Inflammatory and Nutritional Biomarkers in Patients With Esophageal Squamous Cell Carcinoma Undergoing Neoadjuvant Chemotherapy and Radiation Therapy.

OBJECTIVES: To investigate the relationship between pretreatment inflammatory and nutritional biomarkers in patients with esophageal squamous cell carcinoma (ESCC) undergoing neoadjuvant chemotherapy and radiation therapy (nCRT). SAMPLE & SETTING: 213 patients with newly diagnosed stage II-III ESCC who received nCRT at an academic hospital in Taiwan. METHODS & VARIABLES: Electronic health record data were used. Records on inflammatory and nutritional biomarkers and clinical outcomes were extracted. Logistic regression analysis was used to predict treatment-related adverse events, Cox regression was used for survival outcomes, and receiver operating characteristic curve analysis was used to determine optimal cutoff values. RESULTS: There was a significant association between low prognostic nutritional index (PNI) and nCRT toxicities and survival. Advanced cancer stage, high platelet-to-lymphocyte ratio, and occurrence of pneumonia/infection were linked to survival outcomes. IMPLICATIONS FOR NURSING: PNI shows promise in predicting prognosis, helps identify high-risk patients, and enables nurses to apply tailored interventions.

Very high-energy electron therapy as light-particle alternative to transmission proton FLASH therapy - An evaluation of dosimetric performances.

PURPOSE: Clinical translation of FLASH-radiotherapy (RT) to deep-seated tumours is still a technological challenge. One proposed solution consists of using ultra-high dose rate transmission proton (TP) beams of about 200-250 MeV to irradiate the tumour with the flat entrance of the proton depth-dose profile. This work evaluates the dosimetric performance of very high-energy electron (VHEE)-based RT (50-250 MeV) as a potential alternative to TP-based RT for the clinical transfer of the FLASH effect. METHODS: Basic physics characteristics of VHEE and TP beams were compared utilizing Monte Carlo simulations in water. A VHEE-enabled research treatment planning system was used to evaluate the plan quality achievable with VHEE beams of different energies, compared to 250 MeV TP beams for a glioblastoma, an oesophagus, and a prostate cancer case. RESULTS: Like TP, VHEE above 100 MeV can treat targets with roughly flat (within ± 20 %) depth-dose distributions. The achievable dosimetric target conformity and adjacent organs-at-risk (OAR) sparing is consequently driven for both modalities by their lateral beam penumbrae. Electron beams of 400[500] MeV match the penumbra of 200[250] MeV TP beams and penumbra is increased for lower electron energies. For the investigated patient cases, VHEE plans with energies of 150 MeV and above achieved a dosimetric plan quality comparable to that of 250 MeV TP plans. For the glioblastoma and the oesophagus case, although having a decreased conformity, even 100 MeV VHEE plans provided a similar target coverage and OAR sparing compared to TP. CONCLUSIONS: VHEE-based FLASH-RT using sufficiently high beam energies may provide a lighter-particle alternative to TP-based FLASH-RT with comparable dosimetric plan quality.

YY1 modulates the radiosensitivity of esophageal squamous cell carcinoma through KIF3B-mediated Hippo signaling pathway.

Radiotherapy is an important strategy in the comprehensive treatment of esophageal squamous cell carcinoma (ESCC). However, effectiveness of radiotherapy is still restricted by radioresistance. Herein, we aimed to understand the mechanisms underlying ESCC radioresistance, for which we looked into the potential role of YY1. YY1 was upregulated in radioresistant tissues and correlated with poor prognosis of patients with ESCC. YY1 depletion enhanced the radiosensitivity of ESCC in vitro and in vivo. Multi-group sequencing showed that downregulation of YY1 inhibited the transcriptional activity of Kinesin Family Member 3B (KIF3B), which further activated the Hippo signaling pathway by interacting with Integrin-beta1 (ITGB1). Once the Hippo pathway was activated, its main effector, Yes-associated protein 1 (YAP1), was phosphorylated in the cytoplasm and its expression reduced in the nucleus, thus enhancing the radiosensitivity by regulating its targeted genes. Our study provides new insights into the mechanisms underlying ESCC radioresistance and highlights the potential role of YY1 as a therapeutic target for ESCC.

Efficacy of Aidi injection combined with chemotherapy, radiotherapy or chemoradiotherapy for unresectable esophageal cancer treatment: A meta-analysis and systematic review of 29 randomized controlled trials based on Asian populations (China).

