RESUMO
BACKGROUND: Talimogene laherparepvec (T-VEC), a first-in-class oncolytic viral immunotherapy, enhances tumor-specific immune activation. T-VEC combined with atezolizumab, which blocks inhibitor T-cell checkpoints, could provide greater benefit than either agent alone. Safety/efficacy of the combination was explored in patients with triple negative breast cancer (TNBC) or colorectal cancer (CRC) with liver metastases. METHODS: In this phase Ib, multicenter, open-label, parallel cohort study of adults with TNBC or CRC with liver metastases, T-VEC (106 then 108 PFU/ml; ≤4 ml) was administered into hepatic lesions via image-guided injection every 21 (±3) days. Atezolizumab 1200 mg was given on day 1 and every 21 (±3) days thereafter. Treatment continued until patients experienced dose-limiting toxicity (DLT), had complete response, progressive disease, needed alternative anticancer treatment, or withdrew due to an adverse event (AE). The primary endpoint was DLT incidence, and secondary endpoints included efficacy and AEs. RESULTS: Between 19 March 2018 and 6 November 2020, 11 patients with TNBC were enrolled (safety analysis set: n = 10); between 19 March 2018 and 16 October 2019, 25 patients with CRC were enrolled (safety analysis set: n = 24). For the 5 patients in the TNBC DLT analysis set, no patient had DLT; for the 18 patients in the CRC DLT analysis set, 3 (17%) had DLT, all serious AEs. AEs were reported by 9 (90%) TNBC and 23 (96%) CRC patients, the majority with grade ≥3 [TNBC, 7 (70%); CRC, 13 (54%)], and 1 was fatal [CRC, 1 (4%)]. Evidence of efficacy was limited. Overall response rate was 10% (95% confidence interval 0.3-44.5) for TNBC; one (10%) patient had a partial response. For CRC, no patients had a response; 14 (58%) were unassessable. CONCLUSIONS: The safety profile reflected known risks with T-VEC including risks of intrahepatic injection; no unexpected safety findings from addition of atezolizumab to T-VEC were observed. Limited evidence of antitumor activity was observed.
Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Melanoma , Terapia Viral Oncolítica , Neoplasias de Mama Triplo Negativas , Adulto , Humanos , Melanoma/terapia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/etiologia , Estudos de Coortes , Terapia Viral Oncolítica/efeitos adversos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Colorretais/terapiaRESUMO
Resistance to antitumor treatments is one of the most important problems faced by clinicians in the management of colorectal cancer (CRC) patients. Cancer-Associated Fibroblasts (CAFs) are the main producers and remodelers of the extracellular matrix (ECM), which is directly involved in drug resistance mechanisms. Primary Normal Fibroblasts (NFs) and CAFs and cell lines (fibroblasts and tumor cells), were used to generate ECM and to identify its role in the oxaliplatin and cetuximab chemoresistance processes of CRC cells mediated by SNAI1-expressing fibroblasts. Matrices generated by Snai1 KO MEFs (Knockout Mouse Embryonic Fibroblasts) confer less resistance on oxaliplatin and cetuximab than wild-type MEF-derived matrices. Similarly, matrices derived from CAFs cause greater survival of colorectal cancer cells than NF-derived matrices, in a similar way to Snai1 expression levels. In addition, Snail1 expression in fibroblasts regulates drug resistance and metabolism gene expression in tumor cells mediated by ECM. Finally, a series of 531 patients (TCGA) with CRC was used to assess the role of SNAI1 expression in patients' prognosis indicating an association between tumor SNAI1 expression and overall survival in colon cancer patients but not in rectal cancer patients. SNAI1 expression in CRC cancer patients, together with in vitro experimentation, suggests the possible use of SNAI1 expression in tumor-associated fibroblasts as a predictive biomarker of response to oxaliplatin and cetuximab treatments in patients with CRC.
