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1.
Zhonghua Xue Ye Xue Za Zhi ; 42(10): 840-845, 2021 Oct 14.
Artigo em Chinês | MEDLINE | ID: mdl-34788924

RESUMO

Objective: To investigate the interference of daratumumab on immunofixation electrophoresis after treating plasma cell diseases and methods to eliminate the interference. Methods: Serum samples of eight patients with plasma cell diseases treated with daratumumab in Peking University People's Hospital from April 2020 to March 2021 were collected for standard immunofixation electrophoresis and Hydrashift 2/4 daratumumab assay. Results: After treatment, 81.3% (13/16) of the samples showed drug-induced monoclonal antibodies (IgG-κ) . The samples without drug-induced monoclonal bands were related to individual differences, administration intervals, and immunoglobulin levels. Among the samples with IgG-κ monoclonal bands, 76.9% (10/13) could be directly identified as endogenous or exogenous monoclonal bands by immunofixation electrophoresis, and the others (3/13) could be identified by Hydrashift 2/4 daratumumab assay. Conclusion: Hydrashift 2/4 daratumumab assay can remove the band of daratumumab on the immunofixation electrophoresis and help with efficacy evaluation.


Assuntos
Mieloma Múltiplo , Paraproteinemias , Anticorpos Monoclonais , Humanos , Imunoeletroforese
2.
Zhonghua Liu Xing Bing Xue Za Zhi ; 42(8): 1445-1452, 2021 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-34814566

RESUMO

Objective: To identify the threshold of a health warning system based on the association of apparent temperature and years of life lost (YLL). Methods: Daily mortality records and meteorological data were collected from 364 Chinese counties for 2006-2017. Distributed lag nonlinear model and multivariate Meta-analyses were applied to estimate the association between the apparent temperature and YLL rate. A regression tree model was employed to estimate the warning thresholds of the apparent temperature. Stratified analyses were further conducted by age and cause of death. Results: The daily YLL rate was 23.6/105. The mean daily apparent temperature was 15.7 ℃. U-shaped nonlinear associations were observed between apparent temperature and YLL rate. The actual temperature-caused YLL rate for the elderly was higher than the young population. The daily excess deaths rate increased with the higher effect levels. Conclusions: Regression tree model was employed to define the warning threshold for meteorological health risk. The present study provides theoretical support for the weather-related health warning system.

3.
Nat Mater ; 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34750539

RESUMO

Symmetry plays a central role in conventional and topological phases of matter, making the ability to optically drive symmetry changes a critical step in developing future technologies that rely on such control. Topological materials, like topological semimetals, are particularly sensitive to a breaking or restoring of time-reversal and crystalline symmetries, which affect both bulk and surface electronic states. While previous studies have focused on controlling symmetry via coupling to the crystal lattice, we demonstrate here an all-electronic mechanism based on photocurrent generation. Using second harmonic generation spectroscopy as a sensitive probe of symmetry changes, we observe an ultrafast breaking of time-reversal and spatial symmetries following femtosecond optical excitation in the prototypical type-I Weyl semimetal TaAs. Our results show that optically driven photocurrents can be tailored to explicitly break electronic symmetry in a generic fashion, opening up the possibility of driving phase transitions between symmetry-protected states on ultrafast timescales.

4.
Nan Fang Yi Ke Da Xue Xue Bao ; 41(10): 1484-1491, 2021 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-34755663

RESUMO

OBJECTIVE: To investigate the role of vascular endothelial growth factor (VEGF) in regulating triple-negative breast cancer (TNBC) stem cells and the possible pathways involved in this regulatory mechanism. METHODS: The Oncomine database, UALCAN database and Human Protein Atlas (HPA) database were used to analyze the expression of VEGF in breast cancer and its association with the molecular subtypes and prognosis of breast cancer. Sphere formation assay was carried out to examine the effects of hVEGF165 on sphere formation ability of TNBC MDA-MB-231 cell line; Western blotting and RT-qPCR were performed to detect the expression of the tumor stem cell markers including CD44, c-Myc, Nanog, and ALDH1 and the activation of the related pathways. RESULTS: Data from the online databases all showed a significant increase of VEGF expression in breast cancer tissues than in the adjacent tissues (P < 0.0001), and its expression level was associated with the molecular subtypes of breast cancer. Specifically, the expression of VEGF was markedly higher in TNBC than in other subtypes of breast cancer. Survival analysis showed that breast cancer patients with a high VEGF expression had a significantly shortened overall survival (P < 0.0001). In the cell experiments, the sphere formation ability of MDA-MB-231 cells was significantly enhanced after treatment with hVEGF165 (P=0.0029). Compared with the monolayer cells, MDA-MB-231 spheres showed significantly increased expressions of VEGF, NRP-1, CD44, Nanog and c-Myc. Treatment with hVEGF165 resulted in significant time-dependent up-regulation of the expressions of CD44, c-Myc, Nanog and ALDH1 and down-regulation of CD24 expression in the cells. The results of Western blotting demonstrated that treatment with hVEGF165 caused significant activation of the ERK/MAPK pathway in MDA-MB-231 cells. CONCLUSION: VEGF promotes cancer stemness of triple-negative breast cancer possibly through the ERK/MAPK pathway.