OBJECTIVES: This study aimed to assess the efficacy of Aidi combined with standard treatment, including radiotherapy (R), chemotherapy (C), or chemoradiotherapy (CR), for unresectable esophageal cancer (EC). METHODS: Eight online databases were queried to collect randomized controlled trials (RCTs) published from database construction to August 2022. Patients in the control group underwent standard treatment with R, C, or CR, whereas those in the experimental group underwent Aidi combined with standard treatment. RESULTS: In this meta-analysis, 29 reports with 2079 patients were included. The results showed that the Aidi-based combination therapy groups had higher objective response rates (ORRs), disease control rates (DCRs), one-year overall survival (OS) and improvement and stability of Karnofsky performance status (KPS) than the control group (risk ratio (RR) = 1.24 (95% CI = 1.17-1.33), 1.09 (95% CI = 1.05-1.14), 1.50 (95% CI = 1.31-1.72), and 1.28 (95% CI = 1.16-1.41)). The Aidi-based combination therapy groups also had lower total incidence rates of bone marrow suppression (BMS), chemotherapy-induced nausea and vomiting (CINV) and radiation esophagitis (RE) than the control group (RR = 0.48 (95% CI = 0.41-0.56), 0.46 (95% CI = 0.36-0.58), and 0.49 (95% CI = 0.38-0.62)). In addition, subgroup analysis suggested that the optimal dose and cycle of Aidi injection combined therapy was 80-100 ml/time and 30 days/2 cycles. The efficacy of Aidi combined with DP (docetaxel + cisplatin) was better than the Aidi combined with PF (cisplatin plus fluorouracil). CONCLUSION: Aidi-based combination therapy showed high efficacy for unresectable EC treatment and reduced the incidence rates of adverse events. However, further studies including higher-quality RCTs are needed to validate these findings. TRIAL REGISTRATION NUMBER: INPLASY 202290020.

Effect of Oral Nutritional Supplements on Patients with Esophageal Cancer During Radiotherapy.

Background: This study investigated the effect of oral nutritional supplements (ONS) on patients with esophageal cancer during radiotherapy. Materials and Methods: Patients with esophageal cancer undergoing radiotherapy were randomly divided into nutritional intervention (NI) and routine treatment (RT) groups. All patients received one-on-one nutritional counseling and dietary advice, and patients in the NI group received ONS. Body mass index (BMI), a patient-generated subjective global assessment (PG-SGA), serum albumin (ALB), hemoglobin (Hb), white blood cell (WBC) count, prealbumin (PA), and platelets (PLTs) were recorded before and after radiotherapy in both the NI group and the RT group. Further, the adverse reactions during the treatment were evaluated. Results: In the NI group, the BMI after radiotherapy was significantly higher than that before radiotherapy, and the PG-SGA score after radiotherapy was significantly lower than that before radiotherapy (p < 0.05). In the RT group, the levels of BMI, Hb, ALB, PA, PLTs, and WBC after radiotherapy were significantly lower than those before radiotherapy, and the PG-SGA score was worse after radiotherapy (p < 0.05). After radiotherapy, the levels of BMI, Hb, ALB, and PA in the NI group were similar to those in the RT group (p > 0.05); whereas the levels of WBC and PLTs in the NI group were lower than those in the RT group (p < 0.05). During the treatment, the toxic reactions of radiation esophagitis, myelosuppression, nausea, and vomiting were decreased in the NI group compared with the RT group. Conclusions: ONS can reduce weight loss and improve the nutritional status of patients with esophageal cancer during radiotherapy.

Urolithins increased anticancer effects of chemical drugs, ionizing radiation and hyperthermia on human esophageal carcinoma cells in vitro.

Despite progress in diagnosis and treatment of esophageal cancer (EC), it is still considered as a serious malignancy with very poor prognosis. Urolithins are colonic microbiota metabolites with a wide range of pharmacological properties including chemopreventive, anti-inflammatory and anticancer activities. In this study, we hypothesized that urolithins might possess the potential to improve the efficacy of chemical drugs, ionizing radiation (IR) and/or hyperthermia on EC cells. After synthesis of urolithin A (UA), methylurolithin A (mUA) and urolithin B (UB), KYSE30 esophageal cancer cells were treated with urolithins + paclitaxel (PTX), + cisplatin (DDP), + different doses of IR or + heat-shock. Viability of cells was then determined by alamarBlue assay. To further elucidate the effects of UA, we used flow cytometry for investigation of induced apoptosis, and qRT-PCR for evaluating changes in the expression of HSP27, CCND1 and BCL2. Assessment of cell viability demonstrated that mUA increased the toxicity of PTX and DDP (up to 22.4 % and 20 %, respectively) and improved the effects of 6 Gy IR (26.5 %). Our main results achieved after UA treatment were improved toxicity of PTX and 6 Gy IR, beside enhanced effects of hyperthermia (37.3 %), which was confirmed by flow cytometry analysis and downregulation of HSP27, CCND1 and BCL2 expression. Taken together, our findings suggest that UA and mUA could be used as promising agents in combination with therapeutic modalities to improve the clinical outcomes of EC treatment.

ypN0 in Patients With Definitive cN-positive Status After Preoperative Treatment Is a Prognostic Factor in Esophageal Cancer.

