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1.
Eur J Cancer ; 170: 64-72, 2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35594613

RESUMO

BACKGROUND: The availability of new drugs in the chemo-refractory setting opened the way to the concepts of treatment sequencing in mCRC. However, the impact of later line options in the therapeutic route of metastatic colorectal cancer (mCRC) patients and the attrition rate across subsequent lines of therapy are not well established. METHODS: We performed a pooled analysis of treatments administered after the 2nd disease progression in 1187 mCRC patients enrolled in the randomized phase III TRIBE and TRIBE2 studies, where upfront FOLFOXIRI/bev was compared with FOLFOX or FOLFIRI/bev. Per each line, we assessed the attrition rate, treatment choices and clinical outcomes. RESULTS: 625 (53%), 326 (27%) and 136 (11%) patients received a systemic treatment after the 2nd, 3rd and 4th disease progression, respectively. PFS and objective response rate decreased along each line. RAS/BRAF wild-type patients received more likely a 3rd line (75%) compared with RAS (66%, p = 0.005) and BRAF (66%, p = 0.11) mutants. In 3rd line, 67% of RAS/BRAF wild-type patients received anti-EGFRs, achieving longer PFS with respect to other therapies (6.4 vs 3.9 months, p = 0.02). A trend towards longer 3rd line OS was observed in TRIBE patients (9.9 vs 7.2 months, p = 0.05). CONCLUSIONS: A relevant attrition rate across subsequent lines of therapy is evident, and more pronounced in RAS and BRAF mutated patients, thus highlighting the relevance of the choice of the upfront treatment. The efficacy of anti-EGFR agents among RAS/BRAF wild-type patients unexposed to anti-EGFRs is higher than other options. The reintroduction of chemotherapy remains frequent in clinical practice. TRIAL REGISTRATION: Clinicaltrials. gov Identifiers NCT00719797, NCT02339116.

2.
Eur J Cancer ; 167: 23-31, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35366570

RESUMO

BACKGROUND: We performed a pooled analysis of TRIBE and TRIBE2 studies to assess the efficacy and safety of the intensification of upfront chemotherapy backbone - from doublets to the triplet FOLFOXIRI - in combination with bevacizumab (bev) in patients with early-onset metastatic colorectal cancer (EO-mCRC; aged <50 years) and to explore whether EO-mCRCs have a peculiar tumour genomic profiling. MATERIALS AND METHODS: Subgroup analyses according to age (<50 versus ≥50 years) and treatment (FOLFOXIRI/bev versus doublets/bev) were carried out for rates of any grade and grade ≥3 (≥G3) overall and singular adverse events, progression-free survival (PFS), overall survival (OS) and objective response rate (ORR). Tumour genomic profiling was obtained using a DNA-based next-generation sequencing platform. RESULTS: Of 1187 patients included, 194 (16%) patients were aged <50 years. Females were more frequently diagnosed with EO-mCRC (P = 0.04). Patients aged <50 years showed a lower risk of ≥G3 neutropenia (P = 0.07), diarrhoea (P = 0.04), asthenia (P = 0.008) and a higher risk of any grade nausea (P < 0.01) and vomiting (P < 0.01). Patients receiving FOLFOXIRI/bev more frequently experienced ≥G3 chemotherapy-related adverse events respect to doublets/bev, regardless of age (Pinteraction = 0.60). FOLFOXIRI/bev was associated to a lower incidence of neutropenia (P = 0.04) and asthenia (P = 0.01) in patients <50 years old, than those aged ≥50 years. PFS, OS and ORR did not differ according to age (PFS P = 0.81, OS P = 0.44, ORR P = 0.50) and no interaction between age and the benefit from the intensification of upfront chemotherapy was observed (PFS Pinteraction = 0.72, OS Pinteraction = 0.54, ORR Pinteraction = 0.65). Genomic profiling was assessed in 296 patients, showing an enrichment of FBXW7 and POLE mutations in EO-mCRC. CONCLUSIONS: Upfront FOLFOXIRI/bev shows a favourable efficacy/safety balance in EO-mCRC. TRIAL REGISTRATION: Clinicaltrials.gov Identifiers NCT00719797, NCT0233-9116.


