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1.
Oncologist ; 29(4): e526-e534, 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-37995309

RESUMEN

BACKGROUND: Adolescent and young adult cancer survivors (AYAs, aged 18-39 years at first diagnosis) have a higher second cancer risk. Accelerated aging is hypothesized as underlying mechanism and has been described clinically by 6 indicators; fatigue, low quality of sleep, low mood, lack of motivation, subjective memory complaints, and poor exercise tolerance. Using patient-reported outcomes, we aimed to identify clusters of accelerated aging among AYA cancer survivors and to investigate their association with second cancer development. PATIENTS AND METHODS: Patient, tumor, and treatment data were obtained from the Netherlands Cancer Registry. Patient-reported clinical indicators and second cancer data were obtained from the SURVivors (5-20 years) of cancer in AYAs (SURVAYA) questionnaire study between 1999 and 2015. Latent class and multivariable logistic regression analyses were performed. RESULTS: In total, n = 3734 AYA survivors with known second cancer status (n = 278 [7.4%] second cancers) were included. Four latent clusters were identified and named based on their clinical indicator features; (1) high accelerated aging (31.3%), (2) intermediate accelerated aging without poor exercise tolerance (15.1%), (3) intermediate accelerated aging without lack of motivation (27.4%), and (4) low accelerated aging (26.2%). AYAs in the high accelerated aging cluster were more likely to have second cancer (odds ratio: 1.6; 95% CI, 1.1-2.3) compared to the low accelerated aging cluster. CONCLUSION: AYAs with a higher burden of accelerated aging were more likely to develop a second cancer. Validation of the clinical indicators and how to best capture them is needed to improve (early) detection of AYAs at high risk of developing second cancer.


Asunto(s)
Supervivientes de Cáncer , Neoplasias Primarias Secundarias , Neoplasias , Adolescente , Humanos , Adulto Joven , Envejecimiento , Neoplasias/terapia , Neoplasias Primarias Secundarias/complicaciones , Medición de Resultados Informados por el Paciente , Adulto
2.
Eur J Neurol ; : e16457, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39282967

RESUMEN

BACKGROUND AND PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is perceived differently by patients and physicians, complicating its assessment. Current recommendations advocate combining clinical and patient-reported outcomes measures, but this approach can be challenging in patient care. This multicenter European study aims to bridge the gap between patients' perceptions and neurological impairments by aligning both perspectives to improve treatment decision-making. METHODS: Data were pooled from two prospective studies of subjects (n = 372) with established CIPN. Patient and physician views regarding CIPN were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Total Neuropathy Scale-clinical version (TNSc) items, and the disease-specific quality of life - Chemotherapy-Induced Peripheral Neuropathy questionnaire (QLQ-CIPN20) from the European Organization for Research and Treatment of Cancer (EORTC). To identify inherent neurotoxic severity patterns, we employed hierarchical cluster analysis optimized with k-means clustering and internally validated by discriminant functional analysis. RESULTS: Both NCI-CTCAE and TNSc demonstrated a significant difference in the distribution of severity grades in relation to QLQ-CIPN20 scores. However, a proportion of subjects with different neurotoxic severity grades exhibited overlapping QLQ-CIPN20 scores. We identified three distinct clusters classifying subjects as having severely impaired, intermediately impaired, and mildly impaired CIPN based on TNSc and QLQ-CIPN20 scores. No differences in demographics, cancer type distribution, or class of drug received were observed. CONCLUSIONS: Our results confirm the heterogeneity in CIPN perception between patients and physicians and identify three well-differentiated subgroups of patients delineated by degree of CIPN impairment based on scores derived from TNSc and QLQ-CIPN20. A more refined assessment of CIPN could potentially be achieved using the calculator tool derived from the cluster equations in this study. This tool, which facilitates individual patient classification, requires prospective validation.

3.
Support Care Cancer ; 32(2): 104, 2024 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-38217712

RESUMEN

PURPOSE: Adolescent and young adult cancer survivors (AYAs) are at increased risk of long-term and late effects, and experience unmet needs, impacting their health-related quality of life (HRQoL). In order to provide and optimize supportive care and targeted interventions for this unique population, it is important to study HRQoL factors' interconnectedness on a population level. Therefore, this network analysis was performed with the aim to explore the interconnectedness between HRQoL factors, in the analysis described as nodes, among long-term AYAs. METHODS: This population-based cohort study used cross-sectional survey data of long-term AYAs, who were identified by the Netherlands Cancer Registry (NCR). Participants completed a one-time survey (SURVAYA study), including the EORTC survivorship questionnaire (QLQ-SURV111) to assess their long-term HRQoL outcomes and sociodemographic characteristics. The NCR provided the clinical data. Descriptive statistics and a network analysis, including network clustering, were performed. RESULTS: In total, 3596 AYAs (on average 12.4 years post diagnosis) were included in our network analysis. The network was proven stable and reliable and, in total, four clusters were identified, including a worriment, daily functioning, psychological, and sexual cluster. Negative health outlook, part of the worriment cluster, was the node with the highest strength and its partial correlation with health distress was significantly different from all other partial correlations. CONCLUSION: This study shows the results of a stable and reliable network analysis based on HRQoL data of long-term AYAs, and identified nodes, correlations, and clusters that could be intervened on to improve the HRQoL outcomes of AYAs.


