The aim of this study was to investigate the impact of interleukin-27 (IL- 27) gene polymorphism and additional interactions with environmental factors on non-small cell lung cancer (NSCLC) risk based on a Chinese population. SNPStats online software (http://bioinfo.iconcologia.net/SNPstats) was used for Hardy-Weinberg equilibrium (HWE) testing. Stratified analysis was performed by logistic regression model to examine the impact of IL- 27 gene SNPs and environmental factors, and additional gene-environment interaction on NSCLC risk. Logistic regression analysis showed a significant association between rs153109, rs181206 and increased NSCLC risk. However, no significant relationship was found between NSCLC risk and rs17855750 or rs40837 genotype with minor allele. Logistic regression also indicated a significant association between smoking status or alcohol consumption and NSCLC risk in this study. We performed crossover analysis to investigate the interaction between two SNPs (rs153109 and rs181206) and two environmental factors (smoking status and alcohol consumption) using logistic regression. We found that ever or current smokers with rs153109- AG or GG genotype have the highest NSCLC risk, compared with never smokers with the AA genotype after covariate adjustment, OR (95
This secondary analysis of a randomized clinical trial reports the long-term survival rates and cancer- and noncancer-related causes of death associated with concurrent chemoradiotherapy with S-1 in older patients in China. QuestionIs concurrent chemoradiotherapy (CCRT) with S-1 associated with differences in survival compared with radiotherapy alone in older patients with esophageal cancer (EC)?FindingsIn this secondary analysis of a randomized clinical trial involving 298 patients with EC, the first prospective long-term data (median follow-up of 87 months) on treatment outcomes were reported. Patients in the CCRT with S-1 group showed significantly better overall survival than those in the RT-alone group, and long-term follow-up revealed no increase in noncancer-related mortality among patients receiving CCRT with S-1.MeaningThese results support CCRT with S-1 as an effective and tolerable treatment option for older patients with EC, addressing the critical evidence gap for this underrepresented population. ImportanceMost older patients with esophageal cancer (EC) are unable to complete standard platinum-based concurrent chemoradiotherapy (CCRT) due to reduced organ reserve, comorbidities, and malnutrition. A new treatment option-CCRT with S-1-has been found to have high efficacy and fewer toxic effects for this population, yet long-term data supporting its use remain limited.ObjectiveTo evaluate the long-term outcomes of CCRT with S-1 vs radiotherapy (RT) alone in older patients with EC.Design, Setting, and ParticipantsThis secondary analysis of a phase 3 randomized clinical trial conducted at 23 centers in China was not prespecified in the trial protocol. Patients aged 70 to 85 years with histologically confirmed EC were enrolled between June 1, 2016, and August 31, 2018. Data cutoff date was February 1, 2025, with an additional follow-up of 54 months beyond the primary analysis. Data were analyzed from February 1 to April 1, 2025.InterventionsPatients were randomly assigned 1:1 to receive CCRT with S-1 consisting of 54 Gy in 30 fractions with S-1, 70 mg/m2 per day on days 1 to 14 and 29 to 42, or RT alone consisting of 60 Gy in 30 fractions, 2.0 Gy per day 5 days per week.Main Outcomes and MeasuresThe primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS), cause-specific mortality, cumulative incidence of death from EC or other reasons, and cumulative incidences of locoregional or distant metastasis during treatment or relapse after treatment.ResultsA total of 298 patients (median [IQR] age, 77 [74-79] years; 180 males [60.4%]) were enrolled. There were 151 patients (50.7%) clinically diagnosed with stage III to IV disease. With a median (IQR) follow-up of 87 (85-92) months, the median OS was 24.7 (95% CI, 21.2-37.6) months in the CCRT group and 15.1 (95% CI, 12.4-18.6) months in the RT group (hazard ratio [HR], 0.69; 95% CI, 0.53-0.90; P = .005). The 5-year OS rates were 33.5% (95% CI, 26.7%-42.1%) and 24.4% (95% CI, 18.3%-32.4%) for the CCRT and RT groups, respectively; the 8-year OS rates were 26.2% and 16.1%, respectively. The median PFS was 18.7 (95% CI, 13.1-25.8) months in the CCRT group and 9.2 (95% CI, 7.9-12.7) months in the RT group (HR, 0.69; 95% CI, 0.54-0.90; P = .005). Cause-specific analyses showed reduced EC-related mortality with CCRT (HR, 0.67; 95% CI, 0.50-0.89; P = .005), with 8-year absolute risks of 58.5% vs 72.9%, respectively, and no excess noncancer-related mortality.Conclusions and RelevanceIn this secondary analysis of a randomized clinical trial, long-term results showed that CCRT with S-1 was associated with a sustained survival benefit compared with RT alone, without increased noncancer-related mortality. This finding supports CCRT with S-1 as the preferred regimen for patients aged 70 to 85 years with EC.Trial RegistrationClinicalTrials.gov Identifier: NCT02813967
Importance:Most older patients with esophageal cancer (EC) are unable to complete standard platinum-based concurrent chemoradiotherapy (CCRT) due to reduced organ reserve, comorbidities, and malnutrition. A new treatment option-CCRT with S-1-has been found to have high efficacy and fewer toxic effects for this population, yet long-term data supporting its use remain limited. Objective:To evaluate the long-term outcomes of CCRT with S-1 vs radiotherapy (RT) alone in older patients with EC. Design, Setting, and Participants:This secondary analysis of a phase 3 randomized clinical trial conducted at 23 centers in China was not prespecified in the trial protocol. Patients aged 70 to 85 years with histologically confirmed EC were enrolled between June 1, 2016, and August 31, 2018. Data cutoff date was February 1, 2025, with an additional follow-up of 54 months beyond the primary analysis. Data were analyzed from February 1 to April 1, 2025. Interventions:Patients were randomly assigned 1:1 to receive CCRT with S-1 consisting of 54 Gy in 30 fractions with S-1, 70 mg/m2 per day on days 1 to 14 and 29 to 42, or RT alone consisting of 60 Gy in 30 fractions, 2.0 Gy per day 5 days per week. Main Outcomes and Measures:The primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS), cause-specific mortality, cumulative incidence of death from EC or other reasons, and cumulative incidences of locoregional or distant metastasis during treatment or relapse after treatment. Results:A total of 298 patients (median [IQR] age, 77 [74-79] years; 180 males [60.4%]) were enrolled. There were 151 patients (50.7%) clinically diagnosed with stage III to IV disease. With a median (IQR) follow-up of 87 (85-92) months, the median OS was 24.7 (95% CI, 21.2-37.6) months in the CCRT group and 15.1 (95% CI, 12.4-18.6) months in the RT group (hazard ratio [HR], 0.69; 95% CI, 0.53-0.90; P = .005). The 5-year OS rates were 33.5% (95% CI, 26.7%-42.1%) and 24.4% (95% CI, 18.3%-32.4%) for the CCRT and RT groups, respectively; the 8-year OS rates were 26.2% and 16.1%, respectively. The median PFS was 18.7 (95% CI, 13.1-25.8) months in the CCRT group and 9.2 (95% CI, 7.9-12.7) months in the RT group (HR, 0.69; 95% CI, 0.54-0.90; P = .005). Cause-specific analyses showed reduced EC-related mortality with CCRT (HR, 0.67; 95% CI, 0.50-0.89; P = .005), with 8-year absolute risks of 58.5% vs 72.9%, respectively, and no excess noncancer-related mortality. Conclusions and Relevance:In this secondary analysis of a randomized clinical trial, long-term results showed that CCRT with S-1 was associated with a sustained survival benefit compared with RT alone, without increased noncancer-related mortality. This finding supports CCRT with S-1 as the preferred regimen for patients aged 70 to 85 years with EC. Trial Registration:ClinicalTrials.gov Identifier: NCT02813967.
