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1.
Cancer ; 127(21): 3991-3997, 2021 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-34289094

RESUMEN

BACKGROUND: Aggressive large B-cell lymphomas (LBCLs) are curable, but previous studies have shown inferior outcomes in minorities. Nurse navigation programs can improve patient outcomes by providing patient support. This study presents the outcomes of White and minority patients with aggressive LBCL at an institution with an active nurse navigation program. METHODS: The authors prospectively collected baseline characteristics, treatment regimens, and outcome data for patients with aggressive LBCL. Navigation encounters were characterized as low or high intensity. Overall survival (OS) and progression-free survival (PFS) were calculated with Kaplan-Meier methods. Baseline characteristics were compared with Fisher exact tests. RESULTS: Two hundred four consecutive patients (47 minority patients and 157 White patients) were included. Results were presented as minorities versus Whites. There were no differences in prognostic scores (Revised International Prognostic Index score of 3-5, 43% vs 47%; P = .50), frontline chemotherapy (98% vs 96%; P = .68), or the incidence of relapsed/refractory disease (40% vs 38%; P = .74). For relapsed/refractory LBCL, similar proportions of patients underwent hematopoietic stem cell transplantation (32% vs 29%; P > .99) or chimeric antigen receptor T-cell therapy (16% vs 19%; P > .99). Enrollment in clinical trials was comparable (17% vs 14%; P = .64). More than 85% received nurse navigation, but minorities had higher intensity navigation encounters (42% vs 21%; P = .01). The 2-year OS rates were 81% and 76% for minorities and Whites, respectively (P = .27); the 2-year PFS rates were 62% and 65%, respectively (P = .78). CONCLUSIONS: This study shows similar survival between Whites and minorities with aggressive LBCL, which was likely due to equal access to guideline-concordant therapy. Minorities received higher intensity navigation encounters, which may have helped them to overcome socioeconomic disadvantages.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Linfoma de Células B Grandes Difuso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Accesibilidad a los Servicios de Salud , Humanos , Inmunoterapia Adoptiva , Linfoma de Células B Grandes Difuso/terapia , Supervivencia sin Progresión , Estudios Retrospectivos
2.
Oncologist ; 26(10): e1730-e1741, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34288237

RESUMEN

BACKGROUND: Low socioeconomic status (SES) has been linked to worse survival in patients with colorectal cancer (CRC); however, the impact of SES on early-onset CRC remains undescribed. MATERIALS AND METHODS: Retrospective analysis of data from the National Cancer Database (NCDB) between 2004 and 2016 was conducted. We combined income and education to form a composite measure of SES. Logistic regression and χ2 testing were used to examine early-onset CRC according to SES group. Survival rates and Cox proportional hazards models compared stage-specific overall survival (OS) between the SES groups. RESULTS: In total, 30,903 patients with early-onset CRC were identified, of whom 78.7% were White; 14.5% were Black. Low SES compared with high SES patients were more likely to be Black (26.3% vs. 6.1%) or Hispanic (25.3% vs. 10.5%), have T4 tumors (21.3% vs. 17.8%) and/or N2 disease (13% vs. 11.1%), and present with stage IV disease (32.8% vs. 27.7%) at diagnosis (p < .0001, all comparisons). OS gradually improved with increasing SES at all disease stages (p < .001). In stage IV, the 5-year survival rate was 13.9% vs. 21.7% for patients with low compared with high SES. In multivariable analysis, SES (low vs. high group; adjusted hazard ratio [HRadj ], 1.35; 95% confidence interval [CI], 1.26-1.46) was found to have a significant effect on survival (p < .0001) when all of the confounding variables were adjusted. Insurance (not private vs. private; HRadj , 1.38; 95% CI, 1.31-1.44) mediates 31% of the SES effect on survival. CONCLUSION: Patients with early-onset CRC with low SES had the worst outcomes. Our data suggest that SES should be considered when implementing programs to improve the early detection and treatment of patients with early-onset CRC. IMPLICATIONS FOR PRACTICE: Low socioeconomic status (SES) has been linked to worse survival in patients with colorectal cancer (CRC); however, the impact of SES on early-onset CRC remains undescribed. In this retrospective study of 30,903 patients with early-onset CRC in the National Cancer Database, a steady increase in the yearly rate of stage IV diagnosis at presentation was observed. The risk of death increased as socioeconomic status decreased. Race and insurance status were independent predictors for survival. Implementation of programs to improve access to care and early diagnostic strategies among younger adults, especially those with low SES, is warranted.


