Prognostic value of sarcopenia in patients with lung cancer treated with epidermal growth factor receptor tyrosine kinase inhibitors or immune checkpoint inhibitors.

Objectives: It remains controversial whether sarcopenia has any significant impact on the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) or immune checkpoint inhibitors (ICIs) in patients with advanced non-small cell lung cancer (NSCLC). Therefore, in this study, we aimed to assess the association between sarcopenia and clinical outcomes in patients with advanced NSCLC receiving EGFR-TKIs or ICIs as a first-line therapy. Methods: We retrospectively enrolled 131 patients with advanced NSCLC treated with first-line EGFR-TKIs or ICIs between 1 March 2019 and 31 March 2021. To estimate sarcopenia, we calculated skeletal muscle index (SMI) as the ratio of skeletal muscle area (cm2) to height squared (m2). Associations between sarcopenia and overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method and log-rank tests, respectively. A Cox proportional hazards regression model was used to assess the factors associated with OS and PFS. The Student's t-test or Mann-Whitney U test was used to compare the SMI between patients with or without objective response and disease control. The chi-squared test was used to compare adverse events (AEs) between patients with and without sarcopenia. Results: Among the 131 patients, 35 (26.7%) were diagnosed with sarcopenia. Sarcopenia was an independent predictor of poor OS and PFS (p < 0.05) overall and in the EGFR-TKI- and ICI-treated cohorts. Among all patients, those with sarcopenia showed significantly shorter OS and PFS than those without sarcopenia (median OS and PFS: 13.0 vs. 26.0 months and 6.4 vs. 15.1 months; both p < 0.001). These associations were consistent across the subtypes of most clinical characteristics. Statistically significant differences between the objective response (OR) and non-OR groups were also observed in the mean SMI (OR group, 43.89 ± 7.55 vs. non-OR group, 38.84 ± 7.11 cm2/m2; p < 0.001). In addition, we observed similar results with disease control (DC) and non-DC groups (DC group, 42.46 ± 7.64 vs. non-DCR group, 33.74 ± 4.31 cm2/m2; p < 0.001). The AEs did not differ significantly between the sarcopenia and non-sarcopenia groups. Conclusion: Sarcopenia before treatment might be a significant predictor of poor clinical outcomes (shorter OS and PFS, fewer ORs, less DC) in patients with advanced NSCLC treated with EGFR-TKIs or ICIs as the first-line therapy.

Ginsenoside Rg5 enhances the radiosensitivity of lung adenocarcinoma via reducing HSP90-CDC37 interaction and promoting client protein degradation.

Ginsenoside Rg5 is a rare ginsenoside showing promising tumor-suppressive effects. This study aimed to explore its radio-sensitizing effects and the underlying mechanisms. Human lung adenocarcinoma cell lines A549 and Calu-3 were used for in vitro and in vivo analysis. Bioinformatic molecular docking prediction and following validation by surface plasmon resonance (SPR) technology, cellular thermal shift assay (CETSA), and isothermal titration calorimetry (ITC) were conducted to explore the binding between ginsenoside Rg5 and 90 kD heat shock protein alpha (HSP90α). The effects of ginsenoside Rg5 on HSP90-cell division cycle 37 (CDC37) interaction, the client protein stability, and the downstream regulations were further explored. Results showed that ginsenoside Rg5 could induce cell-cycle arrest at the G1 phase and enhance irradiation-induced cell apoptosis. It could bind to HSP90α with a high affinity, but the affinity was drastically decreased by HSP90α Y61A mutation. Co-immunoprecipitation (Co-IP) and ITC assays confirmed that ginsenoside Rg5 disrupts the HSP90-CDC37 interaction in a dose-dependent manner. It reduced irradiation-induced upregulation of the HSP90-CDC37 client proteins, including SRC, CDK4, RAF1, and ULK1 in A549 cell-derived xenograft (CDX) tumors. Ginsenoside Rg5 or MRT67307 (an IKKε/TBK1 inhibitor) pretreatment suppressed irradiation-induced elevation of the LC3-II/ß ratio and restored irradiation-induced downregulation of p62 expression. In A549 CDX tumors, ginsenoside Rg5 treatment suppressed LC3 expression and enhanced irradiation-induced DNA damage. In conclusion, ginsenoside Rg5 may be a potential radiosensitizer for lung adenocarcinoma. It interacts with HSP90α and reduces the binding between HSP90 and CDC37, thereby increasing the ubiquitin-mediated proteasomal degradation of the HSP90-CDC37 client proteins.

