Abstract Purpose: To investigate the interobserver variability (IOV) in target volume delineation of definitive radiotherapy for thoracic esophageal cancer (TEC) among cancer centers in China, and ultimately improve contouring consistency as much as possible to lay the foundation for multi-center prospective studies. Methods: Sixteen cancer centers throughout China participated in this study. In Phase 1, three suitable cases with upper, middle, and lower TEC were chosen, and participants were asked to contour a group of gross tumor volume (GTV-T), nodal gross tumor volume (GTV-N) and clinical target volume (CTV) for each case based on their routine experience. In Phase 2, the same clinicians were instructed to follow a contouring protocol to re-contour another group of target volume. The variation of the target volume was analyzed and quantified using dice similarity coefficient (DSC). Results: Sixteen clinicians provided routine volumes, whereas ten provided both routine and protocol volumes for each case. The IOV of routine GTV-N was the most striking in all cases, with the smallest DSC of 0.37 (95% CI: 0.32-0.42), followed by CTV, whereas GTV-T showed high consistency. After following the protocol, the smallest DSC of GTV-N was improved to 0.64 (95% CI: 0.45-0.83, P=0.005) but the DSC of GTV-T and CTV remained constant in most cases. Conclusion: Variability in target volume delineation was observed, but it could be significantly reduced and controlled using mandatory interventions.
Objective
To compare the dosimetric difference between volumetric modulated arc therapy (VMAT) and static intensity modulated radiotherapy (IMRT) for esophageal carcinoma.
Methods
Thirty patients were selected in this study, including 5 cases in the cervical, 5 the lower thorax, 10 the upper thorax and 10 the middle thorax. VMAT plans with a single arc and IMRT plans with five fields designed for each patients. Planning target volume (PTV) were prescribed to 60 Gy in 30 fractions. Delta 4 was used to verifie the dosimetric of treatment plans. Using paired t-test or Wilcoxon signed-test to compare the dose distribution on planning and organs at risk (OAR). The monitor units and treatment time were also evaluated to measure the treatment efficiency.
Results
All the VMAT and IMRT plans can satisfy the clinical dosimetry requirements. VMAT had better conformal index for PTV than IMRT (P = 0. 008 ). VMAT was better than IMRT by reducing the Dmax of spinal cord (P = 0. 032), while the V30, V40 and Dmean of heart were significantly higher (P = 0. 041,0. 012,0. 002). For cervicals, the V5, V10, V15 and mean dose of lung were significant higher in VMAT than those in IMRT (P = 0. 002 -0. 002, 0. 002). For uppers, the values of heart V30 and Dmean were significantly larger in VMAT than IMRT (P = 0. 030,0. 026). However, the Dmax of spinal cord in VMAT was lower than IMRT (P = 0. 006). For middles, VMAT reduced V10, V15, V20 of lung (P = 0. 015, 0. 028,0. 041). There were no significant differences between VMAT and IMRT in the lowers (P=0. 262-0. 998). The 3 mm/3% γ pass rate was 92. 75% for VMAT and 92. 98% for IMRT (P=0.826). The average MU of VMAT (460. 66 MU) was reduced by 11. 84% compared with IMRT (522.55 MU) (P= 0.001). The delivery time of VMAT (139.6 s) compared with IMRT (298. 73 s) was reduced by an average of 53. 27% (P = 0. 000) .
Conclusions
Compared with IMRT, VMAT improved the OARs dose sparing and the target CI with similar dose distribution to the target. VMAT required fewer MU, shorten the treatment time significantly. The implementation of Synergy is stable and reliable.
Key words:
Esophageal neoplasms/volumetric modulated arc therapy; Esophageal neoplasms/ intensity-modulated radiotherapy; Dosimetry; γ pass rate
Objective
To observe the long-term survival and adverse reactions in patients with stage T4N (+ ) Ⅲ middle and lower thoracic esophageal carcinoma undergoing intensity-modulated radiotherapy (IMRT).
Methods
From 2004 to 2010, 300 patients with stage T4N (+ ) Ⅲ middle and lower thoracic esophageal carcinoma, consisting of 202 treated with three-dimensional conformal radiotherapy (3DCRT) and 98 treated with IMRT, were enrolled as subjects. All patients received conventionally fractionated radiotherapy with a prescribed dose of 60 Gy. The long-term survival and adverse reactions were compared between patients treated with the two different radiotherapy regimens. The survival rates were calculated by the Kaplan-Meier method and analyzed by the log-rank test.
