Accurate location describe and management of lymph node recurrence after esophagectomy for thoracic esophageal squamous cell carcinoma：a retrospective cohort study.

BACKGROUND: Describe the accurate locations of lymph node recurrence LNR of Chinese patients with postoperative thoracic esophageal squamous cell carcinoma (ESCC) is essential for determining the need for further surveillance protocols and treatments. We aimed to evaluate the patterns of postoperative ESCC and its current risk stratification with LNR. METHODS: This population-based cohort study included a retrospective review of the medical records and image material of patients with ESCC who underwent LNR after radical surgery between January 2013 and September 2022, with a median follow-up time of 5.71 years. Clinical features were extracted from these records, and survival analysis was performed. The primary endpoint was the accurate location and range of LNR according to the nomenclature of the Japanese Society for Esophageal Diseases. The second endpoints was to explore the related factors of recurrence range (RR) and overall survival (OS) . RESULTS: A total of 3268 lymph node regions were recurrence from 1129 patients, with a mean of 2.89 regions per patient. No.104, 106 and 107 was the most common recurrence of thoracic ESCC with an LNR rate higher than 15%. In upper thoracic ESCC, No.105 was a common recurrence site and abdominal lymph node recurrence was rare. In lower thoracic ESCC, retroperitoneal lymph node was a unique regions (15.4%). Anastomotic recurrence is an important recurrence pattern in patients with postoperative esophageal cancer, with an incidence of 24.5%. Rates of lymph node recurrence in range of lymph node dissection was low (13.9%). The median time of LRT was 20.0 (1.5-184.0) months. High range of recurrence was associated with significantly poorer OS in patients. Multiple linear regression analysis identified demonstrated N stage, tumor differentiation, adjuvant radiotherapy and total lymph nodes removed were association with recurrence range for patients. CONCLUSIONS: Supraclavicular and upper mediastinums lymph nodes were common recurrence site for ESCC patients , and careful initial staging and surveillance are needed. Thorough lymph node dissection may reduce the range of regional recurrence.

Analysis of heart displacement during thoracic radiotherapy based on electrocardiograph-gated 4-dimensional magnetic resonance imaging.

Background: Periodic cardiac movement may expose the heart to radiation field induced damage, leading to radiation-induced heart disease (RIHD). Studies have proven that delineation of the heart based on planning CT fails to show the real margin of the substructures and a compensatory margin should be applied. The purpose of this study was to quantify the dynamic changes and the compensatory extension range by breath-hold and electrocardiogram gated 4-dimensional magnetic resonance imaging (4D-MRI), which had the advantage of discriminating soft tissues. Methods: Eventually, 15 patients with oesophageal or lung cancers were enrolled, including one female and nine males aged from 59 to 77 years from December 10th, 2018, to March 4th, 2020. The displacement of the heart and its substructures was measured through a fusion volume and the compensatory expansion range was calculated by expending the boundary on the planning CT to that of the fusion volume. The differences were tested through the Kruskal-Wallis H test and were considered significant at a two-side P<0.05. Results: The extent of movement of heart and its substructures during one cardiac cycle were approximately 4.0-26.1 millimetre (mm) in anterior-posterior (AP), left-right (LR), and cranial-caudal (CC) axes, and the compensatory margins should be applied to planning CT by extending the margins by 1.7, 3.6, 1.8, 3.0, 2.1, and 2.9 centimetres (cm) for pericardium; 1.2, 2.5, 1.0, 2.8, 1.8, and 3.3 cm for heart; 3.8, 3.4, 3.1, 2.8, 0.9, and 2.0 cm for interatrial septum; 3.3, 4.9, 2.0, 4.1, 1.1, and 2.9 cm for interventricular septum; 2.2, 3.0, 1.1, 5.3, 1.8, and 2.4 cm for left ventricular muscle (LVM); 5.9, 3.4, 2.1, 6.1, 5.4, and 3.6 cm for antero-lateral papillary muscle (ALPM); and 6.6, 2.9, 2.6, 6.6, 3.9, and 4.8 cm for postero-medial papillary muscle (PMPM) in anterior, posterior, left, right, cranial, and caudal directions, respectively. Conclusions: Periodic cardiac activity causes obvious displacement of the heart and its substructures, and the motion amplitude of substructures differs. Extending a certain margin as the compensatory extension to represent the organs at risk (OAR) and then limiting the dose-volume parameters could be performed in clinical practice.

