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A New Treatment Opportunity for DIPG and Diffuse Midline Gliomas: 5-ALA Augmented Irradiation, the 5aai Regimen.

Al's Comment:

 This is an interesting concept. Traditional photodynamic therapy uses direct light on the tumor after the tumor is sensitized to the light with a drug.  Obviously impossible for a brainstem tumor.  Instead, they propose using radiation therapy as the light souce, sensitizing the tumor with the drug 5-ALA which is already approved and in common use for brain tumors as Gleolan. (It is used at the time of surgery because it makes the tumor glow when a special light is shined upon it so the surgeon can see where the tumor is).   This has not been done it trials yet - so it is only a theory - I would love to see it tested.


Posted on: 02/03/2020

Brain Sci. 2020 Jan 17;10(1). pii: E51. doi: 10.3390/brainsci10010051.
A New Treatment Opportunity for DIPG and Diffuse Midline Gliomas: 5-ALA Augmented Irradiation, the 5aai Regimen.
Kast RE1, Michael AP2, Sardi I3, Burns TC4, Heiland T5, Karpel-Massler G5, Kamar FG6, Halatsch ME5.
 
Author information:
1. IIAIGC Study Center, 148 College Street, suite 202, Burlington, VT 05401, USA.
2. Southern Illinois University School of Medicine, Division of Neurosurgery, PO Box 19638, Springfield, IL 62794, USA.
3. Neuro-Oncology Unit, Department of Pediatric Oncology, Meyer Children's Hospital, viale Pieraccini, 50139 24 Florence, Italy.
4. Department of Neurologic Surgery, Mayo Clinic, Rochester, MN 55905, USA.
5. Department of Neurosurgery, Ulm University Hospital, Albert-Einstein-Allee 23, D-89081 Ulm, Germany.
6. Clemenceau Medical Centre, Department of Hematology-Oncology, Lebanese American University, Byblos Lebanon, City Centre Bldg. Suite 3A, Avenue Nouvelle, P.O. Box 1076, Jounieh, Lebanon.
Abstract
 
Prognosis for diffuse intrinsic pontine glioma (DIPG) and generally for diffuse midline gliomas (DMG) has only marginally improved over the last ~40 years despite dozens of chemotherapy and other therapeutic trials. The prognosis remains invariably fatal. We present here the rationale for a planned study of adding 5-aminolevulinic acid (5-ALA) to the current irradiation of DIPG or DMG: the 5aai regimen. In a series of recent papers, oral 5-ALA was shown to enhance standard therapeutic ionizing irradiation. 5-ALA is currently used in glioblastoma surgery to enable demarcation of overt tumor margins by virtue of selective uptake of 5-ALA by neoplastic cells and selective conversion to protoporphyrin IX (PpIX), which fluoresces after excitation by 410 nm (blue) light. 5-ALA is also useful in treating glioblastomas by virtue of PpIX's transfer of energy to O2 molecules, producing a singlet oxygen that in turn oxidizes intracellular DNA, lipids, and proteins, resulting in selective malignant cell cytotoxicity. This is called photodynamic treatment (PDT). Shallow penetration of light required for PpIX excitation and resultant energy transfer to O2 and cytotoxicity results in the inaccessibility of central structures like the pons or thalamus to sufficient light. The recent demonstration that keV and MeV photons can also excite PpIX and generate singlet O2 allows for reconsideration of 5-ALA PDT for treating DMG and DIPG. 5-ALA has an eminently benign side effect profile in adults and children. A pilot study in DIPG/DMG of slow uptitration of 5-ALA prior to each standard irradiation session-the 5aai regimen-is warranted.
PMID: 31963414
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