RESUMO
BACKGROUND: Small bowel adenocarcinoma is a rare disease. The genomic profiling tumours according to clinical characteristics and its impact on the prognosis remains unclear. METHODS: A pooled analysis of clinical data, genomic profiling and MisMatch Repair (MMR) status from three databases was performed. RESULTS: A total of 188 tumour samples were analysed. A predisposing disease was reported in 22.3%, mainly Lynch syndrome and Crohn's disease. The tumours were localized in 80.2% and metastatic in 18.8%. The most frequent mutations were KRAS (42.0%) among them 7/79 are G12C, TP53 (40.4%), APC (19.1%), PIK3CA (18.6%), SMAD4 (12.8%) and ERBB2 (9.6%). Mutation distribution differed according to predisposing disease for TP53, ERBB2, IDH1, FGFR3, FGFR1 and KDR. KRAS and SMAD4 mutations were more frequent in metastatic tumour, whereas ERBB2 mutations were absent in metastatic tumour. For localized tumour, APC mutation was independently associated with a poor overall survival (OS) (p = 0.0254). 31.8% of localized tumours and 11.3% of metastatic tumours were dMMR (29.8% of the entire cohort). A dMMR status was associated with a better OS (HR = 0.61 [0.39-0.96], p = 0.0316). CONCLUSIONS: There is a different genomic profile according to the stage and predisposing disease. dMMR and APC mutation in localized tumour predict a better prognosis.
Assuntos
Adenocarcinoma , Neoplasias Intestinais , Mutação , Humanos , Adenocarcinoma/genética , Adenocarcinoma/patologia , Neoplasias Intestinais/genética , Neoplasias Intestinais/patologia , Neoplasias Intestinais/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Intestino Delgado/patologia , Adulto , Prognóstico , Idoso de 80 Anos ou mais , Perfilação da Expressão Gênica , Reparo de Erro de Pareamento de DNA/genéticaRESUMO
Small bowel adenocarcinoma (SBA) is a rare tumour. Large genomic analyses with prognostic assessments are lacking. The NADEGE cohort has enrolled 347 patients with all stage SBA from 2009 to 2012. Next-generation sequencing investigates the presence of 740 hotspot somatic mutations in a panel of 46 genes involved in carcinogenesis. The mismatch repair (MMR) status was assessed by immunochemistry. We have collected 196 tumour samples and 125 had conclusive results for mutation analysis. The number of mutations was 0 in 9.6% of tumours, only 1 in 32.0%, 2 in 26.4% and ≥3 in 32.0%. Overall, at least one genomic alteration was observed in 90.4% of tumour. The most frequent genomic alteration was in KRAS (44.0%), TP53 (38.4%), PIK3CA (20.0%), APC (18.4%), SMAD4 (14.4%) and ERBB2 (7.2%) genes. KRAS mutations were more frequent in synchronous metastatic tumours than in localised tumours (72.7% vs 38.2%, P = .003). There was no significant difference in the mutation rates according to primary location for the most frequently altered gene. ATM, FGFR3 and FGFR1 gene alterations were associated with Lynch syndrome and IDH1 mutations with Crohn disease. dMMR tumours were associated with younger age, localised tumours, less KRAS but more SMARCB1 mutations. No genomic alteration was associated with overall survival. There is a trend for better survival in patient with dMMR tumours. In conclusion, there is a different genomic alteration profile in SBA according to predisposing diseases. No association between genomic alterations and prognoses was observed except for a trend of better prognoses associated with dMMR.
Assuntos
Adenocarcinoma/genética , Neoplasias Colorretais/genética , Reparo de Erro de Pareamento de DNA/genética , Doenças Raras/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Proteína da Polipose Adenomatosa do Colo/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas Mutadas de Ataxia Telangiectasia/genética , Classe I de Fosfatidilinositol 3-Quinases/genética , Estudos de Coortes , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Análise Mutacional de DNA , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Proteínas Proto-Oncogênicas p21(ras)/genética , Doenças Raras/metabolismo , Doenças Raras/patologia , Receptor ErbB-2/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Proteína Smad4/genética , Proteína Supressora de Tumor p53/genéticaRESUMO
BACKGROUND: Neoadjuvant treatment (NAT) is debated for borderline resectable pancreatic cancer (BRPC). This retrospective study assessed the impact of NAT on R0 rate and survival for BRPC patients in comparison with upfront surgery (US). MATERIAL AND METHODS: Between 2010 and 2017 patient records for all consecutive patients treated for BRPC according to NCCN 2017 were reviewed. The endpoints analysed were R0 rate, recurrence-free-survival (RFS) and overall survival (OS). RESULTS: Seventy-nine patients were included: 63 (79.7%) patients received NAT and 16 (20.3%) were upfront operated. NAT consisted in FOLFIRINOX (median cycles: 5, range 4-8) followed by chemoradiation (n = 55, 87.3%, median dose: 54 Gy). Thirty-nine (61.9%) patients had resection. R0 rate was higher in the NAT group considering a margin clearance of 0 mm (94.9%) or 1 mm (89.7%) compared to the US group (68.8% and 43.8% respectively). In the whole population, median RFS was 12.6 [95%CI: 10.5-22.1] in the NAT group vs 7.7 [95%CI: 4.4-14] months in the US group (p < 0.01). Median OS was 29.0 [95%CI: 23.5-63.1] and 27.2 [95%CI: 11.6-38.8] months in the NAT and US groups respectively (p = 0.06). In operated patients the NAT group achieved better RFS and OS than the US group (p < 0.01 for both). In multivariate analysis NAT, surgical resection and age <65 (p < 0.01 for both) were prognostic of RFS. NAT, surgical resection and adjuvant chemotherapy were prognostic of OS (p < 0.05 for all). In operated patients (n = 55) multivariate analysis showed that N1 status was associated with decreased RFS; age < 65 and NAT were associated with a longer RFS. Receiving a NAT, an adjuvant chemotherapy and achieving a ypT0-1N0 status were associated with better OS. NAT was well tolerated with 14.3% grade ≥ 3 toxicities. CONCLUSION: NAT permitted a high R0 rate with a 0- or 1-mm clearance margin and was associated with better RFS and OS for patients with BRPC.
Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Terapia Neoadjuvante , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Estudos RetrospectivosRESUMO
PURPOSE: To evaluate changes in tumor vascularization parameters based on contrast-enhanced ultrasound (CEUS) quantification criteria of at least one visible liver metastasis as an early predictor of non-response to chemotherapy, including bevacizumab for colorectal cancer (CRC) liver metastases. MATERIALS AND METHODS: This multicenter prospective study included patients who received first-line bevacizumab-based chemotherapy. Tumor enhancement measured using CEUS within one liver metastasis and in relation to the surrounding healthy liver was quantified within 8 days before the first infusion of bevacizumab (E0), 24 hours after the end of the first infusion of bevacizumab (E1), in the 24 hours before the 2nd and 3ârd infusion of bevacizumab on day 15 (E2) and day 30 (E3), respectively, and after 2 months of treatment (E4). Endpoints were tumor response using RECIST criteria at 2 months, progression-free survival (PFS) and overall survival (OS). RESULTS: Among the 137 patients included in this study, 109 were analyzed. Only CEUS parameters calculated in relation to healthy liver were significant. High wash-in and wash-out rates at baseline were significantly associated with a better tumor response. Increases over time E2-E0 and E3-E0 for peak enhancement were significantly associated with shorter progression-free survival. Increases over time E2-E0 and E3-E0 for peak enhancement and wash-in area under the curve were significantly associated with a shorter overall survival. CONCLUSION: This large study demonstrated that early dynamic changes in the vascularity of liver metastases evaluated by quantified CEUS are associated with outcome in patients receiving first-line bevacizumab-based treatment for metastatic CRC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorretais , Neoplasias Hepáticas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/administração & dosagem , Neoplasias Colorretais/patologia , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Associations between polymorphisms of UDP-glucuronosyltransferases (UGTs) or efflux transporters (e.g., P-glycoprotein and MRP2) and different types of cancer have been described, whereas the role of influx transporters (e.g. OATP1B1 and OATP2B1) has been seldom explored. The GenColon study investigated potential associations between variant alleles of UGTs, efflux and influx transporters and CRC. METHODS: Three hundred CRC cases were matched with 300 controls for age, sex and enrolment site. Fifteen SNPs in UGT1A6-9, UGT2B7, ABCB1, ABCC2, SLCO1B1 and SLCO2B1 genes were characterized using Taqman® PCR. Using multivariate conditional logistic regression, we investigated the relationships between CRC and "environmental" risk factors (physical activity, housing and working areas, consumption of red meat, tobacco, alcohol); genetic polymorphisms, in the study population and in the subgroups with "environmental" risk factors. RESULTS: No significant association was observed for the analyzed SNPs (or haplotypes). However, an increased CRC risk was found in carriers of the UGT1A8 rs1042597-G variant allele (additive risk OR = 3.39[1.29-8.89], p = 0.02951) in the subgroup of meat-consumers (n = 84), and in carriers of the ABCB1 rs1045642-T (exon26) variant allele (additive risk; OR = 1.89[1.10-3.39], p = 0.0257) in the "never alcohol consumption subgroup" (n = 125). In addition, as previously reported, the following CRC risk factors were identified: absence of physical activity (OR = 6.35[3.70-10.9], p < 0.0001), living or working in rural or mix area (OR = 2.50[1.48-4.23], p = 0.0006 and OR = 2.99[1.63-5.48], p = 0.004, respectively) and tobacco exposure >30 years (3.37[1.63-6.96], p = 0.0010). CONCLUSIONS: Variant genotypes of influx transporters (OATP1B1 and 2B1) were not associated with CRC. This study confirmed the influence of lifestyle factors, but not the previously reported detrimental effect of SNPs in intestinal UGTs or efflux transporters, except for a UGT1A8 variant in subjects consuming meat and the exon 26 SNP of ABCB1 in the never alcohol consumption subgroup. TRIAL REGISTRATION: Registered in Direction Générale de la Santé the 1st July 2008 under the number DGS2008-0144.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Predisposição Genética para Doença , Glucuronosiltransferase/genética , Proteínas de Membrana Transportadoras/genética , Polimorfismo de Nucleotídeo Único , Idoso , Estudos de Casos e Controles , Neoplasias Colorretais/patologia , Feminino , Seguimentos , Humanos , Masculino , Proteína 2 Associada à Farmacorresistência Múltipla , Prognóstico , Fatores de RiscoRESUMO
BACKGROUND: Neoadjuvant treatment is considered the standard treatment for locally advanced adenocarcinoma of the esophagus. This study compared the effectiveness of neoadjuvant chemoradiotherapy (CRT) and perioperative chemotherapy (PCT) based on postoperative results and long-term survival. METHODS: All patients with locally advanced adenocarcinoma of the esophagus were treated with a single protocol of neoadjuvant CRT (cisplatin and 5-fluorouracil [5-FU] with 45 Gy of concurrent radiotherapy) or with a single protocol of PCT (docetaxel, cisplatin, 5-FU). The responses to CRT and PCT were evaluated by considering the rates of pathologic complete response (pCR) and radical resection (R0). Overall survival (OS), disease-free survival (DFS), and recurrence were evaluated according to the neoadjuvant treatment. RESULTS: A total of 116 patients underwent CRT or PCT followed by esophagectomy; 61 patients underwent PCT, and 55 patients underwent CRT. R0 was achieved in 98 patients (84.5 %) and was more frequent in the CRT group (94.6 vs. 75.4 %; p = 0.010). pCR was observed in 13 patients (11.2 %) and was more frequent in the CRT group (20 vs. 3.3 %; p = 0.011). OS was comparable between the CRT and PCT groups (41 vs. 45 months; p = 0.284). DFS was comparable between the CRT and PCT groups (21 vs. 36 months; p = 0.522). CONCLUSIONS: In this study, better histological results were observed in patients who had been treated with CRT, although similar survival rates were observed for patients treated with either CRT or PCT. Further study is necessary to select patients who will benefit most from CRT or PCT.