Assuntos
Neoplasias Colorretais , Fibroblastos , Animais , Linhagem Celular Tumoral , Cetuximab/metabolismo , Cetuximab/farmacologia , Cetuximab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Resistência a Medicamentos , Matriz Extracelular/metabolismo , Fibroblastos/metabolismo , Camundongos , Camundongos Knockout , Oxaliplatina/metabolismo , Oxaliplatina/farmacologia , Oxaliplatina/uso terapêuticoRESUMO
PURPOSE: Malnutrition is a common problem among pancreatic cancer (PC) patients that negatively impacts on their quality of life (QoL) and clinical outcomes. The main objective of this consensus is to address the role of Medical Nutrition Therapy (MNT) into the comprehensive therapeutic management of PC patients. METHODS: A Spanish multidisciplinary group of specialists from the areas of Medical Oncology; Radiation Oncology; Endocrinology and Nutrition; and General Surgery agreed to assess the role of MNT as part of the best therapeutic management of PC patients. RESULTS: The panel established different recommendations focused on nutritional screening and nutritional screening tools, MNT strategies according to PC status, and MNT in palliative treatment. CONCLUSIONS: There is an unmet need to integrate nutritional therapy as a crucial part of the multimodal care process in PC patients. Health authorities, health care professionals, cancer patients, and their families should be aware of the relevance of nutritional status and MNT on clinical outcomes and QoL of PC patients.
Assuntos
Desnutrição/dietoterapia , Desnutrição/etiologia , Terapia Nutricional , Neoplasias Pancreáticas/complicações , Procedimentos Clínicos , Humanos , Estado NutricionalRESUMO
BACKGROUND AND AIMS: The overall evidence on the association between gallbladder conditions (GBC: gallstones and cholecystectomy) and pancreatic cancer (PC) is inconsistent. To our knowledge, no previous investigations considered the role of tumour characteristics on this association. Thus, we aimed to assess the association between self-reported GBC and PC risk, by focussing on timing to PC diagnosis and tumour features (stage, location, and resection). METHODS: Data derived from a European case-control study conducted between 2009 and 2014 including 1431 PC cases and 1090 controls. We used unconditional logistic regression models to estimate odds ratios (ORs) and corresponding 95% confidence intervals (CIs) adjusted for recognized confounders. RESULTS: Overall, 298 (20.8%) cases and 127 (11.6%) controls reported to have had GBC, corresponding to an OR of 1.70 (95% CI 1.33-2.16). The ORs were 4.84 (95% CI 2.96-7.89) for GBC diagnosed <3 years before PC and 1.06 (95% CI 0.79-1.41) for ≥3 years. The risk was slightly higher for stage I/II (OR = 1.71, 95% CI 1.15-2.55) vs. stage III/IV tumours (OR = 1.23, 95% CI 0.87-1.76); for tumours sited in the head of the pancreas (OR = 1.59, 95% CI 1.13-2.24) vs. tumours located at the body/tail (OR = 1.02, 95% CI 0.62-1.68); and for tumours surgically resected (OR = 1.69, 95% CI 1.14-2.51) vs. non-resected tumours (OR = 1.25, 95% CI 0.88-1.78). The corresponding ORs for GBC diagnosed ≥3 years prior PC were close to unity. CONCLUSION: Our study supports the association between GBC and PC. Given the time-risk pattern observed, however, this relationship may be non-causal and, partly or largely, due to diagnostic attention and/or reverse causation.
Assuntos
Doenças da Vesícula Biliar , Neoplasias da Vesícula Biliar , Neoplasias Pancreáticas , Estudos de Casos e Controles , Doenças da Vesícula Biliar/cirurgia , Neoplasias da Vesícula Biliar/diagnóstico , Neoplasias da Vesícula Biliar/epidemiologia , Neoplasias da Vesícula Biliar/etiologia , Humanos , Modelos Logísticos , Pâncreas/patologia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/etiologia , Fatores de Risco , Neoplasias PancreáticasRESUMO
Pancreatic cancer (PC) and biliary tract cancer (BTC) are both aggressive and highly fatal malignancies. Nowadays we have a profound knowledge about the molecular landscape of these neoplasms and this has allowed new therapeutic options. Surgery is the only potentially curative therapy in both cancers, but disease recurrence is frequent. In PC, adjuvant treatment with mFOLFIRINOX has improved overall survival (OS) and in BTC adjuvant treatment with capecitabine seems to improve OS and relapse-free survival. Concomitant radio-chemotherapy could also be considered following R1 surgery in both neoplasms. Neoadjuvant treatment represents the best option for achieving an R0 resection in borderline PC. Upfront systemic chemotherapy is the treatment of choice in unresectable locally advanced PC and BTC; then locoregional therapy could be considered after an initial period of at least 3-4 months of systemic chemotherapy. In metastatic PC, FOLFIRINOX or Gemcitabine plus nab-paclitaxel have improved OS compared with gemcitabine alone. In metastatic BTC, cisplatin plus gemcitabine constitute the standard treatment. Progress in the knowledge of molecular biology has enabled the identification of new targets for therapy with encouraging results that could in the future improve the survival and quality of life of patients with PC and BTC.