BACKGROUND:To date, results on relationship between CYP3A4 gene polymorphism were limited and inconclusive, and no study focused on the influence of CYP3A4 gene-obesity interaction on breast cancer risk, especially in Chinese women. The purpose of this study was to evaluate the impact of four single nucleotide polymorphisms (SNPs) of CYP3A4 gene, the SNP-SNP and gene-environment interactions on the susceptibility to breast cancer in Chinese women. METHODS:Logistic regression was used to explore the relationship between four SNPs of CYP3A4 gene and the risk of breast cancer. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best SNP-SNP and gene-abdominal obesity interaction combinations among four SNPs and abdominal obesity. Haplotype examination among 4 SNPs was conducted using the SHEsis web-based platform. RESULTS:Logistic regression analysis showed that carriers of rs2242480- T allele have significantly higher breast cancer risk, than those with rs2242480- CC genotype, adjusted OR (95%CI) was 1.68 (1.23-2.16) and 2.03 (1.53-2.58) for participants with CT genotype and TT genotype under additive model. We did not find any notable interactions between the four SNPs within the CYP3A4 gene. GMDR model found a significant association in a two-locus model involving rs2242480 and obesity, with a p-value of 0.018. Stratified analysis found that breast cancer risk was the highest in obese participants with rs2242480- CT or TT genotype, compared to those non-obese participants with rs2242480- CC genotype, OR (95%CI) was 3.02 (1.83-4.25). We found that all haplotype combinations were not correlated with breast cancer risk. CONCLUSIONS:We found that the T allele of rs2242480 within the CYP3A4 gene and interaction between rs2242480 and obesity were associated with an increased risk of breast cancer. However, the results of this study were only applicable to the Han ethnic group and cannot be generalized to other ethnic groups in China, and more SNPs of CYP3A4 gene should been enrolled in the analysis in the future, to verify the results obtained in this study.
BackgroundPET/CT and planning CT are commonly used medical images in radiotherapy for esophageal and nasopharyngeal cancer. However, repeated scans will expose patients to additional radiation doses and also introduce registration errors. This multimodal treatment approach is expected to be further improved.PurposeA new Transformer model is proposed to obtain pseudo-PET/CT fusion images for esophageal and nasopharyngeal cancer radiotherapy.MethodsThe data of 129 cases of esophageal cancer and 141 cases of nasopharyngeal cancer were retrospectively selected for training, validation, and testing. PET and CT images are used as input. Based on the Transformer model with a "focus-disperse" attention mechanism and multi-consistency loss constraints, the feature information in two images is effectively captured. This ultimately results in the synthesis of pseudo-PET/CT fusion images with enhanced tumor region imaging. During the testing phase, the accuracy of pseudo-PET/CT fusion images was verified in anatomy and dosimetry, and two prospective cases were selected for further dose verification.ResultsIn terms of anatomical verification, the PET/CT fusion image obtained using the wavelet fusion algorithm was used as the ground truth image after correction by clinicians. The evaluation metrics, including peak signal-to-noise ratio, structural similarity index, mean absolute error, and normalized root mean square error, between the pseudo-fused images obtained based on the proposed model and ground truth, are represented by means (standard deviation). They are 37.82 (1.57), 95.23 (2.60), 29.70 (2.49), and 9.48 (0.32), respectively. These numerical values outperform those of the state-of-the-art deep learning comparative models. In terms of dosimetry validation, based on a 3%/2 mm gamma analysis, the average passing rates of global and tumor regions between the pseudo-fused images (with a PET/CT weight ratio of 2:8) and the planning CT images are 97.2% and 95.5%, respectively. These numerical outcomes are superior to those of pseudo-PET/CT fusion images with other weight ratios.ConclusionsThis pseudo-PET/CT fusion images obtained based on the proposed model hold promise as a new modality in the radiotherapy for esophageal and nasopharyngeal cancer.
Four-dimensional imaging (4D-imaging) plays a critical role in achieving precise motion management in radiation therapy. However, challenges remain in 4D-imaging such as a long imaging time, suboptimal image quality, and inaccurate motion estimation. With the tremendous success of artificial intelligence (AI) in the image domain, particularly deep learning, there is great potential in overcoming these challenges and improving the accuracy and efficiency of 4D-imaging without the need for hardware modifications. In this review, we provide a comprehensive overview of how these AI-based methods could drive the evolution of 4D-imaging for motion management. We discuss the inherent issues associated with multiple 4D modalities and explore the current research progress of AI in 4D-imaging. Furthermore, we delve into the unresolved challenges and limitations in 4D-imaging and provide insights into the future direction of this field.