Assuntos
Neoplasias de Mama Triplo Negativas , Fator A de Crescimento do Endotélio Vascular , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Sistema de Sinalização das MAP Quinases , Células-Tronco Neoplásicas , Fator A de Crescimento do Endotélio Vascular/metabolismo
5.
Zhonghua Yi Xue Za Zhi ; 101(40): 3329-3337, 2021 Nov 02.
Artigo em Chinês | MEDLINE | ID: mdl-34758534

RESUMO

Objective: To explore the effect and possible mechanism of circ_0023990 on the radiosensitivity of thyroid cancer cells. Methods: qRT-PCR was used to detect the expression of circ_0023990 in the cancer tissues of 55 patients with thyroid cancer and thyroid cancer cell lines (TPC-1, KTC-1, FTC-133 and CAL-62), and the relationship between the expression of circ_0023990 in cancer tissues and the clinical characteristics of the patients were analyzed. Thyroid cancer cells TPC-1 and KTC-1 were divided into sh-circ_0023990 group, sh-NC group, sh-circ_0023990+anti-miR-873-5p group, sh-circ_0023990+anti-miR-NC group, miR-873-5p group, miR-NC group, miR-873-5p+pcDNA-ANXA2 group and miR-873-5p+pcDNA group, and then clone formation experiment was used to detect cell radiosensitivity. After each group of cells was irradiated with 4Gy radiation, the expression of γH2AX protein in the cells was detected by Western Blot. The dual luciferase reporter gene experiment verified the targeting relationship between circ_0023990 and miR-873-5p or miR-873-5p and ANXA2. Results: The expression of circ_0023990 in thyroid cancer tissues was higher than that in normal tissues (2.15±0.09 vs. 0.97±0.05, P<0.05), and its expression was closely related to tumor size, lymph node metastasis and TNM staging of patients with thyroid cancer (P<0.05). The expression of circ_0023990 in thyroid cancer cell lines (TPC-1, KTC-1, FTC-133 and CAL-62) were higher than that of normal thyroid cells HTori-3 (3.16±0.38, 2.63±0.28, 1.82±0.24, 1.71±0.22 vs. 1.00±0.10, all P<0.05). The survival scores of TPC-1 and KTC-1 cells in the sh-circ_0023990 group were significantly lower than those in the sh-NC group (P<0.05), and the sensitization ratios were 2.482, 1.643; The survival scores of TPC-1 and KTC-1 cells in the sh-circ_0023990+anti-miR-873-5p group were higher than those in the sh-circ_0023990+anti-miR-NC group (P<0.05), and the sensitization ratios were 0.305, 0.441, respectively. The survival scores of TPC-1 and KTC-1 cells in the miR-873-5p group were lower than those in the miR-NC group (P<0.05), and the sensitization ratios were 2.044, 1.653 respectively. The survival scores of TPC-1 and KTC-1 cells in the miR-873-5p+pcDNA-ANXA2 group was higher than that in the miR-873-5p+pcDNA group (P<0.05), and the sensitization ratios were 0.496, 0.686, respectively. The expression of γH2AX protein in TPC-1 and KTC-1 cells of the 4 Gy+sh-circ_0023990 group were higher than that in the 4 Gy+sh-NC group (2.68±0.27 vs. 1.87±0.25, 2.46±0.19 vs. 1.77±0.14; all P<0.05), but the expression of γH2AX protein in TPC-1 and KTC-1 cells of the 4 Gy+sh-circ_0023990+anti-miR-873-5p group were lower than that in the 4 Gy+sh-circ_0023990+anti-miR-NC group (1.13±0.09 vs. 1.69±0.09, 1.11±0.08 vs. 1.60±0.08; both P<0.05). The expression of γH2AX protein in TPC-1 and KTC-1 cells in the 4 Gy+miR-873-5p group were higher than that in the 4 Gy+miR-NC group (2.35±0.16 vs. 1.84±0.14, 2.26±0.12 vs. 1.77±0.13; both P<0.05), but the expression of γH2AX protein in TPC-1 and KTC-1 cells of the 4 Gy+miR-873-5p+pcDNA-ANXA2 group were lower than that in the 4 Gy+miR-873-5p+pcDNA group (1.96±0.12 vs. 2.41±0.12, 1.92±0.07 vs. 2.28±0.12; both P<0.05). circ_0023990 targeted the negative regulation of miR-873-5p, and ANXA2 was the target gene of miR-873-5p. Conclusion: circ_0023990 was highly expressed in thyroid cancer tissues and cell lines, and it may promote the radiotherapy resistance of thyroid cancer cells in vivo through regulating miR-873-5p/ANXA2 axis.