BACKGROUND: Histopathological tumor regression grade is applied not to lymph nodes but primary tumors modified by preoperative treatments. This study focused on patients whose pathological examination at the time of surgery showed no residual tumor after chemo(radio)therapy in the primary lesion (ypT0) or lymph nodes (ypN0). PATIENTS AND METHODS: A total of 87 patients with clinical stage II/III thoracic esophageal cancer underwent esophagectomy following preoperative treatments to evaluate significances between pathological response and clinical outcomes; 51 patients with clinically definitive lymph node metastasis (cN+) were analyzed as a subgroup. RESULTS: ypT0 rates were 20.7% and 23.5%, and ypN0 rates were 47.1% and 27.5% in the whole cohort and in the cN+ subgroup, respectively. Disease-free survival, from surgery to relapse or death, was significantly influenced by ypN status (p=0.035) but not by ypT status in the 51 patients with definitive cN+ disease. Preoperative chemoradiation was an independent favorable factor for achievement of ypN0 in the 51 patients (odds ratio=0.09; p=0.007). CONCLUSION: ypN status was a predictive factor for DFS in patients treated with docetaxel plus low-dose 5-fluorouracil and cisplatin combined chemotherapy, superior to ypT status, especially in patients with definitive cN+ disease.

A Phase II Study of Biodegradable Stents Plus Palliative Radiotherapy in Oesophageal Cancer.

AIMS: Self-expanding metal stents provide rapid improvement of dysphagia in oesophageal cancer but are associated with complications. The aim of the present study was to test the effectiveness of an alternative treatment of combining biodegradable stents with radiotherapy. MATERIALS AND METHODS: A Simon two-stage single-arm prospective phase II trial design was used to determine the efficacy of biodegradable stents plus radiotherapy in patients with dysphagia caused by oesophagus cancer who were unsuitable for radical treatment. Fourteen patients were recruited and data from 12 were included in the final analyses. RESULTS: Five of 12 patients met the primary end point: one stent-related patient death; four further interventions for dysphagia within 16 weeks of stenting (41.7%, 95% confidence interval 15.2-72.3%). The median time to a 10-point deterioration of quality of life was 2.7 weeks. Nine patients died within 52 weeks of registration. The median time to death from any cause was 15.0 weeks (95% confidence interval 9.6-not reached). CONCLUSION: The high re-intervention observed, which met the pre-defined early stopping criteria, meant that the suggested alternative treatment was not sufficiently effective to be considered for a larger scale trial design. Further work is needed to define the place of biodegradable stents in the management of malignant oesophageal strictures.

[Effect of Nutrition Intervention on Skeletal Muscle during Concurrent Chemoradiotherapy for Esophageal Cancer].

Objective To evaluate the role of nutritional intervention during concurrent chemoradiotherapy (CCRT) for esophageal cancer and investigate the incidence and risk factors of skeletal muscle loss after CCRT.Methods The clinical data of patients with esophageal cancer who underwent CCRT in our center from April 2017 to November 2019 were retrospectively collected.The CT images before and after CCRT were analyzed.The incidence of skeletal muscle loss,changes in nutritional indicators,and chemoradiotherapy delay were recorded,and the risk factors associated with declined skeletal muscle index (SMI) were analyzed.Results In the nutritional intervention group,the average daily energy intake per person in the oral nutritional supplement (ONS) subgroup,parenteral nutrition (PN) subgroup,and ONS+PN subgroup were (273.5±252.8), (310.6±311.2),and (745.3±637.8) kcal (1 kcal=4.1868 kJ),respectively,and the difference was statistically significant (F=5.870,P=0.005).After CCRT,the incidence of sarcopenia was 40.3% (n=40) in the nutrition intervention group,which was significantly lower than that (45.2%,n=42) in the control group (χ2=4.247,P=0.038);the decline of SMI in the nutrition intervention group was (1.4±8.3) cm2/m2,which was significantly lower than that in the control group [ (5.4±9.1) cm2/m2] (t=2.187,P=0.031).In the nutrition intervention group,the radiotherapy delay and chemotherapy delay occurred in 18 patients and 10 patients,which were significantly lower than those in the control group [25 patients (χ2=4.501,P=0.039) and 19 patients (χ2=8.929,P=0.005) ].The duration of radiotherapy delay and chemotherapy delay in the nutrition intervention group was (2.3±4.4) and (0.9±1.3) days,which were significantly shorter than those in the control group [ (4.2±5.3) (t=0.691,P=0.047) and (2.2±3.2) days (t=0.847,P=0.041) ].The incidence of sarcopenia was 75.2% before CCRT,which was significantly lower than that (88.2%) after CCRT (χ2=5.183,P=0.023).Multivariate linear regression analysis showed that T stage (P=0.007),N stage (P<0.001),and nutritional intervention (P=0.014) at baseline had significant effects on the decrease of SMI in patients with esophageal cancer after radiotherapy and chemotherapy.Conclusions Nutrition intervention can reduce the incidence of delayed chemoradiotherapy during esophageal cancer CCRT and reduce skeletal muscle loss.The decline of SMI is mainly related to the T stage,N stage,and nutrition intervention at baseline.

Benefits of positron emission tomography scans for the evaluation of radiotherapy.

