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Background: This prospective multicentric phase II study aimed to confirm the results of the C5R protocol of high-dose methotrexate (MTX)-based chemotherapy (CT) for immunocompetent primary central nervous system lymphoma. Patients and methods: A total of 99 patients received age-adapted CT (C5R protocol) followed by radiotherapy. Patients younger than 61 years (group 1, n = 45) received the full C5R with MTX, doxorubicin, vincristine, cyclophosphamide, and cytarabine. Patients aged 61-70 years (group 2, n = 36) received reduced doses. Patients older than 70 years (group 3, n = 18) received four courses of MTX, cyclophosphamide, and etoposide. Results: Median age was 63 years and 51% of patients had performance status of more than one. Seventeen patients died of toxicity during CT. Complete response was achieved in 56%, 53%, and 28% of patients in groups 1, 2, and 3, respectively. With a median follow-up of 83 months, the 5-year progression-free survival was 31%, 28%, and 11% and the 5-year overall survival 42%, 31%, and 17% for groups 1, 2, and 3, respectively. Leukoencephalopathy occurred in 32% of assessable patients, in both group 1 and groups 2-3. Conclusion: The C5R protocol was feasible in the multicentric setting with favorable long-term survival in patients younger than 60 years. Despite dose adaptation, results in older patients were disappointing.

Soft tissue sarcomas are rare tumors. They may occur in any part of the body. Early step of management are essential because they directly affect functional consequences and survival of patients. It is very important to rapidly evoke the diagnostic of soft tissue sarcoma. Multidisciplinary discussion is indispensable at different step of the management: before the diagnostic to organize radiological check up and preoperative biopsy, before resection of localized tumor to decide the surgical procedure, with anatomopathological results to discuss an adjuvant treatment, at metastatic setting to decide a systemic treatment to start or inclusion in a clinical trial.

Aims To assess the antitumour activity, safety, pharmacokinetics and pharmacodynamics of continuous daily sunitinib dosing in patients with imatinib-resistant/intolerant gastrointestinal stromal tumour (GIST) and to assess morning dosing versus evening dosing. Patients and methods In this open-label phase II study, patients were randomised to receive morning or evening dosing of sunitinib 37.5 mg/day. The primary end-point was clinical benefit rate (CBR; percent complete responses + partial responses [PRs] + stable disease [SD] ⩾24 weeks). Secondary end-points included progression-free survival (PFS), overall survival (OS), safety, pharmacokinetic parameters and plasma biomarker levels. Results Sixty of 61 planned patients received treatment (30 per dosing group); 26 completed the study. Overall, the CBR was 53% (95% exact CI, 40–66): eight patients (13%) achieved objective PRs; 24 (40%) achieved SD ⩾24 weeks. Median PFS was 34 weeks (95% CI, 24–49); median OS was 107 weeks (95% CI, 72 – not yet calculable). Most adverse events (AEs) were of grade 1 or 2 in severity, and were manageable through dose modification or standard interventions. No new AEs were apparent compared with the approved intermittent dosing schedule. Antitumour activity and safety were generally similar with morning and evening dosing. Continuous daily sunitinib dosing achieved and sustained effective drug concentrations without additional accumulation across cycles. Decreases from baseline in plasma levels of soluble KIT after 20 and 24 weeks of dosing correlated with longer OS. Conclusion For patients with imatinib-resistant/intolerant GIST, continuous daily sunitinib dosing appears to be an active alternative dosing strategy with acceptable safety.

Gastrointestinal stromal tumours (GISTs) are the most frequent mesenchymal tumours of the digestive tract and occur typically in the stomach for two-third or in the small intestine for 25% in most series (Emile et al, 2004). Gain of function mutations of either KIT or platelet-derived growth factor receptor alpha polypeptide (PDGFRA) receptor tyrosine kinases play a critical role in GIST pathogenesis, and are found in 85% of GISTs (Rubin et al, 2007). Many types of gain of function mutations of KIT and PDGFRA have been described in GISTs, but 60% occurred within the exon 11 of KIT (Corless et al, 2004; Emile et al, 2004), which comprises 33 codons (codons 550–582). The two tyrosines Tyr568 and Tyr570, first residues to be phosphorylated during activation, are consensus sites for binding of Src family kinases and could be implicated in activation of different signalling pathways (Roskoski, 2005). More than 90 mutations of exon 11 have been published, and consist in insertions, substitutions and deletions; however, delWK557–558, in the proximal part of exon 11, is the most frequent, accounting for 8–25% of KIT exon 11 mutations. Others deletions, in the distal part of the exon, include in particular deletions of Tyr568 and/or Tyr570, and may thus have more specific effects on KIT signalling pathways and degradation. Such deletions account for 3–8% of exon 11 mutations in published series (Ernst et al, 1998; Taniguchi et al, 1999; Debiec-Rychter et al, 2004, 2006; Wardelmann et al, 2004; Martin et al, 2005; Penzel et al, 2005; Andersson et al, 2006; Emile et al, 2006; DeMatteo et al, 2008). After surgical resection, the type of KIT mutations may be a prognostic factor of relapse. KIT exon 11 deletions and deletions affecting codons 557–558 of KIT exon 11 were described to be independent adverse prognostic factors in patients with GIST (Wardelmann et al, 2003; Martin et al, 2005; DeMatteo et al, 2008). Conversely, in another study, GISTs in which the last part of exon 11 (codons 562–579) was deleted were most frequently associated with malignancy than GISTs with deletion of the first part of exon 11 (codons 550–561; Emile et al, 2004, 2006). So, the prognostic value of some types of KIT exon 11 mutations for risk of relapse is still debated. The mutational status of KIT or PDGFRA is predictive of clinical response to imatinib (Glivec, Gleevec, Novartis, Basel, Switzerland) and best results are obtained in patients with GISTs harbouring KIT exon 11 mutations (Heinrich et al, 2003; Debiec-Rychter et al, 2006). Nevertheless, the role of the type of KIT exon 11 mutations for the response and survival under imatinib remains to be determined. Thus, to better understand the prognostic significance of the type of KIT exon 11 deletions, we have compared the clinical characteristics and outcome of patients with GIST and deletion of both Tyr568 and Tyr570 with the most frequent deletion of KIT exon 11, delWK557–558.

