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Introduction: Gastric cancer is the fifth most-common cancer and fourth common cause for cancer-related deaths globally. Surgery preceded or followed by chemotherapy or chemoradiotherapy is considered an optimal treatment for locally advanced gastric cancer. This study is a real-world data from a tertiary referral institute in southern India, in its experience with treating gastric adenocarcinoma over a period of four years with a minimum of two-year follow-up. Methods: This was a retrospective analysis of data of patients with histologically proven gastric adenocarcinoma enrolled in the Department of Medical Oncology from 2015 to 2018. The demographic details, presentation, staging, treatment received and outcomes of patients with gastric adenocarcinoma were collected and analyzed in this study. Results: Total 488 patients with gastric adenocarcinoma were included for the study. The stage-wise distribution of patients revealed early and locally advanced (45%) and metastatic (55%). The peritoneum and liver were the common sites of metastasis. The treatment distribution of these patients included perioperative chemotherapy followed by surgery (25 [5%]), surgery followed by adjuvant chemotherapy (65 [13%]), surgery alone (16 [3%]), perioperative chemotherapy alone (23 [4%]), palliative chemotherapy (274 [56%]) and supportive care (85 [17%]). The median overall survival for curative, palliative and supportive treatment was 23 (18–28), nine (7.6–10.4) and four (2.7–5.3) months, respectively. The two-year overall survival in the intention to treat population in the primary surgery (n = 81) and perioperative chemotherapy groups (n = 66) was 67.4% vs. 29.9% (p < 0.0001), respectively. Conclusion: This study highlights the advanced nature of the presentation of gastric cancer patients and the poor rate of treatment completion. The median survival rates in curative patients remain to be dismally poor. The treatment sequence in curable gastric cancer of surgery followed by adjuvant chemotherapy vs. perioperative chemotherapy followed by surgery needs to be explored in our country. [ABSTRACT FROM AUTHOR]

Resumen: Introducción y objetivos: El adenocarcinoma gástrico se ubica entre las neoplasias malignas con mayor frecuencia y mortalidad en el mundo. Se ha observado que el proceso inflamatorio y la actividad del sistema inmunológico están asociados al control oncológico. Nuestro objetivo es identificar si el índice neutrófilo/linfocito (INL), el índice plaqueta/linfocito (IPL) y otros factores son pronósticos para supervivencia en pacientes con cáncer gástrico metastásico en nuestra población. Material y métodos: Pacientes con diagnóstico de adenocarcinoma gástrico metastásico, admitidos de diciembre de 2011 a 2021. A partir de una muestra de sangre al ingreso se calculó el INL, el IPL, la albúmina y la hemoglobina. Además, se consideró el estado funcional (ECOG y Karnofsky), el sexo, la histología y la presencia de células en anillo de sello como otros factores que pudieran ser pronósticos. Por medio de un análisis univariado y multivariado se determinó el valor pronóstico de cada factor para supervivencia global. Resultados: Se incluyeron 956 pacientes con diagnóstico de cáncer gástrico metastásico, 494 (51.7%) fueron hombres y 462 (48.3%) mujeres; la principal histología fue el adenocarcinoma difuso (619; 64.7%), seguido por el adenocarcinoma intestinal (293; 30.6%), y del total de pacientes, 659 (68.9%) tuvieron presencia de células en anillo de sello. En 238 pacientes (24.9%) se realizó laparoscopia diagnóstica para confirmar la carcinomatosis peritoneal. El análisis multivariado demostró que un INL mayor de 3.2 (HR 1.51, IC 95% 1.27-1.8; p

Simple Summary: Metastatic gastric cancer (GC) remains a major clinical challenge due to scarce treatment options and an ominous prognosis, often diagnosed at later stages. Recent progress in identifying molecular targets and integrating immune checkpoint inhibitors with chemotherapy has transformed treatment strategies. The new classification of GC, based on immunologic and molecular markers, has drastically changed the therapeutic approach, focusing on personalized target-based treatments. This review summarizes molecular and immunological targets currently available and explores future approaches like circulating tumor DNA (ctDNA) monitoring, targeting fibroblast growth factor receptor (FGFR) and MET pathways, chimeric antigen receptor (CAR)-T cells, and cancer vaccines for their potential to improve understanding and treatment of this disease. Metastatic gastric cancer (GC) still represents a critical clinical challenge, with limited treatment options and a poor prognosis. Most patients are diagnosed at advanced stages, limiting the chances of surgery and cure. The identification of molecular targets and the possibility of combining immune checkpoint inhibitors with chemotherapy have recently reshaped the therapeutic landscape of metastatic gastric cancer. The new classification of gastric cancer, mainly based on immunologic and molecular criteria such as programmed cell death 1 (PD-1), microsatellite instability (MSI), and human epidermal growth factor receptor 2 (HER2), has made it possible to identify and differentiate patients who may benefit from immunotherapy, targeted therapy, or chemotherapy alone. All relevant and available molecular and immunological targets in clinical practice for the systemic treatment of this disease are presented. Particular attention is given to possible future approaches, including circulating tumor DNA (ctDNA) for therapeutic monitoring, new targeting agents against molecular pathways such as fibroblast growth factor receptor (FGFR) and MET, chimeric antigen receptor (CAR)-T cells, and cancer vaccines. This review aims to provide a comprehensive understanding of current targets in advanced gastric cancer and to offer valuable insights into future directions of research and clinical practice in this challenging disease. [ABSTRACT FROM AUTHOR]

Background: We examined the impact of mismatch repair (MMR) status on efficacy of first-line fluoropyrimidine plus platinum (FP) chemotherapy in patients with HER2-negative metastatic, recurrent, or unresectable gastric cancer (mGC). Methods: Patients with mGC receiving first-line FP between 2015 and 2018 at Asan Medical Center, Korea, were reviewed. We evaluated the clinical characteristics and the efficacy of chemotherapy according to MMR status in patients with available immunohistochemistry results. Results: Of 895 patients, we analyzed 543 with available MMR protein expression results, and deficient MMR (dMMR) was detected in 4.4% (n = 24). Patients with dMMR exhibited a significantly higher median age than those with proficient MMR (pMMR) (64 vs. 58 years, p = 0.044). No signet ring cell carcinoma (SRCC) was detected among dMMR tumors, whereas SRCC was found in 17.5% of pMMR. Objective response rate was 27.3% in dMMR and 34.3% in pMMR (p = 0.556). No difference in progression-free survival was noted between patients with dMMR and pMMR (median, 5.6 vs. 5.8 months, p = 0.266). Patients with dMMR tended to have better overall survival than those with pMMR although this difference was not statistically significant (median, 17.9 vs. 12.2 months, p = 0.183). Conclusions: Efficacy of first-line FP was not different by MMR status in mGC patients. [ABSTRACT FROM AUTHOR]

Abstract Background Patients with metastatic gastric cancer (mGC) have poor prognosis. This real-world study aimed to describe treatment regimens and survival of mGC patients. Methods A retrospective analysis was conducted using anonymized German claims data (AOK PLUS) covering a period from 2010 to 2021. The study population included newly diagnosed mGC cases identified from 2011 to 2020. The index date was defined as the first diagnosis of metastasis on or after gastric cancer diagnosis. Therapy regimens were identified based on inpatient and outpatient data, and subsequently stratified by line of treatment. Survival analyses were conducted using the Kaplan–Meier method. Results The cohort consisted of 5,278 mGC incident cases (mean age: 72.7 years; male: 61.9%). Nearly half of the incident cases received mGC-related treatment (49.8%). Treated patients were more often male, younger, and had fewer comorbidities compared to untreated patients. Of the 2,629 mGC patients who started the first line of treatment (1LOT), 32.8% switched to 2LOT, and 10.2% reached 3LOT. Longer survival time was observed among disease-specific treated cases compared with untreated cases (median real-world overall survival (rwOS): 12.7 months [95%CI 12.1 – 13.3 months] vs. 3.7 months [95%CI 3.4 – 4.0 months]). Conclusion Systemic therapy was not received in almost half of the mGC patients. In those patients, a very short median rwOS was observed. Treatment patterns were generally in line with the guideline recommendations, however, therapy switching rates and poor prognosis indicate high unmet needs also in the treated population.

Leptomeningeal disease, also known as leptomeningeal carcinomatosis, occurs when cancer metastasizes to the meninges. This rare complication is associated with a poor prognosis. It is most commonly seen in patients with metastatic breast cancer, lung cancer, and melanoma. However, it is extremely rare in patients with metastatic gastric cancer. A 64-year-old female with poorly differentiated gastric adenocarcinoma metastatic to the peritoneum developed new neurological symptoms twelve months after initiating palliative chemotherapy. Her uptrending tumor markers, brain magnetic resonance imaging (MRI) findings, and lumbar puncture results were consistent with leptomeningeal disease. The patient was started on treatment with intrathecal methotrexate (IT MTX), which resulted in significant improvement in her neurological symptoms. Leptomeningeal disease in gastric cancer has limited treatment options due to poor blood-brain barrier penetration. IT MTX is a potentially effective treatment for patients with leptomeningeal disease from gastric cancer.

