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1.
Clin Colorectal Cancer ; 22(2): 222-230, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36944559

RESUMEN

BACKGROUND: The bCTC count is a well-established prognostic biomarker in mCRC, as well as in other tumor types. The aim of this analysis was to evaluate the prognostic/predictive role of the bCTC count (≥3 vs. <3) in previously untreated mCRC. PATIENTS AND METHODS: The study involved 589 untreated mCRC patients included in the intention-to-treat population of 2 randomized clinical trials (phase III VISNU-1 [NCT01640405] and phase II VISNU-2 [NCT01640444] studies). RESULTS: Of the 589 patients, 349 (59.2%) had bCTC≥3 and 240 (40.7%) had bCTC<3. Multivariate analysis showed that the bCTC count is an independent prognostic factor for overall survival (OS) (HR 0.59, 95% CI 0.48-0.72; P = 0.000) and potential for progression-free survival (PFS) (P = 0.0549). Median OS was 32.9 and 19.5 months in patients with bCTC<3 and bCTC≥3 (P <0.001), respectively. This effect was also observed comparing OS in RASwt patients from both studies. Other prognostic factors were: ECOG-PS, primary tumor site, number of metastatic sites and surgery of the primary tumor. Median OS was lower for patients treated with anti-VEGF versus anti-EGFR (22.3 vs. 33.3 months, P <0.0001) while there were no significant differences in PFS according to the targeted treatment received. CONCLUSION: This post-hoc analysis of 2 randomized studies confirms the poor prognosis of patients with bCTC≥3 but this is not associated with other adverse independent prognostic factors such as RAS/BRAF mutations.


Asunto(s)
Neoplasias del Colon , Neoplasias Colorrectales , Células Neoplásicas Circulantes , Neoplasias del Recto , Humanos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Ensayos Clínicos Controlados Aleatorios como Asunto , Pronóstico , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Recto/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ensayos Clínicos Fase II como Asunto
2.
Biomed Pharmacother ; 159: 114272, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36706629

RESUMEN

The benefit of adding the antiangiogenic drug aflibercept to FOLFIRI regime in metastatic colorectal cancer (CRC) patients resistant to or progressive on an oxaliplatin-based therapy has been previously demonstrated. However, the absence of validated biomarkers to predict greater outcomes is a major challenge encountered when using antiangiogenic therapies. In this study we investigated profiles of circulating microRNAs (miRNAs) to build predictive models of response to treatment and survival. Plasma was obtained from 98 metastatic CRC patients enrolled in a clinical phase II trial before receiving FOLFIRI plus aflibercept treatment, and the circulating levels of 754 individual miRNAs were quantified using real-time PCR. A distinct signature of circulating miRNAs differentiated responder from non-responder patients. Remarkably, most of these miRNAs were found to target genes that are involved in angiogenic processes. Accordingly, some of these miRNAs had predictive value and entered in predictive models of response to therapy, progression of disease, and survival of patients treated with FOLFIRI plus aflibercept. Among these miRNAs, circulating levels of hsa-miR-33b-5p efficiently discriminated between responder and non-responder patients and predicted the risk of disease progression. Moreover, the combination of circulating VEGF-A and miR-33b-5p levels improved clinical stratification of metastatic CRC patients who were to receive FOLFIRI plus aflibercept treatment. In conclusion, our study supports circulating miRNAs as valuable biomarkers for predicting better outcomes in metastatic CRC patients treated with FOLFIRI plus aflibercept.


Asunto(s)
MicroARN Circulante , Neoplasias del Colon , Neoplasias Colorrectales , MicroARNs , Neoplasias del Recto , Humanos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Camptotecina , Fluorouracilo , Leucovorina/uso terapéutico , Leucovorina/efectos adversos , Receptores de Factores de Crecimiento Endotelial Vascular , Proteínas Recombinantes de Fusión/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Recto/tratamiento farmacológico , MicroARNs/genética , MicroARNs/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica
3.
ESMO Open ; 6(2): 100062, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33711671