Background: Targeted agents have improved the prognosis for patients with advanced gastrointestinal stromal tumours (GISTs). Many patients exhibit intolerance or resistance to first-line therapy with imatinib mesylate. Sunitinib malate is approved multinationally for the treatment of advanced imatinib-refractory GIST. Design: This article reviews responses to imatinib and sunitinib reported in clinical trials in advanced GIST and discusses the effect of mutational status on treatment responses; therapeutic developments in GIST treatment are also reviewed. Results: Imatinib 400 mg/day has shown efficacy for first-line treatment of advanced GIST, particularly in patients with KIT exon 11 mutations. Sunitinib 50 mg/day (Schedule 4/2) has demonstrated effectiveness and tolerability in imatinib-refractory GIST, including patients who would be excluded from clinical trials. Sunitinib is associated with longer median overall survival in patients with primary KIT exon 9 mutations and wild-type GIST compared with KIT exon 11 mutations in a retrospective study. Ongoing studies, including imatinib in the adjuvant setting and the use of targeted agents in sequence or in combination, will further refine the therapeutic pathway for advanced GIST. Conclusions: The availability of targeted therapies and greater knowledge of the effect of mutational status on patient responses will assist in optimising outcomes in advanced GIST.

Rationale: Angiosarcomas of soft tissue represent a heterogenous group of rare sarcomas with specific clinical behaviour and risk factors. Paclitaxel appears to induce tumour control in a higher proportion of patients with angiosarcoma, as compared to other sarcomas. The objective of this retrospective study was to assess the anti-tumour activity of this compound in a multicentre setting. Method: Clinical data from patients with angiosarcomas of soft tissue treated with single agent paclitaxel were collected from the centres of the soft tissue and bone sarcoma group of EORTC, using a standardised data collection form. Paclitaxel could be given every three weeks, or weekly. Statistical analysis was performed using SAS software. Results: Data from 32 patients were collected from 10 centres. There were 17 males, IS females, with a median age of 60.4 years (range, 25-91). Primary angiosarcomas were located in scalp and face in 8 patients (25%) and at other primary sites in 24 patients (75%). All patients had intermediate (n = 13) or high grade (n = 19) primary tumours. Thirteen (40%) patients had been pretreated with doxorubicin-based first-line-chemotherapy and three of them (9%) had also received second-line chemotherapy with ifosfamide. Eleven (34%) patients had been irradiated before as treatment for angiosarcoma. In 8 (25%) patients, the angiosarcoma occurred at sites of prior radiation therapy for other malignancies. The response rate was 62% (21/32) in the whole series, 75% (6/8) in scalp angiosarcomas and 58% (14/24) in other primary sites. The median time to progression was 7.6 months (range, 1-42) for the whole group. For the face/scalp group it was 9.5 months, and for patients with angiosarcomas at other sites it was 7.0 months, respectively. Conclusion: Paclitaxel was found to be an active agent in angiosarcoma of soft tissue in this retrospective analysis. These results need to be confirmed in a prospective randomised phase II study. (C) 2008 Elsevier Ltd. All rights reserved.

Objective To evaluate the impact of surgery as first-line treatment on event-free survival (EFS) of primary aggressive fibromatosis. Patients and methods Treatments were categorized into: surgery with or without radiotherapy and nonsurgical strategies with systemic treatment alone or wait and see policy. Eighty-nine patients had initial resection of their primary tumour followed by postoperative radiotherapy in 13 cases. Twenty-three did not undergo surgery but received systemic treatment or watch and wait policy. Results Median follow-up was 76 months. Overall 3 years EFS was 49%. In the univariate analysis, patients with microscopically complete surgery had a similar outcome to patients in the no-surgery group (3 years EFS of 65% and 68%, respectively). Gender, age, tumour size, treatment period and strategy (surgery versus no-surgery) were not statistically significant. Quality of resection according to margins and the tumour site were the only prognostic factors. There was a significant correlation between tumour site and quality of surgery (p = 0.0002). Conclusions A subset of patients with extra-abdominal fibromatosis could be managed with a nonaggressive policy, as growth arrest concerned 2/3 of nonoperated patients. When surgery is finally necessary, it should be performed with the aim of achieving negative margins.

Contexte La mise a jour des recommandations pour la pratique clinique (RPC) pour la prise en charge des patients atteints d’un sarcome des tissus mous a ete elaboree par la Federation nationale des centres de lutte contre le cancer (FNCLCC), en collaboration avec le Groupe sarcome francais et le Groupe d’etude des tumeurs osseuses (GSF-GETO), des partenaires des secteurs publics (CHU, CHG), prive et de l’Institut national du cancer sur la base de la methodologie developpee par les SOR.

Les sarcomes constituent un groupe heterogene de tumeurs malignes developpees aux depens des cellules composant les tissus de soutien specialises et non specialises. Les progres accomplis dans la comprehension des evenements genetiques conduisant a leur transformation, notamment l’identification des evenements genetiques initiaux dans le processus de transformation, permet actuellement le developpement de therapeutiques moleculaires ciblees sur les proteines critiques dans le processus de transformation. Les tumeurs stromales gastro-intestinales (GIST), dont le developpement est dependant d’une activation constitutionnelle de c-KIT ou de PDGFR, sont ainsi devenues les modeles des therapeutiques ciblees, avec l’imatinib et plus recemment le sunitinib. Cependant, des therapeutiques moleculaires ciblant notamment mTOR (mammalian Target Of Rapamycine) et l’angiogenese sont actuellement en developpement dans differents types histologiques de sarcomes. L’identification des evenements moleculaires initiaux de l’oncogenese, constituant les nouvelles cibles therapeutiques, permet ainsi a la fois la caracterisation de nouvelles entites nosologiques au sein des sarcomes, mais egalement le developpement de nouvelles therapies ciblees.

Background Isolated pelvic perfusion exposes tissue to high drug doses and may benefit patients with advanced malignancy. However, leakage is a limit to this technique. Aims The aim of the study is to increase the perfusion ratio between local and systemic compartments on isolated pelvic perfusion. We hypothesised that an inflated pressure-suit placed above the level of aortic and caval stop flow could decrease leakage from the regional to the systemic blood compartment in a bovine model. Method As the size of the pressure-suit was adapted for use in humans, we performed our experimental study on 6 calves which are big enough to fit into the suit. We used an inflated pressure-suit placed at low (40 mmHg) and high pressures (125 mmHg) above the level of aortic and caval stop-flow. A pharmacokinetic study with cisplatinum was performed in both compartments. Results After injection of the drug, the mean ratio of drug concentration in the locoregional/systemic compartment was 43.1. After 30 min, this mean ratio was 4 and 9.7 for a pressure-suit pressure of 40 mmHg and 125 mmHg, respectively. At pressure-suit pressures of 40 mmHg and 125 mmHg, pelvic perfusion achieved pelvic/systemic exposure ratios of 5.9 and 14.9 at 30 min, respectively. Leakage at 30 min was higher when the pressure-suit was inflated at low pressure (40 mmHg, mean 18%). When the pressure-suit was inflated at high pressure, leakage was lower (125 mmHg, mean 7%). Conclusions The pressure-suit increased the perfusion ratio between pelvic and systemic compartments in a bovine model.

