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BACKGROUND: This study aimed to quantify the benefit of adjuvant radiotherapy (AXRT) for local control, distant metastasis, and long-term survival outcomes in patients with localized soft tissue sarcoma (STS). METHODS: This single-center retrospective observational study enrolled 433 STS patients who underwent surgery with curative intent. An inverse probability of treatment-weighted (IPTW) analysis was implemented to account rigorously for imbalances in prognostic variables between the adjuvant treatment groups. RESULTS: During a median follow-up period of 5.5 years, the study observed 38 local recurrences (9%), 73 occurrences of distant metastasis (17%), 63 STS-related deaths (15%), and 57 deaths from other causes (13%). As expected, patients receiving AXRT (n = 258, 60%) were more likely to have high-grade G3 tumors (p < 0.0001) than patients not receiving AXRT. A crude analysis showed that AXRT was not associated with improved recurrence-free survival [hazard ratio (HR) 1.00; 95% confidence interval (CI) 0.72-1.38; p = 0.98]. However, after IPTW, AXRT was associated with a 38% relative reduction in the risk of recurrence or death (HR 0.62; 95% CI 0.39-1.00; p = 0.05). This benefit was driven by a strong reduction in the risk of local recurrence (HR 0.42; 95% CI 0.19-0.91; p = 0.03), whereas the relative risk of distant metastasis (HR 0.69; 95% CI 0.39-1.25; p = 0.22) and overall survival (HR 0.76; 95% CI 0.44-1.30; p = 0.32) were only nonsignificantly in favor of AXRT. An exploratory analysis showed an overall survival benefit of AXRT for patients with high-grade G3 tumors (HR 0.51; 95% CI 0.33-0.78; p = 0.002). However, this finding may have been attributable to residual confounding. CONCLUSION: In this observational cohort, AXRT was associated with a 58% reduction in the relative risk of local recurrence. No consistent association between AXRT and lower risks of distant metastasis or death was observed.
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Recurrencia Local de Neoplasia/mortalidad , Radioterapia Adyuvante/mortalidad , Sarcoma/mortalidad , Neoplasias de los Tejidos Blandos/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/radioterapia , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Sarcoma/radioterapia , Sarcoma/secundario , Neoplasias de los Tejidos Blandos/patología , Neoplasias de los Tejidos Blandos/radioterapia , Tasa de Supervivencia , Adulto JovenRESUMEN
BACKGROUND: Venous thromoboembolism (VTE) is a frequent and burdensome complication of metastatic colorectal cancer (CRC). However, the epidemiology of VTE in patients with localized CRC after surgery in curative intent is incompletely understood. In this single-center observational cohort study, we investigate patterns of VTE risk in localized CRC, and define its relationship with baseline risk factors, adjuvant chemotherapy and CRC recurrence. METHODS: Five-hundred-sixteen patients with stage II/III CRC were included retrospectively at the time of surgery, and followed until the occurrence of VTE, CRC recurrence, or death (median age = 65.1 years, stage II and III: n = 151 (29.5%), n = 361 (70.5%); adjCTX: n = 339 (65.7%)). RESULTS: During a median follow-up of 2.7 years, 15 VTEs (2.7%) and 116 recurrences (22.5%) occurred, and 46 patients (8.9%) died. Six-month, 1-year, and 5-year VTE risks were 1.6%, 2.0% and 3.2%, respectively. In competing risk time-to-VTE regression, adjCTX was not associated with an increased risk of VTE (Subdistribution hazard ratio = 0.98, 95% CI:0.33-2.88, p = 0.97). The occurrence of disease recurrence strongly increased the risk of VTE (Multi-state model: Transition hazard ratio (THR) = 13.03, 95% CI:4.39-38.74, p < 0.0001)). Conversely, the onset of VTE did not predict for recurrence (THR = 1.95, 95% CI: 0.62-6.16, p = 0.25). CONCLUSION: VTE risk is very low in localized CRC and does not appear to be increased by adjuvant chemotherapy. Thus, primary thromboprophylaxis is unlikely to result in clinical benefit in this population. The strongest determinant of VTE risk appears to be disease recurrence.
