RESUMO
BACKGROUND: Sub-Saharan Africa is simultaneously facing a rising incidence of cancer and a dearth of medical professionals because of insufficient training numbers and emigration, creating a growing shortage of cancer care. To combat this, Massachusetts General Hospital and Beth Israel Deaconess Medical Center partnered with institutions in South Africa, Tanzania, and Rwanda to develop a fellowship exchange program to supplement the training of African oncologists practicing in their home countries. METHODS: In its initial year, 2018, the Program for Enhanced Training in Cancer (POETIC) hosted a pilot cohort of seven fellows for 3-week observerships in their areas of interest. Researchers distributed questionnaires for program evaluation to participants prior to arrival and upon departure; additionally, three participated in semistructured interviews. RESULTS: Five themes emerged from the qualitative data: expectations of POETIC, differences between oncology in the U.S. and in sub-Saharan Africa, positive elements of the program, areas for improvement, and potential impact. Fellows identified several elements of Western health care that will inform their practice: patient-centered care; clinical trials; and collaboration among medical, radiation, and surgical oncologists. From the quantitative data, feedback was primarily around logistical areas for improvement. CONCLUSION: POETIC was found to be feasible and valuable. The results from the pilot year justify the program's continuation in hopes of strengthening global health partnerships to support oncology training in Africa. One weakness is the small number of fellows, which will limit the impact of the study and the relevance of its conclusions. Future research will report on the expansion of the program and follow-up with former participants. IMPLICATIONS FOR PRACTICE: This work presents a novel model for fellowship exchange between lower- and higher-resourced areas. The program is a short-term observership with tumor boards and didactic teaching sessions incorporated. By attracting oncologists who aim to practice in their home countries, it facilitates international collaboration without contributing to the preexisting lack of medical professionals in low- and middle-income countries.
Assuntos
Fortalecimento Institucional/métodos , Oncologia/educação , Assistência Centrada no Paciente/métodos , África , HumanosAssuntos
Custos de Cuidados de Saúde , Avaliação de Processos e Resultados em Cuidados de Saúde/economia , Seguro de Saúde Baseado em Valor/economia , Aquisição Baseada em Valor/economia , Redução de Custos , Análise Custo-Benefício , Custos de Cuidados de Saúde/tendências , Humanos , Avaliação de Processos e Resultados em Cuidados de Saúde/tendências , Resultado do Tratamento , Aquisição Baseada em Valor/tendênciasRESUMO
PURPOSE: High-risk human papillomaviruses (hrHPV) are the primary cause of cervical cancer. Human papillomavirus (HPV) vaccination is expected to prevent cervical cancers caused by the HPV types included in vaccines and possibly by cross-protection from other types. This study sought to determine the hrHPV type distribution in women at a rural Zimbabwe hospital. METHODS: We implemented a cross-sectional study at the Karanda Mission Hospital. Using the Visual Inspection with Acetic Acid Cervicography technique, clinicians collected cervical swabs from 400 women presenting for screening for cervical cancer. Samples were initially analyzed by Cepheid GeneXpert; candidate hrHPV genotypes were further characterized using the Anyplex II HPV28 Detection Kit. RESULTS: Twenty-one percent of the 400 women were positive for a high-risk genotype when using the GeneXpert analyzer; 17% were positive when using the multiplex analysis. Almost two thirds of the hrHPV women had a single DNA type identified, whereas one third had multiple genotypes, ranging from 2 to 5. hrHPV was observed more frequently in HIV-positive than in HIV-negative women (27% v 15%). Of the 113 isolates obtained, 77% were hrHPV genotypes not included in the bivalent or quadrivalent vaccines, and 47% represented DNA types not covered in the nonavalent vaccine. Forty-seven percent of the women with hrHPV harbored a single genotype that was not covered by the nonavalent vaccine. CONCLUSION: A large fraction of hrHPV isolates from women participating in a cervical cancer screening program in northern Zimbabwe are DNA types not covered by the bivalent, quadrivalent, or nonavalent vaccines. These findings suggest the importance of characterizing the hrHPV DNA types isolated from cervical neoplasia in this population and determining whether cross-immunization against these genotypes develops after administration of the vaccines in current use.
