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Percutaneous Image-Guided Radiofrequency Ablation of Painful Metastases Involving Bone: A Multicenter Study

From the Departments of Oncology, Diagnostic Radiology, Anesthesiology, Biostatistics, and Radiation Oncology, Mayo Clinic, Rochester, MN; St Luke's Hospital, Milwaukee, WI; Institute for Cancer Research and Treatment, Torino; Department of Orthopaedic Oncology, CTO, Florence, Italy; Department of Radiology, Northwestern University Medical School, Chicago, IL; Institut for Microtherapy, Department of Radiology and Microtherapy, University Witten/Herdecke, Germany; Department of Radiology, M.D. Anderson Cancer Center, Houston, TX; Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD; Department of Radiology, Institut Gustave Roussy, Villejuif, France

Address reprint requests to J. William Charboneau, MD, Department of Radiology, Mayo Clinic, 200 First St SW, Rochester, MN 55905; e-mail: charboneau.william{at}mayo.edu

	ABSTRACT

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... REFERENCES

 
PURPOSE: Few options are available for pain relief in patients with bone metastases who fail standard treatments. We sought to determine the benefit of radiofrequency ablation (RFA) in providing pain relief for patients with refractory pain secondary to metastases involving bone.

PATIENTS AND METHODS: Thirty-one US and 12 European patients with painful osteolytic metastases involving bone were treated with image-guided RFA using a multitip needle. Treated patients had 4/10 pain and had either failed or were poor candidates for standard treatments such as radiation or opioid analgesics. Using the Brief Pain Inventory–Short Form, worst pain intensity was the primary end point, with a 2-unit drop considered clinically significant.

RESULTS: Forty-three patients were treated (median follow-up, 16 weeks). Before RFA, the mean score for worst pain was 7.9 (range, 4/10 to 10/10). Four, 12, and 24 weeks following treatment, worst pain decreased to 4.5 (P < .0001), 3.0 (P < .0001), and 1.4 (P = .0005), respectively. Ninety-five percent (41 of 43 patients) experienced a decrease in pain that was considered clinically significant. Opioid usage significantly decreased at weeks 8 and 12. Adverse events were seen in 3 patients and included (1) a second-degree skin burn at the grounding pad site, (2) transient bowel and bladder incontinence following treatment of a metastasis involving the sacrum, and (3) a fracture of the acetabulum following RFA of an acetabular lesion.

CONCLUSION: RFA of painful osteolytic metastases provides significant pain relief for cancer patients who have failed standard treatments.

	INTRODUCTION

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Bone metastases are a common problem in cancer patients and can cause significant pain and morbidity [1,2]. In patients who die from breast, prostate, and lung cancer, autopsy studies have shown that up to 85% have evidence for bone metastases at the time of death [2]. Bone metastases frequently give rise to complications that can affect quality of life, including pain, fractures, and decreased mobility, ultimately reducing performance status. In addition, these complications, along with the pain, can cause mood changes, with patients experiencing depression and anxiety [2-4].

Current treatments for patients with bone metastases are primarily palliative and include localized therapies (radiation and surgery), systemic therapies (chemotherapy, hormonal therapy, radiopharmaceuticals, and bisphosphonates), and analgesics (opioids and nonsteroidal anti-inflammatory drugs). Treatment with external beam radiation therapy (RT) is the standard of care for patients with localized bone pain, and results in the palliation of the majority of these patients; however, 20% to 30% of patients treated with RT do not experience pain relief [5-10]. Furthermore, patients who have recurrent pain at a site previously irradiated may not be eligible for further RT secondary to limitations in normal tissue tolerance.

Radiofrequency ablation (RFA) utilizes a high-frequency alternating current that is passed from the needle electrode into the surrounding tissue, resulting in frictional heating and necrosis. RFA has been studied extensively for the treatment of primary and metastatic disease involving the liver [11-13]. Dupuy et al [14] first reported that RFA of metastases involving bone may provide pain relief. Based on these observations, we conducted a feasibility study to determine the safety and benefits of RFA in patients with painful metastatic lesions involving bone [15]. Our preliminary data showed that this procedure was safe and resulted in significant relief of pain; therefore, this study was expanded to enroll patients from other centers in the United States and Europe.

