Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 19.548
Filtrar
1.
Anticancer Res ; 41(4): 1971-1974, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33813403

RESUMEN

BACKGROUND/AIM: Oncological care has faced several challenges during the COVID-19 pandemic, e.g. treatment delay and worsening symptoms. Patient-reported anxiety, depression and sleep quality might have changed due to these special circumstances. Therefore, we analyzed the symptom burden of patients treated with palliative radiotherapy at our center. PATIENTS AND METHODS: A retrospective study was performed of 50 consecutive patients and the results were compared to those obtained in a previous pre-COVID study. The Edmonton Symptom Assessment Scale was employed to assess the preradiotherapy symptoms. RESULTS: The highest mean scores were reported for pain in activity (3.2) and dry mouth (3.1). Regarding anxiety, sadness/depression and sleep, the corresponding scores were 1.5, 1.2 and 2.7, respectively. Compared to the previous study, no significant increases were found. Most items had numerically lower mean values, e.g. anxiety (1.5 vs. 2.7). Both study populations had comparable median age (70.5 vs. 70 years), gender distribution and proportion of patients with bone metastases. However, there were two significant imbalances, namely a lower proportion of patients with prostate cancer (12 vs. 30%, p=0.02) and breast cancer (0 vs. 12%, p=0.02). CONCLUSION: In patients who showed up for radiation treatment planning, the suspected increase in anxiety, sadness/depression and sleep disturbance was not demonstrable. It is not known whether or not patients with substantial worries chose to decline referral to palliative radiotherapy. Therefore, comprehensive large-scale studies of patterns of care are needed to fully understand the impact of COVID-19-related measures.


Asunto(s)
/epidemiología , Costo de Enfermedad , Neoplasias/radioterapia , Cuidados Paliativos/métodos , Pandemias , Anciano , Anciano de 80 o más Años , Ansiedad/epidemiología , Ansiedad/etiología , Neoplasias Óseas/epidemiología , Neoplasias Óseas/secundario , Dolor en Cáncer/diagnóstico , Dolor en Cáncer/epidemiología , Dolor en Cáncer/etiología , Depresión/epidemiología , Depresión/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Neoplasias/epidemiología , Neoplasias/patología , Noruega/epidemiología , Estudios Retrospectivos , Análisis de Supervivencia , Evaluación de Síntomas
2.
Nat Commun ; 12(1): 1714, 2021 03 17.
Artículo en Inglés | MEDLINE | ID: mdl-33731701

RESUMEN

Advanced prostate cancer (PCa) often develops bone metastasis, for which therapies are very limited and the underlying mechanisms are poorly understood. We report that bone-borne TGF-ß induces the acetylation of transcription factor KLF5 in PCa bone metastases, and acetylated KLF5 (Ac-KLF5) causes osteoclastogenesis and bone metastatic lesions by activating CXCR4, which leads to IL-11 secretion, and stimulating SHH/IL-6 paracrine signaling. While essential for maintaining the mesenchymal phenotype and tumorigenicity, Ac-KLF5 also causes resistance to docetaxel in tumors and bone metastases, which is overcome by targeting CXCR4 with FDA-approved plerixafor. Establishing a mechanism for bone metastasis and chemoresistance in PCa, these findings provide a rationale for treating chemoresistant bone metastasis of PCa with inhibitors of Ac-KLF5/CXCR4 signaling.


Asunto(s)
Neoplasias Óseas/secundario , Carcinogénesis , Transición Epitelial-Mesenquimal , Factores de Transcripción de Tipo Kruppel/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/patología , Acetilación , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bencilaminas/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/genética , Neoplasias Óseas/metabolismo , Línea Celular Tumoral , Ciclamas/uso terapéutico , Docetaxel/uso terapéutico , Humanos , Interleucina-11/genética , Interleucina-11/metabolismo , Factores de Transcripción de Tipo Kruppel/genética , Masculino , Ratones , Mutación , Osteogénesis , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Receptores CXCR4/antagonistas & inhibidores , Receptores CXCR4/genética , Receptores CXCR4/metabolismo , Transducción de Señal , Factor de Crecimiento Transformador beta/metabolismo
3.
Medicine (Baltimore) ; 100(8): e24917, 2021 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-33663128

