Long-term follow-up of the multicenter, multidisciplinary treatment study HIT-LGG-1996 for low-grade glioma in children and adolescents of the German Speaking Society of Pediatric Oncology and Hematology

Abstract

The Hirntumorstudien (HIT)-LGG-1996 protocol offered a comprehensive treatment strategy for pediatric patients with low-grade glioma (LGG), ie, observation, surgery, adjuvant radiotherapy, and chemotherapy to defer the start of irradiation in young children. In this current study, we sought to determine clinical factors for progression and survival. Between October 1, 1996 and March 31, 2004, 1031 patients were prospectively recruited into an observation arm (n = 668) and a nonsurgical arm stratifying 12 months of vincristine-carboplatin chemotherapy (n = 216) and conventional radiotherapy/brachytherapy (n = 147) in an age-dependent manner. Median patient age was 6.9 years; 28 patients had diencephalic syndrome, 44 had dissemination, and 108 had neurofibromatosis type 1(NF-1). Main tumor location was the supratentorial midline (40.4%), and the main histology was pilocytic astrocytoma (67.9%). Following a median observation of 9.3 years, 10-year overall survival (OS) was 0.94 and 10-year event-free survival (EFS) was 0.47. Ten-year progression-free survival was 0.62 following radiotherapy and 0.44 following chemotherapy. Sixty-one of 216 chemotherapy patients received radiotherapy 0.3-8.7 years after initial diagnosis. By multivariate analysis, diencephalic syndrome and incomplete resection were found to be unfavorable factors for OS and EFS, age ≥11 years for OS, and supratentorial midline location for EFS. Dissemination, age <1 year, and nonpilocytic histology were unfavorable factors for progression following radiotherapy (138 patients); and diencephalic syndrome, dissemination, and age ≥11 years were unfavorable factors following chemotherapy (210 patients). NF-1 patients and boys experienced prolonged tumor stabilization with chemotherapy. A nationwide multimodal treatment strategy is feasible for pediatric LGG. Extended follow-up yielded results comparable to single-institution series for the treatment groups. Three-quarters of surviving chemotherapy patients have not yet received radiation therapy. Infants with or without diencephalic syndrome and dissemination bear the highest risk for death and progression following diagnosis or treatment.

Clinical and treatment factors determining long‐term outcomes for adult survivors of childhood low‐grade glioma: A population‐based study

“…7,[32][33][34][35][36] Indeed, many of these patients experience multiple tumor progressions, and upfront aggressive treatment options such as radiation therapy are being used to avoid potential patient demise. Despite multiple progressions, we observed >90% survival 20 to 25 years after the diagnosis in the absence of aggressive modalities such as radiotherapy and no late mortality due to tumor progression.…”

“…1 Although patients with PLGG may undergo multiple progressions, 1,2 the short-term (<5 years) and intermediate-term (5-10 years) overall survival (OS) is excellent, and most children survive to adulthood. [3][4][5][6][7] A lack of consistent follow-up poses a challenge for accurate data collection, and the long-term outcomes of adult survivors of PLGG are seldom reported. 5 Determinants of short-term tumor-related outcomes [3][4][5][6][7] include patient-related factors, such as age and an underlying diagnosis of neurofibromatosis type 1 (NF1), 8,9 and tumor-related factors, such as tumor extension and certain pathological subtypes.…”

“…[3][4][5][6][7] A lack of consistent follow-up poses a challenge for accurate data collection, and the long-term outcomes of adult survivors of PLGG are seldom reported. 5 Determinants of short-term tumor-related outcomes [3][4][5][6][7] include patient-related factors, such as age and an underlying diagnosis of neurofibromatosis type 1 (NF1), 8,9 and tumor-related factors, such as tumor extension and certain pathological subtypes. 6,10,11 Although complete surgical resection is consistently associated with improved survival, the extent of resection highly depends on the tumor location, and resection is feasible only for a minority of tumors.…”

Differential imaging characteristics and dissemination potential of pilomyxoid astrocytomas versus pilocytic astrocytomas

“…Treatment strategies of LGGs highly depend on the tumor location. Surgical resection is considered the treatment of choice for most LGGs and is often curative (Gnekow et al, 2012). However, many tumors are not amenable to complete resection and warrant other or additional treatment options such as chemotherapy and/or radiotherapy.…”

Female Pelvis: Genital Organs

“…As a result, overall survival (OS) for children and teenagers with CNS tumors in Germany has increased from below 50 % up to 70 % over the last decades (Kaatsch and Grabow 2012 ). For many patients with medulloblastoma or lowgrade glioma, the most frequent childhood CNS tumors, survival rates even reach 80 % or 90 %, respectively (Friedrich et al 2013 ;von Bueren et al 2011 ;Gnekow et al 2012 ;von Hornstein et al 2011 ). OS varies depending on patient's age, type and site of the tumor, its response to therapy, as well as late effects, which can be caused by the tumor itself and by the intensive treatments, such as neurosurgery, radiotherapy (RT), and chemotherapy.…”