RESUMEN
Patients with R/M HNSCC treated with palliative first-line therapy at Hannover Medical School between October 2005 and December 2016 have been included to show changes in survival following broad utilization of cetuximab. Treatment periods were defined from 10/2005 to 12/2008 (Period A) and 01/2009 to 12/2016. Overall survival did not improve over time. However, in subgroup analysis cetuximab utilized at any time vs. never showed a significant improve of overall survival (11.3 vs. 6.3 months, HR: 0.55, 95%-CI: 0.4-0.8, p = 0.04). Therefore, this study supports the application of cetuximab in this real-world population.
Asunto(s)
Neoplasias de Cabeza y Cuello , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Cetuximab/uso terapéutico , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/etiologíaRESUMEN
INTRODUCTION: Treatment advances in metastatic renal cell carcinoma (mRCC) have improved overall survival (OS) in mRCC patients over the last two decades. This single center retrospective analysis assesses if the purported survival benefits are also applicable in elderly mRCC patients. METHODS: 401 patients with mRCC treated at Hannover Medical School from 01/2003-05/2016 were identified and evaluated by chart review. Treatment periods were defined as 01.01.2003-31.12.2009 (P1) and 01.01.2010-31.05.2016 (P2). Age groups were defined according to WHO classes (≤ 60 years: younger, > 60-75 years: elderly and > 75 years: old). Descriptive statistics, Kaplan-Meier analysis and logistic regression were performed. RESULTS: Median OS improved from 35.1 months in P1 to 59.1 months in P2. Sub-division into the respective age groups revealed median survival of 38.1 (95%-CI: 28.6-47.6) months in younger patients, 42.9 (95%-CI: 29.5-56.3) months among elderly patients and 27.3 (95%-CI: 12.8-41.8) months among old patients. Risk reduction for death between periods was most evident among old patients (young: HR 0.71 (95%-CI: 0.45-1.13, p = 0.2); elderly: HR 0.62 (95%-CI: 0.40-0.97, p = 0.04); old: HR 0.43 (95%-CI: 0.18-1.05, p = 0.06)). Age ≥ 75 years was an independent risk factor for death in P1 but not in P2. CONCLUSION: Improved OS in the targeted treatment period was confirmed. Surprisingly elderly and old patients seem to profit the most form expansion of therapeutic armamentarium, within the TKI-dominated observation period.
Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Anciano , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/patología , Preescolar , Supervivencia sin Enfermedad , Humanos , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Persona de Mediana Edad , Inhibidores de Proteínas Quinasas/uso terapéutico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
INTRODUCTION: Advanced or metastatic soft tissue sarcoma (a/mSTS) is associated with a dismal prognosis. Patient counseling on treatment aggressiveness is pivotal to avoid over- or undertreatment. Recently, evaluation of body composition markers like the skeletal muscle index (SMI) became focus of interest in a variety of cancers. This study focuses on the prognostic impact of SMI in a/mSTS, retrospectively. METHODS: 181 a/mSTS patients were identified, 89 were eligible due to prespecified criteria for SMI assessment. Baseline CT-Scans were analyzed using an institutional software solution. Sarcopenia defining cut-off values for the SMI were established by optimal fitting method. Primary end point was overall survival (OS) and secondary endpoints were progression free survival (PFS), disease control rate (DCR), overall response rate (ORR). Descriptive statistics as well as Kaplan Meier- and Cox regression analyses were administered. RESULTS: 28/89 a/mSTS patients showed sarcopenia. Sarcopenic patients were significantly older, generally tended to receive less multimodal therapies (62 vs. 57 years, P = 0.025; respectively median 2.5 vs. 4, P = 0.132) and showed a significantly lower median OS (4 months [95%CI 1.9-6.0] vs. 16 months [95%CI 8.8-23.2], Log-rank P = 0.002). Sarcopenia was identified as independent prognostic parameter of impaired OS (HR 2.40 [95%-CI 1.4-4.0], P < 0.001). Moreover, DCR of first palliative medical treatment was superior in non-sarcopenic patients (49.2% vs. 25%, P = 0.032). CONCLUSION: This study identifies sarcopenia as a prognostic parameter in a/mSTS. Further on, the data suggest that sarcopenia shows a trend of being associated with first line therapy response. SMI is a promising prognostic parameter, which needs further validation.