Radiotherapy is one of the most effective treatment strategies for lung cancer. However, radioresistance is a main limitation for lung cancer therapy. It is required to identify novel target to improve the radiotherapy efficacy of lung cancer. This study aimed to investigate the role of long non-coding ribonucleic acid lung cancer associated transcript 1 in the radioresistance of lung cancer. The correlation between lung cancer associated transcript 1 and patient survival was analyzed by using the cancer genome Atlas database. The expression of lung cancer associated transcript 1 in cells and lung cancer tissues was measured by real time polymerase chain reaction assay. Cell counting kit-8 assay and colony formation assay were used to determine the sensitivity of cells to ionizing radiation. Western blotting assay was performed to detect protein expressions and bioinformatic strategy was used to predict the target competing endogenous ribonucleic acids of lung cancer associated transcript 1. In the present study, we showed that long non-coding ribonucleic acid lung cancer associated transcript 1 is dramatically elevated in lung cancer cells and tissues, and high expression of lung cancer associated transcript 1 was negatively correlated with poor outcome in terms of overall survival. Moreover, knockdown of this long non-coding ribonucleic acid inhibited cell viability and increased cell apoptosis after irradiation, while lung cancer associated transcript 1 overexpression showed opposite effects. Mechanistically, knockdown of lung cancer associated transcript 1 elevated the activation of apoptosis factors B-cell lymphoma 2-associated X protein and cleaved-caspase 3. And lung cancer associated transcript 1 functions through binding with micro ribonucleic acid-199a-5p to regulate radiation response. In conclusion, we identified lung cancer associated transcript 1 as a factor promoting radioresistance in lung cancer, which provide novel target for cancer therapy.
Supplementary Figure from A Phase III Multicenter Randomized Clinical Trial of 60 Gy versus 50 Gy Radiation Dose in Concurrent Chemoradiotherapy for Inoperable Esophageal Squamous Cell Carcinoma
Background: Cone-beam computed tomography (CBCT) is an important tool for patient positioning in radiotherapy due to its outstanding advantages. However, the CBCT registration shows errors due to the limitations of the automatic registration algorithm and the nonuniqueness of manual verification results. The purpose of this study was to verify the feasibility of using the Sphere-Mask Optical Positioning System (S-M_ OPS) to improve the registration stability of CBCT through clinical trials. Methods: From November 2021 to February 2022, 28 patients who received intensity-modulated radiotherapy and site verification with CBCT were included in this study. S- M_OPS was used as an independent third-party system to supervise the CBCT registration result in real time. The supervision error was calculated based on the CBCT registration result and using the S-M_OPS registration result as the standard. For the head and neck, patients with a supervision error >= 3 or <=-3 mm in 1 direction were selected. For the thorax, abdomen, pelvis, or other body parts, patients with a supervision error >= 5 or <=-5 mm in 1 direction were selected. Then, re-registration was performed for all patients (selected and unselected). The registration errors of CBCT and S-M_OPS were calculated based on the re-registration results as the standard. Results: For selected patients with large supervision errors, CBCT registration errors (mean +/- standard deviation) in the latitudinal (LAT; left/right), vertical (VRT; superior/inferior), and longitudinal (LNG; anterior/posterior) directions were 0.90 +/- 3.20, -1.70 +/- 0.98, and 7.30 +/- 2.14 mm, respectively. The S-M_OPS registration errors were 0.40 +/- 0.14, 0.32 +/- 0.66, and 0.24 +/- 1.12 mm in the LAT, VRT, and LNG directions, respectively. For all patients, CBCT registration errors in the LAT, VRT, and LNG directions were 0.39 +/- 2.69, -0.82 +/- 1.47, and 2.39 +/- 2.93 mm, respectively. The S-M_OPS registration errors were -0.25 +/- 1.33, 0.55 +/- 1.27, and 0.36 +/- 1.34 mm for all patients in the LAT, VRT, and LNG directions, respectively. Conclusions: This study shows that S-M_OPS registration offers comparable accuracy to CBCT for daily registration. S-M_OPS, as an independent third-party tool, can prevent large errors in CBCT registration, thereby improving the accuracy and stability of CBCT registration.
