Radiation (ebt/hdr) for Non-Melanoma Skin Cancers (NMSCC) in the Dermatologist s Office: A Radiation Oncologist s (Generally Positive) Perspective

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Martina Dawson
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1 Radiation (ebt/hdr) for Non-Melanoma Skin Cancers (NMSCC) in the Dermatologist s Office: A Radiation Oncologist s (Generally Positive) Perspective Mohammad K Khan MD Ph.D FACRO Associate Professor Director, Radiation Immuno-Oncology & Medical Student Clerkship Co-Leader, Immuno-Oncology Department of Radiation Oncology Winship Cancer Institute

2 Disclosures None

3 Objectives 1. Review Evidence for MOHs vs RT 2. High Risk Features that Warrant Adjuvant RT Consideration 3. Technical Advances & Clinical Considerations in HDR- BT

4 History of RT for Skin; 1895-Wilhelm Roentgen discovered the Xray; Leopold Freund of Vienna treated nevus pigmentosus on the back of a 5 yr old girl; J.W.Pugh s article Four cases of rodent ulcers treated by Xrays British dermatologist, Sequeira reported similar success in a 31 y/o female with right nasal Ala BCC; th ADA meeting in Washington DC: RT was a considerable dermatological break through at the time % of dermatology offices used radiation as a treatment modality; *integral part of dermatology residency programs* only 12% used superficial radiotherapy; 2009 FDA gave approval for Axxent ebx for surface BT; 2013 FDA gave approval to Nucletron ebx; 2014 Resurgence in use of ebx by dermatologist/radiation oncologist; 26,000 treatments by radiotherapy 30+ dermatology clinics owning XRT equipment/radiation oncologist; 50% of these are MOH s practices and 50% are general dermatology;

5 History of Radiotherapy for Skin (1902) 93 y/o with rodent ulcer pre and 2 yrs post XRT; 83 y/o with rodent ulcer of left temple before/after XRT; 34 sittings of XRT Pugh JW. Br Med J. 1902;1(2154):

Modern Radiotherapy- 2014 Pre RT Lesion 2 Months Post RT 85 y/o (JG)

heard about the XRT option, daughter was employee in healthcare ; Had

radiation option (hated the open defects, took forever to heal, cosmesis

6 Modern Radiotherapy Pre RT Lesion 2 Months Post RT 85 y/o (JG) with bx proven SCCa of left nasal Ala (Dr Khan) Self referred, never had heard about the XRT option, daughter was employee in healthcare ; Had previous MOH s to other areas, and wished he had known about the radiation option (hated the open defects, took forever to heal, cosmesis issues, etc); Technique: HDR Valencia 3 cm applicator; 6 Gy x 7 fractions to 3 mm depth;

7 To avoid the following: Patient should be given all options Concern for the Patient Well Being > Personal Financial Interests;

8 Objectives 1. Review Evidence for MOHs vs RT 2. High Risk Features after MOH s, That Warrant RT Consideration 3. Technical Advances & Clinical Considerations in HDR- BT

9 MOH s vs RT for BCC There are no multi-institutional RCT! RCT from a single institution in Gustov-Roussy, France ; BCCa < 4 cm randomized: 174 surgery ( 2mm margin) vs 173 RT. RT could be interstitial brachytherapy, superficial, or conventional EBRT at discretion of radiotherapist; Exclusion: < 3 yr life expectancy, 5 BCC; 4 yr actuarial failure rate of 0.7% (S) vs 7.5% (RT) (SS); 15 cases in the RT group were more infiltrative (not well balanced); *67 cases (39%) needed re-excisions before closure (not considered as MOH s failure); 44% in MOH s were hospitalized (76 patients); Cosmetic outcome felt to be better with surgery (w/ some pitfalls): * 95 patients (55%) were treated with interstitial brachytherapy. Brachytherapy had higher failure rate (8.8%) than historical rates of < 5%; Cosmetic results of the brachytherapy was actually lower than historical rates; *Their surgical rates were better (0.7%) compared with historical rates of 2-10%; Avril MF, et al. Br J Cancer. 1997;76(1)

10 Cochrane Meta-Analysis: MOH s vs RT? Only observational/outcomes studies reported (fraught with selection bias); Mohs (16 series, 2133 SCCs) pooled LR was 3% (range %); Brachytherapy series (6 series, 88 SCCs) pooled LR of 5.2% (range %); EBRT (14 retrospective, 1018 SCCs); Pooled LR of 6.4% (range 3-11%); Surgical series (12 studies, 1114 patients): pooled LR of 5.4% (range %); Neither was statistically superior or inferior; Comparison of outcomes after different treatments should be interpreted cautiously owing to biases inherent in each type of study; Lansbury L, et al. BMJ. 2013;347:f6153.

