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2.
BMJ Open ; 12(5): e057687, 2022 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-35636783

RESUMO

INTRODUCTION: Colorectal cancer (CRC) screening programmes can reduce incidence and mortality from this condition if adherence to them is high. As patient experience and satisfaction are key factors in determining adherence to screening programmes, they need to be measured. Furthermore, to promote highly patient-centred healthcare, the perception of patients regarding shared decision-making during CRC screening needs to be known. This study aims to assess the experience, satisfaction and participation in decision-making of participants in a CRC screening programme and of patients diagnosed with CRC through this programme in relation to the diagnostic and therapeutic processes of cancer. METHODS AND ANALYSIS: The CyDESA study is a mixed-methods study with a four phase sequential design. In phase 1, we will conduct a systematic review of patient-reported experience measures (PREMs) for patient experience or satisfaction with CRC screening. In case no located PREM can be applied, in phase 2, we will develop a new PREM. We will use the Delphi methodology to reach consensus among experts and patients and will conduct a pilot test of the developed PREM. Phase 3 is a multicentric cross-sectional study based on self-reported questionnaires that will be conducted at three Spanish hospitals (n=843). The objective is to find out about the experience, satisfaction and participation in decision-making of participants in the CRC screening programme who have had a positive screening test result according to their final screening diagnosis: false positives, colorectal polyps or CRC. Phase 4 is a qualitative phenomenological study based on individual interviews. It will explore the experiences of participants in the CRC screening programme and of those diagnosed with CRC. ETHICS AND DISSEMINATION: Ethics approval by the Ethics Committees of Corporació Sanitària Parc Taulí, Hospital de Sant Pau and Parc de Salut Mar. Findings will be published in peer-reviewed journals and presented at conferences. TRIAL REGISTRATION NUMBER: NCT04610086.


Assuntos
Neoplasias Colorretais , Detecção Precoce de Câncer , Neoplasias Colorretais/diagnóstico , Estudos Transversais , Humanos , Avaliação de Resultados da Assistência ao Paciente , Satisfação do Paciente , Satisfação Pessoal , Revisões Sistemáticas como Assunto
4.
Clin. transl. oncol. (Print) ; 24(4): 646-657, abril 2022. ilus
Artigo em Inglês | IBECS | ID: ibc-203769

RESUMO

The management of localized rectal cancer requires a multidisciplinary approach to optimize outcomes, reduce morbidity and prevent under or overtreatments. While early stages may obtain benefit of local resections without any additional therapies, locally advanced rectal cancer becomes a challenge defining the better sequential strategy of surgery, radiotherapy and chemotherapy. The latest results of international phase III studies have positioned the total neoadjuvant therapy as a potential new standard of care in high risk rectal cancers, however, the best schedule is still not well defined.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/métodos , Terapia Neoadjuvante/métodos , Reto/cirurgia , Estadiamento de Neoplasias , Neoplasias Retais/patologia
5.
Clin Transl Oncol ; 24(4): 646-657, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35303269

RESUMO

The management of localized rectal cancer requires a multidisciplinary approach to optimize outcomes, reduce morbidity and prevent under or overtreatments. While early stages may obtain benefit of local resections without any additional therapies, locally advanced rectal cancer becomes a challenge defining the better sequential strategy of surgery, radiotherapy and chemotherapy. The latest results of international phase III studies have positioned the total neoadjuvant therapy as a potential new standard of care in high risk rectal cancers, however, the best schedule is still not well defined.


Assuntos
Segunda Neoplasia Primária , Neoplasias Retais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/métodos , Humanos , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias , Neoplasias Retais/patologia , Reto/cirurgia
6.
Gastric Cancer ; 25(3): 586-597, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34997449

RESUMO

BACKGROUND: Trifluridine and tipiracil (FTD/TPI) demonstrated survival benefit vs placebo and manageable safety in previously treated patients with metastatic gastric/gastroesophageal junction cancer (mGC/GEJC) in the randomized, placebo-controlled, phase 3 TAGS study. This subgroup analysis of TAGS examined efficacy/safety outcomes by age. METHODS: In TAGS, patients with mGC/GEJC and ≥ 2 prior therapies were randomized (2:1) to receive FTD/TPI 35 mg/m2 or placebo, plus best supportive care. A preplanned subgroup analysis was performed to evaluate efficacy and safety outcomes in patients aged < 65, ≥ 65, and ≥ 75 years. RESULTS: Among 507 randomized patients (n = 337 FTD/TPI; n = 170 placebo), 55%, 45%, and 14% were aged < 65, ≥ 65, and ≥ 75 years, respectively. Overall survival hazard ratios for FTD/TPI vs placebo were 0.67 (95% CI 0.51-0.89), 0.73 (95% CI 0.52-1.02), and 0.67 (95% CI 0.33-1.37) in patients aged < 65, ≥ 65, and ≥ 75 years, respectively. Regardless of age, patients receiving FTD/TPI experienced improved progression-free survival and stayed longer on treatment than those receiving placebo. Among FTD/TPI-treated patients, frequencies of any-cause grade ≥ 3 adverse events (AEs) were similar across age subgroups (80% each), although grade ≥ 3 neutropenia was more frequent in older patients [40% (≥ 65 and ≥ 75 years); 29% (< 65 years)]; AE-related discontinuation rates did not increase with age [14% (< 65 years), 12% (≥ 65 years), and 12% (≥ 75 years)]. CONCLUSIONS: The results of this subgroup analysis show the efficacy and tolerability of FTD/TPI treatment regardless of age in patients with mGC/GEJC who had received 2 or more prior treatments.


