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Funding Information: This project was initiated at the Endeavour Breast Project coordinated by Daiichi Sankyo (special thanks to Christian Opitz and Britta Mazur from Daiichi Sankyo). We thank all participants and the steering committee members of the Endeavour Breast Meeting who are not listed as co-authors ( Supplementary Table S4 , available at https://doi.org/10.1016/j.esmoop.2022.100747 ). The authors gratefully acknowledge the support from the AGMT office (particularly Mag. Katrin Dorfinger, Mag. Alexandra Keuschnig, Sebastian Schütz, and Dr. Daniela Wolkersdorfer) and all trial coordinators at the contributing centers. Publisher Copyright: © 2022 The Authors Background: Triple-negative breast cancer (TNBC) is associated with poor prognosis, and new treatment options are urgently needed. About 34%-39% of primary TNBCs show a low expression of human epidermal growth factor receptor 2 (HER2-low), which is a target for new anti-HER2 drugs. However, little is known about the frequency and the prognostic value of HER2-low in metastatic TNBC. Patients and methods: We retrospectively included patients with TNBC from five European countries for this international, multicenter analysis. Triple-negativity had to be shown in a metastatic site or in the primary breast tumor diagnosed simultaneously or within 3 years before metastatic disease. HER2-low was defined as immunohistochemically (IHC) 1+ or 2+ without ERBB2 gene amplification. Survival probabilities were calculated by the Kaplan–Meier method, and multivariable hazard ratios (HRs) were estimated by Cox regression models. Results: In total, 691 patients, diagnosed between January 2006 and February 2021, were assessable. The incidence of HER2-low was 32.0% [95% confidence interval (CI) 28.5% to 35.5%], with similar proportions in metastases (n = 265; 29.8%) and primary tumors (n = 425; 33.4%; P = 0.324). The median overall survival (OS) in HER2-low and HER2-0 TNBC was 18.6 and 16.1 months, respectively (HR 1.00; 95% CI 0.83-1.19; P = 0.969). Similarly, in multivariable analysis, HER2-low had no significant impact on OS (HR 0.95; 95% CI 0.79-1.13; P = 0.545). No difference in prognosis was observed between HER2 IHC 0/1+ and IHC 2+ tumors (HR 0.89; 95% CI 0.69-1.17; P = 0.414). Conclusions: In this large international dataset of metastatic TNBC, the frequency of HER2-low was 32.0%. Neither in univariable nor in multivariable analysis HER2-low showed any influence on OS. publishersversion published

Immune checkpoint inhibitors (ICIs) show limited clinical activity in patients with advanced soft-tissue sarcomas (STSs). Retrospective analysis suggests that intratumoral tertiary lymphoid structures (TLSs) are associated with improved outcome in these patients. PEMBROSARC is a multicohort phase 2 study of pembrolizumab combined with low-dose cyclophosphamide in patients with advanced STS (NCT02406781). The primary endpoint was the 6-month non-progression rate (NPR). Secondary endpoints included objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and safety. The 6-month NPR and ORRs for cohorts in this trial enrolling all comers were previously reported; here, we report the results of a cohort enrolling patients selected based on the presence of TLSs (n = 30). The 6-month NPR was 40% (95% confidence interval (CI), 22.7-59.4), so the primary endpoint was met. The ORR was 30% (95% CI, 14.7-49.4). In comparison, the 6-month NPR and ORR were 4.9% (95% CI, 0.6-16.5) and 2.4% (95% CI, 0.1-12.9), respectively, in the all-comer cohorts. The most frequent toxicities were grade 1 or 2 fatigue, nausea, dysthyroidism, diarrhea and anemia. Exploratory analyses revealed that the abundance of intratumoral plasma cells (PCs) was significantly associated with improved outcome. These results suggest that TLS presence in advanced STS is a potential predictive biomarker to improve patients' selection for pembrolizumab treatment.