RESUMEN

RATIONALE: Patients with lung adenocarcinoma harboring EML4-ALK rearrangements respond well to multiple ALK tyrosine kinase inhibitors (TKIs). However, the tumor will invariably progress due to acquired resistance. Comprehensive genomic profiling appears to be a promising strategy to reveal the underlying molecular mechanisms of ALK-TKIs resistance. PATIENT CONCERNS: A patient with right lung adenocarcinoma harboring an ALK rearrangement received targeted therapy with multiple ALK-TKIs. He sought for follow-up treatment after his disease progressed again. DIAGNOSIS: The patient had a tumor diagnosed with stage I (T1bN0M0) lung adenocarcinoma. INTERVENTIONS: Due to the surgical contraindication, the patient did not undergo surgical resection. Instead, he received crizotinib as the first-line therapy with the progression-free survival of 20 months. Then he switched to alectinib treatment, however the disease rapidly progressed again. OUTCOMES: Next-generation sequencing was performed and revealed that 7 somatic mutations were identified. Among them, 2 mutations, ALK I1171T and BRAF V600E, may be responsible for the resistance of this patient to ALK-TKIs. BRAF V600E mutation may explain the patient's resistance to lorlatinib. LESSONS: We present a case of ALK-rearranged lung adenocarcinoma with acquired resistance to ALK inhibition, in which the BRAF V600E mutation is a novel resistance mechanism. This provides evidence that BRAF V600E mutation is one mechanism of ALK-TKI resistance.


Asunto(s)
Adenocarcinoma del Pulmón/genética , Neoplasias Óseas/secundario , Neoplasias Pulmonares/genética , Adenocarcinoma del Pulmón/tratamiento farmacológico , Quinasa de Linfoma Anaplásico/efectos de los fármacos , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/genética , Proteínas de Ciclo Celular , Crizotinib/farmacología , Crizotinib/uso terapéutico , Resistencia a Antineoplásicos/efectos de los fármacos , Resultado Fatal , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Proteínas Asociadas a Microtúbulos , Persona de Mediana Edad , Mutación , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Serina Endopeptidasas
5.
Anticancer Res ; 41(3): 1471-1474, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33788739

RESUMEN

BACKGROUND/AIM: The aim of this study was to analyze the survival predictions obtained from a web platform allowing for computation of the so-called Bone Metastases Ensemble Trees for Survival (BMETS). This prediction model is based on a machine learning approach and considers 27 prognostic covariates. PATIENTS AND METHODS: This was a retrospective single-institution analysis of 326 patients, managed with palliative radiotherapy for bone metastases. Deviations between model-predicted survival and observed survival were assessed. RESULTS: The median actuarial survival was 7.5 months. In total, 59% of patients survived for a period shorter than predicted. Twenty percent of the predictions of the median survival deviated from the observed survival by at least 6 months. Regarding actual survival <3 months (99 of 326 patients), the BMETS-predicted median survival was <3 months, i.e. correct in 67 of 99 cases (68%), whereas the model predicted a median of 4-6 months in 16 (16%) and of >6 months in another 16 cases. CONCLUSION: The model predicted survival with high accuracy in a large number of patients. Nevertheless, if the model predicts a low likelihood of 3-month survival, actual survival may be very poor (often 1 month or less). Also, in patients who died within 3 months from the start of radiotherapy, the model often predicted longer survival (16% had >6 months predicted median survival). It would, therefore, be interesting to feed the U.S. database utilized to develop the BMETS with additional poor-prognosis patients to optimize the predictions.