Asunto(s)
Supervivientes de Cáncer , Neoplasias , Humanos , Adulto Joven , Adolescente , Supervivientes de Cáncer/psicología , Calidad de Vida/psicología , Estudios de Cohortes , Estudios Transversales , Encuestas y Cuestionarios , Neoplasias/terapia , Neoplasias/psicología
4.
Int J Gynecol Cancer ; 34(2): 239-243, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38184318

RESUMEN

OBJECTIVE: There is a continued need for improvement of second-line systemic treatment for metastatic and/or recurrent endometrial cancer. METHODS: In this phase II, open-label study, eligible patients had histologically or cytologically confirmed endometrial cancer, documented progressive disease, and a WHO performance status of ≤2. All participants received treatment with pazopanib 800 mg once daily until progression, unacceptable toxicity, or patient refusal. The primary endpoint was progression-free survival at 3 months, with secondary outcomes of overall response rate, progression-free survival, overall survival, and toxicity. The study was powered to demonstrate 50% progression-free survival at 3 months with α=0.05 and ß=80%. RESULTS: Between January 2011 and February 2016, 60 eligible patients were included (intention-to-treat population). Median age was 68 (range, 53-85) years. Previous treatment included pelvic radiotherapy (58%), chemotherapy (90%), and hormonal therapy (43%). Three-month progression-free survival was 63.3% in the intention-to-treat population, with median progression-free survival and overall survival of 3.4 and 7.5 months, respectively. Overall response rate was 8.3%, and median follow-up 7.6 months. The most common grade 3 or higher adverse events were gastrointestinal toxicity in 21% of participants, including two patients with a gut perforation, one fatal gastrointestinal hemorrhage, one enterocutaneous fistula, and one fatal enterovaginal fistula. Extensive peritoneal disease existed in 80% of the patients with severe gastrointestinal toxicity. A definite correlation with previous radiotherapy could not be established. CONCLUSIONS: Pazopanib met its primary endpoint of 3 months' progression-free survival in advanced endometrial cancer (63.3%), but response rates were modest. There may be a correlation for rare but severe gastrointestinal toxicity with previous treatments and/or disease site that has yet to be elucidated.


Asunto(s)
Neoplasias Endometriales , Indazoles , Pirimidinas , Sulfonamidas , Humanos , Femenino , Pirimidinas/administración & dosificación , Pirimidinas/efectos adversos , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/patología , Anciano , Persona de Mediana Edad , Sulfonamidas/administración & dosificación , Sulfonamidas/efectos adversos , Anciano de 80 o más Años , Supervivencia sin Progresión , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/efectos adversos , Resistencia a Antineoplásicos , Países Bajos
5.
BJOG ; 130(2): 143-152, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36264251

RESUMEN

BACKGROUND: Fifteen percent of patients with endometrial cancer (EC) have advanced stage disease or develop a recurrence. Progestins have been applied as systemic treatment for decades, but there is limited evidence on response prediction with biomarkers and toxicity. OBJECTIVES: To review the response and toxicity of progestin therapy and stratify response to progesterone receptor (PR) expression and tumour grade. SEARCH STRATEGY: We used the search terms 'Endometrial cancer', 'Progestins', 'Disease progression', 'Recurrence' and related terms in Pubmed, Embase and Cochrane databases. SELECTION CRITERIA: Studies on patients with advanced stage or recurrent EC treated with progestin monotherapy were included. Studies on adjuvant therapy, with fewer than ten cases and with sarcoma histology were excluded. DATA COLLECTION AND ANALYSIS: Evaluation for bias was performed with the Revised Cochrane RoB2 tool for randomised studies and the ROBINS-I tool for non-randomised studies. A random effects meta-analysis was performed with the overall response rate (ORR), clinical benefit rate and toxicity as primary outcome measures. MAIN RESULTS: Twenty-six studies (1639 patients) were included. The ORR of progestin therapy was 30% (95% CI 25-36), the clinical benefit rate was 52% (95% CI 42-61). In PR-positive EC, the ORR was 55%, compared with 12% in PR-negative disease (risk difference 43%, 95% CI 15-71). Severe toxicity occurred in 6.5%. CONCLUSIONS: Progestin therapy is a viable treatment option in patients with advanced stage and recurrent EC with low toxicity and high ORR in PR-positive disease. The role of PR expression in relation to progression-free survival and overall survival is unclear.


