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ABSTRACT: BACKGROUND:: Although a randomized trial demonstrated a survival benefit of cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) over systemic chemotherapy alone, the treatment of peritoneal carcinomatosis from colorectal cancer (CRPC) is still a matter of debate. The aims of this study were to evaluate long-term outcome after CRS and IPC and to identify the prognostic factors associated with a cure. METHODS:: Patients were considered cured if the disease-free survival interval lasted at least 5 years after the treatment of CRPC or its last recurrence. Patients who had died postoperatively, or from non-cancer-related deaths, or patients with a follow-up of less than 5 years since the last curative treatment were excluded from the analysis. RESULTS:: From 1995 to 2006, 107 patients (median age, 48 years; range, 19-67 years) underwent complete CRS, followed by IPC. Postoperative complications occurred in 50 patients (53%), including 4 postoperative deaths. After a median follow-up of 77 months (range, 60-144 months), 5-year and 10-year overall survival rates were 35% and 15%, respectively. Seventeen patients (16%) were considered cured after a disease-free interval of at least 5 years, of whom 14 never developed a recurrence. Cured patients had a significantly lower median peritoneal cancer index than noncured patients, respectively 4 (3-16) and 12 (2-36) (P = 0.0002). In multivariate analysis, a peritoneal cancer index of 10 or less was the only independent factor predicting cure. CONCLUSIONS:: The cure rate (16%) after complete CRS of colorectal peritoneal carcinomatosis, followed by IPC, in selected patients is close to that obtained after resection of colorectal liver metastases.
Annals of surgery 01/2013; · 7.90 Impact Factor
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Diane Goéré,
Léonor Benhaim,
Stéphane Bonnet,
David Malka,
Matthieu Faron,
Dominique Elias,
Jérémie H Lefèvre,
Frédéric Deschamps,
Clarisse Dromain, Valérie Boige,
Frédéric Dumont,
Thierry De Baere,
Michel Ducreux
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ABSTRACT: : After curatively intended surgery for colorectal liver metastases, liver recurrences occur in more than 60% of patients, despite the administration of adjuvant systemic chemotherapy. The aim of this study was to assess the benefit of combined adjuvant hepatic arterial infusion (HAI) and intravenous (IV) 5-FU compared with standard modern adjuvant IV chemotherapy in patients at high risk of hepatic recurrence.
: From January 2000 to December 2009, 98 patients, who had undergone curative resection of at least 4 colorectal liver metastases, were selected from a prospective database. Among them, 44 (45%) had received postoperative HAI combined with systemic 5-FU (HAI group) and 54 (55%) had received "modern" systemic chemotherapy (IV group).
: The 2 groups were similar in terms of age, sex, the stage of the primary, and the administration of preoperative chemotherapy. The median number of HAI cycles received per patient was 7 [range, 1-12]. Twenty-nine patients (66%) had received at least 6 cycles of HAI oxaliplatin, and 22 patients (50%) had received the full planned treatment. For the remaining 22 patients (50%), HAI chemotherapy had been discontinued because of toxicity (n = 8), HAI catheter dysfunction (n = 6), an early recurrence (n = 6), and patient's refusal (n = 2). After a median follow-up of 60 months (51-81 months), 3-year overall survival was slightly higher in the HAI group (75% vs 62%, P = 0.17). Three-year disease-free survival was significantly longer in patients in the HAI group than those in the IV group (33% vs 5%, P < 0.0001). In the multivariate analysis, adjuvant HAI chemotherapy and an R0 resection margin status were the only independent predictive factors for prolonged disease-free survival.
: Postoperative HAI oxaliplatin combined with systemic chemotherapy after curatively intended surgery of colorectal liver metastases is feasible and may significantly improve disease-free survival of patients at high risk of hepatic recurrence compared with adjuvant modern systemic chemotherapy alone. These results should be confirmed in a randomized study.
