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PURPOSE/AIM OF THE STUDY: To summarize and discuss macrophage properties and their roles and mechanisms in the process of osseointegration in a comprehensive manner, and to provide theoretical support and research direction for future implant surface modification efforts. MATERIALS AND METHODS: Based on relevant high-quality articles, this article reviews the role of macrophages in various stages of osseointegration and methods of implant modification. RESULTS AND CONCLUSIONS: Macrophages not only promote osseointegration through immunomodulation, but also secrete a variety of cytokines, which play a key role in the angiogenic and osteogenic phases of osseointegration. There is no "good" or "bad" difference between the M1 and M2 phenotypes of macrophages, but their timely presence and sequential switching play a crucial role in implant osseointegration. In the implant surface modification strategy, the induction of sequential activation of the M1 and M2 phenotypes of macrophages is a brighter prospect for implant surface modification than inducing the polarization of macrophages to the M1 or M2 phenotypes individually, which is a promising pathway to enhance the effect of osseointegration and increase the success rate of implant surgery.
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Macrófagos , Osseointegração , Macrófagos/metabolismo , Citocinas/metabolismo , Próteses e Implantes , Osteogênese , Titânio/metabolismo , Propriedades de SuperfícieRESUMO
This randomized, multicenter, phase II clinical trial was performed to compare the safety and efficacy of concurrent chemoradiotherapy using S-1 (CCRT) with radiotherapy alone (RT) for elderly patients with locally advanced esophageal squamous cell carcinoma (ESCC). All eligible patients were randomly assigned to the CCRT group or the RT group at a 1:1 ratio. The CCRT group received 50.4 Gy radiotherapy concurrent with S-1 and the RT group received 59.4 Gy radiotherapy alone. The primary endpoints were toxicity and the overall response rate (ORR), and the secondary endpoints were overall survival (OS) and progression-free survival (PFS). In total, 157 elderly patients with ESCC were recruited from December 2016 to March 2020. By June 2021, the median follow-up duration had reached 38 months. No grade 5 toxicities occurred in either group and the overall rate of severe toxicities (≥grade 3) was higher in the CCRT group (19.2% vs 7.6%; P = .037), particularly neutropenia (7.7% vs 1.3%; P = .06). The CCRT group presented a significantly higher ORR (83.3% vs 68.4%; P = .009) and prolonged PFS (25.7 vs 13.9 months; P = .026) than the RT group. The median OS was 27.3 months in the CCRT group and 19.1 months in the RT group (P = .59). For patients older than 70 years with locally advanced ESCC, concurrent chemoradiotherapy with S-1 had tolerable adverse effects and improved ORR and PFS compared to radiotherapy alone.
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia/efeitos adversos , Cisplatino/uso terapêutico , Células Epiteliais/patologia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , HumanosRESUMO
Clinically, open wounds caused by accidental trauma and surgical lesion resection are easily infected by external bacteria, hindering wound healing. Antibacterial photodynamic therapy has become a promising treatment strategy for wound infection. In this study, a novel antibacterial nanocomposite material (QMC NPs) was synthesized by curcumin, quaternized chitosan and mesoporous polydopamine nanoparticles. The results showed that 150 µg/mL QMC NPs had good biocompatibility and exerted excellent antibacterial activity against Staphylococcus aureus and Escherichia coli after blue laser irradiation (450 nm, 1 W/cm2). In vivo, QMC NPs effectively treated bacterial infection and accelerated the healing of infected wounds in mice.
