Conclusions and Results (outcome and follow-up)
In April 2022, the patient returned to the hospital due to recurrent falling incidents and an unstable gait that began 10 days prior, alongside low back pain persisting for two days. Clinical evaluations indicated lower limb weakness, left-sided lower limb numbness, decreased sensation to light touch more pronounced on the left side, difficulty standing, reduced or absent lower limb reflexes, and a positive Romberg’s sign. MRI of the spine demonstrated notable enlargement and extensive expansion of the intramedullary lesion, as shown in Figure 2. Treatment was initiated with dexamethasone, administered orally at a dosage of 4 mg every eight hours for five days. This was followed by the introduction of the targeted therapy Larotrectinib, dosed at 100 mg/kg orally, twice daily. The patient exhibited clinical improvement two days post-initiation of Larotrectinib, despite the presence of a positive clonus reflex. Subsequent MRI evaluation, 34 days after starting treatment, showed a decrease in the spinal cord lesion and expansion. However, Larotrectinib treatment was halted for one month due to supply issues but was then resumed as previously.
In August 2022, the patient experienced a decline in her condition, presenting with back pain and worsening weakness in the lower limbs, necessitating hospital admission. MRI displayed a considerable increase in the size of the spinal cord’s intramedullary lesion, alongside significant expansion and edema, as shown in Figure 3. Consequently, the decision was made to recommence treatment with Larotrectinib. A follow-up MRI conducted in December 2022 demonstrated a mixed response to the treatment, with the primary feature being a mild progression of the intramedullary mass.
At the onset of January 2023, the patient was brought to the emergency room, reporting a two-week history of ataxia and a sensation of heaviness in her lower limbs, accompanied by several non-injurious falls. Her condition had deteriorated to the point where she required assistance to walk. Clinical examination revealed lower limb weakness and a reduced sensation below the T10 level. Subsequent MRI with contrast highlighted the further recurrence of disease progression in the spine and infratentorial regions. As a therapeutic intervention, craniospinal irradiation (CSI) was administered to the patient. The CSI treatment involved the utilization of the 6MV-photon Volumetric Modulated Arc Therapy (VMAT) technique. The treatment protocol consisted of a total dose of 54Gy, delivered in 20 fractions, with an additional boost phase of 18 Gy specifically targeting the infratentorial and spinal regions. Following the completion of the treatment, the patient reported the occurrence of dysphagia and a perceptible alteration in the taste of food. In addition, dexamethasone was administered orally at a dosage of 4 mg/kg every six hours for a duration of 14 days to alleviate symptoms.
By the end of January 2023, after tapering of Dexamethasone dosage, the patient’s condition worsened, manifesting as increased lower limb weakness and balance issues, alongside a bilateral decrease in lower limb sensation. An MRI of the brain disclosed a new leptomeningeal lesion affecting the fourth ventricle and the anterior surface of the left cerebellar hemisphere, as indicated in Figure 4.
In February 2023, after a total duration of ten months on Larotrectinib, the treatment was discontinued. Concurrent administration of dexamethasone led to an improvement in the patient’s gait. Due to the ongoing progression of the spinal lesion as indicated by MRI and suspicions of a high-grade transformation, a biopsy of the intramedullary thoracic lesion was performed. Post-surgical outcomes revealed considerable right lower limb weakness, which was more pronounced than on the left; this condition showed improvement a few days later. Subsequent postoperative MRI demonstrated a reduction in tumor burden with a documented 34% resection of the lesion and associated edema. Histological examination showed no signs of high-grade transformation, maintaining consistency with previous samples. Additionally, Bevacizumab was incorporated into the treatment regimen.
In March 2023, the patient commenced a new chemotherapy cycle, adopting a regimen comprising vincristine and carboplatin, as outlined in The Children’s Oncology Group Protocol A9952, intended for maintenance until August. During this period, further molecular assessment was conducted using the OncoRisk Expanded approach, which encompasses a Next-Generation Sequencing (NGS) panel analyzing 96 genes, including Copy Number Variations (CNVs). This extensive genetic analysis revealed no pathogenic variants that could explain the clinical phenotype observed in the patient. This is a twenty-three-month follow-up.