RESUMEN
BACKGROUND: Ofatumumab is a humanized type 1 anti-CD20 monoclonal antibody. Preclinical studies show improved complement-mediated cytotoxicity (CMC) compared to rituximab in mantle cell lymphoma (MCL). This study evaluates the safety and efficacy of combining ofatumumab with HyperCVAD/MA (O-HyperCVAD) in newly diagnosed MCL. METHODS: In this single-arm phase 2 study, 37 patients were treated with the combination of O-HyperCVAD for 4 or 6 cycles, followed by high dose chemotherapy and autologous stem cell transplant. Primary objectives were overall response rate (ORR) and complete response (CR) rate at the end of therapy. Secondary objectives included minimal residual disease (MRD) negativity, progression-free survival (PFS), and overall survival (OS). RESULTS: Median age was 60 years; ORR was 86% and 73% achieved a CR by modified Cheson criteria. The MRD negativity rate was 78% after 2 cycles of therapy, increasing to 96% at the end of induction; median PFS and OS were 45.5 months and 56 months, respectively. Achieving a post-induction CR by both imaging and flow cytometry was associated with improved PFS and OS. Early MRD negativity (post-2 cycles) was also associated with an improved PFS but not OS. There were 3 deaths while on therapy, and grades 3 and 4 adverse events (AEs) were observed in 22% and 68% of the patients. CONCLUSION: The addition of ofatumumab to HyperCVAD/HD-MA led to high rates of MRD negativity by flow cytometry in patients with newly diagnosed MCL. Achieving a CR post-induction by both imaging and flow cytometry is associated with improved overall survival.
Asunto(s)
Anticuerpos Monoclonales Humanizados , Linfoma de Células del Manto , Adulto , Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Humanos , Linfoma de Células del Manto/terapia , Persona de Mediana Edad , Neoplasia Residual/diagnóstico , RituximabRESUMEN
BACKGROUND: In addition to treating hyperlipidemia and atherosclerosis, statins have demonstrated anti-inflammatory and antitumor activity in various cancers. We evaluate this effect in esophageal cancer patients undergoing esophagectomy. METHODS: Esophageal cancer patients undergoing esophagectomy at Roswell Park Comprehensive Cancer Center between March 2007 and December 2015 were included. Association between presurgery statin use and relevant variables with overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) was analyzed using Cox hazards. Survival analyses were independently performed for body mass index (BMI)-based subgroups. RESULTS: There was no significant association between statin use and outcomes overall. However, in subgroup analysis, there was significant association between statin use and outcomes in patients with BMI ≥ 30. Multivariable analysis in obese patients demonstrated the association of statins with improved OS (hazard ratio [HR]: 0.46, p = 0.025), DSS (HR: 0.39, p = 0.015), and RFS (HR: 0.38, p = 0.022). The only other variable significantly associated with all three outcome measures was stage. CONCLUSIONS: Statin use is associated with improved OS, DSS, and RFS of obese patients in resected esophageal cancer. BMI could be investigated as a biomarker for adjunctive statin use in future studies.
Asunto(s)
Neoplasias Esofágicas , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/cirugía , Esofagectomía/efectos adversos , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Obesidad/complicaciones , Obesidad/cirugía , Modelos de Riesgos Proporcionales , Estudios RetrospectivosRESUMEN
In this phase I, dose-escalation study, we sought to determine the maximum tolerated dose (MTD) of the anaplastic lymphoma kinase/c-ROS oncogene 1 receptor (ALK/ROS1) inhibitor ceritinib in combination with gemcitabine-based chemotherapy in patients with advanced solid tumors. Secondary objectives were characterization of the safety profile, pharmacokinetics and preliminary efficacy of these combinations, and identification of potential biomarkers of efficacy. Ceritinib was combined with gemcitabine (Arm 1), gemcitabine/nab-paclitaxel (Arm 2) or gemcitabine/cisplatin (Arm 3). Drug concentrations in plasma were measured by tandem mass spectrometric detection (LC-MS/MS). We analyzed archival tumor tissue for ALK, ROS1, hepatocyte growth factor receptor (c-MET) and c-Jun N-terminal kinase (JNK) expression by immunohistochemistry. Arm 2 closed early secondary to toxicity. Twenty-one patients were evaluable for dose-limiting toxicity (DLT). There was one DLT in Arm 1 (grade 3 ALT increase) and three DLTs in Arm 3 (grade 3 acute renal failure, grade 3 thrombocytopenia, grade 3 dyspnea). The MTD of ceritinib was determined to be 600 mg (Arm 1) and 450 mg orally daily (Arm 3). Main toxicities were hematologic, constitutional and gastrointestinal as expected by the chemotherapy backbone. The apparent clearance for ceritinib decreased substantially after repeated dosing; cisplatin did not significantly affect the pharmacokinetics of ceritinib. The overall response rate was 20%; the median progression-free survival was 4.8 months. Three out of five response-evaluable cholangiocarcinoma patients had clinical benefit. Increased expression of c-MET was associated with a lack of clinical benefit. Ceritinib in combination with gemcitabine and gemcitabine/cisplatin has a manageable toxicity profile. Further development of this strategy in tumors with ALK or ROS1 fusions is warranted.