scholarly journals Prognostic Value of Tumor-infiltrating CD163 + macrophage in Patients with Metastatic Gastric Cancer Undergoing Multidisciplinary Treatment.

2021 ◽  
Author(s):  
Jun Kinoshita ◽  
Sachio Fushida ◽  
Takahisa Yamaguchi ◽  
Hideki Moriyama ◽  
Hiroto Saito ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Multidisciplinary Treatment ◽  
Predictive Biomarkers ◽  
Metastatic Gastric Cancer ◽  
Endoscopic Biopsy ◽  
Optimal Timing ◽  
Conversion Surgery ◽  
Response To Chemotherapy ◽  
Pre Treatment ◽  
High Infiltration

Abstract Background: The multidisciplinary treatment including induction chemotherapy plus conversion surgery (CS) has attracted attention as a new strategy to improve the outcome of metastatic gastric cancer (MGC). However, it is unclear which patients achieve a good response to chemotherapy and successful CS. Tumor-infiltrating immune cells (TIICs) have been reported to be both prognostic and predictive biomarkers not only in immunotherapy but also in chemotherapy in many cancer types. However, there have been no reports on the usefulness of TIICs as biomarkers in conversion surgery for MGC. The aim of the present study was to evaluate the association between the TIICs and treatment outcome for the multidisciplinary treatment in MGC.Methods: We retrospectively analyzed 68 MGC patients who received docetaxel plus cisplatin plus S-1 (DCS) therapy between April 2006 and March 2019 in our institute. The number of tumor-infiltrating CD4+, CD8+, Foxp3+lymphocytes, CD68+, CD163+macrophages in pre-treatment endoscopic biopsy samples were evaluated to investigate their predictive value for multidisciplinary treatment.Results: 50 patients underwent CS following DCS therapy (CS group), whereas 18 patients underwent DCS therapy alone (non-CS group). The MST of CS group was 33.3 months, which was significantly longer than the MST of 9.0 months in non-CS group (p<0.01). The number of CD163+macrophages was extracted as an independent prognostic factor for overall survival in all patients. There were more cases of high infiltration of CD 163+macrophages in non-CS group than in CS group. Furthermore, in CS group, pathological responders to DCS therapy showed low infiltration of CD 163+ macrophages, and high infiltration of CD8+lymphocyte. CD 163 low group showed a significant prolonged survival compared with CD163 high group in patients who underwent CS (p=0.02).Conclusions: The pre-treatment CD163+macrophages infiltration would be a pivotal biomarker for predicting prognosis and pathological response to multidisciplinary treatment among TIICs in MGC.Thus, for patients with low CD163+macrophage infiltration in pre-treatment biopsy sample, diagnostic imaging should be performed frequently during chemotherapy to avoid missing the optimal timing for CS, and CS should be aggressively considered as a treatment option if curative resection is deemed feasible.

scholarly journals New drug developments in metastatic gastric cancer

2018 ◽  
Vol 11 ◽  
pp. 175628481880807 ◽  
Author(s):  
Aaron C. Tan ◽  
David L. Chan ◽  
Wasek Faisal ◽  
Nick Pavlakis
Keyword(s):  
Gastric Cancer ◽  
Clinical Trials ◽  
Targeted Therapies ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Predictive Biomarkers ◽  
Metastatic Gastric Cancer ◽  
New Era

Metastatic gastric cancer is associated with a poor prognosis and novel treatment options are desperately needed. The development of targeted therapies heralded a new era for the management of metastatic gastric cancer, however results from clinical trials of numerous targeted agents have been mixed. The advent of immune checkpoint inhibitors has yielded similar promise and results from early trials are encouraging. This review provides an overview of the systemic treatment options evaluated in metastatic gastric cancer, with a focus on recent evidence from clinical trials for targeted therapies and immune checkpoint inhibitors. The failure to identify appropriate predictive biomarkers has hampered the success of many targeted therapies in gastric cancer, and a deeper understanding of specific molecular subtypes and genomic alterations may allow for more precision in the application of novel therapies. Identifying appropriate biomarkers for patient selection is essential for future clinical trials, for the most effective use of novel agents and in combination approaches to account for growing complexity of treatment options.

scholarly journals A Case of Multidisciplinary Treatment for Metastatic Gastric Cancer from Ovarian Cancer