Asunto(s)
Neoplasias Primarias Secundarias , Sarcoma , Sarcopenia , Neoplasias de los Tejidos Blandos , Humanos , Estudios Retrospectivos , Sarcoma/complicaciones , Sarcoma/tratamiento farmacológico , Neoplasias de los Tejidos Blandos/complicacionesRESUMEN
Aim: Elevated risk of malignancy-related death after renal transplantation is reported and renal malignancy was ranked as the third most frequent site of malignancy-related death. However, there is a lack of data characterizing renal cell carcinoma associated with end-stage renal disease and kidney transplantation. Patients & methods: We retrospectively identified 5250 patients who underwent kidney transplantation at the Hannover Medical School since 1970. Results: 124 patients with renal cell carcinoma (incidence 2.36%) were identified. Among all patients, metastatic recurrence was noted in 4.8%. In multivariate analysis, tumor stage and hemoglobin were identified as independent prognostic markers of OS, while tumor grading was predictive for disease recurrence. Conclusion: Apart from showing the prognostic value of tumor staging and hemoglobin, our data suggest that a risk adapted approach for early transplantation is feasible.
Asunto(s)
Carcinoma de Células Renales/epidemiología , Neoplasias Renales/epidemiología , Trasplante de Riñón/efectos adversos , Carcinoma de Células Renales/sangre , Carcinoma de Células Renales/patología , Femenino , Alemania/epidemiología , Hemoglobinas/análisis , Humanos , Incidencia , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/epidemiología , Neoplasias Renales/sangre , Neoplasias Renales/patología , Trasplante de Riñón/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Análisis de SupervivenciaAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Leucemia/tratamiento farmacológico , Terapia Recuperativa , Enfermedad Aguda , Adolescente , Adulto , Anciano , Compuestos Bicíclicos Heterocíclicos con Puentes/administración & dosificación , Citarabina/administración & dosificación , Femenino , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Sulfonamidas/administración & dosificación , Vidarabina/administración & dosificación , Vidarabina/análogos & derivadosRESUMEN
PURPOSE: Age has been linked to outcome in renal cancer patients, but mainly in North American cohorts. In this study, we hypothesized that age is correlated with metastasis and cancer-specific survival in a German cohort regardless of types of treatments. METHODS: A total of 1,538 patients treated for renal malignancies between 1991 and 2010 were evaluated. Mean age and median age are 61.9 ± 11.6 and 62.6 years. Clinicopathologic [tumor type, size, grade, stage and treatment (surgery, chemotherapy, radiation, immunotherapy)] and outcome parameters (metastasis and survival) were examined for an association with age using logistic regression and Cox proportional hazard model, and Kaplan-Meier plots. RESULTS: Age was associated with stage, metastasis, treatment, cancer-specific and overall mortality (p < 0.01). The metastasis-free and cancer-free survival rates for patients >63 years were lower than those for patients ≤63 years (p < 0.0001). In a multivariate analysis, age was an independent prognostic factor of metastasis, cancer-specific and overall mortality (p < 0.0001) even when data were stratified in different decades and treatment was included as one of the parameters. Patients >63 years of age had 29-35% higher risk of metastasis and cancer-specific mortality than younger patients. Median metastasis-free and cancer-specific survival for patients >63 years of age (months: 84.4; 70.3) was ~50% shorter than in patients ≤63 years (months: 151; 144.6). CONCLUSIONS: This large study shows that, despite advances in surgical and non-surgical treatment modalities over the two decades, age is an independent prognostic indicator of metastasis and cancer-specific mortality in renal cancer patients. Patients >63 years have ~30% increased risk for metastasis and ~50% shorter cancer-specific survival.
