Radiation Oncology/Benign/Keloid

Natural history
Recurrence rate of 50-80% after surgery. Recurrence rate reduced to 50% with intralesional steroid therapy. RT reduces recurrence rate to 12-28%.

Treatment Overview

 * No universally accepted treatment protocol
 * Modalities: surgery, radiation, pressure therapy, cryotherapy, intralesional injections of corticosteroids, interferon, fluorouracil, topical silicone, and pulse-dye laser treatment
 * Surgery only has recurrence rate of 50-80%
 * Post-op RT
 * Success rate 75-90% within 10 year follow-up; however, a recent Dutch study had 70+% recurrence within 2 year, in sharp disagreement with prior studies
 * Usually surgical excision followed immediately with RT
 * Usually 3-4 fractions daily in 3-4 Gy/fx; however, recent Dutch meta-analysis suggests that dose is insufficient for long-term control, and should use BED of >30 Gy (e.g. 13/1, 16/2, 18/3)
 * Sites with high rates of recurrence (eg. high-tension areas) should be treated with escalated dosage

Post-op RT
Meta-analysis
 * Utrecht
 * 2005 PMID 16254707 -- "Biologically effective doses of postoperative radiotherapy in the prevention of keloids. Dose-effect relationship." (Kal HB, Strahlenther Onkol. 2005 Nov;181(11):717-23.)
 * Meta-analysis, 18 studies. Recurrence rate for surgery only 50-80%
 * BED: Recurrence rate decreased as a function of BED, if >30 Gy recurrence was <10%. No difference with high stretch tension sites
 * Conclusion: For effective therapy, need a reasonably high dose (BED >=30 Gy, for example 13/1, 16/2, 18/3 or 27/1 LDR), within 2 days of surgery
 * 2009 PMID 19362243 -- "Dose-effect relationships for recurrence of keloid and pterygium after surgery and radiotherapy." (Kal HB, Int J Radiat Oncol Biol Phys. 2009 May 1;74(1):245-51.)
 * For keloid recurrence after radiotherapy following keloid removal, with either teletherapy or brachytherapy, the recurrence rate after having delivered a BED greater than 30 Gy is less than 10%.
 * Conclusion: "Most of the doses in the radiotherapy schemes used for prevention of keloid recurrence after surgery are too low. A scheme with a BED of 30 to 40 Gy seems to be sufficient to prevent recurrences of keloid"


 * U.Pittsburgh;2011 - PMID 20472370 -- "A Radiobiological Analysis of Multicenter Data for Postoperative Keloid Radiotherapy" (Flickinger JC; Int J Radiat Oncol Biol Phys. 2011 Mar 15;79(4):1164-70.)
 * Review of multiple published studies. For 95% control of keloids with electrons, fractionated (in 3 fx) dose of 18.3-19.2 Gy (earlobe) or 23.4-24.8 Gy (other sites). Single fraction equivalent dose: 11.4 Gy (earlobe) and 14.5 Gy (other sites).

Randomized
 * Beth Israel, 1996 PMID 8646474 -- Steroid injection vs RT
 * 31 keloids treated.
 * "Prevention of earlobe keloid recurrence with postoperative corticosteroid injections versus radiation therapy: a randomized, prospective study and review of the literature." (Sclafani AP, Dermatol Surg. 1996 Jun;22(6):569-74.)
 * Recurrence 2/16, 12.5% (RT) vs 4/12, 33% (Steroids), NS.
 * Conclusion: No statistical difference seen, but small study, likely underpowered.

Single Institution
 * Tokyo; 2007 (2002-2004) PMID 18046154 -- "Postoperative radiation protocol for keloids and hypertrophic scars: statistical analysis of 370 sites followed for over 18 months."
 * Prospective. Compared 109 pts (121 lesions) treated from 2002-2004 on a risk-adapted protocol vs historic controls (218 pts; 249 lesions). Risk-adapted strategy employed 10, 15, or 20 Gy depending on site (higher dose: anterior chest wall, scapular, suprapubic; lower dose: earlobe). Historical controls received 15 Gy standard dose.
 * Minimal f/u 18 months. Recurrence rate 29.3% (historic) vs 14.0% (protocol). The recurrence rate in the anterior chest wall was statistically reduced. Outcomes of earlobe did not differ between irradiation with 15 Gy or 10 Gy.
 * Conclusion: "Keloids and intractable hypertrophic scars should be treated with dose protocols customized by site. Our results suggest that keloid and intractable hypertrophic scar sites with a high risk of recurrence should be treated with 20 Gy in 4 fractions over 4 days and that earlobe should be treated with 10 Gy in 2 fractions over 2 days."


