Superficial radiotherapy (SRT‐100) for refractory plantar warts: An alternative noninvasive treatment strategy

Verrucas that occur on the soles of the feet are called plantar warts, most of which can recur repeatedly and are difficult to eradicate. Hypertrophic and refractory plantar warts are often accompanied by pain and discomfort, which cause many inconveniences in patients' daily lives.


| INTRODUC TI ON
Verruca vulgaris is a common, local, proliferative lesion caused by human papillomavirus (HPV) infection.More than 100 HPV strains have been identified in humans. 1 HPV is responsible for a spectrum of dermatological and gynecological lesions.4][5][6] Verrucas that occur on the soles of the feet are called plantar warts.Refractory hypertrophic plantar warts are often located on the soles of the feet, and long-term walking can cause pain by compressing nerves within normal skin.The wide distribution of this type of warts in the body makes it difficult to implement conventional liquid nitrogen cryotherapy, laser therapy, and surgical treatment.
Patients who have not undergone treatment for a long time will gradually experience increased and thickened warts, which are difficult to self-resolve and can cause many inconveniences in their daily lives.Superficial radiotherapy (SRT-100, Sensus Healthcare, USA) is a recently developed mobile superficial therapy medical system for dermatology.It is mainly used to eradicate skin malignant tumor cells and reduce the probability of tumor recurrence, and for postoperative radiotherapy in keloid patients, it is used to inhibit fibroblast proliferation and prevent the recurrence of keloid.In recent years, studies have reported that radiotherapy has a lethal effect on HPV.

| ME THODS
A retrospective study was conducted on patients with plantar warts who were treated with SRT-100 in the outpatient department of our hospital from January to June 2023.All data used were from outpatient medical records.Plantar warts were diagnosed on the basis of history, characteristic skin lesions, and related imaging examinations such as VivaScope 1500 (VivaScope 1500, NY, USA) or dermatoscopy (FotoFinder Bodystudio ATBM, Germany) and were confirmed by at least two dermatologists.The treatment plan mainly refers to the patient's treatment plan and record of treatment implementation forms (Table 1).The characteristic information includes age, sex, regression of skin lesions, adverse reactions, and recurrence of lesions (Table 2).The therapeutic effects of superficial radiotherapy on the patient's skin lesions are mainly divided into three types: complete resolution (Figure 1), partial resolution (Figure 2), and no response.Recurrent or new skin lesions refer to new skin lesions that have subsided and reappeared after treatment, and the main adverse reactions include erythema, burning pain, edema, or any other discomfort at the irradiation site after treatment.

| RE SULTS
A total of 30 patients were included in the statistical analysis, with 23 men and 7 women.The maximum age among patients was 65 years, and the minimum age was 6 years (median age, 33 years).
Our current statistics show that men are more susceptible to plantar warts than women.At 3-9 months of follow-up after radiotherapy, plantar warts in 23 patients disappeared completely (76.67%),and most warts disappeared in 4 patients (13.33), which means that 27 (90%) patients exhibited good therapeutic effects.Meanwhile, 3 (10%) patients did not show a significant response to treatment, and warts had not significantly decreased or subsided after 9 months of follow-up after radiotherapy.Among the 27 patients who exhibited good therapeutic effects, 7 (23.33)had recurrence or new warts on the plantar area 3-9 months after the disappearance of the primary warts on the plantar area, with varying numbers.No patient exhibited erythema, edema, pain, or any other special discomfort after completing treatment or during the subsequent 3-9 months of follow-up, and most patients exhibited varying degrees of hyperpigmentation at the irradiation site (Table 2; Figures 1 and 2).

| DISCUSS ION
Because of frequent friction and pressure on the soles of the feet, most warts are flat, and some lesions are keratinized and thickened.Some patients have pain and discomfort when walking, which affects their daily lives. 7,8Plantar warts are treated in various ways, including liquid nitrogen freezing, laser cautery, surface grinding, surgery, and chemical corrosion (e.g., imiquimod, podophyllotoxin, and 5-fluorouracil).Different types of laser therapy can be used, such as carbon dioxide laser, neodymium-doped yttrium aluminum garnet laser, pulsed dye laser, or their combination. 91][12][13] Because the treatment process is accompanied by obvious pain and other discomforts, young patients are often unable to cooperate effectively.
Radiotherapy is an early treatment method that was first used to promote tumor cell apoptosis.Because radiation rays act not only on diseased tumor cells but also on normal tissue cells in the human

