CAM 80162

Electronic Brachytherapy for Nonmelanoma Skin Cancer

Category:Therapy   Last Reviewed:June 2019
Department(s):Medical Affairs   Next Review:June 2020
Original Date:June 2015    

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 (eg, 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 two 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: 
Nonmelanoma skin cancer refers to squamous cell carcinoma and basal cell carcinoma. 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 basal and squamous cell carcinomas and may need to be considered on an individual basis.

Coding
There is a specific CPT category III code for application of electronic brachytherapy to the skin surface:

0394T: High dose rate electronic brachytherapy, skin surface application, per fraction, includes basic dosimetry, when performed.

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 one or more intended clinical uses 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 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 Test Purpose
The purpose of electronic brachytherapy in patients who have nonmelanoma skin cancer 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 nonmelanoma skin cancer?

The following PICOTS were used to select literature to inform this review.

Patients
The relevant population of interest is patients with nonmelanoma skin cancer. Nonmelanoma skin cancer refers to squamous cell carcinoma and basal cell carcinoma. 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 basal and squamous cell carcinomas and may need to be considered on an individual basis.

Interventions
The therapy being considered is electronic brachytherapy.

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

The diagnosis of nonmelanoma skin cancer 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.

Timing
Follow-up to adequately detect nonmelanoma skin cancer recurrence should be at least 5 years.

Setting
Electronic brachytherapy is usually administered in a hospital or free-standing facility.

Systematic Reviews
Delishaj et al (2016) published a systematic review of studies on high-dose rate brachytherapy, including electronic brachytherapy, for the treatment of nonmelanoma skin cancer.6, A literature review conducted through May 2016 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 basal cell carcinoma and the second largest group (35%) was squamous cell carcinoma. Reviewers did not pool study findings, reporting that the rates of local control ranged from 83% to 100%. After median follow-up rangingfrom 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.

Case Series
Evidence consists of uncontrolled studies. The main characteristics and results of published case series are summarized in Table 1.

Table 1. Case Series of Electronic Brachytherapy for Nonmelanoma Skin Cancer

Study (Year)

Population

N

MFU, mo

Treatment

Outcomes

         

Recurrence

Toxicity, %

Paravati et al (2015)7  

Basal, squamous, or basosquamous cell carcinoma 

127 16.1 
  • Axxent Xoft system
  • Total dose 40 Gy in 8 fractions delivered 2 times weekly 
1.2%c (2/154) 

Acute:

  • Grade 0-1=53
  • Grade 2=34.4
  • Grade 3=13

Late:

  • Grade 0-1=94
  • Grade 2=6

Delishaj et al (2015)8 

Nonmelanoma skin cancer 

39  12 
  • Valencia applicator
  • Total dose: 40 Gy  in 8 fractions 
0% 

Acute:

  • Grade 1=58
  • Grade 2=5

Late:

  • Grade 1=19
  • Grade 2=2

Tormo et al  (2014)9

Basal cell carcinoma

32  47
  • Valencia applicator
  • Total dose: 42 Gy in 6-7 fractions
3.1%

Grade 1 = NR
Grade 2 = 0
Grade 3 = 0

Bhatnagar (2013)1

Bhatnagar et al(2010)10,a

Nonmelanoma skin cancer

122  10.0 
  • Axxent Xoft system
  • Total dose 40 Gy in8 fractions delivered twice weekly
0%

Grade 1 = 11
Grade 2 = 13
Grade 3 = 0

Gauden et al (2013)11

Small nonmelanoma skin cancers

200  66b 
  • Leipzig applicator
  • Total dose 36 Gy in 12 fractions delivered daily  
2%c       (4/236) Grade 1 = 71
Grade 2 = 34
Grade 3 = 0

Giux et al (2000)12

 

Basal or squamous cell carcinoma

136  60 
  • Brock applicator
  • Total dose 60-65 Gy in 33-36 fractions
2.2%

NR (“no severe complications”) 

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).11, 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 basal cell carcinoma (53%) or squamous cell carcinoma (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 nonmelanoma skin cancer who receive electronic brachytherapy, the evidence includes a systematic review 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%. In the absence of controlled studies, conclusions cannot be drawn about the efficacy and safety of electronic brachytherapy compared with other treatments for nonmelanoma skin cancer. 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 the effects of the technology on health outcomes.

Practice Guidelines and Position Statements
National Comprehensive Cancer Network
National Comprehensive Cancer Networkguidelines on basal cell carcinoma (v.1.2018)13, and squamous cell skin cancer (v.2.2018)14, both contain the following statement on electronic brachytherapy: “There is insufficient long-term efficacy and safety data to support the routine use of electronic surface brachytherapy.”

