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International audience; The frequency of and risk factors for shaken baby syndrome remain poorly documented for several reasons: the real number of "benign" cases of shaken baby syndrome are not known; information sources used are diverse, there have been changes over time in the definition of this pathology and few population-based epidemiological studies are available. Estimate the frequency of fatal shaken baby syndrome and determine its risk factors through research carried out on fatal cases in three regions of France while comparing them to data from international publications. A retrospective epidemiological study of all cases of fatal shaken baby syndrome affecting infants younger than 1 year of age who were examined by the courts during a 5-year period in a defined geographical area. Shaken baby syndrome cases were compared with infanticide cases for risk factors and a comparison was made of family characteristics with those of the general population. Thirty-seven cases of shaken baby syndrome were recorded (a rate of 2.9 for 100,000 live births). As in other studies, we found a strong predominance of male victims (78%), young age (median age: 4 months) and a high rate of prematurity (22%). Conversely, results on family educational and socioeconomical levels differ from those reported in numerous studies. Parent perpetrators of shaken baby syndrome belong to higher social classes than those of other types of homicide and socially reflect the population they come from. Our study suggests 1) that epidemiological studies on shaken baby syndrome should include both medical and judicial information sources and 2) that primary prevention strategies (especially in maternity wards) should target all social classes.

In most countries, including France, the epidemiology of child abuse is nearly nonexistent, especially as concerns measuring the size of the problem. The definition of child abuse should be broadened and include all situations in which the fundamental needs of infants and young children are not recognized. With the exception of figures for homicide, data in many countries are rare. However, homicide is not an extreme form of abuse, it is abuse gone wrong, and risk factors for lethal and nonlethal abuse are the same. A study carried out by Inserm on homicides of under-one children showed official mortality statistics appearing to be 15 times lower than those provided by hospital data. Under-investigation, nondiagnosis, no reporting, or dissimulation of child abuse leads to major risks of repetition of violence. Training of health professionals and setting up effective statistical tools for epidemiological surveillance are needed to reduce child abuse.

Background: However hormone receptor–positive, early-stage breast cancer is a disease with a long natural history and improved survival with 5-year adjuvant endocrine treatments. Yet late recurrence remains an important issue in adjuvant therapy. Predictors of late recurrence are not yet well characterized. Method: A total of 252 breast primary tumors were selected at the Netherlands Cancer Institute from retrospective series of ER+, HER2− breast cancer patients with a follow-up of at least 10 years. Gene expression analysis was performed using Agilent 4×44K microarrays. In order to identify genes associated to late survival differences, we used the survdiff function implemented in the R package survival and we set the parameter rho to −1 to give weight to the later part of the survival curve. The survdiff function was applied to each probe individually for DMFS time considering the probe as a covariate dichotomized into 2 groups (above and below the median expression across all samples). The parameter “strata” was used to stratify the 140 patients based on additional clinico-pathological parameters (Grade, Diameter, Lymph node status and MammaPrint), in order to find genes that add prognostic value to those parameters already known. This approach uses the distant-metastasis free survival (DMFS) time as a continuous variable. Results: After univariate analysis, MammaPrint, diameter, lymph node status and grade were significantly associated to late DMFS differences (Chi-square test p-values equal to 0.016, 0.004, In order to independently validate the prognostic power of these two genes, we tested their performance in the validation set of treated patients (n = 112) and in three publicly available datasets. In all datasets, the CH25H gene confirmed to be significantly associated to metastasis-free survival time in all tested series. Conclusions: These results might indicate that CH25H is an independent marker of late metastatic relapses. CH25H catalyzes the formation of 25-hydroxycholesterol from cholesterol, leading to repress cholesterol biosynthetic enzymes. In the last years, it is emerging that lipid metabolism plays an important role in breast cancer development and progression. Taken together, these findings make the CH25H gene a potential target for late metastasis control in breast cancer. These results warrant further prospective investigation and functional characterization of CH25H in this setting. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-09-05.

Modern challenges in oncology, in particular the advent of targeted therapies and personalized medicine, highlight the need for developing a consortium of comprehensive cancer centers to run clinical trials in rare, molecularly-defined populations, and implement high-throughput technologies for daily practice.

International audience; OBJECTIVES: To measure the extent and analyse the mechanisms of underestimation of neonaticides (infanticides in the first 24 h of life) and to identify characteristics of neonaticidal mothers. DESIGN: A retrospective study was carried out in 26 courts in three French regions covering 34.6% of all births in France. Included in the study were all cases of infants dying on their day of birth during a 5-year period (1996-2000) that were submitted to courts by the state prosecutor. Complete court case data cover 1996-2007. WHO-International Classification of Diseases cause of death codes assigned in the mortality statistics were compared to causes assigned by the courts. Analysis was carried out on the psychiatric assessments of the mothers. RESULTS: 27 cases of neonaticides were analysed. 17 mothers were identified. We observed sizeable underestimation of neonaticides in official mortality statistics (0.39 per 100 000 births vs 2.1 in our study). Mothers' median age was 26 years; one third had at least three children. More than half lived with the child's father. Two thirds were employed and did not differ significantly from women in the general population regarding occupation. These women appeared to have low self-esteem, be immature and dependent, but did not have frank mental illness. There was no true case of 'denial of pregnancy'. Contraception was not used. CONCLUSION: This study has implications for prevention in terms of contraception and appropriate targeting of vulnerable women. It encourages the development of case-control studies on maternal risk factors within the framework of the French birth cohort currently being established.

