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RADIOTHERAPY OF ADULT NODAL NON HODGKIN'S LYMPHOMA: The role of radiotherapy in the treatment of nodal non-Hodgkin's lymphoma has been modified by the introduction of efficient chemotherapy and the development of different pathological classifications. INTERMEDIATE GRADE OR HIGH GRADE LYMPHOMA: The recommended treatment of early-stage aggressive lymphomas is primarily a combination chemotherapy. The interest of adjuvant radiotherapy remains unclear and has to be established through large prospective trials. If radiation therapy has to be delivered, the historical results of exclusive radiation therapy showed that involved-fields and a dose of 35-40 Gy (daily fraction of 1.8 Gy, 5 days a week) are the optimal schedule. The interest of radiotherapy in the treatment of advanced-stage aggressive lymphoma is yet to be proven. Further studies had to stratify localized stages according to the factors of the International Prognostic Index. LOW-GRADE LYMPHOMA: For early-stage low-grade lymphoma, radiotherapy remains the standard treatment. However, the appropriate technique to use is controversial. Involved-field irradiation at a dose of 35 Gy seems to be the optimal schedule, providing a 10-year disease-free survival rate of 50% and no major toxicity. There is no standard indication of radiotherapy in the treatment advanced-stage low-grade lymphoma. RARE AND NEW ENTITY: For "new" nodal lymphoma's types, the indication of radiotherapy cannot be established (mantle-zone lymphoma, marginal zone B-cell lymphoma) or must take into account the natural history (Burkitt's lymphoma, peripheral T-cell lymphoma) and the sensibility to others therapeutic methods.

Examined are history, instructional methodologies, organizational patterns, and current research projects and objectives. (JH)

This paper describes parts of a patent taken out by the INRIA; This paper describes a totally new way to process Xray data in order to reconstruct the external and internal boudaries of objects, which do not involve Computed Tomography (CT). We show that the segmentation can be performed directrly with the raw data, the sinogram produced with the scanner, and that those segmented shapes can be geomtetrically transformed into reconstructed shapes in the usual space. Thus, if we are interested in only the boundaries of the objects, our method eliminates the computationally expensive step of Computed Tomography. Experimental results are presented for both synthetic and real data, leading to subpixel positioning fo the reconstructed boundaries. Our method gives its best results for sparse, high contrasted objects such as bones or blood vessels in angiograms. It can be adapted to any kind of scanner, including 3D scabbers. At last, we present an extension of our method which allows "on the fly" processing of the data and real time tracking of the objects boudnaries.

This paper reviews the anatomical spread and failure patterns of surgical Stage I endometrial cancer. The controversial aspects of the optimal adjuvant treatment are presented. An attempt is made to identify the most effective management approach based on the pertinent literature data.

We genotyped 19 NF1 families from the French Canadians of the Québec population with six intragenic polymorphic markers including 2 RFLPs (EcoRI and RsaI) and 4 microsatellites (IVS26-2.3, IVS27AC28.4, IVS27AC33.1, and IVS38GT53.0). Genotype analysis indicated families 7610 and 7473 bear deletions. In Family 7610 the deletion removed the entire NF1 gene except exons 1 to 4b. The breakpoint of the deletion is located between exons 4a and 4b. The deletion 7473 was derived from the maternal chromosome and exons 1 to 5 were deleted. The breakpoint of the deletion is located between exons 7 and 13. Their phenotypes are reported. The allele frequencies of microsatellites IVS27AC28.4 and IVS38GT53.0 are compared to previously reported data from Caucasians, including Spanish and Italians. The difference is statistically significant (P0.0036) for marker IVS27AC28.4 between the Québec French Canadian and the Italian population.

Using a protein truncation assay, we have identified a new mutation in the neurofibromatosis type 1 (NF1) gene that causes a severe defect in NF1 pre-mRNA splicing. The mutation, which consists of a G to A transition at position +1 of the 5' splice site of exon 12a, is associated with the loss of both exons 11 and 12a in the NF1 mRNA. Through the use of in vivo and in vitro splicing assays, we show that the mutation inactivates the 5' splice site of exon 12a, and prevents the definition of exon 12a, a process that is normally required to stimulate the weak 3' splice site of exon 12a. Because the 5' splice site mutation weakens the interaction of splicing factors with the 3' splice site of exon 12a, we propose that exon 11/exon 12a splicing is also compromised, leading to the exclusion of both exons 11 and 12a. Our results provide in vivo support for the importance of the exon definition model during NF1 splicing, and suggest that the NF1 region containing exons 11 and 12a plays an important role in the activity of neurofibromin.