L’European Society for Medical Oncology (ESMO) est la premiere organisation europeenne dediee a l’oncologie medicale. Creee en 1975 dans le but de promouvoir l’oncologie medicale, elle evolue actuellement pour promouvoir une oncologie multidisciplinaire, integrant les differents acteurs medicaux de toutes specialites, ainsi que les chercheurs, les soignants et les associations de patients. La mission de l’ESMO est de procurer des soins optimaux a tous les patients. Dans cet objectif, l’ESMO propose une large variete d’activites scientifiques et d’enseignement destinees a la communaute de l’ESMO: 1) aux jeunes oncologues — pour aider et soutenir le developpement de leur carriere; 2) pour les oncologues en activite — afin de mettre a jour leurs connaissances medicale et scientifique dans le cadre de programmes accredites; 3) pour les patients — afin de les aider a acquerir une meilleure connaissance de leur maladie, comment la combattre, comment l’assumer au quotidien. Dans ce document, nous decrivons les differentes activites de l’ESMO dans le domaine de l’education et de l’enseignement.

Background Advanced malignant solitary fibrous tumors (SFTs) are rare soft-tissue sarcomas with a poor prognosis. Several treatment options have been reported, but with uncertain rates of efficacy. Our aim is to describe the activity of trabectedin in a retrospective, multi-center French series of patients with SFTs. Methods Patients were mainly identified through the French RetrospectYon database and were treated between January 2008 and May 2013. Trabectedin was administered at an initial dose of 1.5 mg/m2, q3 weeks. The best tumor response was assessed according to the Response Evaluation Criteria In Solid Tumors 1.1. The Kaplan–Meier method was used to estimate median progression-free survival (PFS) and overall survival (OS). The growth-modulation index (GMI) was defined as the ratio between the time to progression with trabectedin (TTPn) and the TTP with the immediately prior line of treatment (TTPn-1). Results Eleven patients treated with trabectedin for advanced SFT were identified. Trabectedin had been used as second-line treatment in 8 patients (72.7 %) and as at least third-line therapy in a further 3 (27.3 %). The best RECIST response was a partial response (PR) in one patient (9.1 %) and stable disease (SD) in eight patients (72.7 %). Disease-control rate (DCR = PR + SD) was 81.8 %. After a median follow-up of 29.2 months, the median PFS was 11.6 months (95 % CI = 2.0; 15.2 months) and the median OS was 22.3 months (95 % CI = 9.1 months; not reached). The median GMI was 1.49 (range: 0.11–4.12). Conclusion Trabectedin is a very promising treatment for advanced SFTs. Further investigations are needed.

The DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials) aims to provide recommendations for definitions of time-to-event end points in cancer randomized controlled trials. We relied on a consensus method based on a multidisciplinary panel of experts to develop these guidelines for trials on sarcomas and gastrointestinal stromal tumors. Background The use of potential surrogate end points for overall survival, such as disease-free survival (DFS) or time-to-treatment failure (TTF) is increasingly common in randomized controlled trials (RCTs) in cancer. However, the definition of time-to-event (TTE) end points is rarely precise and lacks uniformity across trials. End point definition can impact trial results by affecting estimation of treatment effect and statistical power. The DATECAN initiative (Definition for the Assessment of Time-to-event End points in CANcer trials) aims to provide recommendations for definitions of TTE end points. We report guidelines for RCT in sarcomas and gastrointestinal stromal tumors (GIST). Methods We first carried out a literature review to identify TTE end points (primary or secondary) reported in publications of RCT. An international multidisciplinary panel of experts proposed recommendations for the definitions of these end points. Recommendations were developed through a validated consensus method formalizing the degree of agreement among experts. Results Recommended guidelines for the definition of TTE end points commonly used in RCT for sarcomas and GIST are provided for adjuvant and metastatic settings, including DFS, TTF, time to progression and others. Conclusion Use of standardized definitions should facilitate comparison of trials' results, and improve the quality of trial design and reporting. These guidelines could be of particular interest to research scientists involved in the design, conduct, reporting or assessment of RCT such as investigators, statisticians, reviewers, editors or regulatory authorities.

Treatment of metastatic soft tissue sarcoma (mSTS) commonly includes multiple lines of chemotherapy, until a decline in performance status precludes further treatment. The primary objective of this study was to describe the lifetime healthcare resource utilisation and cost among mSTS patients with favourable response to chemotherapy. SABINE was a multi-centre (n=25), multi-country (n=9) retrospective chart review study of mSTS patients with favourable response to chemotherapy following 4 cycles. Healthcare resource utilisation was collected from first line until death or end of follow-up. Costs were analysed by health states (defined by treatment line, chemotherapy use and disease progression) and estimated by multiplying the mean weekly cost per health state by the expected number of weeks spent in each health state. Expected per-patient lifetime medical cost was Euro65616 (95% CI: Euro51454-Euro85003); comprised of IV chemotherapy (31.7%), inpatient care (24.8%), concomitant medication (11.0%), oral chemotherapy (8.9%), outpatient visits (8.8%), radiotherapy (6.3%), hospice (4.0%), imaging (3.7%) and laboratory (0.7%). Weekly costs were 280-330% higher during chemotherapy treatment periods than off-chemotherapy, especially after disease progression. Per-patient costs were highest in the USA and lowest in the Netherlands and UK. The economic burden of mSTS is considerable and the amount of resources devoted to its treatment varies across countries.

