Non-Melanoma Skin Cancer Treated with Electronic Brachytherapy: Results at Two Years Ajay Bhatnagar MD, MBA Cancer Treatment Services Arizona Casa Grande, AZ University of Pittsburgh, School of Medicine Pittsburgh, PA

Disclosure I have received research funding from Xoft — a subsidiary of iCAD, Inc., Sunnyvale, CA, as the Principal Investigator for this study.

Background Non-melanoma skin cancer (NMSC) is the most common malignancy in the US Affects 2 to 3 million people each year 1 High dose rate (HDR) brachytherapy using surface applicators has shown efficacy in the treatment of NMSC An electronic brachytherapy (EBT) system permits treatment of NMSC without the use of a radioactive isotope Xoft Axxent® eBx® system A miniature, electronic, HDR, low energy X-ray tube produces X-rays of 50 keV maximum energy 1 Rogers HW, Martin A. Incidence estimate of nonmelanoma skin cancer in the United States, Arch Dermatol 2010;146:

Ir-192 HDR Surface Applicator vs. Xoft eBx Surface Applicator

Dose Profile of Xoft 35mm Surface Applicator vs. Ir-192 Liepzig Applicator For 10 sources over the 80% field width (per AAPM TG25) Flatness (Mean and S.D.): 3.2 % +/- 1.2% Symmetry (Mean and S.D.): 4.2 % +/- 2.1% Superior Dose Profile with Xoft Applicator Potential to decrease margins compared to Ir-192

Study Purpose The objective of this IRB approved study was to assess adverse effects, cosmesis, and recurrence rates up to two years following HDR electronic brachytherapy for the treatment of non-melanoma skin cancer.

Methods July 2009 – February 2012, 122 patients with 171 NMSC tumors were treated with eBx using surface applicators All received same dose fractionation 5.0 Gy x 8 fractions = 40.0 Gy, 2 fractions per week Prescription depth – Empirically 3 mm for most lesions – Determined by CT only for thick lesions Surface applicator size (10, 20, 35, and 50 mm) was selected to allow for complete coverage of target lesion with acceptable margin Patient care included Petrolatum ointment during treatment Aloe vera gel through 1 month post-treatment Adverse Events Assessment: NCI CTCAEv4 criteria Cosmesis Assessment: RTOG scale

Treatment setup for patient with facial lesion showing a) thermoplastic mask cut out around lesion; b) surface applicator in contact with skin; c) shielding and applicator setup; and d) electronic brachytherapy controller to the right of the patient. a c d b

Results Mean Follow up 11 months (range 1-38 months) No Recurrences to Date PATIENT CHARACTERISTICS N Subjects N Lesions122 Subjects 171 Lesions Mean Age (Range)73 Years (49-97) Gender63% Male 37% Female Ethnicity97% Caucasian non-Hispanic

Tumor Characteristics TYPE (N=171 LESIONS)n% Basal Cell Carcinoma (BCC)9153% Squamous Cell Carcinoma (SCC)7041% Merkle Cell Carcinoma (MCC)21% Cutaneous T-cell Lymphoma (CTCL)32% Basal-Squamous Cell Carcinoma11% STAGE (N=171 LESIONS)n% Tis106% T113881% T242% Recurrence159% Not available42%

Tumor Characteristics LESION LOCATION (N=171 LESIONS)n% Nose4929% Face (forehead, temple, eyelid, glabella, sideburn, cheek, lip, chin) 5029% Ear2213% Extremity2414% Scalp148% Torso127%

Tumor Characteristics TUMOR SIZE (N=171 LESIONS)n% ≤ 1CM 10159% > 1 CM TO ≤ 2CM 6136% > 2 CM TO ≤ 3CM 63% >3 CM TO ≤ 4CM 21% >4 CM TO ≤ 5 CM 11%

Number of Lesions Treated by Applicator Size and Dose Depth Applicator Size Prescription Dose Depth 1 mm3 mm4 mm * 5 mm § 7 mmTOTAL 10 mm mm mm mm TOTAL * Includes prescription dose depths of 4.0 mm to 4.1 mm § Includes prescription dose depths of 4.75 mm to 5.6 mm

Treatment Time and Dose Depth by Histopathology Histopathology (N=171 Lesions) n Treatment Time: mean (range) Basal Cell Carcinoma915.6 (4-8.2) min Squamous Cell Carcinoma705.8 ( ) min Merkle Cell Carcinoma25.8 ( ) min Cutaneous T-cell Lymphoma38.4 ( ) min Basal-Squamous Cell Carcinoma15.2 ( ) min Not available47.3 ( ) min

Adverse Events: Late 6 MONTHS (N=52 LESIONS)n% Hypopigmentation48% Alopecia24% Hyperpigmentation12% Atrophy12% 1 YEAR (N=58 LESIONS)n% Hypopigmentation59% Alopecia23% 2 YEARS (N=30 LESIONS)n% Hypopigmentation413% Alopecia13% All Hypopigmentation was Grade 1 (mild) No Grade 3 or higher Adverse Events

Cosmesis Percent of Lesions with Good or Excellent Cosmesis Post-Treatment Visit Month 624 N=122N=81N=52N=55N= –– 80 –– 60 –– 40 –– 20 –– 0 – 75% 89% 92% 95% 93% No Patients with Fair or Poor Cosmesis

CASE EXAMPLES

Squamous cell carcinoma on right cheek Treated with 40 Gy to a 5 mm depth Pre-treatment Fraction 7 1 Mo 3 Mo 6 Mo 2 Yr

Basal cell carcinoma on chin Treated with 40 Gy to a 3 mm depth Pre-treatment 2 Yr

Basal cell carcinoma on right nostril and nasal bridge Treated with 40 Gy to a 5 mm depth Pre-treatment 2 Yr

Squamous cell carcinoma on left arm Treated with 40 Gy to a 5 mm depth Pre-treatment 2 Yr

Basal cell carcinoma on left tip of nose Treated with 40 Gy to a 3 mm depth Pre-treatment 23 Mo

Basal cell carcinoma on right tip of nose Treated with 40 Gy to a 5 mm depth Pre-treatment 22 Mo

Squamous cell carcinoma below left eye Treated with 40 Gy to a 3 mm depth Pre-treatment 20 Mo

Squamous cell carcinoma on left cheek Treated with 40 Gy to a 5 mm depth Pre-treatment 1 Yr

Squamous cell carcinoma on right antihelix Treated with 40 Gy to a 3 mm depth Pre-treatment 1 Yr

Basal cell carcinoma on right upper eyelid Treated with 40 Gy to a 3 mm depth Pre-treatment 6 Mo

Squamous cell carcinoma on left postauricular scalp Treated with 40 Gy to a 5 mm depth Pre-treatment 3 Mo

Conclusions As of date, treatment of non-melanoma skin cancer with HDR electronic brachytherapy using surface applicators was effective and convenient comparable to Ir-192 HDR brachytherapy Cosmesis was good to excellent up to 2 years post-treatment Toxicities were acceptable No recurrences to date, but longer follow up is being collected Brachytherapy (electronic or traditional) is an ideal modality for patients (especially elderly patients) with NMSC given the excellent results and convenient schedule We (Radiation Oncology) need to take a more prominent role in the treatment of NMSC