Role of advanced MR techniques in predicting response to chemoradiotherapy in glioblastomas

Background and purpose For patients with glioblastomas the standard therapy is represented by maximal safe tumor resection followed by concurrent chemoradiotherapy with temozolomide (TMZ) and adjuvant TMZ. Determination of the response to therapy is entirely dependent on the interpretation of magnetic resonance (MR) imaging findings and clinical manifestations. The purpose of this study was to assess the utility of MR advanced techiques, as diffusion (DWI) and perfusion (PWI) imaging in predicting response or progression of gliomas to chemoradiotherapy. Materials and methods We retrospectively selected 32 patients with high grade glioma treated by surgical resection followed by radiation therapy and temozolomide who underwent to conventional MR imaging and advanced MR techniques. The patients were divided into two groups, progression and response, on the basis of RANO criteria. ROI analysis was performed on pre and postcontrastographic T1-weighted images and on the Apparent Diffusion Coefficient (ADC) and PWI maps coregistrated, selecting the section with the maximum diameter of the enhancing lesion. In that section we calculated Contrast Enhancement, permeability (PSR), minimum value of ADC and maximum value of relative Cerebral Blood Volume (rCBV) before surgery (T0), after surgery before RT (T1) and after RT (T2). In conventional MRI we calculated the incremental ratio of the size of the pre and post operative tumor. Unpaired t-test was used to test difference between groups for above mentioned variable for each time step. Significative data were utilized in the univariate logistic regressions in order to determine odds ratios for assessing risk factors. A multivariate logistic regression was performed on univariate significative variables. Results At unpaired t-test ADC, PSR and rCBV at T1 presented significant differences between the two groups. For the group progression the univariate logistic regressions with these variables, adjusted for gender and age , showed statistical significance for ADC and rCBV (predictors of progression) while in the subsequent multivariate logistic regression only ADC showed statistical significance. For the group response the univariate logistic regressions with these variables, adjusted for gender and age , showed statistical significance for ADC, rCBV and PSR (predictors of response) while in the subsequent multivariate logistic regression only PSR showed statistical significance. Conclusions MR advanced techniques, in particular diffusion with ADC and perfusion with PSR, have proved a valuable aid in predicting response or progression of glioma to chemoradiotherapy

The effectiveness of bevacizumab in radionecrosis after radiosurgery of a single brain metastasis

Radionecrosis (RN) of brain tissue is a serious late complication of brain irradiation and historically has been treated with corticosteroid therapy and alternatively surgical decompression. Recently, bevacizumab has been suggested for treatment of cerebral radiation necrosis. We present a case of a 73- years-old women affected by a primary nonsmall cell lung cancer with a single brain metastasis treated with radiosurgery. Two years after radiosurgery the patient referred neurological symptoms and a brain magnetic resonance confirmed the presence of RN. The patient refused surgical decompression so underwent at the treatment with bevacizumab 7.5 mg/kg/2 weeks for a total of 4 cycles. After two months of treatment the patient reported strumental and clinical improvement. Ten months after bevacizumab discontinuation the patient experienced a recurrence of RN with evident clinical manifestation and confirmed by radiological imaging. A new treatment with bevacizumab was not performed due to the systemic progression disease and the worsening of clinical status. Despite limited to only one clinical case, our study suggests the efficacy of bevacizumab to treat RN. Future studies are needed to confirm its mechanism and to properly define the optimal scheduling, dosage and duration of therapy

Role of perfusion CT in the evaluation of metastatic nodal tumor response after radiochemotherapy in head and neck cancer: preliminary findings

OBJECTIVE: To assess changes of CT perfusion parameters (ΔPCTp) of cervical lymph node metastases from head and neck cancer (HNC) before and after radiochemotherapy (RT-CT) and their association with nodal tumor persistence. PATIENTS AND METHODS: Eligibility criteria included HNC (Stage III-IV) candidates for RT-CT. Patients underwent perfusion CT (PCT) at baseline 3 weeks and 3 months after RT-CT. Blood volume (BV), blood flow (BF), mean transit time (MTT) and permeability surface (PS) were calculated. PET/CT examination was also performed at baseline and 3 months after treatment for metabolic assessment. RESULTS: Between July 2012 and May 2016, 27 patients were evaluated. Overall, only 3 patients (11%) experienced tumor persistence in the largest metastatic lymph node. A significant reduction of all PCTp values (p<0.0001), except MTT (from 6.3 to 5.7 s; p=0.089), was observed at 3 weeks post-RT-CT compared to baseline. All PCTp values including MTT were significantly lower at 3-month follow-up compared to baseline (p<0.05). Moreover, a statistical significant association was observed between nodal tumor persistence and high BF values (p=0.045) at 3 months after treatment that did not occur for the other parameters. CONCLUSIONS: Our preliminary findings show that all PCTp except MTT are significantly reduced after RT-CT. High BF values at 3 months post-RTCT are predictive of nodal tumor persistence

