The role of spleen radiomics model for predicting prognosis in esophageal squamous cell carcinoma patients receiving definitive radiotherapy.

BACKGROUND: The spleen plays an important role in systemic antitumor immune response, but whether spleen imaging features have predictive effect for prognosis and immune status was unknown. The aim of this study was to investigate computed tomography (CT)-based spleen radiomics to predict the prognosis of patients with esophageal squamous cell carcinoma (ESCC) underwent definitive radiotherapy (dRT) and to try to find its association with systemic immunity. METHODS: This retrospective study included 201 ESCC patients who received dRT. Patients were randomly divided into training (n = 142) and validation (n = 59) groups. The pre- and delta-radiomic features were extracted from enhanced CT images. LASSO-Cox regression was used to select the radiomics signatures most associated with progression-free survival (PFS) and overall survival (OS). Independent prognostic factors were identified by univariate and multivariate Cox analyses. The ROC curve and C-index were used to evaluate the predictive performance. Finally, the correlation between spleen radiomics and immune-related hematological parameters was analyzed by spearman correlation analysis. RESULTS: Independent prognostic factors involved TNM stage, treatment regimen, tumor location, pre- or delta-Rad-score. The AUC of the delta-radiomics combined model was better than other models in the training and validation groups in predicting PFS (0.829 and 0.875, respectively) and OS (0.857 and 0.835, respectively). Furthermore, some spleen delta-radiomic features are significantly correlated with delta-ALC (absolute lymphocyte count) and delta-NLR (neutrophil-to-lymphocyte ratio). CONCLUSIONS: Spleen radiomics is expected to be a useful noninvasive tool for predicting the prognosis and evaluating systemic immune status for ESCC patients underwent dRT.

Abdominal lymph node metastasis in non-surgical esophageal squamous cell carcinoma: prognostic significance and a novel staging strategy.

Purpose: This study aimed to evaluate the feasibility of a combination of abdominal lymph node (LN) metastasis and the number of LNs in esophageal squamous cell carcinoma (ESCC) patients to optimize its clinical nodal staging. Methods: A retrospective study, including a total of 707 ESCC patients treated with definitive radiotherapy, was conducted at two participating institutes. Different combinations of LN variables, including abdominal LN metastasis (R1: no-abdominal LN metastasis; R2: abdominal LN metastasis), were further analyzed to propose a potential revised nodal (rN) staging. Results: The multivariate analyses showed that the number of metastatic LN and abdominal LN metastasis were independent prognostic factors for the overall survival (OS). The results showed no significant differences in the OS between the N2 patients with abdominal LN metastasis and N3 patients. The OS of the stage III patients with abdominal LN metastasis was not significantly different from those with stage IVa. The N3R1 and N1-2R2 had similar hazard ratios (HRs). The N1R1 subset was defined as rN1, the N2R1 subset was defined as rN2, and the N3R1-2 and N1-2R2 subsets were defined as rN3. The HRs of OS of the rN2 and rN3 groups increased subsequently. The rN stage could identify the differences in the OS times of each subgroup based on the 8th AJCC cN staging or the 11th JES N staging. Conclusions: The rN staging, including the number of metastatic LNs and abdominal LN metastasis, might serve as a potential prognostic predictor for non-surgical patients with ESCC.

Personalized Intelligent Syndrome Differentiation Guided By TCM Consultation Philosophy.

Traditional Chinese Medicine (TCM) is one of the oldest medical systems in the world, and inquiry is an essential part of TCM diagnosis. The development of artificial intelligence has led to the proposal of several computational TCM diagnostic methods. However, there are few research studies among them, and they have the following flaws: (1) insufficient engagement with the patient, (2) barren TCM consultation philosophy, and (3) inadequate validation of the method. As TCM inquiry knowledge is abstract and there are few relevant datasets, we devise a novel knowledge representation technique. The mapping of symptoms and syndromes is constructed based on the diagnostics of traditional Chinese medicine. As a guide, the inquiry knowledge base is constructed utilizing the "Ten Brief Inquiries," TCM's domain knowledge. Subsequently, a corresponding assessment approach is proposed for an intelligent consultation model for syndrome differentiation. We establish three criteria: the quality of the generated question-answer pairs, the accuracy of model identification, and the average number of questions. Three TCM specialists are asked to undertake a manual evaluation of the model separately. The results reveal that our approach is capable of pretty accurate syndrome differentiation. Furthermore, the model's question and answer pairs for simulated consultations are relevant, accurate, and efficient.