Assuntos
Neoplasias do Sistema Biliar/terapia , Neoplasias Pancreáticas/terapia , Albuminas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Biliar/genética , Neoplasias do Sistema Biliar/patologia , Neoplasias do Sistema Biliar/cirurgia , Capecitabina/uso terapêutico , Quimiorradioterapia/métodos , Quimioterapia Adjuvante/métodos , Cisplatino/uso terapêutico , Fluoruracila/uso terapêutico , Humanos , Irinotecano/uso terapêutico , Leucovorina/uso terapêutico , Oncologia , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias , Oxaliplatina/uso terapêutico , Paclitaxel/uso terapêutico , Cuidados Paliativos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Qualidade de Vida , Sociedades Médicas , EspanhaRESUMO
PURPOSE: The primary aim of this retrospective study was to describe the treatment patterns according to the type of treatment received by patients with metastatic colorectal cancer (mCRC) in Spain. METHODS: This was a retrospective, observational, multicenter study performed by 33 sites throughout Spain that included consecutive patients aged 18 years or older who had received or were receiving treatment for mCRC. RESULTS: At the time of inclusion, of the 873 evaluable patients, 507 (58%) had received two lines, 235 (27%) had received three lines, 106 (12%) had received four lines, and the remaining patients had received up to ten lines. The most frequent chemotherapy schemes were the FOLFOX or CAPOX regimens (66%) for first-line treatment, FOLFOX, CAPOX or FOLFIRI (70%) for second-line treatment, and FOLFOX, FOLFIRI or other fluoropyrimidine-based regimens for third- and fourth-line (over 60%) treatment. Sixty percent of patients received targeted therapy as part of their first-line treatment, and this proportion increased up to approximately 70% of patients as part of the second-line of treatment. A relevant proportion of patients were treated with unknown KRAS, and especially the BRAF, mutation statuses. CONCLUSIONS: This study reveals inconsistencies regarding adherence to the recommendations of the ESMO guidelines for the management of mCRC in Spain. Improved adherence to the standard practice described in such guidelines for the determination of RAS and BRAF mutation statuses and the use of targeted therapies in first-line treatment should be considered to guarantee that patients can benefit from the best therapeutic approaches available.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Fidelidade a Diretrizes/estatística & dados numéricos , Idoso , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular/métodos , Mutação , Metástase Neoplásica , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Estudos Retrospectivos , Espanha/epidemiologia , Resultado do TratamentoRESUMO
INTRODUCTION: Glioblastoma, which is the most commonly diagnosed primary CNS neoplasm, is more frequent in individuals aged 65 years or more. Our purpose is to identify how glioblastoma diagnosed in elderly population is treated by Spanish oncologists. MATERIAL AND METHODS: A survey was emailed to all members of Spanish Group for Neuro-oncology Research (GEINO). RESULTS: Twenty-six neuro-oncologists from 26 hospitals completed the survey. The answers were different depending on the age, performance status, and MGMT methylation status. Patients between 65 and 70 years of age are mainly treated with Stupp treatment. For patients between ages of 70 and 80 years, 46.2% made recommendations for Perry regimen, for both methylated and non-methylated patients. For patients older than 80 years, monotherapy treatment is considered more frequently. In cases of non-MGMT promoter methylation, systemic therapy with temozolomide is still recommended in many hospitals. CONCLUSION: Our research demonstrates there is no uniform approach to the management of elderly patients with glioblastoma among academic neuro-oncologists.
