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Valérie Boige

Publications and source records attributed to Valérie Boige.

At least 37 records · Page 2Linked to original sources
PubMed2005

Hepatectomy plus intraoperative radiofrequency ablation and chemotherapy to treat technically unresectable multiple colorectal liver metastases.

BACKGROUND: Results and indications of intra-operative radiofrequency (RF) ablation of liver metastases (LM) are not well defined in the literature. AIM: To appreciate the survival rate of patients with strictly unresectable LM (defined on technical but not oncological criteria) when undergoing liver resection plus RF, along with optimal systemic chemotherapy. PATIENTS AND METHODS: Sixty three patients with technically unresectable LM (either >5, or bilateral with no sparing of at least one sector of the liver, or with tumor proximity to central major vascular structures) were treated. Extrahepatic metastases were also resected in 27% of patients. All patients received perioperative chemotherapy. The median follow-up was 27.6 months (range: 15-74). RESULTS: There was no postoperative mortality and the morbidity rate was 27%. The 2-year overall survival rate of the 63 patients was 67% with a median survival of 36 months. The local recurrence rates were similar for the three types of local treatments: 7.1% for the 154 RF ablations, 7.2% for the 55 wedge resections, and 9% for the 44 segmental anatomic resections (P = 0.216). Hepatic recurrences occurred in 71% of patients. CONCLUSION: The combination of anatomic segmental and wedge resections, RF ablation, and optimal chemotherapy in patients with technically unresectable LM results in a median survival of 36 months.

Adult↗
PubMed2005

Ex vivo sentinel lymph node study for rectal adenocarcinoma: preliminary study.

Intraoperative sentinel lymph node (SLN) detection has been reported for colon cancer, but no study has focused on rectal cancer. Only an ex vivo technique can be performed easily in this location. We evaluated SLN detection using blue dye injection in patients with rectal adenocarcinoma. This prospective study included 31 patients. Preoperative radiotherapy (45 Gy) was done in 15 cases. After proctectomy the surgical specimen was examined in the operating room. Submucosal peritumoral injections were done. One to three SLNs were retrieved. The SLNs were sectioned at three levels and examined histologically and then, if negative by hematoxylin-eosin (H&E) staining and immunohistochemistry (IHC). There were 7 abdominoperineal resections, 12 colorectal anastomoses, 11 coloanal anastomoses, and 1 Hartmann procedure. The median number of lymph nodes harvested was 21 (7-38). A SLN was identified in 30 cases (feasibility 97%). The mean number of SLNs was 2 (0-3). A micrometastasis was discovered in 3 of 23 pNO cases when H&E was used on multisection levels, thus changing the stage to pN1. Each time the only positive lymph node was the SLN. IHC evaluation did not change the result, as only isolated tumor cells were discovered in one case. Only four of seven N+ patients had a positive SLN, resulting in a false-negative rate of 43%. Ex vivo detection of SLNs is possible for rectal cancer and is a simple technique. Classic analysis using H&E remains the gold standard. However, SLNs detection can change the tumor stage by upstaging nearly 15% of the tumors from T2-3N0 to T2-3 N+.

Adenocarcinoma↗
PubMed2005

Cutaneous side-effects of kinase inhibitors and blocking antibodies.

Although kinase inhibitors raise hope for people with cancer, patients and their clinicians are commonly confronted with the cutaneous side-effects that are associated with the use of these drugs. This review is the result of collaborations between dermatologists, medical oncologists, and pathologists, and discusses the cutaneous side-effects seen after treatment with the inhibitors of epidermal-growth-factor receptor (EGFR), imatinib, sorafenib, and sunitinib. Some of the side-effects caused by these agents are very distressing, partly because they are chronic owing to the long duration of treatment. Therefore, patients need early and appropriate dermatological management. Moreover, several studies have reported a link between the antitumour efficacy of EGFR inhibitors and cutaneous side-effects. Elucidation of this connection could lead to the identification of crucial predictive factors for tumour response.

Antibodies, Blocking↗
PubMed2005

[Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal colorectal carcinomatosis: a newly validated standard whose contribution remains to be assessed].

