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1.
Cancer ; 130(13): 2351-2360, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38400828

RESUMO

BACKGROUND: The objective of this study was to investigate the role of clinical factors together with FOXO1 fusion status in patients with nonmetastatic rhabdomyosarcoma (RMS) to develop a predictive model for event-free survival and provide a rationale for risk stratification in future trials. METHODS: The authors used data from patients enrolled in the European Pediatric Soft Tissue Sarcoma Study Group (EpSSG) RMS 2005 study (EpSSG RMS 2005; EudraCT number 2005-000217-35). The following baseline variables were considered for the multivariable model: age at diagnosis, sex, histology, primary tumor site, Intergroup Rhabdomyosarcoma Studies group, tumor size, nodal status, and FOXO1 fusion status. Main effects and significant second-order interactions of candidate predictors were included in a multiple Cox proportional hazards regression model. A nomogram was generated for predicting 5-year event-free survival (EFS) probabilities. RESULTS: The EFS and overall survival rates at 5 years were 70.9% (95% confidence interval, 68.6%-73.1%) and 81.0% (95% confidence interval, 78.9%-82.8%), respectively. The multivariable model retained five prognostic factors, including age at diagnosis interacting with tumor size, tumor primary site, Intergroup Rhabdomyosarcoma Studies clinical group, and FOXO1 fusion status. Based on each patient's total score in the nomogram, patients were stratified into four groups. The 5-year EFS rates were 94.1%, 78.4%, 65.2%, and 52.1% in the low-risk, intermediate-risk, high-risk, and very-high-risk groups, respectively, and the corresponding 5-year overall survival rates were 97.2%, 91.5%, 74.3%, and 60.8%, respectively. CONCLUSIONS: The results presented here provide the rationale to modify the EpSSG stratification, with the most significant change represented by the replacement of histology with fusion status. This classification was adopted in the new international trial launched by the EpSSG.


Assuntos
Nomogramas , Rabdomiossarcoma , Humanos , Rabdomiossarcoma/mortalidade , Rabdomiossarcoma/patologia , Rabdomiossarcoma/terapia , Masculino , Feminino , Pré-Escolar , Criança , Prognóstico , Lactente , Medição de Risco , Adolescente , Europa (Continente)/epidemiologia , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O1/metabolismo , Proteínas de Fusão Oncogênica/genética
2.
Mem Cognit ; 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38814385

RESUMO

Early in life and without special training, human beings discern resemblance between abstract visual stimuli, such as drawings, and the real-world objects they represent. We used this capacity for visual abstraction as a tool for evaluating deep neural networks (DNNs) as models of human visual perception. Contrasting five contemporary DNNs, we evaluated how well each explains human similarity judgments among line drawings of recognizable and novel objects. For object sketches, human judgments were dominated by semantic category information; DNN representations contributed little additional information. In contrast, such features explained significant unique variance perceived similarity of abstract drawings. In both cases, a vision transformer trained to blend representations of images and their natural language descriptions showed the greatest ability to explain human perceptual similarity-an observation consistent with contemporary views of semantic representation and processing in the human mind and brain. Together, the results suggest that the building blocks of visual similarity may arise within systems that learn to use visual information, not for specific classification, but in service of generating semantic representations of objects.

3.
Mem Cognit ; 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38668991

RESUMO

In her 1926 book Measurement of Intelligence by Drawings, Florence Goodenough pioneered the quantitative analysis of children's human-figure drawings as a tool for evaluating their cognitive development. This influential work launched a broad enterprise in cognitive evaluation that continues to the present day, with most clinicians and researchers deploying variants of the checklist-based scoring methods that Goodenough invented. Yet recent work leveraging computational innovations in cognitive science suggests that human-figure drawings possess much richer structure than checklist-based approaches can capture. The current study uses these contemporary tools to characterize structure in the images from Goodenough's original work, then assesses whether this structure carries information about demographic and cognitive characteristics of the participants in that early study. The results show that contemporary methods can reliably extract information about participant age, gender, and mental faculties from images produced over 100 years ago, with no expert training and with minimal human effort. Moreover, the new analyses suggest a different relationship between drawing and mental ability than that captured by Goodenough's highly influential approach, with important implications for the use of drawings in cognitive evaluation in the present day.