Assuntos
Adenocarcinoma/terapia , Neoplasias Esofágicas/terapia , Adenocarcinoma/patologia , Adulto , Idoso , Quimiorradioterapia , Quimioterapia Adjuvante , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Prognóstico , Análise de SobrevidaRESUMO
PURPOSE: In view of increased response rates and survivals in patients with metastatic pancreatic adenocarcinoma (PAC) with FOLFIRINOX, many centers proposed this regimen as induction chemotherapy for borderline (BR) or locally advanced (LA) PAC. The aim of this study was to assess surgical and oncological outcomes of patients who underwent resection after induction FOLFIRINOX therapy. METHODS: We prospectively identified surgical consecutive BR or LA PAC patients after induction FOLFIRINOX in 20 observational French centers between November 2010 and December 2013. Two independent experts retrospectively evaluated initial CT scan for central review. RESULTS: Eighty patients were included, 47 had BR and 33 had LA PAC. Median number of FOLFIRINOX cycles was 6 (range 1-30) and 65 % of patients received chemoradiation. The 30-day-mortality, major complications, and symptomatic pancreatic fistula rates were 2.5, 22.5, and 4 %, respectively. R0 resection was achieved in 84 %. After a median follow-up of 38.2 months since diagnosis, disease-free survival (DFS) was 17.16 months. The overall survival rates at 12 and 24 months were 92 and 81 %, respectively. A 26 % (n = 21) pathologic major response (pMR) rate was reached. In univariate and multivariate analysis, pMR was a prognostic factor for DFS (hazard ratio 0.33; P = 0.01 and hazard ratio 0.38; P = 0.035). CONCLUSIONS: Resection after induction FOLFIRINOX is safe and associated with similar or better outcomes as upfront surgery in patients with PAC. A pMR was observed in 26 % of cases and was prognostic of DFS. This therapeutic design should be investigated in prospective studies.
Assuntos
Adenocarcinoma/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal Pancreático/patologia , Quimiorradioterapia , Neoplasias Pancreáticas/patologia , Adenocarcinoma/terapia , Adulto , Idoso , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Carcinoma Ductal Pancreático/terapia , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Quimioterapia de Indução , Irinotecano , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Neoplasias Pancreáticas/terapia , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
PURPOSE: To prospectively evaluate the utility of computed tomography (CT) for determination of tumor response and prediction of resectability after neoadjuvant combined chemotherapy and radiation therapy (CRT) in patients with nonmetastatic locally advanced pancreatic cancer. MATERIALS AND METHODS: This study received institutional review board approval, and all participants provided written informed consent. Consecutive patients with cephalic locally advanced pancreatic cancer who underwent surgical exploration and/or resection following neoadjuvant CRT were prospectively enrolled from June 2009 to May 2013. Two radiologists independently analyzed the baseline and post-CRT CT scans for the size, attenuation, and circumferential vascular contacts of the tumor. Associations between the postoperative histologic grade of the tumor response (pTNM) and the clinical, biologic, and CT criteria were assessed by using Spearman correlation coefficients. CT criteria related to the presence of complete (ie, R0) resection were assessed by using logistic regression. RESULTS: Forty-seven patients were included, 33 with an R0 resection and 14 with positive margins (ie, R1) or no resection. Variables demonstrating a significant correlation with the histologic tumor classification of tumor response were post-CRT carbohydrate antigen 19-9 level (r = 0.46), post-CRT largest tumor axis (r = 0.44), post-CRT sum of the largest and smallest tumor axes (r = 0.46), change in the largest axis (r = -0.31), change in the sum of the largest and smallest axes (r = -0.39), change in superior mesenteric vein (SMV) and/or portal vein (hereafter, SMV/portal vein) contact (r = -0.38), and post-CRT superior mesenteric artery contact (r = 0.34). Partial regression of tumor contact with the SMV/portal vein was associated in all cases with R0 resection (10 of 10 patients, positive predictive value = 100%), and partial regression of tumor contact with any peripancreatic vascular axis was associated with R0 resection in 91% of cases (20 of 22 patients, positive predictive value = 91%). Persistence of SMV/portal vein stenosis after CRT was not predictive of R1 resection. CONCLUSION: Partial regression of tumor-vessel contact indicates suitability for surgical exploration, irrespective of the degree of decrease in tumor size or the degree of residual vascular involvement.
