Photodynamic therapy in combination with immune checkpoint inhibitors plus chemotherapy for first-line treatment in advanced or metastatic gastric or gastroesophageal junction cancer: A phase 2–3 clinical trial protocol

Introduction: The immune checkpoint inhibitor (ICI) has been approved as the first-line therapy for metastatic gastric cancer in China. The treatment response of immune checkpoint inhibitor is highly dependent on the immune condition within the tumor microenvironment. Photodynamic therapy (PDT) has a long history in cancer treatment, and recent studies showed it had an immunomodulatory effect on the tumor. Here we will conduct a trial to assess whether or not a combination with Photodynamic therapy will improve the outcomes of immune checkpoint inhibitor-based treatment in patients with advanced or metastatic gastric cancer.Methods: This study is a single-center, open-label, randomized controlled, phase 2–3 trial. Patients (18–65 years old) with untreated gastric or gastroesophageal junction adenocarcinoma will be eligible for this trial. Sixty participants will be enrolled and randomly divided into the test group (n = 30) and control group (n = 30) to receive photodynamic therapy in combination with immune checkpoint inhibitor plus chemotherapy and immune checkpoint inhibitor plus chemotherapy, respectively. The primary is progression-free survival (PFS). The secondary outcomes include objective response rates (ORRs) and the occurrence of adverse events. In addition, we will also assess the changes in peripheral blood mononuclear cells (PBMCs) and tumor microenvironment after photodynamic therapy treatment in the test group. Evaluation of the tumor response will be performed every two cycles for a maximum of eight cycles.Discussion: Photodynamic therapy has an immunomodulatory effect on the tumor microenvironment; however, this has not been demonstrated for gastric cancer in a clinical trial. Based on our experience of photodynamic therapy treatment in digestive tract tumors, we plan to conduct a randomized controlled trial on this topic. This will be the first study to evaluate the synergistic effect of photodynamic therapy with immunochemotherapy for patients with advanced gastric cancer.Ethics and dissemination: It was approved by the Institutional Research Ethics Committee of Lanzhou University Second Hospital (No. 2022A-491). When this trial is completed, it will be shared at conferences and submitted for a potential publication in a peer-reviewed journal.Clinical Trial Registration:http://www.chictr.org.cn/, identifier ChiCTR2200064280

The “Light Knife” for Gastric Cancer: Photodynamic Therapy

Photodynamic therapy (PDT) has been used clinically to treat cancer for more than 40 years. Some solid tumors, including esophageal cancer, lung cancer, head and neck cancer, cholangiocarcinoma, and bladder cancer, have been approved for and managed with PDT in many countries globally. Notably, PDT for gastric cancer (GC) has been reported less and is not currently included in the clinical diagnosis and treatment guidelines. However, PDT is a potential new therapeutic modality used for the management of GC, and its outcomes and realization are more and more encouraging. PDT has a pernicious effect on tumors at the irradiation site and can play a role in rapid tumor shrinkage when GC is combined with cardiac and pyloric obstruction. Furthermore, because of its ability to activate the immune system, it still has a specific effect on systemic metastatic lesions, and the adverse reactions are mild. In this Review, we provide an overview of the current application progress of PDT for GC; systematically elaborate on its principle, mechanism, and the application of a new photosensitizer in GC; and focus on the efficacy of PDT in GC and the prospect of combined use with other therapeutic methods to provide a theoretical basis for clinical application

Advances in the Application of Preclinical Models in Photodynamic Therapy for Tumor: A Narrative Review