Exosomes are nanovesicles originating from late endosomal compartments and secreted by most living cells in ex vivo cell culture conditions. The interest in exosomes was rekindled when B-cell and dendritic cell-derived exosomes were shown to mediate MHC-dependent immune responses. Despite limited understanding of exosome biogenesis and physiological relevance, accumulating evidence points to their bioactivity culminating in clinical applications in cancer. This review focuses on the preclinical studies exploiting the immunogenicity of dendritic cell-derived exosomes (Dex) and will elaborate on the past and future vaccination trials conducted using Dex strategy in melanoma and non-small cell lung cancer patients. Cancer Res; 70(4); 1281–5

There are important gaps in the health status of citizens across Europe, as measured by life expectancy, mortality or morbidity data (Report for the European Commission on the health status of the European Union, 2003). Among the main determinants of the major causes of mortality and morbidity, stated in this report, stands recurrently access to quality healthcare. There is a fundamental need to define quality indicators and set minimal levels of performance quality criteria for healthcare. There is a need to integrate research into healthcare and to provide patients with equity of access to such high quality care. Oncology is a speciality particularly suited to experimenting a first application of accreditation at European level. The Organisation of European Cancer Institutes is a growing network of cancer Centres in Europe. The focus of the OECI is to work with professionals and organisations with regard to prevention, care, research, development, patient's role and education. In order to fulfil its mission, the OECI initiated in 2002 an accreditation project with three objectives: • to develop a comprehensive accreditation system for oncology care, taking into account prevention, care, research, education and networking. • to set an updated database of cancer centres in Europe, with exhaustive information on their resources and activities (in care, research, education and management) • to develop a global labelling tool dedicated to comprehensive cancer centres in Europe, designating the various types of cancer structures, and the comprehensive cancer centres of reference and Excellence. An accreditation tool has been established, defining standards and criteria for prevention, care, research, education and follow-up activities. A quantitative database of cancer centres is integrated in the tool, with a questionnaire, that provides an overall view of the oncological landscape in OECI cancer centres in Europe. Data on infrastructures, resources and activities have been collected. This OECI accreditation tool will be launched in autumn 2008 for all cancer centres in Europe. It serves as a basis for the development of the labelling tool for cancer structures in Europe, with a focus on Comprehensiveness and Excellence labels. Quality assessment and improvement is a critical need in Europe and is addressed by the OECI for cancer care in Europe. Accreditation is a well accepted process and is feasible. Standards and criteria as well as an accreditation tool have been developed. The OECI questionnaire gives an accurate vision of cancer institutions throughout Europe, helping assessing the needs and providing standards. The accreditation project is a long-term complete and voluntary process with external and internal added value, an active process of sharing information and experience that should help the whole cancer community reach comprehensiveness and excellence.

Comprehensive Cancer Centres (CCCs) serve as critical drivers for improving cancer survival. In Europe, we have developed an Excellence Designation System (EDS) consisting of criteria to assess “excellence” of CCCs in translational research (bench to bedside and back), with the expectation that many European CCCs will aspire to this status., Highlights Assessing excellence of translational research is essential to improving its performance so that the time lag in bringing results of research to practice will be reduced.We have developed a set of excellence criteria that can help identify and designate Comprehensive Cancer Centres that perform excellent translational research. Examples of criteria are: organizational strategy; the depth of research programmes from bench to bedside and back; team science; commitment to collaboration; shared resources and critical patient mass.Assessment process requires a flexible peer‐review approach because excellent translational research can be found also in areas that are outside the scope of the assessment and/or the “typical” definition of translational research. The assessment framework was piloted in several cancer centres in Europe and is ready to be implemented.

Purpose: The aim of this multicenter trial was to evaluate the role of ovarian suppression in patients with early breast cancer previously treated with local surgery and adjuvant chemotherapy. Patients and methods: Nine hundred and twenty-six premenopausal patients with completely resected breast cancer and either axillary node involvement or histological grade 2 or 3 tumors were randomized after surgery to adjuvant chemotherapy alone (control arm) or adjuvant chemotherapy plus ovarian suppression (ovarian suppression arm). Ovarian suppression was obtained by either radiation-induced ovarian ablation or triptorelin for 3 years. The analyses were performed with Cox models stratified by center. Results: Median follow-up was 9.5 years. Mean age was 43 years. Ninety per cent of patients had histologically proven positive axillary nodes, 63% positive hormonal receptors and 77% had received an anthracycline-based chemotherapy regimen. Ovarian suppression was by radiationinduced ovarian ablation (45% of patients) or with triptorelin (48%). At the time of randomization, all patients had regular menses or their follicle-stimulating hormone and estradiol levels indicated a premenopausal status. The 10-year disease-free survival rates were 49% [95% confidence interval (CI) 44% to 54%] in both arms (P = 0.51). The 10-year overall survival rates were 66% (95% CI 61% to 70%) for the ovarian suppression arm and 68% (95% CI 63% to 73%) for the control arm (P = 0.19). There were no variations in the treatment effect according to age, hormonal receptor status or ovarian suppression modality. However, in patients

Background: A randomised trial was conducted comparing wide lumpectomy and breast irradiation with modified radical mastectomy. As the follow-up was long (mean duration 22 years), we analysed the variation in the effect of treatment over time. Patients and methods: The trial included 179 patients with a breast cancer measuring ≤2 cm at macroscopic examination. Eighty-eight patients had breast-conserving surgery and radiotherapy, and 91 underwent mastectomy. All patients had axillary dissection. The analyses were based on Cox models with time-dependent treatment effects. Results: The effect of treatment on death or metastasis did not vary with time. The risk of local recurrence was lower during the first 5 years for the breast-conserving surgery group as compared with the mastectomy group, but higher after 5 years (P = 10 –4 for a different treatment effect over time). Similar results were found in a database including 1847 patients with small breast tumours at diagnosis. In this analysis, late breast recurrences were also more frequent in the breast-conserving surgery group and this treatment effect was greater among younger patients (≤40 years at the time of diagnosis). Conclusions: Late breast recurrences were more frequently observed in younger patients treated with breastconserving treatment compared with those submitted to mastectomy. These results require confirmation in other randomised studies so that younger patients with early breast cancer can receive adequate counselling and so that a more stringent long-term follow-up policy can be adopted when breast-conserving treatment is

Purpose: To describe the pathologic characteristics and prognostic factors of primary breast sarcomas (PBSs). Patients and Methods: We reviewed the clinical records and pathologic slides of 83 women with PBS treated in our institution between 1954 and 1991, with a median follow-up of 7.8 years. The majority of patients had undergone surgical treatment. Results: The main histologic type was malignant fibrohistiocytoma (n = 57). For the whole population, the 10-year overall survival (OS) and disease-free survival (DFS) rates were 62% and 50%, respectively. For Fédération Nationale des Centres de Lutte Contre le Cancer grade 1, 2, and 3 tumors, the 10-year OS and DFS rates were 82% and 61%, 62% and 51%, and 36% and 25%, respectively (P = .00007 and .004, respectively). For tumors measuring less than 5 cm, 5 to 10 cm, and more than 10 cm, the 10-year OS and DFS rates were 76% and 66%, 68% and 55%, and 28% and 15%, respectively (P = .002 and .009, respectively). In the multivariate analysis, the tumor size and histologic grade were correlated with the 10-year DFS rate (P = .04 and .01, respectively), but only the histologic grade was correlated with OS (P = .01). Angiosarcoma was the only histologic type significantly associated with a poorer outcome in the multivariate analysis. Conclusion: PBSs have the same clinical history and prognostic factors as sarcomas arising at other sites. Therefore, it is legitimate to use a similar treatment strategy for PBS as for other sarcomas.

