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A technique to improve the accuracy of complete arch implant intraoral digital scans and the accuracy of their virtual casts is described. Obtaining accurate complete arch implant intraoral digital scans with an intraoral scanner is challenging because of the smooth and movable tissues of edentulous areas. The described technique uses auxiliary clips attached to intraoral scan bodies to cover interimplant edentulous spans with immobile tooth-like geometric references that are more favorable for intraoral scanning. The technique is designed to be user friendly and compatible with any intraoral scanner.
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A technique to improve the accuracy of complete arch implant intraoral digital scans and to obtain more accurate virtual casts with them is described. First, 2 complete arch intraoral digital scans were obtained with an intraoral scanner: a multiunit abutment digital scan and an implant digital scan with reusable horizontal intraoral scan bodies (ISBs) placed on the implants. These were previously created by combining the conventional ISBs compatible with the patient's implants with extensional structures with occlusal geometry. Once the digital scans had been acquired, the position of the implants was obtained by superimposing a virtual design of the conventional ISB onto each horizontal ISB of the complete arch implant digital scan. Finally, the virtual cast was obtained by superimposing the complete arch multiunit abutment digital scan on the complete arch implant digital scan.
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A technique to obtain more accurate complete arch implant digital scans and virtual casts is described. In order to obtain complete arch implant digital scans with greater accuracy, short-span intraoral digital scans are superimposed with the aid of a geometric pattern. Therefore, the technique takes advantage of the accuracy of intraoral scanners to obtain digital scans of reduced spans. Two virtual designs of the geometric pattern have been made available online: one for maxillary arches and one for mandibular arches. From these virtual designs, new virtual designs of geometric patterns of different sizes and shapes can be created to better fit different arch forms and implant positions.
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PURPOSE: To develop a risk score based on a prognostic model and a nomogram integrating baseline clinicopathological variables to predict bladder cancer-specific survival (BCSS) to neoadjuvant chemotherapy (NAC) in muscle-invasive bladder cancer (MIBC) patients. METHODS: We retrospectively identified a consecutive sample of 247 MIBC patients treated with cisplatin-based NAC-plus-cystectomy in two Spanish hospitals between 2000 and 2019. Age at MIBC diagnosis, sex, histology, lymphovascular invasion, previous non-MIBC, hydronephrosis, and clinical TNM were included in the initial Cox regression model. A risk score was computed based on the final prognostic model and a nomogram was used to estimate BCSS at 2 and 5 years. RESULTS: Median age was 66 years; 89% were males; 83% had pure urothelial carcinoma; 16.2% had previous non-MIBC. Clinical stage was T2N0, T3-4aN0, and Tx-4N + in 24%, 57%, and 19% of patients, respectively. Complete pathological response was seen in 29.4% and downstaging to non-MIBC (ypT1, ypTa, ypTis) in 12.5% of patients. Overall 5-year BCSS was 59%. Four prognostic factors were identified: variant histology, previous non-MIBC, female sex and hydronephrosis. By adding the points attributed to each of these factors, we categorized patients in three groups: low-risk (0 points); intermediate-risk (1-9 points); high-risk (≥ 10 points). Five-year BCSS was 72%, 53%, and 15%, respectively (p < 0.0001). CONCLUSION: We developed a nomogram and risk score based on four baseline clinicopathological characteristics to predict BCSS to NAC-plus-cystectomy in MIBC patients. If validated in prospective studies, this nomogram can be useful for selecting patients likely to benefit from NAC.