Treatment of advanced colorectal cancer has progressed substantially. However, improvements in response rates have not always translated into significant survival benefits. Doubts have therefore been raised about the usefulness of tumour response as a clinical endpoint.This meta-analysis was done on individual data from 3791 patients enrolled in 25 randomised trials of first-line treatment with standard bolus intravenous fluoropyrimidines versus experimental treatments (fluorouracil plus leucovorin, fluorouracil plus methotrexate, fluorouracil continuous infusion, or hepatic-arterial infusion of floxuridine). Analyses were by intention to treat.Compared with bolus fluoropyrimidines, experimental fluoropyrimidines led to significantly higher tumour response rates (454 responses among 2031 patients vs 209 among 1760; odds ratio 0.48 [95% CI 0.40-0.57], p0.0001) and better survival (1808 deaths among 2031 vs 1580 among 1760; hazard ratio 0.90 [0.84-0.97], p=0.003). The survival benefits could be explained by the higher tumour response rates. However, a treatment that lowered the odds of failure to respond by 50% would be expected to decrease the odds of death by only 6%. In addition, less than half of the variability of the survival benefits in the 25 trials could be explained by the variability of the response benefits in these trials.These analyses confirm that an increase in tumour response rate translates into an increase in overall survival for patients with advanced colorectal cancer. However, in the context of individual trials, knowledge that a treatment has benefits on tumour response does not allow accurate prediction of the ultimate benefit on survival.

We report a HincII polymorphism in the 5' end of the neurofibromatosis type 1 gene (NF1) as detected with a probe made of exons 1 to 4a (nucleotides 2 to 401 of the cDNA). This HincII site is most probably in an intron. Evidence presented suggests the probe reveals not one but two similar polymorphisms.

Metastases confined to the liver is a frequent situation in patients with advanced colorectal cancer. For non-operable patients, 5-FU-based chemotherapy is often proposed but the importance of the choice of first line 5-FU regimen remains debatable.In four previously performed meta-analyses, our group had compared bolus intravenous fluoropyrimidines (bolus FU group) with experimental fluoropyrimidines (experimental FU group), consisting of 5-FU plus leucovorin, 5-FU plus methotrexate, continuous infusion 5-FU, or hepaticartery infusion FUDR. We re-analysed this data set to focus on 1458 patients with non-operable colorectal metastases confined to the liver, randomised in 22 trials. All analyses were stratified by trial and used individual patient data.Median survival times were 11.3 months in the bolus FU group (95% CI: 10.5-12.0 months) compared to 12.7 months in the experimental FU group (95% CI: 120-13.1 months). This difference, although clinically small, was statistically significant, with an overall survival hazard ratio of 0.88 (95% CI: 0.79-0.99, P = 0.037). In a multivariate analysis, performance status was the only significant predictor of survival (P10(-4)), whereas the statistical significance of allocated treatment was borderline (P = 0.058).The outcome of patient with non-operable colorectal metastases confined to the liver is poor, and mainly driven by their initial performance status. Experimental chemotherapy schedules yield a small improvement in their overall survival, indicating the importance of the choice of first-line chemotherapy.

The study presented in this paper tests the hypothesis that the combination of a global similarity transformation and local free-form deformations can be used for the accurate segmentation of internal structures in MR images of the brain. To quantitatively evaluate the authors' approach, the entire brain, the cerebellum, and the head of the caudate have been segmented manually by two raters on one of the volumes (the reference volume) and mapped back onto all the other volumes, using the computed transformations. The contours so obtained have been compared to contours drawn manually around the structures of interest in each individual brain. Manual delineation was performed twice by the same two raters to test inter- and intrarater variability. For the brain and the cerebellum, results indicate that for each rater, contours obtained manually and contours obtained automatically by deforming his own atlas are virtually indistinguishable. Furthermore, contours obtained manually by one rater and contours obtained automatically by deforming this rater's own atlas are more similar than contours obtained manually by two raters. For the caudate, manual intra- and interrater similarity indexes remain slightly better than manual versus automatic indexes, mainly because of the spatial resolution of the images used in this study. Qualitative results also suggest that this method can be used for the segmentation of more complex structures, such as the hippocampus.

