Elsevier

World Neurosurgery

Volume 114, June 2018, Pages e735-e742
World Neurosurgery

Original Article
The Effectiveness of Salvage Treatments for Recurrent Lesions of Oligodendrogliomas Previously Treated with Upfront Chemotherapy

https://doi.org/10.1016/j.wneu.2018.03.069Get rights and content

Highlights

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    28 patients with IDH-mutant, 1p/19q-codeleted oligodendrogliomas were analyzed.

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    Among the 15 relapsed patients, 14 showed only local relapse.

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    Salvage treatment was effective for local relapse with a 5-year OS rate of 92.9%.

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    Clinical deterioration was prevented until dissemination occurred.

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    Salvage surgery may therefore play a significant role in helping prevent relapses.

Background

We previously reported a favorable outcome in a case series of patients with oligodendrogliomas treated with upfront chemotherapy; however, their progression-free survival (PFS) was relatively short considering their long-term overall survival (OS). This suggests that salvage treatments after progression were effective. However, the clinical impact of salvage treatments on outcomes of patients with recurrent oligodendrogliomas has not been precisely investigated.

Methods

Our case series included 28 patients with newly diagnosed isocitrate dehydrogenase–mutant and 1p/19q-codeleted oligodendroglial tumors treated with upfront procarbazine, nimustine, and vincristine. Clinical outcomes and patterns of recurrence were reviewed retrospectively.

Results

The median follow-up period of enrolled patients was 90.2 months. Disease progression occurred in 15 patients (53.6%), whereas the cancer appeared as local relapse alone in 14 (93.3%) patients. Salvage treatments were performed for all local relapses; thereafter, most of the subsequent progressions also appeared as resectable local relapses. The 5-year PFS and OS rates from the first progression were 30.3% and 92.9%, respectively. These relatively short PFS and favorable OS indicated the effectiveness of salvage treatment even after multiple progression. Thus far, 9 (60%) of 15 patients are deterioration-free with locally controlled lesions or complete remission; however, clinical deterioration was observed in 6 patients, and 4 of them experienced dissemination.

Conclusions

In isocitrate dehydrogenase–mutant and 1p/19q-codeleted oligodendrogliomas, most of the tumors that demonstrated early progression appeared as local, nonlethal lesions, which have been well-controlled by salvage treatments. A precise diagnosis of oligodendrogliomas using molecular parameters is crucial to receive the best benefit from salvage treatment.

Introduction

Since the 2016 edition of the World Health Organization (WHO) classification of brain tumors has emerged, the combination of the isocitrate dehydrogenase (IDH) mutation and the 1p/19q codeletion has become an important factor used in the diagnostic criteria of oligodendroglial tumors.1, 2 Several clinical studies proved that IDH-mutant, 1p/19q-codeleted oligodendroglial tumors are chemosensitive and have relatively favorable prognostic features compared with astrocytic tumors.3, 4, 5

In view of the chemosensitive nature of these tumors, we have treated newly diagnosed IDH-mutant, 1p/19q-codeleted oligodendroglial tumors with deferred radiation and upfront procarbazine, nimustine, vincristine (PAV) chemotherapy to avoid early or late radiation side effects such as neurocognitive deterioration. Our previous study revealed that outcomes were comparably favorable with those in patients treated with first-line chemoradiotherapy regimens mentioned in published randomized clinical trials.6 However, the progression-free survival (PFS) of our patients treated with upfront chemotherapy was relatively short considering their long-term overall survival (OS), implying the significance of salvage treatments implemented after tumor relapses. In this study, to clarify the appropriate salvage treatments for IDH-mutant, 1p/19q-codeleted oligodendroglial tumors in their long-term clinical course, we retrospectively analyzed the recurrence patterns of these tumors and investigated the clinical impact of salvage therapies on outcomes of the patients after progression.

Section snippets

Patients

We enrolled 28 patients with newly diagnosed IDH-mutant, 1p/19q-codeleted oligodendroglial tumors treated in our institute from January 1999 to December 2015. The diagnoses of these tumors were molecularly confirmed by the use of genetic analyses described previously.6, 7, 8 The present investigation was approved by the ethics committee of Kyushu University. Upfront PAV treatments were performed as follows: nimustine, 75 mg/body; procarbazine, 100 mg/(body day) on days 8–21. Vincristine 2.0

Patient Characteristics

The median follow-up period for the 28 patients enrolled was 90.2 months. Patient characteristics are summarized in Table 1. Pathologically, 17 and 11 patients were diagnosed as having WHO grade II and III cancer, respectively. Age distributions were similar between the 2 groups. For grade II tumors, 11 of 17 (64.7%) were male, whereas there was a slightly female predominance (6/11) in grade III tumors. Subtotal or more resection, defined as >90% extent of resection, was performed in a similar

Discussion

Our case series showed favorable outcomes regardless of the WHO grading, which validates the significance of IDH and 1p/19q status as a promising prognostic marker in oligodendrogliomas, as shown in international clinical studies.11, 12, 13, 14 Interestingly, the extent of resection did not correlate with the PFS of the patients in our case series, indicating that the progression of these tumors in the long-term follow-up period seems to be inevitable regardless of surgical aggressiveness. It

Conclusions

In this study, the long-term prognosis and recurrence pattern of the IDH-mutant, 1p/19q-codeleted oligodendroglial tumors have been demonstrated. Overall, we found that salvage surgery can play a considerable role in helping prevent relapses. Although randomized trials would help verify these results, we propose that salvage treatments for oligodendroglial tumors need to be stratified by molecular diagnosis according to the recent WHO classification.

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    • Conflict of interest statement: This work was supported by a Japanese Society for the Promotion of Science Grants-in Aid for Scientific Research (KAKENHI) Award (Grant No. 16K20015).

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