Asunto(s)
Factores de Edad , Neoplasias Renales/mortalidad , Neoplasias Renales/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Alemania/epidemiología , Humanos , Estimación de Kaplan-Meier , Neoplasias Renales/epidemiología , Modelos Logísticos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
During the last 15 years, tremendous efforts have been made toward medical treatment of metastatic renal cell carcinoma (mRCC). Checkpoint inhibitors (CPI) and tyrosine kinase inhibitors (TKI) dominate the therapeutic armamentarium, as a combination of either CPIs or CPI/TKI, while the value of TKI monotherapy is decreasing. With increasing efficiency, however, toxicity also increases. Appropriate management of adverse events is therefore pivotal. Recognizing adverse events, judging their etiology and appropriate management, and sometimes expanding the diagnostics of adverse events are mandatory and demand experience and vigilance. Ultimately, appropriate safety management achieves optimal oncological outcomes and maintains patient quality of life.
Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/patología , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Inhibidores de Proteínas Quinasas/uso terapéutico , Calidad de VidaRESUMEN
During the last 15 years, tremendous efforts have been made in the medical treatment of metastatic renal cell carcinoma (mRCC). Immune-oncological (IO) combinations are the current standard of care in the first-line setting of mRCC. Here, the current phase 3 trials CM214 (nivolumab/ipilimumab vs. sunitinib), KN426 (axitinib/pembrolizumab vs. sunitinib), Javelin-ren-101 (axitinib/avelumab vs. sunitinib), CM9ER (cabozantinib/nivolumab vs. sunitinib), and CLEAR (lenvatinib/pembrolizumab vs. sunitinib) were discussed. In the mentioned phase 3 trials, primary and secondary endpoints were discussed. Strengths and weaknesses of each trial were reflected in terms of overall survival, progression-free survival, objective remission, health quality of life, and safety. Reflecting on the data, as well as the current ESMO guidelines, we discuss choosing the appropriate medical treatment for patients' individualized treatment journey and relay the strength and weaknesses of each combination-starting with the appropriate first-line therapy.
Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Humanos , Sunitinib/uso terapéutico , Nivolumab , Axitinib , Calidad de VidaRESUMEN
A 67-year-old female patient with a muscle-invasive, non-metastatic urothelial bladder cancer (UC) (pT2 G3 cN0 cM0) developed metachronous metastases within 6 months after radical cystectomy with ileal conduit urinary diversion. After a good primary response to platinum-based chemotherapy, treatment was switched to the immune checkpoint inhibitor (ICI) pembrolizumab due to progressive disease. Subsequently the patient underwent selective internal radiotherapy (SIRT) of the liver and received vinflunine as well as a re-challenge with pembrolizumab. Two years after the initial diagnosis, rapid disease progression ultimately led to a switch to 5th line therapy with enfortumab vedotin (EV), which had only been approved in the United States at that time. The antibody-drug conjugate was well tolerated by the patient after dose reduction to 1.0 mg/ kg body weight. Simultaneous irradiation of newly occurring precardiac, hepatic and cerebral metastases were necessary. After 10 months of therapy with EV, tumour regression was observed accompanied with good symptom control. The presented case illustrates the efficacy and tolerability of EV in a heavily pre-treated patient with metastatic UC (mUC).
