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PURPOSE: Resistance to HER2 (ErbB2)-targeted therapy may be mediated by other members of the ErbB family. We investigated the efficacy and safety of the irreversible ErbB family blocker, afatinib, alone as first-line therapy in the advanced setting and in combination with vinorelbine or paclitaxel for those who progressed on afatinib monotherapy, in female patients with metastatic breast cancer who had failed or progressed on prior HER2-targeted therapy in the early disease setting. METHODS: In this phase II, single-arm, two-part study (ClinicalTrials.gov: NCT01271725), patients in part A received afatinib 40 mg/day in 21-day cycles until disease progression or intolerable adverse events (AEs). Patients with progressive disease could then receive afatinib plus weekly vinorelbine 25 mg/m2 or paclitaxel 80 mg/m2 until disease progression or intolerable AEs (part B). The primary endpoint was confirmed objective response rate (RECIST v1.1). RESULTS: Eighty-seven patients were enrolled and 74 were treated in part A (median age: 51 years [range 27-76]; 31 [42%] estrogen receptor-positive, 26 [35%] progesterone receptor-positive). Of these, 39 (53%) patients went on to receive afatinib plus vinorelbine (13 patients) or paclitaxel (26 patients) in part B. Thirteen (18%) and 12 (31%) patients achieved an objective response in parts A and B, respectively. The most common treatment-related AEs with afatinib monotherapy (any/grade ≥ 3) were diarrhea (68%/8%) and rash (49%/4%). Combination therapy was generally well tolerated, with no additive toxicity observed. CONCLUSION: Afatinib treatment, alone or in combination with vinorelbine or paclitaxel, was associated with objective responses in ≥ 18% of patients with metastatic breast cancer for whom prior HER2-targeted therapy has failed. Treatment-related AEs were generally manageable, with few grade ≥ 3 AEs reported. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01271725, registered 1 July 2011.
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Neoplasias da Mama , Adulto , Afatinib/efeitos adversos , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Feminino , Humanos , Lapatinib/uso terapêutico , Pessoa de Meia-Idade , Paclitaxel , Quinazolinas , Receptor ErbB-2/genética , Trastuzumab , Resultado do Tratamento , Vinorelbina/uso terapêuticoRESUMO
Breast cancer is increasingly prevalent in older adults and is a substantial part of routine oncology practice. However, management of breast cancer in this population is challenging because the disease is highly heterogeneous and there is insufficient evidence specific to older adults. Decision making should not be driven by age alone but should involve geriatric assessments plus careful consideration of life expectancy, competing risks of mortality, and patient preferences. A multidisciplinary taskforce, including members of the European Society of Breast Cancer Specialists and International Society of Geriatric Oncology, gathered to expand and update the previous 2012 evidence-based recommendations for the management of breast cancer in older individuals with the endorsement of the European Cancer Organisation. These guidelines were expanded to include chemotherapy toxicity prediction calculators, cultural and social considerations, surveillance imaging, genetic screening, gene expression profiles, neoadjuvant systemic treatment options, bone-modifying drugs, targeted therapies, and supportive care. Recommendations on geriatric assessment, ductal carcinoma in situ, screening, primary endocrine therapy, surgery, radiotherapy, adjuvant systemic therapy, and secondary breast cancer were updated.
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Neoplasias da Mama/terapia , Oncologia/normas , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/mortalidade , Tomada de Decisão Clínica , Consenso , Técnicas de Apoio para a Decisão , Feminino , Avaliação Geriátrica , Humanos , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Fatores de RiscoRESUMO
BACKGROUND: Despite the wide use of the Short-Form Supportive Care Needs Survey Questionnaire (SCNS-SF34), the measurement invariance of the SCNS-SF34 across the main groups-gender and age-which might be of interest in the application of the instrument has never been confirmed. To provide an accurate assessment tool to evaluate the unmet needs of Chinese cancer patients, the present study aimed to assess the measurement invariance of the SCNS-SF34 across gender and age groups and to assess the validity and reliability of the Chinese version of the SCNS-SF34. METHODS: The SCNS-SF34 was administrated to 1106 Chinese cancer patients. Other instruments included the Memorial Symptom Assessment Scale-Short Form (MSAS-SF), the Short-Form-12 Health Survey version 2 (SF-12 v2) and the Hospital Anxiety and Depression Scale (HADS). Factor structure, internal construct validity, convergent validity, known-group validity and internal consistency were assessed. RESULTS: Our data fit the original five-factor model. Multi-group confirmatory factor analysis indicated measurement invariance across age and gender groups. The domains of the SCNS-SF34 had moderate correlations with the corresponding domains of the MSAS-SF, the SF-12 v2 and the HADS, which supported convergent validity. Of the 34 items, 33 had an item-total correlation that was corrected for an overlap of > 0.4 to support the internal construct validity. The SCNS-SF34 aptly differentiated patients by age and gender. The Cronbach's alpha coefficient ranged from 0.64 to 0.87. CONCLUSIONS: We confirm the measurement invariance of the Chinese version of the SCNS-SF34 across gender and age group. It is a valid and reliable tool for evaluating the needs of Chinese patients with cancer.