Eccentric Compression Properties of FRP-Concrete-Steel Double-Skin Square Tubular Columns.

FRP (fiber-reinforced polymer)-concrete-steel double-skin square tubular (FCSST) columns are composed of an outside FRP tube, an inside steel tube and the concrete filled between them. Under the continuous constraint of the outside and inside tube, the strain, strength and ductility of concrete are improved significantly compared with those of traditionally reinforced concrete without lateral restraint. Additionally, the outside and inside tube not only function as the permanent formwork in casting but improve the bending and shear resistance of composite columns. Meanwhile, the hollow core also reduces the weight of the structure. Through the compressive testing of 19 FCSST columns subjected to eccentric load, this study focuses on the influence of eccentricity and layers of axial FRP cloth (away from the loading point) on the evolution of axial strain along the cross-section, axial bearing capacity, axial load-lateral deflection curve and other eccentric properties. The results can provide basis and reference for the design and construction of FCSST columns and are of great theoretical significance and practical value for the application of composite columns in the engineering of structures in a corrosive environment and other harsh conditions.

Sintilimab as maintenance treatment for local/regional recurrent esophageal squamous carcinoma after concurrent chemoradiotherapy: a single-arm Ib/II phase study.

Background: Esophageal cancer (EC) is an aggressive neoplasm of the gastrointestinal tract that is usually treated with a combination of chemotherapy, radiotherapy (RT), and/or surgery, according to disease status. Despite the availability of multimodal therapeutic strategies, local recurrence is frequently observed. However, there is no standard treatment or promising therapeutic approach for local recurrence or metastatic esophageal carcinoma after the RT. This study tended to investigate the efficacy and safety of sintilimab maintenance after concurrent chemoradiotherapy (CCRT) for local/regional recurrent esophageal squamous carcinoma. Methods: This study was a single-arm, phase Ib/II trial conducted in a single site in China. Patients previously radically treated (surgery or CCRT), histologically confirmed, local or regional recurrence esophageal squamous carcinoma, qualified for the study design, were treated with 25-28 times radiotherapy plus raltitrexed once every 3 weeks for up to two cycles. Patients who have not progressed after CCRT received sintilimab as maintenance once every 3 weeks up to 1 year. Primary endpoints were overall survival (OS) and safety. Secondary endpoints were progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR). Results: Between September 2019 and March 2022, in a total of 36 enrolled patients, 34 pts completed CCRT. Three patients excluded due to violation of the exclusion criteria (1 pt) and consent withdrawal (2 pts). Finally, 33 pts were included in the final analysis, in which 3 pts had disease progression, and the remaining 30 entered maintenance therapy with sintilimab. The median follow-up time was 12.3 months. Median OS was 20.6 months (95%CI 10.5-NA) and the 1-year OS rate was 64%. Median PFS was 11.5 months (95%CI 5.29-21.3) and the 1-year PFS rate was 43.6%. The ORR was 63.6% (95%CI 44.6-77.8), including 2 cases of CR and 19 cases of PR. The DCR was 19.9%, the median DOR was 19.5 months, and the median TTR was 2.4 months. The rate of any grade TRAEs was 96.7%; ≥Grade 3 TRAE was 23.4%. The incidence of immune-related AE was 60%, most of which were grade 1-2, and only one case of thyroid-stimulating hormone increased was irAE with grade 3 or above. Conclusion: Sintilimab has shown promising clinical efficacy and a manageable safety profile as maintenance therapy after CCRT for local/regional recurrent esophageal squamous carcinoma. In addition, further confirmation from a large-scale real-world study is still needed.

The efficacy and safety of PD-1 inhibitors for EGFR-mutant non-small cell lung cancer after tyrosine kinase inhibitor failure: a retrospective real-world cohort study.