Assuntos
Neoplasias Colorretais , Neoplasias Esofágicas , Demência Frontotemporal , Neoplasias Gástricas , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Colorretais/patologia , Combinação de Medicamentos , Neoplasias Esofágicas/tratamento farmacológico , Junção Esofagogástrica/patologia , Demência Frontotemporal/induzido quimicamente , Demência Frontotemporal/tratamento farmacológico , Humanos , Pirrolidinas , Neoplasias Gástricas/patologia , Timina , Trifluridina/efeitos adversos
7.
Cancers (Basel) ; 13(18)2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34572740

RESUMO

Trifluridine/tipiracil is currently approved for metastatic colorectal cancer (mCRC) refractory to available therapies. However, there is no consensus on factors that predict treatment outcomes in daily practice. We assessed the early clinical experience with trifluridine/tipiracil in Spain and potential survival markers. This was a retrospective cohort study of mCRC patients who participated in the trifluridine/tipiracil early clinical experience programme in Spain. The primary outcome was overall survival (OS). Associations between OS and patient characteristics were assessed using multivariate Cox regression analyses. A total of 379 patients were included in the study. Trifluridine/tipiracil was administered for a median of 3.0 cycles and discontinued mainly due to disease progression (79.2%). The median OS was 7.9 months, with a 12-month OS rate of 30.5%. Cox analyses revealed that the following variables independently enhanced OS: ≤2 metastatic sites, no liver metastasis, alkaline phosphatase < 300 IU, trifluridine/tipiracil dose reductions, and neutrophil/lymphocyte ratio < 5. Grade ≥ 3 toxicities were reported in 141 (37.2%) patients, including mainly afebrile neutropaenia (23.2%), anaemia (12.1%), and thrombocytopaenia (5.3%). This study supports the real-life efficacy and safety of trifluridine/tipiracil for refractory mCRC and identifies tumour burden, liver metastasis, alkaline phosphatase, dose reductions, and neutrophil/lymphocyte ratio as survival markers.

8.
Cancers (Basel) ; 13(15)2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34359589

RESUMO

BACKGROUND: Endorectal ultrasound and rectal magnetic resonance are sometimes unable to differentiate between stages T2 and T3 in rectal adenomas that are possible adenocarcinomas, or between stages T1 and T2 in rectal adenocarcinomas. These cases of diagnostic uncertainty raise a therapeutic dilemma: transanal endoscopic surgery (TES) or total mesorectal excision (TME)? METHODS: An observational study of a cohort of 803 patients who underwent TES from 2004 to 2021. Patients operated on for adenoma (group I) and low-grade T1 adenocarcinoma (group II) were included. The variables related to uncertain diagnosis, and to the definitive pathological diagnosis of adenocarcinoma stage higher than T1, were analyzed. RESULTS: A total of 638 patients were included. Group I comprised 529 patients, 113 (21.4%) with uncertain diagnosis. Seventeen (15%) eventually had a pathological diagnosis of adenocarcinoma higher than T1. However, the variable diagnostic uncertainty was a risk factor for adenocarcinoma above T1 (OR 2.3, 95% CI 1.1-4.7). Group II included 109 patients, eight with uncertain diagnosis (7.3%). Two patients presented a definitive pathological diagnosis of adenocarcinoma above T1. CONCLUSIONS: On the strength of these data, we recommend TES as the initial indication in cases of diagnostic uncertainty. Multicenter studies with larger samples for both groups should now be performed to further assess this strategy of initiating treatment with TES.