Background KL-A167 is a fully humanized monoclonal antibody targeting programmed cell death-ligand 1. This phase 2 study aimed to evaluate the efficacy and safety of KL-A167 in Chinese patients with previously treated recur-rent or metastatic (R/M) nasopharyngeal carcinoma (NPC). Methods This was a multicentre, single-arm, phase 2 study of KL-A167 in R/M NPC (KL167-2-05-CTP) (NCT03848286), conducted at 42 hospitals across the People's Republic of China. Eligible patients had histologi-cally confirmed non-keratinising R/M NPC, and had failed at least two lines of chemotherapy. Patients received KL-A167 900mg intravenously once every 2 weeks until confirmed disease progression, intolerable toxicity, or with-drawal of informed consent. The primary endpoint was objective response rate (ORR) assessed by the independent review committee (IRC) according to RECIST v1.1. Findings Between Feb 26th, 2019 and Jan 13th, 2021, 153 patients were treated. Totally, 132 patients entered full analysis set (FAS) and were evaluated for the efficacy. As of data cutoff date on Jul 13th, 2021, the median follow-up time was 21.7 months (95%CI 19.8-22.5). For FAS population, the IRC-assessed ORR was 26.5% (95%CI 19.2-34.9%), and disease control rate (DCR) was 56.8% (95%CI 47.9-65.4%). Median progression-free survival (PFS) was 2.8 months (95%CI 1.5-4.1) . Median duration of response was 12.4 months (95%CI 6.8-16.5), and median overall survival (OS) was 16.2 months (95%CI 13.4-21.3). When using the cutoff of 1000 copies/ml, 5000 copies/ml and 10,000 copies/ml for plasma EBV DNA titer, baseline low plasma EBV DNA was consistently related with better DCR, PFS and OS. Dynamic change of plasma EBV DNA was significantly associated with ORR and PFS. Among 153 patients, treatment related-adverse events (TRAEs) occurred in 73.2% of patients, and grade >= 3 TRAEs were in 15.0% of patients. No TRAE leading to death was reported. Conclusion In this study, KL-A167 showed promising efficacy and an acceptable safety profile in patients with previ-ously treated R/M NPC. Baseline plasma EBV DNA copy number might be a potentially useful prognostic biomarker for KL-A167 treatment, and post-treatment EBV DNA decrease might be correlated with better response to KL-A167. Copyright (c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
We detected PD-L1 and intra-tumoral CD8(+) T lymphocytes (CD8(+) TIL) in 19 patients with esophageal carcinosarcoma (ECS). The median follow-up period of these patients was 43 months, and the three- and five-year survival rates were 78.9 and 63.2%, respectively. No statistically significant correlation was observed between PD-L1 and CD8(+) TIL in sarcomatous components(SC) (r = -0.262, p = 0.279) and epithelial carcinomatous (EC) (r = 0.055, p = 0.824). This study examined the immunological markers in ECS for the first time. PD-L1 is highly expressed in the SC and is associated with a poorer prognosis.
Abstract Purpose: In this multicenter phase 3 trial, the efficacy and safety of 60 Gy and 50 Gy doses delivered with modern radiotherapy technology for definitive concurrent chemoradiotherapy (CCRT) in patients with inoperable esophageal squamous cell carcinoma (ESCC) were evaluated. Patients and Methods: Patients with pathologically confirmed stage IIA‒IVA ESCC were randomized 1:1 to receive conventional fractionated 60 Gy or 50 Gy to the tumor and regional lymph nodes. Concurrent weekly chemotherapy (docetaxel 25 mg/m2; cisplatin 25 mg/m2) and two cycles of consolidation chemotherapy (docetaxel 70 mg/m2; cisplatin 25 mg/m2 days 1‒3) were administered. Results: A total of 319 patients were analyzed for survival, and the median follow-up was 34.0 months. The 1- and 3-year locoregional progression-free survival (PFS) rates for the 60 Gy group were 75.6% and 49.5% versus 72.1% and 48.4%, respectively, for the 50 Gy group [HR, 1.00; 95% confidence interval (CI), 0.75‒1.35; P = 0.98]. The overall survival rates were 83.7% and 53.1% versus 84.8% and 52.7%, respectively (HR, 0.99; 95% CI, 0.73‒1.35; P = 0.96), whereas the PFS rates were 71.2% and 46.4% versus 65.2% and 46.1%, respectively (HR, 0.97; 95% CI, 0.73‒1.30; P = 0.86). The incidence of grade 3+ radiotherapy pneumonitis was higher in the 60 Gy group (nominal P = 0.03) than in the 50 Gy group. Conclusions: The 60 Gy arm had similar survival endpoints but a higher severe pneumonitis rate compared with the 50 Gy arm. Fifty Gy should be considered as the recommended dose in CCRT for ESCC.