	PATIENTS AND METHODS

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Patients
Throughout 17 months, from October 2000 through February 2002, 22 patients were enrolled and treated at the Mayo Clinic Rochester, and the results of the first 12 patients were reported [15]. Beginning in May 2001 through March 2002, additional patients were enrolled at a total of four other centers in the United States (nine patients) and four centers in Europe (12 patients). The institutional review board or ethics committee at each study center approved the protocol, and each patient provided informed consent. Criteria for enrollment, treatment, and follow-up were similar at all sites. Using the Brief Pain Inventory–Short Form (BPI-SF) [16], patients were required to have 4/10 worst pain scores on a numerical rating scale (0 indicates no pain, and 10 indicates worst pain imaginable) during a 24-hour period from 2 painful sites of metastases involving bone. Patients must have completed chemotherapy or radiation treatment more than 3 weeks before entrance into the study. Selection criteria also included age older than 18 years, the ability to give written consent, and a life expectancy greater than 2 months. The portion of lesions located within 1 cm of the spinal cord, brain, aorta, inferior vena cava, bowel, or bladder, as well as bone lesions with impending fracture, were not treated. Bone lesions that were predominantly blastic were not treated. Histologic proof of the patient's malignancy was available for all patients before treatment. If a patient had no prior history of RT to the proposed site of treatment, a radiation oncology consultation was required. A platelet count 75,000/µL and international normalized ratio 1.5 were required within 24 hours of the procedure. Computed tomography (CT), magnetic resonance (MR), and/or ultrasound (US) imaging, acquired within 8 weeks of entry into the study, were evaluated by one of the participating radiologists before entry into the study.

Treatment
Patients were treated under conscious sedation or general anesthesia at the discretion of the individual investigator. Two dispersive electrode-grounding pads were placed on the patient at equidistant sites from the radiofrequency source. Following sterile preparation, a Starburst XL electrode (RITA Medical Systems, Mountain View, CA) was introduced under CT, US, or fluoroscopic guidance into the lesion to be treated. The energy deposited by the electrode was controlled with a model 1500 generator (RITA Medical Systems). Once the target temperature of 100°C was obtained, this temperature was maintained for a minimum of 5 minutes, with a goal of 5 to 15 minutes. A single ablation was typically performed for lesions 3 cm in diameter. For larger lesions, the lesion was treated using multiple 3- to 5-cm deployments of the electrode. For lesions more than 5 cm in diameter, the ablation treatments were focused on the margin of the lesion involving bone, with the goal of treating the interface between soft-tissue or bone.

Immediate postprocedural pain was treated with either epidural or parenteral opioid analgesics. Depending on the size of the treated lesion and the degree of postoperative pain, patients were typically observed for a period ranging from 4 to 24 hours. Patients with persistent postprocedural pain were provided oral opioid analgesics at the time of discharge.

Re-Treatment of Lesions
Patients were evaluated for re-treatment with RFA if they (1) experienced an initial decrease of two or more points in worst pain within the first 4 weeks, and (2) had recurrence of pain beyond their initial baseline pain within the 6-month follow-up period. Two patients underwent re-treatment for recurrent pain.

Pre- and Posttreatment Assessment and Follow-Up
Worst pain was the primary end point and was measured using the BPI-SF. In the BPI-SF, patients are asked to rate their worst, least, and average pain during the preceding 24 hours, with allowed responses ranging from 0 (no pain) to 10 (worst pain imaginable). Relief of pain secondary to the RFA procedure or to pain medications is scored on a scale of 0% (no relief) to 100% (complete relief). Pain interference with daily living is evaluated with questions concerning general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Pain interference is also scored on a scale of 0 (no interference) to 10 (completely interferes). Each patient was asked to answer these questions with respect to the treated lesion.

Following discharge, the BPI-SF questionnaire was completed by a telephone interview with a study coordinator. Analgesic use was also recorded during these interviews. Patients completed the BPI-SF at baseline, the day following the treatment (US patients only), weekly for 1 month, and then every 2 weeks for the second month. Patients who had no improvement in pain (< two-point drop in worst pain) completed the study at week 8. Patients with a two-point or greater drop in worst pain at week 8 were observed bimonthly for a total follow-up of 6 months. Each patient underwent a contrast-enhanced CT examination or a plain film radiograph of the treated region 1 to 4 weeks after the treatment.

