RESUMO
Advanced, late-stage Epstein-Barr virus (EBV)-positive nasopharyngeal carcinoma (NPC) is incurable, and its treatment remains a clinical and therapeutic challenge. Results from a phase II clinical trial in advanced NPC patients employing a combined chemotherapy and EBV-specific T cell (EBVST) immunotherapy regimen showed a response rate of 71.4%. Longitudinal analysis of patient samples showed that an increase in EBV DNA plasma concentrations and the peripheral monocyte-to-lymphocyte ratio negatively correlated with overall survival. These parameters were combined into a multivariate analysis to stratify patients according to risk of death. Immunophenotyping at serial time points showed that low-risk individuals displayed significantly decreased amounts of monocytic myeloid-derived suppressor cells postchemotherapy, which subsequently influenced successful cytotoxic T-lymphocyte (CTL) immunotherapy. Examination of the low-risk group, 2 weeks post-EBVST infusion, showed that individuals with a greater overall survival possessed an increased frequency of CD8 central and effector memory T cells, together with higher levels of plasma interferon (IFN)-γ, and cytotoxic lymphocyte-associated transcripts. These results highlight the importance of the rational selection of chemotherapeutic agents and consideration of their impact on both systemic immune responses and downstream cellular immunotherapy outcomes.
Assuntos
Imunoterapia Adotiva , Células Supressoras Mieloides/imunologia , Carcinoma Nasofaríngeo/imunologia , Carcinoma Nasofaríngeo/terapia , Linfócitos T/imunologia , Infecções por Vírus Epstein-Barr/imunologia , Herpesvirus Humano 4/imunologia , Humanos , Imunoterapia Adotiva/métodos , Células Supressoras Mieloides/metabolismo , Carcinoma Nasofaríngeo/patologia , Linfócitos T/metabolismo , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/metabolismo , Falha de Tratamento , Resultado do TratamentoRESUMO
PURPOSE: Utility values are critical for cost-utility analyses that guide healthcare decisions. We aimed to compare the utility values of the 5-level EuroQoL-5Dimension (EQ-5D-5L) health states elicited from members of the general public and patients with heart disease or cancer. METHODS: In face-to-face interviews with 157 heart disease patients, 169 cancer patients, and 169 members from the general population, participants valued 10 EQ-5D-5L health states using a composite Time Trade-Off method. RESULTS: Pooling utility values for all health states, heart disease patients and cancer patients had mean utility values lower by 0.11 points (P value = 0.014) and 0.06 points (P value = 0.148), respectively, compared to the general population. Adjusting for sociodemographic characteristics, differences in health state utility values between the patient and the general populations were rendered non-significant, except that heart disease patients gave higher utility values (mean difference = 0.08; P value = 0.007) to mild health states than the general population. Difference in utility values, defined as utility value of a better health state minus that of a poorer health state, was higher among heart disease patients compared to the general population, before and after adjusting for sociodemographic characteristics. CONCLUSIONS: Patients may differ from members of the general population in the strength of their preferences for hypothetical health states. Using utility values derived from the general population may under-estimate the comparative effectiveness of healthcare interventions for certain diseases, such as heart diseases.