Introduction La prise en charge du cancer bronchique non a petites cellules (CBNPC) a ete transformee par le developpement de l’immunotherapie par inhibiteurs de check-points immunitaires (ICI). Cependant, seuls 20% des patients repondent au traitement, soulignant la necessite d’identifier des biomarqueurs predictifs de l’efficacite des ICI. L’objectif de notre travail etait de decrire l’environnement immunitaire des CBNPC traites par ICI et son implication dans la reponse aux ICI. Methodes Notre population etait constituee de patients atteints de CBNPC de stade avance traites en routine par ICI en monotherapie dans notre centre. L’analyse transcriptomique a ete realisee grâce a la technologie nCounter® de Nanostring© avec le panel PanCancer Immune Profiling qui comporte 730 genes, tous impliques dans l’immunite anti-tumorale. L’analyse bio-informatique des donnees a comporte une etape de clustering hierarchique puis une analyse supervisee afin de confronter les donnees transcriptomiques aux donnees cliniques. Resultats Parmi les 65 patients dont l’ARN a ete extrait, 44 disposaient d’une qualite et quantite suffisante pour l’analyse transcriptomique. Le clustering hierarchique a partir des donnees d’expression des 730 genes a permis de distinguer deux groupes de patients en fonction de leur environnement immunitaire. Il n’existait pas de correlation entre les groupes et les donnees histocliniques, notamment de reponse aux ICI (p = 0,135). Nous avons pu distinguer une representation significativement differente des LT CD4 memoires et des cellules NK dans les deux groupes. L’analyse supervisee a identifie les genes TLR3 et ITGA2B comme statistiquement associes a la reponse a l’immunotherapie. Conclusion Notre travail a permis de demontrer qu’il etait possible de determiner des groupes de CBNPC en fonction de leur immunogenicite, sans correlation avec les autres donnees histocliniques ni la reponse aux ICI. L’analyse supervisee nous a permis d’identifier d’autres genes potentiellement impliques dans la reponse aux ICI.

Table S1. Minimum criteria required for the diagnosis of IBC. Table S2. Correlation between PD-L1 and clinicopathological tumour characteristics. Table S3. A logistic multivariate model for PD-L1 expression on immune cells. Table S4. Patient and tumour characteristics of the nIBC control group. Table S5. Frequencies of organ-specific metastases. Table S6. Patient and tumour characteristics of the IBC validation cohort from Marseille. Figure S1. Neo-adjuvant chemotherapy regimens. Figure S2. Kaplan-Meier curves of RFS and OS in the total IBC population (143 patients). Figure S3. Kaplan-Meier curves of significant prognostic variables for RFS. Figure S4. Kaplan-Meier curves of significant prognostic variables for DMFS. Figure S5. Kaplan-Meier curve showing significant survival benefit for HER2-positive IBC patients that received trastuzumab. Figure S6. Clinicopathological characteristics of the validation cohort. Figure S7. PD-L1 immunoreactivity and pCR in the validation cohort. Figure S8. Prognostic clinicopathological variables in the validation cohort. Figure S9. PD-L1 antigenicity decreases over time. (DOCX 10547Â kb)

The natural history of localized high-grade sarcomas of the digestive tract (SDT) excluding GIST has been rarely considered owing to their low incidence and heterogeneity. We describe the histoclinical characteristics of SDT and correlate them with patients' outcomes.We retrospectively collected medical files from a European database covering connective tissue tumors listed in Europe for about twenty years. Only untreated localized primary high-grade SDT were included. A central histological review was performed for each case. Patients' characteristics were compared and correlated with clinical outcomes.A total of 45 patients were identified. Leiomyosarcomas (LMS) and undifferentiated sarcomas (UDS) were predominant, the former having better overall survival (OS) and progressionfree survival (PFS) while the latter having a worse outcome than the other histological types. Complete remission was obtained in 34 patients (75%) and was associated with male sex, age over 40 years and monofocal tumor. Complete surgery and LMS histology were associated with a better prognosis without any significant difference in baseline characteristics or in treatment modalities.Complete surgery and histological type seem to be prognostic indicators of SDT. These results suggest the importance of treating these patients in a reference center.

