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An immunosuppressive scoring system to predict recurrence and assist in decision regarding postoperative adjuvant treatment in gastric cancer.

ABSTRACT: Inhibition of the immune microenvironment is the main cause of tumor recurrence after surgery in patients with gastric cancer (GC). In this study, immunohistochemistry and multiple immunofluorescence staining were used to evaluate immunosuppressive indicators and immune biomarkers in 825 patients with gastric cancer from three centers. We constructed an immunosuppressive recurrence score (IRS) using LASSO Cox regression based on the expression of six immunosuppressive indicators and found that the IRS and IRS-based nomogram were significantly accurate and reliable in predicting recurrence. Moreover, an elevated IRS was associated with locoregional recurrence and postoperative adjuvant chemotherapy failure. Furthermore, an increase in IRS indicated inhibition of the antitumor effect of CD8⁺ tumor-infiltrating lymphocytes in the invasive margin. Thus, we propose that the IRS can predict the recurrence outcome of patients with GC by distinguishing the immunosuppressive status, which is helpful in the selection of individualized adjuvant treatment plans.

SUBMITTER: Wang J

PROVIDER: S-EPMC9185630 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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An immunosuppressive scoring system to predict recurrence and assist in decision regarding postoperative adjuvant treatment in gastric cancer.

Wang Jiabin J Qiu Qingzhu Q Lian Ningzi N Wang Huagen H Zheng Qiaoling Q Yang Yinghong Y Ma Yubin Y Zhao Yajun Y Li Ping P Lin Jianxian J Lu Jun J Chen Qiyue Q Cao Longlong L Lin Mi M Huang Changming C Xie Jianwei J

American journal of cancer research 20220515 5

Inhibition of the immune microenvironment is the main cause of tumor recurrence after surgery in patients with gastric cancer (GC). In this study, immunohistochemistry and multiple immunofluorescence staining were used to evaluate immunosuppressive indicators and immune biomarkers in 825 patients with gastric cancer from three centers. We constructed an immunosuppressive recurrence score (IRS) using LASSO Cox regression based on the expression of six immunosuppressive indicators and found that t ...[more]

PMID: 35693074

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Project description:Background: Most patients with early gastric cancer (EGC) can achieve a better 5-year survival rate after endoscopic resection or surgery. However, indications for adjuvant chemotherapy (ACT) after surgery have not yet been determined. Methods: A total of 4,108 patients with EGC diagnosed in 2004-2016 were retrospectively analyzed using the Surveillance, Epidemiology, and End Results (SEER) database. Of these, 3,521 patients received postoperative ACT and 587 patients did not. Propensity score matching was used to balance the two groups' confounding factors. Kaplan-Meier method was utilized to perform survival analysis. Log-rank test was used to compare the differences between survival curves. Cox proportional-hazards regression model was used to screen independent risk factors and build a nomogram for the non-ACT group. The X-tile software was employed to artificially divide all patients into low-, moderate-, and high-risk groups according to the overall survival score prediction based on the nomogram. A total of 493 patients with EGC diagnosed between 2010 and 2014 in our hospital were included for external validation. Results: Multivariate analysis found that age, sex, race, marital status, primary site, surgical extent, and metastatic lymph node ratio in the non-ACT group were independent prognostic factors for EGC and were included in the construction of the nomogram. The model C-index was 0.730 (95% confidence interval: 0.677-0.783). The patients were divided into three different risk groups based on the nomogram prediction score. Patients in the low-risk group did not benefit from ACT, while patients in the moderate- and high-risk groups did. External validation also demonstrated that moderate- and high-risk patients benefited from ACT. Conclusion: The study nomogram can effectively evaluate postoperative prognosis of patients with EGC. Postoperative ACT is therefore recommended for moderate- and high-risk patients, but not for low-risk patients.

Project description:BackgroundPostoperative/adjuvant radiotherapy of advanced gastric cancer involves a large planning target volume (PTV) with multi-concave shapes which presents a challenge for volumetric modulated arc therapy (VMAT) planning. This study investigates the advantages of automated VMAT planning for this site compared to manual VMAT planning by expert planners.MethodsFor 20 gastric cancer patients in the postoperative/adjuvant setting, dual-arc VMAT plans were generated using fully automated multi-criterial treatment planning (autoVMAT), and compared to manually generated VMAT plans (manVMAT). Both automated and manual plans were created to deliver a median dose of 45 Gy to the PTV using identical planning and segmentation parameters. Plans were evaluated by two expert radiation oncologists for clinical acceptability. AutoVMAT and manVMAT plans were also compared based on dose-volume histogram (DVH) and predicted normal tissue complication probability (NTCP) analysis.ResultsBoth manVMAT and autoVMAT plans were considered clinically acceptable. Target coverage was similar (manVMAT: 96.6 ± 1.6%, autoVMAT: 97.4 ± 1.0%, p = 0.085). With autoVMAT, median kidney dose was reduced on average by > 25%; (for left kidney from 11.3 ± 2.1 Gy to 8.9 ± 3.5 Gy (p = 0.002); for right kidney from 9.2 ± 2.2 Gy to 6.1 ± 1.3 Gy (p < 0.001)). Median dose to the liver was lower as well (18.8 ± 2.3 Gy vs. 17.1 ± 3.6 Gy, p = 0.048). In addition, Dmax of the spinal cord was significantly reduced (38.3 ± 3.7 Gy vs. 31.6 ± 2.6 Gy, p < 0.001). Substantial improvements in dose conformity and integral dose were achieved with autoVMAT plans (4.2% and 9.1%, respectively; p < 0.001). Due to the better OAR sparing in the autoVMAT plans compared to manVMAT plans, the predicted NTCPs for the left and right kidney and the liver-PTV were significantly reduced by 11.3%, 12.8%, 7%, respectively (p ≤ 0.001). Delivery time and total number of monitor units were increased in autoVMAT plans (from 168 ± 19 s to 207 ± 26 s, p = 0.006) and (from 781 ± 168 MU to 1001 ± 134 MU, p = 0.003), respectively.ConclusionsFor postoperative/adjuvant radiotherapy of advanced gastric cancer, involving a complex target shape, automated VMAT planning is feasible and can substantially reduce the dose to the kidneys and the liver, without compromising the target dose delivery.

Dataset Information

An immunosuppressive scoring system to predict recurrence and assist in decision regarding postoperative adjuvant treatment in gastric cancer.

Publications

An immunosuppressive scoring system to predict recurrence and assist in decision regarding postoperative adjuvant treatment in gastric cancer.

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