RESUMEN
BACKGROUND: To evaluate the prognostic significance of the pre-operative C-reactive protein (CRP) serum level in patients with renal cell cancer (RCC). METHODS: We evaluated 1,161 RCC patients with complete patient and tumour specific characteristics as well as information about their pre-operative CRP-level, who had undergone either radical nephrectomy or nephron-sparing surgery at two German high-volume centres (University Hospitals of Hannover and Ulm). The mean follow-up was 54 months. RESULTS: The CRP-level, stratified to three subgroups (CRP ≤ 4, 4-10, and >10 mg/l), correlated significantly with tumour stage (p < 0.001), the risk of presenting nodal disease (2.1, 3.1, and 16.4%) and distant metastasis (2.9, 8.6, and 30.0%; p < 0.001). The Kaplan-Meier 5-year cancer specific survival (CSS) rates were 89.4, 77.9, and 49.5%, respectively (p < 0.001). Multivariate analysis identified CRP as an independent prognosticator for CSS as well as overall survival (p < 0.001). Patients with a CRP of 4-10 and >10 mg/l had a 1.67 and 2.48 fold higher risk of dying due to their RCC compared to those with a pre-operative CRP ≤4 mg/l, respectively. CONCLUSIONS: A high preoperative serum CRP level is an independent predictor of poor survival in patients with RCC. Its routine use could allow better risk stratification and risk-adjusted follow-up of RCC patients.
Asunto(s)
Biomarcadores de Tumor/sangre , Proteína C-Reactiva/metabolismo , Carcinoma de Células Renales/sangre , Neoplasias Renales/sangre , Adolescente , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/epidemiología , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/cirugía , Femenino , Alemania/epidemiología , Humanos , Neoplasias Renales/epidemiología , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Masculino , Persona de Mediana Edad , Análisis Multivariante , Periodo Preoperatorio , Pronóstico , Reproducibilidad de los Resultados , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
UNLABELLED: GATA5 CpG island (CGI) methylation and transcriptional inactivation is involved in colorectal and gastric cancer. Whether DNA methylation of GATA5 affects clinical pathology is still unclear. In the present study, we analysed, for the first time, CGI methylation in RCC and its association with clinicopathological parameters and progression-free survival of patients. We show for the first time GATA5 CGI hypermethylation in RCC. Moreover, we found out that increased methylation is statistically associated with status of metastasis, progressive disease and shortened progression-free survival. The present study underline the necessity for further functional investigations as well as prospective survival analyses to clarify whether GATA5 promoter methylation can provide independent information for future clinical management of patients with RCC. OBJECTIVE: To investigate whether GATA5 CpG island (CGI) methylation occurs in renal cell carcinoma (RCC) and is associated with clinical, histopathological characteristics or progression-free survival of patients. PATIENTS AND METHODS: Methylation was quantified in 117 RCC samples and 89 paired adjacent normal tissues using quantitative combined bisulphite restriction analysis (COBRA). COBRA was evaluated in advance by pyrosequencing analyses of control RCC cell lines (coefficient of correlation, R = 0.95). Statistical analyses were carried out using the paired t-test for matched tumour tissue (TU) and adjacent normal tissue (adN) samples, logistic regression for comparisons of independent sample groups and Cox regression for analysis of progression-free survival. RESULTS: In the present study, we found a significant higher mean relative methylation in TU (20.4%) than in adN (7.9%, P < 0.001) in paired samples of all RCCs. Increased GATA5 methylation in tumours was associated with metastasis (P = 0.005) and decreased progression-free survival (P = 0.005, HR = 4.59) in the clear-cell RCC (ccRCC) group. CGI methylation in advanced ccRCCs (pT ≥3 and/or N1, M1 or G2-3/G3) exceeds those detected in localized tumours (pT ≤2, N0, M0, G1/G1-2) (27.8% vs 11.0%, P < 0.001). CONCLUSIONS: The association of GATA5 hypermethylation with metastasis and progression-free survival of patients indicates that epigenetic alterations of GATA5 participate in renal cell carcinogenesis. Moreover, GATA5 CGI methylation could serve as a biomarker for tumour progression, although prospective and functional investigations are necessary to clarify whether independent information for future clinical management of patients with RCC can be obtained.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma de Células Renales/patología , Islas de CpG/fisiología , Metilación de ADN/fisiología , Factor de Transcripción GATA5/metabolismo , Neoplasias Renales/patología , Anciano , Biomarcadores de Tumor/genética , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/secundario , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Factor de Transcripción GATA5/genética , Humanos , Neoplasias Renales/genética , Neoplasias Renales/metabolismo , Masculino , Células Tumorales CultivadasRESUMEN