Post-treatment serum triglyceride: An effective biomarker for body fat mass and overall survival in esophageal squamous cell cancer patients treated with chemoradiotherapy.

Objectives: Although lipids have been assessed for their possible roles in cancer survival prediction, studies on the association between serum triglyceride (TG) levels and the prognosis of esophageal squamous cell carcinoma (ESCC) patients are limited. This study aimed to evaluate whether serum TG is associated with outcomes in patients with ESCC and investigate any interaction between serum TG and clinical parameters, especially body fat mass. Materials and methods: We conducted a prospective case study on patients diagnosed with ESCC between March 2012 and November 2018. We measured patients' serum TG levels before and after treatment. The association between serum TG and overall survival (OS) was evaluated using hazard ratios. We sought to determine a threshold point using optimal stratification. Survival analysis was performed using Kaplan-Meier curves and a Cox proportional hazards model. Results: Of the 257 participants diagnosed with ESCC, 200 (77.8%) were men. Median follow-up time was 22.4 months (range 3.3-92.4 months). Using univariate Cox proportional hazard analysis and subsequent multivariate analysis, post-TG levels, Karnofsky performance scores, T stages, and chemotherapy cycles were shown to be independent prognostic factors for OS (p < 0.05). The post-TG cut-off point to best classify patients with respect to time to mortality was 1.47 mmol/L. A post-TG level of ≥ 1.47 mmol/L could independently predict a better OS (hazard ratio: 0.55, 95% confidence interval: 0.37-0.79). The associations were consistent across the subtypes of clinical parameters. Furthermore, the post-body mass index, post-subcutaneous adipose tissue area, post-visceral adipose tissue area, post-total adiposity tissue area, and post-total adipose density exhibited a strong positive association with post-TG levels. Conclusion: Post-TG levels were found to be a significant positive prognostic biomarker for body fat mass and OS in ESCC patients.

The development of a nomogram and the prognostic prediction value of patients with esophageal squamous cell carcinoma undergoing radical radiotherapy.

AIM: This study aimed to explore the role of the developed nomogram in the prognosis of esophageal squamous cell carcinoma (ESCC). METHODS: A total of 181 ESCC patients were randomly divided into a training cohort (n = 141) and a validation cohort (n = 40). Significant factors impacting overall survival (OS) were identified in the training set and integrated into the nomogram based on Cox proportional hazards regression. RESULTS: In the training cohort, the median OS in the high group (≥222) was 49.9 months and the median OS in the low group (<222) was 14.4 months. Multivariate analysis revealed that age, Karnofsky performance status score, tumor stage, chemotherapy, BMI, cervical esophageal carcinoma index and neutrophil to lymphocyte ratio were predictors of OS. CONCLUSION: The developed nomogram can effectively predict the survival prognosis of ESCC patients.

Effects of Enteral Nutrition on Patients With Oesophageal Carcinoma Treated With Concurrent Chemoradiotherapy: A Prospective, Multicentre, Randomised, Controlled Study.

Background: The oesophageal carcinoma patients show high incidence of malnutrition, which negatively affects their therapy outcome. Moreover, benefits of enteral nutrition remain to be studied in details in these patients. Therefore, we set to assess the effects of enteral nutrition on the nutritional status, treatment toxicities and survival in the oesophageal carcinoma patients treated with concurrent chemoradiotherapy (CCRT). Materials and Methods: Eligible patients were randomly assigned to either the experimental or control group. The patients in the experimental group were treated with a whole-course enteral nutrition management, while the control group were provided a unsystematic nutrition without setting intake goals for energy and protein. The primary endpoint was a change in body weight, while the secondary endpoints included nutrition-related haematological indicators, toxicities, completion rate of treatment and survival. Results: A total of 222 patients were randomised to either the experimental (n=148) or control (n=74) group. Patients in the experimental group showed significantly less decrease in body weight, serum albumin and haemoglobin levels, a lower incidence rates of grade ≥3 myelosuppression and infection, and a higher completion rate of CCRT than those in the control group. While analyses of the 2 and 3 year overall survival (OS) and progression-free survival (PFS) did not reveal differences between these groups, we observed a significantly higher OS at 1 year (83.6% vs. 70.0%). In the subgroup analysis, patients with patient-generated subjective global assessment (PG-SGA)=C were likely to have better OS and PFS with enteral nutrition. Conclusions: In EC patients treated with CCRT, enteral nutrition conferred positive effects on the nutritional status, treatment toxicities and prognosis, which mandate its inclusion in clinical practice. Clinical Trial Registration: This prospective trial has been registered with www.clinicaltrials.gov as NCT02399306.