Lymph node metastasis is not associated with survival in patients with clinical stage T4 esophageal squamous cell carcinoma undergoing definitive radiotherapy or chemoradiotherapy.

Background: Clinical T4 stage (cT4) esophageal tumors are difficult to be surgically resected, and definitive radiotherapy (RT) or chemoradiotherapy (dCRT) remains the main treatment. The study aims to analyze the association between the status of lymph node (LN) metastasis and survival outcomes in the cT4 stage esophageal squamous cell carcinoma (ESCC) patients that underwent treatment with dCRT or RT. Methods: This retrospective study analyzed the clinical data of 555 ESCC patients treated with dCRT or RT at the Shandong Cancer Hospital and the Liaocheng People's Hospital from 2010 to 2017. Kaplan-Meier and Cox regression analyses was performed to determine the relationship between LN metastasis and survival outcomes of cT4 and non-cT4 ESCC patients. The chi-square test was used to evaluate the differences in the local and distal recurrence patterns in the ESCC patients belonging to various clinical T stages. Results: The 3-year survival rates for patients with non-cT4 ESCC and cT4 ESCC were 47.9% and 30.8%, respectively. The overall survival (OS) and progression-free survival (PFS) rates were strongly associated with the status of LN metastasis in the entire cohort (all P < 0.001) and the non-cT4 group (all P < 0.001) but not in the cT4 group. The local recurrence rates were 60.7% for the cT4 ESCC patients and 45.1% for the non-cT4 ESCC patients (P < 0.001). Multivariate analysis showed that clinical N stage (P = 0.002), LN size (P = 0.007), and abdominal LN involvement (P = 0.011) were independent predictors of favorable OS in the non-cT4 group. However, clinical N stage (P = 0.824), LN size (P = 0.383), and abdominal LN involvement (P = 0.337) did not show any significant correlation with OS in the cT4 ESCC patients. Conclusions: Our data demonstrated that the status of LN metastasis did not correlate with OS in the cT4 ESCC patients that received dCRT or RT. Furthermore, the prevalence of local recurrence was higher in the cT4 ESCC patients.

Clinical outcomes of gefitinib and erlotinib in patients with NSCLC harboring uncommon EGFR mutations: A pooled analysis of 438 patients.

BACKGROUND: The purpose of this study was to investigate the outcomes of gefitinib and erlotinib in patients with non-small cell lung cancer (NSCLC) with uncommon epidermal growth factor receptor (EGFR) mutations. METHODS: Relevant researches were identified by a literature search of the PubMed database. Patients with EGFR mutations other than exon 19 deletion and L858R were eligible for the study. Clinical outcomes included objective response rate (ORR), progression free survival (PFS), and overall survival (OS). We categorized all uncommon EGFR mutations as: single uncommon EGFR mutations and compound mutations that containing 2 or more kinds of EGFR mutations. We also assessed outcomes in patients categorized by EGFR-TKIs: (1) gefitinib group; (2) erlotinib group. RESULTS: A total of 438 patients with NSCLC harboring uncommon EGFR mutations were included in this study. The ORR for gefitinib and erlotinib was 43.8 %, with a median PFS (mPFS) of 6.00 months and a median OS (mOS) of 20.50 months. Patients with compound mutations had an ORR of 56.3 % and an mPFS of 8.10 months. Both of them were significantly better than these in patients with single uncommon EGFR mutation, which were 29.3 % and 3.90 months, respectively (odds ratio (ORa): 2.74, 95 % confidence interval (CI): 1.86-4.05, P < 0.001; hazard ratio (HR): 0.58, 95 % CI: 0.48-0.71, P < 0.001). Moreover, patients with compound mutations containing 19 deletion or L858R had a superior response and survival benefits compared to patients with other compound mutation patterns. In addition, the gefitinib group showed a favorable efficacy advantage (P = 0.003) and PFS benefit (P = 0.021) compared to the erlotinib group. CONCLUSIONS: Uncommon EGFR mutations exhibit favorable but inconsistent treatment responses and survival outcomes to gefitinib and erlotinib, which are closely related to the mutation pattern, the cooccurring partner mutant genes, and the type of EGFR-TKIs received.

Surface specifically modified NK-92 cells with CD56 antibody conjugated superparamagnetic Fe3O4 nanoparticles for magnetic targeting immunotherapy of solid tumors.