11 Contemporary Outcome of Short Course Radiotherapy (SRT) 1715 BCC and SCC treatment with SRT at Dermatology Associates of Florida ; 712 bx proven BCC (631 nodular, 81 superficial); 994 SCC (861 SCIS, 133 invasive SCC); 9 mixed; 2 and 5 yr BCC LR 2% and 4.2%; 2 and 5 yr SCC LR 1.8 and 5.8%; Results not superior to MOHs (comparing contemporary cohorts); Cognetta AB, et al. J Am Acad Dermatol. 2012;67(6):

12 Local Control Rate after Brachytherapy for Skin Cancer The local control rate for HDR Brachytherapy is between 95% - 98% Local Control after Brachytherapy for Skin Cancer Tumor Author Localization n Treatment FUP Local Control Guix (2000) Face 136 HDR brachy 5y 99% if primary treatment 87% if recurrence Maes (2001) Face 173 Iridium months 95% Debois (1994) Nose 370 Cesium 137 2y 97% if primary treatment 94% if recurrence Crook (1990) Nose 468 Iridium-192 5y 97.5% GEC (1989) Nose 1,676 RT min 2y Daly (1984) Eyelid 165 Iridium-192 5y 95% if primary treatment 88% if recurrence 97% if primary treatment 94% if recurrence Gambaro (2001) Eyelid 50 Iridium-192 median 82 96% months Mazeron (1986) Ear 70 Iridium-192 mean 5y 99% Baris (1985) Nasal Vestibule 22 Iridium-192 2y 96.4%

13 Question 1: 1) True or False: There are many multi-institutional randomized trials showing MOH s is superior to radiotherapy for early stage basal cell carcinoma.

14 Objectives 1. Evidence for MOHs vs Radiotherapy 2. High Risk Features after MOH s, That Warrant RT Consideration 3. Technical Advances & Clinical Considerations in HDR- BT

15 High Risk Features Warranting RT Consideration Named Nerves (Typically, CN V branches, or CN VII). Large Nerve (> 0.1 mm); Multi-Focal Nerve Involvement; + margins (& doubtful margins);

16 Question 2: When should a patient with early stage squamous cell carcinoma or basal cell carcinoma be referred for adjuvant radiotherapy after MOHs? a) > 0.1 nerve involvement b) Multi-focal nerve involvement c) Positive margin d) All of the above

17 Objectives 1. Evidence for MOHs vs Radiotherapy 2. High Risk Features after MOH s, That Warrant RT Consideration 3. Technical Advances & Clinical Considerations in HDR- BT

18 Typical HDR unit (Ir-192, average 380 KV energy, max 1.06 MeV)

19 What is ebx? New type of Brachytherapy that delivers radiotherapy without radioactive isotopes Utilizes a miniaturized X-ray source to deliver high dose radiation to the target area, at low energy (50kV) Treatments can now be delivered in a minimally shielded environment, making ebx accessible within the dermatologist office Images courtesy of Ajay Bhatnagar, M.D. Cancer Treatment Services Arizona

personnel to remain in treatment area with the patient This is a mobile system that

20 Advantages of ebx Excellent cosmesis Excellent Local Control Rate Treatment can be delivered on an outpatient basis with minimal shielding needed Allows medical personnel to remain in treatment area with the patient This is a mobile system that adapts well to small practices 4 different surface applicator sizes 10, 20, 35, and 50 mm

21 HDR Applicators (Valencia)

22 Skin/Surface Freiburg Flap stabilized by suturing to Aquaplast

23 Freiburg Flap Immobilization on Thermoplastic mask

24 Clinical Considerations Several different radiation regimens out there: Understand BED concepts to balance short term/long term toxicity, along with adequate tumor control; Typical prescription is to 3 mm depth Beyond 5 mm depth, consider interstitial brachytherapy HDR CTV Margins: BCC ( 5-10 mm) SCCa ( 1 cm margin if lesion < 2 cm; cm margin if lesion > 2.0 cm);

25 Question 3: True or False: 10 mm is the typical depth to which HDR for skin is prescribed.

26 Thank You What a Thumbs Up Presentation!

Summary. Electronic brachytherapy for the treatment of nonmelanoma skin cancer is considered investigational.

Summary. Electronic brachytherapy for the treatment of nonmelanoma skin cancer is considered investigational. Last Review Status/Date: September 2016 Page: 1 of 7 Summary Electronic brachytherapy is a form of radiotherapy that is designed to deliver high-dose rate (HDR) brachytherapy for the treatment of nonmelanoma