MO5-5 Lesion-level response to immune checkpoint inhibitor in patients with advanced gastric cancer and esophageal cancer

306 Background: We intended to evaluate the utility of neutrophil-to-lymphocyte (NLR) in advanced gastric cancer patients treated with immune checkpoint inhibitor (ICI). Methods: We examined NLR at baseline and 6 (±2) weeks later in 139 patients between August 2015 and April 2019. Landmark analysis at 6 weeks was conducted to explore the prognostic value of NLR change on progress-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR). Cox and logistic regression models were adjusted for tumor differention, Lauren classification, line of therapy, type of anti-PD-1/PD-L1 therapy, and baseline NLR. Results: Median duration on therapy was 6 cycles. Median NLR was 3.33 (IQR: 2.26-4.84) at baseline and 2.93 (IQR: 1.67-4.83) at week 6. Patients with a higher baseline NLR showed a trend toward lower DCR, shorter PFS, and shorter OS. Higher NLR at 6 weeks was significantly associated with inferior PFS [hazard ratios (HRs) 1.03, 95% confidence interval (CI): 1.00-1.06 ] and inferior OS (HR 1.08, 95%CI: 1.03-1.12). Relative NLR decrease by ≥ 25% from baseline to 6 weeks after ICI therapy was an independent prognostic factor for ORR (OR 8.11,95% CI:2.40-27.4), DCR (OR 20.03, 95% CI: 3.32-121), PFS (HR 0.37, 95% CI: 0.20-0.68), and OS (HR 0.26, 95% CI: 0.10-0.65). Conclusions: Early decline of NLR (and NLR at 6 weeks) were associated with improved clinical outcomes in advanced gastric cancer patients treated with ICI. [Table: see text]

Download Full-text

When to apply immune checkpoint inhibitor in patients with refractory advanced gastric cancer

Journal of Cancer ◽

10.7150/jca.62853 ◽

2021 ◽

Vol 12 (18) ◽

pp. 5681-5686

Author(s):

Hongsik Kim ◽

Hana Kim ◽

Minsang Lee ◽

Minsuk Kwon ◽

Jung Yong Hong ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitor ◽

Checkpoint Inhibitor

Download Full-text

How to Best Exploit Immunotherapeutics in Advanced Gastric Cancer: Between Biomarkers and Novel Cell-Based Approaches

Journal of Clinical Medicine ◽

10.3390/jcm10071412 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1412

Author(s):

Michele Ghidini ◽

Angelica Petrillo ◽

Andrea Botticelli ◽

Dario Trapani ◽

Alessandro Parisi ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitor ◽

Checkpoint Inhibitors ◽

Predictive Biomarkers ◽

Clinical Implementation ◽

T Cell Therapy ◽

Dismal Prognosis

Despite extensive research efforts, advanced gastric cancer still has a dismal prognosis with conventional treatment options. Immune checkpoint inhibitors have revolutionized the treatment landscape for many solid tumors. Amongst gastric cancer subtypes, tumors with microsatellite instability and Epstein Barr Virus positive tumors provide the strongest rationale for responding to immunotherapy. Various predictive biomarkers such as mismatch repair status, programmed death ligand 1 expression, tumor mutational burden, assessment of tumor infiltrating lymphocytes and circulating biomarkers have been evaluated. However, results have been inconsistent due to different methodologies and thresholds used. Clinical implementation therefore remains a challenge. The role of immune checkpoint inhibitors in gastric cancer is emerging with data from monotherapy in the heavily pre-treated population already available and studies in earlier disease settings with different combinatorial approaches in progress. Immune checkpoint inhibitor combinations with chemotherapy (CT), anti-angiogenics, tyrosine kinase inhibitors, anti-Her2 directed therapy, poly (ADP-ribose) polymerase inhibitors or dual checkpoint inhibitor strategies are being explored. Moreover, novel strategies including vaccines and CAR T cell therapy are also being trialed. Here we provide an update on predictive biomarkers for response to immunotherapy with an overview of their strengths and limitations. We discuss clinical trials that have been reported and trials in progress whilst providing an account of future steps needed to improve outcome in this lethal disease.