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Alphapapillomavirus , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Estudos Transversais , Detecção Precoce de Câncer , Feminino , Hospitais , Humanos , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Prevalência , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Zimbábue/epidemiologiaRESUMO
The global cancer burden is estimated to have risen to 18.1 million new cases and 9.6 million deaths in 2018. By 2030, the number of cancer cases is projected to increase to 24.6 million and the number of cancer deaths, to 13 million. Global data mask the social and health disparities that influence cancer incidence and survival. Inequality in exposure to carcinogens, education, access to quality diagnostic services, and affordable treatments all affect the probability of survival. Worryingly, despite the fact that many cancers could be prevented by stronger public health actions and many others could be largely cured by better access to diagnostics and affordable treatments, the international community has yet to make a substantial move to tackle this challenge. In prostate cancer, studies show that there are geographic and racial/ethnic distribution differences as well as a number of other variables, including environmental factors, limited access to standard cancer treatments, reduced probability to be included in trials, and the financial burden of cancer treatments. Financial burden for the patients can result in poor adherence, increased debt, and poor long-term outcomes. The following article will discuss some of the important causes for disparity in prostate cancer and prostate cancer care, focused on the current situation in the United States, as well as possible remedies to address these causes.
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Disparidades em Assistência à Saúde , Neoplasias da Próstata/epidemiologia , Atenção à Saúde/estatística & dados numéricos , Etnicidade , Saúde Global , Gastos em Saúde , Acessibilidade aos Serviços de Saúde , Disparidades em Assistência à Saúde/estatística & dados numéricos , Humanos , Incidência , Masculino , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/terapia , Grupos Raciais , Fatores de Risco , Fatores SocioeconômicosRESUMO
PURPOSE: To better understand the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS v1.1) and the ASCO Value Framework Net Health Benefit score version 2 (ASCO-NHB v2), ESMO and ASCO collaborated to evaluate the concordance between the frameworks when used to assess clinical benefit attributable to new therapies. METHODS: The 102 randomized controlled trials in the noncurative setting already evaluated in the field testing of ESMO-MCBS v1.1 were scored using ASCO-NHB v2 by its developers. Measures of agreement between the frameworks were calculated and receiver operating characteristic curves used to define thresholds for the ASCO-NHB v2 corresponding to ESMO-MCBS v1.1 categories. Studies with discordant scoring were identified and evaluated to understand the reasons for discordance. RESULTS: The correlation of the 102 pairs of scores for studies in the noncurative setting is estimated to be 0.68 (Spearman's rank correlation coefficient; overall survival, 0.71; progression-free survival, 0.67). Receiver operating characteristic curves identified thresholds for ASCO-NHB v2 for facilitating comparisons with ESMO-MCBS v1.1 categories. After applying pragmatic threshold scores of 40 or less (ASCO-NHB v2) and 2 or less (ESMO-MCBS v1.1) for low benefit and 45 or greater (ASCO-NHB v2) and 4 to 5 (ESMO-MCBS v1.1) for substantial benefit, 37 discordant studies were identified. Major factors that contributed to discordance were different approaches to evaluation of relative and absolute gain for overall survival and progression-free survival, crediting tail of the curve gains, and assessing toxicity. CONCLUSION: The agreement between the frameworks was higher than observed in other studies that sought to compare them. The factors that contributed to discordant scores suggest potential approaches to improve convergence between the scales.
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Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Avaliação de Resultados em Cuidados de Saúde , Antineoplásicos/efeitos adversos , Pesquisa Comparativa da Efetividade , Humanos , Neoplasias/mortalidade , Intervalo Livre de Progressão , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Reprodutibilidade dos Testes , Fatores de Risco , Fatores de TempoRESUMO
In response to rising cancer incidence and mortality rates in low- and middle-income countries and the increasingly global profile of ASCO's membership, the ASCO Board of Directors appointed the Global Oncology Leadership Task Force (Task Force) to provide recommendations on ASCO's engagement in global oncology. To accomplish its work, the Task Force convened meetings of global oncology experts, conducted focus group discussions with member groups, did site visits to South America and India, and met regularly to analyze the findings and develop recommendations. Task Force findings included global concerns, such as access to care, and specific concerns of middle- and low-resource settings. The need to strengthen health systems and the importance of alliances with a range of international cancer stakeholders were emphasized. Task Force recommendations to the ASCO Board of Directors were based on a three-part global oncology strategy of professional development, improvement of access to quality care, and acceleration of global oncology research. Specific areas of focus within each of these strategic pillars are provided along with an update on areas of ASCO activity as these recommendations are implemented.
