The practice of medicine in the 21st century may well be centered in the therapeutic application of interventional radiology techniques. As a direct result of the contributions to therapy made with interventional radiology, patients are experiencing fewer complications, faster recovery times, and lower medical expenses.1
The main focus of this article is to provide a short overview of some advances in radiation-based therapeutic techniques, specifically advances in radioimmunotherapy and radiopharmaceuticals. A brief look at radiofrequency use and Gamma Knife and CyberKnife applications will also be provided.
Background
Twenty-five years ago, less than 40% of all oncology patients had radiation therapy, alone or in combination with surgery and chemotherapy, as part of their management programs. In 1998, about 60% of all oncology patients had radiation therapy as part of their regimens.2
However, predicting the future of interventional radiology in oncology or in any other specialty is somewhat difficult, owing to the rapidly changing advances in technology and the impending financial constraints on the use of that technology. Well controlled trials will be needed not only to define the indications, immediate benefits, and the risks associated with the use of these new technologies, but also to review carefully the total (direct and indirect) cost effectiveness of these procedures, if they are to be used in a reimbursement setting.
Interventional radiology: An overview
Whether it is the intraoperative use of an interventional MRI system to guide neurosurgery, the use of intraoperative duplex ultrasonography in carotid endarterectomy to locate potential plaque emboli, or the use of radioactive antibodies in the treatment of tumors, there is no arguing that interventional radiology is establishing its place in secondary as well as primary therapy. Today, there are widely ranging therapeutic applications being investigated, among which are the uses of radioimmunotherapy and electrophysiologic therapy.
Radioimmunotherapy
Clinical applications of therapy with radiopharmaceutical agents are in progress, and the challenge for the rational design of biospecific, biologically active molecules labeled with metallic radionuclides (bifunctional radiopharmaceuticals) continues. The chelating groups in the molecular structure of radiopharmaceuticals afford opportunities to bind metallic radionuclides without affecting the biospecificity of the mother compounds. These new compounds exhibit high and specific localization of radioactivity into target tissues.3
Radiolabeled monoclonal antibodies can target tumors selectively. In the process, the mechanisms of disease in targeted cells change in response to the receptor-specific antibody presence. Radiolabeled antibody cell targeting has more recently shown itself to have cytotoxic properties, depending on the agents used, giving rise to investigations of its use as direct therapy for a variety of indications.
Radioactive antibodies are showing early promise in the treatment of low-grade, follicular lymphoma that has failed conventional chemotherapy.4 Kaminski et al. describe a two-stage treatment, called Bexxar, in which the antibodies are welded to radioactive iodine-131. The antibodies target the protein cd20, present on the surface of most, if not all, lymphoma cells. The treatment delivers lethal radioactivity to the cells and flags the cells for destruction by the patient's immune system. To date, investigators say the only side effects appear to be flu-like symptoms.
Reports of additional investigative radioimmunotherapy for the treatment of lymphomas are found in the work of Denardo et al. in their investigation of 67Cu-2IT-BAT-Lym-1 and tumor regression in patients with lymphoma,5 and in the work of Vose and colleagues in a multicenter study of iodine-131 tositumomab as chemotherapy for refractory, low-grade B-cell non-Hodgkin's lymphoma.6
Debinski and Thompson report investigations of redirecting interleukin 13 in the treatment of glioblastomas.7 They mutated the cytokine and produced hIL-13.E13Y, concomitantly equipping hIL-13 with additional tyrosine residue for higher specific activity.
