Description:
Electronic brachytherapy is a form of radiotherapy designed to deliver high-dose rate radiation to treat nonmelanoma skin cancer. This technique focuses a uniform dose of X-ray source radiation to the lesion with the aid of a shielded surface application.

For individuals who have nonmelanoma skin cancer who receive electronic brachytherapy, the evidence includes case series. Relevant outcomes are overall survival, disease-specific survival, change in disease status, and treatment-related morbidity. No controlled trials were identified that compared electronic brachytherapy with alternative treatment options. The cases series, which usually contained mixed patient populations of basal and squamous cell carcinomas, reported low rates of recurrence, ranging from 0% to 3%, at follow-up periods ranging from 10 to 66 months. Skin toxicity is relatively common, but usually mild. Controlled trials are needed in defined populations that compare electronic brachytherapy with alternatives, either other forms of radiotherapy or surgical approaches. The evidence is insufficient to determine the effects of the technology on health outcomes.

Background:
Nonmelanoma Skin Cancer
Squamous cell carcinoma and basal cell carcinoma are the most common types of nonmelanoma skin cancer in the United States, affecting between 1 million and 3 million people per year^,1,2 and increasing at a rate of 3% to 8% per year.² Other types (e.g., T-cell lymphoma, Merkel cell tumor, basosquamous carcinoma, Kaposi sarcoma) are much less common. The primary risk factor for nonmelanoma skin cancer is sun exposure, with additional risk factors such as toxic exposures, other ionizing radiation exposure, and immunosuppression playing smaller roles.² Although these cancers are rarely fatal, they can impact the quality of life, functional status, and physical appearance.

Treatment
In general, the most effective treatment for nonmelanoma skin cancer is surgical. If surgery is not feasible or preferred, cryosurgery, topical therapy, or radiotherapy can be considered, though the cure rate may be lower.³ When considering the most appropriate treatment strategy, recurrence rate, preservation of function, patient expectations, and potential adverse events should be considered.

Surgical
The choice of surgical procedure depends on the histologic type, size, and location of the lesion. Patient preferences can also play a factor in surgical decisions due to cosmetic reasons-as well as the consideration of comorbidities and patient risk factors, such as anticoagulation. Local excisional procedures, such as electrodesiccation and curettage or cryotherapy, can be used for low-risk lesions, while surgical excision is indicated for lesions that are not low risk. Mohs surgery is an excisional procedure that uses microscopic guidance to achieve greater precision and sparing of normal tissue. In patients who meet criteria for Mohs surgery, 5-year cure rates for basal cell cancer range from 98% to 99%,⁴ making Mohs surgery the preferred procedure for those who qualify.

Radiotherapy
Radiotherapy is indicated for certain nonmelanoma skin cancers not amenable to surgery. In some cases, this is due to the location of the lesion on the eyelid, nose, or other structures that make surgery more difficult and which may be expected to have a less desirable cosmetic outcome. In other cases, surgery may be relatively contraindicated due to clinical factors, such as bleeding risk or advanced age. In elderly patients with a relatively large tumor that would require extensive excision, the benefit/risk ratio for radiotherapy may be considered favorable. The 5-year control rates for radiotherapy range from 80% to 92%, which is lower than that of surgical excision.⁴ A randomized controlled trial by Avril et al. (1997) reported that radiotherapy for basal cell carcinoma resulted in greater numbers of persistent and recurrent lesions compared with surgical excision.⁵

When radiotherapy is used for nonmelanoma skin cancer, the primary modality is external-beam radiotherapy. A number of different brachytherapy techniques have also been developed, including low-dose rate systems, iridium-based systems, and high-dose ratesystems.⁴

Electronic Brachytherapy
Electronic brachytherapy is a form of radiotherapy delivered locally, using a miniaturized electronic X-ray source rather than a radionuclide-based source. A pliable mold, constructed of silicone or polymethyl-methacrylate, is fitted to the tumor surface. This mold allows treatment to be delivered to nonflat surfaces such as the nose or ear. A radioactive source is then inserted into the mold to deliver a uniform radiation dosage directly to the lesion.⁴ Multiple treatment sessions within a short time period (typically within a month) are required.