Efficacy and Drug Resistance Analysis of ALK Inhibitors in Combination with Stereotactic Body Radiation Therapy for Treating Lung Squamous Carcinoma Patient Harboring EML4-ALK Rearrangement.

EML4-ALK rearrangement is common in lung adenocarcinoma. The ALK inhibitors remarkably inhibit lung adenocarcinoma and reveal long-term beneficial effects in several patients. Advanced genetic testing technology reveals that EML4-ALK rearrangement has been observed in patients with lung squamous cell carcinoma. In the present study, we report a case of a 53-year-old patient with EML4-ALK rearranged in lung squamous carcinoma; PET/CT scan revealed brain and multiple bone metastases. First-line ALK-TKI combined with local stereotactic body radiation therapy indicated progression-free survival of 9 months. After progressive disease, treatment was switched to lorlatinib, with little efficacy and a total overall survival of 11 months. The emergence of drug resistance revealed that the genetic test result was EML4-ALK fusion (V3a/b variants), indicating a poor prognosis. In this study, we analyzed the treatment efficacy of ALK inhibitors and provided a research basis for the treatment of EML4-ALK rearranged in lung squamous cell carcinoma patients.

Clinical utility of the systemic immune-inflammation index for predicting survival in esophageal squamous cell carcinoma after radical radiotherapy.

Aim: To explore the clinical utility of the systemic immune-inflammation index (SII) for predicting the prognosis of esophageal squamous cell carcinoma (ESCC). Patients & methods: After calculating the SII in 180 patients with ESCC, the relationship between SII values and the pre-/post-radiotherapy SII ratio and overall survival was determined. Results: The median overall survival was 649 days for the entire group and 909 and 466 days for the high and low pre-/post-radiotherapy SII ratio groups, respectively. Multivariate analysis identified Karnofsky performance status (p = 0.045), lymphatic metastasis (p = 0.032), mid-radiotherapy SII (p < 0.001) and pre-/post-radiotherapy SII ratio (p = 0.003) as independent prognostic factors. Conclusion: The pre-/post-radiotherapy SII ratio and mid-radiotherapy SII are potentially effective markers for predicting ESCC prognosis.

Lay abstract The systemic immune-inflammation index (SII) is calculated from the counts of peripheral blood platelets (P), neutrophils (N) and lymphocytes (L) per liter according to the formula SII = P × N/L. The SII is associated with poor survival in certain cancer types. However, some reports have examined the prognostic value of the SII in patients with esophageal squamous cell carcinoma (ESCC) who were undergoing radiotherapy or radical chemoradiotherapy. As such, the current study sought to investigate the clinical prognostic value of the SII during radiotherapy and the ratio of the SII before and after radiotherapy in patients with ESCC who were undergoing chemoradiotherapy or radiotherapy. The study found that the pre-/post-radiotherapy SII ratio and mid-radiotherapy SII are potentially effective markers for predicting ESCC prognosis.

Clinical Application Value of the Prognostic Nutritional Index for Predicting Survival in Patients with Esophageal Squamous Cell Carcinoma Undergoing Chemoradiotherapy or Radiotherapy.

BACKGROUND: The prognostic nutrition index (PNI) has been shown to have prognostic value for several common cancers. The study aim was to explore the clinical application value of the PNI for prognosis of patients with esophageal squamous cell carcinoma (ESCC) treated with radical chemoradiotherapy (CRT) or radiotherapy (RT). METHODS: Overall, 193 patients with ESCC who received radiotherapy with or without chemotherapy at Sichuan Cancer Hospital from March 20, 2012 to December 25, 2017 were retrospectively analyzed. Based on serum measurements before treatment, the PNI at ESCC recurrence was calculated as albumin (g/L) + 5 × total lymphocyte count. The Kaplan-Meier method and Cox proportional regression model were used to analyze the relationship between PNI and overall survival (OS). RESULTS: The average PNI of 193 ESCC patients was 49.01 ± 4.68. The optimal cutoff value of PNI was 47.975, and the patients were divided into a low-PNI group (<47.975) and a high-PNI group (≥47.975). PNI was related to tumor length, T-stage and synchronous chemotherapy in ESCC patients (P < 0.05). The median OS for the entire group was 22.37 mo,. The median OS of patients in the high-PNI group and low-PNI group were 32.63 mo, and 15.4 mo, respectively, the 3-year survival rates were 47.5% and 32.2% and the 5-year survival rates were 37.7% and 16.8%, respectively, (all P = 0.001). Univariate analysis showed that PNI, tumor length, T-stage and synchronous chemotherapy were related to the prognosis of ESCC patients (P < 0.05). Multivariate analysis showed that tumor length (P = 0.019), synchronous chemotherapy (P = 0.009) and PNI (P = 0.003) were independent prognostic factors affecting the prognosis of patients in ESCC treated with RT or CRT. CONCLUSIONS: The calculation of PNI value is simple, reliable and repeatable and can improve the accuracy of a patient's prognosis. Confirmation of these results by a large-sample prospective study is desirable.

