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Advanced Gastric Cancer

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (31 August 2021) | Viewed by 41900

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Prof. Dr. Wojciech Piotr Polkowski

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Guest Editor

Department of Surgical Oncology, Medical University of Lublin, Radziwiłłowska 13, 20-080 Lublin, Poland
Interests: advanced gastric cancer; neoadjuvant therapy; hyperthermic intraperitoneal chemotherapy; gastrectomy; metastasectomy; peritonectomy; lymphadenectomy; intraoperative radiotherapy
Special Issues, Collections and Topics in MDPI journals

Dr. Johanna W. van Sandick

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Guest Editor

Department of Surgical Oncology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Postbus, 90203 1006 BE, Amsterdam, The Netherlands
Interests: gastric cancer; oesophageal cancer; multimodality treatment; molecular subtyping; oligometastatic disease

Special Issue Information

Dear Colleagues,

In Western countries, the majority of gastric cancers (GC) is diagnosed in advanced stages reporting a 5-year survival rate of only 20–25%. In order to improve treatment strategy, a most accurate staging process should be completed. Availability of high-quality imaging and access to diagnostic laparoscopy with lavage cytology should be part of the diagnostic pathway for gastric cancer patients. Treatment of nonmetastatic, resectable, locally advanced gastric cancer is based on a combination of surgery and perioperative chemotherapy. In selected groups of patients with high risk of locoregional recurrence, (neo)adjuvant chemoradiotherapy should be considered. New epidemiological trends of GC in the Western countries include an upward shift in the location of the primary tumor and a relative increase of advanced and diffuse type tumors. The Laurén classification of GC (intestinal, diffuse, mixed type) is used in clinical practice since it reflects GC morphology, epidemiology, tumor biology, and clinical management and outcome. Despite the initial promise of individualizing antitumor treatment, molecular classification of GC does not yet guide treatment strategy in GC patients. Current molecular divisions of GC come from three different parts of the world where different standard treatment modalities for nonmetastatic locally advanced GC are recommended.

Today, the standard treatment for advanced GC with peritoneal dissemination is palliative systemic chemotherapy. Direct intraperitoneal chemotherapy has recently attracted major interest since it may potentiate locoregional effects of systemic chemotherapy. In selected patients with limited peritoneal GC, the combination of complete cytoreductive surgery (CRS; including radical gastrectomy) and hyperthermic intraperitoneal chemotherapy (HIPEC) is being investigated. The choice of optimal neoadjuvant systemic chemotherapy regimen preceding the ultimate CRS and HIPEC is not yet known. Susceptibility to novel systemic therapy regimens (such as immunotherapy) is extensively studied. A selection of patients for aggressive (multivisceral) resection with extended lymphadenectomy, targeted adjuvant therapy, and oligometastatic treatment are the subjects of debate in GC care at present.

These unsolved problems dictate the modification of multidisciplinary management towards a more individualized approach for the treatment of advanced GC.

Prof. Dr. Wojciech Piotr Polkowski
Dr. Johanna W. van Sandick
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

advanced gastric cancer
neoadjuvant treatment
extended lymphadenectomy
cytoreductive surgery
hyperthermic intraperitoneal chemotherapy

Published Papers (13 papers)

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13 pages, 4480 KiB

Open AccessArticle

Trans-Umbilical Lymphadenectomy Using an Articulating Bipolar Vessel-Sealing Device (TULAB) during Robotic Surgery for Gastric Cancer: Enhancing the Surgeon’s Eye for Reduced-Port Robotic Gastrectomy

by Raeyoon Jeong, Min-Se Kim, Chang-Min Lee, In-Young Lee, Sungsoo Park and Seong-Heum Park

Cancers 2023, 15(22), 5371; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15225371 - 11 Nov 2023