Asunto(s)
Neoplasias Colorrectales , Clase Social , Neoplasias Colorrectales/epidemiología , Hispánicos o Latinos , Humanos , Cobertura del Seguro , Estudios Retrospectivos , Factores Socioeconómicos , Tasa de Supervivencia
3.
Oncologist ; 25(5): e777-e781, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31771991

RESUMEN

INTRODUCTION: The National Lung Screening Trial (NLST) demonstrated that screening high-risk patients with low-dose computed tomography (CT) of the chest reduces lung cancer mortality compared with screening with chest x-ray. Uninsured and Medicaid patients usually lack access to this hospital-based screening test because of geographic and socioeconomic factors. We hypothesized that a mobile screening unit would improve access and confer the benefits demonstrated by the NLST to this underserved group, which is most at risk of lung cancer deaths. PATIENTS AND METHODS: We created a mobile unit by building a Samsung BodyTom portable 32-slice low-dose CT scanner into a 35-foot coach; it delivers high-quality images for both soft tissue and bone and includes a waiting area and high-speed wireless internet connection for fast image transfer. The unit was extensively tested to show robustness and stability of mobile equipment. This project was designed to screen uninsured and underinsured patients, otherwise with eligibility criteria identical to that of the National Lung Screening Trial, with the only difference being exclusion of patients eligible for Medicare (which provides financial coverage for CT-based lung cancer screening). RESULTS: We screened 550 patients (20% black, 3% Hispanic, 70% rural) with a male-to-female ratio of 1.1:1, median age 61 years (range, 55-64), and found 12 lung cancers at initial screen (2.2%), including 6 at stage I-II (58% of total lung cancers early stage) and 38 Lung-RADS 4 (highly suspicious) lesions that are being followed closely. Incidental findings included nonlung cancers and coronary artery disease. DISCUSSION: In this initial pilot study, using the first mobile low-dose whole body CT screening unit in the U.S., the initial cancer detection rate is comparable to that reported in the NLST, despite excluding patients over the age of 64 years who have Medicare coverage, but with marked improvement of screening rates specifically in underserved sociodemographic, racial, and ethnic groups and with better outcomes than conventionally found in the underserved and at lower cost per case. IMPLICATIONS FOR PRACTICE: This study shows clearly that a mobile low-dose CT scanning unit allows effective lung cancer screening for underserved populations, such as impoverished African Americans, Hispanics, Native Americans, or isolated rural groups, and has a pick-up rate of 1% for early stage disease. If confirmed in a planned randomized trial, this will be policy changing, as these groups usually present with advanced disease; this approach will produce better survival data at lower cost per case.


Asunto(s)
Detección Precoz del Cáncer , Neoplasias Pulmonares , Anciano , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Masculino , Tamizaje Masivo , Medicare , Persona de Mediana Edad , Proyectos Piloto , Tomografía Computarizada por Rayos X , Estados Unidos , Poblaciones Vulnerables
4.
Oncologist ; 24(3): 319-326, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30018131

RESUMEN

BACKGROUND: The incidence of colorectal cancer (CRC) in younger patients is rising, mostly due to tumors in the descending colon and rectum. Therefore, we aimed to explore the molecular differences of left-sided CRC between younger (≤45 years) and older patients (≥65). SUBJECTS, MATERIALS, AND METHODS: In total, 1,126 CRC tumor samples from the splenic flexure to (and including) the rectum were examined by next-generation sequencing (NGS), immunohistochemistry, and in situ hybridization. Microsatellite instability (MSI) and tumor mutational burden (TMB) were assessed by NGS. RESULTS: Younger patients (n = 350), when compared with older patients (n = 776), showed higher mutation rates in genes associated with cancer-predisposing syndromes (e.g., Lynch syndrome), such as MSH6 (4.8% vs. 1.2%, p = .005), MSH2 (2.7% vs. 0.0%, p = .004), POLE (1.6% vs. 0.0%, p = .008), NF1 (5.9% vs. 0.5%, p < .001), SMAD4 (14.3% vs. 8.3%, p = .024), and BRCA2 (3.7% vs. 0.5%, p = .002). Genes involved in histone modification were also significantly more mutated: KDM5C (1.9% vs. 0%, p = .036), KMT2A (1.1% vs. 0%, p = .033), KMT2C (1.6% vs. 0%, p = .031), KMT2D (3.8% vs. 0.7%, p = .005), and SETD2 (3.2% vs. 0.9%, p = .039). Finally, TMB-high (9.7% vs. 2.8%, p < .001) and MSI-high (MSI-H; 8.1% vs. 1.9%, p = .009) were more frequent in younger patients. CONCLUSION: Our findings highlight the importance of genetic counseling and screening in younger CRC patients. MSI-H and TMB-high tumors could benefit from immune-checkpoint inhibitors, now approved for the treatment of MSI-H/deficient mismatch repair metastatic CRC patients. Finally, histone modifiers could serve as a new promising therapeutic target. With confirmatory studies, these results may influence our approach to younger adults with CRC. IMPLICATIONS FOR PRACTICE: The increasing rate of colorectal cancers (CRC), primarily distal tumors, among young adults poses a global health issue. This study investigates the molecular differences between younger (≤45 years old) and older (≥65) adults with left-sided CRCs. Younger patients more frequently harbor mutations in genes associated with cancer-predisposing syndromes. Higher rates of microsatellite instability-high and tumor mutational burden-high tumors occur in younger patients, who could benefit from immune-checkpoint inhibitors. Finally, histone modifiers are more frequently mutated in younger patients and could serve as a new promising therapeutic target. This study provides new insights into mutations that may guide development of novel tailored therapy in younger CRC patients.