Asunto(s)
Neoplasias Óseas/radioterapia , Aprendizaje Automático , Cuidados Paliativos/métodos , Oncología por Radiación/métodos , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/secundario , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/terapia , Estudios Retrospectivos
6.
Anticancer Res ; 41(3): 1693-1699, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33788767

RESUMEN

AIM: To report two cases in which treatment with pembrolizumab for advanced non-small cell lung cancer (NSCLC) with bone metastasis of the long bone of the lower extremity in a state of impending fracture significantly ameliorated both lung tumor and bone metastasis. CASE REPORT: Case 1 was a 74-year-old woman diagnosed with metastasis of NSCLC in the left tibia and case 2 was a 71-year-old man diagnosed with metastasis of NSCLC in the right femur; their bone metastases were in a state of impending fracture. Disease in both cases was already in stage IVB and they received systemic therapy using pembrolizumab, whilst the bone metastases were treated conservatively. After 3 months, both patients showed a complete response with remarkable osteosclerotic changes in bone metastases and the size of lung tumors was reduced. CONCLUSION: These results might imply a novel strategy for systemic treatment with pembrolizumab is required, even in case of impending fracture in advanced NSCLC.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/secundario , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Anciano , Neoplasias Óseas/diagnóstico por imagen , Femenino , Humanos , Masculino
7.
Cancer Treat Rev ; 94: 102168, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33730627

RESUMEN

OBJECTIVE: This systematic review and meta-analysis aimed to develop an evidence-based summary of current knowledge of bone metastases (BMs) in neuroendocrine neoplasms (NENs), inform diagnosis and treatment and standardise management between institutions. METHODS: PubMed, Medline, EMBASE and meeting proceedings were searched for eligible studies reporting data on patients with BMs and NENs of any grade of differentiation and site; poorly-differentiated large/small cell lung cancer were excluded. Data were extracted and analysed using STATA v.12. Meta-analysis of proportions for calculation of estimated pooled prevalence of BM and calculation of weighted pooled frequency and weighted pooled mean for other variables of interest was performed . RESULTS: A total of 149 studies met the eligibility criteria. Pooled prevalence of BMs was 18.4% (95% CI 15.4-21.5). BMs were mainly metachronous with initial diagnosis of NEN (61.2%) and predominantly osteoblastic; around 61% were multifocal, with a predisposition in axial skeleton. PET/CT seemed to provide (together with MRI) the highest sensitivity and specificity for BM detection. Almost half of patients (46.4%) reported BM-related symptoms: pain (66%) and skeletal-related events (SREs, fracture/spinal cord compression) (26.2%; weightedweighted mean time-to-SRE 9.9 months). Management of BMs was multimodal [bisphosphonates and bone-modifying agents (45.2%), external beam radiotherapy (34.9%), surgery (14.8%)] and supported by little evidence. Overall survival (OS) from the time of diagnosis of BMs was long [weighted mean 50.9 months (95% CI 40.0-61.9)]. Patients with BMs had shorter OS [48.8 months (95% CI 37.9-59.6)] compared to patients without BMs [87.4 months (95% CI 74.9-100.0); p = 0.001]. Poor performance status and BM-related symptoms were also associated with worse OS. CONCLUSIONS: BMs in patients with NENs remain underdiagnosed and undertreated. Recommendations for management of BMs derived from current knowledge are provided. Prospective studies to inform management are required.


Asunto(s)
Neoplasias Óseas/secundario , Neoplasias Óseas/terapia , Tumores Neuroendocrinos/patología , Tumores Neuroendocrinos/terapia , Neoplasias Óseas/diagnóstico , Humanos , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/secundario
8.
BMJ Case Rep ; 14(2)2021 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-33542007

RESUMEN

A 65-year-old female patient has a history of malignant triton tumour of the right upper lobe of the lung. She underwent right upper lobectomy and lymphadenectomy in May 2018. She presented in November 2019 with pathological fracture of the left proximal femur. It was not associated with neurofibromatosis. We decided to do an excisional biopsy of the mass and proximal femoral replacement followed by radiotherapy. Four months later, she presented with local recurrence. We organised a multidisciplinary team between the orthopaedic, histopathology and oncology teams. Then, we decided to treat her with chemotherapy. After 2 months of follow-up, she responded well to the chemotherapy with no further deterioration of her condition.


