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1.
N Engl J Med ; 388(3): 228-239, 2023 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-36652354

RESUMO

BACKGROUND: Alterations in fibroblast growth factor receptor 2 (FGFR2) have emerged as promising drug targets for intrahepatic cholangiocarcinoma, a rare cancer with a poor prognosis. Futibatinib, a next-generation, covalently binding FGFR1-4 inhibitor, has been shown to have both antitumor activity in patients with FGFR-altered tumors and strong preclinical activity against acquired resistance mutations associated with ATP-competitive FGFR inhibitors. METHODS: In this multinational, open-label, single-group, phase 2 study, we enrolled patients with unresectable or metastatic FGFR2 fusion-positive or FGFR2 rearrangement-positive intrahepatic cholangiocarcinoma and disease progression after one or more previous lines of systemic therapy (excluding FGFR inhibitors). The patients received oral futibatinib at a dose of 20 mg once daily in a continuous regimen. The primary end point was objective response (partial or complete response), as assessed by independent central review. Secondary end points included the response duration, progression-free and overall survival, safety, and patient-reported outcomes. RESULTS: Between April 16, 2018, and November 29, 2019, a total of 103 patients were enrolled and received futibatinib. A total of 43 of 103 patients (42%; 95% confidence interval, 32 to 52) had a response, and the median duration of response was 9.7 months. Responses were consistent across patient subgroups, including patients with heavily pretreated disease, older adults, and patients who had co-occurring TP53 mutations. At a median follow-up of 17.1 months, the median progression-free survival was 9.0 months and overall survival was 21.7 months. Common treatment-related grade 3 adverse events were hyperphosphatemia (in 30% of the patients), an increased aspartate aminotransferase level (in 7%), stomatitis (in 6%), and fatigue (in 6%). Treatment-related adverse events led to permanent discontinuation of futibatinib in 2% of the patients. No treatment-related deaths occurred. Quality of life was maintained throughout treatment. CONCLUSIONS: In previously treated patients with FGFR2 fusion or rearrangement-positive intrahepatic cholangiocarcinoma, the use of futibatinib, a covalent FGFR inhibitor, led to measurable clinical benefit. (Funded by Taiho Oncology and Taiho Pharmaceutical; FOENIX-CCA2 ClinicalTrials.gov number, NCT02052778.).


Assuntos
Antineoplásicos , Neoplasias dos Ductos Biliares , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma , Inibidores de Proteínas Quinases , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos , Idoso , Humanos , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/metabolismo , Ductos Biliares Intra-Hepáticos/metabolismo , Ductos Biliares Intra-Hepáticos/patologia , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/genética , Colangiocarcinoma/metabolismo , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Qualidade de Vida , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Antineoplásicos/administração & dosagem
2.
Oncologist ; 28(9): 827-e822, 2023 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-37104870

RESUMO

BACKGROUND: Patients with advanced esophageal cancer carry poor prognoses; limited data exist to guide second-line therapy in the metastatic setting. Paclitaxel has been used yet is associated with limited efficacy. There is preclinical evidence of synergy between paclitaxel and cixutumumab, a monoclonal antibody targeting insulin-like growth factor-1 receptor. We conducted a randomized phase II trial of paclitaxel (arm A) versus paclitaxel plus cixutumumab (arm B) in the second-line for patients with metastatic esophageal or gastroesophageal junction (GEJ) cancers. METHODS: The primary endpoint was progression-free survival (PFS); 87 patients (43 in arm A, 44 in arm B) were treated. RESULTS: Median PFS was 2.6 months in arm A [90% CL 1.8-3.5] and 2.3 months in arm B [90% 2.0-3.5], P = .86. Stable disease was observed in 29 (33%) patients. Objective response rates for Arms A and B were 12% [90% CI, 5-23%] and 14% [90% CI, 6-25%]. Median overall survival was 6.7 months [90% CL 4.9-9.5] in arm A and 7.2 months [90% CL 4.9-8.1] in arm B, P = 56. CONCLUSION: The addition of cixutumumab to paclitaxel in second-line therapy of metastatic esophageal/GEJ cancer was well tolerated but did not improve clinical outcomes relative to standard of care (ClinicalTrials.gov Identifier: NCT01142388).


Assuntos
Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Paclitaxel/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Neoplasias Gástricas/tratamento farmacológico , Junção Esofagogástrica/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
3.
J Natl Compr Canc Netw ; 19(2): 122-125, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33545684

RESUMO

BACKGROUND: Translation of basic discoveries to clinical care for patients with cancer is a difficult process greatly enabled by physician-trained researchers. Three categories of physicians, with responsibilities spanning from laboratory and preclinical research to direct patient care, are involved in the translational research continuum: physician-scientist (PS), clinician investigator (CI), and academic clinician (AC). METHODS: To define how protected time for research efforts is supported, the Association of American Cancer Institutes (AACI) conducted a survey of their member institutions, obtaining 56 responses documenting time spent in research and clinical activities across multiple cancer disciplines, and providing information about funding streams for the different categories of cancer physicians. RESULTS: Responses showed that PSs and ACs are minimally involved in clinical research activities; the driver or clinical research in academic cancer centers is the CI. A significant concern was a lack of stable funding streams for nonbillable clinical research activities, putting the sustainability of the CI in jeopardy. Limited funding was derived from hospital sources, with most support derived from cancer center sources. CONCLUSIONS: This study highlights the importance of the CI in translational cancer medicine and represents a call to action for institutions and research funding agencies to develop new programs targeted toward CI support to ensure continued progress against cancer.