Gates et al. investigated nonmyeloablative iodine-131 anti-B1 radioimmunotherapy (RIT) dosimetry for outpatient use. Using the Nuclear Regulatory Commission (NRC) method, the mean dose equivalent (MDE) to the public exposed to an 131I anti-B1 outpatient was 4.9 +/-0.9 mSv (490 +/- 90 mrem). Using the measured dose rate method, the MDE for the exposed public was 2.9 +/- 0.4 mSv (290 +/- 40 mrem). Based on patient-specific exposure data, outpatient RIT with nonmyeloablative doses of 131I should be feasible under current NRC regulations.8
Radiopharmaceutical therapy
In other research, murine studies by Goddu and colleagues were conducted to determine if marrow toxicity from bone-seeking radiopharmaceuticals could be reduced while maintaining efficacy, by using radionuclides that emit short-range particles or conversion electrons.9 They compared 32P-orthophosphate (32P), 33P-orthophosphate (33P), 89Sr-chloride (89Sr), and 186Re-1,1 hydroxyethylidene diphosphate (186Re) in a mouse femur model. In those mice, 33P demonstrated a substantial dosimetric advantage over the other particle emitters tested for irradiating bone and minimizing marrow toxicity. It remains to be seen if these data correlate to human use.
Other advances in interventional radiology
Radiofrequency uses
The scope of procedures for which radiofrequency therapy is being tested and used is widening. Table 1 summarizes research into some of the newest uses of radiofrequency therapy in cardiac, vascular, oncology, nasopharyngeal, and musculoskeletal conditions. Its applications include ablation, tissue volume reduction, and tissue resection.
Conformal radiotherapy
Conformal radiotherapy uses 3-D beams that curve around the malignancy, avoiding healthy tissue. Initially, this technique is being used to limit the spread of prostate cancer.31 The technique permits the delivery of radiotherapy to the tumor at doses 33% higher than possible with conventional treatment. An additional application of 3-D conformal external-beam irradiation currently being explored is for the treatment of pancreatic cancer.32
Gamma Knife radiosurgery
Gamma Knife treatment has four components: frame fixation, imaging, treatment planning, and treatment implementation. Selective beam blocking, weighting, and combining various collimator sizes are methods used to ensure that the radiation field conforms to the target.33
Clinical applications being explored are the treatment of arteriovenous malformations, acoustic schwannoma, meningiomas, pituitary adenomas, and glial tumors.34 Gamma Knife radiosurgery is not without problems, however. Areas of improvement being tested include creating more sophisticated software to deliver radiation that conforms more precisely to the tumor, and new techniques for protecting the optic nerve, which would permit delivery of higher radiation doses.35
CyberKnife
CyberKnife radiotherapy differs from that delivered with a Gamma Knife in that it uses the patient's skeleton as a frame of reference, rather than the metal frame needed for Gamma Knife procedures. The CyberKnife system uses robotics and missile technology to target bursts of radiation to the tumor.
The strengths of the procedure are its ability to reach small volumes of tumor in critical structures, and that the procedure only requires "light" patient restraint, rather than invasive restraint. Its weakness is that it is not the best method for removing large tumors from noncritical structures.36 Using fiducial markers in or around the target, the robot alters the aim of the radiation source in real time, so that the intended target is always in the beam.37
Conclusion
The challenge for interventional radiology-based therapy in the coming years is to explore the benefits of improvement in dose localization expected from protons and conformal therapy. Developments in Hadron therapy (fast neutrons, protons, pions, heavy ions, and boron neutron capture therapy) are examples of efforts to meet this challenge.38 The film Fantastic Voyage, which seemed so futuristic, is now a reality in this age of cameras-in-a-capsule.39 Interventional radiology will be an increasingly integral part of therapy of the future.
By Judith B. PaquetAuntMinnie.com contributing writer
June 26, 2000
About the author
Judith B. Paquet, RN, is an experienced medical writer and editor for national continuing medical education programs, and previously served as senior medical writer and medical liaison for a national continuing medical education company. She can be reached at Paquet Associates, 1811 Edgewood Place, Clementon, NJ 08021, or via email at [email protected].
References
1. Niranjan A, Lunsford LD. Radiosurgery: where we were, are, and may be in the third millennium. Neurosurgery. 2000;46(3):531-543.
2. Brady LW, Levitt SH. Radiation oncology in the third millennium. Rays. 1999;24(3): 361-372.
3. Saji H. Targeted delivery of radiolabeled imaging and therapeutic agents: bifunctional radiopharmaceuticals. Crit Rev Ther Drug Carrier Syst. 1999;16(2):209-244.
