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1.
Front Oncol ; 14: 1378973, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38694788

RESUMO

Introduction: Alongside the improved survival of nasopharyngeal cancer (NPC), late radiation toxicities are alarmingly hampering survivors' quality of life. A patient-reported symptom burden survey is lacking to address the unmet need for symptom management among local NPC survivors. Methods: A single-center cross-sectional survey was conducted on 211 NPC survivors who had completed radiation therapy for three to 120 months. We employed the Chinese version M. D. Anderson Symptom Inventory - Head & Neck Module (MDASI-HN-C), Functional Assessment of Cancer Therapy - Head & Neck (FACT-HN-C), and a question extracted from the Cancer Survivors' Unmet Needs Measure (CaSUN). Results: Two hundred valid responses were collected. Participants suffered from at least four moderate to severe symptoms (mean = 4.84, SD = 4.99). The top five severe symptoms were dry mouth, mucus problems, difficulty swallowing or chewing, teeth or gum problems, and memory problems. MDASI-HN-C subscales were negatively correlated with the physical, emotional, functional, and HN-specific domains of the FACT-HN-C. The unmet need for symptom management was positively associated with symptom burden, either general symptoms (Adjusted odds ratio [ORadj] = 1.566, 95% CI = 1.282 - 1.914, p < 0.001) or top-5 symptoms (ORadj = 1.379, 95% CI = 1.185 - 1.604, p < 0.001), while negatively associated with post-RT time (ORadj = 0.981, 95% CI [0.972, 0.991], p < 0.001). Conclusion: Virtually all NPC survivors suffer from late toxicities, which interplay with survivors' perceptions intricately to affect their unmet needs for symptom management. Personalized supportive care strategies with regular assessments and stratifications are warranted.

2.
Front Oncol ; 14: 1345322, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38357197

RESUMO

Background: Androgen deprivation therapy (ADT) is the foundational treatment for metastatic prostate cancer (PCa). Androgen receptor (AR) axis-targeted therapies are a new standard of care for advanced PCa. Although these agents have significantly improved patient survival, the suppression of testosterone is associated with an increased risk of cardiometabolic syndrome. This highlights the urgency of multidisciplinary efforts to address the cardiometabolic risk of anticancer treatment in men with PCa. Methods: Two professional organizations invited five urologists, five clinical oncologists, and two cardiologists to form a consensus panel. They reviewed the relevant literature obtained by searching PubMed for the publication period from April 2013 to April 2023, to address three discussion areas: (i) baseline assessment and screening for risk factors in PCa patients before the initiation of ADT and AR axis-targeted therapies; (ii) follow-up and management of cardiometabolic complications; and (iii) selection of ADT agents among high-risk patients. The panel convened four meetings to discuss and draft consensus statements using a modified Delphi method. Each drafted statement was anonymously voted on by every panelist. Results: The panel reached a consensus on 18 statements based on recent evidence and expert insights. Conclusion: These consensus statements serve as a practical recommendation for clinicians in Hong Kong, and possibly the Asia-Pacific region, in the management of cardiometabolic toxicities of ADT or AR axis-targeted therapies in men with PCa.

3.
J Natl Cancer Inst ; 115(4): 355-364, 2023 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-36723440

RESUMO

A meeting of experts was held in November 2021 to review and discuss available data on performance of Epstein-Barr virus (EBV)-based approaches to screen for early stage nasopharyngeal carcinoma (NPC) and methods for the investigation and management of screen-positive individuals. Serum EBV antibody and plasma EBV DNA testing methods were considered. Both approaches were found to have favorable performance characteristics and to be cost-effective in high-risk populations. In addition to endoscopy, use of magnetic resonance imaging (MRI) to investigate screen-positive individuals was found to increase the sensitivity of NPC detection with minimal impact on cost-effectiveness of the screening program.


