Advanced Periocular Basal Cell Carcinoma Research Articles

Advanced Periocular Basal Cell Carcinoma with Orbital Invasion: Update on Management and Treatment Advances.

Basal cell carcinoma (BCC) is the most frequent malignant periocular tumor. It is associated with exposure to ultraviolet radiation, and its incidence is gradually increasing. It may occasionally display more aggressive behavior and result in orbital or intracranial invasion. Mortality from periocular BBC with orbital invasion is very low, but the associated morbidity can be significant, from disfigurement to blindness. Traditionally, these cases have been treated with orbital exenteration or with radiotherapy (RT), but in recent years, hedgehog pathway inhibitors (HPIs) have emerged, are effective in more serious cases, and are used primarily or combined with surgery, changing our perspective on the management of these patients. We studied 24 cases of periocular BCC with orbital invasion, some primary and others recurrent, which were treated between 2011 and 2021 in the same hospital. All patients had clinical or radiological evidence of orbital invasion. Orbital exenteration was performed on 9/24 of the patients (1 received vismodegib after surgery), and 12/24 were treated, surgically preserving the eyeball, with 3 of them receiving adjuvant vismodegib. Three of the twenty-four patients were treated exclusively with vismodegib (Erivedge®, Genentech). One patient died due to poor tumor evolution, but the rest evolved favorably and they have had no recurrences. Vismodegib was generally well tolerated, except for in one patient who discontinued treatment due to the side effects. In advanced BBC with orbital invasion, mutilating surgical treatments such as exenteration or potentially vision-threatening treatments such as RT remain as options. In recent years, however, very promising new medical therapies have emerged, such as HPI, which can be used effectively instead of surgery or in combination with it, preserving the eye and vision, which implies a new approach to treatment.

Neoadjuvant vismodegib in the management of locally advanced periocular basal cell carcinoma.

Vismodegib, a hedgehog pathway inhibitor, has been used in the management of locally advanced basal cell carcinoma (BCC) not suitable for surgery or radiation therapy. We report our experience using neoadjuvant vismodegib for locally advanced periocular BCC, followed by surgical excision. Our aim was to assess the effect on the extent of surgical excision and histological response. A retrospective case series of patients treated with neoadjuvant vismodegib, for the management of locally advanced periocular BCC prior to surgical excision, with intraoperative margin control. Patients were treated until a maximum clinical response was seen. The difference between the estimated surgical margins prior to vismodegib and the eventual margins used was compared. Fine (1 mm) vertical sections through the excised tumour were performed to assess the histological response and look for a multifocal tumour. Eight Caucasian patients had neoadjuvant treatment with vismodegib for a median duration of 6 months. Some clinical response was seen in all cases but was only partial in 6/8 patients. Histological evaluation of the excised specimen showed residual BCC in 6/8 cases and thus 2/8 showed complete histological regression. Two cases showed squamous differentiation. Side effects occurred in 7/8 patients all which resolved on cessation of therapy. The mean follow-up was 13.4 ± 5.2 months. Neoadjuvant treatment of periocular BCC showed a mixed clinical and histological response. Final surgical excision achieved clear margins in all patients with no recurrence at 13 months and a reduction in predicted defect size, but possible squamous differentiation in two cases.

Vismodegib (V) for organ preservation for locally advanced (LA) orbital/periocular basal cell carcinoma (BCC).

