated with gastric cancer (GC) progression and metastasis. However, biomarkers specifically capturing EMT-circulating tumor cells (EMT-CTCs) that can be used to noninvasively determine the disease status and prognosis in GC patients have been lacking. Patients and Methods: To fill this gap, we performed a head-to-head comparison clinical study between CSV+CTCs and EpCAM+CTCs using proprietary cell-surface vimentin (CSV) antibody 84-1 from MD Anderson and the epithelial tumor markers EpCAM and CK based on previous established CTCs detection method from 100 resectable and unresectable GC patients and 10 healthy donors. Also, freshly procured GC primary tissues and metastatic lymph nodes were obtained from five patients. Additionally, in vitro experiments were performed to investigate the role of CSV as a specific EMT marker in GC cell lines. Results: Using 84-1 antibody, we detected CSV more exclusively expressing on lymph node metastasis than primary tumor of GC. Subsequent experiments in vitro showed that the expression level of CSV was correlated with EMT phenotype and migration ability in GC cells. A dramatic increase in the levels of vimentin bound to the surface of GC cells after IGF-I stimulation using flow cytometry which indicated CSV as a specific marker in GC cell populations undergoing EMT. We further enumerated relative higher number of CSV+CTCs in unresectable advanced GC patients and EpCAM+CTCs in resectable population with early stage; none was detected from healthy donors. From our observations, we defined a cutoff of < five or ≥ five CTCs as optimal threshold with respect to therapeutic response using ROC curves. CSV+CTC counts were significant in differentiating disease stable and progression populations in comparison to the EpCAM+CTC. Notably, patients with unfavorable CTCs at baseline had a significantly shorter median PFS and OS in advanced GC populations. These results also indicated that a summation of CTCs detected from both methods increased the sensitivity and specificity of CTCs in monitoring therapeutic response and prognosis prediction compared to individual test. Conclusions: Our data demonstrate that CSV is a highly EMT-CTCs specific marker that may assist in assessing treatment efficacy and prognosis in advanced GC patients; however, an independent prospective study with a large population will be necessary to fully validate the efficiency of this method. Note: This abstract was not presented at the meeting. Citation Format: Heming Li, Yuting Liu, Zhi Wang, Shanshan Liang, Xiangyu Kong, Wenzhi Liu, Tong Zhao, Xuening Ji, Gang Wang, Fuguang Wang, Ruoyu Wang. Cell-surface vimentin as a novel biomarker for detecting circulating tumor cells from advanced gastric cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2288.

Efficacy and safety of conversion therapy using chemotherapy plus anti-angiogenic therapy in unresectable gastric cancer.

e15510 Background: Conversion therapy has been a promising option for patients with unresectable gastric cancer (GC) (including Phase IV gastric cancer, N3, lymph node fusion and local progression patients). We aimed to investigate the efficacy and safety of S1/oxaliplatin chemotherapy plus apatinib, a novel inhibitor of VEGFR-2, in the conversion therapy for unresectable GC. Methods: This was a single-center, single-arm, open-label study. unresectable GC patients with unresectable factors were eligible for this study. Apatinib (500mg, qd) was administrated continuously, oxaliplatin (130mg/m2) on day 1, and S1 (<1.25m2, 40mg*2/d; 1.25-1.5m2, 50mg*2/d; >1.5m2, 60mg*2/d) on day 1-14 every 3 weeks. Treatment was given for 4-6 cycles preoperatively, but the last cycle did not include apatinib. The primary objective included R0 resection rate and safety profile of preoperative treatment. Results: Total 17 patients were enrolled, the median age was 57 (55.12±10.08) years old. The histological types were mainly signet ring cell carcinoma 10 (58.82%), poorly differentiated adenocarcinoma 5 (29.41%), and moderately differentiated adenocarcinoma 2 (11.76%). Among the 17 patients eligible for preoperative efficacy evaluation, 13 achieved partial response (PR), 3 achieved stable disease (SD), and 1 had progressive disease (PD), the overall response rate (ORR) was 76.5% and disease control rate was 94.1%. Of the 13 pts with PR, 1 refused consents for surgery, 12 patients underwent surgery and 9(75%) achieved R0 resection. During preoperative treatment, the incidence of adverse events (AEs) was 76.5%. The common hematologic AEs were neutropenia (64.7%), leukopenia (64.7%) and hemoglobin decrease (11.8%), and nonhematologic AEs included hyperbilirubinemia (11.8%), hand-foot syndrome (17.6%), oral mucositis (29.4%), fatigue (70.6%), proteinuria (5.9%). Conclusions: Combination of apatinib with S1/oxaliplatin chemotherapy could induce a sufficient conversion rate and achieve a relative high R0 resection rate for initially unresectable GC, with tolerable safety profile. Clinical trial information: ChiCTR-ONC-17010430 trial.