RESUMEN

BACKGROUND: We explored the influence of BRAF and PIK3CA mutational status on the efficacy of bevacizumab or cetuximab plus 5-fluorouracil/leucovorin and irinotecan (FOLFIRI) as first-line therapy in patients with RAS wild-type metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: VISNÚ-2 was a multicentre, randomised, phase II study. Patients with RAS wild-type mCRC and <3 circulating tumour cells/7.5 ml blood were stratified by BRAF/PIK3CA status (wild-type versus mutated) and number of affected organs (1 versus >1), and allocated to bevacizumab (5 mg/kg every 2 weeks) or cetuximab (400 mg/m2 then 250 mg/m2 weekly) plus FOLFIRI [irinotecan 180 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil 400 mg/m2 (bolus) then 2400 mg/m2 (46-h continuous infusion) every 2 weeks]. The primary endpoint was progression-free survival (PFS). All analyses were exploratory. RESULTS: Two hundred and forty patients with BRAF/PIK3CA wild-type (n = 196) or BRAF- and/or PIK3CA-mutated tumours (n = 44) were enrolled. Median PFS was 12.7 and 8.8 months in patients with BRAF/PIK3CA wild-type and BRAF/PIK3CA-mutated tumours, respectively [hazard ratio (HR) = 1.22; 95% confidence interval (CI) 0.80-1.85; P = 0.3602]. In the BRAF- and/or PIK3CA-mutated cohort, median PFS was 2.8, 8.8 and 15.0 months in patients with BRAF/PI3KCA-mutated (n = 8), BRAF-mutated/PI3KCA wild-type (n = 16) and BRAF wild-type/PI3KCA-mutated (n = 20) tumours, respectively (P = 0.0002). PFS was similar with bevacizumab plus FOLFIRI versus cetuximab plus FOLFIRI in BRAF/PIK3CA wild-type (HR = 0.99; 95% CI 0.67-1.45; P = 0.9486) and BRAF/PIK3CA-mutated tumours (HR = 1.11; 95% CI 0.53-2.35; P = 0.7820). The most common grade 3/4 treatment-related adverse events were neutropenia, diarrhoea and asthenia in both treatment groups. CONCLUSIONS: BRAF/PIK3CA status influences outcomes in patients with RAS wild-type mCRC but does not appear to assist with the selection of first-line targeted therapy.


Asunto(s)
Neoplasias Colorrectales , Células Neoplásicas Circulantes , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab/uso terapéutico , Camptotecina/efectos adversos , Cetuximab/uso terapéutico , Fosfatidilinositol 3-Quinasa Clase I/genética , Fosfatidilinositol 3-Quinasa Clase I/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Humanos , Proteínas Proto-Oncogénicas B-raf/genética
5.
Clin Transl Oncol ; 22(2): 236-244, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31989475

RESUMEN

Gastric cancer (GC) is the fifth most common cancer worldwide with a varied geographic distribution and an aggressive behavior. In Spain, it represents the sixth cause of cancer death. In Western countries, the incidence is decreasing slightly, with an increase in gastroesophageal junction adenocarcinoma (GEJA), a different entity that we separate specifically in the guideline. Molecular biology advances have been done recently, but do not yet lead to the choice in treatment approach except in advanced disease with overexpression of HER2. Endoscopic resection in very early stage, perioperative chemotherapy in locally advanced tumors and preliminary immune therapy resulting in advanced disease are the main treatment innovations in the GC/GEJA treatment. We describe the different evidences and recommendations following the statements of the American College of Physicians.


Asunto(s)
Adenocarcinoma/diagnóstico , Adenocarcinoma/terapia , Ensayos Clínicos como Asunto/normas , Unión Esofagogástrica/patología , Guías de Práctica Clínica como Asunto/normas , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/terapia , Humanos , Oncología Médica , Sociedades Médicas
6.
Ann Oncol ; 31(1): 79-87, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31912800