4.
J Exerc Sci Fit ; 22(2): 97-102, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38188222

RESUMO

Background/objectives: Team sports are characterised by repeated maximal intensity bursts of activity, requiring significant energy contribution from the phosphagen pathways. The objective of this study was to evaluate the impact of different rest periods on repeated maximal intensity efforts. Methods: The effect of three different recovery periods (60 s, 90 s and 120 s) during a 10 × six-seconds intermittent sprint training protocol performed on a cycle ergometer was investigated. Thirteen part-time female athletes from two sports, Rugby Sevens and Netball competing for their state participated in the study. Peak Power (PPO), Mean Power (MPO), "total work" in the form of calorie expenditure, performance decrement, repetitions over 95% PPO, blood lactate, and RPE were recorded. Results: There was a significant effect of condition on MPO and calorie expenditure (p < 0.050). MPO was significantly lower for 60 s compared to 90 s (710.4 vs 734.4 W, ES = 0.27-0.42) and 120 s (710.4 vs 743.3 W, ES = 0.36-0.47). Calorie expenditure was significantly lower for 60 s compared to 90 s (4.41 vs 4.56 cal, ES = 0.25-0.46) and 120 s (4.41 vs 4.59 cal, ES = 0.40-0.48). There was a significant effect of time (60 s 11.7, 90 s 11.1.120 s 10.9 mmol/L, p < 0.010) but not condition (p = 0.617) for blood lactate accumulation, and a significant difference in session RPE between 60 and both 90 s and 120 s (60 s 15.5, 90 s 14.2. p = 0.034 120 s 13.9, p = 0.039). Conclusion: Shorter recovery durations resulted in decreased mean power and calorie expenditure, but higher RPE when compared to longer recovery periods. All three recovery periods may have fallen between the fast and slow phases of PCr resynthesis of approximately 20 and 180 s resulting in partial but not complete recovery. Total training time should be a consideration when determining what protocol to implement.

5.
Pediatr Blood Cancer ; 70(3): e28608, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-32776456

RESUMO

The treatment of extremity rhabdomyosarcoma remains a challenge due to several adverse prognostic factors frequently associated with this tumor site. The International Soft-Tissue Sarcoma Database Consortium (INSTRuCT) is a collaboration of the Children's Oncology Group Soft-Tissue Sarcoma Committee, the European Pediatric Soft-Tissue Sarcoma Study Group, and the Cooperative Weichteilsarkom Studiengruppe. The INSTRuCT surgical committee developed an internationally applicable consensus opinion document for the surgical treatment of extremity rhabdomyosarcoma. This document addresses surgical management, including biopsy, nodal staging, timing of therapy, resection and reexcision, reconstruction, and surgical approach at relapse.


Assuntos
Rabdomiossarcoma , Sarcoma , Criança , Humanos , Consenso , Recidiva Local de Neoplasia , Sarcoma/cirurgia , Rabdomiossarcoma/terapia
6.
Pediatr Blood Cancer ; 70(7): e30374, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37083216

RESUMO

BACKGROUND: To assess the outcomes of pediatric patients with undifferentiated embryonal sarcoma of the liver (UESL) and treatment including at least surgery and systemic chemotherapy. METHODS: This study included patients aged up to 21 years with a pathological diagnosis of UESL prospectively enrolled from 1995 to 2016 in three European trials focusing on the effects of surgical margins, preoperative chemotherapy, use of radiotherapy (RT), and chemotherapy. RESULTS: Out of 65 patients with a median age at diagnosis of 8.7 years (0.6-20.8), 15 had T2 tumors, and one had lymph node spread, 14 were Intergroup Rhabdomyosarcoma Study (IRS) I, nine IRS II, 38 IRS III, and four IRS IV. Twenty-eight upfront surgeries resulted in five operative spillages and 11 infiltrated surgical margins, whereas 37 delayed surgeries resulted in no spillages (p = .0119) and three infiltrated margins (p = .0238). All patients received chemotherapy, including anthracyclines in 47. RT was administered in 15 patients. With a median follow-up of 78.6 months, 5-year overall and event-free survivals (EFS) were 90.1% (95% confidence interval [CI]: 79.2-95.5) and 89.1% (95% CI: 78.4-94.6), respectively. Two out four local relapses had previous infiltrated margins and two out of three patients with metastatic relapses received reduced doses of alkylating agents. Infiltrated margins (p = .1607), T2 stage (p = .3870), use of RT (p = .8731), and anthracycline-based chemotherapy (p = .1181) were not correlated with EFS. CONCLUSIONS: Multimodal therapy improved the outcome of UESL. Neoadjuvant chemotherapy for pediatric patients increases the probability of complete surgical resection. The role of anthracyclines and RT for localized disease remains unclear.


