PHYSICS, RECENT ADVANCES
Year : 2003 | Volume
: 13 | Issue : 3 | Page : 315--322
Image-guided radiofrequency ablation of tumors : Current status
B Nazir, AK Chaturvedi, A Rao
Rajiv Gandhi Cancer Institute and Research Centre, Sector-5, Rohini, New Delhi-110085, India
A K Chaturvedi
Dept of Radiology, Rajiv Gandhi Cancer Institute and Research Centre, Sector-5, Rohini, New Delhi-110085
|How to cite this article:|
Nazir B, Chaturvedi A K, Rao A. Image-guided radiofrequency ablation of tumors : Current status.Indian J Radiol Imaging 2003;13:315-322
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Nazir B, Chaturvedi A K, Rao A. Image-guided radiofrequency ablation of tumors : Current status. Indian J Radiol Imaging [serial online] 2003 [cited 2021 Jan 26 ];13:315-322
Available from: https://www.ijri.org/text.asp?2003/13/3/315/28707
Radiofrequency ablation (RFA) is a relatively nascent treatment modality that uses thermal energy for destroying the tumor. Multiple techniques have been tried for tissue ablation, which includes percutaneous ethanol injection (PEI), interstitial lasers, cryotherapy, microwave ablation, and focused ultrasound therapy. In the present era of minimal invasive surgery, radiofrequency ablation of tumor is an attractive option for local tumor control in patients who are not surgical candidates or who have failed conventional therapies. It has a potential to replace the surgical resection as a curative treatment for tumor, particularly in old and debilitated patients. Recent developments in radiofrequency technology now allow ablation of larger volume of tissue, rendering RFA more effective and safer method for the local control of tumors than ever before.
Heat has been used in medicine as long as history. Ancient Hindu medicine used heated metal bars and the Greeks used heated stones to stop bleeding. D'Arsonval in 1891 first introduced radiofrequency current as a clinical tool in the form of electrocautery and medical diathermy. Electrocautery has been used for decades in surgery to fulgurate, cut tissue and to stop bleeding. The RFA, first pioneered by McGahan and Rossi, is a modification of the same technology to deposit the energy over a precise volume. RFA has been used for years for various clinical applications including ablation of aberrant conduction bundle in Wolff-Parkinson-White (W.P.W.) syndrome and of ganglion in trigeminal neuralgia. RFA application in tumor management is a relatively new development.
Most mammalian cells do not survive temperature exceeding 42°C . Tissue develops coaggulative necrosis within 45 minutes of prolonged exposure at 42-46°C . Death begins to occur with in 4-6 minutes at 50°C and occurs more rapidly with increasing temperature. It becomes near instantaneous above 60°C. At 100°C, the cell membrane melts, intracellular water vaporizes and tissue get desiccated and charred.
Radiofrequency ablation is virtually "Cooking tumors with Needles". It is based on the High frequency induced thermo therapy (HiTT). A high frequency current alternating rapidly at approximately 480 KHz (with in range of radio transmission) is delivered to the tumor tissue via a needle electrode. As the current alternates, the ions in the vicinity of the needle tip rapidly change direction (ionic agitation), which causes frictional heating of the tissue (resistive heating) and cell death by coaggulative necrosis . Thus, the tissue itself is the source of heat rather than the electrode tip. The amount of heat deposited in the tissue is proportional to the strength of the current and the resistance of the tissue (D°a I2R) and falls off approximately at inverse fourth power of the distance. With present system, usually a sphere of 4.5-5 cm of hyperthermia is created at the tip [Figure 1]. Since the temperature falls off drastically at the periphery, the goal of the procedure is to include a margin of 1cm of normal tissue within the sphere. Small vessels less then 3 mm in diameter are cauterized during the procedure. This reduces the risk of hemorrhage during the procedure. Also the ensuing tissue hypoxia contributes to the complete ablation of tumor. The cells are not removed but become scar tissue and eventually shrink.