Although there has been significant progress in the development of tumor immunotherapies, many challenges still exist for the treatment of solid tumors. Natural killer (NK) cells possess broad-spectrum cytotoxicity against tumors, but their limited migration and infiltration abilities restrict their application in solid tumor therapies. Here, we combined a facile and efficient magnetic-targeting strategy with NK cell-based therapy to develop a novel immunotherapy approach for treating solid tumors. Anti-CD56 antibodies were conjugated with Fe3O4 nanoparticles, which could specifically bind with NK-92 cells endowing them with a magnetic field driven targeting ability. These NK-Fe3O4 biohybrid nanoparticles were able to facilitate directional migration to the tumor site in vivo under external magnetic field guidance and efficiently inhibit tumor growth. These functionalized NK cells represent a novel approach for solid tumor therapy and may provide a promising modality for cancer interventions in the future.

Short-term response might influence the treatment-related benefit of adjuvant chemotherapy after concurrent chemoradiotherapy for esophageal squamous cell carcinoma patients.

BACKGROUND: Whether adjuvant chemotherapy (AC) after concurrent chemoradiotherapy (CCRT) could provide benefit to esophageal squamous cell carcinoma (ESCC) patients is controversial. Therefore, we decided to investigate the potential benefit of AC after CCRT for ESCC and to identify biomarkers predictive of a clinical benefit. METHODS: We retrospectively analysed the clinical data of ESCC patients with clinical stage II-IVa who underwent CCRT. Then, we compared patients who received CCRT and AC (CCRT + AC group) with those who received CCRT alone (CCRT group). Propensity score analysis, subgroup analysis and an additional Cox regression model were conducted to analyse the predictive factors. The overall survival (OS) and progression-free survival (PFS) rates were taken as the endpoints. RESULTS: From January 2013 to December 2017, 244 patients were recruited (n = 131 for CCRT + AC; n = 113 for CCRT alone) for the analysis. After propensity score matching was performed (1:1 and 99 patients for each group) with consideration of the basic clinical characteristics, no significant differences were found in OS (HR = 1.024; 95% CI 0.737-1.423; P = 0.886) or PFS (HR = 0.809; 95% CI 0.582-1.126; P = 0.197) between the two groups. The good short-term response subgroup showed a better PFS and favoured CCRT + AC treatment (HR = 0.542; 95% CI 0.336-0.876; P = 0.008), the independent predictive role of which was confirmed in additional multivariate Cox regression analysis. CONCLUSIONS: Although AC did not significantly improve PFS and OS for all ESCC patients after CCRT, the short-term response to CCRT might help identify a subgroup that will benefit, which needs further prospective research to confirm.

Patterns and Treatment Strategies of Osimertinib Resistance in T790M-Positive Non-Small Cell Lung Cancer: A Pooled Analysis.

INTRODUCTION: Osimertinib resistance is inevitable. The purpose of this study was to explore the predictive value of pretreatment clinical characteristics in T790M-positive non-small cell lung cancer NSCLC patients for the resistance pattern of osimertinib during tumor progression as well as the treatment strategy. METHODS: We performed a literature search in the NCBI PubMed database to identify relevant articles and completed a pooled analysis based on 29 related published studies. The relationship between clinical characteristics, EGFR mutation type, previous treatment history and the gene mutation pattern at resistance to osimertinib was analyzed. RESULTS: A total of 38 patients were included in the pooled analysis. Patients with an initial epidermal growth factor receptor EGFR mutation status of 19 deletions were more likely to have T790M loss (HR: 12.187, 95% CI: 2.186-67.945, p = 0.004). Patients with an initial EGFR mutation of L858R were more likely to have C797S mutations (HR: 0.063, 95% CI: 0.011-0.377, p = 0.002). The other factors (age, gender, ethnicity, smoking history, previous EGFR-TKI targeted therapy history, history of radiotherapy and chemotherapy) were not associated with the resistance pattern of osimertinib (all p > 0.05). CONCLUSIONS: The type of EFGR mutation in T790M-positive NSCLC patients prior to treatment can predict the resistance pattern to osimertinib. This finding plays a vital role and theoretical basis in guiding clinicians to formulate treatment strategies at the early stage of treatment and rationally combine drugs to overcome EGFR-TKI resistance.

A nomogram for the predicting of survival in patients with esophageal squamous cell carcinoma undergoing definitive chemoradiotherapy.

