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.