This technique is feasible for well-circumscribed, superficial tumors because it focuses a uniform dose of X-ray source radiation on the lesion with the aid of a shielded surface application. Advantages of this treatment modality compared with standard radiotherapy include a shorter treatment schedule, avoidance of a surgical procedure and hospital stay, less severe side effects because the focused radiation spares healthy tissue and organs, and the avoidance of radioisotopes. 

Regulatory Status: 
Electronic brachytherapy systems for the treatment of nonmelanoma skin cancers are designed to deliver HDR brachytherapy for the treatment of skin surface lesions. This technique focuses a uniform dose of X-ray source radiation to the lesion with the aid of a shielded surface application. The Esteya^® Electronic Brachytherapy System (Nucletron BV) and the Xoft^® Axxent^® Electronic Brachytherapy System (iCAD Inc.) are 2 systems that recently received FDA clearance through the 510(k) process. FDA product code: JAD.

Policy: 
Electronic brachytherapy for the treatment of nonmelanoma skin cancer (see Policy Guidelines section) is considered INVESTIGATIONAL.

Policy Guidelines: 
Coding
Please see the Codes table for details.

Benefit Application 
BlueCard/National Account Issues
State or federal mandates (e.g., FEP) may dictate that certain U.S. Food and Drug Administration (FDA)‒approved biologics may not be considered investigational and, thus, these drugs may be assessed only on the basis of their medical necessity.

Rationale:  
Evidence reviews assess the clinical evidence to determine whether the use of a technology improves the net health outcome. Broadly defined, health outcomes are length of life, quality of life, and ability to function-including benefits and harms. Every clinical condition has specific outcomes that are important to patients and to managing the course of that condition. Validated outcome measures are necessary to ascertain whether a condition improves or worsens; and whether the magnitude of that change is clinically significant. The net health outcome is a balance of benefits and harms.

To assess whether the evidence is sufficient to draw conclusions about the net health outcome of a technology, 2 domains are examined: the relevance and the quality and credibility. To be relevant, studies must represent 1 or more intended clinical use of the technology in the intended population and compare an effective and appropriate alternative at a comparable intensity. For some conditions, the alternative will be supportive care or surveillance. The quality and credibility of the evidence depend on study design and conduct, minimizing bias and confounding that can generate incorrect findings. The randomized controlled trial (RCT) is preferred to assess efficacy; however, in some circumstances, nonrandomized studies may be adequate. Randomized controlled trials are rarely large enough or long enough to capture less common adverse events and long-term effects. Other types of studies can be used for these purposes and to assess generalizability to broader clinical populations and settings of clinical practice.

Electronic Brachytherapy for Nonmelanoma Skin Cancer
Clinical Context and Therapy Purpose
The purpose of electronic brachytherapy in patients who have nonmelanoma skin cancer (NMSC) is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this evidence review is: Does the use of electronic brachytherapy improve the net health outcome in patients with NMSC?

The following PICO was used to select literature to inform this review.

Populations
The relevant population of interest is patients with NMSC. Nonmelanoma skin cancer refers to squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). There are other less common types of skin cancer, such as T-cell lymphoma or Merkel cell tumor, which may have specific treatment options that differ from SCC and BCC and may need to be considered on an individual basis.

Interventions
The therapy being considered is electronic brachytherapy. Electronic brachytherapy is a form of radiotherapy delivered locally, using a miniaturized electronic X-ray source rather than a radionuclide-based source. Multiple treatment sessions within a short time period (typically within a month) are required.

Comparators
The following therapies are currently being used: surgery (excision or Mohs surgery), external-beam radiotherapy (EBRT), and standard brachytherapy.

