# Radiation Oncology/Benign/Randomized

* Front Page: Radiation Oncology | RTOG Trials | Randomized Trials
Benign Diseases and Radiation Therapy

## Graves' Disease

* Amsterdam; 2004 PMID 14715820 -- "A randomized controlled trial of orbital radiotherapy versus sham irradiation in patients with mild Graves' ophthalmopathy." (Prummel MF, J Clin Endocrinol Metab. 2004 Jan;89(1):15-20.)
** Randomized, double-blind. 88 patients (44 orbital RT, 44 sham)
** Outcome: RT 52% vs. 27% at 12 months (SS) in improving eye muscle motility and decreasing diplopial. RT group less need for further treatment (SS). But, QOL improvement similar in both groups. Worsening ophthalmopathy similar (~15%)
** Conclusion: RT effective in mild ophthalmopathy, but no improved QOL or treatment costs
* Mayo, 2001 PMID 11535445 -- "A prospective, randomized, double-blind, placebo-controlled study of orbital radiotherapy for Graves' ophthalmopathy." (Gorman CA, Ophthalmology. 2001 Sep;108(9):1523-34.)
** Randomized, double-blind. 42 patients. Moderate, symptomatic Graves ophthalmopathy. Orbit treated with 20 Gy, sham therapy to other side; 6 months later therapy reversed.
** Outcome: No difference at 6 month cross-over. Slight improvement in muscle volume and proptosis in first treated eye at 12 months.
* Mainz, 2000 (Germany) PMID 10634372 -- "Low- versus high-dose radiotherapy for Graves' ophthalmopathy: a randomized, single blind trial." (Kahaly GJ, J Clin Endocrinol Metab. 2000 Jan;85(1):102-8.)
** Randomized. Euthyroid patients with moderately severe GO. Treated with 1) 20 Gy @ 1 Gy/week over 20 weeks, 2) 10 Gy @ 1 Gy/fx over 2 weeks, or 3) 20 Gy @ 2 Gy/fx over 2 weeks
** Outcomes: response to therapy 67% vs. 59% vs. 55% (SS)
** Conjunctivitis: none vs. 18% vs. 36%
** Conclusion: similar response rates, but 1 Gy/week protocol more effective and better tolerated
* Utrecht, 2000 (Holland) PMID 10801172 -- "Radiotherapy for Graves' orbitopathy: randomised placebo-controlled study." (Mourits MP, Lancet. 2000 Apr 29;355(9214):1505-9.)
** Randomised double-blind. 60 patients. Moderately severe GO. Treated with 1) RT 20/10 or 2) sham RT
** Outcome: success in 60% RT vs. 31% sham (SS). Improvement in diplopia grade, but no reduction in proptosis or eyelid swelling. Also significant improvement in elevation, but no other variables. But only 25% of RT patients spared from additional strabismus surgery
** Conclusion: RT should be used only for motility impairment
* Amsterdam; 1993 PMID 8105213 -- "Randomized double-blind trial of prednisone versus radiotherapy in Graves' ophthalmopathy." (Prummel MF, Lancet. 1993 Oct 16;342(8877):949-54.)
** Randomized double-blind. 56 patients with moderaly severe GO. Treated with 1) 3-month oral prednisone + sham RT vs. 2) RT 20 Gy + placebo capsules
** Conclusion: RT and oral prednisone equally effective, but RT better tolerated

## Heterotopic Ossification

* Cornell, 2003 PMID 14513439 -- "The efficacy of 500 CentiGray radiation in the prevention of heterotopic ossification after total hip arthroplasty: a prospective, randomized, pilot study." (Padgett DE, J Arthroplasty. 2003 Sep;18(6):677-86.)
** Randomized. 59 patients. Treated with 10/5 vs. 5/2 in <=96 hours
** Treatment failure: 10/5 3% vs. 5/2 7% (p=0.09)
** Conclusion: 5/2 appears effective in preventing clinically significant HO
* Erlangen HOP2, 1997 (1992-1995) PMID 9300751 -- "Prevention of heterotopic ossification about the hip: final results of two randomized trials in 410 patients using either preoperative or postoperative radiation therapy." (Seegenschmiedt MH, Int J Radiat Oncol Biol Phys. 1997 Aug 1;39(1):161-71.)
** Randomized. 161 patients. Preop RT 7/1 (<4 hours) vs. Postop RT 17.5/5 (<=96 hours). Portals periacetabular and intertrochanteric soft tissues
** Failure rate: radiological overall 11%; preop 19% vs. postop 5% (SS). Functional 14% Highest failure in pre-op RT for Brooker Grade III-IV (39%), otherwise preo-op and post-op outcomes comparable
** Conclusion: preop RT inferior to postop RT, except in Grade I-II, where no difference
* Erlangen HOP1, 1997 (1987-1992) PMID 9300751 -- "Prevention of heterotopic ossification about the hip: final results of two randomized trials in 410 patients using either preoperative or postoperative radiation therapy." (Seegenschmiedt MH, Int J Radiat Oncol Biol Phys. 1997 Aug 1;39(1):161-71.)
** Randomized. 249 patients, high risk. Post-op RT 10/5 vs. 17.5/5. Portals periacetabular and intertrochanteric soft tissues
** Failure rate: radiological overall 9%; low dose 11% vs. high dose 6% (NS). Functional 7%
** Conclusion: no difference in post-op dose
* Rochester, 1994 PMID 8083129 -- "Randomized trial comparing preoperative versus postoperative irradiation for prevention of heterotopic ossification following prosthetic total hip replacement: preliminary results." (Gregoritch SJ, Int J Radiat Oncol Biol Phys. 1994 Aug 30;30(1):55-62.)
** Randomized, multi-institutional. 98/122 patients with risk factors, following elective hip replacement. Treated with pre-op RT 7-8/1 <4 hours vs. post-op RT 7-8/1 <48 hours. Fields to soft tissues between periacetabular region of pelvis and intertrochanteric portion of femur. Median F/U 9.5 months
** Failure rate: radiographic preop 26% vs. postop 28% (NS); clinical 2% vs. 5% (NS)
** Conclusion: no difference between preop and postop
* Rochester, 1992 PMID 1541613 -- "Prevention of heterotopic ossification with irradiation after total hip arthroplasty. Radiation therapy with a single dose of eight hundred centigray administered to a limited field." (Pellegrini VD Jr, J Bone Joint Surg Am. 1992 Feb;74(2):186-200.)
** Randomized. 62 hips in 55 patients at high risk. Treated with postop RT 8/1 vs. 10/5 limited field (includes lateral aspect of greater trochanter). Minimum F/U 6 months
** Failure rate: Single fraction 21% vs. multifraction 21%
** Conclusion: Single fraction effective.

