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1.
ESMO Open ; 9(6): 103477, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38833964

RESUMEN

BACKGROUND: Sunitinib is an oral anticancer drug approved for the treatment of among others gastrointestinal stromal tumor (GIST). Previous analyses demonstrated an exposure-response relationship at the standard dose, and minimum target levels of drug exposure have been defined above which better treatment outcomes are observed. Therapeutic drug monitoring (TDM) could be used as a tool to optimize the individual dose, aiming at sunitinib trough concentrations ≥37.5 ng/ml for continuous dosing. Nonetheless, data on the added value of TDM-guided dosing on clinical endpoints are currently lacking. Therefore, we evaluate the effect of TDM in patients with advanced and metastatic GIST treated with sunitinib in terms of efficacy and toxicity. PATIENTS AND METHODS: A TDM-guided cohort was compared to a non-TDM-guided cohort in terms of median progression-free survival (mPFS) and overall survival (mOS). Also, mPFS between patients with and without dose-limiting toxicities (DLTs) was compared. Patients in the prospective cohort were included in two studies on TDM-guided dosing (the DPOG-TDM study and TUNE study). The retrospective cohort consisted of patients from the Dutch GIST Registry who did not receive TDM-guided dosing. RESULTS: In total, 51 and 106 patients were included in the TDM-guided cohort and non-TDM-guided cohort, respectively. No statistical difference in mPFS was observed between these two cohorts (39.4 versus 46.9 weeks, respectively; P = 0.52). Patients who experienced sunitinib-induced DLTs had longer mPFS compared to those who did not (51.9 versus 28.9 weeks, respectively; P = 0.002). CONCLUSIONS: Our results do not support the routine use of TDM-guided dose optimization of sunitinib in patients with advanced/metastatic GIST to improve survival.


Asunto(s)
Antineoplásicos , Monitoreo de Drogas , Tumores del Estroma Gastrointestinal , Sunitinib , Humanos , Sunitinib/administración & dosificación , Sunitinib/uso terapéutico , Sunitinib/farmacología , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Tumores del Estroma Gastrointestinal/patología , Femenino , Masculino , Persona de Mediana Edad , Anciano , Antineoplásicos/uso terapéutico , Antineoplásicos/administración & dosificación , Estudios Retrospectivos , Monitoreo de Drogas/métodos , Adulto , Resultado del Tratamiento , Neoplasias Gastrointestinales/tratamiento farmacológico , Neoplasias Gastrointestinales/patología , Neoplasias Gastrointestinales/mortalidad , Relación Dosis-Respuesta a Droga , Anciano de 80 o más Años , Estudios Prospectivos , Supervivencia sin Progresión
2.
J Med Internet Res ; 26: e51059, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38758583

RESUMEN

BACKGROUND: Patients with advanced cancer undergoing chemotherapy experience significant symptoms and declines in functional status, which are associated with poor outcomes. Remote monitoring of patient-reported outcomes (PROs; symptoms) and step counts (functional status) may proactively identify patients at risk of hospitalization or death. OBJECTIVE: The aim of this study is to evaluate the association of (1) longitudinal PROs with step counts and (2) PROs and step counts with hospitalization or death. METHODS: The PROStep randomized trial enrolled 108 patients with advanced gastrointestinal or lung cancers undergoing cytotoxic chemotherapy at a large academic cancer center. Patients were randomized to weekly text-based monitoring of 8 PROs plus continuous step count monitoring via Fitbit (Google) versus usual care. This preplanned secondary analysis included 57 of 75 patients randomized to the intervention who had PRO and step count data. We analyzed the associations between PROs and mean daily step counts and the associations of PROs and step counts with the composite outcome of hospitalization or death using bootstrapped generalized linear models to account for longitudinal data. RESULTS: Among 57 patients, the mean age was 57 (SD 10.9) years, 24 (42%) were female, 43 (75%) had advanced gastrointestinal cancer, 14 (25%) had advanced lung cancer, and 25 (44%) were hospitalized or died during follow-up. A 1-point weekly increase (on a 32-point scale) in aggregate PRO score was associated with 247 fewer mean daily steps (95% CI -277 to -213; P<.001). PROs most strongly associated with step count decline were patient-reported activity (daily step change -892), nausea score (-677), and constipation score (524). A 1-point weekly increase in aggregate PRO score was associated with 20% greater odds of hospitalization or death (adjusted odds ratio [aOR] 1.2, 95% CI 1.1-1.4; P=.01). PROs most strongly associated with hospitalization or death were pain (aOR 3.2, 95% CI 1.6-6.5; P<.001), decreased activity (aOR 3.2, 95% CI 1.4-7.1; P=.01), dyspnea (aOR 2.6, 95% CI 1.2-5.5; P=.02), and sadness (aOR 2.1, 95% CI 1.1-4.3; P=.03). A decrease in 1000 steps was associated with 16% greater odds of hospitalization or death (aOR 1.2, 95% CI 1.0-1.3; P=.03). Compared with baseline, mean daily step count decreased 7% (n=274 steps), 9% (n=351 steps), and 16% (n=667 steps) in the 3, 2, and 1 weeks before hospitalization or death, respectively. CONCLUSIONS: In this secondary analysis of a randomized trial among patients with advanced cancer, higher symptom burden and decreased step count were independently associated with and predictably worsened close to hospitalization or death. Future interventions should leverage longitudinal PRO and step count data to target interventions toward patients at risk for poor outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04616768; https://clinicaltrials.gov/study/NCT04616768. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2021-054675.