2018 ◽  
Vol 79 (2) ◽  
pp. 337-343
Author(s):  
Kurumi TSUCHIHASHI ◽  
Ken YUU ◽  
Sho TOYODA ◽  
Masao OGAWA ◽  
Masayasu KAWASAKI ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Ovarian Cancer ◽  
Multidisciplinary Treatment ◽  
Metastatic Gastric Cancer

Pretreatment skeletal muscle depletion as an adverse prognostic factor in metastatic gastric cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 161-161
Author(s):  
Hiroko Hasegawa ◽  
Kazumasa Fujitani ◽  
Yusuke Yamaoka ◽  
Motohiro Hirao ◽  
Shoichi Nakazuru ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Skeletal Muscle ◽  
Prognostic Factor ◽  
Cancer Patients ◽  
Performance Status ◽  
Metastatic Gastric Cancer ◽  
First Line ◽  
Skeletal Muscle Index ◽  
Pre Treatment ◽  
The Impact

161 Background: Body composition has emerged as an important prognostic factor in cancer patients. Especially, skeletal mass depletion has been associated with poor performance status, toxicity of chemotherapy and shortened survival in cancer patients. However, the impact of pre-treatment skeletal muscle index on survival or toxicity in metastatic gastric cancer patients remains uncertain. Methods: In this retrospective study, we reviewed 98 metastatic gastric cancer (mGC) patients who received S-1 based combination chemotherapy as first-line treatment from April 2006 to March 2013. Pre-treatment skeletal muscle mass was quantified by CT cross sectional area at the third lumbar vertebrae and evaluated as lumbar skeletal muscle index (SMI) (cm2/m2) after normalization for stature (m2). Patients were categorized into 2 groups depending on initial SMI: 35 patients with SMI ≤ 40 and 63 patients with SMI > 40. Results: Median overall survival was significantly shorter in the SMI ≤ 40 group than in the SMI >40 group (439 days versus 565 days; p= 0.03). Progression free survival was also better in the SMI> 40 group without statistical significance (175 days versus 151 days; p= 0.17). Toxicity (grade 3 or 4) was more common in the SMI ≤ 40 group than in the SMI >40 group. (41.1% versus 11.1%; p=0.001). In multivariate analysis, performance status of 2 (HR 4.711, 95%CI 1.065 to 20.832, p=0.04), presence of primary tumor (HR 2.322, 95%CI 1.007 to 5.357, p=0.04) and pre-treatment SMI (HR 2.525, 95%CI 1.145 to 5.568, p=0.02) were independent prognostic factors for OS. Conclusions: The present study suggests that skeletal muscle depletion at the initiation of first-line chemotherapy might be an independent prognostic factor for mGC patients.

The prognostic factor and the optimal timing of conversion surgery in unresectable stage IV gastric cancer: A retrospective analysis.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 78-78
Author(s):  
Tamotsu Sagawa ◽  
Yutaka Okagawa ◽  
Fumito Tamura ◽  
Tsuyoshi Hayashi ◽  
Koshi Fujikawa ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Survival Rate ◽  
Univariate Analysis ◽  
Stage Iv ◽  
Residual Tumor ◽  
Optimal Timing ◽  
Conversion Surgery ◽  
Stage Iv Gastric Cancer ◽  
Metastatic Lesions ◽  
Unresectable Stage

78 Background: Conversion surgery could be an option for unresectable stage IV gastric cancer when distant metastasis (M1) is disappeared by chemotherapy. However, the indication and the optimal timing of conversion surgery in stage IV gastric cancer remain unclear, even if metastatic lesions disappear with chemotherapy. Guideline of National Comprehensive Cancer Network also shows no principle after down-staging. Methods: This retrospective study examined 34 gastric cancer patients who underwent curative conversion surgery at our institute between 2005 and 2014. Clinicopathologic characteristics and patient outcomes were analyzed, with particular focus on the potential to select patients who might benefit from surgical resection. Results: The number of M1 factors was one in 31 patients and two in 3, including metastases to non-regional lymph node in 21, peritoneum in 8, liver in 5, and lung in 3. The regimen of chemotherapy was Docetaxel/CDDP/S-1 in 23 patients, Docetaxel/CDDP/S-1+Trastuzmab in 6, S-1/CDDP in 2, Docetaxel/S-1 in 1, CPT/CDDP in 1, and S-1 monotherapy in 1. The median duration from initiation of chemotherapy to the operation was 114 days (range 37-653 days). Total gastrectomy was performed in 27 patients and distal gastrectomy was performed in 7 patients. Complete resection with no residual tumor (R0) was achieved in 23 of 34 patients, microscopic residual tumor status (R1) in 10, and macroscopic residual tumor (R2) in 1. The 3-year overall survival (OS) rate among the patients who underwent conversion therapy was 58.0% with MST of 1190 days. Univariate analysis among the patents with conversion surgery identified intestinal differentiation, pathological response grade≧1b, R0 resection as significant prognostic factors. Patients operated on more than 91 days from initiation of chemotherapy had the 3-year survival rate of 68.2%, compared to 40.0% for patients operated on less than 90 days. Conclusions: Our data demonstrate the increased 3-year survival rate associated with delayed conversion surgery for stage IV gastric cancer. Delayed conversion surgery should be considered for patients, even if metastatic lesions disappear with chemotherapy.