Asunto(s)
Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/patología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Adulto Joven
5.
Oncologist ; 23(11): 1319-1327, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-29866946

RESUMEN

BACKGROUND: Gastroesophageal cancers are often grouped together even though cancers that originate in the esophagus often exhibit different histological features, geographical distribution, risk factors, and clinical characteristics than those originating in the stomach. Herein, we aimed to compare the molecular characteristics of three different gastroesophageal cancer types: esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), and gastric adenocarcinoma (GAC). SUBJECTS, MATERIALS, AND METHODS: In total, 3,342 gastroesophageal cancers were examined. Next-generation sequencing was performed on genomic DNA isolated from formalin-fixed paraffin-embedded tumor samples using the NextSeq platform. Tumor mutational burden was measured by counting all nonsynonymous missense mutations, and microsatellite instability was examined at over 7,000 target microsatellite loci. Immunohistochemistry and in situ hybridization techniques were also performed. RESULTS: When compared with EAC and GAC, ESCC showed significantly lower mutational rates within APC, ARID1A, CDH1, KRAS, PTEN, and SMAD4, whereas more frequent mutations were observed in BAP1, CDKN2A, FOXO3, KMT2D, MSH6, NOTCH1, RB1, and SETD2. Human epidermal growth receptor 2 (HER2) overexpression was observed in 13% of EAC compared with 6% of GAC and 1% of ESCC (p < .0001). Compared with EAC and GAC, ESCC exhibited higher expression of programmed death-ligand 1 (PD-L1) (27.7% vs. 7.5% vs. 7.7%, p < .0001). We observed that FGF3, FGF4, FGF19, CCND1 (co-localized on 11q13), and FGFR1 were significantly more amplified in ESCC compared with EAC and GAC (p < .0001). CONCLUSION: Molecular comparisons between ESCC, EAC, and GAC revealed distinct differences between squamous cell carcinomas and adenocarcinomas in each platform tested. Different prevalence of HER2/neu overexpression and amplification, and immune-related biomarkers between ESCC, EAC, and GAC, suggests different sensitivity to HER2-targeted therapy and immune checkpoint inhibition. These findings bring into question the validity of grouping patients with EAC and ESCC together in clinical trials and provide insight into molecular features that may represent novel therapeutic targets. IMPLICATIONS FOR PRACTICE: This study highlights the genomic heterogeneity of gastroesophageal cancers, showing striking molecular differences between tumors originating from different locations. Moreover, this study showed that esophageal squamous cell carcinomas exhibit a unique molecular profile, whereas gastric adenocarcinomas and esophageal adenocarcinomas have some similarities, supporting the fact that adenocarcinomas and squamous cell carcinomas are completely different diseases, irrespective of the tumor location. This raises the question of whether treatment of gastroesophageal tumors should be determined according to histological subtype and molecular targets rather than anatomical site. These findings provide insights that could enable physicians to better select patients and inform therapeutic choices in order to improve clinical outcome.


Asunto(s)
Adenocarcinoma/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas de Esófago/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Neoplasias Gástricas/genética , Adenocarcinoma/patología , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Gástricas/patología
6.
Clin Adv Hematol Oncol ; 16(4): 289-295, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29742084

RESUMEN

Castration has been the hallmark of the treatment of advanced prostate cancer for nearly a century. Conventional surgical or medical castration for the management of metastatic prostate cancer has been associated with an initial response rate greater than 60% to 70%, depending on the criteria employed. The median duration of the initial response is usually less than 3 to 5 years, however, depending on the extent of disease. The failure of disease to respond to castration has been associated with an increase in the production of adrenal androgens and/or the evolution of upregulated or mutated androgen receptors. Second-line hormonal treatment with adrenal inhibitors is sometimes used, but remissions usually last for less than a year. Extensive translational research has produced a series of second-line, multitargeted, hormonally active agents that inhibit androgen receptor function and/or multiple sites within the hypothalamic/pituitary/end-organ axis. Abiraterone and enzalutamide have been shown to be active in second-line or subsequent hormonal therapy for castration-resistant prostate cancer, and recent data have shown a substantial anticancer effect in initial therapy. The potential use of abiraterone and enzalutamide as initial therapy for advanced prostate cancer is the focus of this brief review, which emphasizes that new approaches should not become the standard of care until they have been validated in randomized trials. In addition, it remains unclear whether first-line treatment with chemohormones or new-generation hormones should be the current standard for all patients with newly diagnosed metastatic prostate cancer.


Asunto(s)
Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Antagonistas de Andrógenos/administración & dosificación , Antagonistas de Andrógenos/efectos adversos , Antagonistas de Andrógenos/uso terapéutico , Antineoplásicos Hormonales/administración & dosificación , Antineoplásicos Hormonales/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Humanos , Masculino , Estadificación de Neoplasias , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/mortalidad , Neoplasias de la Próstata Resistentes a la Castración/patología , Terapia Recuperativa , Resultado del Tratamiento
7.
Lancet Oncol ; 18(11): e653-e706, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-29208398