The diagnosis of NMSC involves a detailed review of medical history, a clinical exam, and a skin biopsy. Information from the diagnostic process can assess the risk of recurrence, which informs the choice of treatment. Location and size of the skin cancer are also factors in choosing the treatment strategy. Brachytherapy is considered when lesions are located on anatomic curves or are near critical organs.

Outcomes
The general outcomes of interest are survival, recurrence rates, and treatment-related morbidity. Follow-up to adequately detect NMSC recurrence should be at least 5 years.

Study Selection Criteria
Methodologically credible studies were selected using the following principles:

• To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs.
• In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
• To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
• Studies with duplicative or overlapping populations were excluded.

Review of Evidence
Systematic Reviews
Lee et al. (2019) published a meta-analysis of 58 studies including 21,371 patients treated with conventional surgical excision (24 studies), Mohs micrographic surgery (MMS; 13 studies), EBRT (19 studies), or high-dose-rate brachytherapy (7 studies) for indolent BCC and SCC of the skin.⁶ "Good" cosmesis was reported in 81% (95% confidence interval [CI], 70.6% to 89.6%), 74.6% (95% CI, 63% to 84.6%), and 97.6% (95% CI, 91.3% to 100%) of patients treated with conventional excision, EBRT, and brachytherapy, respectively. This was comparable to the 96% "good" cosmesis grade outcome reported in 1 MMS study. The 5-year local recurrence rate for brachytherapy was 2.5% (95% CI, 0.8% to 5.1%), which was comparable to both MMS (1.8%; 95% CI, 1.1% to 2.7%) and conventional excision (2.1%; 95% CI, 1.0% to 3.5%). The authors concluded that interpretation of results may be limited by selection bias and subjective and heterogeneous cosmesis grading systems, warranting further prospective, comparative studies.

Delishaj et al. (2016) published a systematic review of studies on high-dose rate brachytherapy, including electronic brachytherapy, for the treatment of NMSC.⁷ A literature review conducted through May 2019 identified 10 case series with sample sizes of 20 patients or more that reported on nonoverlapping patients. Findings were reported for 1870 patients (N = 1870 lesions). Most lesions (65%) were BCC and the second largest group (35%) was SCC. Reviewers did not pool study findings, reporting that the rates of local control ranged from 83% to 100%. After median follow-up ranging from 9 months to 10 years, recurrence rates ranged from 0% to 17%. Seven of the 10 studies reported recurrence rates of less than 5%, 2 had recurrence rates of 8% to 9%, and 1 study had a recurrence rate of 17%. The 2 studies with recurrence rates in the 8%-to-9% range used Leipzig applicators and the study with a 17% recurrence rate used high-dose rate brachytherapy with surface applicators or custom-made surface molds.

Prospective Cohort Study
Patel et al. (2017)8, published preliminary results from a multi-center prospective matched pair cohort study (NCT03024866) comparing clinical outcomes of NMSC treated with electronic brachytherapy or MMS. Patients from 4 treatment centers who had already received treatment for NMSC with electronic brachytherapy and met eligibility criteria were invited to participate. A retrospective chart review was used to individually match patients with patients who had received MMS for NMSC based on patient age (± 15 years), lesion size, type and location, and treatment dates. All MMS-treated subjects treated in the same time-frame were considered for matching and the final pair was selected based on the closest match of demographics and lesion characteristics. A total of 369 patients were included for study representing 208 matched lesion pairs. Additional eligibility criteria included:

• completion of electronic brachytherapy or MMS for NMSC ≥3 years prior
• age > 40 yrs
• diagnosis of SCC or BCC
• cancer stage 0-2

Exclusion criteria included:

• target area adjacent to burn scar
• surgical resection of the cancer prior to electronic brachytherapy
• presence of actinic keratosis
• known metastatic disease