The limiting factor is an excessive heat deposition (>100°C), which results in charring and gas formation near the needle tip. This reduces the current flow and breaks the circuit . Thus the aim of the RFA is to produce controlled and precise deposition of heat without producing microbubbles and charring. This can be markedly reduced by injection of saline into the tissue or cooling the needle tip with chilled saline ,.
Another liming factor is a large vessel adjacent to a tumor, which prevents adequate hyperthermia due to rapid heat loss in the inflowing blood (the "heat-sink" effect). This explains increased incidence of residual or recurrent disease in the vicinity of a vessel. Method that reduce blood flow like balloon occlusion of vessel  during percutaneous approach or mechanical compression hepatic pedicle during laparotomy ("Pringle maneuver") minimize the heat-sink effect.
In contrast, encapsulated tumors like hepatocellular carcinoma (HCC) are more amenable to ablation as they allow for greater deposition of heat due to compartmentalization of thermal energy by the capsule (the "oven effect").
Chemotherapeutic agent Doxarubicin, particularly the liposome-encapsulated preparation, has been shown to have synergistic effect with radiofrequency ablation if used concomitantly.
The needle used for RFA is a specially designed needle electrode having an insulated shaft and a conducting tip [Figure 2]. The needle commonly used in liver is of 16G. One particular type has internal channel for saline flow for cooling (Radionics) while the other have holes at the tip for injecting saline into the tissue to increase conductivity (Berchtold). Some have expandable multiple arrays at the tip to increase zone of heat coagulation (Radiotherapeutics, RITA) [Figure 3]. Similarly, two needles may be inserted at the same time (Bipolar method) with the same objective.
This procedure is commonly performed under ultrasound, CT (preferably CT-Fluoroscopy) [Figure 4] or MRI guidance. Route of insertion is usually percutaneous [Figure 5] although it can also be done laparoscopically or even per-operatively (Open method). Percutaneous approach is preferred as it is least invasive, can be performed on out patient basis and the procedure can be repeated if needed. Laparoscopic and open approach are used if the lesion is close to the vital structures like diaphragm or when the lesion is small and peripherally located since the needle placement is more precise and accurate with these methods. Open method for liver metastases can be judiciously combined with laparotomy for resection of the primary tumor.
Needle is connected to the high frequency, low voltage current generator [Figure 6] and the patient is turned into an electrical circuit by placing grounding pads on the body surface close to the insertion site [Figure 7]. Generator delivers 50-200 watts of energy depending upon the impedance of the heated tissue. Cooled saline is intermittently perfused into the needle by a pump to maintain the tip temperature less then 100°C in order to prevent charring, which is the most important factor limiting heat generation . An impedance value of less then 50 W indirectly indicates the absence of significant charring.
Pre-procedure evaluation includes cross-sectional studies to determine the extent and number of the lesion, liver function tests, coagulation studies, and ECG. Pretreatment titers of tumor markers like alpha-fetoprotein in HCC and carcinoembryonic antigen in colorectal metastasis are essential for monitoring the response to RFA
The procedure is safely performed on an outpatient basis under conscious sedation (neuroleptanalgesia) with Ketamine and Fentanyl. The typical ablation session last for 10-20 minutes, depending on the size of lesions. Lesions with diameter up to 3-5 cm can be treated in a single session. Larger lesions may need multiple insertions. At the end of session, the needle tract is cauterized by withdrawing the needle at low power output. This prevents bleeding and seeding of the track.
Follow-up is done with a dynamic CT-scan or MRI within a month to access the adequacy of ablation and again at 3 monthly intervals, along with tumor markers to detect residual disease or recurrence. Post-treatment dynamic CT-scan should show a completely non-enhancing hypodense area [Figure 8],[Figure 9],[Figure 10],[Figure 11] with diameter larger or equal to the pretreatment diameter and with no enhancing focus although early in the course, a peripherally enhancing rim may be seen due to inflammatory response of the normal tissue. Power Doppler, using ultrasonic contrast agents, will show absence of blood flow within the lesion suggesting the total ablation of tumor. With time, the lesion becomes more circumscribed. The natural history of treated tumor is slow shrinkage over the course of months to year. Residual disease or recurrence is indicated by appearance of abnormal enhancing focus on CT Scan or MRI. Stagnant or rising titer of tumor makers also suggest residual disease or recurrence although this may be misleading in hepatocellular carcinoma because background cirrhosis can contribute to the titer rise. Moreover, alpha-fetoprotein is normal in 35 % of patients of HCC.