Asunto(s)
Hospitalización , Medición de Resultados Informados por el Paciente , Humanos , Persona de Mediana Edad , Masculino , Hospitalización/estadística & datos numéricos , Femenino , Anciano , Neoplasias/tratamiento farmacológico , Neoplasias/mortalidad , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Antineoplásicos/uso terapéutico , Antineoplásicos/efectos adversos , Neoplasias Gastrointestinales/tratamiento farmacológico , Neoplasias Gastrointestinales/mortalidad
3.
Acta Oncol ; 63: 288-293, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38712513

RESUMEN

INTRODUCTION: Metastatic gastrointestinal stromal tumour (GIST) is considered incurable, and life-long treatment with tyrosine kinase inhibitors is recommended. We investigated whether selected patients with metastatic GIST may remain in durable remission despite imatinib discontinuation. PATIENTS: In this 1-group, prospective, multicentre phase II trial selected patients with oligometastatic (≤3 metastases) GIST discontinued imatinib treatment. Eligible patients had been treated with imatinib >5 years without progression and had no radiologically detectable metastases after metastasectomy, radiofrequency ablation (RFA) or complete response to imatinib. The primary endpoint was progression-free survival (PFS) 3-years after stopping imatinib. Overall survival (OS) and quality of life (QoL) were secondary endpoints. RESULTS: The trial closed prematurely due to slow accrual. Between January 5, 2017, and June 5, 2019, 13 patients were enrolled, of whom 12 discontinued imatinib. The median follow-up time was 55 months (range, 36 to 69) after study entry. Five (42%) of the 12 eligible patients remained progression free, and seven (58%) progressed with a median time to progression 10 months. Median PFS was 23 months and the estimated 3-year PFS 41%. Six of the seven patients who progressed restarted imatinib, and all six responded. Three-year OS was 100%, and all patients were alive at the time of the study analysis. QoL measured 5 and 11 months after discontinuation of imatinib demonstrated improvement compared to the baseline. INTERPRETATION: A substantial proportion of selected patients with oligometastatic GIST treated with imatinib and metastasis surgery/RFA may remain disease-free for ≥3 years with improved QoL after stopping of imatinib.


Asunto(s)
Antineoplásicos , Tumores del Estroma Gastrointestinal , Mesilato de Imatinib , Calidad de Vida , Humanos , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Tumores del Estroma Gastrointestinal/patología , Tumores del Estroma Gastrointestinal/terapia , Tumores del Estroma Gastrointestinal/mortalidad , Tumores del Estroma Gastrointestinal/cirugía , Mesilato de Imatinib/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios Prospectivos , Antineoplásicos/uso terapéutico , Adulto , Neoplasias Gastrointestinales/patología , Neoplasias Gastrointestinales/tratamiento farmacológico , Neoplasias Gastrointestinales/mortalidad , Neoplasias Gastrointestinales/terapia , Privación de Tratamiento , Inducción de Remisión , Supervivencia sin Progresión , Metástasis de la Neoplasia , Anciano de 80 o más Años , Inhibidores de Proteínas Quinasas/uso terapéutico
4.
J Surg Oncol ; 129(8): 1490-1500, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38648421

RESUMEN

BACKGROUND: Social conditions and dietary behaviors have been implicated in the rising burden of gastrointestinal cancers (GIC). The "food environment" reflects influences on a community level relative to food availability, nutritional assistance, and social determinants of health. Using the US Department of Agriculture-Food Environment Atlas (FEA), we sought to characterize the association of food environment on GIC presenting stage and long-term survival. METHODS: Patients diagnosed with GIC between 2013 and 2017 were identified using the SEER database. FEA-scores were based on 282 county-level food security variables, store-restaurant availability, SNAP/WIC enrollment, pricing/taxes, and producer vicinity adjusted-for factors of socioeconomic status, race-ethnicity, transportation access, and comorbidities. Relative FEA rankings across US counties were averaged into a composite score and assigned to patients by county-of-residence. The association of FEA, cancer stage, and survival were analyzed using multiple logistic regression and cox-proportional hazard models relative to White/non-White race/ethnicity. RESULTS: Among 287,148 patients, the most common GIC-sites were colon (n = 97,942, 34%), pancreas (n = 49,785, 17.3%), liver (n = 31,098, 11.0%) and esophagus (n = 16,271, 5.7%). A worse food environment was independently associated with increased odds of late-stage diagnosis (esophageal odds ratio [OR]: 1.03, 95% confidence interval [CI]: 1.01-1.05; hepatic OR: 1.06, 95% CI: 1.03-1.08; pancreatic OR: 1.04, 95% CI: 1.01-1.06) among all patients; in contrast, food environment was associated with colorectal cancer stage among non-White patients only (OR: 1.04, 95% CI: 1.03-1.06). Worse food environment was associated with worse 3-year survival (colon OR: 1.03, 95% CI: 1.01-1.04; hepatic OR: 1.12, 95% CI: 1.08-1.17; gastric OR: 1.07, 95% CI: 1.01-1.13). Similar associations were noted relative to overall survival among the entire cohort (biliary tract hazard ratio [HR]: 1.03, 95% CI: 1.01-1.05; esophageal HR: 1.02, 95% CI: 1.01-1.04; hepatic HR: 1.07, 95% CI: 1.06-1.09; pancreatic HR: 1.04, 95% CI: 1.02-1.05; rectum HR: 1.03, 95% CI: 1.01-1.04; gastric HR: 1.05, 95% CI: 1.03-1.07), as well as among non-White patients (biliary HR: 1.04, 95% CI: 1.01-1.07; colon HR: 1.03, 95% CI: 1.01-1.05; esophageal HR: 1.05, 95% CI: 1.02-1.08; hepatic HR: 1.08, 95% CI: 1.06-1.10) (all p < 0.003). CONCLUSIONS: Food environment was independently associated with late-stage tumor presentation and worse 3-year and overall survival among GIC patients. Interventions to address inequities across communities relative to food environments are needed to alleviate disparities in cancer care.


