Muneeb Ahmed

Principles of and Advances in Percutaneous Ablation

Image-guided tumor ablation with both thermal and nonthermal sources has received substantial attention for the treatment of many focal malignancies. Increasing interest has been accompanied by continual advances in energy delivery, application technique, and therapeutic combinations with the intent to improve the efficacy and/or specificity of ablative therapies. This review outlines clinical percutaneous tumor ablation technology, detailing the science, devices, techniques, technical obstacles, current trends, and future goals in percutaneous tumor ablation. Methods such as chemical ablation, cryoablation, high-temperature ablation (radiofrequency, microwave, laser, and ultrasound), and irreversible electroporation will be discussed. Advances in technique will also be covered, including combination therapies, tissue property modulation, and the role of computer modeling for treatment optimization.

Image-guided Tumor Ablation: Standardization of Terminology and Reporting Criteria—A 10-Year Update

Image-guided tumor ablation has become a well-established hallmark of local cancer therapy. The breadth of options available in this growing field increases the need for standardization of terminology and reporting criteria to facilitate effective communication of ideas and appropriate comparison among treatments that use different technologies, such as chemical (eg, ethanol or acetic acid) ablation, thermal therapies (eg, radiofrequency, laser, microwave, focused ultrasound, and cryoablation) and newer ablative modalities such as irreversible electroporation. This updated consensus document provides a framework that will facilitate the clearest communication among investigators regarding ablative technologies. An appropriate vehicle is proposed for reporting the various aspects of image-guided ablation therapy including classification of therapies, procedure terms, descriptors of imaging guidance, and terminology for imaging and pathologic findings. Methods are addressed for standardizing reporting of technique, follow-up, complications, and clinical results. As noted in the original document from 2003, adherence to the recommendations will improve the precision of communications in this field, leading to more accurate comparison of technologies and results, and ultimately to improved patient outcomes. Online supplemental material is available for this article .

Image-guided tumor ablation: standardization of terminology and reporting criteria--a 10-year update.

Image-guided tumor ablation has become a well-established hallmark of local cancer therapy. The breadth of options available in this growing field increases the need for standardization of terminology and reporting criteria to facilitate effective communication of ideas and appropriate comparison among treatments that use different technologies, such as chemical (eg, ethanol or acetic acid) ablation, thermal therapies (eg, radiofrequency, laser, microwave, focused ultrasound, and cryoablation) and newer ablative modalities such as irreversible electroporation. This updated consensus document provides a framework that will facilitate the clearest communication among investigators regarding ablative technologies. An appropriate vehicle is proposed for reporting the various aspects of image-guided ablation therapy including classification of therapies, procedure terms, descriptors of imaging guidance, and terminology for imaging and pathologic findings. Methods are addressed for standardizing reporting of technique, follow-up, complications, and clinical results. As noted in the original document from 2003, adherence to the recommendations will improve the precision of communications in this field, leading to more accurate comparison of technologies and results, and ultimately to improved patient outcomes.

Small Liver Colorectal Metastases Treated with Percutaneous Radiofrequency Ablation: Local Response Rate and Long-term Survival with Up to 10-year Follow-up

