Clinical outcomes and toxicities of locally advanced esophageal squamous cell carcinoma patients treated with early thoracic radiation therapy after induction chemotherapy.

OBJECTIVE: The purpose of this study was to compare the clinical outcomes and toxicities between induction chemotherapy (IC) + chemo-radiotherapy (CRT) and CRT alone in patients with locally advanced esophageal squamous cell carcinoma (ESCC), to explore the appropriate thoracic radiotherapy (TRT) timing after IC and to identify prognostic factors. METHODS: 450 ESCC patients were included from September 2011 to December 2020, 238 of whom received IC/CRT. Propensity score matching was performed to balance potential confounders between the two groups. Multivariate Cox regression analysis was used to identify the independent prognostic factors. RESULTS: Patients who received IC/CRT experienced improved overall survival (OS) (38.5 vs. 28.8 months) and progression-free survival (PFS) (41.0 vs. 22.0 months) before matching, with similar results after matching. In the IC/CRT group, early TRT had more favorable survival than late TRT both matching before and after. In subgroup analysis, early TRT combination concurrent chemotherapy had better OS and PFS than late TRT combination concurrent chemotherapy. In addition, early TRT had better survival benefits regardless of the N stage. Notably, the IC/CRT group and early TRT group had manageable toxicities reaction compared with CRT alone group and the late TRT group. The nomogram was developed to predict the OS and PFS based on multivariate analysis results. The C-index was 0.743 and 0.722, respectively. CONCLUSION: IC/CRT and early TRT could yield satisfactory clinical outcomes and controllable toxicities in locally advanced ESCC. The IC plus early concurrent CRT might be a promising treatment strategy for improving further survival in ESCC.

A Nutrition-Related Factor-Based Risk Stratification for Exploring the Clinical Benefits in the Treatment of Patients With Locally Advanced Esophageal Squamous Cell Carcinoma Receiving Definitive Chemoradiotherapy: A Retrospective Cohort Study.

Objective: No study has reported the risk stratification of BMI and PNI in patients with locally advanced esophageal squamous cell carcinoma (ESCC) undergoing definitive chemoradiotherapy (dCRT). This study aimed to construct a risk stratification to guide the treatment of ESCC following dCRT. Methods: A total of 1,068 patients with locally advanced ESCC who received dCRT were retrospectively analyzed. The impacts of clinicopathological factors on overall survival (OS) and progression-free survival (PFS) were analyzed. Besides, the novel prognostic indices of pre-therapeutic nutritional index (PTNI) and prognostic index (PI) were developed. Results: The median follow-up period of OS and PFS were 22.9 and 17.4 months, respectively. The high body mass index (BMI) group had better 5-year OS and PFS (36.4 and 34.0%) than the low BMI group (18.8 and 17.2%). The high prognostic nutritional index (PNI) group also had better 5-year OS and PFS (33.4 and 30.9%) than the low PNI group (17.5 and 17.2%). Multivariate Cox regression analysis showed that BMI and PNI were independent prognostic factors for OS and PFS. Based on nutritional indices, patients were categorized into the low-risk (PTNI = 1), medium-risk (PTNI = 2), and high-risk (PTNI = 3) groups with 5-year OS rates of 38.5, 18.9, 17.5%, respectively (p < 0.001) and 5-year PFS rates of 35.8, 17.6, 16.8%, respectively (p < 0.001). Besides, we also constructed a prognostic index (PI) for OS and PFS which was calculated based on statistically significant factors for predicting OS and PFS. The results revealed that the high-risk group had worse OS and PFS than the low-risk group (p < 0.001). Finally, RCS analysis demonstrated a non-linear relationship between the PNI, BMI, and survival for patients with ESCC. The death hazard of PNI and BMI sharply decreased to 41.8 and 19.7. Conclusion: The decreased pre-therapeutic BMI and PNI levels were associated with a worse survival outcome. BMI and PNI are readily available and can be used to stratify risk factors for locally advanced ESCC patients undergoing dCRT. The novel risk stratification may help to evaluate patients' pre-therapeutic status and guide dCRT for locally advanced ESCC patients.

Cost-Effectiveness of Nivolumab Immunotherapy vs. Paclitaxel or Docetaxel Chemotherapy as Second-Line Therapy in Advanced Esophageal Squamous Cell Carcinoma in China.