Assuntos
Rabdomiossarcoma , Sarcoma , Neoplasias de Tecidos Moles , Criança , Humanos , Idoso , Margens de Excisão , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Sarcoma/tratamento farmacológico , Rabdomiossarcoma/terapia , Neoplasias de Tecidos Moles/patologia , Antraciclinas/uso terapêutico , Fígado/patologia
7.
Med Teach ; : 1-6, 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38065689

RESUMO

As medical schools embrace diversity, it is increasingly acknowledged that medical students with disabilities must be welcome and supported in becoming physicians. Students should be able to ask for and receive reasonable accommodations to support their education. However, a practical shared approach to supporting medical students with disabilities is needed. The 12 tips in this article use sense-making theory as a framework to guide medical school faculty in supporting medical students with disabilities. The tips center on perceiving cues, creating interpretations, taking action, and communicating with students. The 12 tips can be utilized by faculty members across universities to take a proactive role in implementing support for medical students with disabilities and, in turn, nurturing an inclusive educational environment.

8.
J Neurosci ; 41(5): 1019-1032, 2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-33334868

RESUMO

The human cortex encodes information in complex networks that can be anatomically dispersed and variable in their microstructure across individuals. Using simulations with neural network models, we show that contemporary statistical methods for functional brain imaging-including univariate contrast, searchlight multivariate pattern classification, and whole-brain decoding with L1 or L2 regularization-each have critical and complementary blind spots under these conditions. We then introduce the sparse-overlapping-sets (SOS) LASSO-a whole-brain multivariate approach that exploits structured sparsity to find network-distributed information-and show in simulation that it captures the advantages of other approaches while avoiding their limitations. When applied to fMRI data to find neural responses that discriminate visually presented faces from other visual stimuli, each method yields a different result, but existing approaches all support the canonical view that face perception engages localized areas in posterior occipital and temporal regions. In contrast, SOS LASSO uncovers a network spanning all four lobes of the brain. The result cannot reflect spurious selection of out-of-system areas because decoding accuracy remains exceedingly high even when canonical face and place systems are removed from the dataset. When used to discriminate visual scenes from other stimuli, the same approach reveals a localized signal consistent with other methods-illustrating that SOS LASSO can detect both widely distributed and localized representational structure. Thus, structured sparsity can provide an unbiased method for testing claims of functional localization. For faces and possibly other domains, such decoding may reveal representations more widely distributed than previously suspected.SIGNIFICANCE STATEMENT Brain systems represent information as patterns of activation over neural populations connected in networks that can be widely distributed anatomically, variable across individuals, and intermingled with other networks. We show that four widespread statistical approaches to functional brain imaging have critical blind spots in this scenario and use simulations with neural network models to illustrate why. We then introduce a new approach designed specifically to find radically distributed representations in neural networks. In simulation and in fMRI data collected in the well studied domain of face perception, the new approach discovers extensive signal missed by the other methods-suggesting that prior functional imaging work may have significantly underestimated the degree to which neurocognitive representations are distributed and variable across individuals.


Assuntos
Mapeamento Encefálico/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Reconhecimento Facial/fisiologia , Redes Neurais de Computação , Humanos , Imageamento por Ressonância Magnética/métodos , Análise Multivariada
9.
Cancer ; 128(23): 4150-4156, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36250420

