Combining Chemotherapy and Radiation Therapy for Liver Cancer: Is the Solution an Intraarterial Approach?
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COMMENTARY
COMMENTARY
Combining Chemotherapy and Radiation Therapy for Liver Cancer: Is the Solution an Intraarterial Approach? Jean-Francois H. Geschwind1 • Nariman Nezami2
Received: 26 June 2020 / Accepted: 4 July 2020 Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2020
The basic principle of radiation therapy is to induce DNA breaks within cancer cells resulting in cellular injury, and ultimately leading to apoptosis, or cell death. Similarly, conventional chemotherapeutic agents act by preferentially disrupting cancer cell mitosis through DNA damage, ultimately inhibiting cellular division [1, 2]. For years, chemotherapy and radiotherapy have been administered concurrently—with great success in some cancers, especially locally advanced solid tumors where the combined approach leads to better local control and improved survival—in an effort to synergize each other. The concept is rather simple: Chemotherapeutic agents are used as radiosensitizing agents, thereby potentiating the effects of radiation therapy. In order to accomplish this task, the chemotherapeutic agent in question must possess properties and characteristics that allow them to perform such a role. Various agents including antimetabolites, platinum-based agents, taxanes, some molecular targeted agents, and others including topoisomerase I inhibitors (such as irinotecan) do possess such properties by (1) directly increasing the initial radiation damage through their incorporation into DNA, (2) inhibiting cellular repair, (3) accumulating cancer cells in a radiosensitive phase or the converse, i.e., eliminating cells in a radioresistant phase, (4) eliminating hypoxic cells, and/ or (5) inhibiting the accelerated repopulation of tumor
& Jean-Francois H. Geschwind [email protected] 1
USA Vein Clinics and Oncology Centers, 304 Wainwright Drive, Northbrook, IL, USA
2
Section of Vascular and Interventional Radiology, Department of Radiology and Radiological Sciences, The Johns Hopkins Hospital, Baltimore, MD, USA
cells. However, if the combination of chemotherapy and radiation is beneficial against cancer, it is also clearly detrimental to normal tissues because of its enhanced toxicity, which has limited its use in cancers located within organs—liver cancer for example—that are especially vulnerable and sensitive to injury. As a result, combining chemotherapy with radiation is only helpful if the therapeutic benefits on tumors far exceed toxicities on normal tissues [2]. This is the main reason why liver cancer has traditionally been off limits for combined therapy. By combining chemotherapy and radiation in the form of irinotecan-loaded beads and yttrium-90 glass beads delivered intraarterially within minutes of each other, the authors of the manuscript in the current issue of CVIR demonstrate, in an animal model of metastatic liver cancer, that such combination is not only feasible technically and more potent than either one alone, but
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