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Desoxicitidina/análogos & derivados , Neoplasias/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/administración & dosificación , Pirimidinas/administración & dosificación , Sulfonas/administración & dosificación , Adulto , Anciano , Quinasa de Linfoma Anaplásico/antagonistas & inhibidores , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/farmacocinética , Femenino , Humanos , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Neoplasias/mortalidad , Neoplasias/patología , Supervivencia sin Progresión , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/farmacocinética , Pirimidinas/efectos adversos , Pirimidinas/farmacocinética , Sulfonas/efectos adversos , Sulfonas/farmacocinética , GemcitabinaRESUMEN
BACKGROUND: In patients with clinical N1 disease, minimally invasive surgery (MIS) has potentially better perioperative outcome compared to open thoracotomy. Additionally, whether adjuvant or neoadjuvant chemotherapy produces the best long-term survival is still debatable. METHODS: We queried The National Cancer Database for patients with clinical N1 NSCLC who underwent surgical resection between 2010 and 2014. Comparison between patients receiving MIS and patients who underwent open thoracotomy was done using an intention-to-treat analysis. Comparison was also done among neoadjuvant, adjuvant chemotherapy, and only surgery. Proportional hazard models were used to evaluate the effects of surgical approach and timing of chemotherapy on overall survival. RESULTS: A total of 1440 and 3942 patients underwent MIS and open thoracotomy respectively. MIS achieved better surgical margins (90.0% versus 88.6%) and shorter length of stay (6.5 ± 6.5 versus 7.3 ± 6.4 d, P ≤ 0.01) compared to open thoracotomy. There were no differences in 30-day and 90-day mortality, nor readmission rates. Neoadjuvant and adjuvant chemotherapy were administered to 13.5% and 57.2% of patients respectively. There was no significant difference in the 5-year overall survival between MIS and open thoracotomy (46% versus 46% P = 0.08). There was significantly better 5-year overall survival in neoadjuvant and adjuvant chemotherapy versus only surgery, but no difference between neoadjuvant and adjuvant chemotherapy (48% versus 47% versus 44%, P < 0.01). CONCLUSIONS: In clinical N1 NSCLC, MIS does not compromise oncological quality or overall survival when compared to open thoracotomy. Overall survival improved in patients treated with chemotherapy but there is no difference when given as neoadjuvant versus adjuvant chemotherapy.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Toracotomía/métodos , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Quimioterapia Adyuvante , Bases de Datos Factuales , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: The incidence of neuroendocrine tumors (NETs) is rapidly rising. There are very few studies investigating the role of sociodemographic factors in NETs. This study was aimed at examining how geographic and sociodemographic characteristics shape outcomes in the NET population. METHODS: A retrospective analysis using the Surveillance, Epidemiology, and End Results database was performed, and the NET patient population from 1973 to 2015 was studied. Univariate and multivariable analyses were performed to evaluate patients' disease-specific survival (DSS) and overall survival (OS). Geographic and sociodemographic factors, including the location of residence (urban area [UA] vs rural area [RA]), sex, race, insurance status, and marital status, were included in the analysis. RESULTS: A total of 53,034 patients (5517 in RAs and 47,517 in UAs) were included in the analysis. The incidence of NETs was found to be rising in both RAs and UAs but more rapidly in RAs (with the highest incidence in 2006-2015: 5.93 per 100,000 in RAs vs 4.10 per 100,000 in UAs). Patients from RAs presented at advanced stages in comparison with patients from UAs (regional, 18% vs 16%; distant, 15% vs 13%; P < .01). In the multivariable model, RA patients had a trend toward poorer OS (hazard ratio, 1.05; P = .053) in comparison with UA patients. The multivariable analysis showed significantly worse DSS and OS for uninsured, single, and male patients in comparison with insured, married, and female patients, respectively. CONCLUSIONS: This study has identified sociodemographic disparities in NET outcomes. Access to health care could be a potential contributing factor, although differences in environmental exposure, health behavior, and tumor biology could also be responsible.