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Avaliação das Necessidades/normas , Neoplasias/psicologia , Qualidade de Vida , Inquéritos e Questionários/normas , Adulto , Idoso , Análise Fatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria/instrumentação , Reprodutibilidade dos TestesRESUMO
BACKGROUND: The present study (1) examined patient satisfaction with care over the first year following the diagnosis of advanced breast cancer and (2) tested if unmet health system and information needs, physical symptom distress, and psychological distress predicted patient satisfaction. METHODS: Prospective study of 213 Chinese women with advanced breast cancer assessed while awaiting or receiving initial chemotherapy (baseline), then again at 1.5-, 3-, 6-, and 12-months post-baseline. Health system and information unmet (HSI) needs, psychological distress, physical symptom distress, and patient satisfaction were assessed at baseline; patient satisfaction was reassessed at each follow-up assessment. Latent growth curve analysis assessed changes in patient satisfaction over the 12 months follow-up; hierarchical multiple regression analysis tested if baseline health system information needs, physical symptom distress, anxiety and depression predicted patient satisfaction at one-year post-baseline. RESULTS: The level of patient satisfaction was high and did not change significantly over time. Only HSI needs (ß = - 0.27, p < 0.005) significantly associated with baseline patient satisfaction. Patient satisfaction at one-year post-baseline was predicted by HSI needs (ß = - 0.26, p < 0.005), Anxiety (ß = 0.23, p < 0.05) and Depression (ß = - 0.28, p < 0.005), adjusting for the effect of baseline patient satisfaction (ß = 0.22, p < 0.005). CONCLUSIONS: Unmet health information needs and greater depressive symptoms at initial treatment phased predicted subsequent poorer patient satisfaction. This highlights a need to reinforce the importance of patient-centered care model in managing advanced breast cancer.
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Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/psicologia , Satisfação do Paciente , Estresse Psicológico/psicologia , Ansiedade/etnologia , Ansiedade/psicologia , Povo Asiático/psicologia , Neoplasias da Mama/etnologia , China , Depressão/etnologia , Depressão/psicologia , Feminino , Necessidades e Demandas de Serviços de Saúde , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Análise de Regressão , Estresse Psicológico/etnologia , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: A diagnosis of advanced breast cancer (ABC) challenges a woman's ambitions. This longitudinal study explored (1) if goal adjustment disposition influenced psychological adjustment patterns among women with ABC and (2) if dispositional hope and optimism moderate effects of goal adjustment on psychological adjustment. METHODS: One hundred ninety three out of 225 women with ABC were assessed while they were awaiting/receiving initial chemotherapy, then again at 6 weeks, 3 months, 6 months, and 12 months post-baseline. Goal disengagement, goal reengagement, optimism, hope, and psychological adjustment (anxiety, depression, and positive affect) were assessed at baseline; psychological adjustment was reassessed at each follow-up. Latent growth curve modeling was used to examine the change of psychological adjustment and test the study objectives. RESULTS: High goal disengagement, low reengagement, and high optimism were associated with lower initial anxiety, while high goal disengagement and optimism predicted a slower rate of change in anxiety. High goal disengagement, reengagement, and optimism were associated with lower initial depression. High goal reengagement, optimism, and hope were associated with initial positive affect scores, while optimism predicted its rate of change. Optimism moderated the effect of goal disengagement on anxiety and depression, whereas hope moderated the effect of goal reengagement on positive affect. CONCLUSION: Goal disengagement and reengagement are two relatively independent processes influencing psychological well-being. These findings will help clinicians to tailor specific interventions to help women coping with the diagnosis of ABC.
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Adaptação Psicológica , Neoplasias da Mama/patologia , Neoplasias da Mama/psicologia , Objetivos , Afeto , Idoso , Ansiedade/psicologia , Depressão/psicologia , Feminino , Seguimentos , Esperança , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Otimismo/psicologia , PersonalidadeRESUMO
PURPOSE: The purpose of the study is to document in Hong Kong Chinese cancer survivors cross-sectional associations between illness perceptions, physical symptom distress and dispositional optimism. METHODS: A consecutive sample of 1036 (response rate, 86.1%, mean age 55.18 years, 60% female) survivors of different cancers recruited within 6 months of completion of adjuvant therapy from Hong Kong public hospitals completed the Brief Illness Perception Questionnaire (B-IPQ), Chinese version of the Memorial Symptom Assessment Scale Short-Form (MSAS-SF), and the revised Chinese version of Life Orientation Test (C-LOT-R), respectively. Stepwise multiple regression analyses examined adjusted associations. RESULTS: IPQ seriousness, symptom identity, illness concern, and emotional impact scores varied by cancer type (p < 0.01). Stress-related, lifestyle, environment, psychological/personality, and health-related factors were most frequently attributed causes of cancer. After adjustment for sample differences, physical symptom distress was significantly associated with all illness perception dimensions (p < 0.01), excepting control beliefs. Optimism was positively correlated with perceived personal and treatment control (p < 0.01) and illness understanding (p < 0.01), but negatively correlated with other IPQ dimensions (all p < 0.01). IPQ domain differences by cancer type were eliminated by adjustment for sample characteristics. CONCLUSION: Illness perceptions did not differ by cancer type. Greater physical symptom distress and lower levels of optimism were associated with more negative illness perceptions. IMPLICATIONS: Understanding how cancer survivors make sense of cancer can clarify an important aspect of adaptation. This in turn can inform interventions to facilitate adjustment. Knowledge contributions include evidence of physical symptom distress correlating with most dimensions of illness perception. Optimism was also associated with cancer survivors' illness perceptions.