The assessment of tumour response during and after radiotherapy determines the subsequent management of patients (adaptation of treatment plan, monitoring, adjuvant treatment, rescue treatment or palliative care). In addition to its role in extension assessment and therapeutic planning, positron emission tomography combined with computed tomography provides useful functional information for the evaluation of tumour response. The objective of this article is to review published data on positron emission tomography combined with computed tomography as a tool for evaluating external radiotherapy for cancers. Data on positron emission tomography combined with computed tomography scans acquired at different times (during, after initial and after definitive [chemo-]radiotherapy, during post-treatment follow-up) in solid tumours (lung, head and neck, cervix, oesophagus, prostate and rectum) were collected and analysed. Recent recommendations of the National Comprehensive Cancer Network are also reported. Positron emission tomography combined with computed tomography with (18F)-labelled fluorodeoxyglucose has a well-established role in clinical routine after chemoradiotherapy for locally advanced head and neck cancers, particularly to limit the number of neck lymph node dissection. This imaging modality also has a place for the evaluation of initial chemoradiotherapy of oesophageal cancer, including the detection of distant metastases, and for the post-therapeutic evaluation of cervical cancer. Several radiotracers for positron emission tomography combined with computed tomography, such as choline, are also recommended for patients with prostate cancer with biochemical failure. (18F)-fluorodeoxyglucose positron emission tomography combined with computed tomography is optional in many other circumstances and its clinical benefits, possibly in combination with MRI, to assess response to radiotherapy remain a very active area of research.

Adaptive radiotherapy in locally advanced esophageal cancer with atelectasis: a case report.

BACKGROUND: To the best of our knowledge, no study has reported mediastinal shift accompanied with obstructive atelectasis due to bulky primary esophageal tumor components treated with adaptive radiotherapy and concurrent chemotherapy. CASE PRESENTATION: Here we report the case of a 65-year-old male patient diagnosed with locally advanced thoracic esophageal squamous cell cancer, clinical T4bN1M0, stage IVA. Bronchoscopy and computed tomography (CT) revealed an almost complete obstruction of the lumen of the left bronchus due to compression by bulky primary esophageal tumor components. On admission, the patient presented with dyspnea and decreased arterial oxygen saturation. Chest radiography and CT on admission revealed mediastinal shift with left atelectasis, as opposed to findings from the chest radiography performed 26 days before admission. Because of the patient's overall good condition, we recommended definitive chemoradiotherapy instead of palliative bronchial stent placement. After obtaining the patient's consent, chemoradiotherapy was initiated on the following day and it comprised three-dimensional conformal radiotherapy with 60 Gy in 30 fractions with concurrent administration of cisplatin and 5-fluorouracil. During chemoradiotherapy, tumor location was monitored with cone-beam CT and chest radiography. Chemoradiotherapy on day 8 revealed no evidence of the mediastinal shift. CT simulation was reperformed to adjust the radiotherapy fields to account for geometrical changes induced by the absence of the mediastinal shift. Subsequently, the mediastinal shift and bronchial obstruction did not recur during the course of chemoradiotherapy. The patient completed the planned radiotherapy with concurrent and adjuvant chemotherapy, and no non-hematological grade ≥ 3 adverse events were observed. Complete response was confirmed 7 months after initiating chemoradiotherapy. Currently, no disease recurrence, dysphagia, or respiratory symptoms have been reported at 13 months after initiating chemoradiotherapy. CONCLUSIONS: In this study, a bulky primary esophageal tumor caused mediastinal shift due to ipsilateral bronchial obstruction. The close follow-up for monitoring resolution of the mediastinal shift during the course of chemoradiotherapy enabled adequate dose delivery to targets, thus reflecting the geometrical changes induced by the absence of the mediastinal shift. Adaptive radiotherapy technique was crucial for favorable patient outcomes in this challenging clinical situation.

Aconselhamento Nutricional em Pacientes com Câncer de Cabeça, Pescoço e Esôfago em Tratamento (Quimio)Radioterápico / Nutritional Cousenling in Patients with Head, Neck and Esophagus Cancer in (Chemo)Radiotherapy / Asesoramiento Nutricional en Pacientes com Cáncer de Cabeza, Cuello y Esófago em Tratamiento (Quimio)Radioterápico

Introdução: A presença de um nutricionista no setor de radioterapia objetiva a recuperação e a manutenção do estado nutricional dos pacientes. Objetivo: Comparar os resultados do aconselhamento nutricional diário com o aconselhamento nutricional semanal em pacientes com câncer de cabeça, pescoço e esôfago em tratamento radioterápico. Método: Foram selecionados 29 pacientes para o estudo e separados aleatoriamente em dois grupos. O grupo intervenção recebeu aconselhamento nutricional diariamente. O grupo padrão recebeu aconselhamento nutricional semanalmente. De ambos os grupos, foram aferidos peso corporal, circunferência braquial ou de panturrilha, avaliação subjetiva global produzida pelo próprio paciente (ASG-PPP) e cálculo do recordatório alimentar diário. Resultados: A maioria dos participantes era do sexo masculino (80%), com média de idade de 62,7 ± 26 anos. A terapia nutricional oral foi necessária para 48% dos indivíduos e, ao final do tratamento, 60% estavam em uso de nutrição enteral. A perda de peso média no grupo intervenção foi de 1,89 ± 2,58 Kg comparada à perda média de peso no grupo padrão de 9,92 ± 6,68 Kg (p=0,017). Metade dos pacientes do grupo intervenção, que iniciaram o tratamento categorizados pela ASG-PPP em A, finalizou o tratamento nessa mesma categoria (41,7%). Mais de 40% dos pacientes do grupo intervenção alcançaram as necessidades calóricas durante cinco semanas do tratamento. Conclusão: Encontraram-se resultados significativos para menor perda de peso em pacientes com aconselhamento nutricional diário que podem futuramente ser precursores de diretrizes que orientem e direcionem profissionais a condutas específicas aos pacientes com esse perfil.

