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Biomedical subjects

J Bourhis

Publications and source records attributed to J Bourhis.

At least 19 recordsLinked to original sources
PubMed2006

Chemotherapy as an adjunct to radiotherapy in locally advanced nasopharyngeal carcinoma.

BACKGROUND: A previous meta-analysis investigated the role of chemotherapy in head and neck locally advanced carcinoma. This work had not been performed on nasopharyngeal carcinoma. OBJECTIVES: The aim of the project was to study the effect of adding chemotherapy to radiotherapy on overall survival (OS) and event-free survival (EFS) in patients with nasopharyngeal carcinoma. SEARCH STRATEGY: We searched MEDLINE (1966 to October 2003), EMBASE (1980 to October 2003) and the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 3, 2003) and trial registers. Handsearches of meeting abstracts, references in review articles and of the Chinese medical literature were carried out. Experts and pharmaceutical companies were asked to identify trials. SELECTION CRITERIA: Randomised trials comparing chemotherapy plus radiotherapy to radiotherapy alone in locally advanced nasopharyngeal carcinoma were included. DATA COLLECTION AND ANALYSIS: The meta-analysis was based on updated individual patient data. The log rank test, stratified by trial, was used for comparisons and the hazard ratios (HR) of death and failure (loco-regional/distant failure or death) were calculated. MAIN RESULTS: Eight trials with 1753 patients were included. One trial with a 2 x 2 design was counted twice in the analysis. The analysis was performed including 11 comparisons based on 1975 patients. The median follow up was six years. The pooled hazard ratio of death was 0.82 (95% confidence interval (CI) 0.71 to 0.95; P = 0.006) corresponding to an absolute survival benefit of 6% at five years from chemotherapy (from 56% to 62%). The pooled hazard ratio of tumour failure or death was 0.76 (95% CI 0.67 to 0.86; P < 0.00001) corresponding to an absolute event-free survival benefit of 10% at five years from chemotherapy (from 42% to 52%). A significant interaction was observed between chemotherapy timings and overall survival (P = 0.005), explaining the heterogeneity observed in the treatment effect (P = 0.03) with the highest benefit from concomitant chemotherapy. AUTHORS' CONCLUSIONS: Chemotherapy led to a small but significant benefit for overall survival and event-free survival. This benefit was essentially observed when chemotherapy was administered concomitantly with radiotherapy.

Chemotherapy, Adjuvant↗
PubMed2006

[Role and perspectives of sentinel node biopsy in head and neck tumors].

PURPOSE: To evaluate the accuracy of sentinel node biopsy for assessing the neck status for those patients with squamous cell carcinoma T1T2N0 of oral cavity. PATIENTS AND METHODS: 55 patients were included in a prospective study between 2000 and 2003. 53 underwent a sentinel node biopsy (SNB) followed by an elective neck dissection (END). Pathological examination with stepped serial sectioning and immunohistochemistry of sentinel node (SN) has been compared with routine pathology examination of remaining END nodes. RESULTS: 12 patients had a positive SN. No false negative was found. Patient follow up on, at less of 3 years, did not show any node recurrence for those patients with negative SN. After that study, 44 patients had a SNB without END. 7 patients had a positive SN. Follow up showed a node recurrence for 3 patients. In two of these, pathological reexamination showed a micrometastase in SN. SN failure rate is less than 3% for those 99 patients. CONCLUSION: SNB is a liable procedure. Failure rate is the same as in END. We plan to use this procedure in orophyngeal tumors where it could be possible to reduce irradiation fields and treatment sequels for those patients with negative SN.

Adult↗
PubMed2005

[Cost of quality assurance in radiotherapy: human and material requirements].

In 2004, three new important laws were passed concerning radiotherapy services. The first two concerns the internal and external quality control of linear accelerators and the last concerns the role of the medical physicist, whose presence was made mandatory during the whole length of the treatments. These laws, which aim to improve the quality and the security of treatments, represent an increase in price that we have calculated, and which prevents them being implemented, as a joint study realised by the SFRO and the SFPM has shown. The cost of quality in radiotherapy requires investment in material and manpower and improvement in availability of the accelerators which entails a complete reorganisation of the services. Cost analysis is included. The difficulties in implementing these laws have also been evaluated and this evaluation already enables us to propose certain elements enabling us to go forward to globally improve the quality and security in radiotherapy.