目的:研究红外定位系统(optical positioning system,OPS)在胸腹部肿瘤放射治疗中对摆位误差的指导意义.方法:选择30例胸腹部肿瘤患者,均采用改进型仰卧位固定技术固定,所有患者均辅以OPS标记.患者治疗时按常规方法对照激光线摆位,行锥形束CT(cone beam computed tomography,CBCT)扫描后移床治疗,记录移床后的CBCT误差值(对照组)以及OPS读数(观察组),包括X(左右方向)、Y(头脚方向)、Z(腹背方向)三个方向的线性误差,并分析比较两种误差结果.结果:以CBCT为标准,常规对激光线摆位的线性误差X、Y、Z三个方向分别为(1.95±1.16)mm、(3.87±1.67)mm、(1.71±1.03)mm;对应的OPS显示误差X、Y、Z三个方向分别为(0.63±0.56)mm、(0.31±0.49)mm、(0.32±0.22)mm.三个方向上OPS误差均小于传统摆位误差,差异有统计学意义(P<0.05).结论:OPS辅助摆位技术与常规对激光线摆位相比,在放疗中可明显减小胸腹部肿瘤患者的摆位误差,提高治疗时的摆位精度,给临床胸腹部肿瘤患者放疗的摆位提供参考.
Background:The setup accuracy plays an extremely important role in the local control of tumors. The purpose of this study is to verify the feasibility of "Sphere-Mask" Optical Positioning System (S-M_OPS) for fast and accurate setup.Methods:From 2016 to 2021, we used S-M_OPS to supervise 15441 fractions in 1981patients (with the cancer in intracalvarium, nasopharynx, esophagus, lung, liver, abdomen or cervix) undergoing intensity-modulated radiation therapy (IMRT), and recorded the data such as registration time and mask deformation. Then, we used S-M_OPS, laser line and cone beam computed tomography (CBCT) for co-setup in 277 fractions, and recorded laser line-guided setup errors and S-M_OPS-guided setup errors with CBCT-guided setup result as the standard.Results:S-M_OPS supervision results: The average time for laser line-guided setup was 31.75s. 12.8% of the reference points had an average deviation of more than 2 mm and 5.2% of the reference points had an average deviation of more than 3 mm. Co-setup results: The average time for S-M_OPS-guided setup was 7.47s, and average time for CBCT-guided setup was 228.84s (including time for CBCT scan and manual verification). In the LAT (left/right), VRT (superior/inferior) and LNG (anterior/posterior) directions, laser line-guided setup errors (mean±SD) were -0.21±3.13mm, 1.02±2.76mm and 2.22±4.26mm respectively; the 95% confidence intervals (95% CIs) of laser line-guided setup errors were -6.35 to 5.93mm, -4.39 to 6.43mm and -6.14 to 10.58mm respectively; S-M_OPS-guided setup errors were 0.12±1.91mm, 1.02±1.81mm and -0.10±2.25mm respectively; the 95% CIs of S-M_OPS-guided setup errors were -3.86 to 3.62mm, -2.53 to 4.57mm and -4.51 to 4.31mm respectively.Conclusion:S-M_OPS can greatly improve setup accuracy and stability compared with laser line-guided setup. Furthermore, S-M_OPS can provide comparable setup accuracy to CBCT in less setup time.