Introduction: The presence of a nutritionist in the radiotherapy sector intends to recover and maintain the nutritional status of the patients. Objective: To compare the results of daily nutritional counseling with weekly nutritional advising for patients with head, neck and esophagus cancer in radiotherapy treatment. Method: 29 patients were assigned to the study and randomly divided into two groups. The intervention group received nutritional advice daily. The standard group received weekly nutritional counseling. For both groups, body weight, calf or calf circumference, global subjective evaluation produced by the patient (ASG-PPP) and calculation of the daily dietary recall were measured. Results: The majority of the participants were male (80%), mean age 62.7 ± 26 years. Oral nutrition therapy was required treatment 60% were in use of enteral nutrition. The mean weight loss in the intervention group was 1.89 ± 2.58 kg compared to the mean weight loss in the standard group of 9.92 ± 6.68 kg (p <0.001). Half of the patients in the intervention group who began treatment categorized by ASG-PPP in A, finished treatment in the same category (41.7%). More than 40% of patients in the intervention group achieved caloric needs during five weeks of treatment. Conclusion: This study found significant results for lower weight loss in patients with daily nutritional counseling. These results may in the future be precursors of guidelines that steer and direct professionals to specific conducts to patients with this profile.

Introducción: La presencia de un nutricionista en el sector de radioterapia intenciona la recuperación y mantenimiento del estado nutricional de los pacientes. Objetivo: Comparar los resultados del asesoramiento nutricional diario con el asesoramiento nutricional semanal en pacientes con cáncer de cabeza, cuello y esófago en tratamiento radioterápico. Método: Fueron seleccionados 29 pacientes para el estudio y separados aleatoriamente en dos grupos. El grupo de intervención recibió asesoramiento nutricional diariamente. El grupo estándar recibió asesoramiento nutricional semanalmente. De ambos grupos se evaluaron peso corporal, circunferencia braquial o de pantorrilla, evaluación subjetiva global producida por el propio paciente (ASG-PPP) y cálculo del recordatorio alimentario diario. Resultados: La mayoría de los participantes eran del sexo masculino (80%), con una media de edad de 62,7 ± 26 años. La terapia nutricional oral fue necesaria para el 48% de los individuos y al final del tratamiento el 60% estaban en uso de nutrición enteral. La pérdida de peso media en el grupo de intervención fue de 1,89 ± 2,58 Kg comparada con la pérdida media de peso en el grupo estándar de 9,92 ± 6,68 Kg (p<0,001). La mitad de los pacientes del grupo intervención que iniciaron el tratamiento categorizados por la ASG-PPP en A, finalizaron el tratamiento en esa misma categoría (41,7%). Más del 60% de los pacientes del grupo de intervención alcanzaron las necesidades calóricas durante cinco semanas del tratamiento. Conclusión: Este estudio encontró resultados significativos para una menor pérdida de peso en pacientes con asesoramiento nutricional diario. Estos resultados pueden en el futuro ser precursores de pautas que orientan y dirigen profesionales a conductas específicas a los pacientes con este perfil.

Clinical Evaluation of Javanica Oil Emulsion Injection Combined with the Radiotherapy in the Treatment of Esophageal Cancer: A Systematic Review and Meta-Analysis.

Objectives: This meta-analysis aimed to assess the clinical effectiveness and safety of Javanica oil emulsion injection (JOEI) combined with the radiotherapy (RT) for treating esophageal cancer (EC). Design: A literature search was conducted for collecting the randomized controlled trials (RCTs) on EC treated by JOEI in the Cochrane Library, PubMed, Embase, the Chinese Biomedical Literature Database (SinoMed), the China National Knowledge Infrastructure Database, the China Science and Technology Journal Database (VIP), and the Wanfang Database from inception to February 4, 2017. The quality of the RCTs was evaluated by the Cochrane risk of bias assessment tool, and objective remission rate, performance status, adverse drug reactions (ADRs), 1-year survival rate, and 2-year survival rate were analyzed by Review Manager 5.3 and Stata 13.0 software. Results: A total of 11 RCTs with 909 participants were involved in this meta-analysis. The results showed that in comparison with RT alone, the JOEI combined with RT was associated with the better effects on improving objective remission rate (relative risk [RR] = 1.33, 95% confidence interval [CI 1.17-1.52], Z = 4.44, p < 0.00001), performance status (RR = 1.52, 95% CI [1.25-1.85], Z = 4.24, p < 0.00001), 1-year survival rate (RR = 1.37, 95% CI [1.17-1.60], Z = 3.86, p < 0.0001), and 2-year survival rate (RR = 1.36, 95% CI [1.09-1.70], Z = 2.68, p = 0.007). The differences between the two groups in objective remission rate, performance status, 1-year survival rate, and 2-year survival rate were statistically significant. Besides, the JOEI combined with RT could reduce the incidence of ADRs. Specifically, the statistically significant difference was detected between these two groups about leukopenia (RR = 0.39, 95% CI [0.25-0.61], Z = 4.19, p < 0.0001), radiation esophagitis (RR = 0.68, 95% CI [0.50-0.93], Z = 2.42, p = 0.02), thrombocytopenia (RR = 0.92, 95% CI [0.12-0.66], Z = 2.95, p = 0.003), and hemoglobin reduction (RR = 0.53, 95% CI [0.35-0.79], Z = 3.14, p = 0.002); however, there was no statistically significant difference for the outcome of nausea and vomiting (RR = 0.61, 95% CI [0.36-1.03], Z = 1.85, p = 0.06) between two groups. Conclusion: This meta-analysis indicated that the combination of JOEI and RT was associated with the more beneficial treatment for patients with EC compared with only receiving RT. However, more well-designed and multicenter RCTs should be carried out to confirm this finding because of the limitations of enrolled 11 RCTs.