Assuntos
Carcinoma , Infecções por Vírus Epstein-Barr , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico , Herpesvirus Humano 4/genética , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , Detecção Precoce de Câncer/métodos , DNA Viral/genética
4.
J Oncol Pharm Pract ; 29(6): 1343-1360, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35971313

RESUMO

OBJECTIVE: To evaluate and validate the recent and emerging data for prognostic and predictive biomarkers with therapeutic targets in breast cancer. DATA SOURCES: A literature search from January 2015 to March 2022 was performed using the key terms breast cancer, clinical practice guidelines, gene mutations, genomic assay, immune cancer therapy, predictive and/or prognostic biomarkers, and targeted therapies. STUDY SELECTION AND DATA EXTRACTION: Relevant clinical trials, meta-analyses, seminal articles, and published evidence- and consensus-based clinical practice guidelines in the English language were identified, reviewed and evaluated. DATA SYNTHESIS: Breast cancer is a biologically heterogeneous disease, leading to wide variability in treatment responses and survival outcomes. Biomarkers for breast cancer are evolving from traditional biomarkers in immunohistochemistry (IHC) such as estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor type 2 (HER2) to genetic biomarkers with therapeutic implications (e.g. breast cancer susceptibility gene 1/2 [BRCA1/2], estrogen receptor α [ESR1] gene mutation, HER2 gene mutation, microsatellite instability [MSI], phosphatidylinositol 3-kinase catalytic subunit 3Cα [PIK3CA] gene mutation, neurotrophic tyrosine receptor kinase [NTRK] gene mutation). In addition, current data are most robust for biomarkers in immunotherapy (e.g. programmed cell death receptor ligand-1 [PD-L1], microsatellite instability-high [MSI-H] or deficient mismatch repair [dMMR]). Oncotype DX assay remains the best validated gene expression assay that is both predictive and prognostic whereas MammaPrint is prognostic for genomic risk. CONCLUSIONS: Biomarker-driven therapies have the potential to confer greater therapeutic advantages than standard-of-care therapies. The purported survival benefits associated with biomarker-driven therapies should be weighed against their potential harms.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Prognóstico , Neoplasias da Mama/genética , Proteína BRCA1/genética , Instabilidade de Microssatélites , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Proteína BRCA2/genética
6.
Eur J Ophthalmol ; 33(1): 171-181, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35675196

RESUMO

PURPOSE: Clinical phenotypes in Immunoglobulin G4-related disease (IgG4-RD) according to the patterns of affecting organs have different risks of malignancies. We attempt to determine the association of malignancies with IgG4-related ophthalmic disease (IgG4-ROD). DESIGN: Retrospective cohort study. METHODS: Review of medical records, orbital images and histopathology reports in a territory-wide cohort of biopsy proven IgG4-ROD patients from 2005-2019. FINDINGS: Among 122 patients who had biopsies taken from adnexal lesions including lacrimal glands (n = 108), orbital mass (n = 30), infiltrated orbital fat (n = 10), conjunctiva (n = 2) or extraocular muscles (n = 3), 13% (16/122) developed malignancies over 73 ± 48months' follow-up. There were 9 cases of ocular adnexal lymphoma (OAL) and 7 extra-orbital malignancies. Compared with the general population, the incidence of OAL was significantly higher (standardized incidence ratios, SIRs = 10.0, 95%CI = 4.5-17.6) while that of extra-orbital malignancies was similar. The SIRs was highest within the first year (SIR = 46.7, 95%CI = 18.5-87.6) when 7 OAL were concomitantly diagnosed. Patients who developed OAL or extra-orbital malignancies were older than other patients at IgG4-ROD diagnosis (64.9 ± 7.1, 68.3 ± 8.5 versus 55.2 ± 15.0 years, P < 0.05). Asymmetric lacrimal gland enlargement (78% versus 13%), lack of frontal (0% versus 12%) or infraorbital nerve enlargement (0% versus 36%) were associated with OAL (all P < 0.05). Pre-treatment serum IgG4 level or extra-orbital IgG4-RD involvement was similar among patients with or without malignancies. CONCLUSION: In this biopsy-proven IgG4-ROD cohort, 7% developed OAL which was 10 times higher than the general population. Patients with asymmetric lacrimal gland enlargement or without trigeminal nerves involvement radiologically were associated with OAL.