Annals of surgery 01/2013; 257(1):114-20. · 7.90 Impact Factor
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Sophie Gourgou-Bourgade,
Caroline Bascoul-Mollevi,
Françoise Desseigne,
Marc Ychou,
Olivier Bouché,
Rosine Guimbaud,
Yves Bécouarn,
Antoine Adenis,
Jean-Luc Raoul, Valérie Boige,
Jocelyne Bérille,
Thierry Conroy
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ABSTRACT: PURPOSETo compare the quality of life (QoL) of patients receiving oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) or gemcitabine as first-line chemotherapy and to assess whether pretreatment QoL predicts survival in patients with metastatic pancreatic cancer.Patients And methodsThree hundred forty-two patients with performance status 0 or 1 were randomly assigned to receive FOLFIRINOX (oxaliplatin, 85 mg/m(2); irinotecan, 180 mg/m(2); leucovorin, 400 mg/m(2); and fluorouracil, 400 mg/m(2) bolus followed by 2,400 mg/m(2) 46-hour continuous infusion, once every 2 weeks) or gemcitabine 1,000 mg/m(2) weekly for 7 of 8 weeks and then weekly for 3 of 4 weeks. QoL was assessed using European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire C30 every 2 weeks.ResultsImprovement in global health status (GHS; P < .001) was observed in the FOLFIRINOX arm and improvement in emotional functioning (P < .001) was observed in both arms, along with a decrease in pain, insomnia, anorexia, and constipation in both arms. A significant increase in diarrhea was observed in the FOLFIRINOX arm during the first 2 months of chemotherapy. Time until definitive deterioration ≥ 20 points was significantly longer for FOLFIRINOX compared with gemcitabine for GHS, physical, role, cognitive, and social functioning, and six symptom domains (fatigue, nausea/vomiting, pain, dyspnea, anorexia, and constipation). Physical functioning, constipation, and dyspnea were independent significant prognostic factors for survival with treatment arm, age older than 65 years, and low serum albumin. CONCLUSIONFOLFIRINOX significantly reduces QoL impairment compared with gemcitabine in patients with metastatic pancreatic cancer. Furthermore, baseline QoL scores improved estimation of survival probability when added to baseline clinical and demographic variables.
Journal of Clinical Oncology 12/2012; · 18.37 Impact Factor
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Aziz Zaanan,
Nicolas Williet,
Mohamed Hebbar,
Tienhan Sandrine Dabakuyo,
Laetitia Fartoux,
Touraj Mansourbakht,
Olivier Dubreuil,
Olivier Rosmorduc,
Stéphane Cattan,
Franck Bonnetain, Valérie Boige,
Julien Taïeb
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ABSTRACT: BACKGROUND & AIMS: The current standard treatment for advanced hepatocellular carcinoma (HCC) is sorafenib. This drug is effective but generally does not induce tumor shrinkage and other treatment options are still needed. METHODS: This retrospective multicenter study included all consecutive patients with advanced HCC treated with gemcitabine and oxaliplatin (GEMOX) between 2001 and 2010. Survival curves were drawn with the Kaplan-Meier method and compared with the log-rank test. Univariate and multivariate analyses were used to evaluate prognostic factors. RESULTS: Two hundred four consecutive patients were treated with GEMOX (median age, 60years; men, 86%; underlying cirrhosis, 76%). Grade 3-4 toxicity was observed in 44% of the patients (thrombocytopenia 24%, neutropenia 18%, diarrhea 14%, neurotoxicity 12%) leading to treatment discontinuation in 16% of the cases. The overall response and disease control rates were 22% (95% CI, 16-27) and 66% (95% CI, 59-72), respectively. No clinical or biological factors were associated with the treatment response, and 8.5% of the patients were subsequently eligible for curative-intent therapies after downstaging. Median PFS, TTP, and OS were 4.5 (95% CI, 4-6), 8 (95% CI, 6-11), and 11months (95% CI, 9-14), respectively. In multivariate analysis, gender (p=0.03), underlying cirrhosis (p=0.01), CLIP score (p=0.03), and response to GEMOX (p<0.0001) were independently associated with OS. CONCLUSIONS: This large study confirms that GEMOX is effective with manageable toxicity in patients with advanced HCC. Tumor responses permitted potentially curative treatment that was not initially feasible in a significant proportion of patients.