BACKGROUND: Definitive chemoradiotherapy (dCRT) is widely accepted for esophageal squamous cell carcinoma (ESCC), although the outcomes can vary. Therefore, we aimed to develop a nomogram for the pre-treatment prediction of survival after dCRT for ESCC. METHODS: This retrospective study evaluated 204 patients (169 patients in a primary cohort and 35 patients in a validation cohort) who received dCRT for ESCC between July 2013 and June 2017. RESULTS: Pre-treatment parameters that predicted long-term survival in this setting were body mass index (BMI), absolute lymphocyte count (ALC), neutrophil-to-lymphocyte ratio (NLR), wall thickness, concurrent chemoradiotherapy, radiotherapy modality, and American Joint Committee on Cancer (AJCC) stage. The nomogram incorporated these factors and provided C-index values of 0.691 [95% confidence interval (CI): 0.641-0.740] in the primary cohort and 0.816 (95% CI: 0.700-0.932) in the validation cohort. The calibration curve analysis revealed that the nomogram had good ability to predict 2-year progression-free survival (PFS). The nomogram also performed better than the AJCC staging system by the C-index values (0.691 vs. 0.560) and the area under the curve values (0.702 vs. 0.576). Decision curve analysis (DCA) also indicated that the nomogram had better clinical utility. CONCLUSIONS: These results suggest that pre-treatment parameters may help predict the efficacy of dCRT for ESCC. Furthermore, as the nomogram provided better prognostic accuracy than the AJCC staging system, the nomogram may be useful in clinical practice for prognostication among patients who are going to receive dCRT for ESCC.

Combined prognostic value of the SUVmax derived from FDG-PET and the lymphocyte-monocyte ratio in patients with stage IIIB-IV non-small cell lung cancer receiving chemotherapy.

BACKGROUND: We evaluated the prognostic potential of tumor 18F-fluorodeoxyglucose (FDG) uptake derived from positron emission tomography (PET) and known inflammatory hematological markers, both individually and in combination, for chemosensitivity and survival in patients with stage IIIB-IV non-small cell lung cancer (NSCLC) receiving first-line chemotherapy. METHODS: A total of 149 patients with stage IIIB and IV NSCLC (based on TNM 7th edition) were retrospectively reviewed. Maximum standardized uptake value (SUVmax) were used to quantitatively assess FDG uptake. The lymphocyte-monocyte ratio (LMR), neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were selected as hematological markers. Receiver operating characteristic (ROC) curves were constructed for the determination of optimal cut-off values to predict chemotherapeutic response. RESULTS: Patients with SUVmax > 11.6 or LMR ≤3.73 exhibited a significantly lower objective response rate (ORR) to chemotherapy (p < 0.001 and p < 0.001). Through multivariable logistic regression analysis, both the SUVmax and LMR were identified as independent predictive factors for chemotherapeutic response (p = 0.001 and p < 0.001). Furthermore, a multivariable Cox proportional hazard model identified a high SUVmax (> 11.6) and low LMR (≤3.73) as independent predictors of poor PFS (p < 0.001 and p = 0.025) and OS (p < 0.001 and p = 0.032). A novel score system was constructed based on the SUVmax and LMR (SUV_LMR score), and patients were stratified into three subgroups. The patients with a score of 0 had a significantly higher ORR (88.9%) than did those with a score of 1 (59.6%) and score of 2 (25.0%) (p < 0.001). Moreover, multivariable Cox analysis further identified the SUV_LMR score as an independent prognostic factor for PFS (p < 0.001) and OS (p < 0.001). CONCLUSIONS: Pre-treatment SUVmax and LMR were not only predictive factors for chemotherapeutic response but also independent prognostic factors of survival in stage IIIB-IV NSCLC. Moreover, the SUV_LMR score, which is based on primary tumor metabolic activity and the systemic inflammatory response, might provide a promising tool to predict chemosensitivity, recurrence and survival of advanced NSCLC.

Prognostic value of the neutrophil-to-lymphocyte ratio and primary tumor location in epidermal growth factor receptor-mutated metastatic non-small cell lung cancer.