Viewed by 773

Abstract

Background: Docking the scope and instruments through a multi-channel trocar has enabled reduced-port robotic distal gastrectomy (RRDG) for gastric cancer. To facilitate lymphadenectomy over the anatomical hindrances during RRDG, we recently introduced the Vessel Sealer Extend^® (VSE) (Intuitive Surgical, Sunnyvale, CA, USA), a bipolar vessel-sealing device (BVSD) with an articulating jaw. Methods: From May 2020 to August 2023, we performed RRDG to treat T1 gastric cancer. One endoscope arm and three instrument arms of the da Vinci^® Xi Surgical System (Intuitive Surgical) were used. During the lymphadenectomy, the endoscope and VSE (Intuitive Surgical) were docked through a multi-channel trocar established on a trans-umbilical incision. Two Cardiere forceps were docked through cannulas established on each flank. A trans-umbilical lymphadenectomy using an articulating BVSD (TULAB) was then performed. Results: A total of 42 patients underwent planned RRDG with the TULAB technique. The number of retrieved lymph nodes did not differ between the patients who underwent RRDG and those who underwent conventional laparoscopic distal gastrectomies (CLDG) (p = 0.362). There was no statistically significant difference in postoperative complications between the RRDG and CLDG group (p = 0.189). The mean time to first semi-fluid diet was shorter in the patients who underwent RRDG than CLDG (p = 0.030), and the incidence of postoperative ileus was lower in the RRDG group than the CLDG group (0% and 9.9%, respectively, p = 0.034). Conclusions: Despite use of fewer ports, RRDG with TULAB had similar outcomes to CLDG in terms of the incidence of postoperative morbidity and the number of harvested lymph nodes. Furthermore, by reducing the number of incisions, the incidence of the intra-abdominal adhesions can potentially be lowered when RRDG is used. Full article

(This article belongs to the Special Issue Advanced Gastric Cancer)

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10 pages, 753 KiB

Open AccessArticle

Comparison of Two Endoscopic Therapeutic Interventions as Primary Treatment for Anastomotic Leakages after Total Gastrectomy

by Moritz Senne, Christoph R. Werner, Ulrike Schempf, Karolin Thiel, Alfred Königsrainer and Dörte Wichmann

Cancers 2022, 14(12), 2982; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14122982 - 16 Jun 2022

Cited by 6 | Viewed by 1753

Abstract

Introduction: An esophagojejunal anastomotic leak following an oncological gastrectomy is a life-threatening complication, and its management is challenging. A stent application and endoscopic negative pressure therapy are possible therapeutic options. A clinical comparison of these strategies has been missing until now. Methods: A retrospective analysis of 14 consecutive patients endoscopically treated for an anastomotic leak after a gastrectomy between June 2014 and December 2019 was performed. Results: The mean time of the diagnosis of the leakage was 7.14 days after surgery. Five patients were selected for a covered stent, and nine patients received endoscopic negative pressure therapy. In the stent group, the mean number of endoscopies was 2.4, the mean duration of therapy was 26 days, and the mean time of hospitalization was 30 days. In patients treated with endoscopic negative pressure therapy, the mean number of endoscopies was 6.0, the mean days of therapy duration was 14.78, and the mean days of hospitalization was 38.11. Treatment was successful in all patients in the stent-based therapy group and in eight of nine patients in the negative pressure therapy group. Discussion: Good clinical results in preserving the anastomosis and providing sepsis control was achieved in all patients. Stent therapy resulted in anastomosis healing with a lower number of endoscopies, a shorter time of hospitalization, and rapid oral nutrition. Full article

(This article belongs to the Special Issue Advanced Gastric Cancer)

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15 pages, 2284 KiB

Open AccessArticle

Can We Reboot the Role of Intraperitoneal Chemotherapy in the Treatment for Gastric Cancer with Peritoneal Carcinomatosis?: A Retrospective Cohort Study Regarding Minimally Invasive Surgery Conjoined with Intraperitoneal plus Systemic Chemotherapy

by Sungho Kim, Chang-Min Lee, Danbi Lee, Jong-Han Kim, Sungsoo Park and Seong-Heum Park

Cancers 2022, 14(9), 2334; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14092334 - 09 May 2022