Journal of Hepatology 09/2012; · 9.26 Impact Factor
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Valérie Boige,
David Malka,
Abderrahmane Bourredjem,
Clarisse Dromain,
Charlotte Baey,
Nathalie Jacques,
Jean-Pierre Pignon,
Nadege Vimond,
Nathalie Bouvet-Forteau,
Thierry De Baere,
Michel Ducreux,
Françoise Farace
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ABSTRACT: Hepatocellular carcinoma (HCC) is a highly vascularized tumor in which neoangiogenesis contributes to growth and metastasis. We assessed the safety, efficacy, and potential biomarkers of activity of bevacizumab in patients with advanced HCC.
In this phase II trial, eligible patients received bevacizumab, 5 mg/kg or 10 mg/kg every 2 weeks. The disease-control rate at 16 weeks (16W-DCR) was the primary endpoint. Circulating endothelial cells (CECs) and plasma cytokines and angiogenic factors (CAFs) were measured at baseline and throughout treatment.
The 16W-DCR was 42% (95% confidence interval, 27%-57%). Six of the 43 patients who received bevacizumab achieved a partial response (objective response rate [ORR], 14%). Grade 3-4 asthenia, hemorrhage, and aminotransferase elevation occurred in five (12%), three (7%), and three (7%) patients, respectively. During treatment, placental growth factor markedly increased, whereas vascular endothelial growth factor (VEGF)-A dramatically decreased (p < .0001); soluble VEGF receptor-2 (p < .0001) and CECs (p = .03) transiently increased on day 3. High and increased CEC counts at day 15 were associated with the ORR (p = .04) and the 16W-DCR (p = .02), respectively. Lower interleukin (IL)-8 levels at baseline (p = .01) and throughout treatment (p ≤ .04) were associated with the 16W-DCR. High baseline IL-8 and IL-6 levels predicted shorter progression-free and overall survival times (p ≤ .04).
Bevacizumab is active and well tolerated in patients with advanced HCC. The clinical value of CECs, IL-6, and IL-8 warrants further investigation.
The Oncologist 06/2012; 17(8):1063-72. · 3.91 Impact Factor
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Boris Guiu,
Frédéric Deschamps,
Serge Aho,
Flore Munck,
Clarisse Dromain, Valérie Boige,
David Malka,
Sophie Leboulleux,
Michel Ducreux,
Martin Schlumberger,
Eric Baudin,
Thierry de Baere
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ABSTRACT: Transarterial chemoembolisation (TACE) is usually performed by injecting an emulsion of a drug and iodised oil. Drug-eluting beads (DEBs) have undeniable pharmacological advantages by offering simultaneous embolisation and sustained release of the drug to the tumour. No data are currently available on liver/biliary injury following DEB-TACE. This study describes and compares liver/biliary injuries encountered with TACE in tumours developed in cirrhotic (hepatocellular carcinoma (HCC)) and non-cirrhotic (endocrine tumours (NETs)) livers.
In consecutive patients treated for a well-differentiated metastatic NET (n=120) or a HCC (n=88), 684 CT- and MR-scans were analysed. Liver/biliary injuries were classified as follows: dilated bile duct, portal vein narrowing, portal venous thrombosis and biloma/liver infarct. A generalised estimating equation logistic regression model was used.
A liver/biliary injury followed 17.2% (82/476) of sessions in 30.8% (64/208) of patients. The occurrence of liver/biliary injury was associated with DEB-TACE (OR=6.63; p<0.001) irrespectively of the tumour type. Biloma/parenchymal infarct was strongly associated with both DEB-TACE (OR=9.78; p=0.002) and NETs (OR: 8.13; p=0.04). Biloma/liver infarcts were managed conservatively but were associated with an increase in serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatases, and gamma glutamyl transpeptidase (p=0.005, p=0.005, p=0.012, and p=0.006, respectively).
Liver/biliary injuries are independently associated with DEB-TACE. Biloma/liver infarct, the most serious injury, is independently associated with both DEB-TACE and NETs. The absence of such an association in TACE of HCC may be explained by the hypertrophied peribiliary plexus observed in cirrhosis, which protects against the ischemic/chemical insult of bile ducts. We suggest caution when using DEB-TACE in the non-cirrhotic liver.