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Antibacterianos , Quitosana , Curcumina , Escherichia coli , Indóis , Nanopartículas , Polímeros , Staphylococcus aureus , Quitosana/química , Quitosana/farmacologia , Indóis/química , Indóis/farmacologia , Curcumina/farmacologia , Curcumina/química , Polímeros/química , Polímeros/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Nanopartículas/química , Animais , Camundongos , Staphylococcus aureus/efeitos dos fármacos , Porosidade , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Cicatrização/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológicoRESUMO
PURPOSE: Neoadjuvant chemoradiotherapy is the recommended treatment for patients with resectable esophageal cancer but is associated with a higher incidence of adverse effects. Given the efficacy of immunotherapy, we propose a chemotherapy-free regimen of neoadjuvant radio-immunotherapy (NRIT) to balance therapeutic efficacy and potential side effects or overtreatment. METHODS AND MATERIALS: In this phase 1b clinical trial, we assessed the safety and efficacy of NRIT in esophageal squamous cell cancer. The enrolled patients received 41.4 Gy of radiation and 4 cycles of 240 mg of toripalimab injection before surgery. The primary endpoint was treatment-related adverse events and the secondary endpoints were pathologic complete response and major pathologic response. Immunohistochemistry and multiplex immunofluorescence staining were used to evaluate the tumor microenvironment before and after neoadjuvant treatment. RESULTS: Of the 22 patients enrolled, 19 underwent R0 surgery. One patient discontinued neoadjuvant immune therapy due to experiencing a grade 3 treatment-related adverse event. Three patients did not undergo surgery due to tumor progression or side effects. Among the patients who underwent surgery, 3 patients experienced serious complications shortly after surgery. Upon pathologic evaluation, the pathologic complete response and major pathologic response rates were 47.4% and 68.4%, respectively. CONCLUSIONS: The NRIT regimen is safe and feasible for patients with esophageal squamous cell cancer.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Terapia Neoadjuvante , Humanos , Terapia Neoadjuvante/efeitos adversos , Masculino , Pessoa de Meia-Idade , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patologia , Feminino , Idoso , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/patologia , Imunoterapia/efeitos adversos , Microambiente Tumoral , Adulto , Resultado do Tratamento , Anticorpos Monoclonais Humanizados/uso terapêuticoRESUMO
BACKGROUND: Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC). However, the optimal radiotherapy regimen, particularly in terms of total dose and planned range of irradiation field, remains unclear. This phase III clinical trial aimed to compare the survival benefits between different radiation doses and different target fields. METHODS: This trial compared two aspects of radiation treatment, total dose and field, using a two-by-two factorial design. The high-dose (HD) group received 59.4 Gy radiation, and the standard-dose (SD) group received 50.4 Gy. The involved field irradiation (IFI) group and elective nodal irradiation (ENI) group adopted different irradiation ranges. The participants were assigned to one of the four groups (HD+ENI, HD+IFI, SD+ENI and SD+IFI). The primary endpoint was overall survival (OS), and the secondary endpoints included progression-free survival (PFS). The synergy indexwas used to measure the interaction effect between dose and field. RESULTS: The interaction analysis did not reveal significant synergistic effects between the dose and irradiation field. In comparison to the target field, patients in IFI or ENI showed similar OS (hazard ratio [HR] = 0.99, 95% CI: 0.80-1.23, p = 0.930) and PFS (HR = 1.02, 95% CI: 0.82-1.25). The HD treatment did not show significantly prolonged OS compared with SD (HR = 0.90, 95% CI: 0.72-1.11, p = 0.318), but it suggested improved PFS (25.2 months to 18.0 months). Among the four groups, the HD+IFI group presented the best survival, while the SD+IFI group had the worst prognosis. No significant difference in the occurrence of severe adverse events was found in dose or field comparisons. CONCLUSIONS: IFI demonstrated similar treatment efficacy to ENI in CCRT of ESCC. The HD demonstrated improved PFS, but did not significantly improve OS. The dose escalation based on IFI (HD+IFI) showed better therapeutic efficacy than the current recommendation (SD+ENI) and is worth further validation.