Costs and Cost Analysis↗
PubMed2005

[Propositions for the selection and the delineation of peritumoral microscopic disease volumes in oral cavity and oropharyngeal cancers (lymph nodes excluded)].

This article reviews the concept of selectivity in peritumoral microscopic disease to be included in the Clinical Target Volume (CTV) for elective treatment for oral cavity and oropharyngeal squamous cell carcinoma, using the local tumoral spread. The objective of the present article is to present a procedure for the delineation of the target volumes, required for an appropriate application of 3-DCRT and IMRT for head and neck cancers. These propositions are for the delineation of microscopic peritumoral target volumes when external beam irradiation is required. CTVs are illustrated on CT sections.

Carcinoma, Squamous Cell↗
PubMed2005

[Individual patient data meta-analyses in head and neck carcinoma: what have we learnt?].

Carcinoma of the upper aerodigestive tract (oral cavity, oropharynx, hypopharynx, nasopharynx, larynx) are frequent tumors for which surgery and/or radiotherapy are the main therapeutic agents. The main results of meta-analyses based on the collection of individual patients data are reported: 1) The meta-analysis on chemotherapy, regrouping data of nearly 11,000 patients issued from 63 randomized trials showed an absolute benefit of 4% at five years in overall survival, in favor of chemotherapy (P<0.0001). Most of the benefit was seen with concomitant radiochemotherapy, however with a relatively large heterogeneity in this subgroup of trials. An update of this meta-analysis was performed including 24 additional trials, which confirmed the magnitude of the benefit due to concomitant chemotherapy (8% at 5 years). 2) The meta-analysis on larynx preservation, using induction chemotherapy in larynx and hypopharynx carcinomas. No significant difference was seen between the control arm with total laryngectomy and the larynx preservation approach. 3) The meta-analysis on chemotherapy in nasopharynx carcinomas, from the data of 11 randomized trials including 2722 patients, and comparing the radiotherapy to radio-chemotherapy (1979-2001). The results showed an absolute benefit of 6% at five years in overall survival, in favor of chemotherapy (P<0.0001). Most of the benefit was seen with concomitant radiochemotherapy. 4) Finally, a meta-analysis on altered fractionated RT, compared to conventional RT in 15 randomized trials regrouping 6515 patients. The results showed a small but significant improvement in favor of altered fractionated RT for overall survival and local control with an absolute benefit at five years of 3 and 6%, respectively.

Combined Modality Therapy↗
PubMed2005

[New strategies to interfere with radiation response: "biomodulation" of radiation therapy].

The development of several new anti cancer agents has been made possible because of recent significant achievements in our global understanding of cancer biology. These new "targeted" agents selectively inhibit targets necessary for tumor cell growth and viability with little toxicity to normal cells compared to conventional cytotoxic agents. So far, the efficacy of many of these new promising agents when used alone treatment remains limited, it is likely that the optimal use of these agents could be obtained in combination with conventional agents such as radiation therapy. The potential benefit of these targeted therapies combined with irradiation seems important. They might offer the advantage of increasing the tumor response to radiation with no or little increase in normal tissue damage. Therefore, these new types of chemo-radiation approaches might respect the normal tissue versus tumor cell "therapeutic ratio". These approaches can be sub divided in three sub groups: 1) Therapeutics targeting selectively one tumor related biochemical activity such as EGFR inhibitors. These approaches are efficient but one mutation of the target might render them inefficient. 2) Therapeutics directed against a widely expressed target. This is the case for anti Insulin Growth Factor-1 (IGF1R) interventions: IGF1R inhibition seems to specifically alter tumor cell viability with a minimal effect on normal cells viability. 3) Strategies which are not targeted against the tumor but the microenvironment, especially angiogenesis. This type of approaches seems to be applicable independently of tumor intrinsic biologic related factors.

Angiogenesis Inhibitors↗
PubMed2005

Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501).