Asunto(s)
Neoplasias Endometriales , Progestinas , Femenino , Humanos , Progestinas/efectos adversos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/patología
6.
Am J Obstet Gynecol ; 225(4): 407.e1-407.e16, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34019887

RESUMEN

BACKGROUND: Approximately 20% of women with endometrial cancer have advanced-stage disease or suffer from a recurrence. For these women, prognosis is poor, and palliative treatment options include hormonal therapy and chemotherapy. Lack of predictive biomarkers and suboptimal use of existing markers for response to hormonal therapy have resulted in overall limited efficacy. OBJECTIVE: This study aimed to improve the efficacy of hormonal therapy by relating immunohistochemical expression of estrogen and progesterone receptors and estrogen receptor pathway activity scores to response to hormonal therapy. STUDY DESIGN: Patients with advanced or recurrent endometrial cancer and available biopsies taken before the start of hormonal therapy were identified in 16 centers within the European Network for Individualized Treatment in Endometrial Cancer and the Dutch Gynecologic Oncology Group. Tumor tissue was analyzed for estrogen and progesterone receptor expressions and estrogen receptor pathway activity using a quantitative polymerase chain reaction-based messenger RNA model to measure the activity of estrogen receptor-related target genes in tumor RNA. The primary endpoint was response rate defined as complete and partial response using the Response Evaluation Criteria in Solid Tumors. The secondary endpoints were clinical benefit rate and progression-free survival. RESULTS: Pretreatment biopsies with sufficient endometrial cancer tissue and complete response evaluation were available in 81 of 105 eligible cases. Here, 22 of 81 patients (27.2%) with a response had estrogen and progesterone receptor expressions of >50%, resulting in a response rate of 32.3% (95% confidence interval, 20.9-43.7) for an estrogen receptor expression of >50% and 50.0% (95% confidence interval, 35.2-64.8) for a progesterone receptor expression of >50%. Clinical benefit rate was 56.9% for an estrogen receptor expression of >50% (95% confidence interval, 44.9-68.9) and 75.0% (95% confidence interval, 62.2-87.8) for a progesterone receptor expression of >50%. The application of the estrogen receptor pathway test to cases with a progesterone receptor expression of >50% resulted in a response rate of 57.6% (95% confidence interval, 42.1-73.1). After 2 years of follow-up, 34.3% of cases (95% confidence interval, 20-48) with a progesterone receptor expression of >50% and 35.8% of cases (95% confidence interval, 20-52) with an estrogen receptor pathway activity score of >15 had not progressed. CONCLUSION: The prediction of response to hormonal treatment in endometrial cancer improves substantially with a 50% cutoff level for progesterone receptor immunohistochemical expression and by applying a sequential test algorithm using progesterone receptor immunohistochemical expression and estrogen receptor pathway activity scores. However, results need to be validated in the prospective Prediction of Response to Hormonal Therapy in Advanced and Recurrent Endometrial Cancer (PROMOTE) study.


Asunto(s)
Antineoplásicos Hormonales/uso terapéutico , Biomarcadores de Tumor/metabolismo , Carcinoma Endometrioide/metabolismo , Neoplasias Endometriales/metabolismo , Receptor alfa de Estrógeno/metabolismo , Recurrencia Local de Neoplasia/metabolismo , Receptores de Progesterona/metabolismo , Anciano , Anciano de 80 o más Años , Inhibidores de la Aromatasa/uso terapéutico , Carcinoma Endometrioide/tratamiento farmacológico , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/patología , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , Antagonistas de Estrógenos/uso terapéutico , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Progestinas/uso terapéutico , Supervivencia sin Progresión , ARN Mensajero/metabolismo , Criterios de Evaluación de Respuesta en Tumores Sólidos , Tamoxifeno/uso terapéutico
7.
Int J Gynecol Cancer ; 31(7): 1014-1020, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34001633

RESUMEN

INTRODUCTION: According to current guidelines, hormonal therapy may be applied in endometrioid type endometrial cancer as an alternative to surgery for fertility preservation and in medically unfit patients. Since it is unknown how often hormonal therapy is applied, the objective of this study was to investigate trends over time in hormonal therapy use in the background of the overall incidence of endometrial cancer. METHODS: All patients with endometrial cancer (n=48 222) registered in the Netherlands Cancer Registry in the period 1989-2018 were included. European age-standardized incidence rates with corresponding estimated annual percentage change were calculated to describe trends in the incidence of endometrial cancer. The use of hormonal therapy was analyzed in the three periods 1989-1998, 1999-2008, and 2009-2018 for the following sub-groups: primary and adjuvant therapy, International Federation of Gynecology and Oncology (FIGO) stage I-II and III-IV, and by age group. RESULTS: The European age-standardized incidence rate of endometrioid endometrial cancer peaked in 2004 with a significant increase from 1989 to 2004 (annual percentage change 0.55; 95% CI 0.10 to 0.99, p=0.020) and a subsequent decrease from 2005 to 2018 (annual percentage change -1.79; 95% CI -2.28 to -1.31, p<0.001). The incidence rate of non-endometrioid type endometrial cancer increased significantly in the study period. Hormonal therapy was used in 1482 (3.5%) patients with endometrioid endometrial cancer. Among patients with FIGO stage I aged ≤40 years, hormonal therapy increased from 0% in 1989-1998 to 27% in 2009-2018. Primary hormonal treatment increased from 175 patients (5.5%) to 329 patients (7.8%) in those aged ≥75 years. Adjuvant hormonal treatment was mostly used in advanced stage endometrial cancer. CONCLUSIONS: The use of primary hormonal therapy in endometrioid type endometrial cancer increased over time in patients aged ≤40 years and among elderly patients. The observed trends in the current use of hormonal therapy support the need to study the effect of hormonal treatment in elderly patients and as adjuvant treatment in advanced stage endometrial cancer.


