Multiparametric MRI evaluation of bone sarcomas in children

Abstract Osteosarcoma and Ewing sarcoma are the most common bone sarcomas in children. Their clinical presentation is very variable depending on the age of the patient and tumor location. MRI is the modality of choice to assess these bone sarcomas and has an important function at diagnosis and also for monitoring recurrence or tumor response. Anatomic sequences include T1- and T2-weighted images and provide morphological assessment that is crucial to localize the tumor and describe anatomical boundaries. Multiparametric MRI provides functional information that helps in the assessment of tumor response to therapy by using different imaging sequences and biomarkers. This review manuscript illustrates the role of MRI in osteosarcoma and Ewing sarcoma in the pediatric population, with emphasis on a functional perspective, highlighting the use of diffusion-weighted imaging and dynamic contrast-enhanced MRI at diagnosis, and during and after treatment

Naxitamab Combined with Granulocyte-Macrophage Colony-Stimulating Factor as Consolidation for High-Risk Neuroblastoma Patients in First Complete Remission under Compassionate Use—Updated Outcome Report

Naxitamab is an anti-GD2 antibody approved for the treatment of relapsed/refractory HR-NB. We report the survival, safety, and relapse pattern of a unique set of HR-NB patients consolidated with naxitamab after having achieved first CR. Eighty-two patients were treated with 5 cycles of GM-CSF for 5 days at 250 μg/m2/day (−4 to 0), followed by GM-CSF for 5 days at 500 μg/m2/day (1–5) and naxitamab at 3 mg/kg/day (1, 3, 5), on an outpatient basis. All patients but one were older than 18 months at diagnosis and had stage M; 21 (25.6%) pts had MYCN-amplified (A) NB; and 12 (14.6%) detectable MRD in the BM. Eleven (13.4%) pts had received high-dose chemotherapy and ASCT and 26 (31.7%) radiotherapy before immunotherapy. With a median follow-up of 37.4 months, 31 (37.8%) pts have relapsed. The pattern of relapse was predominantly (77.4%) an isolated organ. Five-year EFS and OS were 57.9% (71.4% for MYCN A) 95% CI = (47.2, 70.9%); and 78.6% (81% for MYCN A) 95% CI = (68.7%, 89.8%), respectively. EFS showed significant differences for patients having received ASCT (p = 0.037) and pre-immunotherapy MRD (p = 0.0011). Cox models showed only MRD as a predictor of EFS. In conclusion, consolidation with naxitamab resulted in reassuring survival rates for HR-NB patients after end-induction CR

Clinical and Pathological Evidence of Anti-GD2 Immunotherapy Induced Differentiation in Relapsed/Refractory High-Risk Neuroblastoma

Background: Neuroblastic tumors (NBTs) originate from a block in the process of differentiation. Histologically, NBTs are classified in neuroblastoma (NB), ganglioneuroblastoma (GNB), and ganglioneuroma (GN). Current therapy for high-risk (HR) NB includes chemotherapy, surgery, radiotherapy, and anti-GD2 monoclonal antibodies (mAbs). Anti-GD2 mAbs induce immunological cytoxicity but also direct cell death. Methods: We report on patients treated with naxitamab for chemorefractory NB showing lesions with long periods of stable disease. Target lesions with persisting 123I-Metaiodobenzylguanidine (MIBG) uptake after 4 cycles of immunotherapy were further evaluated by functional Magnetic Resonance Imaging (MRI) and/or Fluorodeoxyglucose (FDG)-positron emission tomography (PET). MIBG avid lesions that became non-restrictive on MRI (apparent diffusion coefficient (ADC) > 1) and/or FDG-PET negative (SUV < 2) were biopsied. Results: Twenty-seven relapse/refractory (R/R) HR-NB patients were enrolled on protocol Ymabs 201. Two (7.5%) of the 27 showed persistent bone lesions on MIBG, ADC high, and/or FDG-PET negative. Forty-four R/R HR-NB patients received chemo-immunotherapy. Twelve (27%) of the 44 developed persistent MIBG+ but FDG-PET- and/or high ADC lesions. Twelve (86%) of the 14 cases identified were successfully biopsied producing 16 evaluable samples. Histology showed ganglioneuroma maturing subtype in 6 (37.5%); ganglioneuroma mature subtype with no neuroblastic component in 4 (25%); differentiating NB with no Schwannian stroma in 5 (31%); and undifferentiated NB without Schwannian stroma in one (6%). Overall, 10 (62.5%) of the 16 specimens were histopathologically fully mature NBTs. Conclusions: Our results disclose an undescribed mechanism of action for naxitamab and highlight the limitations of conventional imaging in the evaluation of anti-GD2 immunotherapy clinical efficacy for HR-NB

Eficácia do LED vermelho no aumento da densidade capilar na alopécia androgenética - um estudo autocontrolado

A alopécia androgenética é o tipo de perda capilar mais comum com prejuízo da imagem corporal e qualidade de vida. A fototerapia segura e barata, estimula a proliferação celular e o crescimento capilar, mas não se sabe quais os parâmetros ótimos para este efeito. Avaliar a eficácia do LED de655 nm e 5 mW, durante 7 semanas, no tratamento da alopécia androgenética e compara o seu efeito relativamente ao sexo, tabagismo e presença de caspa. Estudo autocontrolado com 5 homens e 4 mulheres, saudáveis, com alopécia androgenética, com idades entre os 19 e os 54 anos, aos quais foi aplicado LED vermelho num lado do couro cabeludo, aleatório, três vezes por semana em dias não concutíveis, durante 7 semanas. Foram avaliados no momento inicial e após 7 semanas a densidade capilar total, a densidade de cabelos anágenos, terminais e velos e a densidade das diferentes unidades foliculares, através da recolha com o Dino-Lite Edge Digital Microscope AM4115ZT e DinoCapture Software 2.0 com o Software TrichoSciencepro® v.17. Analisaram-se os resultados através dos testes Wilcoxone Mann-Whitney com nível de significância de 0,05. Não se verificaram diferenças significativas nas densidades capilares após a aplicação de LED vermelho. Observou-se um aumento da densidade de cabelos terminais no lado intervencionado, não significativo; um aumento da densidade de cabelos terminais significativo nos indivíduos sem caspa comparativamente aos com caspa; não foram verificadas diferenças significativas no lado intervencionado entre sexos nem entre fumadores e não fumadores, estes últimos com um aumento das densidades de cabelos anágenos e terminais contrariamente aos fumadores. Na avaliação global do couro cabeludo não se verificaram diferenças significativas, apesar da observação de uma melhoria em mais casos no lado intervencionado, coerente com os resultados da avaliação subjetiva dos participantes. A aplicação de 1J/cm2 de LED de 655 nm e 5 mW três vezes por semana durante 7 semanas pode promover o aumento da densidade capilar apenas em alguns indivíduos com AAG, que pode ser prejudicado por fatores como caspa e tabagismo, mas não pelo sexo. São necessários estudos com amostra e duração maiores, com grupo controlo/placebo, comparando os diferentes parâmetros de aplicação da fototerapia de baixa potência