PARP inhibition utilized in combination therapy with Olaparib-Temozolomide to achieve disease stabilization in a rare case of BRCA1-mutant, metastatic myxopapillary ependymoma

Abstract

Myxopapillary ependymoma (MPE) is a primary tumor of the central nervous system (CNS), characteristically an indolent malignancy involving the spinal conus medullaris, Filum terminale or cauda equina. We present a rare case of MPE, recurrent in the pelvic soft tissue with eventual pleural and intra-pulmonary metastasis. Refractory to repeated gross resection, adjuvant radiotherapy, platinum-based chemotherapy and temozolomide exploitation of mutant somatic BRCA1 status with the addition of a poly (ADP-ribose); polymerase inhibitor (PARPi) in a novel combination regimen with olaparib-temozolomide (OT) has achieved stable radiological disease after 10 cycles.

Keywords: Oncology; PARP inhibitor; ependymoma.

Figure 1.

A rare presentation of metastatic myxopapillary ependymoma. Magnetic Resonance Imaging (a and b) demonstrating a rare pelvic presentation of metastatic myxopapillary ependymoma. First presentation of pelvic disease is demonstrated in (a) Pelvic MRI (b) demonstrates disease progression after a 24-month period of disease stabilization with adjuvant radiotherapy, prior to final resection. There is evident a complex lobulated mass centered at the level of the coccyx and extending inferiorly and predominantly to the right of the midline, invading the posterior rectal wall and threatening the sciatic nerve, craniocaudal extent 8.9 cm. Status of pelvic disease, recurrent after multiple resections, at the time of presentation with metastatic disease to the thorax is shown in (c) Computed Tomography (d) demonstrating rare presentation of thoracic disease in metastatic myxopapillary ependymoma. Disease is shown at commencement of olaparib-temozolomide, where there is evident extensive intrathoracic involvement (intrapulmonary and pleural), in addition to small-volume pelvic (inguinal) nodal and hepatic disease (latter not shown).

Figure 2.

Histological and mutational characteristics of pleural disease. Histologically, this tumor comprises a mixture of papillary, solid and glandular architectures (A–D). The cells are arranged around variably well-formed fibrovascular cores (A and B), with prominent areas of myxoid stroma (A and C). Focal tumor necrosis is present (B). At higher magnification (D) the tumor is composed of cells with relatively small, bland, ovoid, vesicular nuclei with abundant fibrillary or focally clear cytoplasm. No pleomorphism or mitotic activity is discernible (hematoxylin and eosin). At low power (E), there is prominent papillary architecture with stromal cores being partly myxoid. A separate area (F) shows organoid nests of mildly atypical cells. Tumor cells stain diffusely for CD56 (G). Most tumor cells stain diffusely for S-100 (G). M-ethylation array profiling of pleural tissue (I) using the Illumina Infinium 850k EPIC array analysed as per the DKFZ Heidelberg algorithm, confirming myxopapillary ependymoma (MPE).

Figure 3.

Treatment response. (1) Carboplatin-etoposide. Disease progression (b) after three cycles of platinum-based chemotherapy is demonstrated, compared to baseline (a) (2) Temozolomide monotherapy. Disease progression (c) after six cycles of temozolomide is demonstrated, compared to pre-treatment (b). (3) Olaparib-Temozolomide combination therapy. Stable bulky thoracic disease (e) after 10 cycles of olaparib-temozolomide is demonstrated, compared to pre-treatment (d). (f) Plateau in rate of growth of target lesions by RECISIT 1.1 after commencement of olaparib-temozolomide.