PURPOSE To determine the long-term (10-year) survival of patients with colorectal liver metastases treated with radiofrequency (RF) ablation and systemic chemotherapy with intention to treat. MATERIALS AND METHODS Institutional review board approval was obtained for this study. From 1997 to 2006, 99 consecutive patients with 202 small (0.8-4.0 cm; mean: 2.2 cm ± 1.1) metachronous colorectal liver metastases underwent ultrasonography-guided percutaneous RF ablation with internally-cooled electrodes in association with systemic chemotherapy. Patients ineligible for surgery (n = 80) or whose lesions were potentially resectable and who refused surgery (n = 19) were included. Patients were followed up with contrast agent-enhanced computed tomography and/or magnetic resonance imaging for a minimum of 3 years to more than 10 years after RF ablation (n = 99, 67, 49, and 25 for 3, 5, 7, and 10 or more years, respectively). Overall local response rates and long-term survival rates were assessed. For each of these primary endpoints, Kaplan-Meier curves were generated and log-rank tests were used to assess for statistically significant differences. RESULTS Primary and secondary technical success rates were 93.1% (188 of 202) and 100% (14 of 14), respectively. Local tumor progression occurred in 11.9% (24 of 202) metastases, and 54.2% (13 of 24) of these were re-treated. Patient survival rates increased with re-treatment versus no re-treatment (P < .001). At follow-up, 125 new liver metastases were found, and of these 32.8% (41 of 125) were treated with RF ablation. Overall survival rates were 98.0%, 69.3%, 47.8%, 25.0%, and 18.0% (median: 53.2 months) at 1, 3, 5, 7, and 10 years, respectively. The major complication rate was 1.3% (two of 156), and there were no procedure-related deaths. At the time this article was written, 32.3% (32 of 99) of the patients were alive, and 67.7% (67 of 99) were deceased, with a median follow-up of 72 months. CONCLUSION Adding RF ablation to systemic chemotherapy achieved local control in a large majority of metachronous colorectal liver metastases. The 3- to 10-year survival rates of this relatively large series of patients were essentially equivalent to those of most surgical series reported in the literature.

Thermal Ablation Therapy for Hepatocellular Carcinoma

Thermal ablation strategies, including the use of radiofrequency, microwaves, lasers, and high-intensity focused ultrasound, are gaining increasing attention as an alternative to standard surgical therapies in the treatment of primary hepatocellular carcinoma. Benefits over surgical resection include the anticipated reduction in morbidity and mortality, low cost, suitability for real-time imaging guidance, ability to perform ablative procedures on an outpatient basis, and the potential application in a wider spectrum of patients-including those who are not surgical candidates. In this review, the authors examine the reported clinical success of each of these four therapies, potential complications, current limitations, and future directions of development.

Combination radiofrequency thermal ablation and adjuvant IV liposomal doxorubicin increases tissue coagulation and intratumoural drug accumulation.

There has been marked interest in minimally-invasive, image-guided radiofrequency (RF) tumour ablation (i.e. coagulating tumour using short duration heating (<15 min) by directly applying temperatures >50°C via needle electrodes) to treat focal liver, renal, breast, bone and lung tumours. In spite of advances in RF technology and improved understanding of tumour biophysiology that now enable experimental treatment of tumours up to 5 cm, investigators have been unable to achieve complete ablation in many cases, particularly at the tumour margins and adjacent to blood vessels. One strategy for overcoming these limitations has been to take advantage of complementary interactions between RF thermal ablation and chemotherapy, particularly liposomal doxorubicin preparations, to attempt more complete tumour destruction. This paper will review published laboratory investigations demonstrating that this combined treatment paradigm has the unique potential both to potentiate preferential delivery of cytotoxic agents in liposome vehicles and to maximize the completeness of ablation of a treated tumour. New confirmatory data describing increased tumour destruction with RF ablation combined with different liposome preparations, documenting increased lipid peroxidation and expanding on previously published tumour growth studies is presented. Additionally, early clinical data including a randomized, pilot clinical study on 10 patients with primary and metastatic liver tumours, in which a non-optimized combination of RF ablation and IV liposomal doxorubicin (Doxil) increased the volume of tumour destruction 25–30% compared to RF alone, will also be described in detail.

Improved Coagulation with Saline Solution Pretreatment during Radiofrequency Tumor Ablation in a Canine Model

