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

Abstract

First-line treatment of pediatric low-grade glioma using surgery, radio-or chemotherapy fails in a relevant proportion of patients. We analyzed efficacy of subsequent surgical and nonsurgical therapies of the German cohort of the SIOP-LGG 2004 study (2004-2012, 1558 registered patients; median age at diagnosis 7.6 years, median observation time 9.2 years, overall survival 98%/96% at 5/10 years, 15% neurofibromatosis type 1 [NF1]). During follow-up, 1078/1558 patients remained observed without (n = 217), with 1 (n = 707), 2 (n = 124) or 3 to 6 (n = 30) tumor volume reductions; 480/1558 had 1 (n = 332), 2 (n = 80), 3 or more (n = 68) nonsurgical treatment-lines, accompanied by up to 4 tumor-reductive surgeries in 215/480; 265/480 patients never underwent any neurosurgical tumor volume reduction (163/265 optic pathway glioma). Patients with progressing tumors after first-line adjuvant treatment were at increased risk of suffering further progressions. Risk factors were young age (<1 year) at start of treatment, tumor dissemination or progression within 18 months after start of chemotherapy. Progression-free survival rates declined with subsequent treatment-lines, yet remaining higher for patients with NF1. In non-NF1-associated tumors, vinblastine monotherapy vs platinum-based chemotherapy was noticeably less effective when used as second-line treatment. Yet, for the entire cohort, results did not favor a certain sequence of specific treatment options. Rather, all can be aligned as a portfolio of choices which need careful balancing of risks and benefits. Future molecular data may predict long-term tumor biology.

Doubling Recruitment of Pediatric Low-grade Glioma within Two Decades does not change Outcome – Report from the German LGG Studies

“…Patients with histologic diagnosis of LGG according to the respective WHO classification of CNS tumors without prior non-surgical therapy were eligible. In defined cases radiological diagnosis was accepted [11,15,17,23], but had to be confirmed by central radiologic review since 2004. Central review for neuropathology and neuroimaging had been recommended following their respective incorporation within the German pediatric brain tumor network and completeness increased throughout the last decade.…”

“…Earlier, pediatric LGG patients were dispersed between various disciplines, each favoring individual approaches and with variable follow-up [27,52]. Since 1996, successive studies for pediatric LGG, initiated within the GPOH and the brain tumor network (HIT), have provided comprehensive treatment strategies in Germany integrating clinical observation, surgical approaches, and non-surgical treatments [15,23]. In general, recruitment numbers for a given oncologic diagnosis tend to improve with the opening of multicenter treatment protocols [3], specifically if centers can report patients without eligibility restrictions [24].…”

“…In general, recruitment numbers for a given oncologic diagnosis tend to improve with the opening of multicenter treatment protocols [3], specifically if centers can report patients without eligibility restrictions [24]. The German LGG studies offered such "simple" registration from the beginning for all patients [15,23], while only a portion was enrolled into the randomized international chemotherapy trial between 2004 and 2012 [17]. Of note, enrollment into the chemotherapy arm of the SIOP-LGG 2004 trial was linked to timely registration, even if non-surgical treatment started at a much later point in time.…”

“…Until 2006, patients up to 16 years had been eligible for the LGG protocols [15,17,23]. Following the international, 2007 "age amendment" of the SIOP-LGG 2004 protocol the share of patients aged 16-18 years ranged from 2.1 to 6.7 % per year in the German cohort.…”

“…Younger age has frequently been identified as unfavorable prognostic factor [5,17,34,45], though impairment of survival for the infant group seemed less pronounced in the LGGregistry cohort. Dissemination has been identified as an unfavorable prognostic condition for progression following treatment [15,17,32], but as well for overall survival [23,48].…”