Peritoneal carcinomatosis represent an advanced form of colorectal cancer but different of others metastatic pathways. However carcinomatosis was associated with stage M in the TNM classification, because of a very poor prognosis, actually resulting despite new chemotherapeutic agents of a single year of survival. In an estimated 30% of patients, no other tumour location can be found. Usually complete tumour resection can not be perform, resulting in the best time with a R1 procedure associated with microscopic residual disease. This is to eradicate microscopic residual disease that hyperthermic intraperitoneal chemotherapy (HIPEC) was proposed. First results of single unit published reported survival after 5 years and that the most important prognosis factor of survival was complete resection of the carcinomatosis (R1 resection). A phase III study publish in 2003 in the Journal of Surgical Oncology by the Zoetmulder's team confirm the phase II results and offer for the first time a factual impact with a level II of demonstration. Between 1998 and 2001, 105 patients were randomly assigned to receive either standard treatment consisting of systemic chemotherapy (fluorouracil-leucovorin) or aggressive cytoreduction (incomplete for some patients) with HIPEC (mitomycin C during 90 minutes) followed by the same systemic chemotherapy regime. In the HIPEC arms, mortality was at 8 % and the median hospital admission was near one month. After a median follow-up period of 21 months, the median survival was 12 months in the standard therapy arm and 22 months in the HIPEC arm (p = 0.032). These results confirm prior reported non randomised study reporting median survival of 12 to 40 months. We had recently published the results of a phase II study including only patient with a R1 resection associated with HIPEC with oxaliplatin. This study had include 24 patients with an overall survival of 65% at 3 years. These survival result was the most prolonged never reported in the treatment of peritoneal colorectal carcinomatosis. HIPEC can be considered as a new standard even the exact place in clinical practice had to be more define because of alls recent progress are publish giving an important number of publications during the 2003-2004 years, some of them coming from French groups.

Carcinoma↗
PubMed2005

[Therapeutic strategies using VEGF inhibitors in colorectal cancer].

Angiogenesis, a complex, coordinated process resulting in the assembly and maturation of new blood vessels, is critical for the growth of tumors. Several lines of evidence argue for angiogenesis inhibition in the treatment of colorectal cancer (CRC) : 1) angiogenesis (as measured by microvessel count), and the expression of pro-angiogenesis factors, such as vascular endothelial growth factor (VEGF), the key regulator of normal and pathological angiogenesis, have been reported to correlate with advanced disease and a worse prognosis ; 2) the expression of VEGF has been shown to correlate with RAS mutations, alterations in the APC-WNT signaling pathway, and overexpression of cyclo-oxygenase-2, which all are frequent in CRC ; 3) bevacizumab, a humanized anti-VEGF monoclonal antibody, is a potent inhibitor of tumor growth of various CRC cell lines in murine xenografts ; 4) the addition of bevacizumab to systemic chemotherapy has been shown to be significantly superior to chemotherapy alone in terms of objective tumor response rate, progression-free survival, and overall survival in patients with metastatic CRC, in the frontline, and more recently in the second-line setting, without worsening of chemotherapy-related toxicity. However, several potential specific adverse events, such as thrombosis, hemorrhages, proteinuria, arterial hypertension, and bowel perforations have been described. Whether the antitumoral efficacy of bevacizumab could be increased when combined to low-dose (metronomic) chemotherapy, or radiotherapy (in rectal cancer), is under development, as well other VEGF-targeted approaches (e.g., dominantnegative mutants, antisense oligonucleotides, antibodies directed against VEGF receptors (VEGFR), VEGFR tyrosine kinase inhibitors, soluble VEGFR,...), or other anti-angiogenesis agents (e.g., thalidomide, celecoxib, angiozyme...).

Angiogenesis Inhibitors↗
PubMed2004

Evolution of missing colorectal liver metastases following inductive chemotherapy and hepatectomy.

BACKGROUND: A dramatic response to chemotherapy in some patients with multiple bilateral and initially unresectable liver metastases (LM) from colorectal cancer sometimes leads to their disappearance from imaging studies. Our study was aimed at assessing the evolution of these metastases when they were also not found during liver surgery. PATIENTS: Among 104 hepatectomized patients for colorectal LM in 4 years, 15 patients were retrospectively eligible. Eligibility criteria were: initially unresectable LM; a dramatic response to chemotherapy; and the complete disappearance of at least one LM on imaging studies (ultrasonography (US), computed tomography, and magnetic resonance) during more than 3 months. In four patients (27%), the disappeared LM could be found and treated at laparotomy. The main selection criterion for the 11 studied patients of this series was the impossibility of finding and treating the disappeared LM sited in the remaining liver after hepatectomy, resulting in "missing LM." RESULTS: After a median follow-up of 31 months (range: 18-55) for the series, eight patients among the eleven (73%) did not present any recurrence of the missing LM. The median follow-up was 31.3 months for these eight patients. The three recurrences occurred respectively at 5, 5, and 8 months after surgery. CONCLUSIONS: The disappearance of LM after chemotherapy on high-quality imaging studies and after intra-operative liver exploration resulted in their definitive cure in approximately 70% of cases. The current dogma stipulating an obligatory resection of the initially affected part of the liver is no longer acceptable.