RESUMO

BACKGROUND: The survival of patients with localized embryonal rhabdomyosarcoma (RMS) completely resected at diagnosis is greater than 90%. Most patients have paratesticular, uterine, or vaginal RMS, limiting specific analyses of RMS localized in other anatomic regions. This international study was conducted to define the outcome for completely resected embryonal RMS at sites other than paratesticular, uterine, or vaginal primary sites. METHODS: A total of 113 patients aged 0-18 years were identified who were enrolled from January 1995 to December 2016 in Children's Oncology Group (COG) (64 patients) and European protocols (49). Genitourinary nonbladder and prostate RMS were excluded. The recommended chemotherapy was vincristine and actinomycin-D (VA) for 24 weeks or ifosfamide plus VA in the European protocols and VA for 48 weeks or VA plus cyclophosphamide in the COG protocols. RESULTS: The most common primary sites were nonparameningeal head and neck (40.7%), other (23.9%), and extremities (20.4%). In the COG studies, 42% of patients received VA and 58% VA plus cyclophosphamide. In Europe, 53% received VA and 47% ifosfamide plus VA. With a median follow-up of 97.5 months, the 5-year progression-free and overall survival was 80.0% (71.2%-86.4%) and 92.5% (85.6%-96.2%), respectively, without significant differences between chemotherapy regimens. Tumor size (< or >5 cm) significantly influenced overall survival: 96.2% (88.6%-98.8%) vs. 80.6% (59.5%-91.4%), respectively (p = .01). CONCLUSIONS: Survival of patients with nonalveolar RMS completely resected at diagnosis is excellent among tumors arising from nonparatesticular, uterine, and vaginal sites, and patients may be treated successfully with low-intensity chemotherapy. To reduce the burden of treatment, VA for 24 weeks may be considered in children with tumors <5 cm.


Assuntos
Rabdomiossarcoma Embrionário , Rabdomiossarcoma , Criança , Masculino , Feminino , Humanos , Lactente , Rabdomiossarcoma Embrionário/tratamento farmacológico , Rabdomiossarcoma Embrionário/cirurgia , Ifosfamida , Rabdomiossarcoma/tratamento farmacológico , Rabdomiossarcoma/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida , Fatores de Risco
10.
Nat Rev Neurosci ; 18(1): 42-55, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27881854

RESUMO

Semantic cognition refers to our ability to use, manipulate and generalize knowledge that is acquired over the lifespan to support innumerable verbal and non-verbal behaviours. This Review summarizes key findings and issues arising from a decade of research into the neurocognitive and neurocomputational underpinnings of this ability, leading to a new framework that we term controlled semantic cognition (CSC). CSC offers solutions to long-standing queries in philosophy and cognitive science, and yields a convergent framework for understanding the neural and computational bases of healthy semantic cognition and its dysfunction in brain disorders.


Assuntos
Inteligência Artificial , Transtornos Cognitivos/fisiopatologia , Transtornos Cognitivos/psicologia , Cognição/fisiologia , Compreensão/fisiologia , Semântica , Animais , Humanos , Testes Neuropsicológicos
11.
Pediatr Blood Cancer ; 69(4): e29589, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35118808

RESUMO

AIM: No widely agreed consensus protocols exist for the management of benign ovarian tumors (BOT) in children. This presents a substantial risk for suboptimal management. We aimed to generate multispecialty consensus guidance to standardize surgical management and provide a clear follow-up protocol for children with BOTs. METHODS: Prospective two-round confidential e-Delphi consensus survey distributed among multispecialty expert panel; concluded by two semistructured videoconferences. MAIN RESULTS: Consensus was generated on these core outcome sets: preoperative/intraoperative management; follow-up; adolescent gynecology referral. (1) Children with BOTs should receive the same management as other patients with potentially neoplastic lesions: Preoperative discussion at a pediatric oncology multidisciplinary meeting to risk stratify tumors, and management by health professionals with expertise in ovarian-sparing surgery and laparoscopy. (2) Ovarian-sparing surgery for BOTs should be performed wherever possible to maximize fertility preservation. (3) Ovarian masses detected during emergency laparoscopy/laparotomy should be left in situ wherever feasible and investigated appropriately (imaging/tumor markers) before resection. (4) Follow-up should be undertaken for all patients after BOT resection. Patients should be offered referral to adolescent gynecology to discuss fertility implications. CONCLUSION: This best practice Delphi consensus statement emphasizes the importance of managing children with BOTs through a well-defined oncological MDT strategy, in order to optimize risk stratification and allow fertility preservation by ovarian-sparing surgery wherever possible.