Background: Patients with metastatic gastric cancer (mGC) have poor prognosis. This real-world study aimed to describe treatment regimens and survival of mGC patients. Methods: A retrospective analysis was conducted using anonymized German claims data (AOK PLUS) covering a period from 2010 to 2021. The study population included newly diagnosed mGC cases identified from 2011 to 2020. The index date was defined as the first diagnosis of metastasis on or after gastric cancer diagnosis. Therapy regimens were identified based on inpatient and outpatient data, and subsequently stratified by line of treatment. Survival analyses were conducted using the Kaplan–Meier method. Results: The cohort consisted of 5,278 mGC incident cases (mean age: 72.7 years; male: 61.9%). Nearly half of the incident cases received mGC-related treatment (49.8%). Treated patients were more often male, younger, and had fewer comorbidities compared to untreated patients. Of the 2,629 mGC patients who started the first line of treatment (1LOT), 32.8% switched to 2LOT, and 10.2% reached 3LOT. Longer survival time was observed among disease-specific treated cases compared with untreated cases (median real-world overall survival (rwOS): 12.7 months [95%CI 12.1 – 13.3 months] vs. 3.7 months [95%CI 3.4 – 4.0 months]). Conclusion: Systemic therapy was not received in almost half of the mGC patients. In those patients, a very short median rwOS was observed. Treatment patterns were generally in line with the guideline recommendations, however, therapy switching rates and poor prognosis indicate high unmet needs also in the treated population. [ABSTRACT FROM AUTHOR]

Background: Currently, there is no recommended standard third-line chemotherapy for metastatic gastric cancer. Objectives: In this study, we aimed to evaluate irinotecan's efficacy and safety in treating metastatic gastric cancer after the failure of first- and second-line chemotherapy. Design: Prospective single-arm, two-center, phase II trial. Methods: Patients were aged 18–70 years, with histologically confirmed gastric adenocarcinoma and an Eastern Cooperative Oncology Group performance status of 0–1, progressed during or within 3 months following the last administration of second-line chemotherapy and had no other severe hematologic, cardiac, pulmonary, hepatic, or renal functional abnormalities or immunodeficiency diseases. Eligible patients received 28-day cycles of irinotecan (180 mg/m2 intravenously, days 1 and 15) and were assessed according to the RECIST 1.1 criteria every two cycles. Patients who discontinued treatment for any reason were followed up every 2 months until death. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and toxicity. Results: A total of 98 eligible patients were enrolled in this study. In the intention-to-treat population, the median OS was 7.17 months, the median PFS was 3.47 months, and the ORR and DCR were 4.08% and 47.96%, respectively. In the per-protocol population, the median OS was 7.77 months, the median PFS was 3.47 months, and the ORR and DCR were 4.82% and 50.60%, respectively. The incidence of grade 3 or 4 hematological and non-hematological toxicities was 19.4%, and none of the patients died owing to adverse events. Cox regression analysis revealed neutropenia and baseline thrombocyte levels were independently correlated with PFS and OS. Conclusion: Irinotecan monotherapy is an efficient, well-tolerated, and economical third-line treatment for patients with metastatic gastric cancer as a third-line treatment. Trial registration: ClinicalTrials.gov identifier: NCT02662959. [ABSTRACT FROM AUTHOR]

Abstract Background This study sought to develop and validate nomograms for screening patients with metastatic gastric cancer (mGC) who are candidates for primary tumor resection (PTR) and evaluating the prognosis of mGC patients after PTR. Methods From 2010 to 2016, we screened mGC patients with complete data from the Surveillance, Epidemiology, and End Results (SEER) database. Depending on whether or not PTR was performed, we categorized patients into surgery and non‐surgery groups. A 1:1 propensity score matching (PSM) analysis was used to balance the characteristics of the two groups. The endpoints were overall survival (OS) and cancer‐specific survival (CSS). Two predictive nomograms were developed using logistic regression to assess the likelihood of benefit. Two additional prognostic nomograms were developed to assess prognosis in mGC patients after PTR by Cox regression. Finally, nomograms were evaluated using a variety of methodologies. Results Our study included 3594 mGC patients who met the criteria. PTR was associated with improved OS and CSS time (median OS time after PSM: 15 vs. 7 months, P

Owing to tumor heterogeneity and individual physiological variations, there remains a necessity to enhance the current prognosis prediction system for metastatic gastric cancer (MGC). This study aimed to establish a prognostic model for patients diagnosed with MGC. Pertinent information pertaining to MGC patients was extracted and assessed from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2016. The Kaplan-Meier method and Cox regression analysis were employed to identify potential prognostic factors. Furthermore, a nomogram model containing possible prognostic factors associated with overall survival (OS) was constructed using R software. A total of 2975 patients from the SEER database were included in this investigation. N-stage, grade, surgery, radiotherapy, chemotherapy, brain metastasis, bone metastasis, liver metastasis, and lung metastasis were identified as independent prognostic factors for OS. These variables were subsequently incorporated into the nomogram model. Calibration curves demonstrated a good correlation between nomogram predictions and actual observations. The nomogram model exhibits the potential to estimate the individualized survival of MGC patients.

Simple Summary: This study aimed to identify early predictive factors associated with the success of conversion surgery with R0 resection in patients with metastatic gastric cancer who underwent systemic chemotherapy. Patients with carcinoembryonic antigen > 5.0 ng/mL at the initial Response Evaluation Criteria in Solid Tumors evaluation showed less expectancy of undergoing conversion surgery with R0 resection. This retrospective study examined early the predictive factors for successful conversion surgery (CS) with R0 resection in patients with metastatic gastric cancer (MGC) who underwent systemic chemotherapy. This study included 204 patients diagnosed with metastatic gastric adenocarcinoma, who received chemotherapy between 2009 and 2019. Of these patients, 31 (15%) underwent CS with R0 resection. The incidence of CS with R0 resection was not affected by the volume of metastatic lesions or the presence of peritoneal metastasis. The overall survival time of the CS with R0 resection group was significantly longer than that of the non-CS group (hazard ratio, 0.12; 95% confidence interval, 0.07–0.23; p < 0.0001), with a 5 year overall survival rate of 50.2%. Multivariate analysis of 150 patients, excluding those with disease progression until the initial Response Evaluation Criteria in Solid Tumors (RECIST) evaluation, showed that carcinoembryonic antigen > 5.0 ng/mL at the initial RECIST evaluation was an independent, significant, and unfavorable predictor of CS with R0 resection (odds ratio, 0.21; p = 0.0108), whereas systemic chemotherapy with trastuzumab for HER2-positive cancer was a favorable factor (odds ratio, 4.20; p = 0.0119). Monitoring serum carcinoembryonic antigen levels during chemotherapy may be a useful predictor of the CS implementation in patients with MGC. [ABSTRACT FROM AUTHOR]

Simple Summary: Advanced gastric cancer (GCa) is associated with poor prognosis due to the challenge of peritoneal disease, the most common site of metastasis at initial diagnosis, staging laparoscopy, and recurrence. Unfortunately, current standards of care for peritoneal metastasis (PM) in GCa are palliative therapies, despite hyperthermic intraperitoneal chemotherapy (HIPEC) being a proven standard of care for other peritoneal malignancies. Fortunately, results from studies investigating the impact of HIPEC in patients suffering from GCa with PM are encouraging. Additionally, several ongoing trials may offer further data and some centers have incorporated HIPEC into their treatment of patients with metastatic GCa. HIPEC can potentially confer improved survival outcomes in select patients with GCa and PM, who historically have dismal outcomes, and further well-designed clinical trials are warranted. This manuscript provides a comprehensive review of the current evidence supporting the use of HIPEC and cytoreductive surgery (CRS) in patients suffering from GCa with PM. Gastric cancer (GCa) is an aggressive malignancy, representing the third leading cause of cancer mortality worldwide. The poor prognosis of GCa can be associated with the prevalence of peritoneal metastasis (PM). Current international and national GCa treatment guidelines only recommend palliative treatment options for patients with PM. Since the 1980s there have been multiple single arm trials, randomized controlled trials, and metanalysis investigating the use of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with advanced GCa, with or without PM. Results from these studies have been encouraging, with some large-volume centers even incorporating HIPEC into their treatment algorithms for patients with advanced GCa. Additionally, there are several ongoing trials that, when completed, will increase our understanding of the efficacy of CRS & HIPEC in patients with GCa metastatic to the peritoneum. Herein we review the current evidence, ongoing trials, consensus guidelines, and future considerations regarding the use of CRS & HIPEC in patients suffering from GCa with PM. [ABSTRACT FROM AUTHOR]