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Carcinoma de Células Transicionales , Hidronefrosis , Neoplasias de la Vejiga Urinaria , Masculino , Humanos , Femenino , Anciano , Neoplasias de la Vejiga Urinaria/patología , Terapia Neoadyuvante , Carcinoma de Células Transicionales/patología , Nomogramas , Estudios Prospectivos , Estudios Retrospectivos , Invasividad Neoplásica , Cistectomía , MúsculosRESUMEN
Since 2010, several treatment options have been available for men with metastatic castration-resistant prostate cancer (mCRPC), including immunotherapeutic agents, although the clinical benefit of these agents remains inconclusive in unselected mCRPC patients. In recent years, however, immunotherapy has re-emerged as a promising therapeutic option to stimulate antitumor immunity, particularly with the use of immune checkpoint inhibitors (ICIs), such as PD-1/PD-L1 and CTLA-4 inhibitors. There is increasing evidence that ICIs may be especially beneficial in specific subgroups of patients with high PD-L1 tumor expression, high tumor mutational burden, or tumors with high microsatellite instability/mismatch repair deficiency. If we are to improve the efficacy of ICIs, it is crucial to have a better understanding of the mechanisms of resistance to ICIs and to identify predictive biomarkers to determine which patients are most likely to benefit. This review focuses on the current status of ICIs for the treatment of mCRPC (either as monotherapy or in combination with other drugs), mechanisms of resistance, potential predictive biomarkers, and future challenges in the management of mCRPC.
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Adenocarcinoma/secundario , Antineoplásicos Inmunológicos/uso terapéutico , Antígeno B7-H1/antagonistas & inhibidores , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inmunoterapia/métodos , Neoplasias de la Próstata Resistentes a la Castración/terapia , Adenocarcinoma/terapia , Antineoplásicos Inmunológicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores , Ensayos Clínicos como Asunto , Reparación del ADN/genética , Resistencia a Antineoplásicos , Predicción , Humanos , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Masculino , Proteínas de Transporte de Membrana/efectos de los fármacos , Estudios Multicéntricos como Asunto , Proteínas de Neoplasias/antagonistas & inhibidores , Compuestos Organoplatinos/administración & dosificación , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Medicina de Precisión/métodos , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Taxoides/administración & dosificaciónRESUMEN
Neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy is the recommended treatment, with the highest level of evidence, for patients with muscle-invasive bladder cancer (MIBC). However, only a minority of patients receive this treatment, mainly due to patient comorbidities, the relatively small survival benefit, and the lack of predictive biomarkers to select those patients most likely to benefit from this multimodal approach. In addition, adjuvant chemotherapy has been recommended for patients with high-risk MIBC, although randomized trials have not provided conclusive evidence on the impact of this approach. At present, however, this situation is changing, largely due to our improved knowledge of the molecular biology of bladder cancer, which has enabled us to identify new prognostic and predictive biomarkers that can be used to select the most appropriate treatment for each patient. Moreover, new active treatments, especially immunotherapy, have shown promising results in the neoadjuvant setting. In addition, the gene expression profile of bladder tumors can be used to classify them into different subtypes, which correlate with specific clinical-pathological characteristics and with treatment response or resistance. Therefore, the main objective for the near future is to introduce these translational breakthroughs into routine clinical practice in order to personalize treatment for each patient.
