Anti-VEGF Molecular Targeted Therapies in Common Solid Malignancies: Comprehensive Update for Radiologists

Abstract

Angiogenesis is an essential component of the growth and dissemination of solid malignancies and is mediated by several proangiogenic factors. The most widely studied proangiogenic factor is vascular endothelial growth factor (VEGF). A major class of molecular targeted therapies (MTTs) inhibit the VEGF axis and are referred to as antiangiogenic MTTs. There are two main types of anti-VEGF MTTs: drugs targeting circulating VEGF and drugs interfering with the activity of the VEGF receptors. The cancers against which antiangiogenic MTTs have had the greatest effect are gliomas, non-small cell lung cancer, colorectal cancer, hepatocellular carcinoma, renal cell carcinoma, and gastrointestinal stromal tumor. These cancers respond to antiangiogenic MTTs in a different way than they respond to conventional chemotherapy. Instead of the traditional Response Evaluation Criteria in Solid Tumors (RECIST), each of these cancers therefore requires its own individualized treatment response criteria (TRC). Examples of individualized TRC include the Response Assessment in Neuro-oncology (RANO) criteria for gliomas, modified RECIST for hepatocellular carcinoma, and Morphology, Attenuation, Size, and Structure (MASS) criteria for renal cell carcinoma. Furthermore, antiangiogenic MTTs have a unique spectrum of class-specific and drug-specific toxic effects, some of which can be detected at imaging. Increasing use of antiangiogenic MTTs in clinical practice necessitates that radiologists be aware of these drugs, their response patterns, and TRC as well as their toxic effect profiles.

Staging of pulmonary metastases using dual-energy computed tomography after anti-angiogenic therapy

“…[1] Additional assessment techniques are therefore necessitated not only by the mechanism of action, but also the criteria of therapy response. [13] Our study was able to demonstrate that quantification of contrast-medium uptake is possible and valid using dualenergy imaging.…”

“…Essential here therefore is a quantification of the tumors' uptake of contrast medium, which can be calculated and visualized by means of dual-energy CT (DECT). [1] For years, DECT has been an established diagnostic procedure with a number of advantages over mono-energy computed tomography. Tissue differentiation can be carried out successfully.…”

Unintended Consequences of Systemic and Ablative Oncologic Therapy in the Abdomen and Pelvis

“…Pseudoprogression.-Although not a complication, pseudoprogression is an important phenomenon related to oncologic treatment that refers to target lesion enlargement as a manifestation of treatment response, potentially causing interpretive errors at CT and MR imaging. Pseudoprogression most frequently occurs in the setting of colorectal or renal cell carcinoma metastases treated with certain immunologic agents (eg, ipilimumab, nivolumab, pembrolizumab) or anti-angiogenic agents (eg, bevacizumab, aflibercept, sunitinib, sorafenib) (93).…”

Molecular Targeted Therapy in Modern Oncology: Imaging Assessment of Treatment Response and Toxicities

“…Ziv-aflibercept is approved for use in metatstatic colorectal cancer in combination with 5-fluorouracil, leucovorin, and irinotecan following treatment with an oxaliplatin-based regimen (14). Small molecule inhibitors of receptor tyrosine kinases inhibit (TKI) the VEGF-receptor and other transmembrane kinases, and include sunitinib (Sutent®; Pfizer, New York, NY, USA), sorafenib (Nexavar®; Bayer Pharmaceuticals Corporation, Wayne, NJ and Onyx Pharmaceuticals Inc., Emeryville, CA, USA), pazopanib (Votrient®; GlaxoSmithKline, Middlesex, United Kingdom) and others (15). TKIs are approved in a variety of malignancies, including metastatic RCC, hepatocellular carcinoma and gastrointestinal stromal tumor, amongst others (161718).…”