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We investigate the spatio-temporal dynamics of a ring cavity filled with a non-instantaneous Kerr medium and driven by a coherent injected beam. We show the existence of a stable mixed-mode solution that can be either extended or localized in space. The mixed-mode solutions are obtained in a regime where Turing instability (often called modulational instability) interacts with self-pulsing phenomenon (Andronov-Hopf bifurcation). We numerically describe the transition from stationary inhomogeneous solutions to a branch of mixed-mode solutions. We characterize this transition by constructing the bifurcation diagram associated with these solutions. Finally, we show stable localized mixed-mode solutions, which consist of time-periodic oscillations that are localized in space.
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Complex spatiotemporal dynamics have been a subject of recent experimental investigations in optical frequency comb microresonators and in driven fiber cavities with Kerr-type media. We show that this complex behavior has a spatiotemporal chaotic nature. We determine numerically the Lyapunov spectra, allowing us to characterize different dynamical behavior occurring in these simple devices. The Yorke-Kaplan dimension is used as an order parameter to characterize the bifurcation diagram. We identify a wide regime of parameters where the system exhibits a coexistence between the spatiotemporal chaos, the oscillatory localized structure, and the homogeneous steady state. The destabilization of an oscillatory localized state through radiation of counter-propagating fronts between the homogeneous and the spatiotemporal chaotic states is analyzed. To characterize better the spatiotemporal chaos, we estimate the front speed as a function of the pump intensity.
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PURPOSE: Optimal timing of neck dissection remains debated in the conservative management of patients with locoregionally advanced squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: The files of 63 patients with radiographic evidence of bulky or necrotic nodal metastases treated by up-front neck dissection and definitive radiotherapy between 2000 and 2012 at two institutions were retrospectively reviewed. RESULTS: The primary site was oropharyngeal, hypopharyngeal or laryngeal in 63%, 21% and 13% cases, respectively. Overall, 83% of the tumours were staged pN2b or more. Extracapsular spread was found in 48 cases (77%). After a 48-month median follow-up, the 3-year locoregional control and overall survival were 88% and 68%, respectively. Only one isolated failure occurred in the dissected neck. CONCLUSION: This combination therapy provides a good locoregional tumour control. It should be considered as an option in laryngeal, hypopharyngeal or oropharyngeal squamous cell carcinomas with bulky or necrotic nodal metastases at presentation.
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Carcinoma de Células Escamosas/terapia , Neoplasias de Cabeça e Pescoço/terapia , Esvaziamento Cervical , Terapia Neoadjuvante , Adulto , Idoso , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Quimioterapia Adjuvante , Fracionamento da Dose de Radiação , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Radioterapia Adjuvante , Estudos RetrospectivosRESUMO
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/m(2), 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.
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Dioxóis/administração & dosagem , Prognóstico , Sarcoma/tratamento farmacológico , Tumores Fibrosos Solitários/tratamento farmacológico , Tetra-Hidroisoquinolinas/administração & dosagem , Adulto , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Sarcoma/patologia , Tumores Fibrosos Solitários/patologia , Trabectedina , Resultado do TratamentoRESUMO
OBJECTIVE: Radical prostatectomy (RP) is an oncologic and functional challenge. Few series compare prospectively the two approaches, open retropubic (ORP) and laparoscopic robot-assisted RP (LRARP). The objective was to compare the oncological and functional results of ORP and LRARP. MATERIAL AND METHODS: From January 2009 to March 2012, two practiced surgeons conducted 304 consecutive RP: respectively 129 ORP and 175 LRARP. Preoperative, perioperative and postoperative data (location and size of positive surgical margins [PSM]) were recorded prospectively and compared with oncological results (PSM, biochemical recurrence-free survival [BCR]) and functional outcomes (urinary and erectile) by self-validated questionnaires (USP, IIEF-15). The comparison was made by the Chi(2) test and Student t-test for qualitative and quantitative variables. RESULTS: The preoperative data 2 groups were comparable. MCP rate was 13.2% for the ORP and 20% for the LRARP (ns) and was 1.4% and 29.6% (ORP) versus 9.4% and 36.7% (LRARP) for pT2 and pT3 for respectively (P=0.078). BCR was the same in both groups (95.2% at 13.1 months). At 12 months, the results of continence showed no difference (P=0.49) and about erectile function, the EF-score was significantly higher in LRARP: 22 versus 17 for the ORP (P=0.03). CONCLUSION: Oncological results were comparable after ORP and LRARP. The recovery of continence was excellent regardless of the surgical technique, the recovery of erectile function a bit faster by LRARP. LEVEL OF EVIDENCE: 3.