Cancer treatment is slowly shifting from an approach in which the tissue of origin and the histology were the guiding principles for the choice of chemotherapy towards a genotype-centric approach in which the changes in the cancer genome are used to select patients for treatment with highly selective and targeted drugs. This transition has all the hallmarks of a disruptive innovation and requires major adjustments in the way that cancer is diagnosed and treated. We discuss here the hurdles on the road ahead to a more personalized treatment of cancer.

Therapies targeting activated oncogenes have been associated with several successes in the last decades that are described in this review, together with their limits and related unsolved questions. Most of the tumours will eventually develop drug resistance potentially due to intratumor heterogeneity and selection of additional molecular events. Moreover, studies in the field of molecular characterisation of cancers have shown that most tumors include large number of rare genomic events. Developing new drugs requires the use of large-scale molecular screening programs to enrich phase I/II trials with patients presenting the genetic alterations to treat them with the appropriate drug(s). Administering one single drug will incur in non-durable results, so the future is to cleverly combine drugs. Development of personalized immunotherapeutics and/or anti-angiogenic agents could change the natural history of several cancers. Finally, other systems including DNA repair and metabolism have become targetable. These considerations justify the development of molecular medicine with the characterisation of each tumour to assess defects in all the systems previously mentioned to propose a unique combination of therapies to each patient. Current drug development is clearly not appropriate, and studies with drugs given in relevant combinations should be favoured by new relationships between academia and industry. New organisational and medico-economics approaches are required to minimize the financial burden of personalized medicine by considering the foreseen decrease of the costs of new technologies, and the money saved by avoiding the use of many costly, useless but nonetheless toxic treatments given after failure of standard therapy.

Injuries cause a substantial part of mortality, morbidity and disability world-wide and are responsible for more years of life lost than other nosological entities. The etiology of injuries is mult...

Background Recombinant human interleukin-2 (aldesleukin) and recombinant human interferon alfa can induce notable tumor regression in a limited number of patients with metastatic renal-cell carcinoma. We conducted a multicenter, randomized trial to determine the effect of each cytokine independently and in combination, and to identify patients who are best suited for this treatment. Methods Four hundred twenty-five patients with metastatic renal-cell carcinoma were randomly assigned to receive either a continuous intravenous infusion of interleukin-2, subcutaneous injections of interferon alfa-2a, or both. The main outcome measure was the response rate; secondary outcomes were the rates of event-free and overall survival. Predictive factors for response and rapid progression were identified by multivariate analysis. Results Response rates were 6.5 percent, 7.5 percent, and 18.6 percent (P

Purpose: Previous studies demonstrated that doxorubicin and vinorelbine combinations in first-line chemotherapy are highly active in metastatic breast cancer. Mitoxantrone is an anthracenedione with low cardiotoxicity, and seems to be effective when combined with vinorelbine after prior exposure to anthracyclines. Patients and Methods: Seventy-two patients with metastatic breast cancer were included in a phase II study. All patients had previously received one anthracycline-containing regimen (doxorubicin or epirubicin) in an adjuvant setting. Vinorelbine was administered at 25 mg/m2 in a 20-min intravenous (i.v.) infusion, days 1 and 8. Mitoxantrone was given at 10 mg/m2 (66 patients) or 12 mg/m2 (6 patients) in a slow i.v. infusion on day 1. Courses were repeated every 3 weeks. Results: Sixty-five patients were evaluable for response; the objective response rate was 49% (95% CI: 37–63%), including four complete and 28 partial responses, with a median duration of response of 7 months (range 2.3–27). Median overall survival was 19 months (range 2–48). Grade 3–4 granulocytopenia was observed in 46% of patients. There were 12 admissions (3% of cycles), involving 17% of patients for febrile neutropenia. Seven patients (10%) experienced grade 3 or 4 cardiotoxicity, and 1 patient died of cardiac heart failure. Other side effects were rare and mild. Conclusions: The vinorelbine and mitoxantrone combination is an active regimen with low toxic complications when cumulative doses of mitoxantrone are limited to 70 mg/m2. The results in this phase II study make it worthwhile including this regimen in a phase III study for patients who have previously received an anthracycline-containing regimen.

The effect of additional treatments after surgery in patients with primary cardiac sarcoma (PCS) remains unknown. The present study aims to evaluate the benefit of chemotherapy in patients with non-metastatic cardiac sarcomas after optimal resection. Between October 1979 and December 1995, 15 patients with a median age of 45 (range 16-66) and a resected primary cardiac sarcoma [angiosarcoma (six), malignant fibrous histiocytoma (three), leiomyosarcoma (two), rhabdomyosarcoma (two), liposarcoma (one) and synoviosarcoma (one)] received a doxorubicin-containing regimen within 6 weeks of surgery. Adjuvant chemotherapy combinations included cyclophosphamide, vincristine and dacarbazine in four patients; ifosfamide in nine; methotrexate and vincristine in one; and doxorubicin alone in one patient. At present, 13 patients have relapsed (five during therapy), with a median time to progression of 10 months. Twelve patients developed local relapse, in four cases without metastatic disease. Two patients remain in complete remission 27 and 25 months after surgery. The median time to progression was shorter in patients presenting a cardiac angiosarcoma than other histological types (3 vs 14 months, P < 0.01). Twelve patients have died, with a median overall survival of 12 months. The 2-year survival rate is 26%. Survival was significantly longer for patients with completely resected tumours (22 vs 7 months; P = 0.02) and those who did not have angiosarcoma (18 vs 7 months; P = 0.04). In conclusion, post-operative conventional doxorubicin-based chemotherapy failed to modify the natural history of patients with resected cardiac sarcomas. Locoregional failure remains the main problem even after histologically complete resection. New approaches must be tested in patients with primary cardiac sarcoma.