Functional Analysis and Molecular Dynamics Simulation of LOX-1 K167N Polymorphism Reveal Alteration of Receptor Activity

The human lectin-like oxidized low density lipoprotein receptor 1 LOX-1, encoded by the ORL1 gene, is the major scavenger receptor for oxidized low density lipoprotein in endothelial cells. Here we report on the functional effects of a coding SNP, c.501G>C, which produces a single amino acid change (K>N at codon 167). Our study was aimed at elucidating whether the c.501G>C polymorphism changes the binding affinity of LOX-1 receptor altering its function. The presence of p.K167N mutation reduces ox-LDL binding and uptake. Ox-LDL activated extracellular signal-regulated kinases 1 and 2 (ERK 1/2) is inhibited. Furthermore, ox-LDL induced biosynthesis of LOX-1 receptors is dependent on the p.K167N variation. In human macrophages, derived from c.501G>C heterozygous individuals, the ox-LDL induced LOX-1 46 kDa band is markedly lower than in induced macrophages derived from c.501G>C controls. Investigation of p.K167N mutation through molecular dynamics simulation and electrostatic analysis suggests that the ox-LDL binding may be attributed to the coupling between the electrostatic potential distribution and the asymmetric flexibility of the basic spine residues. The N/N-LOX-1 mutant has either interrupted electrostatic potential and asymmetric fluctuations of the basic spine arginines

tecniche di risonanza magnetica non convenzionali nel grading dei gliomi cerebrali

Introduzione La valutazione istopatologica mediante biopsia stereotassica e l’imaging convenzionale presentano importanti limiti nella determinazione del grading dei gliomi cerebrali. Le tecniche di Risonanza Magnetica non convenzionali quali perfusione, diffusione e spettroscopia, si sono rivelate validi strumenti di aiuto nel discriminare i gliomi a basso grado da quelli ad alto grado. Scopo Abbiamo cercato di stabilire se le tecniche di imaging non convenzionale siano effettivamente in grado di discriminare in maniera efficace i gliomi di basso grado da quelli ad alto grado. Metodi Sono stati selezionati retrospettivamente 27 pazienti con diagnosi istologica di neoplasia gliale, che fossero stati sottoposti a esame RM convenzionale con e senza mdc ev, esame di DWI, esame di PWI e di MRS. L’rCBV è stato misurato a livello delle regioni di massima perfusione; i valori di ADC sono stati ottenuti dalla regione tumorale di massima diffusività e i rapporti tra i metaboliti colina/creatina, colina/N-acetilaspartato e N-acetilaspartato/creatina sono stati misurati con un TE di 135 ms. Sono stati calcolati la sensibilità, la specificità e l’accuratezza diagnostica delle metodiche RM convenzionali e non convenzionali nel distinguere i gliomi in tumori a basso e ad alto grado dimostrati istologicamente. Risultati Utilizzando il cut-off di 1,5, l’rCBV ratio ha mostrato una sensibilità del 67%, una specificità del 100% e una accuratezza diagnostica del 95,8%. Con il cut-off di 101,5, l’ADC ha mostrato una sensibilità, una specificità e un’accuratezza rispettivamente del 66%, del 58% e del 60%. Con il cut-off di 1,48, l’ADC ratio ha presentato una sensibilità, una specificità e un’accuratezza rispettivamente del 66%, dell’84% e dell’80%. Con il cut-off di 1,6, il rapporto Cho/Cr ha mostrato sensibilità, specificità e accuratezza diagnostica dell’80% mentre il rapporto Cho/NAA, con il cut-off di 1,56 ha presentato sensibilità dell’80%, specificità del 100% e accuratezza del 93%. Conclusioni Le tecniche di RM non convenzionali PWI e MRS si sono dimostrate avere un’elevata accuratezza diagnostica nel grading dei gliomi cerebrali e devono quindi essere integrate nei protocolli di studio RM pre-operatori dei pazienti con glioma cerebrale. Inoltre l’utilizzo della MRS e soprattutto della PWI sono fondamentali per la guida alla biopsia stereotassica al fine di evitare sottostime nel grading della neoplasia

