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OBJECTIVE: There is a lack of effective biomarkers for predicting the distant metastasis in nasopharyngeal carcinoma (NPC). We aimed to explore the expression of FAP+Cancer-associated fibroblasts (CAFs) derived CXCL1 in NPC and its predictive values for distant metastasis and correlation with PD-L1 expression. MATERIALS AND METHODS: A total of 345 patients with locoregionally advanced NPC were retrospectively enrolled (the training cohort: the validation cohort = 160:185). Co-expression of CXCL1 and FAP and the expression of PD-L1 were detected by multi-immunofluorescence staining and immunohistochemistry, respectively. The primary end-point was distant metastasis-free survival (DMFS). The Kaplan-Meier method was used to calculate the survival. The Cox proportional hazards model was used to assess prognostic risk factors. RESULTS: A novel CXCL1+_FAP+ phenotype in CAFs was identified in NPC and then used to divide patients into low and high risk groups. Both in the training cohort and validation cohort, patients in the high risk group had poorer DMFS, overall survival (OS), progression-free survival (PFS) and locoregional relapse-free survival (LRFS) than patients in the low risk group. Multivariate analysis revealed CXCL1+_FAP+ phenotype was an independent prognostic factor for DMFS, OS, PFS and LRFS. Further results showed patients in the high risk group had higher PD-L1 expression than those in the low risk group. CONCLUSION: Our study showed CXCL1+_FAP+ phenotype in CAFs could effectively classified locoregionally advanced NPC patients into different risk groups for distant metastasis and might be a potential biomarker for anti-PD-1/PD-L1 immunotherapy.
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Antígeno B7-H1 , Fibroblastos Asociados al Cáncer , Quimiocina CXCL1 , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Antígeno B7-H1/metabolismo , Masculino , Femenino , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patología , Carcinoma Nasofaríngeo/mortalidad , Persona de Mediana Edad , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/mortalidad , Quimiocina CXCL1/metabolismo , Fibroblastos Asociados al Cáncer/metabolismo , Adulto , Estudios Retrospectivos , Metástasis de la Neoplasia , Pronóstico , Fenotipo , Biomarcadores de Tumor/metabolismo , Anciano , Serina Endopeptidasas/metabolismo , Endopeptidasas/metabolismo , Proteínas de la Membrana/metabolismoRESUMEN
OBJECTIVE: The purpose of this study was to investigate the value of postoperative chemotherapy for locally advanced rectal cancer patients who reached pathological ypT1-4N0 after neo-adjuvant chemoradiotherapy. METHODS: We performed a retrospective study of 104 patients treated with preoperative chemoradiotherapy followed by radical resection, who achieved pathological ypT1-4N0, between Mar 2003 and Dec 2010. There were 73 patients who received postoperative adjuvant chemotherapy, and the other 31 patients did not. The distribution of final pathologic stages for these patients was ypT1-2N0 in 39 cases and ypT3-4N0 in 65 cases. RESULTS: The median follow-up was 41 months. The 3-year overall survival rate (OS) and recurrence-free survival rate (RFS) for the whole group (ypT1-4N0) were 93.4% and 85.3%, respectively. The 3-year OS and RFS in the adjuvant chemotherapy group and non-adjuvant chemotherapy group were 95.5%, 88.6% and 88.6%, 77.2%, respectively. There were no significant differences in 3-year RFS (P = 0.108) and OS (P = 0.106) between the two groups. The 3-year local recurrence and distant metastasis rates in the adjuvant chemotherapy group were 4.1% (3/73) and 5.5% (4/73), while for the non-adjuvant chemotherapy group, the 3-year local recurrence rate and distant metastasis rate were 3.2% (1/31) and 16.1% (5/31), respectively. Significant difference was found in distant metastasis rates (P = 0.030) between the two groups, but not in local recurrence rates (P = 0.676).Further subgroup analysis indicated that for the ypT1-2N0 patients, there were no significant differences in 3-year OS (P = 0.296) and RFS (P = 0.939) between the adjuvant and non-adjuvant chemotherapy groups, while negative results displayed in 3-year local recurrence rates (P = 0.676) and distant metastasis rates (P = 0.414). However, for patients with ypT3-4N0, significant differences were showed in both the 3-year OS (P = 0.034) and RFS (P = 0.025), and further analysis revealed that the 3-year distant metastasis rate was significantly higher in the non-adjuvant chemotherapy group than in the adjuvant chemotherapy group (P = 0.010) , but with non-significant difference in the 3-year local recurrence (P = 0.548). CONCLUSIONS: Adjuvant chemotherapy may not improve survival for ypT1-2N0 patients. However, it may be clinically meaningful for ypT3-4N0 patients by decreasing distant metastasis rate. Further randomized controlled clinical trials are needed to confirm our results.