Background: Acquired drug resistance to various tyrosine kinase inhibitor (TKI) inevitably develops in almost all epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). The present study aimed to evaluate the efficacy and safety of programmed cell death protein 1 (PD-1) inhibitors for such patients after TKI failure and further explore the subpopulation that exhibited the most benefit. Methods: A total of 102 EGFR-mutant NSCLC patients who received PD-1 inhibitors after developing resistance to EGFR-TKIs were included in the study. The primary endpoints were progression-free survival (PFS) and grade 3-5 adverse events (AEs), while the secondary endpoints were overall survival (OS), disease control rate (DCR) and subgroup analyses. Results: All the 102 patients received 2 or more lines of immunotherapy. The overall median PFS was 4.95 months [95% confidence interval (CI): 3.91-5.89 months]. The EGFRL858R group showed a significant PFS benefit compared with the EGFRD19 group (6.4 vs. 3.5 months, P=0.002), and likewise for the DCR between the 2 groups (EGFRL858R vs. EGFRD19 group: 84.3% vs. 66.7%, P=0.049). In addition, median PFS in the EGFRT790M-negative group (6.47 months) was significantly longer than the EGFRT790M-positive group (3.20 months) (P=0.003). The overall OS was 10.70 months (95% CI: 8.92-12.48 months), without a prognostic factor. There was a trend towards improved PFS and OS with combination therapy. The incidence of grade 3-5 treatment-related AEs was 19.6%, while the incidence of grade 3-5 immune-related AEs (irAEs) was 6.9%. Treatment-related AEs were similar in different mutation subtypes. The incidence of grade 3-5 irAEs was higher in the EGFRD19 group (10.3%) compared with the EGFRL858R group (5.9%), and likewise in the EGFRT790M-negative group (10%) compared with the EGFRT790M-positive group (2.6%). Conclusions: After EGFR-TKI failure, PD-1 inhibitors provided better survival in advanced NSCLC for the EGFRL858R subgroup and EGFRT790M-negative subgroup, and there was a trend towards improved outcomes with combination therapy. In addition, toxicity was well tolerated. Our real-world study increased the population size and obtained a similar survival outcome compared from clinical trials.

Reduction of inter-observer variability using MRI and CT fusion in delineating of primary tumor for radiotherapy in lung cancer with atelectasis.

Purpose: To compare the difference between magnetic resonance imaging (MRI) and computed tomography (CT) in delineating the target area of lung cancer with atelectasis. Method: A retrospective analysis was performed on 15 patients with lung cancer accompanied by atelectasis. All positioning images were transferred to Eclipse treatment planning systems (TPSs). Six MRI sequences (T1WI, T1WI+C, T1WI+C Delay, T1WI+C 10 minutes, T2WI, DWI) were registered with positioning CT. Five radiation oncologists delineated the tumor boundary to obtain the gross tumor volume (GTV). Conformity index (CI) and dice coefficient (DC) were used to measure differences among observers. Results: The differences in delineation mean volumes, CI, and DC among CT and MRIs were significant. Multiple comparisons were made between MRI sequences and CT. Among them, DWI, T2WI, and T1WI+C 10 minutes sequences were statistically significant with CT in mean volumes, DC, and CI. The mean volume of DWI, T2WI, and T1WI+C 10 minutes sequence in the target area is significantly smaller than that on the CT sequence, but the consistency is higher than that of CT sequences. Conclusions: The recognition of atelectasis by MRI was better than that by CT, which could reduce interobserver variability of primary tumor delineation in lung cancer with atelectasis. Among them, DWI, T2WI, T1WI+C 10 minutes may be a better choice to improve the GTV delineation of lung cancer patients with atelectasis.

Invar Effect of the Fe13 Cluster.

The Invar effect, which refers to magnetic alloys having an anomalously small thermal expansion, has been under extensive investigations over the past century. However, study on the thermal expansion of clusters and their Invar effect is still lacking. In this letter, we calculate the thermal expansion properties of Fe13-nNin (n = 0, 3, 6, 9, 12, 13) clusters and find that the Fe13 cluster has an abnormally small thermal expansion, which is due to its remarkable magneto-volume effect. It is also revealed that the strong magneto-volume effect of the Fe13 cluster is highly related with the two magnetic states, the same as the interpretation for the Invar effect of a bulk alloy. The anomalously small thermal expansion of the Fe13 cluster is the manifestation of the Invar effect at the cluster scale.

Risk factors of esophageal fistula induced by re-radiotherapy for recurrent esophageal cancer with local primary site.

