Radiation and chemotherapy for high-risk lower grade gliomas: Choosing between temozolomide and PCV.

The 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. We 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. For 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. At 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.

McDuff SGR ，Dietrich J ，Atkins KM ，Oh KS ，Loeffler JS ，Shih HA ... -  《Cancer Medicine》

Impact of 1p/19q codeletion and histology on outcomes of anaplastic gliomas treated with radiation therapy and temozolomide.

Anaplastic gliomas represent a heterogeneous group of primary high-grade brain tumors, and the optimal postoperative treatment remains controversial. In this report, we present our institutional data on the clinical outcomes of radiation therapy (RT) plus temozolomide (RT + TMZ) for anaplastic gliomas, stratified by histology and 1p/19q codeletion. A single-institution retrospective review was conducted of patients with supratentorial anaplastic oligodendroglioma (AO), mixed anaplastic oligoastrocytoma (AOA), and anaplastic astrocytoma (AA). After surgery, RT was delivered at a median total dose of 60 Gy (range, 31.6-63 Gy) in daily fractions. All patients received standard concurrent TMZ, with or without adjuvant TMZ. Histological/molecular subtypes were defined as codeleted AO/AOA, non-codeleted AO/AOA, and AA. From 2000 to 2012, 111 cases met study criteria and were evaluable. Codeleted AO/AOA had superior overall survival (OS) to non-codeleted AO/AOA (91% vs 68% at 5 years, respectively, P=.02), whereas progression-free survival (PFS) was not significantly different (70% vs 46% at 5 years, respectively, P=.10). AA had inferior OS to non-codeleted AO/AOA (37% vs 68% at 5 years, respectively, P=.007) and inferior PFS (27% vs 46%, respectively, P=.03). On multivariate analysis, age, performance status, and histological or molecular subtype were independent predictors for both PFS and OS. Compared to historical controls, RT + TMZ provided comparable OS to RT with procarbazine, lomustine, and vincristine (RT + PCV) for codeleted AO/AOA, superior OS to RT alone for non-codeleted AO/AOA, and similar OS to RT alone for AA. RT + TMZ may be a promising treatment for both codeleted and non-codeleted AO/AOA, but its role for AA remains unclear.

Speirs CK ，Simpson JR ，Robinson CG ，DeWees TA ，Tran DD ，Linette G ，Chicoine MR ，Dacey RG ，Rich KM ，Dowling JL ，Leuthardt EC ，Zipfel GJ ，Kim AH ，Huang J ... -  《-》

Comprehensive Genomic Analysis in NRG Oncology/RTOG 9802: A Phase III Trial of Radiation Versus Radiation Plus Procarbazine, Lomustine (CCNU), and Vincristine in High-Risk Low-Grade Glioma.

Bell EH ，Zhang P ，Shaw EG ，Buckner JC ，Barger GR ，Bullard DE ，Mehta MP ，Gilbert MR ，Brown PD ，Stelzer KJ ，McElroy JP ，Fleming JL ，Timmers CD ，Becker AP ，Salavaggione AL ，Liu Z ，Aldape K ，Brachman DG ，Gertler SZ ，Murtha AD ，Schultz CJ ，Johnson D ，Laack NN ，Hunter GK ，Crocker IR ，Won M ，Chakravarti A ... -  《-》

Upfront Therapy of Aggressive/High-Risk Low-Grade Glioma: Single-Institution Outcome Analysis of Temozolomide-Based Radio-Chemotherapy and Adjuvant Chemotherapy.

To report clinical outcomes of temozolomide (TMZ)-based radio-chemotherapy and adjuvant chemotherapy in patients with aggressive/high-risk low-grade glioma (LGG). Medical records of patients defined as aggressive/high-risk LGG based on clinicoradiologic and/or histomorphologic features treated between 2009 and 2016 in an academic neuro-oncology unit with upfront postoperative radiotherapy at time of initial diagnosis with concurrent and adjuvant TMZ were reviewed, retrospectively. In total, 64 patients with median age of 38 years at initial diagnosis were included. Histomorphologically, patients were classified into oligodendroglioma, mixed oligoastrocytoma, and astrocytoma. Molecular markers such as isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion were used to classify 37 of 64 (58%) patients into molecularly defined entities comprising oligodendroglioma (IDH-mutant with 1p/19q codeletion), IDH-mutant astrocytoma (immunohistochemistry or gene sequencing), and IDH-wild-type astrocytoma (gene sequencing). All 64 patients completed planned conventionally fractionated focal conformal radiotherapy (median dose 55.8 Gy) with concurrent TMZ. Fifty-nine patients received further adjuvant TMZ for a median of 12 cycles. Adjuvant TMZ was stopped prematurely in 6 (9%) patients due to toxicity or early disease progression. At a median follow-up of 56.7 months, 5-year Kaplan-Meier estimates of progression-free survival and overall survival for the study cohort were 74.6% and 84.3%, respectively. Five-year overall survival was 87.5%, 90.4%, and 71.9% for oligodendroglioma, mixed oligoastrocytoma, and astrocytoma, respectively (P = 0.42) Similar estimates for molecularly defined oligodendroglioma, IDH-mutant astrocytoma, and IDH-wild-type astrocytoma were 85.8%, 90%, and 66.7%, respectively (P = 0.87). Upfront TMZ-based concurrent radio-chemotherapy and adjuvant TMZ chemotherapy provides acceptable survival outcomes in aggressive/high-risk LGG with modest toxicity.

Anand S ，Chatterjee A ，Gupta T ，Panda P ，Moiyadi A ，Epari S ，Patil V ，Krishnatry R ，Goda JS ，Jalali R ... -  《-》

Correlation of Molecular Markers in High Grade Gliomas with Response to Chemo-Radiation.

Khurana R ，Rath S ，Singh HB ，Rastogi M ，Nanda SS ，Chauhan A ，Kaif M ，Hussain N ... -  《-》