Although most breast cancers are adenocarcinomas of the mammary gland, primary breast sarcomas may also arise from mammary gland mesenchymal tissue. The annual incidence of primary breast sarcoma is low and has been estimated at 45 new cases per 10 million women. These tumours are at high risk of recurrence and are known to have poor prognosis. Phyllodes tumours represent a specific subset of these breast soft tissue tumours. They are composed of a connective tissue stroma and epithelial elements. Pathological presentation ranges from grade I to malignant phyllodes tumours (grade III) where the stromal component clearly exhibits a sarcoma pattern.SAPHYR (SArcoma and PHYllode Retrospective) is a retrospective study of the experience of Leon Bérard Cancer Centre (Lyon, France) from 1966 to August 2004. SAPHYR aims to describe the characteristics of primary breast sarcomas and to define potential survival factors to be evaluated in future prospective studies.We included 70 patients. Half of them presented at least one recurrence (35/70). Median disease-free-survival (DFS) was 1.15 years. At 3 years, median overall survival had not been reached and more than 61% of the patients were alive. Quality of surgical resection was significantly (p=0.036) different whether patients were in the R0 group (72%) or not (38%). No survival difference was found between malignant phyllodes (grade III) and other primary breast sarcomas (angiosarcomas excluded). Histology revealed three significantly (p=0.0003) different prognostic groups: phyllodes grade I and II (DFS=57%), angiosarcomas (DFS=7%) and phyllodes grade III and other primary breast sarcomas (DFS=45%).Phyllodes tumours and primary breast sarcomas are totally different from epithelial breast cancers and should be considered as a distinct group of rare tumours. The first goal of treatment is to achieve negative margins (R0). We propose to treat the patients according to the clinical practice guidelines in use for soft tissue sarcomas and address them to a reference centre for sarcoma. Treating rare tumours in the same place should permit us to standardise pathological data and to include patients into multicentric radiotherapy or chemotherapy protocols to improve overall survival. As further prospective studies are needed, European oncology groups must join their forces to create a prospective Rare Cancer Network.

Il y a 25 ans, la convergence de plusieurs strategies de recherches independantes vers un petit nombre de genes a permis de fonder le paradigme des oncogenes, les «genes de cancer» dont les de reglements perturbent la proliferation, la differenciation ou la mort des cellules cancereuses. Aujourd'hui, un nouveau paradigme base sur une hypothese formulee il y a plus de 50 ans, selon laquelle la croissance rapide d'une tumeur depend du developpement de nouveaux vaisseaux sanguins (angiogenese) qui apportent aux cellules cancereuses les elements nutritifs. Au cours des dernieres annees, cette hypothese a ete verifiee dans une serie de modeles experimentaux. Aujourd'hui, Les therapies antiangiogeniques suscitent beaucoup d'espoirs, et beaucoup de questions. De nombreuses etudes de phase II et de phase III ont montre le benefice du ciblage de l'angiogenese dans la prise en charge de cancers solides notamment en situation avancee ou metastatique (colon, rein...). A l'evidence, de nombreux travaux cliniques restent a realiser pour definir au mieux la place de ces traitements prometteurs dans la prise en charge des autres tumeurs solides. L'evaluation economique d'un choix therapeutique est loin d’etre immediate et ne saurait se limiter au cout d'acquisition des traitements. Cette revue de la litterature scientifique pointe les recents developpements des inhibiteurs de l'angiogenese et plus particulierement d'anticorps anti-VEGF dans le traitement de plusieurs types de cancers.

This phase I study evaluated the toxicity of first-line combined pegylated liposomal doxorubicin (Caelyx®) and ifosfamide in patients with advanced and/or metastatic soft tissue sarcomas. Five dose levels (L) were studied: Caelyx® 30 mg/m2 (L1–4) or 40 mg/m2 (L5) 1-h infusion d 1 q 3 weeks + ifosfamide and mesna at X g/m2/4 h d 1–3 q 3 weeks at five doses: L1: X = 1.7 g; L2: X = 2 g; L3: X = 2.5 g; L4 and L5: X = 3 g. Cohorts of 3 patients were entered at each level unless a dose-limiting toxicity (DLT) occurred. In case of DLT in 1 of 3 patients a new cohort was added. Toxicity was evaluated by Common Toxicity Criteria (CTC). A total of 28 patients was included: 4 at dose L1, 8 at L2, 3 at L3, 6 at L4, and 7 at L5. Median age was 60 years (range 29–69 years). Male/female ratio was 12/16. Seventy-five percent of patients had a performance status of 1.0 and 36% had leiomyosarcomas. No DLT was observed at dose L1–4. Six patients developed a DLT at dose L5, and thus the recommended dose is level 4 (i.e. Caelyx® 30 mg/m2/1 h d 1 + ifosfamide at 3 g/m2/4 h d 1–3 q 3 weeks). Few haematological and biochemical events were observed and the principal toxicities were granulocytopaenia and leucopaenia. Five patients discontinued therapy because of toxicity, 4 of them at dose level 5. Non-haematological toxicities > grade 2 were also few. Palmar-plantar erythrodysesthesia (PPE) > grade 1 was not seen. Two patients obtained partial response (PR) and 13 stable disease (SD). Median overall survival (OS) was 333 d and median progression-free survival (PFS) 174 d. In conclusion, this seems to be a feasible combination in patients with advanced soft tissue sarcomas, allowing ifosfamide to be given in a dosage similar to that used when given alone. The recommended dose for future studies is Caelyx® 30 mg/m2/1 h d 1 + ifosfamide 3 g/m2/4 h d 1–3 q 3 weeks.

Resume Le developpement de l'immunologie a permis une nouvelle approche dans le traitement des cancers. Les strategies de stimulation du systeme immunitaire se sont revelees globalement decevantes. En revanche, la technologie des anticorps monoclonaux et du ciblage tumoral a permis des avancees majeures dans les traitements anticancereux. En premier lieu en perturbant la molecule de surface ciblee qui est indispensable a la biologie de la cellule cancereuse, mais aussi en stimulant une reponse immunitaire grâce a la cytolyse dependante des anticorps ou du complement. En pratique clinique de nombreux exemples illustrent cette approche fructueuse : le trastuzumab dans les cancers du sein, le cetuximab ou le bevacizumab dans les cancers colorectaux. Les recepteurs cibles par les anticorps etant des recepteurs a tyrosine kinase, des inhibiteurs specifiques ont ete mis au point avec egalement une certaine efficacite. On peut citer les exemples de l'erlotinib dans les cancers pulmonaires, de l'imatinib ou de sunitinib dans les tumeurs stromales gastro-intestinales. De nombreuses autres therapies ciblees sont actuellement en developpement et permettent des espoirs importants pour proposer des traitements toujours plus adaptes.

