Case Descriptions/Results
Patient 1: 23 year old female with Gorham Stout Disease
This patient has an extensive LM in the lumbar spine and sacrum
complicated by a L4/L5 nerve sheath-to-LM fistula causing a chronic
cerebrospinal fluid leak and severe headaches.11 She
failed treatment with interferon alpha and zoledronic acid, was treated
with blood patches with transient relief, and also underwent glue
embolization. She tried sirolimus for a year but had no benefit and
developed hyperlipidemia so discontinued. Secondary to debilitating
headaches, she had both ventricular-peritoneal and lumbar-peritoneal
shunts placed. At age 22, she developed acutely worsening headaches,
leading to multiple ED visits, and inability to attend school.
Sequencing of a lytic bone biopsy demonstrated the EML4::ALK
fusion.12 She was discussed at molecular tumor board,
which recommended the ALK inhibitor alectinib based on its favorable
side effect profile. She was started on 150 mg alectinib BID (starting
dose for lung cancer is 600 mg BID). After 2 weeks, she noted decreased
back swelling, which was present since infancy. However, her headaches
continued and alectinib was increased to 300 mg BID. Subsequently, two
shunt malfunctions were discovered and repaired and she continued on
alectinib. Her headaches resolved, though it was unclear how much the
alectinib verses the shunt revision contributed. She noted continued
decreased swelling and pain in her back, which she attributed to
alectinib and wanted to continue with the medication. After a year on
alectinib, she is doing well and graduated from nursing school. MRI
after 1 year of therapy demonstrated >50% reduction in soft
tissue edema in the area of her LM (Fig. 1).
Patient 2: 10 year old female with GU lymphatic malformation
This patient presented at the age of 10 with a 1 month history of left
labial swelling, purulent drainage, and difficulty wearing pants. She
was diagnosed with an extensive LM with a concurrent abscess. After
resolution of the infection, she was treated with sirolimus (goal trough
10-15 ng/mL) for >4 years. She suffered from frequent mouth
sores yet had no radiographic or symptomatic response with almost
continuous drainage from the lesion, pain, difficulty wearing clothing,
and an inability to participate in physical activity. She stopped
sirolimus and underwent sclerotherapy and labial debulking. Though her
activity improved post-procedure, she continued to have pain and fluid
drainage. Molecular testing of biopsy tissue showed an EML4::ALK fusion.
With the goal of improved symptom control, alectinib, the ALK inhibitor
with the best side effect profile, was prescribed. Despite multiple
attempts, the only ALK inhibitor covered by insurance was crizotinib.
Given this limitation, crizotinib was started at 250 mg BID, which is
half the standard pediatric cancer starting dose for her BSA which was
1.99. Within 3 weeks of initiation, she had complete resolution of fluid
drainage from the skin and pain, with no adverse effects. MRI at 3
months demonstrated over 20% reduction in the labial component of the
malformation (Fig. 2) and she continues on therapy.