Asunto(s)
Cobertura del Seguro/estadística & datos numéricos , Tumores Neuroendocrinos/diagnóstico , Población Rural/estadística & datos numéricos , Programa de VERF/estadística & datos numéricos , Población Urbana/estadística & datos numéricos , Femenino , Geografía , Humanos , Incidencia , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Tumores Neuroendocrinos/epidemiología , Estudios Retrospectivos , Clase Social , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND AND OBJECTIVES: Pasireotide was shown in a randomized trial to decrease the rate of postoperative pancreatic fistula (POPF). However, retrospective series from other centers have failed to confirm these results. METHODS: Patients who underwent pancreatoduodenectomy or distal pancreatectomy between January 2014 and February 2019 were included. Patients treated after November 2016 routinely received pasireotide and were compared to a retrospective cohort. Multivariate analysis was performed for the outcome of clinically relevant POPF (CR-POPF), with stratification by fistula risk score (FRS). RESULTS: Ninety-nine of 300 patients received pasireotide. The distribution of high, intermediate, low, and negligible risk patients by FRS was comparable (P = .487). There were similar rates of CR-POPF (19.2% pasireotide vs 14.9% control, P = .347) and percutaneous drainage (12.1% vs 10.0%, P = .567), with greater median number of drain days in the pasireotide group (6 vs 4 days, P < .001). Multivariate modeling for CR-POPF showed no correlation with operation or pasireotide use. Adjustment with propensity weighted models for high (OR, 1.02, 95% CI, 0.45-2.29) and intermediate (OR, 1.02, CI, 0.57-1.81) risk groups showed no correlation of pasireotide with reduction in CR-POPF. CONCLUSIONS: Pasireotide administration after pancreatectomy was not associated with a decrease in CR-POPF, even when patients were stratified by FRS.
Asunto(s)
Pancreatectomía/métodos , Fístula Pancreática/prevención & control , Pancreaticoduodenectomía/métodos , Somatostatina/análogos & derivados , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pancreatectomía/efectos adversos , Pancreatectomía/estadística & datos numéricos , Fístula Pancreática/epidemiología , Fístula Pancreática/etiología , Neoplasias Pancreáticas/cirugía , Pancreaticoduodenectomía/efectos adversos , Pancreaticoduodenectomía/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Lesiones Precancerosas/cirugía , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Retrospectivos , Riesgo , Somatostatina/administración & dosificaciónRESUMEN
BACKGROUND: Cutaneous leiomyosarcoma is a rare dermal neoplasm usually arising from the pilar smooth muscle. It is considered a relatively indolent neoplasm, and there is debate whether designation as sarcoma is appropriate. Owing to some conflicting data in the literature, however, its behavior warrants further clarification. OBJECTIVE: To determine the clinical behavior and demographic and pathologic characteristics of cutaneous leiomyosarcoma. MATERIALS AND METHODS: The Surveillance, Epidemiology and End Results database was used to collect data on cutaneous leiomyosarcoma and 2 reference populations: cutaneous angiosarcoma (aggressive) and atypical fibroxanthoma (indolent). Demographic and oncologic characteristics were examined, and overall survivals (OS) and disease-specific survivals were compared. RESULTS: Leiomyosarcoma and atypical fibroxanthoma displayed lower stage (localized: 69.7% and 66.8% respectively), smaller size (<3 cm: 90.5% and 72%), and lower rates of disease-specific mortality (2.9% and 7.8%) compared with angiosarcoma. Patients with leiomyosarcoma had a 5-year disease-specific survival rate of 98% and OS rate of 85%. CONCLUSION: Cutaneous leiomyosarcoma shows outcomes similar to atypical fibroxanthoma. It is nearly always indolent and should be distinguished from more aggressive cutaneous and subcutaneous sarcomas. Clear communication of the biologic potential may be best achieved using alternate diagnostic terminology such as "atypical intradermal smooth-muscle neoplasm."