Assuntos
Neoplasias , Médicos , Pesquisadores , Pesquisa Translacional Biomédica , Pessoal de Saúde , Humanos , Neoplasias/terapia , Assistência ao Paciente
4.
J Thromb Thrombolysis ; 51(2): 430-436, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33047244

RESUMO

To study whether a diagnosis of cancer affects the clinical presentation and outcomes of patients with pulmonary embolism (PE). A retrospective analysis was performed of all consecutive patients diagnosed with PE on a computed tomography scan from 2014 to 2016 at an urban tertiary-referral medical center. Baseline characteristics, treatment decisions, and mortality data were compared between study subjects with and without a known diagnosis of active cancer. There were 581 subjects, of which 187 (33.0%) had a diagnosis of cancer. On average, cancer subjects tended to be older (64.8 vs. 58.5 years, p < 0.01), had lower body mass index (BMI) (29.0 vs. 31.5 kg/m2, p = 0.01), and were less likely to be active smokers (9.2% vs. 21.1%, p < 0.01), as compared to non-cancer subjects. Cancer subjects were also less likely to present with chest pain (18.2% vs. 37.4%, p < 0.01), syncope (2.7% vs. 6.6%, p = 0.05), bilateral PEs (50% vs. 60%, p = 0.025), and evidence of right heart strain (48% vs. 58%, p = 0.024). There was no difference in-hospital length of stay (8.9 vs. 9.4 days, p = 0.61) or rate of intensive care unit (ICU) admission (31.9% vs. 33.3%, p = 0.75) between the two groups. Presence of cancer increased the risk of all-cause one-year mortality (adjusted HR 9.7, 95% CI 4.8-19.7, p < 0.01); however, it did not independently affect in-hospital mortality (adjusted HR 2.9, 95% CI 0.86-9.87, p = 0.086). Patients with malignancy generally presented with less severe PE. In addition, malignancy did not independently increase the risk of in-hospital mortality among PE patients.


Assuntos
Neoplasias/complicações , Embolia Pulmonar/complicações , Adulto , Idoso , Feminino , Mortalidade Hospitalar , Hospitalização , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/mortalidade , Estudos Retrospectivos
5.
Int J Mol Sci ; 23(1)2021 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-35008602

RESUMO

Understanding metabolic and immune regulation inherent to patient populations is key to improving the radiation response for our patients. To date, radiation therapy regimens are prescribed based on tumor type and stage. Patient populations who are noted to have a poor response to radiation such as those of African American descent, those who have obesity or metabolic syndrome, or senior adult oncology patients, should be considered for concurrent therapies with radiation that will improve response. Here, we explore these populations of breast cancer patients, who frequently display radiation resistance and increased mortality rates, and identify the molecular underpinnings that are, in part, responsible for the radiation response and that result in an immune-suppressive tumor microenvironment. The resulting immune phenotype is discussed to understand how antitumor immunity could be improved. Correcting nutrient deficiencies observed in these populations should be considered as a means to improve the therapeutic index of radiation therapy.


Assuntos
Neoplasias da Mama/radioterapia , Dieta , Nutrientes , Negro ou Afro-Americano , Feminino , Humanos , Síndrome Metabólica , Obesidade , Resultado do Tratamento
6.
Oncologist ; 25(5): e798-e807, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31852811

RESUMO

BACKGROUND: The addition of bevacizumab to chemotherapy improved outcomes for patients with metastatic colon cancer. E5204 was designed to test whether the addition of bevacizumab to mFOLFOX6, following neoadjuvant chemoradiation and definitive surgery, could improve overall survival (OS) in patients with stage II/III adenocarcinoma of the rectum. SUBJECTS, MATERIALS, AND METHODS: Patients with stage II/III rectal cancer who had completed neoadjuvant 5-fluorouracil-based chemoradiation and had undergone complete resection were enrolled. Patients were randomized to mFOLFOX6 (Arm A) or mFOLFOX6 with bevacizumab (Arm B) administered every 2 weeks for 12 cycles. RESULTS: E5204 registered only 355 patients (17% of planned accrual goal) as it was terminated prematurely owing to poor accrual. At a median follow-up of 72 months, there was no difference in 5-year overall survival (88.3% vs. 83.7%) or 5-year disease-free survival (71.2% vs. 76.5%) between the two arms. The rate of treatment-related grade ≥ 3 adverse events (AEs) was 68.8% on Arm A and 70.7% on Arm B. Arm B had a higher proportion of patients who discontinued therapy early as a result of AEs and patient withdrawal than did Arm A (32.4% vs. 21.5%, p = .029).The most common grade 3-4 treatment-related AEs were neutropenia, leukopenia, neuropathy, diarrhea (without prior colostomy), and fatigue. CONCLUSION: At 17% of its planned accrual, E5204 did not meet its primary endpoint. The addition of bevacizumab to FOLFOX6 in the adjuvant setting did not significantly improve OS in patients with stage II/III rectal cancer. IMPLICATIONS FOR PRACTICE: At 17% of its planned accrual, E5204 was terminated early owing to poor accrual. At a median follow-up of 72 months, there was no significant difference in 5-year overall survival (88.3% vs. 83.7%) or in 5-year disease-free survival (71.2% vs. 76.5%) between the two arms. Despite significant advances in the treatment of rectal cancer, especially in improving local control rates, the risk of distant metastases and the need to further improve quality of life remain a challenge. Strategies combining novel agents with chemoradiation to improve both distant and local control are needed.