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PURPOSE: Although immune checkpoint inhibitor monotherapy has been used as a second-line treatment in advanced non-small cell lung cancer (NSCLC), the improvement in progression-free survival (PFS) remains unsatisfactory. We investigated the feasibility of sintilimab plus chemotherapy as a second-line treatment in advanced NSCLC. METHODS: This was a phase II, single-arm, prospective study in advanced NSCLC patients who had failed standard platinum-based chemotherapy (ChiCTR1900027634, Registered 22 November 2019). Eligible patients received docetaxel 75 mg/m2 (day 1) plus sintilimab 200 mg (day 3) Q3W. Those did not progress after 4-6 cycles received sintilimab 200 mg Q3W as maintenance treatment. The primary endpoint was PFS. RESULTS: Forty patients were enrolled between October 2019 and October 2020. With a median follow-up of 12.2 months, the median PFS was 5.8 months, and the PFS rates at 6 and 12 months were 48% and 30%, respectively. The median overall survival (OS) was 12.6 months, with a 12-month OS rate of 62.0%. The overall response rate was 32.4%, and the disease control rate was 89.2%. The incidence of all and ≥ grade 3 treatment-related adverse events (TRAEs) were 65% (26/40) and 17.5% (7/40), respectively. No TRAEs-related permanent treatment discontinuation or death occurred. bTMB reduction at 6 weeks was associated with a longer PFS (NR vs 3.0 months, P < 0.0001). CONCLUSION: This prospective phase II study in China suggested that sintilimab plus docetaxel might improve PFS and tumor response with good tolerability for Chinese patients with previously treated advanced NSCLC. bTMB reduction at 6 weeks could serve as a potential predictive biomarker for this regimen.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Docetaxel , Estudos Prospectivos , Neoplasias Pulmonares/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
Objective: This study aimed to compare the efficacy and safety of induction chemotherapy followed by concurrent chemoradiotherapy (I-CCRT), induction chemotherapy followed by concurrent chemoradiotherapy and consolidation chemotherapy (I-CCRT-C), and concurrent chemoradiotherapy followed by consolidation chemotherapy (CCRT-C) for locally advanced esophageal squamous cell carcinoma (ESSC). Patients and Methods: Patients with locally advanced ESCC who underwent definitive chemoradiotherapy with cisplatin plus fluorouracil or docetaxel from February 2012 to December 2018 were retrospectively reviewed. Kaplan-Meier curve was used to estimate survival. Efficacy was assessed using RECIST, version 1.0. Prognosis factors were identified with Cox regression analysis. Results: Patients were treated with CCRT-C (n = 59), I-CCRT (n = 20), and I-CCRT-C (n = 48). The median follow-up duration was 73.9 months for the entire cohort. The ORR of the CCRT-C, I-CCRT, and I-CCRT-C groups was 89.8%, 70.0%, and 77.1%, respectively (p = 0.078). The median PFS in the CCRT-C, I-CCRT, and I-CCRT-C groups was 32.5, 16.1, and 27.1 months, respectively (p = 0.464). The median OS of the CCRT-C, I-CCRT, and I-CCRT-C groups was 45.9, 35.5, and 54.0 months, respectively (p = 0.788). Cox regression analysis indicated that I-CCRT-C and I-CCRT did not significantly prolong PFS and OS compared with CCRT-C (p > 0.05). Neutropenia grade ≥3 in CCRT-C, I-CCRT, and I-CCRT-C groups was 47.5%, 15%, and 33.3% of patients, respectively (p = 0.027). Conclusions: I-CCRT and I-CCRT-C using cisplatin plus fluorouracil or docetaxel regimen are not superior to CCRT-C in survival but seem to have less severe neutropenia than CCRT-C. Further randomized controlled studies are warranted.
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Leptomeningeal metastases (LM) are rare and catastrophic for metastatic breast cancer (MBC). The prognosis of HER2-positive breast cancer (BC) with LM is extremely poor. There is no high-quality evidence of treatment regimens in HER2-positive BC with LM yet. Here, we present a case of LM in a 50-year-old woman with HER2-positive BC. Immunohistochemistry revealed invasive ductal carcinoma, estrogen receptor negative, progesterone receptor negative, HER2 3+, P53 positive 80%, and Ki-67 positive 35%. Reported for the first time, the patient was given pyrotinib-targeted therapy (400 mg, oral, every day), metronomic vinorelbine (40 mg, oral, three times a week), and intrathecal methotrexate (10 mg, infrequent and irregular use due to poor compliance) synchronously. The patient received and benefited from the treatment regimen for 16 months. And the quality of life, as self-reported, improved significantly. We also comprehensively summarized all the case reports, observational studies, and clinical trials related to HER2-positive BC with LM in the PubMed database and ClinicalTrials.gov. Intrathecal chemotherapy (methotrexate, cytarabine, thiotepa), intrathecal trastuzumab, whole-brain radiotherapy, and systemic therapy are commonly used treatment options according to a review of the literature and research. Pembrolizumab and trastuzumab deruxtecan (DS-8201) as novel drugs are promising in LM. Furthermore, trastuzumab emtansine (T-DM1) and tyrosine kinase inhibitors (TKIs) such as tucatinib and neratinib have exhibited good efficacy in HER2-positive BC with central nervous system (CNS) metastases and deserve further exploration. In our report, combining pyrotinib-targeted therapy with metronomic chemotherapy is a potential regimen, which has presented satisfactory therapeutic efficacy and also warrants additional investigation in HER2-positive BC with LM.
