Astrocytoma IDH-mutant treatment
Maximal surgical resection, if safely feasible, is the best initial therapeutic approach 1)
Early radiotherapy (as opposed to radiotherapy after disease progression) has been shown to prolong progression-free survival (PFS) but not OS 2)
The use of chemotherapy alone as frontline therapy remains investigational but might be an option if radiotherapy is not feasible, for example, in patients with large tumours. However, the PFS is probably shorter with temozolomide than with radiotherapy in patients with IDH-mutant, grade 2 diffuse astrocytomas 3)
The RTOG 9802 trial reported a major prolongation of OS with the addition of PCV polychemotherapy to radiotherapy (54 Gy), from 7.8 years to 13.3 years in patients with high-risk WHO grade 2 gliomas who were 18–39 years of age and had undergone a subtotal resection or biopsy or in those aged ≥40 years 4)
This benefit was reported across histological subgroups and, although cohort sizes were small, benefit was observed in patients with either IDH-mutant astrocytomas or oligodendrogliomas but not in those with IDH-wild-type tumours 5).
The management of low-grade glioma (LGG) still remains controversial because the effectiveness of early and extensive resection is unclear, and the use of radiation therapy or chemotherapy is not well-defined.
The relatively long survival compared to other brain tumors makes consideration of treatment toxicity, and thus timing of potentially damaging interventions such as surgery, radiation, and chemotherapy, crucial. Moreover, the rarity of these tumors makes clinical trials to ascertain optimal care challenging.
The discovery that most low-grade gliomas harbor isocitrate dehydrogenase (IDH) mutations that confer a favorable prognosis has improved diagnosis and risk stratification of these tumors. Although Level of evidence 1 is still lacking, increasing data support the concept of maximal safe tumor debulking as a first step in tumor management. Preliminary results from a large randomized trial suggest chemotherapy is of comparable effectiveness to radiation therapy for one molecular subtype of low-grade glioma. Importantly, however, the final results of a phase 3 trial comparing radiation with or without procarbazine, CCNU (lomustine), and vincristine (PCV) chemotherapy indicate a large survival advantage to combined chemotherapy and radiation, raising questions about using chemotherapy alone as an initial treatment strategy.
While the combination of radiation and PCVprovides the best proven overall survival with low-grade gliomas, important questions remain. These include whether the better-tolerated temozolomide is as effective as PCV in conjunction with radiation therapy and whether the use of initial chemotherapy as a strategy to defer the potential delayed cognitive toxicity associated with radiation will yield acceptable survival results with a favorable toxicity profile 6).
Choosing the best treatment strategy for each patient with a diffuse low-grade glioma, in other words optimizing the oncologic and functional balance, implies not only a full knowledge of the natural history of this chronic disease, but also an understanding of the adaptation of the brain in response to growth and spread of the glioma 7).
The ideal management of suspected low-grade gliomas (LGGs) has historically been controversial in neurosurgery and neurooncology 8) 9) 10).