Assuntos
Fluoruracila , Neoplasias Retais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/uso terapêutico , Quimioterapia Adjuvante , Intervalo Livre de Doença , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Estadiamento de Neoplasias , Compostos Organoplatínicos/uso terapêutico , Oxaliplatina/uso terapêutico , Qualidade de Vida , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia
7.
Breast Cancer Res Treat ; 177(1): 77-91, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31165373

RESUMO

PURPOSE: Understanding the molecular mediators of breast cancer survival is critical for accurate disease prognosis and improving therapies. Here, we identified Neuronatin (NNAT) as a novel antiproliferative modifier of estrogen receptor-alpha (ER+) breast cancer. EXPERIMENTAL DESIGN: Genomic regions harboring breast cancer modifiers were identified by congenic mapping in a rat model of carcinogen-induced mammary cancer. Tumors from susceptible and resistant congenics were analyzed by RNAseq to identify candidate genes. Candidates were prioritized by correlation with outcome, using a consensus of three breast cancer patient cohorts. NNAT was transgenically expressed in ER+ breast cancer lines (T47D and ZR75), followed by transcriptomic and phenotypic characterization. RESULTS: We identified a region on rat chromosome 3 (142-178 Mb) that modified mammary tumor incidence. RNAseq of the mammary tumors narrowed the candidate list to three differentially expressed genes: NNAT, SLC35C2, and FAM210B. NNAT mRNA and protein also correlated with survival in human breast cancer patients. Quantitative immunohistochemistry of NNAT protein revealed an inverse correlation with survival in a univariate analysis of patients with invasive ER+ breast cancer (training cohort: n = 444, HR = 0.62, p = 0.031; validation cohort: n = 430, HR = 0.48, p = 0.004). NNAT also held up as an independent predictor of survival after multivariable adjustment (HR = 0.64, p = 0.038). NNAT significantly reduced proliferation and migration of ER+ breast cancer cells, which coincided with altered expression of multiple related pathways. CONCLUSIONS: Collectively, these data implicate NNAT as a novel mediator of cell proliferation and migration, which correlates with decreased tumorigenic potential and prolonged patient survival.


Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Genes Modificadores , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , Receptores de Estrogênio/genética , Animais , Biomarcadores Tumorais , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Incidência , Estimativa de Kaplan-Meier , Proteínas de Membrana/metabolismo , Estadiamento de Neoplasias , Proteínas do Tecido Nervoso/metabolismo , Avaliação de Resultados da Assistência ao Paciente , Prognóstico , Ratos , Receptores de Estrogênio/metabolismo , Transdução de Sinais
8.
J Natl Med Assoc ; 110(1): 4-15, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29510842

RESUMO

While much progress has occurred since the civil rights act of 1964, minorities have continued to suffer disparate and discriminatory access to economic opportunities, education, housing, health care and criminal justice. The latest challenge faced by the physicians and public health providers who serve the African American community is the detrimental, and seemingly insurmountable, causes and effects of violence in impoverished communities of color. According to statistics from the Centers for Disease Control (CDC), the number one killer of black males ages 10-35 is homicide, indicating a higher rate of violence than any other group. Black females are four times more likely to be murdered by a boyfriend or girlfriend than their white counterparts, and although intimate partner violence has declined for both black and white females, black women are still disproportionately killed. In addition, anxiety and depression that can lead to suicide is on the rise among African American adolescents and adults. Through an examination of the role of racism in the perpetuation of the violent environment and an exploration of the effects of gang violence, intimate partner violence/child maltreatment and police use of excessive force, this work attempts to highlight the repercussions of violence in the African American community. The members of the National Medical Association have served the African American community since 1895 and have been advocates for the patients they serve for more than a century. This paper, while not intended to be a comprehensive literature review, has been written to reinforce the need to treat violence as a public health issue, to emphasize the effect of particular forms of violence in the African American community and to advocate for comprehensive policy reforms that can lead to the eradication of this epidemic. The community of African American physicians must play a vital role in the treatment and prevention of violence as well as advocating for our patients, family members and neighbors who suffer from the preventable effects of violence.