RESUMEN

BACKGROUND: Preclinical data suggest that dual blockade of the insulin-like growth factor-1 receptor (IGF-1R) and HER3 pathways has superior activity to IGF-1R blockade alone in pancreatic ductal adenocarcinoma (PDAC). We tested whether istiratumab, an IGF-1R- and ErbB3-bispecific antibody, can enhance the efficacy of standard of care (SOC) chemotherapy in patients with metastatic PDAC selected for high IGF-1 serum levels. PATIENTS AND METHODS: CARRIE was an international, randomized, double-blind, placebo-controlled phase II study for patients with previously untreated metastatic PDAC. In part 1, 10 patients were evaluated for pharmacokinetics and safety. In part 2, patients with high free serum IGF-1 levels were randomized 1 : 1 to receive either istiratumab [2.8 g intravenously (i.v.) every 2 weeks] or placebo combined with gemcitabine/nab-paclitaxel at approved dose schedule. The co-primary endpoints were progression-free survival (PFS) in patients with high IGF-1 levels and PFS in patients with both high serum IGF-1 levels and heregulin (HRG)+ tumors. Key secondary endpoints were overall survival (OS), objective response rate (ORR) by RECIST v.1.1, and adverse events (AEs) rate. RESULTS: A total of 317 patients were screened, with 88 patients randomized in part 2 (experimental arm n = 43; control n = 45). In the high IGF-1 cohort, median PFS was 3.6 and 7.3 months in the experimental versus control arms, respectively [hazard ratio (HR) = 1.88, P = 0.027]. In the high IGF-1/HRG+ subgroup (n = 44), median PFS was 4.1 and 7.3 months, respectively (HR = 1.39, P = 0.42). Median OS and ORR for the overall population were similar between two arms. No significant difference in serious or grade ≥3 AEs was observed, although low-grade AEs leading to early discontinuation were higher in the experimental (39.5%) versus control arm (24.4%). CONCLUSIONS: Istiratumab failed to improve the efficacy of SOC chemotherapy in this patient setting. High serum IGF-1 levels did not appear to be an adverse prognostic factor when compared with non-biomarker-selected historic controls. CLINICAL TRIAL REGISTRATION NUMBERS: ClinicalTrials.gov: NCT02399137; EUDRA CT: 2014-004572-34.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Pancreáticas , Albúminas , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Desoxicitidina/análogos & derivados , Humanos , Paclitaxel/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Gemcitabina
7.
Ann Oncol ; 31(2): 246-256, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31959341

RESUMEN

BACKGROUND: The bevacizumab-Avastin® adjuVANT (AVANT) study did not meet its primary end point of improving disease-free survival (DFS) with the addition of bevacizumab to oxaliplatin-based chemotherapy in stage III colon cancer (CC). We report here the long-term survival results (S-AVANT). PATIENTS AND METHODS: Patients with curatively resected stage III CC were randomly assigned to FOLFOX4, FOLFOX4-bevacizumab, or XELOX-bevacizumab. RESULTS: A total of 2867 patients were randomized: FOLFOX4: n = 955, FOLFOX4-bevacizumab: n = 960, XELOX-bevacizumab: n = 952. With a median of 6.73 years follow-up (interquartile range 5.51-10.54), 672 patients died, of whom 198 (20.7%), 250 (26.0%), and 224 (23.5%) were in the FOLFOX4, FOLFOX4-bevacizumab, and XELOX-bevacizumab arms, respectively. The 10-year overall survival (OS) rates were 74.6%, 67.2%, and 69.9%, (P = 0.003) and 5-year disease-free survival (DFS) rates were 73.2%, 68.5%, and 71.0% (P = 0.174), respectively. OS and DFS hazard ratios were 1.29 [95% confidence interval (CI) 1.07-1.55; P = 0.008] and 1.16 (95% CI 0.99-1.37; P = 0.063) for FOLFOX4-bevacizumab versus FOLFOX4 and 1.15 (95% CI 0.95-1.39; P = 0.147) and 1.1 (95% CI 0.93-1.29; P = 0.269) for XELOX-bevacizumab versus FOLFOX4, respectively. CC-related deaths (n = 542) occurred in 157 (79.3%) patients receiving FOLFOX4, 205 (82.0%) receiving FOLFOX4-bevacizumab, and 180 (80.4%) receiving XELOX-bevacizumab (P = 0.764), while non-CC-related deaths occurred in 41 (20.7%), 45 (18.0%), and 44 (19.6%) patients, respectively. Cardiovascular-related and sudden deaths during treatment or follow-up were reported in 13 (6.6%), 17 (6.8%), and 14 (6.3%) patients, in the FOLFOX4, FOLFOX4-bevacizuamb, and XELOX-bevacizumab arms, respectively (P = 0.789). Treatment arm, sex, age, histological differentiation, performance status, T/ N stages, and localization of primary tumor were independent prognostic factors of OS in stage III. CONCLUSIONS: S-AVANT confirms the initial AVANT report. No benefit of the bevacizumab addition to FOLFOX4 adjuvant therapy in patients with stage III CC was observed in terms of DFS with a negative effect in OS, without increase in non-CC related deaths. CLINICAL TRIAL IDENTIFICATION: NCT00112918.