Adult↗
PubMed2004

Biliary tract neoplasms: update 2003.

PURPOSE OF REVIEW: Biliary tract neoplasm is one of the most aggressive malignancies, with a very poor prognosis. Most cancers of the biliary tract will have grown beyond the limits of curative resection by the time they become clinically evident. This reality has fostered therapeutic nihilism, and most physicians and surgeons, in their pessimism, have to run ambitious trials evaluating new diagnostic tools and therapeutic techniques in this disease. RECENT FINDINGS: Advances in imaging over the period of the last 5 years now allow for earlier diagnosis and better surgical planning. Recent improvements in operative technique have substantially improved the outlook of patients with this cancer. Palliative management of obstructive disease recently has been improved with the advent of photodynamic therapy. Among the different drugs tested in this disease, gemcitabine seems to have the best efficacy:toxicity ratio. However, efficacy results remain disappointing, and combination schedules need to be developed to improve the results. Among them, the gemcitabine-oxaliplatin combination seems to be one of the most promising schedules. Biological studies, especially those evaluating mutation-independent activation of the Hedgehog pathway, have provided interesting information on the carcinogenesis of this rare tumor. Furthermore, these results bring us the opportunity of development of future targeted therapies in biliary tract cancer. SUMMARY: Biliary tract neoplasm remains one of the most aggressive malignancies. However, as for other gastrointestinal malignancies, biological studies and diagnostic and therapeutic improvements have provided interesting results that could lead to a major improvement in the prognosis of this disease.

Adenocarcinoma↗
PubMed2004

Results of R0 resection for colorectal liver metastases associated with extrahepatic disease.

BACKGROUND: Extrahepatic malignant disease has always been considered an absolute contraindication to hepatectomy for colorectal liver metastases. This study reports the long-term outcome and prognostic factors of patients undergoing extrahepatic disease resection simultaneously with hepatectomy for liver metastases. METHODS: From January 1987 to January 2001, 75 patients underwent a complete R0 resection of extrahepatic disease simultaneously with hepatectomy for colorectal liver metastases. They were inscribed in a registry and then prospectively followed up. They represented 25% of the 294 patients who underwent an R0 hepatectomy for colorectal liver metastases during the same period. RESULTS: The mortality rate was 2.7%, and morbidity was 25%. After a median follow-up of 4.9 years (range, 1.7-13.4 years), the overall 3- and 5-year survival rates were 45% and 28%, respectively. By using a Cox model, there was a significant difference in survival between patients with single versus multiple sites of extrahepatic disease. Also, the presence of more than five liver metastases was a significant parameter. CONCLUSIONS: Extrahepatic disease in colorectal cancer patients with liver metastases should no longer be considered as a contraindication to hepatectomy. However, this intended R0 resection cannot be performed in 50% of laparotomized patients, and negative prognostic factors for surgery include the presence of multiple extrahepatic disease sites or more than five liver metastases.

Adult↗
PubMed2004

Emerging drugs in pancreatic cancer.

Improving survival in patients with pancreatic cancer remains a formidable challenge. For the few patients with localised stages of the disease, intra-operative radiotherapy, adjuvant chemoradiotherapy and neo-adjuvant therapies remain non-validated and the survival benefit conferred by 5-fluorouracil-folinic acid adjuvant chemotherapy over radical surgery alone is still a matter of debate. Gemcitabine has recently emerged as the standard single agent in advanced stages of the disease and pharmacokinetic refinements such as the use of a fixed-dose infusion rate may further improve still rather modest result figures. At present, most efforts deal with the development of more effective doublet or triplet therapies, combining gemcitabine with either conventional cytotoxic drugs--the most promising being oxaliplatin--or more innovative, targeted therapeutic agents. Among these agents, matrix metalloprotease inhibitors and farnesyltransferase inhibitors have already undergone Phase III trials, alone or in combination with gemcitabine, with rather disappointing results. However, preclinical and Phase I and II studies of cyclooxygenase-2 or lipoxygenase inhibitors, various immunotherapeutic approaches and several tyrosine kinase inhibitors or monoclonal antibodies against growth factors or their receptors are encouraging and may provide some hope for patients with pancreatic cancer.

