The 54th Annual Congress of the International Society of Paediatric Oncology, Barcelona, Spain, 28 September - 01 October 2022, pp.1821
Background and Aims
There is a limited number of reports of successful treatment of central nervous system (CNS) metastases in neuroblastoma (NB)
In this article, we report a rare case of relapsed ALKF1174L mutation–driven NB involving the CNS that was responsive to lorlatinib combined with chemotherapy and craniospinal radiotherapy, a third-generation ALK inhibitor, and in whom we achieved clinical and radiological improvement.
A one-year-old male was admitted with persistent fever and fatigue. Physical examination revealed periorbital ecchymoses and swelling on the parietal bone. Laboratory analysis revealed pancytopenia, and elevated serum lactate dehydrogenase and ferritin levels. Cranial, thoracic, and abdominal computed tomography (CT) showed multiple metastatic bone lesions, and a large tumor originating from the left adrenal gland. Tru-cut biopsy from the abdominal mass confirmed the diagnosis of poorly differentiated NB. Molecular genetic tests of primary tumors showed MYCN amplification, 11q deletion positive and ALKF1174 mutation. After six cycles of induction chemotherapy, a partial response (PR) was achieved, with complete response (CR) of bone marrow. The primary left residual tumor was surgically resected. At the end of three cycles of maintenance therapy, the patient developed multipl CNS metastasis. The hematoma was evacuated surgically, and a ventriculoperitoneal shunt was placed, tumor excision failed. Tumor excision was not possible. The patient was initiated on lorlatinib (45 mg/m2) and a new cycle of chemotherapy including irinotecan (50 mg/m2) and temozolomide (100 mg/m2) was administered. Following the fourth cycle of chemotherapy, the patient underwent craniospinal radiotherapy. He is still asymptomatic for eight months on lorlatinib. Except for moderate hypercholesterolemia (grade 2), no significant side effects were observed due to the use of lorlatinib
In conclusion, high-risk NB with CNS involvement can be rarely cured. Investigation of ALK mutations and the use of an ALK inhibitor such as lorlatinib may yield promising results. Further studies are needed.