Asunto(s)
Hemangiosarcoma/mortalidad , Hemangiosarcoma/patología , Leiomiosarcoma/mortalidad , Leiomiosarcoma/patología , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/patología , Factores de Edad , Anciano , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Programa de VERF , Factores Sexuales , Tasa de Supervivencia , Carga Tumoral , Estados Unidos/epidemiologíaRESUMEN
Disease relapse and toxicity are the shortcomings of reduced-intensity conditioning (RIC) for allogeneic hematopoietic cell transplantation (alloHCT). We hypothesized that adding total body irradiation (TBI) to and decreasing melphalan (Mel) from a base RIC regimen of fludarabine (Flu) and Mel would increase cytoreduction and improve disease control while decreasing toxicity. We performed a phase II trial of Flu 160 mg/m2, Mel 50 mg/m2, and TBI 400 cGy (FluMelTBI-50, nâ¯=â¯61), followed by a second phase II trial of Flu 160 mg/m2, Mel 75 mg/m2, and TBI 400cGy (FluMelTBI-75, nâ¯=â¯94) as RIC for alloHCT. Outcomes were compared with a contemporaneous cohort of 162 patients who received Flu 125 mg/m2 and Mel 140 mg/m2. Eligibility criteria were equivalent for all 3 regimens. All patients were ineligible for myeloablative/intensive conditioning. The median (range) follow-up for all patients was 51 (15 to 103) months. Day 100 donor lymphoid chimerism and transplant-related mortality, neutrophil and platelet engraftment, acute and chronic graft versus host disease incidence, overall survival (OS), and progression-free survival (PFS) were equivalent between FluMel, FluMelTBI-50, and FluMelTBI-75. Stomatitis wasdecreased for FluMelTBI versus FluMel (P < .01). PFS for patients not in complete remission on alloHCT was improved for FluMelTBI-75 versus FluMel (Pâ¯=â¯.03). On multivariate analysis, OS (Pâ¯=â¯.05) and PFS (Pâ¯=â¯.05) were significantly improved for FluMelTBI-75 versus FluMel. FluMelTBI-75 is better tolerated than FluMel, with improved survival and disease control.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Melfalán/uso terapéutico , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo/métodos , Vidarabina/análogos & derivados , Irradiación Corporal Total/métodos , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Niño , Femenino , Humanos , Masculino , Melfalán/farmacología , Persona de Mediana Edad , Vidarabina/farmacología , Vidarabina/uso terapéutico , Adulto JovenRESUMEN
BACKGROUND: Neoadjuvant treatment improves survival for patients undergoing esophagectomy for esophageal cancer. Recent evidence suggests that neoadjuvant chemoradiation offers no advantage over chemotherapy alone before surgical resection for adenocarcinoma histology. We sought to examine if this applies to patients with squamous cell histology. MATERIALS AND METHODS: The National Cancer Database was queried for patients who underwent treatment for squamous cell carcinoma of the esophagus from 2004 to 2012. Patients who underwent neoadjuvant chemotherapy before esophagectomy were compared with those undergoing chemotherapy and radiation before surgical resection. Associations between potential covariates and treatment were analyzed using the Pearson chi-square test for categorical variables and Wilcoxon rank sum test for continuous variables. Univariate and multivariate proportional hazards modeling results were used to assess the effect of treatment on overall survival. Relative prognosis was summarized using estimates and 95% confidence limits for the hazard ratio. Unadjusted differences in overall survival and disease-specific survival between the treatment are shown using Kaplan-Meier methods. RESULTS: A total of 902 patients underwent neoadjuvant therapy before surgical resection during the study period, with 827 receiving chemotherapy and radiation, and 75 receiving chemotherapy alone preoperatively. The 30- and 90-d mortality for patients undergoing neoadjuvant chemotherapy and radiation followed by surgery were 5.4% and 10.4% compared to 5.5% and 11.1% for patients who received chemotherapy alone preoperatively (P = 0.963 and P = 0.856), respectively. Median overall survival for patients receiving chemotherapy and radiation was 36.0 mo versus 40.8 mo for chemotherapy alone. The 5-y survival was 39% for the chemotherapy and radiation group and 43% for the chemotherapy group (logrank P = 0.7212). CONCLUSIONS: For patients undergoing neoadjuvant treatment before planned surgical resection of squamous cell carcinoma of the esophagus, the addition of radiation to neoadjuvant chemotherapy did not improve long-term survival and did not appear to impact short-term outcomes postoperatively. Further study with a randomized phase III trial is needed.
Asunto(s)
Carcinoma de Células Escamosas/terapia , Quimioradioterapia/métodos , Neoplasias Esofágicas/terapia , Esofagectomía , Terapia Neoadyuvante/métodos , Anciano , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Esófago/efectos de los fármacos , Esófago/efectos de la radiación , Esófago/cirugía , Femenino , Estudios de Seguimiento , Mortalidad Hospitalaria , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Early presentation of gingival squamous cell carcinoma (GSCC) is at times misdiagnosed as a benign inflammatory or reactive oral condition. Some misdiagnosed patients undergo unnecessary, invasive dental procedures, resulting in delayed cancer diagnosis and an increased risk of accelerated disease progression due to disruption of the periosteum and cortical bone. The records of 58 patients with biopsy-proven GSCC were retrospectively reviewed. The sample included 32 patients who underwent an invasive dental procedure (IDP) prior to cancer diagnosis and 26 patients who did not undergo an IDP (non-case group). Patients from both groups initially presented with similar symptoms. The median duration of symptoms at initial clinical presentation was 6 months for the IDP group and 2 months for the non-case group. In IDP patients, symptoms worsened after the IDP was rendered, with 37.5% presenting with a severe-grade symptom. In both groups, the majority of lesions were found on the posterior mandible and had a histologic grading of moderately differentiated GSCC. The odds of the IDP group having late-stage disease were 2.94 times greater than the odds for the control group. Stage T3/T4 malignancy was diagnosed in 77.4% of the IDP patients versus 53.8% of non-case patients. Disease-specific mortality was comparable; however, surgical treatment was significantly more extensive in the IDP group than in the non-case group. The disruption of alveolar periosteum in undiagnosed oral cancer patients results in significant delay in diagnosis, necessitating more complicated treatment regimens because of local tumor progression.