Assuntos
Nível de Saúde , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Inquéritos e Questionários , Adulto JovemRESUMO
The outcomes for patients with metastatic or locally recurrent Epstein-Barr virus (EBV)-positive nasopharyngeal carcinoma (NPC) remain poor. Adoptive immunotherapy with EBV-specific cytotoxic T lymphocytes (EBV-CTLs) has proven clinical efficacy, but it has never been evaluated in the first-line treatment setting in combination with chemotherapy. To evaluate the safety and efficacy of a chemotherapy in combination with adoptive EBV-CTL transfer, we conducted a phase 2 clinical trial consisting of four cycles of gemcitabine and carboplatin (GC) followed by up to six doses of EBV-CTL. Thirty-eight patients were enrolled, and 35 received GC and EBV-CTL. GC-CTL therapy resulted in a response rate of 71.4% with 3 complete responses and 22 partial responses. With a median follow up of 29.9 months, the 2-year and 3-year overall survival (OS) rate was 62.9 and 37.1%, respectively. Five patients did not require further chemotherapy for more than 34 months since initiation of CTL. Infusion of CTL products containing T cells specific for LMP2 positively correlated with OS (hazard ratio: 0.35; 95% confidence interval: 0.14-0.84; P = 0.014). Our study achieved one of the best survival outcomes in patients with advanced NPC, setting the stage for a future randomized study of chemotherapy with and without EBV-CTL.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Imunoterapia Adotiva , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/terapia , Adulto , Idoso , Carcinoma , Linhagem Celular Tumoral , Infecções por Vírus Epstein-Barr/imunologia , Feminino , Herpesvirus Humano 4/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/imunologia , Neoplasias Nasofaríngeas/mortalidade , Metástase Neoplásica , Recidiva Local de Neoplasia , Linfócitos T Citotóxicos/imunologia , Resultado do Tratamento , Proteínas da Matriz Viral/imunologiaRESUMO
OBJECTIVE: To examine the measurement properties of and comparability between the English and Chinese versions of the five-level EuroQoL Group's five-dimension questionnaire (EQ-5D) in breast cancer patients in Singapore. METHODS: This is an observational study of 269 patients. Known-group validity and responsiveness of the EQ-5D utility index and visual analog scale (VAS) were assessed in relation to various clinical characteristics and longitudinal change in performance status, respectively. Convergent and divergent validity was examined by correlation coefficients between the EQ-5D and a breast cancer-specific instrument. Test-retest reliability was evaluated. The two language versions were compared by multiple regression analyses. RESULTS: For both English and Chinese versions, the EQ-5D utility index and VAS demonstrated known-group validity and convergent and divergent validity, and presented sufficient test-retest reliability (intraclass correlation = 0.72 to 0.83). The English version was responsive to changes in performance status. The Chinese version was responsive to decline in performance status, but there was no conclusive evidence about its responsiveness to improvement in performance status. In the comparison analyses of the utility index and VAS between the two language versions, borderline results were obtained, and equivalence cannot be definitely confirmed. CONCLUSION: The five-level EQ-5D is valid, responsive, and reliable in assessing health outcome of breast cancer patients. The English and Chinese versions provide comparable measurement results.
Assuntos
Povo Asiático , Neoplasias da Mama , Nível de Saúde , Qualidade de Vida , Inquéritos e Questionários , Povo Asiático/psicologia , Neoplasias da Mama/etnologia , Feminino , Humanos , Idioma , Pessoa de Meia-Idade , Análise Multivariada , Psicometria , Análise de Regressão , Reprodutibilidade dos Testes , SingapuraRESUMO
PURPOSE: To compare the measurement precision and related properties between the 5-level EuroQoL Group's 5-dimension (EQ-5D-5L) questionnaire and the Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire in assessing breast cancer patients. METHODS: An observational study of 269 Singaporean breast cancer patients. To compare discriminative ability and responsiveness, the effect sizes (in standard deviation) of the EQ-5D-5L and the FACT-B in relation to health indicators and the change in performance status or quality of life were estimated. Test-retest reliability was examined using the intraclass correlation (ICC). RESULTS: Using performance status, evidence of disease, and treatment status as the criteria, the differences (FACT-B minus EQ-5D-5L) in the effect size for discriminative ability were negative or closed to zero, and the 90% confidence intervals totally fell within the zone that indicated the non-inferiority of the EQ-5D-5L. For responsiveness and test-retest reliability, the confidence intervals of the differences in effect size and ICC overlapped the non-inferiority margin; thus, non-inferiority in these two aspects could neither be confirmed nor rejected. CONCLUSIONS: The EQ-5D-5L was non-inferior to the FACT-B in discriminating breast cancer patients with different health conditions cross-sectionally. The EQ-5D-5L serves as a reasonable alternative or supplementary instrument to the FACT-B in assessing breast cancer patients' health outcomes.