BACKGROUND: Obesity increases the risk for renal cell carcinoma (RCC). However, it has only recently been identified as an independent positive prognostic factor for localized RCC. OBJECTIVE: To determine whether obesity influences long-term prognosis in metastatic RCC patients receiving vascular endothelial growth factor-targeted therapy. DESIGN, SETTING, AND PARTICIPANTS: In 116 patients with metastatic RCC who received antiangiogenic agents (sunitinib, sorafenib, axitinib, bevacizumab) in 2005-2010, we evaluated whether body mass index (BMI), a body surface area (BSA) above the European average, the visceral fat area (VFA), or s.c. fat area (SFA) were of predictive relevance. MEASUREMENTS: BMI was categorized based on current World Health Organization definitions. BSA was stratified according to the European average for men (1.98 m(2)) and women (1.74 m(2)). VFA and SFA were dichotomized using the median of the observed distribution as the cutoff. The primary endpoints of this study were time to progression and overall survival time. RESULTS AND LIMITATIONS: The whole population had median progression-free and overall survival times of 8.3 months and 20.5 months, respectively. In contrast to BMI and BSA, higher than average VFA and SFA levels were significant predictors of longer progression-free and overall survival times. The major limitations of this study are its retrospective design and its heterogeneous patient population. CONCLUSION: This is the first study to identify high VFA and SFA levels as positive predictive biomarkers for patients who receive first-line antiangiogenic agents for metastatic RCC.
Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Renales/tratamiento farmacológico , Obesidad/patología , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Índice de Masa Corporal , Superficie Corporal , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Grasa Intraabdominal , Neoplasias Renales/metabolismo , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Terapia Molecular Dirigida , Metástasis de la Neoplasia , Obesidad/metabolismo , Pronóstico , Inhibidores de Proteínas Quinasas/uso terapéutico , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia , Factor A de Crecimiento Endotelial Vascular/metabolismoAsunto(s)
Antineoplásicos/sangre , Linfoma de Células B Grandes Difuso/sangre , Linfoma de Células B Grandes Difuso/terapia , Compuestos Organoplatinos/sangre , Diálisis Renal , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapéutico , Humanos , Linfoma de Células B Grandes Difuso/diagnóstico , Persona de Mediana Edad , Compuestos Organoplatinos/farmacocinética , Compuestos Organoplatinos/uso terapéutico , Oxaliplatino , Diálisis Renal/tendenciasRESUMEN
BACKGROUND: Caveolae play a significant role in disease phenotypes such as cancer, diabetes, bladder dysfunction, and muscular dystrophy. The aim of this study was to elucidate the caveolin-1 (CAV1) protein expression in renal cell cancer (RCC) and to determine its potential prognostic relevance. METHODS: 289 clear cell RCC tissue specimens were collected from patients undergoing surgery for renal tumors. Both cytoplasmic and membranous CAV1 expression were determined by immunohistochemistry and correlated with clinical variables. Survival analysis was carried out for 169 evaluable patients with a median follow up of 80.5 months (interquartile range (IQR), 24.5-131.7 months). RESULTS: A high CAV1 expression in the tumor cell cytoplasm was significantly associated with male sex (p = 0.04), a positive nodal status (p = 0.04), and poor tumor differentiation (p = 0.04). In contrast, a higher than average (i.e. > median) CAV1 expression in tumor cell membranes was only linked to male sex (p = 0.03). Kaplan-Meier analysis disclosed significant differences in 5-year overall (51.4 vs. 75.2%, p = 0.001) and tumor specific survival (55.3 vs. 80.1%, p = 0.001) for patients with higher and lower than average cytoplasmic CAV1 expression levels, respectively. Applying multivariable Cox regression analysis a high CAV1 protein expression level in the tumor cell cytoplasm could be identified as an independent poor prognostic marker of both overall (p = 0.02) and tumor specific survival (p = 0.03) in clear cell RCC patients. CONCLUSION: Over expression of caveolin-1 in the tumour cell cytoplasm predicts a poor prognosis of patients with clear cell RCC. CAV1 is likely to be a useful prognostic marker and may play an important role in tumour progression. Therefore, our data encourage further investigations to enlighten the role of CAV1 and its function as diagnostic and prognostic marker in serum and/or urine of RCC patients.