Asunto(s)
Neoplasias del Colon , Compuestos Organoplatinos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab/efectos adversos , Quimioterapia Adyuvante , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Supervivencia sin Enfermedad , Fluorouracilo/efectos adversos , Humanos , Leucovorina/efectos adversos , Estadificación de Neoplasias , Compuestos Organoplatinos/efectos adversos
8.
Clin Transl Oncol ; 22(3): 351-359, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31073972

RESUMEN

INTRODUCTION: Trifluridine/tipiracil combination has shown a benefit over placebo in the treatment of patients with chemorefractory metastatic colorectal cancer (mCRC). We evaluated the efficacy and safety of this combination in the real-life setting at eight Galician centers in Spain. PATIENTS AND METHODS: This is a retrospective study of a cohort of patients with mCRC in treatment with trifluridine/tipiracil within usual clinical practice who have been previously treated or are not considered candidates for treatment with available therapies. RESULTS: A total of 160 mCRC patients were included. Our data showed that 11.9% of patients achieved disease control. Median progression-free survival was 2.75 months; at 5.66 months follow-up, median overall survival was 7.94 months. Asthenia and neutropenia (48.1% both) were the most frequent adverse events. Overall survival was lower in patients with ECOG 2, multiple metastatic sites, platelets count 350,000/µl, alkaline phosphatase > 500 IU/l, and carcinoembryonic antigen > 10 ng/ml. CONCLUSION: The results of this study confirm the efficacy and safety of trifluridine/tipiracil in chemorefractory mCRC patients. However, patients in clinical practice differ from patients in clinical trials. Due to this, prognostic factors have special importance to offer the best therapeutic approach.


Asunto(s)
Neoplasias Colorrectales/tratamiento farmacológico , Nomogramas , Pirrolidinas/uso terapéutico , Trifluridina/uso terapéutico , Uracilo/análogos & derivados , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/patología , Combinación de Medicamentos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Pronóstico , Supervivencia sin Progresión , Pirrolidinas/efectos adversos , Criterios de Evaluación de Respuesta en Tumores Sólidos , Estudios Retrospectivos , España , Tasa de Supervivencia , Timina , Trifluridina/efectos adversos , Uracilo/efectos adversos , Uracilo/uso terapéutico
9.
Clin Transl Oncol ; 22(7): 1049-1058, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31701365

RESUMEN

PURPOSE: The Spanish Society of Medical Oncology (SEOM, for its Spanish acronym) would like to attest to the relevance of training in Oncology as part of the undergraduate education in Medicine program and issue recommendations to improve said training, with the aim of responding better to the challenges that cancer poses to our society. MATERIALS AND METHODS: The curricula of 42 schools of medicine were reviewed with interviews with at least one teaching medical oncologist from each faculty. The qualitative and opinion analysis was completed by means of an online questionnaire targeting lecturers, resident tutors, and residents in Medical Oncology (MO), enabling the detection of needs and areas for improvement at an organizational level and in terms of skill acquisition. RESULTS: While the number of medical schools with a specific, mandatory program in MO has grown by up to 90%, it has not been accompanied by an increase in independent programs. Instead, they largely consist of programs shared with other specialties (61% of the medical faculties). In most of the undergraduate education programs, Oncology contents are fragmented and approached from the perspective of each organ system. CONCLUSIONS: Despite the positive evolution in recent years, the heterogeneity in Oncology contents during undergraduate education training continues to be remarkable. Cross-sectional programs with an integral vision, taught in the final years of undergraduate medical education would be desirable. Among the recommendations for improvement of training in Medical Oncology, the SEOM proposes that updated, theoretical content be incorporated and clinical practice in Medical Oncology departments be promoted.