Resume Contexte La prise en charge des tumeurs stromales gastro-intestinales (GIST) a considerablement evolue recemment, avec notamment la mise a disposition de l’imatinib. Les standards de prise en charge restaient mal definis. Nous rendons compte du travail d’un groupe d’experts francais sur l’adaptation francaise des recommandations de pratiques de l’Europeen Society of Medical Oncology (ESMO) recemment rapportees. Materiels et methodes Un groupe de vingt-deux experts francais s’est reuni pour analyser le document de consensus ESMO et l’adapter a la pratique francaise. Quatre groupes de travail ont ainsi revu les propositions concernant : l’anatomopathologie et la biologie moleculaire, l’imagerie en situation localisee ou metastatique et la prise en charge diagnostique des tumeurs de petite taille, la chirurgie des GIST localisees et metastatiques, le traitement systemique des GIST. Resultats L’examen histologique standard doit etre complete par une analyse immunohistochimique a l’aide des marqueurs CD117, CD34, PS100, Desmine et SMA. Le recours a la biologie moleculaire pour l’identification de la mutation des genes KIT et PDGFRA, est souhaitable pour les GIST presentant un immunomarquage negatif avec CD117 et pour predire la reponse au traitement, mais reste un examen de recherche. La chirurgie de la tumeur primaire doit comprendre une resection tumorale complete, incluant des marges tumorales negatives. L’administration d’imatinib en traitement adjuvant ou neoadjuvant est consideree comme une approche experimentale, a effectuer dans le cadre d’etudes cliniques prospectives. La resection des metastases est egalement consideree comme une procedure experimentale, avant, pendant ou apres echec d’un traitement par imatinib. Il est recommande d’instaurer l’imatinib des le diagnostic de recidive metastatique et de le poursuivre jusqu’a l’intolerance ou la progression multifocale de la maladie. Les criteres optimaux de reponse tumorale a l’imatinib font encore l’objet de travaux prospectifs. Ils peuvent inclure : une reduction de taille de la tumeur ou une stabilisation de la maladie, une diminution de la densite tumorale (unites Hounsfield) sur la TDM, une diminution de l’activite metabolique (mesuree par la captation de FDG sur TEP), la diminution de la vascularisation tumorale, mesuree par echo-Doppler avec injection de produit de contraste. Une augmentation de la taille de la tumeur ne traduit pas necessairement une progression et doit donc etre soigneusement evaluee, sans interrompre le traitement par imatinib avant confirmation definitive. Conclusion Les recommandations francaises pour la prise en charge des GIST adoptent la plupart des recommandations etablies par l’ESMO, et les completent du point de vue du gastroenterologue. Ce travail collegial a ete soumis a une revue de pathologie, de gastroenterologie et d’oncologie et son impact sur les pratiques sera evalue prospectivement.

The soft tissue sarcomas are a rare pathology and patient management complex. Good clinical practice should be delineated by rigorous recommendations. In case of suspicion of a sarcoma, precise assessment imagery must be carried out with a biopsy to allow the preparation of the surgical procedure. The surgical procedure should be extensive and complete to enable a macroscopic and microscopic resection. The adjuvant treatment could involve radiotherapy and chemotherapy whose indications should be specified within a multidisciplinary team. Unfortunately, recent studies showed no optimal management for majority of patients treated for sarcomas.

Chemotherapy of sarcomas includes two major drugs: doxorubicin, ifosfamide and a third, dacarbazine, whose effectiveness remains marginal. The current challenge consists in improving the combination of these drugs, in particular by modulating their amounts. New molecules of chemotherapy show their efficiency in sarcomas. Among those, one will note above all gemcitabine and ET-743, in some sub-types. Target therapies and antiangiogenic treatment have also begun to show results. It is advisable from now on to distinguish the different sub-type of sarcomas in order to assess cytotoxic activity.

Les tumeurs rares de la sphere ovarienne adulte representent moins de 10 % des tumeurs ovariennes de l’adulte. Le traitement des tumeurs rares de l’ovaire est actuellement etabli comme suit: —la chirurgie est calquee sur la chirurgie des adenocarcinomes ovariens, avec une difference majeure: l’objectif d’etre conservateur de la fonction genitale chez les femmes en âge de procreer (cas habituel dans ce type de tumeur); —la chimiotherapie basee sur les donnees de la litterature est calquee sur celle des tumeurs germinales testiculaires; —la chirurgie, la chimiotherapie et une eventuelle chirurgie des lesions residuelles sont fortement intriquees. Cependant, les tumeurs non epitheliales malignes de l’ovaire sont des cancers rares dont l’histoire naturelle est mal connue et dont les facteurs pronostiques ne sont pas precises; pour ces raisons tous les malades devraient etre adresses a des centres specialises ayant un interet specifique pour ce type de tumeur et disposant d’un departement d’anatomopathologie adequat. En effet, les etudes recentes decrivent comme facteurs pronostiques, outre le stade de la maladie, le nombre de patientes pris en charge tant d’un point de vue chirurgical que medical, temoin de la necessite d’une experience importante dans ce domaine. Du fait de l’extreme rarete de ces tumeurs, un site Internet dedie a la prise en charge de ces tumeurs rares a ete elabore puis installe pour mettre a disposition de tous, des avis concernant la prise en charge chirurgicale, oncologique en premiere, deuxieme, etc. ligne de traitement par l’intermediaire d’un forum de discussion accessible par Internet. D’autre part des programmes de recherche cliniques et de l’information pour le public ont ete developpe dans le meme temps. Ce protocole de prise en charge concerne les tumeurs malignes ovariennes germinales, et les tumeurs malignes stromales des cordons sexuels (tumeurs de la granulosa et cellules de Sertoli Leydig).

Purpose In order to decrease loco-regional relapse after complete resection of peritoneal sarcomatosis (PS), the role of intraperitoneal chemotherapy (IPEC) was prospectively evaluated. Methods Patients (pts) with completely resected PS were randomized between adjunction of IPEC or not. IPEC consisted of doxorubicin, 0.1mg/kg and cisplatin, 15mg/m 2 per day for 5 consecutive days. Primary endpoint was survival, measured as time from randomization to death. The scheduled number of patients needed was 40 in order to detect a minimal increase of 40% overall survival with the adjunction of IPEC with a power of 80%. Results Thirty-eight consecutive pts have been randomized, 19 in each group. Ratio of retroperitoneal (RPS) and visceral (VS) sarcomatosis were 9/10 and 6/13 in IPEC− and IPEC+ group, respectively. Histoprognostic grade, Sugarbaker's score and mean number of resected organs were similar in both groups. There were no toxic deaths and morbidity was similar in both groups (four pts in each group). The median follow-up is 60 months. The median local relapse-free, metastatic relapse-free survival and overall survival were identical in both groups (12.5, 18 and 29 months, respectively), with no difference between RPS and VS sarcomatosis. Conclusion Administration of IPEC after a macroscopically complete surgery did not allow to increase greatly the outcome of pts. Complete surgery remains the cornerstone of the treatment of patients with sarcomatosis with best results for low grade sarcomatosis.