scholarly journals Clinical significance of conversion surgery for gastric cancer with peritoneal dissemination: A retrospective study

2020 ◽  
Author(s):  
Takaaki Arigami ◽  
Daisuke Matsushita ◽  
Keishi Okubo ◽  
Takashi Kijima ◽  
Masataka Shimonosono ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Retrospective Study ◽  
Progressive Disease ◽  
Tumor Response ◽  
Peritoneal Dissemination ◽  
Survival Rates ◽  
Prognostic Significance ◽  
Distant Metastases ◽  
Conversion Surgery ◽  
Response To Chemotherapy

Abstract Background: Although chemotherapy has been clinically recommended as the initial treatment for patients with peritoneal dissemination of gastric cancer, poor prognosis has been noted among the same patients. However, the prognostic significance of conversion surgery after chemotherapy remains unclear. The present study therefore aimed to assess the clinical impact of conversion surgery among patients with peritoneal dissemination of gastric cancer.Methods: A total of 93 patients with peritoneal dissemination of gastric cancer undergoing chemotherapy between February 2002 and October 2019 were retrospectively enrolled and subsequently divided into progressive disease (PD) and non-PD groups based on tumor response to chemotherapy.Results: Among the included patients, 17 developed distant metastases at another site besides peritoneal dissemination. Based on tumor response, 24 and 69 patients were determined to have PD and non-PD, respectively, with the former having significantly poorer prognosis than the latter (p < 0.0001). A total of 19 patients underwent conversion surgery after chemotherapy, with the presence or absence of conversion surgery being significantly correlated with age, first-line chemotherapy regimen, and tumor response (p = 0.0134, 0.0337, and 0.0024, respectively). Patients in the non-PD group who underwent conversion surgery or chemotherapy alone had 3-year overall survival rates of 55.6% and 6.6%, respectively. Multivariate analysis identified conversion surgery alone as an independent prognostic factor in the non-PD group (p < 0.0001).Conclusion: Our retrospective study demonstrated that conversion surgery for gastric cancer with peritoneal dissemination might improve the prognosis of responders who developed no peritoneal dissemination after chemotherapy.

scholarly journals The Prognostic Value of Pre-treatment Hemoglobin (Hb) in Patients With Advanced or Metastatic Gastric Cancer Treated With Immunotherapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Miaomiao Gou ◽  
Yong Zhang ◽  
Tiee Liu ◽  
Tongtong Qu ◽  
Haiyan Si ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Multivariate Analysis ◽  
Prognostic Value ◽  
Univariate Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Metastatic Gastric Cancer ◽  
Significant Prognostic Factor ◽  
Angiogenic Therapy ◽  
Pre Treatment