9.
Clin Cancer Res ; 27(10): 2890-2898, 2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-33727257

RESUMO

PURPOSE: Total neoadjuvant treatment (TNT) is a valid strategy for patients with high-risk locally advanced rectal cancer (LARC). Biomarkers of response to TNT are an unmet clinical need. We aimed to determine the value of circulating tumor DNA (ctDNA) to predict tumor response, recurrence, and survival in patients with LARC treated with TNT. EXPERIMENTAL DESIGN: The GEMCAD 1402 was a phase II randomized, multicentric clinical trial that randomized 180 patients with LARC to modified schedule of fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) +/- aflibercept, followed by chemoradiation and surgery. Plasma samples were collected at baseline and after TNT within 48 hours before surgery (presurgery). An ultrasensitive assay that integrates genomic and epigenomic cancer signatures was used to assess ctDNA status. ctDNA results were correlated with variables of local tumor response in the surgery sample, local/systemic recurrence, and survival. RESULTS: A total of 144 paired plasma samples from 72 patients were included. ctDNA was detectable in 83% of patients at baseline and in 15% following TNT (presurgery). No association was found between ctDNA status and pathologic response. Detectable presurgery ctDNA was significantly associated with systemic recurrence, shorter disease-free survival (HR, 4; P = 0.033), and shorter overall survival (HR, 23; P < 0.0001). CONCLUSIONS: In patients with LARC treated with TNT, presurgery ctDNA detected minimal metastatic disease identifying patients at high risk of distant recurrence and death. This study sets the basis for prospective clinical trials that use liquid biopsy to personalize the therapeutic approach following TNT.


Assuntos
Biomarcadores Tumorais , DNA Tumoral Circulante , Período Pré-Operatório , Neoplasias Retais/sangue , Neoplasias Retais/diagnóstico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Metástase Neoplásica , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Neoplasias Retais/mortalidade , Neoplasias Retais/terapia , Resultado do Tratamento
10.
J Gastrointest Surg ; 25(10): 2660-2667, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33629231

RESUMO

BACKGROUND: Surgical treatment of early rectal cancer T1 is either local excision or total mesorectal excision. The choice of surgery is based on the risk of metastatic lymph node involvement. The most important factor to consider is the degree of submucosal invasion. We present a different way to measure tumoral invasion derived from the measurement of the healthy residual submucosa with its prognosis and therapeutic implications METHODS: Observational study of tumor submucosal invasion in patients undergoing transanal endoscopic microsurgery was conducted. Parameters evaluated are submucosal invasion, measuring the healthy residual submucosa at the point of maximum invasion; macroscopic morphology of the tumor; presence of muscularis mucosa, muscularis propria, and measurement of submucosa in the tumor area and the healthy area. The classification proposed is compared with the ones previously published. RESULTS: Eighty consecutive patients diagnosed with T1 rectal cancer underwent transanal endoscopic microsurgery. Seventeen tumors (21.3%) were polypoid. En bloc resection was achieved in 77 (96.3%). The muscularis mucosa was present in 28 (35%), and the muscularis propria in 77 (96.3%) (p < 0.001). The healthy residual submucosa in the tumor area measured 2,343 ± 1,869 µm. Agreement was moderate with the Kikuchi classification (kappa 0.58) and very good with the Kudo classification (kappa 0.87). CONCLUSIONS: We describe a method for measuring submucosal invasion in T1 rectal cancer which does not depend on the morphology of the lesion or on the presence of the muscularis mucosa. It can be applied to all T1 classifications of the digestive tract in which the muscularis propria is present.


Assuntos
Adenocarcinoma , Neoplasias Retais , Microcirurgia Endoscópica Transanal , Adenocarcinoma/cirurgia , Humanos , Invasividade Neoplásica , Prognóstico , Neoplasias Retais/cirurgia
11.
Dis Colon Rectum ; 64(2): 200-208, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33315715