RESUMEN

We are in the midst of a technological revolution that is providing new insights into human biology and cancer. In this era of big data, we are amassing large amounts of information that is transforming how we approach cancer treatment and prevention. Enactment of the Cancer Moonshot within the 21st Century Cures Act in the USA arrived at a propitious moment in the advancement of knowledge, providing nearly US$2 billion of funding for cancer research and precision medicine. In 2016, the Blue Ribbon Panel (BRP) set out a roadmap of recommendations designed to exploit new advances in cancer diagnosis, prevention, and treatment. Those recommendations provided a high-level view of how to accelerate the conversion of new scientific discoveries into effective treatments and prevention for cancer. The US National Cancer Institute is already implementing some of those recommendations. As experts in the priority areas identified by the BRP, we bolster those recommendations to implement this important scientific roadmap. In this Commission, we examine the BRP recommendations in greater detail and expand the discussion to include additional priority areas, including surgical oncology, radiation oncology, imaging, health systems and health disparities, regulation and financing, population science, and oncopolicy. We prioritise areas of research in the USA that we believe would accelerate efforts to benefit patients with cancer. Finally, we hope the recommendations in this report will facilitate new international collaborations to further enhance global efforts in cancer control.


Asunto(s)
Investigación Biomédica/tendencias , Planificación en Salud/tendencias , Prioridades en Salud , National Cancer Institute (U.S.)/tendencias , Neoplasias/terapia , Investigación Biomédica/métodos , Predicción , Humanos , Oncología Médica/tendencias , Neoplasias/diagnóstico , Medicina de Precisión/tendencias , Estados Unidos
8.
N Engl J Med ; 368(14): 1314-25, 2013 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-23550669

RESUMEN

BACKGROUND: Castration resistance occurs in most patients with metastatic hormone-sensitive prostate cancer who are receiving androgen-deprivation therapy. Replacing androgens before progression of the disease is hypothesized to prolong androgen dependence. METHODS: Men with newly diagnosed, metastatic, hormone-sensitive prostate cancer, a performance status of 0 to 2, and a prostate-specific antigen (PSA) level of 5 ng per milliliter or higher received a luteinizing hormone-releasing hormone analogue and an antiandrogen agent for 7 months. We then randomly assigned patients in whom the PSA level fell to 4 ng per milliliter or lower to continuous or intermittent androgen deprivation, with patients stratified according to prior or no prior hormonal therapy, performance status, and extent of disease (minimal or extensive). The coprimary objectives were to assess whether intermittent therapy was noninferior to continuous therapy with respect to survival, with a one-sided test with an upper boundary of the hazard ratio of 1.20, and whether quality of life differed between the groups 3 months after randomization. RESULTS: A total of 3040 patients were enrolled, of whom 1535 were included in the analysis: 765 randomly assigned to continuous androgen deprivation and 770 assigned to intermittent androgen deprivation. The median follow-up period was 9.8 years. Median survival was 5.8 years in the continuous-therapy group and 5.1 years in the intermittent-therapy group (hazard ratio for death with intermittent therapy, 1.10; 90% confidence interval, 0.99 to 1.23). Intermittent therapy was associated with better erectile function and mental health (P<0.001 and P=0.003, respectively) at month 3 but not thereafter. There were no significant differences between the groups in the number of treatment-related high-grade adverse events. CONCLUSIONS: Our findings were statistically inconclusive. In patients with metastatic hormone-sensitive prostate cancer, the confidence interval for survival exceeded the upper boundary for noninferiority, suggesting that we cannot rule out a 20% greater risk of death with intermittent therapy than with continuous therapy, but too few events occurred to rule out significant inferiority of intermittent therapy. Intermittent therapy resulted in small improvements in quality of life. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00002651.).


Asunto(s)
Antagonistas de Andrógenos/administración & dosificación , Anilidas/administración & dosificación , Hormona Liberadora de Gonadotropina/análogos & derivados , Goserelina/administración & dosificación , Nitrilos/administración & dosificación , Neoplasias de la Próstata/tratamiento farmacológico , Calidad de Vida , Compuestos de Tosilo/administración & dosificación , Anciano , Anilidas/efectos adversos , Antineoplásicos Hormonales/administración & dosificación , Antineoplásicos Hormonales/efectos adversos , Intervalos de Confianza , Esquema de Medicación , Estudios de Seguimiento , Hormona Liberadora de Gonadotropina/uso terapéutico , Goserelina/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia/tratamiento farmacológico , Nitrilos/efectos adversos , Erección Peniana/efectos de los fármacos , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Análisis de Supervivencia , Compuestos de Tosilo/efectos adversos
9.
Can J Urol ; 28(3): 10653-10656, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-34129454
10.
Prostate ; 75(6): 628-36, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25560784