Susceptibility-weighted imaging in parenchymal neurosyphilis: Identification of a new MRI finding

BACKGROUND: General paresis (GP) is a late form of parenchymal neurosyphilis causing dementia and neuropsychiatric disorders. The diagnosis is often difficult since the clinical signs are protean. So far, neuroimaging has played a minor role as radiological findings are not specific. METHODS: We studied three immunocompetent patients, admitted to hospital for cognitive impairment. The diagnosis of neurosyphilis was formulated on the basis of serological texts and cerebrospinal fluid analysis. The patients underwent a 3 T MR examination including susceptibility-weighted imaging (SWI) sequence before and after the initiation of penicillin therapy. RESULTS: In all patients, SWI revealed cortical hypointensity, mostly distributed in frontal and temporal lobes. In drug-naive patients, the hypointensity extended over the whole cortical thickness, from the cortical/subcortical junction to the pial surface. After starting the penicillin therapy, the cortical hypointensity partially reversed, involving only the deep cortical layers. CONCLUSIONS: The MRI pattern at SWI observed in patients with GP was not reported in other infectious or inflammatory disease of the central nervous system, thus we suggest it could be a peculiar radiological finding of the disease. On the basis of previous pathological data, we hypothesise that cortical SWI hypointensity could be expression of iron deposits within activated microglia

The effectiveness of bevacizumab in radionecrosis after radiosurgery of a single brain metastasis

Radionecrosis (RN) of brain tissue is a serious late complication of brain irradiation and historically has been treated with corticosteroid therapy and alternatively surgical decompression. Recently, bevacizumab has been suggested for treatment of cerebral radiation necrosis. We present a case of a 73-years-old women affected by a primary non-small cell lung cancer with a single brain metastasis treated with radiosurgery. Two years after radiosurgery the patient referred neurological symptoms and a brain magnetic resonance confirmed the presence of RN. The patient refused surgical decompression so underwent at the treatment with bevacizumab 7.5 mg/kg/2 weeks for a total of 4 cycles. After two months of treatment the patient reported strumental and clinical improvement. Ten months after bevacizumab discontinuation the patient experienced a recurrence of RN with evident clinical manifestation and confirmed by radiological imaging. A new treatment with bevacizumab was not performed due to the systemic progression disease and the worsening of clinical status. Despite limited to only one clinical case, our study suggests the efficacy of bevacizumab to treat RN. Future studies are needed to confirm its mechanism and to properly define the optimal scheduling, dosage and duration of therapy

Itinerari. Temi e palinsesti

Nell’ambito di una collaborazione scientifica tra il Dottorato Paesaggio e Ambiente della Sapienza e la Tenuta di Castelporziano, avviata in seguito all’apertura al pubblico inaugurata nel 2016, si sono tenuti tra il2019 e il 2020 alcuni seminari di studio e un workshop di progettazione per la valorizzazione dell’area protetta. L’attivazione di una accessibilità non esclusiva alla residenza presidenziale e alle terre che la circondano ha reso necessario avviare un ragionamento sul ruolo di questo “giaci-mento” culturale e agro-forestale alla scala metropolitana di Roma, affrontando tematiche che comprendono anche, ma non solo, esigenze legate alla fruizione dell’area. Il risultato sono quattro letture e altrettante prefigurazioni in grado di proporsi come modalità di lavoro e modo di pensare duttile, pragmatiche e creative. Tra queste il tema del capitolo in oggetto, ovvero "Itinerari. Temi e palinsesti" intende operare una riorganizzazione del sistema di visita della Tenuta. Consapevoli che il paesaggio non è più solo da guardare ma in qualche modo da “vivere”; le ipotesi sviluppate puntano a favorire esperienze immersive nel mosaico paesaggistico della Tenuta