Introduction Le dermatofibrosarcome (DFS) est une tumeur rare (6 % des sarcomes des tissus mous) ayant un potentiel eleve de dissemination locale. Le traitement standard repose sur une exerese large. La translocation COL1A1-PDGFB t(17 ; 22) est presente dans > 90 % des DFS et entraine une activation de la voie du PDGF. L’imatinib, tyrosine kinase ciblant entre autres PDGF a ete teste dans les DFS non operables, avec des taux de reponse de 36 a 57 %. Le pazopanib est un inhibiteur de tyrosine kinase ciblant VEGF, PDGF et KIT ayant l’AMM dans les sarcomes des tissus mous. Nous avons evalue l’efficacite et la tolerance du pazopanib dans le DFS. Patients et methodes Nous avons conduit le premier essai de phase II multicentrique en France, chez les patients atteints d’un DFS non operable, recidivant ou metastatique. Les patients ont recu le pazopanib a la dose de 800 mg/j. Le critere de jugement etait le taux de reponse defini par la reduction du plus grand diametre de la tumeur ≥ 30 % (RECIST) a 6 mois ou au moment de la chirurgie. Des analyses pharmacodynamiques ont ete menees sur les tumeurs a baseline, 1 mois, fin de traitement (expression ARNm de PDGF, PDGFR, VEGF, VEGFR et signalisation d’aval). Resultats Vingt-trois patients ont ete inclus entre juillet 2010 et fevrier 2014 (9 centres) : 18 DFS primitif, 4 recidivants et 1 metastatique. La mediane de suivi etait de 6,2 mois. Le taux de reponse etait de 22 %, (5 patients, IC 95 % : 7–22). Le meilleur taux de reponse dans les 6 mois etait de 30 % (7 patients, IC 95 % : 13–53). Au total, 18 patients ont ete operes, dont 12 avec des marges saines. Un patient est decede (metastatique DFS). La mediane de traitement etait de 3,8 mois (2,1–6,0) ; 9 patients (39 %) ont arrete le traitement pour effet secondaire ; 11 patients (48 %) ont eu une reduction de posologie. Les effets secondaires de grades 3–4 etaient : cytolyse (5), cholestase (3), syndrome hemolytique et uremique (1), syndrome nephrotique (1). La translocation COL1A1-PDGFB a ete identifiee chez 18 patients par FISH (5 non evaluable). Le taux plasmatique du VEGFR2 soluble etait associe a la reponse (p = 0,01). Conclusion Nous rapportons pour la premiere fois dans la litterature l’evaluation du pazopanib dans le DFSP dans le cadre d’un essai de phase II. Le pazopanib est une option therapeutique dans le DFS, bien que le rapport benefice risque semble moins bon que celui observe avec l’imatinib, avec une moins bonne tolerance ayant entraine des arrets precoces et reductions de dose.

Background Desmoplastic Small Round Cell Tumor (DSRCT) is a rare disease affecting predominantly children and young adults and for which the benefit of hyperthermic intraperitoneal chemotherapy (HIPEC) after complete cytoreductive surgery (CCRS) remains unknown. Methods To identify patients with DSRCT without extraperitoneal metastases (EPM) who underwent CCRS between 1991 and 2015, a retrospective nation-wide survey was conducted by crossing the prospective and retrospective databases of the French Network for Rare Peritoneal Malignancies, French Reference Network in Sarcoma Pathology, French Sarcoma Clinical Network and French Pediatric Cancer Society. Results Among the 107 patients with DSRCT, 48 had no EPM and underwent CCRS. The median peritoneal cancer index (PCI) was 9 (range: 2–27). Among these 48 patients, 38 (79%) had pre- and/or postoperative chemotherapy and 23 (48%) postoperative whole abdominopelvic radiotherapy (WAP-RT). Intraperitoneal chemotherapy was administered to 11 patients (23%): two received early postoperative intraperitoneal chemotherapy (EPIC) and nine HIPEC. After a median follow-up of 30 months, the median overall survival (OS) of the entire cohort was 42 months. The 2-y and 5-y OS were 72% and 19%. The 2-y and 5-y disease-free survival (DFS) were 30% and 12%. WAP-RT was the only variable associated with longer peritoneal recurrence-free survival and DFS after CCRS. The influence of HIPEC/EPIC on OS and DFS was not statistically conclusive. Conclusion The benefit of HIPEC is still unknown and should be evaluated in a prospective trial. The value of postoperative WAP-RT seems to be confirmed.