Correlation between high FBXW7 expression in pretreatment biopsy specimens and good response to chemoradiation therapy in patients with locally advanced esophageal cancer: A retrospective study.

BACKGROUND AND OBJECTIVES: Esophageal squamous cell carcinoma (ESCC) exhibits good reactivity to chemoradiation therapy (CRT). The dysregulation of F-Box and WD Repeat Domain Containing 7 (FBXW7) is associated with therapeutic resistance in cancer cells. However, the correlation between FBXW7 expression and CRT sensitivity in patients with clinical ESCC has been investigated only in few studies. Therefore, this study aimed to elucidate the significance of FBXW7 expression in pretreatment biopsy specimens from patients with ESCC receiving CRT. METHODS: We investigated the relationship between FBXW7 expression and CRT sensitivity in 30 pretreatment biopsy specimens with histological grades of post-CRT surgically resected tumors. Furthermore, we evaluated the effects of high FBXW7 expression on the sensitivity to cytotoxic agents, including docetaxel and nedaplatin, and radiation in ESCC cells in vitro. RESULTS: High FBXW7 expression before CRT correlated with a good pathological CRT response in patients with advanced ESCC (P < .05). Further, our in vitro data showed that both chemo and radiation sensitivity increased in TE-8 and KYSE140 cells overexpressing FBXW7 compared with mock cells because of the degradation of the anti-apoptotic protein MCL1. CONCLUSIONS: The evaluation of FBXW7 expression before CRT treatment is a potential predictor of good responders among patients with ESCC receiving CRT.

Long-term results of neoadjuvant chemoradiotherapy using cisplatin and 5-fluorouracil followed by esophagectomy for resectable, locally advanced esophageal squamous cell carcinoma.

This study retrospectively evaluated the long-term results of neoadjuvant chemoradiotherapy (NCRT) followed by esophagectomy for the patients with resectable, locally advanced esophageal squamous cell carcinoma (ESCC). Altogether, 49 patients treated from 2008 to 2012 were analyzed. Chemotherapy consisted of 5-fluorouracil and cisplatin. Radiotherapy was performed with a total dose of 40 Gy in 20 fractions for primary tumor, metastatic lymph nodes, and elective nodal area. Subsequently, transthoracic esophagectomy with extensive lymphadenectomy was performed. The median follow-up time for the survivors was 86 (range, 55-111) months. Pathological complete response from NCRT was observed in 17 (35%) patients. The 5-year overall survival and relapse-free survival rates were 56% [95% confidence interval (CI): 43-71%] and 55% (95% CI: 41-69%), respectively. The 5-year locoregional control rate was 84% (95% CI: 74-95%). Multivariate analyses revealed body mass index, N-factor, and %ΔSUVmax as significant factors for overall survival. Recurrences and within-irradiation field failure were observed in 16 (31%) and 4 (8%) patients, respectively. Toxicities of NCRT were generally mild. Postoperative Grade IIIb or worse complications were seen in 14% of patients, including one Grade V case (2%). The 5-year incidence rate of late complications of Grade 3 or worse was 22% (95% CI: 7-36%). The cumulative 5-year incidence rate of metachronous malignancies was 13% (95% CI: 1-26%). NCRT followed by esophagectomy for patients with resectable, locally advanced ESCC showed favorable locoregional control and overall survival, with acceptable postoperative complications. Long-term careful follow-up for late complications and metachronous malignancies is needed.

Hyperbaric oxygenation for tumour sensitisation to radiotherapy.