Asunto(s)
Neoplasias Endometriales/tratamiento farmacológico , Terapia de Reemplazo de Hormonas/métodos , Adulto , Anciano , Femenino , Humanos , Incidencia , Persona de Mediana Edad , Países Bajos
8.
Int J Gynecol Cancer ; 30(6): 837-844, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32276940

RESUMEN

INTRODUCTION: Despite renewed treatment options for advanced epithelial ovarian cancer, survival remains poor. The Patient Association and the Gynecological Oncology Working Party in the Netherlands have identified a need for a tool to improve shared decision-making. The aim of this study was to develop an evidence-based online decision aid for patients with advanced epithelial ovarian cancer and their medical team. METHODS: First, we identified the patients' and clinicians' needs using surveys and in-depth interviews. Second, we conducted multidisciplinary face-to-face meetings with representatives from all stakeholders (clinicians and patient representatives) to determine the content of the decision aid. Third, we developed the decision aid using standardized criteria and national guidelines. Finally, we tested the usability of the tool with patients and clinicians who participated in the needs assessment. RESULTS: Patients and clinicians indicated the need for more sources of reliable information that include all treatment options available in the Netherlands. Although most interviewees were satisfied with the level of information available at the time of their own treatment, the majority (90%) of the patients stated that no choice of treatment was offered. We developed a consultation sheet and an online decision aid based on patient interviews and team discussions. The sheet contains a summary of all treatment options and login codes for the decision aid; it will be offered to patients at their first consultation. The decision aid can be used at home and includes information about epithelial ovarian cancer and all available treatment options and questions about quality of life and treatment preferences, delivering a personalized summary for discussion during the following consultation about the primary treatment choices. DISCUSSION: In cooperation with patients and clinicians, we developed a decision aid for advanced-stage epithelial ovarian cancer patients and their medical team to support shared decision-making, based on a confirmed need for more extensive information sources. The decision aid is currently under assessment in a multicenter implementation trial.


Asunto(s)
Carcinoma Epitelial de Ovario/terapia , Técnicas de Apoyo para la Decisión , Neoplasias Ováricas/terapia , Prioridad del Paciente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Epitelial de Ovario/psicología , Femenino , Humanos , Entrevistas como Asunto , Persona de Mediana Edad , Evaluación de Necesidades , Neoplasias Ováricas/psicología
10.
J Peripher Nerv Syst ; 24(1): 111-119, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30672664

RESUMEN

To test if and how chemotherapy-induced peripheral neurotoxicity (CIPN) is perceived differently by patients and physicians, making assessment and interpretation challenging. We performed a secondary analysis of the CI-PeriNomS study which included 281 patients with stable CIPN. We tested: (a) the association between patients' perception of activity limitation in performing eight common tasks and neurological impairment and (b) how the responses to questions related to these daily activities are interpreted by the treating oncologist. To achieve this, we compared patients' perception of their activity limitation with neurological assessment and the oncologists' blind interpretation. Distribution of the scores attributed by oncologists to each daily life maximum limitation ("impossible") generated three groups: Group 1 included limitations oncologists attributed mainly to motor impairment; Group 2 ones mainly attributed to sensory impairment and Group 3 ones with uncertain motor and sensory impairment. Only a subset of questions showed a significant trend between severity in subjective limitation, reported by patients, and neurological impairment. In Group 1, neurological examination confirmed motor impairment in only 51%-65% of patients; 76%-78% of them also had vibration perception impairment. In Group 2, sensory impairment ranged from 84% to 100%; some degree of motor impairment occurred in 43%-56% of them. In Group 3 strength reduction was observed in 49%-50% and sensory perception was altered in up to 82%. Interpretation provided by the panel of experienced oncologists was inconsistent with the neurological impairment. These observations highlight the need of a core set of outcome measures for future CIPN trials.