Metastatic gastric cancer (mGC) often has a poor prognosis and may benefit from a few targeted therapies. Ramucirumab-based anti-angiogenic therapy targeting the VEGFR2 represents a milestone in the second-line treatment of mGC. Several studies on different cancers are focusing on the major VEGFR2 ligand status, meaning VEGFA gene copy number and protein overexpression, as a prognostic marker and predictor of response to anti-angiogenic therapy. Following this insight, our study aims to examine the role of VEGFA status as a predictive biomarker for the outcome of second-line therapy with Ramucirumab and paclitaxel in mGC patients. To this purpose, the copy number of the VEGFA gene, by fluorescence in situ hybridization experiments, and its expression in tumor tissue as well as the density of micro-vessels, by immunohistochemistry experiments, were assessed in samples derived from mGC patients. This analysis found that amplification of VEGFA concomitantly with VEGFA overexpression and overexpression of VEGFA with micro-vessels density are more represented in patients showing disease control during treatment with Ramucirumab. In addition, in the analyzed series, it was found that amplification was not always associated with overexpression of VEGFA, but overexpression of VEGFA correlates with high micro-vessel density. In conclusion, overexpression of VEGFA could emerge as a potential biomarker to predict the response to anti-angiogenic therapy. [ABSTRACT FROM AUTHOR]

Background: This study sought to develop and validate nomograms for screening patients with metastatic gastric cancer (mGC) who are candidates for primary tumor resection (PTR) and evaluating the prognosis of mGC patients after PTR. Methods: From 2010 to 2016, we screened mGC patients with complete data from the Surveillance, Epidemiology, and End Results (SEER) database. Depending on whether or not PTR was performed, we categorized patients into surgery and non‐surgery groups. A 1:1 propensity score matching (PSM) analysis was used to balance the characteristics of the two groups. The endpoints were overall survival (OS) and cancer‐specific survival (CSS). Two predictive nomograms were developed using logistic regression to assess the likelihood of benefit. Two additional prognostic nomograms were developed to assess prognosis in mGC patients after PTR by Cox regression. Finally, nomograms were evaluated using a variety of methodologies. Results: Our study included 3594 mGC patients who met the criteria. PTR was associated with improved OS and CSS time (median OS time after PSM: 15 vs. 7 months, P < 0.05; median CSS time after PSM: 17 vs. 7 months, P < 0.05). The OS‐related predictive nomogram, including age, histologic type, grade, T stage, and chemotherapy, was developed. Moreover, the CSS‐related predictive nomogram, including age, histologic type, grade, and chemotherapy, was developed. Sex, histologic type, grade, T stage, N stage, and chemotherapy were found to be correlated with OS. Furthermore, the CSS correlated with histologic type, grade, T stage, N stage, and chemotherapy. Both predictive and prognostic nomograms were found to be valuable and reliable after different types of validation. Conclusion: Predictive nomograms were developed and validated for identifying the optimal PTR mGC candidates. Prognostic nomograms were developed and validated for assessing the prognosis of mGC patients after PTR. [ABSTRACT FROM AUTHOR]

Background: Metastatic gastric cancer (MGC) patients with progression on firstline treatment still have poor outcomes on chemotherapy. The KEYNOTE-061 study demonstrated that pembrolizumab, a PD-1inhibitor, was not better than paclitaxel as second-line therapy for MGC. Herein, we explored the efficacy and safety of PD-1inhibitor based treatment for MGC patients in the second line. Methods: In this observational, retrospective study, we enrolled MGC patients treated with anti-PD-1 based therapy as second-line in our hospital. We primarily assessed the treatment's efficacy and safety. We also evaluated the relationship between clinical features and outcomes using univariate and multivariate analyses. Results: We enrolled 129 patients with an objective response rate (ORR) of 16.3% and a disease control rate (DCR) of 79.1%. Patients treated with PD-1inhibitor combined with chemotherapy and anti-angiogenic agents had ORR of 19.6% and higher DCR of 94.1%. The median progression-free survival (PFS) was 4.10 months, and the median overall survival (OS) was 7.60 months. In univariate analysis, patients treated with PD-1inhibitor combined with chemotherapy and anti-angiogenic agents and with prior anti-PD-1 history were significantly associated with favorable PFS and OS. In the multivariate analysis, different combination therapy and prior anti-PD-1 history were independent prognosis biomarkers for PFS and OS. Grade 3 or 4 treatment-related adverse events (TRAEs) occurred in 28 (21.7%) patients. Common adverse events (AEs) included fatigue, hyper/hypothyroidism, neutrophil decrease, anemia, skin reactions, proteinuria, and hypertension. We did not observe treatment-related deaths. Conclusion: Our current results indicated that PD-1-inhibitor and chemo-antiangiogenic agents combination therapy and prior PD-1 treatment history might improve clinical activity for GC immunotherapy as second-line treatment with acceptable safety profiles. Further studies are needed to verify those outcomes for MGC in other centers. [ABSTRACT FROM AUTHOR]

Abstract Background Gastric carcinoma is one of the most frequent malignancies worldwide. Gastric cancer metastasis to the appendix is uncommon in incidence, and has been rarely described in acute-appendicitis-related literature reviews. In this presented case, we have reported a rare case of appendiceal phlegmon, due to a diagnosis of metastatic gastric adenocarcinoma with uncommon symptoms. Case presentation A 79-year-old Caucasian male presented to the emergency department with history of weakness, anorexia, lethargy, and mood changes for 2 months. Abdominopelvic computed tomography showed an abscess in right iliac muscle. After percutaneous drainage of the abscess and 6 weeks antibiotic therapy, an appendectomy was done for the patient. Histopathologic findings revealed the involvement of the appendiceal wall by adenocarcinoma, most probably with gastrointestinal origin. Gastric cancer was confirmed later by upper endoscopy and pathologic report. Conclusions Although the presence of tumor in appendectomy specimens is rare, and metastasis to appendix is even rarer, it should be considered as a cause of appendicitis, especially in elderly patients.

In recent years, advances of anticancer and supportive therapies have determined a gradual improvement in survival rates and patients’ general conditions in metastatic gastric cancer (mGC), allowing them to receive further treatments. The choice of treatment is driven by performance status, age, stage of disease, number of metastatic sites and time from the first to third line of treatment. Targets such as microsatellite instability, PD-L1 expression, and HER2 overexpression or amplification may be addressed to personalise treatment and prolong survival. Despite a growing number of third line options that have provided clinicians with greater opportunities to customise treatments, up to date few agents have been demonstrated as effective after two standard lines for mGC; for these reasons, chemotherapy, immunotherapy, and targeted therapy were all widely investigated in both phase II and phase III studies. Overall, TAS-102, apatinib, regorafenib, nilotinib, trastuzumab, and pembrolizumab were demonstrated to be valid options in the third line scenario for mGC patient refractory to at least two lines of therapy. A multimodal approach based on chemotherapy, immunotherapy, targeted agents, a personalised nutritional programme as well as the research of new predictive biomarkers may pave the way to new strategies to identify the best treatment for each patient.

Background: Metastatic gastric cancer (GC) is the third most common cause of cancer-related death. At the time of metastatic stage treatment is given for palliative purposes. Therefore parameters other than performance status are needed to determine the prognosis. Objectives: It is aimed demonstrate that the modified Glasgow Prognostic Score (mGPS) is prognostic factor for overall survival and mGPS is a sensitive marker in patients diagnosed with metastatic GC in Turkish population. Materials and Methods: Clinical and laboratory data were collected and evaluated in the form of retrospective file scanning of One hundred forty-five patients with metastatic GC in Private Izmir Kent Hospital between 2017 and 2022. Analyzed factors included age, gender, precense of de novo or recurrent disease, first line treatment, ECOG-PS score, mGPS, CRP, and albumin levels, Progression Free Survival (PFS) and Overal Survival (OS). Results: The median age at diagnosis was 67 years, the median progression-free survival (PFS) was 5.3 months, and the median overall survival (OS) was 9.5 months. OS was 15.1 months in patients with an mGPS of 0, 9.3 months in patients with an mGPS of 1, and 6.4 months in patients with an mGPS of 2 (*p=0.001). Conclusions: mGPS is an easy to use and applicable parameter in Metastatic GC. High mGPS is poor prognostic factor for both PFS and OS in metastatic GC.