PURPOSE: The purpose of the present study was to investigate risk factors for esophageal fistula (EF) in patients with recurrent esophageal cancer receiving re-radiotherapy with or without chemotherapy. METHODS: We reviewed retrospectively the clinical characters and dosimetric parameters of 96 patients with recurrent esophageal cancer treated with re-radiotherapy in Cancer Hospital Affiliated to Shandong First Medical University between August 2014 and January 2021.Univariate and multivariate logistic regression analyses were provided to determine the risk factors of EF induced by re-radiotherapy. RESULTS: The median time interval between two radiotherapy was 23.35 months (range, 4.30 to 238.10 months). EF occurred in 19 patients (19.79%). In univariate analysis, age, T stage, the biologically equivalent dose in the re-radiotherapy, total biologically equivalent dose, hyperfractionated radiotherapy, ulcerative esophageal cancer, the length of tumor and the maximum thickness of tumor had a correlation with the prevalence of EF. In addition, age (HR = 0.170, 95%CI 0.030-0.951, p = 0.044), T stage (HR = 8.369, 95%CI 1.729-40.522, p = 0.008), ulcerative esophageal cancer (HR = 5.810, 95%CI 1.316-25.650, p = 0.020) and the maximum thickness of tumor (HR = 1.314, 95%CI 1.098-1.572, p = 0.003) were risk factors of EF in multivariate logistic regression analysis. CONCLUSIONS: The incidence of EF was significantly increased in patients with recurrent esophageal cancer who underwent re-radiotherapy. This study revealed that age, T stage, ulcerative esophageal cancer and the maximum thickness of the tumor were risk factors associated with EF. In clinical work, patients with risk factors for EF ought to be highly concerned and individualized treatment plans should be taken to reduce the occurrence of EF.

Clinical outcomes of extensive-stage small cell lung cancer patients treated with thoracic radiotherapy at different times and fractionations.

OBJECTIVE: The purpose of this study was to assess whether thoracic radiotherapy (TRT) combined with chemotherapy (CHT) showed promising anti-tumour activity in extensive-stage small cell lung cancer (ES-SCLC), to explore practice patterns for the radiation time and dose/fractionation and to identify prognostic factors for patients who would benefit from CHT/TRT. METHODS: A total of 492 ES-SCLC patients were included from January 2010 to March 2019, 244 of whom received CHT/TRT. Propensity score matching was performed to minimize bias between the CHT/TRT and CHT-alone groups. Patients in the CHT/TRT group were categorized into four subgroups based on the number of induction CHT cycles. For effective dose fractionation calculations, we introduced the time-adjusted biological effective dose (tBED). Categorical variables were analysed with chi-square tests and Fisher's exact tests. Kaplan-Meier curves were generated to estimate survival rates using the R-project. Multivariate prognostic analysis was performed with Cox proportional hazards models. RESULTS: Patients who received CHT/TRT experienced improved overall survival (OS) (18.1 vs 10.8 months), progression-free survival (PFS) (9.3 vs 6.0 months) and local recurrence-free survival (LRFS) (12.0 vs 6.6 months) before matching, with similar results after matching. In the CHT/TRT group, the median LRFS times for the groups based on the radiation time were 12.7, 12.0, 12.0, and 9.0 months, respectively. Early TRT had a tendency to prolong PFS (median 10.6 vs 9.8 vs 9.0 vs 7.7 months, respectively, p = 0.091) but not OS (median 17.6 vs 19.5 vs 17.2 vs 19.0 months, respectively, p = 0.622). Notably, patients who received TRT within 6 cycles of CHT experienced prolonged LRFS (p = 0.001). Regarding the radiation dose, patients in the high-dose group (tBED > 50 Gy) who achieved complete response and partial response (CR and PR) to systemic therapy had relatively short OS (median 27.1 vs 22.7, p = 0.026) and PFS (median 11.4 vs 11.2, p = 0.032), but the abovementioned results were not obtained after the exclusion of patients who received hyperfractionated radiotherapy (all p > 0.05). CONCLUSION: CHT/TRT could improve survival for ES-SCLC patients. TRT performed within 6 cycles of CHT and hyperfractionated radiotherapy (45 Gy in 30 fractions) may be a feasible treatment scheme for ES-SCLC patients.

Atomistic Origin of the Complex Morphological Evolution of Aluminum Nanoparticles during Oxidation: A Chain-like Oxide Nucleation and Growth Mechanism.