Antibodies, Monoclonal↗
PubMed2004

[Docetaxel and gastric cancer].

There are very few active drugs in the treatment of metastatic gastric carcinoma. Among new drugs, docetaxel has shown one of the most important activity. With precise evaluation of objective response, this drug has demonstrated a 20% response rate in monotherapy. The favorable toxicity profile of this compound allowed combination therapy with other active drugs in this disease: 5-fluorouracil (5FU), cisplatin and epiadriamycin. Two of the most interesting combinations are: bitherapy with docetaxel cisplatin and three therapy with docetaxel, continuous infusion of 5FU and cisplatin (TCF). Several large phase III trials are on-going to compare these new schedules to classical combination chemotherapies of this disease (5FU cisplatin or ECF). The potential place of docetaxel in gastric cancer is not restricted to metastatic disease and the same three-therapy with TCF is currently under evaluation as a neoadjuvant or adjuvant treatment in resectable lesions. With a high activity in terms of radiosensitization, docetaxel could also become a major drug in the design of new radiochemotherapy protocols for neoadjuvant or adjuvant disease.

Antineoplastic Agents, Phytogenic↗
PubMed2003

Microsatellite instability is a predictive factor of the tumor response to irinotecan in patients with advanced colorectal cancer.

The aim of our study was to assess the relationship between colorectal tumor responsiveness to irinotecan and microsatellite instability (MSI), a feature of colorectal tumors with DNA mismatch repair defect. Seventy-two patients with metastatic colorectal cancer were included in our retrospective study. A complete response to irinotecan was observed in 1 patient and a partial response in 10 patients, whereas 61 patients did not respond to this treatment. We analyzed the protein expression of hMLH1, hMSH2, and BAX by immunohistochemistry, determined the MSI phenotype, and looked for mutations in the coding repeats located in the transforming growth factor beta-RII, BAX, hMSH3, and hMSH6 genes. All 44 tumors analyzed expressed detectable levels of hMLH1; 1 tumor lacked hMSH2 staining, whereas 4 tumors showed a marked decrease in BAX expression. A better response to irinotecan was observed in the patients whose tumors have lost BAX expression (P < 0.001). Among the 7 tumors that displayed a MSI-H phenotype, 4 responded to irinotecan, whereas only 7 of the 65 MSI-L/ microsatellite stable tumors did (P = 0.009). Seven of the 72 tumors had inactivating mutations in the coding repeats of the target genes. Three tumors displayed a mutation in the poly-A10 tract of the transforming growth factor beta-RII gene, associated with a 1-bp deletion in the poly-A8 tract of hMSH3 in one tumor and with a 1-bp deletion in the poly-G8 tract of BAX in another. Four tumors displayed mutations in the poly-G8 repeat of BAX, whereas 2 mutations in hMSH6 and hMSH3 were characterized. Among the 7 tumors with mutations in these target genes, 5 responded to irinotecan, whereas only 6 of the other 65 tumors did (P < 0.001), indicating that MSI-driven inactivation of target genes modifies tumor chemosensitivity. Our observations allowed us to define the first useful predictive criteria for irinotecan response in patients with colorectal cancer.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Liver resection (and associated extrahepatic resections) for metastatic well-differentiated endocrine tumors: a 15-year single center prospective study.

BACKGROUND: The timing and benefits of hepatectomy remain controversial for metastatic well-differentiated endocrine neoplasms, which are generally considered slow growth tumors. However, surveillance alone yields only a 22% 5-year survival when metastases occur. The aim of this study was to determine the results of hepatic and extra hepatic resections and to clarify the indications of surgery. METHODS: To define the role of hepatic resection, a database regrouping all patients (n = 47) who underwent hepatectomy with curative intent (R0 status) for well-differentiated endocrine neoplasms in the Gustave-Roussy Institute was constructed in 1984. New prognostic factors such as tumor growth and liver tumor mitotic index were studied. Median follow-up was 62 months. RESULTS: Hepatectomy was associated with extrahepatic tumor resection in 77% of the patients (primary tumor in 51%, lymph nodes in 21%, peritoneal carcinomatosis in 25%, and other in 6%). Resection was curative (R0) only in 53% of the patients, despite removing at least 97% of the tumor in each patient. Mortality was 5%, and morbidity was 45%. Median survival was 91 months, 5-year and 10-year overall survival rates were 71% and 35%, respectively. Liver recurrence rate was 75% at 10 years. No prognostic factor was correlated with overall survival in this population in which at least 97% of the tumor load was resected. The completeness of surgery, the presence of bilateral liver metastases, the number of liver metastases (>10) and a primary tumor from pancreatic origin were all significantly correlated with the disease-free survival. Preoperative tumor growth rate, mitotic index, and Ki67 expression were not predictive of prognosis. No significant prognostic factors could be found by the comparison of the patients who did and did not recur during the 3 years after hepatectomy. CONCLUSION: Hepatectomy for liver metastases from well-differentiated endocrine neoplasms is indicated when all visible intra- and extra hepatic lesions can be resected safely. The number, size, and localization of the tumor sites are less important than performing a complete (or near-complete) resection.