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Neoplasias/mortalidade , Sobreviventes/psicologia , Adaptação Psicológica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/psicologia , Percepção , Inquéritos e Questionários , Adulto JovemRESUMO
PURPOSE: This longitudinal study examined if the evolution of supportive care needs differed over the first year following the diagnosis of advanced breast cancer and examined factors differentiating these trajectories. METHODS: Two hundred twenty-eight of 276 Chinese women with advanced breast cancer were assessed while they were awaiting or receiving initial chemotherapy, then again at 6 weeks, 3 months, 6 months, and 12 months post-baseline. Supportive care needs (SCNS-34-Ch), psychological distress (Hospital Anxiety and Depression scale), symptom distress (MSAS-Ch), and patient satisfaction (PSEQ-9) were assessed at baseline; supportive care needs were reassessed at each follow-up assessment. Latent growth mixture modeling explored if trajectories differed within each of four need domains: health system, information, and patient support (HSIPS); psychological; physical daily living (PDL); and sexuality needs. Logistic regression identified factors predicting trajectory patterns. RESULTS: Two distinct trajectories were identified for HSIPS and sexuality need domains and three distinct trajectories for psychological and physical daily living need domains. Most women showed stable low levels of HSIPS (78.9 %), psychological (82.4 %), PDL (83.7 %), and sexuality (97.4 %) supportive care needs. One in five and one in eight women showed high initial supportive care needs in HSIPS and psychological and PDL domains, respectively. With the exception of sexuality needs, trajectory patterns were predicted by physical symptom distress. Women in the high-decline group reported greater physical symptom distress. CONCLUSIONS: Most Chinese women with advanced breast cancer showed low stable supportive care needs. Physical symptom distress predicted high supportive care needs. Interventions should focus on optimizing symptom assessment and management.
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Neoplasias da Mama/psicologia , Neoplasias da Mama/terapia , Necessidades e Demandas de Serviços de Saúde , Administração dos Cuidados ao Paciente , Atividades Cotidianas/psicologia , Adulto , China , Feminino , Humanos , Modelos Logísticos , Estudos Longitudinais , Pessoa de Meia-Idade , Satisfação do Paciente/estatística & dados numéricos , Escalas de Graduação Psiquiátrica , Saúde Reprodutiva , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: This study attempted to use a validated and standardised psychometric tool to identify the specific needs of parents of children with visual impairment studying in mainstream schools in Hong Kong. The second aim was to compare their needs with those of parents of mainstream school children without special education needs and parents having children with learning and behavioural problems. DESIGN: Cross-sectional survey. SETTING: Mainstream schools in Hong Kong. PARTICIPANTS: Parents of 30 children with visual impairment who were studying in mainstream schools and attended assessment by optometrists at Child Assessment Service between May 2009 and June 2010 were recruited in the study (visual impairment group). Parents of 45 children with learning and behavioural problems recruited from two parent support groups (learning and behavioural problems group), and parents of 233 children without special education needs studying in mainstream schools recruited in a previous validation study on Service Needs Questionnaire (normal group) were used for comparison. Participants were invited to complete a self-administered Service Needs Questionnaire and a questionnaire on demographics of the children and their responding parents. The visual impairment group was asked additional questions about the ability of the child in coping and functioning in academic and recreational activities. RESULTS: Needs expressed by parents of the visual impairment group were significantly higher than those of parents of the normal group, and similar to those in the learning and behavioural problems group. Parents of children with visual impairment expressed more needs for future education and school support than resources for dealing with personal and family stress. CONCLUSION: Service needs of children with visual impairment and their families are high, particularly for future education and school support. More study on the various modes of accommodation for children with visual impairment and more collaborative work among different partners working in the field of rehabilitation will foster better service for these children and their families.