Statistical Methods
Design and procedures. This study was a single-arm prospective study using patients as their own controls. The initial efficacy observation period was 8 weeks, followed by a supplementary observational period of 4 months for patients who reported successful pain reduction within the initial period.

The primary end point was worst pain, scored on a 10-point numerical rating scale. We a priori defined a two-unit drop in pain as clinically significant [17].

The initial accrual goal for the evaluation of effectiveness was 36 patients. For the primary end points, a mean pretreatment pain score of 7 and a standard deviation of 2.0 units were assumed. Using a two-sided paired t test and a 5% type I error rate, 36 patients would provide greater than 90% power to detect a difference of two units between the pretreatment and 4-week follow-up scores. An interim analysis was performed and reported [15] once 12 patients had provided assessable data to determine the preliminary effectiveness and safety of the procedure. This provided justification for expansion of the trial.

Statistics. Analysis of the primary end point was undertaken via paired comparison procedures. This involved paired t tests across individual time points supplemented by repeated measures analysis of variance. The end points were further examined by calculating the proportion of patients who experienced a drop of at least two points on the pain scale from the pretreatment level. Similar comparisons were performed using the additional quality of life questions.

Opioid analgesic medication use was translated into a morphine-equivalent dose and recorded [18]. Pain interference with activities of daily living was analyzed analogous to the primary pain end point data. Missing values were handled via complete-case analysis and imputation via the nearest neighbor, mean value, last value, and worst value carried forward approaches [19,20].

	RESULTS

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Patient and Treatment Characteristics
During the 18-month period of this study, 137 patients had radiographs evaluated for possible entry onto the study, and 46 were enrolled. The most common reasons patients were not eligible are listed in Table 1. Of the 46 patients enrolled, three were not treated with RFA. One patient received a nerve block, which provided adequate pain relief; a second patient was not treated because it was determined that the patient's specific focus of pain was not arising from the lesion that was to be ablated; and a third patient elected to postpone RFA until she completed a course of interleukin-2 therapy. Thus, 43 patients (median age, 64 years) underwent RFA of painful metastases involving bone, including 28 men and 15 women (Table 2). The median follow-up was 16 weeks. Colorectal (n = 10), renal (n = 9), and lung (n = 4) were the most common tumor types treated. Other (n = 17) tumor types included sarcoma (n = 3), thyroid (n = 2), prostate (n = 2), unknown primary (n = 2), melanoma (n = 1), endometrial (n = 1), breast (n = 1), urachal (n = 1), desmoid (n = 1), esophageal (n = 1), meningioma (n = 1), and paraganglioma (n = 1). The most common sites of tumor involvement were the pelvis (n = 12), sacrum (n = 12), rib (n = 6), and vertebrae (n = 4).

View larger version (74K): [in this window] [in a new window]   Fig 1. Two computed tomography images demonstrating the percutaneously placed radiofrequency ablation electrode. (A) A 63-year-old man with metastatic squamous cell carcinoma of unknown origin involving the left sacrum. (B) A 51-year-old man with metastatic non–small-cell lung carcinoma involving the right scapula.

View larger version (26K): [in this window] [in a new window]   Fig 2. Mean Brief Pain Inventory–Short Form (BPI-SF) pain scores over time for patients treated with radiofrequency ablation (RFA). (A) Worst pain. (B) Average pain. (C) Pain relief from RFA or medications. (D) Interference of pain in daily activities. Error bars represent the 95% CIs. n, the number of patients completing BPI-SF at each time point.

Of the 20 patients who did not complete the 24-week follow-up, 11 died due to progression of their cancer. One patient withdrew at week 2 after entering hospice care. Another patient withdrew at week 8 after undergoing a surgical procedure at the site of RFA (acetabulum). The remaining seven patients withdrew after a median follow-up of 8 weeks (range, 4 to 20 weeks) because of recurrent pain (five patients) or inadequate pain relief (two patients).