RESUMO

BACKGROUND: Unfavorable adenocarcinoma after transanal endoscopic microsurgery requires "completion surgery" with total mesorectal excision. The literature on this procedure is very limited. OBJECTIVE: This study aims to assess the percentage of transanal endoscopic microsurgery that will require completion surgery. DESIGN: This is an observational study with prospective data collection and retrospective analysis from patients who were operated on consecutively. SETTINGS: The study was conducted at a single academic institution. PATIENTS: Patients undergoing transanal endoscopic microsurgery from June 2004 to December 2018 who later required total mesorectal excision were included. MAIN OUTCOME MEASURES: All the patients followed the same protocol: preoperative study, indication of transanal endoscopic microsurgery with curative intent, performance of transanal endoscopic microsurgery, and completion surgery indication 3 to 4 weeks after transanal endoscopic microsurgery. RESULTS: Seven hundred seventy-four patients underwent transanal endoscopic microsurgery, 622 with curative intent (group I: adenoma, 517; group II: adenocarcinoma, 105). Completion surgery was indicated in 64 of 622 (10.3%) patients: group I, 40 of 517 (7.7%) and group II, 24 of 105 (22.9%). After applying exclusion criteria, completion surgery was performed in 55 patients (8.8%). Abdominoperineal resection was performed in 23 (45.1%); the initial lesion was within 6 cm of the anal verge in 19 of these 23 (82.6%). The clinical morbidity rate (Clavien Dindo> II) was 3 of 51 (5.9%). Total mesorectal excision was graded as complete in 42 of 49 (85.7%). The circumferential resection margin was tumor-free in 47 of 50 (94%). Median follow-up was 58 months. Local recurrence was recorded in 2 of 51 (3.9%) and systemic recurrence was recorded in 7 of 51 (13.7%); 5-year disease-free survival was 86%. LIMITATIONS: The limitations are defined by the study's observational design and the retrospective analysis. CONCLUSION: The indication of completion surgery after transanal endoscopic microsurgery is low, but is higher in the indication of adenocarcinoma. Compared with initial total mesorectal excision, completion surgery requires a higher rate of abdominoperineal resection, but has similar postoperative morbidity, total mesorectal excision quality, and oncological results. See Video Abstract at http://links.lww.com/DCR/B423. CIRUGA COMPLEMENTARIA EN CNCER DE RECTO DESFAVORABLE DESPUS DE UNA TEM SE OBTIENE SATISFACTORIAMENTE PRESERVACIN DEL ESFNTER, CALIDAD DE MUESTRA DE ETM Y RESULTADOS ONCOLGICOS A LARGO PLAZO: ANTECEDENTES:El adenocarcinoma con evolución desfavorable luego de una de microcirugía endoscópica transanal (TEM) requiere "cirugía de finalización" con la excisión total del mesorecto. La literatura sobre este procedimiento es muy limitada.OBJETIVO:Evaluar el porcentaje de microcirugía endoscópica transanal que requerió cirugía completa.DISEÑO:Estudio observacional con recolección prospectiva de datos y análisis retrospectivo de pacientes operados consecutivamente.AJUSTES:El estudio se realizó en una sola institución académica.PACIENTES:Aquellos pacientes sometidos a microcirugía endoscópica transanal desde junio de 2004 hasta diciembre de 2018 que luego requirieron excisón toztal del mesorecto.PRINCIPALES MEDIDAS DE RESULTADO:Todos los pacientes siguieron el mismo protocolo: estudio preoperatorio, indicación de microcirugía endoscópica transanal con intención curativa, realización de microcirugía endoscópica transanal e indicación de cirugía complementaria 3-4 semanas después de la microcirugía endoscópica transanal.RESULTADOS:Setecientos setenta y cuatro pacientes fueron sometidos a microcirugía endoscópica transanal, 622 con intención curativa (grupo I, adenoma: 517, grupo II, adenocarcinoma: 105). la cirugía complementaria fué indicada en 64/622 (10.3%), grupo I: 40/517 (7.7%) y grupo II 24/105 (22.9%). Después de aplicar los criterios de exclusión, la cirugía complementaria se realizó en 55 pacientes (8,8%). La resección abdominoperineal fué realizada en 23 (45,1%); en 19 de estos casos 23 (82,6%) la lesión inicial se encontraba dentro los 6 cm del margen anal. La tasa de morbilidad clínica (Clavien-Dindo > II) fue de 3/51 (5,9%). La excisión total del mesorecto se calificó como completa en 42/49 (85,7%). El margen de resección circunferencial se encontraba libre de tumor en 47/50 (94%). La mediana de seguimiento fue de 58 meses. La recurrencia local se registró en 2/51 (3.9%) y la recurrencia sistémica en 7/51 (13.7%); La supervivencia libre de enfermedad a 5 años fue del 86%.LIMITACIONES:Todas definidas por el diseño observacional y el análisis retrospectivo del mismo.CONCLUSIÓN:La indicación de completar la cirugía después de una TEM es baja, pero es más alta cuando la indicación es por adenocarcinoma. En comparación con la excisión total del mesorecto inicial, la cirugía complementaria requiere una tasa más alta de resección abdominoperineal, pero tiene una morbilidad postoperatoria, una calidad de excisión total del mesorecto y resultados oncológicos similares. ConsulteVideo Resumen en http://links.lww.com/DCR/B423. (Traducción-Dr. Xavier Delgadillo).