Assuntos
Preservação da Fertilidade , Neoplasias Ovarianas , Adolescente , Criança , Técnica Delphi , Feminino , Humanos , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Estudos Prospectivos , Estudos Retrospectivos
12.
Pediatr Blood Cancer ; 69(9): e29739, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35460336

RESUMO

BACKGROUND/OBJECTIVES: Rhabdomyosarcoma of the perianal/perineal region (PRMS) is rare, with poor survival and limited understanding of the functional consequences of treatment. DESIGN/METHODS: International Society of Pediatric Oncology (SIOP) malignant mesenchymal tumor (MMT) 95, Italian RMS 96, and European paediatric Soft tissue sarcoma Study Group (EpSSG) RMS 2005 studies were interrogated to identify factors that impact survival; in RMS 2005, functional outcomes were analyzed. RESULTS: Fifty patients (nonmetastatic) were identified, median age 6.4 years (range: 0.1-19.6): 29 male, 21 female. Tumors were >5 cm in 33 patients. Histopathological subtype was alveolar in 35. Lymph nodes were involved in 23 patients. In RMS 2005, 16/21 (76%) tested alveolar tumors had positive FOXO1 fusion status. Diagnostic biopsy was performed in 37. Primary resection (13) was complete (R0) in one. Delayed primary excision (16) was complete in three. Radiotherapy (RT) in 34/50 patients included external beam (28), brachytherapy (3), and both (3). Nodal RT was given in 16/23 N1 patients (70%). Median follow-up of alive patients (29) was 84.1 months (range: 3.6-221.1). Relapse or progression occurred in 24 patients (48%), 87% were fatal and most events (63%) were locoregional. Five-year event-free survival (EFS) was 47.8 (95% CI: 32.8-61.3), and 5-year overall survival (OS) was 52.6 (95% CI: 36.7-66.2), with age ≥10 years and tumor size >5 cm impacting 5-year EFS and OS (p < .05). Functional outcome data showed bowel, genito-urinary, and psychological issues; fecal incontinence in four of 21 survivors, and urinary symptoms in two of 21. CONCLUSIONS: About 60% of patients with nonmetastatic PRMS survive; older patients and those with large tumors have the worst outcomes. Biopsy should be the initial procedure, and definitive local therapy individualized. Quality-of-life and functional studies are needed to better understand the consequences of treatment.


Assuntos
Rabdomiossarcoma Embrionário , Rabdomiossarcoma , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Adulto Jovem , Mesenquimoma , Recidiva Local de Neoplasia/radioterapia , Rabdomiossarcoma/patologia
13.
Sensors (Basel) ; 23(1)2022 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-36616783

RESUMO

Ultrasonic guided waves offer a convenient and practical approach to structural health monitoring and non-destructive evaluation. A key property of guided waves is the fully defined relationship between central frequency and propagation characteristics (phase velocity, group velocity and wavenumber)-which is described using dispersion curves. For many guided wave-based strategies, accurate dispersion curve information is invaluable, such as group velocity for localisation. From experimental observations of dispersion curves, a system identification procedure can be used to determine the governing material properties. As well as returning an estimated value, it is useful to determine the distribution of these properties based on measured data. A method of simulating samples from these distributions is to use the iterative Markov-Chain Monte Carlo (MCMC) procedure, which allows for freedom in the shape of the posterior. In this work, a scanning-laser Doppler vibrometer is used to record the propagation of Lamb waves in a unidirectional-glass-fibre composite plate, and dispersion curve data for various propagation angles are extracted. Using these measured dispersion curve data, the MCMC sampling procedure is performed to provide a Bayesian approach to determining the dispersion curve information for an arbitrary plate. The distribution of the material properties at each angle is discussed, including the inferred confidence in the predicted parameters. The percentage errors of the estimated values for the parameters were 10-15 points larger when using the most likely estimates, as opposed to calculating from the posterior distributions, highlighting the advantages of using a probabilistic approach.


Assuntos
Ondas Ultrassônicas , Teorema de Bayes
14.
Behav Res Methods ; 54(4): 1688-1700, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-34591284