Metal nanoparticles usually show different oxidation dynamics from bulk metals, which results in various oxide nanostructures because of their size-related surface effects. In this work, we have found and investigated the chain-like nucleation and growth of oxides on the aluminum nanoparticle (ANP) surface, using molecular dynamics simulations with the reactive force-field (ReaxFF). After nucleation, the chain-like oxide nuclei could stay on the ANP surface and continue growing into an oxide shell, extend outward from the surface to form longer oxide chains, or detach from the ANP to generate independent oxide clusters, which is highly dependent on the oxygen content, temperature, and nanoparticle size. Our results emphasize the complicated interplay between the surface structure of nanoparticles and the environmental conditions in determining the formation of oxides, which provides insights into the atomic-scale oxidation mechanism of metal nanoparticles.

Exploration of the Radiotherapeutic Clinical Target Volume Delineation for Gastric Cancer from Lymph Node Metastases.

AIM: To clarify the clinical target volume of regional lymph nodes (CTVn) delineation of gastric adenocarcinoma. MATERIALS AND METHODS: The pattern of lymph node metastases (LNM) of a total of 1,473 patients with gastric cancer (GC) who had undergone gastrectomy and lymphadenectomy with more than 15 lymph nodes retrieved was retrospectively examined. RESULTS: A univariate analysis showed that T stage (p<0.001), macroscopic type (p=0.001), tumor differentiation (p<0.001), maximum diameter of tumor (p<0.001) as well as cancer embolus (p<0.001) were closely associated with the rate of LNM. While by multivariate analysis, gender [odds ratio (OR=0.687, p<0.05], maximum diameter (OR=1.734, p<0.001), tumor differentiation (OR=1.584, p<0.001), T stage (OR=2.066, p<0.001) and cancer embolus (OR=4.912, p<0.001) were strongly associated with the rate of LNM. CONCLUSION: In conclusion, for male patients with GC with large, deeply invasive, poorly differentiated, diffusely infiltration and positive cancer embolus, the radiation fields should be enlarged appropriately.

MicroRNA-337 inhibits cell proliferation and invasion of cervical cancer through directly targeting specificity protein 1.

Cervical cancer is the fourth most commonly occurring malignancy in females worldwide. Accumulated studies have demonstrated that the aberrant expression of microRNAs plays important roles in tumorigenesis and tumor development and potentially serves as therapeutic targets in various cancers including cervical cancer. Therefore, the identification of specific microRNAs contributed to cervical cancer formation and progression would provide critical clues for the treatments for patients with this disease. In this study, we aimed to detect microRNA-337 expression pattern and investigate the biological roles of microRNA-337 in the regulation of the malignant phenotypes of cervical cancer and its underlying mechanisms. We found that microRNA-337 expression was significantly downregulated in cervical cancer tissues and cell lines. In addition, its aberrant expression levels were positively correlated with tumor size, International Federation of Gynecology and Obstetrics stage, and lymph node metastasis of cervical cancer. The ectopic expression of microRNA-337 suppressed cell proliferation and invasion of cervical cancer in vitro. Furthermore, specificity protein 1 was identified as a direct target of microRNA-337 in cervical cancer. The expression of specificity protein 1 increased in cervical cancer tissues and negatively correlated with microRNA-337 expression level. Moreover, rescue experiments revealed that upregulation of specificity protein 1 could rescue the effects of microRNA-337 on cervical cancer cells. Taken together, these findings collectively demonstrate that microRNA-337 exerts its tumor-suppressing roles in cervical cancer by directly targeting specificity protein 1, thereby indicating a potential novel potential therapeutic target for patients with cervical cancer.

Re-irradiation alternatives for recurrent high-grade glioma.

Despite advances in the fields of surgery, chemotherapy and radiotherapy, the prognosis for high-grade glioma (HGG) remains unsatisfactory. The majority of HGG patients experience disease recurrence. To date, no standard treatments have been established for recurrent HGG. Repeat surgery and chemotherapy demonstrate moderate efficacy. As recurrent lesions are usually located within the previously irradiated field, a second course of irradiation was once considered controversial, as it was considered to exhibit unsatisfactory efficacy and radiation-related toxicities. However, an increasing number of studies have indicated that re-irradiation may present an efficacious treatment for recurrent HGG. Re-irradiation may be delivered via conventionally fractionated stereotactic radiotherapy, hypofractionated stereotactic radiation therapy, stereotactic radiosurgery and brachytherapy techniques. In the present review, the current literature regarding re-irradiation treatment for recurrent HGG is summarized with regard to survival outcome and side effects.

Prognostic significance of miR-126 in various cancers: a meta-analysis.