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 Fifty patients underwent CS following DCS therapy (CS group), whereas 18 patients underwent DCS therapy alone (non-CS group). The median survival time (MST) of CS group was 33.3 months, which was significantly longer than the MST of 9.0 months in non-CS group (p

Background: Gastric carcinoma is one of the most frequent malignancies worldwide. Gastric cancer metastasis to the appendix is uncommon in incidence, and has been rarely described in acute-appendicitis-related literature reviews. In this presented case, we have reported a rare case of appendiceal phlegmon, due to a diagnosis of metastatic gastric adenocarcinoma with uncommon symptoms. Case presentation: A 79-year-old Caucasian male presented to the emergency department with history of weakness, anorexia, lethargy, and mood changes for 2 months. Abdominopelvic computed tomography showed an abscess in right iliac muscle. After percutaneous drainage of the abscess and 6 weeks antibiotic therapy, an appendectomy was done for the patient. Histopathologic findings revealed the involvement of the appendiceal wall by adenocarcinoma, most probably with gastrointestinal origin. Gastric cancer was confirmed later by upper endoscopy and pathologic report. Conclusions: Although the presence of tumor in appendectomy specimens is rare, and metastasis to appendix is even rarer, it should be considered as a cause of appendicitis, especially in elderly patients. [ABSTRACT FROM AUTHOR]

Owing to tumor heterogeneity and individual physiological variations, there remains a necessity to enhance the current prognosis prediction system for metastatic gastric cancer (MGC). This study aimed to establish a prognostic model for patients diagnosed with MGC. Pertinent information pertaining to MGC patients was extracted and assessed from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2016. The Kaplan-Meier method and Cox regression analysis were employed to identify potential prognostic factors. Furthermore, nomogram model containing possible prognostic factors associated with overall survival (OS) was constructed using R software. A total of 2975 patients from the SEER database were included in this investigation. N-stage, grade, surgery, radiotherapy, chemotherapy, brain metastasis, bone metastasis, liver metastasis, and lung metastasis were identified as independent prognostic factors for OS. These variables were subsequently incorporated into the nomogram model. Calibration curves demonstrated a good correlation between nomogram predictions and actual observations. The nomogram model exhibits the potential to estimate the individualized survival of MGC patients. [ABSTRACT FROM AUTHOR]

Background: There are few models to predict the survival of patients of different ethnicities initially diagnosed with metastatic gastric cancer (mGC). Therefore, the aim of this study was to construct a nomogram to predict the cancer-specific survival (CSS) of these patients. Methods: Data for 994 patients initially diagnosed with mGC between 2000 and 2013 were extracted from the Surveillance, Epidemiology, and End Results database. Patients were randomly classified into a training (n = 696) or internal validation (n = 298) cohort, and a cohort of 133 patients from Fudan cohort was used for external validation. A nomogram to predict the CSS of mGC patients was derived and validated using a concordance index (C-index), calibration curves, and decision-curve analysis (DCA). Results: Multivariate Cox regression indicated that five factors were independent predictors of CSS: differentiation grade, T stage, N stage, metastatic site at diagnosis, and with or without chemotherapy. Thus, these factors were integrated into the nomogram model. The C-index value of the nomogram model was 0.63 (95% CI: 0.60–0.65), and those of the internal and external validation cohorts were 0.60 (95%: CI 0.55–0.64) and 0.63 (95%: CI 0.57–0.69), respectively. The calibration curves showed good consistency between the actual and predicted survival rates in both the internal and external validation cohorts. The DCA also showed the clinical utility of the nomogram model. Conclusions: We established a practical nomogram to predict the CSS of patients initially diagnosed with mGC. The nomogram can be used for individualized prediction of survival and to guide clinicians in making treatment decisions. [ABSTRACT FROM AUTHOR]

Abstract Aim Much attention has been paid to conversion therapy for stage IV gastric cancer, however, its operative comorbidities and survival benefit have not yet been clarified. CONVO‐GC‐1, an international retrospective cohort study, was designed to investigate the role of conversion surgery in Japan, Korea, and China. Methods The rate of operative complications was the primary endpoint and the overall survival (OS), according to the four‐category criteria previously published (Gastric Cancer:19; 2016), was analyzed as the secondary endpoint. Results A total of 1206 patients underwent surgery after chemotherapy with curative intent. Operative complications were observed in 290 (24.0%) patients in all grades, including pancreatic fistula and surgical site infection. The median survival time (MST) of all resected patients was 36.7 mo (M) and those of R0, R1, and R2 resection were 56.6 M, 25.8 M, and 21.7 M, respectively. Moreover, the MST of R0 patients were 47.8 M, 116.7 M, 44.8 M in categories 1, 2, and 3, respectively, and not reached in category 4. Interestingly, the MST of P1 patients was as favorable as that of P0CY1 patients if R0 resection was achieved. The MST of patients with liver metastasis was also favorable regardless of the number of lesions, and the MST of patients with para‐aortic lymph node (LN) No 16a1/b2 metastasis was not inferior to that of patients with para‐aortic LN No 16a2/b1 metastasis. Conclusion Conversion therapy for stage IV gastric cancer is safe and could be a new therapeutic strategy to improve the survival of patients, especially those with R0 resection.

Metastatic gastric cancer (mGC) often has a poor prognosis and may benefit from a few targeted therapies. Ramucirumab-based anti-angiogenic therapy targeting the VEGFR2 represents a milestone in the second-line treatment of mGC. Several studies on different cancers are focusing on the major VEGFR2 ligand status, meaning VEGFA gene copy number and protein overexpression, as a prognostic marker and predictor of response to anti-angiogenic therapy. Following this insight, our study aims to examine the role of VEGFA status as a predictive biomarker for the outcome of second-line therapy with Ramucirumab and paclitaxel in mGC patients. To this purpose, the copy number of the VEGFA gene, by fluorescence in situ hybridization experiments, and its expression in tumor tissue as well as the density of micro-vessels, by immunohistochemistry experiments, were assessed in samples derived from mGC patients. This analysis found that amplification of VEGFA concomitantly with VEGFA overexpression and overexpression of VEGFA with micro-vessels density are more represented in patients showing disease control during treatment with Ramucirumab. In addition, in the analyzed series, it was found that amplification was not always associated with overexpression of VEGFA, but overexpression of VEGFA correlates with high micro-vessel density. In conclusion, overexpression of VEGFA could emerge as a potential biomarker to predict the response to anti-angiogenic therapy.

Gastric cancer (GC) is recognized as one of the most common deadly malignancies worldwide and about 40–50% of patients present at diagnosis with an unresectable disease due to a locally advanced or already metastatic condition. Recently, therapeutic options for management of metastatic GC (mGC) have been approved allowing a potential improvement of patient cancer treatment response and also an establishment of a continuum of care for this aggressive disease. This report is the result of a literature review by an expert panel. The aim of this document is to provide evidence, wherever it is lacking, to provide expert opinion directed at strategic management of mGC, and in particular aspect at practical management where appropriate guidelines are not available. Treatment landscape with new therapeutic strategies for third line and beyond, role of imaging, prognostic factors, symptoms, and markers as well as the importance of multidisciplinary approach particularly the nutritional aspects are discussed.

Background: Immunotherapy has shown promising results for metastatic gastric cancer (MGC) patients. Nevertheless, not all patients can benefit from anti-PD-1 treatment. Thus, this study aimed to develop and validate a prognostic nomogram for MGC patients that received immunotherapy. Methods: Herein, MGC patients treated with anti-PD-1 between 1 October 2016 and 1 June 2022 at two separate Chinese PLA General Hospital centers were enrolled and randomly divided into training and validation sets (186 and 80 patients, respectively). The nomogram was constructed based on a multivariable Cox model using baseline variables from the training cohort. Its predictive accuracy was validated by the validation set. The consistency index (C-index) and calibration plots were used to evaluate the discriminative ability and accuracy of the nomogram. The net benefit of the nomogram was evaluated using decision curve analysis (DCA). Finally, we stratified patients by median total nomogram scores and performed Kaplan–Meier survival analyses. Results: We developed the nomogram based on the multivariate analysis of the training cohort, including four parameters: surgery history, treatment line, lung immune prognostic index (LIPI), and platelet-to-lymphocyte ratio (PLR). The C-index of the nomogram was 0.745 in the training set. The calibration curve for 1- and 2-year survival showed good agreement between nomogram predictions and actual observations. In the validation group, the calibration curves demonstrated good performance of the nomogram, with a C-index for overall survival (OS) prediction of 0.713. The OS of patients with a score greater than the median nomogram score was significantly longer than patients with a score lower or equal to the median (p < 0.001). Conclusion: We constructed a nomogram to predict the outcomes of MGC patients that received immunotherapy. This nomogram might facilitate individualized survival predictions and be helpful during clinical decision-making for MGC patients under anti-PD-1 therapy. [ABSTRACT FROM AUTHOR]

