66. Late effects of CNS prophylactic irradiation in childhood due to LLA using Magnetic Resonance Spectro-skopy. (preliminary report)

PurposeThe aim of this study was to evaluate changes in magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) of the brain in survivars with Acute Lymphoblastic Leukemia to assess neurotixicity follow profilactic brain irradiation.MethodsTen from 100 patients with LLA treated in Department of Pediatric Hematology from 1990 to 1995 and irradiated in Centre of Oncology were icluded in MRI and MRS studies. The study group included 6 male and 4 female. All patients had been irradiated for brain using fraction dose of 1,8 Gy up to total dose of 18 Gy and had recived MTX based chemotherapy in doses depending on level of risk. Two of them were included in low risk and eight in intermediate risk.ResultsMRI of brain was abnormal in 5 cases. There were mild white matter changes.The changes were Been in H- MRS metabolite ratios. In one of these cases we observed a impair of verbal functions.ConclusionsThe MRS could be valuable method to access brain tissue metabolism after radiotherapy. That noninvasive method may be recomended for children with LLA to observe neurotoxicity of profilactic irradiation

66. Late effects of CNS prophylactic irradiation in childhood due to LLA using Magnetic Resonance Spectro-skopy. (preliminary report)

PurposeThe aim of this study was to evaluate changes in magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) of the brain in survivars with Acute Lymphoblastic Leukemia to assess neurotixicity follow profilactic brain irradiation.MethodsTen from 100 patients with LLA treated in Department of Pediatric Hematology from 1990 to 1995 and irradiated in Centre of Oncology were icluded in MRI and MRS studies. The study group included 6 male and 4 female. All patients had been irradiated for brain using fraction dose of 1,8 Gy up to total dose of 18 Gy and had recived MTX based chemotherapy in doses depending on level of risk. Two of them were included in low risk and eight in intermediate risk.ResultsMRI of brain was abnormal in 5 cases. There were mild white matter changes.The changes were Been in H- MRS metabolite ratios. In one of these cases we observed a impair of verbal functions.ConclusionsThe MRS could be valuable method to access brain tissue metabolism after radiotherapy. That noninvasive method may be recomended for children with LLA to observe neurotoxicity of profilactic irradiation

Dose escalation for stereotactic arrhythmia radioablation of recurrent ventricular tachyarrhythmia - a phase II clinical trial

BACKGROUND: Stereotactic arrhythmia radioablation (STAR) is delivered with a planning target volume (PTV) prescription dose of 25 Gy, mostly to the surrounding 75-85% isodose line. This means that the average and maximum dose received by the target is less than 35 Gy, which is the minimum threshold required to create a homogenous transmural fibrosis. Similar to catheter ablation, the primary objective of STAR should be transmural fibrosis to prevent heterogenous intracardiac conduction velocities and the occurrence of sustained ventricular arrhythmias (sVA) caused by reentry. We hypothesize that the current dose prescription used in STAR is inadequate for the long-term prevention of sVA and that a significant increase in dose is necessary to induce transmural scar formation. OBJECTIVE: A single arm, multi-center, phase II, dose escalation prospective clinical trial employing the i3 + 3 design is being conducted to examine the safety of a radiation dose-escalation strategy aimed at inducing transmural scar formation. The ultimate objective of this trial is to decrease the likelihood of sVA recurrence in patients at risk. METHODS: Patients with ischemic or non-ischemic cardiomyopathy and recurrent sVA, with an ICD and history of ≥ 1 catheter ablation for sVA will be included. This is a prospective, multicenter, one-arm, dose-escalation trial utilizing the i3 + 3 design, a modified 3 + 3 specifically created to overcome limitations in traditional dose-finding studies. A total of 15 patients will be recruited. The trial aims to escalate the ITV dose from 27.0 Gy to an ITV prescription dose-equivalent level of maximum 35.1 Gy by keeping the PTV prescription dose constant at 25 Gy while increasing the dose to the target (i.e. the VT substrate without PTV margin) by step-wise reduction of the prescribing isodose line (85% down to 65%). The primary outcome of this trial is safety measured by registered radiation associated adverse events (AE) up to 90 days after study intervention including radiation associated serious adverse events graded as at least 4 or 5 according to CTCAE v5, radiation pneumonitis or pericarditis requiring hospitalization and decrease in LVEF ≥ 10% as assessed by echocardiography or cardiac MRI at 90 days after STAR. The sample size was determined assuming an acceptable primary outcome event rate of 20%. Secondary outcomes include sVA burden at 6 months after STAR, time to first sVA recurrence, reduction in appropriate ICD therapies, the need for escalation of antiarrhythmic drugs, non-radiation associated safety and patient reported outcome measures such as SF-36 and EQ5D. DISCUSSION: DEFT-STAR is an innovative prospective phase II trial that aims to evaluate the optimal radiation dose for STAR in patients with therapy-refractory sVA. The trial has obtained IRB approval and focuses on determining the safe and effective radiation dose to be employed in the STAR procedure

Inhibition of Pediatric Glioblastoma Tumor Growth by the Anti-Cancer Agent OKN-007 in Orthotopic Mouse Xenografts

We thank the Peggy and Charles Stephenson Cancer Center at the University of Oklahoma, Oklahoma City, OK, for funding, who received an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20 GM103639 for the use of the Histology and Immunohistochemistry Core for providing immunohistochemistry and photographic services. This work was also supported by Oklahoma State University, Center of Veterinary Health Science (Support Grant AE-1-50060 to P.C.S.), the Musella Foundation (R.A.T.), and the Childhood Brain Tumor Foundation (R.A.T.).Pediatric glioblastomas (pGBM), although rare, are one of the leading causes of cancer-related deaths in children, with tumors essentially refractory to existing treatments. Here, we describe the use of conventional and advanced in vivo magnetic resonance imaging (MRI) techniques to assess a novel orthotopic xenograft pGBM mouse (IC-3752GBM patient-derived culture) model, and to monitor the effects of the anti-cancer agent OKN-007 as an inhibitor of pGBM tumor growth. Immunohistochemistry support data is also presented for cell proliferation and tumor growth signaling. OKN-007 was found to significantly decrease tumor volumes (p<0.05) and increase animal survival (p<0.05) in all OKN-007-treated mice compared to untreated animals. In a responsive cohort of treated animals, OKN-007 was able to significantly decrease tumor volumes (p<0.0001), increase survival (p<0.001), and increase diffusion (p<0.01) and perfusion rates (p<0.05). OKN-007 also significantly reduced lipid tumor metabolism in responsive animals (Lip1.3 and Lip0.9)-to-creatine ratio (p<0.05), as well as significantly decrease tumor cell proliferation (p<0.05) and microvessel density (p<0.05). Furthermore, in relationship to the PDGFRα pathway, OKN-007 was able to significantly decrease SULF2 (p<0.05) and PDGFR-α (platelet-derived growth factor receptor-α) (p<0.05) immunoexpression, and significantly increase decorin expression (p<0.05) in responsive mice. This study indicates that OKN-007 may be an effective anti-cancer agent for some patients with pGBMs by inhibiting cell proliferation and angiogenesis, possibly via the PDGFRα pathway, and could be considered as an additional therapy for pediatric brain tumor patients.Yeshttp://www.plosone.org/static/editorial#pee