To evaluate for the effect of dropout, we evaluated the difference in pain scores (worst pain, average pain, pain interference, pain relief) for the group that was observed for at least 12 weeks (n = 26) versus those who dropped out before 12 weeks (n = 17), and found no significant differences for weeks 1 to 12 (data not shown). In addition, we explored the impact of the missing data using various imputation methods (average value carried forward, last value carried forward, and maximum value carried forward). These data (Fig 3) indicate continued improvement in those patients who were observed the longest. Hence, our results are likely a conservative estimate of the actual impact on the total patient population.

View larger version (17K): [in this window] [in a new window]   Fig 3. Graph shows the difference between mean worst pain-imputed values for those who dropped out before 12 weeks (n = 17), versus those who were observed for 12 weeks (n = 26). Imputed values are as follows: average value carried forward (AVCF); maximum value carried forward (MVCF); and least value carried forward (LVCF).

Adverse events occurred in three patients. One patient developed a second-degree skin burn at the grounding pad site. Another patient developed transient bowel and bladder incontinence following RFA of a previously irradiated metastasis involving the upper sacrum. A third patient developed an acetabular fracture 6 weeks following RFA of a metastasis involving the ileum, ischium, and acetabulum. The fracture required surgical treatment with total hip arthroplasty and acetabular reconstruction.

	DISCUSSION

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The presence of bone metastases is the most common cause of cancer-related pain [1]. RT is considered the standard care for management of painful bony metastases [5]; however, few options exist for patients who fail to obtain adequate pain relief following radiation. In these patients, disease is often refractory to chemotherapy or hormonal therapy. Surgery, which is usually reserved for impending fracture, is not always an option when patients present with advanced disease and poor functional status. For these patients, opioid analgesics remain the only alternative treatment option and for some patients, side effects such as constipation, nausea, and sedation, can be significant [21].

We report highly significant reductions in pain scores and improvement in quality of life following RFA of painful metastases involving bone. These findings are significant, not only because of the magnitude of the benefit, but because the findings were achieved in a cohort of patients traditionally refractory to most conventional treatments. In total, 95% experienced at least a two-point drop in worst pain following RFA. Furthermore, relief of pain was achieved rapidly, as 41% (17 of 41 patients) achieved at least a two-point drop in worst or average pain by week 1, and 59% (24 of 41 patients) did so by week 4. In conjunction with decreased pain scores, we found significant decreases in opioid requirements at weeks 8 and 12. This finding, however, was not persistent at week 24, despite continued reductions in pain scores. It is possible that despite persistent pain relief at the treated site, the increased opioid requirements are indicative of the development of pain at other sites of metastases, as many of these patients were at the end of life.

Although breast, prostate, and lung cancer make up the majority of patients who present with bone metastases, in our study, only one patient with breast cancer and two with prostate cancer were treated. Because these two tumor types are known to be radiosensitive, and because prior radiation was an eligibility requirement, it is possible that fewer of these patients "fail" radiation, thus negating the need for further treatment. Furthermore, patients with breast and prostate cancer involving bone often present with diffuse bony metastatic disease with multiple painful sites. In our study, patients were required to have two or fewer painful lesions. Lastly, because of the technical inability to expand the RFA tip into the blastic metastases, we required treated lesions to be either lytic or have a lytic component. Because nearly all prostate cancers involving bone are blastic, this also may have contributed to the small numbers of prostate cancer patients.

RFA of metastatic lesions involving bone is a safe procedure. One patient experienced transient bowel and bladder incontinence following treatment of a previously irradiated sacral metastasis. Another patient sustained an acetabular fracture 6 weeks following RFA of a metastatic lesion involving the ileum, ischium, and acetabulum. Although the etiology of the fracture was believed to be multifactorial, RFA may have induced necrosis of the tumor involving the acetabulum, thus contributing to the development of the acetabular fracture.