Cited by 1 | Viewed by 1904

Abstract

Background: Peritoneal carcinomatosis (PC) is the most common form of metastasis in gastric cancer (GC) and is related with a poor prognosis. Several treatment modalities including systemic chemotherapy and intraperitoneal chemotherapy have been studied and adopted in treatment of GC patients with PC. Nevertheless, few studies have reported the comparison of the oncologic outcomes between minimally invasive surgery (MIS) with intraperitoneal (IP) chemotherapy and conventional chemotherapy for GC with PC. Methods: We retrospectively reviewed the clinical records of 74 patients who had been diagnosed as GC with PC via either intra-abdominal exploration or abdominopelvic computed tomography between January 2011 and April 2021. After performing propensity score-matching for this retrospective data, we compared the outcomes of 26 patients who underwent MIS followed by IP combined systemic chemotherapy (MIS-IP group) and 26 patients who underwent systemic chemotherapy only (SC-only group). Results: The 2-year progression free survival rate of the MIS-IP group was significantly higher than the SC-only groups (36.4% and 10.5%, respectively; p = 0.010). In multivariate analysis to detect relevant factors on PFS, IP chemotherapy (HR 0.213; p < 0.001), Eastern Cooperative Oncology Group performance status (HR 3.689; p = 0.002), and the amount of ascites (p = 0.011) were significant prognostic factors. Conclusions: This study demonstrated the therapeutic potential of MIS conjoined IP plus systemic chemotherapy for GC patients with PC. MIS conjoined by IP plus systemic chemotherapy can be adopted as a treatment option to reboot the role of IP chemotherapy in GC patients with PC. Full article

(This article belongs to the Special Issue Advanced Gastric Cancer)

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12 pages, 1986 KiB

Open AccessArticle

Prognostic Value of Systemic Inflammatory Response Markers in Patients Undergoing Neoadjuvant Chemotherapy and Gastrectomy for Advanced Gastric Cancer in the Eastern European Population

by Agnieszka Pikuła, Magdalena Skórzewska, Zuzanna Pelc, Radosław Mlak, Katarzyna Gęca, Katarzyna Sędłak, Bogumiła Ciseł, Magdalena Kwietniewska, Karol Rawicz-Pruszyński and Wojciech P. Polkowski

Cancers 2022, 14(8), 1997; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14081997 - 14 Apr 2022

Cited by 11 | Viewed by 1694

Abstract

The prognostic value of the systemic inflammatory response markers, namely neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) has not yet been clarified in patients undergoing neoadjuvant chemotherapy (NAC) and gastrectomy for advanced gastric cancer (GC) in the Eastern European population. This study aimed to verify the prognostic value of NLR, PLR, and LMR in GC patients undergoing multimodal treatment. One hundred six GC patients undergoing NAC and gastrectomy between 2012 and 2020 were included. Analysed blood samples were obtained prior to NAC (pre-NAC group) and before surgical treatment (post-NAC group). To evaluate the prognostic value of the NLR, LMR, and PLR, univariable and multivariable overall survival (OS) analyses were performed. In the pre-NAC group, elevated NLR and PLR were associated with significantly higher risk of death (mOS: 36 vs. 87 months; HR = 2.21; p = 0.0255 and mOS: 30 vs. 87 months; HR = 2.89; p = 0.0034, respectively). Additionally, a significantly higher risk of death was observed in patients with elevated NLR in the post-NAC group (mOS: 35 vs. 87 months; HR = 1.94; p = 0.0368). Selected systemic inflammatory response markers (NLR, PLR) are significant prognostic factors in patients with advanced GC treated with NAC and gastrectomy, as shown in the Eastern European population. Full article

(This article belongs to the Special Issue Advanced Gastric Cancer)

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15 pages, 2524 KiB

Open AccessArticle

Characterization of Total RNA, CD44, FASN, and PTEN mRNAs from Extracellular Vesicles as Biomarkers in Gastric Cancer Patients

by Philipp Rhode, Matthias Mehdorn, Orestis Lyros, Christoph Kahlert, Thomas Kurth, Tom Venus, Katrin Schierle, Irina Estrela-Lopis, Boris Jansen-Winkeln, Florian Lordick, Ines Gockel and René Thieme

Cancers 2021, 13(23), 5975; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13235975 - 27 Nov 2021