Breast cancer is a major health problem in developed countries. Pathological and clinical heterogeneity, partly responsible of therapeutic failures, reflects its poorly documented complex and combinatory molecular basis. Thorough molecular typing could allow not only better tackling that diversity and improving the current prognostic classifications, but also could help in the identification of new molecular therapeutic targets. The recently developed DNA microarray technology allows the analysis of the RNA expression of several thousands of genes simultaneously in a sample. Recent studies have shown the promising prognostic impact of gene expression profiling in breast cancer by identifying new prognostic subclasses unidentifiable by conventional parameters.

Sound production by the dusky grouper Epinephelus marginatus was monitored both in captivity and at two Mediterranean spawning sites during the summers of 2012 and 2013. The results of long-term passive acoustic recordings provide for the first time a description of the sounds produced by E. marginatus. Two types of sounds were mainly recorded and consisted of low-frequency booms that can be produced singly or in series with dominant frequencies below 100 Hz. Recordings in captivity validated these sounds as belonging to E. marginatus and suggested that they may be associated with reproductive displays usually performed during early stages of courtship behaviour. This study also allowed the identification of a third, low-frequency growl-like type of sound typically found in other grouper species. These growls were, however, not recorded in tanks and it is cautiously proposed that they are produced by E. marginatus. Acoustic signals attributed to E. marginatus were produced throughout the spawning season, with a diel pattern showing an increase before dusk, i.e., from 1900 to 2200 hours, before decreasing until the morning. The occurrence of sounds during the spawning season of this species suggests that they are probably involved in social activity occurring close to aggregation sites. Passive acoustics offer a helpful tool to monitor aggregation sites of this emblematic species in order to improve conservation efforts.

Prognostic factors for disease-free survival in patients treated before 2005 September: multivariate analysis. (DOCX 15Â kb)

The aim of this study was to document how breast cancer patients perceive their prognosis and a tailored treatment based on tumour gene expression analysis, and to identify the features of this approach that may impact its clinical application. In-depth interviews were conducted at three French cancer centres with 37 women (35-69 years of age) with node-positive breast cancer undergoing an adjuvant chemotherapy regimen defined on the basis of the genomic signature predicting the outcome after chemotherapy. Several concerns were identified. First, some misconceptions about these methods were identified due to semantic confusions between the terms 'genomic' and 'genetic', which generated anxiety and uncertainty about the future. Second, the 'not done' and 'not interpretable' signatures were misinterpreted by the women and associated with highly negative connotations. However, the use of tumour genomic analysis to adapt the treatment to each patient received most of the patients' approval because it was perceived as an approach facilitating personalised medicine. In conclusion, improving the quality of provider/patient communications should enable patients to play a more active part in the decision making about their treatment. This will ensure that those who agree to have tumour gene analysis have realistic expectations and sound deductions about the final result disclosure process.

Despite debulking surgery and taxane/platinum-based chemotherapy, ovarian cancer is the most lethal pelvic gynaecological cancer in western countries, with a 25% 5-years survival. Current histo-clinical prognostic factors are insufficient to capture the heterogeneous clinical outcome of patients. A better molecular characterization of the disease is crucial to refine the prognostic classifications and to identify new therapeutic targets. DNA microarrays, which allow the quantitative measurement of expression level of the whole genome simultaneously in a single tumor sample, have been recently used towards this objective with promising results. Here, we present and discuss the main published studies and the issues to address in the future to allow the expected transfer to clinical practice.