Context: Few studies have reported on the relationship between complete blood count (CBC) parameters and progression-free survival (PFS) in nonsmall cell lung cancer (NSCLC) treated with tyrosine kinase inhibitors (TKIs). Aims: Evaluate the prognostic value of pretreatment in patient CBC with advanced NSCLC when treated with epidermal growth factor receptor-TKIs as first-line to third-line therapy. Settings and Design: We retrospectively analyzed 190 patients receiving TKIs with metastatic NSCLC harboring an exon del19, 21 L858R mutations, or other rare mutations. Materials and Methods: Pretreatment blood data were obtained from electronic medical records. Patient imaging results were used to identify tumor location. Methods: Baseline clinical characteristics were compared by Pearson's Chi-square and Student's t-tests. Cox regression analyses were used to evaluate the prognostic value of peripheral blood parameters on PFS. All prognostic factors were explored with multivariable regression. Results: Patients with high Neu% (13.0 vs. 18.8 months, P= 0.003), Neu (12.0 vs. 14.5 months, P = 0.014), and neutrophil-to-lymphocyte ratio (NLR) (7.0 vs. 15.2 months, P < 0.001) had worse PFS. In contrast, patients with higher Lym (13.0 vs. 16.5 months, P = 0.012) and Lym% (8.8 vs. 15.3 months, P < 0.001) showed better PFS. In addition, tumor location was also an important factor for prognosis (11.6 vs. 14.3 months, P = 0.003). Discussion: Our data indicated that Lym, LLym%, HNeu, HNeu%, and HNLR were associated with poor prognosis in NSCLC patients treated with TKIs. NLR and primary tumor location were both identified as independent risk indicators for worse PFS based on multivariate analysis.

The PET-Derived Tumor-to-Liver Standard Uptake Ratio (SUV TLR ) Is Superior to Tumor SUVmax in Predicting Tumor Response and Survival After Chemoradiotherapy in Patients With Locally Advanced Esophageal Cancer.

Background: The maximum standardized uptake values (SUVmax) derived from 18F-fluorodeoxy-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) have some well-known shortcomings in predicting treatment response and prognosis in oncology. The standardized SUVmax with an appropriate reference background may overcome this problem in some instances. This study explored the prognostic value of the tumor-to-liver SUVmax ratio (SUVTLR) and the tumor-to-blood pool SUVmax ratio (SUVTBR) in predicting the objective response (OR) and overall survival (OS) in patients with locally advanced esophageal cancer after concurrent chemoradiotherapy (CCRT). Methods: We retrospectively analyzed 128 newly diagnosed esophageal squamous cell carcinoma (ESCC) patients who were treated with CCRT. The SUVmax of primary tumor, SUVTLR, SUVTBR and clinicopathologic features data were analyzed. Univariate and multivariate analyses were used to determine the predictors of tumor response. Survival analysis was performed using the Kaplan-Meier method and Cox proportional hazards model. Results: Receiver operating characteristic (ROC) curve analysis demonstrated that SUVTLR was superior to SUVmax and SUVTBR in predicting treatment response. Univariate and multivariate analyses revealed that advanced tumor stage (hazard ratio [HR] = 9.67; 95% CI: 1.15-81.28; P = 0.037) and high SUVTLR (HR = 21.92; 95% CI: 2.26-212.96; P = 0.008) were independent predictors of poor treatment response. Cox regression analysis showed that good clinical tumor response (p < 0.014, HR =0.501; 95% CI: 0.288-0.871) was a favorable independent predictive factor for OS, while an advanced tumor stage (p = 0.018, HR = 1.796; 95% CI: 1.107-2.915) and a high SUVTLR (p < 0.002, HR = 2.660; 95% CI: 1.425-4.967) were prognostic factors for poor OS. The median OS of patients in the low SUVTLR and high SUVTLR groups was 13.47 vs. 19.30 months, respectively. Conclusions: PET-derived SUVTLR is superior to tumor SUVmax and SUVTBR in predicting treatment response and overall survival in patients with ESCC undergoing CCRT. High SUVTLR was an independent predictor of poor treatment response and shorter overall survival.

Research Progress and Existing Problems for Abscopal Effect.

Radiation therapy plays a vital role in the treatment of tumours. In particular, the occurrence of the "abscopal effect" brings about a favourable turn for the treatment of patients with advanced metastatic malignant tumours. Because of the abscopal effect, non-irradiated areas are also treated. However, the abscopal effect occurs by chance, not through seeking. Although the abscopal effect has been studied enthusiastically, the desired result does not appear to be achieved. Moreover, its combination with immunotherapy appears to be overwhelming. There is an opinion that abscopal effect is difficult to achieve by irradiation of a single tumour, and irradiation of multiple or total lesions is advocated to increase the possibility of obtaining clinically meaningful outcomes. Obviously, there are still questions about the mechanism, condition and possibility underlying the occurrence of the abscopal effect. Can the abscopal effect truly change the future treatment strategy as the researchers expect? What are the current problems? This article reviewed the research in recent years to explore the progress and controversy surrounding the abscopal effect of radiation therapy.