Cited by 6 | Viewed by 2128

Abstract

In-depth characterization has introduced new molecular subtypes of gastric cancer (GC). To identify these, new approaches and techniques are required. Liquid biopsies are trendsetting and provide an easy and feasible method to identify and to monitor GC patients. In a prospective cohort of 87 GC patients, extracellular vesicles (EVs) were isolated from 250 µL of plasma. The total RNA was isolated with TRIZOL. The total RNA amount and the relative mRNA levels of CD44, PTEN, and FASN were measured by qRT-PCR. The isolation of EVs and their contained mRNA was possible in all 87 samples investigated. The relative mRNA levels of PTEN were higher in patients already treated by chemotherapy than in chemo-naïve patients. In patients who had undergone neoadjuvant chemotherapy followed by gastrectomy, a decrease in the total RNA amount was observed after neoadjuvant chemotherapy and gastrectomy, while FASN and CD44 mRNA levels decreased only after gastrectomy. The amount of RNA and the relative mRNA levels of FASN and CD44 in EVs were affected more significantly by chemotherapy and gastrectomy than by chemotherapy alone. Therefore, they are a potential biomarker for monitoring treatment response. Future analyses are needed to identify GC-specific key RNAs in EVs, which could be used for the diagnosis of gastric cancer patients in order to determine their molecular subtype and to accompany the therapeutic response. Full article

(This article belongs to the Special Issue Advanced Gastric Cancer)

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14 pages, 12250 KiB

Open AccessArticle

Risk Factors for Metachronous Isolated Peritoneal Metastasis after Preoperative Chemotherapy and Potentially Curative Gastric Cancer Resection: Results from the CRITICS Trial

by Irene A. Caspers, Karolina Sikorska, Astrid E. Slagter, Romy M. van Amelsfoort, Elma Meershoek-Klein Kranenbarg, Cornelis J. H. van de Velde, Pehr Lind, Marianne Nordsmark, Edwin P. M. Jansen, Marcel Verheij, Johanna W. van Sandick, Annemieke Cats and Nicole C. T. van Grieken

Cancers 2021, 13(18), 4626; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13184626 - 15 Sep 2021

Cited by 7 | Viewed by 1706

Abstract

Gastric cancer (GC) patients at high risk of developing peritoneal metastasis (PM) as a single site of metastasis after curative treatment may be candidates for adjuvant prophylactic strategies. Here we investigated risk factors for metachronous isolated PM in patients who were treated in the CRITICS trial (NCT00407186). Univariable and multivariable analyses on both metachronous isolated PM and ‘other events’, i.e., (concurrent) distant metastasis, locoregional recurrence or death, were performed using a competing risk model and summarized by cumulative incidences. Isolated PM occurred in 64 of the 606 (11%) included patients. Diffuse or mixed histological subtype, ypT4 tumor stage and LN^high (ypN3 lymph node stage or a lymph node ratio >20%) were independent risk factors for isolated PM in both univariable and multivariable analyses. Likewise, LN^high was an independent risk factor for ‘other events’. Patients with tumors who were positive for all three independent risk factors had the highest two-year cumulative incidence of 43% for isolated PM development. In conclusion, diffuse or mixed histological subtype, ypT4 and LN^high were identified as independent risk factors for isolated PM in patients treated with preoperative chemotherapy followed by surgical resection. The combination of these factors may identify a subgroup that may benefit from PM-preventing treatment strategies. Full article

(This article belongs to the Special Issue Advanced Gastric Cancer)

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14 pages, 1587 KiB

Open AccessArticle

Are Borrmann’s Types of Advanced Gastric Cancer Distinct Clinicopathological and Molecular Entities? A Western Study

by Cristina Díaz del Arco, Luis Ortega Medina, Lourdes Estrada Muñoz, Elena Molina Roldán, M. Ángeles Cerón Nieto, Soledad García Gómez de las Heras and M. Jesús Fernández Aceñero

Cancers 2021, 13(12), 3081; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13123081 - 21 Jun 2021

