Grade II/III Glioma Clinical Trial
Official title:
A Prospective Study of Concurrent Chemoradiotherapy With Temozolomide Versus Radiation Therapy Alone in Patients With IDH Wild-type/TERT Promoter Mutation Grade II/III Gliomas
The management of lower-grade gliomas (Diffuse low-grade and intermediate-grade gliomas, WHO
II and III) is largely based on surgery followed by radiotherapy. Recent studies showed that
lower-grade glioma patients with IDH wild-type (IDH-wt) and TERT promoter mutation
(TERTp-mut) had dismal clinical outcomes. These results suggested that current treatment
strategies are not adequate for this subtype of lower-grade glioma.
The present study aims to examine the efficacy and safety of concurrent chemoradiotherapy
with temozolomide followed by adjuvant temozolomide for lower- grade glioma patients with
IDH-wt and TERTp-mut.
Diffuse low-grade and intermediate-grade gliomas (which together make up the lower-grade
gliomas, World Health Organization grades II and III) are infiltrative neoplasms that arise
most often in the cerebral hemispheres of adults and include astrocytomas,
oligodendrogliomas, and oligoastrocytomas. The management of lower-grade gliomas is largely
based on surgery followed by radiotherapy.
Lower-grade gliomas have highly variable clinical behavior that is not adequately predicted
on the basis of histologic class. Consequently, clinicians increasingly rely on genetic
classification to guide clinical decision making. Mutations in IDH1 and IDH2 characterize
the majority of lower-grade gliomas in adults and define a subtype that is associated with a
favorable prognosis. Mutations of the telomerase reverse transcriptase (TERT) promoter,
which result in enhanced telomerase activity and lengthened telomeres, have been observed in
several human cancers including glioma. Accumulating evidence suggest that TERT promoter
mutation is another molecular marker which can stratify lower-grade gliomas into prognostic
subgroups in combination with IDH mutation. In our previous study, patients(28/377, 7.4%)
who had lower-grade gliomas with IDH wild-type (IDH-wt) and TERT promoter mutation
(TERTp-mut) had the poorest clinical outcomes (median OS, 27.7mo; 5-year OS, 29%). These
results were accordant with the recent studies and suggested that current treatment
strategies are not adequate for this subtype of lower-grade glioma.
Radiotherapy plus temozolomide has emerged as a new standard of care for patients with good
PS non-elderly glioblastoma. There are some data that support temozolomide as adjuvant
therapy for lower-grade glioma. Given that the IDH-wt/TERTp-mut subgroup of lower-grade
gliomas has dismal prognosis, a more aggressive therapy such as concurrent chemoradiotherapy
seems to be reasonable. The present study aims to examine the efficacy and safety of
concurrent chemoradiotherapy with temozolomide followed by adjuvant temozolomide for
lower-grade glioma patients with IDH-wt and TERTp-mut. Half the patients will be randomly
assigned to receive concurrent chemoradiotherapy (surgery + concurrent chemoradiotherapy
with temozolomide followed by adjuvant temozolomide) and half the patients will be randomly
assigned to receive conventional therapy (surgery + radiotherapy only).
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