Assuntos
Neoplasias Colorretais , Neutropenia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Astenia/induzido quimicamente , Bevacizumab/efeitos adversos , Camptotecina/análogos & derivados , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Feminino , Fluoruracila/efeitos adversos , Humanos , Leucovorina/efeitos adversos , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Compostos Organoplatínicos
3.
BMJ Open ; 12(1): e055814, 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35017254

RESUMO

INTRODUCTION: ONCO-TreC platform consists of a mobile application delivered to patients as electronic diary and a web-based dashboard managed by healthcare professionals. We aim to compare the effectiveness of ONCO-TreC electronic diary with a standard paper diary, in improving adherence to oral cancer therapy in patients with solid and haematological tumours. METHODS AND ANALYSIS: This is an open label, superiority, randomised controlled trial conducted in two Italian oncology units. Patients will be randomised with a 1:1 ratio to electronic or paper diary. For both groups a counsellor will be responsible for drug and diary delivery. The evaluation period will end after six cycles of therapy. The primary aim is to compare the proportion of non-adherent patients in the two arms. Adherence will be measured through pill count; anyone who takes less than 90% of the total prescribed drug dose will be considered non-adherent. Assuming a percentage of non-adherent patients to oral therapy of 40% in arm B, and a 60% reduction in this percentage in arm A, a sample of 124 patients will provide 80% power to identify an absolute difference greater than 24 percentage points using a bilateral Fisher's exact test with a significance level of 0.05. Considering a dropout rate of 10%, approximately 136 patients will have to be enrolled. The primary analysis will be performed on the intention-to-treat population. Secondary aims are to describe the reasons for non-adherence, the level of satisfaction of patients and healthcare professionals with the paper and electronic diary, and the impact of non-adherence in terms of healthcare costs. ETHICS AND DISSEMINATION: Ethical approval was obtained from Romagna Ethics Committee (CEROM), study ID 2108, prot. n. IRST 100.28 of 10/04/2020. Informed consent will be obtained from all study participants. Findings will be disseminated through peer-reviewed journals, conferences and event presentations. PROTOCOL VERSION: Version 2, 6 April 2021. TRIAL REGISTRATION NUMBER: NCT04826458.


Assuntos
COVID-19 , Neoplasias Hematológicas , Neoplasias Bucais , Eletrônica , Neoplasias Hematológicas/tratamento farmacológico , Humanos , Neoplasias Bucais/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2
4.
Cancer Treat Rev ; 103: 102326, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35016085

RESUMO

BACKGROUND: Retrospective series suggest that bevacizumab-induced hypertension (HTN) is a prognostic and potentially predictive biomarker of efficacy of the antiangiogenic drug in the upfront treatment of metastatic colorectal cancer (mCRC) patients. The immortal-time bias and the effect of pre-existing HTN might affect these findings. We conducted a pooled, post hoc analysis of 2 prospective randomized trials of chemotherapy plus bevacizumab in mCRC, and performed a systematic review of the available literature focusing on how the immortal-time bias was taken into account and how pre-existing HTN potentially requiring the use of antihypertensive drugs was managed. METHODS: The pooled-analysis included patients enrolled in the phase III TRIBE and TRIBE-2 studies that compared upfront FOLFOXIRI + bevacizumab to FOLFIRI or FOLFOX + bevacizumab, respectively. Association between HTN and survival outcomes was assessed by incorporating a time-dependent Cox regression model to consider the time-dependency of the probability of HTN onset during the treatment. The systematic review was conducted according to PRISMA guidelines. RESULTS: The systematic review retrieved 14 eligible and highly heterogeneous studies. A positive prognostic impact of bevacizumab-induced HTN was reported in the 58% of the analyses reporting Progression Free Survival (PFS) and in the 54% of the analyses reporting Overall Survival (OS) data. Immortal-time bias was incorporated in 4 studies (28%). In TRIBE and TRIBE-2 study populations (N = 1175), patients experiencing ≥ G2 HTN during first-line bevacizumab administration showed longer PFS (median: 14.7 versus 10.3 months, p < 0.001) and OS (median: 31.7 versus 24.2 months, p < 0.001). The association with OS retained statistical significance after correction for time-dependency (p = 0.003) and was confirmed in the multivariable model including HTN as a time-dependent variable (p = 0.02). Moreover, in patients with pre-existing HTN, no difference in terms of PFS and OS was observed compared with the subgroup of patients who never experienced ≥G2 HTN (HR 1.01, p = 0.86 and HR 1.02, p = 0.78 respectively. CONCLUSIONS: Bevacizumab-induced HTN during the first-line treatment of mCRC is an independent prognostic factor, also adopting a time-dependency correction. Toxicity should be interpreted as a time-dependent variable when exploring its association with clinical outcome.