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Comitês Consultivos , Liderança , Oncologia/organização & administração , Oncologia/normas , Sociedades Médicas , Atenção à Saúde , Humanos , Melhoria de Qualidade , Qualidade da Assistência à Saúde , América do SulRESUMO
Clinical trials and meta-analyses investigating bisphosphonates as an adjuvant breast cancer therapy have shown a consistent trend, with postmenopausal women and women receiving ovarian suppression with gonadotropin-releasing hormone therapy gaining improved breast cancer outcomes with the use of adjuvant bisphosphonate therapy. The interpretation of these data is controversial, because the primary endpoints of the majority of adjuvant bisphosphonate studies have been negative. Pros and cons as well as the value of adjuvant bisphosphonate therapy are discussed here.
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Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Difosfonatos/uso terapêutico , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/fisiopatologia , Neoplasias da Mama/patologia , Feminino , Hormônio Liberador de Gonadotropina/uso terapêutico , HumanosRESUMO
PURPOSE: Members of a family with hereditary gastrointestinal stromal tumors (GISTs) and a germline KIT oncogene mutation were evaluated for other potential syndrome manifestations. A tumor from the proband was analyzed to compare features with sporadic GISTs. PATIENTS AND METHODS: Members of a kindred in which six relatives in four consecutive generations comprised an autosomal dominant pattern of documented GISTs and cutaneous lesions underwent physical examination, imaging studies, and germline KIT analysis. A recurrent GIST from the proband was studied using microarray, karyotypic, immunohistochemical, and immunoblotting techniques. RESULTS: In addition to evidence of multiple GISTs, lentigines, malignant melanoma, and an angioleiomyoma were identified in relatives. A previously reported gain-of-function missense mutation in KIT exon 11 (T --> C) that results in a V559A substitution within the juxtamembrane domain was identified in three family members. The proband's recurrent gastric GIST had a 44,XY-14,-22 karyotype and immunohistochemical evidence of strong diffuse cytoplasmic KIT expression without expression of actin, desmin, or S-100. Immunoblotting showed strong expression of phosphorylated KIT and downstream signaling intermediates (AKT and MAPK) at levels comparable with those reported in sporadic GISTs. cDNA array profiling demonstrated clustering with sporadic GISTs, and expression of GIST markers comparable to sporadic GISTs. CONCLUSION: These studies provide the first evidence that gene expression and mechanisms of cytogenetic progression and cell signaling are indistinguishable in familial and sporadic GISTs. Current investigations of molecularly targeted therapies in GIST patients provide opportunities to increase the understanding of features of the hereditary syndrome, and risk factors and molecular pathways of the neoplastic phenotypes.