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Laparoscopia , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos , Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Ereção Peniana , Estudos Prospectivos , Resultado do Tratamento , MicçãoRESUMO
BACKGROUND: Papillary renal cell carcinoma (PRCC), type 1 and type 2, represents 10%-15% of renal cell carcinomas (RCC). There is no standard first-line treatment of metastatic PRCC (mPRCC). Anti-angiogenics have shown activity in retrospective studies but no prospective studies in pure papillary histology have been reported, but one with foretinib. PATIENTS AND METHODS: A prospective phase II study evaluated sunitinib in first-line treatment of mPRCC. The primary end point was overall response rate (ORR). Secondary end points were progression-free survival (PFS) and overall survival (OS). RESULTS: Fifteen and 46 patients, respectively, with type 1 and type 2 mPRCC were enrolled. Using the MSKCC scoring system: 12 (20%), 33 (55%) and 9 (15%) patients were, respectively, in the favourable, intermediate or poor risk group and 7 undetermined. Median follow-up is 51.4 months. In type 1, 2 patients 13% [95% confidence interval (CI) 0.1-30.5] had a partial response (PR), 10 had stable disease (SD) with 5 (33%) ≥12 weeks. In type 2, 5 patients 11% (95% CI 1.9-20.3) had a PR, 25 had SD with 10(22%) ≥12 weeks. Median PFS was 6.6 months (95% CI 2.8-14.8) in type 1 and 5.5 months (95% CI 3.8-7.1) in type 2. Median OS was 17.8 (95% CI 5.7-26.1) and 12.4 (95% CI 8.2-14.3) months, respectively, in type 1 and 2. Safety was as expected with sunitinib for metastatic RCC. CONCLUSION: Sunitinib showed activity in treatment of type 1 and 2 mPRCC but lower than in clear-cell mRCC. Both PFS and OS are longer in type I PRCC. Sunitinib represents an acceptable option in first-line treatment of mPRCC.
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Inibidores da Angiogênese/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Indóis/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Pirróis/uso terapêutico , Idoso , Inibidores da Angiogênese/efeitos adversos , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/secundário , Progressão da Doença , Intervalo Livre de Doença , Feminino , França , Humanos , Indóis/efeitos adversos , Estimativa de Kaplan-Meier , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Pirróis/efeitos adversos , Fatores de Risco , Sunitinibe , Fatores de Tempo , Resultado do TratamentoRESUMO
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.
