Prognostic value of pre-therapeutic nutritional risk factors in elderly patients with locally advanced esophageal squamous cell carcinoma receiving definitive chemoradiotherapy or radiotherapy.

BACKGROUND: The nutritional status of cancer patients is a crucial factor in determining their prognosis. The objective of this study was to investigate and compare the prognostic value of pretreatment nutrition-related indicators in elderly esophageal squamous cell carcinoma (ESCC). Risk stratification was performed according to independent risk factors and a new nutritional prognostic index was constructed. METHODS: We retrospectively reviewed 460 older locally advanced ESCC patients receiving definitive chemoradiotherapy (dCRT) or radiotherapy (dRT). This study included five pre- therapeutic nutrition-related indicators. The optimal cut-off values for these indices were calculated from the Receiver Operating Curve (ROC). Univariate and multivariate COX analyses were employed to determine the association between each indicator and clinical outcomes. The predictive ability of each independently nutrition-related prognostic indicator was assessed using the time-dependent ROC (time-ROC) and C-index. RESULTS: Multivariate analyses indicated that the geriatric nutrition risk index (GNRI), body mass index (BMI), the controlling nutritional status (CONUT) score, and platelet-albumin ratio (PAR) could independently predict overall survival (OS) and progression-free survival (PFS) in elderly patients with ESCC (all p < 0.05), except for prognostic nutritional index (PNI). Based on four independently nutrition-related prognostic indicators, we developed pre-therapeutic nutritional prognostic score (PTNPS) and new nutritional prognostic index (NNPI). No-risk (PTNPS = 0-1 point), moderate-risk (PTNPS = 2 points), and high-risk (PTNPS = 3-4 points) groups had 5-year OS rates of 42.3%, 22.9%, and 8.8%, respectively (p < 0.001), and 5-year PFS rates of 44.4%, 26.5%, and 11.3%, respectively (p < 0.001). The Kaplan-Meier curves showed that the mortality of elderly ESCC patients in the high-risk group was higher than that in the low-risk group according to the NNPI. Analysis of time-AUC and C-index revealed that the NNPI (C-index: 0.663) had the greatest predictive power on the prognosis in older ESCC patients. CONCLUSIONS: In elderly ESCC patients, the GNRI, BMI, CONUT score, and PAR can be used as objective assessment measures for the risk of nutrition-related death. Compared to the other four indexes, the NNPI has the greatest prognostic value for prognosis, and elderly patients with a higher nutritional risk have a poor prognosis, which is helpful in guiding early clinical nutrition intervention.

Higher radiation dose on immune cells is associated with radiation-induced lymphopenia and worse prognosis in patients with locally advanced esophageal squamous cell carcinoma.

Background: To explore the effective dose to immune cells (EDIC) for better prognosis while avoiding radiation-induced lymphopenia (RIL) in patients with locally advanced esophageal squamous cell carcinoma (ESCC). Materials and methods: Overall, 381 patients with locally advanced ESCC receiving definitive radiotherapy with or without chemotherapy (dRT ± CT) between 2014 and 2020 were included in this study. The EDIC model was calculated by radiation fraction number and mean doses to the heart, lung, and integral body. The correlation between EDIC and clinical outcomes was analyzed using Cox proportional hazards regression, and risk factors for RIL were determined by logistic regression analysis. Results: The median EDIC was 4.38 Gy. Multivariate analysis revealed that low-EDIC significantly improved the OS of patients when compared with high-EDIC (HR = 1.614, P = 0.003) and PFS (HR = 1.401, P = 0.022). Moreover, high-EDIC was associated with a higher incidence of grade 4 RIL (OR = 2.053, P = 0.007) than low-EDIC. In addition, we identified body mass index (BMI), tumor thickness, and nodal stage as independent prognostic factors of OS and PFS, while BMI (OR = 0.576, P = 0.046) and weight loss (OR = 2.214, P = 0.005) as independent risk factors of grade 4 RIL. In subgroup analyses, the good group had better clinical outcomes than the remaining two groups (P< 0.001). Conclusion: This study demonstrated that EDIC significantly correlates with poor clinical outcomes and severe RIL. Optimizing treatment plans to decrease the radiation doses to immune cells is critical for improving the outcomes.

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.

Using inflammatory indexes and clinical parameters to predict radiation esophagitis in patients with small-cell lung cancer undergoing chemoradiotherapy.