Introduction Breast cancer risk of recurrence is known to span 20 years, yet existing prognostic signatures are best at predicting early recurrences (≤5 years). There is a critical need to identify those patients at risk of late-relapse (>5 years), in order to select potential candidates for further treatment and to identify molecular targets for such treatment. Methods A total of 252 breast primary tumors were selected at the Netherlands Cancer Institute from a retrospective series of ER+, HER2− breast cancer patients with a follow-up of at least 10 years. Gene expression analysis was performed using Agilent 4x44K microarrays. Patients were classified in 3 groups: no relapse (M0); relapse before 5 years (M0-5) or after 5 years (M5-15). We assessed the correlation of clinico-pathological variables with late Distant Metastases (DM). We divided the patient series into a training set of untreated patients ( n = 140) and a test set of treated patients ( n = 112), to investigate whether a gene-signature or single genes could be identified for predicting late DM. Pathway level late DM correlates were identified using PARADIGM and DAVID. Results Of the clinico-pathologic variables tested, only lymph node status associated with late DM. A 241-gene signature developed on the NKI training set was able to classify M5-15 patients in the test set with a sensitivity of 77% and a specificity of 33% (AUC 0.654). This signature showed enrichment in genes involved in immune response and extracellular matrix. An alternative analysis of individual genes identified CH25H as an independent predictor of distant metastasis in our patient series. Conclusions We identified a gene signature for late metastasis in breast cancer. Our data are consistent with a model in which suppressed anti-tumoral immunity enables dormant tumor cells to re-enter the cell cycle to form metastases in response to extrinsic events in the microenvironment.

Background : despite vigorous efforts at curbing tobacco consumption and aggressive combined modality treatment programmes, both incidence and mortality from lung cancer have remained virtually unchanged in the last 10 years and there is a clear need for more effective innovative therapies. The direct transfer of tumour suppressor genes or toxic gene products that specifically promote tumour cell death and spare non-malignant cells is a potentially novel anticancer treatment approach that should be investigated. Purpose : based on compelling preclinical data, we conducted a phase I study in humans to evaluate the feasibility, tolerance and clinical, biological and immunological effects of the intratumoral administration of a recombinant, replication-deficient adenovirus (Ad RSVB-gal), using the RSV promoter to drive transcription of the Escherichia coli lacZ marker gene that encodes for the bacterial enzyme beta-galactosidase (B-gal), in patients with inoperable lung cancer and an endobronchial lesion accessible by bronchoscopy. The first single dose level was 10 7 (3 patients), the second was 10 8 (3 patients) and the third was 10 9 plaque forming unit (pfu) (2 patients). Biopsies of tumour and surrounding mucosa, performed at days 8, and at 1, 2 and 3 months following injection, were analysed using PCR and X-gal staining. Patients and medical staff were monitored for wildtype and rAd infections by PCR, culture and serologic analyses. Patients remained in TL2 isolation until negative results of PCR and cultures of biologic fluid specimens were confirmed. All patients received concomitant chemotherapy. Results : seven patients with NSCLC and one with neuroendocrine tumour entered this ongoing study. Expression of B-gal was observed in five out of eight tumour biopsies (one at 10 7 , two at 10 8 and two at 10 9 dose level). Bronchoalveolar lavage collected immediately after injection were positive for recombinant adenovirus by culture and PCR. All biological fluids were negative by PCR after day 12. The three and two patients treated at 10 8 and 10 9 pfu respectively had PCR positive blood samples on day 1. Patients were in isolation for a median of 17 days. Moderate bleeding (two patients) during bronchoscopy and fever (four patients) were the most common toxicities. Endoscopic and clinical objective tumour responses were seen in five patients. The three patients treated at the second dose level, all with stage IIIB disease, were deemed resectable after chemotherapy. They all had a complete surgical resection of their tumour 112–152 days after viral injection. Hospital staff remained negative for recombinant adenovirus infection throughout the study. Conclusion : this ongoing study demonstrates that a marker gene can be safely introduced into humans using an rAd vector and that the gene product is expressed by host lung tumour cells. We will continue our programme by using this methodology to study the antitumour effects mediated by transfer of tumour suppressor or cytokine genes into endobronchial lesions in lung cancer patients.

BACKGROUND Several reports have shown a prolonged survival after surgical treatment of pulmonary metastases from soft tissue sarcomas. However, it is still unclear which prognostic factors predict a favorable outcome. Series are not comparable and the data are conflicting. Therefore, a multi-institutional study was undertaken to analyze prognostic factors in selecting patients for resection of pulmonary metastases from soft tissue sarcomas. METHODS This report is a retrospective study of the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group. Two hundred fifty-five patients underwent complete resection of lung metastases from soft tissue sarcomas. Cases with chondrosarcoma and small round cell sarcomas like Ewing sarcoma were excluded. RESULTS The 3 year and 5 year overall postmetastasectomy survival rates were 54% and 38%, respectively. The disease free postmetastasectomy survival rates were 42% and 35%, respectively. Analysis of prognostic factors for a more favorable outcome revealed disease free intervals of 2.5 years or more, following a resection with microscopically free margins, age less than 40 years, and Grade I and II tumors. These prognostic factors have an independent influence on overall survival, using a multivariate Cox regression model. CONCLUSIONS Surgical excision of lung metastases from soft tissue sarcomas is well accepted and should be considered as a first line of treatment if preoperative evaluation indicates that complete clearance of the metastases is possible. Further investigation is needed before chemotherapy can be recommended as additional therapy. Cancer 1996; 77:675-82.

Resume Dans l'ensemble des pays industrialises. les accidents constituent le premier probleme de sante publique dans l'adolescence, et le devenir a long terme des enfants accidentes reste peu etudie. Population et methodes . - Une enquete epidemiologique longitudinale realisee dans 17 etablissements scolaires secondaires de Paris et de Cote-d'Or (sur 8 140 eleves) a suivi durant une annee le devenir de 777 adolescents accidentes en 1990. Tous les accidents (scolaires et extrascolaires) ont ete inclus s'ils repondaient a l'un des criteres suivi as: absence scolaire ou dispense d'atelier superieuse ou egale a 2 jours, ou dispense d'education physique d'au moins 14 jours. Resultats . - Un an apres l'accident, 13% des adolescents ont conserve une gene, plus particulierement les plus âges et les filles. Parmi les deficiences decrites, ce sont essentiellement des deficiences du squelette et de l'appareil de soutien (88% des cas). Ces deficiences se sont localisees preferentiellement aux membres inferieurs (53%). Des cicatrices inesthetiques sont presentes dans 17% des cas, et un retentissement psychologique a ete retrouve chez 16,5% des adolescents. La presence de sequelles est liee au type de la lesion initiale (24% des traumatismes crâniens, 16% en cas d'atteinte des membres inferieurs). Ce sont les luxations, entorses graves et fractures qui ont genere le plus de gene. Un an apres l'accident, la gravite des sequelles est importante dans 10% des cas, et dans 36% des cas, elles ont des retentissements dans la vie quotidienne des adolescents, soit chez 5% de l'ensemble des adolescents accidentes. Ces sequelles sont generatrices d'une consommation medicale elevee. Conclusions . - Malgre la relative benignite des sequelles observees, la grande frequence des accidents a l'adolescence ainsi que leur cout economique eleve justifient, d'une part, une prise en charge appropriee des victimes d'accidents, meme apparemment benins, d'autre part, la mise au point d'etudes longitudinales utilisant des outils adaptes (echelles d'evaluation et de gravite des sequelles accidentelles).