Assuntos
Negro ou Afro-Americano , Centers for Disease Control and Prevention, U.S./estatística & dados numéricos , Vigilância da População , Violência/etnologia , Distribuição por Idade , Causas de Morte , Bases de Dados Factuais , Humanos , Grupo Associado , Distribuição por Sexo , Estados Unidos/epidemiologia
9.
Cancer ; 123(9): 1536-1544, 2017 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28055108

RESUMO

BACKGROUND: Prostate cancer (PCa) outcomes are impacted by socioeconomic and biologic factors. Ethnicity plays a role in the former, but little is known about the responsiveness of metastatic PCa to androgen-deprivation therapy (ADT) among races. METHODS: The Surveillance, Epidemiology, and End Results (SEER) registry was used to identify men who were diagnosed with distant, de novo, metastatic PCa from 2004 to 2012. Patterns of presentation, overall survival (OS), and PCa-specific mortality (PCSM) were determined for each race. E3805 clinical trial data also were retrospectively reviewed to assess outcomes of ADT and ADT plus docetaxel by race. RESULTS: Of all PCa diagnoses in SEER, distant, de novo, metastatic disease was diagnosed in 4.2% of non-Hispanic whites, 5.8% of Hispanic whites, 5.7% of blacks, 5.5% of Asians/Pacific Islanders, and 8.8% of American Indians/Alaska Natives (P < .001; chi-square test). The median OS differed by race, with superior OS observed among Asian men (30 months) than among men of other races (range, 24-25 months; P < .001). Asians also had a superior median PCSM (54 months) compared with the other races (range, 35-40 months; P < .001). In E3805, chemohormonal therapy was associated with a median OS of 58.1 months (95% confidence interval, 48.8-72.9 months) and 57.6 months (95% confidence interval, 27.7-57.6 months) in non-Hispanic whites and blacks, respectively. Few Asians participated in the E3805 trial. CONCLUSIONS: Asian men have superior median OS and PCSM for distant, de novo, metastatic PCa than men of other race. Non-Hispanic whites and blacks who receive treatment with ADT or chemohormonal therapy have comparable outcomes. Cancer 2017;123:1536-1544. © 2017 American Cancer Society.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Antineoplásicos/uso terapêutico , Etnicidade , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/etnologia , Taxoides/uso terapêutico , Negro ou Afro-Americano , Idoso , Asiático , Intervalo Livre de Doença , Docetaxel , Hispânico ou Latino , Humanos , Indígenas Norte-Americanos , Masculino , Havaiano Nativo ou Outro Ilhéu do Pacífico , Metástase Neoplásica , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Programa de SEER , Taxa de Sobrevida , Resultado do Tratamento , População Branca
10.
Mod Pathol ; 29(10): 1143-54, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27312066

RESUMO

Protein marker levels in formalin-fixed, paraffin-embedded tissue sections traditionally have been assayed by chromogenic immunohistochemistry and evaluated visually by pathologists. Pathologist scoring of chromogen staining intensity is subjective and generates low-resolution ordinal or nominal data rather than continuous data. Emerging digital pathology platforms now allow quantification of chromogen or fluorescence signals by computer-assisted image analysis, providing continuous immunohistochemistry values. Fluorescence immunohistochemistry offers greater dynamic signal range than chromogen immunohistochemistry, and combined with image analysis holds the promise of enhanced sensitivity and analytic resolution, and consequently more robust quantification. However, commercial fluorescence scanners and image analysis software differ in features and capabilities, and claims of objective quantitative immunohistochemistry are difficult to validate as pathologist scoring is subjective and there is no accepted gold standard. Here we provide the first side-by-side validation of two technologically distinct commercial fluorescence immunohistochemistry analysis platforms. We document highly consistent results by (1) concordance analysis of fluorescence immunohistochemistry values and (2) agreement in outcome predictions both for objective, data-driven cutpoint dichotomization with Kaplan-Meier analyses or employment of continuous marker values to compute receiver-operating curves. The two platforms examined rely on distinct fluorescence immunohistochemistry imaging hardware, microscopy vs line scanning, and functionally distinct image analysis software. Fluorescence immunohistochemistry values for nuclear-localized and tyrosine-phosphorylated Stat5a/b computed by each platform on a cohort of 323 breast cancer cases revealed high concordance after linear calibration, a finding confirmed on an independent 382 case cohort, with concordance correlation coefficients >0.98. Data-driven optimal cutpoints for outcome prediction by either platform were reciprocally applicable to the data derived by the alternate platform, identifying patients with low Nuc-pYStat5 at ~3.5-fold increased risk of disease progression. Our analyses identified two highly concordant fluorescence immunohistochemistry platforms that may serve as benchmarks for testing of other platforms, and low interoperator variability supports the implementation of objective tumor marker quantification in pathology laboratories.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/metabolismo , Imunofluorescência/métodos , Processamento de Imagem Assistida por Computador/métodos , Feminino , Humanos , Reprodutibilidade dos Testes
11.
J Cancer Educ ; 31(3): 481-7, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26048632

RESUMO

This study assessed adult patient's psychosocial support needs and treatment barriers in an urban diverse cancer center. A needs assessment was conducted with a convenience sample of adult oncology patients (n = 113; 71.7 % African American). Most patients were parenting school-age children and worried about them (96 %); 86.7 % would attend a family support program. Among patients who were married or partnered (68 %), 63.7 % were concerned about communication, coping, and emotional support; 53.9 % would attend a couple support program. Patients identified similar treatment barriers: transportation, babysitting for younger children, convenience of time/place, and refreshments. Findings suggest that behavioral health care providers should be available to screen cancer patients and improve access to appropriate psychosocial oncology support programs.