In recent years, advances of anticancer and supportive therapies have determined a gradual improvement in survival rates and patients' general conditions in metastatic gastric cancer (mGC), allowing them to receive further treatments. The choice of treatment is driven by performance status, age, stage of disease, number of metastatic sites and time from the first to third line of treatment. Targets such as microsatellite instability, PD-L1 expression, and HER2 overexpression or amplification may be addressed to personalise treatment and prolong survival. Despite a growing number of third line options that have provided clinicians with greater opportunities to customise treatments, up to date few agents have been demonstrated as effective after two standard lines for mGC; for these reasons, chemotherapy, immunotherapy, and targeted therapy were all widely investigated in both phase II and phase III studies. Overall, TAS-102, apatinib, regorafenib, nilotinib, trastuzumab, and pembrolizumab were demonstrated to be valid options in the third line scenario for mGC patient refractory to at least two lines of therapy. A multimodal approach based on chemotherapy, immunotherapy, targeted agents, a personalised nutritional programme as well as the research of new predictive biomarkers may pave the way to new strategies to identify the best treatment for each patient. [ABSTRACT FROM AUTHOR]

Gastric cancer is the second most prevalent cancer and the second leading cause of cancer-related death in China. The prognosis of metastatic gastric cancer is poor with a median overall survival of 8-10 months. Apatinib, an oral small-molecule, selective vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor, is approved as third-line or subsequent therapy for gastric cancer in China. Several recent small-scale studies and case reports showed that it may be great help in improvement of prognosis as second-line treatment in patients with advanced or metastatic gastric cancer. Here, we present a case of advanced gastric adenocarcinoma with multiple hepatic metastases who was treated with apatinib plus paclitaxel as second-line therapy, realized a long progression-free survival of 37 months. Until 29 January 2022, the disease remains an efficacy of partial response. We believe that the good outcome of this case is not an accident, because of the typically hyper-vascular of his liver metastases, the treatment toxicities of hypertension and proteinuria, all may be potential predictive biomarkers for anti-angiogenic treatments. [ABSTRACT FROM AUTHOR]

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: Fifty patients underwent CS following DCS therapy (CS group), whereas 18 patients underwent DCS therapy alone (non-CS group). The median survival time (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 CD163+macrophages in non-CS group than in CS group. Furthermore, in CS group, pathological responders to DCS therapy showed low infiltration of CD163+ macrophages, and high infiltration of CD8+lymphocyte. CD163 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. [ABSTRACT FROM AUTHOR]

The survival benefits of conversion surgery in patients with metastatic gastric cancer (mGC) remain unclear. Thus, this study aimed to determine the outcomes of conversion surgery compared to in-front surgery plus palliative chemotherapy (PCT) or in-front surgery alone for mGC. We recruited 182 consecutive patients with mGC who underwent gastrectomy, including conversion surgery, in-front surgery plus PCT, and in-front surgery alone at Linkou Chang Gung Memorial Hospital from 2011 to 2019. The tumor was staged according to the 8th edition of the American Joint Committee on Cancer. Patient demographics and clinicopathological factors were assessed. Overall survival (OS) was evaluated using the Kaplan–Meier curve and compared among groups. Conversion surgery showed a significantly longer median OS than in-front surgery plus PCT or in-front surgery alone (23.4 vs. 13.7 vs. 5.6 months; log rank p < 0.0001). The median OS of patients with downstaging (pathological stage I–III) was longer than that of patients without downstaging (stage IV) (30.9 vs. 18.0 months; p = 0.016). Our study shows that conversion surgery is associated with survival benefits compared to in-front surgery plus PCT or in-front surgery alone in patients with mGC. Patients who underwent conversion surgery with downstaging had a better prognosis than those without downstaging. [ABSTRACT FROM AUTHOR]

Background: We aimed to classify metastatic pyloric/antral gastric cancer in terms of macroscopic morphology and metastatic form. Methods: Thirty-eight patients with pyloric/antral gastric cancer were included in the study. Patients were classified according to a combination of Borrmann classification type and metastatic type, and the clinicopathological characteristics of each group were compared. Result: Of the 38 patients, 33 (type II: 9 and type III: 24) (87%) had ulcerative gastric cancer. Ulcerative gastric cancer was classified into four groups: lymphatic only group (L+H-P-), lymphatic + hematogenous group (L+H+P-), disseminated ± lymphatic group (L±H-P+), and lymphatic + hematogenous + disseminated group (L+H+P+). In the L+H-P-group, all patients had bulky lymph nodes and serum levels of both carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were high; the condition of patients was good, and the therapeutic response was good. In the L+H+P- group, metastases other than liver metastases were rare, and serum CEA levels were high. In the L±H-P+ group, the predominant histological type was signet ring cell carcinoma; both serum CEA and CA19-9 levels were low. Patients in the L+H+P+ group had higher serum CA19-9 levels and were more prone to hematogenous metastasis to various organs; these patients had worse patient status and lower treatment response. Gastric cancer other than ulcerative type was only detected in five patients (type V: 3, type IV: 1, type I: 1). Conclusion: Classification by a combination of macroscopic and metastatic form in pyloric/antral metastatic gastric cancer might be useful for diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Aim: Much attention has been paid to conversion therapy for stage IV gastric cancer, however, its operative comorbidities and survival benefit have not yet been clarified. CONVO‐GC‐1, an international retrospective cohort study, was designed to investigate the role of conversion surgery in Japan, Korea, and China. Methods: The rate of operative complications was the primary endpoint and the overall survival (OS), according to the four‐category criteria previously published (Gastric Cancer:19; 2016), was analyzed as the secondary endpoint. Results: A total of 1206 patients underwent surgery after chemotherapy with curative intent. Operative complications were observed in 290 (24.0%) patients in all grades, including pancreatic fistula and surgical site infection. The median survival time (MST) of all resected patients was 36.7 mo (M) and those of R0, R1, and R2 resection were 56.6 M, 25.8 M, and 21.7 M, respectively. Moreover, the MST of R0 patients were 47.8 M, 116.7 M, 44.8 M in categories 1, 2, and 3, respectively, and not reached in category 4. Interestingly, the MST of P1 patients was as favorable as that of P0CY1 patients if R0 resection was achieved. The MST of patients with liver metastasis was also favorable regardless of the number of lesions, and the MST of patients with para‐aortic lymph node (LN) No 16a1/b2 metastasis was not inferior to that of patients with para‐aortic LN No 16a2/b1 metastasis. Conclusion: Conversion therapy for stage IV gastric cancer is safe and could be a new therapeutic strategy to improve the survival of patients, especially those with R0 resection. [ABSTRACT FROM AUTHOR]

Introduction and Aims: Gastric adenocarcinoma is among the high-ranking tumors, with respect to frequency and mortality, worldwide. The inflammatory process and immune system activity are associated with oncologic control. Our aim was to identify whether the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and other variables are prognostic factors for survival in patients with metastatic gastric cancer in a Mexican population., Material and Methods: Patients diagnosed with metastatic gastric adenocarcinoma, hospitalized within the time frame of December 2011 to 2021, were analyzed. The NLR, PLR, and albumin and hemoglobin levels obtained from blood samples were calculated. Functional status (ECOG and Karnofsky), sex, histology, and the presence of signet ring cells were also considered possible prognostic factors. Each factor's prognostic value for overall survival was determined through univariate and multivariate analyses., Results: The study included 956 patients diagnosed with metastatic gastric cancer, of whom 494 (51.7%) were men and 462 (48.3%) were women. The main histologic finding was diffuse adenocarcinoma (n = 619, 64.7%), followed by intestinal adenocarcinoma (n = 293, 30.6%), and the presence of signet ring cells was found in 659 (68.9%) patients. Diagnostic laparoscopy was performed on 238 patients (24.9%) to confirm peritoneal carcinomatosis. The multivariate analysis showed that an NLR above 3.2 (HR 1.51, 95% CI 1.27-1.8; p < 0.001), albumin below 3.5 g/dl (HR 1.25, CI 1.06-1.47; p = 0.006), and an ECOG performance status of 2 or higher (HR 1.39, CI 1.10-1.76; p = 0.005) were independent factors that predicted a lower survival rate, whereas a Karnofsky score above 70% (HR 0.69, CI 0.53-0.91; p = 0.008) was associated with a better survival rate. Lastly, the PLR was not statistically significant in the multivariate analysis., Conclusions: The NLR, nutritional status assessed through albumin measurement, and functional status can act as independent prognostic survival factors in hospitalized Mexican patients diagnosed with metastatic gastric adenocarcinoma and be taken into account during therapeutic decision-making., (Copyright © 2023 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.)