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Neoplasias Colorrectales/complicaciones , Tromboembolia Venosa/etiología , Adulto , Anciano , Anciano de 80 o más Años , Quimioterapia Adyuvante , Estudios de Cohortes , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Pronóstico , Riesgo , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/mortalidad , Adulto JovenRESUMEN
BACKGROUND: Exploration of the complex relationship between prognostic indicators such as tumor grade and size and clinical outcomes such as local recurrence and distant metastasis in patients with cancer is crucial to guide treatment decisions. However, in patients with soft tissue sarcoma, there are many gaps in our understanding of this relationship. Multistate analysis may help us in gaining a comprehensive understanding of risk factor-outcome relationships in soft tissue sarcoma, because this methodology can integrate multiple risk factors and clinical endpoints into a single statistical model. To our knowledge, no study of this kind has been performed before in patients with soft tissue sarcoma. QUESTIONS/PURPOSES: We implemented a multistate model of localized soft tissue sarcoma to statistically evaluate the relationship among baseline risk factors, recurrence, and death in patients with localized soft tissue sarcoma undergoing curative surgery. METHODS: Between 1998 and 2015, our center treated 539 patients for localized soft tissue sarcoma with surgery as curative intent. Of those, 96 patients (18%) were not included in this single-center retrospective study owing to missing baseline histopathology data (n = 3), not yet observed followup (n = 80), or because a neoadjuvant treatment approach in the presence of synchronous distant metastasis was used (n = 13), leaving 443 patients (82%) for the current analysis, of which 40 were lost to followup during the first year after surgery. All patients had tumors of the stages I to III according to the American Joint Committee on Cancer Stages. The median age of the patients was 62 years (range, 16-96 years), and 217 patients (49%) were female. Three hundred-forty-six patients (78%) had tumors of high grade (Grades 2 and 3), and 310 (70%) tumors were greater than 5 cm in maximum diameter. Patients who had died during the first year of followup were included in this analysis. Median followup for the 443 study patients was 6 years, with 84%, 52%, and 23% of patients being followed for more than 1, 5, and 10 years, respectively. The 15-year cumulative incidences of local recurrence, distant metastasis, and death from any cause, using a competing risk analysis, were 16% (95% CI, 11%-22%), 21% (95% CI, 17%-26%), and 55% (95% CI, 44%-67%), respectively. Wide resection with a margin of 1 mm was the preferred treatment for all patients, except for those with Grade 1 liposarcoma where a marginal resection was considered adequate. Multistate models were implemented with the mstate library in R. RESULTS: In multistate analysis, patients who experienced a local recurrence were more likely to have distant metastasis develop (hazard ratio [HR] = 8.4; 95% CI, 4.3-16.5; p < 0.001), and to die (HR = 3.4; 95% CI, 2.1-5.6; p < 0.001). The occurrence of distant metastasis was associated with a strong increase in the risk of death (HR = 12.6; 95% CI, 8.7-18.3; p < 0.001). Distant metastasis occurring after a long tumor-free interval was not associated with a more-favorable prognosis with respect to mortality than distant metastasis occurring early after surgery (estimated relative decrease in the adverse effect of distant metastasis on mortality for 1-year delay in the occurrence of distant metastasis = 0.9; 95% CI, 0.7-1.1; p = 0.28). High-grade histology (Grades 2 and 3) was associated with a higher risk of overall recurrence (defined as a composite of local recurrence and distant metastasis, HR = 3.8; 95% CI, 1.8-7.8; p = 0.0003) and a higher risk of death after recurrence developed (HR = 4.4; 95% CI, 1.1-18.2; p = 0.04). Finally, the multistate model predicted distinct outcome patterns depending on baseline covariates and how long a patient has remained free from recurrence after surgery. CONCLUSIONS: In patients with localized soft tissue sarcoma undergoing resection, the occurrence of local recurrence and distant metastasis contributes to a dramatically impaired long-term survival outcome. Local recurrences are a substantial risk factor for distant metastasis. Multistate modeling is a very powerful approach for analysis of sarcoma cohorts, and may be used in the future to obtain highly personalized, dynamic predictions of outcomes in patients with localized soft tissue sarcoma. LEVEL OF EVIDENCE: Level III, therapeutic study.
