Transformation of Plexiform Neurofibromas to Malignant Peripheral Nerve Sheath Tumors in Neurofibromatosis Type 1

This is an interventional diagnostic trial for Neurofibromatosis focused on measuring Genetic Analysis, Biopsy, FDG-PET, FLT-PET Read More

• INCLUSION CRITERIA:

  1. Age:

• No upper age limit for patient enrollment.

  • FLT PET: will only be performed in patients greater than or equal to 10 years old

  • Research biopsies in consenting patients with MPNST: will only be performed in patients greater than or equal to 18 years old

    2. Diagnosis:

• Patients who are diagnosed with NF1 using the NIH Consensus Conference criteria or have a confirmed NF1 mutation with analysis performed in a CLIA certified laboratory. NF1 mutation testing to confirm eligibility will not be performed on this protocol, but as part the POB separate screening study.

• For the clinical diagnosis of NF1 all study subjects must have at two or more diagnostic criteria for NF1 listed below (NIH Consensus Conference):

  1. Six or more caf(SqrRoot)(Copyright)-au-lait spots (greater than or equal to 0.5 cm in prepubertal subjects or greater than or equal to 1.5 cm in postpubertal subjects)
  2. Greater than or equal to 2 neurofibromas or 1 plexiform neurofibroma
  3. Freckling in the axilla or groin
  4. Optic glioma
  5. Two or more Lisch nodules
  6. A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)
  7. A first-degree relative with NF1

  3. NFI tumor manifestations

Subjects must have:

1. Diagnosis of NF1 with a lesion concerning for MPNST

   -Criteria include pain, growth of a known plexiform neurofibroma, abnormality on functional imaging study (FDG-PET) or change in clinical exam.

   OR

2. Diagnosis of NF1 with a histologically confirmed MPNST.

4. Subjects must be eligible for and willing to participate and sign consent for NCI protocol 08-C-0079: Natural History Study and Longitudinal Assessment of Children, Adolescents, and Adults with Neurofibromatosis Type 1, for the clinical evaluation necessary for this study.

5. Prior and current therapy:

For NF1 related benign tumor manifestations there is no standard effective medical treatment, and surgery is the only standard treatment. Chemotherapy and radiation therapy are additional treatment options for malignant NF1 related tumors. For the purpose of this study subjects who have not previously received medical or surgical treatment, patients who have previously received medical or surgical treatment, and subjects who are currently receiving medical treatment and or radiation for a NF1 related manifestation will be eligible.

Patients must be recovered from acute toxicities of prior therapy in order to be able to safely undergo biopsies proposed on the trial. Prior and current treatment for NF1 related manifestations will be recorded on protocol 08-C-0079.

Prior radiation therapy and chemotherapy in patients with MPNST must not have been administered within 4 weeks prior to enrollment.

6. Performance Status:

ECOG less than or equal to 3. Subjects who are wheelchair bound because of paralysis will be considered ambulatory when they are up in their wheelchair. Subjects have to be able to travel to the NIH for evaluations.

7. Informed Consent:

All patients or their legal guardians (if the patients is<18 years old) must sign an IRB-approved document of informed consent to demonstrate their understanding of the investigational nature and the risks of this study before any protocol-related studies are performed. When appropriate, pediatric subjects will be included in all discussions.

8. Hematologic criteria (applicable only in patients undergoing biopsy)

• Platelet count has to be greater than or equal to 100,000/microL
• Patients should have INR<1.4 and PT less than or greater to 40 seconds (unless due to lupus anticoagulant). In patients not meeting these parameters, clearance by hematology will be required prior to undergoing biopsy.

EXCLUSION CRITERIA:

1. Allergy or relative contraindications to MRI contrast agents.
2. Patients who require sedation for imaging studies will be excluded from the FLT PET scan research test. They will undergo only the standard of care MRI and FDG PET scan.
3. Contraindication to MRI scanning, such as surgery that involves metal clips or wires or metal prostheses which might be expected to cause tissue damage or produce image artifacts.
4. Patients with severe chronic renal insufficiency (glomerular filtration rate < 30 mL/min/1.73 m(2)), hepatorenal syndrome or post-liver transplantation.
5. History of prior fluorothymidine allergy or intolerance.
6. Participants with severe claustrophobia not relieved by oral anxiolytic medication or patients weighing >136 kg (weight limit for scanner table)
7. Pregnant women are excluded from this study because of the effects of radioactive materials with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with radioactive materials, breastfeeding should be discontinued.
8. Requirement for medications, which interfere with platelet function, such as aspirin, which cannot be stopped within 1 week prior to the biopsy (applicable only to patients undergoing biopsy).