Assuntos
Adenocarcinoma/cirurgia , Protectomia/métodos , Neoplasias Retais/cirurgia , Reoperação/métodos , Microcirurgia Endoscópica Transanal , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/prevenção & controle , Neoplasias Retais/patologia , Estudos Retrospectivos , Resultado do Tratamento
12.
BMC Cancer ; 20(1): 1164, 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33246428

RESUMO

BACKGROUND: Preoperative chemoradiotherapy with capecitabine is considered as a standard of care for locally advanced rectal cancer. The "Tratamiento de Tumores Digestivos" group (TTD) previously reported in a randomized Ph II study that the addition of Bevacizumab to capecitabine-RT conferred no differences in the pre-defined efficacy endpoint (pathological complete response). We present the follow-up results of progression-free survival, distant relapse-free survival, and overall survival data at 3 and 5 years. METHODS: Patients (pts) were randomized to receive 5 weeks of radiotherapy (45 Gy/25 fractions) with concurrent Capecitabine 825 mg/m2 twice daily, 5 days per week with (arm A) or without (arm b) bevacizumab (5 mg/kg once every 2 weeks). RESULTS: In our study, the addition of bevacizumab to capecitabine and radiotherapy in the neoadjuvant setting shows no differences in pathological complete response (15.9% vs 10.9%), distant relapse-free survival (81.0 vs 80.4 and 76.2% vs 78.2% at 3 and 5 years respectively), disease-free survival (75% vs 71.7 and 68.1% vs 69.57% at 3 and 5 years respectively) nor overall survival at 5-years of follow-up (81.8% vs 86.9%). CONCLUSIONS: the addition of bevacizumab to capecitabine plus radiotherapy does not confer statistically significant advantages neither in distant relapse-free survival nor in disease-free survival nor in Overall Survival in the short or long term. TRIAL REGISTRATION: EudraCT number: 2009-010192-24 . Clinicaltrials.gov number: NCT01043484 .


Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia , Adenocarcinoma/patologia , Bevacizumab/administração & dosagem , Capecitabina/administração & dosagem , Quimiorradioterapia , Feminino , Humanos , Masculino , Intervalo Livre de Progressão , Neoplasias Retais/patologia
13.
Cancers (Basel) ; 12(10)2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33019720

RESUMO

Long non-coding RNAs (lncRNAs) play important roles in cancer and are potential new biomarkers or targets for therapy. However, given the low and tissue-specific expression of lncRNAs, linking these molecules to particular cancer types and processes through transcriptional profiling is challenging. Formalin-fixed, paraffin-embedded (FFPE) tissues are abundant resources for research but are prone to nucleic acid degradation, thereby complicating the study of lncRNAs. Here, we designed and validated a probe-based enrichment strategy to efficiently profile lncRNA expression in FFPE samples, and we applied it for the detection of lncRNAs associated with colorectal cancer (CRC). Our approach efficiently enriched targeted lncRNAs from FFPE samples, while preserving their relative abundance, and enabled the detection of tumor-specific mutations. We identified 379 lncRNAs differentially expressed between CRC tumors and matched healthy tissues and found tumor-specific lncRNA variants. Our results show that numerous lncRNAs are differentially expressed and/or accumulate variants in CRC tumors, thereby suggesting a role in CRC progression. More generally, our approach unlocks the study of lncRNAs in FFPE samples, thus enabling the retrospective use of abundant, well documented material available in hospital biobanks.

14.
Cancers (Basel) ; 12(8)2020 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-32806731

RESUMO

Background: The prospective phase IV AVAMET study was undertaken to correlate response evaluation criteria in solid tumors (RECIST)-defined response rates with computed tomography-based morphological criteria (CTMC) and pathological response after liver resection of colorectal cancer metastases. Methods: Eligible patients were aged ≥18 years, with Eastern Cooperative Oncology Group (ECOG) performance status 0/1 and histologically-confirmed colon or rectal adenocarcinoma with measurable liver metastases. Preoperative treatment was bevacizumab (7.5 mg on day 1) + XELOX (oxaliplatin 130 mg/m2, capecitabine 1000 mg/m2 bid on days 1-14 q3w). After three cycles, response was evaluated by a multidisciplinary team. Patients who were progression-free and metastasectomy candidates received one cycle of XELOX before undergoing surgery 3-5 weeks later, followed by four cycles of bevacizumab + XELOX. Results: A total of 83 patients entered the study; 68 were eligible for RECIST, 67 for CTMC, and 51 for pathological response evaluation. Of these patients, 49% had a complete or partial RECIST response, 91% had an optimal or incomplete CTMC response, and 81% had a complete or major pathological response. CTMC response predicted 37 of 41 pathological responses versus 23 of 41 responses predicted using RECIST (p = 0.008). Kappa coefficients indicated a lack of correlation between the results of RECIST and morphological responses and between morphological and pathological response rates. Conclusion: CTMC may represent a better marker of pathological response to bevacizumab + XELOX than RECIST in patients with potentially-resectable CRC liver metastases.