Results
The 5-and 7-year sample sizes were 239 and 120, respectively. The 3DCRT group had significantly lower 1-, 3-, 5-, and 7-year local control (LC) and overall survival (OS) rates than the IMRT group (64.4% vs. 68.3%, 40.6% vs. 55.3%, 38.3% vs. 51.9%, 34.2% vs. 51.9%, P=0.048; 54.5% vs. 63.3%, 19.8% vs. 34.7%, 14.7% vs. 24.4%, 10.9% vs. 20.3%, P=0.013). The stratified analysis showed that for patients older than 65 years, with the length of esophageal lesion>8.0 cm before radiotherapy, the largest diameter of esophageal lesion in computed tomography image>4.6 cm, gross tumor volume (GTV)>60 cm3, metastases to adjacent tissues or organs, stage N2, and without chemotherapy, the IMRT group had a significantly higher OS rate than the 3DCRT group (P=0.022, 0.003, 0.022, 0.034, 0.016, 0.044, 0.047). The GTVDmin and GTVD100 were significantly higher in the IMRT group than in the 3DCRT group (P=0.000, 0.000), while the Dmax of the spinal cord was significantly lower in the IMRT group than in the 3DCRT group (P=0.000). Compared with the 3DCRT group, the IMRT group had a significantly higher incidence of acute radiation-induced esophagitis, particularly grade 1-2 esophagitis (P=0.000). The mortality rate caused by local tumor was significantly higher in the 3DCRT group than in the IMRT group (P=0.039).
Conclusions
In the treatment of locally advanced middle and lower thoracic esophageal carcinoma, IMRT is safe and effective; it significantly improves the LC rate and long-term survival without severe toxicity to normal tissues. The results of this retrospective study need to be confirmed by prospective randomized controlled studies.
Key words:
Esophageal neoplasms/radiotherapy; Radiotherapy, three-dimensional; Radiotherapy, intensity-modulated; Prognosis
Abstract Background Radiotherapy is a main therapeutic method for cancers, including colon cancer. In the current study, we aim to explore the effects of circular RNA (circRNA) circ_0055625 in the progression and radiosensitivity of colon cancer and the underlying mechanism. Methods The expression of circ_0055625 and musashi homolog 1 (MSI1) mRNA was detected by quantitative real-time polymerase chain reaction (qRT-PCR). MSI1 protein expression was determined by Western blot. Cell proliferation was assessed by cell counting kit-8 (CCK-8) and colony formation assays. Cell survival fraction, apoptosis, and invasion were investigated by colony formation assay, flow cytometry analysis, and transwell invasion assay, respectively. Cell migration was detected by wound-healing and transwell migration assays. The binding relationship between microRNA-338-3p (miR-338-3p) and circ_0055625 or MSI1 was predicted by online databases and identified by Dual-Luciferase Reporter Assay. The effects of circ_0055625 silencing on the tumor formation and radiosensitivity of colon cancer in vivo were explored by in vivo tumor formation assay. Results Circ_0055625 and MSI1 were upregulated in colon cancer tissues and cells relative to control groups. Radiation treatment apparently increased the expression of circ_0055625 and MSI1 in colon cancer cells. Circ_0055625 knockdown or MSI1 silencing repressed cell proliferation, migration, and invasion and promoted cell apoptosis and radiosensitivity in colon cancer. Also, circ_0055625 silencing-mediated effects were attenuated by MSI1 overexpression. Additionally, circ_0055625 silencing reduced MSI1 expression, which could be attenuated by miR-338-3p inhibitor. Mechanically, circ_0055625 acted as a sponge for miR-338-3p to regulate MSI1. Furthermore, circ_0055625 knockdown hindered tumor growth and improved radiosensitivity in vivo. Conclusion Circ_0055625 repression inhibited the progression and radioresistance of colon cancer by downregulating MSI1 through sponging miR-338-3p. This result might provide a theoretical basis for improving the therapy of colon cancer with radiation.
Digital down-converter is an important part of wideband digital receivers.The variable-bandwidth digital down-con-verter(VB-DDC),which is suitable for wideband digital receiver,is implemented in FPGA chip Stratix II EP2S60F672C4.The VB-DDC combines the advantages of traditional digital down-conversion architectures and poly-phase filter architectures,realizes effi-cient high-speed processing for input IF signal,and could configure the bandwidth of signal processing flexibly in a large range.Hardware test result shows the effectiveness of this design.
