Favorable prognosis in pediatric brainstem low‐grade glioma: Report from the German SIOP‐LGG 2004 cohort

Abstract

Reports on pediatric low-grade glioma (LGG) of the caudal brainstem are retrospective with heterogeneous cohorts, variable treatments and inconsistent outcome data. We analyzed their natural history and asked whether brainstem location proved unfavorable for survival within the framework of the comprehensive SIOP-LGG 2004 management strategy. Within the prospectively registered, population-based German SIOP-LGG 2004 cohort 116 patients (age 0.2-16.5 years, 10% Neurofibromatosis NF1) were diagnosed with LGG of the pons (27%) and medulla oblongata (73%). After biopsy (23%), variable resection (63%) or radiologic diagnosis only (14%), 59 patients received no adjuvant treatment. Radiologic progression or severe neurologic symptoms prompted chemo-(n = 39) or radiotherapy (n = 18). After further progression (28/57), salvage treatments included multiple treatment lines for 12/28 patients. Five-years event-free survival dropped to 0.40, while 5-years overall survival was 0.95 (median observation time 6.8 years). Higher extent of resection yielded lower progression rate (p = 0.001), but at a cost of 21/100 patients suffering from new postsurgical complications including respiratory insufficiency. Central review confirmed pilocytic astrocytoma (56%), diffuse astrocytoma (8%) or glioneuronal histology (16%) (others 4%, no histology 17%). Malignant evolution was documented in five patients associated with Histone3 mutation in 2/5. Our treatment algorithm conveyed high overall survival for pediatric brainstem LGG. Extensive neurosurgical resection did increase additional postoperative neurologic deficits but not overall survival in this often-chronic disease. More than half of all patients can be Additional Supporting Information may be found in the online version of this article.safely followed by observation, while multimodal adjuvant treatment can control progressive tumors. Molecular assessment should confirm low-grade diagnosis and may detect patterns prognostic for malignant evolution. What's new?Outcome studies for pediatric low-grade gliomas (LGG) of the brainstem have generally been small and of low quality, making it difficult to determine prognosis. In this prospective, multicenter study, the authors developed a detailed description of the natural history, treatment response, and prognostic factors associated with favorable survival when a comprehensive treatment strategy was used. This treatment algorithm resulted in high overall survival for pediatric brainstem LGG. The study also emphasizes the importance of the predictive value of molecular patterns, as malignant evolution can occur even in lowgrade tumors.Favorable prognosis in pediatric brainstem LGG Int.

Loss of efficacy of subsequent nonsurgical therapy after primary treatment failure in pediatric low‐grade glioma patients—Report from the German SIOP‐LGG 2004 cohort

“…Corroborating previous series, the extent of tumor removal impacted strikingly upon overall and EFS. Progression was less frequent in cerebellar and hemispheric sites than in LGG of the SML, caudal brainstem or spinal cord where limited surgical approaches resulted in mostly incompletely resected LGG 1,14,34‐36 . Yet, relapse in our cohort was observed in one out of six patients even after complete resection, implying an invasive growth pattern on the microscopic level even in LGG 37,38 .…”

“…Progression was less frequent in cerebellar and hemispheric sites than in LGG of the SML, caudal brainstem or spinal cord where limited surgical approaches resulted in mostly incompletely resected LGG. 1,14,[34][35][36] Yet, relapse in our cohort was observed in one out of six patients even after complete resection, implying an invasive growth pattern on the microscopic level even in LGG. 37,38 Though there was a trend for more frequent progressions/relapses in pediatric LGG WHO-grade II and less in glioneuronal tumors, the impact of histology has to be related to its frequency at certain tumor sites.…”

A case report of pilocytic astrocytoma of the brainstem

“…Согласно недавно опубликованным данным крупнейшего мультицентрового проспективного исследования SIOP-LGG 2004, в которое вошли 116 детей с ГНСЗ ствола головного мозга, более половины пациентов (n = 59) были только на динамическом наблюдении и не получали никакого адъювантного лечения после частичной резекции или биопсии опухоли, 57 (49%) больным потребовалось назначение лучевой или химиотерапии. Выполнение радикальной резекции опухоли приводило к развитию тяжелых постоперационных неврологических осложнений, но не влияло на показатели общей выживаемости [10]. Ретроспективное исследование, проведенное в госпитале St. Jude (США), продемонстрировало высокие показатели выживаемости у 25 детей с ГНСЗ ствола головного мозга.…”

“…Таким образом, более половины всех пациентов с ГНСЗ ствола головного мозга можно безопасно наблюдать, в то время как адъювантное лечение при прогрессии может контролировать заболевание. Благоприятный исход в группе адъювантной терапии с 5-летней общей выживаемостью 89% после химиотерапии и 94% после лучевой терапии подчеркивает целесообразность данной стратегии [10].…”

“…Наиболее частой генетической находкой при ГНСЗ у детей, в частности при ПА, является химерный транскрипт KIAA1549-BRAF [3]. Согласно данным J. Holzapfel и соавт., химерный транскрипт KIAA1549-BRAF был обнаружен у 5 (29%) из 17 протестированных ГНСЗ ствола головного мозга, гетерозиготные мутации в гене H3F3A с заменой лизина на метионин в положении 28 (K28M) выявлены в 2 (11,8%) случаях, в гене BRAF (V600E) -в 1 (6%) случае [10]. Мутация V600E в гене BRAF, согласно данным другого исследования, при ГНСЗ ствола головного мозга встречается в 15% случаев [4].…”