Asunto(s)
Neoplasias Óseas/radioterapia , Neoplasias Óseas/cirugía , Fémur , Fracturas Espontáneas/cirugía , Neoplasias Pulmonares/cirugía , Anciano , Artroplastia de Reemplazo de Cadera , Neoplasias Óseas/secundario , Femenino , Humanos , Recurrencia Local de Neoplasia , Tomografía Computarizada por Rayos X
9.
Medicine (Baltimore) ; 100(6): e24751, 2021 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-33578627

RESUMEN

ABSTRACT: Bone metastasis seriously affects the survival of breast cancer. Therefore, the study aimed to explore the independent prognostic factors in bone metastatic breast cancer (BMBC) and to construct a prognostic nomogram that can accurately predict the survival of BMBC and strictly divide the patients into different risk stratification.Four thousand three hundred seventy six patients with BMBC from the surveillance, epidemiology, and end results database in 2010 to 2015 were collected and randomly divided into training and validation cohort. Multivariate Cox regression identified the independent prognostic factors of BMBC. A nomogram for predicting cancer-specific survival (CSS) in BMBC was created using R software. The predictive performance of the nomogram was evaluated by plotting receiver operating characteristic (ROC) curves and calibration curves.Marital status, race, age, T stage, tumor grade, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, brain metastasis, liver metastasis, lung metastasis, chemotherapy, and breast surgery were identified as independent prognostic factors for CSS of BMBC. The area under the ROC curve at 1-, 3-, and 5-year of the nomogram were 0.775, 0.756, and 0.717 in the internal validation and 0.785, 0.737, and 0.735 in the external validation, respectively. Calibration curves further confirmed the unbiased prediction of the model. Kaplan-Meier analysis verified the excellent risk stratification of our model.The first prognostic nomogram for BMBC constructed in our study can accurately predict the survival of BMBC, which may provide a practical tool to help clinicians evaluate prognosis and stratify the prognostic risk for BMBC, thereby determining which patients should be given intensive treatment and optimizing individual treatment strategies for BMBC.


Asunto(s)
Neoplasias Óseas/secundario , Neoplasias de la Mama/mortalidad , Carcinoma Ductal/secundario , Nomogramas , Anciano , Neoplasias Óseas/mortalidad , Huesos/patología , Neoplasias de la Mama/patología , Carcinoma Ductal/mortalidad , Femenino , Humanos , Persona de Mediana Edad , Programa de VERF , Estados Unidos/epidemiología
11.
J Surg Oncol ; 123(5): 1316-1327, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33523514

RESUMEN

Symptomatic peri-acetabular metastatic lesions are often treated with open surgery such as modified Harrington procedures. In an effort to avoid surgical complications inherently associated with open surgical approaches, we developed and recently reported a novel Tripod percutaneous screw technique. The tripod technique is minimally invasive and was found to yield excellent outcomes regarding both pain control and functionality. The procedure is performed in a standard operative theater using fluoroscopic guided percutaneous screws. Despite the simplicity of intraoperative set-up and instrumentation, it is technically demanding. Obtaining the correct fluoroscopic views and troubleshooting intraoperative hurdles can be challenging for even an experienced orthopedic surgeon. The technique and bony conduits were previously described in the trauma literature, however, there are key points of difference in the setting of metastatic disease. Here we provide a compilation of a stepwise graphic guide for the tripod model in the setting of metastatic peri-acetabular lesions, as well as the tips and tricks based on our own experience. These encompass preoperative preparation, operating room settings, intraoperative fluoroscopic guidance, postoperative care, and subsequent conversion to a cemented total hip arthroplasty, if needed.


Asunto(s)
Acetábulo/cirugía , Artroplastia de Reemplazo de Cadera/métodos , Neoplasias Óseas/cirugía , Tornillos Óseos , Fijación Interna de Fracturas/métodos , Neoplasias/cirugía , Procedimientos Quirúrgicos Reconstructivos/métodos , Neoplasias Óseas/secundario , Fluoroscopía , Humanos , Neoplasias/patología , Pronóstico
12.
Br J Radiol ; 94(1120): 20210043, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33571003