Patients were evaluated for follow-up at 2.3 to 5.0 years post-treatment. Treatment with electronic brachytherapy was performed with a miniature, high dose rate electronic X-ray source using standard surface applicators. A dose of 40.0 Gy in 8 fractions (5 Gy twice weekly) was used to delivered to a depth of 2 to 3 mm but in some cases a customized dose, depth, or schedule. Mohs micrographic surgery was performed by clinicians according to guidelines of the American College of Mohs Surgery. Matching of patients based on lesion characteristics was based on histopathology of BCC or SCC , cancer staging (Stage 0, Stage 1, Stage 2), size (≤1 cm, >1 cm and ≤2 cm, >2 cm and ≤3 cm), and location (head, ear, eyelid, face/neck, lip, scalp, nose, torso, lower extremity, upper extremity). The mean follow-up length was 3.3 years for the electronic brachytherapy group and 3.5 years for the MMS group. The primary outcome was absence of NMSC recurrence at follow-up. Secondary outcomes included late toxicities, cosmetic outcomes, and patient satisfaction with treatment. All patients completed all evaluations.

The main characteristics and results are summarized in Table 1.

Table 1. Prospective Cohort Study of Electronic Brachytherapy for Nonmelanoma Skin Cancer⁸

BCC: basal cell carcinoma; CI: confidence interval; EBT: electronic brachytherapy; MFU: mean follow-up; MMS: Mohs micrographic surgery; NMSC: nonmelanoma skin cancer; SCC: squamous cell carcinoma; SD: standard deviation
a Standardized scale adapted from Cox et al. (1995).⁹
b A score of 5 represents the maximum positive or favorable response to each question.

No statistically significant difference was found between electronic brachytherapy (97.6%) and MMS (95.7%) groups for local recurrence absence (p = 1.000). However, 1 recurrence was reported in the EBT group at 1 year post-treatment. No recurrences occurred in the MMS group. No statistically significant differences were noted for secondary endpoints of cosmesis (p = .277) and patient satisfaction with both groups demonstrating predominantly excellent cosmesis grades and high patient satisfaction scores. Late toxicities appeared at similar rates with telangiectiasa being reported slightly more in the electronic brachytherapy vs MMS group (31.4% vs. 11.1%).

A summary of the electronic brachytherapy study relevance limitations is provided in Table 2.

Table 2. Study Relevance Limitations

The study limitations stated in this table are those notable in the current review; this is not a comprehensive gaps assessment.
a Population key: 1. Intended use population unclear; 2. Clinical context is unclear; 3. Study population is unclear; 4. Study population not representative of intended use
b Intervention key: 1. Not clearly defined; 2. Version used unclear; 3. Delivery not similar intensity as comparator; 4. Not the intervention of interest
c Comparator key: 1. Not clearly defined; 2. Not standard or optimal; 3. Delivery not similar intensity as intervention; 4. Not delivered effectively
d Outcomes key: 1. Key health outcomes not addressed; 2. Physiologic measures, not validated surrogates; 3. No CONSORT reporting of harms; 4. Not established and validated measurements; 5. Clinical significant difference not prespecified; 6. Clinical significant difference not supported
e Follow-Up key: 1. Not sufficient duration for benefit; 2. Not sufficient duration for harms
A summary of the electronic brachytherapy study design and conduct limitations is provided in Table 3.

