Changes in clinical management of diffuse IDH-mutated lower-grade gliomas: patterns of care in a 15-year period

Abstract

Background Isocitrate dehydrogenase (IDH) mutated diffuse lower-grade gliomas (dLGG) are infiltrating brain tumors and increasing evidence is in favor of early multimodal treatment. In a Scandinavian population-based setting, we wanted to study treatment patterns over the last 15 years, focusing on the short-term postoperative course to better understand the potential negative consequences of treatment. Methods Patients ≥ 18 years with primary IDH-mutated dLGG grade 2 and 3, operated between January 2007–June 2021 were identified. Patients were divided into subgroups (2007–2011, 2012–2016, and 2017–2021) and comparisons regarding tumor- and disease characteristics, treatment, and postoperative outcome were performed. Results We identified 202 patients (n = 61, 2007–2011; n = 72, 2012–2016; n = 69, 2017–2021), where of 193 underwent resection without change in proportion of resections over time. More patients underwent complete resections in recent times (6.1%; 15.7%; 26.1%, respectively; p = 0.016). Forty-two patients had any neurological deficit postoperatively (14.8%; 23.6%; 23.2%; p = 0.379), mostly minor and transient. Differences in oncological therapy were seen between the investigated subgroups. Early radiotherapy alone (32.8%; 7%; 2.9%; p < 0.001), concomitant chemoradiotherapy (23%; 37.5%; 17.4%; p = 0.022), sequential chemoradiotherapy (0%; 18%; 49.3%; p < 0.001), and no adjuvant treatment (42.6%; 23.6%; 18.8%; p = 0.009) shifted during the studied period. Increasingly more patients received proton radiotherapy compared to photon radiotherapy during the later time periods (p < 0.001). Conclusion Complete resections were performed more often in later time periods without an apparent increase in surgical morbidity. Early adjuvant oncological treatment shifted towards providing chemotherapy and combined chemoradiotherapy more often in later time periods. Protons replaced photons as the radiation modality of choice.

Surgical treatment for insular gliomas. A systematic review and meta-analysis on behalf of the EANS neuro-oncology section

“…The pooled >90% resection rate was 60.8% (95% CI: 50.7–69.9%) which actually compares reasonably with glioma cohorts not selected for tumor location. Gross total or complete resection rates in the range of 17.0–64.0% have been reported in more recent publications ( Gousias et al, 2014 ; Hervey-Jumper et al, 2023 ; Obara et al, 2020 ; Stupp et al, 2017 ; Svenjeby et al, 2022 ). Collectively, these figures suggest that specialized institutions may be able to achieve quite acceptable deficit and resection rates for tumors in difficult locations.…”

“…Awad et al report a mean postoperative KPI of 80.0 ± 16.6 in a cohort of 330 glioblastoma patients ( Awad et al, 2017 ). The paper by Svenjeby and co-workers details overall 4.0% severe (any: 21.8%) motor and 3.0% severe (any: 15.8%) language deficits in a series of 202 IDH1 mutant “lower” grade gliomas ( Svenjeby et al, 2022 ). Zhang et al describe 734 cases with gliomas of all WHO grades and found a 10.6% late motor and 7.2% late language deficit rate ( Zhang et al, 2018 ).…”

Brain Plasticity Profiling as a Key Support to Therapeutic Decision-Making in Low-Grade Glioma Oncological Strategies

“…Of note, current guidelines and ongoing trials do not account for this volume threshold and keep on employing the historical dichotomy between "low risk" and "high risk" LGG patients [47][48][49], with the age and a less-than-total gross resection as criteria to recommend early adjuvant therapies. Beyond the necessary need to integrate molecular mutations (e.g., IDH mutation, 1p19q codeletion, CDKN2A/B homozygous deletion), the arbitrary cutoff of 40 years and the lack of consideration of recent studies regarding the prognosis impact of the volumetric threshold reduce the scope of this dichotomy [50], and current oncological teams tend to defer adjuvant treatment in subcategories of "high risk" profiles [51], including in selected patients with grade 3/4 foci [52]. The aim of this attitude is to reduce the late adverse effects of oncological treatments (especially radiotherapy, see below).…”

“…LGGs [47]), temozolomide was finally adopted by a vast majority of oncological centers, because of its better tolerance profile in comparison to PCV [51].…”

“…The effects of modern radiation technologies (including intensity modulated radiotherapy, volumetric modulated arc therapy, or proton therapy) on long-term cognitive functioning remain unknown, with reports only reaching a limited follow-up [111,112] and usually based on restrained neuropsychological batteries (e.g., mini-mental state examination) [112,113]. Over the past 15 years, significant changes have been observed regarding the use of radiotherapy in IDH-mutant LGGs [23,51]. Most teams seem to postpone the introduction of radiotherapy at later stages of the disease, especially in 1p19q codeleted LGGs [114] and MGMT-methylated LGGs [115], to reduce the neurocognitive effects of radiotherapy in patients now surviving 16 years or more in median [23,45,106].…”