BACKGROUND: In 2004, level I evidence was established for the postoperative adjuvant treatment of patients with selected high-risk locally advanced head and neck cancers, with the publication of the results of two trials conducted in Europe (European Organization Research and Treatment of Cancer; EORTC) and the United States (Radiation Therapy Oncology Group; RTOG). Adjuvant chemotherapy-enhanced radiation therapy (CERT) was shown to be more efficacious than postoperative radiotherapy for these tumors in terms of locoregional control and disease-free survival. However, additional studies were needed to identify precisely which patients were most suitable for such intense treatment. METHODS: Both studies compared the addition of concomitant relatively high doses of cisplatin (on days 1, 22, and 43) to radiotherapy vs radiotherapy alone given after surgery in patients with high-risk cancers of the oral cavity, oropharynx, larynx, or hypopharynx. A comparative analysis of the selection criteria, clinical and pathologic risk factors, and treatment outcomes was carried out using data pooled from these two trials. RESULTS: Extracapsular extension (ECE) and/or microscopically involved surgical margins were the only risk factors for which the impact of CERT was significant in both trials. There was also a trend in favor of CERT in the group of patients who had stage III-IV disease, perineural infiltration, vascular embolisms, and/or clinically enlarged level IV-V lymph nodes secondary to tumors arising in the oral cavity or oropharynx. Patients who had two or more histopathologically involved lymph nodes without ECE as their only risk factor did not seem to benefit from the addition of chemotherapy in this analysis. CONCLUSIONS: Subject to the usual caveats of retrospective subgroup analysis, our data suggest that in locally advanced head and neck cancer, microscopically involved resection margins and extracapsular spread of tumor from neck nodes are the most significant prognostic factors for poor outcome. The addition of concomitant cisplatin to postoperative radiotherapy improves outcome in patients with one or both of these risk factors who are medically fit to receive chemotherapy.

Antineoplastic Agents↗
PubMed2005

[Building Clinical Target Volume in laryngeal cancers using knowledge about modes of invasion of each location].

The purpose of this article is to propose a building model to delineate Clinical Target Volume in laryngeal cancers (squamous cell carcinoma). This model uses histological knowledge about the spread of laryngeal cancers. Firstly is described the spread, depending on primary location and anatomic structures. Then illustrated examples on Computed Tomography are provided. This delineation approach appears to be useful with 3D-CRT and IMRT for adapting dose delivery to the complex spread of laryngeal cancer.

Carcinoma, Squamous Cell↗
PubMed2005

A retrospective analysis of the outcome of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck refractory to a platinum-based chemotherapy.

AIMS: Recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) develops in around 72,000 people in Europe every year. Treatment options are limited, mainly consisting of platinum-based palliative chemotherapy, with median overall survival times of only 6-8 months. No standard second-line treatment after progression on platinum-based chemotherapy is available. Few data have reported the efficacy of these treatments and the outcome of the patients. In an effort to generate such data, this retrospective study analysed clinical records from 151 patients with SCCHN refractory to platinum-based chemotherapy treated between 1990 and 2000 at seven different centres around Europe. MATERIALS AND METHODS: Most patients (45%) received only best supportive care (BSC), and had a median survival of 56 days. A total of 28.5% of the patients received second-line chemotherapies: 16.6% radiotherapy and 9.9% chemoradiotherapy. RESULTS: No objective response was observed with the various second-line chemotherapies. The overall median survival was 103 days (95% confidence interval [CI]: 77-126 days) for the whole cohort. The overall objective response rate (ORR) to second-line treatment in this population was calculated to be 2.6%. CONCLUSION: These results highlight the need for additional treatment options for this disease. Similar, if not superior, response rates have already been observed in initial clinical studies of novel, targeted anti-cancer agents.

Adult↗
PubMed2005

New approaches to enhance chemotherapy in SCCHN.

Chemotherapy is the standard approach to the treatment of patients with recurrent and metastatic squamous cell carcinoma of the head and neck (SCCHN) and is also now a common component of treatment for patients with locoregionally advanced, non-metastatic disease. Cisplatin has for many years been the agent of choice, alone or in combination with other agents, particularly 5-FU. The advent of the taxanes, which demonstrate good non-clinical activity against SCCHN, spawned a series of investigations aimed at integrating these agents into treatment regimens. Molecular targeted agents, which do not demonstrate overlapping toxicities with commonly used chemotherapy agents for SCCHN, represent a promising avenue of investigation. The epidermal growth factor receptor (EGFR) is expressed both widely and at high levels in SCCHN and is associated with poor prognosis. The EGFR-directed monoclonal antibody (MAb) cetuximab (Erbitux) in combination with chemotherapy has shown some activity in the treatment of recurrent/metastatic disease both as first-line therapy and following cisplatin failure, and preliminary results suggest single-agent activity in platinum-resistant disease. Promising activity has also been observed with a number of other EGFR inhibitors, both MAbs and tyrosine kinase inhibitors.