Table 3. Study Design and Conduct Limitations

  
The study limitations stated in this table are those notable in the current review; this is not a comprehensive gaps assessment.
a Allocation key: 1. Participants not randomly allocated; 2. Allocation not concealed; 3. Allocation concealment unclear; 4. Inadequate control for selection bias
b Blinding key: 1. Not blinded to treatment assignment; 2. Not blinded to treatment outcome; 3. Outcome assessed by treating physician
c Selective Reporting key: 1. Not registered; 2. Evidence of selective reporting; 3. Evidence of selective publication
d Data Completeness key: 1. High loss to follow-up or missing data; 2. Inadequate handling of missing data; 3. High number of crossovers; 4. Inadequate handling of crossovers; 5. Inappropriate exclusions; 6. No intent to treat analysis (per protocol for non-inferiority trials)
e Power key: 1. Power calculations not reported; 2. Power not calculated for primary outcome; 3. Power not based on clinically important difference
f Statistical key: 1. Analysis is not appropriate for outcome type: (a) continuous; (b) binary; (c) time to event; 2. Analysis is not appropriate for multiple observations per patient; 3. Confidence intervals and/or p values not reported; 4. Comparative treatment effects not calculated
Major limitations of this study include the presence of selective publication and lack of blinding as patients were clinically evaluated for follow-up by the physician who had administered electronic brachytherapy or MMS. The study is registered but result submissions have been canceled twice and have not been submitted as of January 2019. Since some patients received customized treatments, all intervention characteristics are unclear. Eligibility and exclusion criteria seemed to introduce bias with regard to age and low tumor stage. No statistically significant outcomes were reported for the use of electronic brachytherapy compared to MMS in NMSC.

Case Series
Evidence also includes uncontrolled studies. The main characteristics and results of published case series are summarized in Table 4.

Table 4. Case Series of Electronic Brachytherapy for Nonmelanoma Skin Cancer

Gy: gray; MFU: mean follow-up; NR: not reported.
a Overlapping case series; results from larger, more recent publication reported.
b Median.
c Calculated based on number lesions not patients.

The largest series was published by Gauden et al. (2013) and included 200 patients with 236 lesions (121 basal cell, 115 squamous cell).¹⁵ Brachytherapy was the primary treatment modality in 69% of the lesions, while in the remaining 31% (74/236) brachytherapy was a follow-up treatment to surgery when there were positive margins. Outcomes included treatment efficacy, as measured by local recurrence rate, skin toxicity measured using Radiation Therapy Oncologic Group criteria, and cosmetic outcome using the Radiation Therapy Oncologic Group Cosmesis Scale. After a median follow-up of 66 months, there were recurrences in 2% (4/236) of treated lesions. Cosmetic outcome was judged to be excellent or good in 88% (208/236) of treated lesions. Grade 1 skin toxicity was common (71% of treated lesions); grade 2 toxicity was less common (34%); and no instances of grade 3 or higher toxicities were noted. Late hypopigmentation of treated skin was reported in 5.5% (13/236) of treated lesions.

Bhatnager (2013) published a case series using a commercially available device (Axxent eBx System).¹ The series included 122 patients with 171 nonmelanoma skin lesions. Most patients had either BCC (53%) or SCC (41%); 10 (5.8%) patients had other types of cancer. Outcome measures included recurrence rates, adverse events using version 3.0 of the Common Terminology Criteria for Adverse Events, and cosmetic results using a standardized Cosmesis Scale. After a mean 10-month follow-up, there were no local recurrences. Dermatitis and pruritus were common early adverse events, occurring in 83% and 18% of the treated lesions, respectively. Skin hypopigmentation was the most common late adverse event, occurring in 10.9% of lesions at 1 year. Other late complications included rash (6.5%), alopecia (2.2%), and dry desquamation (2.2%). All patients had their cosmetic outcomes rated as good or excellent.

Summary of Evidence
For individuals who have NMSC who receive electronic brachytherapy, the evidence includes 2 systematic reviews, a prospective cohort study, and case series. Relevant outcomes are overall survival, disease-specific survival, change in disease status, and treatment-related morbidity. No controlled trials were identified that have compared electronic brachytherapy with alternative treatment options. A 2016 systematic review of case series found local control rates ranging from 83% to 100% and recurrence rates ranging from 0% to 17%. In most studies, the recurrence rate was less than 5%. A 2019 meta-analysis reported brachytherapy cosmesis grades and 5-year local control rates that were comparable to both MMS and conventional excision. Preliminary results from a prospective matched pair cohort study reported no statistically significant difference in outcomes for the use of electronic brachytherapy compared to MMS in NMSC, but confidence in these findings is low due to study design and conduct limitations. In the absence of randomized controlled studies, conclusions cannot be drawn about the efficacy and safety of electronic brachytherapy compared with other treatments for NMSC. Controlled trials are needed in defined populations that compare electronic brachytherapy with alternatives, specifically other forms of radiotherapy or surgical approaches. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

The purpose of the following information is to provide reference material. Inclusion does not imply endorsement or alignment with the evidence review conclusions.