RESUMEN

OBJECTIVE: A new Bayesian penalized likelihood reconstruction algorithm for positron emission tomography (PET) (Q.Clear) is now in clinical use for fludeoxyglucose (FDG) PET/CT. However, experience with non-FDG tracers and in special patient populations is limited. This pilot study aims to compare Q.Clear to standard PET reconstructions for 18F sodium fluoride (18F-NaF) PET in obese patients. METHODS: 30 whole body 18F-NaF PET/CT scans (10 patients with BMI 30-40 Kg/m2 and 20 patients with BMI >40 Kg/m2) and a NEMA image quality phantom scans were analyzed using ordered subset expectation maximization (OSEM) and Q.Clear reconstructions methods with B400, 600, 800 and 1000. The images were assessed for overall image quality (IQ), noise level, background soft tissue, and lesion detectability, contrast recovery (CR), background variability (BV) and contrast-to-noise ratio (CNR) for both algorithms. RESULTS: CNR for clinical cases was higher for Q.Clear than OSEM (p < 0.05). Mean CNR for OSEM was (21.62 ± 8.9), and for Q.Clear B400 (31.82 ± 14.6), B600 (35.54 ± 14.9), B800 (39.81 ± 16.1), and B1000 (40.9 ± 17.8). As the ß value increased the CNR increased in all clinical cases. B600 was the preferred ß value for reconstruction in obese patients. The phantom study showed Q.Clear reconstructions gave lower CR and lower BV than OSEM. The CNR for all spheres was significantly higher for Q.Clear (independent of ß) than OSEM (p < 0.05), suggesting superiority of Q.Clear. CONCLUSION: This pilot clinical study shows that Q.Clear reconstruction algorithm improves overall IQ of 18F-NaF PET in obese patients. Our clinical and phantom measurement results demonstrate improved CNR and reduced BV when using Q.Clear. A ß value of 600 is preferred for reconstructing 18F-NaF PET/CT with Q.Clear in obese patients. ADVANCES IN KNOWLEDGE: 18F-NaF PET/CT is less susceptible to artifacts induced by body habitus. Bayesian penalized likelihood reconstruction with18F-NaF PET improves overall IQ in obese patients.


Asunto(s)
Neoplasias Óseas/diagnóstico por imagen , Radioisótopos de Flúor , Interpretación de Imagen Asistida por Computador/métodos , Obesidad/complicaciones , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Fluoruro de Sodio , Algoritmos , Teorema de Bayes , Neoplasias Óseas/complicaciones , Neoplasias Óseas/secundario , Huesos/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Imagen de Cuerpo Entero/métodos
13.
Nat Commun ; 12(1): 723, 2021 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-33526787

RESUMEN

Bone metastatic prostate cancer (PCa) promotes mesenchymal stem cell (MSC) recruitment and their differentiation into osteoblasts. However, the effects of bone-marrow derived MSCs on PCa cells are less explored. Here, we report MSC-derived interleukin-28 (IL-28) triggers prostate cancer cell apoptosis via IL-28 receptor alpha (IL-28Rα)-STAT1 signaling. However, chronic exposure to MSCs drives the selection of prostate cancer cells that are resistant to IL-28-induced apoptosis and therapeutics such as docetaxel. Further, MSC-selected/IL-28-resistant prostate cancer cells grow at accelerated rates in bone. Acquired resistance to apoptosis is PCa cell intrinsic, and is associated with a shift in IL-28Rα signaling via STAT1 to STAT3. Notably, STAT3 ablation or inhibition impairs MSC-selected prostate cancer cell growth and survival. Thus, bone marrow MSCs drive the emergence of therapy-resistant bone metastatic prostate cancer yet this can be disabled by targeting STAT3.


Asunto(s)
Adenocarcinoma/secundario , Neoplasias Óseas/secundario , Células Madre Mesenquimatosas/patología , Neoplasias de la Próstata/patología , Receptores de Interferón/metabolismo , Ácidos Aminosalicílicos/farmacología , Ácidos Aminosalicílicos/uso terapéutico , Animales , Apoptosis/efectos de los fármacos , Bencenosulfonatos/farmacología , Bencenosulfonatos/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Diferenciación Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular , Medios de Cultivo Condicionados/metabolismo , Modelos Animales de Enfermedad , Docetaxel/farmacología , Docetaxel/uso terapéutico , Humanos , Interferones/genética , Interferones/metabolismo , Masculino , Ratones Noqueados , Osteoblastos/patología , Cultivo Primario de Células , Neoplasias de la Próstata/tratamiento farmacológico , ARN Interferente Pequeño/metabolismo , Receptores de Interferón/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Factor de Transcripción STAT1/metabolismo , Factor de Transcripción STAT3/antagonistas & inhibidores , Factor de Transcripción STAT3/metabolismo , Tibia/patología
14.
Medicine (Baltimore) ; 100(4): e24558, 2021 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-33530285