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Biomarcadores de Tumor/genética , Carcinoma de Células Transicionales/terapia , Cisplatino/uso terapéutico , Cistectomía/métodos , Neoplasias de la Vejiga Urinaria/terapia , Carcinoma de Células Transicionales/genética , Quimioterapia Adyuvante , Terapia Combinada , Comorbilidad , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Medicina de Precisión , Nivel de Atención , Análisis de Supervivencia , Neoplasias de la Vejiga Urinaria/genéticaRESUMEN
TMPRSS2-ERG expression in blood has been correlated with low docetaxel benefit in metastatic castration-resistant prostate cancer (mCRPC). This multicenter study aimed to prospectively asses its role as a taxane-resistance biomarker in blood and retrospectively in tumors, exploring also the impact of prior abiraterone/enzalutamide (A/E) in patients and in vitro. TMPRSS2-ERG was tested by quantitative reverse-transcription PCR. We included 204 patients (137 blood and 124 tumor samples) treated with taxanes. TMPRSS2-ERG expression was correlated with prostate-specific antigen (PSA)-progression-free survival (PFS), radiological-PFS (RX-PFS), and overall survival (OS). Independent association with survival was evaluated by multivariate Cox modeling. In vitro ERG knockdown and combinatorial and sequential experiments with enzalutamide and docetaxel were performed in VCaP cells. Prior A/E (HR 1.8, 95% CI 1.2-2.8) and blood TMPRSS2-ERG detection (HR 2, 95% CI 1.1-3.7) were independently associated to lower PSA-PFS. In patients without prior A/E, blood and tumor TMPRSS2-ERG independently predicted lower PSA-PFS (HR 3.3, 95% CI 1.4-7.9 and HR 1.8, 95% CI 1.02-3.3, respectively) to taxanes. When prior A/E was administered, TMPRSS2-ERG was not associated with outcome. There was a significant interaction between blood TMPRSS2-ERG and prior A/E related to PSA-PFS (p = 0.032) and RX-PFS (p = 0.009). In vitro stable ERG inhibition did not sensitize VCaP cells to docetaxel. Concomitant enzalutamide and taxanes were synergistic, but prior enzalutamide reduced docetaxel cytotoxicity in VCaP cells. Enzalutamide induced the expression of neuroendocrine markers and reduced that of E-cadherin. We conclude that prior hormone-therapy may influence taxanes response and TMPRSS2-ERG prognostic value. Thus, multiple and sequential biomarkers are needed in CRPC follow-up evaluation.
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Biomarcadores de Tumor/genética , Docetaxel/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Proteínas de Fusión Oncogénica/genética , Feniltiohidantoína/análogos & derivados , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Benzamidas , Biomarcadores de Tumor/sangre , Hidrocarburos Aromáticos con Puentes , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Supervivencia sin Enfermedad , Sinergismo Farmacológico , Técnicas de Inactivación de Genes , Humanos , Masculino , Nitrilos , Proteínas de Fusión Oncogénica/sangre , Feniltiohidantoína/farmacología , Neoplasias de la Próstata Resistentes a la Castración/sangre , Neoplasias de la Próstata Resistentes a la Castración/genética , Estudios Retrospectivos , Taxoides , Regulador Transcripcional ERG/genéticaRESUMEN
STATEMENT OF PROBLEM: Obtaining reliable digital scans of edentulous patients is challenging because of the absence of anatomic landmarks/geometric variations along the dental arch. Whether adding an auxiliary geometric device (AGD) will improve scanning is unclear. PURPOSE: The purpose of this in vitro study was to analyze the accuracy of complete-arch digital scans of completely edentulous arches by placing a consumable AGD. MATERIAL AND METHODS: A stainless-steel model of the maxilla of a completely edentulous arch with 4 implants was built. The model was scanned using a reference industrial scanner as the control and using 3 intraoral scanners (True Definition [3M ESPE], TRIOS 3 [3Shape A/S], and iTero [Align Technology, Inc]). Each intraoral scanner was used 10 times without the AGD in place and 10 more times with the AGD fixed on the model. Accuracy in terms of trueness and precision was established by comparing 5 reference distances with or without the AGD in place. A software program for analyzing 3D data was used to measure these 5 distances, and a data analysis software program was used for statistical and measurements analysis (α=.05). RESULTS: Significant differences (P<.05) were found in all reference distances for trueness and in 4 of the 5 reference distances for precision depending on whether the AGD had been used or not. Without the AGD in place, trueness ranged from 21 ±16 µm in the shortest reference distance to 125 ±80 µm in the largest reference distance. With the AGD in place, trueness ranged from 11 ±8 µm in the shortest reference distance to 64 ±51 µm in the largest reference distance. Precision ranged from 18 ±14 µm in the shortest reference distance to 84 ±74 µm in the largest reference distance without the AGD and from 7 ±7 µm in the shortest to 63 ±46 µm in the largest with it. CONCLUSIONS: Complete-arch digital scans of edentulous jaws are more accurate when an AGD is used to resolve the lack of anatomic landmarks. An additional advantage is that the use of the AGD allows for a more fluent scanning process.