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OBJECTIVE: Robust biomarker predicting efficacy of immunotherapy is limited. Circulating tumor DNA (ctDNA) sought to effectively monitor therapeutic response as well as disease progression. This study aims to investigate predictive role of ctDNA short-term dynamic change (6 weeks postimmunotherapy) in a single-arm, phase 2 trial of sintilimab plus docetaxel for previously treated advanced non-small cell lung cancer (NSCLC) patients. METHODS: A total of 33 patients with advanced NSCLC with disease progression during or after any first-line treatment were prospectively enrolled between 2019 and 2020. Patients received sintilimab (200 mg, day 1, every 3 weeks) plus docetaxel (75 mg/m2, day 3, every 3 weeks) for 4-6 cycles, followed by maintenance therapy with sintilimab (200 mg, day 1, every 3 weeks) until disease progression or unacceptable toxic effects. Blood samples were prospectively collected at baseline, and after 2 cycles of treatment (6 weeks post-treatment). All samples were subjected to targeted next-generation sequencing with a panel of 448 cancer-related genes. The landscape of high-frequency genomic profile of baseline and 6th week was described. Major molecular characteristics in preselected genes of interest associated with response to second-line chemoimmunotherapy were analyzed. The curative effects and prognosis of patients were evaluated. RESULTS: Patients with ctDNA clearance at 6th week had decreased tumor volume, while most patients with positive ctDNA at 6th-week experienced an increase in tumor volume. Positive 6th-week ctDNA was associated with significantly shorter progression-free survival (PFS) (91 vs NR days; p<0.0001) and overall survival (47 vs 467 days; p =0.0039). Clearance of clonal mutations and none new clonal formation at 6th week were associated with longer PFS (mPFS 89 vs 266 days, p =0.003). ctDNA clearance at 6th week was an independent risk factor for progression or death (HR=100 (95% CI 4.10 to 2503.00), p=0.005). CONCLUSION: ctDNA status and ctDNA mutation clearance putatively serve as predictive biomarkers for sintilimab combined with docetaxel chemotherapy in pretreated advanced NSCLC patients.
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Carcinoma Pulmonar de Células não Pequenas , DNA Tumoral Circulante , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Docetaxel/uso terapêutico , DNA Tumoral Circulante/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Progressão da DoençaRESUMO
PURPOSE: The aim of this study is to investigate the role of standard uptake values (SUVs) and metabolic tumor volume (MTV) in [(18)F]fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) to predict the short-term outcome of chemoradiotherapy (CRT) in patients with advanced non-small cell lung cancer (NSCLC). METHODS: A total of 37 patients were included in the prospective study. All patients were evaluated by FDG PET before and following 40 Gy radiotherapy (RT) with a concurrent cisplatin-based chemotherapy regimen. Semiquantitative assessment was used to determine maximum and mean SUVs (SUV(max)/SUV(mean)) and metabolic tumor volume (MTV). Short-term outcome using the treatment response evaluation was assessed according to the Response Evaluation Criteria in Solid Tumors. The receiver-operating characteristic (ROC) curve analysis was used to determine the diagnostic accuracy of (18)F-FDG PET in identifying responders. RESULTS: Changes in SUV(max), SUV(mean), and MTV were significantly more pronounced in responders than in nonresponders (p = 0.002, 0.002, 0.000). The thresholds of SUV(max), SUV(mean), and MTV changes defined by ROC curve analysis were 37.2, 41.7, and 29.7%, respectively. The sensitivity, specificity, and accuracy of SUV(max) change for predicting tumor response were 83.3, 84.6, and 84.9%, respectively. The sensitivity, specificity, and accuracy of SUV(mean) change for predicting tumor response were 79.2, 100, and 88.8%, respectively. The sensitivity, specificity, and accuracy of MTV change for predicting tumor response were 91.7, 84.6, and 92.3%, respectively. CONCLUSION: SUV and MTV changes from two serial (18)F-FDG PET/CT scans, before and after initial CRT, allow prediction of the treatment response in advanced NSCLC.