We report the results of a randomised phase II trial of docetaxel tested as a single agent in patients with recurrent head and neck cancer using methotrexate as a control arm to validate the results. Eligibility criteria included: histologically-confirmed squamous cell carcinoma, measurable disease, adequate haematological, renal and hepatic functions, no prior chemotherapy for recurrent cancer, signed informed consent. 40 mg/m 2 methotrexate was given as a short weekly bolus i.v. injection, and 40 mg/m 2 docetaxel was administered as a one hour weekly infusion. A total of 57 patients were randomised based on a ratio of 2/1:37 and 20 patients received docetaxel and methotrexate, respectively. Patient characteristics included 49 males and 8 females; the median age was 59 years (range: 43–82 years). Twenty-eight patients had a local-regional relapse and 29 had distant metastasis, the median disease-free interval was 7.9 months (range: 0–165 months). For patients treated with docetaxel, the following grade 3–4 toxicities occurred: neutropenia (12.5%) with febrile neutropenia in one patient (1%), anaemia (19%) mucositis (9%) and ungueal toxicity (9%). In the methotrexate arm, the grade 3–4 toxicities were: anaemia (15%) and mucositis (5%). The response rate was significantly higher in the docetaxel arm with 27% (95% confidence interval (CI): 21.7–32.3%) of objective responses versus 15% (95% CI: 11.2–18.8%) in the methotrexate arm. Overall survival and time to progression were super-imposable between the docetaxel and methotrexate treatments. Docetaxel given as a weekly infusion has a high activity in patients with head and neck cancer. A phase III trial is needed to test if this translates into a survival benefit for docetaxel use.

Introduction Des carcinomes epidermoides cutanes (CEC) surviennent chez environ 20 % des patients atteints de melanome (M) sous vemurafenib (V), essentiellement pendant les 3 premiers mois. L’objectif etait de determiner la frequence des CEC sous V chez les patients atteints de tumeurs non melanocytaires dans l’etude pilote de phase II d’acces au V « AcSe-V » et d’etudier leurs caracteristiques cliniques, histologiques et moleculaires. Materiel et methodes Les patients inclus dans l’etude AcSe-V ont un suivi dermatologique organise sous l’egide du Groupe de cancerologie cutanee (GCC). Le schema de suivi comporte une visite de pre-inclusion, puis a M1, puis tous les 3 mois jusqu’a 6 mois apres l’arret du V. Seuls les patients qui ont un suivi ≥ 4 mois et qui n’ont pas d’antecedent de M sont incluables. Les comptes rendus des carcinomes epidermoides et de leurs precurseurs sont revus par un pathologiste. Une revue histologique centralisee et une caracterisation moleculaire des CEC sont en cours. La frequence des CEC etait comparee a celle de l’etude BRIM3. Resultats Parmi 56 patients inclus dans AcSe-V, six (11 % ; 4F, 2H) traites pour un cancer BRAF V600E-mute du poumon, de la thyroide et cerebral ont developpe 10 lesions cutanees qui ont ete analysees histologiquement. La taille mediane des lesions etait de 5,5 mm (5–10 mm). La localisation etait le membre superieur (n = 4) ou inferieur (n = 3), la tete et le cou (n = 2), et le tronc (n = 1). Apres revue des comptes rendus (7/8 disponibles), il y avait 8 CEC, 1 papillome avec une architecture evoquant un keratoacanthome et 1 keratose pre-epitheliomateuse. Au total, cinq patients (9 %) d’âge median 76 ans (23–83 ans) avaient des CE qui etaient multiples dans 2 cas. Il s’agissait de CEC crateriformes (n = 4) ou papilliformes (n = 2), bien differencies (n = 6) ou mal differencie (n = 1). Le delai median de diagnostic du premier CEC etait de 71 jours (29–161 jours) ; 5/6 patients avaient un phototype 3 ; aucun n’avait d’histoire medicale de cancer cutane mais 3 presentaient des keratoses actiniques avant l’initiation du V. Discussion Les CEC induits par le V chez les patients non atteints de M correspondaient le plus souvent a des tumeurs de petite taille bien differenciees diagnostiquees dans les premiers mois de traitement et relevant d’une chirurgie simple. Conclusion Les CEC induits par le V semblent avoir des caracteristiques cliniques et histologiques similaires chez les patients atteints de M et ceux atteints d’autres cancers. La plus faible frequence des CEC chez les patients non atteints de M en comparaison a ceux atteints de M dans l’etude BRIM3 (p = 0,039) pourrait etre due a des differences dans les facteurs de risques. Des facteurs de risques potentiels des CEC induits par le V sont l’âge eleve d’apres une etude australienne recente. Une analyse plus avancee des resultats de cette etude sera presentee. Elle devrait permettre de guider la surveillance dermatologique de ces pts.

Open biopsy is recommended for a soft-tissue sarcoma (s-t-S) diagnosis. Core needle biopsy (CNB) was recently associated with minimal morbidity, cost and time-consumption, but also potential inaccuracy. Its diagnostic utility was investigated retrospectively in 110 patients with soft-tissue masses (s-t-M) undergoing CNB between September 1994 and September 2000. Sensitivity (Se), specificity (Sp), positive (PPV) and negative (NPV) predictive values were determined for malignancy (benign/malign), soft-tissue tumour (yes/no), and sarcoma diagnosis (yes/no), comparing CNB and the best standard test available; concordance was evaluated. 103/110 CNB were suitable for analysis. Final diagnosis was 23 benign tumours (19%), 65 s-t-S (59%), 9 lymphomas (8%), 6 fibromatoses (desmoid) (5%) and 7 carcinomas (6%). CNB Sp and PPV were 100%, Se was 95, 99 and 92%, and NPV 85, 95 and 88% for diagnosing malignancy, soft-tissue tumour and sarcoma. CNB Se and NPV were 100% for malignancy, connective tumour and sarcoma in lymphomas, high-grade sarcomas and desmoid tumours. In low grade sarcomas, Se was 94 and 85%, and NPV 84 and 77% for malignancy and sarcoma. Histological grade on CNB seems uneasy, except for grade-III tumours. CNB is accurate, not misleading for s-t-M diagnosis, avoids open biopsy complications, and allows one-surgery or neo-adjuvant chemotherapy planning when combined with appropriate imaging.