Doubtful focus may warrant a selective hepatic arteriography, which will show tumor vascularity at the site. An FNAC from the suspicious focus is confirmatory. Preliminary results shows PET scan more effective then CT-scan or MRI for the detection of residual and recurrent disease. Residual or recurrent disease can be treated with another session of RFA.
Patient selection and Outcome
Some of the following diseases like hepatocellular carcinoma and liver metastases have become standard RFA indication while in other diseases, the initial experience is still limited and the technique is under evaluation.
Hepatocellular Carcinoma: RFA was primarily developed for treating hepatocellular carcinoma [Figure 10],[Figure 11]. HCC have poor response to chemotherapy and radiotherapy. Surgical resection has been considered the only potentially curative option but the majority of patients are not amenable to resection due to the large size, location near major intra-hepatic blood vessels, underlying cirrhosis or a multicenteric disease. Percutaneous ethanol injection has been used as local treatment for small HCC but its response is unpredictable due to inhomogeneous distribution of alcohol with in the tumor. RFA is a safe and quick alternative to surgery with a curative potential. After RFA treatment, median survival is 44 months with 10% local recurrence , which is comparable to that found in surgical series. Early recurrences (within 2 years) are due to both local and new lesions while late recurrences (after 2 years) are due to new lesions. Local recurrence rate is less than PEI while the total recurrence is similar to that reported after surgery or PEI . Due to the "oven effect", encapsulated HCC has least recurrence rate among all liver tumors treated with RFA. The effectiveness of RFA treatment is significantly dependent on tumor size. Lesions up to 3 cm undergo complete ablation while the larger lesion requires multiple RFA treatment to prevent recurrence .
RFA is particularly indicated in certain special situations. Cirrhosis of liver is a common background in Asian and European countries. These patients have friable liver and the multicenteric form of HCC, which largely rules out a surgical intervention. For both of these reasons, RFA is being used as first line of treatment in HCC patients with cirrhotic background. RFA may be repeated for residual or recurrent tumor. For both the local and systemic control of the disease, RFA can be combined with other modalities like surgery, chemotherapy, PET or chemoembolization.Liver metastasis: Patients with liver metastasis do not survive beyond one year if left untreated . Such patients rarely die due to primary disease. The most common and immediate cause of death in these patients is liver failure due to extensive hepatic involvement. Reduction in the tumor load in liver prolongs the survival. Long-term survival can be achieved in such patients if the metastatectomy is performed (90% at 1 year and 20-40% at 5 year). However, only 5-10% of patients are suitable for surgical resection due to the advanced age, extra-hepatic involvement and comorbid conditions. RFA is an equally affective alternative to surgical resection [Figure 8],[Figure 9]. The goal is to reduce the tumor burden on the patient. Lesions too numerous to be resected or multiple in number are effectively treated with radio frequency ablation. Presently, RFA is being used for liver metastases from primaries in colon, breast, carcinoid and lung . RFA is particularly suitable for colorectal metastases since their metastatic predilection for liver is both high and specific. Half of these patients develop liver metastases and in 20% of cases it is confined only to liver without involvement of extra-hepatic sites. In patients of carcinoid syndrome who have paraneoplastic symptoms, marked symptomatic relief can be achieved after ablation of metastatic deposits in liver. The overall survival rate after RFA is 86-94% at one year and 89% at 1.5 years. Fifty-three percent of patients remain disease free at one year and thirty-three percent at 18 months . This is significantly higher than the survival rate without treatment . Local recurrence rate after RFA is about 19% at one year. Local recurrence is particularly more common with lesion of diameter larger than 3 cm. Metastatic adenocarcinoma and sarcoma tend to have higher recurrence rate.Renal cell carcinoma: Radical nephrectomy is the mainstay of treatment in renal cell carcinoma (RCC). However, RFA provides an alternative to surgery in patients where renal conservation is desired . These include patients with solitary kidney, bilateral and recurrent tumors (as in von Hippel Lindau syndrome) & nonfunctioning opposite kidney. It