Clinical and neuropsychological outcome of pediatric non‐midline central nervous system germinoma treated with chemotherapy and reduced dose/volume irradiation: The Children's Hospital Los Angeles experience

Abstract

Background Germ cell tumors (GCT) arising from non‐midline structures (basal ganglia, thalamus, and posterior fossa) are rare. Although patients with midline (pineal and suprasellar) germinoma have excellent survival with chemotherapy and whole ventricular irradiation (WVI), germinoma in non‐midline locations have traditionally been treated with craniospinal irradiation (CSI) or whole brain irradiation (WBI) to achieve similar outcomes. However, CSI and WBI are associated with significant long‐term neuropsychological sequelae. Methods We describe the clinical and neuropsychological outcomes of patients with non‐midline germinoma treated at the Children's Hospital Los Angeles between 1990 and 2015. Results Nine patients had basal ganglia/thalamic germinoma and one patient had a cerebellar primary. Eight patients received chemotherapy followed by reduced dose/volume irradiation, whereas two patients received chemotherapy alone as upfront therapy. One patient in the chemotherapy alone group relapsed after 4.3 years and was salvaged with CSI plus boost. The overall survival for the entire cohort was 100% at a median follow‐up of 8.5 years. Neuropsychological data were available for six patients at a median of five months (baseline) and 4.2 years (follow‐up) post‐diagnosis. At four‐year follow‐up, data available revealed intact overall cognitive ability, verbal memory, and executive functioning, but persistent deficits in fine motor function. Comparison of baseline to follow‐up suggests a downward trend in working memory, planning/problem‐solving, verbal memory, and visuospatial integration. Conclusion Chemotherapy followed by reduced dose/volume of irradiation is an effective strategy resulting in long‐term survival in patients with non‐midline germinoma. Neuropsychological data suggest relatively minimal morbidity over time.

Multi‐institutional analysis of treatment modalities in basal ganglia and thalamic germinoma

“…Median follow‐up was 87 months. Given the rarity of these tumors, this cohort includes the 10 patients previously reported in the single‐institutional experience at Children's Hospital of Los Angeles 16 …”

Precise detection of the germinomatous component of intracranial germ cell tumors of the basal ganglia and thalamus using placental alkaline phosphatase in cerebrospinal fluid

“…In addition to the complexity and di culty in locating the target tissue for histological diagnosis for IGCTs in the basal ganglia or thalamus, how to decide on the optimal eld for radiation therapy is still being debated owing to the inconspicuous and vague ndings on MRI [24,2]. Generally, whole-brain irradiation or craniospinal irradiation is performed for basal ganglionic IGCTs [24,16,2,10]. Extended focal irradiation can be a treatment option, but there is an attendant risk with irradiating an insu cient area, because some IGCTs in the basal ganglia or thalamus can barely be identi ed on neuroimaging.…”

Thalamic germinoma: A case report

“…Germinomas are considered to be highly radiosensitive tumors and have long-term progression-free survival rates (>85% Online First Indian J Child Health 3 over 5 years with radiation alone) [2,4,5]. Recently, the late effects of radiation such as visual field impairments, endocrinopathies, cognitive decline, and learning disabilities were emphasized and the efficacy and safety of combining chemotherapy with radiation therapy at the lower volumes and doses were explored [12]. At present, chemotherapy in conjunction with total ventricular field irradiation plus primary site boost is recommended for localized germinomas as an effective strategy for long-term survival [5,6].…”