Management of Diffuse Low-Grade Glioma: The Renaissance of Robust Evidence

Abstract

The surgical management of diffuse low-grade gliomas (DLGGs) has undergone a paradigm shift toward striving for maximal safe resection when feasible. While extensive observational data supports this transition, unbiased evidence in the form of high quality randomized-controlled trials (RCTs) is lacking. Furthermore, despite a high volume of molecular, genetic, and imaging data, the field of neuro-oncology lacks personalized care algorithms for individuals with DLGGs based on a robust foundation of evidence. In this manuscript, we (1) discuss the logistical and philosophical challenges hindering the development of surgical RCTs for DLGGs, (2) highlight the potential impact of well-designed international prospective observational registries, (3) discuss ways in which cutting-edge computational techniques can be harnessed to generate maximal insight from high volumes of multi-faceted data, and (4) outline a comprehensive plan of action that will enable a multi-disciplinary approach to future DLGG management, integrating advances in clinical medicine, basic molecular research and large-scale data mining.

Lesión difusa de médula espinal, ¿cirugía o tratamiento paliativo?: a propósito de un caso

“…De acuerdo a la nueva clasificación propuesta por la Organización Mundial de la Salud (OMS) del 2021, los gliomas difusos del adulto (GDA) pueden ser de 3 tipos histológicos: astrocitoma, oligodendroglioma y glioblastoma; este último es de alto grado (IV) (8,13) . Los gliomas difusos de bajo grado (GDBG), con una media de aparición a los 37 años (10) , son tumores que no cumplen con las características histológicas de malignidad y presentan crecimiento infiltrativo. Tienen una tasa de supervivencia fluctuante (5-13 años) sometida a variables como mutaciones de la isocitrato deshidrogenasa (IDH), las codeleciones del cromosoma 1p19q, la resección completa, entre otras (9) .…”

“…Sin embargo, debido a la característica difusa y expansiva que poseen los gliomas de la médula espinal, la resección completa de estos tumores puede ser demandante, y muchas veces imposible en el caso de los gliomas de alto grado. La radioterapia con o sin quimioterapia adyuvante, de acuerdo al grado de malignidad, representa una alternativa terapéutica en estos pacientes (3,5,9,10) .…”

Early costs and complications of first-line low-grade glioma treatment using a large national database: Limitations and future perspectives

“…Due to the relatively low prevalence of DLGG and their heterogeneity, prospective studies may prove challenging. Large-scale registries of prospective observational data may alleviate some of these challenges by allowing for large scale analysis more efficiently than true prospective trials or RCTs (33). However, the benefits of this approach must be weighed against the expected limitations.…”

Molecular Biology in Treatment Decision Processes—Neuro-Oncology Edition

“…To improve outcomes and personalise management, the neuro-oncology field has accurately recognised that both the need for tumor sequencing and computational interpretation of imaging are crucial [14]. However, efforts here have focused largely on diagnosis, grading and the type and timing of systemic management [28,48]. Molecular profiling has been evaluated in the CATNON and CODEL trials [49,50] to identify the appropriate chemotherapy to administer in conjunction with RT but has not been used prospectively to evaluate the ideal delivery of RT.…”

“…Molecular profiling has been evaluated in the CATNON and CODEL trials [49,50] to identify the appropriate chemotherapy to administer in conjunction with RT but has not been used prospectively to evaluate the ideal delivery of RT. LGG is a particularly challenging entity in that randomised trials may take many years to produce results [45,46], traditional endpoints such as overall survival and progression free survival may not reflect challenges in patient outcomes and hence observational large scale data may carry a large role if appropriately employed [48]. Research efforts in LGG have focused on two major areas: radiomics and genomics [3,6,14,28].…”