Assuntos
Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Pesquisas sobre Atenção à Saúde , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Alquilantes/uso terapêutico , Astrocitoma/terapia , Quimiorradioterapia/métodos , Metilases de Modificação do DNA/metabolismo , Enzimas Reparadoras do DNA/metabolismo , Humanos , Metilação , Oncologistas/estatística & dados numéricos , Desempenho Físico Funcional , Dosagem Radioterapêutica , Espanha , Temozolomida/uso terapêutico , Proteínas Supressoras de Tumor/metabolismoRESUMO
BACKGROUND: Treatment of frail patients with advanced colorectal cancer (CRC) is controversial. This pilot phase II trial aimed to assess the efficacy and safety of regorafenib when administered in first-line to frail patients with advanced CRC. METHODS: Frail patients without prior advanced colorectal cancer treatment were included in the study. Definition of frailty was defined per protocol based on dependency criteria, presence of chronic comorbid pathologies and/or geriatric features. MAIN OBJECTIVE: to assess progression-free survival (PFS) rate at 6 months. Treatment consisted of 28-day cycles of orally administered regorafenib 160 mg/day (3 weeks followed by 1 week rest). RESULTS: Forty-seven patients were included in the study. Median age was 81 years (range 63-89). Frailty criteria: dependency was observed in 26 patients (55%), comorbidities in 27 (57%) and geriatric features in 18 (38%). PFS rate at 6 months was 45% (95% confidence interval [CI] 30-60]. Median PFS was 5.6 months (95%CI 2.7-8.4). Median overall survival (OS) was 16 months (95%CI 7.8-24). Complete response, partial response and stable disease were observed in one, two and 21 patients respectively (objective response rate 6.4%; disease control rate 51%). Thirty-nine patients (83%) experienced grade 3-4 adverse events (AEs). The most common grade 3-4 AEs were hypertension (15 patients; 32%), asthenia (14; 30%), hypophosphatemia (6; 13%); diarrhea (4; 8%), hand-foot-skin reaction (4; 8%). There were two toxic deaths (4.2%) (grade 5 rectal bleeding and death not further specified). Dose reduction was required in 26 patients (55%) and dose-delays in 13 patients (28%). CONCLUSIONS: The study did not meet the pre-specified boundary of 55% PFS rate at 6 months. Toxicity observed (83% patients experienced grade 3 and 4 AEs) preclude its current use in clinical practice on this setting. Disease control rate and overall survival results are interesting and might warrant further investigation to identify those who benefit from this approach. TRIAL REGISTRATION: This trial was prospectively registered at EudraCT ( 2013-000236-94 ). Date of trial registration: April 9th, 2013.
Assuntos
Neoplasias Colorretais/tratamento farmacológico , Idoso Fragilizado , Compostos de Fenilureia/efeitos adversos , Compostos de Fenilureia/uso terapêutico , Piridinas/efeitos adversos , Piridinas/uso terapêutico , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Astenia/etiologia , Neoplasias Colorretais/mortalidade , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Hipertensão/etiologia , Hipofosfatemia/etiologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Compostos de Fenilureia/administração & dosagem , Projetos Piloto , Intervalo Livre de Progressão , Piridinas/administração & dosagem , Espanha , Resultado do TratamentoRESUMO
BACKGROUND: Extended RAS analysis is mandatory in metastatic colorectal cancer (mCRC) patients. The optimal threshold of RAS mutated subclones to identify patients most likely to benefit from antiepidermal growth factor receptor (EGFR) therapy is controversial. Our aim was to assess the clinical impact of detecting mutations in RAS, BRAF, PIK3CA and EGFRS492R in basal tissue tumour samples by using a highly sensitive next-generation sequencing (NGS) technology in mCRC patients treated with chemotherapy plus anti-EGFR or anti-vascular endothelial growth factor. PATIENTS AND METHODS: Five hundred and eighty-one tumour samples from untreated mCRC patients from 7 clinical studies were collected. Mutational analysis was carried out by standard-of-care (therascreen pyro) with a sensitivity detection of 5% mutant allele fraction (MAF), and compared with NGS technology using 454GS Junior platform (Roche Applied Science, Germany) with a sensitivity of 1%. Molecular results were correlated with clinical outcomes. RESULTS: After quality assessment, 380 samples were evaluable for molecular analysis. Standard-of-care mutational analysis detected RAS, BRAFV600E or PIK3CA mutations in 56.05% of samples compared with 69.21% by NGS (P = 0.00018). NGS identified coexistence of multiple low-frequency mutant alleles in 96 of the 263 mutated cases (36.5%; range 2-7). Response rate (RR), progression-free survival (PFS) and overall survival (OS) were increasingly improved in patients with RAS wild-type, RAS/BRAF wild-type or quadruple (KRAS/NRAS/BRAF/PIK3CA) wild-type tumours treated with anti-EGFR, assessed by standard-of-care. No additional benefit in RR, PFS or OS was observed by increasing the detection threshold to 1% by NGS. An inverse correlation between the MAF of the most prevalent mutation detected by NGS and anti-EGFR response was observed (P = 0.039). EGFRS492Rmutation was not detected in untreated samples. CONCLUSIONS: No improvement in the selection of patients for anti-EGFR therapy was obtained by adjusting the mutation detection threshold in tissue samples from 5% to 1% MAF. Response to anti-EGFR was significantly better in patients with quadruple wild-type tumours.