Many different mechanisms may contribute to the relief of bone tumor pain by RFA. The stimulation of sensory afferent nerves endings located in the bone cortex, periosteum, and surrounding soft tissue are ultimately involved in pain transmission [22]. The intense heat from RFA may be destroying local sensory nerves, thereby interrupting pain transmission. In addition, there is evidence that tumor cells can produce cytokines and tumor–derived factors such as tumor necrosis factor- [23-25], interleukins [23,25,26], and endothelins [27-29] capable of sensitizing sensory nerves to painful stimuli [30]. Furthermore, certain tumor-derived factors are involved in promoting painful osteoclastic activity [31,32]. Thus, by destroying tumor cells, RFA may decrease the production of cytokines and tumor factors involved in both nerve sensitization and osteoclastic activity. RFA may also prevent the painful consequences of disease progression by inhibiting tumor growth into the periosteum and surrounding tissues, and by preventing the development of painful micro and macro fractures secondary to the mechanical stress of weakened bone. In our study, the initial decrease in pain intensity was sustained for up to 6 months, suggesting that RFA may inhibit several different mechanisms involved in bone tumor pain.

This study demonstrates that RFA provides effective palliation of localized, painful osteolytic metastases involving bone. This procedure should provide cancer patients with an additional method to relieve bone pain when standard treatments fail. A randomized study comparing RFA with radiation in patients who present with previously untreated painful bony metastases is currently being developed.

	Authors' Disclosures of Potential Conflicts of Interest

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The authors indicated no potential conflicts of interest.

	Acknowledgment

 
We thank Karen Frishmeyer, DVM, for her assistance with the study database. We also thank Drs. Massimo Aglietta, Cinzia Ortega, and Giovanni Carlo Anselmetti, as well as Kathy Brown and Deitra Pitckett for assisting with the follow-up of the patients in this study.

	NOTES

 
Supported in part by RITA Medical Systems, Mountain View, CA

Presented in part at the American Society of Clinical Oncology 2002 Annual Meeting (May 18-21, 2002, Orlando, FL) and the Radiological Society of North America 2002 Annual Meeting, December 1-6, 2002, Chicago, IL.

M.P.G. and M.R.C. contributed equally to this article.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

	REFERENCES

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... REFERENCES

 
1. Mercadante S: Malignant bone pain: Pathophysiology and treatment. Pain 69:1-18, 1997[CrossRef][Medline]

2. Nielsen OS, Munro AJ, Tannock IF: Bone metastases: Pathophysiology and management policy. J Clin Oncol 9:509-524, 1991[Abstract]

3. Massie MJ, Holland JC: The cancer patient with pain: Psychiatric complications and their management. J Pain Symptom Manage 7:99-109, 1992[CrossRef][Medline]

4. Spiegel D, Sands S, Koopman C: Pain and depression in patients with cancer. Cancer 74:2570-2578, 1994[CrossRef][Medline]

5. Jeremic B, Shibamoto Y, Acimovic L, et al: A randomized trial of three single-dose radiation therapy regimens in the treatment of metastatic bone pain. Int J Radiat Oncol Biol Phys 42:161-167, 1998[CrossRef][Medline]

6. Price P, Hoskin PJ, Easton D, et al: Prospective randomised trial of single and multifraction radiotherapy schedules in the treatment of painful bony metastases. Radiother Oncol 6:247-255, 1986[Medline]

7. Cole DJ: A randomized trial of a single treatment versus conventional fractionation in the palliative radiotherapy of painful bone metastases. Clin Oncol (R Coll Radiol) 1:59-62, 1989

8. Gaze MN, Kelly CG, Kerr GR, et al: Pain relief and quality of life following radiotherapy for bone metastases: A randomised trial of two fractionation schedules. Radiother Oncol 45:109-116, 1997[CrossRef][Medline]

9. Nielsen OS, Bentzen SM, Sandberg E, et al: Randomized trial of single dose versus fractionated palliative radiotherapy of bone metastases. Radiother Oncol 47:233-240, 1998[CrossRef][Medline]

10. Steenland E, Leer JW, van Houwelingen H, et al: The effect of a single fraction compared to multiple fractions on painful bone metastases: A global analysis of the Dutch Bone Metastasis Study. Radiother Oncol 52:101-109, 1999[CrossRef][Medline]