Asunto(s)
Curriculum , Educación de Pregrado en Medicina , Oncología Médica/educación , Competencia Clínica , Docentes Médicos , Humanos , Medicina Paliativa/educación , Sociedades Médicas , España , Encuestas y Cuestionarios , Enseñanza
10.
Injury ; 50 Suppl 4: S26-S29, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30691923

RESUMEN

INTRODUCTION: Hip fracture is a common serious injury that occurs mainly in elderly. Dual-mobility hip arthroplasty or bipolar emiarthroplasty for its treatment remains a controversial decision. Co-morbidities and risk of fall represent additional aspects to be considered. The aim of our study was to determine the rate of mechanical complications for these two types of implants related to fall risk status of patients. PATIENTS AND METHODS: Our study is a retrospective clinical trial of patients operated with a biarticular hemiarthroplasty or a dual-mobility total hip arthroplasty. Primary outcome was dislocation rate and need for any revision procedure. Patients were treated in a single center from January 2013 to March 2017. In all cases Morse Fall Scale (MSF) was calculated at patient admission to evaluate the risk of postoperative fall. Inclusion criteria to the study were: subcapital or femoral neck fracture of non-pathologic nature, patients with neuromuscular disorders or cognitive dysfunction, age > 75 years with MFS ≥ 45. The patients were reviewed postoperatively at 8 weeks, 6 months, 12 months, and then annually. Patients had clinical (Harris hip score) and radiological assessment. RESULTS: The mean duration of the follow-up was 283 months. There were five dislocations in Group A (5,6%) and no dislocations in Group B (0%). All dislocations occurred within the first 6 months after surgery. The mean Harris Hip score was 81,7 in Group A patients and 79, 8 in Group B patients. DISCUSSION: Treatment of hip fractures on non-cooperative patients still represents a dilemma. Falls and runaway motions represent high risk factors of dislocation. Use of dual-mobility cup has been found to be associated with a not statistically proved decrease of dislocation compared to traditional cups. CONCLUSION: Dual-mobility cups might be considered a valuable option to prevent postoperative dislocation but further study is needed before extending the indications for dual-mobility following a fracture of the femoral neck, to assess the potential cost and complications of a longer procedure. So far, despite a lower dislocation risk, the authors actually cannot recommend widely use of a dual-motility cup instead of emiarthroplasty in high falls risk patients.


Asunto(s)
Accidentes por Caídas/estadística & datos numéricos , Geriatría , Hemiartroplastia/efectos adversos , Luxación de la Cadera/prevención & control , Inestabilidad de la Articulación/prevención & control , Diseño de Prótesis/instrumentación , Femenino , Humanos , Masculino , Falla de Prótesis , Estudios Retrospectivos , Medición de Riesgo
11.
Eur J Cancer ; 101: 263-272, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-30054049