The 70 gene-signature (MammaPrint(®)) is a prognostic profile of distant recurrence and survival of primary breast cancer (BC). BC patients with 4-9 positive nodes (LN 4-9) are considered clinically at high-risk. Herein we examined MammaPrint(®) added prognostic value in this group.MammaPrint(®) profiles were generated from frozen tumours of patients operated from primary BC. Samples were classified as genomic Low Risk (GLR) or genomic High Risk (GHR).Among the 173 samples, 70 (40%) were classified as GLR and 103 (60%) as GHR. Tumours in the GHR group were significantly more often ductal carcinomas (93%), grade 3 (60%), oestrogen and progesterone-negative, Her2 positive (25%). In the GLR category, the 5-year overall survival was 97% vs. 76% for in the GHR group (p0.01); Distant Metastasis Free Survival (DMFS) at 5 years was 87% for GLR patients and 63% for GHR patients (p0.01). In the Luminal A subgroup, the genomic profile was the only independent risk factor for DM and BC specific death.In the Luminal A subgroup, MammaPrint(®) is an independent prognostic marker in BC patients with LN 4-9 and may be integrated in a selection strategy of patients candidate for more aggressive therapeutic approaches.

International audience

PURPOSE The study investigated the therapeutic effects of a combination of Navelbine (vinorelbine or 5'noranhydrovinblastine; Pierre Fabre Médicament, Boulogne, France) and doxorubicin in women who had received no prior chemotherapy for locally advanced or metastatic breast cancer. PATIENTS AND METHODS Ninety-seven patients with progressive and assessable advanced or metastatic breast cancer who had received no prior chemotherapy except in an adjuvant setting were entered onto the study. Eighty-nine patients were assessable for toxicity and response by World Health Organization (WHO) criteria; the other eight patients were excluded because they did not meet entry criteria or because of protocol violations. Navelbine was administered at 25 mg/m2 by 30-minute intravenous (IV) infusion on days 1 and 8, and doxorubicin at 50 mg/m2 by slow IV infusion on day 1, with each course repeated at 3-week intervals. Patients were treated for a maximum of 11 cycles or until progression or major toxicity. RESULTS Objective responses were observed in 66 of 89 assessable patients (74%; 95% confidence interval, 63% to 85%). There were nineteen (21%) complete responses (CRs) and 47 (53%) partial responses (PRs). In addition, 20 patients (22.5%) had stable disease and three (3.5%) progressed while on treatment. Responses were observed at all sites of metastatic disease. Forty-one of 58 patients with visceral disease responded (71%) and 25 of 31 with soft tissue and bone disease experienced an objective response (81%). The median duration of response was 12 months (range, 2.4 to 40.5), and the median overall survival was 27.5 months (range, 4 to 46). Neutropenia was dose-limiting, with 36 patients (41%) experiencing grade 3 or 4 toxicity. Of 727 cycles administered, there were 20 admissions (3%) for treatment of febrile neutropenia, involving 14 of 89 patients (16%). Treatment-related cardiotoxicity at grade 2 to 4 was experienced by 10% of patients and necessitated the interruption of treatment in 1.5% of cycles. Other side effects were uncommon or manageable by conventional means. CONCLUSION The encouraging response rates and duration achieved with this combination of Navelbine/doxorubicin under the conditions of this study deserve further randomized comparative trials with standard regimens.

Summary Background Current regimens for treatment of distant metastases of soft tissue sarcomas result in response rates of about 25%. Therefore the search for active drugs remains a task for investigationaJ groups. Taxoids offer a new class of cytostatic drugs. Docetaxel has been studied as a second line chemotherapy in advanced soft tissue sarcomas of the adult. Patients and methods In a multi-center non-randomized phase II study docetaxel was administered at a dose of 100 mg/m2 in a 1-hour i.v. infusion q 3 weeks. Results Twenty-nine patients (pts), median age 52 yr, performance status WHO 0: 16 pts, WHO 1: 11 pts, WHO 2: 2 pts, were eligible. One patient had early death due to malignant disease, 1 patient died due to toxicity and progression, 1 pt refused after 1 course. Five partial responses (5/29 – 17%, C.I. 6%–36%) have been observed. Grade ≥3 leucopenia occurred in 76% of patients and grade ≥3 thrombopenia did not occur. Median nadir of neutrophils was 0.23 × 109/1. Episodes of fever and documented infection have been observed in 10 and 5 pts respectively. Anaphylactoid type reactions occurred in 5 patients: ranging from flushing in 5 pts to cardiovascular symptoms in 1 pt. Sensory neurotoxicity was observed in 14 pts grade 1: 10 pts, grade 2: 3 pts, grade 3: 1 pt). Grade 1 motor neurotoxicity was experienced by 3 pts. Skin reactions (pruritus, erythema, urticaria, exfoliation grade 1: 11 pts, grade 2: 7 pts, grade 3: 1 pt, grade 4: 1 pt) in 20 pts, among them 9 patients with nail changes. Peripheral edema and fluid retention has been observed in 12 pts. Conclusion Taxotere has activity in adult soft tissue sarcoma in second line, warranting studies on first line efficacy.