Asunto(s)
Carcinoma de Células Escamosas/patología , Neoplasias Gingivales/patología , Procedimientos Quirúrgicos Orales/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/etiología , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Neoplasias Gingivales/diagnóstico , Neoplasias Gingivales/etiología , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Four-dimensional computed tomography (4D CT) has emerged as an extremely sensitive preoperative imaging modality for primary hyperparathyroidism compared with the historical use of sestamibi and ultrasound (US). Specialized volume rendering and technical modifications further enhance this technique for operative guidance while reducing radiation exposure. METHODS: Patients undergoing parathyroidectomy for primary hyperparathyroidism from December 2010 to September 2013, carried out by two surgeons at a tertiary cancer center, were evaluated. Comparison was made between the three imaging modalities (4D CT, sestamibi, and US) for preoperative localization rate and accuracy. Biochemical parameters and radiation exposure were also analyzed. RESULTS: A total of 202 patients were identified from the database and 200 patients were included in the analysis. All patients underwent 4D CT (100 %), 185 sestamibi (92.5 %) and 186 US (93 %). In patients with single-gland disease (n = 153), 4D CT, sestamibi, and US were positive in 96 %, 65.4 % and 57.7 % of patients, respectively and, when positive, were accurately localized in 97.2 %, 93.4 % and 96.3 % of patients, respectively. In patients with multigland disease (MGD) [n = 47], 4D CT, sestamibi, and US predicted MGD in 32 %, 0 %, and 13.6 % of patients, respectively. With our technique modification, radiation exposure from 4D CT approached that of sestamibi. CONCLUSIONS: Low-dose, modified 4D CT with volume rendering when compared with sestamibi has a statistically significant higher positivity rate, improved accuracy rate, provides excellent images, superior surgical planning, and has a comparable radiation exposure risk profile. Consideration should be made for the abandonment of routine sestamibi single-positron emission computed tomography (SPECT), with 4D CT as the preoperative imaging modality of choice.
Asunto(s)
Tomografía Computarizada Cuatridimensional/estadística & datos numéricos , Hiperparatiroidismo Primario/diagnóstico , Radiofármacos , Tecnecio Tc 99m Sestamibi , Tomografía Computarizada de Emisión de Fotón Único/estadística & datos numéricos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Estudios de Seguimiento , Humanos , Hiperparatiroidismo Primario/cirugía , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Prospectivos , Adulto JovenRESUMEN
INTRODUCTION: Sparse information is available about GISTs in uncommon locations. Our large database analysis aims to determine the characteristics of GISTs in the esophagus, colon and rectum and compare to gastric GISTs. METHODS: The Surveillance Epidemiology and End Results (SEER) database was queried from 1990 to 2009 using CS SCHEMA v0203. Characteristics of each location were compared to gastric GISTs. RESULTS: 4411 GIST (29 esophageal, 2658 stomach, 1463 small intestine, 126 colonic, and 135 rectal) from 1990 to 2009 were identified. Univariate and multivariate predictors of worse disease specific survival in both the entire cohort and surgical resection group include older age, male gender, tumor size > 5 cm, no surgical intervention and anatomical location. Although less likely to undergo surgical resection, esophageal GIST (all patients and resected) had a comparable survival to gastric GIST. A higher proportion of colonic GISTs presented with distant disease and had a worse disease specific survival when compared to rectal GISTs. CONCLUSION: Our results show a rising incidence in GISTs and highlight the characteristics of GISTs based on anatomical location. In addition, this is the first study to demonstrate that colonic GISTs behave differently when compared to rectal GISTs and warrants further prospective evaluation.