Prediction of survival for patients with metastatic breast cancer is often inaccurate and may be helped by new biological parameters. Tumour growth being angiogenesis-dependent, it has been hypothesised that the assessment of angiogenic factor production might reflect the clinical behaviour of cancer progression. This study was designed to investigate the clinical significance of vascular endothelial growth factor (VEGF) and interleukin 6 (IL-6) in hormone-refractory metastatic breast cancer. Serum and plasma concentrations of VEGF and serum concentration of IL-6 were measured in 87 patients with a fully documented history of metastatic breast cancer using an enzyme-linked immunoassay. All patients had detectable levels of VEGF, whereas 39% patients had detectable serum levels of IL-6. There was a positive correlation between IL-6 levels and the theoretical VEGF load of platelets (P

A risk model for febrile neutropenia (FN) after conventional cytotoxic chemotherapy, based on early (day 5) lymphopenia and the dose of chemotherapy, has been described. A risk index based on parameters available at day 1 would be easier in daily practice. The objectives of this work were (1) to investigate a risk model for FN using only day 1 blood cell count and (2) to compare the day 1 and day 5 risk models. Three series of patients were used for the delineation and/or validation of these two risk models: (1) the exhaustive cohort of 950 patients treated in the Department of Medicine of the CLB in 1996 (CLB-1996 series), (2) the Elypse 1 series, a prospective series of 321 patients treated in community hospitals and regional cancer centres, and (3) a previously reported Elypse 0 series of 329 patients. Day 1 blood cell count was available in all three series, while day 5 blood cell count was available only in the Elypse 0 and 1 series. In the CLB-1996 series, 92 (9.7%) patients experienced FN; only chemotherapy dose and day 1 lymphopenia < or =700 microl(-1) had an independent prognostic value for FN in multivariate analysis. In patients with both risk factors ('high-risk group'), the incidence of FN was 44, 50 and 61% in the CLB-1996. Elypse 1 and 0 series, respectively, indicating that the 'day 1' risk model enables one to identify patients at high-risk for FN. Besides, the observed incidence of FN in the high-risk group of the 'day 5' model (i.e. patients with day 5 lymphopenia < or =700 microl(-1) and receiving high-risk CT) was 45 and 69% in the Elypse 0 and 1 series, respectively. In the Elypse 1 and 0 series, 15 and 12% of all patients who experienced FN were in the high-risk group of the 'day 1' risk model as compared to 25 and 62% for the high-risk group of the 'day 5' risk model. Both day 1 and day 5 lymphopenia are associated with an increased risk of FN in patients treated with chemotherapy. The 'day 1' model identifies a small population of patients at high risk for FN, but has a lower sensitivity than the day 5 model.

PURPOSE: To evaluate the safety, pharmacokinetics, and efficacy of three different dose levels of pegylated granulocyte colony-stimulating factor (Ro 25-8315) on progenitor cell mobilization and hematologic recovery in cancer patients. PATIENTS AND METHODS: Breast cancer patients (n = 36) were randomly assigned to receive before (part I) and after (part II) chemotherapy either a single-dose injection of Ro 25-8315 (20 μg/kg, n = 9; 60 μg/kg, n = 9; 100 μg/kg, n = 10) or a standard daily dose of filgrastim (part I, 10 μg/kg/d; part II, 5 μg/kg/d) (control group, n = 8). RESULTS: Overall, Ro 25-8315 was well tolerated. In part I, more progenitor cell mobilization was observed with Ro 25-8315 100 μg/kg. The peak of circulating CD34+ cells was obtained at day +5 in the four groups, and the absolute neutrophil count (ANC) returned to less than 20 × 109/L by day +15. In part II, high levels of circulating CD34+ cells (> 20 cells/μL) were obtained in all four groups. The chemotherapy-induced neutropenia (< 1 × 109/L) was similar in the four groups. Ro 25-8315 100 μg/kg was more effective than filgrastim in reducing the number of patients with an ANC less than 0.5 × 109/L on day +12 after chemotherapy. CONCLUSION: A single injection of Ro 25-8315 100 μg/kg might be the optimal dose for steady-state peripheral-blood progenitor cell mobilization. A single injection of 20, 60, or 100 μg/kg could be as efficient as daily administration of filgrastim to correct chemotherapy-induced cytopenia. The optimal dose of Ro 25-8315 should be determined according to the planned chemotherapy regimen.

Purpose/Objective(s) Breast cancer (BC) patients with comparable prognostic features have heterogeneous outcomes, partly because of radiotherapy resistance leading to loco-regional recurrences (LRR). The ProfiLER (Profilage LYric et Region, NCT01774409) clinical trial aims at establishing a simple genetic profile of metastatic cancers in order to offer patients personalized molecular targeted therapies. In the breast cancer area, the genomic profiling of a population who ultimately became metastatic, and its correlation with the patient outcome years after LRR, provided an opportunity to identify post hoc biomarkers of the initial radiation resistance. The aim of the present study was to determine if specific tumor genetic alterations were associated with radiation resistance, defined as a LRR despite optimal surgery, radiotherapy, and systemic adjuvant therapies, in a ProfiLER series. Materials/Methods Genetic profile of 162 BC patients’ tumors included in ProfiLER between 2013 and 2016 were analyzed using Next-Generation-Sequencing and Comparative-Genomic-Hybridization tests. Patients and tumor characteristics were analyzed for association with genomic rearrangements (mutations, amplification, homozygous deletions). Only gene alterations observed in >3% of the tumors, or included in well-known molecular pathways (PI3 Kinases pathway, MAP Kinases pathway, Tyrosine Kinase receptors family) were selected. The Cox multivariate analysis was based on (P3% of tumors. PIK3CA and ROS1 mutations were statistically correlated to the risk of LRR. A median loco-regional progression free survival (LRPFS) of 19.8 years was reported for PIK3CA mutation carriers (n = 34, 21%) versus 9.1 years for wild-type patients (HR = 0.29, 95% CI = 0.13-0.64, P = 0.002 in univariate analysis). PIK3CA mutation was identified as an independent protective factor of LRR using multivariate analysis (HR = 0.27, 95% CI = 0.09-0.82), P = 0.02). ROS1 mutated cancer patients (n = 8, 4.9%) had a median LRPFS of 4 years versus 16.1 years for wild-type patients (HR = 2.5, 95% CI = 1.74-7.05, P = 0.08 in univariate analysis), but was not identified as an independent LRR risk factor (HR = 2.45 95% CI = 0.83-7.26, P = 0.11 in multivariate analysis). Other mutations and amplifications were not associated with LRR. Among relapsing patients, the median time to LRR was nearly significantly different regarding status of the PIK3CA mutations, with 8.6 years for mutated patients versus4.7 years for non-mutated patients (P = 0.09). Conclusion PIK3CA mutation was associated with a lower risk of LRR in this BC population. ROS1 mutation was marginally associated with a higher risk of LRR, possibly because of a limited population. Results suggest PIK3CA and ROS1to be possible biomarkers of radio-sensitivity.