BACKGROUND: Cancer is a common disease and radiotherapy is one well-established treatment for some solid tumours. Hyperbaric oxygenation therapy (HBOT) may improve the ability of radiotherapy to kill hypoxic cancer cells, so the administration of radiotherapy while breathing hyperbaric oxygen may result in a reduction in mortality and recurrence. OBJECTIVES: To assess the benefits and harms of administering radiotherapy for the treatment of malignant tumours while breathing HBO. SEARCH METHODS: In September 2017 we searched the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Library Issue 8, 2017, MEDLINE, Embase, and the Database of Randomised Trials in Hyperbaric Medicine using the same strategies used in 2011 and 2015, and examined the reference lists of included articles. SELECTION CRITERIA: Randomised and quasi-randomised studies comparing the outcome of malignant tumours following radiation therapy while breathing HBO versus air or an alternative sensitising agent. DATA COLLECTION AND ANALYSIS: Three review authors independently evaluated the quality of and extracted data from the included trials. MAIN RESULTS: We included 19 trials in this review (2286 participants: 1103 allocated to HBOT and 1153 to control).For head and neck cancer, there was an overall reduction in the risk of dying at both one year and five years after therapy (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.70 to 0.98, number needed to treat for an additional beneficial outcome (NNTB) = 11 and RR 0.82, 95% CI 0.69 to 0.98, high-quality evidence), and some evidence of improved local tumour control immediately following irradiation (RR with HBOT 0.58, 95% CI 0.39 to 0.85, moderate-quality evidence due to imprecision). There was a lower incidence of local recurrence of tumour when using HBOT at both one and five years (RR at one year 0.66, 95% CI 0.56 to 0.78, high-quality evidence; RR at five years 0.77, 95% CI 0.62 to 0.95, moderate-quality evidence due to inconsistency between trials). There was also some evidence with regard to the chance of metastasis at five years (RR with HBOT 0.45 95% CI 0.09 to 2.30, single trial moderate quality evidence imprecision). No trials reported a quality of life assessment. Any benefits come at the cost of an increased risk of severe local radiation reactions with HBOT (severe radiation reaction RR 2.64, 95% CI 1.65 to 4.23, high-quality evidence). However, the available evidence failed to clearly demonstrate an increased risk of seizures from acute oxygen toxicity (RR 4.3, 95% CI 0.47 to 39.6, moderate-quality evidence).For carcinoma of the uterine cervix, there was no clear benefit in terms of mortality at either one year or five years (RR with HBOT at one year 0.88, 95% CI 0.69 to 1.11, high-quality evidence; RR at five years 0.95, 95% CI 0.80 to 1.14, moderate-quality evidence due to inconsistency between trials). Similarly, there was no clear evidence of a benefit of HBOT in the reported rate of local recurrence (RR with HBOT at one year 0.82, 95% CI 0.63 to 1.06, high-quality evidence; RR at five years 0.85, 95% CI 0.65 to 1.13, moderate-quality evidence due to inconsistency between trials). We also found no clear evidence for any effect of HBOT on the rate of development of metastases at both two years and five years (two years RR with HBOT 1.05, 95% CI 0.84 to 1.31, high quality evidence; five years RR 0.79, 95% CI 0.50 to 1.26, moderate-quality evidence due to inconsistency). There were, however, increased adverse effects with HBOT. The risk of a severe radiation injury at the time of treatment with HBOT was 2.05, 95% CI 1.22 to 3.46, high-quality evidence. No trials reported any failure of local tumour control, quality of life assessments, or the risk of seizures during treatment.With regard to the treatment of urinary bladder cancer, there was no clear evidence of a benefit in terms of mortality from HBOT at one year (RR 0.97, 95% CI 0.74 to 1.27, high-quality evidence), nor any benefit in the risk of developing metastases at two years (RR 2.0, 95% CI 0.58 to 6.91, moderate-quality evidence due to imprecision). No trial reported on failure of local control, local recurrence, quality of life, or adverse effects.When all cancer types were combined, there was evidence for an increased risk of severe radiation tissue injury during the course of radiotherapy with HBOT (RR 2.35, 95% CI 1.66 to 3.33, high-quality evidence) and of oxygen toxic seizures during treatment (RR with HBOT 6.76, 96% CI 1.16 to 39.31, moderate-quality evidence due to imprecision). AUTHORS' CONCLUSIONS: We found evidence that HBOT improves local tumour control, mortality, and local tumour recurrence for cancers of the head and neck. These benefits may only occur with unusual fractionation schemes. Hyperbaric oxygenation therapy is associated with severe tissue radiation injury. Given the methodological and reporting inadequacies of the included studies, our results demand a cautious interpretation. More research is needed for head and neck cancer, but is probably not justified for uterine cervical or bladder cancer. There is little evidence available concerning malignancies at other anatomical sites.

The Role of Systemic Therapy in Resectable Gastric and Gastro-oesophageal Junction Cancer.

OPINION STATEMENT: Approximately 20% of patients with cancer of the stomach or gastro-oesophageal junction (GOJ) present with resectable disease. Long-term outcome after surgery alone in these patients is poor, and a combined treatment approach is the standard of care. The two approaches to managing patients with cancer of the GOJ are perioperative chemotherapy or preoperative chemoradiotherapy. Based upon the most recent evidence, patients treated with a perioperative approach and deemed suitable for a triplet regimen should be considered for pre- and post-operative FLOT (5-fluorouracil [5-FU], leucovorin, oxaliplatin and docetaxel) and those suitable for a doublet regimen should be considered for a fluoropyrimidine/platinum combination such as capecitabine and oxaliplatin. Alternatively, such patients may be considered for preoperative chemoradiotherapy according to the CROSS regimen. True gastric cancers may be treated with a perioperative approach or, as is commonly used in Asia, postoperative adjuvant chemotherapy.