Assuntos
Bevacizumab/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/mortalidade , Hipertensão/induzido quimicamente , Idoso , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/administração & dosagem , Ensaios Clínicos Fase III como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
5.
J Med Internet Res ; 24(1): e27349, 2022 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-35080505

RESUMO

BACKGROUND: A platform designed to support the home management of oral anticancer treatments and provide a secure web-based patient-health care professional communication modality, ONCO-TreC, was tested in 3 cancer centers in Italy. OBJECTIVE: The overall aims of the trial are to customize the platform; assess the system's ability to facilitate the shared management of oral anticancer therapies by patients and health professionals; and evaluate system usability and acceptability by patients, caregivers, and health care professionals. METHODS: Patients aged ≥18 years who were candidates for oral anticancer treatment as monotherapy with an Eastern Cooperative Oncology Group performance status score of 0 to 1 and a sufficient level of familiarity with mobile devices were eligible. ONCO-TreC consisted of a mobile app for patients and a web-based dashboard for health care professionals. Adherence to treatment (pill count) and toxicities reported by patients through the app were compared with those reported by physicians in medical records. Usability and acceptability were evaluated using questionnaires. RESULTS: A total of 40 patients were enrolled, 38 (95%) of whom were evaluable for adherence to treatment. The ability of the system to measure adherence to treatment was high, with a concordance of 97.3% (95% CI 86.1%-99.9%) between the investigator and system pill count. Only 60% (3/5) of grade 3, 54% (13/24) of grade 2, and 19% (7/36) of grade 1 adverse events reported by physicians in the case report forms were also reported in the app directly by patients. In total, 94% (33/35) of patients had ≥1 app launch each week, and the median number of daily accesses per patient was 2. Approximately 71% (27/38) and 68% (26/38) of patients used the app for messages and vital sign entering, respectively, at least once during the study period. CONCLUSIONS: ONCO-TreC is an important tool for measuring and monitoring adherence to oral anticancer drugs. System usability and acceptability were very high, whereas its reliability in registering toxicity could be improved. TRIAL REGISTRATION: ClinicalTrials.gov NCT02921724; https://www.clinicaltrials.gov/ct2/show/NCT02921724.


Assuntos
Aplicativos Móveis , Adolescente , Adulto , Humanos , Monitorização Fisiológica , Assistência ao Paciente , Estudos Prospectivos , Reprodutibilidade dos Testes
6.
J Natl Cancer Inst ; 114(2): 271-279, 2022 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-34469533

RESUMO

BACKGROUND: Tumors with homologous recombination deficiency (HRD) show high sensitivity to platinum salts and poly(ADP-ribose) polymerase-inhibitors in several malignancies. In colorectal cancer (CRC), the role of HRD alterations is mostly unknown. METHODS: Next-generation sequencing, whole transcriptome sequencing, and whole exome sequencing were conducted using CRC samples submitted to a commercial Clinical Laboratory Improvement Amendments certified laboratory. Tumors with pathogenic and/or presumed pathogenic mutations in 33 genes involved in the homologous recombination pathway were considered HRD, the others were homologous recombination proficient (HRP). Furthermore, tumor samples from patients enrolled in the phase III TRIBE2 study comparing upfront FOLFOXIRI+bevacizumab vs FOLFOX+bevacizumab were analyzed with next-generation sequencing. The analyses were separately conducted in microsatellite stable or proficient mismatch repair (MSS/pMMR) and microsatellite instable-high or deficient mismatch repair (MSI-H/dMMR) groups. All statistical tests were 2-sided. RESULTS: Of 9321 CRC tumors, 1270 (13.6%) and 8051 (86.4%) were HRD and HRP, respectively. HRD tumors were more frequent among MSI-H/dMMR than MSS/pMMR tumors (73.4% vs 9.5%; P < .001; q < 0.001). In MSS/pMMR group, HRD tumors were more frequently tumor mutational burden high (8.1% vs 2.2%; P < .001; q < 0.001) and PD-L1 positive (5.0% vs 2.4%; P < .001; q = 0.001), enriched in all immune cell and fibroblast populations and genomic loss of heterozygosity-high (16.2% vs 9.5%; P = .03). In the TRIBE2 study, patients with MSS/pMMR and HRD tumors (10.7%) showed longer overall survival compared with MSS/pMMR and HRP tumors (40.2 vs 23.8 months; hazard ratio [HR] = 0.66, 95% confidence interval [CI] = 0.45 to 0.98; P = .04). Consistent results were reported in the multivariable model (HR = 0.67, 95% CI = 0.45 to 1.02; P = .07). No interaction effect was evident between homologous recombination groups and treatment arm. CONCLUSIONS: HRD tumors are a distinctive subgroup of MSS/pMMR CRCs with specific molecular and prognostic characteristics. The potential efficacy of agents targeting the homologous recombination system and immune checkpoint inhibitors in this subgroup is worthy of clinical investigation.