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Adenocarcinoma , Quimioradioterapia Adyuvante , Terapia Neoadyuvante , Neoplasias del Recto , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Adenocarcinoma/radioterapia , Adenocarcinoma/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Capecitabina , Quimioterapia Adyuvante , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Femenino , Fluorouracilo/análogos & derivados , Fluorouracilo/uso terapéutico , Estudios de Seguimiento , Humanos , Leucovorina/uso terapéutico , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Compuestos Organoplatinos/uso terapéutico , Oxaloacetatos , Periodo Posoperatorio , Radioterapia Conformacional , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/patología , Neoplasias del Recto/radioterapia , Neoplasias del Recto/cirugía , Estudios Retrospectivos , Tasa de Supervivencia , Adulto JovenRESUMEN
Background: Whether concurrent chemotherapy could bring about better oncological outcomes in elderly patients receiving definitive radiotherapy is still unknown. So, the purpose of this study was to find out whether it is essential for elderly patients to undergo concurrent chemotherapy. Methods: We performed a retrospective study of 246 elderly cervical cancer patients who were treated with definitive radiotherapy or chemo-radiation between August 2004 and August 2015. All patients were divided into two groups according to whether they were receiving concurrent chemotherapy or not. Overall survival (OS) and disease-free survival (DFS) were compared between the two groups. Recurrence patterns were also analyzed. Multivariate analysis was performed to explore clinical factors significantly associated with DFS, local recurrence-free survival, and distant metastasis-free survival (DMFS). Results: The 5-year OS in the radiotherapy and chemo-radiation groups were 72.89% and 82.25%, respectively. A significant difference was found between the two groups (P=0.016). The 5-year DFS in the radiotherapy and chemo-radiaton groups were 58.19% and 75.52%, respectively, also with a significant difference between the two groups (P=0.028). Further subgroup analysis showed that in patients with negative lymph nodes, there were no differences in both OS and DFS between patients who did and did not receive concurrent chemotherapy. However, in patients with positive lymph nodes, patients who received concurrent chemotherapy acquired better OS and DFS than those who did not. Multivariable analysis showed that concurrent chemotherapy was an independent predictor of DFS and DMFS. Conclusion: Concurrent chemotherapy could improve oncological outcomes in elderly cervical cancer patients with positive lymph nodes, but not in those with negative lymph nodes.
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BACKGROUND: The optimal care for pT3N0 rectal cancer remains controversial. And whether tumor location can be used to guide the administration of adjuvant radiotherapy for pT3N0 rectal cancer is not fully confirmed. The current study was designed to identify the benefit of adjuvant radiotherapy for pT3N0 rectal cancer. METHODS: We performed a retrospective study of 265 pT3N0 rectal cancer patients who were treated by surgery and adjuvant therapy from Mar. 2005 to Sept. 2015. All patients were divided into two groups according to receiving adjuvant radiotherapy or not. Overall survival (OS), disease-free survival (DFS) were compare between patients who did and did not receive adjuvant radiotherapy. Multivariate analysis was performed to explore clinical factors significantly associated with DFS, local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS). RESULTS: For patients with lower tumor, DFS in adjuvant chemo-radiotherapy group was higher than that in adjuvant chemotherapy group. Besides, the rates of local recurrence and distant metastasis were found lower in patients who did receive adjuvant radiotherapy than those who did not. For patients with upper tumor, the 5-year OS and DFS were similar between groups of adjuvant chemotherapy and adjuvant chemo-radiotherapy. Multivariable analysis indicated both the CEA and tumor location were independent predictors of LRFS. And adjuvant radiotherapy predicted the DFS, LRFS and DMFS in lower rectal cancer patients. CONCLUSION: Tumor location can serve as an indication for the administration of adjuvant radiotherapy in pT3N0 rectal cancer patients.