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Técnica de Impresión Dental , Boca Edéntula , Diseño Asistido por Computadora , Arco Dental , Humanos , Imagenología Tridimensional , Modelos DentalesRESUMEN
Management of low-grade gliomas (LGG) is based on clinical and radiologic features, including the Pignatti prognostic scoring system, which classifies patients as low- or high-risk. To determine whether molecular data can offer advantages over these features, we have examined the prognostic impact of several molecular alterations in LGG. In a cohort of 58 patients with LGG, we have retrospectively analyzed clinical and molecular characteristics, including the Pignatti criteria, IDH mutations, TP53 mutations, the 1p/19q deletion, and MGMT methylation, and correlated our findings with progression-free survival (PFS) and overall survival (OS). Mean age of patients was 45 years; 71% were classified as low-risk by the Pignatti system. IDH mutations were detected in 62%, p53 mutations in 17%, the 1p/19q codeletion in 46%, and MGMT methylation in 40% of patients. Survival analyses were performed in the 49 patients without contrast enhancement. In the univariate analysis, IDH mutations, the 1p/19q codeletion, and the combination of IDH mutations with the 1p/19q codeletion were associated with both longer PFS (P = 0.006, P = 0.037, and P = 0.003, respectively) and longer OS (P < 0.001, P = 0.02, and P < 0.001, respectively). The multivariate analysis identified absence of IDH mutations as a factor for greater risk of progression [hazard ratio (HR) = 3.1; P = 0.007]and death (HR = 6.4; P < 0.001). We suggest that IDH mutations may be more effective than the Pignatti score in discriminating low- and high-risk patients with LGG.
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Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Glioma/diagnóstico , Glioma/genética , Isocitrato Deshidrogenasa/genética , Mutación , Adolescente , Adulto , Anciano , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/terapia , Niño , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Predisposición Genética a la Enfermedad , Glioma/patología , Glioma/terapia , Humanos , Masculino , Análisis Multivariante , Clasificación del Tumor , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Análisis de Supervivencia , Adulto JovenRESUMEN
The virtual technique described in this article integrates reverse engineering and mandibular dynamics into dental computer-aided design and computer-aided manufacturing (CAD-CAM) systems. This technique aims to provide more objective information to the dental technician for the diagnosis, planning, and treatment phases. In order to carry out this protocol, the following devices, currently available in many practices, are necessary: an intraoral scanner, a T-Scan system, and some specific open reverse engineering software. By means of a virtual procedure, the T-Scan system detects the occlusal contacts, and the occlusal surfaces are obtained using an intraoral scanner. Once the alignment between the 3-dimensional occlusal surface and the T-Scan registration is carried out, the resulting contacts are projected onto the patient's occlusal surfaces; in this way, occlusal forces are obtained over time. The results obtained with this procedure demonstrate the feasibility of integrating different tools and software and the full integration of this procedure into a dental digital workflow.
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Diseño Asistido por Computadora , Oclusión Dental , Diseño de Prótesis Dental/métodos , Humanos , Reproducibilidad de los Resultados , Programas InformáticosRESUMEN
Sequential targeted therapies are the standard of care for patients with metastatic renal cell carcinoma (mRCC). Several drugs are available for patients whose disease progresses while they receive initial tyrosine kinase inhibitor (TKI) therapy; these include nivolumab (an inhibitor of PD-1 receptor), everolimus (an inhibitor of the mechanistic target of rapamycin) or additional TKIs. Until now, there has been no clinical evidence to support the use of one strategy versus another, so investigators and physicians rely on experience, judgement and findings from molecular analyses to select the appropriate treatment. However, with the arrival of nivolumab and cabozantinib that provide an overall survival higher than other alternative treatments, therapeutic strategies may have changed. Here, we discuss findings from preclinical and clinical studies that might help clinicians to choose the optimal treatment approach for patients with mRCC who progress to initial therapy.