Asunto(s)
Neoplasias Gastrointestinales , Humanos , Estados Unidos/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Neoplasias Gastrointestinales/mortalidad , Neoplasias Gastrointestinales/epidemiología , Anciano , Tasa de Supervivencia , Programa de VERF , Estudios de Seguimiento , Seguridad Alimentaria/estadística & datos numéricos , Pronóstico
5.
Int J Cardiol ; 406: 132001, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38561107

RESUMEN

BACKGROUND: Pulmonary embolism (PE) is described as a prognostic factor in patients with cancer however, the prognostic impact of PE remains unknown. This study investigated, the 1-year prognosis following PE in patients with breast-, gastrointestinal-, or lung cancer stratified by cancer status. METHODS: All Danish patients with first-time PE from 2008 to 2018 were included. Cancer status was categorized as no cancer, history of cancer, non-active cancer and active cancer. Unadjusted and age-stratified 1-year risk of death was estimated using the Kaplan-Meier estimator. Cause of death was reported using the Aalen-Johansen method. RESULTS: Of 35,679 patients with PE, 18% had a breast-, gastrointestinal-, or lung cancer. Patients with cancer were older compared with no cancer (69.8 years [IQR: 56.2-79.8]). One-year risk of death (95% confidence interval) for active breast-, gastrointestinal-, and lung cancer was 49.5% (44.0%-54.9%), 75.0% (72.5%-77.4%) and 80.1% (78.0%-82.3%) respectively, compared with 18.9% (18.4%-19.3%) for no cancer. Age-stratified analysis revealed no association with increasing age in non-active lung cancer and all active cancers. Further, non-cardiovascular death accounted for an increasing proportion by cancer status (no cancer < history of cancer < non-active cancer < active cancer). CONCLUSIONS: One-year risk of death was dependent on both cancer type and status; no association with age was found for patients with active cancers. Non-cardiovascular death was leading in non-active and active cancers. Thus, the occurrence of first-time PE could be regarded as a marker of cancer severity for patients with breast-, gastrointestinal-, and lung cancer.


Asunto(s)
Neoplasias de la Mama , Neoplasias Gastrointestinales , Neoplasias Pulmonares , Embolia Pulmonar , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/mortalidad , Estudios de Cohortes , Dinamarca/epidemiología , Estudios de Seguimiento , Neoplasias Gastrointestinales/complicaciones , Neoplasias Gastrointestinales/diagnóstico , Neoplasias Gastrointestinales/mortalidad , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidad , Pronóstico , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/epidemiología , Embolia Pulmonar/etiología , Sistema de Registros , Factores de Riesgo , Adulto Joven , Adulto
6.
World J Surg ; 48(6): 1424-1432, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38647223

RESUMEN

BACKGROUND: Gastrointestinal Stromal Tumors (GISTs) are the most common mesenchymal tumors of the GI tract. SEER is an extensive cancer database which proves useful in analyzing population trends. This analysis investigated GIST outcomes between geriatric & non-geriatric patients. METHODS: SEER*STAT 8.4.0.1 was used to extract relevant GIST data from 2000 to 2019. Geriatric age was defined as ≥70 years. Variables included age, sex, surgery, cancer-specific death, and overall survival. Statistical tests included univariate analysis using KM survival estimate (95% confidence interval) to calculate 5-year survival (5YS). Log-Rank tests determined statistical significance. Multivariable Cox's PH regression estimated the geriatric hazard death ratio adjusted for sex, stage, and surgery. RESULTS: The number of patients included was 13,579, yielding overall 5YS of 68.6% (95% CI 67.7-69.5). Cancer-specific death was 39.11% in 2000 & 3.33% in 2019. Non-geriatric & geriatric patient data yielded 5YS of 77.4% (76.4%-78.3%) and 53.3% (51.7%-54.8%) respectively (p < 0.0001). For no surgery/surgery, younger patient data yielded 5YS of 48.7% (45.8%-51.4%) and 83.7% (82.7%-84.7%) respectively (p < 0.0001); geriatric data yielded 5YS of 29.3% (26.5%-32.1%) and 62.8% (60.8%-64.6%) respectively (p < 0.0001). Multivariable analysis yielded a geriatric hazard death of 2.56 (2.42-2.70) (p < 0.0001). CONCLUSIONS: Cancer-specific death decreased since 2000, indicating an improvement in survival & treatment methods. Observed lower survival rates overall in the geriatric group. Surgery appeared to enhance survival rates in both groups, suggesting that surgery is an important factor in GIST survival regardless of age. Large prospective studies will help define clinical management for geriatric patients.