RESUMEN

BACKGROUND: Understanding the progression of prostate cancer to androgen-independence/castrate resistance and development of preclinical testing models are important for developing new prostate cancer therapies. This report describes studies performed 30 years ago, which demonstrate utility and shortfalls of xenografting to preclinical modeling. METHODS: We subcutaneously implanted male nude mice with small prostate cancer fragments from transurethral resection of the prostate (TURP) from 29 patients. Successful xenografts were passaged into new host mice. They were characterized using histology, immunohistochemistry for marker expression, flow cytometry for ploidy status, and in some cases by electron microscopy and response to testosterone. Two xenografts were karyotyped by G-banding. RESULTS: Tissues from 3/29 donors (10%) gave rise to xenografts that were successfully serially passaged in vivo. Two, (UCRU-PR-1, which subsequently was replaced by a mouse fibrosarcoma, and UCRU-PR-2, which combined epithelial and neuroendocrine features) have been described. UCRU-PR-4 line was a poorly differentiated prostatic adenocarcinoma derived from a patient who had undergone estrogen therapy and bilateral castration after his cancer relapsed. Histologically, this comprised diffusely infiltrating small acinar cell carcinoma with more solid aggregates of poorly differentiated adenocarcinoma. The xenografted line showed histology consistent with a poorly differentiated adenocarcinoma and stained positively for prostatic acid phosphatase (PAcP), epithelial membrane antigen (EMA) and the cytokeratin cocktail, CAM5.2, with weak staining for prostate specific antigen (PSA). The line failed to grow in female nude mice. Castration of three male nude mice after xenograft establishment resulted in cessation of growth in one, growth regression in another and transient growth in another, suggesting that some cells had retained androgen sensitivity. The karyotype (from passage 1) was 43-46, XY, dic(1;12)(p11;p11), der(3)t(3:?5)(q13;q13), -5, inv(7)(p15q35) x2, +add(7)(p13), add(8)(p22), add(11)(p14), add(13)(p11), add(20)(p12), -22, +r4[cp8]. CONCLUSIONS: Xenografts provide a clinically relevant model of prostate cancer, although establishing serially transplantable prostate cancer patient derived xenografts is challenging and requires rigorous characterization and high quality starting material. Xenografting from advanced prostate cancer is more likely to succeed, as xenografting from well differentiated, localized disease has not been achieved in our experience. Strong translational correlations can be demonstrated between the clinical disease state and the xenograft model.


Asunto(s)
Neoplasias de la Próstata/patología , Animales , Línea Celular Tumoral , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Trasplante de Neoplasias , Tumores Neuroendocrinos/patología , Neoplasias de la Próstata/genética , Testosterona/farmacología , Trasplante Heterólogo
11.
Oncologist ; 19(5): 498-506, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24718515

RESUMEN

Postchemotherapy surgery for advanced testicular cancer has evolved over the last couple of decades. Patients with nonseminomatous germ cell tumors and residual retroperitoneal mass ≥1 cm should undergo postchemotherapy retroperitoneal lymph node dissection (RPLND). For seminoma, RPLND is considered in those patients with masses ≥3 cm that are also positron emission tomography positive. Masses that occur outside of the retroperitoneum should be completely resected with the possible exception of bilateral lung masses when resection of the first mass shows necrosis. The role of surgery in patients with extragonadal germ cell tumors is most vital in those with primary mediastinal nonseminomatous germ cell tumors. Importantly, patient selection, surgical planning, and consideration of referral to centers with this expertise are important to optimize success.


Asunto(s)
Escisión del Ganglio Linfático , Neoplasias de Células Germinales y Embrionarias/cirugía , Seminoma/cirugía , Neoplasias Testiculares/cirugía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada , Humanos , Ganglios Linfáticos/cirugía , Metástasis Linfática , Masculino , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Espacio Retroperitoneal/patología , Seminoma/tratamiento farmacológico , Neoplasias Testiculares/tratamiento farmacológico , Resultado del Tratamiento
12.
JCO Oncol Pract ; 20(9): 1152-1154, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39008788

RESUMEN

Oncologists use molecular prediction/pharmacogenomics to improve Rx of cancer. Voltaire now wrong.


Asunto(s)
Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/terapia
13.
Invest New Drugs ; 31(4): 1044-50, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23435622

RESUMEN

PURPOSE: Enzastaurin is an oral serine/threonine kinase inhibitor that inhibits the beta isoform of protein kinase C and which may have therapeutic activity in prostate cancer. We explored the efficacy of docetaxel/prednisone with or without enzastaurin in patients with castration-resistant metastatic prostate cancer. METHODS: A nonrandomized safety cohort consisting of 14 patients was followed by a double-blind randomized Phase II trial. Patients received standard doses of docetaxel (75 mg/m(2)) with prednisone 10 mg daily with or without 500 mg/day of enzastaurin. RESULTS: There was no difference in the objective response rate between the enzastaurin and placebo arms (placebo: 7 [15.2 %]; enzastaurin: 6 [15.0 %]; P = 1.00). The median PFS was 229 days for patients in the enzastaurin arm versus 213 days for the placebo arm (P = 0.524). The 1-year overall survival rates were almost identical, with 76.7 % and 75.1 % in the enzastaurin and placebo arms, respectively. Therapy was well tolerated although the combination of enzastaurin and docetaxel was more myelosuppressive than with docetaxel alone. CONCLUSIONS: The clinical activity of docetaxel/prednisone plus enzastaurin cannot be distinguished from docetaxel/prednisone alone, given the limitations of a randomized Phase II design. Although the toxicity profile was favorable for the enzastaurin-containing regimen, there is no compelling rationale to move this combination forward for the treatment of castration-resistant metastatic prostate cancer.