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Antineoplásicos/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/secundario , Neoplasias Renales/tratamiento farmacológico , Humanos , Neoplasias Renales/patologíaRESUMEN
Patients with unresectable glioblastoma or anaplastic astrocytoma have a dismal prognosis. The role of neoadjuvant chemotherapy prior to irradiation in these patients has been studied primarily in non-randomized studies. We have compared the effect of neoadjuvant chemotherapy plus radiotherapy versus concomitant radiotherapy plus temozolomide in a retrospective analysis of two consecutive series of patients in whom surgery consisted of biopsy only. From 2003 to 2005, 23 patients received two cycles of temozolomide plus cisplatin followed by radiotherapy (Cohort 1), and from 2006 to 2010, 23 additional patients received concomitant radiotherapy and temozolomide followed by adjuvant temozolomide (Cohort 2). In Cohort 1, 91.3 % of patients received all planned chemotherapy cycles. Progression-free and overall survival were 3.3 and 8.5 months, respectively. In Cohort 2, progression-free and overall survival were 5.1 and 11.2 months, respectively. No differences between the two groups were observed in rate of completion of radiotherapy, progression-free or overall survival. MGMT methylation was assessed in 91.3 % of patients. In Cohort 1, patients without MGMT methylation showed a trend towards shorter progression-free survival (P = 0.09), while in Cohort 2, patients without MGMT methylation had longer progression-free survival (P = 0.04). In the overall patient population, neoadjuvant temozolomide plus cisplatin had neither a positive nor negative influence on outcome. However, our findings indicate that patients with methylated MGMT may derive greater benefit from neoadjuvant temozolomide than those with unmethylated MGMT.
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Antineoplásicos Alquilantes/uso terapéutico , Astrocitoma/terapia , Neoplasias Encefálicas/terapia , Cisplatino/uso terapéutico , Dacarbazina/análogos & derivados , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Adulto , Anciano , Antineoplásicos Alquilantes/administración & dosificación , Astrocitoma/metabolismo , Neoplasias Encefálicas/metabolismo , Quimioterapia Adyuvante , Cisplatino/administración & dosificación , Metilasas de Modificación del ADN/metabolismo , Enzimas Reparadoras del ADN/metabolismo , Dacarbazina/administración & dosificación , Dacarbazina/uso terapéutico , Femenino , Glioblastoma/metabolismo , Glioblastoma/terapia , Humanos , Masculino , Metilación , Persona de Mediana Edad , Terapia Neoadyuvante , Fármacos Sensibilizantes a Radiaciones/administración & dosificación , Estudios Retrospectivos , Análisis de Supervivencia , Temozolomida , Resultado del Tratamiento , Proteínas Supresoras de Tumor/metabolismo , Adulto JovenRESUMEN
The clinical procedure described provides a quantifiable, repeatable, and reliable method of transferring the location of the maxillary dental arch from the patient directly to a virtual articulator (virtual facebow transfer) by means of reverse engineering devices to design a customized dental restoration. This procedure allows the dentist and the dental laboratory technician to work in a fully digital environment without having to mount stone casts on a mechanical articulator. In addition, specific suggestions are provided for designing the transfer device to enhance patient comfort during the data transfer process and reduce deviation.