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Técnicas de Apoyo para la Decisión , Modelos Estadísticos , Recurrencia Local de Neoplasia , Sarcoma/secundario , Sarcoma/cirugía , Neoplasias de los Tejidos Blandos/patología , Neoplasias de los Tejidos Blandos/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Austria , Progresión de la Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Sarcoma/mortalidad , Neoplasias de los Tejidos Blandos/mortalidad , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
PURPOSE: Aminotransaminases, which are strongly involved in cellular metabolism and cancer cell turnover, represent easily measureable, potential blood based biomarkers. We evaluated the prognostic value of the preoperatively assessed AST/ALT (De Ritis) ratio on clinically meaningful end points in a large European cohort of patients with nonmetastatic renal cell carcinoma. MATERIALS AND METHODS: We retrospectively evaluated clinicopathological data on 698 patients with nonmetastatic renal cell carcinoma operated on between 2005 and 2013 at a single tertiary academic center. The potential prognostic value of the AST/ALT ratio was analyzed using the Kaplan-Meier method, and univariate and multivariate Cox proportional regression models. The impact of the ratio on the predictive accuracy of the Leibovich prognosis score was determined by the Harrell c-index. RESULTS: An increased (1.26 or greater) preoperative AST/ALT ratio was statistically significantly associated with several well established prognostic factors, including pathological T stage, as well as with histological tumor necrosis (p <0.05). On multivariate analysis an increased preoperative AST/ALT ratio was an independent prognostic factor for metastasis-free survival (HR 1.61, 95% CI 1.25-2.07, p <0.001) and overall survival (HR 1.76, 95% CI 1.34-2.32, p <0.001). The Harrell c-index was 0.77 using the Leibovich prognosis score and 0.81 when AST/ALT was added. CONCLUSIONS: In our study cohort with nonmetastatic renal cell carcinoma the preoperatively assessed AST/ALT ratio represented an independent prognostic factor. This ratio might further improve the predictive accuracy of well established prognosis scores.
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Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Carcinoma de Células Renales/sangre , Carcinoma de Células Renales/cirugía , Neoplasias Renales/sangre , Neoplasias Renales/cirugía , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Periodo Preoperatorio , Pronóstico , Estudios RetrospectivosRESUMEN
BACKGROUND: Catumaxomab, the first anti-EpCAM antibody, was approved in 2009 for the treatment of malignant ascites in cancer patients with EpCAM positive tumors. We consider this case of interest as treatment with catumaxomab not only prolonged the puncture-free interval but also showed a systemic effect in a patient with metastasized colorectal cancer by regression of a pulmonary metastasis. CASE PRESENTATION: We describe the case of a 78 year old patient initially diagnosed with locally advanced colon cancer and one synchronous liver metastasis in September 2010 who was treated by hemicolectomy and simultaneous atypical liver resection. During adjuvant chemotherapy the patient developed a peritoneal carcinomatosis with ascites in March 2011. Palliative chemotherapy was not well tolerated and therefore refused by the patient. Because of disease progression in June 2011 with one pulmonary metastasis and clinically predominant ascites an immunotherapy with intraperitoneal catumaxomab was started in December 2011. After treatment with catumaxomab a puncture free survival of 12 months as well as a regression of the pulmonary lesion was achieved until January 2013. CONCLUSION: This case suggests that treatment with catumaxomab does not only improve quality of life by local suppression of malignant ascites but also might have a systemic antitumor effect.
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Anticuerpos Biespecíficos/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Anciano , Neoplasias Colorrectales/diagnóstico , Progresión de la Enfermedad , Humanos , Masculino , Metástasis de la Neoplasia , Neoplasias Peritoneales/diagnóstico , Neoplasias Peritoneales/secundario , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
In the past few years there have been major changes in the treatment landscape in oncology; lung cancer is affected by those changes like almost no other solid tumor. The rise of further second- and third-line tyrosine kinase inhibitors offers sequential therapy for patients with mutated non-small-cell lung cancer. Immunotherapy has found its way into clinical routine and presents us with new challenges in managing side effects, evaluating treatment response and deciding on how long we treat our patients. The treatment algorithm of lung cancer has changed in the last month and further practice-changing trials are coming up, so treating lung cancer patients shows nowadays a more challenging perspective with the possibility of subsequently applied individual therapies. This article provides a brief overview of the highlights presented at the ASCO (American Society of Clinical Oncology) annual meeting this year in Chicago.