Asunto(s)
Neoplasias Gastrointestinales , Tumores del Estroma Gastrointestinal , Programa de VERF , Humanos , Tumores del Estroma Gastrointestinal/mortalidad , Tumores del Estroma Gastrointestinal/cirugía , Tumores del Estroma Gastrointestinal/patología , Anciano , Femenino , Masculino , Anciano de 80 o más Años , Neoplasias Gastrointestinales/mortalidad , Neoplasias Gastrointestinales/cirugía , Neoplasias Gastrointestinales/patología , Factores de Edad , Persona de Mediana Edad , Tasa de Supervivencia , Adulto , Estados Unidos/epidemiología , Resultado del Tratamiento , Estudios Retrospectivos
7.
J Geriatr Oncol ; 15(4): 101747, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38513310

RESUMEN

INTRODUCTION: Muscle and adipose tissue measures can be quantified from routinely obtained computed tomography (CT) images and are predictors of chemotherapy-related toxicities and survival among patients with gastrointestinal (GI) malignancies. Most studies to date have consisted of predominantly White patients, and the role of body composition among minoritized racial groups is unknown. We examined racial differences in body composition and survival among patients with GI malignancies. MATERIALS AND METHODS: This was a prospective cohort study of patients with GI malignancies. Single slices of axial CT images from L3 segments were analyzed using Slice-O-Matic software. The skeletal muscle area (cm2) was divided by height to obtain the skeletal muscle index (SMI, cm2/m2). Skeletal muscle radiodensity (SMD) in Hounsfield units (HU) was used for muscle composition. We compared body composition parameters between non-Hispanic (NH)-White and NH-Black participants. Cox models were used to examine the impact of body composition on survival. We proposed new race-specific cutoffs for body composition using optimal stratification. RESULTS: Five hundred forty patients were included, of which 24% were NH-Black. In Cox models stratified by race, each 5 cm2/m2 decrease in SMI was associated with increase in risk of all-cause mortality in NH-Black patients (hazard ratio [HR] 1.25; 95% confidence interval [CI] 1.04-1.49 p = 0.02). With the existing cut points, neither sarcopenia nor myosteatosis was associated with worse survival. Using a new cutoff for sarcopenia in NH-Black patients, NH-Black patients with sarcopenia (HR 2.31 95%CI 1.10-4.88 p = 0.03) and myosteatosis (HR 2.63 95% CI 1.25-5.53 p = 0.01) had worse survival. DISCUSSION: NH-Black older patients with GI cancers and sarcopenia or myosteatosis have worse overall survival.


Asunto(s)
Composición Corporal , Neoplasias Gastrointestinales , Tomografía Computarizada por Rayos X , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Negro o Afroamericano/estadística & datos numéricos , Neoplasias Gastrointestinales/mortalidad , Neoplasias Gastrointestinales/etnología , Neoplasias Gastrointestinales/patología , Músculo Esquelético/diagnóstico por imagen , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Sarcopenia/etnología , Sarcopenia/diagnóstico por imagen , Blanco
8.
Br J Haematol ; 204(5): 1771-1779, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38447995

RESUMEN

Primary gastrointestinal follicular lymphoma (PGI-FL) is a rare extra-nodal lymphoma. Its epidemiology and prognosis remain unclear. We performed a retrospective analysis of eligible patients with 1648 PGI-FL and 34 892 nodal FL (N-FL) in the Surveillance, Epidemiology and End Results (SEER) database. The age-adjusted average annual incidence of PGI-FL was 0.111/100000. The median overall survival (OS) for PGI-FL and N-FL patients was 207 and 165 months respectively. The 5-year diffuse large B-cell lymphoma (DLBCL) transformation rates were 2.1% and 2.6% respectively. Age, sex, grade, Ann Arbor stage, primary site and radiation were independent prognostic factors (p < 0.05). Nomograms were constructed to predict 1-, 5- and 10-year OS and disease-specific survival (DSS). The receiver operating characteristic curves and calibration plots showed the established nomograms had robust and accurate performance. Patients were classified into three risk groups according to nomogram score. In conclusion, the incidence of PGI-FL has increased over the past 40 years, and PGI-FL has a better prognosis and a lower DLBCL transformation rate than N-FL. The nomograms were developed and validated as an individualized tool to predict survival. Patients were divided into three risk groups to assist clinicians in identifying high-risk patients and choosing the optimal individualized treatments.


Asunto(s)
Neoplasias Gastrointestinales , Linfoma Folicular , Programa de VERF , Humanos , Linfoma Folicular/mortalidad , Linfoma Folicular/epidemiología , Linfoma Folicular/terapia , Linfoma Folicular/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Anciano , Neoplasias Gastrointestinales/epidemiología , Neoplasias Gastrointestinales/mortalidad , Neoplasias Gastrointestinales/diagnóstico , Neoplasias Gastrointestinales/terapia , Adulto , Estudios Retrospectivos , Pronóstico , Anciano de 80 o más Años , Nomogramas , Incidencia , Linfoma de Células B Grandes Difuso/epidemiología , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/terapia , Adolescente , Adulto Joven
9.
Scand J Gastroenterol ; 59(5): 600-607, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38351653

RESUMEN

BACKGROUND AND AIMS: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a precursor of pancreatic cancer. While earlier research has shown a high prevalence of synchronous/metachronous extrapancreatic tumors in IPMN patients, these studies have often been small with retrospective data collection. The aim of the study was to examine absolute and relative risks of non-pancreatic gastrointestinal (GI) cancer precursors and mortality in histologically confirmed IPMN. METHODS: Through the nationwide ESPRESSO histopathology cohort, we retrieved data on IPMN between 1965 and 2016. Each index case was matched to ≤5 general population controls. Through Cox regression, we estimated hazard ratios (HRs) for future GI cancer precursors and death. RESULTS: A total of 117 patients with IPMN and 539 age- and sex-matched controls were included. Over a median of 2.1 years of follow up, we confirmed two (1.7%) incident GI cancer precursors in IPMN vs. four (0.7%) in controls, corresponding to an HR of 1.89 (95%CI = 0.34-10.55). By contrast, IPMN patients were at increased risk of death (HR 3.61 (95%CI = 1.79-7.27)). The most common cause of death in IPMN was pancreatic cancer (n = 14; 45.2% of all deaths). CONCLUSIONS: We found no association between IPMN and other GI cancer precursors. This argues against comprehensive routine surveillance for other GI cancer precursors in IPMN patients. Mortality was increased in IPMN with pancreatic cancer being the most common cause of death, indicating the need for lifelong follow up in all resected and non-resected patients with IPMN. However, results should be confirmed in larger cohorts.


