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Earlier Pseudoprogression Seen in Patients With Oligodendroglioma Treated With Proton Therapy

Lisa Astor
Published Online:5:39 PM, Wed March 21, 2018
brain cancer
Patients with oligodendroglioma developed pseudoprogression earlier after treatment with proton therapy compared with after photon therapy, according to the results of a retrospective study comparing the rates of pseudoprogression that occurred in patients with anaplastic gliomas following treatment with different radiation therapy modalities.

Greater survival rates were seen in patients who developed pseudoprogression compared with those who did not, with a 3-year progression-free survival (PFS) rate of 100% versus 61.6%, respectively. The study authors suggested that due to the improved PFS, pseudoprogression could potentially be a predictive biomarker after treatment with radiation therapy for patients with glioma.

Researchers performed a retrospective analysis of 99 patients with grade II or III gliomas who had been treated with either proton or photon radiation therapy between 2004 and 2015.

In the study, pseudoprogression was defined as contrast enhancing changes within 6 months of radiation treatment that can mimic tumor progression and be confused with true progression.

The analysis included 67 patients with oligodendroglioma and 32 with astrocytoma or a not otherwise specified glioma. Sixty-five patients underwent treatment with photon therapy, including 42 with oligodendroglioma and 23 with astrocytoma, and 34 received proton radiation therapy, consisting of 25 patients with oligodendroglioma and 9 with astrocytoma.

The median age was 48 and the majority of patients were male. Sixty-three patients had grade III disease and the remaining 36 had grade II disease, which was based on the 2007 World Health Organization classification of brain tumors. Among the 70 patients tested for IDH status, 52 had an IDH mutation.

Concurrent chemotherapy was received by 14 patients, whereas 54 patients had received adjuvant chemotherapy. Gross total resection was completed in 34 patients and 65 had subtotal surgical resection. The median total dose of radiation was 57 GyRBE (range, 40-60).

The frequency of pseudoprogression did not differ based on tumor type or radiation modality. Pseudoprogression developed in 14 patients, including 10 (14.9%) with oligodendroglioma and 4 (12.5%) with astrocytoma. In patients with oligodendrogliomas, pseudoprogression developed in 6 patients (14.3%) treated with photon therapy and 4 (16%) treated with proton therapy. In patients with astrocytoma, 3 patients (13%) treated with photon therapy and 1 (11.1%) treated with proton therapy developed pseudoprogression.

Among all patients treated with photon therapy, 9 (13.8%) had pseudoprogression versus 5 (14.7%) treated with proton therapy.
Patients who developed pseudoprogression tended not to have received prior or concurrent chemotherapy, except for 1 patient who received prior temozolomide (Temodar) and 1 who received concurrent temozolomide. Eleven of the patients who developed pseudoprogression had subtotal surgical resection of their tumor. Three patients (21.4%) who had pseudoprogression were symptomatic; 2 had headaches and 1 had an increase in seizure frequency.

Time to pseudoprogression (range, 18-158 days) was shorter in patients with oligodendroglioma who were treated with proton therapy (48 vs 131 days; P <.01). On the other hand, time to pseudoprogression did not vary in patients with astrocytoma.

“Although the patient numbers are small, this observation suggests a differential biological effect of proton radiation in oligodendroglioma that is not present in astrocytoma,” the study authors wrote.

The median follow-up of patients who developed pseudoprogression was 45 months among patients treated with photon therapy and 22 months for those treated with protons. PFS and overall survival (OS) were both improved in patients who had pseudoprogression.

At 3 years, the PFS rate was 100% in patients with pseudoprogression compared with 61.6% in patients without pseudoprogression (P = .03). The median time to progression was 100 months versus 21 months, respectively (P = .02). The 3-year OS rate was 100% for patients who had pseudoprogression versus 82.6% in those who did not (P = .04).

On univariate analysis, pseudoprogression, gross total resection, and IDH mutation were all associated with improved PFS. On multivariate analysis, gross total resection and pseudoprogression both correlated with improved PFS. IDH mutation status was associated with improved OS rates on both univariate and multivariate analysis (P <.01).

“Our data did not show an association between the rate of pseudoprogression and the use of more aggressive therapy including adjuvant chemotherapy, gross total resection, or increased radiation dose for grade II and III gliomas,” the authors noted.
Bronk JK, Guha-Thakurta N, Allen PK, Mahajan A, Grosshans DR, McGovern SL. Analysis of pseudoprogression after proton or photon therapy of 99 patients with low grade and anaplastic glioma. Clin Transl Radiat Oncol. 2018;9:30-34. doi: 10.1016/j.ctro.2018.01.002.

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