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Quimioradioterapia Adyuvante/mortalidad , Terapia Neoadyuvante , Recurrencia Local de Neoplasia/patología , Radioterapia Adyuvante/mortalidad , Neoplasias del Recto/patología , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/radioterapia , Recurrencia Local de Neoplasia/terapia , Estadificación de Neoplasias , Neoplasias del Recto/radioterapia , Neoplasias del Recto/terapia , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Objectives: Patients with early-stage distal rectal cancer, if treated with radical surgery, usually suffer a poor quality of life. Definitive radiotherapy or chemoradiotherapy may be another treatment option for them. The aim of this study was to evaluate the role of definitive external beam radiotherapy or chemoradiotherapy in treating distal rectal cancer with stage cT1-2N0. Methods: We performed a retrospective study of 231 distal rectal cancer patients who were staged as cT1-2N0 from March 2002 to March 2015. All patients were treated by definitive radiotherapy or chemoradiotherapy. Overall survival (OS), progression-free survival (PFS), and short-term efficacy were analyzed. Multivariate analysis was performed to explore clinical factors significantly associated with PFS, local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) for the whole group. Results: For the whole group, 135 patients (58.4%) achieved clinical complete response (cCR). The 5-year OS, PFS, and LRFS were 86.19%, 83.30%, and 92.50%, respectively. Patients with cCR acquired better survival than those with non-cCR. In multivariable analysis, it revealed that clinical stage, carcinoembryonic antigen (CEA level) and concurrent chemotherapy were independent predictors of PFS. Conclusion: Definitive radiotherapy or chemoradiotherapy may be feasible in some early-stage distal rectal cancer regarding its favorable efficacy.
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Objectives: To evaluate the prognostic significance of Adult Comorbidity Evaluation-27 (ACE-27) for elderly patients (age ≥70 years) with locoregionally advanced nasopharyngeal carcinoma (NPC) treated with Intensity-Modulated Radiotherapy (IMRT), with or without chemotherapy. Methods: 206 elderly patients with locoregionally advanced NPC treated from December 2006 to December 2016 were involved into analysis as the training cohort. Besides, a separate cohort of 72 patients from the same cancer center collected between January 2003 and October 2006 served as the validation cohort. By using propensity score matching (PSM), we created a balanced cohort by matching patients who received chemoradiotherapy with patients who received IMRT alone. Treatment toxicities were calculated between CRT and RT groups using the χ2 test. The primary endpoint was cancer-specific survival (CSS). Multivariate analysis was performed to assess the relative risk for each factor by using a Cox's proportional hazards regression model. Results: The median follow-up was 39.0 months (range = 3-137 months). In the PSM cohort, patients in the CRT group achieved comparable survival compared with patients in the RT group. The 3-year CSS rate was 64.3% and 65.2%, respectively (P =0.764). In multivariate analysis, the addition of chemotherapy to IMRT was not an independent prognostic factor for CSS, whereas a high ACE-27 score was an independent risk factor. In subgroup analysis with ACE-27 score ≥ 2, the 3-year CSS rate was worse in patients from the CRT group (63.5% vs. 46.3%, P = 0.041). Conclusions: CRT is comparable to IMRT alone for elderly patients with locoregionally advanced NPC. The ACE-27 tool may help to identify high-risk subgroup for poor disease outcome and tailor individualized treatment.
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OBJECTIVE: To evaluate the prognostic effects of combining serum circulating tumor cells (CTCs) and squamous cell carcinoma antigen (SCC-Ag) levels on patients with locally advanced cervical cancer treated with radiotherapy. METHODS: Ninety-nine patients with locally advanced cervical cancer ([FIGO] stage IIB-IVA) undergoing radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) were identified. The association between serum CTC level and clinicopathological parameters was examined. Univariate and multivariate survival analyses were performed by using Cox's proportional hazards regression model. RESULTS: Elevated CTC and SCC-Ag levels were significantly associated with poor disease-free survival (DFS). Multivariate analysis suggest that serum CTC level, FIGO stage and serum SCC-Ag level were independent prognostic factors for two-year DFS. When CTC and SCC-Ag levels were combined into a new risk model to predict disease progression of cervical cancer patients, it performed a significantly better predictive efficiency compared with either biomarker alone. CONCLUSION: Serum CTC and SCC-Ag levels are potentially useful biomarkers for prediction of prognosis in locally advanced cervical cancer patients and their combination significantly improves predictive ability for survival in locally advanced cervical cancer patients.