Antibodies, Monoclonal↗
PubMed2005

Inhibition of Rho kinase modulates radiation induced fibrogenic phenotype in intestinal smooth muscle cells through alteration of the cytoskeleton and connective tissue growth factor expression.

BACKGROUND: Late radiation enteritis in humans is associated with accumulation of extracellular matrix and increased connective tissue growth factor (CTGF) expression that may involve intestinal muscular layers. AIMS: We investigated the molecular pathways involved in maintenance of radiation induced fibrosis by gene profiling and postulated that alteration of the Rho pathway could be associated with radiation induced fibrogenic signals and CTGF sustained expression. PATIENTS AND METHODS: Ileal biopsies from individuals with and without radiation enteritis were analysed by cDNA array, and primary cultures of intestinal smooth muscle cells were established. Then, the effect of pharmacological inhibition of p160 Rho kinase, using Y-27632, was studied by real time reverse transcription-polymerase chain reaction, western blot, and electrophoretic mobility shift assay. RESULTS: Molecular profile analysis of late radiation enteritis showed alterations in expression of genes coding for the Rho proteins. To investigate further the involvement of the Rho pathway in intestinal radiation induced fibrosis, primary intestinal smooth muscle cells were isolated from radiation enteritis. They retained their fibrogenic differentiation in vitro, exhibited a typical cytoskeletal network, a high constitutive CTGF level, increased collagen secretory capacity, and altered expression of genes coding for the Rho family. Rho kinase blockade induced a simultaneous decrease in the number of actin stress fibres, alpha smooth muscle actin, and heat shock protein 27 levels. It also decreased CTGF levels, probably through nuclear factor kappaB inhibition, and caused decreased expression of the type I collagen gene. CONCLUSION: This study is the first showing involvement of the Rho/Rho kinase pathway in radiation fibrosis and intestinal smooth muscle cell fibrogenic differentiation. It suggests that specific inhibition of Rho kinase may be a promising approach for the development of antifibrotic therapies.

Actins↗
PubMed2004

Tyrosine kinase inhibitor AG1024 exerts antileukaemic effects on STI571-resistant Bcr-Abl expressing cells and decreases AKT phosphorylation.

Chronic myelogenous leukaemia (CML) is a clonal malignancy of the pluripotent haematopoietic stem cell, characterised by an uncontrolled proliferation and expansion of myeloid progenitors expressing a fusion oncogene, BCR-ABL, the molecular counterpart of the Ph1 chromosome. The tyrosine kinase (TK) activity of BCR-ABL is known to activate several major signalling pathways in malignant cells, including Ras, JAK/STAT and PI3K/Akt with evidence of proteasome-mediated degradation of other targets such as the DNA repair protein DNA-PKcs and cyclin-dependent kinases inhibitor p27. Targeting these abnormalities by blocking TK of BCR-ABL with STI571 provided a promising approach for the therapy of CML. The recent development of resistance to STI571 illustrates, however, that the use of other TK inhibitors could be of major interest for therapeutic purposes. To this end, the TK inhibitor Tyrphostin AG1024 was used to evaluate effect on regulation of BCR-ABL expression, inhibition of cell proliferation and tumour formation in vivo in human and murine BCR-ABL expressing cell lines. Tyrphostin AG1024 was shown to downregulate expression of BCR-ABL and P-Akt, and to upregulate DNA-PKcs expression. In addition, Tyrphostin AG1024 was able to inhibit cell proliferation, and delay tumour growth in vivo. Thus, AG1024 is able to interfere with three major targets of BCR-ABL in leukaemic cells. Interestingly, Tyrphostin AG1024 was also effective against cells resistant to STI571 by distinct mechanisms including Bcr-Abl mutation. Therefore, these data suggest that Tyrphostin AG1024 could represent the basis of a novel therapy for STI571 refractory CML.

Animals↗