11. de Baere T, Elias D, Dromain C, et al: Radiofrequency ablation of 100 hepatic metastases with a mean follow-up of more than 1 year. AJR Am J Roentgenol 175:1619-1625, 2000[Abstract/Free Full Text]

12. Solbiati L, Livraghi T, Goldberg SN, et al: Percutaneous radio-frequency ablation of hepatic metastases from colorectal cancer: Long-term results in 117 patients. Radiology 221:159-166, 2001[Abstract/Free Full Text]

13. McGhana JP, Dodd GD: Radiofrequency ablation of the liver: Current status. AJR Am J Roentgenol 176:3-16, 2001[Free Full Text]

14. Dupuy D, Ahmed M, Rodrigues B, et al: Percutaneous radiofrequency ablation of painful osseous metastases: A phase II trial. Proc Am Soc Clin Oncol 20:385a, 2001 (abstr 1537)

15. Callstrom MR, Charboneau JW, Goetz MP, et al: Painful metastases involving bone: Feasibility of percutaneous CT- and US-guided radio-frequency ablation. Radiology 224:87-97, 2002[Abstract/Free Full Text]

16. Daut RL, Cleeland CS, Flanery RC: Development of the Wisconsin Brief Pain Questionnaire to assess pain in cancer and other diseases. Pain 17:197-210, 1983[CrossRef][Medline]

17. Farrar JT, Young JP Jr, LaMoreaux L, et al: Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain 94:149-158, 2001[CrossRef][Medline]

18. Pereira J, Lawlor P, Vigano A, et al: Equianalgesic dose ratios for opioids: A critical review and proposals for long-term dosing. J Pain Symptom Manage 22:672-687, 2001[CrossRef][Medline]

19. Fairclough DL: Summary measures and statistics for comparison of quality of life in a clinical trial of cancer therapy. Stat Med 16:1197-1209, 1997[CrossRef][Medline]

20. Fairclough DL, Peterson HF, Cella D, et al: Comparison of several model-based methods for analysing incomplete quality of life data in cancer clinical trials. Stat Med 17:781-796, 1998[CrossRef][Medline]

21. Ventafridda V, Tamburini M, Caraceni A, et al: A validation study of the WHO method for cancer pain relief. Cancer 59:850-856, 1987[CrossRef][Medline]

22. Mach DB, Rogers SD, Sabino MC, et al: Origins of skeletal pain: Sensory and sympathetic innervation of the mouse femur. Neuroscience 113:155-166, 2002[CrossRef][Medline]

23. Watkins LR, Goehler LE, Relton J, et al: Mechanisms of tumor necrosis factor-alpha (TNF-alpha) hyperalgesia. Brain Res 692:244-250, 1995[CrossRef][Medline]

24. Sorkin LS, Xiao WH, Wagner R, et al: Tumour necrosis factor-alpha induces ectopic activity in nociceptive primary afferent fibres. Neuroscience 81:255-262, 1997[CrossRef][Medline]

25. Woolf CJ, Allchorne A, Safieh-Garabedian B, et al: Cytokines, nerve growth factor and inflammatory hyperalgesia: The contribution of tumour necrosis factor alpha. Br J Pharmacol 121:417-424, 1997[CrossRef][Medline]

26. Opree A, Kress M: Involvement of the proinflammatory cytokines tumor necrosis factor-alpha, IL-1 beta, and IL-6 but not IL-8 in the development of heat hyperalgesia: Effects on heat-evoked calcitonin gene-related peptide release from rat skin. J Neurosci 20:6289-6293, 2000[Abstract/Free Full Text]

27. Davar G, Hans G, Fareed MU, et al: Behavioral signs of acute pain produced by application of endothelin-1 to rat sciatic nerve. Neuroreport 9:2279-2283, 1998[Medline]

28. Gokin AP, Fareed MU, Pan HL, et al: Local injection of endothelin-1 produces pain-like behavior and excitation of nociceptors in rats. J Neurosci 21:5358-5366, 2001[Abstract/Free Full Text]

29. Zhou Z, Davar G, Strichartz G: Endothelin-1 (ET-1) selectively enhances the activation gating of slowly inactivating tetrodotoxin-resistant sodium currents in rat sensory neurons: A mechanism for the pain-inducing actions of ET-1. J Neurosci 22:6325-6330, 2002[Abstract/Free Full Text]

