Radiologic and histologic consequences of radiosurgery for brain tumors

Abstract

Progressively enlarging encephalopathic changes are now well-documented effects of gamma knife radiosurgery (GKRS) occurring ~3-30 months after treatment of both benign and malignant brain lesions. These changes can be variably associated with inflammatory demyelination and necrosis and/or recurrent tumor. While radiographic differentiation between encephalopathic changes and recurrent tumor is of high clinical relevance, confident interpretation of post-radiosurgery imaging changes can be challenging or even impossible in some cases. Gadolinium-enhanced MRI of these lesions reveals variable amounts of enhancing and non-enhancing components within these lesions that have not been clearly correlated with structural-pathologic change. The goal of this study is to characterize the histopathological changes associated with enhancing versus non-enhancing regions of GKRS-treated lesions. MRI images of patients with progressive, etiologically ambiguous brain lesions following GKRS were reviewed prior to explorative neurosurgery. Chosen for this study were lesions in which distinct areas of enhancement and non-enhancement of at least 5 mm in size could be identified (n = 16). Distinctly enhancing and non-enhancing areas were separately biopsied and histologically evaluated. Only cases with uniform histological results are presented in this study. Enhancing and non-enhancing areas in post GKRS lesions represent separate pathological changes. Radiographically enhancing areas correlate either with recurrent tumor growth or inflammatory demyelinating changes. Lack of radiographic enhancement correlates with coagulative necrosis if the sample is taken from the center of the lesion, or with reactive astrocytosis if the sample is taken from the periphery. Separate biopsy of enhancing and non-enhancing regions of post-GKRS encephalopathy was able to confirm that the pathologies in these areas are distinct. These findings allow for better-informed correlation of histological and radiological changes and a better understanding of post-treatment tissue pathology.

Possible Interaction of Anti–PD-1 Therapy with the Effects of Radiosurgery on Brain Metastases

“…Another important consideration is the characteristics of the histologic findings. Although the current report did not show significant histologic differences from our previously reported cases of post-SRS leukoencephalopathy (2,4), it is possible that as more cases are identified in the future, potential subtle differences in histopathologic appearance after SRS with immunotherapy versus SRS alone will be identified.…”

“…Radiographic changes-unrelated to tumor after stereotactic radiosurgery (SRS) for brain metastasis are well documented (1)(2)(3)(4)(5). Classically, these changes manifest clinically months to years after SRS (5,6).…”

Detection of residual metastatic tumor in the brain following Gamma Knife radiosurgery using a single or a series of magnetic resonance imaging scans: An autopsy study

“…In previous studies, correlations between MRI and pathology using surgical or biopsy specimens were studied while relying on insufficient orientation; the locations of the MRI features were not adapted to the location of pathological features directly (15,18). To resolve this problem, the slices of the reconstructed MRIs were adapted to the macroscopically viewed slices of the brain in autopsy cases.…”

“…It is often hypothesized that pathological confirmation of remnant viable tumors by surgical specimen may be an overdiagnosis in view of the clinical course (15,19). …”

Mathematical Modeling in Radiation Oncology

“…In order to tailor optimized RT treatment plans to the biology of the individual patient's tumor, whether that be a genomically adjusted dose as suggested by Alomari et al (2014), or dynamic biologically conformal radiation therapy (DBCRT) (Kim et al 2012), one must identify appropriate biological targets. A systems oncology perspective incorporates multiple scales of tumor biology, including proliferation rate, cell signaling, DNA damage repair rate, and organ-level responses as biological targets for optimization (Powathil et al 2015).…”