PURPOSE To determine whether pretreatment with local NaCl injection can increase radiofrequency (RF)-induced coagulation in a large animal model. MATERIAL AND METHODS Multiple canine venereal sarcomas (n = 25) were implanted subcutaneously in eight mildly immunosuppressed dogs (25 mg/kg cyclosporin A twice daily). Tumors were incubated for 8-12 weeks to a diameter of 4.2-6.3 cm (5.1 cm +/- 0.7). Internally cooled RF ablation (1-cm tip; 12 min; pulsed technique; 2,000-mA maximum) was performed. Tumors were pretreated with 6 mL of 18%, 24%, or 36% NaCl injected intratumorally under direct ultrasound guidance after RF electrode insertion, and this treatment was compared to RF treatment without NaCl injection and to 36% NaCl injection without RF ablation. Impedance measurements and remote thermometry were performed. These measurements and resultant coagulation were compared. RESULTS Significantly greater RF heating (73 degrees C +/- 11 degrees C at 20 mm) was observed when the tumors were treated with 24% or 36% NaCl pretreatment, compared to the 47 degrees C +/- 5 degrees C observed when 18% or no NaCl was injected (P <.02). In the 36% NaCl group, the entire tumor (5.2 cm +/- 0.8 diameter) was completely ablated in every case, with coagulation extending several centimeters into the surrounding tissues. By comparison, control tumors (without NaCl injection) contained coagulation measuring 3.1 cm +/- 0.2, surrounded by viable, well-perfused tumor (P <.01), and 36% NaCl alone produced 2.7 cm +/- 0.6 of patchy necrosis. CONCLUSIONS Pretreatment with intratumoral injection of small volumes of highly concentrated NaCl markedly increases RF heating and coagulation in a large animal tumor model. The complete destruction of tumors 5 cm in diameter or larger suggests that this substantial increase may be achieved for tumor ablation in clinical practice.

Characterization of the RF ablation-induced ‘oven effect’: The importance of background tissue thermal conductivity on tissue heating

Purpose: To determine the effect of background tissue thermal conductivity on RF ablation heating using ex vivo agar phantoms and computer modelling. Method: Two-compartment cylindrical agar phantom models (5% agar, 5% NaCl, 3% sucrose) were constructed. These included a standardized inner compartment (2 cm diameter, 4 cm length, 0.25% agar) representing a tumour, surrounded by an outer compartment representing background tissue. The thermal conductivity of the outer compartment was varied from 0.48 W m−1°C (normal liver) to 0.23 W m−1°C (fat) by adding a fat-saturated oil-based solute (10–90%) to the agar. RF ablation was applied at 2000 mA current for 2 min. Temperatures were recorded up to 4 cm from the electrode tip at 1 cm intervals. Subsequently, a 2-D finite element computer model was used to simulate RF ablation of 2–24 min duration for tumours measuring 2–4 cm in diameter surrounded by tissues of different thermal conductivity with the presence or absence of perfusion (0–5 kg m−3 s−1) (n = 44). A comparison of results was performed. Results: In agar phantoms, the amount of fat in the background tissue correlated with thermal conductivity as a negative exponential function (r2 = 0.98). Significantly increased temperatures were observed at the edge of the inner compartment (1 cm from the electrode tip) as the fat content of the outer compartment increased (p < 0.01). Thus, temperatures at 2 min measured 31.5 ± 2.2°C vs 45.1 ± 3.1°C for thermal conductivities of 0.46 W m−1°C (10% fat) and 0.23 W m−1°C (90% fat), respectively. On the other hand, higher levels of fat led to lower temperature increases in the background compartment (0.2 ± 0.3°C for 90% fat vs. 1.1 ± 0.05°C for 10% fat, p < 0.05). Phantom thermal heating patterns correlated extremely well with computer modelling (r2 = 0.93), demonstrating that background tissues with low thermal conductivity increase heating within the central tumour, particularly for longer durations of RF ablation and in smaller tumours. Furthermore, computer modelling demonstrated that increases in temperature at the tumour margin for background tissues of lower thermal conductivity persisted in the presence of perfusion, with a clinically relevant 4.5°C difference between background thermal conductivities of fat and soft tissue for a 3 cm tumour with perfusion of 2 kg m−3 s−1, treated for 12 min. Conclusion: Lower thermal conductivity of background tissues significantly increases temperatures within a defined ablation target. These findings provide insight into the ‘oven effect’ (i.e. increased heating efficacy for tumours surrounded by cirrhotic liver or fat) and highlight the importance of both the tumour and the surrounding tissue characteristics when contemplating RF ablation efficacy.

