Superficial radiation therapy (SRT) greatly reduces keloid recurrence rates and, for keratinocytic skin cancers, provides short-term cure rates similar to those in previous SRT research and of surgical options including Mohs surgery, Brian Berman, MD, PhD, told Dermatology Times®.Using ultrasound-based image guidance may improve nonmelanoma skin cancer (NMSC) out- comes, added Berman, Professor Emeritus of dermatology and cutaneous surgery at the University of Miami Miller School of Medicine and codirector of the Center for Clinical and Cos- metic Research in Aventura, both in Florida. Berman presented on SRT for keloid treatment as part of a conference track on dermatology updates for the therapy along with new and emerging medicines to treat skin cancers at the Music City Scale Symposium 16th Annual Meeting, August 18-22, 2021, in Nashville, Tennessee.1
VISUALIZING SKIN CANCERS
He pointed to a recent review of 2917 invasive and in situ keratinocytic carcinomas treated with image-guided SRT (IGSRT) which showed an overall control rate of 99.3% at patients’ last follow-up.2 Based on these results, authors led by Lio Yu, MD, suggested considering IGSRT as a first-line option for keratinocytic tumors in suitable early-stage patients. Yu is a radiation oncologist at Laserderm Dermatology in Smithtown, New York. “These results, while observed with approximately 55% of patients having follow-up for 12 months or more, appear at this time to be at least consistent with the results of standard surgical and nonsurgical modalities used to treat NMSC,” wrote the study authors.
Performing 22-MHz ultrasound imaging before SRT (SRT-100 Vision; Sensus Health- care) facilitates visualizing tumor depth up to 6 mm, said Berman, a consultant and investigator with Sensus. “Once you know the depth of the tumor, you can correlate it with percentage depth dose tables,” he said. Whereas the study’s 99.3% tumor control rate “at last follow-up” is a rather broad statement in his view, Berman said control rates were equally impressive when one considers only tumors with at least 1 year of follow-up (n = 1639, also 99.3%), and only invasive BCC and squamous cell carcinoma (n = 1242, 99.2%).
In fact, said Berman, the study’s 99% control rate is higher than the 90% to 96% rates reported in most SRT studies,3,4 and on par with results of Mohs surgery.5 “It’s not counterintuitive that if you can visualize the tumor, then you know where to aim the beam and how deep the beam needs to go,” he added. “[And] maybe you’re going to get a higher cure rate than what’s been in the literature, which has very robust data supporting the effectiveness of SRT on NMSC.”
“Having said that, I am not advocating using SRT for all nonmelanoma skin cancers in all patients,” he cautioned. “Surgery is the standard of care for nonmelanoma skin cancers.”
However, he said, SRT is well suited for patients who resist or cannot undergo surgery. In his experience practicing in Florida, Berman reported that patients who have undergone previous skin cancer excisions may reject additional scarring surgeries. Additionally, elderly patients with other comorbidities—Berman explained that, generally, relevant comorbidities increase with age—or those on anticoagulants may benefit by avoiding surgery, he noted.
David J. Goldberg, MD, JD, director of Skin Laser & Surgery Specialists; director of cos- metic dermatology and clinical research with the Schweiger Dermatology Group; clinical professor of dermatology and past director of Mohs surgery and laser research at Icahn School of Medicine at Mount Sinai, and adjunct professor of law at Fordham University School of Law, in New York, New York, also noted positive outcomes for this therapy. “Having an SRT unit added to my busy Mohs surgery office has greatly added to our ability to treat many more patients with nonmelanoma skin cancer,” he said. “Each technique has its benefits. With an increasingly older population of patients who are not good surgical candidates, SRT provides high cure rates for many people. Similarly, for a younger, cosmetically concerned patient base, SRT can lead to elegant cosmetic results with a high cure rate.”
The IGSRT study’s retrospective nature requires interpreting results cautiously, Berman said. However, he added, long-term prospective skin cancer studies are very difficult to perform. The 99% cure rate remains impressive, in his view. “If there’s a recurrence 3 years later, let’s say, in the margin where the port didn’t catch the original tumor, you’re not handcuffed from using surgery at that point,” he said.
TREATING KELOID RECURRENCE
Keloids commonly occur in high-visibility locations such as the face and earlobes. “When a patient comes to me with a keloid, I try to talk them out of surgery,” Berman said. Without adjunctive therapy such as SRT, recurrence rates are high, Berman added. In unpublished research, he reviewed 13 studies incorporating 343 patients and calculated a weighted-average postkeloidectomy recurrence rate of 71.2%.9,10“Very often, I’ll say, ‘You have a small keloid. If I were able to take away the burning, itching, and tenderness and get it softer and maybe a little flatter, would that be sufficient?’ And I hope they say yes, because there are other modalities to treat an existing keloid without cutting it out,” Berman said. With a referral-based practice, though, his patients typically want surgery because conservative treatments have failed.Berman explains to patients that postsurgical SRT offers a noninvasive tool for reducing recurrence risk. Separate studies show that this treatment reduces postsurgical recurrence rates to 3.0% and 10.4%, respectively.11,12 “Dropping the recurrence rate from 7 out of 10 to 1 out of 10, with at least 1 year of follow-up, is very helpful to the clinician to be able to hold out hope to patients,” he said.13
Radiation therapy is believed to treat keloid recurrence by reducing fibroblast proliferation, arresting the cell cycle, and inducing apoptosis.13 Although these mechanisms delay healing in normal skin, they are tailor-made for treating keloids with their excessive scarring and for destroying malignant, abnormal cells in nonmelanoma skin tumors arising from bro- blast or keratinocyte hyperproliferation, accord- ing to Berman.
