Miracles do happen! This one was sparked by a simple question to Dr. Whelan by a concerned grandfather – can photodynamic (PDT) that you are using to treat pediatric brain cancer work for neurofibromatosis (NF)? Long story short – Dr. Whelan applied his trademark boundless energy, vision, knowledge, resourcefulness, and enthusiasm to answer this question. After promising cell studies and mouse studies, he organized an incredible team of MDs and PhDs to perform human studies treating cutaneous NF using PDT. The Phase I accomplishments and successes are reported below.
PHASE I COMPLETED WITH VERY ENCOURAGING RESULTS AND PHASE II IS UNDERWAY!
The Whelan Team has completed Phase I of the Photodynamic Therapy (PDT) Study for Benign Cutaneous Neurofibromas. Near Infra-Red (NIR) treatment light was used. The 630 nanometer cherry red light is benign and safe. The results were presented before the Society for Investigative Dermatology by Edit Olasz MD, PhD (“Photodynamic Therapy for Benign Neurofibromas”, Edit B. Olasz, et.al.) Continuing progress using PDT for treatment of Neurofibromatosis (NF) tumors marches on in Milwaukee. Phase II is underway with 30 Patients.
PHASE I RESULTS
The Objective of Phase I was to assess the safety and efficacy of PDT in the treatment of NF1 tumors in the skin.
The Phase I study demonstrated definite advantages treating NF tumors with PDT. NF tumors entangle with healthy nerve cells making surgery dicey; especially when dealing with critical nerves. In the more risky cases NO treatment can be the recommendation when the downside risk of surgery is too ominous.
A DEMONSTRATED FINDING OF PHASE I is that PDT selectively kills NF cells that are entangled with healthy cells! This is a phenomenal result! The ability for PDT to kill the bad and spare the good can provide immeasurable advantage. As the treatment progresses to larger plexiform tumors that can involve nerves that are critical to life; and brain, critical organ, & muscle function, sparing critical nerves becomes ALL important. Funding has not been identified at this time to progress the PDT studies to larger plexiform tumors.
MOST IMPORTANTLY, the PDT results showed a significant kill of tumor cells! Thin slices of treated tumor were compared to placebo treated tumor. TUNEL Assay (dead cells in the slice are counted) showed 42.5±8.9 dead cells in the treated slice and only 1.13±0.64 in the placebo slice. HARD EVIDENCE THAT PDT IS WORKING!
PDT did not cause blister formation, erosion, or crusting. The light treatment did cause marked pain and discomfort when used with the photosensitive chemical. 1 of the 19 cases opted to stop treatment because of pain.
Several secondary, yet important challenges, were met and solved. How do you know if the photosensitive chemical is getting to the place where it is needed? A technique using florescence imaging was successfully developed by S. Kumar PhD after tedious unsuccessful attempts. Florescence imaging demonstrated that the photosensitive killer chemical was in the tumor cells and NOT the healthy cells. Microneedling was found to enhance the uptake of the ALA precursor of the photosensitive chemical by the Olasz dermatology team. The microneedle is a dermatology tool that makes micro breaks in the skin allowing better penetration of the topical chemical. Searching for the appropriate NIR LED treatment light lead to several blind alleys before the Omnilux light was found by B. Quirk, PhD. The Omnilux provides the advertised intensity and wavelength that are critical to PDT in addition to user friendly operation. Earlier hand held lab lights would cycle off for cooling; that required Dr. Olasz to constantly scurry around to restart the lights. In addition, the intensity was about 15% of the Omnilux. An earlier large light did not perform as advertised.
An amazing team of MDs and PhDs provided a symphony of medicine and science that resulted in good advances in the treatment of, and knowledge how to treat cutaneous neurofibromas. In addition to expanding the treatment knowledge for cutaneous tumors, the basic treatment science and knowledge developed will be an invaluable foundation for treatment of more critical plexiform tumors. Overall, the Whelan team completed a VERY SUCCESSFUL Phase I. CONGRATULATIONS TO ALL!
The objective of Phase II is to treat NF skin tumors when they are small a barely perceptible and hopefully stop, or drastically slow their growth. If the objective is met, the Whelan team envisions using this treatment on young patients to avoid the problems that clearly visible tumors bring. Other children can inflict extreme psychosocial pain. High sensitivity and self-consciousness can be triggered by visible tumors and disfigurement. Keeping the tumors imperceptibly small can help the child eliminate those painful experiences.
PDT will be performed on each patient. Part of the affected area will be treated and part will not. In this way each patient will be their control case – treated and non-treated areas will be compared and observed. After treatment, there will be follow-ups every 4 months for 3 years to document changes or not.
OBJECTIVE MEASUREMENT OF TUMOR SIZE
NTAP (Neurofibromatosis Therapeutic Acceleration Program) is a privately funded organization dedicated to development of treatments for NF. NTAP is located at the Johns Hopkins School of Medicine but operates independently. NTAP sponsored a meeting of several researchers studying treatments for cutaneous NF tumors. M D Anderson Cancer Center, University of Alabama Birmingham, and Medical College of Wisconsin were represented. At this Chicago meeting on 1 August 2016 a concern arose on how to objectively measure the size and change in size of cutaneous tumors. They discussed a need for a standard measure that would be comparable and consistent from one research group to another.
Brendan Quirk, PhD on the Whelan team had developed a 2D method to approximate the surface size of the tumor. The technique was able to track significant growths of the tumor. But now he is currently investigating a much-improved 3D imaging technique to measure the volume of the tumor. More later as this project progresses.
CONTRIBUTION BY DR. VINCENT RICCARDI
Dr. Riccardi is a NF research pioneer who dedicated his career to NF research in 1972. He has been associated with much of the NF research throughout the world. He is an encyclopedia of everything NF and an important contributor to the development of NF knowledge and research.
Dr. Riccardi was kind enough to provide a writeup on the current 2017 status of NF1 research. We have included his writeup under the tab What Is NF?. His write up is titled What is NF1? A take away from his write up is the following quote: “In sum, we are entering into a new era and there is strong reason to expect – soon – an expansion of current treatments, as well as realistic new treatments to avoid major NF1 problems.”