Asunto(s)
Actividades Cotidianas , Síndromes de Neurotoxicidad/diagnóstico , Oncólogos , Medición de Resultados Informados por el Paciente , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Índice de Severidad de la Enfermedad , Adulto , Humanos
11.
Eur Arch Otorhinolaryngol ; 273(2): 455-64, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25876000

RESUMEN

For patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN), chemotherapy can prolong life and alleviate symptoms. However, expected gains may be small, not necessarily outweighing considerable toxicity and high costs. Treatment choice is to a large extent dependent on preferences of doctors and patients and data on these choices are scarce. The purpose of this study is to obtain real-world information on palliative systemic treatment and costs of R/M SCCHN in the Netherlands. In six Dutch head and neck treatment centers, data were collected on patient and tumor characteristics, treatment patterns, disease progression, survival, adverse events, and resource use for R/M SCCHN, between 2006 and 2013. 125 (14 %) out of 893 R/M SCCHN patients received palliative, non-trial first-line systemic treatment, mainly platinum + 5FU + cetuximab (32 %), other platinum-based combination therapy (13 %), methotrexate monotherapy (27 %) and capecitabine monotherapy (14 %). Median progression-free survival and overall survival were 3.4 and 6.0 months, respectively. 34 (27 %) patients experienced severe adverse events. Mean total hospital costs ranged from € 10,075 (± € 9,891) (methotrexate monotherapy) to € 39,459 (± € 21,149) (platinum + 5FU + cetuximab). Primary cost drivers were hospital stays and anticancer drug treatments. Major health care utilization and costs are involved in systemically treating R/M SCCHN patients with a limited survival.


Asunto(s)
Carcinoma de Células Escamosas/terapia , Costo de Enfermedad , Neoplasias de Cabeza y Cuello/terapia , Recurrencia Local de Neoplasia/terapia , Anciano , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/secundario , Terapia Combinada/economía , Costos y Análisis de Costo , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Neoplasias de Cabeza y Cuello/epidemiología , Neoplasias de Cabeza y Cuello/secundario , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/economía , Recurrencia Local de Neoplasia/epidemiología , Países Bajos/epidemiología , Carcinoma de Células Escamosas de Cabeza y Cuello , Tasa de Supervivencia/tendencias
12.
J Peripher Nerv Syst ; 19(2): 127-35, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24814100

RESUMEN

Chemotherapy-induced peripheral neuropathy (CIPN) lacks standardized clinical measurement. The objective of the current secondary analysis was to examine data from the CIPN Outcomes Standardization (CI-PeriNomS) study for associations between clinical examinations and neurophysiological abnormalities. Logistic regression estimated the strength of associations of vibration, pin, and monofilament examinations with lower limb sensory and motor amplitudes. Examinations were classified as normal (0), moderately abnormal (1), or severely abnormal (2). Among 218 participants, those with class 1 upper extremity (UE) and classes 1 or 2 lower extremity (LE) monofilament abnormality were 2.79 (95% confidence interval [CI]: 1.28-6.07), 3.49 (95%CI: 1.61-7.55), and 4.42 (95%CI: 1.35-14.46) times more likely to have abnormal sural nerve amplitudes, respectively, compared to individuals with normal examinations. Likewise, those with class 2 UE and classes 1 or 2 LE vibration abnormality were 8.65 (95%CI: 1.81-41.42), 2.54 (95%CI: 1.19-5.41), and 7.47 (95%CI: 2.49-22.40) times more likely to have abnormal sural nerve amplitudes, respectively, compared to participants with normal examinations. Abnormalities in vibration and monofilament examinations are associated with abnormal sural nerve amplitudes and are useful in identifying CIPN.


Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/complicaciones , Conducción Nerviosa/fisiología , Examen Neurológico , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Potenciales de Acción/fisiología , Anciano , Conjuntos de Datos como Asunto/estadística & datos numéricos , Quimioterapia , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Nervio Sural/fisiopatología
13.
J Cancer Surviv ; 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38740702

RESUMEN

BACKGROUND: With 5-year survival rates > 85%, gaining insight into the long-term and late health-related conditions of cancer survivors diagnosed in adolescence and young adulthood is of utmost importance to improve their quantity and quality of survival. This study examined the prevalence of and factors associated with, patient-reported health-related conditions and their latency times among long-term adolescent and young adult (AYA) cancer survivors. METHODS: AYA cancer survivors (5-20 years after diagnosis) were identified by the population-based Netherlands Cancer Registry (NCR), and invited to participate in the SURVAYA questionnaire study. Participants reported the prevalence and date of diagnosis of health-related conditions. Clinical data were retrieved from the NCR. RESULTS: Three thousand seven hundred seventy-six AYA cancer survivors (response rate 33.4%) were included for analyses. More than half of the AYAs (58.5%) experienced health-related conditions after their cancer diagnosis, of whom 51.4% were diagnosed with two or more conditions. Participants reported conditions related to vision (15.0%), digestive system (15.0%), endocrine system (14.1%), cardiovascular system (11.7%), respiratory system (11.3%), urinary tract system (10.9%), depression (8.6%), hearing (7.4%), arthrosis (6.9%), secondary malignancy (6.4%), speech-, taste and smell (4.5%), and rheumatoid arthritis (2.1%). Time since diagnosis, tumor type, age at diagnosis, and educational level were most frequently associated with a health-related condition. CONCLUSIONS: A significant proportion of long-term AYA cancer survivors report having one or more health-related conditions. IMPLICATIONS FOR CANCER SURVIVORS: Future research should focus on better understanding the underlying mechanisms of, and risk factors for, these health-related conditions to support the development and implementation of risk-stratified survivorship care for AYA cancer survivors to further improve their outcomes. CLINICAL TRIALS REGISTRATION: NCT05379387.