Asunto(s)
Neoplasias Gastrointestinales , Neoplasias Intraductales Pancreáticas , Neoplasias Pancreáticas , Humanos , Femenino , Masculino , Anciano , Persona de Mediana Edad , Neoplasias Gastrointestinales/mortalidad , Neoplasias Gastrointestinales/patología , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Neoplasias Intraductales Pancreáticas/mortalidad , Neoplasias Intraductales Pancreáticas/patología , Estudios Retrospectivos , Estudios de Casos y Controles , Modelos de Riesgos Proporcionales , Anciano de 80 o más Años , Adulto , Adenocarcinoma Mucinoso/mortalidad , Adenocarcinoma Mucinoso/patología , Factores de Riesgo , Carcinoma Ductal Pancreático/mortalidad , Carcinoma Ductal Pancreático/patología
10.
Histopathology ; 84(7): 1079-1091, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38362762

RESUMEN

Tumour budding shows promise as a prognostic factor in various cancers, but its widespread application is hindered by the lack of large, validated studies and standardized criteria. This meta-analysis aims to review and examine the prognostic role of tumour budding specifically in noncolorectal gastrointestinal and pancreatobiliary tract cancers, broadening our perspective on its clinical relevance. The literature review was conducted through PubMed, Embase, and Web of Science from inception till 20 February 2023. Pooled odds ratio (OR) and hazard ratio (HR) with 95% confidence interval (CI) were calculated to assess the relation between tumour budding and clinicopathologic features, as well as overall survival. Each study was evaluated using the Newcastle-Ottawa Scale and both heterogeneity and publication bias were analysed. In this meta-analysis of 57 studies across various cancer types, multivariate HR revealed worse overall survival in oesophageal squamous cell carcinoma (HR 3.34 [95% CI 2.21-5.04]), gastric adenocarcinoma (2.03 [1.38-2.99]), pancreatic ductal adenocarcinoma (2.56 [2.02-3.25]), and biliary tract adenocarcinoma (3.11 [2.46-3.93]) with high-grade tumour budding. Additionally, high-grade tumour budding consistently correlated with adverse clinicopathological features, including lymph node metastasis, lymphovascular invasion, and distant metastasis without any observed inverse association. High heterogeneity was noted. Our study suggests that tumour budding is a valuable prognostic marker in various cancers. Nonetheless, standardized criteria tailored to specific organ types are necessary to enhance its clinical utility.


Asunto(s)
Neoplasias Gastrointestinales , Neoplasias Pancreáticas , Humanos , Pronóstico , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/mortalidad , Neoplasias Gastrointestinales/patología , Neoplasias Gastrointestinales/mortalidad , Neoplasias del Sistema Biliar/patología , Neoplasias del Sistema Biliar/mortalidad , Adenocarcinoma/patología , Adenocarcinoma/mortalidad , Tracto Gastrointestinal/patología
12.
J Gastrointest Cancer ; 55(2): 599-624, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38411875

RESUMEN

PURPOSE: This study aimed to determine if Ki-67, a commonly used marker to measure tumor proliferation, is a reliable prognostic factor in various types of gastrointestinal (GI) cancers based on current high-quality multivariable evidence. METHODS: A comprehensive search was conducted in PubMed, Embase, Scopus, and ISI Web of Science databases to investigate the association between Ki-67 positivity and overall survival (OS) and disease/recurrence-free survival (DFS/RFS) in GI cancers. Heterogeneity was assessed using Chi-square-based Q and I2 analyses and publication bias using funnel plots and Egger's analysis. In addition, Ki-67 levels in different GI cancers were examined by different platforms. The prognostic capability of Ki-67, gene ontology (GO), and pathway enrichment analysis were obtained from GEPIA2 and STRING. RESULTS: Totally, 61 studies, involving 13,034 patients, were deemed eligible for our evaluation. The combined hazard ratios (HRs) demonstrated the prediction ability of overexpressed Ki-67 for a worse OS (HR: 1.67, P < 0.001; HR: 1.37, P = 0.021) and DFS/RFS (HR: 2.06, P < 0.001) in hepatocellular and pancreatic malignancies, respectively, as confirmed by multi-omics databases. However, similar correlation was not found in esophageal, gastric, and colorectal cancers. Furthermore, most of the associations were identified to be robust based on different subcategories and publication bias assessment. Finally, enriched Ki-67-related genes were found to be involved in various important signaling pathways, such as cell cycle, P53 signaling network, and DNA damage responses. CONCLUSION: This study supports that Ki-67 can serve as an independent prognostic biomarker for pancreatic and hepatocellular malignancies in clinical settings.