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Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia , Fluordesoxiglucose F18 , Neoplasias Pulmonares/terapia , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Carga Tumoral , Transporte Biológico , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Fluordesoxiglucose F18/metabolismo , Glucose/metabolismo , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/efeitos da radiaçãoRESUMO
The purpose of this study was to investigate clinical-biological factors which could predict the sensitivity to chemoradiotherapy of esophageal squamous cell carcinoma (ESCC). One hundred eighty-one patients with stages I-IV ESCC were evaluated. The cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), carcinoembryonic antigen (CEA), albumin (A) as well as hemoglobin (HB) concentration were measured before the initiation of chemoradiotherapy (CRT). The cutoff values of CYFRA21-1, CEA, and A were defined as 3.4 ng/ml, 3.3 ng/ml, 3.5 g/dl, respectively. HB was divided into three levels: <12.0, 12.0-14.0, and >14.0 g/dl. Clinical factors such as sex, age, tumor location, primary cancer length, and tumor-node-metastasis stage were also evaluated. The effective rate (complete response + partial response) of the primary tumor estimated by computed tomography was 60.71% (17 out of 28) in patients with CEA high group while 92.54% (62 out of 67) in patients with CEA low group (P = 0.000) and 62.50% (20 out of 32) in patients with CYFRA21-1 high group while 92.98% (53 out of 57) in patients with CYFRA21-1 low group (P = 0.000). HB levels before and during CRT were also associated with the effectiveness (P = 0.005, 0.033, respectively). HB levels before CRT at 12.0-14.0 g/dl were associated with the best effectiveness, followed by >14.0 and <12.0 g/dl (effective rates 88.89% vs. 83.75%, 62.07%, respectively, P = 0.005). HB levels during CRT also showed similar results (effective rates 87.80% vs. 85.41%, 70.59%, respectively, P = 0.033). Furthermore, according to numbers of the above risk factors, the sensitivity of CRT was higher in patients with zero to one risk factors than those with two to four risk factors (P = 0.023). CYFRA21-1 and CEA as well as HB and their combination may be helpful in predicting the sensitivity to CRT of ESCC. However, the results should be further confirmed in larger, more homogeneous studies.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/radioterapia , Adulto , Idoso , Albuminas/metabolismo , Antígenos de Neoplasias/sangue , Antígeno Carcinoembrionário/sangue , Carcinoma de Células Escamosas/patologia , Cisplatino/administração & dosagem , Terapia Combinada , Resistencia a Medicamentos Antineoplásicos , Neoplasias Esofágicas/patologia , Feminino , Fluoruracila/administração & dosagem , Hemoglobinas/metabolismo , Humanos , Queratina-19/sangue , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Dosagem RadioterapêuticaRESUMO
OBJECTIVE: To study the pattern of lymph node metastasis of thoracic esophageal squamous cell carcinoma (ESCC) after esophagectomy and its impact on the clinical target volume (CTV) delineation in radiotherapy fpr thoracic ESCC. METHODS: The pattern of lymph node metastasis was retrospectively analyzed in 1077 patients with primary thoracic ESCC. All patients received esophagectomy with two- or three-field lymphadenectomy. The clinicopathologic factors related to lymph node metastasis were then analyzed using logistic regression analysis. RESULTS: The rates of cervical, upper mediastinal, middle mediastinal, lower mediastinal and abdominal cavity lymph node metastasis were 16.7%, 33.3%, 11.1%, 5.6% and 5.6%, respectively. The rates of those node metastasis in the middle thoracic ESCC were 4.0%, 3.8%, 28.5%, 7.1% and 17.1%, respectively, and the rates of those node metastasis in the lower thoracic ESCC were 1.5%, 3.0%, 22.7%, 37.0% and 33.2%, respectively. The depth of tumor invasion, histologic differentiation and the length of tumor were showed to be statistically most significant risk factors of lymph node metastasis of ESCC (P < 0.001). CONCLUSION: The depth of tumor invasion, histologic differentiation, and length of tumor were closely correlated with lymph node metastasis of ESCC. All these factors and tumor location should be considered comprehensively when designing the target volume for radiotherapy.