Comparison between the effects of elective nodal irradiation and involved-field irradiation on long-term survival in thoracic esophageal squamous cell carcinoma patients: A prospective, multicenter, randomized, controlled study in China.

BACKGROUND: This study's initial results revealed significant decreases in treatment-related esophagitis and pneumonitis cases in patients with thoracic esophageal squamous cell carcinoma (ESCC) treated with involved-field irradiation (IFI), compared to elective nodal irradiation (ENI). This report outlines the long-term trial results, specifically; overall survival (OS), progression-free survival (PFS), metastasis-free survival (MFS), and locoregional progression-free survival (LRFS). MATERIALS AND METHODS: Stage II-III thoracic ESCC patients were assigned randomly, in a 1:1 ratio, into either the ENI or IFI arm. Radiation therapy was delivered once a day in 1.8-2.0 Gy fractions to a total dose of 60.0-66.0 Gy to the gross tumor volume and 50.0-54.0 Gy to the clinical target volume. The primary endpoints were acute treatment-related esophagitis and pneumonitis. The results for the primary endpoints were previously published in 2018. In this article, we analyzed the secondary endpoints including PFS, LRFS, MFS, and OS. RESULTS: Between April 2012 and October 2016, 228 patients from nine participating centers in China were enrolled into this study and randomly assigned to two treatment groups. For ENI and IFI groups, respectively, the results showed similarity and were as follows: median PFS (20.3 months vs 21.4 months), OS (32.5 months vs 34.9 months), MFS (28.2 months vs 26.0 months), and LRFS (25.0 months vs 26.6 months). In particular, respective OS rates in the ENI and IFI groups were 84.6% and 82.5% after 1 year, 45.1% and 48.7% after 3 years, and 29.8% and 30.7% at 5 years. PFS rates after 1, 3, and 5 years were 58.9%, 34.2%, and 26.9%, respectively, in the ENI arm compared to 64.4%, 30.8%, and 27.7%, respectively, in the IFI arm. Multivariate analysis identified clinical stage and tumor responses as independent predictors of OS. Meanwhile, tumor location, cStage, and tumor response were identified as independent factors influencing PFS. CONCLUSION: IFI was associated with similar survival as ENI in patients with thoracic ESCC, suggesting that IFI is an acceptable treatment method for thoracic ESCC.

Comparison  of  efficacy, safety, and costs between neoadjuvant hypofractionated radiotherapy and conventionally fractionated radiotherapy for esophageal carcinoma.

BACKGROUND: We compared the efficacy, safety, and costs of hypofractionated radiotherapy (HFRT) and conventional fractionated radiotherapy (CFRT) for the neoadjuvant treatment of esophageal cancer. MATERIALS AND METHODS: Overall, 110 patients with esophageal cancer treated with neoadjuvant chemoradiotherapy from October 2002 to July 2017 were retrospectively included and divided into a HFRT group (42 patients received 30 Gray [Gy]/10 fractions for 2 weeks) and a CFRT group [68 patients received 40 Gy/20 fractions for 4 weeks]. Concurrent chemotherapy comprised cisplatin combined with either 5-FU or taxane. Surgery was performed 3-8 weeks after radiotherapy. We compared the outcomes, adverse events, and costs between the two groups. RESULTS: Pathological downstaging was achieved in 78.6% of the HFRT group and 83.8% of the CFRT group (P = 0.612). Compared with the CFRT group, the HFRT group had similar pathological complete response (pCR) (33.3% vs 35.3%; P = 0.834), median overall survival (OS) (40.8 months vs 44.9 months; P = 0.772) and progression free survival (32.7 months vs 35.4 months; P = 0.785). The perioperative complication rates were also similar between the groups, but the treatment time and costs were significantly reduced in the HFRT group (P < 0.05). Finally, multivariate analysis identified cN0 stage, pathological downstaging and pCR as independent predictors of better OS. CONCLUSION: Preoperative HFRT is effective and safe for esophageal cancer. Moreover, it is similar to CFRT in terms of overall survival and toxicity and is cost effective and less time consuming.

