Ablation techniques produce unique tissue effects

New York-Optimizing outcomes using focal tumor ablation techniques depends on acquiring a better understanding of the tissue effects of these technologies, according to a recent study.

With that goal in mind, a study was undertaken in a porcine model directly comparing histologic changes in solid organs treated by radiofrequency ablation (RFA), cryotherapy, irreversible electroporation (IRE), and vascular-targeted photodynamic therapy (VTP) using the photosensitizer WST-11 (TOOKAD Soluble, Steba Biotech). Overall, the results showed that each of the four methods produced different effects specific to the modality being used and influenced by organ tissue architecture and vascularization.

A. RFA works by generating heat that destroys tissue by denaturing proteins. B. Cryotherapy relies on rapid cooling to provoke coagulative necrosis and tissue destruction. C. VTP is a non-thermal ablation technology that exerts its action when a photosensitive compound, WST-11 (blue spheres), is delivered intravenously, then activated by light delivered by laser fibers. Reactive oxygen and nitrogen species are created that cause vascular occlusion, tissue necrosis, and apoptosis. D. In IRE, pulses of electrical current delivered through needles create pores in cellular membranes to produce irreversible cellular effects such as apoptosis and tissue necrosis. (Illustrations courtesy of Simon Kimm, MD)

In the study, each technology was used under image guidance to create multiple ablations in the liver, kidney, and pancreas. Contrast-enhanced computed tomography imaging was performed immediately after treatment and again after 24 hours, and the treated organs from individual animals were removed at 4 or 24 hours for histologic evaluation.

“Increasingly, we are identifying patients with early, small, localized cancers, providing an opportunity for focal treatment of tumors while sparing surrounding normal tissues,” said first author Simon Kimm, MD, clinical fellow in urologic oncology at Memorial Sloan-Kettering Cancer Center, New York. “There is a great diversity of energy delivery systems under development, with each capable of eradicating cancer. Our research shows there are clear differences in the tissue effects of these therapies, which may impact how patients respond. In designing trials to evaluate individual techniques, there needs to be an understanding of the capabilities and limitations of each technology."

The research marks the first direct comparison of the four modalities, according to Dr. Kimm, who presented the findings at the AUA annual meeting in San Diego.

“Our study shows the procedures invoke different and complex tissue responses, both acutely and at intermediate time points. Describing these technologies only as to whether they cause thermal or non-thermal injury is too simplistic, and we believe better characterizing these effects will help to optimize outcomes and provide benchmarks for assessment of tumor response in clinical trials,” added Dr. Kimm, who worked on the study with principal investigators Jonathan Coleman, MD, of Memorial Sloan-Kettering, and Avigdor Scherz, PhD, of the Weizmann Institute of Science in Rehovot, Israel, and colleagues.

Acute tissue necrosis after RFA, cryotherapy

Summarizing the study findings, Dr. Kimm reported that the detailed histologic analyses revealed acute tissue necrosis and collagen denaturation after use of the thermal technologies (RFA and cryotherapy), whereas after VTP and IRE there were well-demarcated areas of hyperemia and hemorrhage followed by progression to coagulative necrosis at 24 hours. Pronounced infiltration of inflammatory cells was noted at 4 hours following cryotherapy, but was not observed in tissues treated by RFA.

Other observations included the presence of a “heat sink” effect after treatment with RFA, resulting in findings of irregular lesion boundaries, and areas of tissue sparing around blood vessels. VTP created sharp areas of complete ablation, while demonstrating treatment effect around blood vessels up to 400 microns in size. RFA, cryotherapy, and IRE ablated all blood vessels within the treatment zone.

The techniques also varied in their extracellular matrix effects as significant collagen denaturation was observed early after RFA and cryotherapy, while collagen architecture was preserved after ablation with IRE and VTP.

Dr. Kimm noted that further studies are needed to determine whether the sparing of smaller vessels and collagen after VTP is clinically significant in the recovery of tissues after ablation. In addition, an ongoing study is investigating whether VTP, like cryotherapy, invokes an immune response that may have value for enhancing tumor immunity.

The Thompson Family Foundation provided funding for the study.UT

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