Assuntos
Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/terapia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/terapia , Tomografia Computadorizada por Raios X , Adenocarcinoma/patologia , Adulto , Idoso , Quimiorradioterapia , Meios de Contraste , Feminino , Humanos , Iohexol , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Invasividade Neoplásica , Estadiamento de Neoplasias , Pancreatectomia , Neoplasias Pancreáticas/patologia , Estudos Prospectivos , Interpretação de Imagem Radiográfica Assistida por Computador , Resultado do TratamentoRESUMO
BACKGROUND: Visceral fat produces angiogenic factors such as vascular endothelial growth factor that promote tumoral growth. However, its influence on outcome for patients with advanced cancer treated with anti-angiogenic agents is controversial. AIMS: The aim of this study was to determine whether visceral fat volume, visceral fat area and body mass index are associated with outcome in patients receiving first-line bevacizumab-based treatment for metastatic colorectal cancer. METHODS: This multicenter prospective study included 103 patients with metastatic colorectal cancer who received first-line bevacizumab-based chemotherapy. Computed tomography was used to measure visceral fat volume and visceral fat area. Endpoints were tumoral response at 2 months, progression free survival and overall survival. RESULTS: Visceral fat volume and visceral fat area, but not body mass index, were significantly associated with better outcome. Using sex-specific median values progression free survival was significantly longer in patients with high visceral fat volume (13.2 versus 9.4 months; p = 0.0043). In the same way, high visceral fat volume and visceral fat area were associated with a significantly better overall survival: 31.3 versus 20.5 months (p = 0.0072) and 29.3 versus 20.5 months (p = 0.0078), respectively. By multivariate analysis, visceral fat volume was associated with longer progression free survival and overall survival. CONCLUSION: This study demonstrates that a high visceral fat volume is associated with better outcome in patients receiving first-line bevacizumab-based chemotherapy for metastatic colorectal cancer.
Assuntos
Bevacizumab , Neoplasias Colorretais , Gordura Intra-Abdominal , Humanos , Bevacizumab/uso terapêutico , Bevacizumab/administração & dosagem , Gordura Intra-Abdominal/diagnóstico por imagem , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Idoso , Resultado do Tratamento , Adulto , Antineoplásicos Imunológicos/uso terapêutico , Índice de Massa Corporal , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Metástase Neoplásica , Intervalo Livre de Progressão , Idoso de 80 Anos ou mais , Taxa de Sobrevida , Fluoruracila/uso terapêuticoRESUMO
IMPORTANCE: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) can affect patient health-related quality of life (HRQoL). Appropriate information may improve their adherence to treatment and quality of life. OBJECTIVE: To evaluate the change in patient's perceptions of the level of information at lanreotide (LAN) treatment initiation for GEP-NETs vs after 6 months. DESIGN: OPERA (NCT03562091) was a prospective, longitudinal, noninterventional study. SETTING: Thirty-one centers in France specialized in the management of patients with NETs. INTERVENTION: Planned clinical visits at enrollment and end-of-study visits at month 6, with completion of the European Organisation for Research and Treatment of Cancer 25-item Quality of Life Questionnaire-Information Module (QLQ-INFO25) and 30-item Quality of Life Questionnaire-Core. MAIN OUTCOME: Absolute change in the patient's perception of the information between baseline and month 6, using the relevant domains of the QLQ-INFO25. Endpoints measured at baseline and month 6 for at least 1 of the 3 targeted QLQ-INFO25 dimensions of the primary endpoint. RESULTS: Ninety-three of the 115 patients enrolled completed ≥1 primary endpoint information dimension. Mean (SD) scores for the primary endpoint information dimensions were high at baseline (disease, 63.41 [20.71]; treatment, 58.85 [19.00]; supportive care, 26.53 [24.69]; maximum 100). There were no significant changes between baseline (98.34% CI) and 6 months (disease, -2.84 [-8.69, 3.01; P = .24]; treatment, -4.37 [-11.26, 2.52; P = .13]; supportive care, 0.46 [-6.78, 7.70; P = .88]), and in HRQoL between baseline and 6 months. CONCLUSIONS AND RELEVANCE: The lack of change in patient's perceptions of the disease, treatment, and supportive care information provided over the first 6 months of LAN treatment may suggest that physicians provided adequate information at the treatment initiation.