Assuntos
Doença Relacionada a Imunoglobulina G4 , Doenças Orbitárias , Neoplasias Orbitárias , Humanos , Doença Relacionada a Imunoglobulina G4/diagnóstico , Doença Relacionada a Imunoglobulina G4/epidemiologia , Estudos Retrospectivos , Doenças Orbitárias/diagnóstico , Doenças Orbitárias/epidemiologia , Imunoglobulina G
7.
Biomed Phys Eng Express ; 8(6)2022 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-36130477

RESUMO

Objective.To study the effects of magnetic field gradients on the dose deposition in an inhomogeneous medium and to present the benefits offered by magnetic-field-modulated radiotherapy (MagMRT) under multiple radiation beams.Approach.Monte Carlo simulations were performed using the Geant4 simulation toolkit with a 7 MV photon beam from an Elekta Unity system. A water cuboid embedded with material slabs of water, bone, lung or air was used to study the effects of MagMRT within inhomogeneous medium. Two cylindrical water phantoms, with and without a toroidal lung insert embedded, were used to study the effects of MagMRT under single, opposing or four cardinal radiation beams. Optimized magnetic field variations in the form of a wavelet were used to induce dose modulation within the material slabs or at the iso-center of the phantoms.Main results.The magnitudes of the dose enhancement and reduction induced by the magnetic field gradients become more prominent in a medium of lower density. A maximum dose increase of 6.5% and a decrease of 4.8% were found inside bone, while an increase of 20.4% and a decrease of 13.9% were found in lung tissue. Under multiple radiation beams, the dose enhancement can be induced at the iso-center while the dose reduction occurs in regions around the tumor. For the case with four cardinal beams irradiating a homogeneous water cylinder, an 8.4% of dose enhancement and a 2.4% of dose reduction were found. When a toroidal lung insert was embedded, a maximum dose enhancement of 9.5% and a reduction of 17.0% were produced for anterior-posterior opposing fields.Significance.With an optimized magnetic field gradient, MagMRT can induce a dose boost to the target while producing a better sparing to the surrounding normal tissue, resulting in a sharper dose fall-off in all directions outside the target volume.


Assuntos
Pulmão , Campos Magnéticos , Pulmão/efeitos da radiação , Método de Monte Carlo , Imagens de Fantasmas , Água
8.
Cancer Treat Rev ; 105: 102361, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35231870

RESUMO

Locally advanced and recurrent/ metastatic (R/M) head and neck cancers have poor prognosis generally. Radiotherapy (RT) is known to have multiple immunomodulatory effects, and various immune checkpoint inhibitors (ICIs) have been shown to be efficacious in the R/M setting in recent years. Hence, it is logical to combine RT and ICIs to improve the outlook for such patients, especially in view of the promising pre-clinical data on this novel combination. In this review, we highlighted the key mechanisms underlying the immunostimulatory and immunoinhibitory effects of RT, with a view to suggesting strategies to overcome radioresistance. We also discussed how the unique immune landscapes of virus-induced cancers, namely Epstein-Barr virus-induced nasopharyngeal carcinoma and human papillomavirus-mediated oropharyngeal cancer, could be exploited with ICIs. The landmark clinical trials in both the locally advanced and R/M settings were reviewed, and these trials showed that the combination of RT and ICIs is generally well tolerated. The potential reasons behind the largely negative results of these studies were also explored, focusing on various parameters including dose fractionation, sequencing, irradiated volume and the use of predictive biomarkers.


Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias de Cabeça e Pescoço , Neoplasias Nasofaríngeas , Infecções por Vírus Epstein-Barr/complicações , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Herpesvirus Humano 4 , Humanos , Imunoterapia/métodos , Recidiva Local de Neoplasia/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço
9.
Cancers (Basel) ; 14(2)2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35053569

RESUMO

Progression to metastatic disease occurs in about half of all men who develop prostate cancer (PC), one of the most common cancers in men worldwide. Androgen deprivation therapy has been the mainstay therapy for patients with metastatic PC (mPC) since the 1940s. In the last decade, there has been unprecedented advancement in systemic therapies, e.g., taxane, androgen-signalling pathway inhibitors, and biomarker-driven targeted therapies for various stages of disease, resulting in overall survival improvement. Adding to ongoing controversies over how best to treat these patients is the recognition that ethnicity may influence prognosis and outcomes. This review discusses recent evidence for the impacts of Asian ethnicity specifically, which includes environmental, sociocultural, and genetic factors, on the approach to pharmacological management of mPC. Clear inter-ethnic differences in drug tolerability, serious adverse events (AEs), and genetic heterogeneity must all be considered when dosing and scheduling for treatment, as well as designing future precision studies in PC.