BackgroundBiomarkers such as prevailing PD-L1 expression and TMB have been proposed as a way of predicting the outcome of immunotherapy in patients with advanced gastric cancer (AGC) and metastatic gastric cancer (MGC). Our study aims to investigate whether there is a link between pretreatment hemoglobin (Hb) levels and survival to immunotherapy in patients with AGC and MGC.MethodsWe retrospectively reviewed patients with AGC or MGC treated at the oncology department of the Chinese PLA general hospital receiving PD-1 inhibitor. The Propensity Score Matching (PSM) (1:1) was performed to balance potential baseline confounding factors. Progression-free survival (PFS) and overall survival (OS) was analyzed among different Hb level (normal Hb group and decreased Hb group). Objective response rate (ORR), disease control rate (DCR) were also analyzed. Univariate analysis and multivariate analysis were performed further to validate the prognostic value of Hb level.ResultsWe included 137 patients with AGC and MGC who received PD-1 inhibitors (including Pembrolizumab, Nivolumab, Sintilimab, Toripalimab) in this study. After PSM matching, there were no significant differences between the two groups for baseline characteristics. Within the matched cohort, the median PFS was 7.8 months in the normal Hb level group and 4.3 months in the decreased Hb group (HR 95% CI 0.5(0.31, 0.81), P=0.004). The OS was 14.4 months with normal Hb level as compared with 8.2 months with decreased Hb level(HR 95% CI 0.59(0.37, 0.94), P=0.024). The ORR was 40.7% and DCR was 83.0% in the normal Hb group, while the ORR was 25.5% and DCR was 85.1% in the decreased Hb group. No significant differences were found in the ORR and DCR between the two groups (P=0.127, P=0.779). Univariate analysis and multivariate analysis showed that Hb level was only independent predictor for PFS and baseline Hb level was significant prognostic factor influencing the OS. Only when patients had normal Hb level, anti-pd-1 monotherapy or combined with chemotherapy was superior to anti-pd-1 plus anti-angiogenic therapy with respect to PFS (10.3 m vs 2.8 m, HR 95% CI 0.37(0.15, 0.95), P=0.031) and OS(15 m vs 5.7 m, HR 95% CI 0.21 (0.08, 0.58), P=0.001).ConclusionsOur study have demonstrated that pretreatment Hb level was an independent prognostic biomarker in term of PFS and OS with immunotherapy for AGC and MGC patients. Correction of anemia for GC patients as immunotherapy would be a strategy to improve the survival. More data was warranted to further influence this finding.

Vascular endothelial growth factor A (VEGF-A) amplification and long-term response to ramucirumab (ram) in metastatic gastric cancer (mGC): The VERA study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3143-3143
Author(s):  
Alessandra Raimondi ◽  
Patrizia Gasparini ◽  
Sara Lonardi ◽  
Salvatore Corallo ◽  
Lorenzo Fornaro ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Single Agent ◽  
Predictive Biomarkers ◽  
Metastatic Gastric Cancer ◽  
Second Line ◽  
Best Response ◽  
Ffpe Tumor ◽  
Pre Treatment ◽  
Term Response

3143 Background: The anti-VEGFR-2 monoclonal antibody ram, alone or with paclitaxel, is a cornerstone of second-line treatment of mGC. Even if about half patients do not benefit from ram, no predictive biomarkers have been identified so far. In TCGA, VEGF-A amplification was found in 7% of cases, almost exclusively in chromosomal instability subtype. We hypothesize that VEGF-A amplification in tumor cells could lead to autocrine/paracrine stimulation of tumor growth beside angiogenesis, potentially identifying a patients’ subgroup with exceptional responses to ram. Methods: VERA was a multicentric, prospective study based on a translational hypothesis. mGC patients were included according to the following criteria: 1) complete (CR) or partial response (PR) to single-agent ram; 2) >6 months PFS to single-agent ram; 3) >10 months PFS to paclitaxel+ram. According to a Fleming single-stage design, hypothesizing a prevalence of VEGF-A amplification of 1% and 15% among all-comers and exceptional responders, 20 exceptional responders were required to reject the null hypothesis of low prevalence of VEGF-A amplification, with alpha- and beta- errors of 0.05 and 0.10, respectively. VEGF-A amplification (defined as >10% tumor cells with ≥10 VEGF-A copies, variably sized signal clusters or a ratio of VEGF-A gene to centromere of ≥2) was centrally assessed through fluorescent in situ hybridization on pre-treatment FFPE tumor tissue. Results: At 7 Italian Centers, we included 20 patients satisfying the 1st (n=1), 2nd (n=2), or 3rd (n=17) criterion. Clinical-pathological features were: M/F, 11/9; median age 63 years; gastric/GEJ, 17/3; intestinal/diffuse, 14/6, HER2+/HER2-, 4/16. Median PFS and overall survival to ram-based treatment were 15.6 and 25.7 months, with best response: CR/PR/SD, 0/10/10. VERA met its primary endpoint, revealing 3/20 (15%) tumors with VEGF-A amplification (1 case presenting big clusters, 1 small clusters and 1 with >10% tumor cells with ≥10 VEGF-A copies). Conclusions: Validation analyses of first- and second-line randomized trials could confirm VEGF-A amplification as a biomarker of long-term response to ram-based treatment in mGC patients, advancing treatment personalization.

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