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Diseño Asistido por Computadora , Arco Dental/anatomía & histología , Articuladores Dentales , Maxilar/anatomía & histología , Modelos Dentales , Interfaz Usuario-Computador , Adulto , Puntos Anatómicos de Referencia/anatomía & histología , Simulación por Computador , Marcadores Fiduciales , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Registro de la Relación Maxilomandibular , MasculinoRESUMEN
BACKGROUND: Cancer is a risk factor for developing severe COVID19. Additionally, SARS-CoV2 has a special tropism for renal cells and complications like thrombosis or cytokine storm could be enhanced by standard treatments in kidney cancer (i.e., antiangiogenics or immunotherapy). Thus, understanding the impact of COVID19 in patients with this tumor is key for their correct management. METHODS: We designed a retrospective case-control study comparing the outcome of three groups of advanced kidney cancer patients on systemic treatment: cohort A (developed COVID19 while on antiangiogenics), cohort B (developed COVID19 while on immunotherapy) and cohort C (non-infected). Matching factors were age, gender, and treatment. RESULTS: 95 patients were recruited in 16 centers in Spain from September 2020 to May 2021. Finally, 85 were deemed as eligible (23 cohort A, 21 cohort B, 41 cohort C). Patients with COVID required more dose interruptions (25 vs. six) and hospitalizations (10 vs. none) than those without COVID (both p = 0.001). No difference between cohorts A and B was observed regarding hospitalization or length of stay. No ICU admission was registered and one patient in cohort B died due to COVID19. Regarding cancer evolution, three patients in cohort A presented progressive disease after COVID19 compared to two in cohort B. One case in cohort B, initially deemed as stable disease, achieved a partial response after COVID19. CONCLUSIONS: Kidney cancer patients who developed COVID19 while on systemic therapy required more treatment interruptions and hospitalizations than those non-infected. However, no significant impact on cancer outcome was observed. Also, no difference was seen between cases on antiangiogenics or immunotherapy.
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COVID-19 , Neoplasias Renales , Humanos , SARS-CoV-2 , Estudios de Casos y Controles , Estudios Retrospectivos , ARN Viral , Neoplasias Renales/terapia , InmunoterapiaRESUMEN
This article describes a digital technique to transfer the location of digitized casts obtained directly from the patient to a virtual articulator (digital/virtual facebow transfer). The primary advantage of this technique is that it allows the dentist and the dental laboratory technician to work in a fully digital environment without having to mount stone casts on a physical articulator. This results in a significant time reduction and a higher degree of accuracy in the cast location.
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Simulación por Computador , Articuladores Dentales , Modelos Dentales , Humanos , Imagenología Tridimensional/métodos , Registro de la Relación Maxilomandibular , Interfaz Usuario-ComputadorRESUMEN
When designing a custom-made dental restoration, using a digital workflow represents an important advance over mechanical tools such as facebows or mechanical articulators. When using virtual scanning procedures, there is a direct transfer from the patient to the articulator. This paper presents a novel methodology to design custom-made restorations. This new approach permits the transfer of all data directly from the patient to the virtual articulator, always taking into account the kinematics of the mandible. Rapid further developments can be expected in the near future.
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Diseño Asistido por Computadora , Articuladores Dentales , Diseño de Prótesis Dental/métodos , Registro de la Relación Maxilomandibular/métodos , Interfaz Usuario-Computador , Adulto , Simulación por Computador , Arco Dental/anatomía & histología , Oclusión Dental , Diseño de Prótesis Dental/instrumentación , Humanos , Registro de la Relación Maxilomandibular/instrumentación , Masculino , Mandíbula/fisiología , Maxilar/anatomía & histología , Tecnología OdontológicaRESUMEN
Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy is the standard treatment for patients with muscle-invasive bladder cancer (MIBC). However, the implementation of NAC is lower than desirable mainly due to its limited impact on overall survival, patients' comorbidities and the lack of predictive biomarkers to select those patients most likely to benefit from NAC. In the last decade, improved molecular MIBC characterisation, the identification of potential predictive and prognostic biomarkers as well as the incorporation of new effective therapies with a better toxicity profile, such as immunotherapy, has changed the treatment paradigm for MIBC. Therefore, the main goal for the near future is to introduce these clinical and translational advances into routine clinical practice to personalise treatment for each patient and increase the opportunity to implement bladder preservation strategies. The present review focuses on the current status of NAC in MIBC, unsolved questions and future therapeutic approaches.
