New and Emerging Therapies: Non-Melanoma Skin Cancers. David J. Goldberg, MD, JD Skin Laser and Surgery Specialists of NY/NJ

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New and Emerging Therapies: Non-Melanoma Skin Cancers David J. Goldberg, MD, JD Skin Laser and Surgery Specialists of NY/NJ

Disclosure Research Grant form Sensus

Superficial Radiation Therapy (SRT)

Modern SRT Equipment Utilizes low energy photon X-rays operating at variable peak voltages of 50, 70, and 100 kvp.

Modern SRT Equipment Planned calibrated dose delivery is accurate with internal filtration technology.

Modern SRT Equipment Unit automatically stops when cumulative amount of radiation is delivered.

Modern SRT Equipment Easy to administer Effectively targets and treats lesions Delivers gentle indirect radiation which does not penetrate and impact the underlying healthy tissue.

Evidence Based Therapy The cure rate for 1715 primary nonaggressive NMSC treated with the SRT-100 was 98% (Cognetta et al, JAAD 2012).

Tumor and Patient Selection: Treatment Objectives To eradicate the tumor while maintaining or improving the patient s quality of life.

Tumor and Patient Selection: Treatment Objectives To deliver a measured dose of radiation to a defined volume with minimal damage to surrounding normal tissue, resulting in eradication of the tumor.

Tumor and Patient Selection: Treatment Objectives Prolongation of lifespan

Evaluation of Patient History Clinical examination Histopathology

Tumor and Patient Selection History Age of lesion and tissue density Older tumors can yield an area were a lack of oxygen exists( hypoxic and anoxic tissue) Lesions that have hard scabs may consist of an area with a higher density than water. This is important for selecting dosage of energy for therapy. KV energies are Z dependent and penetration through such areas of lesions can be hindered by this higher density. Manson et al. Photo-Ionization in the Soft x-ray Range: 1Z Dependence Phys. NBS.1968Rev. 165

Clinical Examination Anatomical location, surrounding tissue and adjacent structures # of tumors Proper illumination is the gold standard of margin delineation Ill-defined lesion, scouting biopsies may be warranted Palpation depth, mobility R/O lymphadenopathy R/O metastasis

Histopathology Histologic subtype of NMSCs must be determined prior to selecting tumors for SRT Certain subtypes confer a higher risk of recurrence, aggression and metastasis.

Histopathology Helps to define tumor margins along with clinical examination of lesion. Guides energy selection which is based on the deepest portion of the lesion.

Histopathology CAVEAT! High risk lesions need higher energy for penetration due to the fact biopsy reports can yield insufficient depth data.

NMSC Tumor Selection

NMSC SRT provides a viable nonsurgical option for the treatment of primary NMSC in eligible patients.

NMSC Most commonly treated with SRT Basal Cell Carcinoma Squamous Cell Carcinoma

Tumor Site SRT may be used to treat tumors on all skin surface areas However, lesions on the central face are at higher risk of recurrence

SRT may give a better cosmetic outcome: Scalp Eyelid External ear canal and helix Nasal ala

Large Tumors SRT may present a simpler option than extensive surgery and reconstruction(skin grafting) However, higher risk of recurrence than surgery

Important factors to consider Biologic behavior of specific tumor types. Potential areas of metastasis. Goal of SRT: Curative versus palliative treatment.

Important factors to consider Treatment margin 8-10mm margins are common for BCC 10mm is used for SCC. Ill-defined and more aggressive tumors may warrant a wider margin.

Factors Affecting Eradication of Tumor Radio sensitivity Tolerance of surrounding normal tissue. Tissue toxicity factors : - size and volume of the area -vascularity -underlying and supporting tissues.

Factors Affecting SRT Dosage for NMSC and Prognosis Definition of clinical margins - poorly defined lesions are at higher risk of recurrence

Factors Affecting SRT Dosage for NMSC and Prognosis Histological subtype - certain subtypes confer higher risk of recurrence (ex. morpehaform basosquamous ) and Histological features of aggression - perineural and or perivascular involvement confers higher risk of recurrence

Nguyen T et al, Nonmelanoma skin cancer Current Treatment Options in Oncology,2002 Factors Affecting SRT Dosage for NMSC and Prognosis Failure of previous treatment - recurrent lesions are at higher risk of further recurrence Immunosuppression - possibly confers increased risk of recurrence

Ideal Patients for SRT Elderly Poor surgical candidates

Indications for SRT Medically unfit for surgery/limiting diseases Contraindications for anesthesia Potential for significant cosmetic, neural or functional limitations post op

Indications for SRT Poor Wound Healing Poor Functional Status or Disabilities Need for Simultaneous Treatment of Multiple Tumors Inability to Perform Necessary Post-Operative Wound Care

Limiting: Systemic Diseases CHF Cardiac Disease Poor Local Circulation Pacemakers Pulmonary Disease Requires O2

Limiting: Systemic Diseases PVD Bleeding Disorder Anticoagulation Immune suppression Diabetes Advanced Dementia

Limiting: Local Disease Local infection, Hx of MRSA LE edema Cutaneous Atrophy Poor Tissue Mobility

SRT Ideal for Poor Surgical Candidates Prefer not to be treated by surgery Decline surgical intervention Exhibit significant fear of surgery and scarring Not likely to tolerate surgery

Contraindications for SRT Pacemaker or defibrillator within the treatment area Previous radiation therapy to the area of concern

Factors to Consider Prior to Selecting SRT Past injury to the dermis Areas that have been burned, frozen, scared, or that have had any chemical change done to the areas at a cellular level.

Reference Cognetta AB, Wolfe CM, Goldberg DJ, and Hong HG. Practice and Educational Gaps in Radiation Therapy in Dermatology. Dermatol Clin. 34: 319-333, 2016