10069 Background: LA BCC of the eye/lacrimal drainage system most often requires disfiguring radical surgery, possibly including exenteration. As an alternative to radical surgery, we evaluated ophthalmologic outcomes following treatment with V using a novel Visual Assessment Weighted Score (VAWS) in patients (pts) with locally advanced periocular BCC. Methods: In this open label, non-randomized trial, pts with globe- and lacrimal-threatening orbital/periocular BCC were scored with VAWS prior to treatment with 150 mg of V daily. Pts were evaluated by ophthalmic exam (OE) every 3 mo & with MRI/CT at 5-9 mo. Pts with progressive disease (PD) were offered salvage surgery. Tumor response was assessed by RECIST v1.1. Responders (CR, PR, SD) continued V if tolerating therapy. Pts with intolerable side effects stopped V & were offered surgery of their residual tumor. Post-surgical specimens were assessed for histologic presence of BCC by a dermatopathologist. The primary endpoint, maintenance of visual function, was evaluated by VAWS at final post treatment assessment (FPTA), 1 yr after the start of V or 2 mo post-surgery. A VAWS of 21/50 was considered successful, representing preservation of a functional eye. Results: 50 pts were planned for enrollment, but the study was stopped early for benefit. From 06/25/2015 to 05/16/2019, 35 pts signed consent; 1 was a screen failure; 34 (97%) received V & 35 were evaluable for analysis by ITT; 1 died from aspiration pneumonia. The median time on study was 261 days. Average treatment with V was 223 days. 32 (91%) underwent OE & 27 (77%) had an MRI/CT. 27 (77%) underwent surgery & 33 (94%) attained organ preservation. Overall response rate (ORR) on OE was 84% (0%-PD,6%-SD,29%-PR,54%-CR, 11% not assessed(NA)). ORR by MRI/CT was 72% (0%-PD,6%-SD, 26%-PR,46%-CR,22% NA). 31 (89%) were scored with VAWS at 3 mo & 30 (86%) at FPTA. The mean VAWS at baseline was 44/50, 46/50 at 3 mo, & 47/50 at FPTA. Of the 35 pts scored at baseline by VAWS, 1 (3%) had a major decline during follow up, 5 (14%) a minor decline, 27 (77%) stable/improved, & 2 (6%) NA. No pts experienced grade 3-5 events. Of the 27 post-surgical pathologic specimens evaluated for histological response, 67% had NED, 22% had clear margins, & 11% had BCC to the margin. Two pts have recurred & underwent Mohs surgery. Conclusions: Treatment with V led to organ preservation for pts with LA periocular BCC, with preservation of visual function. Vismodegib is practice changing as neoadjuvant therapy for LA BCC of the eye/lacrimal drainage system in which surgery would result in unacceptable morbidity. Clinical trial information: NCT02436408.

Vismodegib for periocular basal cell carcinoma: an international multicentre case series.

Vismodegib (Erivedge, Genentech) is a first-in-class inhibitor of the hedgehog (Hh) pathway, which is licensed for use in locally advanced basal cell carcinoma (BCC) and metastatic BCC. The National Institute for Health and Care Excellence withdrew recommendation for use of vismodegib secondary to a lack of data comparing vismodegib to standard supportive care. The purpose of this multicentre, international case series is to report outcomes of patients with locally advanced periocular BCC who have been treated with vismodegib. The medical records of all patients treated with vismodegib were retrospectively reviewed across seven institutions in the United Kingdom, Australia, and New Zealand. Thirteen patients were identified. Seven (54%) patients were male. All BCCs were ill-defined, with seven (58%) having orbital involvement at presentation. Median treatment time was 7 months (range 2-36 months). Eleven out of 13 patients developed side effects, the most common being fatigue in six patients (46%). Median follow-up was 24 months (range 12-48 months). Complete response was found in 5/13 patients (38%) and a partial response in 8/13 patients (62%). Six patients had further surgery after vismodegib, with three classed as globe-sparing operations. Three patients developed recurrence (23%). Three patients (23%) ultimately underwent exenteration. This study demonstrates vismodegib to be a well-tolerated treatment which may, in some cases, facilitate globe-sparing surgery and hence avoid disfiguring operations such as exenteration. Uncertainty does remain regarding the long-term outcomes of patients treated with vismodegib.

Impact of Food and Drug Administration Approval of Vismodegib on Prevalence of Orbital Exenteration as a Necessary Surgical Treatment for Locally Advanced Periocular Basal Cell Carcinoma.

To test the hypothesis that the US Food and Drug Administration approval of vismodegib in early 2012 has reduced the prevalence of orbital exenteration for locally advanced periocular basal cell carcinoma (BCC). Following institutional review board approval, the authors reviewed clinical and pathological data of patients with locally advanced periocular BCC (T4 per the eyelid carcinoma classification in the 8th edition of the AJCC Cancer Staging Manual) treated by the senior author during 2006-2018. Patients were grouped into those who were treated before February 2012 ("before vismodegib approval") and those who presented later ("after vismodegib approval"). Forty-two patients with locally advanced periocular BCC were treated during the study period, of whom 31 were men. The median age at presentation was 66 years (range, 43-90). Twenty-two patients had T4a and 20 had T4b tumors. Thirteen patients were treated before and 29 were treated after vismodegib approval. The 2 groups did not differ in age distribution (p = 0.164), sex distribution (p = 0.270), prevalence of recurrent tumor at presentation (p = 0.317), or duration of treatment with vismodegib (p = 0.605). Orbital exenteration was significantly more prevalent in patients treated before vismodegib approval than after (46% vs. 10%, p = 0.016), and vismodegib treatment was significantly more prevalent in patients treated after vismodegib approval than before (when vismodegib was given in clinical trials; 69% vs. 23%, p = 0.008). There was a trend toward more patients retaining their eyes at last follow-up in patients treated after vismodegib approval (83% vs. 54%, p = 0.066). The prevalence of orbital exenteration as a necessary surgical procedure in patients with a locally advanced periocular BCC has fallen since the Food and Drug Administration approval of vismodegib. Although vismodegib is not specifically approved for organ-sparing, it has changed the authors' practice and enabled eye preservation in patients with locally advanced periocular BCC, who would otherwise require an orbital exenteration.