Asunto(s)
Neoplasias Gastrointestinales/mortalidad , Neoplasias Gastrointestinales/patología , Tumores del Estroma Gastrointestinal/mortalidad , Tumores del Estroma Gastrointestinal/patología , Distribución por Edad , Anciano , Femenino , Neoplasias Gastrointestinales/terapia , Tumores del Estroma Gastrointestinal/terapia , Humanos , Masculino , Persona de Mediana Edad , Grupos Raciales/estadística & datos numéricos , Programa de VERF , Análisis de Supervivencia , Estados Unidos/epidemiologíaRESUMEN
Y15 or inhibitor 14 (1,2,4,5-benzenetetramine tetrahydrochloride) is a potent and specific inhibitor of focal adhesion kinase that inhibits its autophosphorylation activity, decreases the viability of cancer cells, and blocks tumor growth. In this preclinical study, we analyzed the pharmacokinetics of Y15 in mice plasma, its metabolic stability in mouse and human liver microsomes and toxicity in mice. The pharmacokinetics study in mice demonstrated that, following intraperitoneal administration at 30 mg/kg dose, Y15 was very rapidly absorbed in mice, reaching maximum plasma concentration in 4.8 min. Y15 rapidly metabolized in mouse and human liver microsomes with half-life t1/2 of 6.9 and 11.6 min, respectively. The maximal tolerated dose of single-dose administration of Y15 by oral administration was 200 mg/kg, and the multiple maximum tolerated dose of Y15 was 100 mg/kg by PO during 7 day study. Y15 did not cause any mortality or statistically significant differences in the body weight at 30 mg/kg by IP during 28-day study, and at 100 mg/kg by PO during the 7-day study. There were no clinical chemical, hematological, or histopathological changes in different mice organs at 30 mg/kg by IP during 28 days and at 100 mg/kg dose by PO during 7 days. Thus, this is the first preclinical toxicity, pharmacokinetics, and metabolic stability study of Y15 inhibitor. Further development of Y15 will provide a basis for new therapeutic and future clinical studies.
Asunto(s)
Compuestos de Anilina/farmacocinética , Compuestos de Anilina/toxicidad , Antineoplásicos/farmacocinética , Antineoplásicos/toxicidad , Quinasa 1 de Adhesión Focal/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/farmacocinética , Inhibidores de Proteínas Quinasas/toxicidad , Administración Oral , Compuestos de Anilina/administración & dosificación , Compuestos de Anilina/sangre , Animales , Antineoplásicos/administración & dosificación , Biotransformación , Estabilidad de Medicamentos , Femenino , Quinasa 1 de Adhesión Focal/metabolismo , Semivida , Humanos , Inyecciones Intraperitoneales , Masculino , Dosis Máxima Tolerada , Ratones , Microsomas Hepáticos/metabolismo , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/sangre , Medición de Riesgo , Pruebas de ToxicidadRESUMEN
BACKGROUND: Endoscopic resection (ER) is an important advance in the management of esophageal tumors. It has been used successfully for superficial esophageal cancer and high-grade dysplasia (HGD) arising out of Barrett epithelium. METHODS: From a single institution within the Department of Surgery, patients who underwent ER for esophageal tumors between December 2001 and January 2012 were evaluated. Demographic, clinical, and pathologic variables were collected and reviewed. RESULTS: We identified 81 patients who underwent ER for esophageal lesions. Median patient age was 69 years, and the median follow-up was 3.25 years. In patients with HGD, at the time of last endoscopy, the complete eradication rate of HGD was 84 % and cancer-specific survival was 100 %. During surveillance, one patient developed an invasive carcinoma that required endoscopic therapy. Patients with T1a and negative deep margins on ER had a recurrence-free and cancer-specific survival of 100 %. There were seven patients with T1b and negative margins on ER. Three patients underwent esophagectomy; final pathology revealed no residual malignancy or lymph node metastasis. Two patients had definitive chemoradiation, and two patients were observed. To date, there has been no cancer recurrence. In all patients who underwent ER, there was one episode of bleeding that required endoscopic treatment and admission for observation. CONCLUSIONS: ER can be performed safely and can adequately stage and often treat patients with HGD and superficial cancers. Patients with HGD and T1a disease with negative margins are cured with ER alone. Observation and surveillance may be an option for select patients with low-risk, early submucosal disease (T1b) and negative margins.