Assuntos
Neoplasias Colorretais , Instabilidade de Microssatélites , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Reparo de Erro de Pareamento de DNA/genética , Recombinação Homóloga , Humanos , Prognóstico
7.
Front Pharmacol ; 12: 745701, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34858176

RESUMO

Liquid biopsy represents a valid strategy for tumor molecular characterization. It gives the opportunity to bypass tumor heterogeneity, to monitor tumor characteristics during the course of treatment, and to perform the analysis even when tumor tissue is not available or inadequate. In the clinical practice of metastatic colorectal cancer, tumor molecular characterization is crucial for patient management, as RAS and BRAF status could influence the treatment choice. Although for this type of cancer tumor tissue is usually available at diagnosis, liquid biopsy could give complementary information and could permit monitoring of the mutation status during the course of treatment. At present, there are no clinical indications for its use in clinical practice. However, we report four clinical cases for which liquid biopsy analysis gave integrative information with respect to tumor tissue characterization, which permits us to understand the unresponsiveness of patients to treatment, with potential implications in patient's management.

8.
Cancers (Basel) ; 13(24)2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34944966

RESUMO

International experts in the study of metastatic colorectal cancer (mCRC) present this series of 14 articles (eleven original articles and three literature reviews) [...].

9.
J Med Internet Res ; 23(12): e31321, 2021 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-34932001

RESUMO

BACKGROUND: Accurate medication reconciliation reduces the risk of drug incompatibilities and adverse events that can occur during transitions in care. Community pharmacies (CPs) are a crucial part of the health care system and could be involved in collecting essential information on conventional and supplementary drugs used at home. OBJECTIVE: The aim of this paper was to establish an alliance between our cancer institute, Istituto Romagnolo per lo Studio dei Tumori (IRST), and CPs, the latter entrusted with the completion of a pharmacological recognition survey. We also aimed to integrate the national information technology (IT) platform of CPs with the electronic medical records of IRST. METHODS: Cancer patients undergoing antiblastic treatments were invited to select a CP taking part in the study and to complete the pharmacological recognition step. The information collected by the pharmacist was sent to the electronic medical records of IRST through the new IT platform, after which the oncologist performed the reconciliation process. RESULTS: A total of 66 CPs completed surveys for 134 patients. An average of 5.9 drugs per patient was used at home, with 12 or more used in the most advanced age groups. Moreover, 60% (80/134) of the patients used nonconventional products or critical foods. Some potential interactions between nonconventional medications and cancer treatments were reported. CONCLUSIONS: In the PROF-1 (Progetto di Rete in Oncologia con le Farmacie di comunità della Romagna) study, an alliance was created between our cancer center and CPs to improve medication reconciliation, and a new integrated IT platform was validated. TRIAL REGISTRATION: ClinicalTrials.gov NCT04796142; https://clinicaltrials.gov/ct2/show/NCT04796142.


Assuntos
Reconciliação de Medicamentos , Farmacêuticos , Registros Eletrônicos de Saúde , Humanos , Estudos Prospectivos
10.
Biomolecules ; 11(8)2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34439866

RESUMO

In locally advanced pancreatic cancer (LAPC), the combination of chemotherapy and radiotherapy is a widely used treatment option. We performed a pooled analysis, including an exploratory analysis for prognostic and predictive factors, of two phase 2 trials including 73 patients with LAPC, treated with gemcitabine and oxaliplatin (GEMOX) and hypofractionated tomotherapy. With a median follow-up of 36 months (range 1-65), median progression-free (PFS) and overall survival (OS) were 10.2 (95% confidence interval [CI] 7.8-13.2) and 14.3 (95% CI 12.0-18.1) months, respectively. The overall resectability rate was 23.3% (95% CI 13.6-33.0), and the R0 resection rate was 13.7% (95% CI 5.8-21.6). In the multivariate analysis, ECOG performance status (PS) 0 and low levels of CA 19-9 were associated with improved OS and PFS. Concerning OS, log(CA19-9) resulted in a hazard ratio (HR) of 1.20 (95% CI 1.02-1.42), p = 0.027. For ECOG PS 0, HR was 1.00; for PS 1, HR was 2.69 (95% CI 1.46-4.96); for PS 2, HR was 4.18 (95% CI 0.90-19.46); p = 0.003. Low CA19-9 levels were also predictive for resection, with an odds ratio of 0.71 (95% CI 0.52-0.97), p = 0.034. In conclusion, GEMOX and hypofractionated radiotherapy is a treatment option in LAPC. Further studies are needed to identify differences in tumor biology, which may help to predict resectability and prognosis.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ensaios Clínicos Fase II como Assunto/métodos , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/radioterapia , Radioterapia de Intensidade Modulada/métodos , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Terapia Combinada/métodos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Fadiga/induzido quimicamente , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Neoplasias Pancreáticas/diagnóstico
11.
Eur J Cancer ; 155: 73-84, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34365081