10.
Phys Med Biol ; 66(20)2021 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-34587609

RESUMO

Objective.The feasibility of magnetic-field-modulated radiotherapy (MagMRT) with an MR-LINAC was investigated by studying the effects of dose enhancement and reduction using a transverse magnetic field with a longitudinal gradient applied along a photon radiation beam.Approach.Geant4 simulation toolkit was used to perform Monte Carlo simulations on a water phantom with the energy spectrum of a 7 MV flattening-filter-free photon beam from an Elekta Unity system as the source of radiation. Linear magnetic field gradients with magnitudes ranged from 1 to 6 T cm-1and spatial extents of 1-3 cm were used to study the dependence of dose modulation on these two parameters. The effects of radiation field size and the ability of dose modulation through optimizing the waveform of magnetic field variation were also explored.Main results.Our results show that dose enhancement and reduction can be achieved by applying a transverse magnetic field with a longitudinal field gradient along a photon beam. The steeper the gradient, the more prominent is the effect. A dose enhancement of 33% and a dose reduction of 22% are found for a magnetic gradient of 6 T cm-1and -6 T cm-1respectively. The spatial extent of the dose modulation effect which is greater than 3% is found to be around 1-2 cm. Both the dose enhancement and reduction effects are independent of the radiation field sizes, but they exhibit different behaviors with the spatial extents of the gradient. Multiple locations of dose enhancement and reduction can be produced by modulating the waveform of the magnetic field variation along the radiation beam, demonstrating a vast degree of freedom in the modulation aspect of MagMRT.Significance.MagMRT is a conceptually feasible and promising new radiotherapy modulation technique along the direction of the radiation beam.


Assuntos
Aceleradores de Partículas , Radioterapia (Especialidade) , Campos Magnéticos , Método de Monte Carlo , Imagens de Fantasmas , Dosagem Radioterapêutica
11.
Nat Rev Clin Oncol ; 18(11): 679-695, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34194007

RESUMO

The past three decades have borne witness to many advances in the understanding of the molecular biology and treatment of nasopharyngeal carcinoma (NPC), an Epstein-Barr virus (EBV)-associated cancer endemic to southern China, southeast Asia and north Africa. In this Review, we provide a comprehensive, interdisciplinary overview of key research findings regarding NPC pathogenesis, treatment, screening and biomarker development. We describe how technological advances have led to the advent of proton therapy and other contemporary radiotherapy approaches, and emphasize the relentless efforts to identify the optimal sequencing of chemotherapy with radiotherapy through decades of clinical trials. Basic research into the pathogenic role of EBV and the genomic, epigenomic and immune landscape of NPC has laid the foundations of translational research. The latter, in turn, has led to the development of new biomarkers and therapeutic targets and of improved approaches for individualizing immunotherapy and targeted therapies for patients with NPC. We provide historical context to illustrate the effect of these advances on treatment outcomes at present. We describe current preclinical and clinical challenges and controversies in the hope of providing insights for future investigation.


Assuntos
Carcinoma Nasofaríngeo , Humanos
12.
Clin Cancer Res ; 27(10): 2827-2836, 2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-33692028