Assuntos
Povo Asiático/psicologia , Neoplasias da Mama/psicologia , Indicadores Básicos de Saúde , Psicometria/instrumentação , Qualidade de Vida , Inquéritos e Questionários , Intervalos de Confiança , Estudos Transversais , Feminino , Humanos , Idioma , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados da Assistência ao Paciente , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , SingapuraRESUMO
BACKGROUND: In 2008, the Federation of Gynecology and Obstetrics (FIGO) revised their 1988 staging system for uterine leiomyosarcomas. In this article, we compare performance of the 2008 and 1988 FIGO systems. METHODS: Individual case data were manually culled. Staging was retrospectively assessed according to revised and 1998 FIGO criteria. Overall survival distribution was assessed by the Kaplan-Meier method. Harrell's concordance index was used to assess the discriminative ability of a fitted Cox model to predict overall survival. RESULTS: A total of 110 cases of uterine leiomyosarcomas were reviewed and data from 88 patients were analyzed. In all, 71% of cases were classified as stage I, 7% as stage II, 3% as stage III, and 19% as stage IV under the revised FIGO staging system. Nine patients (10.2%) were downstaged and none were upstaged. The revised FIGO system did not show a significant improvement over the 1988 FIGO system in the ability to discriminate the risk of death of patients between stages, with concordance indexes of 0.70 and 0.71, respectively. Most patients were classified as stage I with age, tumor grade, tumor size, and lymphovascular invasion as prognostic factors. CONCLUSION: The 2008 revised FIGO staging system for uterine leiomyosarcomas does not perform better than the 1988 system for uterine endometrial carcinomas. A better staging system is needed for these cases.
Assuntos
Leiomiossarcoma/patologia , Neoplasias Uterinas/patologia , Adulto , Idoso , Povo Asiático , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Análise de SobrevidaRESUMO
The objective of the study was to examine the measurement properties of and comparability between the English and Chinese versions of the Functional Assessment of Cancer Therapy-Breast (FACT-B) in breast cancer patients in Singapore. This is an observational study of 271 Singaporean breast cancer patients. The known-group validity of FACT-B total score and Trial Outcome Index (TOI) were assessed in relation to performance status, evidence of disease, and treatment status cross-sectionally; responsiveness to change was assessed in relation to change in performance status longitudinally. Internal consistency and test-retest reliability were evaluated by the Cronbach's alpha and intraclass correlation coefficient (ICC), respectively. Multiple regression analyses were performed to compare the scores on the two language versions, adjusting for covariates. The FACT-B total score and TOI demonstrated known-group validity in differentiating patients with different clinical status. They showed high internal consistency and test-retest reliability, with Cronbach's alpha ranging from 0.87 to 0.91 and ICC ranging from 0.82 to 0.89. The English version was responsive to the change in performance status. The Chinese version was shown to be responsive to decline in performance status but the sample size of Chinese-speaking patients who improved in performance status was too small (N = 6) for conclusive analysis about responsiveness to improvement. Two items concerning sexuality had a high item non-response rate (50.2 and 14.4%). No practically significant difference was found in the total score and TOI between the two language versions despite minor differences in two of the 37 items. The English and Chinese versions of the FACT-B are valid, responsive, and reliable instruments in assessing health-related quality of life in breast cancer patients in Singapore. Data collected from the English and Chinese versions can be pooled and either version could be used for bilingual patients.