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Crianças com Deficiência , Inclusão Escolar , Relações Pais-Filho , Pais , Transtornos da Visão/psicologia , Adulto , Criança , Feminino , Hong Kong , Humanos , Masculino , Avaliação das Necessidades , Índice de Gravidade de Doença , Inquéritos e Questionários , Transtornos da Visão/patologiaRESUMO
In this study, we report the identification of a novel role of SIRT6 in both epirubicin and paclitaxel resistance in breast cancer. We found that SIRT6 protein levels are elevated in paclitaxel- and epirubicin-resistant MCF-7 cells compared with the parental sensitive cells. SIRT6 knockout and depletion sensitized cells to both paclitaxel and epirubicin treatment, whereas SIRT6 ectopic overexpression led to increased resistance to paclitaxel and epirubicin. Moreover, our data suggest that SIRT6 could be mediating epirubicin resistance through enhancing the DNA repair response to epirubicin-induced DNA damage. Clonogenic assays also revealed that mouse embryonic fibroblasts (MEFs) lacking SIRT6 have decreased long-term viability in response to epirubicin. The tumour suppressor FOXO3a increases its levels of acetylation in MEFs depleted of SIRT6, whereas its induction by epirubicin is attenuated in breast cancer cells overexpressing SIRT6. Further cell viability studies demonstrate that deletion of FOXO1/3/4 in MEFs can confer sensitivity to both paclitaxel and epirubicin, suggesting that SIRT6 reduces paclitaxel and epirubicin sensitivity, at least in part, through modulating FOXO acetylation and expression. Consistently, immunohistochemical analysis of 118 breast cancer patient samples revealed that high SIRT6 nuclear staining is significantly associated with poorer overall survival (P = 0.018; Kaplan-Meier analysis). Multivariate Cox analysis demonstrated that nuclear SIRT6 staining remained associated with death after correcting for tumour stage and lymph-node involvement (P = 0.033). Collectively, our data suggest that SIRT6 has a role in paclitaxel and epirubicin sensitivity via targeting FOXO proteins and that SIRT6 could be a useful biomarker and therapeutic target for paclitaxel- and epirubicin-resistant cancer.
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Neoplasias da Mama/patologia , Resistencia a Medicamentos Antineoplásicos , Epirubicina/farmacologia , Paclitaxel/farmacologia , Sirtuínas/metabolismo , Acetilação , Animais , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Morte Celular , Núcleo Celular/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA , Reparo do DNA , Feminino , Proteína Forkhead Box O3 , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Regulação Neoplásica da Expressão Gênica , Técnicas de Inativação de Genes , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Células MCF-7 , Camundongos , Modelos de Riscos Proporcionais , Sirtuínas/genéticaRESUMO
Apart from ß-catenin accumulation, loss of 3p21 is one of the most frequent genetic alterations in numerous malignancies including nasopharyngeal carcinoma (NPC). Herein, we characterized a novel candidate tumor suppressor gene (TSG) CACNA2D3, a voltage-dependent subunit alpha 2 delta 3 of a calcium channel complex. Downregulation of CACNA2D3 was frequently detected in primary NPCs and NPC cell lines compared with their nontumorigenic counterparts. Attenuated CACNA2D3 expression may be associated with loss of heterozygosity (LOH) at intragenic single-nucleotide polymorphism sites (rs589281, rs1449325 and rs6797113) and/or epigenetic silencing by methylation and histone deacetylation. Given the extensive effects of calcium in cancer, we then investigated the tumor suppressive role and underlying mechanism of CACNA2D3 in the development and progression of NPC. CACNA2D3 was stably transfected into NPC cell lines (C666 and SUNE1) at levels comparative with the normal nasopharynx, alongside siRNA-mediated silencing in an immortalized nasopharyngeal epithelial cell line (NP69) to conduct in vivo and in vitro functional assays. Our findings show that CACNA2D3-mediated increase in intracellular calcium (Ca2+) can induce mitochondrial-mediated apoptosis and activation of NLK (through the Wnt/Ca2+ pathway) to antagonize Wnt signaling-mediated anchorage-dependent and independent cell proliferation (via CCND1 and CMYC), invasion (via MMP7) and epithelial-to-mesynchemal transition (via SNAIL). As the expression pattern of calcium channels and their degree of functionality can change with the progression of cancer, CACNA2D3 may indeed be a promising biomarker for NPC. Our study also warrants further exploration in the potential therapeutic use of existing epigenetic targeting drugs (e.g., 5-azacytidine, SAHA) to reconstitute CACNA2D3-associated tumor suppression in NPC.