RESUMO

PURPOSE: To study the dynamic changes in plasma Epstein-Barr virus (pEBV) DNA after radiotherapy in nasopharyngeal cancer (NPC). EXPERIMENTAL DESIGN: We conducted a randomized controlled trial of adjuvant chemotherapy versus observation in patients with NPC who had detectable pEBV DNA at 6 weeks post-radiotherapy. Randomized patients had a second pEBV DNA checked at 6 months post-randomization. The primary endpoint was progression-free survival (PFS). RESULTS: We prospectively enrolled 789 patients. Baseline post-radiotherapy pEBV DNA was undetectable in 573 (72.6%) patients, and detectable in 216 (27.4%) patients, of whom 104 (13.2%) patients were eligible for randomization to adjuvant chemotherapy (n = 52) versus observation (n = 52). The first post-radiotherapy pEBV DNA had a sensitivity of 0.48, specificity of 0.81, area under receiver-operator characteristics curve (AUC) of 0.65, false positive (FP) rate of 13.8%, and false negative (FN) rate of 14.4% for disease progression. The second post-radiotherapy pEBV DNA had improved sensitivity of 0.81, specificity of 0.75, AUC of 0.78, FP rate of 14.3%, and FN rate of 8.1%. Patients with complete clearance of post-radiotherapy pEBV DNA (51%) had survival superior to that of patients without post-radiotherapy pEBV DNA clearance (5-year PFS, 85.5% vs. 23.3%; HR, 9.6; P < 0.0001), comparable with patients with initially undetectable post-radiotherapy pEBV DNA (5-year PFS, 77.1%), irrespective of adjuvant chemotherapy or observation. CONCLUSIONS: Patients with NPC with detectable post-radiotherapy pEBV DNA who experienced subsequent pEBV DNA clearance had superior survival comparable with patients with initially undetectable post-radiotherapy pEBV DNA. Post-radiotherapy pEBV DNA clearance may serve as an early surrogate endpoint for long-term survival in NPC.


Assuntos
DNA Viral , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4/genética , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/etiologia , Carga Viral , Biomarcadores Tumorais , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/métodos , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , DNA Viral/sangue , Gerenciamento Clínico , Progressão da Doença , Suscetibilidade a Doenças , Humanos , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/terapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prognóstico , Análise de Sobrevida , Carga Viral/métodos
13.
Curr Oncol ; 29(1): 27-37, 2021 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-35049677

RESUMO

BACKGROUND: Stereotactic body radiotherapy (SBRT) has potential radiobiologic and economic advantages over conventional fractionated radiotherapy (CFRT) in localized prostate cancer (PC). This study aimed to compare the effects of these two distinct fractionations on patient-reported quality of life (PRQOL) and tolerability. METHODS: In this prospective phase II study, patients with low- and intermediate-risk localized PC were randomly assigned in a 1:1 ratio to the SBRT (36.25 Gy/5 fractions/2 weeks) or CFRT (76 Gy/38 fractions/7.5 weeks) treatment groups. The primary endpoint of variation in PRQOL at 1 year was assessed by changes in the Expanded Prostate Cancer Index Composite (EPIC) questionnaire scores and analysed by z-tests and t-tests. RESULTS: Sixty-four eligible Chinese men were treated (SBRT, n = 31; CFRT, n = 33) with a median follow-up of 2.3 years. At 1 year, 40.0%/46.9% of SBRT/CFRT patients had a >5-point decrease in bowel score (p = 0.08/0.28), respectively, and 53.3%/46.9% had a >2-point decrease in urinary score (p = 0.21/0.07). There were no significant differences in EPIC score changes between the arms at 3, 6, 9 and 12 months, but SBRT was associated with significantly fewer grade ≥ 1 acute and 1-year late gastrointestinal toxicities (acute: 35% vs. 87%, p < 0.0001; 1-year late: 64% vs. 84%, p = 0.03), and grade ≥ 2 acute genitourinary toxicities (3% vs. 24%, p = 0.04) compared with CFRT. CONCLUSION: SBRT offered similar PRQOL and less toxicity compared with CFRT in Chinese men with localized PC.


Assuntos
Neoplasias da Próstata , Radiocirurgia , China , Fracionamento da Dose de Radiação , Humanos , Masculino , Estudos Prospectivos , Neoplasias da Próstata/radioterapia , Qualidade de Vida
14.
Radiother Oncol ; 150: 97-103, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32544605