Effects of javanica oil emulsion injection combined with radiotherapy versus radiotherapy alone on the efficacy and safety in patients with esophageal cancer: a pooled analysis of 1269 cases.

PURPOSE: To assess the effectiveness and safety of javanica oil emulsion injection (JOEI) when combined with radiotherapy (RT) in patients with esophageal cancer. METHODS: Electronic databases including EMBASE, PUBMED, the COCHRANE Library, China Academic Journals Full-text Database, Chinese Biomedical Literature Database, and Chinese Scientific Journals Database were searched. Two reviewers performed the search, identified and extracted eligible studies. Items including response rate, survival and safety were extracted and analyzed using Review Manager 5.3. RESULTS: A total of 16 clinical studies with 1269 esophageal cancer patients were included. The results showed that adding JOEI to RT could improve the complete response (CR rate) (Odds Ratio/OR 1.63; 95% confidence interval (CI), 1.27 to 2.10; p=0.0001), partial response (PR) (OR 1.25; 95% CI, 0.97 to 1.60; p=0.09), Relative Risk/RR (OR 1.42; 95% CI, 1.19 to 1.70; p<0.0001), quality of life (OR 3.01; 95% CI, 1.72 to 5.25; p=0.0001), and reduce the incidence of adverse events including nausea and vomiting (OR 0.81; 95% CI, 0.45 to 1.44; p=0.46) and radiation esophagitis (OR 0.47; 95% CI, 0.33 to 0.68; p<0.0001). The 1-, 2-, and 3-year survival rates in the JOEI group were significantly higher than those in the RT alone group (p<0.001). CONCLUSIONS: JOEI in combination with RT could benefit esophageal cancer patients with improved rate of response and quality of life, prolonged survival, and reduced incidence of adverse events. However, these results should be viewed with caution due to the limited quality of the included studies.

Concurrent chemo-radiotherapy with S-1 as an alternative therapy for elderly Chinese patients with non-metastatic esophageal squamous cancer: evidence based on a systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis aims to systematically assess the effects of concurrent chemo-radiotherapy (CRT) compared with radiotherapy (RT) alone for elderly Chinese patients with non-metastatic esophageal squamous cancer. METHODS: We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), China Biomedical Literature Database (CBM), and China National Knowledge Infrastructure (CNKI) databases. We retrieved randomized controlled trials on concurrent CRT with Gimeraciland Oteracil Porassium (S-1) compared with RT alone for aged Chinese patients with non-metastatic esophageal squamous cancer performed until August 2016. RESULTS: Eight eligible studies involving 536 patients were subjected to meta-analysis. As a response rate measure, a relative risk (RR) of 1.37 [95% confidence intervals (CIs): 1.24, 1.53; P = 0.00], which reached statistical significance, was estimated when concurrent CRT with S-1 was performed compared with RT alone. Sensitivity analysis on response rate confirmed the robustness of the pooled result. The RR values of 1.44 (95% CIs: 1.22, 1.70; P = 0.00) and 1.77 (95% CIs: 1.26, 2.48; P = 0.00) estimated for 1- and 2-year survival rate indices, respectively, were also statistically significant. The incidence of adverse events was similar in both groups. CONCLUSION: This review concluded that concurrent CRT with S-1 can improve the efficacy and prolong the survival period of elderly Chinese patients with non-metastatic esophageal squamous cancer and does not significantly increase the acute adverse effects of RT alone.

Treatment of esophageal cancer with radiation therapy -a pan-Chinese survey of radiation oncologists.

Lots of controversies were found about the treatment in relation to radiation therapy (RT) for esophageal squamous cell carcinoma (ESCC). We designed a questionnaire of these controversies to do a pan-Chinese survey of radiation oncologists (ROs). For operable ESCC, 53% ROs chose surgery plus postoperative chemoradiotherapy (CRT), while 40% chose preoperative CRT plus surgery. For target volume of postoperative RT, most ROs (92%) would delineate tumor bed plus involved lymph nodes region before surgery. For definitive RT, most ROs (81%) would give patients higher RT dose to 60-65Gy. For radiation target volume, most ROs would give patients prophylactic irradiation of the bilateral superclavicular-lymph nodes region for cervical ESCC (93%), and the left gastric lymph nodes region for lower thoracic ESCC (72%). For the treatment of mediastinal lymph nodes, 72% ROs preferred elective nodal irradiation, while 28% did the involved nodal irradiation. For concurrent chemotherapy regimen, PF (5-Fu + cisplatin) and TP (cisplatin + paclitaxel) were used widely (49% and 46%, respectively). During simulation, four-dimensional computer tomography (4D CT) was not widely used (48%), even for cervical or lower thoracic ESCC (52%). For daily RT delivery, only 66% ROs would perform imaging guidance RT daily. In summary, more controversies existed in the treatment of ESCC with RT in China, including treatment strategy, radiation dose and target contour. Future goals include standardization of treatment strategy, radiation dose, and target contour, and application of 4D CT and daily imaging guidance, and pursuit of randomized trials in Chinese population.