Assuntos
Neoplasias da Mama/epidemiologia , Adulto , Povo Asiático/psicologia , Povo Asiático/estatística & dados numéricos , Neoplasias da Mama/psicologia , Neoplasias da Mama/terapia , Feminino , Humanos , Idioma , Pessoa de Meia-Idade , Qualidade de Vida , Reprodutibilidade dos Testes , Singapura/epidemiologia , Singapura/etnologia , Inquéritos e QuestionáriosRESUMO
INTRODUCTION: Advanced hepatocellular carcinoma (HCC) has a dismal prognosis and is notoriously chemo-resistant. We conducted a Phase II prospective study to evaluate the activity and tolerability of gemcitabine and cisplatin in chemo-naïve advanced hepatocellular carcinoma. The trial considered a "no further interest" response rate of 10% and a target response rate of 30%. Utilising a Simon's minimax two-stage design with a type I error of 0.05 and power of 80%, 25 subjects would be required. Fifteen patients would be needed in stage 1 and if fewer than 2 responses were observed, the trial would be stopped and lack of efficacy claimed. MATERIALS AND METHODS: Patients with advanced HCC, diagnosed based on histology or by World Health Organization (WHO) criteria, were administered gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2 on day 1 and day 8 of a 21-day schedule. Assessment of response based on computer tomography was performed after every 2 cycles of chemotherapy. RESULTS: The trial was stopped early due to a lack of efficacy. A total of 15 patients were accrued. Twelve patients were hepatitis B positive and the other 3 patients were negative for both hepatitis B and C. Only 1 patient had a history of prior heavy alcohol use. Two patients had Child C liver cirrhosis, 5 patients had Child B cirrhosis, and the remaining 8 patients had Child A cirrhosis. This regime was well tolerated and there was only 1 patient who experienced grade IV toxicities. Only 5 of 15 patients experienced grade III toxicities (nausea and emesis, 1 patient; anemia, 1 patient; thrombocytopenia, 1 patient; and neutropaenia, 2 patients). Only 1 patient experienced a partial response to the combination of gemcitabine and cisplatin. A further 3 patients experienced stable disease and 11 patients progressed on chemotherapy. The median time to progression was 6 weeks. The progression-free curve showed a sharp descent in the initial part of the study, suggesting that many patients had disease progression after enrollment. The median overall survival was 18 weeks. CONCLUSION: The progression-free survival and overall survival in our study were extremely short. Based on the results of our phase 2 study, we are unable to recommend further studies utilising gemcitabine and cisplatin combination in patients with advanced HCC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Adulto , Carcinoma Hepatocelular/etiologia , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Hepáticas/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento , GencitabinaRESUMO
BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal metastases from ovarian cancer have been shown to have a role in recurrent ovarian cancer, but are still not considered standard therapy. METHODS: From March 2005 to July 2013, 41 patients who underwent 44 CRS and HIPEC for peritoneal metastases in recurrent ovarian cancer were included in this study. Details were obtained from a prospectively maintained database. Our aim was to report our 5-year overall and disease-free survivals, as well as prognostic factors for survival. RESULTS: Median age was 50 years old (range 23-73). Median duration of surgery was 510âmin (range 230-840) and median peritoneal carcinomatosis index (PCI) score was 9.5 (range 0-31). About 92.7% of the patients had completeness of cytoreduction (CC) scores of 0 or 1. Median follow-up was 43.9 months (range 0.7-108.9). There were no mortalities and the high-grade morbidity rate was 31.8%. Median overall survival was 42.8 months (range 28.6-99.9) 5-year overall and disease-free survivals were 49.3% and 7.5% respectively. On multivariate analysis, histology and CC score were significantly associated with overall survival while histology and disease-free interval were associated with disease-free survival. The odds of developing a high-grade complication more than doubled for each additional surgical procedure performed (p=0.01). CONCLUSIONS: CRS and HIPEC can attain prolonged survival in selected patients with peritoneal metastasis in recurrent ovarian cancer.
RESUMO
Phaeochromocytoma is a rare condition that provides a diagnostic challenge as a result of its variable presentation. Treatment of metastatic malignant phaeochromocytoma is also not well defined owing to its rarity. We present four such cases and a review of the literature. The database of the Singapore Cancer Registry was used to trace all cases of metastatic malignant phaeochromocytoma from 1984 to 2004, and the case records were then reviewed retrospectively. There were four patients with metastatic malignant phaeochromocytoma seen in Singapore in the last 20 years. Their variable clinical courses were reviewed and compared with current knowledge and overseas experience in the literature. We further discuss the difficulties in diagnosis, and the dilemma in appropriate management of such cases. Phaeochromocytoma remains a commonly missed diagnosis unless a high index of suspicion is maintained. Malignant phaeochromocytoma has a variable clinical course. There is a place for radical surgery if this can render the patient free of gross disease, or when it can achieve symptom control for palliation and improvement in quality of life. In the metastatic context, debulking surgery does not appear to be of curative benefit, although it may be undertaken for good palliation.