Assuntos
Adaptação Psicológica , Negro ou Afro-Americano/psicologia , Disparidades em Assistência à Saúde , Avaliação das Necessidades , Neoplasias/psicologia , Apoio Social , Adolescente , Adulto , Criança , Comunicação , Feminino , Acessibilidade aos Serviços de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/terapia
12.
J Natl Med Assoc ; 116(2 Pt 2): 219-227, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38368233

RESUMO

Pregnancy and lactation are special life stages that require regular nutritional and medical attention to help protect the health of the mother and promote the growth and development of the offspring. Despite an increased focus on maternal and fetal health over the last several decades, the rates of pregnancy-related morbidity and mortality are increasing in the United States (US). On average, Black women who are pregnant or lactating face greater health disparities and birth complications than other racial/ethnic groups in the US. The issues contributing to these disparities are multi-faceted and include sociocultural, economic, medical, and dietary factors. For example, Black women face greater rates of food insecurity, worse access to healthcare, and lower nutrient status when compared to White women. A growing body of research suggests that consuming a healthier dietary pattern is one of the most potent modifiable risk factors associated with improved fertility and reducing pregnancy-related complications. Recent publications have also shed light on the role of dairy foods in improving diet quality and nutrient status among Black women and for impacting maternal and fetal health outcomes, such as preeclampsia, spontaneous abortion, preterm birth, and fetal growth. To support healthy pregnancy and lactation, the current national dietary guidelines recommend the consumption of 3 servings of dairy foods per day. However, the vast majority of Black women in the US are falling short of these recommendations and are not meeting nutrient requirements for calcium and vitamin D. Therefore, strategies that target misconceptions surrounding lactose intolerance and focus on the health value of adequate dairy intake among Black women of child-bearing age may benefit both prenatal and postpartum health. This review presents the current evidence on health disparities faced by pregnant and lactating Black women in the US, and the role of dairy foods in supporting healthy pregnancy, fetal development, and lactation outcomes in this population.


Assuntos
Complicações na Gravidez , Nascimento Prematuro , Gravidez , Recém-Nascido , Feminino , Humanos , Estados Unidos/epidemiologia , Lactação , Aleitamento Materno , Desenvolvimento Fetal , Complicações na Gravidez/prevenção & controle , Ingestão de Alimentos
13.
Cancer Med ; 13(3): e6790, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38234214

RESUMO

This review describes the barriers and challenges faced by older adults of color with cancer and highlights methods to improve their overall care. In the next decade, cancer incidence rates are expected to increase in the United States for people aged ≥65 years. A large proportion will be older adults of color who often have worse outcomes than older White patients. Many issues contribute to racial disparities in older adults, including biological factors and social determinants of health (SDOH) related to healthcare access, socioeconomic concerns, systemic racism, mistrust, and the neighborhood where a person lives. These disparities are exacerbated by age-related challenges often experienced by older adults, such as decreased functional status, impaired cognition, high rates of comorbidities and polypharmacy, poor nutrition, and limited social support. Additionally, underrepresentation of both patients of color and older adults in cancer clinical research results in a lack of adequate data to guide the management of these patients. Use of geriatric assessments (GA) can aid providers in uncovering age-related concerns and personalizing interventions for older patients. Research demonstrates the ability of GA-directed care to result in fewer treatment-related toxicities and improved quality of life, thus supporting the routine incorporation of validated GA into these patients' care. GA can be enhanced by including evaluation of SDOH, which can help healthcare providers understand and address the needs of older adults of color with cancer who face disparities related to their age and race.


Assuntos
Disfunção Cognitiva , Neoplasias , Humanos , Idoso , Qualidade de Vida , Avaliação Geriátrica , Instalações de Saúde , Neoplasias/epidemiologia , Neoplasias/terapia
14.
Patient Educ Couns ; 129: 108395, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39182417

RESUMO

OBJECTIVE: Health disparities in lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ+), or sexual and gender minority (SGM) people are known. SGM people have higher cancer risk, but lower rates of screenings, resulting in a higher likelihood of late-stage disease. This study evaluates medical students' clinical cultural awareness in cancer care of SGM patients to identify gaps in education. METHODS: This was a cross-sectional survey distributed to medical students at a academic center. There were 38 questions on demographics, attitudes, and knowledge of SGM topics. Descriptive statistics were used for demographic information and stratified analyses assessed responses by demographic subgroups. RESULTS: There were 238 responses from 1145 students (response rate = 20.7 %). Of the responders, 91.2 % and 79 % were comfortable treating lesbian, gay, bisexual (LGB) and transgender patients respectively. Only 28.6 % and 21.8 % were confident treating LGB and transgender patients respectively after taking the survey. 91.2 % of students were interested receiving education regarding SGM health needs. CONCLUSION: While most medical students are comfortable treating LGBTQ+ patients, most are not confident in their knowledge. This difference is most profound in knowledge of transgender patients. PRACTICE IMPLICATIONS: Schools must provide more education in SGM topics to improve student knowledge to produce competent providers.