15.
BMC Palliat Care ; 19(1): 103, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32650765

RESUMO

BACKGROUND: Despite advances in surgery, radiotherapy, and chemotherapy, pancreatic adenocarcinoma often progresses rapidly and causes death. The physical decline of these patients is expected to impact their quality of life (QoL). Therefore, in addition to objective measures of effectiveness, the evaluation of health-related QoL should be considered a matter of major concern when assessing therapy outcomes. METHODS: Observational, prospective, multicenter study including patients with metastatic pancreatic adenocarcinoma who started first-line chemotherapy in 12 Spanish centers. Treatment and clinical characteristics were recorded at baseline. Patients' health-related quality of life, ECOG, and Karnofsky index were measured at baseline, at Days 15 and 30, and every four weeks up to 6 months of chemotherapy. Health-related quality of life was measured using the EORTC-QLQ-C30 and EQ-5D questionnaires. Other endpoints included overall survival and progression-free survival. RESULTS: The study sample included 116 patients (median age of 65 years). Mean (SD) scores for the QLQ-C30 global health status scale showed a significant increasing trend throughout the treatment (p = 0.005). Patients with either a Karnofsky index of 70-80 or ECOG 2 showed greater improvement in the QLQ-C30 global health status score than the corresponding groups with better performance status (p ≤ 0.010). Pain, appetite, sleep disturbance, nausea, and constipation significantly improved throughout the treatment (p < 0.005). Patients with QLQ-C30 global health status scores ≥50 at baseline had significantly greater overall survival and progression-free survival (p = 0.005 and p = 0.021, respectively). No significant associations were observed regarding the EQ-5D score. CONCLUSIONS: Most metastatic pancreatic adenocarcinoma patients receiving first-line chemotherapy showed an increase in health-related quality of life scores throughout the treatment. Patients with lower performance status and health-related quality of life at baseline tended to greater improvement. The EORTC QLQ-C30 scale allowed us to measure the health-related quality of life of metastatic pancreatic adenocarcinoma patients receiving first-line chemotherapy.


Assuntos
Tratamento Farmacológico/psicologia , Neoplasias Pancreáticas/complicações , Qualidade de Vida/psicologia , Adulto , Idoso , Distribuição de Qui-Quadrado , Tratamento Farmacológico/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/diagnóstico , Neoplasias Pancreáticas/psicologia , Estudos Prospectivos , Inquéritos e Questionários
16.
Clin Colorectal Cancer ; 19(3): 165-177, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32507561

RESUMO

Colorectal cancer (CRC) is a public health problem: it is the third most common cancer in men (746,000 new cases/year) and the second in women (614,000 new cases/year), representing the second leading cause of death by cancer worldwide. The survival of patients with metastatic CRC (mCRC) has increased prominently in recent years, reaching a median of 25 to 30 months. A growing number of patients with mCRC are candidates to receive a treatment in third line or beyond, although the optimal drug regimen and sequence are still unknown. In this situation of refractoriness, there are several alternatives: (1) To administer sequentially the 2 oral drugs approved in this indication: trifluridine/tipiracil and regorafenib, which have shown a statistically significant benefit in progression-free survival and overall survival with a different toxicity profile. (2) To administer cetuximab or panitumumab in treatment-naive patients with RAS wild type, which is increasingly rare because these drugs are usually indicated in first- or second-line. (3) To reuse drugs already administered that were discontinued owing to toxicity or progression (oxaliplatin, irinotecan, fluoropyrimidine, antiangiogenics, anti-epidermal growth factor receptor [if RAS wild-type]). High-quality evidence is limited, but this strategy is often used in routine clinical practice in the absence of alternative therapies especially in patients with good performance status. (4) To use specific treatments for very selected populations, such as trastuzumab/lapatinib in mCRC human epidermal growth factor receptor 2-positive, immunotherapy in microsatellite instability, intrahepatic therapies in limited disease or primarily located in the liver, although the main recommendation is to include patients in clinical trials.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/normas , Neoplasias Colorretais/tratamento farmacológico , Guias de Prática Clínica como Assunto , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Tomada de Decisão Clínica/métodos , Ensaios Clínicos como Assunto , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Resistencia a Medicamentos Antineoplásicos , Prova Pericial , Humanos , Instabilidade de Microssatélites , Seleção de Pacientes , Intervalo Livre de Progressão , Espanha/epidemiologia
17.
Int J Colorectal Dis ; 35(4): 739-746, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32062727