Assuntos
Neoplasias das Glândulas Suprarrenais , Metástase Neoplásica , Feocromocitoma , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/mortalidade , Neoplasias das Glândulas Suprarrenais/patologia , Neoplasias das Glândulas Suprarrenais/cirurgia , Glândulas Suprarrenais/patologia , Adrenalectomia , Adulto , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/terapia , Cuidados Paliativos , Feocromocitoma/diagnóstico , Feocromocitoma/mortalidade , Feocromocitoma/patologia , Feocromocitoma/cirurgia , Qualidade de Vida , Estudos Retrospectivos , Fatores de TempoRESUMO
Nasopharyngeal carcinoma (NPC) is associated with the Epstein-Barr virus (EBV) and characterized by peritumoral immune infiltrate. Advanced NPC has high lethality. Immunotherapy directed against EBV antigen targets has been previously explored in clinical trials, and is likely to be validated as an important target in NPC as randomized data emerges in the future. Cancer vaccines and adoptive T cell therapy have been explored in the clinic, with the latter showing the greatest success. Recent advances in gene sequencing technology now allow personalized tumor epitope mapping, whilst the advent of immune checkpoint inhibitors targeting the PD-1/PD-L1 axis offers the opportunity to activate adaptive T cell response in vivo. Anti-PD1 antibodies have shown promising activity in early phase clinical trials, and randomized studies against chemotherapy are underway. As immunotherapy is incorporated into standard treatment paradigms, issues of optimal combinations with targeting agents, immune adjuvants, and sequence with chemotherapy and radiation therapy will need to be addressed. Effective strategies to increase tumor antigenicity, improve immunological memory and reduce immune escape, will need to be developed to improve treatment outcomes. Here we present a brief history of the evolution of immunotherapy in NPC, and highlight key concepts relevant to its further development in the clinic.
Assuntos
Vacinas Anticâncer/farmacologia , Imunoterapia/métodos , Neoplasias Nasofaríngeas/terapia , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/imunologia , Herpesvirus Humano 4/patogenicidade , Humanos , Terapia de Alvo Molecular/métodos , Neoplasias Nasofaríngeas/etiologia , Neoplasias Nasofaríngeas/patologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/metabolismo , Microambiente TumoralRESUMO
BACKGROUND: Recent observational studies suggest that postoperative aspirin use may improve Colorectal cancer (CRC)-specific survival and overall survival (OS). In this study, we aimed to assess the effects of aspirin use on outcomes in a predominantly Asian cohort of patients with CRC. PATIENTS AND METHODS: Case records of patients undergoing curative resection for stage I-III CRC were retrieved for clinical data and patterns of aspirin use and vital data were determined from hospital electronic prescription records, hospital pharmacy dispensing records, national clinical and prescription databases. CRC-specific and recurrence-free survival (RFS) amongst aspirin users and non-users were analyzed and compared using the Cox proportional hazards model. RESULTS: Out of 726 patients with CRC, 103 were regular aspirin users and 623 were non-users. The median age of the cohort was 65 years (range=22-94 years) and the majority of patients were Chinese (90%). Nineteen percent, 31% and 47% had stage I, II and III CRC respectively; tumor staging was unknown for 3%. After adjusting for prognostic factors (age, stage, lymph node stage, grade, lesion site, perineural invasion, lymphvascular invasion), the risk of CRC relapse or death from CRC was approximately 60% lower compared to patients who were not postoperative aspirin users (Hazard Ratio=0.38, 95% Confidence Interval=0.17-0.84, p=0.017). No benefit was observed for preoperative use of aspirin. CONCLUSION: In this single-Institution study, with long-term follow-up of patients with stage I-III-resected CRC, postoperative aspirin use was associated with reduced risk of relapse of and death from CRC.