Asunto(s)
Biomarcadores de Tumor , Neoplasias Gastrointestinales , Antígeno Ki-67 , Humanos , Antígeno Ki-67/metabolismo , Antígeno Ki-67/análisis , Neoplasias Gastrointestinales/mortalidad , Neoplasias Gastrointestinales/patología , Neoplasias Gastrointestinales/metabolismo , Neoplasias Gastrointestinales/genética , Pronóstico , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/análisis , Multiómica
13.
Vet Comp Oncol ; 22(2): 186-197, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38356238

RESUMEN

Specific data regarding outcome of cats with high-grade and large granular lymphocyte alimentary lymphoma (HGAL and LGL, respectively) treated with multi-agent chemotherapy are scarce. The aims of this multi-centric, retrospective study were to describe the outcome of cats with HGAL and LGL treated with COP- or CHOP-based chemotherapy and to identify potential prognostic factors. Cats with a cytological or histological diagnosis of HGAL or LGL lymphoma treated with COP- or CHOP-based protocol as first-line chemotherapy were included. Data regarding diagnosis, staging, treatment and follow-up were collected. Fifty-seven cats treated with CHOP (n = 37) or COP (n = 20) protocols were included. Complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) were observed in 20%, 22%, 36% and 22% of cats, respectively, for an overall response rate of 42%. Median progression-free interval (PFI) was 148 days and overall median survival time (OST) was 131 days. Cats achieving CR, PR or SD showed significantly longer PFI (p < .01) and OST (p < .015) compared with cats with PD. Other positive prognostic factors in multi-variate analysis were rescue treatment (p < .001) and absence of lymph node involvement (p < .03). Negative prognostic factors were diffuse infiltration of the gastrointestinal tract (p = .035) and infiltration of a non-haematopoietic organ (p < .01).


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Enfermedades de los Gatos , Ciclofosfamida , Doxorrubicina , Prednisona , Vincristina , Gatos , Animales , Enfermedades de los Gatos/tratamiento farmacológico , Enfermedades de los Gatos/patología , Estudios Retrospectivos , Masculino , Femenino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Prednisona/uso terapéutico , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Vincristina/uso terapéutico , Linfoma/veterinaria , Linfoma/tratamiento farmacológico , Linfoma/patología , Neoplasias Gastrointestinales/veterinaria , Neoplasias Gastrointestinales/tratamiento farmacológico , Neoplasias Gastrointestinales/patología , Neoplasias Gastrointestinales/mortalidad , Resultado del Tratamiento
14.
Qual Life Res ; 33(6): 1455-1468, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38227073

RESUMEN

PURPOSE: A consensus has not been reached on the value of quality of life (QoL) as a prognostic factor for survival in gastrointestinal cancer. This meta-analysis aimed to investigate the association between functioning scales of the EORTC QoL Questionnaire Core 30 (QLQ-C30) and the overall survival (OS) in patients with gastrointestinal cancer. METHODS: A systematic literature search was conducted in PubMed, Web of Science, and Embase databases, until February 7, 2023. The studies included were those that investigated the association between baseline QoL measured by the functioning scales of EORTC QLQ-C30 and OS in patients with gastrointestinal cancer. The prognostic capacity of QoL was calculated by pooling the adjusted hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: Twenty-four studies' analyses reported by 22 eligible articles involving 11,609 patients were included. When compared with good parameters of QoL, poor global QoL (HR 1.81; 95% CI 1.53-2.13), physical functioning (HR 1.51; 95% CI 1.31-1.74), social functioning (HR 1.67; 95% CI 1.30-2.15), and role functioning scale (HR 1.42; 95% CI 1.20-1.29) were significantly associated with decreased OS. For each 10-point increase in QLQ-C30 parameters, the pooled HR of OS was 0.87 (95% CI 0.83-0.92) for global QoL, 0.87 (95% CI 0.83-0.92) for physical functioning, and 0.93 (95% CI 0.88-0.97) for role functioning. However, each 10-point increase in social, emotional, or cognitive functioning scale did not significantly predict OS. CONCLUSIONS: Baseline health-related QoL defined by the physical functioning or global QoL scale of EORTC QLQ-C30 significantly predicts OS in patients with gastrointestinal cancer.


Asunto(s)
Neoplasias Gastrointestinales , Calidad de Vida , Humanos , Neoplasias Gastrointestinales/psicología , Neoplasias Gastrointestinales/mortalidad , Calidad de Vida/psicología , Encuestas y Cuestionarios , Pronóstico , Análisis de Supervivencia
15.
J Cancer Res Clin Oncol ; 149(13): 12177-12189, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37428248

RESUMEN

PURPOSE: Due to the rarity of primary gastrointestinal lymphoma (PGIL), the prognostic factors and optimal management of PGIL have not been clearly defined. We aimed to establish prognostic models using a deep learning algorithm for survival prediction. METHODS: We collected 11,168 PGIL patients from the Surveillance, Epidemiology, and End Results (SEER) database to form the training and test cohorts. At the same time, we collected 82 PGIL patients from three medical centres to form the external validation cohort. We constructed a Cox proportional hazards (CoxPH) model, random survival forest (RSF) model, and neural multitask logistic regression (DeepSurv) model to predict PGIL patients' overall survival (OS). RESULTS: The 1-, 3-, 5-, and 10-year OS rates of PGIL patients in the SEER database were 77.1%, 69.4%, 63.7%, and 50.3%, respectively. The RSF model based on all variables showed that the top three most important variables for predicting OS were age, histological type, and chemotherapy. The independent risk factors for PGIL patient prognosis included sex, age, race, primary site, Ann Arbor stage, histological type, symptom, radiotherapy, and chemotherapy, according to the Lasso regression analysis. Using these factors, we built the CoxPH and DeepSurv models. The DeepSurv model's C-index values were 0.760 in the training cohort, 0.742 in the test cohort, and 0.707 in the external validation cohort, which demonstrated that the DeepSurv model performed better compared to the RSF model (0.728) and the CoxPH model (0.724). The DeepSurv model accurately predicted 1-, 3-, 5- and 10-year OS. Both calibration curves and decision curve analysis curves demonstrated the superior performance of the DeepSurv model. We developed the DeepSurv model as an online web calculator for survival prediction, which can be accessed at http://124.222.228.112:8501/ . CONCLUSIONS: This DeepSurv model with external validation is superior to previous studies in predicting short-term and long-term survival and can help us make better-individualized decisions for PGIL patients.