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Determinação de Ponto Final/normas , Tumores do Estroma Gastrointestinal/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Projetos de Pesquisa/normas , Sarcoma/terapia , Terminologia como Assunto , Consenso , Técnica Delphi , Progressão da Doença , Intervalo Livre de Doença , Determinação de Ponto Final/classificação , Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/mortalidade , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto/classificação , Sarcoma/diagnóstico , Sarcoma/mortalidade , Fatores de Tempo , Falha de TratamentoRESUMO
AIMS: Recent data suggest that patients with pulmonary metastases from sarcomas might benefit from ablation of their metastases. Some data are available regarding osteosarcomas/angiosarcomas and lung metastases. The purpose of this study was to assess the efficacy of local ablative treatment on the survival of patients with oligometastases (one to five lesions, any metastatic site, any grade/histology) from sarcomas. MATERIALS AND METHODS: A multicentric retrospective study of the French Sarcoma Group was conducted in sarcoma patients with oligometastases who were treated between 2000 and 2012. Survival was analysed using multivariate sensitivity analyses with propensity scores to limit bias. RESULTS: Of the 281 patients evaluated, 164 patients received local treatment for oligometastases between 2000 and 2012. The groups' characteristics were similar in terms of tumour size and remission of the primary tumours. The median follow-up was 25.7 months; 129 (45.9%) patients had died at this point. The median overall survivals were 45.3 (95% confidence interval = 34-73) months for the local treatment group and 12.6 for the other group (95% confidence interval = 9.33-22.9). Survival was better among patients who received local treatment (hazard ratio = 0.47; 95% confidence interval = 0.29-0.78; P < 0.001). Subgroup analyses revealed similar findings in the patients with single oligometastases (hazard ratio = 0.48; 95% confidence interval = 0.28-0.82; P = 0.007); a significant benefit was observed for grade 3, and a trend was observed for grade 2. CONCLUSION: Local ablative treatment seemed to improve the overall survival of the patients who presented with oligometastatic sarcomas, including soft tissue and bone sarcomas. The survival benefit remained after repeated local treatments for several oligometastatic events. Surgery yielded the most relevant results, but alternative approaches (i.e. radiofrequency ablation and radiotherapy) seemed to be promising. The relevance of these results is strengthened by our analysis, which avoided biases by restricting the population to patients with oligometastatic disease and used propensity scores.
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Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Sarcoma/secundário , Sarcoma/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Metástase Neoplásica , Prognóstico , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: The EORTC-STBSG coordinated two large trials of adjuvant chemotherapy (CT) in localized high-grade soft tissue sarcoma (STS). Both studies failed to demonstrate any benefit on overall survival (OS). The aim of the analysis of these two trials was to identify subgroups of patients who may benefit from adjuvant CT. PATIENTS AND METHODS: Individual patient data from two EORTC trials comparing doxorubicin-based CT to observation only in completely resected STS (large resection, R0/marginal resection, R1) were pooled. Prognostic factors were assessed by univariate and multivariate analyses. Patient outcomes were subsequently compared between the two groups of patients according to each analyzed factor. RESULTS: A total of 819 patients had been enrolled with a median follow-up of 8.2 years. Tumor size, high histological grade and R1 resection emerged as independent adverse prognostic factors for relapse-free survival (RFS) and OS. Adjuvant CT is an independent favorable prognostic factor for RFS but not for OS. A significant interaction between benefit of adjuvant CT and age, gender and R1 resection was observed for RFS and OS. Males and patients >40 years had a significantly better RFS in the treatment arms, while adjuvant CT was associated with a marginally worse OS in females and patients <40 years. Patients with R1 resection had a significantly better RFS and OS favoring adjuvant CT arms. CONCLUSION: Adjuvant CT is not associated with a better OS in young patients or in any pathology subgroup. Poor quality of initial surgery is the most important prognostic and predictive factor for utility of adjuvant CT in STS. Based on these data, we conclude that adjuvant CT for STS remains an investigational procedure and is not a routine standard of care.
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Antibióticos Antineoplásicos/uso terapêutico , Doxorrubicina/uso terapêutico , Sarcoma/tratamento farmacológico , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Masculino , PrognósticoRESUMO
We have carried out nanoindentation studies of gold in which the indenter is atomically characterized by field-ion microscopy and the scale of deformation is sufficiently small to be directly compared with atomistic simulations. We find that many features of the experiment are correctly reproduced by molecular dynamics simulations, in some cases only when an atomically rough indenter rather than a smooth repulsive-potential indenter is used. Heterogeneous nucleation of dislocations is found to take place at surface defect sites. Using input from atomistic simulations, a model of indentation based on stochastic transitions between continuum elastic-plastic states is developed, which accurately predicts the size distributions of plastic 'pop-in' events and their dependence on tip geometry.