Assuntos
Competência Cultural , Neoplasias , Minorias Sexuais e de Gênero , Estudantes de Medicina , Humanos , Estudantes de Medicina/psicologia , Masculino , Minorias Sexuais e de Gênero/psicologia , Feminino , Estudos Transversais , Neoplasias/terapia , Neoplasias/etnologia , Adulto , Inquéritos e Questionários , Conhecimentos, Atitudes e Prática em Saúde , Conscientização , Pessoas Transgênero/psicologia
15.
J Natl Cancer Inst ; 116(9): 1487-1494, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38775718

RESUMO

BACKGROUND: Early studies showed promise of combined anti-epidermal growth factor receptor (EGFR) plus anti-vascular endothelial growth factor (VEGF) antibodies for advanced colorectal cancer (CRC), yet this was later rejected as toxic and ineffective in studies not selected for RAS status. We studied advanced KRAS wild-type CRC, as second-line treatment, using irinotecan-cetuximab with or without the anti-VEGF receptor antibody ramucirumab. METHODS: Patients with 1 prior regimen including fluoropyrimidine, oxaliplatin, and bevacizumab, with KRAS wild-type tumors were stratified by Eastern Cooperative Oncology Group Performance Score, time since last chemotherapy, and progression on oxaliplatin to irinotecan-cetuximab (IC) (180 mg/m2 and 500 mg/m2 every 2 weeks) vs modified ICR (irinotecan-cetuximab with ramucirumab 150 mg/m2 and 400 mg/m2 plus 6 mg/kg, respectively). A total of 102 patients were compared for progression-free survival (PFS) as primary endpoint (85% power for 70% improvement in median PFS from 4.5 to 7.65 months). RESULTS: Of the 102 enrolled, 44 treated with irinotecan-cetuximab and 45 with modified ramucirumab were evaluable. Median PFS was 6.0 months vs 9.2 months, respectively (hazard ratio = 0.75, P = .07; statistically significant by study design for P < .128). Response rate was 23% vs 36% (P = .27), and disease-control rate was 52% vs 73% (P = .05). Grade 3 or higher toxicity was equivalent. Overall survival was not significantly different at approximately 19 months. CONCLUSION: Previous phase 3 trials without RAS genotyping rejected combining anti-epidermal growth factor receptor and anti-VEGF drugs. In this randomized multicenter phase 2 study for KRAS wild-type CRC (all previously bevacizumab treated), the addition of ramucirumab to irinotecan and cetuximab improved PFS and disease control rate, showing the combination is feasible and effective. Further, phase 3 trials with appropriate patient-selection are required. (NCT01079780).


Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Cetuximab , Neoplasias Colorretais , Receptores ErbB , Irinotecano , Ramucirumab , Humanos , Irinotecano/administração & dosagem , Irinotecano/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Masculino , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Cetuximab/administração & dosagem , Cetuximab/efeitos adversos , Cetuximab/uso terapêutico , Idoso , Pessoa de Meia-Idade , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Adulto , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Idoso de 80 Anos ou mais , Intervalo Livre de Progressão
16.
JCO Precis Oncol ; 8: e2300454, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38591867

RESUMO

PURPOSE: The National Cancer Institute Molecular Analysis for Therapy Choice trial is a signal-finding genomically driven platform trial that assigns patients with any advanced refractory solid tumor, lymphoma, or myeloma to targeted therapies on the basis of next-generation sequencing results. Subprotocol E evaluated osimertinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in patients with EGFR mutations. METHODS: Eligible patients had EGFR mutations (T790M or rare activating) and received osimertinib 80 mg once daily. Patients with lung cancer with EGFR T790M were excluded. The primary end point was objective response rate (ORR), and the secondary end points were 6-month progression-free survival (PFS), overall survival, and toxicity. RESULTS: A total of 19 patients were enrolled: 17 were evaluable for toxicity and 13 for efficacy. The median age of the 13 included in the efficacy analysis was 63 years, 62% had Eastern Cooperative Oncology Group performance status 1, and 31% received >three previous systemic therapies. The most common tumor type was brain cancers (54%). The ORR was 15.4% (n = 2 of 13; 90% CI, 2.8 to 41.0) and 6-month PFS was 16.7% (90% CI, 0 to 34.4). The two confirmed RECIST responses were observed in a patient with neuroendocrine carcinoma not otherwise specified (EGFR exon 20 S768T and exon 18 G719C mutation) and a patient with low-grade epithelial carcinoma of the paranasal sinus (EGFR D770_N771insSVD). The most common (>20%) treatment-related adverse events were diarrhea, thrombocytopenia, and maculopapular rash. CONCLUSION: In this pretreated cohort, osimertinib did not meet the prespecified end point threshold for efficacy, but responses were seen in a neuroendocrine carcinoma with an EGFR exon 20 S768T and exon 18 G719C mutation and an epithelial carcinoma with an EGFR D770_N771insSVD mutation. Osimertinib was well tolerated and had a safety profile consistent with previous studies.


