RESUMO
BACKGROUND: Prior trials validated triplet chemotherapy (Tri-CT) with bevacizumab as first line treatment for metastatic colorectal cancer (mCRC) but real-world data are scarce and practices remain heterogeneous. AIMS: To evaluate Tri-CT +/- bevacizumab efficacy and safety, and to identify factors influencing treatment decisions. METHODS: The COLOTRIP retrospective study enrolled mCRC patients treated from 2014 to 2019 in 14 French centers. RESULTS: Of 299 patients (81% PS 0-1, 58% RAS-mutated and 19% BRAF-mutated), 51% received Tri-CT and 49% Tri-CT + bevacizumab. Metastatic disease was classified as resectable (6.5%), potentially resectable (40%), and unresectable (54%). Bevacizumab use was associated with primary tumor location, mutational status and number of metastases. Median overall survival was 33.5 months in the Tri-CT group and 23.9 months in the Tri-CT + bevacizumab group, with median progression-free survival being 14.5 and 11.4 months. After adjusting for initial characteristics, no difference in survival was noted. Around 30% of patients experienced grade ≥3 adverse events. CONCLUSIONS: This study highlights several factors influencing Tri-CT use +/- bevacizumab decision and confirms the real-world good oncological outcomes and tolerability of these regimens in mCRC patients. Our results suggest that Tri-CT alone may by an appropriate option for specific subgroups of patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab , Neoplasias Colorretais , Humanos , Bevacizumab/administração & dosagem , Bevacizumab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Masculino , Feminino , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , França , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/administração & dosagem , Intervalo Livre de Progressão , Adulto , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Oesophageal stents have several well-known respiratory complications, including aspiration pneumonia, fistula and airway compression. However, bilateral vocal cord paralysis has rarely been described. METHODS: We describe two patients who presented with refractory dysphagia due to malignant proximal oesophageal strictures. Both received palliative treatment consisting of fully covered self-expandable metal stents that were placed across the strictures. RESULTS: Both patients developed inspiratory stridor and acute hypoxemic respiratory failure shortly after the stent was placed. Flexible bronchoscopy revealed vocal cord paralysis in paramedian position, potentially due to extrinsic compression of the posterior branch of the recurrent laryngeal nerve following the progressive opening of the esophageal prosthesis. One patient recovered after the stent was removed. CONCLUSIONS: Bilateral vocal cord paralysis is a rare but potentially fatal complication of proximal esophagus stenting.
Assuntos
Endoscopia/efeitos adversos , Cuidados Paliativos/métodos , Complicações Pós-Operatórias/etiologia , Stents Metálicos Autoexpansíveis/efeitos adversos , Paralisia das Pregas Vocais/etiologia , Idoso de 80 Anos ou mais , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/cirurgia , Estenose Esofágica/etiologia , Estenose Esofágica/cirurgia , Evolução Fatal , Humanos , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
PURPOSE: The role of chemotherapy has not been established in the treatment of metastatic squamous cell oesophageal cancer (mESCC). PATIENTS AND METHODS: E-DIS is a discontinuation trial, aimed at estimating efficacy, quality of life and safety of chemotherapy continuation (CT-CONT) in patients with mESCC who are free from progression after a selection phase of chemotherapy. The primary end-point was overall survival. RESULTS: Sixty-seven patients were randomised. The 9-month survival rate was 50% (85% confidence interval [CI]: 37-62%) and 48% (85% CI: 35-60%) in the CT-CONT arm and in the chemotherapy discontinuation (CT-DISC) arm, respectively. The time until definitive deterioration of the global health status (European Organisation for Research and Treatment of Cancer [EORTC] core quality of life questionnaire) was 6.6 months (95% CI: 3.3-12.4) for the CT-CONT arm and 4.2 months (95% CI: 2.9-6.3) for the CT-DISC arm, with a hazard ratio (HRCT-DISC/CT-CONT) = 1.44 (95% CI: 0.82-2.53). We observed a beneficial trend in favour of CT-CONT (HR > 1) for most dimensions, including an improvement for three dimensions (dysphagia, eating and oesophageal pain) of the EORTC Oesophageal Cancer Module QLQ-OES18. CONCLUSION: CT-CONT provides an overall survival rate that is similar to CT-DISC. E-DIS trial provides valuable data to support shared decision-making between physicians and patients regarding CT-CONT/DISC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Neoplasias Esofágicas/mortalidade , Carcinoma de Células Escamosas do Esôfago/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Resultado do TratamentoRESUMO
BACKGROUND: There is an increasing interest for Notch signalling pathway and particularly Delta-like ligand 4 (DLL4) as potential therapeutic target to improve outcome for patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: Using immunohistochemistry (IHC) and tissue microarray (TMA), we assessed the expression patterns of DLL4, Notch1 and Notch3 in 151 patients from two independent cohorts of resected PDAC. We investigated the prognostic and the predictive significance of these proteins. RESULTS: High IHC DLL4 expression in cancer cells was associated with worse overall survival (OS) and disease-free survival (DFS) than low DLL4 expression (median OS: 12.9 vs 30.4 months, P=0.004 and median DFS: 8.8 vs 17.4 months, P=0.02). High DLL4 expression remained a significant negative prognostic factor in multivariate analysis (HR for OS: 2.1, P=0.02 and HR for DFS: 2.0, P=0.02). Low DLL4 abundance was associated with a longer OS-only for patients who received an adjuvant gemcitabine-based chemotherapy (P<0.001) but not for patients who did not receive gemcitabine (P=0.72). Furthermore, the interaction test for adjuvant gemcitabine therapy was statistically significant (P<0.001). The validating cohort recapitulated the findings of the training cohort. CONCLUSIONS: Low DLL4 abundance in tumour cells may predict the benefit from adjuvant gemcitabine therapy after PDAC resection.