Asunto(s)
Aprendizaje Profundo , Neoplasias Gastrointestinales , Linfoma , Análisis de Supervivencia , Humanos , Neoplasias Gastrointestinales/mortalidad , Linfoma/mortalidad , Programa de VERF , Pronóstico , Modelos de Riesgos Proporcionales , Bosques Aleatorios , Modelos Logísticos , Masculino , Femenino , Persona de Mediana Edad , Anciano
16.
J Cancer Res Clin Oncol ; 149(10): 8039-8050, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36966394

RESUMEN

PURPOSE: Dysregulated expression of heat shock proteins (HSP) plays a fundamental role in tumor development and progression. Consequently, HSP90 may be an effective tumor target in oncology, including the treatment of gastrointestinal cancers. METHODS: We carried out a systematic review of data extracted from clinicaltrials.gov and pubmed.gov, which included all studies available until January 1st, 2022. The published data was evaluated using primary and secondary endpoints, particularly with focus on overall survival, progression-free survival, and rate of stable disease. RESULTS: Twenty trials used HSP90 inhibitors in GI cancers, ranging from phase I to III clinical trials. Most studies assessed HSP90 inhibitors as a second line treatment. Seventeen of the 20 studies were performed prior to 2015 and only few studies have results pending. Several studies were terminated prematurely, due to insufficient efficacy or toxicity. Thus far, the data suggests that HSP90 inhibitor NVP-AUY922 might improve outcome for colorectal cancer and gastrointestinal stromal tumors. CONCLUSION: It currently remains unclear which subgroup of patients might benefit from HSP90 inhibitors and at what time point these inhibitors may be beneficial. There are only few new or ongoing studies initiated during the last decade.


Asunto(s)
Antineoplásicos , Neoplasias Gastrointestinales , Proteínas HSP90 de Choque Térmico , Terapia Molecular Dirigida , Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Proteínas HSP90 de Choque Térmico/metabolismo , Neoplasias Gastrointestinales/tratamiento farmacológico , Neoplasias Gastrointestinales/metabolismo , Neoplasias Gastrointestinales/mortalidad , Humanos , Isoxazoles/efectos adversos , Isoxazoles/uso terapéutico , Resorcinoles/efectos adversos , Resorcinoles/uso terapéutico , Ensayos Clínicos como Asunto
17.
BMC Cancer ; 22(1): 179, 2022 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-35177018

RESUMEN

BACKGROUND: Sarcopenia predicts poor prognosis of a variety of gastrointestinal malignancies. However, there is a lack of study on the association between skeletal muscle index (SMI) and the prognosis of gastrointestinal stromal tumor (GIST). The aim of this study is to develop a novel nomogram based on sarcopenia for GIST patients to predict overall survival (OS). METHODS: SMI was measured by computed tomography scan of 107 patients who underwent resection for primary localized gastrointestinal stromal tumor (GIST). Sarcopenia was defined by cutoff values for SMI as 40.1 cm2/m2 and 39.8 cm2/m2 using optimum stratification for males and females respectively. Factors were included in the nomogram were specified by univariate and multiple Cox proportional hazard analysis. Concordance index (C-index) and calibration curves were conducted to measure the discrimination and accuracy of the nomogram. The utility of the nomogram was assessed by the decision curve analysis (DCA). RESULTS: Twenty-eight (26.2%) of 107 patients were sarcopenic. Sarcopenia was correlated significantly with body mass index, albumin, female sex, resection style, mitotic index, rupture status, survival. Sarcopenia was significantly related to decreased overall survival (p = 0.003).The nomogram including sarcopenia status, resection style and mitotic index had an excellent discrimination with C-index 0.794. The calibration curves represented a good accordance between the actual observation and nomogram prediction for overall survival. Decision curve analysis illustrated that the nomogram was helpful in clinic. CONCLUSIONS: We developed a nomogram based on sarcopenia to predict overall survival after resection of GISTs which is an effective and favorable prognostication tool.


Asunto(s)
Neoplasias Gastrointestinales/mortalidad , Tumores del Estroma Gastrointestinal/mortalidad , Nomogramas , Sarcopenia/mortalidad , Tomografía Computarizada por Rayos X/estadística & datos numéricos , Femenino , Neoplasias Gastrointestinales/complicaciones , Tumores del Estroma Gastrointestinal/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/patología , Periodo Posoperatorio , Pronóstico , Estudios Retrospectivos , Sarcopenia/diagnóstico por imagen , Sarcopenia/etiología
18.
Am J Clin Oncol ; 45(1): 22-27, 2022 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-34864778