Summary Background Docetaxel, a semisynthetic analog of paclitaxel, made for the needles of the European yew, Taxus baccata, is a potentially important chemotherapeutic agent for the treatment of cancer. Patients and methods In a phase II study patients with advanced and/or metastatic breast cancer and bidimensionally measurable disease, were treated with docetaxel 100 mg/ m2 every 3 weeks as a 1 hour infusion without any premedication. Treatment was evaluated after 2 courses and every 2 subsequent courses. Results Thirty-nine patients were entered, 32 were eligible. The eligible patients had a median age of 51 years (range 30–73) and a performance status WHO 1 median, (range 0–2). Twenty-eight patients had been treated with surgery, 24 with radiation. Hormonal treatment was previously given in 23, chemotherapy in 32. Of 24 patients treated as second line strategy, 13 achieved a partial remission, 1 a complete remission (overall response rate 58% (95% CI 37%-78%)). Eight patients treated as first line: 2 PR's, 1 CR. The median overall response duration was 38 weeks. The main toxicity consisted of transient grade 4 neutropenia in 149 of 167 evaluable courses (89%). However, the related infection rate was low. Re-treatment at 3 weeks, as scheduled, was nearly always possible. Other toxicities consisted of skin reactions (81%) and nail changes (41%), neurosensory toxicity (59%) and occasionally hypersensitivity reactions (16%). Fluid retention was a toxicity of major concern, observed in 59% of patients. Conclusion Docetaxel is a very active drug against breast cancer. Further studies are required to alleviate the non-hematological toxicities.

The importance of appropriate patient selection necessitates novel clinical trial design and biomarker-driven trials to allow delivery of the right drug to the right patient at the right time—personalized cancer medicine. The WIN Consortium promotes collaboration between critical stakeholders and offers diverse populations of cancer patients the opportunity to participate in clinical trials with new drugs and biologics that target their tumor.

The presence of Epstein-Barr virus (EBV) genomes in the DNA of tumor cells of undifferentiated carcinoma of nasopharyngeal type (UCNT), associated with significant lymphocytic infiltration of tumor led to therapeutic trials with interferon (IFN) because of its antiviral, antiproliferative, and immunomodulatory properties. Fourteen patients with histologically proven UCNT (2 had locoregional disease alone and 12 metastatic disease) who were refractory to conventional chemotherapy, were treated with IFN gamma 20 x 10(6) U twice a week. Treatment was well tolerated. No objective response were achieved in the 13 evaluated patients, and all patients progressed after a median treatment duration of 10 weeks (6-32). IFN gamma seems unable to induce antitumor activity alone in such heavily pretreated patients. Its possible place in the management of UCNT is probably earlier in the natural history of this disease.

PURPOSE This study was designed to test the feasibility of administering doxorubicin at an optimal dose-intensity (> 70 mg/m2 per 21 days) in combination with ifosfamide under recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) cover in patients with metastatic soft tissue sarcomas. PATIENTS AND METHODS One hundred four eligible patients (of 111 entered) in 16 centers received doxorubicin 75 mg/m2 plus ifosfamide 5 g/m2 every 3 weeks for up to seven cycles. rhGM-CSF (250 micrograms/m2) was administered once or twice daily by subcutaneous injections for up to 14 days between cycles of chemotherapy. RESULTS Full protocol dose-intensity of chemotherapy was administered to the majority of patients with only 15 of 293 cycles being complicated by febrile episodes that required hospitalization. There were two treatment-related deaths: one from septicemia and one from cardiac failure. The main toxicities attributed to rhGM-CSF were pruritus and rash. A 45% response rate (10% complete remission [CR]) was seen, with a median response duration of 9 months and median survival of 15 months. CONCLUSION This high-dose regimen of chemotherapy was feasible under rhGM-CSF cover and produced a higher response rate and median survival than previously seen by the European Organization for Research and Treatment of Cancer (EORTC) Soft Tissue Sarcoma Group. A randomized phase III study is now underway comparing this regimen with conventional-dose doxorubicin/ifosfamide to test the dose-response relationship.

Dendritic cell-derived exosomes (Dex) are nanovesicles bearing major histocompatibility complexes promoting T-cell-dependent antitumor effects in mice. Two phase I clinical trials aimed at vaccinating cancer patients with peptide-pulsed Dex have shown the feasibility and safety of inoculating clinical-grade Dex, but have failed to show their immunizing capacity. These low immunogenic capacities have led us to develop second-generation Dex with enhanced immunostimulatory properties. Here, we show that interferon-γ is a key cytokine conditioning the dendritic cell to induce the expression of CD40, CD80, CD86, and CD54 on Dex, endowing them with direct and potent peptide-dependent CD8(+) T-cell-triggering potential in vitro and in vivo. In this study, we describe the clinical grade process to manufacture large-scale interferon-γ-Dex vaccines and their quality control parameters currently used in a phase II trial.

To improve outcomes in localized osteosarcoma and to reduce the duration of preoperative chemotherapy, we conducted a phase ii trial assessing the efficacy of an intensive protracted regimen without methotrexate (api-ai regimen) in adolescent and adult patients with newly diagnosed disease. Induction chemotherapy consisted of 2 cycles (4 courses) of doxorubicin 60 mg/m2 (days 1 and 15), cisplatin 100 mg/m2 (day 1), and ifosfamide 5 g/m2 (days 2 and 15). The primary endpoint was good histologic response [ghr (&le, 5% identifiable tumour cells)]. From March 1993 to March 2000, 32 patients [median age: 21 years (range: 15&ndash, 49 years)] were administered 126 induction courses. The median time between chemotherapy courses was 15 days (range: 12&ndash, 32 days). All but 3 patients underwent conservative surgery. Toxicity was mainly hematologic, with febrile neutropenia occurring in 35% of patients and grades 3&ndash, 4 thrombocytopenia in 35%. The ghr rate was 47%. The median follow-up was 64 months (range: 30&ndash, 115 months). The 5-year event-free and overall survivals were 65% [95% confidence interval (ci): 48%&ndash, 79%] and 69% (95% ci: 50%&ndash, 83%) respectively. Two secondary hematologic malignancies occurred: 1 acute myelocytic leukemia (M5) in a poor responder with concomitant relapse, and 1 myelodysplastic syndrome in a patient achieving ghr. Despite hematologic toxicity, the results observed with the api-ai regimen compare favourably with those observed during previous induction chemotherapy containing methotrexate in adult patients and the pediatric population treated at our institution. These promising results have to be validated by an ongoing national multicentre trial coordinated by the French Sarcoma Group.