Assuntos
Neoplasias Colorretais/tratamento farmacológico , GTP Fosfo-Hidrolases/genética , Proteínas de Membrana/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cetuximab/administração & dosagem , Classe I de Fosfatidilinositol 3-Quinases/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Análise Mutacional de DNA , Intervalo Livre de Doença , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Feminino , Alemanha , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Metástase Neoplásica , Inibidores de Proteínas Quinases/administração & dosagem , Resultado do TratamentoRESUMO
Data regarding management of frail patients with pancreatic ductal adenocarcinoma practice is currently very scarce. Randomized clinical trials usually exclude these subgroup of patients and the majority of the publications only consider chronological age and ECOG performance status for their classification. Therefore, the current available data do not reflect daily clinical practice. Only data from a phase two study (FRAGANCE study), designed to select a tolerable dose-schedule of nab-placitaxel + gemcitabine (Phase one) and to evaluate the efficacy of the selected regimen (Phase two) in patients with ECOG-2 and previously untreated advanced PDAC, are currently available. Management of these particular patients is exceedingly complex and requires collaboration of multidisciplinary teams and intensive support treatment. This article reviews the literature available regarding the management of the so-called frail patients and provide guidance for chemotherapy as well as supportive care treatments.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Ductal Pancreático/tratamento farmacológico , Fragilidade/fisiopatologia , Neoplasias Pancreáticas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Albuminas/administração & dosagem , Albuminas/efeitos adversos , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Ductal Pancreático/complicações , Carcinoma Ductal Pancreático/psicologia , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Idoso Fragilizado/psicologia , Fragilidade/complicações , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Neoplasias Pancreáticas/psicologia , Ensaios Clínicos Controlados Aleatórios como Assunto , GencitabinaRESUMO
Development of hyperbilirubinaemia is common in patients with advanced pancreatic adenocarcinoma, both at diagnosis as well throughout disease evolution. For this reason, hyperbilirubinaemia determines chemotherapy treatment selection, and therefore it should be considered one of the most relevant conditions. There is very little evidence for the use of chemotherapy in this setting. This article summarises the main causes of hyperbilirubinaemia, how to treat them as well as their differential diagnosis. The current clinical evidence of the available drugs as well as the recommendations of use different combinations in the context of hyperbilirubinaemia are also reviewed.
Assuntos
Carcinoma Ductal Pancreático/complicações , Hiperbilirrubinemia/etiologia , Hiperbilirrubinemia/terapia , Neoplasias Pancreáticas/complicações , Humanos , Hiperbilirrubinemia/diagnósticoRESUMO
Background: Family history (FH) of pancreatic cancer (PC) has been associated with an increased risk of PC, but little is known regarding the role of inherited/environmental factors or that of FH of other comorbidities in PC risk. We aimed to address these issues using multiple methodological approaches. Methods: Case-control study including 1431 PC cases and 1090 controls and a reconstructed-cohort study (N = 16 747) made up of their first-degree relatives (FDR). Logistic regression was used to evaluate PC risk associated with FH of cancer, diabetes, allergies, asthma, cystic fibrosis and chronic pancreatitis by relative type and number of affected relatives, by smoking status and other potential effect modifiers, and by tumour stage and location. Familial aggregation of cancer was assessed within the cohort using Cox proportional hazard regression. Results: FH of PC was associated with an increased PC risk [odds ratio (OR) = 2.68; 95% confidence interval (CI): 2.27-4.06] when compared with cancer-free FH, the risk being greater when ≥ 2 FDRs suffered PC (OR = 3.88; 95% CI: 2.96-9.73) and among current smokers (OR = 3.16; 95% CI: 2.56-5.78, interaction FHPC*smoking P-value = 0.04). PC cumulative risk by age 75 was 2.2% among FDRs of cases and 0.7% in those of controls [hazard ratio (HR) = 2.42; 95% CI: 2.16-2.71]. PC risk was significantly associated with FH of cancer (OR = 1.30; 95% CI: 1.13-1.54) and diabetes (OR = 1.24; 95% CI: 1.01-1.52), but not with FH of other diseases. Conclusions: The concordant findings using both approaches strengthen the notion that FH of cancer, PC or diabetes confers a higher PC risk. Smoking notably increases PC risk associated with FH of PC. Further evaluation of these associations should be undertaken to guide PC prevention strategies.