RESUMO

BACKGROUND: We performed a comprehensive genomic profiling of tumour samples from metastatic colorectal cancer (mCRC) patients enrolled in the TRIBE2 study to assess the concordance among different techniques to evaluate mismatch repair (MMR) and microsatellite instability (MSI) status, to characterize tumours according to the tumour mutational burden (TMB) and explore the clinical relevance of different TMB cutpoints, and to investigate the prevalence of alterations actionable with targeted approaches or immune checkpoint inhibitors. MATERIAL AND METHODS: Tumour samples of 296 (44%) of 679 enrolled patients underwent 592-gene DNA next-generation sequencing (NGS). MMR status was assessed by immunohistochemistry (MMR-IHC), and MSI status was assessed by NGS (MSI-NGS). TMB was defined as low, intermediate, or high if <7, 7-16, or ≥17 mutations/megabase (mut/Mb) were found. The performance of TMB to predict MSI status was tested by receiver operating characteristic (ROC) curve. Actionable alterations included BRAF V600E, KRAS G12C, POLE mutations, HER2 amplification and mutations, and MSI-H. RESULTS: Of 216 paired cases, concordance between MMR-IHC and MSI-NGS was 98.6%. Among 11 TMB-high tumours, eight (73%) were MSI-H and three (27%) were microsatellite stable and harboured POLE or MSH6 mutations. High TMB had a trend for a better outcome than low/intermediate TMB (hazard ratio for overall survival 0.45, 95% confidence interval 0.28-1.33; P = 0.106). No interaction effect between TMB and treatment arm was observed. Seventeen mut/Mb was identified as the optimal threshold of TMB for predicting MSI status. Actionable alterations were found in 62 (21%) of 296 patients. CONCLUSIONS: Genomic profiling provides an overview of the genomic landscape of mCRC in a single analysis, including actionable targets and markers of immune sensitivity.


Assuntos
Neoplasias Colorretais/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Carga Tumoral/genética , Idoso , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Mutação
12.
Pancreatology ; 21(7): 1342-1348, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34215498

RESUMO

BACKGROUND: Local ablation of pancreatic cancer has been suggested as an option to manage locally advanced pancreatic cancer (LAPC) although no robust evidence has been published to date to support its application. The aim of this study is to compare overall survival (OS) and progression-free survival (PFS) in patients receiving both radiofrequency ablation (RFA) and conventional chemoradiotherapy (CHRT) with patients receiving CHRT only. METHODS: This is a multicentre prospective randomized controlled trial (RCT). Patients with LAPC diagnosed by the Pancreas-Ablation-Team-Verona were randomly assigned to open RFA (Group A) or CHRT (Group B). Survival analyses were performed using the Kaplan-Meier method and compared using the log-rank test. Statistical significance was set at p < 0.05. RESULTS: One hundred LAPC patients were enrolled from January 2014 to August 2016. 33% of patients in Group A did not receive the designated procedure because of intraoperative findings of liver (18.7%) or peritoneal metastases (43.8%), or technical contraindications (37.5%). We did not observe any statistically significant survival benefit from RFA compared to CHRT, neither in terms of OS (medians of 14.2 months and 18.1 months, respectively, p = 0.639) nor PFS (medians of 8 months and 6 months respectively, p = 0.570). Mortality was nil and RFA-related morbidity was 15.6%. In 13% of subjects, conversion to surgery occurred (2 after RFA and 11 after CHRT). CONCLUSIONS: This is the first RCT evaluating the impact of upfront RFA in the multimodal treatment of LAPC. Compared to CHRT, RFA alone did not provide any advantage in terms of OS or PFS. It could be considered as a therapeutic option for LAPC within a multimodal context and after neoadjuvant therapies.