4. Kaminski M. in a presentation on radioimmunotherapy for low-grade, follicular lymphoma. Presented at the American Society of Clinical Oncology Annual Meeting, June 22, 2000, New Orleans, Louisiana.
5. DeNardo SJ, DeNardo GL, Kukis DL, et al. 67Cu-2IT-BAT-Lym-1 pharmacokinetics, radiation dosimetry, toxicity and tumor regression in patients with lymphoma. J Nucl Med. 1999;40(2):302-310.
6. Vose JM, Wahl RL, Saleh M, et al. Multicenter phase II study of iodine-131 tositumomab for chemotherapy-relapsed/refractory low-grade and transformed low-grade B-cell non-Hodgkin's lymphomas. J Clin Oncol. 2000;186:1316-1323.
7. Debinski W, Thompson JP. Retargeting interleukin 13 for radioimmunodetection and radioimmunotherapy of human high-grade glioma. Clin Canc Res. 1999;5(10) (Suppl):3143s-3147s.
8. Gates VL, Carey JE, Siegel JA, Kaminski MS, Wahl RL. Nonmyeloablative iodine-131 anti-B1 radioimmunotherapy as outpatient therapy. J Nucl Med. 1998;39(7):1230-1236.
9. Goddu SM, Bishayee A, Bouchet LG, Bolch WE, Rao DV, Howell RW. Marrow toxicity of 33P- versus 32P-Orthophosphate: implications for therapy of bone pain bone metastases. J Nucl Med. 2000;41:941-951.
10. Lopez GM, Arribas F, Cosio FG. Radiofrequency ablation of atrial tachycardia and atrial flutter. Z Kardiol. 2000;89(Suppl 3):144-152.
11. Ramanna H, Derlson R, Elvan A, et al. Ventricular tachycardia as a complication of atrial flutter ablation. J Cardiovasc Electrophysiol. 2000;11(4):472-474.
12. Haissaquerre M, Jais P, Shah DC, et al. Catheter ablation of chronic atrial fibrillation targeting the reinitiating triggers. J Cardiovasc Electrophysiol. 2000;11(1):2-10.
13. Clinical outcomes after ablation and pacing therapy for atrial fibrillation: a meta-analysis. Wood MA, Brown-Mahoney C, Kay GN, Ellenbogen KA. Circulation. 2000;101(10):1138-1144.
14. Alwi M, Geetha K, Bilkis AA, et al. Pulmonary atresia with intact ventricular septum percutaneous radiofrequency-assisted valvotomy and balloon dilation versus surgical valvotomy and Blalock Taussig shunt. J Am Coll Cardiol. 2000;35(2):468-476.
15. Hluchy J. Mahaim fibers: electrophysiologic characteristics and radiofrequency ablation. Z Kardiol. 2000;89(Suppl 3):136-143.
16. Goldman MP. Closure of the greater saphenous vein with endoluminal radiofrequency thermal heating of the vein wall in combination with ambulatory phlebectomy: preliminary 6-month follow up. Dermatol Surg. 2000;26(5):452-456.
17. Wood BJ, Gervais DA, Spies J, Goldberg SN, McGovern F, Mueller PR. Radiofrequency ablation of renal tumors: early experience. Presented at the SCVIR Annual Meeting, March 25-30, 2000, San Diego, California. Accessed 6-11-00.
18. Parrent AG. Stereotactic radiofrequency ablation for the treatment of gelastic seizures associated with hypothalamic hamartoma. Case report. J Neurosurg. 1999;91(5):881-884.
19. Dimitri M. TURP with the new superpulsed radiofrequency energy: more than a gold standard. Eur Urol. 1999;36(4):331-334.
20. Bohm T, Hilger I, Muller W, Reichenbach JR, Fleck M, Kaiser WA. Saline-enhanced radiofrequency ablation of breast tissue: an in vitro feasibility study. Invest Radiol. 2000;35(3):149-157.
