Optic Pathway Hypothalamic Gliomas in Children under Three Years of Age: The Role of Chemotherapy

Abstract

Objectives: Optic pathway/hypothalamic gliomas (OPHGs) tend to occur in young children. Treatment options consist of surgical resection, radiation therapy (RT) and chemotherapy. Due to complications induced by surgery and RT, chemotherapy has gained significant recognition for the treatment of OPHG in young children. Chemosensitivity of OPHG in very young children under 3 years of age has not been well documented. We analyzed 14 patients who were treated with chemotherapy with or without surgery. Materials and Methods: Fourteen children younger than 3 years (median age of 10 months) with OPHG were treated between 1988 and 1998. Magnetic resonance imaging was obtained in all cases. Hydrocephalus was present in 8 patients and diencephalic syndrome was noted in 6. Only 3 of these had evidence of neurofibromatosis-1. Five patients had partial tumor resection and 4 had endoscopic biopsy at the time of ventriculoperitoneal shunt placement. Pathological examination revealed low-grade astrocytoma in 5 and juvenile pilocytic astrocytoma in 4. All patients received chemotherapy: carboplatin in 8, a combination of carboplatin and vincristine in 4 and a combination of other agents in 2. Results: Eight (57%) of 14 patients had a sustained reduction of tumor during the follow-up time between 15 months and 8 years. The 5-year progression-free survival was 63%. These tumor reductions were often accompanied by clinical improvements. Diencephalic syndrome responded to chemotherapy alone in 4 of 6 patients. However, 5 others had progressive disease; 3 during the treatment and 2 following the treatment (9 months and 2 years, respectively). All these 5 patients had a partial tumor resection prior to chemotherapy. Conclusion: A majority of OPHGs responds to chemotherapy. Due to slow progression of these tumors and adverse effects of other therapeutic modalities, we recommend chemotherapy as a primary treatment for OPHGs. Our present data indicates that partial surgical resection does not enhance chemotherapy effectiveness for OPHGs in infants or children younger than 3 years.

Optic glioma warranting treatment in children

“…30 At the macroscopic level, growth of OPG has been reported to be associated with sporadic, non-NF1 cases and younger age at presentation. 2,10 All of our patients were 4 years of age or younger at presentation, and four out of seven had sporadic OPG. In a series reported by Singhal et al 16 , 11 out of 17 NF1-associated OPG patients and 14 out of 17 sporadic OPG patients received treatment for progressive OPG disease.…”

“…Carboplatin, cisplatin, vincristine, vinblastine, actinomycin D, lomustine, thioguanine, procarbazine, dibromodulcitol, etoposide, tamoxifen, and temozolomide, alone or in combination, as primary treatment or as adjuvant, have all been utilized. [10][11][12][13]19,[32][33][34][35][36][37][38][39][40] Although chemotherapy has emerged as promising therapy, no regimen has yet to be universally accepted, hence the current Children's Oncology Group trial.…”

“…5 Overall, a more favourable outcome with OPGs is seen in patients older than 2 years of age, with NF1, and with optic nerve and/or chiasmatic lesions. 2,6,10,13 Determining the best treatment for your next patient with progressive OPG is not currently defined in the medical literature. Comparing the success rates of the various treatment modalities, across the multiple publications on the subject, is fraught with pitfalls: many of the studies are retrospective, inclusion, and exclusion criteria are lacking, treatments are not standardized or randomized, and outcomes are not clearly stated.…”

“…2 Younger age at presentation is also a risk factor for growth. 10 Treatment for progressive OPG is available with chemotherapy, radiotherapy, or surgery. Multiple studies have been reported on the advantage of chemotherapy for OPG in young children, but no widely accepted protocol yet exists.…”

The role of early intra-operative MRI in partial resection of optic pathway/hypothalamic gliomas in children

“…Optic pathway/hypothalamic gliomas (OPHG) account for approximately 2-7% of intracranial tumours in the paediatric population, with 65% of these tumours found in children less than 5 years of age [2,11,16,24,28,33]. They comprise a broad spectrum of tumour sizes and localisations, and typically follow an unpredictable course.…”