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AIM: Brostallicin is a DNA minor groove binder that has shown activity in patients with soft tissue sarcoma (STS) failing first-line therapy. The present study assessed the safety and efficacy of first-line brostallicin in patients with advanced or metastatic STS >60 years or not fit enough to receive combination chemotherapy. A prospective explorative pharmacogenetic analysis was undertaken in parallel. METHODS: Patients were randomised in a 2:1 ratio between IV brostallicin 10mg/m(2) and doxorubicin 75 mg/m(2) once every 3 weeks for a maximum of six cycles. Disease stabilisation at 26 weeks (primary end-point) was considered a 'success'. Further testing of brostallicin was warranted if ≥ 35 'successes' were observed in the first 72 eligible patients treated with brostallicin. In addition, patients were genotyped for glutathione S transferase (GST) polymorphisms. RESULTS: One hundred and eighteen patients were included (79 brostallicin and 39 doxorubicin). Brostallicin was well tolerated in comparison to doxorubicin with less grade 3-4 neutropenia (67% versus 95%), grade 2-3 systolic dysfunction (0% versus 11%), alopecia (17% versus 61%) and grade 2-3 mucositis (0% versus 18%). For brostallicin versus doxorubicin, 'successes' were observed in 5/77 versus 10/36, progression free survival at 1 year was 6.5% versus 15.6%, objective response rate was 3.9% versus 22.2% and overall survival at 1 year was 50.5% versus 57.9%, respectively. Only GSTA1 genotype was significantly associated with success rate of doxorubicin treatment. CONCLUSION: Brostallicin cannot be recommended at this dose and schedule in this patient population as first-line therapy. GSTA1 genotype may be predictive for doxorubicin efficacy but warrants further study.
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Neoplasias Ósseas/tratamento farmacológico , Doxorrubicina/uso terapêutico , Guanidinas/uso terapêutico , Pirróis/uso terapêutico , Sarcoma/tratamento farmacológico , Adulto , Antibióticos Antineoplásicos/uso terapêutico , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Intervalo Livre de Doença , Esquema de Medicação , Europa (Continente) , Frequência do Gene , Genótipo , Glutationa Transferase/genética , Humanos , Isoenzimas/genética , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Metástase Neoplásica , Farmacogenética , Polimorfismo Genético , Sarcoma/genética , Sarcoma/patologia , Resultado do TratamentoRESUMO
BACKGROUND: To determine the activity of radiotherapy in patients with inoperable desmoid-type fibromatosis (DF) a multicenter prospective phase II trial was carried out. MATERIALS AND METHODS: Patients with inoperable progressive disease of primary, recurrent or incompletely resected lesions received a dose of 56 Gy in 28 fractions. Follow-up MRI studies were carried out every 3 months for 2 years and thereafter every 6 months. The primary end point was local control rate at 3 years, estimated by a nonparametric method for interval-censored survival data. Secondary end points were objective tumor response, acute and late toxic effect. RESULTS: Forty-four patients (27 F/17 M) were enrolled from 2001 to 2008. Median age was 39.5 years. Main tumor sites included trunk 15 (34.1%) and extremities 27 (61.3%). Median follow-up was 4.8 years. The 3-year local control rate was 81.5% (90% one-sided confidence interval 74% to 100%). Best overall response during the first 3 years was complete response (CR) 6 (13.6%), partial response (PR) 16 (36.4%), stable disease 18 (40.9%), progressive disease 3 (6.8%) and nonassessable 1 (2.3%). Five patients developed new lesions. After 3 years, the response further improved in three patients: (CR 2, PR 1). Acute grade 3 side-effects were limited to skin, mucosal membranes and pain. Late toxic effect consisted of mild edema in 10 patients. CONCLUSIONS: Moderate dose radiotherapy is an effective treatment of patients with DF. Response after radiation therapy is slow with continuing regression seen even after 3 years.
