ID #877 Case report: intrathecal chemotherapy to achieve remission in relapsed/ refractory CNS germ cell tumors

Abstract

Relapsed or refractory central nervous system (CNS) non-germinomatous germ cell tumors (NGGCTs) are associated with dismal outcomes, especially when recurrence occurs after craniospinal irradiation (CSI). High-dose chemotherapy with autologous stem-cell transplantation (HDSCT), often with additional radiotherapy, are common treatment approaches. Achieving disease remission prior to HDSCT is often considered a key determinant of outcome, however can be very challenging in heavily pretreated patients.[1] [2]

We present the case of a 19-year-old male with multiply recurrent CNS GCT, who progressed despite multiple lines of prior platinum-based chemotherapy, two courses of CSI, and targeted therapy with imatinib and sotorasib.

He presented to our institutions after a third relapse with diffuse leptomeningeal disease and markedly elevated serum and CSF alpha-fetoprotein (CSF AFP 3843 ng/mL). Given the extensive disease burden, intrathecal (IT) methotrexate, cytarabine, and hydrocortisone (MAH) was incorporated into the reinduction regimen, in addition to systemic chemotherapy. This approach, to our knowledge, has not previously been reported in this setting, and was extrapolated from experience in management of brain metastases of extra-CNS GCTs.

Following a single cycle of reinduction systemic chemotherapy intensified with ten total doses of IT MAH, the patient achieved disease remission. He then proceeded to tandem carboplatin-thiotepa-etoposide and cyclophosphamide-melphalan HDSCTs, followed by consolidative re-irradiation with a third course of CSI and boosts to areas of intracranial leptomeningeal disease. He tolerated treatment overall well, without significant unexpected toxicity. Now 18 months post-treatment, he remains in sustained remission.

This case highlights the potential role for IT chemotherapy as an adjunct to salvage therapy to achieve remission in relapsed/refractory GCTs, particularly in the setting of leptomeningeal dissemination. However, given the high risk of additive neurotoxicity, the intensification of CNS-directed therapy in heavily pretreated patients should be undertaken with caution. The role for IT methotrexate in upfront treatment of CNS NGGCTs is currently being explored in an ongoing trial in Japan.[3]

1. Modak S, Gardner S, Dunkel IJ, Balmaceda C, Rosenblum MK, Miller DC, et al. Thiotepa-based high-dose chemotherapy with autologous stem-cell rescue in patients with recurrent or progressive CNS germ cell tumors. J Clin Oncol. 2004;22(10):1934–43.

2. Baek HJ, Park HJ, Sung KW, Lee SH, Han JW, Koh KN, et al. Myeloablative chemotherapy and autologous stem cell transplantation in patients with relapsed or progressed central nervous system germ cell tumors: results of Korean Society of Pediatric Neuro-Oncology (KSPNO) S-053 study. J Neurooncol. 2013;114(3):329–38.

3. Arakawa Y, Takami H, Isobe K, Yamasaki K, Maebayashi K, Hashimo T, et al. PEDT-6 A RANDOMIZED CONTROLLED CLINICAL STUDY OF RADIOTHERAPY COMBINED WITH CHEMOTHERAPY IN PATIENTS WITH NEWLY DIAGNOSED CENTRAL NERVOUS SYSTEM GERM CELL TUMOR, JCCG CNSGCT2021. (2632-2498 (Electronic)).