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OBJECTIVES: Despite successful surgery, 30-50% of patients with resectable non-small cell lung cancer develop tumor recurrence within 5 years of surgery. MATERIALS AND METHODS: In this prospective study, we performed CTC enumerations in 40 patients with non-metastatic lung adenocarcinoma (NMLA) using a size-based microfilter. Additionally, cfDNA isolated from plasma was analyzed in 35 out of 40 patients. RESULTS: CTCs were identified in 15 out of 40 patients (37.5%) with a range of 1-44 cells, whereas mutated cfDNA was only detected in 3 out of 35 patients (8.6%). Disease-free survival (DFS) was significantly associated with CTC positivity (log-rank p=0.025), grading (log-rank p=0.019), tumor stage (log-rank p=0.025) and lymph node status (log-rank p=0.029). Multivariate analysis, including tumor stage and grading, showed that CTC positivity (p=0.006), grading (0.039) and tumor stage (p=0.022) were independently associated with DFS. CONCLUSION: Our study found that microfilter-based CTC enumeration in NMLA patients is an independent predictor of worse DFS. The used NGS-based cfDNA characterization had limited sensitivity to be clinically informative in our study cohort. CTC assessment before surgery can thus identify NMLA patients at high risk of disease recurrence.
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Adenocarcinoma/sangre , Biomarcadores de Tumor/sangre , Neoplasias Pulmonares/sangre , Células Neoplásicas Circulantes/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Ácidos Nucleicos Libres de Células/sangre , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Células Neoplásicas Circulantes/patología , Periodo Preoperatorio , Pronóstico , Estudios ProspectivosRESUMEN
BACKGROUND/AIM: Growing evidence suggests that human cancers are stem cell diseases and recent data support the existence of cancer stem cells (CSCs) in a variety of malignancies, including colon cancer. These CSCs were shown to be capable of initiating tumor development and progression. Several studies have suggested CD133, CD26 and CD44 as markers of tumor-initiating cells of colon cancer. The purpose of the present study was to assess the impact of single-nucleotide polymorphisms (SNPs) in stem cell-related genes on clinical outcome in a large cohort of colon cancer patients with clinical stage II and III. PATIENTS AND METHODS: Data from 599 consecutive patients with colon cancer stage II and III, treated between 1995 and 2011 at a single centre, were retrospectively evaluated. Genomic DNA was extracted from paraffin-embedded normal tissue distant from the tumor to obtain germline DNA. Allelic distribution of polymorphisms was tested for deviation from Hardy-Weinberg equilibrium using χ2-test. The association of polymorphisms with time to recurrence (TTR) and overall survival (OS) was analyzed using Kaplan-Meier curves and compared by the log-rank test. Case-wise deletion for missing polymorphisms was used in univariable and multivariable analyses. RESULTS: CD44 rs187115 showed a statistically significant association with TTR; patients carrying at least one G allele had a significant reduced risk of recurrence compared to patients with the homozygous A/A variant (hazard ratio (HR)=0.67, 95% confidence interval (CI)=0.48-0.94, p=0.019). CD44 rs13347 showed a statistically significant association with OS. Patients carrying at least one T allele in rs13347 had a significantly reduced risk of death compared to patients with the homozygous C/C variant (HR=0.61, 95% CI=0.41-0.92, p=0.019). None of the other investigated polymorphisms (CD44 rs187116, CD44 rs7116432, CD44 rs353639, DPP4 rs2268889, DPP4 rs3788979, DPP4 rs7608798 and CD133 rs2240688) were associated with either TTR or OS. CONCLUSION: Germline variants rs13347 and rs187115 in the stem cell gene CD44 are prognostically relevant in stage II and III colon cancer patients.