RESUMO

Semantic diversity refers to the degree of semantic variability in the contexts in which a particular word is used. We have previously proposed a method for measuring semantic diversity based on latent semantic analysis (LSA). In a recent paper, Cevoli et al. (2020) attempted to replicate our method and obtained different semantic diversity values. They suggested that this discrepancy occurred because they scaled their LSA vectors by their singular values, while we did not. Using their new results, they argued that semantic diversity is not related to ambiguity in word meaning, as we originally proposed. In this reply, we demonstrate that the use of unscaled vectors provides better fits to human semantic judgements than scaled ones. Thus we argue that our original semantic diversity measure should be preferred over the Cevoli et al. version. We replicate Cevoli et al.'s analysis using the original semantic diversity measure and find (a) our original measure is a better predictor of word recognition latencies than the Cevoli et al. equivalent and (b) that, unlike Cevoli et al.'s measure, our semantic diversity is reliably associated with a measure of polysemy based on dictionary definitions. We conclude that the Hoffman et al. semantic diversity measure is better-suited to capturing the contextual variability among words and that words appearing in a more diverse set of contexts have more variable semantic representations. However, we found that homonyms did not have higher semantic diversity values than non-homonyms, suggesting that the measure does not capture this special case of ambiguity.


Assuntos
Julgamento , Semântica , Humanos
15.
Pediatr Blood Cancer ; 68(4): e28938, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33522706

RESUMO

The treatment of paratesticular rhabdomyosarcoma (PT-RMS) has varied over time and by cooperative group. The International Soft Tissue Sarcoma Database Consortium (INSTRuCT) is a collaboration of the Children's Oncology Group (COG) Soft Tissue Sarcoma Committee, European pediatric Soft tissue sarcoma Study Group (EpSSG), and the Cooperative Weichteilsarkom Studiengruppe (CWS). The INSTRuCT surgical committee has been given charge of the development of internationally applicable consensus guidelines for the surgical treatment of rhabdomyosarcoma. This clinical consensus opinion document addresses accepted principles and areas of controversy, such as scrotal violation and retroperitoneal nodal evaluation, providing an evidence-based guideline for the surgical treatment for PT-RMS.


Assuntos
Rabdomiossarcoma/cirurgia , Neoplasias Testiculares/cirurgia , Criança , Gerenciamento Clínico , Europa (Continente) , Humanos , Linfonodos/patologia , Linfonodos/cirurgia , Masculino , Prognóstico , Rabdomiossarcoma/diagnóstico , Rabdomiossarcoma Embrionário/diagnóstico , Rabdomiossarcoma Embrionário/cirurgia , Escroto/patologia , Escroto/cirurgia , Neoplasias Testiculares/diagnóstico
16.
Pediatr Blood Cancer ; 67(9): e28479, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32573979

RESUMO

BACKGROUND: Paratesticular rhabdomyosarcoma (PT RMS) is rare compared to benign scrotal pathology. Inappropriate first surgery (InFS) required supplementary treatment to maintain excellent outcomes. Initial staging of regional lymph nodes is important. The aim of this study was to determine to what extent the quality of locoregional approach impacted on patient morbidity and survival. DESIGN/METHODS: Analysis was performed on all nonmetastatic PT RMS patients enrolled in the European paediatric Soft tissue sarcoma Study Group (EpSSG) RMS 2005 protocol. Aspects assessed were adherence to surgical guidelines and impact of protocol violations, relapse analysis, and survival outcomes. RESULTS: Analysis was performed on 237 patients, with median follow up of 67.1 months. Median age was 9.0 years. InFS occurred in 75 of 237 (32%) patients. InFS required intensified chemotherapy (10) and local therapy. After InFS, 61 required primary reexcision and five delayed surgery. Of 26 recurrences, the risk of relapse was higher in patients ≥10 years (21/26) and was mainly locoregional in 16 of 26 recurrences (± metastatic). Sixteen of 26 died with 14 of 16 patients ≥10 years. Nodal relapse neither occurred when N1 nodes were identified at diagnosis, nor after surgical staging. Five-year overall survival (OS) at age <10 years versus ≥10 years was 98.1 and 86.7%, respectively (P = .0013). Event-free survival (EFS) at age <10 years versus ≥10 years was 95.8 and 79.6%, respectively (P = .0004). OS and EFS did not highlight a significant difference in patients undergoing appropriate versus InFS (P = .8479, P = .2780, respectively). CONCLUSIONS: InFS required intensified therapy to maintain excellent OS and EFS, so better anticipation of malignancy is required. Surgical staging of the retroperitoneal lymph nodes should be performed in patients ≥10 years old.


