Brachytherapy
Also known as radiotherapy, this technique involves delivering local radiation to a coronary artery. There are several delivery strategies currently under study. In addition, the appropriate dosing and long-term effects are also being examined.
Here at Stanford we are currently participating in a number of clinical trials examining the role of b-radiation in the treatment of in-stent restenosis. Previously, we were one of three centers participating in the Proliferation REduction Vascular ENergy Trial (PREVENT)1 as well as the INHIBIT trial . Both studies have utilized an investigational delivery system designed by Guidant VI utilizing a spiral centering balloon with a 32P wire delivered by a high-dose rate afterloader.
There are currently several isotopes under study which can be divided into b-emitters and g-emitters. The b-emitters include 32P, 90 Sr/Y, and 188Re. They are characterized by high-energy with low tissue penetration and can easily be shielded by distance and lead. Dwell times are typically short (under 5 minutes). The g-emitters include 192Ir. They have a lower energy but have higher tissue penetration and thus have longer dwell times (up to 30 minutes).
b-emitters |
g-emitters |
32P, 90 Sr/Y, 188Re, 166Ho, 133Xe |
192Ir, 103Pd, 125I, 145Sm |
High-energy with low tissue penetration |
Lower energy with high tissue penetration |
Easily shielded |
Not easily shielded; should leave cath lab |
Short dwell times |
Longer dwell times |
?Edge effects |
?No edge effects |
Studies with both b- and g-emitters have been performed. With respect to studies with g-radiation, Condado et al 2 reported upon 21 patients (22 arteries) who were treated with a 192Ir source after intervention. Two-year follow-up3 revealed a 28% restenosis rate with 4 patients developing pseudoaneurysms. The SCRIPPS Trial4 also employed g-radiation with a 192Ir source after stenting in previously restenotic lesions and found a significant reduction in restenosis rates (17% in treated patients, 54% in placebo; p=0.01). Finally, the recently reported WRIST study in 130 patients found that treatment of in-stent lesions with 192Ir reduced the restenosis rate from 58% to 19% with a combined endpoint (death, repeat TLR, and acute MI) reduction of 63%.
b-emitters have also been investigated. BERT5 revealed that as an adjunct to angioplasty alone, delivery of b-radiation (90 Sr/Y) via encapsulated steel sources to a target lesion had a six-month restenosis rate of 24.4% with a late-loss index of 0.08. PREVENT1 was a recently completed Phase I study using a 32P source wire delivered through a spiral centering balloon catheter by a high-dose rate afterloader. 72 patients were enrolled at three sites and six-month restenosis rates were equivalent between the three treated groups and the placebo group (31% vs. 33%). In both of these major b-radiation studies, there has been some concern raised about the possibility of "edge effects," i.e. proliferation at the edges of radiation treatment which had also been previously reported with some animal studies. Whether these findings are in part due to radiation are under active investigation.
In addition, there has been some recent concern regarding late thrombosis. Early trials have indicated that late thrombosis (>30 days) may be causing late events, including acute MI and death. The data suggest a strong relationship between implantation of a 'fresh' stent and late thrombosis. Postulated mechanisms have focused upon delayed healing after stent implantation. As a result, in most current brachytherapy trials, antiplatelet therapy has been prolonged (3-6 months) after brachytherapy.
A multitude of clinical studies are currently underway. Much excitement has been generated by the early studies regarding brachytherapy and several new delivery systems and radioisotopes are under study. Because of the burgeoning interest in this field, we have provided a short glossary of terms commonly used in brachytherapy:
Term |
Definition or description |
Activity |
A quantity defining the amount of radioactive material (typically expressed in Ci) |
Becquerel (Bq) |
1 disintegration/sec |
Curie (Ci) |
3.7x1010 Bq; a unit of source decay |
Dose |
Energy absorbed by target (typically expressed in Gy) |
Gray (Gy) |
1 joule/kg (SI unit)=100 rads; a unit of dose absorption |
Half-life |
Time of decay to 1/2 original energy |
Rad |
Dose delivered (old unit) |
Radioisotope |
Unstable isotope |
Rem |
Dose absorbed by tissue (old unit) |
Roentgen |
A unit of radiation exposure |
Sievert (Sv) |
Energy absorbed by tissue (SI unit)=100 rems |
References
1. Lee DP, Lo S, Forster KM, Tate DJ and SN Oesterle (1998). Intracoronary radiation with a 32 P source wire. Herz 23 362-5.
2. Condado JA, Waksman R, Gurdiel O, Espinosa R, Gonzales J, Burger B, Villoria G, Acquatella H, Crocker IR, Sueng KB and SF Liprie (1997). Long-term angiographic and clinical outcome after percutaneous transluminal coronary angioplasty and intracoronary radiation in humans. Circulation 96 :727-32.
3. Condado JA, Saucedo JF, Caldera C, Proctor B, Fadoul M, Gurdiel O and R Waksman (1997). Two year angiographic evaluation after intracoronary 192-iridium in humans. Circulation 96 :I-220.
4. Tierstein PS, Massullo V, Jani S, Popma JJ, Mintz GS, Russo RJ, Schatz RA, Guarneri EM, Steuterman S, Morris NB, Leon MB and P Tripuraneni (1997). Catheter-based radiotherapy to inhibit restenosis after coronary stenting. N Engl J Med 336 :1697-1703.
5. King III SB, Williams DO, Chougele P, Klein JL, Waksman R, Hilstead R, Macdonald J, Anderberg K and IR Crocker (1998). Endovascular b -radiation to reduce restenosis after balloon angioplasty: results of the Beta Energy Restenosis Trial (BERT). Circulation 97 :2025-30.
David P. Lee, M.D.