Background: Individuals with metastatic gastric cancer (MGC) are incurable and have a poor prognosis. To date, surgical resection with curative intent is the only treatment providing hope for a cure, but the role of surgical resection is still controversial., Objectives: To assess the effects of gastrectomy compared to non-resection on MGC patient survival., Material and Methods: PubMed, Embase, Cochrane Library, and Web of Science databases were searched up to October 10, 2023. Primary outcomes were 1-, 2-, 3-, and 5-year overall survival (OS), OS, and OS time., Results: Forty-six studies with 7,152 MGC patients were included. Compared to MGC patients receiving no resection, MGC patients with gastrectomy had significantly improved 1-year OS (pooled relative risk (RR):1.90, 95% confidence intervals (95% CIs): 1.50, 2.41), 2-year OS (pooled RR: 2.23, 95% CI: 1.40, 3.53), 3-year OS (pooled RR: 6.09, 95% CI: 3.12, 11.87), 5-year OS (pooled RR: 4.30, 95% CI: 1.35, 13.74), and reduced risk of death (pooled hazard ratio (HR): 0.49, 95% CI: 0.37, 0.65). Gastrectomy combined with metastasectomy or not also revealed similar results regarding OS and risk of death. Additionally, OS time was significantly longer in patients receiving gastrectomy than patients not receiving resection (pooled weighted mean difference (WMD): 6.06, 95% CI: 1.36, 10.760). No significant difference in postoperative morbidity was detected between the patients receiving gastrectomy and patients not receiving resection (pooled RR: 2.54, 95% CI: 0.13, 51.39)., Conclusion: Gastrectomy, with or metastasectomy, may provide MGC patients with survival benefits.

Bladder metastasis from gastric cancer is a unique clinical entity, which can be revealed infrequently in patients with metastatic gastric cancer. Secondary neoplasms to the bladder are also a less frequent clinical entity representing only 15% of all bladder neoplasms. Gastric cancers consist of an exceptionally small percentage of all secondary bladder neoplasms. Until now only 27 cases were recorded in the international medical literature. The current work analyzes a 65-year old male patient who presented initially with a locally advanced gastric adenocarcinoma. He was treated with a combination of total gastrectomy and perioperative chemotherapy. Eight months later presented a relapse with bladder metastasis, liver metastasis and peritoneal involvement. Furthermore, in this manuscript, we conducted a review of the recorded cases with bladder metastasis from gastric cancer. In the most of cases the diagnosis of bladder metastasis was metachronous with an average time of presentation in four years after the primary diagnosis of gastric cancer and most of the patients of our review presented with urinary symptoms at the time of diagnosis of bladder metastasis. Concerning the management of the metastatic disease surgical management with total or partial cystectomy was performed in 11% of patients and TUR was performed in 22% of patients. Palliative chemotherapy for the management of metastatic disease was initiated in 46% of patients. [ABSTRACT FROM AUTHOR]

Nivolumab monotherapy is a standard treatment of metastatic gastric cancer, and this type of cancer involves vascular endothelial growth factor (VEGF) signaling in the tumor immunological environment. The subgroup analysis of the ATTRACTION-2 trial revealed that prior treatment with ramucirumab (RAM), a VEGF inhibitor, affected the therapeutic effect of nivolumab. The present retrospective study aimed to review patients with metastatic gastric cancer who were treated with paclitaxel (PTX) and RAM followed by nivolumab. A total of 29 patients with metastatic gastric cancer were treated with PTX + RAM as second-line treatment, followed by nivolumab monotherapy as third-line treatment. The therapeutic efficacy of nivolumab was compared in 13 patients with progression-free survival (PFS) of <5 months and 16 patients with PFS ≥5 months after PTX + RAM therapy. The present study included 22 male and seven female patients, with a median age of 68 years (range, 45-82 years). Human epidermal growth factor receptor 2 positivity was observed in six patients. The disease control rate was 62.1%. The PFS and overall survival (OS) were 4.4 and 11.9 months, respectively. Patients with PFS ≥5 months after PTX + RAM therapy showed better outcome in both PFS (5.3 months vs. 2.8 months, P=0.039) and OS (6.9 months vs. 15.2 months, P=0.066) after nivolumab treatment than patients with PFS of <5 months after PTX + RAM therapy. However, no significant relationship was observed between the outcome of first-line treatment and nivolumab. The therapeutic effect of nivolumab was associated with prior PTX + RAM treatment in advanced gastric cancer. [ABSTRACT FROM AUTHOR]

Abstract Background The aim of this study is to profile the cytokines and immune cells of body fluid from metastatic gastric cancer (mGC), and evaluate the potential role as a prognostic factor and the feasibility as a predictive biomarker or monitoring source for immune checkpoint inhibitor. Methods Body fluid including ascites and pleural fluid were obtained from 55 mGC patients and 24 matched blood. VEGF-A, IL-10, and TGF-β1 were measured and immune cells were profiled by fluorescence assisted cell sorting (FACS). Results VEGF-A and IL-10 were significantly higher in body fluid than in plasma of mGC. Proportion of T lymphocytes with CD69 or PD-1, memory T cell marked with CD45RO, and number of Foxp3+ T regulatory cells (Tregs) were significantly higher in body fluid than those in blood of mGC. Proportion of CD8 T lymphocyte with memory marker (CD45RO) and activation marker (HLA-DR), CD3 T lymphocyte with PD-1, and number of FoxP3+ Tregs were identified as independent prognostic factors. When patients were classified by molecular subgroups of primary tumor, VEGF-A was significantly higher in genomically stable (GS)-like group than that in chromosomal instability (CIN)-like group while PD-L1 positive tumor cells (%) showed opposite results. Monitoring immune dynamics using body fluid was also feasible. Early activated T cell marked with CD25 was significantly increased in chemotherapy treated group. Conclusions By analyzing cytokines and proportion of immune cells in body fluid, prognosis of patients with mGC can be predicted. Immune monitoring using body fluid may provide more effective treatment for patients with mGC.

Abstract Background Preclinical studies suggest synergistic effectiveness of ascorbic acid (AA, vitamin C) and cytotoxic agents in gastrointestinal malignancies. This phase 1 study aimed to establish the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of AA combined with mFOLFOX6 or FOLFIRI regimens in patients with metastatic colorectal cancer (mCRC) or gastric cancer (mGC). Methods In the dose-escalation phase, patients received AA (0.2–1.5 g/kg, 3-h infusion, once daily, days 1–3) with mFOLFOX6 or FOLFIRI in a 14-day cycle until the MTD was reached. In the speed-expansion phase, AA was administered at the MTD or at 1.5 g/kg if the MTD was not reached at a fixed rate of 0.6, 0.8 or 1 g/min. Pharmacokinetics and preliminary efficacy were also assessed. Results Thirty-six patients were enrolled. The MTD was not reached. The RP2D was established as AA at 1.5 g/kg/day, days 1–3, with mFOLFOX6 or FOLFIRI. No dose-limiting toxicity (DLT) was detected during dose escalation. The most common treatment-emergent adverse events (TRAEs) were sensory neuropathy (50%), nausea (38.9%), vomiting (36.1%) and neutropenia (27.8%). Grade 3–4 TRAEs were neutropenia (13.9%), sensory neuropathy (2.8%), vomiting (2.8%), diarrhea (2.8%) and leukopenia (2.8%). AA exposure was dose-proportional. The objective response rate was 58.3%, and the disease control rate was 95.8%. No difference in efficacy was found between mCRC patients with wild-type RAS/BRAF and mutant RAS or BRAF. Conclusions The favorable safety profile and preliminary efficacy of AA plus mFOLFOX6/FOLFIRI support further evaluation of this combination in mCRC or mGC. Trial registration ClinicalTrial.gov Identifier: NCT02969681.

