Long-term outcomes of adult medulloblastoma patients treated with radiotherapy

Abstract

Medulloblastoma (MB) is rare in adults and treatment guidelines are consequently not well-established. Few modern series have reported long-term follow-up and treatment sequelae. We examined long-term outcomes of adult MB patients at one institution. Records of 29 consecutive patients (18 male, 11 female) aged ≥ 18 years who received radiotherapy (RT) for primary MB from 1990 to 2016 were reviewed. Median age at diagnosis was 28 years (range 18-72 years). Seventeen patients were standard risk and 12 were high risk. Nineteen patients had gross total resection, seven had subtotal resection, and three had biopsy only. Median craniospinal irradiation and boost doses were 36 Gy (range 23.4-39.6 Gy) and 55.8 Gy (range 54-59.4 Gy), respectively. Of 24 patients receiving chemotherapy, 20 received concurrent + adjuvant and 4 received adjuvant only. At median follow-up of 9.0 years (range 1.1-20.5 years), five patients recurred: four in the posterior fossa and one in both the posterior fossa and above the tentorium. Five patients died: two of disease progression and three after possible treatment complications (seizure, lobar pneumonia, and multifactorial sepsis). At last follow-up, 23 patients were alive with no evidence of disease. Long-term effects include executive dysfunction (n = 17), weakness/ataxia (n = 16), and depression/anxiety (n = 13). Kaplan-Meier estimates of 10-year overall survival and failure-free survival are 83% (95% confidence interval [CI] 59-93%) and 79% (CI 55-91%), respectively. Despite encouraging disease control in this cohort, long-term sequelae may limit quality of life. Multimodality pediatric regimens using lower RT doses may be considered to reduce treatment-related morbidity.

Neurocognitive functioning and health-related quality of life in adult medulloblastoma patients: long-term outcomes of the NOA-07 study

“…The impact of treatment on neurocognition and HRQoL in adult medulloblastoma patients is understudied. A recent study reported impaired neurocognitive functioning (learning and memory, and executive function) shortly after diagnosis [13], while another study reported that adult medulloblastoma patients had problems with executive dysfunction, weakness, ataxia, depression or anxiety about nine years after radiotherapy [14]. These long-term sequelae may subsequently have a negative impact on HRQoL.…”

“…Long-term radiotherapyinduced structural sequelae as leukoencephalopathy and radiation-induced vasculopathy relate to neurocognitive deficits [45,46]. Neurocognitive impairment after cranial irradiation is more severe in children, but also prevalent in adults [14]. The boost radiotherapy volume can be reduced to the tumor bed only in children without losing efficacy in comparison to posterior fossa irradiation, if a dose of 50 Gy is sustained [47,48].…”

“…Although it has been shown that a large proportion of adult medulloblastoma patients have impaired neurocognitive functioning shortly after diagnosis, particularly in the domains learning, memory, and executive function [13], data on the short-and long-term impact of treatment on outcomes such as neurocognition and HRQoL are limited. One study reported impaired executive function, weakness, ataxia, depression and anxiety about nine years after radiotherapy [14]. A review on core deficits and quality of survival in childhood medulloblastoma survivors showed long-term neurological and sensory (e.g.…”

Medulloblastoma in adults – reviewing the literature from a surgeon’s point of view

“…Surgical removal of the tumor should be followed by craniospinal irradiation and a boost to the posterior fossa in any patient. Radiotherapy increases local tumor control and leads to a prolonged progression free survival [ 4 , 66 ].…”

Targeting Upstream Kinases of STAT3 in Human Medulloblastoma Cells

“…Tremendous improvements in therapy using a combination of surgery, craniospinal radiotherapy and chemotherapy with vincristine, cisplatin and cyclophosphamide have yielded an overall survival of 70–80%, however, radio-polychemotherapy increases the risk of significant toxicities including neurocognitive impairment, endocrinopathy and neurologic deficits [6, 7]. In addition, many patients need to receive craniospinal irradiation to protect against developing metastasis, which places patients at the risk for significant long-term neurocognitive side-effects and sequelae that may impair their quality of life [8]. Targeted treatment is hence strongly desired based on the aggressive nature of the tumor and treatment-related side effects [9, 10].…”