RADIOTHERAPY OF ADULT NODAL NON HODGKIN'S LYMPHOMA: The role of radiotherapy in the treatment of nodal non-Hodgkin's lymphoma has been modified by the introduction of efficient chemotherapy and the development of different pathological classifications. INTERMEDIATE GRADE OR HIGH GRADE LYMPHOMA: The recommended treatment of early-stage aggressive lymphomas is primarily a combination chemotherapy. The interest of adjuvant radiotherapy remains unclear and has to be established through large prospective trials. If radiation therapy has to be delivered, the historical results of exclusive radiation therapy showed that involved-fields and a dose of 35-40 Gy (daily fraction of 1.8 Gy, 5 days a week) are the optimal schedule. The interest of radiotherapy in the treatment of advanced-stage aggressive lymphoma is yet to be proven. Further studies had to stratify localized stages according to the factors of the International Prognostic Index. LOW-GRADE LYMPHOMA: For early-stage low-grade lymphoma, radiotherapy remains the standard treatment. However, the appropriate technique to use is controversial. Involved-field irradiation at a dose of 35 Gy seems to be the optimal schedule, providing a 10-year disease-free survival rate of 50% and no major toxicity. There is no standard indication of radiotherapy in the treatment advanced-stage low-grade lymphoma. RARE AND NEW ENTITY: For "new" nodal lymphoma's types, the indication of radiotherapy cannot be established (mantle-zone lymphoma, marginal zone B-cell lymphoma) or must take into account the natural history (Burkitt's lymphoma, peripheral T-cell lymphoma) and the sensibility to others therapeutic methods.

Evaluating precisely the temporal variations of lesion volumes is very important for at least three types of practical applications: pharmaceutical trials, decision making for drug treatment or surgery and patient follow-up. The authors present a volumetric analysis technique, combining precise rigid registration of 3D medical images, nonrigid deformation computation and flowfield analysis. Their analysis technique has two outcomes: the detection of evolving lesions and the quantitative measurement of volume variations. The originality of their approach is that no precise segmentation of the lesion is needed but the approximative designation of a region of interest, which can be automatized. They distinguish between tissue transformation (image intensity changes without deformation) and expansion or contraction effects reflecting a change of mass within the tissue; a real lesion being generally the combination of both effects. The method is tested with synthesized 3D image sequences and applied, in a first attempt to quantify in vivo a mass effect, to the analysis of a patient with multiple sclerosis (MS).

The rôle of chemotherapy in the treatment of operable soft tissue sarcomas is still debatable. In high-grade tumors, randomized trials using adjuvant chemotherapy have resulted in controversial results. A recent meta-analysis showed a higher median disease-free survival in groups with chemotherapy compared to controls. Doxorubicin, ifosfamide and dacarbazine are the majors drugs. Their combination in adjuvant treatment is currently being investigated. Neoadjuvant chemotherapy has allowed conservative surgery in initially unoperable tumors, but its role in primarily operable tumors remains to be defined.

We present the concept of non-rigid matching based on demons, by reference to Maxwell's demons. We contrast this concept with the more conventional viewpoint of attraction. We show that demons and attractive points are clearly distinct for large deformations, but also that they become similar for small displacements, encompassing techniques close to optical flow. We describe a general iterative matching method based on demons, and derive from it three different non-rigid matching algorithms, one using all the image intensities, one using only contours, and one for already segmented images. At last, we present results with synthesized and real deformations, with applications to Computer Vision and Medical Image Processing.

Presents a method, based on the filtered backprojection technique (FBP), to extract directly the boundaries of X-ray images, without previous image reconstruction. The author preprocess the raw data in order to compute directly the reconstructed values of the gradient or of the Laplacian at any location in the plane (defined with real coordinates). The reconstructed value of the gradient and of the Laplacian correspond to the exact mathematical definition of the differentials of the image. For noisy data, the author proposes also to use an extension of existing FBP techniques, adapted to the computation of the gradient and of the Laplacian. Finally, the author shows how to use the corresponding operators to perform the segmentation of a slice, without image reconstruction. Images of the reconstructed gradient, Laplacian, and segmented objects are presented. >