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Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/radioterapia , Linfonodos/patologia , Idoso , Esofagectomia , Feminino , Humanos , Excisão de Linfonodo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Radioterapia Conformacional/métodos , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Chemoradiotherapy (CRT) is currently performed for patients with advanced esophageal carcinoma. Sensitivity of tumours to CRT differs from one case to another and may be influenced by the expression of biological molecules. The aim of this study was to identify biological markers which could predict sensitivities of esophageal squamous cell carcinoma (ESCC) to CRT. METHODS: A total of 84 patients with stage I-IV ESCC were evaluated. The cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) and carcinoembryonic antigen (CEA) levels were measured before CRT by enzyme-linked immunosorbent assays in patients with primary ESCCs using 3.4 ng ml(-1) and 3.3 ng ml(-1), respectively, as cut-off values. The relationships between pretreatment expression of CYFRA 21-1 and CEA and the effectiveness of CRT were analysed. RESULTS: The complete response (CR) rates of the primary tumours estimated by computed tomography in patients with high levels of CYFRA21-1 and CEA were 10% (3/30) and 4.2% (1/24), while in cases with low CYFRA21-1 and CEA the CR rates were 50% (27/54) and 48.3% (29/60), respectively (p = 0.002 and 0.003). The effective rates (CR+PR) in CYFRA21-1 high and low groups were 60% (18/30) and 96.3% (52/54), while in CEA high and low groups they were 58.3% (14/24) and 93.3% (56/60), respectively (p = 0.013 and 0.013). CONCLUSION: CYFRA21-1 and CEA may be helpful in predicting the responsiveness in ESCC of primary lesions to CRT, although the results should be confirmed in larger, more homogeneous studies.
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Antígenos de Neoplasias/sangue , Biomarcadores Tumorais/sangue , Antígeno Carcinoembrionário/sangue , Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/terapia , Queratina-19/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/sangue , Terapia Combinada , Tratamento Farmacológico , Neoplasias Esofágicas/sangue , Feminino , Humanos , Técnicas Imunoenzimáticas , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Radioterapia , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the impact of PET/CT on the clinical staging, target volume delineation and precise radiotherapy (PAR) planning for patients with non-small cell lung cancer (NSCLC). METHODS: PET/CT scanning was performed in 58 histologically proven NSCLC patients for radical radiotherapy or surgery. The clinical staging of all patients was determined by PET/CT according to 1997 World Health Organization (WHO) staging system. The gross tumor volume (GTV) was delineated and three-dimensional conformal radiotherapy (3D-CRT) planning was established with identical parameters based on CT image and PET/CT fused image, respectively. The indexes including volume of GTV (V(GTV)), percentage of the total lung volume which received more than 20 Gy (V(20)), mean lung dose (MLD), tumor control probability (TCP), normal tissue complication probability (NTCP), and dose to spinal cord (Ds) were selected and evaluated. The quality of the two plans and the impact of PET/CT on PAR planning was compare and analyzed. RESULTS: 1. PET/CT image results changed the clinical stages in 21 of 58 (36.2%) patients with 14 upstaged and 7 downstaged, therefore, the management decisions were modified in 16 (27.6%) patients. 2. Among 32 patients who underwent surgery, PET/CT staging result was consistent with pathologic staging in 29 with one false negative and 2 false positive in lymph node staging. The sensitivity of PET/CT was 96.9% and accuracy 90.6%. 3. The differences of indexes including V(GTV) (P = 0.004), V(20) (P = 0.000) and MLD (P = 0.004) between the two radiotherapy plannings were statistically significant, whereas, the Ds, TCP and NTCP (left lung, right lung, skin and spinal cord) was not. CONCLUSION: 1. The impact PET/CT on clinical staging of NSCLC and PAR planning was remarkable. 2. PET/CT is more consistent with pathology in staging than CT and, therefore, is an important compensatory staging measure. 3. Compared with CT, PET/CT can reduce the V(GTV) in patients with atelectasis and obstructive pneumonitis when contouring the target volume, so can provide better protection for normal surrounding lung tissue. On the other hand, PET/CT is more sensitive in detecting mediastinal lymph node metastasis than CT, and the V(GTV) can be more precise and guaranteed. 4. Radiopneumonitis may be more effectively prevented because of significant decrease in V(20) and MLD by more precise planning based on PET/CT results. 5. PET/CT not only can provide satisfactory Ds, TCP and NTCP within clinical demand, but also more precise delineation of the radiation target volume and precise radiotherapy planning for NSCLC.