“The mechanisms are consistent, but there are different reasons why we’d use it for keloids vs a tumor,” he said. The SRT-100 is FDA 510(k) cleared for treating NMSC and keloids. Berman said colleagues have told him that they bought the machine for NMSC but now use it more often for postsurgical keloid recurrences.Patients may worry about radiation therapy and carcinogenesis, Berman said. “I appreciate that. But I explain to them the historical safety of SRT, and the fact that it only goes a few milli- meters deep at most into the skin, [meaning] it’s truly super cial radiation therapy.”
Moreover, a 10-year retrospective analysis of 264 excised keloids, of which most received sub- sequent external-beam radiation or high dose- rate interstitial brachytherapy, showed no development of malignancy.14 Similarly, a search of Medline and PubMed between 1901 and March 2009 uncovered only 5 cases of carcinogenesis associated with, but not likely caused by, postkeloidectomy radiation therapy, Berman said. The cancers included BCC, thyroid cancer, breast cancer, and fibrosarcoma.
“Intuitively, it doesn’t make sense that radiation therapy induced the development of BCC because we use radiation therapy to treat BCC,” Berman said. Breast cancers originate at deeper levels than SRT penetrates, and the noted thyroid cancer did not develop in the treated area, he added. The single fibrosarcoma investigators found was probably a fibrosarcoma before surgery, authors allowed. These tumors typically take a decade to develop, Berman explained, whereas study follow-up periods generally are considerably shorter.
Pacemakers implanted in the treatment area are a contraindication for SRT, in his opinion. Regarding adverse effects, Berman said he warns patients about the potential for postradiation pigmentary changes, most often hyperpigmentation. In a chart review of 96 excised keloids followed for at least 1 year on which he was lead author, 56% of subjects experienced hyperpigmentation. Usually transient, he said, less than 5% of patients experienced persistent hyperpigmentation.
Because of the safety and efficacy of SRT, Berman suggested that more dermatologists con- sider o ering this therapy. “It’s part of our armamentarium to treat a patient who has disfiguring keloids that have an impact physically, cosmetically, and psychologically,” he said. In appropriately selected patients with keratinocytic skin cancers, results are commensurate with the standard of care, he added.
DisclosuresBerman is a consultant and investigator for Sensus. Goldberg reports no relevant nancial interests.
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ble option in select patients. J Am Acad Dermatol. 2012;67(6):1235-1241. doi:10.1016/j.jaad.2012.06.0015 Tolkachjov SN, Brodland DG, Coldiron BM, et al. Understanding Mohs micro- graphic surgery: a review and practical guide for the nondermatologist. Mayo Clin Proc. 2017;92(8):1261-1271. doi:10.1016/j.mayocp.2017.04.0096 Rodriguez JM, Deutsch GP. The treatment of periocular basal cell carcinomas by radiotherapy. Br J Ophthalmol. 1992;76(4):195-197. doi:10.1136/bjo.76.4.1957 Grossi Marconi D, da Costa Resende B, Rauber E, et al. Head and neck non-mela- noma skin cancer treated by super cial x-ray therapy: an analysis of 1021 cases. PLoS One. 2016;11(7):e0156544. doi:10.1371/journal.pone.01565448 Lawrence WT. In search of the optimal treatment of keloids: report of a series and a review of the literature. Ann Plast Surg. 1991;27(2):164-178. doi:10.1097/00000637-199108000-000129 Shaffer JJ, Taylor SC, Cook-Bolden F. Keloidal scars: a review with a critical look at therapeutic options. J Am Acad Dermatol. 2002;46(2 Suppl Understand- ing):S63-S97. doi:10.1067/mjd.2002.12078810 Berman B, Nestor MS, Gold MH, Goldberg DJ, Fox J, Schmieder G. Low rate of keloid recurrences following treatment of keloidectomy sites with a biologically effective dose 30 of super cial radiation. SKIN The Journal of Cutaneous Medi- cine. 2018;2(6):402-403. doi:10.25251/skin.2.6.711 Berman B, Nestor MS, Gold MH, Goldberg DJ, Weiss ET, Raymond I. A retro- spective registry study evaluating the long-term ef cacy and safety of super – cial radiation therapy following excision of keloid scars. J Clin Aesthet Dermatol. 2020;13(10):12-16.12 Liu X, Liu JZ, Zhang E, et al. Impaired wound healing after local soft x-ray irra- diation in rat skin: time course study of pathology, proliferation, cell cycle, and apoptosis. J Trauma. 2005;59(3):682-690.13 Hoang D, Reznik R, Orgel M, Li Q, Mirhadi A, Kulber DA. Surgical excision and adjuvant brachytherapy vs external beam radiation for the effective treat- ment of keloids: 10-year institutional retrospective analysis. Aesthet Surg J. 2017;37(2):212-225. doi:10.1093/asj/sjw12414 Ogawa R, Yoshitatsu S, Yoshida K, Miyashita T. Is radiation therapy for keloids acceptable? The risk of radiation-induced carcinogenesis. Plast Reconstr Surg. 2009;124(4):1196-1201. doi:10.1097/PRS.0b013e3181b5a3ae