is particularly useful in small incidental RCC, unresectable tumors, and in patients with borderline kidney functions. In bulky tumors, RFA may be done preoperatively to decrease intraoperative blood loss. Large pararenal fat allow extra deposition of heat in the kidney resulting in adequate ablation ,. Breast Cancer: Advances in imaging have resulted in detection of more and more small sized breast cancers. The standard treatment has been the radical mastectomy. Lumpectomy although less disfiguring, still causes cosmetic defect and surgical morbidity. RFA is an ideal breast-conserving procedure for the management of small breast cancers, detected incidentally on screening mammography. Needle is introduced into the tumor through a nick in the skin under ultrasound guidance and the total procedure lasts for 10 to 15 minutes with no associated complications. Presently, tumors less 1.5cm are suitable for "RF lumpectomy" . RFA can also help patients with larger tumors that require removal of the entire breast. Preoperative RFA in these patients can shrink these tumors so they become small enough to be treated with lumpectomy. It is also suitable for elderly who are unfit for surgery . It is simple, safe and without cosmetic deformity. In small carcinoma treated with RFA, chemotherapy or radiotherapy can be exempted if sentinel nodes are negative.Lung tumors: There are many advantages of radiofrequency ablation over an open surgical procedure. Patients with multiple lung metastases cannot be treated with surgery because too much healthy lung tissue would have to be removed in order to rid the lung of all of the cancerous tissue. Radiofrequency ablation can be used to destroy the tumor while the remainder of the lung is spared. Patients with primary lung cancer who cannot tolerate surgical resection can be offered percutaneous radiofrequency ablation if it is technically feasible. Most patients treated with radiofrequency ablation need radiation or chemotherapy pertinent for their cell type and tolerance by the patient. Brain tumors: Radiofrequency is being used for ablating brain tumors. Procedure is performed under MR guidance using stereotactic probe guide and MR compatible needle . This technique is less invasive as needle is introduced through a burr hole under local anesthesia and it allows precise destruction of tumors without injury to vital structures. The technique is also less costly than open craniotomy & the morbidity is much reduced as vital centers in brain are preserved. Moreover, interventions like thalamotomy, pallidotomy and leucotomy can be done with RFA in certain neurological disorders.Bone tumors: RFA has been safely used for years to treat osteoid osteomas. In fact, some prefer RFA as primary modality for treating osteoid osteoma. Painful osseous metastases are effectively treated by RFA and it provides an additional way to treat refractory pain in patients who have exhausted conventional therapy. It provides prompt relief in bone pain unlike radiation therapy that takes weeks to show effect. RFA can also be combined with conventional treatment like radiation therapy.RF Nerve ablation: Neuralgic pain is common in cancer patients due to infiltration of nerves by tumor. Neuralgic pain is usually intractable to conventional analgesics and account for the major morbidity in cancer patients. Ablating the sensory nerves with RFA give prompt & gratifying relief in pain in these patients. Prior infiltration of local anesthetic at the nerve ablation site helps to assess the effectiveness of the procedure and foresee any potential complication like motor paralysis. Adrenal: RFA is being safely performed on adrenal tumor, including unresectable adrenocortical carcinoma, adrenal metastases, and even pheochromocytoma. RFA may be effective for the short-term local control of adrenal tumors. The local disease control can potentially influence survival as well.Pancreatic tumors: Role of RF ablation in pancreas is still under evaluation. Pancreatic tumors need radical surgery like Whipple's procedure. Small size tumors can be ablated with percutaneous RFA with low morbidity. Many of these tumors like those of Islet cells origin are detected only on intraoperative sonography. These tumors can be treated with the intraoperative RFA in the same sitting. Spleen masses: RFA is an effective minimally invasive option for patients with splenic masses who need splenectomy . Splenectomy results in morbidity, requires hospitalization with lengthy recovery & has a high cost. Radiofrequency ablation preserves normal parenchyma and hence the splenic function. Infections after splenectomy are not seen after treatment with RFA. It is a safe procedure in patients with multiple medical