Gastric cancer presents substantial management challenges, and the advent of immunotherapy has ignited renewed hope among patients. Nevertheless, a significant proportion of patients do not respond to immunotherapy, and adverse events associated with immunotherapy also occur on occasion, underscoring the imperative to identify suitable candidates for treatment. Several biomarkers, including programmed death ligand-1 expression, tumor mutation burden, mismatch repair status, Epstein–Barr Virus infection, circulating tumor DNA, and tumor-infiltrating lymphocytes, have demonstrated potential in predicting the effectiveness of immunotherapy in gastric cancer. However, the quest for the optimal predictive biomarker for gastric cancer immunotherapy remains challenging, as each biomarker carries its own limitations. Recently, multi-omics technologies have emerged as promising platforms for discovering novel biomarkers that may help in selecting gastric cancer patients likely to respond to immunotherapy. The identification of reliable predictive biomarkers for immunotherapy in gastric cancer holds the promise of enhancing patient selection and improving treatment outcomes. In this review, we aim to provide an overview of clinically established biomarkers of immunotherapy in gastric cancer. Additionally, we introduce newly reported biomarkers based on multi-omics studies in the context of gastric cancer immunotherapy, thereby contributing to the ongoing efforts to refine patient stratification and treatment strategies.

Background: Apoptosis is a major mode of hematological tumor death after radiation. Early detection of apoptosis may be beneficial for cancer adaptive treatment. ^99mTc-HYNIC-annexinV has been reported as a promising agent for in vivo apoptosis imaging. The purpose of this study is to evaluate the feasibility of in vivo^99mTc-HYNIC-annexinV imaging of radiation- induced apoptosis, and to investigate its correlation with radiosensitivity. Methods: Ten days after inoculation of tumor cells in the right upper limbs, the mice were randomly divided into two groups. The imaging group (4 mice each level, 4 dose levels) was injected with 4-8 MBq ^99mTc-HYNIC-annexinV 24 hours after irradiation and imaged 1 hr post-injection, and the mice were sacrificed immediately after imaging for biodistribution analysis of annexin V. The observation group (4 mice each level, 2 dose levels) was only observed for tumor regression post-radiation. The number of apoptotic cells in a tumor was estimated with TUNEL assay. Results: The ^99mTc-HYNIC-annexin V uptake in E14 lymphoma significantly increased as the radiation dose escalated from 0 to 8 Gy, and significantly correlated with the number of TUNEL-positive cells (r = 0.892, P < 0.001). The Annexin-V uptake and the number of TUNEL-positive cells in El4 lymphoma were significantly greater than those in S180 sarcoma. With 8 Gy, S180 sarcoma tumor showed scanty apoptosis and less shrinkage while El4 lymphoma showed remarkable apoptosis and complete remission. Conclusion: ⁹⁹mTc-HYNIC-annexinV in vivo imaging is a feasible method to detect early radiation-induced apoptosis in different tumors, and might be predictive for radiation sensitivity.

To assess the safety and efficacy of simultaneous integrated boost (SIB) or late course accelerated boost (LCAB) with external beam radiotherapy (EBRT) to the vaginal cuff for high risk cervical cancer patients after radical hysterectomy. Between October 2009 and January 2012, patients with high risk cervical cancer who had undergone radical surgery followed by EBRT to the vaginal cuff were enrolled. Patients were treated with either intensity modulated radiotherapy (IMRT)/volumetric modulated arc therapy (VMAT) with SIB (arm A) or IMRT/VMAT to the pelvis followed by LCAB (arm B) to vaginal cuff. In arm A, the pelvic and boost doses were 50.4 Gy and 60.2 Gy in 28 fractions, respectively. In arm B, pelvic irradiation to 50 Gy in 25 fractions followed by a boost of 9 Gy in 3 fractions were delivered. Chemotherapy was given concurrently. Overall, 80 patients were analyzed in this study (42 in arm A, 38 in arm B). In arm A and B, median follow-up was 37 and 32 months, respectively. The 3-year disease-free survival and overall survival in arms A vs B were 88.7% vs. 93.4% (p = 0.89), and 91.8% vs.100% (p = 0.21), respectively. The 3-year local-regional control and distant failure were 97.6% vs. 100% (p = 0.34), and 4.8% vs. 5.3% (p = 0.92), respectively. Grade 3–4 acute leukopenia and dermatitis were seen in 11 (26.2%) and 8 (19.0%) patients in Arm A, vs. 7 (17.8%) and 6 (15.8%) patients in Arm B, respectively (p > 0.05). Only Grade 1–2 chronic gastrointestinal (GI) and genitourinary (GU) toxicities were observed. Our results indicate that both SIB and LCAB to vaginal cuff for high risk cervical cancer patients after radical hysterectomy are associated with excellent survival, local control and low toxicity.