Asunto(s)
Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Indoles/uso terapéutico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Taxoides/uso terapéutico , Anciano , Anciano de 80 o más Años , Docetaxel , Método Doble Ciego , Humanos , Indoles/efectos adversos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Placebos , Taxoides/efectos adversos , Resultado del Tratamiento
14.
JCO Precis Oncol ; 7: e2300378, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38061006

RESUMEN

PURPOSE: Homologous recombination deficiency (HRD) is a well-described phenotype of some prostate cancers; however, current biomarkers for HRD are imperfect and rely on detection of single gene alterations in the homologous recombination repair (HRR) pathway, which may not capture the complexity of HRD biology. RNA signature-based methods of HRD identification present a potentially dynamic assessment of the HRD phenotype; however, its relationship with HRR gene alterations is not well characterized in prostate cancer. METHODS: A HRD assay on the basis of an RNA signature associated with biallelic BRCA1/2 loss was applied to a retrospective cohort study of 985 men with prostate cancer analyzed on the Tempus xT platform. HRD status was defined by a binary threshold on a continuous scale. RESULTS: In this cohort, of the 126 (13%) patients found to be HRD+ by RNA signature (HRD-RNA+), 100 (79%) had no coexisting HRR gene alteration. Among samples with biallelic BRCA1/2 loss, 78% (7/9) were classified as HRD-RNA+, while 8% (2/25) of samples with BRCA1/2 monoallelic loss were HRD-RNA+. Biallelic and monoallelic ATM loss exhibited HRD-RNA+ at a lower prevalence: 6.7% (1/15) and 7.1% (1/14), respectively, compared with HRD-RNA+ prevalence among samples without any HRR gene loss (13%; 100/782). HRD-RNA+ was associated with a significantly higher prevalence of TP53 and AR gene alterations relative to HRD-RNA- after correction for multiple comparisons, 59% versus 39% (q = 0.003) and 23% versus 12% (q = 0.024), respectively. CONCLUSION: Use of an RNA-based HRD signature significantly expands the fraction of patients with prostate cancer who may derive benefit from poly (ADP-ribose) polymerase inhibitors (PARPis) compared with using HRR gene mutations alone. Further studies are needed to evaluate functional HRD significance and inform future usage as a predictive biomarker for PARPi selection.


Asunto(s)
Proteína BRCA1 , Neoplasias de la Próstata , Masculino , Humanos , Proteína BRCA1/genética , Reparación del ADN por Recombinación/genética , Recombinación Homóloga/genética , Estudios Retrospectivos , Proteína BRCA2/genética , Neoplasias de la Próstata/genética , Inhibidores de Poli(ADP-Ribosa) Polimerasas
15.
Urol Oncol ; 41(8): 357.e23-357.e29, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37295980

RESUMEN

OBJECTIVES: Novel regimens targeting immune checkpoints and the cMET or HER2 pathways are under investigation in metastatic urothelial carcinoma (mUC) though co-expression of these molecular targets has not been defined. We sought to characterize the protein co-expression rates of PD-L1, cMET and HER2 in primary and metastatic mUC lesions and agreement rates in paired biopsies. MATERIALS AND METHODS: We assessed PD-L1, cMET and HER2 protein expression by immunohistochemistry (IHC) in archival mUC samples identified from an institutional database (n = 143). Correlation of expression between primary and metastatic biopsies was performed in patients with available paired biopsies (n = 79). Protein expression levels by predefined thresholds were measured, and Cohen's kappa statistics (κ) were utilized to assess the agreement in expression between paired primary and metastatic samples. RESULTS: In primary tumors (n = 85), high expression of PD-L1, cMET, and HER2 was observed in 14.1%, 34.1%, and 12.9%, respectively. In metastatic samples (n = 143), high expression of PD-L1, cMET and HER2 was detected in 9.8%, 41.3%, and 9.8%, respectively. Expression agreement rates between paired specimens (n = 79) were PD-L1: 79.7% (κ = 0.09), cMET: 69.6% (κ = 0.35), HER2: 84.8% (κ = 0.17). High PD-L1/cMET co-expression was observed in only 5.1% (n = 4) of primary and 4.9% (n = 7) of metastatic specimens. High co-expression of PD-L1/HER2 occurred in 3.8% (n = 3) of primary samples and no metastatic samples. The overall co-expression agreement between paired samples was 55.7% (κ = 0.22) for PD-L1/cMET and 67.1% (κ = 0.06) for PD-L1/HER2, but agreement for high co-expression between paired samples was very low (2.5% for PD-L1/cMET and 0% for PD-L1/HER2). CONCLUSIONS: Tumor co-expression of high cMET or HER2 and PD-L1 is low in this cohort. Agreement of high co-expression between primary and metastatic sites is rare. Biomarker-based strategies used in selection of patients for contemporary trials testing combinations of immune checkpoint inhibitors with either cMET or HER2-targeted agents should account for discordant biomarker expression between primary and metastatic sites.