Efficacy of Vismodegib for the Treatment of Orbital and Advanced Periocular Basal Cell Carcinoma

To evaluate the effectiveness of vismodegib, a Hedgehog pathway inhibitor, in treating orbital and advanced periocular basal cell carcinoma (BCC) in Israeli multidisciplinary medical centers. Retrospective case series. Background, treatment, and outcome data were retrospectively collected from the medical records of all patients with locally advanced and metastatic orbitalor periocular BCC treated with vismodegib in 2012-2017 at 2 tertiary medical centers. The cohort included 21 patients (16 male) of median age 76 years with periocular (n=6) or orbital (n=15) BCC. Median duration of treatment was 9months, with follow-up of 26months (range 9-60months) overall and 17months after treatment cessation. Clinical response was complete in 10 patients, partial in 10 patients, and stable in 1 patient. Among the complete responders, 5 maintained a complete response at 16months, and 3 who stopped treatment had a recurrence 8months later. Almost all treatment-related adverse reactions were graded 1 or 2 (low-grade). The most common grade 1 or 2 complications were muscle spasm (76%), followed by dysgeusia (57%), alopecia (47%), weight loss (47%) and decreased appetite (19%). The only grade 3 or 4 adverse event was hepatotoxicity (10%). Eight patients discontinued treatment because of side effects. Five patients died, most from reasons unrelated to vismodegib therapy, except for 1 patient who died from possibly treatment-related sepsis (grade 5 adverse event). To our knowledge, this is the only study generated outside the United States and Europe, and it represents the largest study to date on vismodegib therapy for locally advanced periocular BCC. Treatment according to an individualized maximally tolerated dose may achieve a comparable response to the ERIVANCE protocol. Longer-term studies are needed to assess prognosis.

Neoadjuvant Vismodegib and Mohs Micrographic Surgery for Locally Advanced Periocular Basal Cell Carcinoma.

Vismodegib has shown a significant response rate in locally advanced periocular basal cell carcinoma. Long-term monotherapy is very difficult to accomplish due to primary or secondary resistance and side effects that limit the length of treatment. The use of Vismodegib as neoadjuvant followed by Mohs micrographic surgery is an option. To report the use of neoadjuvant Vismodegib as an option for operable locally advanced basal cell carcinoma followed by Mohs surgery. The authors treated 8 locally advanced periocular basal cell carcinomas. Mean age was 76, and 6 of 8 were women. Mean size was 18 mm (12-30). Three were recurrent after surgery. Maximal clinical response was obtained at 4.8 months. Patients were operated at the mean time of 7.3 months. Seven patients (87.5%) had a complete response and 1 (12.5%) progressed. Mohs micrographic surgery allowed to confirm a complete histologic response in 5 of 6 (83.3%) cases, and 1 patient refused surgery. All 7 patients are disease free after a mean follow-up of 12.4 months. All patients experienced adverse events. The most common included dysgeusia (100%) and muscle spasms (100%). Weight loss was present in 75% of the patients with a mean loss of 12.6 pounds and hair loss was seen in 50%. Only 1 (12.5%) patient withdraw from treatment because of intolerable muscle spasms. The authors believe there is a clear role for Vismodegib as neoadjuvant in locally advanced periocular basal cell carcinoma, even in operable cases. Specific indications beyond those already approved should be further discussed. Prospective studies to assess the combination of neoadjuvant Vismodegib followed by Mohs micrographic surgery in locally advanced periocular basal cell carcinoma with long-term follow-up are needed.