RESUMO

PURPOSE: To determine the efficacy and safety data of aflibercept + FOLFIRI in wt RAS mCRC patients after progression to standard chemotherapy + anti-EGFR treatment. METHODS: Retrospective, observational study in real life conducted in wt RAS mCRC patients treated with FOLFIRI-aflibercept after progression to standard first line chemotherapy + anti-EGFR treatment. RESULTS: A total of 120 patients from 12 Spanish hospitals were enrolled. Median age is 60 years (62.5%/37.5%male/female). Primary tumor site is 24.1%/75.9% right/left-side colon, and 40.8% of patients had a prior resection. All patients had wild-type RAS tumors including 5% of patients with BRAF mutations and received anti-EGFR treatment. At the time aflibercept was initiated, ECOG PS is 0/1 in 96% of patients. Median number of FOLFIRI-aflibercept cycles is 12. Efficacy results: Overall response rate is 33%; progression-free survival (PFS) is 6.9 months (95%CI: 6.1-7.8). Primary tumor resection was the only significant variable related to PFS in the multivariate analysis. Median overall survival (OS) is 14.5 months (95%CI: 9.7-19.3). ECOG and number of metastatic sites were related to OS in multivariate analysis. About 54.1% of patients received a third-line therapy including TAS-102 (23%), regorafenib (18.5%), and capecitabine (9.2%). TOXICITY: Grade 3-4 toxicities were observed in 37.5% of the patients (hematologic 16.6%, hypertension 7.5%, asthenia 5.9%, and perforation 2.5%). Aflibercept dose was reduced in 18.3% of patients. CONCLUSIONS: The results show that patients with wt RAS mCRC who received an anti-EGFR as part of the first-line treatment achieved similar RR, PFS, OS, and toxicities to those reported in VELOUR trial. These results suggest that FOLFIRI-aflibercept after first-line treatment with anti-EGFR is an appropriated option for RAS wt mCRC.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Receptores ErbB/antagonistas & inibidores , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Proteínas ras/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/análogos & derivados , Camptotecina/farmacologia , Camptotecina/uso terapêutico , Intervalo Livre de Doença , Receptores ErbB/metabolismo , Feminino , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Humanos , Leucovorina/farmacologia , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Proteínas Recombinantes de Fusão/farmacologia , Análise de Sobrevida
18.
Cir. Esp. (Ed. impr.) ; 97(8): 459-464, oct. 2019. tab
Artigo em Espanhol | IBECS | ID: ibc-187620

RESUMO

Los adenocarcinomas de la unión esofagogástrica representan un 27% de todos los tumores gástricos. En los últimos años se está clasificando como una entidad propia, con tratamientos específicos y en ocasiones diferenciados de los tratamientos de los adenocarcinomas de cuerpo gástrico. El esquema de tratamiento puede basarse en quimioterapia (QT) o quimiorradioterapia (QTRT), que se administra de forma preoperatoria (neoadyuvante), postoperatoria (adyuvante) o perioperatoria. Existen estudios que han testado las diversas modalidades de tratamiento, pero en estos momentos no se dispone de una única secuencia protocolizada válida. Los resultados apuntan a una mejoría de la supervivencia cuando administramos tratamiento preoperatorio, con evidencia a favor de la QTRT y de la QT. Ya están en marcha estudios con tratamientos dirigidos que pretenden conseguir aumentar la actividad de la QT tradicional y en los próximos años deberemos conocer el papel de la inmunoterapia en este grupo de pacientes


Adenocarcinomas of the gastroesophageal junction represent 27% of all gastric tumors. n recent years, it has been classified as an entity of its own, with specific treatments that are sometimes differentiated from gastric treatments. Treatment can be based on chemotherapy (CTx) or chemoradiotherapy (CRTx) that is administered preoperatively (neoadjuvant), postoperatively (adjuvant) or perioperatively. There are studies that have tested several treatment modalities, but there is currently no single protocolized sequence. The results point to an improvement in survival when we administer preoperative treatment, with evidence in favor of CRTx and CTx. Studies are already underway with targeted treatment that aim to increase the activity of traditional chemotherapy. In the next few years, we should know the role of immunotherapy in this group of patients


Assuntos
Humanos , Adenocarcinoma/terapia , Antineoplásicos/uso terapêutico , Junção Esofagogástrica , Terapia Neoadjuvante/métodos , Neoplasias Gástricas/terapia , Adenocarcinoma/secundário , Quimioterapia Adjuvante , Imunoterapia/normas , Cuidados Pré-Operatórios , Neoplasias Gástricas/patologia
19.
Br J Cancer ; 121(5): 378-383, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31363167