Progress in conversion therapy for originally unresectable gastric cancer

Conversion therapy is adopted to achieve radical cure for patients with originally unresectable but potentially resectable late stage gastric cancer, who obtain partial or complete remission after systemic chemotherapy, to acquire relatively longer postoperative survival and recurrence-free survival. Some of the previous researches on conversion therapy for originally unresectable gastric cancer suggest that high chemotherapy response rate, high pathological response rate and R0 resection rate are associated with favorable prognosis. And the efficacy of patients with lymphatic metastasis is better than that of those with peritoneal metastasis. The protocol of conversional chemotherapy varies and so does its efficacy according to different reports. Latest clinical researches indicate that initially unresectable gastric cancer gained higher remission rate and better chance of R0 operation and consequently prolonged survival from paclitaxel based triplet chemotherapy. However, not all originally unresectable gastric cancer can benefit from conversion therapy due to the high heterogeneity of its biological behavior. Regarding the enormous number of originally unresectable gastric cancer patients, it will be a research hot spot in the field of surgical oncology, on screening criteria to select cases suitable for conversion. Exploration on conversion therapy for gastric cancer is still at initial stage, and reports that have been published are mostly single-centered with limited sample, lacking of sufficient evidence on its feasibility, safety and efficacy. Expert consensus on conversion indication, case selection, chemotherapy regimen, efficacy assessment and resection range is absent. So it is in urgent need for higher level clinical evidence to support and guide this practice. Such goal can never be achieved without joint efforts of all parties to carry out clinical trial to modify the practice of conversion therapy for late stage gastric cancer, and determine the proper selection of suitable candidates for conversion therapy, eventually to offer optimal strategy for originally unresectable gastric cancer patients. Thus, this article focuses on reviewing research progress of conversion therapy for originally unresectable late stage gastric cancer.

The clinical impact of the novel tumor marker DR-70 in unresectable gastric cancer patients

BackgroundGastric cancer tumor markers, such as carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA 19-9), have been applied in clinical practice to screen or monitor treatment responses. However, their sensitivity and specificity are unsatisfactory. Therefore, we assessed the novel tumor marker DR-70 and evaluated its performance in screening and response monitoring. MethodsThe study included newly diagnosed patients with advanced gastric cancer from March 2012 to October 2015. We measured the DR-70, CEA, and CA 19-9 levels at the time of enrollment. The patients subsequently underwent chemotherapy. We followed-up the patients every 3 months; DR-70 levels and abdominal computed tomography scans were re-evaluated and repeated, respectively, at each follow-up. The correlation between treatment response and DR-70 level after chemotherapy was analyzed. The overall survival and progression-free survival rates were also evaluated. ResultsA total of 51 patients with gastric cancer were enrolled. Most (82.4%) had metastatic disease. At enrollment, the sensitivity of DR-70 in our study group was 78.4%, compared with 52.9% and 43.1% for CEA and CA 19-9, respectively. When we used the three tumor markers together, the sensitivity increased to 80.4%. We observed a correlation between treatment response and DR-70 level after chemotherapy. No difference in either overall survival or progression-free survival was observed between the DR-70 positive and negative groups. However, a trend toward poorer overall survival was observed for the high DR-70 group, although this was not statistically significant. ConclusionDR-70 is a powerful tool not only for screening unresectable gastric cancer but also for treatment response evaluation.

PCN62 - Real World Treatment Patterns in Metastatic and/or Unresectable Gastric Cancer Patients. Preliminary Results From Colombia

PCN62 - Real World Treatment Patterns in Metastatic and/or Unresectable Gastric Cancer Patients. Preliminary Results From Colombia

E‐Poster Presentations – A2) Gastric and Duodenal

E‐Poster Presentations – A2) Gastric and Duodenal

Efficacy of Conversion Surgery Following S-1 plus Cisplatin or Oxaliplatin Chemotherapy for Unresectable Gastric Cancer.

To evaluate the efficacy of conversion surgery following S-1 plus cisplatin (CS) or oxaliplatin (SOX) chemotherapy. We retrospectively analyzed clinicopathological and survival data of 74 patients with unresectable gastric cancer receiving CS or SOX. Fifty-five and nineteen patients received CS and SOX, respectively. Conversion surgery (odds ratio (OR), 0.17; 95% confidence interval (CI), 0.04-0.64; p=0.01) was the only significant independent predictor of longer survival in multivariate Cox regression analysis. Patients (median age, 74 years) receiving SOX were significantly older than those receiving CS (median age=67 years) (p<0.01), although the rates of response, severe toxicity or conversion surgery did not differ significantly between the two treatment groups. Conversion surgery after a response to CS or SOX chemotherapy may have survival benefit in selected unresectable gastric cancer patients, for both non-elderly and elderly patients responding to SOX.