Assuntos
Antineoplásicos , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Humanos , Tumores Neuroendócrinos/terapia , Qualidade de Vida , Estudos Prospectivos , Antineoplásicos/uso terapêutico , Peptídeos Cíclicos/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , PercepçãoRESUMO
BACKGROUND: Small bowel adenocarcinoma is a rare cancer, and the role of adjuvant chemotherapy for localized disease is still debated. METHODS: This retrospective multicenter study included all consecutive patients who underwent curative surgical resection for localized small bowel adenocarcinoma between 1996 and 2019 from 3 French cohort studies. Prognostic and predictive factors of adjuvant chemotherapy efficacy were analyzed for disease-free survival and overall survival. The inverse probability of treatment weighting method was applied in the Cox regression model using the propensity score derived from multivariable logistic regression. RESULTS: A total of 354 patients were included: median age, 63.5 years; duodenum location, 53.5%; and tumor stage I, II, and III in 31 (8.7%), 144 (40.7%), and 179 (50.6%) patients, respectively. The adjuvant chemotherapy was administered in 0 (0%), 66 (48.5%), and 143 (80.3%) patients with stage I, II, and III, respectively (P < .0001). In the subgroup analysis by inverse probability of treatment weighting method, a statistically significant disease-free survival and overall survival benefit in favor of adjuvant chemotherapy was observed in high-risk stage II (T4 and/or <8 lymph nodes examined) and III (T4 and/or N2) but not for low-risk stage II (T3 and ≥8 lymph nodes examined) and III (T1-3/N1) tumors (Pinteraction < .05). Furthermore, tumor location in jejunum and ileum was also a statistically significant predictive factor of response to adjuvant chemotherapy in stage II and III tumors (Pinteraction < .05). CONCLUSION: In localized small bowel adenocarcinoma, adjuvant chemotherapy seems to provide a statistically significant survival benefit for high-risk stage II and III tumors and for jejunum and ileum tumor locations.
Assuntos
Adenocarcinoma , Intestino Delgado , Humanos , Pessoa de Meia-Idade , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Adenocarcinoma/patologia , Quimioterapia Adjuvante , Intestino Delgado/patologia , Intestino Delgado/cirurgia , Estadiamento de Neoplasias , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: Colon adenocarcinoma mainly occurs in older patients. Oxaliplatin-based adjuvant chemotherapy improved disease-free survival after stage III colon cancer resection, but this improvement was not demonstrated in older patients. METHODS: The purpose of ADAGE-PRODIGE 34, randomized open phase III trial is to compare in patients over 70 years oxaliplatin plus fluoropyrimidine with fluoropyrimidine alone in fit patients (Group 1) and fluoropyrimidine with observation in frail patients (Group 2) after resection of stage III colon adenocarcinoma. We report a preliminary tolerance analysis on 50% of the first patients enrolled. RESULTS: The analysis was conducted on 491 patients (378 in Group 1 and 113 in Group 2). Patients in Group 2 were older and showed more frailty criteria than those in Group 1. Cumulative grade 3-5 toxicities were more frequent in patients treated with oxaliplatin in Group 1 or with fluoropyrimidine in Group 2 than in patients treated with fluoropyrimidine in Group 1. At least one course was deferred in more than half of the patients in all groups. Early treatment cessation was more frequent in Group 2. CONCLUSION: No safety concerns were raised for the continuation of accrual. The frailty criteria distribution suggests that the investigator's evaluation for group allocation was accurate.
Assuntos
Adenocarcinoma , Neoplasias do Colo , Fragilidade , Humanos , Idoso , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/cirurgia , Neoplasias do Colo/patologia , Oxaliplatina/uso terapêutico , Fluoruracila/uso terapêutico , Capecitabina/efeitos adversos , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Adenocarcinoma/etiologia , Intervalo Livre de Doença , Quimioterapia Adjuvante/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Estadiamento de Neoplasias , Leucovorina/uso terapêuticoRESUMO
BACKGROUND & AIMS: Liver stiffness can be measured noninvasively to assess liver fibrosis in patients with chronic hepatitis C. In patients with chronic liver diseases, level of fibrosis predicts liver-related complications and survival. We evaluated the abilities of liver stiffness, results from noninvasive tests for fibrosis, and liver biopsy analyses to predict overall survival or survival without liver-related death with a 5-year period. METHODS: In a consecutive cohort of 1457 patients with chronic hepatitis C, we assessed fibrosis and, on the same day, liver stiffness, performed noninvasive tests of fibrosis (FibroTest, the aspartate aminotransferase to platelet ratio index, FIB-4), and analyzed liver biopsy samples. We analyzed data on death, liver-related death, and liver transplantation collected during a 5-year follow-up period. RESULTS: At 5 years, 77 patients had died (39 liver-related deaths) and 16 patients had undergone liver transplantation. Overall survival was 91.7% and survival without liver-related death was 94.4%. Survival was significantly decreased among patients diagnosed with severe fibrosis, regardless of the noninvasive method of analysis. All methods were able to predict shorter survival times in this large population; liver stiffness and results of FibroTest had higher predictive values. Patient outcomes worsened as liver stiffness and FibroTest values increased. Prognostic values of stiffness (P<.0001) and FibroTest results (P<.0001) remained after they were adjusted for treatment response, patient age, and estimates of necroinflammatory grade. CONCLUSIONS: Noninvasive tests for liver fibrosis (measurement of liver stiffness or FibroTest) can predict 5-year survival of patients with chronic hepatitis C. These tools might help physicians determine prognosis at earlier stages and discuss specific treatments, such as liver transplantation.
