Cancer of the External Auditory Canal with Extensive Osteoradionecrosis of the Skull Base after Re-Irradiation with Particle Beams: A Case Report

Re-irradiation with X-rays and particle beams can be used to treat localized recurrence of unresectable head and neck cancer after initial irradiation therapy. However, re-irradiation therapy increases the risk of severe and late sequelae by 4-to 8-fold. It can also result in fatal outcomes, such as rupture of the carotid artery and cerebral necrosis or abscess. A 41-year-old woman was diagnosed with squamous cell carcinoma of the external auditory canal. The patient was initially treated with X-ray irradiation. However, the patient underwent re-irradiation with heavy particle beams and neutron rays for a recurrent tumor. The patient developed necrosis of the skull base involving the facial skin and temporal bone 2 months after the last session of re-irradiation therapy. The tissue in the parapharyngeal and masticatory regions also became completely necrotic, resulting in extensive exposure of the brain parenchyma. Although the patient underwent conservative and surgical treatment, necrosis of the tissue progressed, and a large part of the brain was exposed. Approximately 2.5 years later, although the brain is still exposed, the patient is alive without disease. Although the tumor had subsided and long-term survival was achieved, our patient developed serious osteoradionecrosis of the skull base with extensive brain exposure. For patients who are not candidates for surgery, re-irradiation alone is an option, albeit with poor prospects. This approach should be discussed with the patient while balancing the potential survival gain against the burden of treatment and the risk of complications.

Neuroprotective Effect of L-carnitine. Focus on Changing Mitochondrial Function

Introduction: In this study, the neuroprotective effect of L-carnitine administered per os in a dose of 25 mg/kg – 800 mg/kg was evaluated. The effects of L-carnitine on changes in mitochondrial function were also studied. Materials and Methods: The neuroprotective effect and mitochondrial function were evaluated in a model of permanent focal ischemia in Wistar-line rats. L-carnitine was administered to rats orally for 72 hours from the moment of modeling ischemia. On the 4th day after the ischemia simulation, the change in the respiratory function of the mitochondria, the opening time of the mitochondrial permeability transition pore, the mitochondrial membrane potential, the concentration of intracellular calcium and the size of the cerebral necrosis zone were determined in rats’ brain supernatant. Results: As a result, it was found that the administration of L-carnitine contributed to the restoration of mitochondrial function and a decrease in the size of the brain necrosis zone. At the same time, the administration of L-carnitine in low doses (25 mg/kg – 100 mg/kg) did not have a significant effect on the change in the concentration of intracellular calcium. It should be noted that an increase in the dose of L-carnitine from 200 mg/kg to 800 mg/kg was not accompanied by a significant increase in the therapeutic effect. Discussion: L-carnitine is one of the key biomolecules that directly affect metabolic processes. It is known that L-carnitine acts as a ”shuttle” for long-chain fatty acids and thus can affect the alteration of mitochondrial function. However, the detailed nature of the mitochondriotropic action of L-carnitine has not been yet established. This was the focus of this study, which showed that the mitochondrion-oriented effect of L-carnitine is dose-dependent and expressed in the form of restoring the respiratory function of mitochondria, restoring the mitochondrial potential and increasing the latent opening time of the mitochondrial permeability transition pore, reducing the level of intracellular calcium. Conclusion: The study allowed us to expand our understanding of the L-carnitine neuroprotective effect and the effect of this compound on changes in mitochondrial function. Graphical abstract

NCMP-07. TREATMENT-INDUCED CEREBRAL NECROSIS IN GLIOMAS: THE OHIO STATE UNIVERSITY COMPREHENSIVE CANCER CENTER (OSUCCC) EXPERIENCE