Dans toutes ces etudes, les signatures multigeniques pronostiques et/ou predictives paraissaient plus performantes que les classifications conventionnelles basees sur des facteurs histo-cliniques et moleculaires. Des etudes de validation sont, bien entendu, necessaires avant toute application clinique sur de plus grandes series retrospectives de patientes. Certaines sont en cours de maniere uni- ou multicentrique, et precederont l’eventuelle incorporation de ces signatures dans des essais cliniques prospectifs, premier niveau d’application clinique de cette approche. Le succes de ces etudes dependra de collaborations etroites entre chercheurs de differentes disciplines (cliniciens, anatomo-pathologistes, biologistes, bio-informaticiens, mathematiciens...;), de la qualite et de la quantite des echantillons tumoraux disponibles (avec leurs annotations informatisees cliniques, histologiques et moleculaires), de l’amelioration de la technologie et des outils d’analyse, et, bien sur, du bon design des essais.

Breast cancer is a major health problem in developed countries. Pathological and clinical heterogeneity, partly responsible of therapeutic failures, reflects its poorly documented complex and combinatory molecular basis. Thorough molecular typing could allow not only better tackling that diversity and improving the current prognostic classifications, but also could help in the identification of new molecular therapeutic targets. The recently developed DNA microarray technology allows the analysis of the RNA expression of several thousands of genes simultaneously in a sample. Recent studies have shown the promising prognostic impact of gene expression profiling in breast cancer by identifying new prognostic subclasses unidentifiable by conventional parameters.

Breast cancer is a complex and heterogeneous disease resulting from various molecular alterations, the identification of which should have profound impact on the management of patients.The discovery of germline mutations within breast cancer susceptibility genes, such as BRCA1 and BRCA2, which are associated with a major risk of breast cancer during lifetime, has improved the assessment of the individual risk toward the disease, allowing appropriate strategies of screening and prevention. The identification of key molecular actors in the mammary oncogenesis may help to better assess the prognosis of the disease, while providing new therapeutic targets. Large-scale molecular technologies, which allow simultaneous assessment of a high number of molecular parameters in a single assay, should provide new tools to tackle complexity and heterogeneity of breast cancer. Hence, by examining transcriptional profiles of breast cancer using DNA microarrays, it was possible to reveal new prognostic tumor subgroups, previously indistinguishable. Further improvements are awaited with the recent development of high throughput and large-scale technologies investigating the tumor proteome.Precise knowledge of molecular alterations involved in each individual breast cancer will allow more effective and less toxic, tailored therapies.

Aim: Retrospective data suggest that T maintenance beyond 6 cycles (cy) of treatment in responding pts with ASTS is associated with better outcome. We report here the result of a randomized phase II trial investigating clinical benefit of continuation of treatment until progression vs. drug-holiday (T-Dis trial; EudraCT 2010-022613-26). Methods: After the initial 6 cy of T (1.5 mg/m2 as 24-h infusion every 3 weeks), pts free from progressive disease (PD) were randomly assigned either to continuous treatment with T (C arm) or therapy interruption (I arm). Pts who declined randomization could continue with T. Pts allocated to the I arm could restart T in case of PD. Primary endpoint was PFS rate at 6 months (m) after randomization. Results: From February 2011 to March 2013, 178 pretreated pts have been enrolled. At inclusion, the pts had a median age of 57.5 years (range 19-82) and a median performance status of 1 (range 0-3) and most had leiomyo- (30%), lipo- (18%) or synovial sarcoma (12%). Among evaluable pts (n=178), the rate of non-progression after the initial 6 cycles of T was higher than expected (n=53; 29.7%). After 6 cy of T, 27 and 26 non progressive pts were randomized to C and I arm, respectively, and received a similar median number of T cy: 5 (range 2-17) for C arm and 5 (range 1-12) for I arm. In May 2014, the median PFS after randomization was 7.2 m in C and 4.0 m in I arm (p=0.031), the 6-m PFS of 51.9% (31.9-68.6) and 23.1% (9.4-40.3) for C and I arm. The 12-m OS rate after randomization was 84.6% (63.9-93.9) and 69.2% (43.3-85.0) for C and I arm, respectively. T has been reintroduced in 21/26 pts who progressed in I arm (PFS at re-challenge: 3.8 months). Occurrence of grade 3 (16.0 vs. 14.3%), grade 4 (4.0 vs. 0.0%) related toxicities and SAEs (0 vs. 0%) were similar in both arms. Conclusions: The rate of non-progression after 6 cy of T was higher than previously reported, probably due to a better selection of ASTS pts in referral centers and a better management of T. Continuation of T beyond the 6th cy until progression was associated with statistically significant improvement of PFS. Analysis of impact on OS requires longer follow-up. Disclosure: A. Le Cesne: Research Grant from Pharmamar; J. Blay: Research Grant from Pharmamar A. Italiano: Research Grant from Pharmamar; N. Badri: Employed by Pharmamar; N. Penel: Research Grant from Pharmamar. All other authors have declared no conflicts of interest.