Assuntos
Anexina A2 , MicroRNAs , Neoplasias da Glândula Tireoide , Linhagem Celular Tumoral , Proliferação de Células , Humanos , MicroRNAs/genética , Tolerância a Radiação/genética , Neoplasias da Glândula Tireoide/genética
6.
Clin Transl Oncol ; 2021 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-34741724

RESUMO

PURPOSE: Glioblastoma multiforme (GBM) is one of the most common malignant brain tumors in adults and has high mortality and relapse rates. Over the past few years, great advances have been made in the diagnosis and treatment of GBM, but unfortunately, the five-year overall survival rate of GBM patients is approximately 5.1%. Inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKBKE) is a major oncogenic protein in tumors and can promote evil development of GBM. Snail1, a key inducer of the epithelial-mesenchymal transition (EMT) transcription factor, is subjected to ubiquitination and degradation, but the mechanism by which Snail1 is stabilized in tumors remains unclear. Our study aimed to investigate the mechanism of IKBKE regulating Snail1 in GBM. METHODS: First, we analyzed the correlation between the expression of IKBKE and the tumor grade and prognosis through public databases and laboratory specimen libraries. Second, immunohistochemistry (IHC) and western blot were used to detect the correlation between IKBKE and Snail expression in glioma samples and cell lines. Western blot and immunofluorescence (IF) experiments were used to detect the quality and distribution of IKBKE and Snail1 proteins. Third, In situ animal model of intracranial glioma to detect the regulatory effect of IKBKE on intracranial tumors. RESULTS: In this study, Our study reveals a new connection between IKBKE and Snail1, where IKBKE can directly bind to Snail1, translocate Snail1 into the nucleus from the cytoplasm. Downregulation of IKBKE results in Snail1 destabilization and impairs the tumor cell migration and invasion capabilities. CONCLUSION: Our studies suggest that the IKBKE-Snail1 axis may serve as a potential therapeutic target for GBM treatment.

7.
Clin Radiol ; 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34756700

RESUMO

AIM: To explore the association between haemorrhagic transformation (HT) subtypes and functional outcome in acute ischaemic stroke (AIS) patients with successful recanalization treated by endovascular thrombectomy (EVT). MATERIALS AND METHODS: Consecutive patients with AIS due to large-vessel occlusion in the anterior circulation, who were treated between January 2015 and June 2019 and achieved successful EVT, were enrolled in this retrospective study. HT was categorized according to the Heidelberg Bleeding Classification. Functional outcome was evaluated using the 90-day modified Rankin Scale (mRS) after stroke onset. Ordinal logistic regression analysis was performed to determine the association of HT subtypes with functional outcomes. RESULTS: A total of 243 patients were included for further analysis. Among them, 121 (49.8%) had HT. Ten (4.1%) patients were classified as haemorrhagic infarction (HI) subtype 1, 61 (25.1%) as HI subtype 2, 17 (7.0%) as parenchymal haematoma (PH) subtype 1, and 33 (13.6%) as PH subtype 2. Ordinal logistic regression analysis suggested that HI subtype 2 (adjusted common OR 0.357, 95% CI: 0.192-0.667), PH1 (adjusted common OR 0.254, 95% CI: 0.093-0.696) and PH subtype 2 (adjusted common OR 0.017, 95% CI: 0.006-0.051) were significantly associated with poor functional outcomes. CONCLUSION: The present study shows that HI subtype 2, PH subtype 1, and PH subtype 2 are independently associated with poor clinical outcomes in AIS patients with successful recanalization after EVT.

8.
Br J Dermatol ; 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34632574

RESUMO

BACKGROUND: A new autoinflammatory syndrome related to somatic mutations of UBA1 was recently described and called VEXAS syndrome. OBJECTIVE: To describe clinical characteristics, laboratory findings and outcomes of VEXAS syndrome. DESIGN: Case-series. SETTING: Patients referred to a French multicenter registry between November 2020 and May 2021. PATIENTS: 116 patients with VEXAS syndrome. MEASUREMENTS: Frequency and median of parameters and vital status, from diagnosis to the end of the follow-up. RESULTS: Main clinical features were skin lesions (83.5%), non-infectious fever (63.6%), weight loss (62%), lung involvement (49.6%), ocular symptoms (38.8%), relapsing chondritis (36.4%), venous thrombosis (34.7%), lymph nodes (33.9%), and arthralgia (27.3%). Hematological disease was present in 58 cases (50%), considered as myelodysplastic syndrome (MDS, n= 58) and monoclonal gammapathy of unknown significance (n=12).UBA1 mutations included p.M41T (44.8%), p.M41V (30.2%), p.M41L (18.1%), and splice mutations (6.9%). After a median follow-up of 3.0 years, 18 patients died (15.5%), from infectious origin (n=9) and MDS progression (n=3). Unsupervised analysis identified 3 clusters: cluster 1 (47%) with mild-to-moderate disease; cluster 2 (16%) with underlying MDS and higher mortality rates; cluster 3 (37%) with constitutional manifestations, higher C-reactive protein levels and less frequent chondritis. Five-year probability of survival was 84.2% in cluster 1, 50.5 % in cluster 2, and 89.6% in cluster 3. UBA1 p.Met41Leu mutation was associated with a better prognosis. CONCLUSION: VEXAS syndrome displays a large spectrum of organ manifestations and shows different clinical and prognostic profiles. It also raises a potential impact of the identified UBA1 mutation.