Assuntos
Neoplasias Pancreáticas/epidemiologia , Fumar/efeitos adversos , Adulto , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Diabetes Mellitus/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Anamnese , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Neoplasias Pancreáticas/genética , Medição de Risco , Fatores de RiscoRESUMO
Background: There has been little progress toward personalized therapy for patients with metastatic colorectal cancer (mCRC). TYMS-3' untranslated region (UTR) 6 bp ins/del and ERCC1-118C/T polymorphisms were previously reported to facilitate selecting patients for fluoropyrimidine-based treatment in combination with oxaliplatin as first-line therapy. We assessed the utility of these markers in selecting therapy for patients with mCRC. Patients and methods: This randomized, open-label phase II trial compared bevacizumab plus XELOX (control) versus treatment tailored according to TYMS-3'UTR 6 bp ins/del and ERCC1-118C/T polymorphisms. Patients randomized to the experimental treatment received bevacizumab plus FUOX, FUIRI, XELIRI, or XELOX depending on their combination of favorable polymorphisms for FUOX treatment (TYMS-3'UTR ins/del or del/del; ERCC1-118T/T). Progression-free survival (PFS) was the primary end point. Results: Overall, 195 patients were randomized (control n = 65; experimental n = 130). The primary objective was not met: median PFS was 9.4 months in the control group and 10.1 months in the experimental group (P = 0.745). Median overall survival was similar in both groups (16.5 versus 19.1 months, respectively; P = 0.797). Patients in the experimental group had a significantly higher overall response rate (ORR; 65% versus 47% in the control group; P = 0.042) and R0 resection rate (86% versus 44%, respectively; P = 0.018). Neuropathy, hand-foot syndrome, thrombocytopenia, and dysesthesia were significantly less common in the experimental group. Conclusions: This study did not show survival benefits after treatment personalization based on polymorphisms in mCRC. However, the improved ORR and R0 resection rate and fewer disabling toxicities suggest that tailoring therapy by TYMS-3'UTR and ERCC1-118 polymorphisms warrants further investigation in patients with mCRC. ClinicalTrials.gov: NCT01071655.
Assuntos
Neoplasias Colorretais/tratamento farmacológico , Proteínas de Ligação a DNA/genética , Endonucleases/genética , Testes Farmacogenômicos/métodos , Variantes Farmacogenômicos/genética , Timidilato Sintase/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Medicina de Precisão/métodos , Intervalo Livre de Progressão , Resultado do TratamentoRESUMO
Pancreatic ductal adenocarcinoma (PDAC) is currently the third most frequent form of malignancy. The role of biomarkers in the diagnostic and therapeutic strategy of cancer is constantly expanding. Translational research is already changing paradigms in tumours encompassing from early diagnosis to precision medicine in advanced disease. Nomenclature for molecular subtypes of tumours is gradually gaining acceptance and there are growing expectations it will further go from the bench to the bedside. However, the clinical relevance of biomarkers in PDAC is still far behind the relevance of biomarkers in other solid tumours. This article is part of a wider project (GALLgo) involving over forty specialists devoted to the multidisciplinary management of PDAC which concluded in recommendations based on scientific evidence. The aim of the present article is to review the diagnostic, prognostic and predictive biomarkers, either in localised or advanced disease, which have been lately subjected to study and analysis and others currently available for PDAC in order to give strength-graded recommendations linked to quality of evidence that can be used as guidelines in routine clinical practice.