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Fibromatose Agressiva/radioterapia , Recidiva Local de Neoplasia/radioterapia , Adolescente , Adulto , Idoso , Feminino , Fibromatose Agressiva/diagnóstico por imagem , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Radiografia , Análise de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
INTRODUCTION: The frequency of neuropsychiatric symptoms in systemic lupus varies between 14 and 75%. Their mechanisms are multiple and their non-specificity makes the etiological diagnosis more difficult. The MRI lesions are dominated by small white matter hyperintensities. CASE REPORT: We report a case of 17-year-old girl without medical, surgical or familial past, who presented an acute psychotic episode with fever. The neurological examination showed a pyramidal syndrome. The brain MRI objectified diffuse, bilateral and symmetrical white and gray matter hyperintensities. The diagnosis of neuropsychiatric lupus was retained with association of more than four criteria among the 11 ARA revised criteria: pleural effusion, neuropsychiatric manifestations, anemia, lymphopenia and positive ANA. The treatment was based on corticosteroids. The evolution was fatal. DISCUSSION: Psychiatric disorders are polymorphic and appear during the course of the disease or at diagnosis; they can be seen in 20% of cases and are a sign of a poor prognosis. Most often these disorders are a non-specific reaction, but severe clinical forms can be observed as suicidal risk or mood disorders (depression, mania...), or acute psychotic episode. CONCLUSION: The diagnosis of neuropsychiatric lupus must be evoked systematically in atypical neuropsychiatric disorders especially when confronted with minimal biological and brain imaging abnormalities.
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Encéfalo/patologia , Imagem de Difusão por Ressonância Magnética , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Imageamento por Ressonância Magnética , Transtornos Psicóticos/diagnóstico , Doença Aguda , Corticosteroides/uso terapêutico , Adulto , Diagnóstico Diferencial , Evolução Fatal , Feminino , Humanos , Vasculite Associada ao Lúpus do Sistema Nervoso Central/tratamento farmacológico , Exame Neurológico , Transtornos Psicóticos/tratamento farmacológicoRESUMO
INTRODUCTION: The mechanical repercussions of distal radius malunion on the distal radio-ulnar (DRU) joint are common and inconsistently corrected by radius osteotomy alone. Ulnar resection has thus become a palliative solution. HYPOTHESES: Does ulna resection influence the outcomes of distal radius malunion corrective osteotomies? What preoperative factors warrant preserving the distal radio-ulnar joint? PATIENTS AND METHODS: Twenty-one corrective osteotomies of the radius were retrospectively reviewed. Ulna resection was performed in cases of cartilage damage, joint incongruence, or persistent stiffness in pronosupination after osteotomy of the radius. After the osteotomies, two groups were identified: 10 cases with preservation of the distal end of the ulna (DRU+) and eleven with distal resections (DRU-). RESULTS: At review, all the osteotomies had united, with comparable anatomical restoration of the radial epiphysis for the two groups. We noted a statistically significant gain in mobility after osteotomy for both techniques (but no difference between them) and comparable grip strengths with 89.8% of the contralateral side for the DRU+ group versus 90.4% for the DRU- group. Pain (scale, 0-3) had significantly diminished for both groups decreasing from 1.9 to 0.3 for the DRU+ group and from 2.5 to 1.1 for the DRU- group, with no significant difference between them. The Mayo Clinic Wrist Score and the DASH score did not differ significantly with 73/100 and 13.5 for the DRU+ group compared with 68.2/100 and 20.2 for the DRU- group, respectively. DISCUSSION: These results show that the impact of ulna resection after distal osteotomy of the radius is limited as reflected by radiological correction, mobility and grip strength. However, after resection pain in the ulnar tilt of the wrist due to instability of the distal ulnar stump was noted. Besides cartilage damage, ulnar deviation of over 5mm was, for this series, a constant factor in non-preservation of the DRU joint. LEVEL OF EVIDENCE: Level IV. Retrospective study.