9.
Zhonghua Bing Li Xue Za Zhi ; 50(10): 1157-1162, 2021 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-34619870

RESUMO

Objective: To investigate the clinicopathological features, immunophenotype, molecular genetics and prognosis of extraskeletal mesenchymal chondrosarcoma in central nerve system (CNS). Methods: The clinicopathological findings, immunohistochemistry and genetic analysis of four cases of extraskeletal mesenchymal chondrosarcoma in Xuanwu Hospital between 2014 and 2019 were reviewed and followed up. Results: The ages of patients ranged from 20-35 years. Three patients had intracranial lesions and one had intradural tumor. The characteristic histologic features were undifferentiated small cells together with scattered islands of hyaline cartilage. There was hemangiopericytoma-like pattern with calcification and ossification. The tumor cells were positive for VIM and SOX9; and the small cells were positive for CD99, NSE and NKX3.1. The cells in chondroid matrix were positive for S-100. All tumor cells were negative for markers including CKpan, EMA and desmin. At molecular analysis, HEY1-NCOA2 fusion transcripts were identified in three patients. The fusion points were between exon 4 of HEY1 and exon 13 of NCOA2. Follow-up information was obtained in two patients, and both were free from recurrence or metastasis at 8 and 20 months. Conclusions: Extraskeletal mesenchymaI chondrosarcoma is a rare CNS disease with poor prognosis. In addition to SOX9, NKX3.1 can be another useful antibody for the differential diagnosis. The combination of pathological characteristics, immunophenotype and genetic profile of tumor is essential for diagnosis.


Assuntos
Condrossarcoma Mesenquimal , Condrossarcoma , Hemangiopericitoma , Adulto , Sistema Nervoso Central , Condrossarcoma Mesenquimal/genética , Condrossarcoma Mesenquimal/cirurgia , Humanos , Imuno-Histoquímica , Adulto Jovem
10.
Zhonghua Yi Xue Za Zhi ; 101(38): 3157-3160, 2021 Oct 19.
Artigo em Chinês | MEDLINE | ID: mdl-34674427

RESUMO

To summarize the clinical characteristics and surgical treatment experience of pregnant women with acute Stanford type A aortic dissection.We collected the clinical data of 12 cases with acute aortic dissection during pregnancy and puerperal period from June 2010 to July 2020 in Beijing Anzhen Hospital and analyzed retrospectively, and summarize the clinical characteristics, treatment and outcomes for both mother and fetus. The age of these patients was(29±5)years old, and the onset time was from 16 weeks of gestation and 1 month after delivery. All the 12 patients underwent surgical treatment. The patients in the puerperium received aortic surgery after delivery. Four of them received the aortic surgery and continued pregnancy. Five of them underwent aortic repair and cesarean section simultaneously. Surgical treatment should be actively considered in pregnancy complicated with acute Stanford type A aortic dissection. Multi-disciplinary team cooperation can effectively improve the safety of the patients and fetus.


Assuntos
Aneurisma Dissecante , Complicações Cardiovasculares na Gravidez , Adulto , Aneurisma Dissecante/cirurgia , Cesárea , Feminino , Feto , Humanos , Gravidez , Estudos Retrospectivos , Adulto Jovem
12.
Zhonghua Yi Xue Za Zhi ; 101(37): 3029-3032, 2021 Oct 12.
Artigo em Chinês | MEDLINE | ID: mdl-34638196

RESUMO

This retrospective analysis was conducted on clinical obtained DCE-MR images of 198 patients, age from 21 to 79 years(45.5±13.7). The CBAM-ResNet model was developed to perform the classification automatically at the image-level based on deep learning method using the pathological examination as the reference standard,then the classification result of each individual patient was obtained by ensemble learning. The proposed method can have an accuracy of 82.69% for correctly distinguishing between benign and malignant breast tumors at the slice-level based on CBAM-ResNet model and with a sensitivity of 85.67%.. After the voting mechanism is applied, the classification accuracy can reach up to 88.24% at the patient-level with a sensitivity of 87.50%. Our experimental results demonstrated the proposed approach have a high classification accuracy.