Assuntos
Fidelidade a Diretrizes , Rabdomiossarcoma , Neoplasias Testiculares , Adolescente , Adulto , Criança , Pré-Escolar , Intervalo Livre de Doença , Seguimentos , Humanos , Lactente , Masculino , Rabdomiossarcoma/mortalidade , Rabdomiossarcoma/terapia , Taxa de Sobrevida , Neoplasias Testiculares/mortalidade , Neoplasias Testiculares/terapia
17.
Pediatr Blood Cancer ; 66(7): e27725, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30920113

RESUMO

OBJECTIVES: To evaluate the impact of local therapies on the outcome of patients with liver-bile duct rhabdomyosarcoma (LBDRMS). METHODS: Data of 30 patients included in the EpSSG-RMS 2005 study were analyzed. RESULTS: The median age at diagnosis was 3 years (11 months-8 years). All patients had non-alveolar histology. Fifteen patients had a tumor > 5 cm and six had enlarged regional lymph nodes on imaging. Eight patients (27%) had primary surgery (1 R0). Six of them received external beam radiotherapy (EBRT). All are in first complete remission (CR1) except one (R1, EBRT+ , local relapse, death). Six patients (20%) received EBRT without surgery: one had local relapse and died. Sixteen patients (53%) underwent delayed surgery, with 12 achieving R0 margins, which were higher than those in the primary surgery group (P = 0.003). Three patients with R0 margins received EBRT; one had a metastatic relapse and died. Nine patients with R0 resection did not receive EBRT, three relapsed locally (two deaths). Four R1 patients received additional EBRT without relapses. Local relapse occurred in two among 19 patients with EBRT and three among 11 without EBRT (P = 0.326). At a median follow-up of 61 months (48-84 months), five patients died; all had a tumor size > 5 cm (P = 0.01). The five-year overall survival was 85% (95% CI, 65-94), and event-free survival was 76% (95% CI, 54-89). CONCLUSION: This analysis did not show any significant difference in outcome between irradiated and nonirradiated patients. Local relapse in LBDRMS is related to initial tumor size and is often fatal.


Assuntos
Neoplasias dos Ductos Biliares , Recidiva Local de Neoplasia , Rabdomiossarcoma , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/radioterapia , Neoplasias dos Ductos Biliares/cirurgia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Metástase Neoplásica , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/cirurgia , Rabdomiossarcoma/diagnóstico por imagem , Rabdomiossarcoma/mortalidade , Rabdomiossarcoma/radioterapia , Rabdomiossarcoma/cirurgia
18.
Cancer ; 124(15): 3201-3209, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29797665

RESUMO

BACKGROUND: Alveolar rhabdomyosarcoma (aRMS) with lymph node involvement (N1 classification) accounts for up to 10% of all cases of RMS. The prognosis is poor, and is comparable to that of distant metastatic disease. In the European Paediatric Soft Tissue Sarcoma Study Group (EpSSG) RMS2005 protocol, patients with a histologic diagnosis of aRMS/N1 received intensified chemotherapy with systematic locoregional treatment. METHODS: Patients with aRMS/N1 were enrolled prospectively after primary surgery/biopsy and fusion status was assessed in tumor samples. All patients received 9 cycles of induction chemotherapy and 6 months of maintenance therapy. Local treatment included radiotherapy to the primary site and lymph nodes with or without secondary surgical resection. RESULTS: A total of 103 patients were enrolled. The clinical characteristics of the patients were predominantly unfavorable: 90% had macroscopic residual disease after initial surgery/biopsy, 63% had locally invasive tumors, 77% had a tumor measuring >5 cm, and 81% had disease at unfavorable sites. Fusion genes involving forkhead box protein O1 (FOXO1) were detected in 56 of 84 patients. Events occurred in 52 patients: 43 developed disease recurrence, 7 had disease that was refractory to treatment, and 2 patients developed second neoplasms. On univariate analysis, unfavorable disease site, tumor invasiveness, Intergroup Rhabdomyosarcoma Study group III, and fusion-positive status correlated with worse prognosis. The 5-year event-free survival rate of patients with fusion-positive tumors was 43% compared with 74% in patients with fusion-negative tumors (P = .01). On multivariate analysis, fusion positivity and tumor invasiveness proved to be unfavorable prognostic markers. CONCLUSIONS: Fusion status and tumor invasiveness appear to have a strong impact on prognosis in patients with aRMS/N1. Fusion status will be used to stratify these patients in the next EpSSG RMS study, and treatment will be intensified in patients with fusion-positive tumors. Cancer 2018. © 2018 American Cancer Society.