TA B L E 1
Treatment plan for patients with plantar warts.
body, radiotherapy is generally only used for keloids with obvious hyperplasia in dermatology, and it is rarely used for any other benign lesions. 14,15In recent years, with the advancement of science and technology, radiotherapy has become more precise.In superficial radiotherapy (SRT-100), a computer is used to accurately calculate and deliver the doses so that the radiation can be concentrated on the superficial part of the skin while minimizing damage to normal cells.Therefore, superficial radiotherapy is suitable not only for skin tumors and keloids but also for benign lesions such as hemangiomas, dermatitis, eczema, psoriasis, and viral warts.Because its rays are precisely controlled, harmful and useless rays that scatter can be reduced to the minimum.It can even be used to treat infantile hemangioma.
We performed superficial radiotherapy for refractory plantar warts.However, because of the limited treatment available throughout the world, there is a dearth of literature available for reference in formulating treatment plans.To address this, we reviewed radiotherapy plans for similar skin diseases (keloids), with radiation treatment ranging from 1 to 5 fractions, radiation doses ranging from 2 to 10 Gy per fraction, and total doses ranging from 8 to 20 Gy.The voltage was generally 50-70 kV.The efficacy varied, but there were no obvious adverse reactions. 16Referring to the literature on safe radiotherapy doses, 17 we developed a treatment plan of four fractions with a voltage of 70 kV, a dose of 3-3.5 Gy per fraction, and a total dose of 12-14 Gy.In our study, the plantar warts of most patients subsided within 3-6 months after radiotherapy, whereas those of a few patients had mostly subsided with only a few remaining, and only a few patients had no response to treatment.
On this basis, we can conclude that superficial radiotherapy as an alternative noninvasive treatment option is indeed effective in treating refractory plantar warts.Meanwhile, except for temporary hyperpigmentation at the irradiation site, patients who received treatment did not have any other special discomfort.Therefore, superficial radiotherapy within the safe dose range has good tolerance, and patients do not experience pain.The treatment only takes a short time and is suitable for various patients.However, similar to other viruses, there is currently no effective method to eradicate HPV.This means that patients with plantar warts may experience recurrence or new onset after warts subside, as confirmed by some of the recurrence or new cases in our follow-up patients.Based on the literature and clinical experience, radiotherapy combined with immunosuppression, immune regulation, cryotherapy, laser therapy, and other treatment options may help reduce the recurrence of lesions.However, as a radiotherapy option, superficial radiotherapy has inevitable radiation damage, so pregnant or lactating women are not suitable for this treatment.In addition, there are strict restrictions on the safe cumulative dose of radiotherapy, so multiple courses of treatment cannot be repeated, which is the limitation of this treatment strategy.Furthermore, the sample size included in our study was only 30 cases, lacking statistical analysis of large clinical cases.Therefore, the statistical results cannot fully reflect the actual effect of SRT-100 superficial radiotherapy and the incidence of adverse reactions after treatment, which is the limitation of this study.

TA B L E 2
Patients' information and 3-9 months of follow-up after treatment completion (N = 30).

| CON CLUS ION
Compared with other traditional methods of treatment for refractory plantar warts, superficial radiotherapy has the advantages of short treatment time, fewer adverse reactions, a painless and noninvasive treatment process, and a curative effect.It can effectively and quickly remove warts when other treatment methods are not effective.Therefore, as a relatively novel treatment scheme for warts that has emerged in recent years, superficial radiotherapy for patients with refractory plantar warts is a therapeutic scheme worthy of promotion or is an effective supplement to traditional treatment options.However, HPV has the characteristic of recurrent attacks; therefore, subsequent combination therapy plans should be implemented to consolidate efficacy and reduce virus recurrence.

ACK N OWLED G M ENTS
We thank LetPub (www.letpub.com) for its linguistic assistance during the preparation of this manuscript.

CO N FLI C T O F I NTER E S T S TATEM ENT
There are no conflicts of interest involved in the publication of this report.

DATA AVA I L A B I L I T Y S TAT E M E N T
The data that support the findings of this study are available on request from the corresponding author.The data are not publicly available due to privacy or ethical restrictions.

E TH I C S S TATEM ENT
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (ethical code of the Universit`a degli Studi della Campania "L.Vanvitelli," approved with D. R. 992/2012) and with the Helsinki Declaration of 1964, as revised in 2013.

CO N S E NT
The patients in this manuscript have provided written informed consent for the publication of their case details.

R E FE R E N C E S
Abbreviation: SSD, source-skin distance.

F I G U R E 1
or new occurrence of warts, n (%) 7 (23.33)Adverse reactions (erythema, pain, desquamation), n 0 Before and after superficial radiotherapy for right plantar warts.Left, warts before radiotherapy.Middle, 1 month after radiotherapy, most of the warts disappeared.Right, 6 months after radiotherapy, the warts disappeared completely.