RESUMEN

ABSTRACT: Melanoma can spread to the bone by metastasis and is relevant to a poor outcome. However, because of the rarity of melanoma patients with bone metastasis, the prognostic postoperative survival factors of them have not been elucidated. The aim of this special population-based cohort was to elucidate the prognostic factors associated with postoperative survival. The Surveillance, Epidemiology, and End Results database was used to extract postoperative survival data relating to patients with melanoma and bone metastasis at diagnosis between 2010 and 2016, along with data on a range of potential postoperative prognostic factors. We then investigated the potential postoperative prognostic roles of these factors using a Cox regression model and the Kaplan-Meier analysis. In all, the Surveillance, Epidemiology, and End Results database included 186 cases. Regarding overall survival, the 1-, 3-, and 5-year overall survival rates for the entire cohort were 36.2%, 15.4%, and 9.5%, respectively. Regarding cancer-specific survival, the 1-, 3-, and 5-year cancer-specific survival rates were 42.0%, 23.2%, and 16.6%, respectively. Within a cohort of melanoma patients with bone metastasis after surgery, our analysis showed that a smaller tumor size and the lack of metastases at other sites were predictors of survival.


Asunto(s)
Neoplasias Óseas/secundario , Melanoma/mortalidad , Anciano , Neoplasias Óseas/patología , Neoplasias Óseas/cirugía , Bases de Datos Factuales , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Melanoma/patología , Melanoma/terapia , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Programa de VERF , Análisis de Supervivencia
15.
JAMA Netw Open ; 4(2): e2037120, 2021 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-33570575

RESUMEN

Importance: Despite approximately 40% of patients having Eastern Cooperative Oncology Group (ECOG) performance status (PS) scores of at least 2 in the real world, most landmark clinical trials that led to the use of pembrolizumab as standard of care in advanced non-small cell lung cancer (NSCLC) excluded this group. Objective: To evaluate whether an ECOG PS score of at least 2 at the start of therapy is associated with progression-free survival (PFS) and overall survival (OS) in advanced NSCLC treated with pembrolizumab monotherapy. Design, Setting, and Participants: This cohort study included all consecutive patients with advanced NSCLC who underwent treatment with palliative pembrolizumab monotherapy from February 2016 to October 2019 at a single academic cancer center, with data censoring on January 15, 2020. Exposures: ECOG PS score at start of therapy, with 0 and 1 indicating fully active or restricted in strenuous activity and scores of 2 and higher indicating increasing disability. Main Outcomes and Measures: PFS and OS, measured from initiation of pembrolizumab monotherapy. Results: Of 74 patients (median [range] age, 68.5 [33-87] years; 36 [48.7%] women; 53 [71.6%] White individuals) with median follow-up of 19.5 (95% CI, 13.4-27.8) months, 45 (60.8%) had an ECOG PS of 0 or 1, while 29 (39.2%) had an ECOG PS of at least 2. There were no significant differences in the baseline characteristics, except in age. Compared with patients with PS scores of 0 or 1, those with PS scores of at least 2 had significantly lower disease control rates (38 [88.4%] vs 15 [53.6%]; P = .002), shorter median PFS (7.9 [95% CI, 4.6-15.4] months vs 2.3 [95% CI, 1.8-4.8] months; P = .004), and shorter median OS (23.2 [14.0 vs 35.7] months vs 4.1 [95% CI, 2.1-6.9] months; P < .001). Among those potentially eligible for subsequent cancer-directed therapy beyond pembrolizumab monotherapy, patients in the group with PS scores of at least 2 were less likely to receive it than those with PS scores of 0 or 1 (2 [8.3%] vs 14 [45.2%]; P = .003). Multivariable adjustment for baseline characteristics confirmed ECOG PS of at least 2 as an independent risk factor for worse PFS (HR, 2.02; 95% CI, 1.09-3.74; P = .03) and worse OS (HR, 2.87; 95% CI, 1.40-5.89; P = .004). Conclusions and Relevance: In this cohort study, having an ECOG PS score of at least 2 was associated with poorer prognosis for treatment of advanced NSCLC with palliative pembrolizumab monotherapy. Further prospective studies are needed to evaluate more objective and consistent measures of functional status to facilitate identification of patients with borderline performance status who may achieve durable clinical benefit from treatment with pembrolizumab monotherapy.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias de las Glándulas Suprarrenales/tratamiento farmacológico , Neoplasias de las Glándulas Suprarrenales/secundario , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/secundario , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/secundario , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/fisiopatología , Carcinoma de Pulmón de Células no Pequeñas/secundario , Estudios de Cohortes , Toma de Decisiones Conjunta , Femenino , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/fisiopatología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Cuidados Paliativos , Neoplasias Pleurales/tratamiento farmacológico , Neoplasias Pleurales/secundario , Pronóstico , Supervivencia sin Progresión , Tasa de Supervivencia
16.
Clin Exp Metastasis ; 38(2): 209-217, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33634347