This study aimed to evaluate and compare nivolumab's cost-effectiveness with chemotherapy in patients with advanced esophageal squamous cell carcinoma from the Chinese healthcare system perspective. To this end, the researchers utilized a partitioned survival model with three mutually exclusive health stages. The characteristics of the patients used as inclusion and exclusion criteria in this model were the same as those used for patients with advanced esophageal squamous cell carcinoma in the ATTRACTION-3 study. The ATTRACTION-3 trial, which took place between January 7, 2016 and November 12, 2018, also yielded important clinical data. Data on medical and economic preferences were collected from real-world clinical practices. Costs, quality-adjusted life years, and incremental cost-effectiveness ratio were calculated for the two therapy options. The model uncertainty was investigated using a deterministic and probabilistic sensitivity analysis. When compared to chemotherapy, nivolumab was linked with an increase of 0.28 quality-adjusted life years with an increased cost of US$ 36,956.81 per patient in the base case analysis of a hypothetical sample of 419 patients. The incremental cost-effectiveness ratio in the deterministic sensitivity analysis was US$ 132,029.46/quality-adjusted life year, with a 48.02% probability of being cost-effective at willingness-to-pay thresholds of US$ 132,029.22/quality-adjusted life year. The incremental cost-effectiveness ratio remained greater than US$ 80,000/quality-adjusted life year in the deterministic sensitivity analyses. To be more cost-effective and remain below the threshold of 37,653 US$/quality-adjusted life year, which the Chinese population can afford, nivolumab's price would have to be lowered sharply by 53.50%. Nivolumab is clinically beneficial but not cost-effective when compared to chemotherapy. A substantial reduction in nivolumab's drug acquisition cost would be necessary to make it cost-effective for immunotherapy.

A New Nomogram and Risk Stratification of Brain Metastasis by Clinical and Inflammatory Parameters in Stage III Small Cell Lung Cancer Without Prophylactic Cranial Irradiation.

Background: This study was conducted to determine risk factors for developing brain metastasis (BM) and to predict brain metastasis free survival (BMFS) and overall survival (OS) by combining several clinical parameters and inflammatory indexes. Materials and Methods: A nomogram and risk stratification were developed based on multivariate analysis results. The prognostic index (PI) predicting the high risk of BM was calculated by multiplying the weighted factor (ß coefficient) with each variable. Results: Thirty-two of one hundred patients (32.0%) developed BM. Multivariate cox regression analysis revealed that concurrent chemoradiotherapy (CCRT; hazard ratio (HR), 3.356; p = 0.020), monocyte-lymphocyte ratio (MLR; HR, 4.511; p = 0.002), neutrophil-lymphocyte ratio (NLR; HR, 4.023; p = 0.033), and prognostic-nutrition index (PNI; HR, 2.902; p = 0.018) were independent prognostic factors of BMFS. The nomogram has good accuracy in predicting BMFS, and the C-index was 0.73. The ROC curve showed that these risk factors have good discriminant ability. Similarly, tumor location (HR, 1.675; p = 0.035) and MLR (HR, 2.076; p = 0.013) were independent prognostic factors of OS. In the subgroup analysis of OS, the good group had a better prognosis than the other groups. Risk stratification by PI: the high-risk group had worse BMFS than the low-risk group, which also has certain practical significance for clinical practice in OS. Conclusion: We developed a nomogram and corresponding risk stratification in stage III SCLC patients who developed BM. This model and risk stratification can help clinicians improve patient treatment management and better deliver personalized therapy.

A Novel Model Combining Tumor Length, Tumor Thickness, TNM_Stage, Nutritional Index, and Inflammatory Index Might Be Superior to the 8th TNM Staging Criteria in Predicting the Prognosis of Esophageal Squamous Cell Carcinoma Patients Treated With Definitive Chemoradiotherapy.

Background: We aimed to determine whether the tumor length and tumor thickness should be used as prognostic factors for esophageal squamous cell carcinoma (ESCC) patients treated with definitive chemoradiotherapy (dCRT). Methods: A retrospective analysis consists of 902 non-operative ESCC patients received dCRT. The nomogram was used to predict the survival. Besides, Restricted Cubic Splines (RCS) was used to examine the relationship between prognostic factors and survival outcomes. Finally, the prognostic index (PI) scores were constructed according to the tumor length and tumor thickness, and the patients were divided into the low-, medium-, and high-risk groups. Results: The median follow-up of overall survival (OS) and progression-free survival (PFS) were 23.0 months and 17.5 months. Multivariate Cox regression analysis showed that tumor length and tumor thickness were independent prognostic factors associated with survival. Our novel nomograms for OS and PFS were superior to the TNM classification (p < 0.001). Besides, RCS analysis demonstrated that the death hazard of tumor length and tumor thickness sharply increased at 7.7 cm and 1.6 cm (p < 0.001). Finally, there were significant differences for ESCC patients with clinical TNM stage group of the OS and PFS in different risk groups. The higher risk group was significantly associated with shorter OS and PFS in ESCC patients (both p < 0.001 for all). Conclusion: The study results suggest that the novel models integrating tumor length and tumor thickness may provide a simple and widely available method for evaluating the prognosis of non-operative ESCC patients. The tumor length and tumor thickness should be considered as prognostic factors for ESCC.