Asunto(s)
Esófago de Barrett/cirugía , Endoscopía Gastrointestinal/métodos , Neoplasias Esofágicas/cirugía , Esofagectomía/métodos , Medición de Riesgo/métodos , Adulto , Anciano , Anciano de 80 o más Años , Esófago de Barrett/diagnóstico , Supervivencia sin Enfermedad , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/secundario , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Metástasis Linfática , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Estadificación de Neoplasias , New York/epidemiología , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Factores de Tiempo , Resultado del TratamientoRESUMEN
PURPOSE: Early-onset colorectal cancer (EOCRC), defined as CRC diagnosed before age 50 years, has increased significantly worldwide. The majority of EOCRCs do not appear to be driven by genetic factors and may be influenced by environmental factors. We hypothesized that sociodemographic disparities exist in EOCRC. The purpose was of the study was to examine the geographic disparities in patients with EOCRC. METHODS: We retrospectively examined the SEER database from 1976 to 2016 to examine the geographic disparities in EOCRC. A total of 73,378 patients with EOCRC were included in the analysis. We performed univariate and multivariable analyses to evaluate overall survival (OS) and disease-specific survival (DSS). Sociodemographic factors, including the location of residence (metropolitan areas [MA] or rural areas [RA]), sex, race, insurance status, and marital status, were included in the statistical analysis. RESULTS: The incidence and mortality rates were consistently higher in RA versus MA during the study period. Multivariable analysis showed that patients living in RA had worse OS (hazard ratio [HR], 1.14; P < .01) and DSS (HR, 1.15; P < .001) compared with those living in MA. Similarly, non-Hispanic Black ethnicity and uninsured patients had significantly worse survival when compared with non-Hispanic White and insured patients, respectively. Married status showed better survival outcomes. CONCLUSION: Patients with EOCRC living in RA have worse outcomes. Understanding the mechanisms behind such socioeconomic disparities is important so that future studies can reduce these disparities.
Asunto(s)
Neoplasias Colorrectales , Humanos , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto , Edad de Inicio , Demografía , Programa de VERFRESUMEN
The National Comprehensive Cancer Network guidelines provide evidence-based consensus for optimal individual site- and stage-specific treatments. This is a cohort study of 11,121 late-stage oral cancer patients in the National Cancer Database from 2010 to 2016. We hypothesized that patient travel distance may affect treatment choices and impact outcome. We split travel distance (miles) into quartiles (D1-4) and assessed treatment choices, type of facility, and survival outcome in relation to distance traveled. Univariate and multivariate analyses addressed contributions of specific variables. White patients were most likely to travel farthest (D4) for treatment compared to Black patients (D1). Urban area patients traveled shorter distances than those from rural areas. Greater travel distance was associated with patients undergoing surgical-based therapies and treatment at academic centers. Patients in D1 had the lowest median survival of all distance quartiles. Surgery-based multimodality treatment (surgery and radiation) had a median survival significantly greater than for non-surgical therapy. Several factors including travel distance and treatment facility were associated with survival outcomes for late-stage oral cavity cancers. Consideration of these factors may help improve the outcome for this patient population.
RESUMEN
PURPOSE: There is compelling evidence that CD4+ and CD8+T cells are dysfunctional in multiple myeloma, compromising their ability to control disease progression. Pre-clinical models suggest that exercise represents a non-pharmacologic means to reduce immune exhaustion, but no studies to date have examined the relationship between an exercise intervention and biomarkers of immune exhaustion in multiple myeloma patients. PATIENTS AND METHODS: The current study includes 24 multiple myeloma patients who participated in a six-month physical activity intervention, consisting of supervised strength training (n = 12) and unsupervised home-based walking arms (n = 12). Comprehensive flow cytometry was utilized to assess the frequency of CD4+ and CD8+T cells and subpopulations expressing the markers of exhaustion PD-1, TIGIT, TIM3 and/or LAG3. Ratios of exhausted to non-exhausted cell populations, and percentages of exhausted to total populations of the same lineage, were calculated for the baseline and final timepoints. RESULTS: Eighteen of 20 exhaustion measures were lower at the end of the intervention than at baseline, and several were significantly or borderline significantly reduced in the entire sample or in one of the arms. The entire sample saw improvements in the ratios of CD4+ TIGIT+ to non-exhausted CD4+ (0.7 [0.6] to 0.6 [0.4], P = .04) and CD8+ PD1+ to non-exhausted CD8+ (1.8 [2.6] to 1.5 [2.0], P = .06), and in total exhausted CD8+ as a percent of total CD8+ (72.9 [21.9] to 68.3 [19.6], P < .01). CONCLUSIONS: This pilot study suggests that physical activity induces changes in MM patients' immune systems, potentially rendering a less exhausted T cell state.
