Leaving residual tumours

June 10, 2020 0 By FM

Two-thirds of brain metastases give off fluorescence following administration of 5-aminolevulinic acid (5-ALA), which could potentially assist surgeons in identifying such tumours. 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. 

Performing an operation after administering 5-aminolevulinic acid (5-ALA) could potentially enable surgeons to pinpoint these hard-to-visualize
parts of tumours during surgery. Particularly in tumour cells, 5-ALA creates easily recognisable fluorescence, which in turn simplifies identification of residual tumours. 

This already is an established method of treating primary brain tumours, but so far there has been no systematic investigation of its use in connection with brain metastases (BM). 

According to a recent study, the majority of BM showed only heterogeneous fluorescence as well as the absence of a strong fluorescence effect that is frequently observed in glioblastomas or meningiomas.

“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 and lead author of the study titled, ‘Detailed analysis of 5-aminolevulinic acid-induced fluorescence in different brain metastases at two specialized neurosurgical centers: experience in 157 cases’, published in the Journal. 

“But this fluorescence was often vague and heterogeneously distributed, which unfortunately means its practical applicability is limited,” he added.

The researchers examined a total of 157 brain metastases in 154 patients from two specialized neurosurgical centres. 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.

High in breast cancers; low in melanoma

Brain metastases are the most common type of tumour 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 tumours remain after around 20 percent of surgical resections.

A key feature of this study was the correlation between the fluorescence characteristics – status (i.e. visible or not), quality (i.e. intensity) and homogeneity – and the primary tumour 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 tumours, and least often in melanoma cases. The heterogeneous distribution and low intensity of fluorescence in the tumour was a feature shared by all forms of cancer.”

The researchers were unable to find the causes of the often vague fluorescence in brain metastases, but the data and tumour samples collected will pave the way for future research into the possible reasons, they hope. 

“We suspect there are differences in the distribution of certain metabolites within a tumour. They react with 5-ALA, leading to heterogeneous levels of fluorescence,” Dr Marhold commented.