Favorable long-term outcome of low-grade oligodendrogliomas irrespective of 1p/19q status when treated without radiotherapy

Abstract

Despite the accumulating evidences of high chemosensitivity especially in anaplastic oligodendrogliomas with loss of chromosomes 1p and 19q, the optimal management strategy for low-grade tumors using the 1p/19q information remains controversial. We have treated all low-grade oligodendrogliomas by a chemotherapy-preceding strategy without radiotherapy, and here we analyzed the survival outcomes of 36 consecutive patients in relation to 1p/19q status. The treatment protocol was as follows: (1) simple observation after gross total resection, and (2) modified PCV chemotherapy for postoperative residual tumors or recurrence after total resection. The 1p and 19q status were analyzed by fluorescence in situ hybridization. The median follow-up period was 7.5 years and no patient was lost during the follow-up periods. 1p/19q co-deletion was observed in 72% of the patients, and there was no significant association between 1p/19q co-deletion and chemotherapy response rate. The 5- and 10-year progression-free survival (PFS) rate was 75.1 and 46.9%, respectively, and the median PFS was 121 months for 1p/19q-deleted tumors and 101 months for non-deleted tumors (log-rank test: P = 0.894). Extent of surgery did not affect PFS (P = 0.685). In contrast, the elder patients (>50) had significantly shorter PFS (P = 0.0458). Recurrent tumors were well controlled by chemotherapy irrespective of 1p/19q status, and 35 out of 36 patients survived without receiving radiotherapy. The 5- and 10-year overall survival rates were 100 and 93.8%, respectively. Two of the patients in their sixties (29%) suffered from severe cognitive dysfunctions and marked brain atrophy following chemotherapy alone. These results show that low-grade oligodendrogliomas could be successfully treated by surgical resection and nitrosourea-based chemotherapy alone without radiotherapy irrespective of 1p/19q status.

Differentiation between Oligodendroglioma Genotypes Using Dynamic Susceptibility Contrast Perfusion-Weighted Imaging and Proton MR Spectroscopy

“…25 Although most anaplastic oligodendrogliomas are chemosensitive, the responsiveness of low-grade oligodendrogliomas and the most appropriate timing for therapy are unclear and debatable. [26][27][28] On the contrary, some studies 8,9 have demonstrated that oligodendrogliomas harboring 1p/19q LOH, irrespective of histologic grade, present a favorable outcome to PCV chemotherapy, thus corroborating the need for a genetic profile to guide clinical management in such patients. Previous studies have reported that both dynamic susceptibility contrast-PWI and arterial spin-labeling PWI can distinguish histologic grades of gliomas.…”

Adult Low-grade Glioma

“…In specimens with 1p/19q data, 80% of oligodendrogliomas and 43% of oligoastrocytomas had 1p/19q codeletions, further validating our histologic classification. 27,28 Because of their overall better prognosis compared with astrocytomas, RT in oligodendrogliomas may not improve 29-31 or could reduce 16 OS in oligo-predominant tumors.…”

Indications for Treatment: Is Observation or Chemotherapy Alone a Reasonable Approach in the Management of Low-Grade Gliomas?

“…However, PFS associated with temozolomide (3.75- 4.6 years) was dramatically inferior to the median of 10.1 years among patients with 1p deleted oligodendrogliomas (all of which also harbored 19q deletion on further analysis) treated with a PCV like regimen (substituting nimustine, ACNU, for lomustine, CCNU) in one Japanese retrospective series. 71 Again, differences in study design and patient population confound interpretation; nonetheless, the shorter PFS reported with temozolomide is concerning.…”