Cited by 11 | Viewed by 11849

Abstract

Most studies on the clinicopathological impact of Borrmann classification for gastric cancer (GC) have been performed in Asian patients with type IV tumors, and immunohistochemical features of Borrmann types have scarcely been analyzed. We assessed the clinicopathological, molecular features and prognostic value of Borrmann types in all patients with advanced GC resected in a Western institution (n = 260). We observed a significant relationship between Borrmann types and age, systemic symptoms, tumor size, Laurén subtype, presence of signet-ring cells, infiltrative growth, high grade, tumor necrosis, HERCEPTEST positivity, microsatellite instability (MSI) and molecular subtypes. Polypoid GC showed systemic symptoms, intestinal-type histology, low grade, expansive growth and HERCEPTEST positivity. Fungating GC occurred in symptomatic older patients. It presented intestinal-type histology, infiltrative growth and necrosis. Ulcerated GC showed smaller size, intestinal-type histology, high grade and infiltrative growth. Most polypoid and ulcerated tumors were stable-p53-not overexpressed or microsatellite unstable. Flat lesions were high-grade diffuse tumors with no MSI, and occurred in younger and less symptomatic patients. No association was found between Borrmann classification and prognosis. According to our results, Borrmann types may represent distinct clinicopathological and biological entities. Further research should be conducted to confirm the role of Borrmann classification in the stratification of patients with advanced GC. Full article

(This article belongs to the Special Issue Advanced Gastric Cancer)

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13 pages, 7026 KiB

Open AccessArticle

Sexual Difference Matters: Females with High Microsatellite Instability Show Increased Survival after Neoadjuvant Chemotherapy in Gastric Cancer

by Meike Kohlruss, Katja Ott, Bianca Grosser, Moritz Jesinghaus, Julia Slotta-Huspenina, Alexander Novotny, Alexander Hapfelmeier, Thomas Schmidt, Matthias M. Gaida, Wilko Weichert and Gisela Keller

Cancers 2021, 13(5), 1048; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13051048 - 02 Mar 2021

Cited by 11 | Viewed by 2009

Abstract

We aimed to investigate patients with gastric/gastro-esophageal adenocarcinomas for sex- and age-specific differences regarding overall survival (OS) and response to neoadjuvant chemotherapy (CTx) under consideration of tumor specific molecular subtypes. Overall, 717 patients were analyzed, including 426 patients treated with and 291 treated without neoadjuvant CTx. Microsatellite instability (MSI) and Epstein-Barr virus positivity (EBV+) were determined previously. Females demonstrated a significantly increased OS (p = 0.035), particularly in the subgroup treated with CTx (p = 0.054). No significant differences regarding age were found. In the molecular subgroups, no sex-related differences were observed in the non-CTx group. However in the CTx group, females with MSI-high (H) tumors showed the best OS (p = 0.043), followed by the male MSI-H (p = 0.198) and female MSS (p = 0.114) compared to the male MSS group as reference. The interaction between sex and MSI in this patient group was noticeable (p = 0.053) and was included as a relevant factor in multivariable analyses. In conclusion, our results show an effect of sex on OS in gastric/gastro-esophageal cancer specifically for patients treated with neoadjuvant CTx. The superior survival of women with MSI-H tumors after neoadjuvant CTx implies that combined consideration of these factors could contribute to an individualized treatment of the patients. Full article

(This article belongs to the Special Issue Advanced Gastric Cancer)

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18 pages, 3699 KiB

Open AccessArticle

Human Ccr4 and Caf1 Deadenylases Regulate Proliferation and Tumorigenicity of Human Gastric Cancer Cells via Modulating Cell Cycle Progression

by Xiao-Hui Song, Xiao-Yan Liao, Xu-Ying Zheng, Jia-Qian Liu, Zhe-Wei Zhang, Li-Na Zhang and Yong-Bin Yan

Cancers 2021, 13(4), 834; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13040834 - 17 Feb 2021

Cited by 4 | Viewed by 2058

Abstract

Cancer cells generally have reprogrammed gene expression profiles to meet the requirements of survival, continuous division, and metastasis. An interesting question is whether the cancer cells will be affected by interfering their global RNA metabolism. In this research, we found that human Ccr4a/b (hCcr4a/b) and Caf1a/b (hCaf1a/b) deadenylases, the catalytic components of the Ccr4-Not complex, were dysregulated in several types of cancers including stomach adenocarcinoma. The impacts of the four deadenylases on cancer cell growth were studied by the establishment of four stable MKN28 cell lines with the knockdown of hCcr4a/b or hCaf1a/b or transient knockdown in several cell lines. Depletion of hCcr4a/b or hCaf1a/b significantly inhibited cell proliferation and tumorigenicity. Mechanistic studies indicated that the cells were arrested at the G2/M phase by knocking down hCaf1a, while arrested at the G0/G1 phase by depleting hCaf1b or hCcr4a/b. The four enzymes did not affect the levels of CDKs and cyclins but modulated the levels of CDK–cyclin inhibitors. We identified that hCcr4a/b, but not hCaf1a/b, targeted the p21 mRNA in the MKN28 cells. Furthermore, depletion of any one of the four deadenylases dramatically impaired processing-body formation in the MKN28 and HEK-293T cells. Our results highlight that perturbating global RNA metabolism may severely affect cancer cell proliferation, which provides a potential novel strategy for cancer treatment. Full article

