Surgical and molecular considerations in the treatment of pediatric thalamopeduncular tumors

Abstract

<jats:sec><jats:title>OBJECTIVE</jats:title><jats:p>Thalamopeduncular tumors are a group of pediatric low-grade gliomas that arise at the interface of the thalamus and brainstem peduncle. They typically occur within the first 2 decades of life, presenting with progressive spastic hemiparesis. Treatment strategies, including surgical intervention, have varied significantly. The authors present their experience in the treatment of 13 children, ages 2–15 years, with non-neurofibromatosis–related pilocytic astrocytomas located in the thalamopeduncular region.</jats:p></jats:sec><jats:sec><jats:title>METHODS</jats:title><jats:p>Between 2003 and 2016, 13 children presenting with progressive spastic hemiparesis due to a pilocytic astrocytoma at the interface of the thalamus and cerebral peduncles were identified. Medical records were reviewed retrospectively for clinical, radiological, pathological, and surgical data. Formalin-fixed, paraffin-embedded tissue was obtained for 12 cases and tested for <jats:italic>KIAA1549-BRAF</jats:italic> fusion and <jats:italic>BRAF</jats:italic> V600E point mutation.</jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p>On preoperative diffusion tensor imaging tractography (performed in 12 patients), the ipsilateral corticospinal tract was displaced laterally in 1 case (8.3%), medially in 1 case (8.3%), anterolaterally in 10 cases (83%), and posteriorly in no cases. Ten patients underwent resection via a transtemporal, transchoroidal approach, which was chosen to avoid further damage to motor function in cases of tumors that caused anterolateral or medial corticospinal tract displacement. With this approach, complications included hemianopia, oculomotor palsy, and tremor at a rate of 50%. Among the 12 patients with obtainable follow-up (mean 50.9 months), none received adjuvant therapy, and only 2 (17%) experienced recurrence or progression. <jats:italic>KIAA1549-BRAF</jats:italic> fusions were present in 10 cases (83%), while <jats:italic>BRAF</jats:italic> V600E was absent (0%). The 2 fusion-negative tumors had clinical features atypical for the series, including multi-focality and infiltration.</jats:p></jats:sec><jats:sec><jats:title>CONCLUSIONS</jats:title><jats:p>Transcortical, transchoroidal resection of thalamopeduncular tumors through the middle temporal gyrus allows for a high rate of gross-total resection and cure. Diffuse tensor tractography is a critical component of the preoperative planning process to determine the location of white matter tracts in proximity. Molecular status may correlate with clinical features, and the presence of <jats:italic>BRAF</jats:italic> lesions offers an additional target for future novel therapeutics.</jats:p></jats:sec>

Introductory Chapter: Glioma - Merciless Medical Diagnosis

“…Lesions previously considered inoperable are today more accessible and safer for resection; the surgeon has greater self-confidence and better preoperative knowledge about the tumor and can expect better result of the glioma resection itself; and patients can expect a better outcome. This is particularly important for those lesions for which neurosurgical resection and the extent of resection (EOR) is still the most important part of treatment and standard of care [14][15][16].…”

“…Al-Tamimi and Duffau's group [23] suggest that after radical resection, the presence of foci of transformation within a background of grade II tumor does not necessarily require immediate adjuvant therapy. They suggest that a tailored approach should be used, taking into account the extent of resection, the full histopathologic and molecular profile of the tumor, and careful evaluation of the resection margins [15,17,23].…”

“…Primary brain tumors remain hard and challenging work despite the progress in understanding their genetics and technological progress that enabled safe and extensive tumor resection [3,15,17]. As gliomas include a variety of different histological tumor types and malignancy grades, contemporary achievements in terms of molecular imaging have given us a unique Glioma -Contemporary Diagnostic and Therapeutic Approaches chance for a comprehensive interdisciplinary assessment of the glioma pathophysiology, with direct implications in terms of the medical and surgical treatment strategies available for patients [26].…”

“…Extension of surgical excision is still an important predictor of outcome. Achieving a gross total resection of the tumor without significant complication requires a thorough understanding of available surgical approaches [15,17,[30][31][32]. For majority of those patients, short-course radiotherapy with concurrent and adjuvant TMZ will bring a benefit, while gain from bevacizumab is limited [13].…”

Pediatric Glioma at the Optic Pathway and Thalamus

“…Clinicians previously favored a conservative approach comprising stereotactic biopsy and radiotherapy over radical resection, given the risks of postoperative morbidity and mortality [ 16 , 25 ]. However, recent improvements in imaging modalities, neuronavigation systems, microsurgical techniques, and intraoperative electrophysiological monitoring have yielded clear anatomical pictures of these deeply seated lesions; therefore, radical resection of a selected subset of these tumors is associated with minimal morbidity and mortality [ 14 , 37 , 50 , 74 ]. Generally, patients who have undergone total or subtotal resections of thalamic tumors experience improved outcomes and survival prognoses compared to those who do not undergo surgery [ 85 ].…”