Assuntos
Proteína Forkhead Box O1/genética , Recidiva Local de Neoplasia/tratamento farmacológico , Prognóstico , Rabdomiossarcoma Alveolar/tratamento farmacológico , Rabdomiossarcoma Alveolar/epidemiologia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Linfonodos/efeitos dos fármacos , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática , Masculino , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Pediatria , Rabdomiossarcoma Alveolar/genética , Rabdomiossarcoma Alveolar/patologia , Fatores de Risco , Adulto Jovem
19.
AIDS Behav ; 22(8): 2575-2583, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29536283

RESUMO

Timely presentation to care for people newly diagnosed with HIV is critical to optimize health outcomes and reduce onward HIV transmission. Studies describing presentation to care following diagnosis during a hospital admission are lacking. We sought to assess the timeliness of presentation to care and to identify factors associated with delayed presentation. We conducted a population-level study using health administrative databases. Participants were all individuals older than 16 and newly diagnosed with HIV during hospital admission in Ontario, Canada, between April 1, 2007 and March 31, 2015. We used modified Poisson regression models to derive relative risk ratios for the association between sociodemographic and clinical variables and the presentation to out-patient HIV care by 90 days following hospital discharge. Among 372 patients who received a primary HIV diagnosis in hospital, 83.6% presented to care by 90 days. Following multivariable analysis, we did not find associations between patient sociodemographic or clinical characteristics and presentation to care by 90 days. In a secondary analysis of 483 patients diagnosed during hospitalization but for whom HIV was not recorded as the principal reason for admission, 73.1% presented to care by 90 days. Following multivariable adjustment, we found immigrants from countries with generalized HIV epidemics (RR 1.265, 95% CI 1.133-1.413) were more likely to present to care, whereas timely presentation was less likely for people with a mental health diagnosis (RR 0.817, 95% CI 0.742-0.898) and women (RR 0.748, 95% CI 0.559-1.001). Future work should evaluate mechanisms to facilitate presentation to care among these populations.


Assuntos
Assistência ao Convalescente/estatística & dados numéricos , Assistência Ambulatorial/estatística & dados numéricos , Infecções por HIV/diagnóstico , Hospitalização , Adulto , Emigrantes e Imigrantes/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Ontário , Fatores de Tempo , Adulto Jovem
20.
Pediatr Blood Cancer ; 64(9)2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28205365

RESUMO

PURPOSE: To report the results from International Society of Pediatric Oncology (SIOP) Malignant Mesenchymal Tumors studies (MMT 89 and 95) of males with nonmetastatic paratesticular rhabdomyosarcoma. METHODS: From 1989 to 2003, 159 patients were included. Radical inguinal orchidectomy was recommended, but retroperitoneal lymph node (LN) assessment was based on imaging alone. The treatment was stratified by stage (SIOP tumor-node-metastasis staging system) and histology. RESULTS: Median age at presentation was 5.6 years (range 0.3-17.6) and 120 patients were of <10 years (75%). Patients ≥10 years had tumors of >5 cm more frequently compared to patients of <10 years (54% vs. 22%, P = 0.0004). The 5- year overall and progression-free survivals were 94% and 83%, respectively. Seventy-eight percent of relapses occurred in the retroperitoneal LN. Thirty-one percent of stage N0 patients of age ≥10 years developed node relapse, compared with 8% of N0 patients aged <10 years (P = 0.0005). CONCLUSIONS: Older patients with paratesticular rhabdomyosarcoma have a significant risk of LN relapse. These results support a surgical approach to LN staging in this subgroup of patients.


Assuntos
Estadiamento de Neoplasias/métodos , Neoplasias Retroperitoneais/patologia , Rabdomiossarcoma/patologia , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Terapia Combinada , Intervalo Livre de Doença , Humanos , Lactente , Estimativa de Kaplan-Meier , Metástase Linfática/diagnóstico , Masculino , Orquiectomia/métodos , Neoplasias Retroperitoneais/mortalidade , Neoplasias Retroperitoneais/terapia , Rabdomiossarcoma/mortalidade , Rabdomiossarcoma/terapia , Escroto/cirurgia , Adulto Jovem
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