Assuntos
Ablação por Cateter , Neoplasias Pancreáticas , Ablação por Radiofrequência , Humanos , Neoplasias Hepáticas , Pâncreas , Neoplasias Pancreáticas/cirurgia , Intervalo Livre de Progressão , Resultado do Tratamento
13.
Int J Mol Sci ; 22(14)2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34299099

RESUMO

The present editorial aims to summarise the six scientific papers that have contributed to this Special Issue, focusing on different aspects of molecular and translational research on colorectal cancer. We believe that the present Special Issue might contribute to the expansion of the current knowledge concerning potential molecular predictive and/or prognostic biomarkers in CRC, as well as new targets for anticancer treatment. This may help in identifying new strategies to improve diagnostic and therapeutic approaches.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/terapia , Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Humanos
14.
Cancer Med ; 10(12): 3974-3985, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34061453

RESUMO

BACKGROUND: The experience of cancer is highly stressful and potentially traumatic. We assessed the presence of Post-Traumatic Stress Symptoms (PTSS) in long-term cancer survivors and their caregivers, while examining the association between PTSS and clinical, demographic and psychological variables in the long term. METHODS: In this cross-sectional study 212 survivor-family caregiver dyads completed measures of post-traumatic stress symptoms (PTSS) (Impact of Event Scale), depression and anxiety (Hospital Anxiety Depression Scale). Coping strategies, fatigue, cognitive decline, stressful life events and psychopathological history were also assessed among survivors. Data were analyzed using mixed models, accounting both for individual and dyadic effects. RESULTS: Cancer survivors and their caregivers were assessed after a mean of 6 years after treatment. Twenty per cent of survivors and 35.5% of caregivers had possible posttraumatic stress disorder (PTSD), while 23 patients (11.0%) and 33 caregivers (15.6%) had probable PTSD. Among cancer patients, the severity of post-traumatic symptoms was associated with an anxious coping style, previous psychopathology and depression (p < 0.001), whereas among caregivers it was associated with depression and having a closer relationship with patients (p < 0.001). Patients' depression was associated with caregivers' intrusion symptoms. CONCLUSIONS: High levels of cancer-related PTSS were still present several years after treatment in both survivors and caregivers. Psychopathology may derive from complex interactions among coping, previous disorders and between-person dynamics.


Assuntos
Adaptação Psicológica , Sobreviventes de Câncer/psicologia , Cuidadores/psicologia , Neoplasias/psicologia , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Ansiedade/epidemiologia , Neoplasias da Mama/psicologia , Neoplasias da Mama/terapia , Sobreviventes de Câncer/estatística & dados numéricos , Cuidadores/estatística & dados numéricos , Disfunção Cognitiva/epidemiologia , Estudos Transversais , Depressão/epidemiologia , Intervalo Livre de Doença , Família/psicologia , Fadiga/epidemiologia , Feminino , Humanos , Relações Interpessoais , Itália , Masculino , Pessoa de Meia-Idade , Neoplasias/terapia , Prevalência , Angústia Psicológica , Fatores Socioeconômicos , Neoplasias Testiculares/psicologia , Neoplasias Testiculares/terapia
15.
Biomolecules ; 11(6)2021 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-34067288

RESUMO

FOLFIRINOX (FFX) and gemcitabine + nab-paclitaxel (GN) are the most common chemotherapy regimens in first-line treatment of metastatic pancreatic cancer (PC). They have not been compared each other in a prospective trial, but only in retrospective studies, which can thus be affected by several biases. In order to overcome these biases, we took advantage of matching-adjusted indirect comparison (MAIC), that allows an indirect comparison by reducing cross-trial differences, and compared data from 268 patients treated with GN in a real-world setting with data from the 171 patients included in the FFX arm of the PRODIGE trial. Survival outcomes did not differ between the two populations. Overall survival was 11.1 months for both treatments (hazard ratio (HR) of FFX 1.10, 95% confidence interval (CI) 0.81-1.49; p = 0.527). Progression-free survival was 6.0 months with GN and 6.4 months with FFX (HR of FFX 1.11, 95% CI 0.82-1.50; p = 0.520). On the other hand, we observed a difference in the toxicity profiles: grade 3/4 anemia was more frequent with GN, whereas a higher occurrence of grade 3/4 vomiting and diarrhea was reported with FFX. FFX and GN show an equivalent efficacy but different safety profiles in the first-line therapy of metastatic pancreatic cancer. Searching for reliable predictive biomarkers is advised in order to improve therapeutic strategy in metastatic PC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Desoxicitidina/análogos & derivados , Paclitaxel/administração & dosagem , Neoplasias Pancreáticas , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Irinotecano/administração & dosagem , Irinotecano/efeitos adversos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos , Paclitaxel/efeitos adversos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Taxa de Sobrevida
16.
Eur J Cancer ; 153: 16-26, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34126333