Assuntos
Inteligência Artificial , Neoplasias da Mama , Adulto , Idoso , Neoplasias da Mama/diagnóstico por imagem , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
13.
Zhonghua Gan Zang Bing Za Zhi ; 29(9): 830-836, 2021 Sep 20.
Artigo em Chinês | MEDLINE | ID: mdl-34638200

RESUMO

Objective: To mine the signals of adverse drug reaction (ADR) of entecavir and tenofovir by using the US FDA Adverse Event Reporting System (FAERS) database, so as to provide reference for the safe clinical use of these two drugs. Methods: Reporting odds ratio (ROR) and proportion of report ratio (PRR) method were used to conduct data mining on the 26 quarterly reports of the US Food and Drug Administration Adverse Event Reporting System (FAERS) database between the fourth quarter of 2012 to the first quarter of 2019. The ADR descriptive terminology in the report were standardized by using the World Health Organization Adverse Reaction Terminology (System-Organ Class). ROR and PRR methods common signals were screened. Results: 104 and 187 signals of ADR of entecavir and tenofovir dipivoxil were obtained by ROR and PRR methods. The main screened system-organ classes affected by signals of ADR of entecavir were systemic damage, hepatobiliary system damage, and urinary system damage. The main screened system-organ classes affected by signals of ADR of tenofovir were urinary system damage, skeletal and musculoskeletal system damage, and metabolic and nutritional disorders. Conclusion: The mining signals of adverse drug reaction of entecavir and tenofovir dipivoxil indicate that these two drugs can cause female reproductive system damage, fetal abnormalities, neonatal and infant abnormalities, and male reproductive system damage. However, in addition to the above-mentioned ADR, the ADR instruction manual excludes entecavir and tenofovir dipivoxil primarily for respiratory and visual system damage, and the tenofovir disoproxil primarily for skin and appendage damage, and hearing and vestibular function damage. Therefore, in clinical medication management, it is suggested to pay close attention to the choice of drugs for special population infected with HBV, monitor possible ADR during medication course, and provide pharmacological monitoring to achieve personalized medication.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Guanina/análogos & derivados , Humanos , Recém-Nascido , Masculino , Tenofovir/efeitos adversos , Estados Unidos/epidemiologia , United States Food and Drug Administration
14.
Beijing Da Xue Xue Bao Yi Xue Ban ; 53(5): 942-945, 2021 Oct 18.
Artigo em Chinês | MEDLINE | ID: mdl-34650299

RESUMO

OBJECTIVE: With the rapid development of sleep medicine, there are various methods for detecting sleep diseases. This study compared the correlation between the lightweight watch-type sleep monitor (Actiwatch) and the "gold standard" polysomnography (PSG) in the Chinese population, in order to provide a basis for clinical application. METHODS: From August 2018 to December 2019, 121 subjects who simultaneously performed sleep breathing monitoring (PSG) and wearing a watch-type sleep monitor (Actiwatch) in the Sleep Center of Peking University People's Hospital were enrolled. All subjects received PSG and Actiwatch at the same time, and filled out the sleep diary next morning. Monitoring indicators were collected for linear correlation analysis and paired t test to compare the differences. RESULTS: Under low sensitivity conditions, the correlation coefficient of total sleep time (TST) between PSG and Actiwatch was 0.53 (P < 0.05). Paired t test analysis showed that there was no significant difference between the TSTs of Actiwatch and PSG (t=-0.890, P=0.36). According to age stratification, the smaller the age, the stronger the correlation between the TSTs of Actiwatch and PSG, and the coefficient could be up to 0.92 (P < 0.05). Paired t test showed that there was no significant difference between them (t=-1.057, P=0.35). According to the stratification by diagnosis, the correlation coefficient between the TSTs of Actiwatch and PSG in normal PSG group could be as high as 0.79 (P < 0.05), the results of paired t test showed that there was no significant difference between the TSTs of Actiwatch and PSG in normal PSG group (t=-0.784, P=0.44). CONCLUSION: As a wearable home recorder, when the analysis parameters of Actiwatch were set as low sensitivity, PSG and Actiwatch had the highest TST correlation. The younger the age, the stronger correlation between the TSTs of Actiwatch and PSG. The PSG and Actiwatch subjects with normal PSG presentation had a higher TST correlation.