Prognostic significance of platelet-to-albumin ratio in patients with esophageal squamous cell carcinoma receiving definitive radiotherapy.

Accumulating evidence indicates that inflammation and nutrition status are associated with clinical outcomes in patients with various malignancies. This study aimed to evaluate the prognostic significance of the pretreatment platelet to albumin ratio (PAR) in esophageal squamous cell carcinoma (ESCC) patients undergoing definitive radiotherapy. A total of 470 patients who underwent definitive radiotherapy with or without chemotherapy were enrolled. The optimal cut-off values of PAR and other indicators were determined by the X-tile. The Kaplan-Meier method, multivariate analyses Cox regression were conducted to identify the association between those indicators and the survival outcomes. The median follow-up time was 23.5 months. The optimal cut-off value of PAR was 5.7 × 109 and patients were stratified as the low PAR group and the high PAR group. In the univariate analysis, a low overall survival rate was significantly associated with T stage (P = 0.005), TNM stage (P < 0.001), Adjuvant chemotherapy (P = 0.007), neutrophil to lymphocyte ratio (NLR) (P = 0.006), platelet to lymphocyte ratio (P < 0.001), systemic immune-inflammation index (P < 0.001), prognostic nutritional index (P < 0.001) and platelet to albumin ratio (PAR) (P < 0.001). Patients with high PAR were associated with poorer OS and PFS than patients with low PAR. On multivariate analysis, TNM stage (P = 0.001), adjuvant chemotherapy (P < 0.001), and PAR (P = 0.033) were independent prognostic factors in ESCC treated with definitive radiotherapy. PAR is a novel, convenient, and inexpensive prognostic indicator for patients with ESCC undergoing definitive radiotherapy. Future validation from prospective larger-scale studies is warranted.

Factors associated with immunotherapy respond and survival in advanced non-small cell lung cancer patients.

OBJECTIVES: This study aimed to explore factors associated with immunotherapy respond and survival in advanced non-small cell lung cancer (aNSCLC) patients treated with immune checkpoint inhibitors (ICIs). METHODS: A total of 101 patients with aNSCLC receiving ICIs were included. The association between clinical factors and multiple endpoints including objective response rate (ORR), disease control rate (DCR), overall survival (OS) and progression-free survival (PFS) were investigated by multivariate analyses. RESULTS: Multivariate logistic analyses revealed that clinical stage, lactate dehydrogena (LDH), and any grade immune-related adverse events (irAEs) were independent predictors of ORR, while LDH and ICIs treatment type were independent predictors of DCR. In Multivariate Cox analysis, Eastern Cooperative Oncology Group performance status (ECOG PS), LDH, albumin (Alb), platelet to lymphocyte ratio (PLR), and any grade irAEs were independent factors for OS. Similarly, clinical stage, LDH, Alb, and any grade irAEs were independent factors for PFS. Pre-treatment prognostic score was established based on clinical stage, ECOG PS, LDH, Alb and PLR to classify patients into three groups: the good group (0-1 score), the intermediate group (2 scores) and the poor group (3-4 scores). The immunotherapy response was significantly different in various prognostic groups. Subset analyses showed pre-treatment prognostic score ≥ 3 tended to have a strong negative impact on survival among patients with programmed cell death-ligand 1 (PD-L1) expression ≥ 50%. CONCLUSIONS: Pre-treatment prognostic score based on clinical stage, ECOG PS, LDH, Alb and PLR may help to identify aNSCLC patients who may benefit from ICIs.

Prognostic value of SEC61G in lung adenocarcinoma: a comprehensive study based on bioinformatics and in vitro validation.

BACKGROUND: Studies have shown that the Sec61 gamma subunit (SEC61G) is overexpressed in several tumors and could serve as a potential prognostic marker. However, the correlation between SEC61G and lung adenocarcinoma (LUAD) remains unclear. In the current study, we aimed to demonstrate the prognostic value and potential biological function of the SEC61G gene in LUAD. METHODS: Public datasets were used for SEC61G expression analyses. The prognostic value of SEC61G in LUAD was investigated using the Kaplan-Meier survival and Cox analyses. The correlation between the methylation level of SEC61G and its mRNA expression was evaluated via cBioPortal. Additionally, MethSurv was used to determine the prognostic value of the SEC61G methylation levels in LUAD. Functional enrichment analysis was conducted to explore the potential mechanism of SEC61G. Also, single sample GSEA (ssGSEA) and TIMER online tool were applied to identify the correlation between SEC61G and immune filtration. Furthermore, cell functional experiments were conducted to verify the biological behavior of SEC61G in lung adenocarcinoma cells (LAC). RESULTS: SEC61G was upregulated in pan-cancers, including LUAD. High SEC61G expression was significantly correlated with worse prognosis in LUAD patients. Multivariate analysis demonstrated that high SEC61G expression was an independent prognostic factor in the TCGA cohort. (HR = 1.760 95% CI: 1.297-2.388, p < 0.001). The methylation level of SEC61G negatively correlated with the SEC61G expression (R = - 0.290, p < 0.001), and patients with low SEC61G methylation had worse overall survival. (p = 0.0014). Proliferation-associated terms such as cell cycle and cell division were significantly enriched in GO and KEGG analysis. Vitro experiments demonstrated that knockdown of SEC61G resulted in decreased cell proliferation, invasion and facilitated apoptosis in LAC. GSEA analysis found that SEC61G expression was associated with the E2F targets. Moreover, SEC61G expression was negatively correlated with the immune cell infiltration including CD4+ T cell, CD8+ T cell, B cell, macrophage, neutrophil, and dendritic cell. CONCLUSION: Our study indicated that overexpression of SEC61G was significantly associated with poor prognosis of LUAD patients and the malignant phenotypes of LUAD cells, suggesting that it could be a novel prognostic biomarker and potential therapeutic target of LUAD.