RESUMEN

Implementation of COVID-19 measures may have induced concerns about access and quality of health care for cancer patients with bone metastases, and it may have affected their quality of life. In this study, we evaluated the effect of the first COVID-19 lockdown on quality of life and emotional functioning of patients with stage IV cancer treated for painful bone metastases in the UMC Utrecht, the Netherlands. A COVID-19 specific questionnaire was sent to active participants in the Prospective Evaluation of interventional StudiEs on boNe meTastases (PRESENT) cohort, consisting of patients irradiated for metastatic bone disease. Patient reported outcomes (PROs) were compared with the last two PROs collected within the PRESENT cohort before the COVID-19 lockdown in the Netherlands on the 16th of March. For the 169 (53%) responders, median age at start of lockdown was 68 years (range 38-92) and 62% were male. Patients reported a statistically significant decrease in emotional functioning (83.6 to 79.2, P = 0.004) and in general quality of life score during the COVID-19 lockdown (72.4 to 68.7, P = 0.007). A steep increase in feeling isolated was reported (18% before and 67% during lockdown). This study has shown a strong increase in the experience of isolation and a decrease of emotional functioning and general quality of life during the COVID-19 lockdown in cancer patients with bone metastases. Due to the nature of the treatment of this patient population, efforts should be made to minimize these changes during future lockdowns.


Asunto(s)
Neoplasias Óseas/radioterapia , Emociones , Calidad de Vida , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/psicología , Neoplasias Óseas/secundario , Femenino , Humanos , Masculino , Salud Mental , Persona de Mediana Edad , Países Bajos , Medición de Resultados Informados por el Paciente , Estudios Prospectivos , Aislamiento Social , Encuestas y Cuestionarios , Resultado del Tratamiento
17.
Gene ; 775: 145419, 2021 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-33444686