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Antígenos de Neoplasias/sangre , Células Neoplásicas Circulantes , Serpinas/sangre , Neoplasias del Cuello Uterino/sangre , Neoplasias del Cuello Uterino/radioterapia , Adulto , Biomarcadores de Tumor/sangre , Quimioradioterapia , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/patologíaRESUMEN
BACKGROUND: Gamma-glutamyltransferase (GGT) is a membrane-bound enzyme involved in the metabolism of glutathione. Studies suggested that GGT played an important role in the tumor development, progression, invasion and drug resistance and prognosis. The association between GGT and prognosis of patients with nasopharyngeal carcinoma (NPC) was unknown. This study was conducted to investigate the association of pretherapeutic serum level of GGT with clinical-pathological parameters and survival in patients with NPC. METHODS: Two hundred and twenty-two patients with NPC were recruited in this study and were stratified into two GGT risk groups (≤ 34.5 U/L, > 34.5 U/L). The association of pretherapeutic serum GGT levels with clinical-pathological parameters was examined. Univariate and multivariate survival analyses were performed. FINDINGS: The pretherapeutic serum level of GGT was not associated with gender, age, pathology, T stage, N stage, TNM stage, chemotherapy or radiotherapy in patients with NPC. Patients in the high-risk GGT group had a poorer survival than the low-risk GGT group (3-year overall survival, 74.2% vs. 50.2%, P = 0.001; 3-year progression-free survival, 76.4% vs. 47.1%, P < 0.001; 3-year loco-regional relapse-free survival, 76.4% vs. 51.3%, P < 0.001; 3-year distant metastasis-free survival, 89.5% vs. 66.4%, P < 0.001). Multivariate analysis suggested that patients in the high-risk GGT group had 2.117 (95% confidence interval [CI], 1.225 â¼ 3.659, P = 0.007) times the risk of death, 2.836 (95% CI, 1.765 â¼ 4.557, P < 0.001) times the risk of progression, 2.551 (95% CI, 1.573 â¼ 4.138, P < 0.001) times the risk of relapse, and 3.331 (95% CI, 1.676 â¼ 6.622, P < 0.001) times the risk of metastasis compared with those in the low-risk GGT group. CONCLUSION: The pretherapeutic serum level of GGT might serve as a novel independent prognostic factor for overall-survival, progression-free survival, loco-regional relapse-free survival and distant metastasis-free survival in patients with NPC.
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Carcinoma/diagnóstico , Neoplasias Hepáticas/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico , gamma-Glutamiltransferasa/sangre , Adulto , Carcinoma/enzimología , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Resistencia a Antineoplásicos , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/enzimología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Análisis Multivariante , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/enzimología , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/patología , Pronóstico , Curva ROC , Resultado del TratamientoRESUMEN
Neoadjuvant chemoradiotherapy followed by surgery is the standard treatment for patients with locally advanced rectal cancer. Controversy on whether patients should receive radical surgery after pathological complete response (pCR) after neoadjuvant chemoradiotherapy has remained since pCR patients have shown favorable long-term outcome. Progress in multidisciplinary modalities has been made, including MRI, PET/CT imaging studies, genetic expression profiling, etc. The methods of predicting pCR response are inspiring. In this article, we review the methods for prediction and prognostic effect of pCR response when patients with locally advanced rectal cancer are treated with neoadjuvant chemoradiotherapy.
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Quimioradioterapia , Terapia Neoadyuvante , Neoplasias del Recto/terapia , Humanos , Inducción de Remisión , Resultado del TratamientoRESUMEN
OBJECTIVE: To explore the value of transrectal ultrasonography (TRUS) for tumor node metastasis (TNM) restaging for patients with locally advanced rectal cancer after neoadjuvant chemoradiotherapy (neo-CRT). METHODS: One hundred and forty-nine patients with locally advanced rectal cancer (cT3-4 or cN+) who underwent TRUS after neo-CRT were retrospectively reviewed. TRUS restaging was compared with the results of post-operative pathological TNM findings. RESULTS: After neo-CRT, the accuracy of TRUS for diagnosing T-staging was 30.9%, with 60.4% (90/149) of cases overestimated. The sensitivity of TRUS for T-staging (T0 vs T1 vs T2 vs T3 vs T4) were 16.3%, 0%, 12.5%, 42.6% and 75.0%, respectively. The accuracy of TRUS for diagnosing N-staging after neo-CRT was 81.2%, with the sensitivities of N0 and N+ were 93.3% and 31.0%, respectively. After neo-CRT, 27.5% (41/149) of patients achieved pathologically complete response (pCR). The sensitivity, specificity, positive predictive value and negative predictive values of TRUS for pCR were 17.1%, 99.1%, 87.5% and 75.9%, respectively. CONCLUSIONS: TRUS can be applied for restaging T4 and N0, and has potential for screening out patients with pCR in those with locally advanced rectal cancer after neo-CRT, although some stages are overestimated for T-staging and its sensitivity for predicting pCR is low.