Cost-Effectiveness Analysis of Camrelizumab Immunotherapy versus Docetaxel or Irinotecan Chemotherapy as Second-Line Therapy for Advanced or Metastatic Esophageal Squamous Cell Carcinoma.

PURPOSE: The aim of this study was to assess the cost-effectiveness of camrelizumab immunotherapy versus docetaxel or irinotecan chemotherapy as second-line therapy for advanced esophageal squamous cell carcinoma (ESCC), which was evaluated in the ESCORT trial. MATERIALS AND METHODS: A partitioned survival model was developed to reflect the costs and effectiveness of the ESCORT trial. The clinical efficacy data, safety data, and health-related costs and utilities were derived from published data from clinical trials or health administration departments in China. Adverse event-related costs, drug administration, and other expenses were derived from a single center of Fujian Medical University Cancer Hospital in 2021. All survival analyses were performed with SPSS software. Overall survival was estimated with the Kaplan-Meier method, and progression-free survival was estimated with the life table method. Sensitivity analyses were conducted to assess the uncertainty of the model. Incremental cost, quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER) were calculated. RESULTS: Camrelizumab therapy had 0.232 QALYs at an incremental cost of USD$9959.44 compared with the chemotherapy group with 0.158 QALYs at an incremental cost of USD$8601.67. The ICER was USD$18393.12/QALY. Probabilistic sensitivity analyses showed that when the willingness-to-pay threshold reached USD$31200/QALY, which is nearly three times the Chinese gross domestic product per capita, camrelizumab had an 80% possibility of being cost-effective versus docetaxel or irinotecan chemotherapy. CONCLUSION: Camrelizumab is a cost-effective option compared with docetaxel or irinotecan chemotherapy in patients with advanced ESCC as second-line therapy in China.

Benefit of chemotherapy based on platinum with definitive radiotherapy in older patients with locally advanced esophageal squamous cell carcinoma.

OBJECTIVE: There is still no definitely therapeutic evidence of a beneficial effect of chemotherapy with radiotherapy for older patients with esophageal squamous cell carcinoma (ESCC). We aim to determine the influence of chemoradiotherapy (CRT) and radiotherapy (RT) alone in patients aged 65 years or older with locally advanced ESCC. METHODS: We retrospectively analyzed 581 ESCC patients who underwent CRT and RT alone. Univariate and multivariate Cox regression analysis was used to analyze the impact of clinical factors on long-term overall survival (OS) and progression-free survival (PFS). Finally, we compared the toxicity rates of these patients. RESULTS: The median OS and PFS of the overall population were 23.2 months (2.0-162.6 months) and 18.6 months (1.1-159.6 months). Multivariate Cox regression analysis showed that chemotherapy (p < 0.05), tumor thickness (p < 0.01), and N stage (p < 0.05) were independent prognostic factors associated with both OS and PFS. In the chemotherapy subgroup, patients who received 2-8 cycles of chemotherapy had better OS than those who received 1 cycle (p = 0.015). The results also revealed that the CRT group has better OS and PFS than RT alone group for patients aged 65-74 years (both p < 0.01). However, for patients aged 75 years or older, there was no statistically significant difference between CRT and RT alone (both p > 0.05). Besides, higher staged ESCC has the inferior OS and PFS than lower staged ESCC for patients received RT alone and aged 65-74 years (both p < 0.05). Finally, there were significantly more severe hematologic toxicities in the CRT group than in those treated with RT alone in this study (p < 0.001). CONCLUSIONS: The present study suggested that CRT for locally advanced ESCC in patients aged 65 years or older had a significant benefit over RT alone in terms of OS and PFS. However, for patients aged 75 years or older, there was no statistically significant difference between CRT and RT alone. CRT should be performed with special attention in patients aged 75 years or older.