Download Full-text

Identification of Ferroptosis-Related Long Noncoding RNA and Construction of a Novel Prognostic Signature for Gastric Cancer

Disease Markers ◽

10.1155/2021/7724997 ◽

2021 ◽

Vol 2021 ◽

pp. 1-14

Author(s):

WenZheng Chen ◽

ZongFeng Feng ◽

JianFeng Huang ◽

PengCheng Fu ◽

JianBo Xiong ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Death ◽

High Risk ◽

Programmed Cell Death ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitor ◽

Checkpoint Inhibitor ◽

Gene Set Enrichment Analysis ◽

Prognostic Signature ◽

Cox Regression Analysis

Background. Gastric cancer is the most common malignant tumor of the digestive system. It has a poor prognosis and is clinically challenging to treat. Ferroptosis is a newly defined mode of programmed cell death. The roles and prognostic value of ferroptosis-related long noncoding RNAs (lncRNAs) in gastric cancer remain unknown. Results. In the current study, 20 ferroptosis-related lncRNAs were identified via univariate Cox analysis, least absolute shrinkage, and selection operator Cox regression analysis and used to construct a prognostic signature and classify gastric cancer patients into high-risk and low-risk groups. The signature was validated using TCGA training and testing cohorts. The risk signature was an independent prognostic indicator of survival and accurately predicted the prognoses of patients with gastric cancer. It was also associated with immune cell infiltration. Gene set enrichment analysis was used to investigate underlying mechanisms that the 20 ferroptosis-related lncRNAs were involved in. Chemosensitivity and immune checkpoint inhibitor analyses indicated that high-risk patients were more sensitive to the immune checkpoint inhibitor programmed cell death protein 1. Conclusions. The important role of ferroptosis-related lncRNAs in immune infiltration identified in the current study may assist the determination of personalized prognoses and treatments in patients with gastric cancer. These 20 lncRNAs can be used as the diagnostic and prognostic markers for gastric cancer.

Download Full-text

Esophageal cancer responsive to the combination of immune cell therapy and low-dose nivolumab: two case reports

Journal of Medical Case Reports ◽

10.1186/s13256-020-02634-z ◽

2021 ◽

Vol 15 (1) ◽

Author(s):

Rishu Takimoto ◽

Takashi Kamigaki ◽

Takuji Gotoda ◽

Toshimi Takahashi ◽

Sachiko Okada ◽

...

Keyword(s):

Esophageal Cancer ◽

Cell Therapy ◽

Immune Checkpoint ◽

Low Dose ◽

Immune Checkpoint Inhibitor ◽

Immune Cell ◽

Checkpoint Inhibitor ◽

Checkpoint Inhibitors ◽

Chemoradiation Therapy ◽

Advanced Esophageal Cancer

Abstract Background Blocking the programmed death 1 pathway by immune checkpoint inhibitors induces dramatic antitumor activity in patients with malignant tumors. However, the clinical response to immune checkpoint inhibitors remains limited owing to the patients’ immunological status, such as the number of lymphocytes, programmed death ligand 1 expression, and tumor mutation burden. In this study, we successfully treated two patients with advanced esophageal cancer who responded to the combination of adoptive immune cell therapy and a low-dose immune checkpoint inhibitor, nivolumab. Case presentation Two Asian (Japanese) patients with advanced esophageal cancer who were resistant to conventional chemoradiation therapy were referred to our hospital for immune therapy. Case 1 was a 66-year-old woman who was diagnosed as having esophageal cancer. She received concurrent chemoradiation therapy and then underwent subtotal esophagectomy, after which she became cancer free. However, she relapsed, and cancer cells were found in the lung and lymph nodes 6 months later. She enrolled in a clinical trial at our institution (clinical trial number UMIN000028756). She received adoptive immune cell therapy twice at a 2-week interval followed by low-dose nivolumab with adoptive immune cell therapy four times at 2-week intervals. A follow-up computed tomography scan showed partial response, with mass reduction of the metastatic lung and mediastinal lesions. Case 2 was a 77-year-old man. He received concurrent chemoradiation therapy with fluoropyrimidine/platinum, and gastroscopy revealed complete remission of esophageal cancer. He was disease free for 5 months, but routine computed tomography revealed multiple metastases in his lungs and lymph nodes. He visited our clinic to receive adoptive immune cell therapy and immune checkpoint inhibitor combination therapy. Radiographic evidence showed continuous improvement of lesions. There was no evidence of severe adverse events during the combination therapy. Conclusion The combination of adoptive immune cell therapy and an immune checkpoint inhibitor might be a possible treatment strategy for advanced esophageal cancer. Trial registration UMIN000028756. Registered 14 September 2017

Download Full-text