14.
Heliyon ; 10(1): e23170, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38187310

RESUMEN

Objective: Ovarian cancer is the fifth cause of cancer-related death among women. The benefit of targeted therapy for ovarian cancer patients is limited even if treatment is stratified by molecular signature. There remains a high unmet need for alternative diagnostics that better predict targeted therapy, as current diagnostics are generally inaccurate predictors. Quantitative assessment of functional signal transduction pathway (STP) activity from mRNA measurements of target genes is an alternative approach. Therefore, we aim to identify aberrantly activated STPs in tumour tissue of patients with recurrent ovarian cancer and start phenotype-guided targeted therapy to improve survival without compromising quality of life. Study design: Patients with recurrent ovarian cancer and either 1) have platinum-resistant disease, 2) refrain from standard therapy or 3) are asymptomatic and not yet eligible for standard therapy will be included in this multi-centre prospective cohort study with multiple stepwise executed treatment arms. Targeted therapy will be available for patients with aberrantly high functional activity of the oestrogen receptor, androgen receptor, phosphoinositide 3-kinase or Hedgehog STP. The primary endpoint of this study is the progression-free survival (PFS) ratio (PFS2/PFS1 ratio) according to RECIST 1.1 determined by the PFS on matched targeted therapy (PFS2) compared to PFS on prior therapy (PFS1). Secondary endpoints include among others best overall response, overall survival, side effects, health-related quality of life and cost-effectiveness. Conclusion: The results of this study will show the clinical applicability of STP activity in selecting recurrent ovarian cancer patients for effective therapies.

15.
J Cancer Surviv ; 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38224397

RESUMEN

PURPOSE: For adolescent and young adult (AYA) cancer survivors with a good prognosis, having a healthy lifestyle prevents morbidity and mortality after treatment. The aim of this study was to investigate the prevalence of (un)healthy lifestyle behaviors and related determinants in AYA cancer survivors. METHODS: A population-based, cross-sectional study was performed among long-term (5-20 years) AYA cancer survivors (18-39 years old at diagnosis) registered within the Netherlands Cancer Registry. Self-reported questionnaires data about health behaviors were used to calculate the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) adherence score. Associations between the score and clinical/sociodemographic determinants of (un)healthy behaviors were investigated using logistic regression models. RESULTS: The mean WCRF/AICR score was low to moderate, 3.8 ± 1.2 (0.5-7.0) (n = 3668). Sixty-one percent adhered to "limit the consumption of sugar sweetened drinks," 28% to "be a healthy weight," 25% to "fruit and vegetable consumption," and 31% to "limit alcohol consumption." Moderate and high adherence were associated with being a woman (ORmoderate = 1.46, 95% CI = 1.14-1.85, and ORhigh = 1.87, 95% CI = 1.46-2.4) and highly educated (ORmoderate = 1.54, 95% CI = 1.30-1.83, and ORhigh = 1.87, 95% CI = 1.46-2.4). Low adherence was associated with smoking (ORmoderate = 0.68, 95% CI = 0.50-0.92, and ORhigh = 0.30, 95% CI = 0.21-0.44) and diagnosis of germ cell tumor (ORmoderate = 0.58, 95% CI = 0.39-0.86, and ORhigh = 0.45, 95% CI = 0.30-0.69). CONCLUSIONS: Adherence to the 2018 WCRF/AICR lifestyle recommendations was low to moderate, especially regarding body weight, fruit, vegetables, and alcohol consumption. Men, current smokers, lower-educated participants, and/or those diagnosed with germ cell tumors were less likely to have a healthy lifestyle. IMPLICATIONS FOR CANCER SURVIVORS: Health-promotion programs (e.g., age-specific tools) are needed, focusing on high-risk groups.