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Biomarcadores de Tumor/genética , Neoplasias del Colon/genética , Neoplasias del Colon/patología , Receptores de Hialuranos/genética , Células Madre Neoplásicas/patología , Polimorfismo de Nucleótido Simple/genética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Invasividad Neoplásica , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Células Madre Neoplásicas/metabolismo , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
INTRODUCTION: Inflammatory biomarkers are useful prognostic tools in cancer patients. However, the prognostic and predictive value of inflammatory biomarkers beyond the 1st-line setting in metastatic colorectal cancer (mCRC) is unclear. RESULTS: In multivariate analysis 1 standard deviation increase in neutrophil-lymphocyte-ratio (NLR) was associated with an 8.5% absolute lower objective-response-rate (ORR) in 1st-line (p<0.0001), 3% lower ORR in 2nd-line (p< 0.0001), and 3% lower ORR in 3rd-line (p=0.24), respectively. Regarding progression free survival (PFS), an increase in the NLR was significantly associated with rising hazard-ratios (HR) over all treatment lines (HR=1.30, p= 0.021 1st-line); (HR=1.37, p<0.0001 2nd-line); (HR=1.44, p=0.042 3rd-line). The platelet-lymphocyte-ratio (PLR) was associated with 6-month PFS over all three treatment lines. Higher C-reactive-protein (CRP) predicted for worse PFS in the first two chemotherapy lines and in best supportive care (BSC). (HR=1.49 (p<0.0001 1st-line); HR=1.25 (p=0.007 2nd-line); HR=1.09 (95%CI 0.81-1.48, p=0.552 3rd-line and HR=1.43 (p= 0.002 in BSC)). METHODS: Two-hundred-fifty-eight patients with mCRC undergoing palliative chemo(immuno-)therapy were retrospectively included. Primary endpoints were 6-month PFS and ORR during 1st-line, 2nd-line, and 3rd-line treatment, and 6-month overall survival during BSC. CONCLUSION: This study shows that inflammatory biomarkers are useful predictors of disease outcome and treatment response over several treatment lines in mCRC patients.
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BACKGROUND: Patients with testicular germ cell tumors (TGCT) have an increased risk for venous thromboembolism (VTE). We identified risk factors for VTE in this patient cohort and developed a clinical risk model. METHODS: In this retrospective cohort study at the Medical University of Graz we included 657 consecutive TGCT patients across all clinical stages. A predictive model for VTE was developed and externally validated in 349 TGCT patients treated at the University Hospital Zurich. RESULTS: Venous thromboembolic events occurred in 34 (5.2%) patients in the Graz cohort. In univariable competing risk analysis, higher clinical stage (cS) and a retroperitoneal lymphadenopathy (RPLN) were the strongest predictors of VTE (p<0.0001). As the presence of a RPLN with more than 5cm in greatest dimension without coexisting visceral metastases is classified as cS IIC, we constructed an empirical VTE risk model with the following four categories (12-month-cumulative incidence): cS IA-B 8/463 patients (1.7%), cS IS-IIB 5/86 patients (5.9%), cS IIC 3/21 patients (14.3%) and cS IIIA-C 15/70 patients (21.4%). This risk model was externally validated in the Zurich cohort (12-month-cumulative incidence): cS IA-B (0.5%), cS IS-IIB (6.0%), cS IIC (11.1%) and cS IIIA-C (19.1%). Our model had a significantly higher discriminatory performance than a previously published classifier (RPLN-VTE-risk-classifier) which is based on the size of RPLN alone (AUC-ROC: 0.75 vs. 0.63, p = 0.007). CONCLUSIONS: According to our risk stratification, TGCT patients with cS IIC and cS III disease have a very high risk of VTE and may benefit from primary thromboprophylaxis for the duration of chemotherapy.
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Neoplasias de Células Germinales y Embrionarias/patología , Neoplasias Testiculares/patología , Tromboembolia Venosa/etiología , Adulto , Humanos , Masculino , Neoplasias de Células Germinales y Embrionarias/complicaciones , Estudios Retrospectivos , Factores de Riesgo , Neoplasias Testiculares/complicacionesRESUMEN
BACKGROUND: Inflammatory blood count biomarkers may improve recurrence risk stratification and inform long-term prognosis of cancer patients. Here, we quantify the prognostic impact of blood-based biomarkers on recurrence risk and long-term survival in a large cohort of gastrointestinal stroma tumor (GIST) patients after curative surgery. METHODS: One-hundred-forty-nine consecutive GIST patients were followed-up for a median period of 4.8 years. Local recurrence, distant metastasis, and death occurred in 9, 21, and 31 patients, respectively. Time-to-event and competing risk analysis were applied to study the association between haemoglobin (Hb) level, white blood cell count (WBC), neutrophil/lymphocyte ratio (NLR), derived NLR (dNLR), lymphocyte/monocyte ratio (LMR), and platelet/lymphocyte ratio (PLR) with risk of local or distant recurrence (RR), recurrence free survival (RFS), and overall survival (OS). RESULTS: A low Hb (p = 0.029), and elevations in the parameters WBC (p = 0.004), NLR (p = 0.015) and dNLR (p = 0.037) were associated with a poor OS in GIST patients in multivariate analysis. Moreover, a low Hb (p = 0.049) and an elevated WBC (p = 0.001), NLR (p = 0.007), dNLR (p = 0.043) and PLR (p = 0.024) were independently associated with decreased RFS after adjusting for Miettinen score. However, only an increase of dNLR/NLR showed a significant association to higher RR (p = 0.048). Inclusion of NLR or PLR to Miettinen risk score did not reasonably improve the clinical risk prediction of 2-year RFS. CONCLUSION: Low Hb, elevated WBC, elevated dNLR, and elevated PLR are independent prognostic factors for a worse clinical outcome in GIST patients after curative resection.