Assuntos
Adenocarcinoma/diagnóstico , Biomarcadores Tumorais/metabolismo , Carcinoma Ductal Pancreático/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Adenocarcinoma/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Humanos , Neoplasias Pancreáticas/metabolismo , Medicina de Precisão , Neoplasias PancreáticasRESUMO
The management of pancreatic ductal adenocarcinoma (PDAC) is a major public health concern worldwide. Currently, most PDAC patients are diagnosed in advanced stages. The signs and symptoms of the disease, except for jaundice, are non-specific. Thus, the current challenge is to identify earlier those individuals for whom specific screening tools and specific treatments would be beneficial. On the basis of the recommendations of the group of experts of multiple medical specialties of the GALLgo Project, the patients with PDAC should be managed by a multidisciplinary team to assess the personal and family history, the best diagnostic and staging procedures and consider all important aspects for treatment decisions. In this article, the group of experts proposes strategies to shorten the diagnosis times in PDAC patients.
Assuntos
Carcinoma Ductal Pancreático/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Carcinoma Ductal Pancreático/classificação , Humanos , Estadiamento de Neoplasias , Neoplasias Pancreáticas/classificaçãoRESUMO
Pancreatic ductal adenocarcinoma (PDAC) is one of the cancers with poorest prognosis and represents the third leading cause of cancer-related deaths in Western countries. Despite advances in diagnostic procedures and treatment, diagnosis is made in most cases when the disease is locally advanced or metastatic. Supportive care aims to improve symptoms, reduce hospital admission rates, and preserve quality of life. Proper symptomatic management is critical to allow administration of chemotherapy and radiotherapy. Symptomatic management should be accomplished in a multidisciplinary fashion. Its primary aims include relief of biliary or duodenal obstruction, prevention and/or treatment of thromboembolic disease, and control cancer-related pain. Nutritional support and optimal replacement therapy in patients with endocrine and/or exocrine insufficiency, is mandatory. This manuscript highlights the most significant problems faced when caring for patients with advanced PDAC and provides an evidence-based approach to symptomatic management.
Assuntos
Adenocarcinoma/terapia , Carcinoma Ductal Pancreático/terapia , Cuidados Paliativos , Neoplasias Pancreáticas/terapia , Qualidade de Vida , HumanosRESUMO
Surgical resection is the only potentially curative option in the treatment of pancreatic ductal adenocarcinoma. Preoperative radiological imaging allows to rule out the presence of metastases. Three resectability categories are established based on the radiological findings depending on the degree of contact between the tumor and the blood vessels. Histological confirmation of malignancy is only required in cases of borderline or non-resectable tumors, prior to neoadjuvant treatment initiation. Diagnostic laparoscopy is recommended in the presence of large tumors of the body or tail and in borderline tumors to explore the possibility of resection and to apply treatment with curative intent, as well as in those cases with high level of biomarkers to rule out peritoneal involvement. Prior to surgery preoperative nutritional measures as well as endoscopic biliary drainage can be applied to optimize patient's conditions. Cephalic pancreaticoduodenectomy is the recommended surgical technique in tumors located in the head of the pancreas. The benefits from pyloric preservation, type or reconstruction (one vs. two loops), type of anastomosis (pancreaticojejunostomy vs. pancreaticogastrostomy), intraoperative biopsy of the pancreatic resection margin or the use of intraperitoneal drainages are inconclusive. Total pancreatectomy and/or portal resection should only be performed in particular cases; however, arterial resections have shown no benefits. Radical antegrade modular pancreaticosplenectomy, that can be performed laparoscopically, is the technique used for those tumors located in the pancreatic body-tail.