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Canais de Cálcio/genética , Genes Supressores de Tumor , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patologia , Proteínas Supressoras de Tumor/genética , Apoptose/genética , Cálcio/metabolismo , Canais de Cálcio/metabolismo , Carcinoma , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Regulação para Baixo , Epigênese Genética , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Transição Epitelial-Mesenquimal , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Mitocôndrias/genética , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/metabolismo , Nasofaringe/metabolismo , Nasofaringe/patologia , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Metástase Neoplásica , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Proteínas Wnt/genética , Proteínas Wnt/metabolismoRESUMO
BACKGROUND: Women with advanced breast cancer (ABC) are living longer, so understanding their needs becomes important. This cross-sectional study investigated the type and extent of unmet supportive care needs in Hong Kong Chinese women with advanced breast cancer. METHODS: Face-to-face interviews were conducted among women with stage III or stage IV disease mostly awaiting chemotherapy (76%) to identify unmet needs using the Supportive Care Needs Survey Short Form, psychological morbidity using the Hospital Anxiety and Depression Scale, symptom distress using the Memorial Symptom Assessment Scale, and satisfaction with care using the Patient satisfaction questionnaire (PSQ-9). RESULTS: About 27-72% of 198/220 (90%) women (mean age = 53.4 ± 9.74 (standard deviation) years) identified needs from the health system, information, and patient support (HSIPS) domain as the top 15 most prevalent unmet needs. 'having one member of hospital staff with whom you can talk to about all aspect of your condition, treatment, and follow-up' was most cited by 72% of the patients, with remaining unmet needs addressing mostly desire for information. Unmet need strength did not differ between women with stage III and stage IV disease, whereas women with first time diagnosis reported greater health system and information unmet needs compared with women with recurrent disease. Stepwise multiple regression analyses revealed that symptom distress was consistently positively associated with all but sexuality need domains, whereas low satisfaction with care was associated with HSIPS (ß = 3.270, p < 0.001) and physical and daily living (ß = 2.810, p < 0.01) domains. DISCUSSIONS: Chinese women with ABC expressed need for continuity of care and improved information provision. High symptom distress was associated with lower levels of satisfaction with care. These unmet needs appear to reflect current care services shortcomings.
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Neoplasias da Mama/psicologia , Necessidades e Demandas de Serviços de Saúde , Ansiedade/etiologia , Ansiedade/prevenção & controle , Estudos Transversais , Depressão/etiologia , Depressão/prevenção & controle , Feminino , Hong Kong/epidemiologia , Humanos , Entrevistas como Assunto , Pessoa de Meia-Idade , Avaliação das Necessidades , Satisfação do Paciente , Escalas de Graduação Psiquiátrica , Estresse Psicológico/etiologia , Estresse Psicológico/prevenção & controle , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Understanding cancer patients' supportive care needs can help optimize health-care systems and inform services development. We therefore examined the prevalence of supportive care needs in Chinese breast (BC) and colorectal cancer (CRC) patients to identify prevalence and correlates of unmet needs. METHODS: We assessed supportive care needs (Supportive Care Needs Survey-Short Form), psychological distress (the Hospital Anxiety and Depression Scale), symptom distress (The Memorial Symptom Assessment Scale-Short Form), and satisfaction with care (Patient Satisfaction Questionnaire) among 210 Chinese BC (97) or CRC (104) outpatient clinic attendees. RESULTS: Breast cancer patients (89.7%) reported more unmet needs (χ(2) = 4.409, p = 0.027), but both CRC and BC samples ranked unmet needs prevalence similarly, with health system and information needs reported as the most common. Younger patients reported higher health system and information and sexuality needs. After multivariate adjustment, the strength of unmet needs did not differ by cancer type. Unmet psychological, physical and daily living, and sexuality needs were positively associated with greater symptom distress. Greater health system information needs were associated with high global distress and low depression scores, whereas greater psychological needs were associated with higher anxiety scores. CONCLUSIONS: Hong Kong Chinese BC and CRC patients strongly prioritized needs related to health systems and information provision. Symptoms and psychological distress were associated with unmet needs, reflecting a service shortfall in symptom management. Improving care provision by optimizing communication and clinic organization can better prepare cancer patients for their rehabilitation and improve symptom control.
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Neoplasias da Mama/psicologia , Neoplasias Colorretais/psicologia , Avaliação das Necessidades , Apoio Social , Adaptação Psicológica , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Ansiedade/etnologia , Ansiedade/etiologia , Povo Asiático/psicologia , Povo Asiático/estatística & dados numéricos , Neoplasias da Mama/etnologia , China/epidemiologia , Neoplasias Colorretais/etnologia , Depressão/etnologia , Depressão/etiologia , Feminino , Necessidades e Demandas de Serviços de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Educação de Pacientes como Assunto , Satisfação do Paciente , Prevalência , Escalas de Graduação Psiquiátrica , Fatores Socioeconômicos , Estresse Psicológico , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: To test for the measurement invariance of the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) in patients with colorectal neoplasms between two modes of administration (self- and interviewer administrations). It is important to establish the measurement invariance of the FACT-C across different modes of administration to ascertain whether it is valid to pool FACT-C data collected by different modes or to assess each group separately. METHODS: A cross-sectional sample of 391 Chinese patients with colorectal neoplasms was recruited from specialist outpatient clinics between September 2009 and July 2010. Confirmatory factor analysis (CFA) was used to test the original five-factor model of the FACT-C on data collected by self- and interviewer administrations in single-group analysis. Multiple-group CFA was then used to compare the factor structure between the two modes of administration using chi-square tests and other goodness-of-fit statistics. RESULTS: The hypothesized five-factor model of FACT-C demonstrated good fit in each group. Configural invariance and metric invariance were fully supported in multiple-group CFA. Some item intercepts and their corresponding error variances were not identical between administration groups, suggesting evidence of partial strict factorial invariance. CONCLUSIONS: Our results confirmed that the five-factor structure of FACT-C was invariant in Chinese patients using both self- and interviewer administrations. It is appropriate to pool or compare data in the emotional well-being and colorectal cancer subscale scores collected by both administrations. Measurement invariance in three items, one from each of the other subscales, may be contaminated by response bias between modes of administration.