Background: Immunochemotherapy was an emerging neoadjuvant treatment mode that can potentially benefit patients with esophageal carcinoma, but its synergistic mechanism and impact on the tumor immune microenvironment were still unclear. The purpose of this study was to investigate the outcomes of neoadjuvant chemotherapy (nCT) and neoadjuvant immunochemotherapy (nICT) in tumor microenvironment (TME) remodeling among patients with esophageal squamous cell carcinoma (ESCC) and to evaluate the prognostic value of immune-related biomarkers and clinicopathological characteristics. Methods: Patients with locally advanced ESCC who underwent neoadjuvant therapy followed by esophagectomy at the Fourth Hospital of Hebei Medical University between December 2019 and March 2022 were enrolled in this retrospective study. We examined TME features and immune antigen-related biomarkers before and after neoadjuvant therapy. Logistic and Cox regression model were used to evaluate the correlation between these factors and other clinical features and outcomes. Results: A total of 50 eligible participants were analyzed, including 31 males (62%), 25 patients of ≥65 years old, 4/28/18 of upper/middle/lower thoracic cancer, 25/17/8 of poor/moderate/high tumor differentiation, 8/42 of cT1+2/T3+4 stages and 30/20 of cN0/N+ stages. In the entire cohort, the rates of pathological complete response (pCR) and major pathological response (MPR) were 18% and 30%, respectively. pCR rates were 7.1% and 22.2% (χ2=0.699; P=0.40) MPR rates were 7.1% and 38.9% (χ2=4.837; P=0.03) in the nCT and nICT groups, respectively. Compared with the non-pCR patients, the pCR patients had a higher baseline programmed cell death ligand-1 (PD-L1) tumor proportion score (TPS) positive expression rate (16.7% vs. 77.8%, χ2=13.089; P<0.001). Following neoadjuvant therapy, the expression rates of PD-L1, CD3+ T cells, and CD8+ T cells in the tumor tissue was higher in the nICT group compared to the nCT group (P<0.05). Deficient expression of mismatch repair (MMR) genes was only observed in one patient (2%). Among patient-related biomarkers, lymphocyte and neutrophil counts decreased after treatment, with no significant changes in the neutrophil-to-lymphocyte ratio or platelet-to-lymphocyte ratio (PLR). Cox regression analysis showed that pretreatment, well-differentiated tumors and positive PD-L1 status were positive predictors of MPR (P<0.05). MPR was an independent predictor of disease-free survival (DFS) (P=0.03). Conclusions: Compared to nCT, nICT could more significantly upregulates PD-L1 TPS, PD-L1 combined positive score (CPS), CD3+ T cells, and CD8+ T cells. Pretreatment tumor differentiation and PD-L1 TPS level could be predictive of MPR. Our findings suggested that the combination of chemotherapy and immunotherapy may be more beneficial for activating anti-tumor immunity in the TME.
To evaluate the impact of radiation dose escalation on overall survival (OS) in patients with non-metastatic esophageal squamous cell carcinoma (ESCC) treated with radical radiotherapy.The clinical data of ESCC patients treated with three-dimensional (3D) radiotherapy alone or chemoradiotherapy were collected from multiple institutes and retrospectively analyzed. Patients who received radiation dose ≥40 Gy were included. Radiation dose as a continuous variable was entered into the Cox regression model by using penalized spline regression to allow for a nonlinear relationship between radiation dose and OS to be identified. Patients were stratified into five groups according to EQD2. The Kaplan-Meier method was used to assess the OS in different dose groups. Univariate and multivariate analyses were performed to evaluate the factors associated with OS.A total of 2,469 patients were included from 10 institutes across China. The median follow-up time was 58.3 months [95% confidence interval (CI): 56.4-60.2 months]. The median OS and PFS time were 24.3 months (95% CI: 22.5-26.2 months) and 18.0 months (95% CI: 16.4-19.6 months), respectively. The risk of death decreased sharply with a dose up to 60 to 62 Gy, before increasing slightly after the dose was elevated beyond 62 Gy. Multivariate analysis indicated that the chance of death was significantly decreased in patients who received radiotherapy doses of 60-62 Gy [P=0.028, hazard ratio (HR) 0.85, 95% CI: 0.73-0.98)], compared with those who received radiotherapy doses of 40-60 Gy.Our results reveal radiation dose is a significant prognostic factor of survival for ESCC patients. Higher radiation dose contributes to much more favorable survival outcomes for ESCC patients receiving radical radiotherapy by modern techniques, and 60 Gy or above might be the most optimal radiation dose.
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