Enteral nutrition in esophageal cancer patients treated with radiotherapy: a Chinese expert consensus 2018.

Esophageal cancer (EC) patients receiving radiotherapy are at a high risk of malnutrition, which can increase the side effects of radiotherapy, reduce the accuracy and sensitivity of radiotherapy and decrease treatment effect. Therefore, timely and correct nutritional treatment is crucial. To date, however, neither consensus nor guidelines on enteral nutrition (EN) specifically for EC patients receiving radiotherapy exist. Accordingly, an expert consensus conference was held to establish consensus on the use of EN in EC patients receiving radiotherapy. It reflected the opinions of a multidisciplinary group of experts and a review of the current literature, and established common guidelines for nutritional screening and assessment, nutrition counseling, indication for EN, access and formulas of EN, effect evaluation, nutrition plan adjustment, and home enteral nutrition.

Outcomes of concurrent chemoradiotherapy versus chemotherapy alone for stage IV esophageal squamous cell carcinoma: a retrospective controlled study.

BACKGROUND: The purpose of this study is to compare the efficacy and safety of concurrent chemoradiotherapy (CCRT) versus chemotherapy alone for patients with stage IV esophageal squamous cell carcinoma (ESCC). METHODS: Eligible patients were retrospectively enrolled at the authors's institution from January 2010 to October 2015. Of the 141 patients enrolled, 55 (39.0%) received CCRT and 86 (61.0%) received chemotherapy alone. The outcomes and adverse events (AEs) were compared between the two groups. RESULTS: The baseline clinical characteristics of the two groups were similar. However, the CCRT group showed a significantly better primary tumor objective response rate (ORR) than that of the chemotherapy group (74.5% versus 45.3%, p = 0.001). The 1-year, 2-year, 3-year overall survival (OS) rates and median OS were 58.0% versus 43.0%, 25.5% versus 14.0%, 10.7% versus 4.7%, and 14 months versus 11 months for patients treated with CCRT or chemotherapy, respectively (p = 0.007). The 1-year and median progression-free survival (PFS) were 29.8% versus 14.9% and 8 months versus 6 months (p = 0.005). Multivariate analysis identified CCRT (p = 0.013) and solitary metastasis (p = 0.037) as independent factors for greater OS. The frequency of leucocytopenia (grade 3 or higher) was significantly higher in the CCRT group than in the chemotherapy-alone group (p = 0.040), whereas the rates of other AEs did not differ. CONCLUSIONS: In this study, it is suggested that CCRT is more effective than chemotherapy alone for stage IV ESCC, yielding better primary responses and survival outcomes with tolerable side effects.

[Evaluation of endoscopy assisted vitrectomy for the treatment of severe traumatic eyes with no light perception].

OBJECTIVE: To evaluate the effect of endoscopy assisted pars plana vitrectomy for severe ocular trauma with no light perception. METHODS: A retrospective case-series study. Medical records of 6 eyes of 6 patients undergoing endoscopy assisted vitrectomy for severe ocular trauma with no light perception from December 2006 to August 2009 were studied. Four patients were male and 2 patients were female. Their age ranged from 6 to 67 years old with an mean age of 38 years. History of trauma, visual acuity prior to vitrectomy and at final follow-up, bacterial culture results and surgical approaches were recorded. RESULTS: Visual acuity prior to vitrectomy was no light perception in all the 6 patients with a mean intraocular pressure of 3 mmHg (1 mmHg=0.133 kPa) . All the patients had diffuse corneal edema along with opacities caused by corneal perforation from trauma in 3 patients, blood staining of cornea in 2 patients and endophthalmitis in 1 patient. B-scan ultrasound echography carried out before surgery showing that all the patients had retinal detachment. Three patients' vitreous samples were sent for bacterial culture. Bacillus cereus, S.epidermidis and Aeromonas Hydrophila were identified respectively. Patients were followed up for 18 to 36 months. Postoperatively, 5 of the patients' visual acuity was better than light perception, ranging from light perception to 0.04. The retina was reattached in 4 patients. CONCLUSION: Endoscopy assisted vitrectomy is a safe and effective option for the treatment of severe traumatic eye with no light perception.