Journal of Hepatology 03/2012; 56(3):609-17. · 9.26 Impact Factor
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ABSTRACT: The only currently validated treatment for advanced hepatocellular carcinoma (HCC) is sorafenib. However, sorafenib has been mainly studied in patients with HCC developed in cirrhotic liver. Chemotherapy might be more suitable for patients with HCC in non-cirrhotic liver. We report the case of a young woman with fibrolamellar HCC in a non-cirrhotic liver, with histologically proven metastatic ganglionary relapse after surgical resection of the primary tumour. Chemotherapy with gemcitabine and oxaliplatin (GEMOX regimen) achieved a complete response without relapse five years after discontinuation of chemotherapy. This exceptional case raises the question of clinical trials specifically designed for patients with HCC in non-cirrhotic liver.
Case Reports in Oncology 01/2012; 5(1):169-72.
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Gut 12/2011; 61(5):637-8. · 10.11 Impact Factor
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ABSTRACT: An Asian study showed that gamma glutamyl transpeptidase (GGT) can predict survival after transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC). This study was designed to validate in a European population this biomarker as an independent predictor of outcome after TACE of HCC and to determine a threshold value for clinical use.
In 88 consecutive patients treated by TACE for HCC, the optimal threshold for GGT serum level was determined by a ROC analysis. Endpoints were time-to-treatment failure (TTTF) and overall survival (OS). All multivariate models were internally validated using bootstrapping (90 replications).
Median follow-up lasted 373 days, and median overall survival was 748 days. The optimal threshold for GGT was 165 U/L (sensitivity: 89.3%; specificity: 56.7%; area under the ROC curve: 0.7515). Median TTTF was shorter when GGT was ≥165 U/L (281 days vs. 850 days; P < 0.001). GGT ≥165 U/L (hazard ratio (HR) = 2.06; P = 0.02), WHO PS of 2 (HR = 5.4; P = 0.002), and tumor size (HR = 1.12; P = 0.014) were independently associated with shorter TTTF. Median OS was shorter when GGT was ≥165 U/L (508 days vs. not reached; P < 0.001). GGT ≥ 165 U/L (HR = 3.05; P = 0.029), WHO PS of 2 (HR = 12.95; P < 0.001), alfa-fetoprotein (HR = 2.9; P = 0.01), and tumor size (HR = 1.096; P = 0.013) were independently associated with shorter OS. The results were confirmed by bootstrapping.
Our results provide in a European population the external validation of GGT as an independent predictor of outcome after TACE of HCC. A serum level of GGT ≥ 165 U/L is independently associated with both shorter TTTF and OS.
CardioVascular and Interventional Radiology 10/2011; 35(5):1102-8. · 2.09 Impact Factor
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Marc Ychou, Valérie Boige,
Jean-Pierre Pignon,
Thierry Conroy,
Olivier Bouché,
Gilles Lebreton,
Muriel Ducourtieux,
Laurent Bedenne,
Jean-Michel Fabre,
Bernard Saint-Aubert,
Jean Genève,
Philippe Lasser,
Philippe Rougier
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ABSTRACT: After curative resection, the prognosis of gastroesophageal adenocarcinoma is poor. This phase III trial was designed to evaluate the benefit in overall survival (OS) of perioperative fluorouracil plus cisplatin in resectable gastroesophageal adenocarcinoma.
Overall, 224 patients with resectable adenocarcinoma of the lower esophagus, gastroesophageal junction (GEJ), or stomach were randomly assigned to either perioperative chemotherapy and surgery (CS group; n = 113) or surgery alone (S group; n = 111). Chemotherapy consisted of two or three preoperative cycles of intravenous cisplatin (100 mg/m(2)) on day 1, and a continuous intravenous infusion of fluorouracil (800 mg/m(2)/d) for 5 consecutive days (days 1 to 5) every 28 days and three or four postoperative cycles of the same regimen. The primary end point was OS.