OBJECTIVES: Test the hypothesis of an underestimation of infant homicides in mortality statistics in France; identify its causes; examine data from the judicial system and their contribution in correcting this underestimation. METHODS: A retrospective, cross-sectional study was carried out in 26 courts in three regions of France of cases of infant deaths submitted to the courts, 1996-2000, with follow-up of their files until case closing (1996-2008). For each case, cause of death established by the courts was compared with ICD cause of death as coded in official mortality statistics. RESULTS: We examined 247 cases. Shortcomings in investigations were noted (autopsies: 75% of cases; fundus examination: 11%; diagnosis of sudden infant death syndrome SIDS without autopsy: 41%). Eighty deaths were considered homicides by the courts. Homicide rates in the court study are 2-3.6 times higher than those in mortality statistics. Nearly 1/3 of "accidental" deaths and 1/4 of deaths from unknown cause in mortality statistics are homicides. Mechanisms of underascertainment are: physicians' inappropriate death certification and underreporting of suspicious cases; inadequate investigation of cases; incomplete communication of final medical and forensic results to the mortality statistics department. CONCLUSIONS: In a country where neither transportation of the body to a hospital nor autopsy is obligatory, judicial data can make an important contribution to correcting mortality statistics. PRACTICE IMPLICATIONS: This study led to the first French protocol for investigating sudden unexpected deaths in infancy (SUDI). The protocol includes a physician "training" section focused on understanding the symptomatology and risk factors of violence, as well as the quality of death certification. Language: en

Thirty nine patients with metastatic breast cancer, all previously treated with chemotherapy including anthracycline, were given Elliptinium acetate (80 mg/m2/day) and a continuous infusion of Vinblastine (2 mg/m2/day) for 3 consecutive days every 4 weeks. Twenty nine patients had measurable metastatic disease. Nine (31%) achieved a partial response. No complete response was observed. Median duration of response was 6 months. The response rate was dependent on the number of metastatic sites and independent of the number of previous chemotherapy regimes. Side effects were dry mouth (27 patients), vomiting (9), neutropenia (3 patients with grade IV, 2 with grade III), muscle cramps (5) and thrombosis (3). Xerostomia and vomiting contributed to weight loss and fatigue (8 patients). We conclude that Elliptinium-Vinblastine combination has moderate activity as second line treatment in metastatic breast cancer. This combination causes xerostomia and fatigue with moderate myelosuppression.

The morphology and clinical outcome of 30 patients with malignant small round cell tumors located in the thoracopulmonary region (Askin tumor) are reported. Histologically, all tumors had similar patterns, with small round-to-oval cells and a lobulated stroma. Immunohistochemical analysis always resulted in positive staining for one or several neural markers. No significant differences were found compared with the immunomarkers in 26 typical Ewing's sarcomas located outside the thoracic wall. In three specimens, electron microscopy confirmed the presence of membrane-bound neurosecretory granules. It was confirmed that there is a remarkable similarity among all malignant small round cell tumors, including Askin tumor and Ewing's sarcoma. Overall survival was poor with a 2-year rate of 38% and a 6-year rate of 14%.

The first case of primary Wilms' tumor of the prostatic gland is described. It occurred in a 32-year-old man. Histologically, it consisted of a triphasic tumor; tubular and glomeruloid structures were identified, among prominent blastematous sheets and in an edematous stroma. No teratomatous components were encountered. We propose that this prostatic primary, nonteratomatous Wilms' tumor can arise from persistent, nephrogenic, blastematous rests in the prostate, in relation to the Wolffian duct system.

This Phase II study evaluated the combination of two active agents in small cell lung carcinoma (SCLC): carboplatin and ifosfamide. Thirty previously untreated patients (27 men and 3 women) with a median age of 59 years were included in this study. Twelve patients had one metastatic site and 18 had two or more metastatic sites. The median performance status was 80%. The chemotherapy (CT) regimen administered during the course of this study consisted of carboplatin (300 mg/m2) and ifosfamide (4 g/m2) plus mesna every 4 weeks. All 30 patients were evaluable: 1 achieved a complete remission (CR) and 18 achieved a partial remission (PR) (objective response rate, 63%). The median response time was 3 months and the median survival time was 8 months (range, 1 to 25+ months). Bone marrow toxicity was Grade III in three patients and Grade IV in four patients. The carboplatin and ifosfamide combination was well tolerated. No cross-resistance with the doxorubicin and etoposide regimen was established because 4 of 11 patients responded to this combination (+/- cisplatin) after failing to respond to the ifosfamide and carboplatin regimen. The ifosfamide and carboplatin combination may be considered for inclusion in non-cross-resistant alternating CT schedules.

The treatment against cancer is being flooded by targeted therapies. Imatinib mesylate (Gleevec©) was the first molecule to provide the proof of principle that targeting an aberrant tyrosine kinase responsible for the uncontrolled cell cycle progression allows for the eradication of tumors. The ideal targeted therapy should eliminate the molecular event responsible for the disease, an oncogenic product such as c-KIT, ABL/BCR and PDGFRα in the case of Gleevec©. Two issues related to this conceptual advance are raised in clinical practice. First, these therapies might target additional pathways generating side effects. Secondly, non tumoral cells bearing the molecular target might respond and induce additional biological outcomes. This review will summarize the by-stander immune modulations promoted by the paradigmatic compound Gleevec©, leading to unexpected new therapeutic indications.

Within a population-based register of childhood injuries, 641 home accidents to children aged under 2 years were recorded in six hospitals. The annual rate was higher in children over 1 year (6.6 per 100) than in infants (2.7 per 100). A male predominance was observed only after the first birthday. Most injuries were related to physical trauma (mainly falls), but burns and poisonings were frequent in the second year. Most lesions were benign, except in the case of falls from a height (from a window or baby furniture). Nineteen per cent of the children were admitted to hospital. There were 15 skull fractures, two fatal cases and two severe sequelae. Child abuse was seldom suspected and the reasons for this are discussed. The study of the circumstances in which accidents occur leads to the conclusion that the main aspect of prevention should be passive protection ensured by the creation of a safe environment (compulsory safety standards for baby furniture, child resistant packaging), but that parents' information and education should also be developed, with emphasis on knowledge of children's normal psychological and motor development and abilities. Language: en