RESUMEN

BACKGROUND: Breast cancer is the most commonly diagnosed cancer among women and its metastases results in poor survival rates in patients. The ability to alter metabolism is a key attribute cancer cells use to survive within different metastatic microenvironments and cause organ failure. We hypothesized that evaluation of metabolic alterations within tumor cells could provide a better understanding of cancer metastasis. Therefore, to investigate underlying metabolic alterations during metastases, we utilized human MDA-MB-231 and mouse 4T1 models that closely mimic human breast cancer metastasis. METHODS: The glycolysis and glutamine pathway-related changes were examined in bone metastatic cells by XF-24 extracellular flux analyzer and western blotting. The expression levels of genes related to metabolism were examined by PCR arrays. RESULTS: The MDA-MB-231 cells isolated after bone metastases showed reduced glucose uptake and glycolysis compared to parental cells, suggesting that these cells could alter metabolic requirements for survival. To understand these metabolic changes, we investigated glutamine, a common and naturally occurring non-essential amino acid. Interestingly, in reduced glucose conditions both cell lines showed dependence on glutamine for cell survival, and with glutamine withdrawal significantly increasing apoptotic cell death. Glutamine was also critical for normal cell proliferation even in the presence of high glucose concentrations. To further understand this metabolic switch in metastatic cells, we examined the genes related to metabolism and identified a more than seven-fold downregulation of protein kinase C zeta (PKC-ζ) expression levels in bone-derived MDA-MB-231 cells compared to the parental population. The PKC-ζ levels were also significantly reduced in metastatic 4T1 cells compared to non-metastatic MT1A2 cells. Since PKC-ζ deficiency promotes glutamine utilization via the serine biosynthesis pathway, we examined glutamine metabolism. The ectopic expression of PKC-ζ inhibited glutamine conversion to glutamate, while mutant PKC-ζ reversed this effect. Furthermore, the gene expression levels of enzymes involved in serine biosynthesis, phosphoserine phosphatase (PSPH), phosphoserine aminotransferase (PSAT1), and phosphoglycerate dehydrogenase (PHGDH) showed upregulation following glucose deprivation with PKC-ζ deficiency. The PHGDH upregulation was inhibited by ectopically expressing wild type but not mutated PKC-ζ in glucose-deprived conditions. CONCLUSIONS: Our results support the upregulation of serine biosynthesis pathway genes and downregulation of PKC-ζ as potential metabolic alterations for bone metastatic breast cancer cells.


Asunto(s)
Neoplasias Óseas/metabolismo , Neoplasias Óseas/secundario , Neoplasias de la Mama/metabolismo , Glutamina/metabolismo , Proteína Quinasa C/genética , Proteína Quinasa C/metabolismo , Animales , Vías Biosintéticas , Neoplasias Óseas/genética , Neoplasias de la Mama/genética , Línea Celular Tumoral , Proliferación Celular , Supervivencia Celular , Regulación hacia Abajo , Femenino , Regulación Neoplásica de la Expresión Génica , Glucólisis , Humanos , Ratones , Modelos Biológicos , Microambiente Tumoral
19.
Clin Nucl Med ; 46(1): 43-44, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33156044

RESUMEN

Metastatic involvement of the thyroid cartilage is rare due to the absence of vessels within the cartilaginous tissue. We present the case of a 65-year-old woman recently diagnosed with breast cancer referred for skeletal staging with F-NaF PET/CT. She was found to have multiple osteoblastic metastases along with thyroid cartilage metastasis. Rare thyroid cartilage metastasis on F-NaF PET/CT may have prognostic significance in cancer patients.


Asunto(s)
Neoplasias de la Mama/patología , Radioisótopos de Flúor , Neoplasias Laríngeas/diagnóstico por imagen , Neoplasias Laríngeas/secundario , Tomografía Computarizada por Tomografía de Emisión de Positrones , Fluoruro de Sodio , Cartílago Tiroides/diagnóstico por imagen , Anciano , Neoplasias Óseas/secundario , Femenino , Humanos , Pronóstico
20.
Clin Nucl Med ; 46(1): 69-70, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33208621

RESUMEN

A 74-year-old man with a history of prostate cancer with proven osseous metastatic disease underwent Ga-prostate-specific membrane antigen (PSMA) PET/CT under antiandrogen therapy. The scan revealed a long segment of increased PSMA tracer uptake within the right sciatic nerve, which appeared edematous and swollen, and the respective ganglia. Clinically, the patient suffered from pain and paresis in the right leg. As infiltration of a long segment of a single nerve seems unlikely, primarily neuronal disease such as neuritis (induced by metastases or radiotherapy) was considered. The observed uptake of PSMA-targeting PET tracers may then represent a peripheral nerve disorder.


Asunto(s)
Ácido Edético/análogos & derivados , Ganglios/metabolismo , Nervios Periféricos/metabolismo , Tomografía Computarizada por Tomografía de Emisión de Positrones , Anciano , Transporte Biológico , Neoplasias Óseas/secundario , Ácido Edético/metabolismo , Ganglios/diagnóstico por imagen , Ganglios/patología , Humanos , Masculino , Nervios Periféricos/diagnóstico por imagen , Nervios Periféricos/patología , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...