Compared with the S group, the CS group had a better OS (5-year rate 38% v 24%; hazard ratio [HR] for death: 0.69; 95% CI, 0.50 to 0.95; P = .02); and a better disease-free survival (5-year rate: 34% v 19%; HR, 0.65; 95% CI, 0.48 to 0.89; P = .003). In the multivariable analysis, the favorable prognostic factors for survival were perioperative chemotherapy (P = .01) and stomach tumor localization (P < .01). Perioperative chemotherapy significantly improved the curative resection rate (84% v 73%; P = .04). Grade 3 to 4 toxicity occurred in 38% of CS patients (mainly neutropenia) but postoperative morbidity was similar in the two groups.
In patients with resectable adenocarcinoma of the lower esophagus, GEJ, or stomach, perioperative chemotherapy using fluorouracil plus cisplatin significantly increased the curative resection rate, disease-free survival, and OS.
Journal of Clinical Oncology 03/2011; 29(13):1715-21. · 18.37 Impact Factor
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The lancet oncology 12/2010; 11(12):1110-2. · 14.47 Impact Factor
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ABSTRACT: To investigate whether there is any correlation between standard efficacy endpoints-specifically, tumor response, progression-free survival, and overall survival-and tumor perfusion parameters measured by using dynamic contrast material-enhanced ultrasonography (US) in patients with advanced hepatocellular carcinoma (HCC) treated with bevacizumab.
The institutional review board approved the study, and all patients provided written informed consent before their enrollment. Between June 3, 2005, and September 28, 2007, 42 patients (33 men, nine women; median age, 62 years; age range, 23-84 years) participated in this phase II study of single-agent bevacizumab treatment. Tumor response (based on RECIST [response evaluation criteria in solid tumors]) at 2 months was assessed in 37 patients, and progression-free survival and overall survival were assessed in all 42 patients. Dynamic contrast-enhanced US (ie, dynamic US) was performed before treatment (day 0); on days 3, 7, 14, and 60 after treatment; and every 2 months thereafter. Tumor perfusion parameters were estimated quantitatively from contrast material uptake curves constructed from raw linear data. The changes in dynamic US functional parameters between day 0 and the later time points were compared between treatment responders and nonresponders by using nonparametric tests. Given multiple comparisons, P < .001 indicated significance.
The percentage decrease in several dynamic US parameters between day 0 and day 3 showed trends toward correlation with (a) tumor response in terms of total area under the time-intensity curve (AUC) (P = .02), AUC during wash in (P = .04), AUC during washout (P = .02), and time to peak intensity (P = .03); (b) progression-free survival in terms of time to peak intensity (P = .028); and (c) overall survival in terms of AUC (P = .002) and AUC during washout (P = .003).
Dynamic US can be used to quantify dynamic changes in tumor vascularity as early as 3 days after bevacizumab administration in patients with HCC. These early changes in tumor perfusion may be predictive of tumor response at 2 months, progression-free survival, and overall survival, and they may be potential surrogate measures of the effectiveness of antiangiogenic therapy in patients with HCC.
Radiology 10/2010; 258(1):291-300. · 5.73 Impact Factor
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Geraldine Perkins,
Astrid Lièvre,
Carole Ramacci,
Tchao Méatchi,
Aurélien de Reynies,
Jean-François Emile, Valérie Boige,
Gorana Tomasic,
Jean-Baptiste Bachet,
Fréderic Bibeau,
Olivier Bouché,
Frédérique Penault-Llorca,
Jean-Louis Merlin,
Pierre Laurent-Puig
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ABSTRACT: KRAS mutations are a strong predictive marker of resistance to anti-epidermal growth factor receptor (EGFR) antibodies in advanced colorectal cancer (CRC) but only a subset of wild-type (WT) KRAS patients are responders, suggesting the existence of additional markers of resistance to this treatment. The activation of EGFR downstream signaling pathways may be one of these ones. In a series of 42 patients with advanced CRC treated with cetuximab/panitumumab, for whom KRAS status was previously determined, we retrospectively analyzed the intratumor expression of EGFR downstream signaling phosphoproteins of the RAS/MAPK and PI3K/AKT pathways (pERK1/2, pMEK1, pAKT, pP70S6K and pGSK3beta) using Bio-Plex phosphoprotein array. Association with tumor response, progression-free survival (PFS) and overall survival (OS) was assessed. The expression of all the phosphoproteins was higher in KRAS mutated tumors than in WT tumors. The expression of pP70S6K was lower in responders than in nonresponder patients. In univariate analysis, patients with high pMEK1 or pP70S6K expression had a shorter PFS than those with low expression. Patients with high pP70S6K expression also had a shorter OS. In multivariate analysis, PFS was shorter for patients with high pMEK1 or pP70S6K expression, independently of KRAS status, as OS for patients with high pP70S6K expression. Therefore, WT KRAS patients with high pP70S6K expression had a shorter survival than those with low expression. Our results suggest the importance of EGFR downstream signaling phosphoproteins expression in addition to KRAS status to define the subgroup of patients who will not benefit from anti-EGFR therapy.