Asunto(s)
Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Humanos , Carcinoma de Células Transicionales/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Antígeno B7-H1/metabolismo , Inmunohistoquímica , Tirosina , Biomarcadores de Tumor/metabolismo
16.
J Clin Oncol ; 41(22): 3772-3781, 2023 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-37499357

RESUMEN

PURPOSE: To evaluate our long-term experience with patients treated uniformly with radical cystectomy and pelvic lymph node dissection for invasive bladder cancer and to describe the association of the primary bladder tumor stage and regional lymph node status with clinical outcomes. PATIENTS AND METHODS: All patients undergoing radical cystectomy with bilateral pelvic iliac lymphadenectomy, with the intent to cure, for transitional-cell carcinoma of the bladder between July 1971 and December 1997, with or without adjuvant radiation or chemotherapy, were evaluated. The clinical course, pathologic characteristics, and long-term clinical outcomes were evaluated in this group of patients. RESULTS: A total of 1,054 patients (843 men [80%] and 211 women) with a median age of 66 years (range, 22 to 93 years) were uniformly treated. Median follow-up was 10.2 years (range, 0 to 28 years). There were 27 (2.5%) perioperative deaths, with a total of 292 (28%) early complications. Overall recurrence-free survival at 5 and 10 years for the entire cohort was 68% and 66%, respectively. The 5- and 10-year recurrence-free survival for patients with organ-confined, lymph node-negative tumors was 92% and 86% for P0 disease, 91% and 89% for Pis, 79% and 74% for Pa, and 83% and 78% for P1 tumors, respectively. Patients with muscle invasive (P2 and P3a), lymph node-negative tumors had 89% and 87% and 78% and 76% 5- and 10-year recurrence-free survival, respectively. Patients with nonorgan-confined (P3b, P4), lymph node-negative tumors demonstrated a significantly higher probability of recurrence compared with those with organ-confined bladder cancers (P < .001). The 5- and 10-year recurrence-free survival for P3b tumors was 62% and 61%, and for P4 tumors was 50% and 45% , respectively. A total of 246 patients (24%) had lymph node tumor involvement. The 5- and 10-year recurrence-free survival for these patients was 35%, and 34%, respectively, which was significantly lower than for patients without lymph node involvement (P < .001). Patients could also be stratified by the number of lymph nodes involved and by the extent of the primary bladder tumor (p stage). Patients with fewer than five positive lymph nodes, and whose p stage was organ-confined had significantly improved survival rates. Bladder cancer recurred in 311 patients (30%) . The median time to recurrence among those patients in whom the cancer recurred was 12 months (range, 0.04 to 11.1 years). In 234 patients (22%) there was a distant recurrence, and in 77 patients (7%) there was a local (pelvic) recurrence. CONCLUSION: These data from a large group of patients support the aggressive surgical management of invasive bladder cancer. Excellent long-term survival can be achieved with a low incidence of pelvic recurrence.

17.
Transl Androl Urol ; 12(2): 228-240, 2023 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-36915891

RESUMEN

Background: Galectin-1 (Gal-1) and Galectin-3 (Gal-3) are carbohydrate binding proteins with a wide range of biological activity, including regulation of cellular adhesion, proliferation, and apoptosis in solid tumors. Prior small studies have reported that Gal-3 expression is associated with progression of disease in urothelial carcinoma (UC), from non-muscle invasive UC progression to muscle invasive UC. We assessed Gal-1 and Gal-3 protein expression H-score utilizing a tissue microarray (TMA) created from 301 cystectomy specimens. Methods: Immunohistochemistry for Gal-1 and Gal-3 was performed on TMA generated from tumor blocks from chemotherapy naïve cystectomy specimens. The variable of interest, H-score, was defined as the product of the percentage of cells staining positive (0-100) and intensity score (0-3) scored by a single pathologist. Survival end points were analyzed using Kaplan-Meier and Cox Proportional Hazards methods. Clinical data including Charlson Comorbidity Index (CCI), pathologic tumor (T) stage, tumor size, node stage, and surgical margins, were included in multivariable analysis. Results: We found that Gal-1 and Gal-3 expression correlated with intratumoral T stage (median Gal-1 H-score was 0 across non-invasive tissue types and 200 in invasive, P<0.01 and median Gal-3 score was 270 across non-invasive tissue types and 70 in invasive, P<0.01). However, the highest intratumoral H-score per cystectomy core did not independently predict for recurrence-free survival (RFS) (Gal-1: HR =1.02, P=0.44, Gal-3: HR =1.01, P=0.65) or OS (Gal-1: HR =1.02, P=0.44, Gal-3: HR =1.01, P=0.72) in this cohort. Significant intratumoral heterogeneity was present for both Gal-1 and Gal-3, with an average difference between the highest and lowest H score was 95 for Gal-1 and 109 for Gal-3 for cystectomy specimens with more than one biopsy. Conclusions: Gal-1 and Gal-3 H-score per bladder did not independently predict for RFS or OS. Intra-tumoral Gal-1/Gal-3 heterogeneity complicates the use of Gal-1 and Gal-3 expression as a prognostic biomarker. Future studies should consider the evaluation of serum and urinary galectins as an approach to mitigate tumor heterogeneity.