Asunto(s)
Biomarcadores de Tumor/sangre , Carcinoma de Células Renales/sangre , Carcinoma de Células Renales/mortalidad , Caveolina 1/sangre , Neoplasias Renales/sangre , Neoplasias Renales/mortalidad , Femenino , Alemania/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/sangre , Prevalencia , Reproducibilidad de los Resultados , Medición de Riesgo/métodos , Factores de Riesgo , Sensibilidad y Especificidad , Análisis de Supervivencia , Tasa de SupervivenciaRESUMEN
Regorafenib is a multi-target tyrosine kinase inhibitor that has been approved for the treatment of metastatic colorectal cancer, advanced hepatocellular carcinoma, and metastatic gastrointestinal stromal tumors (GIST). Severe hepatobiliary toxicity has been reported in patients with colorectal cancer treated with regorafenib, but not in those with GIST. Therefore, the aim of the present study was to investigate the incidence and clinical course of regorafenib-associated hepatic toxicity (HT) in patients with GIST in a real-world setting. Patients with metastatic GIST treated with regorafenib between September 2012 and May 2014 at three German tertiary care centers were followed up until August 2017. Patient records were retrospectively analyzed and descriptive statistics were employed. HT was defined as alterations in the serum values of aspartate aminotransferase, alanine aminotransferase, γ-glutamyltransferase, alkaline phosphatase and bilirubin (according to the Common Terminology Criteria for Adverse Events, version 4.0), and/or corresponding clinical signs. The time to clinical progression and the overall survival were calculated by Kaplan-Meier curves. Overall, 21 patients were treated with regorafenib and 5 (23.5%) of those heavily pretreated patients suffered from severe HT during regorafenib treatment. In 4 (80%) of these cases, regorafenib treatment was continued, optimizing individual treatment benefit. Clinical monitoring and adequate therapy management are crucial for ensuring continuation of regorafenib treatment in order to achieve an optimal clinical outcome.
RESUMEN
BACKGROUND: The association of sarcoid-like lesions and malignancy is well described. Nonetheless, pulmonary lesions in malignant disease are typically presumed metastatic, and do not routinely receive histological validation. Here, we report on pulmonary sarcoid-like lesions identified in patients with a primary malignancy where pulmonary metastatic disease was suspected. METHODS: Patients who underwent thoracic surgical procedures for confirmation or treatment of suspected pulmonary metastasis were retrospectively analysed. RESULTS: In 8/186 patients (4.3%), histology revealed sarcoid-like lesions. In these cases, there were no clinical symptoms suggestive of sarcoidosis. All underlying primary malignancies in the sarcoid-like patients were treated with curative intent. The median age of patients with sarcoid-like lesions was 46.3 years (range 26-61). The median interval between primary diagnosis of malignancy and diagnosis of pulmonary lesions was 188 days (range 0-794), with thoracic surgical intervention performed at a median of 250 days (range 183-675). FDG-avidity was demonstrated in the sarcoid-like lesions in 2 out of 3 patients who underwent PET-CT. CONCLUSION: Sarcoid-like lesions may be challenging to identify and can mimic pulmonary metastases. Therefore, considering sarcoidosis as a differential diagnosis whenever first pulmonary metastasis is suspected is warranted. Carefully considered, histological validation of initial suspected pulmonary metastasis may avoid subsequent over- or undertreatment.