Introduction Chez l’adulte, les sarcomes des tissus mous forment un groupe heterogene de tumeurs malignes rares. L’histoire naturelle de ces tumeurs differe en fonction de facteurs pronostiques intrinseques (sous type histologique, grade…) et extrinseques (qualite de la chirurgie, centre de prise en charge…). Les sarcomes dits a translocation recurrente constituent un sous-ensemble de tumeurs (Synovialosarcome, Ewing…) qui possede une mutation caracterisee par un echange reciproque de materiel chromosomique. Ils representent 20 % des sarcomes, surviennent generalement chez les personnes jeunes, sont agressifs et ont un potentiel metastatique important. L’objectif de cette etude est de decrire les caracteristiques diagnostiques et les traitements des patients atteints d’un sarcome a translocation et de comparer ces caracteristiques dans les deux groupes de patients : sarcomes a translocation versus les autres. Methodes Cette etude retrospective multicentrique a ete conduite chez les patients atteints d’un sarcome traite dans l’un des 22 centres de reference du Groupe Sarcome Francais (GSF) et enregistres dans la « Conticabase ». Cette base de donnees clinico–biologique a grande dimension comporte 16 422 patients dont 12 711 atteints de sarcomes, sur la periode 1980–2016. Elle contient les informations liees a la tumeur primaire, au traitement et au suivi des patients. Dans cette base, les diagnostics ont ete relus de maniere systematique par des pathologistes experts et codes selon la classification de l’Organisation mondiale de la sante 2013. Les comparaisons entre les deux groupes de patients (sarcomes a translocation versus les autres) ont ete realisees a l’aide de test non parametrique pour les variables quantitatives et test du Chi-deux pour les variables qualitatives. Resultats Parmi les 10 262 patients presentant un sarcome et inclus dans la Conticabase entre le 1er janvier 1980 et le 31 decembre 2013, 2143 (20,8 %) sont atteints d’un sarcome a translocation, dont 1135 hommes (53,0 %). Ces patients ont principalement des tumeurs dites profondes (93,3 %) et localisees dans les membres (60,5 %). Compare aux autres sarcomes, les patients avec un sarcome a translocation ont un âge median plus faible (40,6 versus 60,0 ; p Conclusion Les sarcomes a translocation presentent un profil specifique et different en termes de caracteristiques initiales (demographiques, traitements anterieurs, caracteristiques de la tumeur primaire). La qualite des donnees bio-pathologiques comme des donnees cliniques enregistrees dans cette base au niveau national via les reseaux de tumeurs rares est un apport pour identifier ou valider des caracteristiques utiles pour etudier le pronostic des patients.

Background Retroperitoneal sarcomas (RPS) are heterogeneous. Advanced stages include unresectable locoregional (LR) disease, abdominal sarcomatosis and distant metastasis. There is no available report assessing palliative chemotherapy in advanced RPS. This study analyzes management and outcome in a large cohort of patients with advanced RPS, considering main histological subtypes separately. Patients and methods We conducted a retrospective analysis of adult patients diagnosed with a RPS between 1 January 1988 and 31 December 2008 across 12 centers of the French Sarcoma Group. All cases were centrally reviewed by an expert pathologist. Results Five-hundred eighty-six patients were included, 299 patients received palliative chemotherapy, with a median of two lines (range 0–8). Fifty patients underwent palliative surgery. Two hundred fifty-five patients (85%) were assessable for response after first line of chemotherapy. Among them, 69 patients (27%) had progressive disease, 145 (57%) had stable disease, 37 (14.5%) had partial response and 4 (1.5%) complete response. Median time from first line of palliative chemotherapy to progression was 5.9 months [4.9–7.3] and median overall survival (OS), 15.8 months [13–18]. In multivariate analysis, prognosis factors independently associated with poor OS were male gender, performance status (PS) >1 and grade >1. There was no difference according to stage of disease. Palliative surgery did not appear to add any survival benefit. Conclusion These results emphasize the scarcity of available options for RPS in the advanced setting and the urgent need to develop new strategies. Patients with good PS should be included in clinical trials and best supportive care should be considered in those with poor PS.

Desmoid-type fibromatosis (DF) is a rare locally aggressive monoclonal proliferation of myofibroblasts lacking metastatic capacity. It may be observed in nearly every part of the body. Considering the variable clinical presentations, anatomic locations, and biologic behaviors, an individualized treatment approach is required. The pathogenesis of DF is not completely understood even if a high prevalence (∼85%) of CTNNB1 mutations discovered in sporadic DF underlies the importance of the Wnt/β-catenin pathway. No established and evidence-based approach for the treatment of this neoplasm is available as of today. Considering the unpredictable behavior and the heterogeneity of this disease, we propose a treatment algorithm approved by the French and the Italian Sarcoma Group, based on a front-line wait and see approach and subsequent therapy in the case of progression. A careful counseling at a referral center is mandatory and should be offered to all patients affected by sporadic DF from the time of their diagnosis.

1–5% of cancer patients treated with cytotoxic chemotherapy die within a month after the administration of chemotherapy. Risk factors for these early deaths (ED) are not well known. The purpose of this study was to establish a risk model for ED after chemotherapy applicable to all tumour types. The model was delineated in a series of 1051 cancer patients receiving a first course of chemotherapy in the Department of Medicine of the Centre Leon Berard (CLB) in 1996 (CLB-1996 cohort), and then validated in a series of patients treated in the same department in 1997 (CLB-1997), in a prospective cohort of patients with aggressive non-Hodgkin's lymphoma (NHL) (CLB-NHL), and in a prospective cohort of patients with metastatic breast cancer (MBC series) receiving first-line chemotherapy. In the CLB-1996 series, 43 patients (4.1%) experienced early. In univariate analysis, age > 60, PS > 1, lymphocyte (ly) count ≤ 700 μl−1 immediately prior to chemotherapy (d1), d1-platelet count ≤ 150 Gl−1, and the type of chemotherapy were significantly correlated to the risk of early death (P ≤ 0.01). Using logistic regression, PS > 1 (hazard ratio 3.9 (95% Cl 2.0–7.5)) and d1-ly count ≤ 700 μl−1 (3.1 (95% Cl 1.6–5.8)) were identified as independent risk factors for ED. The calculated probability of ED was 20% (95% Cl 10–31) in patients with both risk factors, 6% (95% Cl 4–9) for patients with only 1 risk factor, and 1.7% (95% Cl 0.9–3) for patients with none of these 2 risk factors. In the CLB-97, CLB-NHL and MBC validation series, the observed incidences of early death in patients with both risk factors were 19%, 25% and 40% respectively and did not differ significantly from those calculated in the model. In conclusion, poor performance status and lymphopenia identify a subgroup of patients at high risk for early death after chemotherapy. © 2001 Cancer Research Campaignhttp://www.bjcancer.com