Assuntos
Actigrafia , Transtornos do Sono-Vigília , Humanos , Polissonografia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Sono , Tempo
15.
Int J Radiat Oncol Biol Phys ; 111(3S): e385-e386, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34701329

RESUMO

PURPOSE/OBJECTIVE(S): Induction chemotherapy followed by concurrent chemoradiotherapy (IC+CCRT) and concurrent chemoradiotherapy (CCRT) are both recommended by guidelines for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). Two recent randomized control studies confirmed IC+CCRT had superior treatment outcomes than CCRT. However, most patients enrolled in these studies were staged as N2-N3 and subgroup analysis failed to identify the difference between IC+CCRT and CCRT for T4N0-1 NPC patients. Until now, little is unknown about the treatment modality for T4N0-1 NPC patients because of low incidence for this part of disease. Therefore, we designed this multicenter retrospective study to evaluate these two treatment modalities or T4N0-1 NPC patients. MATERIALS/METHODS: Between May 2010 and September 2017, a total of 75 NPC patients with T4N0-1 were reviewed from three hospitals of North West China. All patients received CCRT with or without IC. The IC regimens included TP regimen (docetaxel 75mg/m2, cisplatin 75mg/m2), GP regimen (gemcitabine 1000mg/m2, cisplatin 75mg/m2) and TPF regimen (docetaxel 75mg/m2, cisplatin 75 mg/m2, 5-fluorouracil 750 mg/m2 days1 to 5) every 3 weeks for 2-3 cycles. Concurrent chemotherapy was only consisted of cisplatin (100mg/m2 every 3 weeks). The primary endpoint was disease-free survival (DFS). The secondary endpoints included overall survival (OS), distant metastasis-free survival (DMFS), locoregional recurrence-free survival (LRFS) and toxicities. The measurement data between two groups was compared with χ2 test. Log-rank test were used to analyze the survival outcomes in groups. A 2-sided P value of less than 0.05 was considered as significant. RESULTS: The median follow-up time was 38 months (rang: 7-99 months). Of 75 patients, 11 patients died, 6 patients developed distant metastasis disease, and no patients experienced local regional recurrence during the follow-up period. The estimated 3-year OS, DFS and DMFS rates were 83.1%, 86.0% and 91% for all patients, respectively. No significant difference was detected between IC+CCRT and CCRT concerning 3-year DFS (85.6% vs. 80.8%, P = 0.455), OS (93.0% vs. 80.8%, P = 0.247) and DMFS (85.6% vs. 95.1%, P = 0.246) in the whole cohort, respectively. Moreover, we failed to detect statistically significant difference in adverse events between two treatment groups (P > 0.05). By subgroup analysis, IC+CCRT group had significant better OS than CCRT group in patients with N1 stage subgroup (92.0% vs. 65.9%, P = 0.044). Although no statistically significant difference was detected by subgroup analysis, IC+CCRT had a trend to have a better DFS in patients with stage N1 (88.0% vs. 65.9%, P = 0.054). CONCLUSION: IC followed by CCRT did not improve survival outcome in patients with T4N0-1 disease when compared with CCRT. However, patients with N1 stage might get survival benefit from IC+CCRT. Prospective studies and large sample retrospective studies are needed to further confirm this result.

16.
Int J Radiat Oncol Biol Phys ; 111(3S): e470, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34701530

RESUMO

PURPOSE/OBJECTIVE(S): Concurrent twice-daily 45Gy radiotherapy (concurrent-BID) remains the standard treatment for limited stage small-cell lung cancer (LS-SCLC). However, this regime is inconvenient and not universally adopted across different institutions, therefore hypofractionated schedule is more and more investigated. The aim of this study was to compare concurrent -BID with sequential hypofractionated radiotherapy (sequential-Hypo) in LD-SCLC by propensity score-matched analysis. We hypothesize that sequential-Hypo could be used as an alternative without increased toxicities. MATERIALS/METHODS: A retrospective analysis was conducted in 108 LS-SCLC patients treated between January 2015 and July 2019 in our institution. All patients received BID (45Gy/30F, n = 79, twice daily) or sequential-Hypo (54Gy/18F, n = 18; 45Gy/15F, n = 6; 60Gy/20F, n = 5, once daily) radiotherapy. After matching by propensity score, the survival, failure patterns and toxicities were compared. RESULTS: After propensity score matching, the confounders of patient characteristics between BID group (n = 24) and sequential-Hypo group (n = 24) were well balanced (age, P = 0.718; T staging, P = 0.149; N staging, P = 0.712; PCI, P = 0.755; performance status, P = 0.578). Before PSM, multivariate analysis showed that patients treated with sequential-Hypo had significantly better OS and DMFS (P = 0.009, HR = 0.353; P = 0.020, HR = 0.315, respectively). Total radiotherapy time≥24 days and stage III (P = 0.004, HR = 2.452; P = 0.055, HR = 2.310, respectively) were poor prognostic indicators for OS. Patients with T3 and T4 were more likely to recur than others (HR = 3.269, P = 0.040). N 2-3 and PS = 1 (P = 0.006, HR = 7.342; P = 0.023, HR = 10.384, respectively) were poor prognostic indicators for DMFS. After PSM by multivariable analyses, age≥65 years and total radiotherapy time≥24 days were associated with poorer OS (P = 0.004, HR = 4.222; P = 0.046, HR = 2.671, respectively). Although there was no significant difference, the patients in sequential-Hypo group had a trend to have a better OS. Before PSM, distant metastasis was the dominant failure pattern and was significantly less in sequential-Hypo group (17.7% vs 40.5%, P < 0.05). No significant difference was observed between BID group and Hypo group before and after PSM. CONCLUSION: Sequential-Hypo schedule was associated with comparable survival and toxicity outcomes and may be considered as an alternative to concurrent-BID. Prospective trials are needed to confirm this result.