Practice Guidelines and Position Statements
Guidelines or position statements will be considered for inclusion in ‘Supplemental Information' if they were issued by, or jointly by, a U.S. professional society, an international society with U.S. representation, or National Institute for Health and Care Excellence (NICE). Priority will be given to guidelines that are informed by a systematic review, include strength of evidence ratings, and include a description of management of conflict of interest.

American Academy of Dermatology
In 2018, the American Academy of Dermatology published guidelines on the management of basal cell carcinoma,³ and the management of squamous cell carcinoma.¹⁷ Electronic brachytherapy was rated as a C recommendation, with a level of evidence of II and III. By comparison, surgery, cryosurgery, topical therapies, and photodynamic therapies are rated as A and B recommendations.

American Brachytherapy Society
The American Brachytherapy Society issued a consensus statement on electronic brachytherapy following a literature review focused on trials, prospective studies, multi-institutional series, and single institution reports addressing clinical outcomes and toxicities.¹⁸ Due to a lack of comparative data to traditional treatments and limited long-term follow-up, prospective studies with a larger number of patients undergoing electronic brachytherapy for nonmelanoma skin cancer are recommended. At this time, the statement recommends that treatment with electronic brachytherapy in this patient population should be performed in the context of a clinical registry or trial.

American Society for Radiation Oncology
The American Society for Radiation Oncology (ASTRO) issued clinical practice guidelines regarding definitive and postoperative radiation therapy for basal and squamous cell cancers of the skin.¹⁹ Key questions were addressed by a systematic literature review and recommendations were developed via consensus with a modified Delphi approach. Consensus recommendations for specific dose-fractionation schemes are detailed for the definitive and post-operative settings. The guideline also states that appropriate use of any of the 4 major radiation modalities, including electronically generated low energy sources such as electronic brachytherapy, result in similar local control and cosmetic outcomes. Therefore, "the decision of which modality and fractionation scheme to use should be based on both tumor characteristics (e.g., shape, contour, depth, and location) and normal tissue considerations."

National Comprehensive Cancer Network
The National Comprehensive Cancer Network guidelines on basal cell carcinoma (v.2.2021 )²⁰ and squamous cell skin cancer (v.1.2021 )²¹ both contain the following statement on brachytherapy: "There is insufficient long-term efficacy and safety data to support the routine use of radioisotope or electronic surface brachytherapy."

U.S. Preventive Services Task Force Recommendations
Not applicable

Ongoing and Unpublished Clinical Trials
Some currently unpublished trials that might influence this review are listed in Table 5.

Table 5. Summary of Key Ongoing Trials

NCT: national clinical trial.
a Denotes industry-sponsored or cosponsored trial.

References: 