OBJECTIVE: Recent studies have demonstrated that microRNA-126 (miR-126) might be a promising prognostic factor for cancer patients. This meta-analysis was conducted to assess the effectiveness of miR-126 as a prognostic biomarker for various cancers. METHODS: The search of studies was performed by using PubMed and Embase until January 22, 2016. Pooled hazard ratio (HR) with 95% confidence interval (CI) for patients' survival was calculated. A fixed-effect or random-effects model was applied according to heterogeneity. The trim and fill method was used to adjust pooled HR. RESULTS: In all 17 articles comprising of 2,437 participants were included in this meta-analysis. The results indicated that a high level of miR-126 played a favorable role in the overall survival (HR 0.70, 95% CI: 0.62-0.79, random-effects model), with a heterogeneity measure index of I (2)=63.2% (P<0.01). Subgroup analyses showed that pooled HR was more significant in patients with digestive system cancers (HR 0.70, 95% CI: 0.59-0.83, fixed-effects model) and respiratory system cancers (HR 0.71, 95% CI: 0.59-0.85, random-effects model). Owing to publication bias, HR was adjusted to 0.59 (0.463-0.752, P<0.01) by the trim and fill method. CONCLUSION: miR-126 could be a promising biomarker for cancer prognosis prediction, especially in patients with digestive or respiratory system cancers.

Phase I study of concurrent selective lymph node late-course accelerated hyperfractionated radiotherapy and S-1 plus cisplatin for locally advanced oesophageal squamous cell carcinoma.

OBJECTIVE: This Phase I study aimed to assess the safety and efficacy of concurrent selective lymph node (SLN) late-course accelerated hyperfractionated (LCAF) intensity-modulated radiotherapy (IMRT) and S-1 plus cisplatin (CDDP) for the locally advanced oesophageal squamous-cell carcinoma (ESCC). METHODS: The total dose of SLN LCAF IMRT was 59.6 Gy/34 fractions in 5.4 weeks. The concurrent chemotherapy (CCRT) was administered as follows: CDDP 25 mg m(-2) on Days 1-3 and Days 22-24; S-1 was applied in a de-escalating dosage with a decrement of 10 mg m(-2) per day, from its full dose level of 80 mg m(-2), orally twice daily on Days 1-14 and Days 22-35. We inferred the maximum-tolerated dose (MTD), dose-limiting toxicities (DLTs) and recommended dose, according to adverse reaction during CCRT. RESULTS: Totally, 15 patients with ESCC with T2-4N0-1M0-1a were enrolled in Dose Level 1 (80 mg m(-2)). In the initial five patients, two patients developed DLTs. As MTD was not reached, five additional patients were treated with the same dose level, and DLTs occurred in only one patient. Similar results were found in the last five patients. After CCRT, the objective response rates were 100% for primary tumours and 86.2% for metastatic lymph nodes, respectively. Totally, the observed Grade 3 toxicities during CCRT were leukopenia (20%), neutropenia (20%) and dermatitis (13.3%), and no Grade 4 toxicity occurred. The Kaplan-Meier-estimated overall and progression survival rates were 86.7% and 66.7% (1 year), 73.3% and 60% (2 years) and 73.3% and 60% (3 years). CONCLUSION: The concurrent SLN LCAF IMRT and chemotherapy with S-1 and CDDP was well tolerated and showed promising efficacy. The dose of S-1 in this regimen was recommended with 80 mg m(-2) orally twice daily on Days 1-14 and Days 22-35. ADVANCES IN KNOWLEDGE: CCRT with S-1 plus CDDP exhibited encouraging results with milder toxicities, high objective response rates and ideal overall survival time.

Diagnostic and predictive significance of serum microRNA-7 in esophageal squamous cell carcinoma.