(This article belongs to the Special Issue Advanced Gastric Cancer)

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15 pages, 24867 KiB

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LncRNA PVT1 Is a Poor Prognosticator and Can Be Targeted by PVT1 Antisense Oligos in Gastric Adenocarcinoma

by Yuan Li, Shumei Song, Melissa Pool Pizzi, Guangchun Han, Ailing W. Scott, Jiankang Jin, Yan Xu, Ying Wang, Longfei Huo, Lang Ma, Christopher Vellano, Xiaolin Luo, Robert MacLeod, Linghua Wang, Zhenning Wang and Jaffer A. Ajani

Cancers 2020, 12(10), 2995; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12102995 - 15 Oct 2020

Cited by 13 | Viewed by 2159

Abstract

Gastric adenocarcinoma (GAC) is inherently resistant or becomes resistant to therapy, leading to a poor prognosis. Mounting evidence suggests that lncRNAs can be used as predictive markers and therapeutic targets in the right context. In this study, we determined the role of lncRNA-PVT1 in GAC along with the value of inhibition of PVT1 using antisense oligos (ASOs). RNA scope in situ hybridization was used to analyze PVT1 expression in tumor tissue microarrays (TMAs) of GAC and paired normal tissues from 792 patients. Functional experiments, including colony formation and invasion assays, were performed to evaluate the effects of PVT1 ASO inhibition of PVT1 in vitro; patient-derived xenograft models were used to evaluate the anti-tumor effects of PVT1 ASOs in vivo. LncRNA-PVT1 was upregulated in GACs compared to the matched adjacent normal tissues in the TMA. LncRNA PVT1 expression was positively correlated with larger tumor size, deeper wall invasion, lymph node metastases, and short survival duration. Inhibition of PVT1 using PVT1 ASOs significantly suppressed tumor cell growth and invasion in vitro and in vivo. PVT1 expression was highly associated with poor prognosis in GAC patients and targeting PVT1 using PVT1 ASOs was effective at curtailing tumor cell growth in vitro and in vivo. Thus, PVT1 is a poor prognosticator as well as therapeutic target. Targeting PVT1 using PVT1 ASOs provides a novel therapeutic strategy for GAC. Full article

(This article belongs to the Special Issue Advanced Gastric Cancer)

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16 pages, 1023 KiB

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Ramucirumab in Combination with Pembrolizumab in Treatment-Naïve Advanced Gastric or GEJ Adenocarcinoma: Safety and Antitumor Activity from the Phase 1a/b JVDF Trial

by Ian Chau, Nicolas Penel, Andres O. Soriano, Hendrik-Tobias Arkenau, Jennifer Cultrera, Rafael Santana-Davila, Emiliano Calvo, Christophe Le Tourneau, Lars Zender, Johanna C. Bendell, Gu Mi, Ling Gao, Samuel Clark McNeely, Joana M. Oliveira, David Ferry, Roy S. Herbst and Charles S. Fuchs

Cancers 2020, 12(10), 2985; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12102985 - 15 Oct 2020