Low Lymphocyte Count Is Associated With Radiotherapy Parameters and Affects the Outcomes of Esophageal Squamous Cell Carcinoma Patients.

Purpose: Lymphocytes are central players in systemic anti-tumor immune responses. In this study, we aimed to identify the relationship between absolute lymphocyte count (ALC) nadir during definitive radiotherapy (RT) and survival outcomes in patients with esophageal squamous cell carcinoma (ESCC), as well as evaluate the effect of RT parameters on ALC during RT. Materials and methods: We retrospectively reviewed 189 patients with stage I-IVA ESCC, who were treated with definitive RT at a single institution between 2012 and 2015. ALC values were assessed before, weekly during RT, and 1 month after the end of RT. Kaplan-Meier and Cox regression analyses were used to evaluate the relationship between ALC nadir during RT and patient outcomes. Predictors of low ALC nadir were assessed using univariate and multivariate logistic regression analyses. Results: The median ALC before treatment was 1.73 × 103 cells/µL. Fifty-eight (58.2) percent of the patients exhibited low ALC nadir (≤ 0.38 × 103 cells/µL) during RT. A low ALC nadir during RT was significantly associated with poor OS, PFS, and LRFS. The planning target volume (PTV) was larger in patients with low ALC nadir compared with patients with high ALC nadir (418.5 vs. 347.7 cm3, P = 0.023). Multivariate logistic regression analysis revealed that tumor stage III-IVA (P = 0.002), low ALC before treatment (P = 0.028), large Log10(PTV) (P = 0.01), high heart V10 (P = 0.003), and high heart V20 (P = 0.028) were associated with low ALC nadir during RT. Conclusions: In ESCC patients who received definitive RT, a low ALC nadir during RT was associated with large PTVs, and it was an independent prognostic factor of outcomes.

Clinical response to chemoradiotherapy in esophageal carcinoma is associated with survival and benefit of consolidation chemotherapy.

PURPOSE: Few studies have reported the impact of the clinical response of patients with Esophageal Carcinoma to chemoradiotherapy (CRT). Our study examines the association between clinical response and pretreatment variables, survival, patterns of failure, and benefit of consolidation chemotherapy in subjects with esophageal squamous cell carcinoma (ESCC) patients receiving CRT. METHODS: Data from ESCC patients treated at Shandong Cancer Hospital between January 2013 and December 2016 were analyzed retrospectively. By definition, we considered a poor response as progressive disease (PD) and stable disease (SD), while complete response (CR) and partial response (PR) were considered as a good response. Multivariate analyses were carried out using Cox proportional hazards models and patient survival was assessed using the Kaplan-Meier and log-rank test. RESULTS: After CRT, 136 (48.9%) patients responded well (good response) and 152 (51.1%) patients responded poorly (poor response). Overall survival (OS) and progression-free survival (PFS) differed significantly between patients responded well and those responded poorly. Patients with an early-stage or the upper location of the tumor were more likely to achieve a good response. Patients showing poor responses tended to experience local failure. The 3-year OS and PFS rates of patients showing poor response were 38.9% and 25.5%, respectively, for the CRT with consolidation chemotherapy (CRT + C) group, and 22.7% and 16.7%, respectively, for the CRT group. However, patients with a good response did not benefit from the consolidation chemotherapy. Primary tumor location, T category, N category, and clinical response to chemoradiotherapy were independent factors predicting OS and PFS in ESCC. CONCLUSION: Clinical response to CRT substantially improves patient survival and is associated with failure patterns in ESCC. Consolidated chemotherapy may benefit patients with a poor response.

A review of radiation-induced lymphopenia in patients with esophageal cancer: an immunological perspective for radiotherapy.