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Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/patologia , Perfilação da Expressão Gênica , Proteínas Proto-Oncogênicas c-kit/genética , Adulto , Idoso , Análise Mutacional de DNA , Progressão da Doença , Feminino , Mutação em Linhagem Germinativa , Humanos , Imuno-Histoquímica , Cariotipagem , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Linhagem , Exame Físico , Transdução de Sinais , SíndromeRESUMO
BACKGROUND: Many antiangiogenic molecules are proteolytically cleaved from larger plasma proteins. For example, plasminogen activators cleave plasminogen into plasmin, and plasmin is converted into angiostatin in the presence of sulfhydryl donors. We thus investigated whether the antiangiogenic activity in plasma could be increased by treatment with recombinant tissue plasminogen activator (rt-PA) and the sulfhydryl donor captopril. METHODS: Human plasma was treated with rt-PA (10 micro g/mL) and/or captopril (1 micro M). Angiogenesis was measured in vitro by human endothelial cell tube formation and endothelial cell proliferation and in vivo in mice with the Matrigel plug assay. Angiostatin was removed from treated plasma by affinity chromatography, immunoprecipitation, or ion-exchange chromatography, and the antiangiogenic activity of the depleted plasma was assessed by tube formation. Three cancer patients were treated with rt-PA and captopril, and their pretreatment and post-treatment plasmas were tested for antiangiogenic activity in vitro. RESULTS: Angiogenesis in vitro was stimulated by untreated plasma and inhibited by plasma that had been treated with rt-PA and captopril but was not affected by treatment with rt-PA and/or captopril alone. In vivo angiogenesis in Matrigel plugs was substantially lower in mice treated with rt-PA and captopril than in untreated control mice. Antiangiogenic activity in treated plasma was largely retained after angiostatin was removed: treated plasma inhibited angiogenesis by 64.3% (95% confidence interval [CI] = 46.4% to 82.2%), relative to untreated plasma, and treated plasma depleted of angiostatin by affinity chromatography or immunoprecipitation inhibited angiogenesis by 65.1% (95% CI = 53.8% to 76.4%) or 63.7% (95% CI = 50.9% to 76.5%), respectively. Antiangiogenic activity of plasma from three cancer patients was higher after treatment with rt-PA and captopril than before such treatment. CONCLUSION: Treatment with rt-PA and captopril induced antiangiogenic activity in vitro and in vivo that appears to be independent of angiostatin.
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Inibidores da Angiogênese/farmacologia , Captopril/farmacologia , Neovascularização Patológica/tratamento farmacológico , Fragmentos de Peptídeos/farmacologia , Plasma/efeitos dos fármacos , Ativadores de Plasminogênio/farmacologia , Plasminogênio/farmacologia , Inibidores da Angiogênese/administração & dosagem , Angiostatinas , Animais , Captopril/administração & dosagem , Técnicas de Cultura de Células , Cromatografia , Colágeno , Combinação de Medicamentos , Eletroforese em Gel de Poliacrilamida , Endotélio Vascular/efeitos dos fármacos , Feminino , Humanos , Laminina , Camundongos , Pessoa de Meia-Idade , Neovascularização Patológica/metabolismo , Fragmentos de Peptídeos/administração & dosagem , Plasma/metabolismo , Plasminogênio/administração & dosagem , Ativadores de Plasminogênio/administração & dosagem , Testes de Precipitina , Proteoglicanas , Proteínas Recombinantes/farmacologiaRESUMO
PURPOSE: Physicians frequently receive payment for enrolling subjects onto clinical trials. Some view these payments as conflicts of interest. Others contend that these payments are necessary reimbursements for conducting clinical research. We evaluated the clinical and nonclinical hours and costs associated with conducting a mock phase III clinical research trial. METHODS: We collected data from representatives of 21 clinical sites, on the numbers of hours associated with 13 activities necessary to the conduct of clinical research. The hours were based on enrolling 20 patients in a 12-month randomized placebo-controlled trial of a new chemotherapeutic agent. The outcome measures were disease progression and quality-of-life reports. These costs were evaluated for both government and pharmaceutical industry-sponsored trials. RESULTS: On average, 4,012 hours (range, 1,512 to 13,319 hours) were required for a government-sponsored trial, and 3,998 hours (range: 1735 to 15,699) were required for a pharmaceutical industry-sponsored trial involving 20 subjects with 17 office visits, or approximately 200 hours per subject. Thirty-two percent of the hours were devoted to nonclinical activities, such as institutional review board submission and completion of clinical reporting forms. On average, excluding overhead expenses, it cost slightly more than 6,094 dollars (range, 2,098 dollars to 19,285 dollars) per enrolled subject for an industry-sponsored trial, including 1,999 dollars devoted to nonclinical costs. CONCLUSION: Based on the results of our mock trial, the time required for nontreatment trial activities is considerable, and the associated costs are substantial.