PCN308 - Real World Treatment Patterns in Metastatic and/or Unresectable Gastric Cancer Patients in Brazil

PCN308 - Real World Treatment Patterns in Metastatic and/or Unresectable Gastric Cancer Patients in Brazil

Prognostic Role of the Circulating Tumor Cells Detected by Cytological Methods in Gastric Cancer: A Meta-Analysis.

Objective. We performed a meta-analysis of available studies to assess the prognostic value of circulating tumor cells detected by cytological methods for patients with gastric cancer. Methods. Two authors systematically searched the studies independently with key words in PubMed, MEDLINE, EMBASE, Science Citation Index Expanded, and Cochrane Library (from inception to April 2016). The estimated hazard ratio, risk ratio, odds ratio, and their 95% confidence intervals were set as effect measures. All analyses were performed by STATA 12.0. Results. Sixteen studies were included in this meta-analysis. CTCs-high status was significantly associated with poor overall survival (HR = 2.23, 95% CI: 1.86–2.66) and progression-free survival (HR = 2.02, 95% CI: 1.36–2.99). CTCs-high status was also associated with depth of infiltration (OR = 2.07, 95% CI: 1.16–3.70), regional lymph nodes metastasis (OR = 1.85, 95% CI: 1.26–2.71), and distant metastasis (OR = 2.83, 95% CI: 1.77–4.52). For unresectable gastric cancer patients, CTCs-high status was significantly associated with poor overall survival, progression-free survival, and disease control rate before and during chemotherapy group. Conclusions. Our meta-analysis has evidenced the significant prognostic value of CTCs detected for both PFS and OS in gastric cancer patients. For patients treated with chemotherapy alone, we proved that CTCs detected by cytological method showed a significant prognostic value and poor response to chemotherapy.

P1-10-6 - Survival Analysis of Unresectable Gastric Cancer Patients Judged Resectable by Initial Ct

Background: Some cases of initially resectable advanced gastric cancer (AGC) are found unresectable during operation due to metastasis or organ invasion. In those cases S1 plus cisplatin (SP) is the standard chemotherapy in Japan. However the clinical outcome remains unknown precisely.Patients and methods: To clarify the clinical feature and outcome of patients with AGC judged resectable by initial CT (CT resectable group) treated with chemotherapy, we retrospectively compared CT resectable group and CT unresectable group (patients with AGC judged unresectable by initial CT) who received SP as the first-line chemotherapy in Cancer Institute Hospital of JFCR between 2007 and 2011.Results: In the period there were 687 patients with AGC who received systemic chemotherapy and 223 (CT resectable group 22 and CT unresectable group 201) patients received SP as first-line chemotherapy. CT resectable group was more likely to have prior gastrectomy (68.2% vs. 30.8%; P < 0.001) and linitis plastica gastric cancer (54.5% vs. 25.4%; P = 0.001). CT resectable group was less likely to have elevated CEA (9.1% vs. 38.3%; P = 0.004), and elevated ALP (9.1% vs. 29.4%; P = 0.040). Median overall survival of CT resectable group was significantly longer than that of CT unresectable group (777 days vs. 412 days; P = 0.001). Multivariate analysis showed that CT resectable group was not associated with overall survival (P = 0.463). Median time to treatment failure of CT resectable group was significantly longer than that of CT unresectable group (524 days vs. 178 days; P < 0.001).Conclusion: In stage4 gastric cancer patients, significant benefit of prognosis were observed in the patients judged resectable by initial CT than others received SP.

HER2 status as an independent prognostic marker in patients with advanced gastric cancer receiving adjuvant chemotherapy after curative gastrectomy.