1. Bhatnagar A. Nonmelanoma skin cancer treated with electronic brachytherapy: results at 1 year. Brachytherapy. Mar-Apr 2013; 12(2): 134-40. PMID 23312675
2. Madan V, Lear JT, Szeimies RM. Non-melanoma skin cancer. Lancet. Feb 20 2010; 375(9715): 673-85. PMID 20171403
3. Kim JYS, Kozlow JH, Mittal B, et al. Guidelines of care for the management of basal cell carcinoma. J Am Acad Dermatol. Mar 2018; 78(3): 540-559. PMID 29331385
4. Alam M, Nanda S, Mittal BB, et al. The use of brachytherapy in the treatment of nonmelanoma skin cancer: a review. J Am Acad Dermatol. Aug 2011; 65(2): 377-388. PMID 21496952
5. Avril MF, Auperin A, Margulis A, et al. Basal cell carcinoma of the face: surgery or radiotherapy? Results of a randomized study. Br J Cancer. 1997; 76(1): 100-6. PMID 9218740
6. Lee CT, Lehrer EJ, Aphale A, et al. Surgical excision, Mohs micrographic surgery, external-beam radiotherapy, or brachytherapy for indolent skin cancer: An international meta-analysis of 58 studies with 21,000 patients. Cancer. Oct 15 2019; 125(20): 3582-3594. PMID 31355928
7. Delishaj D, Rembielak A, Manfredi B, et al. Non-melanoma skin cancer treated with high-dose-rate brachytherapy: a review of literature. J Contemp Brachytherapy. Dec 2016; 8(6): 533-540. PMID 28115960
8. Patel R, Strimling R, Doggett S, et al. Comparison of electronic brachytherapy and Mohs micrographic surgery for the treatment of early-stage non-melanoma skin cancer: a matched pair cohort study. J Contemp Brachytherapy. Aug 2017; 9(4): 338-344. PMID 28951753
9. Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys. Mar 30 1995; 31(5): 1341-6. PMID 7713792
10. Pellizzon ACA, Fogaroli R, Chen MJ, et al. High-dose-rate brachytherapy using Leipzig applicators for non-melanoma localized skin cancer. J Contemp Brachytherapy. Oct 2020; 12(5): 435-440. PMID 33299432
11. Paravati AJ, Hawkins PG, Martin AN, et al. Clinical and cosmetic outcomes in patients treated with high-dose-rate electronic brachytherapy for nonmelanoma skin cancer. Pract Radiat Oncol. Nov-Dec 2015; 5(6): e659-64. PMID 26432680
12. Delishaj D, Laliscia C, Manfredi B, et al. Non-melanoma skin cancer treated with high-dose-rate brachytherapy and Valencia applicator in elderly patients: a retrospective case series. J Contemp Brachytherapy. Dec 2015; 7(6): 437-44. PMID 26816500
13. Tormo A, Celada F, Rodriguez S, et al. Non-melanoma skin cancer treated with HDR Valencia applicator: clinical outcomes. J Contemp Brachytherapy. Jun 2014; 6(2): 167-72. PMID 25097557
14. Bhatnagar A, Loper A. The initial experience of electronic brachytherapy for the treatment of non-melanoma skin cancer. Radiat Oncol. Sep 28 2010; 5: 87. PMID 20875139
15. Gauden R, Pracy M, Avery AM, et al. HDR brachytherapy for superficial non-melanoma skin cancers. J Med Imaging Radiat Oncol. Apr 2013; 57(2): 212-7. PMID 23551783
16. Guix B, Finestres F, Tello J, et al. Treatment of skin carcinomas of the face by high-dose-rate brachytherapy and custom-made surface molds. Int J Radiat Oncol Biol Phys. Apr 01 2000; 47(1): 95-102. PMID 10758310
17. Kim JYS, Kozlow JH, Mittal B, et al. Guidelines of care for the management of cutaneous squamous cell carcinoma. J Am Acad Dermatol. Mar 2018; 78(3): 560-578. PMID 29331386
18. Tom MC, Hepel JT, Patel R, et al. The American Brachytherapy Society consensus statement for electronic brachytherapy. Brachytherapy. May 2019; 18(3): 292-298. PMID 30497939
19. Likhacheva A, Awan M, Barker CA, et al. Definitive and Postoperative Radiation Therapy for Basal and Squamous Cell Cancers of the Skin: Executive Summary of an American Society for Radiation Oncology Clinical Practice Guideline. Pract Radiat Oncol. Jan 2020; 10(1): 8-20. PMID 31831330
20. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Basal Cell Skin Cancer. Version 2.2021. https://www.nccn.org/professionals/physician_gls/pdf/nmsc.pdf. Accessed June 6, 2021.
21. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Squamous Cell Skin Cancer. Version 1.2021. https://www.nccn.org/professionals/physician_gls/pdf/squamous.pdf. Accessed June 6, 2021.

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