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Neoplasias de la Vejiga Urinaria , Quimioterapia Adyuvante , Cisplatino , Cistectomía , Humanos , Músculos , Terapia Neoadyuvante , Invasividad Neoplásica , Neoplasias de la Vejiga Urinaria/tratamiento farmacológicoRESUMEN
Cancer of unknown primary site (CUP) is defined as a heterogeneous group of tumors that appear as metastases, and of which standard diagnostic work-up fails to identify the origin. It is considered a separate entity with a specific biology, and nowadays molecular characteristics and the determination of actionable mutations may be important in a significant group of patients. In this guide, we summarize the diagnostic, therapeutic, and possible new developments in molecular medicine that may help us in the management of this unique disease entity.
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Neoplasias Primarias Desconocidas , Humanos , Neoplasias Primarias Desconocidas/diagnóstico , Neoplasias Primarias Desconocidas/genética , Neoplasias Primarias Desconocidas/terapiaRESUMEN
Neoadjuvant chemotherapy followed by a cystectomy is the standard treatment in muscle-invasive bladder cancer (MIBC). However, the role of chemotherapy in the adjuvant setting remains controversial, and therefore new prognostic and predictive biomarkers are needed to improve the selection of MIBC patients. While lipid metabolism has been related to several biological processes in many tumours, including bladder cancer, no metabolic biomarkers have been identified as prognostic in routine clinical practice. In this multicentre, retrospective study of 198 patients treated with cystectomy followed by platinum-based adjuvant chemotherapy, we analysed the immunohistochemical expression of CD36 and correlated our findings with clinicopathological characteristics and survival. CD36 immunostaining was positive in 30 patients (15%) and associated with more advanced pathologic stages (pT3b-T4; p = 0.015). Moreover, a trend toward lymph node involvement in CD36-positive tumours, especially in earlier disease stages (pT1-T3; p = 0.101), was also observed. Among patients with tumour progression during the first 12 months after cystectomy, disease-free survival was shorter in CD36-positive tumours than in those CD36-negative (6.51 months (95% CI 5.05-7.96) vs. 8.74 months (95% CI 8.16-9.32); p = 0.049). Our results suggest an association between CD36 immunopositivity and more aggressive features of MIBC and lead us to suggest that CD36 could well be a useful prognostic marker in MIBC.
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INTRODUCTION: The purpose of this investigation was to explore patients' and oncologists' preferences for the characteristics of a pharmacological regimen for patients with advanced renal cell carcinoma (aRCC). MATERIAL AND METHODS: Cross-sectional observational study based on a discrete choice experiment (DCE) conducted in Spain. A literature review, a focus group with oncologists and interviews with patients informed the DCE design. Five attributes were included: progression survival gain, risk of serious adverse events (SAEs), health-related quality of life (HRQoL), administration mode, and treatment cost. Preferences were analyzed using a mixed-logit model to estimate relative importance (RI) of attributes (importance of an attribute in relation to all others), which was compared between aRCC patients and oncologists treating aRCC. Willingness to pay (WTP, payer: health system) for a benefit in survival or in risk reduction and maximum acceptable risk (MAR) in SAEs for improving survival were estimated from the DCE. Subgroup analyses were performed to identify factors that influence preference. RESULTS: A total of 105 patients with aRCC (77.1% male, mean age 65.9 years [SD: 10.4], mean time since RCC diagnosis 6.3 years [SD: 6.1]) and 67 oncologists (52.2% male, mean age 41.9 years [SD: 8.4], mean duration of experience in RCC 10.2 years [SD: 7.5]) participated in the study. The most important attribute for patients and oncologists was survival gain (RI: 43.6% vs. 54.7% respectively, p<0.05), followed by HRQoL (RI: 35.5% vs. 18.0%, respectively, p<0.05). MAR for SAEs was higher among oncologists than patients, while WTP (for the health system) was higher for patients. Differences in preferences were found according to time since diagnosis and education level (patients) or length of professional experience (oncologists). CONCLUSION: Patients' and oncologists' preferences for aRCC treatment are determined mainly by the efficacy (survival gain) but also by the HRQoL provided. The results of the study can help to inform decision-making in the selection of appropriate aRCC treatment.