Abstract
PurposeThe majority of patients with high‐risk lower grade gliomas (LGG) are treated with single‐agent temozolomide (TMZ) and radiotherapy despite three randomized trials showing a striking overall survival benefit with adjuvant procarbazine, lomustine, and vincristine (PCV) chemotherapy and radiotherapy. This article aims to evaluate the evidence and rationale for the widespread use of TMZ instead of PCV for high‐risk LGG.Methods and MaterialsWe conducted a literature search utilizing PubMed for articles investigating the combination of radiotherapy and chemotherapy for high‐risk LGG and analyzed the results of these studies.ResultsFor patients with IDH mutant 1p/19q codeleted LGG tumors, there is limited evidence to support the use of TMZ. In medically fit patients with codeleted disease, existing data demonstrate a large survival benefit for PCV as compared to adjuvant radiation therapy alone. For patients with non‐1p/19q codeleted LGG, early data from the CATNON study supports inclusion of adjuvant TMZ for 12 months. Subset analyses of the RTOG 9402 and EORTC 26951 do not demonstrate a survival benefit for adjuvant PCV for non‐1p/19q codeleted gliomas, however secondary analyses of RTOG 9802 and RTOG 9402 demonstrated survival benefit in any IDH mutant lower grade gliomas, regardless of 1p/19q codeletion status.ConclusionsAt present, we conclude that current evidence does not support the widespread use of TMZ over PCV for all patients with high‐risk LGG, and we instead recommend tailoring chemotherapy recommendation based on IDH status, favoring adjuvant PCV for patients with any IDH mutant tumors, both those that harbor 1p/19q codeletion and those non‐1p/19q codeleted. Given the critical role radiation plays in the treatment of LGG, radiation oncologists should be actively involved in discussions regarding chemotherapy choice in order to optimize treatment for their patients.
Highlights
High‐risk lower‐grade gliomas (LGG) constitute a heterogeneous group of tumors arising from glial cells in the central nervous system (CNS), often afflicting otherwise healthy young adults while exhibiting a more indolent course compared to adults with glioblastoma.[1]
The final report of this study is pending; a preplanned interim analysis showed that patients who received 1 year adjuvant TMZ compared to radiotherapy alone exhibited a significant improvement in overall survival (HR 0.65, 99.145% CI: 0.45‐0.93, P = .0014).[38]
While awaiting the initial and mature reporting of CODEL, physicians are faced with the question of whether to administer PCV or the better‐tolerated TMZ to patients with lower grade gliomas
Summary
High‐risk lower‐grade gliomas (LGG) constitute a heterogeneous group of tumors arising from glial cells (astrocytes and oligodendrocytes) in the central nervous system (CNS), often afflicting otherwise healthy young adults while exhibiting a more indolent course compared to adults with glioblastoma.[1]. Three major randomized trials have demonstrated a survival advantage among patients treated with adjuvant PCV compared to radiotherapy alone after resection of LGG.[5,10,11] In the landmark RTOG 9802 study, 251 patients with newly diagnosed supratentorial WHO grade II astrocytoma, oligodendroglioma, or oligoastrocytoma with unfavorable features as defined by age ≥ 40 and/or subtotal resection (STR) were enrolled between 1998 and 2002 and randomized to receive radiotherapy alone or radiotherapy followed by six, 8‐week cycles of PCV chemotherapy.[5,16] Histologic review was required prior to randomization Radiation therapy in both arms consisted of 54 Gy delivered in 1.8‐Gy daily fractions prescribed to isocenter. In those for whom PCV is considered too toxic, TMZ is a balanced choice
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