The purpose of this study was to investigate whether the primary tumor site in stage I extranodal natural killer/T-cell lymphoma (ENKTCL) had a prognostic value.Between January 2009 and December 2015, 152 stage I ENKTCL patients with primary disease in the nasal cavity and Waldeyer's ring were enrolled for this retrospective study.All patients received extended field intensity-modulated radiotherapy alone without prophylactic cervical node irradiation at a total dose of 50 Gy.In this study, there were 122 patients whose primary tumors were localized in the nasal cavity (NC group), and no adjacent structures were involved.A total of 18 patients had a primary disease involving the nasal cavity and Waldeyer's ring (NC-WR group), and the remaining 12 patients had primary tumors confined to Waldeyer's ring (WR group).We found that there was no significant difference in cervical lymph node failure rates among the NC, NC-WR, and WR groups.In terms of the 5-year overall survival (OS) rates, there was a significant difference among the NC, NC-WR, and WR groups (p=0.004), with the WR group having the worst OS.Multivariate analyses showed that the primary site (p=0.011)and ECOG (Eastern Cooperative Oncology Group) score (p=0.013) were independent prognostic factors for OS.In summary, patients with stage I ENKTCL had a good local control rate with radiotherapy alone and without prophylactic cervical node irradiation (PCNI), regardless of the site of the primary tumor.So, we think PCNI for stage I ENKTCL patients is not necessary.Patients with a primary tumor site located in Waldeyer's ring had the worst prognosis.And combined treatment with radiotherapy and chemotherapy should be considered in patients with primary tumors located outside the nasal cavity.
Abstract Background Nasopharyngeal carcinoma (NPC) is a malignancy of head and neck cancer. miR-433 was downregulated in various of cancers. However, the roles and underlying mechanisms of miR-433 in the hypoxic microenvironment of NPC have not been clarified. Methods Real-time quantitative PCR, Western blot assay were performed to examine miR-433 and hypoxia-inducible factor-1α (HIF-1α) levels in NPC tissue and cells. Cell proliferation, migration of differentially expressed miR-433 cells was measured by Cell Counting Kit-8, Transwell analysis in vitro. Nude mice and zebrafish model were used to confirm the effect of miR-433 in vivo. Luciferase reporter assays was used to determine whether HIF-1α was a direct target of miR-433. Results RT-qPCR, Western blot assay were performed to show that miR-433 was down-regulated while hypoxia-inducible factor-1α (HIF-1α) was overexpressed in NPC. Cell proliferation, migration of differentially expressed miR-433 cells was measured by CCK8, Transwell analysis in vitro. Our data showed that miR-433 suppressed proliferation and migration of hypoxic NPC cells by directly binding the 3'-untranslated region (UTR) of HIF-1α. Knockdown the expression of HIF-1α in the miR-433 inhibitor treated hypoxic CNE2 cells partially reversed the effect. Nude mice and zebrafish model were used to confirm the effect of miR-433 in vivo. Luciferase reporter assays was used to determine whether HIF-1α was a direct target of miR-433. Conclusions NPC cells proliferation, migration, cell cycle arrest, colony formation, and the epithelial mesenchymal transition (EMT) progression were all inhibited by miR-433 by directly targeting HIF-1α. miR-433 could act as cancer suppressor miRNA and represent an effective therapeutic strategy for NPC.
目的 探讨宫颈癌放射治疗(放疗)中摆位误差的影响因素.方法 回顾性分析148例宫颈癌放疗患者摆位误差情况,运用Lasso回归模型分析各因素对放疗摆位误差的影响.结果 通过散点趋势图可见,年龄、膀胱尿量、体质量指数(BMI)等对摆位误差有正向影响,患者采用体板加体膜固定方式的摆位误差小于采用负压真空垫.Lasso回归分析表明,固定方式会对线性误差左右(LR)、腹背(AP)方向和旋转误差LR、头脚(CC)方向有影响(P均<0.05),对线性误差CC方向和旋转误差AP方向无影响(P均>0.05);膀胱尿量只对线性误差CC方向有影响(P<0.05);年龄、BMI对摆位误差无影响(P均>0.05).结论 宫颈癌放疗患者膀胱尿量、固定方式会对摆位误差产生一定影响.