Assuntos
Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/psicologia , Psicometria/instrumentação , Qualidade de Vida , Inquéritos e Questionários , Idoso , Análise de Variância , Distribuição de Qui-Quadrado , Estudos Transversais , Análise Fatorial , Feminino , Indicadores Básicos de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Resultado do TratamentoRESUMO
BACKGROUND: Recommendations about funding of interventions through the full spectrum of the disease often have been made in isolation. The authors of this report optimized budgetary allocations by comparing cost-effectiveness data for different preventive and management strategies throughout the disease course for breast cancer in Hong Kong (HK) Chinese women. METHODS: Nesting a state-transition Markov model within a generalized cost-effectiveness analytic framework, costs and quality-adjusted life-years (QALYs) were compared to estimate average cost-effectiveness ratios for the following interventions at the population level: biennial mass mammography (ages 40-69 years or ages 40-79 years), reduced waiting time for postoperative radiotherapy (by 15% or by 25%), adjuvant endocrine therapy (either upfront aromatase inhibitor [AI] therapy or sequentially with tamoxifen followed by AI) in postmenopausal women with estrogen receptor-positive disease, targeted immunotherapy in those with tumors that over express human epidermal growth factor receptor 2, and enhanced palliative services (either at home or as an inpatient). Usual care for eligible patients in the public sector was the comparator. RESULTS: In descending order, the optimal allocation of additional resources for breast cancer would be the following: a 25% reduction in waiting time for postoperative radiotherapy (in US dollars: $5000 per QALY); enhanced, home-based palliative care ($7105 per QALY); adjuvant, sequential endocrine therapy ($17,963 per QALY); targeted immunotherapy ($62,092 per QALY); and mass mammography screening of women ages 40 to 69 years ($72,576 per QALY). CONCLUSIONS: Given the lower disease risk and different age profiles of patients in HK Chinese, among other newly emergent and emerging economies with similar transitioning epidemiologic profiles, the current findings provided direct evidence to support policy decisions that may be dissimilar to current Western practice.
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Neoplasias da Mama/prevenção & controle , Neoplasias da Mama/terapia , Detecção Precoce de Câncer/economia , Alocação de Recursos para a Atenção à Saúde/economia , Mamografia/economia , Adulto , Idoso , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Análise Custo-Benefício , Tomada de Decisões , Feminino , Hong Kong , Humanos , Cadeias de Markov , Pessoa de Meia-Idade , Cuidados Paliativos , Formulação de Políticas , Anos de Vida Ajustados por Qualidade de VidaRESUMO
BACKGROUND: Epstein-Barr virus (EBV) microRNAs are abundant in nasopharyngeal carcinoma (NPC) tumors. With recent advances in serum microRNA detection, the distinct presence of EBV microRNAs in serum could aid in screening endemic regions for NPC. A proposed network of genes targeted by these microRNAs could also shed light on EBV-associated tumorigenesis. METHODS: MicroRNA microarray profiling of 5 paired NPC biopsies was followed by validation of 12 up-regulated EBV microRNAs (BART1-3p, 2-5p, 5, 6-5p, 6-3p, 7, 8, 9, 14, 17-5p, 18-5p, 19-3p) in 15 additional cases by real-time polymerase chain reaction. Tumor (cellular) and serum microRNA copy numbers from the same 15 patients were correlated. Expression of the same microRNAs were also examined in EBV-positive cell lines C666 and NP460hTERT+EBV. Bioinformatic tools helped predict cellular target genes, which were later confirmed by gene expression analysis. RESULTS: The authors' high-throughput approach shows that EBV microRNAs are generally more up-regulated than microRNAs of human origin. Twenty-nine of 39 EBV microRNAs were significantly up-regulated in tumor versus their nontumor biopsies (P < .05). Upon successfully validating 12 selected EBV microRNAs in 15 additional paired NPC cases, the authors found that their distinct presence in the serum of NPC patients positively correlated with cellular copy numbers of EBV microRNAs. Further investigation of potential EBV microRNA target genes revealed inhibition of tumor suppressor genes (eg, PTEN) and extensive deregulation of several pathways frequently involved in NPC (eg, Wnt signaling). CONCLUSIONS: Increasing knowledge of host-virus interaction via microRNAs may provide feasible explanations underlying NPC tumorigenesis along with the development of biomarkers for screening high-risk populations.