RESUMEN

BACKGROUND: This multicentre, randomised, and phase II study evaluated mFOLFOX+cetuximab followed by maintenance mFOLFOX+cetuximab or single-agent cetuximab in metastatic colorectal cancer (mCRC) patients (NCT01161316). PATIENTS AND METHODS: Previously, untreated mCRC patients (wild-type KRAS) were randomised to receive cetuximab+mFOLFOX-6 (8 cycles for 2 weeks) followed by maintenance therapy: single-agent cetuximab (Arm-A) or mFOLFOX-6 + cetuximab (Arm-B) until progression. Primary endpoint was progression-free survival (PFS) at 9 months. RESULTS: One hundred ninety-three patients (median [range] age 60 [33-74] years) were randomised (2:1): 129 Arm-A versus 64 Arm-B. PFS at 9 months (95% confidence interval) showed non-inferiority between arms (Arm-A/Arm-B: 60 [52, 69]%/72 [61, 83]%, p [non-inferiority]<0.1). There were no statistically significant differences in the PFS (Arm-A/Arm-B: 9 [95% CI 7, 10] months/10 [7,13] months, hazard ratio [HR] = 1.19 [0.80, 1.79]) or overall survival (23 [19, 28] months/27 [18, 36] months, HR = 1.24 [0.85, 1.79]) between arms. The objective response rate was also similar (48 [39, 57]%/39 [27, 52]%). The safety profile was similar between arms, and all patients experienced at least one adverse event (AE) (Arm-A/Arm-B grade ≥III AEs: 70%/68%). The most common grade ≥III AEs were as follows: neutropenia (Arm-A/Arm-B: 28%/26%), rash acneiform (15%/24%) and sensory neuropathy (2%/15%) in any group. Arm-A was associated with less grade ≥III rash and sensory neuropathy and a lower rate of serious AEs (20%/27%). CONCLUSION(S): This phase II exploratory trial with a non-inferiority design suggests that maintenance therapy with single-agent cetuximab following mFOLFOX+cetuximab induction could be a valuable option compared with mFOLFOX+cetuximab treatment continuation. We await phase III trials to confirm single-agent cetuximab as maintenance therapy in mCRC patients.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cetuximab/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cetuximab/administración & dosificación , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Supervivencia sin Enfermedad , Exantema/inducido químicamente , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Quimioterapia de Mantención , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Neutropenia/inducido químicamente , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/efectos adversos , Proteínas Proto-Oncogénicas p21(ras)/genética
12.
Clin Transl Oncol ; 20(4): 467-475, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28808872

RESUMEN

PURPOSE: Breast cancer is the most common neoplasm in women and has the highest associated mortality rate. Rapid detection programmes can provide early diagnosis and increase the chances of survival. There are no specific tumor biomarkers for the early phase of the disease. The primary aim of this study was to search a blood biomarker with levels that exceeded the normal range established in the general population that could be used to screen breast cancer. METHODS/PATIENTS: Case-control study. Conventional as well as research (NGAL, EGFR and 8-OHdG) tumor biomarkers were analyzed. RESULTS: A total of 126 women were enrolled (cases: 63 patients with local breast cancer; Controls: 63 healthy women). Significant differences were found in patients with higher levels of the conventional markers, Ca15.3, CEA, Cyfra 21.1 and NSE. However, when commercial cut-off values were used, only Ca 15.13 was significant. In the group of research biomarkers, significantly higher levels of EGFR were found in the control group, and of 8-OHdG in the case group. Using logistic regression analysis and a ROC curve, an equation composed of five markers, Ca 15.3, NSE, NGAL, EGFR and 8-OHdG, which yielded a correct diagnostic probability of breast cancer of 91.8% was obtained. CONCLUSIONS: 8-OHdG has been identified as a new potential marker for screening early stage breast cancer. In addition, a model that combines five blood markers that can be used as a diagnostic test in certain groups of patients has been developed. New studies with a larger sample size are needed to verify the results obtained.


Asunto(s)
Biomarcadores de Tumor/sangre , Neoplasias de la Mama/diagnóstico , Desoxiguanosina/análogos & derivados , Detección Precoz del Cáncer/métodos , 8-Hidroxi-2'-Desoxicoguanosina , Adulto , Anciano , Antígenos de Neoplasias/sangre , Neoplasias de la Mama/sangre , Antígeno CA-19-9/sangre , Antígeno Carcinoembrionario/sangre , Estudios de Casos y Controles , Desoxiguanosina/sangre , Femenino , Humanos , Queratina-19/sangre , Persona de Mediana Edad , Fosfopiruvato Hidratasa/sangre , alfa-Fetoproteínas/análisis
13.
Gastric Cancer ; 21(1): 96-105, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-28393278