International Journal of Cancer 09/2010; 127(6):1321-31. · 5.44 Impact Factor
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Valérie Boige,
Jean Mendiboure,
Jean-Pierre Pignon,
Marie-Anne Loriot,
Marine Castaing,
Michel Barrois,
David Malka,
David-Alexandre Trégouët,
Olivier Bouché,
Delphine Le Corre,
Isabelle Miran,
Claire Mulot,
Michel Ducreux,
Philippe Beaune,
Pierre Laurent-Puig
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ABSTRACT: The aim was to investigate whether germline polymorphisms within candidate genes known or suspected to be involved in fluorouracil (FU), oxaliplatin, and irinotecan pathways were associated with toxicity and clinical outcome in patients with metastatic colorectal cancer (mCRC).
Blood samples from 349 patients included in the Fédération Francophone de Cancérologie Digestive 2000-05 randomized trial, which compared FU plus leucovorin (LV5FU2) followed by FU, leucovorin, and oxaliplatin (FOLFOX) followed by FU, leucovorin, and irinotecan (FOLFIRI; sequential arm) with FOLFOX followed by FOLFIRI (combination arm) in terms of progression-free survival (PFS) and overall survival, were collected. Twenty polymorphisms within the DPD, TS, MTHFR, ERCC1, ERCC2, GSTP1, GSTM1, GSTT1, and UGT1A1 genes were genotyped.
The ERCC2-K751QC allele was independently associated with an increased risk of FOLFOX-induced grade 3 or 4 hematologic toxicity (P = .01). In the sequential arm, TS-5'UTR3RG and GSTT1 alleles were independently associated with response to LV5FU2 (P = .009) and FOLFOX (P = .01), respectively. The effect of oxaliplatin on tumor response increased with the number of MTHFR-1298C alleles (test for trend, P = .008). The PFS benefit from first-line FOLFOX was restricted to patients with 2R/2R (hazard ratio [HR] = 0.39; 95% CI, 0.23 to 0.68) or 2R/3R (HR = 0.59; 95% CI, 0.42 to 0.82) TS-5'UTR genotypes, respectively. Conversely, patients with the TS-5'UTR 3R/3R genotype did not seem to benefit from the adjunction of oxaliplatin (HR = 0.96; 95% CI, 0.66 to 1.40; trend between the three HRs, P = .006).
A pharmacogenetic approach may be a useful strategy for personalizing and optimizing chemotherapy in mCRC patients and deserves confirmation in additional prospective studies.
Journal of Clinical Oncology 04/2010; 28(15):2556-64. · 18.37 Impact Factor
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ABSTRACT: The aim of this study was to analyze the impact of hepatic arterial infusion (HAI) of oxaliplatin with systemic 5-Fluorouracil and leucovorin on patients with isolated unresectable liver metastases.
A total of 87 patients treated in our hospital with HAI of oxaliplatin with systemic 5-Fluorouracil and leucovorin for isolated unresectable colorectal liver metastases from May 1999 to May 2007 were extracted from a prospective database and analyzed. The resectability rate, perioperative findings, postoperative outcomes, and long-term follow-up were evaluated.
HAI was delivered after failure of previous systemic chemotherapy in 69 patients (79%). The main criterion for unresectability was massive liver involvement (86% of patients). Most patients had synchronous (85%), bilateral metastases (89%). The median number of HAI courses was 8 (0-25). About 31 patients experienced technical catheter-related problems, which were responsible for withdrawal of HAI in only 7 patients (8%). Finally, a total of 23 patients (26%) were operated on, and resection or radiofrequency ablation was performed in 21 patients (24%). No postoperative mortality was observed and the morbidity rate was 35%. Five-year overall survival was 56% in the surgery group versus none in the nonsurgery group (P < 0.0001). After a median follow-up of 63 months, intrahepatic recurrence occurred in 10 patients among the 23 operated patients.