International audience; Breast cancer is characterized by an important histoclinical heterogeneity that currently hampers the selection of the most appropriate treatment for each case. This problem could be solved by the identification of new parameters that better predict the natural history of the disease and its sensitivity to treatment. A large-scale molecular characterization of breast cancer could help in this context. Using cDNA arrays, we studied the quantitative mRNA expression levels of 176 candidate genes in 34 primary breast carcinomas along three directions: comparison of tumor samples, correlations of molecular data with conventional histoclinical prognostic features and gene correlations. The study evidenced extensive heterogeneity of breast tumors at the transcriptional level. A hierarchical clustering algorithm identified two molecularly distinct subgroups of tumors characterized by a different clinical outcome after chemotherapy. This outcome could not have been predicted by the commonly used histoclinical parameters. No correlation was found with the age of patients, tumor size, histological type and grade. However, expression of genes was differential in tumors with lymph node metastasis and according to the estrogen receptor status; ERBB2 expression was strongly correlated with the lymph node status (P < 0.0001) and that of GATA3 with the presence of estrogen receptors (P < 0.001). Thus, our results identified new ways to group tumors according to outcome and new potential targets of carcinogenesis. They show that the systematic use of cDNA array testing holds great promise to improve the classification of breast cancer in terms of prognosis and chemosensitivity and to provide new potential therapeutic targets.

It has now been clearly established that quantitative immunohistochemical methods applied to tumour angiogenesis under suitable quality control conditions are a powerful prognostic tool for use in the initial assessment of breast carcinomas. Appropriate parameters for predicting the aggressiveness of tumours and their sensitivity to treatment are, however, still required. To determine whether the microvessel count (MVC) may serve to predict the chemotherapeutic response, a retrospective study was carried out on a series of 162 patients with breast carcinoma, who were all treated with the same standard adjuvant chemotherapy. Angiogenesis was assessed by performing CD31 immunostaining and MVC per mm2. Several other factors such as P53, ERBB2, BCL2, and Ki67 were also measured, and their prognostic value was compared with that of the MVC. The MVC was not found to be correlated with any of the other prognostic parameters, but turned out to be of great prognostic value whatever the threshold value chosen, which suggests that it is continuously valid at all levels. The median value of the MVC (43.5 per mm2) divided this series into two significantly different prognostic categories, in terms of both disease-free survival (P = 0.0002) and overall survival (P = 0.037). Univariate analysis showed that most of the parameters analysed were of prognostic value regarding the disease-free survival, namely grade (P = 0.029), mitotic index (P = 0.049), size (P = 0.015), oestrogen receptors (P = 0.022), progesterone receptors (P = 0.018), P53 (P = 0.0045), ERBB2 (P = 0.046), and Ki67 (P = 0.0008). As regards overall survival, grade and ERBB2 showed a loss of prognostic value. In multivariate analysis on disease-free survival, the MVC was the most accurate prognostic factor (RR = 2.64), followed by Ki67 (RR = 2.06) and P53 (RR = 1.69). With respect to overall survival, the MVC ranked third among the prognostic parameters analysed. Standard chemotherapy did not reduce the high prognostic value of the MVC performed on tumour angiogenesis. This suggests that the MVC may predict the degree of resistance to chemotherapy. Patients with high levels of angiogenesis, particularly node-negative patients, might therefore be able to benefit from adjuvant therapy of another kind.