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Biomarcadores Tumorais/genética , Herpesvirus Humano 4/genética , MicroRNAs/genética , Neoplasias Nasofaríngeas/genética , Oncogenes , RNA Viral/genética , Adulto , Idoso , Western Blotting , Estudos de Casos e Controles , Infecções por Vírus Epstein-Barr/sangue , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/virologia , Feminino , Perfilação da Expressão Gênica , Herpesvirus Humano 4/isolamento & purificação , Humanos , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/sangue , Neoplasias Nasofaríngeas/virologia , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , RNA Viral/sangue , Reação em Cadeia da Polimerase em Tempo RealRESUMO
OBJECTIVES: To map Functional Assessment of Cancer Therapy-General (FACT-G) and Functional Assessment of Cancer Therapy-Colorectal (FACT-C) subscale scores onto six-dimensional health state short form (derived from short form 36 health survey) (SF-6D) preference-based values in patients with colorectal neoplasm, with and without adjustment for clinical and demographic characteristics. These results can then be applied to studies that have used FACT-G or FACT-C to predict SF-6D utility values to inform economic evaluation. METHODS: Ordinary least square regressions were estimated mapping FACT-G and FACT-C onto SF-6D by using cross-sectional data of 537 Chinese subjects with different stages of colorectal neoplasm. Mapping functions for SF-6D preference-based values were developed separately for FACT-G and FACT-C in four sequential models for addition of variables: 1) main-effect terms, 2) squared terms, 3) interaction terms, and 4) clinical and demographic variables. Predictive performance in each model was assessed by the R(2), adjusted R(2), predicted R(2), information criteria (Akaike information criteria and Bayesian information criteria), the root mean square error, the mean absolute error, and the proportions of absolute error within the threshold of 0.05 and 0.10. RESULTS: Models including FACT variables and clinical and demographic variables had the best predictive performance measured by using R(2) (FACT-G: 59.98%; FACT-C: 60.43%), root mean square error (FACT-G: 0.086; FACT-C: 0.084), and mean absolute error (FACT-G: 0.065; FACT-C: 0.065). The FACT-C-based mapping function had better predictive ability than did the FACT-G-based mapping function. CONCLUSIONS: Models mapping FACT-G and FACT-C onto SF-6D reached an acceptable degree of precision. Mapping from the condition-specific measure (FACT-C) had better performance than did mapping from the general cancer measure (FACT-G). These mapping functions can be applied to FACT-G or FACT-C data sets to estimate SF-6D utility values for economic evaluation of medical interventions for patients with colorectal neoplasm. Further research assessing model performance in independent data sets and non-Chinese populations are encouraged.
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Neoplasias Colorretais/classificação , Inquéritos Epidemiológicos/instrumentação , Preferência do Paciente , Idoso , China/etnologia , Neoplasias Colorretais/etnologia , Feminino , Hong Kong , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida/psicologia , AutorrelatoRESUMO
PURPOSE: Breast cancer (BC) treatment has shifted from chemotherapy to targeted therapy. Several targeted agents have demonstrated an improvement in survival. Given that national healthcare resources were correlated with the cancer mortality-to-incidence ratio, we compared access to BC drugs in Thailand with that in other Asian countries. METHODS: BC experts involved in the Breast International Group (BIG)-Asia in six representative groups for countries or special administrative region (SAR) in Asia (Hong Kong SAR, Japan, Korea, Taiwan, Thailand, and Singapore) were invited to participate in the survey. The questionnaire addressed national health reimbursement schemes, molecular testing for early BC (EBC), availability and accessibility of BC drugs. Accessibility and reimbursement of the drugs were reported based on their listing as essential medicines in the World Health Organization Model List of Essential Medicines (WHO-EML) and their nomination as effective drugs in the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS). The study was approved by all participating BIG-Asia organizations in November 2021. RESULTS: Genomic tests for EBC were non-reimbursable in all surveyed territories. Reimbursement and co-payment of BC drugs vary between and within these regions (particularly Thailand). Most drugs in the WHO-EML and ESMO-MCBS (A/B for EBC and 4/5 for advanced BC) were accessible in all surveyed territories. However, the accessibility of effective but costly WHO-EML and ESMO-MCBS drugs was not uniform in Thailand. There was an evident disparity for individuals covered by the Thai Social Security/Universal Health Coverage schemes. CONCLUSION: Essential BC drugs are generally accessible in selected BIG-Asia countries or SAR. There is a disparity in accessing high-cost drugs in Thailand compared with other Asian territories.