HAI of oxaliplatin with systemic 5-Fluorouracil and leucovorin offers a second chance to remove initially unresectable isolated colorectal liver metastases in 24% of patients, and appears to be more efficient when performed as first-line therapy. Long-term overall survival can be obtained with this approach.
Annals of surgery 03/2010; 251(4):686-91. · 7.90 Impact Factor
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Pierre Laurent-Puig,
Anne Cayre,
Gilles Manceau,
Emmanuel Buc,
Jean-Baptiste Bachet,
Thierry Lecomte,
Philippe Rougier,
Astrid Lievre,
Bruno Landi, Valérie Boige,
Michel Ducreux,
Marc Ychou,
Fréderic Bibeau,
Olivier Bouché,
Julia Reid,
Steven Stone,
Frédérique Penault-Llorca
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ABSTRACT: The occurrence of KRAS mutation is predictive of nonresponse and shorter survival in patients treated by anti-epidermal growth factor receptor (anti-EGFR) antibody for metastatic colorectal cancer (mCRC), leading the European Medicine Agency to limit its use to patients with wild-type KRAS tumors. However, only half of these patients will benefit from treatment, suggesting the need to identify additional biomarkers for cetuximab-based treatment efficacy.
We retrospectively collected tumors from 173 patients with mCRC. All but one patient received a cetuximab-based regimen as second-line or greater therapy. KRAS and BRAF status were assessed by allelic discrimination. EGFR amplification was assessed by chromogenic in situ hybridization and fluorescent in situ hybridization, and the expression of PTEN was assessed by immunochemistry.
In patients with KRAS wild-type tumors (n = 116), BRAF mutations (n = 5) were weakly associated with lack of response (P = .063) but were strongly associated with shorter progression-free survival (P < .001) and shorter overall survival (OS; P < .001). A high EGFR polysomy or an EGFR amplification was found in 17.7% of the patients and was associated with response (P = .015). PTEN null expression was found in 19.9% of the patients and was associated with shorter OS (P = .013). In multivariate analysis, BRAF mutation and PTEN expression status were associated with OS.
BRAF status, EGFR amplification, and cytoplasmic expression of PTEN were associated with outcome measures in KRAS wild-type patients treated with a cetuximab-based regimen. Subsequent studies in clinical trial cohorts will be required to confirm the clinical utility of these markers.
Journal of Clinical Oncology 11/2009; 27(35):5924-30. · 18.37 Impact Factor
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Nature Clinical Practice Oncology 04/2009; 6(3):180. · 8.00 Impact Factor
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ABSTRACT: Hyperthermic intraperitoneal chemotherapy (HIPEC) after complete surgical resection is currently accepted as a therapeutic option for peritoneal carcinomatosis. However, considerable morbidity is reported after HIPEC.
We aimed to evaluate the impact of HIPEC on the quality of life (QoL) of survivors without recurrences of disease according to socio-demographic and medical variables. For that purpose, HIPEC was used as a global concept including the surgical procedure effects.
A cross-sectional study was performed by analyzing questionnaires concerning socio-demographic data, the psychological status, and general and specific QoL scores.
Sixty-eight patients (86% of those contacted) completed and returned mailed questionnaires. For 19/21 QoL dimensions explored, survivors reported good to very good QoL with a median score >/=67%. The two adversely affected dimensions were future prospects and sexual functioning with a mean score of 57% and 23%, respectively. The burden of carcinomatosis, evaluated by a peritoneal index, was not correlated with statistically identified sequels in QoL. The extent of morbidity due to HIPEC, evaluated by the hospital stay, was statistically correlated with only one score, namely, embarrassment during social activities (p = 0.01) but not during familial life.
Even though HIPEC is considered as an aggressive treatment, survivors reported good to very good QoL. However, specific care for the psychological aspect, as reflected by anxiety regarding future prospects and sexual activity, needs to be developed for survivors.