American Academy of Dermatology
The American Academy of Dermatology (2018) published guidelines on the management of basal cell carcinoma3, and the management of squamous cell carcinoma.15, Electronic brachytherapy was rated as a C recommendation, with the level of evidence of II and III. By comparison, surgery, cryosurgery, topical therapies, and photodynamic therapies are rated as A and B recommendations.

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 2.

Table 2. Summary of Key Ongoing Trials

NCT No. Trial Name Planned Erollment Completion Date
Ongoing

NCT03024866ª 

Electronic Brachytherapy: A Multi-Center Retrospective-Prospective Matched Pairs Cohort Study to Assess Long Term Clinical Outcomes of Nonmelanoma Skin Cancer Patients Treated with eBx Compared to Nonmelanoma Skin Cancer Patients Treated with Mohs Surgery 

500  Jan 2018 (ongoing) 

NCT01016899a

Xoft Electronic Brachytherapy Clinical Protocol for the Primary Treatment of Non-Melanoma Skin Cancer

100 Feb 2016 (ongoing)

NCT02131805

Electronic Skin Surface Brachytherapy for Cutaneous Basal Cell and Squamous Cell Carcinoma

26  May 2018 

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):134-140. PMID 23312675
  2. Madan V, Lear JT, Szeimies RM. Non-melanoma skin cancer. Lancet. Feb 20 2010;375(9715):673-685. PMID 20171403
  3. American Academy of Dermatology (AAD). 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, Kim NA, Yoo S. 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):100-106. PMID 9218740
  6. 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
  7. 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):e659-664. PMID 26432680
  8. 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):437-444. PMID 26816500
  9. 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):167-172. PMID 25097557
  10. 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
  11. Gauden R, Pracy M, Avery AM, Hodgetts I, Gauden S. HDR brachytherapy for superficial non-melanoma skin cancers. J Med Imaging Radiat Oncol. Apr 2013;57(2):212-217. PMID 23551783
  12. 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 1 2000;47(1):95-102. PMID 10758310
  13. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Basal Cell Skin Cancer. Version 1.2018. https://www.nccn.org/professionals/physician_gls/pdf/nmsc.pdf. Accessed May 29, 2018.
  14. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Squamous Cell Skin Cancer. Version 2.2018. https://www.nccn.org/professionals/physician_gls/pdf/squamous.pdf. Accessed May 29, 2018.
  15. American Academy of Dermatology (AAD). Guidelines of care for the management of cutaneous squamous cell carcinoma. J Am Acad Dermatol. Mar 2018;78(3):560-578. PMID 29331386

Coding Section 

Codes Number Description
CPT  0394T 

High dose rate electronic brachytherapy, skin surface application, per fraction, includes basic dosimetry, when performed (new code 07/01/15)

ICD-9 Procedure    
ICD-9 Diagnosis  

Investigational for all relevant diagnoses

HCPCS    
ICD-10-CM (effective 10/01/15)  

Investigational for all relevant diagnoses

   

Codes for basal cell and squamous cell carcinomas of the skin (C44.00- C44.99) are dependent on the anatomic location of the lesion. There are too many to list here so the following codes are just examples.

  C44.211- C44.219

Basal cell carcinoma of skin of ear and external auricular canal code range

  C44.221-C44.229

Squamous cell carcinoma of skin of ear and external auricular canal code range

  C44.310-C44.319

Basal cell carcinoma of skin of other and unspecified parts of face code range (includes nose)

  C44.320-C44.329

Squamous cell carcinoma of skin of other and unspecified parts of face code range (includes nose)

  C44.41

Basal cell carcinoma of skin of scalp and neck

  C44.42

Squamous cell carcinoma of skin of scalp and neck

ICD-10-PCS (effective 10/01/15)  

ICD-10-PCS codes are only used for inpatient services. There is no specific ICD-10-PCS code for this proceduresurface application.

Type of Service    
Place of Service    

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross and Blue Shield Association technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies and accredited national guidelines.

"Current Procedural Terminology© American Medical Association.  All Rights Reserved" 

History From 2015 Forward     

06/04/2019 

Annual review, no change to policy intent. Updating background, rationale and references. 

06/01/2018 

Annual review, no change to policy intent. Updating rationale and references. 

06/06/2017 

Annual review, no change to policy intent. Updating background, description, guidelines, rationale and references. 

06/06/2016 

Annual review, no change to policy intent. Updating guidelines and coding.

12/1/2015

Updated CPT codes with 2016 codes. No change to intent of policy.

06/09/2015

NEW POLICY


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