30. Mantyh PW, Clohisy DR, Koltzenburg M, et al: Molecular mechanisms of cancer pain. Nat Rev Cancer 2:201-209, 2002[CrossRef][Medline]

31. Honore P, Luger NM, Sabino MA, et al: Osteoprotegerin blocks bone cancer-induced skeletal destruction, skeletal pain and pain-related neurochemical reorganization of the spinal cord. Nat Med 6:521-528, 2000[CrossRef][Medline]

32. Luger NM, Honore P, Sabino MA, et al: Osteoprotegerin diminishes advanced bone cancer pain. Cancer Res 61:4038-4047, 2001[Abstract/Free Full Text]

Submitted March 17, 2003; accepted November 4, 2003.

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				E. Liapi and J.-F. H. Geschwind Transcatheter and Ablative Therapeutic Approaches for Solid Malignancies J. Clin. Oncol., March 10, 2007; 25(8): 978 - 986. [Abstract] [Full Text] [PDF]

				Y.-Y. Lai, S.-C. Chen, and N.-C. Chien Video-Assisted Thoracoscopic Neurectomy of Intercostal Nerves in a Patient With Intractable Cancer Pain American Journal of Hospice and Palliative Medicine, January 1, 2007; 23(6): 475 - 478. [Abstract] [PDF]

				M. R. Callstrom, T. D. Atwell, J. W. Charboneau, M. A. Farrell, M. P. Goetz, J. Rubin, J. A. Sloan, P. J. Novotny, T. J. Welch, T. P. Maus, et al. Painful Metastases Involving Bone: Percutaneous Image-guided Cryoablation--Prospective Trial Interim Analysis. Radiology, November 1, 2006; 241(2): 572 - 580. [Abstract] [Full Text] [PDF]

				X. Buy, A. Basile, G. Bierry, J. Cupelli, and A. Gangi Saline-infused bipolar radiofrequency ablation of high-risk spinal and paraspinal neoplasms. Am. J. Roentgenol., May 1, 2006; 186(5 Suppl): S322 - S326. [Abstract] [Full Text] [PDF]

				C. J. Simon, D. E. Dupuy, and W. W. Mayo-Smith Microwave Ablation: Principles and Applications RadioGraphics, October 1, 2005; 25(suppl_1): S69 - S83. [Abstract] [Full Text] [PDF]

				J. M. Lee, S. H. Choi, H. S. Park, M. W. Lee, C. J. Han, J.-i. Choi, J.-Y. Choi, S. H. Hong, J. K. Han, and B. I. Choi Radiofrequency Thermal Ablation in Canine Femur: Evaluation of Coagulation Necrosis Reproducibility and MRI-Histopathologic Correlation Am. J. Roentgenol., September 1, 2005; 185(3): 661 - 667. [Abstract] [Full Text] [PDF]

				K. L. Weber What's New in Musculoskeletal Oncology J. Bone Joint Surg. Am., June 1, 2005; 87(6): 1400 - 1410. [Full Text] [PDF]

				C. Horkan, K. Dalal, J. A. Coderre, J. L. Kiger, D. E. Dupuy, S. Signoretti, E. F. Halpern, and S. N. Goldberg Reduced Tumor Growth with Combined Radiofrequency Ablation and Radiation Therapy in a Rat Breast Tumor Model Radiology, April 1, 2005; 235(1): 81 - 88. [Abstract] [Full Text] [PDF]

				G. Belfiore, G. Moggio, E. Tedeschi, M. Greco, R. Cioffi, F. Cincotti, and R. Rossi CT-Guided Radiofrequency Ablation: A Potential Complementary Therapy for Patients with Unresectable Primary Lung Cancer--A Preliminary Report of 33 Patients Am. J. Roentgenol., October 1, 2004; 183(4): 1003 - 1011. [Abstract] [Full Text] [PDF]

				K. L. Weber What's New in Musculoskeletal Oncology J. Bone Joint Surg. Am., May 1, 2004; 86(5): 1104 - 1109. [Full Text] [PDF]

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