Assuntos
Acrilamidas , Compostos de Anilina , Antineoplásicos , Carcinoma Neuroendócrino , Carcinoma Pulmonar de Células não Pequenas , Indóis , Neoplasias Pulmonares , Pirimidinas , Estados Unidos , Humanos , Pessoa de Meia-Idade , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , National Cancer Institute (U.S.) , Antineoplásicos/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Mutação , Carcinoma Neuroendócrino/tratamento farmacológico
17.
J Clin Oncol ; 42(24): 2899-2907, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-38828938

RESUMO

PURPOSE: Black women experience higher rates of taxane-induced peripheral neuropathy (TIPN) compared with White women when receiving adjuvant once weekly paclitaxel for early-stage breast cancer, leading to more dose reductions and higher recurrence rates. EAZ171 aimed to prospectively validate germline predictors of TIPN and compare rates of TIPN and dose reductions in Black women receiving (neo)adjuvant once weekly paclitaxel and once every 3 weeks docetaxel for early-stage breast cancer. METHODS: Women with early-stage breast cancer who self-identified as Black and had intended to receive (neo)adjuvant once weekly paclitaxel or once every 3 weeks docetaxel were eligible, with planned accrual to 120 patients in each arm. Genotyping was performed to determine germline neuropathy risk. Grade 2-4 TIPN by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 was compared between high- versus low-risk genotypes and between once weekly paclitaxel versus once every 3 weeks docetaxel within 1 year. Patient-rated TIPN and patient-reported outcomes were compared using patient-reported outcome (PRO)-CTCAE and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity. RESULTS: Two hundred and forty of 249 enrolled patients had genotype data, and 91 of 117 (77.8%) receiving once weekly paclitaxel and 87 of 118 (73.7%) receiving once every 3 weeks docetaxel were classified as high-risk. Physician-reported grade 2-4 TIPN was not significantly different in high- versus low-risk genotype groups with once weekly paclitaxel (47% v 35%; P = .27) or with once every 3 weeks docetaxel (28% v 19%; P = .47). Grade 2-4 TIPN was significantly higher in the once weekly paclitaxel versus once every 3 weeks docetaxel arm by both physician-rated CTCAE (45% v 29%; P = .02) and PRO-CTCAE (40% v 24%; P = .03). Patients receiving once weekly paclitaxel required more dose reductions because of TIPN (28% v 9%; P < .001) or any cause (39% v 25%; P = .02). CONCLUSION: Germline variation did not predict risk of TIPN in Black women receiving (neo)adjuvant once weekly paclitaxel or once every 3 weeks docetaxel. Once weekly paclitaxel was associated with significantly more grade 2-4 TIPN and required more dose reductions than once every 3 weeks docetaxel.


Assuntos
Negro ou Afro-Americano , Neoplasias da Mama , Docetaxel , Paclitaxel , Doenças do Sistema Nervoso Periférico , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/genética , Pessoa de Meia-Idade , Estudos Prospectivos , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Adulto , Docetaxel/administração & dosagem , Docetaxel/efeitos adversos , Idoso , Negro ou Afro-Americano/genética , Taxoides/efeitos adversos , Taxoides/administração & dosagem , Estadiamento de Neoplasias , Mutação em Linhagem Germinativa , Hidrocarbonetos Aromáticos com Pontes/efeitos adversos , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem
18.
Clin Cancer Res ; 30(13): 2709-2718, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38640040

RESUMO

PURPOSE: Aromatase inhibitor (AI)-associated musculoskeletal symptoms (AIMSS) are common and frequently lead to AI discontinuation. SNPs in candidate genes have been associated with AIMSS and AI discontinuation. E1Z11 is a prospective cohort study designed to validate the association between 10 SNPs and AI discontinuation due to AIMSS. PATIENTS AND METHODS: Postmenopausal women with stage I to III hormone receptor-positive breast cancer received anastrozole 1 mg daily and completed patient-reported outcome measures to assess AIMSS (Stanford Health Assessment Questionnaire) at baseline, 3, 6, 9, and 12 months. We estimated that 40% of participants would develop AIMSS and 25% would discontinue AI treatment within 12 months. Enrollment of 1,000 women with a fixed number per racial stratum provided 80% power to detect an effect size of 1.5 to 4. SNPs were found in ESR1 (rs2234693, rs2347868, and rs9340835), CYP19A1 (rs1062033 and rs4646), TCL1A (rs11849538, rs2369049, rs7158782, and rs7159713), and HTR2A (rs2296972). RESULTS: Of the 970 evaluable women, 43% developed AIMSS and 12% discontinued AI therapy within 12 months. Although more Black and Asian women developed AIMSS than White women (49% vs. 39%, P = 0.017; 50% vs. 39%, P = 0.004, respectively), the AI discontinuation rates were similar across groups. None of the SNPs were significantly associated with AIMSS or AI discontinuation in the overall population or in distinct cohorts. The OR for rs2296972 (HTR2A) approached significance for developing AIMSS. CONCLUSIONS: We were unable to prospectively validate candidate SNPs previously associated with AI discontinuation due to AIMSS. Future analyses will explore additional genetic markers, patient-reported outcome predictors of AIMSS, and differences by race.