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Biomarcadores , Tumores del Estroma Gastrointestinal/sangre , Tumores del Estroma Gastrointestinal/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Causas de Muerte , Femenino , Estudios de Seguimiento , Tumores del Estroma Gastrointestinal/mortalidad , Tumores del Estroma Gastrointestinal/cirugía , Humanos , Recuento de Leucocitos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neutrófilos , Periodo Posoperatorio , Pronóstico , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: To validate the potential prognostic significance of preoperatively assessed inflammatory parameters leucocytosis, thrombocytosis and anemia in patients with non-metastatic renal cell carcinoma (RCC). MATERIALS AND METHODS: We retrospectively evaluated a cohort comprising 736 consecutive patients with non-metastatic RCC, operated on between 2004 and 2012 with curative radical or partial nephrectomy at a single tertiary academic centre. Laboratory parameters were assessed within one week before surgical intervention. Patients were categorized using laboratory parameter cut-off values according to receiver operating characteristics (ROC) analyses. Cancer-specific survival (CSS) was assessed using the Kaplan-Meier method. To evaluate the potential prognostic significance of the preoperative laboratory parameters, multivariate Cox regression models were applied. RESULTS: Multivariable analysis identified preoperative thrombocytosis (≥285,000/µl) as an independent prognostic factor for CSS (Hazard ratio=2.28, 95% confidence interval=1.24-4.20, p=0.008). CONCLUSION: Regarding CSS, an elevated preoperative platelet count represented an independent prognostic factor of poor survival. Our findings strengthen the potential prognostic significance of preoperative thrombocytosis in patients with non-metastatic RCC.
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Anemia/patología , Carcinoma de Células Renales/cirugía , Pronóstico , Trombocitosis/patología , Adulto , Anciano , Anemia/complicaciones , Anemia/diagnóstico , Carcinoma de Células Renales/complicaciones , Carcinoma de Células Renales/patología , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Nefrectomía , Periodo Preoperatorio , Modelos de Riesgos Proporcionales , Trombocitosis/complicaciones , Trombocitosis/diagnósticoRESUMEN
AIMS: Increasing evidence suggests that the serum-gamma-glutamyltransferase (GGT) might correlate with tumour development and growth rates in various human cancer types. Thus, we decided to investigate the potential prognostic impact of the preoperatively assessed serum-GGT in a European cohort of patients with non-metastatic renal cell carcinoma (RCC). METHODS: Clinicopathological data from 700 consecutive patients with non-metastatic RCC, operated between 2000 and 2010 at a single tertiary academic centre, were evaluated retrospectively. Preoperative serum-GGT was assessed 1â day before surgery. Patients were categorised using a serum-GGT cut-off value of 40â U/L according to a calculation by receiver operating curve analysis. Patients' cancer-specific survival (CSS), metastasis-free survival (MFS), as well as overall survival (OS) were assessed using the Kaplan-Meier method and Cox proportional models. RESULTS: In univariate analysis, an elevated preoperative serum-GGT level (<40 U/L vs ≥40â U/L) was statistically significantly associated with a shorter MFS (HR=1.517, 95% CI 1.047 to 2.197, p=0.027). In multivariate analyses, pathological T-Stage (pT-1 vs pT-2-4, HR=2.065, 95% CI 1.665 to 2.560), tumour grade (G-1+G-2 vs G-3+G-4, HR=1.671, 95% CI 1.261 to 2.213), as well as the presence of histological tumour necrosis (No vs Yes, HR=2.031, 95% CI 1.355 to 3.046) were independent predictors of MFS in patients with RCC, whereas the preoperative serum-GGT failed to reach independent predictor status (<40 U/L vs ≥40â U/L, HR=1.156, 95% CI 0.791 to 1.690). No prognostic role for GGT in OS or CSS could be identified. CONCLUSIONS: In the cohort studied, patients with an elevated (≥40â U/L) preoperative serum-GGT had a subsequently shorter MFS only in univariate analysis. In contrast to previous studies, our data failed to demonstrate preoperatively assessed serum-GGT as an independent prognostic factor in patients with non-metastatic RCC.