Assuntos
Aspartato Aminotransferases/sangue , Ensaios Enzimáticos Clínicos , Técnicas de Imagem por Elasticidade , Hepatite C Crônica/diagnóstico , Cirrose Hepática/diagnóstico , Adulto , Idoso , Biomarcadores/sangue , Biópsia , Distribuição de Qui-Quadrado , Feminino , França , Hepatite C Crônica/sangue , Hepatite C Crônica/complicações , Hepatite C Crônica/mortalidade , Hepatite C Crônica/terapia , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/mortalidade , Cirrose Hepática/terapia , Cirrose Hepática/virologia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Análise de Sobrevida , Taxa de Sobrevida , Fatores de TempoRESUMO
PURPOSE: Whether triplet chemotherapy is superior to doublet chemotherapy in advanced biliary tract cancer (BTC) is unknown. METHODS: In this open-label, randomized phase II-III study, patients with locally advanced or metastatic BTC and an Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned (1:1) to receive oxaliplatin, irinotecan, and infusional fluorouracil (mFOLFIRINOX), or cisplatin and gemcitabine (CISGEM) for a maximum of 6 months. We report the results of the phase II part, where the primary end point was the 6-month progression-free survival (PFS) rate among the patients who received at least one dose of treatment (modified intention-to-treat population) according to Response Evaluation Criteria in Solid Tumors version 1.1 (statistical assumptions: 6-month PFS rate ≥ 59%, 73% expected). RESULTS: A total of 191 patients (modified intention-to-treat population, 185: mFOLFIRINOX, 92; CISGEM, 93) were randomly assigned in 43 French centers. After a median follow-up of 21 months, the 6-month PFS rate was 44.6% (90% CI, 35.7 to 53.7) in the mFOLFIRINOX arm and 47.3% (90% CI, 38.4 to 56.3) in the CISGEM arm. Median PFS was 6.2 months (95% CI, 5.5 to 7.8) in the mFOLFIRINOX arm and 7.4 months (95% CI, 5.6 to 8.7) in the CISGEM arm. Median overall survival was 11.7 months (95% CI, 9.5 to 14.2) in the mFOLFIRINOX arm and 13.8 months (95% CI, 10.9 to 16.1) in the CISGEM arm. Adverse events ≥ grade 3 occurred in 72.8% of patients in the mFOLFIRINOX arm and 72.0% of patients in the CISGEM arm (toxic deaths: mFOLFIRINOX arm, two; CISGEM arm, one). CONCLUSION: mFOLFIRINOX triplet chemotherapy did not meet the primary study end point. CISGEM doublet chemotherapy remains the first-line standard in advanced BTC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Biliar/tratamento farmacológico , Cisplatino/uso terapêutico , Desoxicitidina/análogos & derivados , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Sistema Biliar/mortalidade , Neoplasias do Sistema Biliar/patologia , Cisplatino/efeitos adversos , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Progressão da Doença , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , França , Humanos , Irinotecano/efeitos adversos , Irinotecano/uso terapêutico , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Oxaliplatina/efeitos adversos , Oxaliplatina/uso terapêutico , Intervalo Livre de Progressão , Fatores de Tempo , GencitabinaRESUMO
AIM: Stratification of colon cancer (CC) of patients with stage II and III for risk of relapse is still needed especially to drive adjuvant therapy administration. Our study evaluates the prognostic performance of two known biomarkers, CDX2 and CD3, standalone or their combined information in stage II and III CC. PATIENTS AND METHODS: CDX2 and CD3 expression was evaluated in Prodige-13 study gathering 443 stage II and 398 stage III primary CC on whole slide colectomy. We developed for this study an H-score to quantify CDX2 expression and used our artificial intelligence (AI)-guided tissue analysis ColoClass to detect CD3 in tumour core and invasive margin. Association between biomarkers and relapse-free survival was investigated. RESULTS: Univariate analysis showed that the combined variable CD3-TC and CD3-IM was associated with prognosis in both stage II and stage III. CDX2, on the contrary, was associated with prognosis only in stage III. We subsequently associated CDX2 and combined immune parameters only in stage III. This multivariate analysis allowed us to distinguish a proportion of stage III CC harbouring a high CDX2 expression and a high immune infiltration with a particularly good prognosis compared to their counterpart. CONCLUSION: This study validated the prognostic role of CDX2 and CD3 evaluated with immunohistochemistry procedures in stage III but not in stage II. This association would be conceivable in a routine pathology laboratory and could help oncologist to consider chemotherapy de-escalation for a part of stage III patients.