Adult↗
PubMed2003

MR imaging of hepatic metastases caused by neuroendocrine tumors: comparing four techniques.

OBJECTIVE: The aim of our prospective study was to assess the MR imaging characteristics of hepatic metastases of neuroendocrine tumors and to determine the optimal MR sequence for their detection. SUBJECTS AND METHODS: Thirty-seven consecutive patients with liver metastases from neuroendocrine tumors underwent 1.5-T MR imaging of the liver comprising T2-weighted fast spin-echo with respiratory monitoring, breath-hold T2-weighted single-shot fast spin-echo, and T1-weighted gradient-recalled echo sequences before and after the injection of gadoterate dimeglumine. Images were reviewed independently by three observers for the number, location, and pattern of signal and enhancement of metastases. RESULTS: A total of 359 metastases were detected, 279 on T2-weighed fast spin-echo, 231 on T2-weighed single-shot fast spin-echo, 272 on unenhanced T1-weighted, 322 on hepatic arterial phase, and 228 on portal venous phase images. Hepatic arterial phase images revealed the greatest number of metastases in 70% of patients, including 35 metastases seen only on this sequence, and was significantly superior to the unenhanced T1-weighted and portal venous phase sequences (p < 0.01). The lesion-to-liver contrast was significantly greatest with T2-weighed fast spin-echo sequences. The enhancement patterns of metastases were predominantly hypervascular, hypovascular, peripheral with progressive fill-in, and delayed in, respectively, 27, four, four, and two patients. Most metastases with peripheral enhancement and progressive fill-in were heterogeneous on T2-weighted images and were without globular peripheral enhancement. CONCLUSION: Hepatic metastases of neuroendocrine tumors had a typical hypervascular pattern in 73% of patients. Hepatic arterial phase and fast spin-echo T2-weighed sequences are the most sensitive.

Adult↗
PubMed2002

Dosage adjustment and pharmacokinetic profile of irinotecan in cancer patients with hepatic dysfunction.

PURPOSE: To determine the recommended dose (RD) and the pharmacokinetic profile of irinotecan and its metabolites in cancer patients with hyperbilirubinemia. PATIENTS AND METHODS: Patients were assigned to four treatment groups according to their baseline total bilirubin level. Patients in group I (bilirubin within normal range) and group II (bilirubin 1.0 to 1.5 times upper limit of normal [ULN]) received a dose of 350 mg/m(2) every 3 weeks. Patients in groups III (bilirubin 1.51 to 3.0 times ULN) and IV (bilirubin > 3.1 times ULN) received starting doses of 175 and 100 mg/m(2), respectively. RDs were defined according to the dose-limiting toxicity (DLT) experienced at cycle 1. RESULTS: Thirty-three patients including 21 gastrointestinal cancers were included. Grade 4 febrile neutropenia and diarrhea were common DLTs in patients with hyperbilirubinemia. At a dose of irinotecan 350 mg/m(2), DLTs were observed in two of seven and one of five patients in groups I and II, respectively. In group III, escalated doses of irinotecan 175, 200, and 240 mg/m(2) were associated with DLTs in one of seven, one of five, and three of six patients, respectively. No DLT was observed in group IV. High bilirubin and alkaline phosphatase levels were associated with an exponential decrease in the clearance of irinotecan. Pharmacokinetic analysis showed that the relative increase in exposure was likely caused by reduced biliary excretion. CONCLUSION: We showed that baseline total bilirubin level could be used to determine the appropriate dose of irinotecan in cancer patients with hepatic dysfunction. Doses of 350 mg/m(2) and 200 mg/m(2) were considered RDs in patients with bilirubin values <or= 1.5 times ULN and 1.51 to 3.0 times ULN, respectively.

Adult↗