4084 Background: It has been recently confirmed that trastuzumab, a monoclonal antibody against HER2, improves the overall survival in HER2 overexpressing gastric cancers. We investigated the prognostic significance of HER2 status in gastric cancers after curative gastrectomy and adjuvant chemotherapy. Methods: HER2 status was evaluated in 679 gastric cancer patients who recieved curative gastrectomy and adjuvant chemotherapy. All were enrolled in a phase III clinical trial from January 2002 to July 2006 in Asan Medical Center. Tissue microarrays were constructed using two independent cores form each case. Immunohistochemical (IHC) staining was scored by gastric cancer scoring system. Double silver-enhanced in situ hybridization (SISH) was done using HER2 probe and chromosome 17 centromere oligoprobe (CEP17). IHC score 2+ or 3+, and HER2/CEP17 ratio ≥2.0 were considered positive for IHC and SISH, respectively. IHC 3+ or IHC 2+ and SISH positive cases were defined as “HER2 status-positive”. Results: HER2 IHC-positivity (9.7%), SISH-positivity (12.2%) and HER2 status-positivity (8.3%) were all associated with differentiated or intestinal type histology and distal gastrectomy. IHC-positivity (P = 0.315), SISH-positivity (P = 0.382) and HER2 status-positivity (P = 0.277) showed negative correlation with the recurrence-free survival (RFS) but did not show statistical significance. However, in subgroup analyses according to the stage grouping (II vs. III+IV), HER2 status-positivity was a poor prognostic factor in advanced stage group (P = 0.001) but not in earlier stage (P = 0.827). The HER2 status-positivity remained as an independent prognostic factor after multivariate analysis (P = 0.023, HR = 1.709). Conclusions: HER2 status, taking both protein expression and gene amplification into consideration, was proved to be an independent poor prognostic marker for RFS in advanced stage gastric cancers after curative gastrectomy. Since it has been shown that HER2 status-positive patients benefited from trastuzumab therapy in unresectable gastric cancer patients, trastuzumab may play a role in locally advanced gastric cancer patients as adjuvant therapy.

Biological Markers as a Predictor for Response and Prognosis of Unresectable Gastric Cancer Patients Treated with Irinotecan and Cisplatin

Previously we reported that immunohistochemical examination of p53, bcl-2, glutathione S-transferase-pi (GST-pi), thymidylate synthase (TS) and vascular endothelial growth factor (VEGF) in biopsy samples was a useful method for predicting clinical outcome of gastric cancer patients treated with 5-fluorouracil and cisplatin. Here, we investigated if these biological markers can predict chemoresponse and survival of unresectable gastric cancer patients treated with irinotecan and cisplatin. The subjects were 55 unresectable gastric cancer patients treated with irinotecan (70 mg/m(2), Days 1 and 15) and cisplatin (80 mg/m(2), Day 1). Expression of p53, bcl-2, VEGF was examined immunohistochemically in biopsy samples. The overall response rate and the median survival time were 55% (30/55) and 321 days, respectively. Thirty patients with intestinal-type adenocarcinoma survived longer than 25 patients with diffuse-type (median survival time: 446, 259 days, P = 0.013). The favorable phenotypes for chemoresponse were p53-negative, bcl-2-negative and VEGF-positive, which were in accordance with previous findings. The response rate was significantly correlated with the total number of these favorable phenotypes (P = 0.043). The 39 patients having 2 or 3 favorable phenotypes (p53-negative, bcl-2-negative and VEGF-positive) survived longer than the remaining 16 patients (median survival time: 444, 259 days, P = 0.021). In the Cox model, the number of the favorable phenotypes showed a tendency to correlate with survival after adjustment for potentially prognostic factors such as histological type or performance status (P = 0.070). Immunohistochemical examination of biological markers may be useful in predicting the clinical outcome of unresectable gastric cancer patients treated with irinotecan and cisplatin.

Intensive preoperative radiotherapy with local hyperthermia for the treatment of gastric carcinoma

In order to devitalize maximally tumour tissue and improve the prognosis of gastric cancer patients, a method employing preoperative intensive radiotherapy with local hyperthermia as adjuvant treatment was evaluated. In order to estimate the effectiveness of preoperative intensive radiation and radiation with local microwave hyperthermia in radical gastric cancer treatment, 293 patients were randomized into three respective treatment groups: surgery alone, surgery preceded by preoperative radiation; and surgery followed by preoperative radiation and hyperthermia. Preoperative radiation therapy to a total dose of 20 Gy in four 5 Gy fractions did not improve 3-or 5-year survival in gastric cancer patients in comparison with surgery alone. Local hyperthermia in combination with radiation therapy followed by surgery produced a significant improvement in 3-year survival of 22.1% (from 35.5 ± 4.9% to 57.6 ± 6.3%, P < 0.05) and 5-year survival of 21.3% (from 30.1 ± 4.7 to 51.4 ± 6.6%, P < 0.05). In unresectable gastric cancer patients, radiation therapy and radiation therapy with hyperthermia both increase mean survival. In conclusion; intensive preoperative radiation therapy in total dose 20 Gy plus local microwave hyperthermia significantly improved 3- and 5-year survival in comparison with surgery alone. Further development and evaluation of equipment to produce reliable and safe delivery systems for hyperthermia is needed.