RESUMO

BACKGROUND: Targeted agents are standard treatment for RAS wild-type metastatic colorectal cancer in the first- and second-line settings. This phase 2 study determined the benefit of targeting the epidermal growth factor receptor (EGFR) with panitumumab plus irinotecan in irinotecan-refractory patients. METHODS: KRAS exon-2 wild-type patients failing prior irinotecan received panitumumab (6 mg/kg) and irinotecan (180 mg/m²) every 2 weeks. The primary endpoint was the overall response rate (ORR). Secondary endpoints included safety, progression-free survival (PFS) and overall survival (OS). KRAS exon-2 status was evaluated centrally, along with NRAS, BRAF mutations, epiregulin, amphiregulin, PTEN and EGFR copy number status, and correlated with efficacy. RESULTS: Sixty-one patients were treated. Among the 46 wild-type RAS patients, the ORR was 15.2% (seven partial responses), with median PFS of 3.8 months (95% CI 2.7-4.3) and median OS of 12.5 months (95% CI 6.7-15.9). Wild-type BRAF patients showed a 13.0% response rate. No significant correlations between response and baseline biomarker expression were identified. Common grade 3-4 adverse events were diarrhoea and rash (18.0% each), hypomagnesaemia and asthenia (8.2% each). CONCLUSIONS: The addition of panitumumab to irinotecan as salvage therapy is feasible but has limited activity in irinotecan-refractory metastatic colorectal cancer. No biomarkers predictive of response were identified.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Terapia de Salvação , Adenocarcinoma/genética , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Anfirregulina/genética , Astenia/induzido quimicamente , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Diarreia/induzido quimicamente , Erupção por Droga , Epirregulina/genética , Receptores ErbB/genética , Feminino , GTP Fosfo-Hidrolases/genética , Humanos , Irinotecano/administração & dosagem , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundário , Linfonodos/patologia , Magnésio/sangue , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , PTEN Fosfo-Hidrolase/genética , Panitumumabe/administração & dosagem , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/secundário , Intervalo Livre de Progressão , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Taxa de Sobrevida , Resultado do Tratamento , Desequilíbrio Hidroeletrolítico/induzido quimicamente
20.
JAMA Oncol ; 5(11): 1566-1573, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31465088

RESUMO

Importance: Preclinical studies suggest that a vascular endothelial growth factor (VEGF) blockade may play a role in the preoperative treatment of rectal adenocarcinoma; however, how to combine anti-VEGF drugs with neoadjuvant chemotherapy (CT) and/or chemoradiotherapy (CRT) remains controversial. Objective: To study the effect of aflibercept plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) induction CT prior to standard CRT and total mesorectal excision (TME) surgery in patients with high-risk rectal adenocarcinoma. Design, Setting, and Participants: In the Grupo Español Multidisciplinar En Cancer Digestivo (GEMCAD) 1402 phase 2 randomized clinical trial, 180 patients aged 18 to 75 years, identified by centrally reviewed magnetic resonance imaging to have mrT3c-d/T4/N2 rectal adenocarcinoma, were enrolled from 20 treatment centers in Spain between January 2015 and March 2017. Patients were randomized in a 2:1 treatment to control arm ratio. The primary end point was evaluated at 2 interim and 1 final analyses. The study was designed to perform hypothesis testing at α = .2 and ß = .2. A 2-sided P value of <.1984 in the final analysis of the intention-to-treat population was the threshold for considering the experimental treatment to be more effective than the control. Interventions: Patients received neoadjuvant mFOLFOX6 with (arm A; n = 115) or without (arm B; n = 65) aflibercept, 4 mg/kg (every 2 weeks, 6 cycles, and 3 months) prior to standard CRT and TME surgery. Main Outcomes and Measures: The primary end point was a pathologic complete response (pCR) (ypT0N0). Secondary end points included toxic effects, surgical morbidity, R0 resections, compliance, and 3-year disease-free survival. Results: For the 115 patients who received treatment with mFOLFOX6 plus aflibercept, the median (range) age was 60 (32-75) years, 77 men (66.9%) and 38 women (33.0%). For the 65 patients who received induction CT treatment with only mFOLFOX6, the median (range) age was 65 (39-75) years, 39 men (60.0%) and 26 women (40.0%). The pCR rate in the intention-to-treat population was 22.6% (95% CI, 15.3%-31.3%) in arm A and 13.8% (95% CI, 6.5%-24.6%) in arm B (P = .15). The main differential toxic effect was grade 3/4 hypertension during the induction phase. Postoperative complications were similar in both arms (15.5% in arm A and 12.9% in arm B). A total of 106 patients (92.1%) in arm A and 63 (96.9%) in arm B received all treatment cycles. Conclusions and Relevance: The study met its primary end point. The findings suggest that adding aflibercept to an induction regimen using mFOLFOX6 plays a role in increasing the pCR rate in patients with high-risk rectal adenocarcinoma, without substantially increasing surgical complications. The GEMCAD 1402 trial provides a rationale for phase 3 trials. Trial Registration: ClinicalTrials.gov identifier: NCT02340949.

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