Assuntos
Adenocarcinoma/cirurgia , Carcinoma Ductal Pancreático/cirurgia , Neoplasias Pancreáticas/cirurgia , Qualidade de Vida , HumanosRESUMO
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is usually diagnosed in late adulthood; therefore, many patients suffer or have suffered from other diseases. Identifying disease patterns associated with PDAC risk may enable a better characterization of high-risk patients. METHODS: Multimorbidity patterns (MPs) were assessed from 17 self-reported conditions using hierarchical clustering, principal component, and factor analyses in 1705 PDAC cases and 1084 controls from a European population. Their association with PDAC was evaluated using adjusted logistic regression models. Time since diagnosis of morbidities to PDAC diagnosis/recruitment was stratified into recent (<3 years) and long term (≥3 years). The MPs and PDAC genetic networks were explored with DisGeNET bioinformatics-tool which focuses on gene-diseases associations available in curated databases. RESULTS: Three MPs were observed: gastric (heartburn, acid regurgitation, Helicobacter pylori infection, and ulcer), metabolic syndrome (obesity, type-2 diabetes, hypercholesterolemia, and hypertension), and atopic (nasal allergies, skin allergies, and asthma). Strong associations with PDAC were observed for ≥2 recently diagnosed gastric conditions [odds ratio (OR), 6.13; 95% confidence interval CI 3.01-12.5)] and for ≥3 recently diagnosed metabolic syndrome conditions (OR, 1.61; 95% CI 1.11-2.35). Atopic conditions were negatively associated with PDAC (high adherence score OR for tertile III, 0.45; 95% CI, 0.36-0.55). Combining type-2 diabetes with gastric MP resulted in higher PDAC risk for recent (OR, 7.89; 95% CI 3.9-16.1) and long-term diagnosed conditions (OR, 1.86; 95% CI 1.29-2.67). A common genetic basis between MPs and PDAC was observed in the bioinformatics analysis. CONCLUSIONS: Specific multimorbidities aggregate and associate with PDAC in a time-dependent manner. A better characterization of a high-risk population for PDAC may help in the early diagnosis of this cancer. The common genetic basis between MP and PDAC points to a mechanistic link between these conditions.
Assuntos
Carcinoma Ductal Pancreático/epidemiologia , Biologia Computacional , Neoplasias Pancreáticas/epidemiologia , Análise de Sistemas , Biologia de Sistemas , Biomarcadores Tumorais/genética , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/genética , Estudos de Casos e Controles , Análise por Conglomerados , Comorbidade , Bases de Dados Genéticas , Europa (Continente)/epidemiologia , Análise Fatorial , Humanos , Modelos Logísticos , Análise Multivariada , Razão de Chances , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Análise de Componente Principal , Medição de Risco , Fatores de Risco , Fatores de TempoRESUMO
The NCCN-evidence-based oncology guidelines are consensus-based management documents, to ensure that all patients receive the most appropriate diagnosis, treatment and support services to achieve the best results. However, the use of these guidelines for decision-making by physicians in Spain is sometimes controversial, as treatments or diagnostic procedures are recommended which might not be authorised in our country, or other management options may exist. In March 2015, the ECO Foundation reached an agreement to translate and adapt the NCCN's clinical practice guidelines in oncology for the Spanish sector. Consequently, ECO is the first European organization to reach an agreement of this type with the NCCN. This agreement will allow all agents involved in managing the cancer patients to have available guidelines that are adapted to the specific needs of Spain.
Assuntos
Oncologia/normas , Neoplasias/terapia , Guias de Prática Clínica como Assunto/normas , Gerenciamento Clínico , Humanos , EspanhaRESUMO
BACKGROUND: Solitary fibrous tumors (SFTs) are a rare type of soft tissue sarcoma of unpredictable clinical behavior. Some clinicopathologic characteristics have also been related to patient outcome. METHODS: This study is a retrospective review of 30 patients. We analyzed the clinical course and pathological factors to predict recurrence. RESULTS: The mean age was 55.9 years. Forty-five percent were located in the thoracic region. The mean tumor size was 10 cm (max24). Thirty-three percent had a relapse and 20 % have died. Median time to relapse was 7.18 (1-13) years. Median overall survival (OS) was 15.5 years (0-32). On histopathologic analysis, 6 % percent had >4 mitoses, 23 % had necroses, and 36 % had atypia/pleomorphism. Forty-three percent had tumor size >10 cm. Forty-six percent had at least one characteristic of malignancy. None of this data could predict clinical behavior by itself. CONCLUSIONS: SFT can be an aggressive disease and relapses can occur several years from diagnosis. We did not find any clinicopathologic factors that could predict the tumor behavior accurately. Nevertheless, it should be consider that we included different tumor locations and the sample size is small.