16.
Clin Cancer Res ; 30(1): 50-62, 2024 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-37939124

RESUMEN

PURPOSE: Early results from the phase II MEDIOLA study (NCT02734004) in germline BRCA1- and/or BRCA2-mutated (gBRCAm) platinum-sensitive relapsed ovarian cancer (PSROC) showed promising efficacy and safety with olaparib plus durvalumab. We report efficacy and safety of olaparib plus durvalumab in an expansion cohort of women with gBRCAm PSROC (gBRCAm expansion doublet cohort) and two cohorts with non-gBRCAm PSROC, one of which also received bevacizumab (non-gBRCAm doublet and triplet cohorts). PATIENTS AND METHODS: In this open-label, multicenter study, PARP inhibitor-naïve patients received olaparib plus durvalumab treatment until disease progression; the non-gBRCAm triplet cohort also received bevacizumab. Primary endpoints were objective response rate (ORR; gBRCAm expansion doublet cohort), disease control rate (DCR) at 24 weeks (non-gBRCAm cohorts), and safety (all cohorts). RESULTS: The full analysis and safety analysis sets comprised 51, 32, and 31 patients in the gBRCAm expansion doublet, non-gBRCAm doublet, and non-gBRCAm triplet cohorts, respectively. ORR was 92.2% [95% confidence interval (CI), 81.1-97.8] in the gBRCAm expansion doublet cohort (primary endpoint); DCR at 24 weeks was 28.1% (90% CI, 15.5-43.9) in the non-gBRCAm doublet cohort (primary endpoint) and 74.2% (90% CI, 58.2-86.5) in the non-gBRCAm triplet cohort (primary endpoint). Grade ≥ 3 adverse events were reported in 47.1%, 65.6%, and 61.3% of patients in the gBRCAm expansion doublet, non-gBRCAm doublet, and non-gBRCAm triplet cohorts, respectively, most commonly anemia. CONCLUSIONS: Olaparib plus durvalumab continued to show notable clinical activity in women with gBRCAm PSROC. Olaparib plus durvalumab with bevacizumab demonstrated encouraging clinical activity in women with non-gBRCAm PSROC. No new safety signals were identified.


Asunto(s)
Antineoplásicos , Neoplasias Ováricas , Humanos , Femenino , Bevacizumab/efectos adversos , Inhibidores de Poli(ADP-Ribosa) Polimerasas/efectos adversos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Estudios de Cohortes , Mutación de Línea Germinal , Antineoplásicos/uso terapéutico , Ftalazinas/efectos adversos , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico
17.
Cancers (Basel) ; 16(11)2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38893205

RESUMEN

BACKGROUND: Response to hormonal therapy in advanced and recurrent endometrial cancer (EC) can be predicted by oestrogen and progesterone receptor immunohistochemical (ER/PR-IHC) expression, with response rates of 60% in PR-IHC > 50% cases. ER/PR-IHC can vary by tumour location and is frequently lost with tumour progression. Therefore, we explored the relationship between ER/PR-IHC expression and tumour location in EC. METHODS: Pre-treatment tumour biopsies from 6 different sites of 80 cases treated with hormonal therapy were analysed for ER/PR-IHC expression and classified into categories 0-10%, 10-50%, and >50%. The ER pathway activity score (ERPAS) was determined based on mRNA levels of ER-related target genes, reflecting the actual activity of the ER receptor. RESULTS: There was a trend towards lower PR-IHC (33% had PR > 50%) and ERPAS (27% had ERPAS > 15) in lymphogenic metastases compared to other locations (p = 0.074). Hematogenous and intra-abdominal metastases appeared to have high ER/PR-IHC and ERPAS (85% and 89% ER-IHC > 50%; 64% and 78% PR-IHC > 50%; 60% and 71% ERPAS > 15, not significant). Tumour grade and previous radiotherapy did not affect ER/PR-IHC or ERPAS. CONCLUSIONS: A trend towards lower PR-IHC and ERPAS was observed in lymphogenic sites. Verification in larger cohorts is needed to confirm these findings, which may have implications for the use of hormonal therapy in the future.

18.
Ther Adv Med Oncol ; 16: 17588359241277656, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39346117

RESUMEN

Background: In Part 1 of the phase III RUBY trial (NCT03981796) in patients with primary advanced or recurrent endometrial cancer (EC), dostarlimab plus carboplatin-paclitaxel (CP) significantly improved progression-free survival and overall survival compared with CP alone. Limited safety data have been reported for the combination of immunotherapies plus chemotherapy in this setting. Objectives: The objective of this analysis was to identify the occurrence of treatment-related adverse events (TRAEs) and immune-related adverse events (irAEs) and to describe irAE management in Part 1 of the RUBY trial. Design: RUBY is a phase III, randomized, double-blind, multicenter study of dostarlimab plus CP compared with CP alone in patients with primary advanced or recurrent EC. Methods: Patients were randomized 1:1 to dostarlimab 500 mg, or placebo, plus CP every 3 weeks for 6 cycles, followed by dostarlimab 1000 mg, or placebo, every 6 weeks for up to 3 years. Adverse events (AEs) were assessed according to Common Terminology Criteria for Adverse Events, version 4.03. Results: The safety population included 487 patients who received ⩾1 dose of treatment (241 dostarlimab plus CP; 246 placebo plus CP). Treatment-emergent AEs were experienced by 100% of patients in both arms. TRAEs occurred in 97.9% of the dostarlimab arm and 98.8% of the placebo arm.The most common TRAEs occurred at similar rates between arms and were mostly low grade. IrAEs occurred in 58.5% of patients in the dostarlimab arm and 37.0% of patients in the placebo arm. Dostarlimab- or placebo-related irAEs were reported in 40.7% of patients in the dostarlimab arm and 16.3% of the placebo arm. Conclusion: The safety profile of dostarlimab plus CP was generally consistent with that of the individual components. Dostarlimab plus CP has a favorable benefit-risk profile and is a new standard of care for patients with primary advanced or recurrent EC. Trial registration: NCT03981796.