## Heel Spurs

* Offenbach, 2007 (Germany) PMID 17225939 -- "Radiation Therapy for Painful Heel Spurs : Results of a Prospective Randomized Study." (Heyd R, Strahlenther Onkol. 2007 Jan;183(1):3-9.)
** Randomized. 130 patients with painful heel spurs. RT low-dose 3 Gy in 0.5 Gy/fx twice weekly vs. high-dose 6 Gy in 1.0 Gy/fx twice weekly
** Outcome: 6-month excellent/good LD 66% vs. 68% (NS)
** Conclusion: RT effective, shouldn't give more than 3 Gy

## Rheumatoid Arthritis

* Stanford -- total lymphoid irradiation 20 Gy vs 2 Gy
** Randomized. 26 patients, intractable rheumatoid arthritis. Arm 1) total lymphoid irradiation 20 Gy vs. Arm 2) total lymphoid irradiation 2 Gy
** 1985 PMID 3883868 -- "Efficacy of total lymphoid irradiation in intractable rheumatoid arthritis. A double-blind, randomized trial." (Strober S, Ann Intern Med. 1985 Apr;102(4):441-9.)
*** Outcome: Alleviation of joint disease significantly better in 20 Gy group at 3 and 6 months. Marked reduction in T-lymphocyte function and numbers in 20 Gy group, no change in 2 Gy group
*** Toxicity: Transient neutropenia, thrombocytopenia, pericarditis, and pleurisy
*** Conclusion: 20 Gy dose more effective, but also more side effects

## Vascular Brachytherapy
### De novo lesions

* BetAce; 2007 PMID 17307419 -- "Intracoronary beta-irradiation for the treatment of de novo lesions: 5-year clinical follow-up of the BetAce randomized trial." (Ferrero V, Am Heart J. 2007 Mar;153(3):398-402.)
** Randomized. 64 de novo coronary lesions. Treated with 1) bare metal stents (control) vs. 2) intracoronary beta RT. Median F/U 5 years
** EFS: 6-month control 35% vs. RT 13% (SS), 5-years: control 43% vs. RT 45% (NS)
** Conclusion: Significant benefit at 6 months, no difference at 5 years

### In-stent restenosis

* Vienna; 2007 PMID 16971011 -- "Randomized comparison between intracoronary beta-radiation brachytherapy and implantation of paclitaxel-eluting stents for the treatment of diffuse in-stent restenosis." (Schukro C, Radiother Oncol. 2007 Jan;82(1):18-23. Epub 2006 Sep 12.). F/U 6 months
** Randomized. 37 patients with diffuse in-stent restenosis. Arm 1) Beta-Cath vs. Arm 2) Taxus-Express2
** Outcome: restenosis >50% Beta-Cath 3 patients vs. Taxus-Express2 0 patients (SS). No difference in major adverse cardiac outcomes.
** Procedure time: Beta-Cath 60 min vs. Taxus-Express2 31 min (SS)
** Conclusion: Significanly better restenosis rate in Taxus arm, no clinical difference
* TAXUS V ISR; 2006 (2003-2004) PMID 16531618 -- "Paclitaxel-eluting stents vs vascular brachytherapy for in-stent restenosis within bare-metal stents: the TAXUS V ISR randomized trial." (Stone GW, JAMA. 2006 Mar 15;295(11):1253-63.)
** Randomized. 396 patients, in-stent restenosis of previously implanted bare-metal coronary stent. Treated with angioplasty plus beta-source vascular brachy vs. paclitaxel-eluting stent. DM in 35% patients. Angiography at 9 months
** 9-month outcome: need for ischemic revascularization: 17% vs. 10% (SS); major cardiac events: VBT 20% vs. TAXUS 11% (SS); similar rate of cardiac death and MI (4-5%)
** Conclusion: Paclitaxel-eluting stents better than VBT for in-stent restenosis
* SISR; 2006 (2003-2004) PMID 16531619 -- "Sirolimus-eluting stents vs vascular brachytherapy for in-stent restenosis within bare-metal stents: the SISR randomized trial." (Holmes DR Jr, JAMA. 2006 Mar 15;295(11):1264-73.)
** Randomized. 384 patients, in-stent restenosis of previously implanted bare-metal stent. Treated with VBT or sirolimus-eluting stent. Angiography at 9 months
** 9-month outcome: need for revascularization: VBT 19% vs. sirolimus stent 8% (SS)
** Conclusion: Sirolimus-eluting stents superior than VBT for in-stent restenosis