Computer modeling of the effect of perfusion on heating patterns in radiofrequency tumor ablation

Purpose: To use an established computer simulation model of radiofrequency (RF) ablation to further characterize the effect of varied perfusion on RF heating for commonly used RF durations and electrode types, and different tumor sizes. Methods: Computer simulation of RF heating using 2-D and 3-D finite element analysis (Etherm) was performed. Simulated RF application was systematically modeled on clinically relevant application parameters for a range of inner tumor perfusion (0–5 kg/m3-s) and outer normal surrounding tissue perfusion (0–5 kg/m3-s) for internally cooled 3-cm single and 2.5-cm cluster electrodes over a range of tumor diameters (2–5 cm), and RF application times (5–60 min; n = 4618 simulations). Tissue heating patterns and the time required to heat the entire tumor ± a 5-mm margin to >50°C were assessed. Three-dimensional surface response contours were generated, and linear and higher order curve-fitting was performed. Results: For both electrodes, increasing overall tissue perfusion exponentially decreased the overall distance of the 50°C isotherm (R2 = 0.94). Simultaneously, increasing overall perfusion exponentially decreased the time required to achieve thermal equilibrium (R2 = 0.94). Furthermore, the relative effect of inner and outer perfusion varied with increasing tumor size. For smaller tumors (2 cm diameter, 3-cm single; 2–3 cm diameter, cluster), the ability and time to achieve tumor ablation was largely determined by the outer tissue perfusion value. However, for larger tumors (4–5 cm diameter single; 5 cm diameter cluster), inner tumor perfusion had the predominant effect. Conclusion: Computer modeling demonstrates that perfusion reduces both RF coagulation and the time to achieve thermal equilibrium. These results further show the importance of considering not only tumor perfusion, but also size (in addition to background tissue perfusion) when attempting to predict the effect of perfusion on RF heating and ablation times.

Computer modeling of the combined effects of perfusion, electrical conductivity, and thermal conductivity on tissue heating patterns in radiofrequency tumor ablation

Purpose. To use an established computer simulation model of radiofrequency (RF) ablation to characterize the combined effects of varying perfusion, and electrical and thermal conductivity on RF heating. Methods. Two-compartment computer simulation of RF heating using 2-D and 3-D finite element analysis (ETherm) was performed in three phases (n = 88 matrices, 144 data points each). In each phase, RF application was systematically modeled on a clinically relevant template of application parameters (i.e., varying tumor and surrounding tissue perfusion: 0–5 kg/m3-s) for internally cooled 3 cm single and 2.5 cm cluster electrodes for tumor diameters ranging from 2–5 cm, and RF application times (6–20 min). In the first phase, outer thermal conductivity was changed to reflect three common clinical scenarios: soft tissue, fat, and ascites (0.5, 0.23, and 0.7 W/m-°C, respectively). In the second phase, electrical conductivity was changed to reflect different tumor electrical conductivities (0.5 and 4.0 S/m, representing soft tissue and adjuvant saline injection, respectively) and background electrical conductivity representing soft tissue, lung, and kidney (0.5, 0.1, and 3.3 S/m, respectively). In the third phase, the best and worst combinations of electrical and thermal conductivity characteristics were modeled in combination. Tissue heating patterns and the time required to heat the entire tumor ±a 5 mm margin to >50°C were assessed. Results. Increasing background tissue thermal conductivity increases the time required to achieve a 50°C isotherm for all tumor sizes and electrode types, but enabled ablation of a given tumor size at higher tissue perfusions. An inner thermal conductivity equivalent to soft tissue (0.5 W/m-°C) surrounded by fat (0.23 W/m-°C) permitted the greatest degree of tumor heating in the shortest time, while soft tissue surrounded by ascites (0.7 W/m-°C) took longer to achieve the 50°C isotherm, and complete ablation could not be achieved at higher inner/outer perfusions (>4 kg/m3-s). For varied electrical conductivities in the setting of varied perfusion, greatest RF heating occurred for inner electrical conductivities simulating injection of saline around the electrode with an outer electrical conductivity of soft tissue, and the least amount of heating occurring while simulating renal cell carcinoma in normal kidney. Characterization of these scenarios demonstrated the role of electrical and thermal conductivity interactions, with the greatest differences in effect seen in the 3–4 cm tumor range, as almost all 2 cm tumors and almost no 5 cm tumors could be treated. Conclusion. Optimal combinations of thermal and electrical conductivity can partially negate the effect of perfusion. For clinically relevant tumor sizes, thermal and electrical conductivity impact which tumors can be successfully ablated even in the setting of almost non-existent perfusion.