Two-thirds of brain metastases give
off fluorescence following administration of 5-aminolevulinic acid,
which could potentially assist surgeons in identifying such tumors.
However, fluorescence patterns are often heterogeneous or vague, which
limits their practical benefits. These were the key findings of a major
study performed by Karl Landsteiner University of Health Sciences in
Krems (KL Krems) and headed by the Medical University of Vienna,
published in the Journal of Neurosurgery. The study looked at 150
patients, making this the world’s most comprehensive research project of
its kind to date. It has also delivered significant results, which will
form a valuable basis for developing this potentially useful technique.

Brain metastases are the most common type of tumor that affects the
brain, occurring in 20-40 percent of all systemic cancers. They are
often removed surgically, which is an important treatment option aside
from radiotherapy, gamma knife radiosurgery or chemotherapy. In most
cases, they can be effectively removed, as metastases can often be
clearly distinguished from the surrounding tissue. However, recent
research found that residual tumors remain after around 20 percent of
surgical resections. Performing an operation after administering
5-aminolevulinic acid (5-ALA) could enable surgeons to pinpoint these
hard-to-visualize parts of tumors during surgery. Particularly in tumor
cells, 5-ALA creates easily recognizable fluorescence, which in turn
simplifies identification of residual tumors. This already is an
established method of treating primary brain tumors, but so far there
has been no systematic investigation of its use in connection with brain
metastases. This was what the team from KL Krems and MedUni Vienna set
out to achieve in the largest study of its kind to be performed anywhere
in the world – and their findings were sobering.

MARKING METASTASES

“We demonstrated visible fluorescence in two-thirds of all metastases
following preoperative administration of 5-ALA,” explained Dr. Franz
Marhold (Department of Neurosurgery, University Hospital St. Pölten, KL
Krems ), lead author of the study, which was published in the Journal of
Neurosurgery. “But this fluorescence was often vague and heterogeneously
distributed, which unfortunately means its practical applicability is
limited.” The researchers examined a total of 157 brain metastases in
154 patients. 5-ALA fluorescence was identified in 104 metastases, and
53 demonstrated no fluorescence. However, in over 80 percent of cases,
fluorescence was so heterogeneous that it provided little support to the
surgeons performing the resection.

A key feature of this wide-ranging study was the correlation between the
fluorescence characteristics – status (i.e. visible or not), quality
(i.e. intensity) and homogeneity – and the primary tumor type. According
to Prof. Georg Widhalm of the Department of Neurosurgery at MedUni
Vienna, who was the head of the study: “We mainly examined brain
metastases in patients with lung, breast, colorectal and renal cell
cancer, and melanoma. Our evaluation showed that visible fluorescence
was observed most frequently in certain kinds of breast tumors, and
least often in melanoma cases. The heterogeneous distribution and low
intensity of fluorescence in the tumor was a feature shared by all forms
of cancer.”

SOLID FOUNDATIONS

The researchers were unable to find the causes of the often vague
fluorescence in brain metastases, but the data and tumor samples
collected will pave the way for future research into the possible
reasons. The same goes for the heterogeneous fluorescence within
individual metastases. ““We suspect there are differences in the
distribution of certain metabolites within a tumor. They react with
5-ALA, leading to heterogeneous levels of fluorescence,” Dr. Marhold
commented. This is one of the questions that researchers will aim to
address in future projects.

The work performed by the team headed by Dr. Marhold and Prof. Widhalm
demonstrates the strong practical relevance of the neuro-oncological
research carried out at KL Krems and MedUni Vienna. The research
addresses the needs of day-to-day clinical practice, and makes a
significant contribution to discovering, developing, improving and
evaluating treatment options.