Assuntos
Aspirina/administração & dosagem , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Recidiva Local de Neoplasia/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Período Pós-Operatório , Modelos de Riscos Proporcionais , Adulto JovemRESUMO
BACKGROUND & AIMS: Recent observational studies showed that post-operative aspirin use reduces cancer relapse and death in the earliest stages of colorectal cancer. We sought to evaluate the cost-effectiveness of aspirin as an adjuvant therapy in Stage I and II colorectal cancer patients aged 65 years and older. METHODS: Two five-state Markov models were constructed separately for Stage I and II colorectal cancer using TreeAge Pro 2014. Two hypothetical cohorts of 10,000 individuals at a starting age of 65 years and with colorectal cancer in remission were put through the models separately. Cost-effectiveness of aspirin was evaluated against no treatment (Stage I and II) and capecitabine (Stage II) over a 20-year period from the United States societal perspective. Extensive one-way sensitivity analyses and multivariable Probabilistic Sensitivity Analyses (PSA) were performed. RESULTS: In the base case analyses, aspirin was cheaper and more effective compared to other comparators in both stages. Sensitivity analyses showed that no treatment and capecitabine (Stage II only) can be cost-effective alternatives if the utility of taking aspirin is below 0.909, aspirin's annual fatal adverse event probability exceeds 0.57%, aspirin's relative risk of disease progression is 0.997 or more, or when capecitabine's relative risk of disease progression is less than 0.228. Probabilistic Sensitivity Analyses (PSA) further showed that aspirin could be cost-effective 50% to 80% of the time when the willingness-to-pay threshold was varied from USD 20,000 to USD 100,000. CONCLUSION: Even with a modest treatment benefit, aspirin is likely to be cost-effective in Stage I and II colorectal cancer, thus suggesting a potential unique role in secondary prevention in this group of patients.
Assuntos
Aspirina/economia , Aspirina/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Cadeias de Markov , Idoso , Anti-Inflamatórios não Esteroides/economia , Anti-Inflamatórios não Esteroides/uso terapêutico , Antimetabólitos Antineoplásicos/economia , Antimetabólitos Antineoplásicos/uso terapêutico , Capecitabina , Quimioterapia Adjuvante/métodos , Neoplasias Colorretais/patologia , Análise Custo-Benefício , Desoxicitidina/análogos & derivados , Desoxicitidina/economia , Desoxicitidina/uso terapêutico , Fluoruracila/análogos & derivados , Fluoruracila/economia , Fluoruracila/uso terapêutico , Humanos , Modelos Econômicos , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Avaliação de Resultados em Cuidados de Saúde/economia , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Anos de Vida Ajustados por Qualidade de Vida , Indução de Remissão , Reprodutibilidade dos Testes , Prevenção Secundária/métodosRESUMO
Probably more than any country, Singapore has made significant investment into the biomedical enterprise as a proportion of its economy and size. This focus recently witnessed a shift towards a greater emphasis on translational and clinical development. Key to the realisation of this strategy will be Academic Medical Centres (AMCs), as a principal tool to developing and applying useful products for the market and further improving health outcomes. Here, we explore the principal value proposition of the AMC to Singapore society and its healthcare system. We question if the values inherent within academic medicine--that of inquiry, innovation, pedagogy and clinical exceptionalism--can be compatible with the seemingly paradoxical mandate of providing cost-effective or rationed healthcare.
