BACKGROUND: MRI-guided laser interstitial thermal therapy (LITT) is a minimally invasive, cytoreductive surgery useful for managing unresectable brain tumors. LITT disrupts the blood brain barrier (BBB) and facilitates chemotherapy delivery. We report the toxicity and outcome for pediatric brain tumors treated on a pilot trial of LITT and chemotherapy. The primary objectives were to quantify peritumoral BBB disruption following LITT and evaluate toxicity and efficacy. METHODS: The trial had two arms, A: patients with newly diagnosed gliomas underwent LITT followed by standard of care management, and B: patients with relapsed malignant brain tumors received 6 weeks of weekly doxorubicin post-LITT followed by maintenance etoposide. RESULTS: Between 2015 – 2018, six patients were enrolled: five on arm A (four with low-grade gliomas, one with high-grade glioma), one on Arm B with progressive anaplastic astrocytoma. All patients tolerated the procedure well; four experienced a transient hemiparesis post-LITT. The Arm B patient progressed and died of disease 2 months and 22 months post-LITT, respectively. The HGG patient received standard therapy and remains without disease progression 44 months post-LITT. One patient with LGG required additional treatment for disease progression 14 months post-LITT. Two patients with LGGs did not require additional therapy, now 51 and 41 months post-LITT. One patient was alive 24 weeks post-LITT and subsequently lost to follow-up. Peritumoral BBB disruption was analyzed in two ways: serum abundance of brain-derived proteins and MRI Dynamic contrast enhancement (DCE). Neuron-specific enolase were measurable in the serum of all patients, using ELISA up to 84 days post-LITT. DCE 2 weeks post-LITT demonstrated increased enhancement and FLAIR signal, consistent with BBB disruption and vasogenic edema. This effect was evident up to 4 months post-procedure. CONCLUSION: LITT is safe in children with brain tumors and can be combined with chemotherapy. DCE and serum brain-derived proteins can measure BBB disruption.
INTRODUCTION: Congenital intracranial teratomas (CITs) are rare tumors occurring in the first 60 days of life, often associated with dismal prognosis, posing challenges in both oncologic and surgical management. METHODS: We report a patient with a congenital mature teratoma diagnosed prenatally, who underwent successful surgical resection following neoadjuvant chemotherapy. We also performed an updated literature review on CIT outcomes. RESULTS: A newborn female, diagnosed prenatally with a complex midline intracranial echogenic mass, underwent postnatal brain MRI which demonstrated a supratentorial large complex enhancing mass with solid and cystic components, with associated obstructed hydrocephalus. Serum alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin were normal for age. Tumor biopsy revealed mature teratoma. AFP obtained from cyst fluid during fenestration was significantly elevated at 8 weeks of life. Due to concerns for possible malignant transformation and in an attempt to alter tumor vascularity facilitating surgical resection, the patient received two cycles of neoadjuvant carboplatin and etoposide, followed by tumor resection without significant intraoperative bleeding. There was no evidence of immature components on final pathology. The patient remains without tumor recurrence, now 9 months, since surgical resection. Review of literature yielded 76 cases of CITs: eight patients with mature teratoma, of which six remained alive following tumor resection. Five patients with immature teratoma received chemotherapy prior to resection; three remained alive post-resection (follow-up range 3-20 years). DISCUSSION: CITs are typically associated with poor prognosis, with reported one-year survival of 7.2-12%. Surgical excision is the mainstay of treatment, often limited by intraoperative hemorrhage. Neoadjuvant chemotherapy has been employed as a successful strategy to reduce tumor volume and vascularity in a variety of pediatric brain tumors; more specifically, carboplatin and etoposide are utilized as neoadjuvant chemotherapy for non-germinomatous germ cell tumors to facilitate excision in older children. Their role in CITs requires further evaluation.