Radiotherapy is a frequently utilized therapeutic modality in the treatment of esophageal cancer (EC). Even though extensive studies are carried out in radiotherapy for EC, the design of the clinical target volume and the radiation dose is not satisfactorily uniform. Radiotherapy acts as a double-edged sword on the immune system; it has both an immunostimulatory effect and an immunosuppressive effect. Radiation-induced lymphopenia and its potential association with tumor control and survival outcomes remain to be understood. The advent of immunotherapy has renewed the focus on preserving a pool of functioning lymphocytes in the circulation. In this review, we summarize the potential impact mechanisms of radiotherapy on peripheral blood lymphocytes and the prognostic role of radiation-induced lymphopenia in patients with EC. We also propose the concept of organs-at-risk of lymphopenia and discuss potential strategies to mitigate its effects on patients with EC. From an immunological perspective, we put forward the hypothesis that optimizing radiation modalities, radiation target volume schemes, and radiation doses could help to reduce radiation-induced lymphopenia risks and maximize the immunomodulatory role of radiotherapy. An optimized radiotherapy plan may further enhance the feasibility and effectiveness of combining immunotherapy with radiotherapy for EC.

A predictive model for treatment response in patients with locally advanced esophageal squamous cell carcinoma after concurrent chemoradiotherapy: based on SUVmean and NLR.

BACKGROUND: We conducted this study to combine the mean standardized uptake value (SUVmean) and neutrophil to lymphocyte ratio (NLR) to establish a strong predictive model for patients with esophageal squamous cell carcinoma (ESCC) after concurrent chemoradiotherapy (CCRT). METHODS: We retrospectively analyzed 163 newly diagnosed ESCC patients treated with CCRT. Eighty patients (training set) were randomly selected to generate cut-off SUVmean and NLR values by receiver operating characteristic (ROC) curve analysis and to establish a predictive model by using the independent predictors of treatment outcomes. Then, we evaluated the performance of the prediction model regarding treatment outcomes in the testing set (n = 83) and in all sets. RESULTS: A high SUVmean (> 5.81) and high NLR (> 2.42) at diagnosis were associated with unfavorable treatment outcomes in patients with ESCC. The prediction model had a better performance than the simple parameters (p < 0.05). With a cut-off value of 0.77, the prediction model significantly improved the specificity and positive predictive value for treatment response (88.9 and 92.1% in the training set, 95.8 and 97.1% in the testing set, and 92.2 and 91.8% in all sets, respectively). CONCLUSIONS: The pretreatment SUVmean and NLR were independent predictors of treatment response in ESCC patients treated with CCRT. The predictive model was constructed based on these two parameters and provides a highly accurate tool for predicting patient outcomes.

The flow-metabolism ratio might predict treatment response and survival in patients with locally advanced esophageal squamous cell carcinoma.

BACKGROUND: Perfusion CT can offer functional information about tumor angiogenesis, and 18F-FDG PET/CT quantifies the glucose metabolic activity of tumors. This prospective study aims to investigate the value of biologically relevant imaging biomarkers for predicting treatment response and survival outcomes in patients with locally advanced esophageal squamous cell cancer (LA ESCC). METHODS: Twenty-seven patients with pathologically proven ESCC were included. All patients had undergone perfusion CT and 18F-FDG PET/CT using separate imaging systems before receiving definitive chemoradiotherapy (dCRT). The perfusion parameters included blood flow (BF), blood volume (BV), and time to peak (TTP), and the metabolic parameters included maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). The flow-metabolism ratio (FMR) was defined as BF divided by SUVmax. Statistical methods used included Spearman's rank correlation, Mann-Whitney U test or two-sample t test, receiver operating characteristic (ROC) curve analysis, the Kaplan-Meier method, and Cox proportional hazards models. RESULTS: The median overall survival (OS) and progression-free survival (PFS) were 18 and 11.6 months, respectively. FMR was significantly positively correlated with BF (r = 0.886, p < 0.001) and negatively correlated with SUVmax (r = - 0.547, p = 0.003) and TTP (r = - 0.462, p = 0.015) in the tumors. However, there was no significant correlation between perfusion and PET parameters. After dCRT, 14 patients (51.9%) were identified as responders, and another 13 were nonresponders. The BF and FMR of the responders were significantly higher than those of the nonresponders (42.05 ± 16.47 vs 27.48 ± 8.55, p = 0.007; 3.18 ± 1.15 vs 1.84 ± 0.65, p = 0.001). The ROC curves indicated that the FMR [area under the curve (AUC) = 0.846] was a better biomarker for predicting treatment response than BF (AUC = 0.802). Univariable Cox analysis revealed that of all imaging parameters, only the FMR was significantly correlated with overall survival (OS) (p = 0.015) and progression-free survival (PFS) (p = 0.017). Specifically, patients with a lower FMR had poorer survival. Multivariable analysis showed that after adjusting for age, clinical staging, and treatment response, the FMR remained an independent predictor of OS (p = 0.026) and PFS (p = 0.014). CONCLUSIONS: The flow-metabolism mismatch demonstrated by a low FMR shows good potential in predicting chemoradiotherapy sensitivity and prognosis in ESCC.