MicroRNA-7 has been reported to participate in tumorigenesis and progression by several signaling pathways in various tumors. However, its potential as a serum diagnostic factor and predictive biomarker for esophageal squamous cell carcinoma (ESCC) has not been studied. Serum samples were collected from 105 pathologically proven ESCC patients and 30 age- and gender-matched healthy controls. All patients were treated with concurrent chemoradiotherapy (CRT). Real­time polymerase chain reaction was carried out to measure the serum miR-7 expression level. The data were compared among radio-sensitive and radio-resistant groups, and healthy volunteers to elucidate the diagnostic and predictive value of miR-7 expression. Finally, in vitro experiments are used to clarify the mechanisms of the miR-7. In the present study, we found that the serum miR-7 level of ESCC patients was 4.74-fold lower as compared with healthy subjects, indicating that serum miR-7 expression could be an excellent diagnostic factor. The serum miR-7 expression level for these responsive patients was 2.34­fold higher than that for non-responsive patients, indicating it as a valuable biomarker for predicting treatment response of ESCC patients to concurrent chemoradiation treatment. We also found that miR-7 levels are strongly correlated with tumor length and the status of lymph node metastasis (P<0.05). In contrast, the responsiveness of therapy is significantly correlated with CEA (P<0.05), Cyfra21-1 (P<0.05), serum miR-7 level (P<0.05) and myelosuppression (P<0.01). In addition, the experimental data also suggest that miR-7 can interfere with EGFR mRNA translation. In ESCC patients, serum miR-7 has the potential to serve as a noninvasive biomarker of diagnosis and predicting treatment responses to concurrent chemoradiation therapy. ESCC patients with lower Cyfra21-1 and CEA, higher miR-7 and severe myelosuppression were much more sensitive to CRT. In addition, miR-7 may function by interfering with EGFR mRNA translation, but not degradation.

Morphological factors and cardiac doses in whole breast radiation for left-sided breast cancer.

BACKGROUND: To investigate the impact of the breast size, shape, maximum heart depth (MDH), and chest wall hypotenuse (the distance connecting middle point of the sternum and the length of lung draw on the selected transverse CT slice) on the volumetric dose to heart with whole breast irradiation (WBI) of left-sided breast cancer patients. MATERIALS AND METHODS: Fifty-three patients with left-sided breast cancer undergoing adjuvant intensity-modulated radiotherapy (IMRT) were enrolled in the study. The primary breast size and shape, MHD and DCWH (chest wall hypotenuse) were contoured on radiotherapy (RT) planning CT slices. The dose data of hearts were obtained from the dose-volume histograms (DVHs). Data were analyzed by one-way analysis of variance (ANOVA), Student's t-test and linear regression analysis. RESULTS: Breast size was independent of heart dose, whereas breast shape, MHD and DCWH were correlated with heart dose. The shapes of breasts were divided into four types, as the flap type, hemisphere type, cone type and pendulous type with heart mean dose being 491.8±234.6 cGy, 752.7±219.0 cGy, 620.2±275.7 cGy, and 666.1±238.0 cGy, respectively. The flap type of breasts shows a strong statistically reduction in heart dose, compared to others (p=0.008 for V30 of heart). DCWH and MHD were found to be the most important parameters correlating with heart dose in WBI. CONCLUSIONS: More attention should be paid to the heart dose of non-flap type patients. The MHD was found to be the most important parameter to correlate with heart dose in tangential WBI, closely followed by the DCWH, which could help radiation oncologists and physicsts evaluate heart dose and design RT plan in advance.

The expression of miR-21 and miR-375 predict prognosis of esophageal cancer.

BACKGROUND: MicroRNA is a class of small, well-conserved, non-coding RNAs, and could play a potential role as diagnostic and prognostic biomarkers of esophageal cancers. We aimed to review comprehensively the evidence of microRNA as prognostic biomarkers in esophageal cancers. METHODS: Studies were identified by searching PubMed, Embase and Web of Science until November 2013. Descriptive characteristics of studies were described and an additional meta-analysis for specific microRNAs which were studied most frequently was performed. Pooled hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated. Fixed model or random model method was chosen depending on the heterogeneity among the studies. RESULTS: Twenty-two studies including a total of 1946 participants were enrolled after a strict filtering and qualifying process. Among 33 prognostic microRNAs identified for esophageal cancer, miR-21 and miR-375 appeared more frequently. The median study size was 70.5 patients (29-249 patients) and the median HR was 3.305 (IQR=1.615-7.31). For the studies evaluating miR-21's association with overall survival (OS), the pooled HR suggested that high level of miR-21 has a negative impact on OS (HR=1.52[1.17-1.98], P=0.001). As for miR-375, the pooled HR for OS (high/low) was 0.53 (95% CI: 0.39-0.73, P<0.001), indicated that low level of miR-375 has a negative impact on OS. These results indicated that microRNAs show promising associations with prognosis in esophageal cancer. Up-regulation of miR-21 and down-regulation of miR-375 can predict unfavourable prognosis in esophageal cancer.