Cited by 19 | Viewed by 3711

Abstract

Ramucirumab (anti-VEGFR2) plus pembrolizumab (anti-PD1) demonstrated promising antitumor activity and tolerability among patients with previously treated advanced cancers, supporting growing evidence that combination therapies modulating the tumor microenvironment may expand the spectrum of patients who respond to checkpoint inhibitors. Here we present the results of this combination in first-line patients with metastatic G/GEJ cancer. Twenty-eight patients (≥18 years) with no prior systemic chemotherapy in the advanced/metastatic setting received ramucirumab (8 mg/kg days 1 and 8) plus pembrolizumab (200 mg day 1) every 3 weeks as part of JVDF phase 1a/b study. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and overall survival (OS). Tumors were PD-L1-positive (combined positive score ≥ 1) in 19 and -negative in 6 patients. Eighteen patients experienced grade 3 treatment-related adverse events, most commonly hypertension (14%) and elevated alanine/aspartate aminotransferase (11% each), with no grade 4 or 5 reported. The ORR was 25% (PD-L1-positive, 32%; PD-L1-negative, 17%) with duration of response not reached. PFS was 5.6 months (PD-L1-positive, 8.6 months; PD-L1-negative, 4.3 months), and OS 14.6 months (PD-L1-positive, 17.3 months; PD-L1-negative, 11.3 months). Acknowledging study design limitations, ramucirumab plus pembrolizumab had encouraging durable clinical activity with no unexpected toxicities in treatment-naïve biomarker-unselected metastatic G/GEJ cancer, and improved outcomes in patients with PD-L1-positive tumors. Full article

(This article belongs to the Special Issue Advanced Gastric Cancer)

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Review

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Open AccessReview

Lymph Node Involvement in Advanced Gastric Cancer in the Era of Multimodal Treatment—Oncological and Surgical Perspective

by Zuzanna Pelc, Magdalena Skórzewska, Karol Rawicz-Pruszyński and Wojciech P. Polkowski

Cancers 2021, 13(10), 2509; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13102509 - 20 May 2021

Cited by 12 | Viewed by 2786

Abstract

Gastric cancer (GC) continues to be one of the major oncological challenges on a global scale. The role of neoadjuvant chemotherapy (NAC) in GC is to downstage primary tumour, eliminate potential micrometastases, and increase the chance for radical resection. Although systemic treatment prolongs the survival in advanced GC, persistent lymph node (LN) metastases indicate poor prognosis. Further identification of prognostic factors after NAC is urgent and could positively influence clinical outcomes. This article aimed to review the actual trends and future perspectives in multimodal therapy of advanced GC, with a particular interest in the post-neoadjuvant pathological nodal stage. A favourable prognostic impact for ypN0 patients is observed, either due to truly negative LN before the start of therapy or because preoperative therapy achieved a pathologically complete nodal response. Ongoing trials investigating the extent of lymphadenectomy after neoadjuvant therapy will standardise the LN dissection from the multimodal therapy perspective. Since downstaged and primarily node-negative patients show a similar prognosis, the main target for NAC in advanced GC should be nodal clearance. Adequate staging and personalised perioperative therapy seem to be of great importance in the multimodal treatment of GC. Full article

(This article belongs to the Special Issue Advanced Gastric Cancer)

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20 pages, 1610 KiB

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Predicting Peritoneal Dissemination of Gastric Cancer in the Era of Precision Medicine: Molecular Characterization and Biomarkers

by Yanyan Chen, Quan Zhou, Haiyong Wang, Wei Zhuo, Yongfeng Ding, Jun Lu, Guanghao Wu, Nong Xu and Lisong Teng

Cancers 2020, 12(8), 2236; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12082236 - 10 Aug 2020

Cited by 34 | Viewed by 5330

Abstract

Gastric cancer (GC) is a leading cause of worldwide cancer-related death. Being a highly heterogeneous disease, the current treatment of GC has been suboptimal due to the lack of subtype-dependent therapies. Peritoneal dissemination (PD) is a common pattern of GC metastasis associated with poor prognosis. Therefore, it is urgently necessary to identify patients at high risk of PD. PD is found to be associated with Lauren diffuse type GC. Molecular profiling of GC, especially diffuse type GC, has been utilized to identify molecular alterations and has given rise to various molecular classifications, shedding light on the underlying mechanism of PD and enabling identification of patients at higher PD risk. In addition, a series of diagnositc and prognostic biomarkers of PD from serum, peritoneal lavages and primary GCs have been reported. This comprehensive review summarizes findings on the multi-omic characteristics of diffuse type GC, the clinical significance of updating molecular classifications of GC in association with PD risk and research advances in PD-associated biomarkers. Full article

(This article belongs to the Special Issue Advanced Gastric Cancer)

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