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Antineoplásicos/economia , Pesquisa Biomédica/economia , Ensaios Clínicos Fase III como Assunto/economia , Custos de Cuidados de Saúde , Neoplasias/economia , Ensaios Clínicos Controlados Aleatórios como Assunto/economia , Antineoplásicos/uso terapêutico , Custos e Análise de Custo , Farmacoeconomia , Financiamento Governamental , Humanos , Estudos Multicêntricos como Assunto , Neoplasias/tratamento farmacológico , PlacebosRESUMO
PURPOSE: To perform a phase I trial of recombinant human endostatin (rhEndostatin; EntreMed, Rockville, MD) given as a daily 20-minute intravenous (IV) injection in adult patients with refractory solid tumors. PATIENTS AND METHODS: The daily dose was increased from 15 to 240 mg/m(2) by a factor of 100% in cohorts of three patients. In the absence of dose-limiting toxicity, uninterrupted treatment was continued until the tumor burden increased by more than 50% from baseline. Correlative studies included dynamic contrast-enhanced magnetic resonance imaging of tumor blood flow, urinary vascular endothelial growth factor and basic fibroblast growth factor levels, rhEndostatin serum pharmacokinetics, and monitoring of circulating antibodies to rhEndostatin. RESULTS: There were no notable treatment related toxicities among 15 patients receiving a total of 50 monthly cycles of rhEndostatin. One patient with a pancreatic neuroendocrine tumor had a minor response and two patients showed disease stabilization. Linearity in the pharmacokinetics of rhEndostatin was indicated by dose-proportionate increases in the area under the curve for the first dose and the peak serum concentration at steady state. Daily systemic exposure to rhEndostatin in patients receiving 240 mg/m(2)/d was approximately 50% lower than that provided by the therapeutically optimal dose in preclinical studies. CONCLUSION: rhEndostatin administered as a 20-minute daily IV injection at doses up to 240 mg/m(2) showed no significant toxicities. Evidence of clinical benefit was observed in three patients. Due to high variability between the peak and trough serum concentrations associated with the repeated short IV infusion schedule, daily serum drug levels only briefly exceeded concentrations necessary for in vitro antiangiogenic effects.
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Inibidores da Angiogênese/uso terapêutico , Colágeno/uso terapêutico , Neoplasias/tratamento farmacológico , Fragmentos de Peptídeos/uso terapêutico , Adulto , Idoso , Inibidores da Angiogênese/efeitos adversos , Inibidores da Angiogênese/farmacocinética , Colágeno/efeitos adversos , Colágeno/farmacocinética , Creatinina/metabolismo , Endostatinas , Fatores de Crescimento Endotelial/urina , Feminino , Fator 2 de Crescimento de Fibroblastos/urina , Humanos , Infusões Intravenosas , Linfocinas/urina , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias/patologia , Fragmentos de Peptídeos/efeitos adversos , Fragmentos de Peptídeos/farmacocinética , Proteínas Recombinantes/uso terapêutico , Fatores de Tempo , Distribuição Tecidual , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularAssuntos
Oncologia/tendências , Feminino , Humanos , Masculino , Neoplasias/diagnóstico , Neoplasias/terapiaRESUMO
The national cost of cancer care is projected to reach $173 billion by 2020, increasing from $125 billion in 2010. This steep upward cost trajectory has placed enormous an financial burden on patients, their families, and society as a whole and raised major concern about the ability of the health care system to provide and sustain high-quality cancer care. To better understand the cost drivers of cancer care and explore approaches that will mitigate the problem, the National Cancer Policy Forum of the Institute of Medicine held a workshop entitled "Delivering Affordable Cancer Care in the 21st Century" in October 2012. Workshop participants included bioethicists, health economists, primary care physicians, and medical, surgical, and radiation oncologists, from both academic and community settings. All speakers expressed a sense of urgency about the affordability of cancer care resulting from the future demographic trend as well as the high cost of emerging cancer therapies and rapid diffusion of new technologies in the absence to evidence indicating improved outcomes for patients. This article is our summary of presentations at the workshop that highlighted the overuse and underuse of screening, treatments, and technologies throughout the cancer care continuum in oncology practice in the United States.