RESUMEN

BACKGROUND: Although anthracycline-based triplets are one of the most widely used schedules to treat advanced gastric cancer (AGC), the benefit of including epirubicin in these therapeutic combinations remains unknown. This study aims to evaluate both the efficacy and tolerance of triplets with epirubicin vs. doublets with platinum-fluoropyrimidine in a national AGC registry. METHODS: Patients with AGC treated with polychemotherapy without trastuzumab at 28 hospitals in Spain between 2008 and 2016 were included. The effect of anthracycline-based triplets against doublets was evaluated by propensity score matching (PSM) and Cox proportional hazards (PH) regression. RESULT: A total of 1002 patients were included (doublets, n = 653; anthracycline-based triplets, n = 349). The multivariable Cox PH regression failed to detect significantly increased OS in favor of triplets with anthracyclines: HR 0.90 (95% CI, 0.78-1.05), p = 0.20035. After PSM, the sample contained 325 pairs with similar baseline characteristics. This method was also unable to reveal an increase in OS: 10.5 (95% CI, 9.7-12.3) vs. 9.9 (95% CI, 9.2-11.4) months, HR 0.91 (CI 95%, 0.76-1.083), and (log-rank test, p = 0.226). Response rates (42.1 vs. 33.1%, p = 0.12) and PFS (HR 0.95, CI 95%, 0.80-1.13, log-rank test, p = 0.873) were not significantly higher with epirubicin-based regimens. The triplets were associated with greater grade 3-4 hematological toxicity, and increased hospitalization due to toxicity by 68%. The addition of epirubicin is viable, but 23.7% discontinued treatment because of adverse effects or patient decision. CONCLUSION: Anthracyclines added to platinum-fluoropyrimidine doublets did not improve the response rate or survival outcomes in patients with AGC but entailed greater toxicity.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Adulto , Anciano , Antraciclinas/administración & dosificación , Antraciclinas/efectos adversos , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Pirimidinas/administración & dosificación , Pirimidinas/efectos adversos , Sistema de Registros
14.
Ann Oncol ; 29(2): 439-444, 2018 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-29145602

RESUMEN

Background: There has been little progress toward personalized therapy for patients with metastatic colorectal cancer (mCRC). TYMS-3' untranslated region (UTR) 6 bp ins/del and ERCC1-118C/T polymorphisms were previously reported to facilitate selecting patients for fluoropyrimidine-based treatment in combination with oxaliplatin as first-line therapy. We assessed the utility of these markers in selecting therapy for patients with mCRC. Patients and methods: This randomized, open-label phase II trial compared bevacizumab plus XELOX (control) versus treatment tailored according to TYMS-3'UTR 6 bp ins/del and ERCC1-118C/T polymorphisms. Patients randomized to the experimental treatment received bevacizumab plus FUOX, FUIRI, XELIRI, or XELOX depending on their combination of favorable polymorphisms for FUOX treatment (TYMS-3'UTR ins/del or del/del; ERCC1-118T/T). Progression-free survival (PFS) was the primary end point. Results: Overall, 195 patients were randomized (control n = 65; experimental n = 130). The primary objective was not met: median PFS was 9.4 months in the control group and 10.1 months in the experimental group (P = 0.745). Median overall survival was similar in both groups (16.5 versus 19.1 months, respectively; P = 0.797). Patients in the experimental group had a significantly higher overall response rate (ORR; 65% versus 47% in the control group; P = 0.042) and R0 resection rate (86% versus 44%, respectively; P = 0.018). Neuropathy, hand-foot syndrome, thrombocytopenia, and dysesthesia were significantly less common in the experimental group. Conclusions: This study did not show survival benefits after treatment personalization based on polymorphisms in mCRC. However, the improved ORR and R0 resection rate and fewer disabling toxicities suggest that tailoring therapy by TYMS-3'UTR and ERCC1-118 polymorphisms warrants further investigation in patients with mCRC. ClinicalTrials.gov: NCT01071655.


Asunto(s)
Neoplasias Colorrectales/tratamiento farmacológico , Proteínas de Unión al ADN/genética , Endonucleasas/genética , Pruebas de Farmacogenómica/métodos , Variantes Farmacogenómicas/genética , Timidilato Sintasa/genética , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/genética , Neoplasias Colorrectales/genética , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Selección de Paciente , Medicina de Precisión/métodos , Supervivencia sin Progresión , Resultado del Tratamiento
15.
Nanoscale ; 9(30): 10721-10732, 2017 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-28714508

RESUMEN

Dendritic cell-based (DC-based) vaccines are promising immunotherapies for cancer. However, several factors, such as the lack of efficient targeted delivery and the sources and types of DCs, have limited the efficacy of DCs and their clinical potential. We propose an alternative nanotechnology-based vaccine platform with antibacterial prophylactic abilities that uses gold glyconanoparticles coupled to listeriolysin O 91-99 peptide (GNP-LLO91-99), which acts as a novel adjuvant for cancer therapy. GNP-LLO91-99, when used to vaccinate mice, exhibited dual antitumour activities, namely, the inhibition of tumour migration and growth and adjuvant activity for recruiting and activating DCs, including those from melanoma patients. GNP-LLO91-99 nanoparticles caused tumour apoptosis and induced antigen- and melanoma-specific cytotoxic Th1 responses (P ≤ 0.5). We propose this adjuvant nanotherapy for preventing the progression of the first stages of melanoma.