Despite important initial chemosensitivity, advanced ovarian cancer has a bad prognosis with a median survival of 20 to 30 months. These results might be better with intensive chemotherapy. We analysed 67 patients treated by intensive chemotherapy with autologous stem cell transplantation for advanced ovarian cancer at Institute Paoli-Calmettes between 1980 and 1994. Population was divided in two groups: salvage group (n = 30) for initial chemotherapy-refractory patients and consolidation group (n = 37) for sensitive patients. Several successive conditioning regimens were used, all based on alkylating agents. Principal toxicities were severe aplasia and mucositis. Four patients died from toxicity related to infection during strong immunosuppression. In salvage group, 9 out of 21 evaluable patients responded (43%), but duration of responses was short (median range of 5 months) and 2-year overall survival rate was 8% after transplantation. In consolidation group, 19 patients are alive and 15 are without disease progression with a median follow-up of 42 months (17, 161) after diagnosis. Five-year disease-free survival rate is 28% (median range of 35 months) and 5-year overall survival rate is 48% (median range of 41 months). Intensification does not seem to be long term beneficial for initial chemotherapy refractory patients, despite objective responses rate better than classical treatment. On the other hand, results seem better than conventional treatments in case of chemosensitive disease and should be confirmed prospectively in larger cohort of patients. Moreover, other research directions are open like intensification supported by hematopoietic growth-factors and peripheral stem cells, definition of best conditioning regimen, use of taxanes, and intensification in first line chemotherapy after initial surgery.

15054 Background: The use of adjuvant therapy in stage II colorectal cancer (CRC) remains controversial. There is clearly a need to identify better predictors than the traditional staging system to...

10016 Background: IM the first-line treatment for advanced GIST, must be given continuously until disease progression (PD) or intolerance (Blay et al, ASCO 2004). The impact on long term overall survival (OS) of IM discontinuation in responding patients (pts) and its re-introduction at progression is unknown. Methods: This prospective multicenter BFR14 study was initiated in June 2002. After 1 year of IM 400mg/day, 58 pts free from progression were randomly offered to continue or interrupt IM until PD. Pts allocated to the interruption (I) arm could restart IM (same dose) in case of PD. Primary endpoint was progression-free survival (PFS); secondary endpoints were OS, secondary response after IM re-introduction, identification of molecular determinants of response. Survival data were compared using the log-rank test. Results: Pt characteristics were well balanced between the two arms. Current median follow- up after randomization is 37 months (range 0–42): 29/32 pts (91%) in arm I vs. 16/26 pts (62%) in continuous (C) arm experienced PD. IM interruption was significantly associated with reduced PFS (p-4) with a median of 6 months (95% CI, 3.5–9.5) for arm I. Among the 26 pts of I arm who restarted IM after first progression, 24 (92%) achieved tumor control (OR or SD), one progressed, one died from an unrelated cause. The 2-yr OS rates were 87% and 92% for arms I and C, respectively (P = 0.78). Conclusions: Despite a significant increase of PD in the experimental arm, IM re-introduction is safe and allows a tumor control in the majority of pts. No unfavourable impact of IM interruption on OS was reported. Treatment interruption could be a therapeutic option in advanced GIST pts exhibiting intolerance to IM. Updated results including mutational analysis will be presented at the meeting. No significant financial relationships to disclose.

A new approach for quantification of global strain and twist of ventricular wall is presented, it utilizes the theoretical framework of dynamical systems faking into account the large time-varying displacements that occur during the beating of the heart. Topological features of the 3D optical flow have been analysed; such features summarize the global behaviour of the motion field and can be used as cardiac function indexes. In particular the eigenvalues and eigenvectors of the vector field critical points give useful information about deformation and rotation of the entire left ventricle during cardiac cycle. The eigenvectors directions are related to the principal axis of deformation and to the rotation axis. The eigenvalues are related to deformation and rotation magnitudes, therefore they provide an estimate of the relative variation of volume and twisting for each time step.