INTRODUCTION Treatment-induced cerebral necrosis (TN) is a challenging complication encountered in neuro-oncology. Diagnosis and treatment of TN remains poorly defined. METHODS In this single institution, retrospective study, consecutive patients with gliomas and TN between 01/01/2012 and 04/20/2020 at the OSUCCC were identified. Details of the tumor treatment, molecular markers, radiological and pathological findings of TN, as well as treatment, recurrence rate and management upon recurrence were collected. RESULTS Of the 53 patients analyzed, 37 had glioblastoma, 7 had anaplastic oligodendroglioma and 9 had grade II or III astrocytoma. MGMT promoter hypermethylation was present in 31/50 (59%) and IDH mutation in 17/53 (32%). Diagnosis of TN was based on histology in 43/53 (81%) or clinical/radiographic features in 10/53 (19%). Worsening of focal weakness (36%), seizures (9%) or being (30%) were common presentations at TN diagnosis. Patient with right compared to left hemisphere involvement were more symptomatic at TN diagnosis. (p=0.049). Bevacizumab (BEV) (51%), resection (28%), steroids only (9%) or Laser Interstitial Thermal Therapy (6%) were used to treat TN. Steroids were weaned off in 20/27 (74%) after receiving BEV. Among all treatments, BEV was significantly associated with a better outcome (resolution or partial improvement of enhancement in 84.6%) (p=0.0006, Bonferroni corrected p< 0.005). TN Recurrence occurred in 36%, 70% and 100% of the patients treated with BEV, resection and LITT respectively. The median duration to TN recurrence was 10 weeks (range: 3–70 weeks). Initial treatment used for TN, MGMT methylation and IDH mutation status did not predict TN recurrence. (p=0.074; p=0.819; p=0.607 respectively). CONCLUSIONS BEV appears to be a superior treatment to control TN overall. Recurrence of TN in patients previously treated with BEV was 36%. There was no difference in the risk of developing recurrent TN based on MGMT or IDH status.

Impact of Mouse Strain and Sex when Modeling Radiation Necrosis

Background: Murine models are among the most common type of preclinical animal models used to study the human condition, but a wide selection of different mice is currently in use with these differences potentially compromising study results and impairing the ability to reconcile interstudy results. Our goal was to determine how the train and sex of the mice selection would affect the development of radiation necrosis in our murine model of radiation-induced cerebral necrosis. Methods: We generated this model by using a preclinical irradiator to irradiate a sub-hemispheric portion of the brain of mice with single-fraction doses of 80 Gy. Eight possible combinations of mice made up of two different with two substrains each(BALB/cN, BALB/cJ, C57BL/6N, and C57BL/6J) and both sexes were irradiated in this study. Radiation necrosis development was tracked up to eight weeks with a 7T Bruker MRI utilizing T2-weighted and post-contrast T1-weighted imaging. MRI results were compared to and validated with the use of histology which utilized a scale from 0-3 in ascending order of damage. Results: Both time post-irradiation and strain (BALB/c vs C57BL/6) were significant factors affecting radiation necrosis development. Sex was in general not a statistically significant parameter in terms of radiation necrosis development. Conclusion: Mouse strain thus need to be considered when evaluating the results of necrosis models. However, sex does not appear to be a variable needing major consideration.

Impact of Mouse Strain and Sex when Modeling Radiation Necrosis

Background: Murine models are among the most common type of preclinical animal models used to study the human condition, but a wide selection of different mice is currently in use with these differences potentially compromising study results and impairing the ability to reconcile interstudy results. Our goal was to determine how the train and sex of the mice selection would affect the development of radiation necrosis in our murine model of radiation-induced cerebral necrosis.Methods: We generated this model by using a preclinical irradiator to irradiate a sub-hemispheric portion of the brain of mice with single-fraction doses of 80 Gy. Eight possible combinations of mice made up of two different with two substrains each(BALB/cN, BALB/cJ, C57BL/6N, and C57BL/6J) and both sexes were irradiated in this study. Radiation necrosis development was tracked up to eight weeks with a 7T Bruker MRI utilizing T2-weighted and post-contrast T1-weighted imaging. MRI results were compared to and validated with the use of histology which utilized a scale from 0-3 in ascending order of damage.Results: Both time post-irradiation and strain (BALB/c vs C57BL/6) were significant factors affecting radiation necrosis development. Sex was in general not a statistically significant parameter in terms of radiation necrosis development.Conclusion: Mouse strain thus need to be considered when evaluating the results of necrosis models. However, sex does not appear to be a variable needing major consideration.