Lu-Ping Yang,1 Zi-Xian Wang,1 Ming-Ming He,1 Hao-Xiang Wu,1 Shu-Qiang Yuan,2 Wei Wang,2 Ying Jin,1 Chao Ren,1 Zhi-Qiang Wang,1 Feng-Hua Wang,1 Yu-Hong Li,1 Feng Wang,1 Rui-Hua Xu11Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, People’s Republic of China; 2Department of Gastric and Pancreatic Surgery, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, People’s Republic of ChinaBackground: The benefit of palliative gastrectomy for patients with metastatic gastric cancer (mGC) is controversial, and suitable candidates for surgery and treatment strategies remain unclear. The present study aimed to investigate the efficacy of palliative gastrectomy plus chemotherapy among patients with mGC and to identify the potential patients for such treatment using real-world data.Methods: A dataset of 236 patients with mGC diagnosed at the Sun Yat-Sen University Cancer Center from January 1, 2006 to December 31, 2012 were analyzed retrospectively. The cohort comprised 80 patients who had palliative gastrectomy plus chemotherapy (SC) and 156 patients who had chemotherapy only (CO). Propensity score matching (PSM) was employed to minimize the influence of confounders.Results: The median overall survival of the SC group was significantly better than that of the CO group (Before PSM: 17.0 months vs 12.0 months, P=0.038; after PSM: 17.0 months vs 13.0 months, P=0.017). In the multivariate analysis, SC (Before PSM: hazard ratio (HR) =0.68, P=0.023; after PSM: HR =0.64, P=0.021) was favored for better survival after adjustment for sex, age, year of diagnosis, primary tumor location, and tumor grade. Total gastrectomy (P=0.026) was associated with worse survival for the SC group. The significant survival advantage of SC over CO was retained in patients with single organ metastasis (P=0.016), peritoneal seedings (P=0.039), and those receiving taxane-based chemotherapy (P=0.011).Conclusion: SC could improve the overall survival of patients with mGC as compared with CO. The chemotherapy regimen and type of resection were proven to influence efficacy. Patients who received taxane-based regimens might be suitable for palliative gastrectomy.Keywords: first-line chemotherapy, metastatic gastric cancer, palliative gastrectomy, propensity score matching, survival

Abstract Background Platinum/fluoropyrimidine regimens are the backbone of first-line chemotherapy for advanced gastric cancer (AGC). However response rates to first line chemotherapy range from 30 to 50% and disease progression occurs after 4–6 cycles. The optimal duration of first-line therapy is still unknown and its continuation until disease progression represents the standard. However this strategy is often associated with cumulative toxicity and rapid development of drug resistance. Moreover, only about 40% of AGC pts. are eligible for second-line treatment. Methods This is a randomized, open-label, multicenter phase III trial. It aims at assessing whether switch maintenance to ramucirumab plus paclitaxel will extend the progression-free survival (PFS) of subjects with HER-2 negative AGC who have not progressed after 3 months of a first-line with a platinum/fluoropyrimidine regimen (either FOLFOX4, mFOLFOX6 or XELOX). The primary endpoint is to compare Progression-Free Survival (PFS) of patients in ARM A (switch maintenance to ramucirumab and placlitaxel) versus ARM B (continuation of the same first-line therapy with oxaliplatin/fluoropyrimidine). Secondary endpoints are: overall survival, time-to-treatment failure, overall response rate, duration of response, percentage of patients that will receive a second line therapy according to arm treatment, safety, quality of life. Exploratory studies including Next-Generation Sequencing (NGS) in archival tumor tissues are planned in order to identify potential biomarkers of primary resistance and prognosis. Discussion The ARMANI study estimates if patients treated with early swich with ramucirumab plus paclitaxel received benefit when compared to those treated with continuation of first line therapy. The hypothesis is that the early administration of an active, non-cross resistant second-line regimen such as ramucirumab plus paclitaxel may prolong the time in which patients are progression-free, and consequently have a better quality of life. Moreover, this strategy may rescue all those subjects that become ineligible for second-line therapy due to the rapid deterioration of health status after the first disease progression. Trial registration ARMANI is registered at ClinicalTrials.gov (NCT02934464, October 17, 2016) and EudraCT(2016–001783-12, April 202,016).

Background: The most common age at which gastric cancer is diagnosed is 70 years, and the majority of patients diagnosed are at the metastatic stage. However, although gastric cancer is a geriatric disease, there is no suggestion to discriminate treatment for the general geriatric patient population. Here, we evaluated patients receiving palliative chemotherapy for gastric cancer owing to advanced age. Patients and Methods: Multicenter data of geriatric patients receiving palliative chemotherapy because of metastatic gastric cancer were retrospectively reviewed. Results: In total, 262 geriatric patients with gastric cancer were included in the study. Of these, 167 patients, including 134 (51.8%) patients with metastasis at diagnosis and 33 patients with relapse after surgery, were evaluated for palliative therapy. Chemotherapy was started in 87 (52.1%) of 167 patients. The overall median survival of the patients receiving chemotherapy was 9.3 months. There was no difference in overall survival (OS) between patients aged >70 and <70 years. However, a significant difference was detected in OS of patients depending on their Eastern Cooperative Oncology Group (ECOG) performance status(PS) before treatment; survival was 15 months in the group with PS 0–1 and 7 months in the group with PS ≥2. Conclusion: Advanced age chemotherapy receiving rates in patients with metastatic gastric cancer is decreasing. Survival is not associated with age, but pretreatment ECOG PS is important. Therefore, ECOG PS and comorbidities should be evaluated in detail, and combination therapies could contribute to patient survival. [ABSTRACT FROM AUTHOR]

Background: Clinical management of metastatic gastric cancer (mGC) remains a major challenge due to a lack of specific biomarkers and effective therapeutic targets. Recently, accumulating evidence has suggested that exosomes play an essential role in cancer metastasis and can be an excellent reservoir of novel biomarkers and candidate therapeutic targets for cancer. Therefore, in this study, we aimed to reveal the proteomic profile of mGC-derived exosomes.Methods: Exosomes were isolated from pooled serum samples of 20 mGC patients and 40 healthy controls (HC) by ultracentrifugation. Next, quantitative proteomic analyses were applied to analyze the protein profiles of the exosomes, and bioinformatic analyses were conducted on the proteomic data. Finally, the expression of exosomal protein candidates was selectively validated in individual subjects by western blot analysis.Results: We isolated exosomes from serum samples. The size of the serum derived exosomes ranged from 30 to 150 nm in diameter. The exosomal markers CD9 and CD81 were observed in the serum exosomes. However, the exosomal negative marker calnexin, an endoplasmic reticulum protein, was not detected in exosomes. Overall, 443 exosomal proteins, including 110 differentially expressed proteins (DEPs) were identified by quantitative proteomics analyses. The bioinformatics analyses indicated that the upregulated proteins were enriched in the process of protein metabolic, whereas the downregulated proteins were largely involved in cell-cell adhesion organization. Surprisingly, 10 highly vital proteins (UBA52, PSMA1, PSMA5, PSMB6, PSMA7, PSMA4, PSMA3, PSMB1, PSMA6, and FGA) were filtered from DEPs, most of which are proteasome subunits. Moreover, the validation data confirmed that PSMA3 and PSMA6 were explicitly enriched in the serum derived exosomes from patients with mGC.Conclusion: The present study provided a comprehensive description of the serum exosome proteome of mGC patients, which could be an excellent resource for further studies of mGC.

Background: Therapies targeting human epidermal growth factor receptor 2 (HER2) have become a focus for improving treatment outcomes in patients with gastric cancer. This literature review sought to assesses clinical outcomes, including safety, survival, and treatment outcomes, of patients who received trastuzumab for the treatment of HER2+ metastatic gastric cancer. Methods: Searches were conducted in PubMed and Embase to identify observational research studies investigating the clinical outcomes of trastuzumab and combination therapies for the treatment of HER2+ metastatic gastric cancer, published January 1, 2014–August 22, 2019. Article screening was a two-phase process, and the results of each screening level were documented in accordance with PRISMA. Results: Twenty articles met the selection criteria for data extraction. Studies focused on treatment patterns or survival, safety, and clinical outcomes, as well as the natural history of disease. In the combined HER2+ patient populations included in this review, tumors were located in the stomach (33.7%), gastroesophageal junction (GEJ, 14.2%), unspecific GEJ or stomach (50.3%), or esophagus (1.9%). Studies observed increases in both overall survival and progression-free survival with the use of trastuzumab-based chemotherapy compared with chemotherapy treatment alone. Additionally, trastuzumab-based chemotherapy appeared to improve survival and clinical outcomes regardless of the presence of multi-organ metastases or tumor location. Conclusions: Trastuzumab-treated patients have longer survival times than those not treated with trastuzumab and tolerate treatment well, with few serious adverse events. New treatments for second- and subsequent-line therapies would increase regimen options. Mini-abstract: The treatment patterns and clinical outcomes observed in this literature review suggest patients treated with trastuzumab have longer survival times compared with chemotherapy treatment alone and tolerate treatment

Abstract Background Oxaliplatin + S-1 is a recognized treatment regimen in Japan, but there are no Japanese clinical data on an oxaliplatin dose of 130 mg/m2. The current research involves a single-arm, prospective, phase II clinical trial to examine the efficacy and safety of oxaliplatin + S-1 with an oxaliplatin dose of 130 mg/m2 to treat HER2-negative advanced/recurrent gastric cancer previously untreated with chemotherapy in Japan. Methods/design The primary endpoint of this trial will be the response rate, and the secondary endpoints will be the safety profile of oxaliplatin + S-1, progression-free survival, the response rate in subjects under the age of 75, overall survival, time to treatment failure, duration of treatment, time to failure of strategy, and dose intensity. The threshold response rate is 45% and the expected response rate is 60%. Assuming that a one-tailed score test will be performed with an α of 0.05, 68 patients are needed to ensure a statistical power of 80%. Planned enrollment is 70 subjects and the total duration of this trial is expected to be 3 years. Discussion Since replacing cisplatin with oxaliplatin should provide the same level of therapeutic efficacy while limiting adverse events and simplifying treatment, oxaliplatin + S-1 may be increasingly used to treat gastric cancer in Japan. Verifying the efficacy and safety of oxaliplatin + S-1 with an oxaliplatin dose of 130 mg is an important task that the current trial has set out to achieve. Trial registration The protocol was registered at the website of the University Hospital Medical Information Network (UMIN), Japan (protocol ID UMIN000017550) on May 29, 2015. The details are available at the following web address: http://www.umin.ac.jp/ctr/ .

