Nimustine Hydrochloride

Diffuse intrinsic pontine glioma (DIPG) is a very challenging‐to‐treat pediatric malignant tumor, with a median survival time of < 12 months. Convection‐enhanced delivery (CED) allows for direct drug administration into the tumor site, showing potential as a novel therapeutic approach. This study evaluated the efficacy of CED of nimustine hydrochloride (ACNU) in children with DIPG. This phase 2, single‐arm, multicenter study enrolled patients aged 3–21 years and diagnosed with DIPG. The investigational treatment commenced 1 month after completing radiotherapy (local 50–60 Gy). The treatment involved stereotactic brain surgery for catheter placement, followed by ACNU administration via a CED catheter at a concentration of 0.75 mg/mL for 2–3 days until a cumulative dose of 7 (±0.3) mL was achieved. The primary endpoint was the 1‐year survival rate. From April 2018 to March 2020, 21 children were enrolled in the trial and treated, with 20 evaluable for the primary endpoint. The 1‐year survival rate from the start of radiotherapy was 60%, and the median survival time was 15 months. The response rate was analyzed in 20 patients, with one complete response (CR), six partial responses (PR), nine stable diseases, and four progressive diseases, resulting in a response rate of 35% (CR + PR). The CED of ACNU in the brainstem of children with DIPG after radiotherapy appears to be an effective therapeutic strategy. This approach warrants further development as a treatment for children with DIPG. This study is registered with jRCT (No. jRCT2021190003).

T2-fluid-attenuated inversion recovery (FLAIR) mismatch sign is a specific imaging finding of isocitrate dehydrogenase (IDH)-mutant astrocytomas. Histologically, a hypointense area on FLAIR images indicates the presence of microcysts. Here we report a case of IDH-mutant astrocytoma that shrunk spontaneously.

A 26-year-old woman presented with a complaint of headache. Her magnetic resonance (MR) images revealed a lesion mass with a T2-FLAIR mismatch sign in the left frontal lobe. Subsequently, after 1 month, she was referred to our department, and we found that the lesion had unexpectedly shrunk; however, no further shrinkage was observed in the next 3 months. Furthermore, a biopsy was performed, and the results indicated a diagnosis of astrocytoma, IDH-mutant CNS WHO grade 3. Thus, she underwent subtotal resection. We found no neurological deficits in the patient, and she received 60 Gy of radiotherapy at the local site and chemotherapy with nimustine hydrochloride (ACNU), followed by the administration of ACNU every 8 weeks for 2 years. Overall, after 36 months of tumour resection, she was in good health and exhibited no recurrence. Notably, her histological and MR image findings suggested that the macroscopic cyst was formed by the fusion of microcysts, which is a characteristic feature of IDH-mutant astrocytoma with a T2-FLAIR mismatch sign, and that the tumour shrunk because of the rupture of the cyst in the Sylvian cistern.

The present case report suggests that IDH-mutant astrocytoma cannot be ruled out even when the lesion shrinks spontaneously.