Objective: Radiation esophagitis (RE) is a common adverse effect in small cell lung cancer (SCLC) patients undergoing thoracic radiotherapy. We aim to develop a novel nomogram to predict the acute severe RE (grade≥2) receiving chemoradiation in SCLC patients. Materials and methods: the risk factors were analyzed by logistic regression, and a nomogram was constructed based on multivariate analysis results. The clinical value of the model was evaluated using the area under the receiver operating curve (ROC) curve (AUC), calibration curves, and decision curve analysis (DCA). The correlations of inflammation indexes were assessed using Spearman correlation analysis. Results: Eighty-four of 187 patients (44.9%) developed grade ≥2 RE. Univariate analysis indicated that concurrent chemoradiotherapy (CCRT, p < 0.001), chemotherapy cycle (p = 0.097), system inflammation response index (SIRI, p = 0.048), prognostic-nutrition index (PNI, p = 0.073), platelets-lymphocyte radio (PLR, p = 0.026), platelets-albumin ratio (PAR, p = 0.029) were potential predictors of RE. In multivariate analysis, CCRT [p < 0.001; OR, 3.380; 95% CI, 1.767-6.465], SIRI (p = 0.047; OR, 0.436; 95% CI, 0.192-0.989), and PAR (p = 0.036; OR, 2.907; 95% CI, 1.071-7.891) were independent predictors of grade ≥2 RE. The AUC of nomogram was 0.702 (95% CI, 0.626-0.778), which was greater than each independent predictor (CCRT: 0.645; SIRI: 0.558; PAR: 0.559). Calibration curves showed high coherence between the predicted and actual observation RE, and DCA displayed satisfactory clinical utility. Conclusion: In this study, CCRT, SIRI, and PAR were independent predictors for RE (grade ≥2) in patients with SCLC receiving chemoradiotherapy. We developed and validated a predictive model through these factors. The developed nomogram with superior prediction ability can be used as a quantitative model to predict RE.

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.

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.

The novel pretreatment immune prognostic index discriminates survival outcomes in locally advanced non-operative esophageal squamous cell carcinoma patients treated with definitive chemoradiotherapy: a 6-year retrospective study.

OBJECTIVE: We aimed to construct risk stratification to help set individualized treatment strategies and intensities for different subgroups of patients. METHODS: The Esophagus Immune Prognostic Index (EIPI) scores were constructed according to the levels of derived neutrophil-to-lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH) before treatment, and the patients were divided into low-, medium-, and high-risk groups. Finally, restricted cubic splines (RCS) were used to explore the relationship between dNLR, LDH, and survival outcomes. RESULTS: The median follow-up period of overall survival (OS) and progression-free survival (PFS) were 25.2 and 17.6 months, respectively. Multivariate Cox regression analysis showed dNLR were the independent prognostic factors that were associated with OS and PFS. The 3-year OS and PFS rates in the low-, medium-, and high-risk groups were 44.4% and 38.2%, 26.1% and 23.6%, and 10.5% and 5.3%, respectively. Patients who received chemotherapy had better OS and PFS than those who did not receive chemotherapy in low-risk and medium/high-risk groups (all p < 0.05). Besides, the results also revealed significant differences for patients with clinical T, N, and TNM stage groups of the OS and PFS in different risk groups. Finally, RCS analysis indicated a nonlinear relationship between the dNLR, LDH, and survival for esophageal squamous cell carcinoma (ESCC) patients. The death hazard ratios of dNLR and LDH sharply increased at 1.97 and 191, respectively. CONCLUSIONS: In summary, the EIPI, a novel inflammatory-based and immune-related prognostic score, is an independent prognostic indicator in locally advanced ESCC patients undergoing definitive chemoradiotherapy (dCRT).

Preparation and Characterization of Octenyl Succinate ß-Cyclodextrin and Vitamin E Inclusion Complex and Its Application in Emulsion.

Vitamin E (VE) and ß-cyclodextrin (ß-CD) can form an inclusion complex; however, the inclusion rate is low because of the weak interaction between VE and ß-CD. The results of a molecular docking study showed that the oxygen atom in the five-membered ring of octenyl succinic anhydride (OSA) formed a strong hydrogen bond interaction (1.89 Å) with the hydrogen atom in the hydroxyl group of C-6. Therefore, ß-CD was modified using OSA to produce octenyl succinic-ß-cyclodextrin (OCD). The inclusion complexes were then prepared using OCD with VE. The properties of the inclusion complex were investigated by Fourier-transform infrared spectroscopy (FT-IR), 13C CP/MAS NMR, scanning electron microscopy (SEM), and atomic force microscopy (AFM). The results demonstrated that VE had been embedded into the cavity of OCD. Furthermore, the emulsifying properties (particle size distribution, ζ-potential, and creaming index) of the OCD/VE inclusion-complex-stabilized emulsion were compared with that stabilized by ß-CD, OCD, and an OCD/VE physical mixture. The results showed that the introduction of the OS group and VE could improve the physical stability of the emulsion. In addition, the OCD/VE inclusion complex showed the strongest ability to protect the oil in the emulsion from oxidation. OCD/VE inclusion complex was able to improve the physical and oxidative stability of the emulsion, which is of great significance to the food industry.