Asunto(s)
Linfocitos T CD8-positivos , Ejercicio Físico , Mieloma Múltiple , Humanos , Mieloma Múltiple/terapia , Mieloma Múltiple/inmunología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Biomarcadores , Receptor de Muerte Celular Programada 1/metabolismo , Terapia por Ejercicio/métodos , Proteína del Gen 3 de Activación de Linfocitos , Agotamiento de Células TRESUMEN
BACKGROUND: Signet ring cell esophageal adenocarcinoma histology has been difficult to study in single institution series because of its relative rarity, yet has an anecdotal reputation for poor prognosis. The Surveillance, Epidemiology, and End Results (SEER) database was examined to assess the prognostic implications of this esophageal adenocarcinoma subtype. METHODS: All patients with esophageal adenocarcinoma in the SEER database from 2004 to 2009 were included. Univariate and multivariate analyses examining the relationship of signet ring cell histology with overall survival were performed in all patients, as well as those undergoing surgical resection. RESULTS: A total of 596 of 11,825 (5%) study patients had signet ring cell histology. Patients with signet ring cell histology were similar in age, race, and sex distribution, but had a higher grade (P < .001) and higher stage (P < .001) at diagnosis. In both the all-patient group as well as those undergoing surgical resection, univariate analyses showed a worse survival in patients with signet ring cell esophageal cancer (hazard ratio [HR] = 1.24; 95% confidence interval [CI] = 1.13-1.36 and HR = 1.57; 95% CI = 1.29-1.93, respectively). In multivariate analyses adjusting for covariates, patients with signet ring cell cancer had a worse prognosis than those without (HR = 1.18; 95% CI = 1.07-1.30). In surgically resected patients, this remained a trend, but did not reach statistical significance (HR = 1.16; 95% CI = 0.94-1.42). CONCLUSIONS: This large study of esophageal adenocarcinoma confirms the clinical impression that signet ring cell variant of adenocarcinoma is associated with an advanced stage at presentation and a worse prognosis independent of stage of presentation.
Asunto(s)
Carcinoma de Células en Anillo de Sello/epidemiología , Carcinoma de Células en Anillo de Sello/patología , Neoplasias Esofágicas/epidemiología , Neoplasias Esofágicas/patología , Adenocarcinoma/epidemiología , Adenocarcinoma/patología , Adulto , Anciano , Análisis de Varianza , Carcinoma de Células en Anillo de Sello/cirugía , Neoplasias Esofágicas/cirugía , Esofagectomía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Pronóstico , Programa de VERF , Estados Unidos/epidemiologíaRESUMEN
Mortality improvements in young women with breast cancer (BC) may be attributable to treatment advances; screening likely plays a less significant role as mammography is not recommended <40. We examined time-trends in outcome in a cohort of young women. Our goal was to determine the contributions of treatment and screening to mortality improvements and evaluate whether differential outcomes by ER status exist. Using SEER, patients (73,447) were divided into three categories by diagnosis year (1990-1994, 1995-1999, 2000-2004) and also categorized as <40 or 40-50 years. Multivariate analysis was done to investigate the association of survival with time period for both age groups by ER status. Hazard ratios (HR) for mortality in women 40-50 with ER positive BC declined over time. With 1990-1994 as referent, the HR in 1995-1999 was 0.77 (0.69-0.86) and 0.65 (0.59-0.71) in 2000-2004 (p < 0.001). Women <40 with ER positive BC also had improvements over time. In ER negative patients, the degree of improvements over time was less than that seen in ER positive women. We report a survival disparity over time in young women by ER status. Patients with ER negative disease have not had the degree of improvements over time as seen in ER positive disease. Therefore, mortality improvements in young women with ER positive BC may be attributed to treatment advances with endocrine agents.
Asunto(s)
Neoplasias de la Mama/epidemiología , Programa de VERF , Adulto , Factores de Edad , Neoplasias de la Mama/mortalidad , Femenino , Humanos , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Receptores de Estrógenos/metabolismo , Análisis de Supervivencia , Adulto JovenRESUMEN
BACKGROUND: Small cell cancer (SCC) of the esophagus is an uncommon malignancy with perceived poor prognosis, but there are few data to guide therapeutic decisions. We examined the Surveillance, Epidemiology, and End Results (SEER) database to identify prognostic factors for survival. METHODS: All patients with esophageal cancer in the SEER database between 1973 and 2009 were included. Univariate and multivariate analyses were performed in patients with and without SCC, examining the relationship of small cell histology, surgery, and other potential prognostic factors with overall survival (censored at 72 months). RESULTS: Of 64,799 esophageal cancer patients identified in the SEER database, 387 (0.6 %) had small cell histology. As compared with non-small cell histology, patients with small cell histology were similar in age and race but had a higher proportion of women (p < 0.001), had a higher stage at diagnosis (p < 0.001), and were less likely to undergo surgical resection (p < 0.01). Multivariate predictors associated with poor survival in the overall cohort included age, female gender, black race, and stage. In patients treated with surgery, multivariate predictors associated with poor survival included age, male gender, race, and stage but not small cell histology. In patients with small cell histology, both age and stage were associated with poor survival, but surgery and preoperative radiotherapy were associated with improved survival. CONCLUSIONS: SCC of the esophagus presents at an advanced stage and confers a poor prognosis. The survival benefit of surgery and radiotherapy suggests that all esophageal SCC patients should be considered for preoperative radiotherapy and surgery in a stage-appropriate fashion.