RESUMEN

INTRODUCTION: There are no formal guidelines for the management of patients with primary gastrointestinal (GI) cancers who have lung-exclusive or lung-predominant metastases. We performed a retrospective analysis to evaluate host and tumor characteristics of this patient population, model patterns and rates of growth, and describe treatment approaches. MATERIALS AND METHODS: Eligible patients had a GI cancer with either synchronous or metachronous lung metastases but no other visceral or peritoneal sites of involvement. In addition to collecting detailed patient-specific and tumor-specific information, all imaging studies (computed tomography±positron emission tomography scans) were reviewed by an independent radiologist. Up to 5 lung metastases were tracked through each patient's clinical course. Growth rate was estimated using a linear mixed model analysis. RESULTS: Forty patients met eligibility criteria (18 pancreatic, 15 colorectal, 6 hepatobiliary, 1 gastroesophageal; synchronous vs. metachronous, 13 and 27, respectively). Median time from original cancer diagnosis to onset of metachronous lung lesions was 16 months. Interval from first appearance of lung metastases to treatment initiation was 6.2 months. Average growth rate of the largest lesion was 0.21 mm/mo (95% confidence interval, 0.12-0.30), with substantial intrapatient and interpatient variability. Sixty percent of patients underwent locoregional interventions in addition to or in lieu of systemic therapy for their lung metastases. Median survival of the entire study cohort from first appearance of lung metastases was 54 months. CONCLUSIONS: Lung metastases from primary GI cancers have a variable but overall indolent natural history and are generally associated with prolonged survival outcomes. Further efforts to define patterns of growth of lung metastases, informed by size, number, and clinical/molecular features, are needed to guide appropriate timing and selection of therapy as well as surveillance strategies.


Asunto(s)
Neoplasias Gastrointestinales/patología , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/terapia , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Neoplasias Gastrointestinales/mortalidad , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
19.
Diagn Pathol ; 16(1): 113, 2021 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-34895274

RESUMEN

BACKGROUND: Many studies reporting that down-regulation of SOCS6 plays vital roles in promoting progression of malignant tumors have been published. The present study was performed to evaluate whether SOCS6 was significantly associated with prognosis of GIST patients. METHODS: Immunohistochemical staining was accomplished to evaluate the expression levels of SOCS6 among GIST patients. The impacts of SOCS6 expression on overall survival (OS) and recurrence-free survival (RFS) of GIST patients were assessed by Cox proportional hazard regression model analysis and Kaplan-Meier curve analysis. RESULTS: It was demonstrated that the expression level of SOCS6 was significantly associated with tumor size (P=0.001). Then according to Kaplan-Meier curve analysis, low expression of SOCS6 was significantly correlated with worse OS and RFS of GIST patients. Ultimately, it was revealed by Cox proportional regression model analysis that low expression of SOCS6 was an independent predictive factor for OS and RFS. CONCLUSIONS: Low expression of SOCS6 was an independent prognostic factor for GIST, suggesting its potential as a novel biomarker predicting survival of GIST patients.


Asunto(s)
Biomarcadores de Tumor/análisis , Neoplasias Gastrointestinales/química , Tumores del Estroma Gastrointestinal/química , Proteínas Supresoras de la Señalización de Citocinas/análisis , Anciano , Regulación hacia Abajo , Femenino , Neoplasias Gastrointestinales/mortalidad , Neoplasias Gastrointestinales/patología , Neoplasias Gastrointestinales/cirugía , Tumores del Estroma Gastrointestinal/mortalidad , Tumores del Estroma Gastrointestinal/patología , Tumores del Estroma Gastrointestinal/cirugía , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Valor Predictivo de las Pruebas , Supervivencia sin Progresión , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo
20.
BMC Cancer ; 21(1): 1246, 2021 Nov 19.
Artículo en Inglés | MEDLINE | ID: mdl-34798858

RESUMEN

BACKGROUND: Atypical tumor response patterns during immune checkpoint inhibitor therapy pose a challenge to clinicians and investigators in immuno-oncology practice. This study evaluated tumor burden dynamics to identify imaging biomarkers for treatment response and overall survival (OS) in advanced gastrointestinal malignancies treated with PD-1/PD-L1 inhibitors. METHODS: This retrospective study enrolled a total of 198 target lesions in 75 patients with advanced gastrointestinal malignancies treated with PD-1/PD-L1 inhibitors between January 2017 and March 2021. Tumor diameter changes as defined by immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST) were studied to determine treatment response and association with OS. RESULTS: Based on the best overall response, the tumor diameter ranged from - 100 to + 135.3% (median: - 9.6%). The overall response rate was 32.0% (24/75), and the rate of durable disease control for at least 6 months was 30.7% (23/75, one (iCR, immune complete response) or 20 iPR (immune partial response), or 2iSD (immune stable disease). Using univariate analysis, patients with a tumor diameter maintaining a < 20% increase (48/75, 64.0%) from baseline had longer OS than those with ≥20% increase (27/75, 36.0%) and, a reduced risk of death (median OS: 80 months vs. 48 months, HR = 0.22, P = 0.034). The differences in age (HR = 1.09, P = 0.01), combined surgery (HR = 0.15, P = 0.01) and cancer type (HR = 0.23, P = 0.001) were significant. In multivariable analysis, patients with a tumor diameter with a < 20% increase had notably reduced hazards of death (HR = 0.15, P = 0.01) after adjusting for age, combined surgery, KRAS status, cancer type, mismatch repair (MMR) status, treatment course and cancer differentiation. Two patients (2.7%) showed pseudoprogression. CONCLUSIONS: Tumor diameter with a < 20% increase from baseline during therapy in gastrointestinal malignancies was associated with therapeutic benefit and longer OS and may serve as a practical imaging marker for treatment response, clinical outcome and treatment decision making.


Asunto(s)
Neoplasias Gastrointestinales , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Criterios de Evaluación de Respuesta en Tumores Sólidos , Carga Tumoral , Adulto , Factores de Edad , Análisis de Varianza , Reparación de la Incompatibilidad de ADN , Femenino , Neoplasias Gastrointestinales/tratamiento farmacológico , Neoplasias Gastrointestinales/inmunología , Neoplasias Gastrointestinales/mortalidad , Neoplasias Gastrointestinales/patología , Genes ras , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Carga Tumoral/efectos de los fármacos
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