Assuntos
Centros Médicos Acadêmicos/economia , Financiamento Governamental , Custos de Cuidados de Saúde , Qualidade da Assistência à Saúde , Centros Médicos Acadêmicos/organização & administração , Análise Custo-Benefício , Alocação de Recursos para a Atenção à Saúde , SingapuraRESUMO
CONTEXT: The Functional Assessment of Cancer Therapy--Breast Symptom Index (FBSI) is an eight-item instrument extracted from the Functional Assessment of Cancer Therapy--Breast (FACT-B). There has been no formal assessment of this eight-item version. OBJECTIVES: This study aimed to examine the measurement properties of and comparability between the English and the Chinese versions of the FBSI and to compare it with its parent instrument, the FACT-B, in breast cancer patients in Singapore. METHODS: This was an observational study of 271 breast cancer patients. Known-group validity of FBSI scores was assessed using four health indicators. Convergent and divergent validity was examined by correlation coefficients between the FBSI and the FACT-B. Responsiveness was assessed in relation to longitudinal changes in performance status. Test-retest reliability was evaluated by the intraclass correlation coefficient. Multiple regression analyses were performed to compare the scores on the two language versions. Receiver operating characteristic curve analyses were used for comparison between the FBSI and the FACT-B. RESULTS: For both language versions, the FBSI demonstrated known-group validity, convergent and divergent validity, and sufficient test-retest reliability (intraclass correlation coefficient = 0.75-0.77). The English version was responsive to changes in performance status. The Chinese version was responsive to decline in performance status, but there was no conclusive evidence about its responsiveness to improvement in performance status. No practical significant difference was found in the outcomes between the two language versions despite minor difference in one item. The FBSI performed comparably with the FACT-B. CONCLUSION: The English and Chinese versions of the FBSI are valid and reliable and provide comparable FBSI scores. The English version is responsive to change, whereas the responsiveness of the Chinese version warrants further study.
Assuntos
Atitude Frente a Saúde , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/terapia , Avaliação de Resultados em Cuidados de Saúde/métodos , Satisfação do Paciente/estatística & dados numéricos , Qualidade de Vida , Inquéritos e Questionários , Idoso de 80 Anos ou mais , Feminino , Humanos , Prevalência , Singapura/epidemiologia , Resultado do TratamentoRESUMO
BACKGROUND: Leiomyosarcomas (LMS) comprise 25% of soft tissue sarcomas. Recent reports suggest differences in treatment outcomes between uterine (uLMS) and extrauterine (eLMS) disease that may reflect distinct disease biologies. We sought to identify prognostic factors in LMS and clinicopathologic differences between uLMS and eLMS. METHODS: This is a single-center retrospective study evaluating 97 eligible patients treated for LMS between 2002 and 2010. RESULTS: Median follow-up was 21.2 months. uLMS affected 53% of patients, and was less common beyond age 60 years compared with eLMS (10% vs. 37%, P = 0.002). Seventy-two percent of patients presented with nonmetastatic disease. Of these, 94% underwent curative surgery, among whom more uLMS patients achieved negative surgical margins (90% vs. 45%, P = 0.003). There were no significant differences in adjuvant therapy use and relapse patterns between uLMS and eLMS. Half of metastatic patients received palliative chemotherapy, among whom 76% received anthracycline-based chemotherapy in first line to which response rate was 31%. Median overall survival was 45.2 months, 49.8 months in uLMS, and 40.5 months in eLMS (P = 0.294). Among patients without metastases, median survival was 60.8 months (77.3 vs. 48.1 mo in uLMS and eLMS, respectively, P = 0.194). In metastatic disease, median survival was 20.7 months (22.0 vs. 17.5 mo in uLMS and eLMS, respectively, P = 0.936). Advanced disease stage, bone metastases and lack of metastasectomy prognosticated for inferior survival. CONCLUSIONS: While demonstrating interesting clinicopathologic differences, the evidence for uLMS and eLMS being biologically distinct remains inconclusive. Disease stage is prognostically most important in LMS.