17.
Int J Radiat Oncol Biol Phys ; 111(3S): e518, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34701643

RESUMO

PURPOSE/OBJECTIVE(S): Tissue spacers, including vaginal wall spacers, are used in a number of cancer diagnoses including soft tissue sarcomas, prostate cancer, cervical and uterine cancers. In proton therapy, the benefit of tissue spacers can be even greater as the device can serve as a beam stopper where protons reach their end of range in the material of the spacer instead of adjacent tissues. MATERIALS/METHODS: Commercially available hollow vaginal spacers which come in sizes ranging from 1.46 cm to 3.65 cm in diameter were filled with air-free silicone in a custom-made vacuum chamber. Two adolescent patients with pelvic soft tissue sarcomas receiving proton therapy were CT-simulated with and without a vaginal spacer. The relative stopping power of silicone was measured in a water tank to estimate the water equivalent thickness from 1.56 cm to 3.91 cm used in the treatment planning system for dosimetric comparisons. The dosimetric advantages of the silicone-filled vaginal spacer were investigated in three different dosimetric scenarios: (1) no vaginal spacer, (2) hollow vaginal spacer, (3) silicone-filled vaginal spacer in terms of plan quality and sparing of contralateral vaginal wall during primary and boost phases for two patients. RESULTS: While the target coverages remained comparable for the phase I (CTV, Rx = 36 Gy) and the phase II (GTV, Rx = 59.4 Gy), the dose distributions of ipsilateral and contralateral vaginal walls varied across these scenarios. After the phase II, the dosimetric sparing of contralateral vaginal wall was chiefly achieved in the patient A as the mean dose was 8.4 Gy with the silicone-filled spacer, and 17.1 Gy with hollow spacer, and 30.8 Gy with no spacer. However, due to the size and location of the tumor relative to the vagina, the sparing of contralateral vaginal was not observed in the patient B. While the patient A had a unilateral tumor with smaller GTV volume (23.3 cc) irradiated by straight lateral and posterior beams, the patient B had bilaterally located larger GTV volume (342.2 cc) covered by two posterior oblique beams. CONCLUSION: The study suggested that when the vagina is adjacent but located distal to the tumor, a significant dose reduction can be achieved with the insertion of a silicon-filled vaginal spacer.

18.
Int J Radiat Oncol Biol Phys ; 111(3S): e524, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34701660

RESUMO

PURPOSE/OBJECTIVE(S): To quantitatively model a precise spot-scanning proton arc (SPArc) delivery sequence and assess its efficiency improvement in the routine proton clinical operation. MATERIALS/METHODS: The SPArc delivery sequence model (DSMSPArc) includes two kinds of parameters: (1) mechanical parameters (the maximum gantry velocity, acceleration, and deceleration speed). (2) irradiation parameters (tolerance window and buffer, spot scanning speed, energy layer switching time, and burst switching time). An independent gantry inclinometer was used to measure mechanical parameters. Log files were used to derive the irradiation parameters through a series of SPArc test plans. The in-house DSMSPArc was established by fitting both mechanical and irradiation parameters. Eight SPArc plans from different disease sites (brain, HN, lung, and liver cancer) were used to validate the model's accuracy. To quantitatively assess the treatment efficiency improvement compared to the clinical IMPT, a random clinical operation date of our proton center (total 21 cases on Jan 6th 2021) was selected, and SPArc plans were generated for all the cases. The DSMSPArc was used to simulate the SPArc treatment delivery sequence and compared to the clinical IMPT treatment logfiles. RESULTS: The relative difference of treatment time between log files and DSMSPArc's prediction was 6.1% ± 3.9% on average, and the gantry angle vs. delivery time showed a good agreement between the DSMSPArc and log file. Additionally, the SPArc plan could effectively save two hours out of 10 hours of clinical operation by simplifying the treatment workflow for a single room proton therapy center. The average treatment delivery time (including gantry rotation and irradiation) per patient was reduced to 226 ± 149s using SPArc compared to 665 ± 407s using IMPT (P < 0.01). CONCLUSION: This is the first modeling of the SPArc delivery sequence, which paves the roadmap for implementing the delivery speed and time into the SPArc optimization algorithm. Additionally, SPArc can offer a superior delivery efficiency to improve clinical treatment throughput, compared to IMPT.

