Liquid Biopsy Strategies to Distinguish Progression from Pseudoprogression and Radiation Necrosis in Glioblastomas

Abstract

despite aggressive treatment. [1] Currently, maximal resection followed by radiation therapy with concurrent temozolomide (TMZ) and adjuvant TMZ treatment is the standard of care. Post-treatment surveillance involves serial MRI. A challenge faced by clinicians is the diagnosis and management of a gadolinium enhancing lesion on a follow-up MRI post-treatment. This suspicious lesion could be progressive disease (PD) or a mere post-treatment radiation effects such as pseudoprogression or radiation necrosis (RN). Pseudoprogression and RN are distinct clinical entities, which when identified and managed appropriately result in better outcomes, while PD of the tumor is often dismal. Patients with PD have a median survival of 3-6 months, [2] and there is no standard of care. Systemic options include TMZ rechallenge, lomustine, and antiangiogenic therapy such as bevacizumab, but their effectiveness is limited. Reradiation and reresection can be considered depending on the location of the tumor and the condition of the patient. [3] Conversely, antiangiogenic drugs like bevacizumab or cediranib decrease contrast enhancement by altering permeability of tumor vasculature without actual reduction in tumor burden, referred to as pseudoresponse. Distinguishing these clinical entities from PD is crucial to avoid unnecessary reoperations, premature discontinuation of adjuvant TMZ or its substitution with second line agents. MR imaging based monitoring is the current standard of care for post-surgical monitoring. Contrast enhancement on imaging is indicative of disrupted blood brain barrier (BBB), but not tumor presence. [4] Currently, MRI-based Response Assessment in Neuro-Oncology (RANO) criteria is used to monitor treatment response in GBM patients. The criteria included T1 gadolinium enhancing disease, T2/FLAIR changes, new lesions, corticosteroid use, and clinical status. [5] Adoption of RANO criteria for monitoring response is not without limitations. There is ambiguity in identifying radiation effects, enrolling patients into clinical trials and monitoring immunotherapy response. [6] Advanced imaging modalities including diffusion-tensor imaging, perfusion imaging, MR spectroscopy (MRS), and positron emission tomography (PET) imaging Liquid biopsy for the detection and monitoring of central nervous system tumors is of significant clinical interest. At initial diagnosis, the majority of patients with central nervous system tumors undergo magnetic resonance imaging (MRI), followed by invasive brain biopsy to determine the molecular diagnosis of the WHO 2016 classification paradigm. Despite the importance of MRI for long-term treatment monitoring, in the majority of patients who receive chemoradiation therapy for glioblastoma, it can be challenging to distinguish between radiation treatment effects including pseudoprogression, radiation necrosis, and recurrent/progressive disease based on imaging alone. Tissue biopsy-based monitoring is high risk and not always feasible. However, distinguishing these entities is of critical im...

Horizons in Veterinary Precision Oncology: Fundamentals of Cancer Genomics and Applications of Liquid Biopsy for the Detection, Characterization, and Management of Cancer in Dogs

“…In addition, hyperprogression (faster-than-expected tumor growth while under treatment) ( 257 ) and pseudoprogression (an initial apparent increase in tumor size or appearance of a new lesion on imaging during treatment, followed by tumor regression) ( 258 , 259 ) can confound the interpretation of imaging for evaluation of treatment response. Lesion growth observed on imaging after treatment initiation may be due to advancing disease (secondary to ineffective treatment), an inflammatory response (resulting from tumor destruction by the treatment or from a direct side effect of the treatment), or simply ongoing tumor growth in the setting of a delayed treatment effect ( 257 ).…”

Glioblastoma: Is There Any Blood Biomarker with True Clinical Relevance?

“…Despite the technical challenges and the very low concentrations of nucleic acid in biofluids, the information obtained is of paramount importance [88]. In normal individual and in early-stage cancers the ctDNA concentrations are very low, but these levels significantly increase with tumor progression and there is growing evidence that ctDNA concentrations are related to tumor burden, cellular turnover, cancer stage, and therapy response [89]. ctDNA could be obtained regularly over time, reflecting the real composition, the tumoral heterogeneity and the evolution of the tumor throughout time [90].…”

“…ctDNA allows us to overcome some difficulties of the magnetic resonance imaging (MRI) in the follow-up of the patients. Treatment effects (pseudoprogression), progressive disease and radiation necrosis are not always easy to distinguish in advanced brain imaging modalities or metabolic imaging such as PET scan [89].…”

Apoptotic Bodies in the Pancreatic Tumor Cell Culture Media Enable Label‐Free Drug Sensitivity Assessment by Impedance Cytometry

“…[ 11 ] Furthermore, given the short timeframe available to pancreatic cancer patients, who have a median survival duration of just 3–7 months, there is a need for in vitro cell‐based assays to screen pre‐clinical drug targets to gauge clinical benefit by using patient derived tumor materials. [ 12,13 ]…”