Assuntos
Leiomiossarcoma/mortalidade , Leiomiossarcoma/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias Uterinas/mortalidade , Neoplasias Uterinas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos de Coortes , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Histerectomia/métodos , Estimativa de Kaplan-Meier , Leiomiossarcoma/terapia , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/mortalidade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Sarcoma/mortalidade , Sarcoma/patologia , Sarcoma/terapia , Análise de Sobrevida , Resultado do Tratamento , Neoplasias Uterinas/terapiaRESUMO
A high-quality body of evidence supports the use of aspirin in reducing sporadic and hereditary adenomatous polyps, and numerous observational studies point to a reduction in colorectal cancer (CRC) risk. However, using aspirin as an adjuvant therapy in established CRC was until recently inconceivable. Now, evidence from both observational and clinical trials of aspirin for other indications suggests that aspirin initiation after (or before) the diagnosis of CRC improves CRC-specific mortality. These exciting findings need to be confirmed in prospective randomized trials that are underway. The recent failure of adjuvant irinotecan, bevacizumab, and cetuximab clinical trials compels us to reconsider our assumptions and paradigms for treating CRC. In this Review, we summarize clinical and preclinical evidence supporting aspirin use in established CRC and outline a framework for better understanding aspirin activity in the pathogenesis of CRC. We describe the data supporting adjuvant aspirin in resected CRC, including the issues of dose, duration and toxicity, and discuss potential biomarkers that may help better select patients for aspirin therapy.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Quimioterapia Adjuvante , Humanos , PrognósticoRESUMO
Considerable evidence supports the effectiveness of aspirin for chemoprevention of colorectal cancer (CRC) in addition to its well-established benefits in the prevention of vascular disease. Epidemiologic studies have consistently observed an inverse association between aspirin use and risk of CRC. A recent pooled analysis of a long-term posttrial follow-up of nearly 14,000 patients from four randomized, cardiovascular disease prevention trials showed that daily aspirin treatment for about five years was associated with a 34% reduction in 20-year CRC mortality. A separate metaanalysis of nearly 3,000 patients with a history of colorectal adenoma or cancer in four randomized adenoma prevention trials showed that aspirin reduced the occurrence of advanced adenomas by 28% and any adenoma by 17%. Aspirin has also been shown to be beneficial in a clinical trial of patients with Lynch syndrome, a hereditary CRC syndrome; in those treated with aspirin for at least two years, there was a 50% or more reduction in the risk of CRC commencing five years after randomization and after aspirin had been discontinued. A few observational studies have shown an increase in survival among patients with CRC who use aspirin. Taken together, these findings strengthen the case for consideration of long-term aspirin use in CRC prevention. Despite these compelling data, there is a lack of consensus about the balance of risks and benefits associated with long-term aspirin use, particularly in low-risk populations. The optimal dose to use for cancer prevention and the precise mechanism underlying aspirin's anticancer effect require further investigation.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Neoplasias Colorretais/prevenção & controle , HumanosRESUMO
BACKGROUND: High quality evidence indicates that aspirin is effective in reducing colorectal polyps; and numerous epidemiological studies point towards an ability to prevent colorectal cancer. However the role of Aspirin as an adjuvant agent in patients with established cancers remains to be defined. Recently a nested case-control study within the Nurses Health cohort suggested that the initiation of Aspirin after the diagnosis of colon cancer reduced overall colorectal cancer specific mortality. Although this data is supportive of Aspirin's biological activity in this disease and possible role in adjuvant therapy, it needs to be confirmed in a randomized prospective trial. METHODS/DESIGN: We hypothesize through this randomized, placebo-controlled adjuvant study, that Aspirin in patients with dukes C or high risk dukes B colorectal cancer (ASCOLT) can improve survival in this patient population over placebo control. The primary endpoint of this study is Disease Free Survival and the secondary Endpoint is 5 yr Overall Survival. This study will randomize eligible patients with Dukes C or high risk Dukes B colorectal cancer, after completion of surgery and standard adjuvant chemotherapy (+/- radiation therapy for rectal cancer patients) to 200 mg Aspirin or Placebo for 3 years. Stratification factors include study centre, rectal or colon cancer stage, and type of adjuvant chemotherapy (exposed/not exposed to oxaliplatin). After randomization, patient will be followed up with 3 monthly assessments whilst on study drug and for a total of 5 years. Patients with active peptic ulcer disease, bleeding diathesis or on treatment with aspirin or anti-platelet agents will be excluded from the study. DISCUSSION: This study aims to evaluate Aspirin's role as an adjuvant treatment in colorectal cancer. If indeed found to be beneficial, because aspirin is cheap, accessible and easy to administer, it will positively impact the lives of many individuals in Asia and globally. TRIALS REGISTRATION: Clinicaltrials.gov: NCT00565708.