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Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Tomografia por Emissão de Pósitrons/métodos , Radioterapia Conformacional/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Tomografia Computadorizada por Raios XRESUMO
To clarify the effects of selenium level on the risk of gastric cancer (GC) and GC mortality, a meta-analysis was performed. Related studies were identified from PubMed, EMBASE, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM). Pooled ORs and 95% CIs were used to assess the strengthof the associations. A total of 8 studies including 17834 subjects were involved in this meta-analysis. High selenium level was associated with GC risk in case-control study (OR = 0.62, 95% CI 0.44-0.89, P = 0.009; I2 = 52%) and cohort study (OR = 0.87, 95% CI 0.78-0.97, P = 0.01; I2 = 25%). In addition, high selenium level was associated with GC mortality risk (OR = 0.90, 95% CI 0.84-0.97, P = 0.006, I2 = 49%). In summary, this meta-analysis suggested that selenium might inversely associated with GC risk and GC mortality.
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Selênio/sangue , Neoplasias Gástricas/epidemiologia , Feminino , Humanos , Masculino , Fatores de RiscoRESUMO
Our aim was to evaluate the efficacy and safety of cisplatin with pemtrexed or vinorelbine and concurrent late course accelerated hyperfractionated radiotherapy (LCAHRT). Patients with unresectable stage III non-small-cell lung cancer (NSCLC) were randomly assigned to two regimens. The experimental (PP) arm included cisplatin, pemtrexed and concurrent LCAHRT based on bilateral lung V20 = 33%. The control (NP) arm used cisplatin, vinorelbine with the same radiotherapy protocol. The primary endpoint was overall survival. Median survival times were 26.0 months (95% CI 23.2 to 28.7 months) and 28.5 months (95% CI 17.1 to 39.9 months) for the NP and PP arms, respectively (P = 0.26). Median progression-free survival was 12.5 months and 17.5 months in the NP and PP arms (P = 0.07). In both arms of the study, there were no differences in overall survival between patients with squamous and nonsquamous NSCLC. The incidences of grade 3 or 4 toxicity were higher in NP than PP arm. With concurrent LCAHRT, pemetrexed/cisplatin was equally as efficacious as vinorelbine/cisplatin, but showed a more favorable toxicity profile.
Assuntos
Adenocarcinoma/terapia , Carcinoma de Células Grandes/terapia , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia , Neoplasias Pulmonares/terapia , Recidiva Local de Neoplasia/terapia , Adenocarcinoma/secundário , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Grandes/secundário , Carcinoma Pulmonar de Células não Pequenas/secundário , Carcinoma de Células Escamosas/secundário , Cisplatino/administração & dosagem , Fracionamento da Dose de Radiação , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Pemetrexede/administração & dosagem , Prognóstico , Taxa de Sobrevida , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , VinorelbinaRESUMO
UNLABELLED: The aim of this study was to investigate the value of standardized uptake values (SUVs) and metabolic tumor volume (MTV) in (18)F-FDG PET/CT to predict the survival of patients with locally advanced non-small cell lung cancer during the early stage of concurrent chemoradiotherapy. METHODS: A total of 53 patients were included in the prospective study. All patients were evaluated by (18)F-FDG PET before and after 40 Gy of radiotherapy with a concurrent cisplatin-based chemotherapy regimen. Semiquantitative assessment was used to determine the maximum and mean SUVs (SUV(max) and SUV(mean), respectively) and MTV of the primary tumor. The cutoffs for changes in SUV(max), SUV(mean), and MTV (37.2%, 41.7%, and 29.7%, respectively) determined in a previous study were used with Kaplan-Meier curves to separate the groups. The prognostic significance of PET/CT parameters and other clinical variables was assessed using Cox regression analysis. RESULTS: Overall survival (OS) at 1 and 2 y was 83.0% (46/53) and 52.8% (28/53), respectively. Survival curves for SUV(mean) and MTV were significantly different using the cutoffs. However, Cox regression analysis showed that the only prognostic factor for OS was a decrease in MTV. CONCLUSION: The use of repeated (18)F-FDG PET to assess survival early during concurrent chemoradiotherapy is possible in patients with locally advanced non-small cell lung cancer. A decrease in MTV according to (18)F-FDG uptake by the primary tumor correlates with higher long-term OS.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Quimiorradioterapia/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Cisplatino/uso terapêutico , Feminino , Fluordesoxiglucose F18 , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Tomografia por Emissão de Pósitrons/métodos , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Análise de Regressão , Análise de Sobrevida , Tomografia Computadorizada por Raios X/métodos , Resultado do TratamentoRESUMO