The Prognostic Significance of Metastatic Nodal Size in Non-surgical Patients With Esophageal Squamous Cell Carcinoma.

Background: The present study aimed to determine the prognostic value of the size of metastatic lymph node (LN) in non-surgical patients with esophageal squamous cell carcinoma (ESCC). Methods: Three hundred seventy-six ESCC patients treated with definitive (chemo-) radiotherapy from January 2013 to March 2016 were reviewed. We analyzed potential associations of metastatic nodal size with responses, patterns of failure, and survival. Log-rank testing and Cox proportional hazards regression models were used to assess the impact of the clinical factors on survival. Results: The 3-years over survival (OS) rates following a median follow-up of 28.2 months were 53.2, 46.2, 35.5, and 22.7% for the N0 group, the >0.5 to ≤1 cm group, the >1 to ≤2 cm group, and the >2 cm group, respectively. The progression-free survival (PFS) rates for 2 years were 50.9, 44.2, 26.6, and 23.4% for the N0 group, the >0.5 to ≤1 cm group, the >1 to ≤2 cm group, and the >2 cm group, respectively. The objective response rates (ORR) for the 280 patients with metastatic LNs were 43.1% for the LN >0.5 to ≤1 cm group, 46.9% for the LN >1 to ≤2 cm group, and 25.5% for the LN ≥2 cm group. The LN >2 cm group had the worst ORR of the three groups with LNs. Gross tumor volume (GTV) failure was the most common failure pattern, followed by distant failure and out of GTV LN failure, with incidences of 47.9% (180 of 376), 42% (158 of 376), and 13.8% (52 of 376), respectively. Nodal size correlated statistically with GTV failure and distant failure but not with out-of-GTV nodal failure. After adjusting for age, sex, T category, Primary tumor location, and CRT, the size of metastatic LNs was an independent prognostic factor for OS and PFS in multivariate analyses. Conclusions: Nodal size is one of prognostic factors for non-surgical patients with ESCC and correlated statistically with GTV failure and distant failure.

Lymphocyte-monocyte ratio as a predictive marker for pathological complete response to neoadjuvant therapy in esophageal squamous cell carcinoma.

BACKGROUND: The hematological markers of systemic inflammation has been proved to be significantly associated with clinical outcomes in esophageal cancer. This retrospectively study was to evaluate the value of the hematological markers in predicting pathological complete response (pCR) and overall survival (OS) in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC) who received neoadjuvant chemoradiotherapy (nCRT). METHODS: A total of 87 patients with newly diagnosed LA-ESCC were retrospectively analyzed. The pretreatment lymphocyte-monocyte ratio (LMR), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) were selected as hematological markers. RESULTS: After nCRT, 26 (29.9%) patients achieved pCR and 61 (70.1%) patients had non-pCR. The LMR was significantly higher in patients who achieved pCR compared to that in patients who did not achieve pCR (4.35±1.68 vs. 3.33±1.13, P=0.002). Based on the receiver operating characteristic (ROC) curve, the optimal cut off value of LMR that predicted pCR was 3.73 [area under the curve: 0.712; 95% confidence interval (CI): 0.594-0.830; P=0.002], with a sensitivity of 65.4% and specificity of 77.0%. The pCR rate of patients with LMR ≥3.73 was 53.1%, while the pCR rate of patients with LMR <3.73 was only 16.4% (P<0.001). The univariate and multivariate logistic regression analysis confirmed that LMR was an independent predictor of pCR [odds ratio: 5.093; 95% CI: 1.658-15.646; P=0.004]. However, in the prediction of OS, a multivariate Cox proportional hazard model revealed that only clinical stage [hazard ratio (HR): 1.970; 95% CI: 1.144-3.391; P=0.014] and pCR (HR: 0.469; 95% CI: 0.237-0.928; P=0.030) were independent prognostic factors. CONCLUSIONS: Pre-treatment LMR may predict pCR in LA-ESCC patients who were treated with nCRT. Having pCR is an independent prognostic factor for prolonged survival.