Assuntos
Inibidores da Aromatase , Neoplasias da Mama , Polimorfismo de Nucleotídeo Único , Humanos , Feminino , Inibidores da Aromatase/uso terapêutico , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Pessoa de Meia-Idade , Idoso , Estudos Prospectivos , Anastrozol/uso terapêutico , Anastrozol/efeitos adversos , Anastrozol/administração & dosagem , Estudos de Coortes , Pós-Menopausa , Idoso de 80 Anos ou mais , Medidas de Resultados Relatados pelo Paciente , Aromatase/genética
19.
Clin Cancer Res ; 30(7): 1273-1280, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38433347

RESUMO

PURPOSE: NCI-MATCH assigned patients with advanced cancer and progression on prior treatment, based on genomic alterations in pretreatment tumor tissue. Arm J (EAY131-J) evaluated the combination of trastuzumab/pertuzumab (HP) across HER2-amplified tumors. PATIENTS AND METHODS: Eligible patients had high levels of HER2 amplification [copy number (CN) ≥7] detected by central next-generation sequencing (NGS) or through NCI-designated laboratories. Patients with breast/gastroesophageal adenocarcinoma and those who received prior HER2-directed therapy were excluded. Enrollment of patients with colorectal cancer was capped at 4 based on emerging data. Patients received HP IV Q3 weeks until progression or unacceptable toxicity. Primary endpoint was objective response rate (ORR); secondary endpoints included progression-free survival (PFS) and overall survival (OS). RESULTS: Thirty-five patients were enrolled, with 25 included in the primary efficacy analysis (CN ≥7 confirmed by a central lab, median CN = 28). Median age was 66 (range, 31-80), and half of all patients had ≥3 prior therapies (range, 1-11). The confirmed ORR was 12% [3/25 partial responses (colorectal, cholangiocarcinoma, urothelial cancers), 90% confidence interval (CI) 3.4%-28.2%]. There was one additional partial response (urothelial cancer) in a patient with an unconfirmed ERBB2 copy number. Median PFS was 3.3 months (90% CI 2.0-4.1), and median OS 9.4 months (90% CI 5.0-18.9). Treatment-emergent adverse events were consistent with prior studies. There was no association between HER2 CN and response. CONCLUSIONS: HP was active in a selection of HER2-amplified tumors (non-breast/gastroesophageal) but did not meet the predefined efficacy benchmark. Additional strategies targeting HER2 and potential resistance pathways are warranted, especially in rare tumors.


Assuntos
Neoplasias da Mama , Receptor ErbB-2 , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/patologia , Intervalo Livre de Progressão , Receptor ErbB-2/metabolismo , Trastuzumab/efeitos adversos , Trastuzumab/uso terapêutico
20.
JCO Precis Oncol ; 8: e2300407, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38603650

RESUMO

PURPOSE: Subprotocol K2 (EAY131-K2) of the NCI-MATCH platform trial was an open-label, single-arm, phase II study designed to evaluate the antitumor efficacy of the oral FGFR1-4 inhibitor, erdafitinib, in patients with tumors harboring FGFR1-4 mutations or fusions. METHODS: Central confirmation of tumor FGFR1-4 mutations or fusions was required for outcome analysis. Patients with urothelial carcinoma were excluded. Enrolled subjects received oral erdafitinib at a starting dose of 8 mg daily continuously until intolerable toxicity or disease progression. The primary end point was objective response rate (ORR) with key secondary end points of safety, progression-free survival (PFS), and overall survival (OS). RESULTS: Thirty-five patients were enrolled, and 25 patients were included in the primary efficacy analysis as prespecified in the protocol. The median age was 61 years, and 52% of subjects had received ≥3 previous lines of therapy. The confirmed ORR was 16% (4 of 25 [90% CI, 5.7 to 33.0], P = .034 against the null rate of 5%). An additional seven patients experienced stable disease as best-confirmed response. Four patients had a prolonged PFS including two with recurrent WHO grade IV, IDH1-/2-wildtype glioblastoma. The median PFS and OS were 3.6 months and 11.0 months, respectively. Erdafitinib was manageable with no new safety signals. CONCLUSION: This study met its primary end point in patients with several pretreated solid tumor types harboring FGFR1-3 mutations or fusions. These findings support advancement of erdafitinib for patients with fibroblast growth factor receptor-altered tumors outside of currently approved indications in a potentially tumor-agnostic manner.


Assuntos
Neoplasias , Pirazóis , Quinoxalinas , Humanos , Pessoa de Meia-Idade , Mutação , Pirazóis/uso terapêutico , Pirazóis/efeitos adversos , Neoplasias da Bexiga Urinária , Neoplasias/tratamento farmacológico , Neoplasias/genética , Receptores de Fatores de Crescimento de Fibroblastos/genética
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