Combination of peptide receptor radionuclide therapy with fractionated external beam radiotherapy for treatment of advanced symptomatic meningioma

Abstract

Background: External beam radiotherapy (EBRT) is the treatment of choice for irresectable meningioma. Due to the strong expression of somatostatin receptors, peptide receptor radionuclide therapy (PRRT) has been used in advanced cases. We assessed the feasibility and tolerability of a combination of both treatment modalities in advanced symptomatic meningioma.

Methods: 10 patients with irresectable meningioma were treated with PRRT (177Lu-DOTA0,Tyr3 octreotate or - DOTA0,Tyr3 octreotide) followed by external beam radiotherapy (EBRT). EBRT performed after PRRT was continued over 5-6 weeks in IMRT technique (median dose: 53.0 Gy). All patients were assessed morphologically and by positron emission tomography (PET) before therapy and were restaged after 3-6 months. Side effects were evaluated according to CTCAE 4.0.

Results: Median tumor dose achieved by PRRT was 7.2 Gy. During PRRT and EBRT, no side effects > CTCAE grade 2 were noted. All patients reported stabilization or improvement of tumor-associated symptoms, no morphologic tumor progression was observed in MR-imaging (median follow-up: 13.4 months). The median pre-therapeutic SUV(max) in the meningiomas was 14.2 (range: 4.3-68.7). All patients with a second PET after combined PRRT + EBRT showed an increase in SUV(max) (median: 37%; range: 15%-46%) to a median value of 23.7 (range: 8.0-119.0; 7 patients) while PET-estimated volume generally decreased to 81 ± 21% of the initial volume.

Conclusions: The combination of PRRT and EBRT is feasible and well tolerated. This approach represents an attractive strategy for the treatment of recurring or progressive symptomatic meningioma, which should be further evaluated.

Figure 1

Intensity modulated radiotherapy isodose map of patient no. 2. This patient has a large meningioma with bitemporal spread surrounding the optic nerves and chiasm. Shown are transversal (upper left), sagittal (lower left) and coronal (right) views. In order to err on the side of caution due to the estimated 6.6 Gy PRRT dose, the optic tract was limited to 45 Gy (thick green line) and the PTV encompassing dose was limited to 49 Gy (thick orange line) instead of the originally planned 54 Gy.

Figure 2

Post-therapeutic whole body scans (anterior and posterior views) obtained 23 hours after PRRT of patient 2. Strong persistent uptake of the radiotherapeutic agent can be observed in the meningioma (thick arrow), which also extends to the contralateral side (thin arrow).

Figure 3

Side effects during EBRT according to CTCAE 4.0.

Figure 4

Model dose distribution (absorbed dose) comparing peptide radionuclide therapy with¹⁷⁷Lu and⁹⁰Y respectively. A homogeneous radionuclide dose distribution inside the tumor is assumed.