Interstitial Photodynamic Therapy Using 5-ALA for Malignant Glioma Recurrences
by
, , , , , , , ,
Stefanie Lietke
1,2,†,
Michael Schmutzer
1,2,†,
Christoph Schwartz
1,3,
Jonathan Weller
1,2,
Sebastian Siller
1,2,
Maximilian Aumiller
4,5,
Christian Heckl
4,5,
Robert Forbrig
6,
Maximilian Niyazi
2,7,
Rupert Egensperger
8,
Herbert Stepp
4,5,
Ronald Sroka
4,5,
Jörg-Christian Tonn
1,2,
Adrian Rühm
4,5,‡ and
Niklas Thon
1,2,*,‡ 
1
Department of Neurosurgery, University Hospital, LMU Munich, 81377 Munich, Germany
2
German Cancer Consortium (DKTK), Partner Site Munich, 81377 Munich, Germany
3
Department of Neurosurgery, University Hospital Salzburg, Paracelsus Medical University Salzburg, 5020 Salzburg, Austria
4
Laser-Forschungslabor, LIFE Center, University Hospital, LMU Munich, 81377 Munich, Germany
5
Department of Urology, University Hospital, LMU Munich, 81377 Munich, Germany
6
Institute for Clinical Neuroradiology, University Hospital, LMU Munich, 81377 Munich, Germany
7
Department of Radiation Oncology, University Hospital, LMU Munich, 81377 Munich, Germany
8
Center for Neuropathology and Prion Research, University Hospital, LMU Munich, 81377 Munich, Germany
*
Author to whom correspondence should be addressed.
†
Both authors contributed equally.
‡
This study is guided by AR and NT equally thus both serve as shared last authors.
Cancers 2021, 13(8), 1767; https://doi.org/10.3390/cancers13081767
Submission received: 23 February 2021
/
Revised: 26 March 2021
/
Accepted: 29 March 2021
/
Published: 7 April 2021
(This article belongs to the Special Issue Recurrent Glioblastoma)
Simple Summary
Malignant glioma has a poor prognosis, especially in recurrent situations. Interstitial photodynamic therapy (iPDT) uses light delivered by implanted light-diffusing fibers to activate a photosensitizing agent to induce tumor cell death. This study examined iPDT for the treatment of malignant glioma recurrences. Forty-four patients treated at one institution were retrospectively analyzed and patient-, tumor- and treatment-related factors were retrieved from hospital charts. Most of the patients (37) had glioblastomas, the most aggressive type of glioma. Brain swelling or small bleedings caused worsening of symptoms in 18 patients, but only in one case severe symptoms persisted for more than six weeks. After iPDT, tumors recurred after a median of 7.1 months and patients lived for a median of 13.0 months. Two years after iPDT treatment, 25% of the patients were still alive. These promising results should be evaluated further in a prospective study.
Abstract
Interstitial photodynamic therapy (iPDT) using 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) as a cytotoxic photosensitizer could be a feasible treatment option for malignant gliomas. In a monocentric cohort of consecutive patients treated between 2006 and 2018, a risk profile analysis of salvage iPDT for local malignant glioma recurrences and associated outcome measures are presented here. It was considered indicated in patients with circumscribed biopsy-proven malignant glioma recurrences after standard therapy, if not deemed eligible for safe complete resection. A 3D treatment-planning software was used to determine the number and suitable positions of the cylindrical diffusing fibers placed stereotactically to ensure optimal interstitial irradiation of the target volume. Outcome measurements included the risk profile of the procedure, estimated time-to-treatment-failure (TTF), post-recurrence survival (PRS) and prognostic factors. Forty-seven patients were treated, of which 44 (median age, 49.4 years, range, 33.4–87.0 years, 27 males) could be retrospectively evaluated. Recurrent gliomas included 37 glioblastomas (WHO grade IV) and 7 anaplastic astrocytomas (WHO grade III). Thirty (68.2%) tumors were O-6-methylguanine-DNA methyltransferase (MGMT)-methylated, 29 (65.9%)—isocitrate dehydrogenase (IDH)-wildtype. Twenty-six (59.1%) patients were treated for their first, 9 (20.5%)—for their second, 9 (20.5%)—for the third or further recurrence. The median iPDT target volume was 3.34 cm3 (range, 0.50–22.8 cm3). Severe neurologic deterioration lasted for more than six weeks in one patient only. The median TTF was 7.1 (95% confidence interval (CI), 4.4–9.8) months and the median PRS was 13.0 (95% CI, 9.2–16.8) months. The 2- and 5-year PRS rates were 25.0% and 4.5%, respectively. The treatment response was heterogeneous and not significantly associated with patient characteristics, treatment-related factors or molecular markers. The promising outcome and acceptable risk profile deserve further prospective evaluation particularly to identify mechanisms and prognostic factors of favorable treatment response.