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Biomarcadores de Tumor/sangre , Carcinoma de Células Renales/enzimología , Neoplasias Renales/enzimología , gamma-Glutamiltransferasa/sangre , Anciano , Área Bajo la Curva , Austria/epidemiología , Carcinoma de Células Renales/sangre , Carcinoma de Células Renales/etnología , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Renales/sangre , Neoplasias Renales/etnología , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Masculino , Análisis Multivariante , Necrosis , Clasificación del Tumor , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Curva ROC , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Regulación hacia Arriba , Población BlancaRESUMEN
Testicular germ cell tumors (TGCTs) represent the most common type of solid tumors among men aged 15 to 40 years. An increasing incidence has been recorded in developed countries. In clinical practice, TGCTs are classified as seminomas and non-seminomatous tumors. Non-seminomatous tumors often contain multiple different cell types and can be further sub-divided according to the histological and cellular phenotype in embryonal carcinomas, choriocarcinomas, yolk sac tumors and teratomas. For the clinical management of TGCTs, blood-based markers such as lactate dehydrogenase, alpha-fetoprotein and human chorionic gonadotropin are essential tools for diagnosis, risk assessment and patient's prognosis. However, only 60% of patients with TGCTs show increased serum levels of these tumor markers. This proportion of patients is even lower for those with seminomas or pure embryonal carcinomas as alpha-fetoprotein is predominantly related to yolk sac tumor and human chorionic gonadotropin to choriocarcinoma.
Asunto(s)
MicroARNs/genética , Neoplasias Testiculares , Biomarcadores de Tumor/sangre , Humanos , Masculino , Pronóstico , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/etiología , Neoplasias Testiculares/terapiaRESUMEN
FOLFIRINOX is a highly active regimen for the treatment of patients with unresectable pancreatic cancer. However, treatment with FOLFIRINOX is associated with relevant toxicity and predictors for response to therapy are warranted. We retrospectively analyzed 49 patients with unresectable pancreatic cancer treated with FOLFIRINOX in order to evaluate a possible predictive role of clinical parameters and tumor characteristics for response to chemotherapy. Tumor samples were characterized histopathologically before treatment and expression of p53 and Ki67 was analyzed using automated immunohistochemistry. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method. The overall objective response rate was 55.1%, the disease control rate was 70.6%. Female gender was associated with a significantly higher disease control rate of 91.7 compared to 48.0% in male patients (p=0.001) which reached 100% in female patients when primarily treated compared to treatment after surgical resection and relapse (77.8%, p=0.057). For all patients median PFS was 3.5 months (95% CI, 2.7-4.3 months) and median OS was 13 months (95% CI, 9.4-16.6 months). Female patients showed a tendency towards a longer median PFS (5.0 months, 95% CI, 3.6-6.4 months) compared to males (3.0 months, 95% CI, 2.4-3.6 months) (p=0.099). Serum levels of CA19.9 and CEA were significantly higher in female patients compared to male patients (p=0.037, p=0.05). Tumors of patients with response to FOLFIRINOX showed a higher expression level of p53 and Ki67 as well as higher serum levels of CA19.9 compared to non-responders, which was statistically not significant. Our study indicates that female gender is a positive predictor for therapy response to FOLFIRINOX in patients with unresectable pancreatic cancer. Female gender in turn was associated with increased levels of tumor markers CEA and CA19.9 and patients with higher serum levels of CA19.9 were more responsive to FOLFIRINOX.