目的:研究红外定位系统(optical positioning system,OPS)辅助摆位新技术在肝癌放射治疗中对摆位误差的影响及其在肝癌精确放疗中的应用价值.方法:本研究选取30例肝癌患者,均应用OPS技术辅助摆位.将CBCT扫描作为标准,比较OPS技术和室内激光系统(十字线)在X(左右)、Y(头脚)、Z(面背)三个方向的线性误差;并根据摆位误差折线图分别计算出OPS和十字线的临床摆位一致性百分比.结果:通过OPS摆位在X、Y、Z方向上的摆位误差分别为(2.74±1.27)mm、(3.45±1.17)mm、(2.85±1.11)mm;通过十字线摆位在X、Y、Z方向上的摆位误差分别为(4.37±1.45)mm、(5.79±1.52)mm、(4.27±1.55)mm,各方向对应的P均<0.001.以±5 mm为标准,OPS在三个方向上的临床一致性分别为96.7%、90.0%、98.7%;十字线在三个方向上的临床一致性分别为68.0%、32.7%、72.7%.结论:OPS在肝癌放射治疗定位摆位方面非常有效.作为一种无辐射、低成本、简便快捷的定摆位新技术,OPS比室内激光系统更能提高整体的摆位精度.
This study introduced a lattice Weaire-Phelan (LWP) structure to the Ti6Al4V (TC4) porous scaffold manufactured by selective laser melting (SLM) technology with sizes of 10 x 10 x 10 mm and porosities from 61.6% to 69.4%. The developed biomaterials were evaluated on the aspects of microstructure, mechanical properties and energy absorption capacity. The built scaffolds exhibited anisotropic microstructure dominated by acicular <<' phase and columnar beta grains. Design requirements of the cellular biomaterial for bone repair were proposed in terms of mechanical performance. Also, design space and adequate relative density range were developed to achieve the quantitative evaluation on load bearing capacity of porous structures. A quasi-static finite element model (FEM) was established to simulate the mechanical behaviors of elastic plastic, plateau stress and material densification during compression tests. Overall, our developed TC4 biomaterial was proved to be exhibited excellent mechanical performance combined with relatively low elastic modulus and high yield strength for human bone substitution, as well as the superior energy absorption capacity to other reported energy absorption materials. (c) 2021 Published by Elsevier B.V.
Importance Most older patients with esophageal cancer cannot complete the standard concurrent chemoradiotherapy (CCRT). An effective and tolerable chemoradiotherapy regimen for older patients is needed. Objective To evaluate the efficacy and toxic effects of CCRT with S-1 vs radiotherapy (RT) alone in older patients with esophageal cancer. Design, Setting, and Participants A randomized, open-label, phase 3 clinical trial was conducted at 23 Chinese centers between June 1, 2016, and August 31, 2018. The study enrolled 298 patients aged 70 to 85 years. Eligible participants had histologically confirmed esophageal cancer, stage IB to IVB disease based on the 6th edition of the American Joint Committee on Cancer (stage IVB: only metastasis to the supraclavicular/celiac lymph nodes) and an Eastern Cooperative Oncology Group performance status of 0 to 1. Data analysis was performed from August 1, 2020, to March 10, 2021. Interventions Patients were stratified according to age (<80 vs ≥80 years) and tumor length (<5 vs ≥5 cm) and randomly assigned (1:1) to receive either CCRT with S-1 or RT alone. Main Outcomes and Measures The primary end point was the 2-year overall survival rate using intention-to-treat analysis. Results Of the 298 patients enrolled, 180 (60.4%) were men. The median age was 77 (interquartile range, 74-79) years in the CCRT group and 77 (interquartile range, 74-80) years in the RT alone group. A total of 151 patients (50.7%) had stage III or IV disease. The CCRT group had a significantly higher complete response rate than the RT group (41.6% vs 26.8%; P = .007). Surviving patients had a median follow-up of 33.9 months (interquartile range: 28.5-38.2 months), and the CCRT group had a significantly higher 2-year overall survival rate (53.2% vs 35.8%; hazard ratio, 0.63; 95% CI, 0.47-0.85; P = .002). There were no significant differences in the incidence of grade 3 or higher toxic effects between the CCRT and RT groups except that grade 3 or higher leukopenia occurred in more patients in the CCRT group (9.5% vs 2.7%; P = .01). Treatment-related deaths were observed in 3 patients (2.0%) in the CCRT group and 4 patients (2.7%) in the RT group. Conclusions and Relevance In this phase 3 randomized clinical trial, CCRT with S-1 was tolerable and provided significant benefits over RT alone in older patients with esophageal cancer. Trial Registration ClinicalTrials.gov Identifier: NCT02813967.