21. Jeffrey SS, Bierdwell RL, Ikeda DM, et al. Radiofrequency ablation of breast cancer: first report of an emerging technology. Arch Surg. 1999;134(10):1064-1068.
22. Rose DM, Allegra DP, Bostick PJ, Foshag LJ, Bilchik AJ. Radiofrequency ablation: a novel primary and adjunctive ablative technique for hepatic malignancies. Am Surg. 1999;65(11):1009-1014.
23. Siperstein A, Garland A, Engle K, et al. Local recurrence after laparoscopic radiofrequency thermal ablation of hepatic tumors. Ann Surg Oncol. 2000;72):106-113.
24. Solbiati L, Goldberg N, Ierace T, et al. Radiofrequency ablation of hepatic metastases: postprocedural assessment with a US microbubble contrast agent: early experience. Radiology. 1999;211:643-649.
25. Barei DP, Moreau G, Scarborough MT, Neel MD. Percutaneous radiofrequency ablation of osteoid osteoma. Clin Orthop. 2000;Apr(373):115-124.
26. Hukins CA, Mitchell IC, Hillman DR. Radiofrequency tissue volume reduction of the soft palate in simple snoring. Arch Otolaryngol Head Neck Surg. 2000;126(5):602-606.
27. Exar EN, Collup NA. The upper airway resistance syndrome. Chest. 1999;115(4):1127-1130.
28. InteliHealth Professional Network. Tonsillectomy alternative proposed. Interview with Monsoor Madani, MD. Released February 21, 2000. Dateline: Philadelphia, PA. In advance of a scheduled presentation at ACOMS Annual Meeting, April, 2000, Washington DC.
29. Smith TL, Correa AJ, Kuo T, Reinisch L. Radiofrequency tissue ablation of the inferior turbinates using a thermocouple feedback electrode. Laryngoscope. 1999;109(11):1760-1765.
30. Ketroser DB. Whiplash, chronic neck pain, and zygapophyseal joint disorders. A selective review. Minn Med. 2000;83(2):51-54.
31. InteliHealth Professional Network. 3-D radiotherapy helps to combat prostate cancer. Press release March 30, 2000. Dateline London, England. As seen at www.InteliHealth.com Accessed 6-10-00.
32. Bodner WR, Hilaris BS, Mastoras DA. Radiation therapy in pancreatic cancer: current practice and future trends. J Clin Gastroenterol. 2000;30(3):230-233.
33. Gamma Knife. Treatment procedure. As seen at http://www.elekta.com Accessed 5-28-00.
34. Yamamoto M. Gamma Knife radiosurgery: technology, applications, and future directions. Neurosurg Clin N Am. 1999;10(2):181-202.
35. Wilner AN. Gamma Knife for pituitary adenomas. Key reports from the 68th annual meeting of the Association of Neurological Surgeons. Conference Report. As seen at http://cardiology.medscape.com/Medscape/Neurology/journal/2000/v02n03/mn0524.wiln/mn0524.wiln.html#2 Accessed 6-8-00.
36. CyberKnife. As seen at http://www.zdnet.com/zdtv/thesite/0897w4/life/life794jump1_082097.html Accessed 5-28-00.
37. Macklis RM, Weinhous MS. CyberKnife. Image-directed Robotic Radiation Therapy. The Callahan Center for Radiation Oncology and Robotics, Cleveland Clinic Foundation. Accessed 5-28-00.
38. Wambersie A, Auberger T, Gahbauer RA, Jones DT, Potter R. A challenge for high-precision radiation therapy: the case for hadrons. Strahlenther Onkol. 1999;175(Suppl 2):122-128.
39. InteliHealth Professional Network. Scientists develop camera that can record your insides. Release May 24, 2000. As seen at http://ipn.intelihealth.com/IPN/ihtIPN?st=23883&t=7223&c=283231 Accessed 5-25-00.
Let AuntMinnie.com know what you think about this story.
Copyright © 2000 AuntMinnie.com
