P17.80 * ANAPLASTIC GLIOMA: AN UPDATE ON TREATMENT STRATEGIES

Abstract

Anaplastic Gliomas (AG) include 6-10% of all newly diagnoses of primary brain tumors. They've an unfavourable prognosis: median survival ranging between two years for Anaplastic Astrocytoma and four years for Anaplastic Oligodendroglioma. Moreover, there is not an established treatment for AG: standard of care still remains one of the unresolved challenges and medical care are largely determined by histopathology-genetic diagnosis(in particular loss of heterozygosis 1p 19q).We reviewed the scientific literature, in order to define the better sequence and timing of chemo-radiotherapy for AG patients that improves progression-free-survival (PFS) and overall-survival(OS). Four recent randomized clinical trials (RCT) were identified for a total of 1170 patients (anaplastic-astrocytomas, anaplastic-oligoastrocytoma, anaplastic-oligodendroglioma). Three studies compared radiotherapy (RT) treatment vs radio-chemotherapy with procarbazine-lomustine-vincristine (PCV) or temozolomide(TMZ) or dibromodulcitol and bichloroethylnitrosurea (DBD/BCNU) and only one compared RT vs chemotherapy (CT) with PCV or TMZ. Results show no significant differences in terms of PFS/OS between RT/CT alone or combined treatment although a trend toward an improvement of OS was observed after RT + CT treatment (m-OS in RT + adjuvant PCV was 42.3 months vs 30.6 months in RT alone p = 0.0003).Grade 3-4 mielotoxicity has been observed in almost all cases of patients treated with PCV + RT. None of four studies reviewed conducted a head to head comparison between PCV vs TMZ. Only a study randomized patients to PCV/TMZ without however providing data in terms of PSF and OS between the two treatments. It found no significant differences in PFS from initial RT and adjuvant chemotherapy (PCV-TMZ) at progression compared to initial chemotherapy followed by RT at progression. Regarding the timing, no differences were demonstrated between the initial CT group and initial RT alone group. By considering the four RCTs, there seems to be a trend regarding PFS and OS in favour of the combined modality of chemo-radiotherapy. This type of treatment has certainly more risk to develop mielotoxicity and late neurotoxicity linked to RT. Clinical data do not allow to determine the optimal therapeutic approach in AG and this uncertain situation stresses the importance to conducting new randomized trials in the future to achieve reliable data in term of a possible prognostic/predictive role of bio-molecular factors. The optimal treatment of AG should reasonably consider not only the histology as well as the molecular markers of the tumor, but also clinical conditions, age of patients, life expectancy, Karnofsky-Performance-Status and tumor resection to achieve in future the personalization of care.