19.
Int J Radiat Oncol Biol Phys ; 111(3S): e529-e530, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34701672

RESUMO

PURPOSE/OBJECTIVE(S): Proton Pencil Beam Scanning (PBS) delivery sequence is critical in the evaluation of the motion interplay effect. We proposed an experimental approach to build a precise machine-specific model for standard delivery, volumetric repainting delivery, and layer repainting delivery based on a cyclotron accelerator system and assessed the interplay effect quantitatively. MATERIALS/METHODS: Test fields and clinical treatment plans were used to derive each beam delivery parameters experimentally. The machine delivery log files were retrospectively analyzed to model beam delivery parameters, such as energy layer switching time (ELST), spot switching time, and spot drill time, for standard, volumetric and layer repainting delivery techniques. To quantitatively evaluate the interplay effect, a series of digital thoracic 4DCT image sets were used through 4D dynamic dose accumulation method. A small tumor in radius 5mm (labeled by R5) and a large tumor in radius 2cm (R20) phantom were created to simulate the mobile target with different sizes. Target motion was simulated based on the periodic respiratory motion with an amplitude 5 mm. The breathing cycle is 4s. Two-field Single Field Uniform Dose (SFUD) plans were generated using PA and lateral field. Different delivery techniques such as standard delivery, volumetric repainting delivery (n = 2,3,4) and layer repainting delivery (n = 2,3,5,25) were simulated based on the machine-specific delivery sequence model and a simplified model published by West German Proton Therapy Essen (WPE). D99 (Dose received by 99% of target volume) of the target is used to estimate the delivery accuracy. RESULTS: The results showed that the WPE model's spot delivery sequence deviated from the log file significantly compared to the machine-specific model, which results the difference in the interplay effect evaluation. More specifically, for a lung treatment plan with target size (65 mm³) and layer repainting 25 times, the difference is about 21.01% due to a coarse spot scanning speed modeling and an oversimplified assumption of a constant ELST from WPE model. Such a difference also resulted in a very different interplay effects estimation between the two models even though both institutions used the same proton system from IBA and calculated using the same 4DCT imaging set. CONCLUSION: A precise machine-specific delivery sequence model is highly recommended to ensure an accurate estimation of mobile target treatment's interplay effect for each institution.

20.
Int J Radiat Oncol Biol Phys ; 111(3S): e538, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34701695

RESUMO

PURPOSE/OBJECTIVE(S): In comparison with large and expensive conventional linear and circular accelerator, miniaturized laser-driven proton accelerator provides the potential to reduce the overall costs. This could allow a widespread use of the superior properties of protons and ions in radiation therapy. However, the key to success is to improve the particle energy which is not high enough to meet the requirement for the treatment. With the development of high-repetition-rate petawatt class laser technology matures gradually, different acceleration mechanisms have been able to raise the energy of protons to close to 100MeV. MATERIALS/METHODS: To confirm the feasibility of proton beam generated in petawatt-laser irradiating nano-array target, three-dimensional particle-in-cell (3D-PIC) simulations were performed with the QED-PIC code EPOCH. The simulation box has a size of 30 µm(x) × 20 µm (y) × 20 µm (z), which is sampled by cells of 1500 × 400 × 400 with 125 pseudo-electrons, eight pseudo-carbons, and four protons in each cell. The Gaussian laser pulse propagates along the x-direction with y-direction polarization, a wavelength λ0 of 1µm, a peak power of 50 PW, and a duration of 30 fs in full width at half maximum (FWHM). With an initial focal spot radius σ = 3µm. In order to reduce the computational requirements. The array wires have an initial density of ne = 300nc (where nc = 1.1 × 1021 cm-3 is the critical plasma density) and are attached to a 4-µm-thick CH foil. In these simulations, periodic boundary conditions were employed for the laser field in the transverse directions and absorbing boundary conditions for the particles. RESULTS: Three-dimensional particle-in-cell simulation show that the laser-driven proton beam keep quite different characteristics compared with other accelerators proton beam, such as ultra-short beam duration (ns), high strength (107 / cm2 / pulse), large divergence angle (2°) and poly real-energetic spectrum. Meanwhile, we show that under optimal interaction conditions protons can be accelerated up to relativistic energies of 300 MeV by a petawatt laser field. The proton acceleration is due to the dragging Coulomb force arising from charge separation induced by the ponderomotive pressure ∼light pressure! of high-intensity laser. CONCLUSION: We investigate the impact of nano-structure array on the proton spectrum for different laser-plasma conditions. Our simulated data show that the nanostructures lead to a significant enhancement of absorption over the entire range of laser plasma conditions investigated. At conditions that do not allow for efficient laser absorption by plane targets, nano-structure array is found to significantly enhance the proton cut-off energy and conversion efficiency. AUTHOR DISCLOSURE: S. Wu: None. Z. Wang: None. X. Sun: None. W. Wang: None. F. Xiao: None. L. Zhao: None.

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