Photodynamic therapy (PDT) is a non-invasive laser light local treatment that has been utilized in the management of a wide variety of solid tumors. Moreover, the evaluation of efficacy, adverse reactions, the development of new photosensitizers and the latest therapeutic regimens are inseparable from the preliminary exploration in preclinical studies. Therefore, our aim was to better comprehend the characteristics and limitations of these models and to provide a reference for related research. Methods: We searched the databases, including PubMed, Web of Science and Scopus for the past 25 years of original research articles on the feasibility of PDT in tumor treatment based on preclinical experiments and animal models. We provided insights into inclusion and exclusion criteria and ultimately selected 40 articles for data synthesis. Results: After summarizing and comparing the methods and results of these studies, the experimental model selection map was drawn. There are 7 main preclinical models, which are used for different research objectives according to their characteristics. Conclusions: Based on this narrative review, preclinical experimental models are crucial to the development and promotion of PDT for tumors. The traditional animal models have some limitations, and the emergence of organoids may be a promising new insight

Table_1_Coagulation- and fibrinolysis-related genes for predicting survival and immunotherapy efficacy in colorectal cancer.docx

BackgroundColorectal cancer (CRC) is a common cancer and has a poor prognosis. The coagulation system and fibrinolysis system are closely related to the progression of malignant tumors and is also related to the immunotherapy of malignant tumors. Herein, we tried to predict survival and the immunotherapy effect for patients with CRC using a novel potential prognostic model.MethodsThrough online data of TCGA and GEO, we screened significantly differentially expressed genes (DEGs) to construct a prognostic model, followed by obtaining immune-related genes (IRGs) from the ImmPort database and coagulation- and fibrinolysis-related genes (CFRGs) from the GeneCards database. The predictive power of the model is assessed by Kaplan–Meier survival curves as well as the time-dependent ROC curve. Moreover, univariate and multivariate analyses were conducted for OS using Cox regression models, and the nomogram prognostic model was built. In the end, we further studied the possibility that CXCL8 was associated with immunocyte infiltration or immunotherapy effect and identified it by immunohistochemistry and Western blot.ResultsFive DEGs (CXCL8, MMP12, GDF15, SPP1, and NR3C2) were identified as being prognostic for CRC and were selected to establish the prognostic model. Expression of these genes was confirmed in CRC samples using RT-qPCR. Notably, those selected genes, both CFRGs and IRGs, can accurately predict the OS of CRC patients. Furthermore, CXCL8 is highly correlated with the tumor microenvironment and immunotherapy response in CRC.ConclusionOverall, our established IRGPI can very accurately predict the OS of CRC patients. CXCL8 reflects the immune microenvironment and reveals the correlation with immune checkpoints among CRC patients.</p

Image_1_Coagulation- and fibrinolysis-related genes for predicting survival and immunotherapy efficacy in colorectal cancer.tif

BackgroundColorectal cancer (CRC) is a common cancer and has a poor prognosis. The coagulation system and fibrinolysis system are closely related to the progression of malignant tumors and is also related to the immunotherapy of malignant tumors. Herein, we tried to predict survival and the immunotherapy effect for patients with CRC using a novel potential prognostic model.MethodsThrough online data of TCGA and GEO, we screened significantly differentially expressed genes (DEGs) to construct a prognostic model, followed by obtaining immune-related genes (IRGs) from the ImmPort database and coagulation- and fibrinolysis-related genes (CFRGs) from the GeneCards database. The predictive power of the model is assessed by Kaplan–Meier survival curves as well as the time-dependent ROC curve. Moreover, univariate and multivariate analyses were conducted for OS using Cox regression models, and the nomogram prognostic model was built. In the end, we further studied the possibility that CXCL8 was associated with immunocyte infiltration or immunotherapy effect and identified it by immunohistochemistry and Western blot.ResultsFive DEGs (CXCL8, MMP12, GDF15, SPP1, and NR3C2) were identified as being prognostic for CRC and were selected to establish the prognostic model. Expression of these genes was confirmed in CRC samples using RT-qPCR. Notably, those selected genes, both CFRGs and IRGs, can accurately predict the OS of CRC patients. Furthermore, CXCL8 is highly correlated with the tumor microenvironment and immunotherapy response in CRC.ConclusionOverall, our established IRGPI can very accurately predict the OS of CRC patients. CXCL8 reflects the immune microenvironment and reveals the correlation with immune checkpoints among CRC patients.</p