 * Utrecht; 2007 (Netherlands)(1998-2004) PMID 17967309 -- "Postoperative high-dose-rate brachytherapy in the prevention of keloids." (Veen RE, Int J Radiat Oncol Biol Phys. 2007 Nov 15;69(4):1205-8.)
 * Retrospective. 35 patients with 54 keloids (earlobe/auricle n=23, sternum n=17, others n=14), treated with HDR BT. First dose with 6 hours after surgery, 2 additional doses next day 6 hours apart.
 * Outcome: 45% recurrence after HDR 4/1 + 6/2; 3% recurrence after HDR 6/1 + 8/2; no recurrence after HDR 18/3. Better cosmetic results after higher doses
 * Conclusion: HDR effective; recommend 3 x 6 Gy


 * Amsterdam, 2007 (Netherlands) PMID 17519728 -- "The results of surgical excision and adjuvant irradiation for therapy-resistant keloids: a prospective clinical outcome study." (Van de Kar AL, Plast Reconstr Surg. 2007 Jun;119(7):2248-54.
 * Retrospective. 21 patients with 32 keloids. RT 12 Gy in 3-4 fxs. Mean F/U 19 months
 * Recurrence (elevation of the lesion not confined to the original wound area): 72%
 * Conclusion: RT may not be as efficacious as suggested by other studies


 * U. Washington, 1989 (1966-87) - PMID 2745211 &mdash; "Radiation therapy following keloidectomy: a 20-year experience." Kovalic JJ et al. Int J Radiat Oncol Biol Phys. 1989 Jul;17(1):77-80.
 * 75 pts with 113 keloids with follow-up mean time of 9.7 yrs. 74% involved earlobe. 60% no prior treatment. Superficial X-rays used in 89%, 12 Gy in 3 fx over 3 days most common.
 * Control rate 73%. Failure 19% if no prior treatment, 42% if recurrent.
 * Toxicity: No treatment-related complications. 5% mild hyperpigmentation. Carcinogenesis never reported to their knowledge
 * Prognostic: Higher recurrence in those >2cm, previous therapy, in men. No advantage to starting treatment within 24 hrs versus more than 1 day (range 4-21 days). Mean time to recurrence 12.8 months

Patterns of Care
 * Germany, 2003 (1997-2000) - PMID 12540986 -- "Radiotherapy of keloids. Patterns of care study -- results" [Article in German] (Kutzner J, Strahlenther Onkol. 2003 Jan;179(1):54-8.)
 * See also: ASTRO Abstract 2001 #2271
 * 101 institutions. 1672 patients treated over 35 years. 880 pts with follow-up. Total doses 10-20 Gy using 2-3 Gy fractions, 3-5 times/week.
 * 101 relapses; 11.4%. Most relapses occurred within 2 years. Side effects were low. No secondary malignancies seen.
 * Conclusion: post-operative radiotherapy for keloids is effective.

Specfic sites
Earlobe:
 * SUNY-Brooklyn, 1994 PMID 7805600 -- "Ear lobe keloids, surgical excision followed by radiation therapy: a 10-year experience." (Chaudhry MR, Ear Nose Throat J. 1994 Oct;73(10):779-81.)
 * Retrospective. 36 pts. Mean f/u of 5.6 yrs (minimum of 2 yrs for all pts). Treated with 18 Gy (6 Gy x 3) over 5-7 days.
 * Only 1 recurrence (2.8%).

Toxicity

 * London, 1999 PMID 10703484 -- "The risks of treating keloids with radiotherapy." (Botwood N, Br J Radiol. 1999 Dec;72(864):1222-4.)
 * Case report. 20F with severe chest burns, then developed keloids. RT 13/5 to bilateral chest wall. At age 57, L invasive BCA with LN-. At age 59 R invasive multifocal BCA.
 * Lit review conclusion: No carcinogenicity reported thus far. Causal relationship in this case strong. Two other potential patients reviewed, although causality in one is suspect, and other probably received too high a dose by today's standards

Review

 * UT San Antonio, 2006 PMID 16730305 -- "The role of radiation therapy in benign diseases." (Eng TY, Hematol Oncol Clin North Am. 2006 Apr;20(2):523-57.)