18.
Vaccine X ; 14: 100289, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37020982

RESUMEN

Purpose: Cancer patients are at high risk of developing severe illness from SARS-CoV-2 infection, but risk is lowered with receipt of COVID-19 vaccine. COVID-19 vaccination uptake among previously infected cancer patients may be influenced by an assumption of natural immunity, predicted weak immune response, or concerns about vaccine safety. The objective of this study was to evaluate COVID-19 vaccine uptake trends in cancer patients previously infected with SARS-CoV-2. Materials and Methods: Medical records of 579 sequential cancer patients undergoing active treatment at Levine Cancer Institute who tested positive for COVID-19 between January 2020 and January 2021 were evaluated. Patients who died prior to vaccine eligibility were excluded from the analysis. Demographic, clinical, and COVID-19 related characteristics were analyzed to identify prognostic factors for COVID-19 vaccine uptake as this information could be important for health policy design for future pandemics. Results: Eighty-one patients died prior to the availability of COVID-19 vaccines. The acceptance rate of COVID-19 vaccination among 498 previously infected cancer patients was 54.6%. Of the patients with known vaccination dates, 76.8% received their first vaccine by April 17th, 2021. As of November 30, 2021, 23.7.% of eligible patients were boosted. In univariate models, older age, female sex, higher income, solid tumor cancer type, and hormone therapy were significantly associated with higher vaccine uptake, while Hispanic/Latino ethnicity was significantly associated with lower vaccine uptake. In a multivariable model, age (OR 1.18, 95% CI 1.10-1.28; p < 0.001), female sex (OR 1.80, 95% CI 1.22-2.66; p = 0.003), and higher income (OR 1.11, 95% CI 1.01-1.22; p = 0.032), were predictive of COVID-19 vaccine uptake. Conclusions: Overall, vaccine uptake was low among our cohort of previously infected cancer patients. Older age, female sex, and higher income were the only variables associated with COVID-19 vaccine uptake within this vulnerable patient population.

19.
Cancer ; 118(17): 4271-9, 2012 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-22213271

RESUMEN

BACKGROUND: A study was undertaken to compare survival and 5-year mortality by Medicaid status in adults diagnosed with 8 select cancers. METHODS: Linking records from the Ohio Cancer Incidence Surveillance System (OCISS) with Ohio Medicaid enrollment data, the authors identified Medicaid and non-Medicaid patients aged 15 to 54 years and diagnosed with the following incident cancers in the years 1996-2002: cancer of the testis; Hodgkin and non-Hodgkin lymphoma; early stage melanoma, colon, lung, and bladder cancer; and pediatric malignancies (n = 12,703). Medicaid beneficiaries were placed in the pre-diagnosis group if they were enrolled in Medicaid at least 3 months before cancer diagnosis, and in the peri/post-diagnosis group if they enrolled in Medicaid upon or after being diagnosed with cancer. The authors also linked the OCISS with death certificates and data from the US Census. By using Cox and logistic regression analysis, they examined the association between Medicaid status and survival and 5-year mortality, respectively, after adjusting for patient covariates. RESULTS: Nearly 11% of the study population were Medicaid beneficiaries. Of those, 45% were classified in the peri/post-diagnosis group. Consistent with higher mortality, findings from the Cox regression model indicated that compared with non-Medicaid, patients in the Medicaid pre-diagnosis and peri/post-diagnosis groups experienced unfavorable survival outcomes (adjusted hazard ratio [AHR], 1.52; 95% confidence interval [CI], 1.27-1.82 and AHR, 2.01; 95% CI, 1.70-2.38, respectively). CONCLUSIONS: Medicaid status was associated with unfavorable survival, even after adjusting for confounders. The findings reflect the vulnerability of Medicaid beneficiaries and possible inadequacies in the process of care.


Asunto(s)
Disparidades en Atención de Salud , Medicaid , Neoplasias/mortalidad , Adolescente , Adulto , Bases de Datos como Asunto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ohio , Análisis de Supervivencia , Estados Unidos/epidemiología , Adulto Joven
20.
Oncology (Williston Park) ; 26(12): 1216-21, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23413606

RESUMEN

In recent years, management of prostate cancer has benefited from an expanding array of new pharmacological options that are the result, in part, of an increased understanding of, and ability to target, androgen signaling. Further characterization of additional molecular pathways relevant to prostate cancer tumorigenesis has identified new molecular targets in prostate cancer that may be amenable to therapeutic intervention with novel agents. In addition, novel radioisotope therapies and cytotoxic agents have shown significant anticancer efficacy with manageable patterns of toxicity, and will eventually have to be integrated into our algorithms of therapy. This review summarizes recent findings in clinical prostate cancer research reported at the 2012 Annual Scientific Meeting of the American Society of Clinical Oncology (ASCO) and addresses their relevance to clinical practice.


Asunto(s)
Antineoplásicos Hormonales/uso terapéutico , Neoplasias Óseas/terapia , Neoplasias de la Próstata/terapia , Radiofármacos/uso terapéutico , Neoplasias Óseas/secundario , Medicina Basada en la Evidencia , Humanos , Masculino , Terapia Molecular Dirigida , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Terapia Recuperativa , Transducción de Señal/efectos de los fármacos , Transducción de Señal/efectos de la radiación , Resultado del Tratamiento
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