Artikel
The Metinfilt study – molecular biopsy of the macro metastasis/brain parenchyma interface
Die Metinfilt Studie – molekulare Biopsie der Hirnmetastasen-Infiltrationszone
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Veröffentlicht: | 4. Juni 2021 |
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Gliederung
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Objective: Brain metastases (BM) are considered to be circumscript lesions with very little infiltration of the adjacent brain. However, recent studies demonstrated extensive colonization of the macro metastasis / brain parenchyma interface (MMBPI). Importantly, these studies showed a correlation between higher degree of MMBPI infiltration and poor prognosis. Several molecular pathways responsible for MMPI invasion have been identified in vitro, but no in vivo validation of these signals has been performed. One challenge of such experiments is the aspect of precise and reproducible tissue sampling from the exact area of MMBPI. We therefore designed a prospective study design in which we combined imaging - based identification of the MMBPI, intraoperative neuronavigation, and fluorescence supported tissue acquisition to ensure reproducible sampling from the MMBPI.
Methods: On the day of surgery, the study team consisting of the neuroradiologist, the neurosurgeon and the basic scientists, identified the MMBPI based on the preoperative, contrast enhanced T1 weighted MRI. Subsequent to craniotomy and durotomy, neuronavigation was employed to re – identify the MMBPI, carefully preventing any csf draninage to avoid significant brain shift. Subsequently, MMBPI defined as the transition zone between tissue areas with either absent or low to moderate fluorescence signal was visualized with a YELLOW 560 nm filter integrated into the surgical microscope. At least four wedge – shaped samples representing the MMBPI were acquired, and divided into two groups, one for histological confirmation of MMBPI and one for molecular analyses.
Results: The study has recruited 24 patients (9 female, 15 male; mean age 59.8 years). The most frequent primary tumor was lung cancer (n= 8), frontal lobe was the most frequent site (n = 11). No additional morbidity was induced, surgery time was not significantly prolonged. Histological analysis revealed an excellent representation of the MMBPI in all cases including the detection of infiltrating tumor cells, as well as microglial and astroglial activation. The samples prepared for molecular analysis showed high yields of high quality RNA, DNA and proteins.
Conclusion: The results of this ongoing study demonstrate the successful tissue acquisition from the MMBPI with high precision and reproducibility by combining presurgical imaging analysis, intraoperative neuronavigation, and fluorescence supported tissue sampling.