Asunto(s)
Neoplasias Pulmonares/secundario , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Sarcoidosis/diagnóstico por imagen , Adulto , Diagnóstico Diferencial , Femenino , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sarcoidosis/patología , Sarcoidosis/cirugía , Análisis de Supervivencia , Procedimientos Quirúrgicos TorácicosRESUMEN
Currently, about 50% of patients with metastatic renal cell carcinoma (mRCC) receive a second-line therapy. Therefore, the choice at each subsequent treatment line remains an important issue. In this retrospective study, we sought to identify pretreatment clinical parameters that could predict the likelihood of a patient receiving a second-line therapy. One hundred and sixty-one mRCC patients who received targeted therapy were evaluated. Descriptive statistics, Kaplan-Meier overall survival (OS), Cox regression, and binary logistic regression models were used for data analysis. Second-line therapy was given to 105 patients (65%). Patients with grade 1 tumor received second-line therapy more frequently than those with grade 2/3 tumors (P = 0.03). Only tumor grade was significantly different between patients receiving, or not receiving, second-line treatment. Median OS was significantly superior in patients receiving second-line therapy (32 versus 14 months; P = 0.007; hazard ratio [HR], 1.75; P = 0.008), patients with grade 1 tumors (130 versus 29 months in G2/3 tumors; HR, 3.85; P = 0.009), and in patients without early tumor progression (41 versus 11 months; HR, 5.04; 95% confidence interval [CI], 3.06-8.31; P < 0.001). In binary logistic regression, we identified early progression to be significantly associated with a higher probability of not receiving a second-line therapy (HR, 2.50; 95% CI, 1.01-6.21; P = 0.048). This study hypothesizes that pretreatment grade and early progression are predictive parameters for the selection of patients for second-line therapy.
RESUMEN
Clinical trials targeting programmed death 1 (PD-1) and its ligand PD-L1 (PD-L1) for metastatic renal cell cancer (RCC) are ongoing. The aim of this study is to validate their roles as prognostic markers in non-clear cell (non-cc) RCC. Sixty-four non-cc RCC tissue specimens were collected from patients undergoing renal tumor surgery. Expressions of biomarkers were assessed using immunohistochemistry and compared with clinical characteristics. Survival analyses were performed with a median follow-up of 77.5 (range: 0-176) months. No significant correlations were found for PD-1(+) tumor-infiltrating mononuclear cells (TIMC) or PD-L1(+) expression and clinical attributes in patients with non-cc RCC. Kaplan-Meier analysis revealed no differences in 5- and 10-year cancer-specific survival (CSS) for PD-1(-) TIMC compared to PD-1(+) TIMC (71.4 and 63 % versus 72.2 and 61.9 %; p = 0.88). Intratumoral expression of PD-L1 did not appear to influence the 5- and 10-year CSS significantly, even though a trend was identified (68 and 53.6 % versus 80.1 and 75.7 %; p = 0.08). In multivariate analysis, neither PD-1(+) TIMC nor intratumoral PD-L1(+) expression proved to be independent predictors of CSS (p = 0.99 and p = 0.68, respectively). Our study demonstrates that PD-1(+) TIMC and intratumoral PD-L1(+) expression did not significantly impact tumor aggressiveness or clinical outcome in non-ccRCC specimens. Due to rare incidence of non-cc RCC in particular according to PD-L1 expression, further analyzes are warranted.