Asunto(s)
Toxinas Bacterianas/química , Vacunas contra el Cáncer/administración & dosificación , Células Dendríticas/inmunología , Proteínas de Choque Térmico/química , Proteínas Hemolisinas/química , Melanoma Experimental/terapia , Nanopartículas del Metal , Adyuvantes Inmunológicos/química , Animales , Células CHO , Línea Celular Tumoral , Cricetulus , Femenino , Oro , Humanos , Ratones , Ratones Endogámicos C57BL , Péptidos
17.
Clin Transl Oncol ; 19(4): 508-518, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28005259

RESUMEN

PURPOSE: The SEOM Future Plan is aimed at identifying the main challenges, trends and needs of the medical oncology speciality over the next years, including potential oncologist workforce shortages, and proposing recommendations to overcome them. METHODS: The estimations of the required medical oncologists workforce are based on an updated Medical Oncologist Register in Spain, Medical Oncology Departments activity data, dedication times and projected cancer incidence. Challenges, needs and future recommendations were drawn from an opinion survey and an advisory board. RESULTS: A shortage of 211 FTE medical oncologist specialists has been established. To maintain an optimal ratio of 158 new cases/FTE, medical oncology workforce should reach 1881 FTE by 2035. CONCLUSIONS: Main recommendations to face the growing demand and complexity of oncology services include a yearly growth of 2.5% of medical oncologist's workforce until 2035, and development and application of more accurate quality indicators for cancer care and health outcomes measure.


Asunto(s)
Necesidades y Demandas de Servicios de Salud , Oncología Médica , Neoplasias/prevención & control , Oncólogos , Planificación de Atención al Paciente/normas , Humanos , España
18.
Clin Transl Oncol ; 19(2): 135-148, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27206566

RESUMEN

Colorectal cancer (CRC) is one of the world's most common cancers, and has one of the highest mortality rates. The last few decades have seen great progress in preventing, diagnosing and treating this disease, providing undeniable impact on patients' prognosis and quality of life. At all these stages of CRC management, imaging techniques play an essential role. This article reviews some important issues concerning the use of various radiological techniques in the screening, diagnosis, staging, assessment of treatment response, and follow-up of patients with CRC. It also includes a number of practical recommendations on indications for use, technical requirements, minimum information required in the radiology report, evaluation criteria for the response to various drugs, and the recommended frequency at which different examinations should be performed. This consensus statement is the result of cooperation between the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Radiology (SERAM).


Asunto(s)
Neoplasias Colorrectales/diagnóstico por imagen , Diagnóstico por Imagen , Oncología Médica , Radiología , Sociedades Médicas , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/terapia , Consenso , Humanos , Pronóstico , Calidad de Vida
19.
Clin Transl Oncol ; 18(12): 1179-1186, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27900538

RESUMEN

Esophageal cancer (EC) is an aggressive tumor that represents the 6th most common cause of cancer death worldwide. The estimated incidence in Spain is 2090 cases/year. Two main pathological subtypes exist, squamous cell carcinoma and adenocarcinoma. The main differences between them are localization and underlying factors which are the principal cause of the recent incidence changes observed in west countries. Staging techniques and treatment options which combine surgery, chemotherapy and radiotherapy, reflected the high complexity of the EC management. An undeniably multidisciplinary approach is, therefore, required. In this guide, we review the status of current diagnosis and treatment, define evidence and propose recommendations.


Asunto(s)
Adenocarcinoma/diagnóstico , Adenocarcinoma/terapia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/terapia , Guías de Práctica Clínica como Asunto , Humanos , España
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