RESUMO

BACKGROUND AND PURPOSE: Nasopharyngeal carcinoma (NPC) is one of the most common cancers in southern China and the first-line treatment is radiotherapy. Intensity-modulated radiation therapy (IMRT) can deliver high dose to cancer and low dose to normal tissue, but xerostomia is still one of the complications after IMRT. However, how the concentration of saliva electrolytes be affected by IMRT and the effects on the quality of life are still unknown. In this prospective study, 76 NPC patients were recruited from hospitals in Hong Kong to identify the change of saliva electrolytes and xerostomia-related quality of life before and after IMRT. METHODS AND MATERIALS: Saliva and questionnaire were collected before IMRT, 1 month, 3 months, 6 months and 12 months after IMRT. The concentration of saliva electrolytes was detected using inductively coupled plasma-optical emission spectroscopy (ICP-OES). RESULTS: Saliva flow rate significantly decreased after IMRT. Decrease in the mean value of pH was observed but the difference is not statistically significant. The concentrations of potassium, iodine, and calcium decreased and chloride concentration increased after IMRT, while the concentrations of sodium, magnesium, copper or zinc were kept at the same level before and after treatment. Xerostomia-related quality of life was adversely affected by IMRT, but partially recovered after 1 year. CONCLUSIONS: Our study revealed the change of saliva electrolytes and xerostomia-related quality of life in patients undergone IMRT for NPC.


Assuntos
Neoplasias Nasofaríngeas , Radioterapia de Intensidade Modulada , Xerostomia , China , Eletrólitos , Humanos , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Estudos Prospectivos , Qualidade de Vida , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/efeitos adversos , Saliva , Xerostomia/etiologia
15.
Clin Genitourin Cancer ; 16(5): 402-412.e1, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30126765

RESUMO

BACKGROUND: The present study retrospectively evaluated the efficacy and safety of enzalutamide in different lines of metastatic castration-resistant prostate cancer (mCRPC) treatment in a real-world setting. PATIENTS AND METHODS: The clinical records of patients with mCRPC treated with enzalutamide between August 2015 and October 2017 were retrieved from all 7 public oncology centers in Hong Kong and reviewed. The primary endpoint was progression-free survival (PFS) in first (1L), second (2L), and third or fourth lines (3L or 4L) of CRPC treatment. Secondary endpoints included overall survival (OS), prostate-specific antigen (PSA) response, and tolerance. RESULTS: Among a total of 117 patients (median age of 73 years [range, 52-90 years]), 34 (29.1%), 57 (48.7%), and 26 (19.3%) patients had enzalutamide as their 1L (chemo-naive), 2L (post-docetaxel or -abiraterone), and 3L or above treatment options. The overall PSA response rates were 43.6%, and were 73.5%, 35.1%, and 19.2% for 1L, 2L, and 3L or 4L treatment, respectively. PFS and OS were significantly associated with the line of treatment in the univariate survival analysis (1L/2L/3L and 4L; PFS, 7.1/3.9/2.2 months; OS, not reached/15.8/7.4 months; both P = .0002) but not in the multivariate analysis. The observed incidence of any fatigue (grade 1 or 2, 54.7%; grade 3 or 4, 9.4%) was much higher than reported in the AFFIRM (A Study Evaluating the Efficacy and Safety of the Investigational Drug MDV3100 [ClinicalTrials.gov Identifier: NCT00974311]) (any grade, 34%) and PREVAIL (A Multinational Phase 3, Randomized, Double-blind, Placebo-controlled Efficacy And Safety Study Of Oral Mdv3100 In Chemotherapy-naïve Patients With Progressive Metastatic Prostate Cancer Who Have Failed Androgen Deprivation Therapy [ClinicalTrials.gov Identifier: NCT00974311]) (any grade, 36%) trials; as well, grade ≥ 2 fatigue was significantly associated with 3L or 4L treatment (P = .01 in both univariate and multivariate analyses). CONCLUSION: In the real-life setting, there was a higher incidence of enzalutamide-related fatigue than reported in the trials. Earlier lines of enzalutamide treatment were associated with longer PFS and OS, more frequent PSA response, and less fatigue.


Assuntos
Fadiga/induzido quimicamente , Fadiga/epidemiologia , Feniltioidantoína/análogos & derivados , Antígeno Prostático Específico/metabolismo , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Benzamidas , Método Duplo-Cego , Hong Kong/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Nitrilas , Feniltioidantoína/administração & dosagem , Feniltioidantoína/efeitos adversos , Intervalo Livre de Progressão , Neoplasias de Próstata Resistentes à Castração/metabolismo , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
16.
Oncologist ; 23(12): 1436-1445, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29802221