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Fraturas Mal-Unidas/cirurgia , Osteotomia/métodos , Fraturas do Rádio/cirurgia , Ulna/cirurgia , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Articulação do PunhoRESUMO
BACKGROUND: We investigated prognostic factors (PFs) for 90-day mortality in a large cohort of advanced/metastatic soft tissue sarcoma (STS) patients treated with first-line chemotherapy. METHODS: The PFs were identified by both logistic regression analysis and probability tree analysis in patients captured in the Soft Tissue and Bone Sarcoma Group (STBSG) database (3002 patients). Scores derived from the logistic regression analysis and algorithms derived from probability tree analysis were subsequently validated in an independent study cohort from the French Sarcoma Group (FSG) database (404 patients). RESULTS: The 90-day mortality rate was 8.6 and 4.5% in both cohorts. The logistic regression analysis retained performance status (PS; odds ratio (OR)=3.83 if PS=1, OR=12.00 if PS ≥2), presence of liver metastasis (OR=2.37) and rare site metastasis (OR=2.00) as PFs for early death. The CHAID analysis retained PS as a major discriminator followed by histological grade (only for patients with PS ≥2). In both models, PS was the most powerful PF for 90-day mortality. CONCLUSION: Performance status has to be taken into account in the design of further clinical trials and is one of the most important parameters to guide patient management. For those patients with poor PS, expected benefits from therapy should be weighed up carefully against the anticipated toxicities.
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Sarcoma/tratamento farmacológico , Sarcoma/mortalidade , Neoplasias de Tecidos Moles/tratamento farmacológico , Neoplasias de Tecidos Moles/mortalidade , Adulto , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Sarcoma/patologia , Neoplasias de Tecidos Moles/patologia , Resultado do TratamentoRESUMO
BACKGROUND: the role of chemotherapy in advanced malignant peripheral nerve sheath tumor (MPNST) is unclear. PATIENTS AND METHODS: chemotherapy-naive soft tissue sarcomas (STS) patients treated on 12 pooled nonrandomized and randomized European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group trials were retrospectively analyzed. Clinical outcomes, overall survival, progression-free survival (PFS) and response were determined for MPNST and other STS histotypes and compared. Additionally, prognostic factors within the MPNST population were defined. Studied cofactors were demographics, sarcoma history, disease extent and chemotherapy regimen. RESULTS: after a median follow-up of 4.1 years, 175 MPNST out of 2675 eligible STS patients were analyzed. Outcome was similar for MPNST versus other STS histotypes, with a response rate, median PFS and overall survival of 21% versus 22%, 17 versus 16 weeks and 48 versus 51 weeks, respectively. Performance status was an independent prognostic factor for overall survival. Chemotherapy regimen was an independent prognostic factor for response (P < 0.0001) and PFS (P = 0.009). Compared with standard first-line doxorubicin, the doxorubicin-ifosfamide regimen had the best response, whereas ifosfamide had the worst prognosis. CONCLUSION: this series indicates the role of chemotherapy in treatment of advanced MPNST. This first comparison showed similar outcomes for MPNST and other STS histotypes. The apparent superiority of the doxorubicin-ifosfamide regimen justifies further investigations of this combination in randomized trials.
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Neoplasias de Bainha Neural/tratamento farmacológico , Sarcoma/tratamento farmacológico , Adolescente , Adulto , Idoso , Criança , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: The prognosis of advanced soft tissue sarcoma remains poor. Many phase II trials investigating new regimens have been published in the last 10 years. MATERIALS AND METHODS: Full English-language reports of phase II clinical trials from January 1999 to October 2009 have been reviewed. We have defined those that provided 3- and 6-month progression-free survival rates (PFSR) >39% and 14%, respectively, as promising second-line regimens. For studies enrolling both chemonaive and pretreated patients, we have compared the reported PFSR3 to the expected PFSR3 of an active treatment administered in the same proportions of pretreated and nonpretreated patients. RESULTS: Forty-nine trials were identified. Among the trials investigating new regimens in pretreated patients alone, the promising second-line regimens were ifosfamide, brostallicin, pazopanib (except in liposarcoma), temozolomide, trabectedin, dacarbazine-gemcitabine and docetaxel (Taxotere)-gemcitabine combinations (in uterine leiomyosarcoma). Among the trials enrolling both chemonaive and pretreated patients, most regimens reached the level of efficacy; moreover, in three trials, the reported PFSR3 was particularly high: weekly paclitaxel (Taxol) in angiosarcoma, docetaxel-gemcitabine combination (in uterine leiomyosarcoma) and oral perifosine. CONCLUSIONS: In the past 10 years, several drugs or combinations have demonstrated promising activity in exploratory phase II trials and warrant further investigation in appropriate phase III trials.