problems, comorbid conditions or who have high surgical risk.Prostate: Surgery for benign prostatic hyperplasia and prostate cancer is not without morbidity. These patients are usually old & have multiple comorbid conditions. RFA provides a safer option for removing abnormal prostatic tissue. It predictably destroys the entire gland with a very low complication rate.Uterine Fibroid: RFA can ablate uterine fibroids. Multiple fibroids can be treated without resorting to hysterectomy. It is particularly useful in patients of reproductive group where uterus conservation is desired. Procedure is performed laparoscopically with a very low incidence of hemorrhage or infertility.Soft tissue tumor: Unresectable large and recurrent tumor can respond to RFA. Patient who are not surgical candidates or who have exhausted chemotherapy and radiation therapy may still be a candidate for percutaneous RFA. For large tumor, the goal may be palliation instead of cure. Several tumors can be treated during one procedure, which typically takes one to two hours to complete.Lymph nodes: RFA is being evaluated for ablating lymph nodes with metastasis from tumor such as skin melanoma. Nodal masses in axilla or groin can be ablated after the primary tumor is resected through surgery. Thus, an open and radical node dissection can be avoided by using this technique.
It is an extremely safe procedure. The incidence of complication is usually less then 5 percent. These include:
Post ablation syndrome: It is a tissue lyses-related phenomenon characterized by transient "flu like" symptoms, low-grade fever, lethargy and sweating. It is self-limiting and usually resolves without treatment within 5 days. It is common after ablation of large tumor volume . Adequate hydration before and after procedure reduces the incidence and severity of symptoms.Thermal Injury: This includes skin burns at ground pad site [Figure 12]. As such, thermal injury to vessels is unknown due to "heat-sink" effect.Collateral visceral injuries: Diaphragm and bowel necrosis can occur if the lesion is close to these structures.Pleural effusion: It is reactive phenomenon and is usually mild and transient. It is commonly seen in lesions close to the diaphragm.Hemorrhage: This can be prevented by correcting the coagulation profile and by ablating the needle track. Hepatic hematoma and abscess. Accelerated liver failure.
RFA has many advantages over surgery including low complication rate, reduced cost and increased patient compliance. It is simple, safe, and an effective treatment modality. It is less risky and has low morbidity & mortality as compared to surgery. Most of these procedures are performed without general anesthesia on outpatient basis. Hospital stay is short and most patients can resume normal activities within a few days. The procedure can be repeated if necessary and can be combined with other available treatment modalities.
RFA is preferred over other techniques available for local control of tumors. As compared to percutaneous ethanol injection, RFA produces a more predictable volume of necrosis and is not impaired by hard consistency of metastatic tissue. PEI requires greater number of sessions (approximately 5 to 8) resulting in poor patients compliance and increased morbidity.
Compared to laser therapy, RFA is cheaper, does not require multiple fiber insertions and produces a larger volume of ablation.
RFA can be done percutaneously unlike Cryotherapy, which needs open surgery and liver mobilization. There is less morbidity since the needle used is thinner than the cryotherapy probe.
However, RFA treats only the macroscopic disease unlike systematic or hepatic arterial infusion chemotherapy and it does not address the microscopic disease or macroscopic tumor other than the one treated. RFA is designed to work in conjunction with surgery, radiotherapy and chemotherapy and is not intended to replace these modalities. RFA can be used to treat larger lesions while smaller lesions can be dealt with chemotherapy. Similarly, RFA can debulk large tumors, which can be treated with chemotherapy. Post RFA chemotherapy prevents recurrences due to occult micrometastates. Surgery can be performed to remove the primary tumor while RFA can be used to treat metastatic disease in other organs like liver, lung or spleen. The two procedures can be performed in the same sitting during a laparotomy. RFA is, therefore a welcome addition to the armamentarium of an interventional radiologist and its immense potential needs to be fully explored & exploited.
We are grateful to Dr Athar H. Siddiqui and Mr Navaid Mohsin for their help in the preparation of the manuscript and illustrations.
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