Supportive Care in Cancer 02/2009; 17(10):1255-61. · 2.09 Impact Factor
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ABSTRACT: Regarding the evolution of the treatments of colorectal cancer during the last five years, it appears that numerous questions have to be considered with a strategic point of view. In order to avoid inclusion of a lot of patients in clinical patients, we urgently need the help of biology to give us arguments to choose one treatment or another. The fact that ten years after their approval, we are not able to select responders to oxaliplatin or irinotecan, confirm that this is difficult problem to solve. The contribution of biology to the prescription of drugs commonly used in colorectal cancer is discussed in this paper. There are already situations where the contribution of biology to clinical practice and prescription is not debatable : this is the case for the use of UGT1A1 status determination when using irinotecan and the determination of KRAS status for the prescription of panitumumab (and cetuximab in a few months). This individual adaptation is a dream that becomes reasonable when we look on the recent results concerning EGFR inhibitors, but a lot of work has to be done and it is not sure that biological assessment of the tumour will be able to solve all the problems. For instance, to determine predictive factors of response to angiogenesis inhibitors, it is likely that solutions will come from new techniques of imaging rather than from biology. However, new tools such as proteomics or metabolomics, as well as a better dialogue between clinician and biologist, will allow fast improvements. It must be emphasised that, for the first time in 2008, it is possible to prescribe targeted therapies to a specific "targeted" group of patients with metastatic colorectal cancer.
Bulletin du cancer 11/2008; 95(10):931-4. · 0.67 Impact Factor
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ABSTRACT: To prospectively evaluate the technical feasibility, effectiveness, and complications of percutaneous radiofrequency (RF) ablation for hepatic malignancies during temporary percutaneous balloon occlusion (PBO) of a large hepatic or portal vein.
During a 4-year period, RF ablation was performed in 201 patients (106 men, 95 women; age range, 41-88 years) with 233 liver tumors. Institutional review board approval was obtained to attempt RF ablation during PBO for 18 tumors that were larger than 35 mm (mean, 43 mm +/- 7.6 [standard deviation]; range, 36-60 mm) and did not abut a portal or hepatic vein 4 mm in diameter or larger (group 1), 58 tumors 35 mm or smaller (mean, 23 mm +/- 7.3; range, 12-35 mm) that abutted a large vessel (group 2), and 20 tumors that were both larger than 35 mm (mean, 42 mm +/- 5.7; range, 38-50 mm) and abutted a large vessel (group 3). RF ablation without PBO was performed for 137 tumors 35 mm or smaller (mean, 22 mm +/- 6.8; range, 9-35 mm) and remote from large vessels (group 4). Rate of local tumor progression was estimated with the Kaplan-Meier method, and tumor progression-free rates were compared between the four groups with the log-rank test. Complications were compared by using the Fisher exact test between the four groups and between the two RF devices used.
PBO was achieved in 94 of 96 attempts (98%), including 64 of 64 hepatic veins and 30 of 32 portal branches. After a mean follow-up of 18 months +/- 9, 10 tumors in eight patients were lost to follow-up. Local tumor progression was observed in six (40%) of 15 tumors in group 1, in six (11%) of 56 tumors in group 2, in eight (40%) of 20 tumors in group 3, and in 12 (9%) of 130 tumors in group 4. Combined analysis of tumor size and the use of PBO showed that size was the only prognostic factor for tumor progression, with a hazard ratio of 4.9 (95% confidence interval: 2.4, 9.9) (P < .001). There were no differences between groups 2 and 4. Asymptomatic, transient postprocedure venous thrombosis was seen in nine of 94 RF ablations with PBO, while occlusion of one permanent portal branch induced segmental liver atrophy. There were no differences in rates of complications (5% and 6% for RF ablation with and that without PBO, respectively).
RF ablation with PBO provides tumor control for tumors smaller than 35 mm in diameter that abut vessels 4 mm or larger, equivalent to tumor control of the same-size tumors away from vessels. PBO does not seem to affect the results of RF ablation for tumors 35 mm or larger.
Radiology 09/2008; 248(3):1056-66. · 5.73 Impact Factor
