RESUMO
The use of Digital Healthcare Products is leading to significant improvements in clinical practice. Herein, we discuss the development of PROACT 2.0 (Patient Reported Opinions About Clinical Tolerability v2.0), a novel open-source mobile and web application developed at Fondazione IRCCS Istituto Nazionale Tumori in Milan. It was developed in collaboration with The Christie, Manchester, in the context of work package 2 of the UpSMART Accelerator project, involving a consortium of referral cancer centers from the UK, Spain and Italy. PROACT 2.0 enhances communication between patients and healthcare providers in cancer clinical trials, allowing patients to report adverse events and side effects, and healthcare teams to collect valuable patient-reported outcome measures for treatment management. PROACT 2.0 supports text, audio, and video messaging, offering a secure, non-urgent communication channel that integrates with, or replaces, traditional methods. Its user-friendly and multilingual interface provides a new route for patient engagement and streamlines the handling of logistical information. Positive feedback from initial testing warrants future enhancements for broader applicability in cancer research and treatment.
Assuntos
Ensaios Clínicos como Assunto , Comunicação , Relações Médico-Paciente , Humanos , Neoplasias/terapia , Medidas de Resultados Relatados pelo Paciente , Aplicativos Móveis , ItáliaRESUMO
PURPOSE: The standard treatment of peritoneal pseudomyxoma is based on cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC). The establishment of newer systemic treatments is an unmet clinical need for unresectable or relapsed peritoneal pseudomyxoma. The aim of our study was to assess the activity of chemotherapy with 5-fluorouracil and oxaliplatin (FOLFOX-4 regimen) in terms of response rate in this subset of patients. MATERIALS AND METHODS: Patients were included in a single-center, observational study and treated with FOLFOX-4 administered every 2 weeks for up to 12 cycles or until progressive disease or unacceptable toxicity. RESULTS: Twenty consecutive patients were reviewed from July 2011 to September 2013. Only partial responses were observed, with an objective response rate of 20%. Median progression-free survival and overall survival were 8 months and 26 months, respectively. Two patients were able to undergo laparotomy with complete cytoreduction and HIPEC in one case. Safety data for FOLFOX-4 were consistent with the literature. By means of a mutant enriched polymerase chain reaction, KRAS mutation was found in 16 of 19 cases (84%), and MGMT promoter methylation was found in 8 (42%, all KRAS mutant). CONCLUSION: FOLFOX-4 chemotherapy is tolerable and active in patients with peritoneal pseudomyxoma when disease is deemed unresectable or relapsed after peritonectomy and HIPEC. The identification of predictive biomarkers, such as KRAS for resistance to anti-epidermal growth factor receptor monoclonal antibodies and MGMT for response to temozolomide, is a priority for the development of evidence-based treatment strategies for peritoneal pseudomyxoma.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Peritoneais/tratamento farmacológico , Pseudomixoma Peritoneal/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Metilação de DNA/genética , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Seguimentos , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/patologia , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas p21(ras) , Pseudomixoma Peritoneal/genética , Pseudomixoma Peritoneal/patologia , Resultado do Tratamento , Proteínas Supressoras de Tumor/genética , Proteínas ras/genéticaRESUMO
Mesenchymal-epithelial transition (MET) is a member of a distinct subfamily of heterodimeric receptor tyrosine kinase receptors that specifically binds the hepatocyte growth factor (HGF). Binding to HGF leads to receptor dimerization/multimerization and phosphorylation, resulting in its catalytic activation. MET activation drives the malignant progression of several tumor types, including colorectal cancer (CRC), by promoting signaling cascades that mainly result in alterations of cell motility, survival, and proliferation. MET is aberrantly activated in many human cancers through various mechanisms, including point mutations, gene amplification, transcriptional up-regulation, or ligand autocrine loops. MET promotes cell scattering, invasion, and protection from apoptosis, thereby acting as an adjuvant pro-metastatic gene for many tumor types. In CRC, MET expression confers more aggressiveness and worse clinical prognosis. With all of this rationale, inhibitors that target the HGF/MET axis with different types of response have been developed. HGF and MET are new promising targets to understand the pathogenesis of CRC and for the development of new, targeted therapies.