BACKGROUND: In this phase II study, we evaluated the efficacy, toxicity, and patterns of failure of elective lymph node irradiation (ENI) late course accelerated hyper-fractionated radiotherapy (LCAHRT) concurrently with cisplatin-based chemotherapy (CHT) for esophageal squamous cell carcinoma (ESCC). METHODS: Patients with clinical stage II-IVa (T1-4N0-1M0 or M1a) ESCC were enrolled between 2004 and 2011. Radiation therapy (RT) comprised two courses: The first course of radiation covered the primary and metastatic regional tumors and high risk lymph nodal regions, given at 2 Gy per fraction for a dose of 40 Gy. In the second course, LCAHRT was delivered to the boost volume twice a day for an additional 19.6 Gy in 7 treatment days, using 1.4 Gy per fraction. Two cycles of CHT were given at the beginning of RT. RESULTS: The median age and Karnofsky performance status were 63 years and 80, respectively. The American Joint Committee on Cancer stage was II in 14 (20.6%) patients, III in 32 (47.1%), and IVa in 22 (32.3%). With a median follow-up of 18.5 months, the overall survival at 1-, 3-, 5-year were 75.5%, 46.5%, 22.7% for whole group patients, versus 78.6%, 49.4%, 39.9% for patients with stage II-III. The patterns of first failure from local recurrence, regional failure, and distant metastasis were seen in 20.6%, 17.6%, and 19.1%, respectively. The most frequent acute high-grade (≥ 3) toxicities were esophagitis and leucopenia, occurred in 26.4% and 32.4%. CONCLUSIONS: ENI LCAHRT concurrently with CHT was appeared to be an effective regimen for ESCC patient with a favorable and tolerated profile. Further observation with longer time and randomized phase III trial is currently underway. TRIAL REGISTRATION: ChiCTR-TRC-09000568.
Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Quimiorradioterapia/métodos , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/radioterapia , Linfonodos/efeitos da radiação , Recidiva Local de Neoplasia/prevenção & controle , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Carcinoma de Células Escamosas/patologia , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Fracionamento da Dose de Radiação , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologiaAssuntos
Tomografia Computadorizada Quadridimensional , Neoplasias Hepáticas/radioterapia , Neoplasias Pulmonares/radioterapia , Neoplasias da Próstata/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Radioterapia de Intensidade Modulada/métodosRESUMO
OBJECTIVES: Concurrent chemoradiotherapy in well-selected locally advanced non-small cell lung cancer (LANSCLC) is considered as standard therapy. However, the choice of anticancer agents is still unresolved. Our objectives were to determine the maximum tolerated dose and recommended dose of pemetrexed in combination with cisplatin, with concurrent late course accelerated hyperfractionated (LCAF) intensity modulated radiotherapy (IMRT) in patients with LANSCLC and to investigate the safety and efficacy. METHODS: The chemotherapy was cisplatin (25 mg/m(2) × 3 days) plus pemetrexed with doses escalating from 400 to 500 mg/m(2). The dose level was increased every 3 patients. The gross tumor volumes of concurrent LCAF IMRT were delineated according to [(18)F] fluorodeoxyglucose positron emission tomography computed tomography imaging. To spare functional lung, single photon emission photography lung perfusion imaging was used to optimize the plans. The total radiation dose was limited such that the V20 of bilateral lung is no more than 35%. RESULTS: Nine patients with LANSCLC were enrolled in this study. The median radiation dose was 70.8 Gy. The response rate was 66.7% with a complete remission rate of 33.3%. Toxicity was mild with only 1 patient experiencing dose limiting toxicity in 500 mg/m(2) level. Obviously, the maximum tolerated dose was not reached as per the definition. As the systemically active chemotherapy dose was reached, further dose escalation was discontinued, and the recommended dose of pemetrexed for a phase II study was 500 mg/m(2). CONCLUSIONS: The combination of pemetrexed and cisplatin with concurrent LCAF IMRT optimized based on single photon emission photography lung perfusion imaging is well tolerated in patients with LANSCLC. Full therapeutic doses of the chemotherapy can be safely administered. The initial results showed signs of efficacy.