Hedgehog Pathway Inhibition for Locally Advanced Periocular Basal Cell Carcinoma and Basal Cell Nevus Syndrome.
OBJECTIVE
To review our experience treating patients with the Hedgehog pathway inhibitor, vismodegib, in patients with orbital or periocular locally advanced or metastatic basal cell carcinoma (BCC) or basal cell nevus syndrome.


METHODS
Retrospective interventional case series.


METHODS
We reviewed all patients with locally advanced or metastatic orbital or periocular BCC or basal cell nevus syndrome treated with the Hedgehog pathway inhibitor, vismodegib, at a comprehensive cancer center from 2009 through 2015. Reviewed data included age; sex; American Joint Commission on Cancer tumor, node, metastasis staging system designation; type and grade of drug-related side effects; response to treatment; duration of follow-up, and status at last follow-up.


RESULTS
The study included 10 white men and 2 white women; the median age was 64.5 years. Ten patients had locally advanced BCC; 2 had basal cell nevus syndrome. Among the patients with locally advanced BCC, 5 had T3bN0M0 disease at presentation; 1 each had T3aN0M0, T3bN1M0, T2N1M1, T4N1M1, and T4N2cM1 disease. Overall, 3 patients had a complete response, 6 had a partial response, and 3 had stable disease at last follow-up. Two patients developed progressive disease after a complete response for 38 months and stable disease for 16 months, respectively. All patients developed grade I drug-related adverse effects, most commonly muscle spasms (12 patients), weight loss (10), dysgeusia (9), alopecia (9), decreased appetite (5), and fatigue (4). Five patients developed grade II adverse effects. At last follow-up, none of the 5 patients presenting with T3bN0M0, nor the patient with T3bN1M0 disease, had required orbital exenteration.


CONCLUSIONS
Hedgehog pathway inhibition produces a significant clinical response in most patients with locally advanced or metastatic orbital or periocular BCC or basal cell nevus syndrome and can obviate orbital exenteration in some patients. Drug-related adverse effects are manageable in most patients.
Department of Plastic Surgery, Orbital Oncology and Ophthalmic Plastic Surgery Program, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Omar K
OK
Ozgur
Department of Plastic Surgery, Orbital Oncology and Ophthalmic Plastic Surgery Program, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Vivian
V
Yin
Department of Plastic Surgery, Orbital Oncology and Ophthalmic Plastic Surgery Program, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Eva
E
Chou
Department of Plastic Surgery, Orbital Oncology and Ophthalmic Plastic Surgery Program, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Sharon
S
Ball
Department of Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Merrill
M
Kies
Department of Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
William N
WN
William
Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Michael
M
Migden
Department of Plastic Surgery, Orbital Oncology and Ophthalmic Plastic Surgery Program, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Bradley A
BA
Thuro
Department of Plastic Surgery, Orbital Oncology and Ophthalmic Plastic Surgery Program, The University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address: besmaeli@mdanderson.org.
Bita
B
Esmaeli
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000813:Anilides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001478:Basal Cell Nevus Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002280:Basal Cell Carcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D000813:Anilides; D000970:Antineoplastic Agents; C538724:HhAntag691; D011725:Pyridines