Safety of dostarlimab plus carboplatin-paclitaxel compared with carboplatin-paclitaxel in primary advanced or recurrent endometrial cancer For many years, patients with primary advanced or recurrent endometrial cancer were treated with chemotherapy, specifically with a combination of carboplatin and paclitaxel. Recently, new treatments called immune checkpoint inhibitors have been used to treat endometrial cancer. Dostarlimab, an immune checkpoint inhibitor, is being tested to treat many types of cancer, including endometrial cancer. In the RUBY trial, a combination of dostarlimab plus chemotherapy was compared with chemotherapy alone as treatment for primary advanced or recurrent endometrial cancer. Results showed that patients treated with dostarlimab plus chemotherapy had a lower risk of their cancer becoming worse and a lower risk of dying. Results in this article describe the safety of dostarlimab plus chemotherapy compared with chemotherapy alone. All patients in the RUBY trial experienced at least one adverse event (an undesired effect that happens while receiving treatment or shortly after stopping treatment); most were determined to be caused by the cancer treatments. No differences in the frequency of the overall cancer treatment-related adverse events were seen in patients who received dostarlimab plus chemotherapy compared with those patients who received chemotherapy alone. Some patients experienced an immune-related adverse event. These are a specific type of undesired effect that can occur when patients are treated with immune checkpoint inhibitors. Immune-related adverse events occurred more frequently in patients who received dostarlimab plus chemotherapy than in those who received chemotherapy alone. Physicians were generally able to treat the immune-related adverse events, and only a low percentage of patients discontinued treatment because they experienced an immune-related adverse event. The types of adverse events seen were similar to a combination of those seen in patients who received dostarlimab alone or patients who received chemotherapy alone as treatment for endometrial cancer. Dostarlimab plus chemotherapy is a new standard of care for patients with primary advanced or recurrent endometrial cancer.

19.
J Cancer Surviv ; 2024 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-38316726

RESUMEN

PURPOSE: To describe recall of fertility-related consultations and cryopreservation and to examine reproductive goals and reproduction post-treatment in long-term survivors of adolescent and young adult (AYA) (age, 18-39 years) cancer. METHODS: This study included n = 1457 male and n = 2112 female long-term survivors (Mage = 43-45 years; 5-22 years from diagnosis) who provided self-report. Clinical data were supplied by the Netherlands Cancer Registry. RESULTS: Most male survivors (72.7%) recalled fertility-related consultations and 22.6% completed sperm cryopreservation. Younger age (OR = 2.8; 95%CI [2.2-3.6]), not having children (OR = 5.0; 95%CI [3.2-7.7]), testicular cancer or lymphoma/leukemia (OR = 2.8/2.5 relative to "others"), and more intense treatments (OR = 1.5; 95%CI [1.1-2.0]) were associated with higher cryopreservation rates. Time since diagnosis had no effect. Of men who cryopreserved, 12.1% utilized assisted reproductive technologies (ART). Most men (88.5%) felt their diagnosis did not affect their reproductive goals, but 7.6% wanted no (additional) children due to cancer. Half of female survivors (55.4%; n = 1171) recalled fertility-related consultations. Rates of cryopreservation were very low (3.6%), but increased after 2013 when oocyte cryopreservation became non-experimental. Of women who cryopreserved, 13.2% successfully utilized ART. Most women (74.8%) experienced no effects of cancer on reproductive goals, but 17.8% wanted no (additional) children due to cancer. CONCLUSIONS: Cryopreservation in men varied by patient/clinical factors and was very low in women, but data of more recently treated females are needed. Utilizing cryopreserved material through ART was rare, which questions its cost-effectiveness, but it may enhance survivors' well-being. IMPLICATIONS FOR CANCER SURVIVORS: The extent to which cryopreservation positively affects survivors' well-being remains to be tested. Moreover, effects of cancer on reproductive goals require further attention, especially in women who refrain from having children due to cancer.

20.
J Patient Rep Outcomes ; 7(1): 93, 2023 09 13.
Artículo en Inglés | MEDLINE | ID: mdl-37702884

RESUMEN

The health-related quality of life (HRQoL) among long-term Adolescent and Young Adult Cancer Survivors (AYACS) and an age- and sex-matched normative population was examined. Although the HRQoL of AYACS was worse compared to the normative population before and during the COVID-19 pandemic, the scores of AYACS improved over time in contrast to the normative population. Presumably, AYACS are used to adjusting their lives to stressful life events. Furthermore, the lockdown may have been beneficial for AYACS who face difficulties fully participating in society due to the impact of cancer. AYACS who encounter HRQoL issues could benefit from support interventions to empower them and build resilience.


Asunto(s)
COVID-19 , Supervivientes de Cáncer , Neoplasias , Humanos , Adolescente , Adulto Joven , COVID-19/epidemiología , Interacción Social , Pandemias , Calidad de Vida , Control de Enfermedades Transmisibles , Fatiga/epidemiología , Neoplasias/epidemiología
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