Assuntos
Inteligência Artificial , Neoplasias do Colo , Biomarcadores Tumorais/metabolismo , Complexo CD3 , Fator de Transcrição CDX2/metabolismo , Neoplasias do Colo/patologia , Humanos , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , PrognósticoRESUMO
BACKGROUND: Circulating tumor cells (CTCs) allow the real-time monitoring of tumor course and treatment response. This prospective multicenter study evaluates and compares the early predictive value of CTC enumeration with EPISPOT, a functional assay that detects only viable CTCs, and with the CellSearch® system in patients with metastatic colorectal cancer (mCRC). METHODS: Treatment-naive patients with mCRC and measurable disease (RECIST criteria 1.1) received FOLFIRI-bevacizumab until progression or unacceptable toxicity. CTCs in peripheral blood were enumerated at D0, D14, D28, D42, and D56 (EPISPOT assay) and at D0 and D28 (CellSearch® system). Progression-free survival (PFS) and overall survival (OS) were assessed with the Kaplan-Meier method and log-rank test. RESULTS: With the EPISPOT assay, at least 1 viable CTC was detected in 21% (D0), 15% (D14), 12% (D28), 10% (D42), and 12% (D56) of 155 patients. PFS and OS were shorter in patients who remained positive, with viable CTCs between D0 and D28 compared with the other patients (PFS = 7.36 vs. 9.43 months, p = 0.0161 and OS = 25.99 vs. 13.83 months, p = 0.0178). The prognostic and predictive values of ≥3 CTCs (CellSearch® system) were confirmed. CONCLUSIONS: CTC detection at D28 and the D0-D28 CTC dynamics evaluated with the EPISPOT assay were associated with outcomes and may predict response to treatment.
RESUMO
INTRODUCTION: Streptozocin can impair renal function. The purpose of this study was to evaluate the evolution of renal function in patients receiving this anti-mitotic for the treatment of locally advanced/metastatic digestive well differentiated neuroendocrine tumours. METHODS: A prospective and a retrospective cohort of patients with normal baseline renal function were analysed. The primary endpoint was the incidence of a decrease in the estimated glomerular filtration rate ≥ 25% during treatment. Secondary endpoints were the evaluation of glomerular filtration rate changes, the impact of combined nephrotoxic treatments, other toxicities, compliance, and the objective response rate. RESULTS: After screening 142 patients, 27 were included in the prospective and 84 in the retrospective cohort. A decrease in estimated glomerular filtration rate ≥ 25% was observed in 32 patients (30%): respectively four (15.4%) and 28 patients (34.1%) among respectively 26 and 82 patients with numerous measures (Pâ¯=â¯0.0097). Altogether, 39 patients (35%) experienced grade 1-2 renal toxicity, while no grade 3-4 occurred in the prospective and 1 occurred in the retrospective cohort. Renal toxicity was more frequent in the retrospective cohort with a less careful follow up. As best responses, objective response was achieved in 27% of patients with pancreatic primary tumours, disease control in 78.9% of patients with pancreatic primary tumours, in 87% of those with small bowel tumours and in 72.7% of patients with other primary locations. CONCLUSIONS: Strongly recommended for pancreatic NET, streptozocin is associated with frequent mild renal toxicity but low occurrence of renal impairment in patients with baseline normal renal function and under adequate hydration.
Assuntos
Neoplasias do Sistema Digestório , Rim , Tumores Neuroendócrinos , Estreptozocina , Neoplasias do Sistema Digestório/tratamento farmacológico , Humanos , Rim/fisiologia , Tumores Neuroendócrinos/tratamento farmacológico , Estudos Prospectivos , Estudos Retrospectivos , Estreptozocina/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: A surveillance program was performed in colorectal cancer (CRC) patients after surgery, to diagnose asymptomatic recurrence. AIMS: To assess whether 18-FDG positron emission tomography/CT (PET/CT) improved the detection of recurrence during a 3-year follow-up. METHODS: A multicentre, two-arm randomised prospective trial comparing different 36-month follow-up strategies. Complete colonoscopy was performed at baseline and after 3 years and clinical exams with imaging every 3 months. The conventional arm (A) received carcinoembryonic antigen, liver echography, and alternated between lung radiography and computed tomography (CT) scans. The experimental arm (B) received PET/CT. RESULTS: A total of 365 patients with colon (79.4%) or rectal cancer (20.6%), stages II (48.2%) or III (50.8%), were enroled in this study. At 36 months, intention-to-treat analysis revealed recurrence in 31 (17.2%) patients in arm A and 47 (25.4%) in arm B (pâ¯=â¯0.063). At 3 years, 7 of 31 relapses (22.5%) in arm A were surgically treated with curative intent, compared to 17 of 47 (36.2%) in arm B (pâ¯=â¯0.25). The rates of recurrence and new cancers were higher in arm B than arm A (pâ¯=â¯0.038). CONCLUSIONS: PET/CT follow-up every 6 months did not increase the rate of recurrence at 3 years or the rate of surgically treated recurrence compared with conventional follow-up.