RESUMO

BACKGROUND: Recent data from the TRIBE2 study have failed to suggest a higher magnitude of benefit from upfront FOLFOXIRI/bevacizumab in patients with BRAF-mutant metastatic colorectal cancer (mCRC) as previously reported in the TRIBE study. PATIENTS AND METHODS: Clinical characteristics and gene expression signatures of patients with BRAF-mutant mCRC enrolled in the TRIBE2 study were evaluated with the aim of understanding that patients may derive benefit from the intensification of the upfront chemotherapy. RESULTS: Of 46 BRAF-mutant tumour samples analysed, 24 (52%) and 22 (48%) were classified as BM1 and BM2, respectively, and 27 (59%) and 19 (41%) were assigned to ligand-independent (LI) and ligand-dependent (LD) Wnt pathway subgroups, respectively. No prognostic impact was shown for both BM1/BM2 and LI/LD subtypes. No interaction was evident between BM1/BM2 or LI/LD signatures and the benefit provided by FOLFOXIRI/bevacizumab. Significant interaction effect was evident in terms of progression-free survival between treatment arm and primary tumour sidedness (P = 0.05) and Eastern Cooperative Oncology Group performance status (ECOG-PS; P < 0.001). CONCLUSIONS: Gene expression analysis failed to identify patients with BRAF-mutant mCRC candidate to upfront FOLFOXIRI/bevacizumab. ECOG-PS >0 and left-sidedness seem associated with no benefit from the intensified treatment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Camptotecina/análogos & derivados , Neoplasias Colorretais/tratamento farmacológico , Expressão Gênica/genética , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Bevacizumab/farmacologia , Camptotecina/farmacologia , Camptotecina/uso terapêutico , Feminino , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Humanos , Leucovorina/farmacologia , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Compostos Organoplatínicos/farmacologia , Compostos Organoplatínicos/uso terapêutico , Prognóstico
17.
BMC Cancer ; 21(1): 611, 2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34034685

RESUMO

BACKGROUND: Pancreatic cancer (PC) is a major cause of cancer death. In an effort to improve treatment strategies and outcomes, DNA damage repair (DDR) pathways have been introduced as a new target in PC and in other cancers, through the exploitation of synthetic lethality. Furthermore, genes involved in DDR are among the major determinants of cancer susceptibility. In addition to the well-known BRCA1 and BRCA2 genes, a plethora of other targets in the same pathways are now emerging. METHODS: We analyzed samples from 60 patients, affected by PC and already tested for BRCA, using a panel with 24 other cancer susceptibility genes. RESULTS: We detected 8 pathogenic or likely pathogenic mutations (13.3% of samples analyzed), 4 of which were found in non-BRCA genes (2 in ATM, 1 each in PALB2 and RAD50). Furthermore, 4 pathogenic or likely pathogenic mutations were found in patients without a personal or familial history of cancer. CONCLUSIONS: Our results suggest that genetic testing with a comprehensive gene panel should be perfomed in all patients with PC, in order to allow screening for PC and other gene-related cancers in all at risk family members and to assess patients' eligibility for emerging therapeutic options.


Assuntos
Biomarcadores Tumorais/genética , Reparo do DNA , Detecção Precoce de Câncer/métodos , Testes Genéticos/métodos , Neoplasias Pancreáticas/diagnóstico , Hidrolases Anidrido Ácido/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteína BRCA1/genética , Proteína BRCA2/genética , Dano ao DNA , Análise Mutacional de DNA/estatística & dados numéricos , Proteínas de Ligação a DNA/genética , Detecção Precoce de Câncer/estatística & dados numéricos , Proteína do Grupo de Complementação N da Anemia de Fanconi/genética , Feminino , Testes Genéticos/estatística & dados numéricos , Humanos , Masculino , Anamnese , Pessoa de Meia-Idade , Neoplasias Pancreáticas/genética
18.
Therap Adv Gastroenterol ; 14: 1756284821989559, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33717209

RESUMO

The gastrointestinal tract is an uncommon site of metastasis in melanoma. However, when the primary melanoma cannot be found, the diagnosis of gastric melanoma by endoscopic biopsy is problematic mainly because some tumors are amelanotic and do not contain melanin granules detectable by microscopy. A 56-year-old Caucasian man with melanoma was referred to us following an initial histopathological diagnosis via gastroscopy of poorly differentiated primary gastric carcinoma. A computerized tomography (CT) scan showed metastatic disease and on the basis of this information we started palliative chemotherapy. However, the atypical presentation of the disease with subcutaneous metastases prompted us to make a more in-depth evaluation. Immunohistochemical evaluation modified the diagnosis to melanoma. After only one cycle of chemotherapy, treatment was changed to dabrafenib + trametinib, which was better tolerated and initially induced a partial response. The patient is currently in good clinical condition 20 months after diagnosis. Our case report highlights the difficulty in diagnosing melanoma of the gastrointestinal tract and indicates the need for pathologists and clinicians to consider such a possibility when they are faced with a diagnosis of poorly differentiated gastric cancer and unusual sites of metastasis.