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BACKGROUND: Selection of patients with local failure of nasopharyngeal carcinoma (NPC) for appropriate type of salvage treatment can be difficult due to the lack of data on comparative efficacy of different salvage treatments. The purpose of the present study was to validate a previously published prognostic scoring system for local failures of NPC treated by radiosurgery based on reported results in the literature. METHODS: A literature search yielded 3 published reports on the use of radiosurgery as salvage treatment of NPC that contained sufficient clinical information for validation of the scoring system. Prognostic scores of 18 patients from these reports were calculated and actuarial survival rates were estimated and compared to the original cohort used to design the prognostic scoring system. The area under the receiver operating characteristic curve was also determined and compared between the current and original patient groups. RESULTS: The calculated prognostic scores ranged from 0.32 to 1.21, with 15 patients assigned to the poor prognostic group and 3 to the intermediate prognostic group. The actuarial 3-year survival rates in the intermediate and poor prognostic groups were 67% and 0%, respectively. These results were comparable to the observed 3-year survival rates of 74% and 23% in the intermediate and poor prognostic group in the original reports. The area under the receiver operating characteristic curve for the current patient group was 0.846 which was similar to 0.841 in the original group. CONCLUSION: The previously published prognostic scoring system demonstrated good prediction of treatment outcome after radiosurgery in a small group of NPC patients with poor prognosis. Prospective study to validate the scoring system is currently being carried out in our institution.
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Neoplasias Nasofaríngeas/cirurgia , Radiocirurgia/métodos , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia , Prognóstico , Reprodutibilidade dos Testes , Literatura de Revisão como Assunto , Análise de Sobrevida , Resultado do TratamentoRESUMO
Breast cancer is the most frequent malignancy in women worldwide and is curable in ~70-80% of patients with early-stage, non-metastatic disease. Advanced breast cancer with distant organ metastases is considered incurable with currently available therapies. On the molecular level, breast cancer is a heterogeneous disease; molecular features include activation of human epidermal growth factor receptor 2 (HER2, encoded by ERBB2), activation of hormone receptors (oestrogen receptor and progesterone receptor) and/or BRCA mutations. Treatment strategies differ according to molecular subtype. Management of breast cancer is multidisciplinary; it includes locoregional (surgery and radiation therapy) and systemic therapy approaches. Systemic therapies include endocrine therapy for hormone receptor-positive disease, chemotherapy, anti-HER2 therapy for HER2-positive disease, bone stabilizing agents, poly(ADP-ribose) polymerase inhibitors for BRCA mutation carriers and, quite recently, immunotherapy. Future therapeutic concepts in breast cancer aim at individualization of therapy as well as at treatment de-escalation and escalation based on tumour biology and early therapy response. Next to further treatment innovations, equal worldwide access to therapeutic advances remains the global challenge in breast cancer care for the future.
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Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Adulto , Proteína BRCA2/análise , Proteína BRCA2/genética , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Neoplasias da Mama/epidemiologia , Feminino , Humanos , Receptor ErbB-2/análise , Receptor ErbB-2/genética , Sobreviventes/estatística & dados numéricos , Ubiquitina-Proteína Ligases/análise , Ubiquitina-Proteína Ligases/genéticaRESUMO
PURPOSE: BioPATH is a non-interventional study evaluating the relationship of molecular biomarkers (PTEN deletion/downregulation, PIK3CA mutation, truncated HER2 receptor [p95HER2], and tumor HER2 mRNA levels) to treatment responses in Asian patients with HER2+ advanced breast cancer treated with lapatinib and other HER2-targeted agents. MATERIALS AND METHODS: Female Asian HER2+ breast cancer patients (n=154) who were candidates for lapatinib-based treatment following metastasis and having an available primary tumor biopsy specimen were included. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, overall survival on lapatinib, correlation between biomarker status and PFS for any previous trastuzumab-based treatment, and conversion/conservation rates of the biomarker status between tissue samples collected at primary diagnosis and at recurrence/metastasis. Potential relationships between tumor mRNA levels of HER2 and response to lapatinib-based therapy were also explored. RESULTS: p95HER2, PTEN deletion/downregulation, and PIK3CA mutation did not demonstrate any significant co-occurrence pattern and were not predictive of clinical outcomes on either lapatinib-based treatment or any previous trastuzumab-based therapy in the metastatic setting. Proportions of tumors positive for p95HER2 expression, PIK3CA mutation, and PTEN deletion/down-regulation at primary diagnosis were 32%, 31.2%, and 56.2%, respectively. Despite limited availability of paired samples, biomarker status patterns were conserved in most samples. HER2 mRNA levels were not predictive of PFS on lapatinib. CONCLUSION: The prevalence of p95HER2 expression, PIK3CA mutation, and PTEN deletion/downregulation at primary diagnosis were similar to previous reports. Importantly, no difference was observed in clinical outcome based on the status of these biomarkers, consistent with reports from other studies.