Asunto(s)
Antígeno B7-H1/biosíntesis , Carcinoma de Células Renales/metabolismo , Neoplasias Renales/metabolismo , Receptor de Muerte Celular Programada 1/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/patología , Femenino , Humanos , Inmunohistoquímica , Neoplasias Renales/patología , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/patología , Linfocitos Infiltrantes de Tumor/metabolismo , Linfocitos Infiltrantes de Tumor/patología , Masculino , Persona de Mediana Edad , Estadificación de NeoplasiasRESUMEN
Until today, there is no reliable prognostic or predictive parameter for the prognosis of patients with metastatic urothelial cancer of the bladder prior to chemotherapy. Recently, serum C-reactive protein (CRP) level has been shown to be associated with survival of patients with various malignancies including localized and metastatic renal cell carcinoma, upper urinary tract as well as penile cancer. The aim of this study was to evaluate the prognostic impact of the pretreatment CRP serum level in patients with metastatic urothelial cancer of the bladder. We retrospectively evaluated 34 patients with metastatic urothelial cancer of the bladder and information about the CRP level prior to chemotherapy. The CRP level was correlated with patient- and tumor-specific characteristics. Kaplan-Meier and log-rank analyses were employed to calculate progression-free (PFS) and overall survival (OS). Receiver operating characteristics (ROC) analysis was used to determine an optimal prognostic CRP cutoff value to predict cancer-specific death. The median PFS to first-line chemotherapy and the OS for the whole cohort were 3.3 and 24.3 months, respectively. Serum CRP in mg/l was significantly associated with patients' survival (HR 1.02, p < 0.001, univariate Cox-regression). ROC analysis identified a CRP value of 80 mg/l to be the optimal cutoff. The median PFS was 4.5 and 3.0 months (p = 0.08; Mann-Whitney test), and the calculated 1-year OS was 82.6 and 22.2 % for patients with a CRP <80 and ≥80 mg/l, respectively (log-rank, p < 0.001). In contrast, neither T-stage, tumor grade, sex, age nor the body mass index was related to the CRP level or associated with overall survival. This is the first analysis revealing that the CRP value prior to systemic treatment might be of prognostic significance and could enable better risk stratification for patients with metastatic urothelial cancer of the bladder.
Asunto(s)
Proteína C-Reactiva/metabolismo , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/sangre , Urotelio/metabolismo , Urotelio/patologíaRESUMEN
BACKGROUND & AIM: Caveolae play a significant role in disease phenotypes, such as cancer, diabetes, bladder dysfunction and muscular dystrophy. The aim of this study was to elucidate the expression of caveolin (CAV)1 in the development of renal cell cancer (RCC) and to determine a possible prognostic relevance for optimal clinical management. MATERIAL & METHODS: 109 RCC and 81 corresponding normal tissue specimens from the same kidney were collected from patients undergoing surgery for renal tumors and subjected to total RNA extraction. Quantification of CAV1 mRNA expression was performed using real-time reverse transcription PCR with three endogenous controls for renal proximal tubular epithelial cells and the ΔΔCt method for calculation of relative quantities. Expression levels were correlated to clinical variables. RESULTS: Tissue-specific mean CAV1 expression was significantly increased in RCC compared with normal renal tissue (p = 0.0003; paired Wilcoxon rank sum test). CAV1 expression was increased 1.9-fold in clear cell RCC compared with papillary RCC (p = 1.48 × 10(-7); unpaired Wilcoxon rank sum test). Patients with advanced disease had higher CAV1 expression when compared with organ-confined disease (p = 0.019; unpaired Wilcoxon rank sum test). Moreover, mean tissue-specific CAV1 expression was increased in patients with distant metastasis at the time of diagnosis compared with patients without metastasis (p = 0.0058; unpaired Wilcoxon rank sum test). CONCLUSION: To our knowledge, this is the first study to show that CAV1 mRNA expression, using quantitative real-time PCR, is significantly higher in RCC compared with normal renal tissue and increases with tumor stage. CAV1 mRNA expression might serve as a candidate biomarker for objective prognosis indicating RCC aggressiveness. Our data encourage further investigations to determine the role of CAV1 in RCC.