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Purpose. The purpose of this study was to retrospectively review the outcomes of patients with high-risk endometrial cancer treated with adjuvant radiotherapy with concurrent paclitaxel and cisplatin (TP). Methods. Patients with endometrial cancer who underwent radical surgery were screened between Jan 2005 and Dec 2018. Patients with high-risk factors who received adjuvant chemoradiotherapy were included in the study. High risks included stage I, endometrioid-type grade 3 with deep myometrial invasion or lymphovascular space invasion (or both), endometrioid-type stage II to IVa, or stage I to III with serous or clear cell histology. The adjuvant treatment regimen included one cycle of TP chemotherapy, followed by pelvic intensity-modulated radiotherapy (IMRT) with concurrent TP, followed by an additional one cycle of TP. Failure free survival (FFS) and overall survival (OS) were estimated. Patterns of recurrence and occurrence of adverse events were described. Results. A total of 450 patients with high-risk endometrial cancer were screened, 231 of whom were included in this study. After a median follow-up of 70 months, the 5-year OS was 94.7%, and the 6-year OS was 91.8%. The 5-y and 6-y FFS were 90.8% and 87.9%, respectively, which were related to stage ( ). A total of 14 patients experienced tumor recurrence, including 7 pelvic recurrence and 7 distant metastases. Seven patients died, all due to tumor progression. A total of 164 patients (71%) completed the prescribed course of treatment. A total of 205 patients had adverse events, 46 patients (20%) had grade 1, 92 patients (40%) had grade 2, 49 patients (21%) had grade 3, and 18 patients (8%) had grade 4. There were 83 nonhematologic and 122 hematologic toxicities (26 grade 3 and 18 grade 4). Conclusion. Adjuvant pelvic radiotherapy combined with synchronous TP chemotherapy can achieve excellent long-term survival for high-risk endometrial cancer patients. Moreover, this combination therapy has good safety and feasibility, which is worthy of further study and verification.

Background: Breast cancer (BC) is clinically defined as a cold tumor due to its low immunogenicity, which is usually insensitive to immunosuppressive agents. Herein, we investigated the predictive potential of novel immune-related genes (IRGs) in BC, with the objective of more effectively guiding the immunotherapy for patients with BC. Methods: The least absolute shrinkage and selection operator (LASSO) regression analysis was used to conduct the BC prognostic model based on IRGs, and univariate/multivariate Cox proportional hazards models were employed to establish the BC predictive nomograms. Then, we investigated the expression patterns of these IRGs utilizing The Cancer Genome Atlas (TCGA) database. Moreover, we also performed correlation analyses between IRGs and multiple immune features, including infiltration of immune cells, immune checkpoint members, and immune therapy response. Results: In our study, six IRGs were finally identified to construct the BC prognostic model, including HMGB3, TNFSF4, CORO2A, SOCS3, TACR1, and FREM1. This model exhibited excellent predictive performance, with area under the curve (AUC) values of 0.676, 0.646, and 0.621 for the 1-, 3-, and 5-year timeframes, respectively. Analysis of expression profiles indicated that HMGB3, CORO2A, and TNFSF4 exhibited significant upregulation in BC tissues, displaying strong correlations with diminished overall survival. The three overexpressed genes showed statistically significant correlations with multiple important immune cells, including Tregs, macrophages, and CD4+/CD8+ T cells. Notably, distinct patterns of integrating gene expression and immune infiltration significantly affected the clinical outcomes of BC patients. These upregulated genes demonstrated significant co-expression patterns with key immune checkpoint regulators, suggesting close immunomodulatory interactions in BC. The Tumor Immune Dysfunctional and Exclusion (TIDE) scores were lower in the high-expression groups of HMGB3 and CORO2A, whereas the TIDE score was higher in the high-expression group of TNFSF4. Conclusions: This prognostic model reliably assessed risk for BC patients, providing critical guidance for precision oncology protocols and dynamic surveillance of disease progression.