Assuntos
Antígeno Carcinoembrionário/sangue , Neoplasias Colorretais/diagnóstico por imagem , Fluordesoxiglucose F18 , Recidiva Local de Neoplasia/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/sangue , Neoplasias Colorretais/cirurgia , Feminino , Seguimentos , França , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Estudos ProspectivosRESUMO
BACKGROUND: Changes in skeletal muscle mass (SMM), total adipose tissue mass (TAT) or bone mineral density (BMD) have been described in patients with cancer undergoing various treatments; simultaneous variations of all 3 tissues has not been reported. METHODS: Data were prospectively collected in a clinical study (NCT00489697) including patients with liver metastases of colorectal cancer who received 4 cycles of bevacizumab in combination with cytotoxic chemotherapy. Computerized tomography (CT) at baseline and after chemotherapy was used to quantify skeletal muscle and adipose tissue cross-sectional areas, and mean lumbar spine BMD using validated approaches. RESULTS: After exclusion of patients lacking adequate CT images or missing data, 72 subjects were included. Patients were 63% male, aged 63.2 ± 10.3 years, 100% had liver metastases and 54%, 24% and 22% respectively has 0, 1 and ≥2 extrahepatic metastases. 100% tolerated 4 cycles of treatment and none showed progressive disease at the end of treatment. The scan interval was 70 days (95% CI, 62.3 to 80.5). Thresholds for loss of tissue were defined as loss ≥ measurement error. 10% of patients showed no loss of any tissue and a further 43% lost one tissue (SMM, TAT or BMD); 47% of patients lost 2 tissues (16.5% lost SMM + TAT, 8% lost SMM + BMD, 10% lost TAT + BMD) or all 3 tissues (12.5%). Catabolic behavior (2 or 3 tissue loss vs 0 or 1 tissue loss) associated with disease burden, including unresectable primary tumor (p = 0.010), presence of extrahepatic (EH) metastases (p = 0.039) and number of EH metastases (p = 0.004). No association was found between the number of tissues lost and treatment response, which was uniformly high, or treatment toxicity, which was uniformly low. CONCLUSION: Multiple tissues can be measured in routine CT images and these show considerable inter-individual variation. Substantial losses in some individuals appear to associate with disease burden.
Assuntos
Tecido Adiposo/diagnóstico por imagem , Antineoplásicos/efeitos adversos , Bevacizumab/efeitos adversos , Densidade Óssea/fisiologia , Neoplasias Colorretais/tratamento farmacológico , Músculo Esquelético/diagnóstico por imagem , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/patologia , Idoso , Densidade Óssea/efeitos dos fármacos , Neoplasias Colorretais/patologia , Monitoramento de Medicamentos , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Estudos Prospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento , UltrassonografiaRESUMO
BACKGROUND: Chemotherapy is effective in metastatic pancreatic adenocarcinoma (mPA), but new approaches are still needed to improve patients' survival and quality of life. We have previously published good efficacy and tolerability results on a sequential treatment strategy of gemcitabine followed by an intensified FOLFIRI (5FU+irinotecan) regimen. In the present study, we evaluated the same sequence but replaced gemcitabine by the new gemcitabine + nab-paclitaxel standard first-line combination. PATIENTS AND METHODS: We randomised chemotherapy-naive patients with proven mPA, bilirubin levels ≤1.5 upper limit of normal values and performance status 0-2 to alternately receive gemcitabine + nab-paclitaxel for 2 months then FOLFIRI.3 for 2 months in arm A, or gemcitabine + nab-paclitaxel alone until progression in arm B. The primary objective was to increase the 6-month progression-free survival (PFS) rate from 40% (H0) to 60% (H1); using the binomial exact method, 124 patients were required. Analyses were carried out in preplanned modified intention-to-treat (mITT) and per-protocol (PP) populations. RESULTS: Between November 2015 and November 2016, 127 patients were enrolled. Main grade III-IV toxicities (% in arm A/B) were: diarrhoea (12.5/1.7), neutropenia (46.9/31, including febrile neutropenia: 1.6/0), skin toxicity (6.3/13.8), and peripheral neuropathy (6.3/8.6). No toxic deaths occurred. The objective response rate was 40.3% (95% confidence interval [CI]: 28.1-53.6) in arm A and 26.7% (95% CI: 16.1-39.7) in arm B. The primary end-point (6-month PFS rate) was 45.2% [one-sided 95% CI: 34.3-56.4] in arm A and 23.3% in arm B [one-sided 95% CI: 14.3-32.3] in the mITT population. In the PP population, median PFS and OS were 7.6 months and 6 months and 14.5 months and 12.2 months in arm A and B, respectively. CONCLUSIONS: The FIRGEMAX strategy with gemcitabine + nab-paclitaxel alternating with FOLFIRI.3 every 2 months, appears feasible and effective, with manageable toxicities, in patients able to reach >2mo of treatment. TRIAL REGISTRATION INFORMATION: EudraCT: 2014-004449-28: NCT: 0282701.