BACKGROUND: The management of childhood central nervous system (CNS) tumors is complex and often faces numerous challenges in low- and middle- income countries (LMICs), including delayed diagnosis and limited treatment resources. Twinning initiatives between LMICs with high- income countries are feasible and proven to be highly effective at exchanging skills and expertise to improve diagnosis, treatment and care for children with brain tumors. METHODS: A monthly multidisciplinary international pediatric neuro-oncology tumor board via zoom videoconferencing was established in January 2021. This effort is a collaboration between Washington University School of Medicine, in St. Louis, Missouri, USA and nine international sites. Given the significant contributions of this international effort, it has since grown to include 20 institutions and cancer centers from 12 countries in the Middle East, Europe, Australia and South America. RESULTS: As of January 2022, we have held 11 tumor boards, 35 cases were reviewed, and have had 320 experts attend from several specialties – neuro-oncology, neurology, neurosurgery, neuroradiology and neuropathology. A multidisciplinary team of physicians reviewed each case and recommendations were given accordingly. We also started a quarterly neurofibromatosis (NF) meeting focused to leverage the expertise of dedicated specialists in the NF center. Two NF-focused meetings took place since establishing the program, and total of five cases were discussed. CONCLUSION: Virtual videoconferencing promotes a multi-disciplinary approach for the management of pediatric CNS tumors, and it allows access for medical expertise. We anticipate the current initiative will also provide a platform for future international research collaborations and deliver the optimal medical care for neuro-oncology patients globally. Multiple potential collaborative projects are currently underway.
INTRODUCTION: Medulloblastoma is the most common malignant brain tumor in children, with 5-year overall survival (OS) ranging from 60%-95% depending on subgroup and risk status. The POG 8631/CCG 923 trial (accrual 1986-1990) found a 63% 5 year OS for patients with local disease after gross total resection treated with radiation at a dose of 23.4 Gy craniospinal radiation and posterior fossa boost to 54 Gy, vs. 80.5% 5-year OS for patients treated as per full ACNS0331 therapy including maintenance chemotherapy. Herein, we describe a long-term survival with standard-risk medulloblastoma who only received surgical resection and radiation therapy. CASE: A 17-year-old male presented with acute onset of hypertension, bradycardia, headache, and blurry vision and was found to have a heterogeneously enhancing posterior fossa mass with mass effect on the fourth ventricle and hydrocephalus on brain MRI. He underwent gross total resection of the tumor and histopathology revealed medulloblastoma with classic and large cell features. Fluorescence in situ hybridization (FISH) was negative for MYC, MYCN amplification, or HER2 gain. Cerebrospinal fluid cytology was negative for neoplastic cells, and spinal MRI did not reveal any drop metastases. The patient initiated therapy per ACNS0331 with craniospinal irradiation posterior fossa boost. He also received weekly vincristine. After completion of radiation therapy, the family declined further chemotherapy despite medical advice. He had no evidence of relapse most recently at 51 months from completion of therapy. Next generation sequencing and methylation testing are currently pending. CONCLUSION: Current efforts aim at optimizing therapy based on molecular subgrouping, to minimize long-term adverse events associated with current therapies. We report a unique case of an adolescent male with an standard-risk medulloblastoma, who achieved remission with only radiotherapy. Further molecular tumor analysis may elucidate the response of the tumor.
INTRODUCTION: Ganglioglioma is a low grade neoplasm consisting of dysplastic neuronal and neoplastic glial cells and accounts for 5% of pediatric CNS tumors. Management often includes CNS diversion. There have been case reports in which platinum containing chemotherapy has been thought to contribute to CSF malabsorption leading to ascites. CASE: A 13 month old male developed progressive macrocephaly, developmental delay, chronic emesis, and intermittent bilateral cranial nerve VI palsy over the 5 months prior to presentation. MRI brain/spine was significant for an enhancing nodule in the left posterior lateral medulla, nodular thickening and enhancement along the brainstem down to the conus medullaris and in the tentorium, with associated hydrocephalus. Biopsy of the medullary nodule and of the enhancement were consistent with ganglioglioma with BRAF-KIAA1549 fusion, equivocal MYCN amplification, and no BRAF V600E mutation. A ventriculo-peritoneal shunt was placed at the time of biopsy. Therapy was initiated with vincristine (1.5 mg/m2) and carboplatin (175 mg/m2.) Following the 12 week induction phase of therapy, he developed increasing diarrhea, emesis, and abdominal ascites. Peritoneal fluid analysis had no malignant cells and low protein compared to CSF. Ascites was responsive to drainage but would rapidly re-accumulate. Ultimately the patient’s chemotherapy was discontinued after 2 maintenance cycles due to continued symptoms. Acetazolamide was trialed but discontinued due to side effects, so its efficacy could not be determined. He underwent shunt externalization followed by venticulo-atrial (VA) shunt re-internalization. He has not had ascites since that time, at 4 months from surgery. His CNS disease burden has been stable at 6 months off therapy. DISCUSSION: Ascites was most likely due to CSF malabsorption in the abdomen with a possible contribution from platinum containing chemotherapy and less likely secondary to malignant peritoneal cells. Resolution since VA shunt internalization makes alternate explanations less likely.
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