RESUMO

BACKGROUND: Folate level was proposed to be a predictor for fluoropyrimidine-related toxicity. We conducted a prospective study to determine the association between serum and red-cell folate and capecitabine-related toxicity in patients with colorectal cancers. MATERIALS AND METHODS: Eligibility criteria included diagnosis of colorectal cancers; eligible patients who were scheduled to undergo capecitabine monotherapy or capecitabine-oxaliplatin (CAPOX) for adjuvant or palliative purposes. Exclusion criteria included concomitant radiotherapy or chemotherapy other than capecitabine or CAPOX and creatinine clearance <30 mL/min. Fasting serum and red-cell folate were measured prior to chemotherapy. Capecitabine was administered at 2,500 mg/m2 per day (monotherapy) or 2,000 mg/m2 per day (CAPOX) for 14 days every 3 weeks. The toxicity of the first four cycles was documented by clinical investigators who were blinded to folate levels. RESULTS: A total of 144 patients were recruited, of whom 126 were eligible; 40 patients had capecitabine alone, and 86 patients received CAPOX. The rates of grade 2 and grade 3 toxicity were 63.5% and 14.3%, respectively. Nausea and vomiting were the most common grade ≥2 adverse event (47.7%), followed by hand-foot syndrome (25.4%), diarrhea (23.1%), and neutropenia (22.3%). Combination with oxaliplatin (odds ratio [OR], 2.77; p = .043) and serum folate (OR, 10.33; p = .002) were independent predictors of grade ≥2 toxicity. Red-cell folate was not predictive of toxicity. For every 10 nmol/L increment in serum folate, the risk of grade ≥2 toxicity increased by 9%. CONCLUSION: Serum folate level, but not red-cell folate, was associated with higher rate of grade ≥2 toxicity during capecitabine-based treatment. Excessive folate intake may be avoided before and during capecitabine-based chemotherapy. IMPLICATIONS FOR PRACTICE: This is the first prospective study to evaluate the association between serum folate level and capecitabine-related toxicity in patients with colon cancers. It shows that higher serum folate level is associated with increased risks of moderate to severe toxicity during capecitabine-based treatment. Excessive folate intake should be avoided before and during capecitabine-based chemotherapy.


Assuntos
Capecitabina/efeitos adversos , Capecitabina/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Ácido Fólico/uso terapêutico , Idoso , Capecitabina/farmacologia , Neoplasias Colorretais/patologia , Feminino , Ácido Fólico/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
18.
Hong Kong Med J ; 17(6): 460-4, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22147315

RESUMO

OBJECTIVE: Paediatric Allergic Disease Quality of Life Questionnaire is a health-related assessment tool designed for children with allergic diseases. This study aimed to translate the original English version of the Questionnaire to Chinese and to provide psychometric evidence on the validity and reliability of the translated version. DESIGN: Cross-sectional study. SETTING: Out-patient clinic of a non-teaching hospital in Hong Kong. PARTICIPANTS: The Paediatric Allergic Disease Quality of Life Questionnaire was translated to Chinese and then completed by a group of 115 Hong Kong Chinese children (66 male and 49 female; mean age, 11 years) with allergic disease(s). All subjects were asked to respond using visual analogue scales dealing with issues related to the perceived morbidity of allergic diseases. To assess test-retest reliability, 2 weeks later a subgroup of 16 individuals was retested with the same Questionnaire. RESULTS: The internal consistency of the Chinese Paediatric Allergic Disease Quality of Life Questionnaire was satisfactory (Cronbach alpha=0.92). The correlation between the total Questionnaire score and the visual analogue scale score was moderately significant (Spearman's rho=0.49; 95% confidence interval, 0.34-0.62). Structural validity as studied by confirmatory factor analysis found that the structure of subscales was remarkably similar to the original English version. The intra-class correlation between the Questionnaire score from the first and the second test in the subgroup of 16 subjects was 0.75, indicating adequate repeatability. CONCLUSION: The validity and reliability of the Chinese version of the Paediatric Allergic Disease Quality of Life Questionnaire was established for clinical use.


Assuntos
Hipersensibilidade/psicologia , Qualidade de Vida/psicologia , Inquéritos e Questionários , Adolescente , Criança , Estudos Transversais , Feminino , Hong Kong , Humanos , Idioma , Masculino , Psicometria , Reprodutibilidade dos Testes
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