NF TUMOR TREATMENT AND PDT; THE PERFECT MATCH – NeuroFibromatosis (NF) tumors grow along nerves. They can be simple tumors that exist on the skin or just below the skin; not involving critical nerves. These cutaneous and subcutaneous tumors can be a significant cosmetic problem but generally are not health or life threatening. On the other hand, plexiform tumors tend to be larger and can involve major nerves associated with critical organs such as heart, lungs, brain, spine, eyes, etc. Plexiform neurofibromas can be life threatening, and/or cruelly disfiguring. While the physical disfiguration can be substantial and cruel, the collateral psychological injury especially to children can be as bad or worse.
At this time surgery is the only option for removal of NF tumors. For plexiform neurofibromas, surgery is often highly risky and many times the risk renders them inoperable
PhotoDynamic Therapy(PDT) has strong appeal because it can selectively kill tumor cells while sparing neighboring healthy cells. Dr. Whelan’s previous studies show that PDT provides good promise for brain cancers. PDT potentially can become a panacea for NF.
Dr. Whelan’s Ultimate Vision – Is to treat all NF tumors and especially PLEXIFORM tumors in children when the tumors are small and virtually imperceptible to the naked eye. The NF dream is that early treatment can avoid cruel physical and psychological pain and suffering. Wouldn’t it be a miracle if NF children could escape visually obvious tumors and their effects?!
PRIOR STUDIES – Earlier investigations included cell and mouse studies with human NF cells. The mouse studies included subcutaneous and plexiform tumors on the sciatic nerve. The results were highly successful demonstrating that the NF cells are killed using PDT. NF cells were completely eliminated in the cell studies and the subcutaneous tumors. The sciatic plexiform tumor showed graded elimination indicating treatment adjustments may be necessary.
CURRENT CLINICAL STUDIES – A detailed plan has been written and approved by the MCW Institutional Review Board. The general objective is to assess the safety and efficacy of PhotoDynamic Therapy (PDT) for neurofibromatosis 1 (NF1) tumors – first in the skin of adults, and then children.
This is a light-dose escalation pilot study to determine the safety and efficacy of PDT using Levulan Kerastick (ALA) and 633 nm light in the treatment of benign dermal neurofibromas. Specifically, the primary goal of the current study is to determine the optimum protocol for applying the ALA and the light, and the maximum tolerable light doses that can be administered to subjects.
The study began with adults to determine the optimum combination of variables. Once the variable combinations are defined, and the safety of the protocol is demonstrated the plan is to progress to pediatric patients.
SIGNIFICANT PRELIMINARY FINDINGS TO DATE –
1. The (sub)cutaneous (cutaneous and subcutaneous) tumors provide an excellent “fish bowl” for the study of PDT treatment of NF tumors. The tumors can be seen with the naked eye, they can be treated non-invasively (topical application of chemical, LED light is applied externally and directly to the skin), and the effects and results can be readily seen and felt. Treated tumors are also studied under light microscopy.
2. The chemical being used as a photosensitizer is Levulan Kerastick (ALA) or 5-aminolevulinic acid. The ALA is applied topically (directly to the skin). The ALA migrates inwardly and metabolizes to Protoporphyrin IX (PpIX). PpIX is photosensitive; and when exposed to the NIR light it produces oxidants that kill the tumor cells.
3. A highly SIGNIFICANT phenomenon seems to be in play. The conversion of ALA to PpIX appears to selectively occur in the tumor cells, and NOT the healthy cells. If this phenomenon continues to prove valid, this can be extremely important in the treatment of NF. PDT for NF may be THE answer for treatment of (sub)cutaneous NF tumors. The ability to selectively treat JUST THE BAD CELLS is huge and potentially very exciting!
4. So far the clinical studies confirm that the ALA is converted to PpIX in the tumor cells. Patients are being accepted for the next round of studies as this is being written (11/2013). The researchers are looking for death of the tumor cells in this current work. The goal is for PDT treatment of (sub)cutaneous tumors to occur when the tumors are small and nearly imperceptible; thus preventing cosmetic problems from ever arising.
5. Analysis of Tumors – The tumor sizes are measured before and after treatment. Selected treated tumors are removed for light microscopy.