A total of 29 patients with advanced malignancy were treated with recombinant interferon gamma (rIFN gamma, specific activity = 2.10(7) units/mg, purity greater than 95%) given by intravenous bolus at doses escalating from 0.01 mg/m2 to 5 mg/m2 (2 x 10(5) - 10(8) IU/m2) in nine successive steps (at least 3 patients/step). Injections of rIFN gamma were repeated every 72 h for 15 days. Toxicity was evaluated according to the WHO scale. Fever and chills occurred in all patients treated without clear dose effect. Nausea and vomiting appeared at the fifth dose level and their frequency seemed to be dose-related. Cardiovascular side-effects (first-degree atrioventricular reversible block) were observed at the 2 mg/m2 and 5 mg/m2 levels (3 patients). Hematological toxicities were mild (2 grade 1 and 1 grade II cases of granulocytopenia). Minor biological modifications included a transitory rise in hepatic enzymes (12 patients), which correlated with the presence of liver metastasis. Hypocholesterolemia was observed in 18 patients. The appearance of antibodies against rIFN gamma was not detected. One partial clinical response was observed in a patient receiving 2 mg/m2. During rIFN gamma therapy this patient had the highest scores in this series for peripheral T lymphocytes with an activated phenotype (HLA DR+, TAC+) = 15% and for natural killer (NK) cells (NKH1, Leu19+) = 17%. rIFN gamma appears as a well-tolerated and promising therapeutic agent with toxicities and mode of action probably distinct from IFN alpha and beta.

For the last four decades, the treatment of cancer has relied on four treatment modalities, namely surgery, radiotherapy, cytotoxic chemotherapy, and hormonotherapy. Most of these therapies are believed to directly attack and eradicate tumor cells. The emerging concept that cancer is not just a disease of a tissue or an organ but also a host disease relies on evidence of tumor-induced immunosuppression and polymorphisms in genes involved in host protection against tumors. This theory is now gaining new impetus, based on our recent data showing that optimal therapeutic effects require the immunoadjuvant effect of tumor cell death induced by cytotoxic anticancer agents. Here, we show that the release of the high mobility group box 1 protein (HMGB1) by dying tumor cells is mandatory to license host dendritic cells (DCs) to process and present tumor antigens. HMGB1 interacts with Toll-like receptor 4 (TLR4) on DCs, which are selectively involved in the cross-priming of anti-tumor T lymphocytes in vivo. A TLR4 polymorphism that affects the binding of HMGB1 to TLR4 predicts early relapse after anthracycline-based chemotherapy in breast cancer patients. This knowledge may be clinically exploited to predict the immunogenicity and hence the efficacy of chemotherapeutic regimens.

The purpose of this study was to determine the predictive value of breast cancer molecular subclassification regarding the benefit of adjuvant anthracycline-based chemotherapy.Tumor samples from 823 patients included in two randomized trials that compared an anthracycline-based chemotherapy with no treatment were used to construct a tissue array. Estrogen receptor (ER), Her2, epidermal growth factor receptor, cytokeratine 5/6 expressions were determined by immunohistochemistry (IHC). The potential predictive factors of treatment effect on disease-free survival (DFS) were assessed by interaction tests and multivariate analysis.Sixty-four (8%), 98 (12%), 109 (14%) and 527 (66%) patients presented a Her2+/ER-, basal-like, Her2-/ER-/nonbasal and luminal-like breast cancer. ER expression, when assessed by IHC, was an independent predictive factor for the benefit of chemotherapy on DFS (test for interaction, P = 0.0015). The molecular subclassification significantly predicted the efficacy of chemotherapy (test for interaction, P = 0.01), but had no significant added value (P = 0.32) as compared to the ER by treatment interaction. Adjuvant chemotherapy was associated with an adjusted hazard ratio for relapse or death of 0.42 [95% confidence interval (CI): 0.17-1.05], 0.54 (95% CI: 0.27-1.08), 0.35 (95% CI: 0.18-0.68), 1.07 (95% CI: 0.81-1.41) for patients with Her2+/ER-, basal-like, Her2-/ER-/nonbasal and luminal-like tumors, respectively.The breast cancer molecular subclassification was predictive for chemotherapy efficacy in adjuvant setting, but did not provide significant additional information to ER.

Conventional cancer treatments rely on radiotherapy and chemotherapy. Such treatments supposedly mediate their effects via the direct elimination of tumor cells. Here we show that the success of some protocols for anticancer therapy depends on innate and adaptive antitumor immune responses. We describe in both mice and humans a previously unrecognized pathway for the activation of tumor antigen-specific T-cell immunity that involves secretion of the high-mobility-group box 1 (HMGB1) alarmin protein by dying tumor cells and the action of HMGB1 on Toll-like receptor 4 (TLR4) expressed by dendritic cells (DCs). During chemotherapy or radiotherapy, DCs require signaling through TLR4 and its adaptor MyD88 for efficient processing and cross-presentation of antigen from dying tumor cells. Patients with breast cancer who carry a TLR4 loss-of-function allele relapse more quickly after radiotherapy and chemotherapy than those carrying the normal TLR4 allele. These results delineate a clinically relevant immunoadjuvant pathway triggered by tumor cell death.

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BACKGROUND Adjuvant cisplatin-based chemotherapy improves survival among patients with completely resected non-small-cell lung cancer, but there is no validated clinical or biologic predictor of the benefit of chemotherapy. METHODS We used immunohistochemical analysis to determine the expression of the excision repair cross-complementation group 1 (ERCC1) protein in operative specimens of non-small-cell lung cancer. The patients had been enrolled in the International Adjuvant Lung Cancer Trial, thereby allowing a comparison of the effect of adjuvant cisplatin-based chemotherapy on survival, according to ERCC1 expression. Overall survival was analyzed with a Cox model adjusted for clinical and pathological factors. RESULTS Among 761 tumors, ERCC1 expression was positive in 335 (44%) and negative in 426 (56%). A benefit from cisplatin-based adjuvant chemotherapy was associated with the absence of ERCC1 (test for interaction, P=0.009). Adjuvant chemotherapy, as compared with observation, significantly prolonged survival among patients with ERCC1-negative tumors (adjusted hazard ratio for death, 0.65; 95% confidence interval [CI], 0.50 to 0.86; P=0.002) but not among patients with ERCC1-positive tumors (adjusted hazard ratio for death, 1.14; 95% CI, 0.84 to 1.55; P=0.40). Among patients who did not receive adjuvant chemotherapy, those with ERCC1-positive tumors survived longer than those with ERCC1-negative tumors (adjusted hazard ratio for death, 0.66; 95% CI, 0.49 to 0.90; P=0.009). CONCLUSIONS Patients with completely resected non-small-cell lung cancer and ERCC1-negative tumors appear to benefit from adjuvant cisplatin-based chemotherapy, whereas patients with ERCC1-positive tumors do not.