Ocular preservation with neoadjuvant vismodegib in patients with locally advanced periocular basal cell carcinoma

Locally advanced (T4 perAmerican Joint Committee on Cancer (AJCC) 8th edition) periocular basal cell carcinoma (BCC) can lead to loss of the eye. We report the neoadjuvant use of vismodegib followed by surgery in patients with such lesions with eye preservation as primary goal. This retrospective interventional study includes all patients with a T4 periocular BCC (per 8th edition AJCC for eyelid carcinoma) treated by the senior author between 2013and2017 with neoadjuvant vismodegib prior to definitive surgery. Eight patients had a T4 tumour. Six patients presented with recurrent disease. Indications for neoadjuvant treatment were an unresectable tumour in onepatient, an attempt to avoid an orbital exenteration in sixpatients and an attempt to avoid disfiguring facial surgery in onepatient. Patients were treated for a median of 14 months (range: 4-36 months). All patients underwent an eye-sparing surgery following neoadjuvant vismodegib and all final surgical margins were negative for tumour. Five patients had a complete response to vismodegib with no microscopic residual BCC found during surgery; threepatients had a significant partial response with residual tumour found on pathology. At last follow-up, a mean of 18 (range:6-43) months after surgery, all patients were off-vismodegib and alive without evidence of disease. Neoadjuvant vismodegib for locally advanced (T4) periocular BCC enabled an eye-sparing surgery in all patients in our cohort. Prolonged treatment was welltolerated by most patients. Over half of patients achieved a complete response with no residual microscopic disease. Careful long-term follow-up is needed to confirm long-term disease-free survival.

The best of the best: a review of select oculoplastic case series published in 2015.

This review summarizes three case series published in the field of oculoplastic surgery in the year 2015. The first article describes the use of hedgehog pathway inhibitors for medical therapy of advanced periocular basal cell carcinoma and basal cell nevus syndrome. The second describes the use of c-reactive protein as a marker for starting treatment with steroids in children with orbital cellulitis. The third article presents an endoscopic medial orbital fat decompression technique for treatment of proptosis in thyroid eye disease.

Role of Vismodegib in the Management of Advanced Periocular Basal Cell Carcinoma.

Vismodegib is the first selective hedgehog pathway inhibitor approved to treat locally advanced and metastatic basal cell carcinoma (BCC). Limited information is available concerning its role in managing advanced BCC around the eye. The medical literature was searched for cases of nonsyndromic periocular BCC treated with vismodegib. Clinical information was abstracted and analyzed. In addition, a review of the pharmacology of vismodegib, including general effectiveness and safety, was conducted. Thirty study patients with nonsyndromic periocular BCC treated with vismodegib were found in the literature. Vismodegib was used in 3 ways: medical therapy, adjuvant therapy prior to surgery or radiotherapy, and treatment of positive surgical margins. Complete regression was reported in 9 study patients (30%), with follow-up visits after therapy averaging fewer than 5 months. Four study participants developed squamous cell carcinoma while receiving treatment. Too few cases exist to draw any conclusions on the role that vismodegib might play in the management of periocular BCC. In addition, long-term follow-up data are not yet available. Although the objective response rate of advanced BCC is impressive in study patients receiving vismodegib, well-controlled clinical studies are needed to determine whether vismodegib has any impact on survival or quality of life.

Efficacy of Vismodegib (Erivedge) for Basal Cell Carcinoma Involving the Orbit and Periocular Area.

Evaluate the effectiveness of vismodegib in the management of basal cell carcinoma with orbital extension and/or extensive periocular involvement. Retrospective chart review of 6 consecutive patients with biopsy-proven orbital basal cell carcinoma and 2 additional patients with extensive periocular basal cell carcinoma who were treated with oral vismodegib (150 mg/day) was performed. Basal cell carcinoma extended in the orbit in 6 of 8 patients (involving orbital bones in 1 patient), and 2 of 8 patients had extensive periocular involvement (1 with basal cell nevus syndrome). Vismodegib therapy was the only treatment in 6 patients, off-label neoadjuvant in 1 patient, and adjuvant treatment in 1 patient. Orbital tumors in all 4 patients who received vismodegib as sole treatment showed partial response with a mean 83% shrinkage in tumor size after a median of 7 months of therapy. In the 2 patients receiving vismodegib as neoadjuvant or adjuvant therapies, there was complete response after a median of 7 months of therapy and no evidence of clinical recurrence after discontinuing therapy for a median of 15 months. The 2 patients with extensive periocular involvement experienced complete clinical response after a median 14 months of treatment. During treatment, the most common side effects were muscle spasm (75%) followed by alopecia (50%), dysgeusia (25%), dysosmia, and episodes of diarrhea and constipation (13%). Basal cell carcinoma with orbital extension and extensive periocular involvement responds to vismodegib therapy. The long-term prognosis remains unknown, and additional prospective studies are indicated.