19.
Oncologist ; 26(8): e1314-e1319, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33764600

RESUMO

LESSONS LEARNED: The use of sodium levofolinate (Na-Lev) is safe in combination with continuous infusion 5-fluorouracil in patients with gastrointestinal tumors treated with the FOLFIRI regimen. A comparison with calcium levofolinate (Ca-Lev) showed a similar toxicity profile. The advantages of Na-Lev over Ca-Lev might be the faster drug preparation and the shorter time of drug administration. BACKGROUND: The objectives of this study were to compare the safety profiles of sodium levofolinate (Na-Lev) and calcium levofolinate (Ca-Lev) in combination with 5-fluorouracil (5-FU) in the FOLFIRI regimen and to measure the organizational impact of the introduction of Na-Lev on drug production and administration. METHODS: The study opened in November 2015 and closed in August 2019. Patients with gastrointestinal cancers who were candidates for treatment with the FOLFIRI regimen were included in this nonrandomized study. Age ≥18 years, life expectancy >3 months, adequate bone marrow reserve, adequate hepatic and renal function, and an ECOG performance status of 0-2 were required. Patients in the Ca-Lev arm received a 2-hour infusion of Ca-Lev followed by 5-FU, whereas those in the Na-Lev arm received Na-Lev and 5-FU administered in a single 48-hour pump. RESULTS: Sixty patients were enrolled, 30 in each arm. Patient characteristics were balanced. Grade (G)1-2 adverse events occurred in 18 (60.0%) and 19 (63.4%) patients of Na-Lev and Ca-Lev cohorts, respectively, whereas G3-4 adverse events occurred in 12 (40.0%) and 11 (36.6%) patients, respectively. The use of Na-Lev enabled us to save approximately 13 minutes for drug preparation and 2 hours for treatment administration, per patient per cycle. CONCLUSION: Na-Lev showed a reassuring toxicity profile and a favorable impact on drug preparation and administration.


Assuntos
Cálcio , Neoplasias Colorretais , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/efeitos adversos , Humanos , Leucovorina/efeitos adversos , Sódio/uso terapêutico
20.
Med Oncol ; 38(2): 17, 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33528694

RESUMO

SBA classification is still based on the location of the primary tumor, without genetic information. in the current study, an extensive genetic profile of SBA, was performed in order to identify and quantify targetable alterations for a future precision medicine in SBA. Clinical-pathological information for 24 patients affected by SBA were retrospectively reviewed. Whole genome analysis of the primary tumors was performed by the FOUNDATION Cdx technology. We carried out a functional enrichment analysis of the mutated genes with BioPlanet. Integrative clustering analysis revealed three distinct subtypes characterized by different genomic alterations. Cluster 1exhibited significant correlations with MSI status, high TMB, celiac disease and Jejunual site.We defined cluster 1 as "immunological subtype" (29.2% of patients). Driver mutations in this subtype suggest that 100% of patients may benefit from immunotherapy. Enrichment analysis of cluster 2 highlighted that the main affected pathway was that of homologous DNA pairing and strand exchange (16.7% of patients). We defined this cluster as "DNA Damage Repair (DDR) like". On the basis of these driver molecular alterations, 100% of patients could benefit from PARPi. Finally, Cluster 3 had no significant correlations with clinical-pathological characteristics (54.1% of patients). Enrichment analysis revealed that this cluster has remarkable similarities with CRA genomic profile, so we defined it as "Colon-like". SBA is a genetically distinct tumor entity and deep mutation heterogeneity indicates that different driver genes play a role in the biology of these tumors. The identification of clusters based on genetic profile suggest the possibility to go beyond chemotherapy in several patients.


Assuntos
Adenocarcinoma/genética , Neoplasias Intestinais/genética , Intestino Delgado/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise por Conglomerados , Reparo do DNA , Neoplasias Duodenais/genética , Feminino , Humanos , Neoplasias Intestinais/classificação , Neoplasias Intestinais/terapia , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Mutação , Estudos Retrospectivos
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