• Metastatic gastric cancer has a poor prognosis. • Multimodal era in gastric cancer has changed the outcomes of those patients. • Good responders of metastatic gastric cancer should be discussed in multidisciplinary. Although no consensus has been reached on the role of surgical treatment for metastatic gastric cancer, some reports suggest promising results on patients with a small disease volume upon presentation. We present two cases of metastatic disease with a favorable outcome following surgical treatment. The first case presented with an adenocarcinoma of the cardia, which was staged as oligometastatic due to a small liver nodule on segment III. Treatment consisted of neoadjuvant chemotherapy followed by laparoscopic esophagectomy and hepatectomy. The patient remains disease-free 62 months after surgery. Unlike the first case, the second case presented with a large number of liver nodules upon diagnosis, ruling out metastasectomy as a possible treatment. The tumor expressed HER2 receptors and responded favorably to chemotherapy plus trastuzumab for 34 months. At this point, disease progression was observed on the primary site, but the hepatic lesions remained stable. The patient underwent gastrectomy, resumed the chemotherapy regimen, and had a favorable outcome, with stability of the liver metastasis and no local recurrence following primary tumor resection. We illustrate through these two cases the effectiveness of a combined approach featuring perioperative chemotherapy and radical surgery for selected cases of oligometastatic gastric cancer, which we hope will spur further research on the topic. Systemic treatment in metastatic gastric cancer may represent a novel treatment approach that allows surgical resection of the primary tumor in select cases. [ABSTRACT FROM AUTHOR]

Background: Clinical management of metastatic gastric cancer (mGC) remains a major challenge due to a lack of specific biomarkers and effective therapeutic targets. Recently, accumulating evidence has suggested that exosomes play an essential role in cancer metastasis and can be an excellent reservoir of novel biomarkers and candidate therapeutic targets for cancer. Therefore, in this study, we aimed to reveal the proteomic profile of mGC-derived exosomes. Methods: Exosomes were isolated from pooled serum samples of 20 mGC patients and 40 healthy controls (HC) by ultracentrifugation. Next, quantitative proteomic analyses were applied to analyze the protein profiles of the exosomes, and bioinformatic analyses were conducted on the proteomic data. Finally, the expression of exosomal protein candidates was selectively validated in individual subjects by western blot analysis. Results: We isolated exosomes from serum samples. The size of the serum derived exosomes ranged from 30 to 150 nm in diameter. The exosomal markers CD9 and CD81 were observed in the serum exosomes. However, the exosomal negative marker calnexin, an endoplasmic reticulum protein, was not detected in exosomes. Overall, 443 exosomal proteins, including 110 differentially expressed proteins (DEPs) were identified by quantitative proteomics analyses. The bioinformatics analyses indicated that the upregulated proteins were enriched in the process of protein metabolic, whereas the downregulated proteins were largely involved in cell-cell adhesion organization. Surprisingly, 10 highly vital proteins (UBA52, PSMA1, PSMA5, PSMB6, PSMA7, PSMA4, PSMA3, PSMB1, PSMA6, and FGA) were filtered from DEPs, most of which are proteasome subunits. Moreover, the validation data confirmed that PSMA3 and PSMA6 were explicitly enriched in the serum derived exosomes from patients with mGC. Conclusion: The present study provided a comprehensive description of the serum exosome proteome of mGC patients, which could be an excellent resource for further studies of mGC. [ABSTRACT FROM AUTHOR]

Trifluridine/tipiracil or TAS-102 (Taiho Oncology, Lonsurf®, Princeton, NJ, USA) is a combination tablet of trifluridine, a thymidine-based nucleoside analog, and tipiracil, a thymidine phosphorylase inhibitor, in a 1:0.5 molar ratio. This drug was first approved for use in metastatic colorectal cancer patients. Recently, the U S Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have granted approval of trifluridine/tipiracil for treatment of metastatic gastric and gastroesophageal junction adenocarcinoma in patients following at least two lines of chemotherapy including fluoropyrimidine and platinum chemotherapy agents, as well as taxanes or irinotecan. This approval was granted after the findings from first a Phase II trial (EPOC1201) investigating trifluridine/tipiracil, and later a global Phase III trial (TAGS trial) that compared trifluridine/tipiracil vs placebo with best supportive care. Both trials primarily utilized trifluridine/tipiracil at a dose of 35 mg/m2 twice daily. In the EPOC1201 trial, the primary end point of disease control rate was greater than 50% after eight weeks of therapy. The most common grade three or four adverse event was neutropenia; additional toxicities included leukopenia, anemia, and anorexia. In the TAGS trial, overall survival in patients treated with trifluridine/tipiracil (5.7 months) was significantly improved as compared to the placebo-controlled group (3.6 months). Treatment with trifluridine/tipiracil not only did not impair quality of life but also tended to reduce the risk of deterioration of quality of life. The results of these studies along with the subsequent FDA and EMA approval have generated an important breakthrough in regard to treatment options for patients with refractory metastatic gastric or gastroesophageal junction adenocarcinoma. [ABSTRACT FROM AUTHOR]

Aim: This study explored whether chemotherapy combined with palliative surgery and/or radiotherapy is a possible treatment for metastatic gastric cancer. Materials & methods: Patients were divided into groups according to treatments. COX models were used to explore prognostic factors. Kaplan-Meier models and log-rank tests were used to analyze outcomes. Outcomes were analyzed before and after propensity score matching. Results: Chemotherapy combined with gastrectomy or metastasectomy prolongs the survival time compared with chemotherapy alone (p < 0.05). Chemotherapy combined with gastrectomy plus metastasectomy and/or radiation therapy also prolongs the survival time (p < 0.05). Conclusion: Chemotherapy combined with gastrectomy could be a more effective treatment for metastatic gastric cancer. Chemotherapy combined with gastrectomy plus metastasectomy and/or radiation therapy could also be a promising treatment. [ABSTRACT FROM AUTHOR]

Abstract Background Historical data indicate that surgical resection may benefit select patients with metastatic gastric and gastroesophageal junction cancer. However, randomized clinical trials are lacking. The current RENAISSANCE trial addresses the potential benefits of surgical intervention in gastric and gastroesophageal junction cancer with limited metastases. Methods This is a prospective, multicenter, randomized, investigator-initiated phase III trial. Previously untreated patients with limited metastatic stage (retroperitoneal lymph node metastases only or a maximum of one incurable organ site that is potentially resectable or locally controllable with or without retroperitoneal lymph nodes) receive 4 cycles of FLOT chemotherapy alone or with trastuzumab if Her2+. Patients without disease progression after 4 cycles are randomized 1:1 to receive additional chemotherapy cycles or surgical resection of primary and metastases followed by subsequent chemotherapy. 271 patients are to be allocated to the trial, of which at least 176 patients will proceed to randomization. The primary endpoint is overall survival; main secondary endpoints are quality of life assessed by EORTC-QLQ-C30 questionnaire, progression free survival and surgical morbidity and mortality. Recruitment has already started; currently (Feb 2017) 22 patients have been enrolled. Discussion If the RENAISSANCE concept proves to be effective, this could potentially lead to a new standard of therapy. On the contrary, if the outcome is negative, patients with gastric or GEJ cancer and metastases will no longer be considered candidates for surgical intervention. Trial registration The article reports of a health care intervention on human participants and is registered on October 12, 2015 under ClinicalTrials.gov Identifier: NCT02578368 ; EudraCT: 2014–002665-30.

In preclinical cancer models, fibroblast growth factor receptor (FGFR) gene aberration has been known to be associated with increased tumor cell proliferation and survival in several cancer types. Oncogenic fusions consisting of FGFR3 and transforming acid coiled coil 3 (TACC3) had been identified as potential therapeutic target. We report on a gastric cancer patient with liver metastases who harbored FGFR3-TACC3 fusion which is extremely rare in gastrointestinal cancer. Herein, we report a case presentation with literature review of FGFR3-TACC3 fusion.