Neoadjuvant chemotherapy for advanced eyelid and periocular sebaceous gland carcinoma: a study of 25 cases.

PURPOSE: To report the outcomes of platinum-based neoadjuvant chemotherapy (NACT) for eyelid and periocular sebaceous gland carcinoma (eSGC). METHODS: Retrospective study of 25 patients. RESULTS: The mean age at presentation of eSGC was 59 years. The mean tumor basal diameter was 46 mm. By the 8th edition of AJCC classification, tumors belonged T2 (n = 2, 8%), T3 (n = 6, 24%), and T4 (n = 17, 68%); N1 (n = 12,48%); and M1 (n = 1, 4%). NACT with 5-fluorouracil (5-FU) and cisplatin/carboplatin was administered in 21 (84%)/4 (16%) patients, respectively. The mean number of cycles of neoadjuvant systemic chemotherapy per patient was 2 (median, 3). The mean percentage reduction of tumor basal volume after neoadjuvant chemotherapy was 65% (median, 60%). After NACT, 12 (48%) patients underwent surgical treatment, 6 (12%) patients underwent EBRT, and 4 (8%) underwent adjuvant chemotherapy. A total of 11 (44%) patients were lost to follow-up during the course of treatment, of whom 3 died from metastatic disease. In 16 patients followed up for ≥ 3 months, complete tumor control was achieved in 11 (69%) patients, local tumor control in 14 (88%), and globe salvage in 7 (44%) at a mean follow-up of 25 months (median, 7 months; range, 3 to 110 months). No tumor recurrence was seen in any case. One (4%) serious adverse event of cardiotoxicity was noted. CONCLUSION: Platinum-based NACT is a suitable option for eSGC with advanced tumors and locoregional metastasis. Adverse events are rare and in patients compliant with treatment, NACT-based combination therapy offers globe salvage and systemic tumor control.

Recurrent squamous cell carcinoma of the upper eyelid treated with combination therapy of ALA photodynamic therapy and surgery with secondary healing.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) frequently occurs in photoexposed areas. Surgery remains the mainstay of treatment in attempts to reduce recurrence, but it must be combined with other therapy because of the limited excision possible in the region of the eyelid, lip, and nose. Photodynamic therapy (PDT) is a relatively new treatment modality that involves the administration of a photosensitizing drug and its subsequent activation by specific wavelengths of light to produce reactive oxygen species that specifically destroy target cells. CASE REPORT: An 87-year-old female presented 4 weeks after initial resection with recurrent medium-differentiated cSCC measuring 5.2 cm × 3 cm × 2 cm in the left upper eyelid. Subsequent treatment involved palliative resection with an additional 1 cm at 3 margins of the tumor (excluding the bottom edge of the double eyelid line) and 3 applications of PDT using 5-aminolevulinic acid as the photosynthesizing agent in the open wound over a 2-week period. The wound healed well within 6 weeks. During the following 4 years, the patient showed satisfactory progress in both aesthetics and function, with no sign of recurrence or metastasis. CONCLUSION: Refractory cSCC was successfully managed using a combination of PDT and secondary healing, and functions of the head and face were well protected. These results suggest that such management warrants consideration in clinical settings.

Marginal resection and infracyanine green-mediated photodynamic therapy in the management of feline eyelid squamous cell carcinoma: Two cases.

OBJECTIVE: Describe the presenting features, surgical procedure, and clinical outcomes of two cats managed with marginal resection and photodynamic therapy (PDT) for eyelid squamous cell carcinoma (SCC). ANIMALS STUDIED: A 12-year-old female spayed domestic shorthair cat (case 1) and a 10-year-old female spayed domestic shorthair cat (case 2). PROCEDURES: Following marginal resection of the eyelid neoplasm, hemostasis was achieved using a handheld cautery unit then 1 mL of infracyanine green was injected into the surgical wound bed. Photodynamic therapy was performed using an 810 nm diode laser in two consecutive steps: (i) six cycles at 500 mW for 30 s per cycle, using a rapid movement; then (ii) one (case 1) or two cycles (case 2) of 30 s at 2000 mW, using a slow deliberate movement to effect (charred surface). RESULTS: Histopathology was consistent with SCC resected with incomplete margins in both cats. Follow-up duration was 416 and 161 days in case 1 and case 2, respectively. Consecutive exams and photo-documentation (in clinic or by owners) showed appropriate healing of the lower eyelid, with a smooth lid margin, and no evidence of tumor regrowth or ocular irritation. Subtle trichiasis was noted in case 1 on day 185, but not at the last follow-up. CONCLUSIONS AND CLINICAL RELEVANCE: Marginal resection followed by PDT may be a valid alternative to complete surgical resection of periocular SCC in cats. The procedure was easy to perform, post-operative recovery was uncomplicated, and neither cat developed recurrent disease during the follow-up period.

[Activity of the Russian antitumor compound chlonisol in models of eyelid tumors (experimental study)]. / Aktivnost' otechestvennogo protivoopukholevogo soedineniya khlonizol na modelyakh opukholei vek (eksperimental'noe issledovanie).

Eyelid tumors are the most common neoplasms in everyday ophthalmic practice and cover a wide range of benign and malignant lesions. Surgical methods, cryodestruction, laser therapy and radiation therapy are used in the treatment of malignant eyelid tumors. Chemotherapy does not occupy a prominent place in the treatment of malignant eyelid tumors, its use is limited to sensitive tumors. OBJECTIVE: To assess the antitumor activity of the Russian-developed chemical compound 2-[3-(2-chloroethyl)-3-nitrosoureido]-1.3-propandiol (chlonisol) on the models of transplantable tumors of various histogenesis implanted into the lower eyelid. MATERIAL AND METHODS: The study was carried out on 67 mice of lines 129/SN, BALB/c and C57BL/6 that had Ehrlich carcinoma, sarcoma 37, lymphosarcoma LIO-1 and B16 melanoma transplanted into the eyelid. Tumor transplantation was done by injecting 0.05 ml of sterile sodium chloride solution containing 106 cells of Ehrlich carcinoma, sarcoma 37, lymphosarcoma LIO-1, or 10% suspension of tumor tissue of B16 melanoma. The injection was performed into the right lower eyelid in the direction from the outer towards the inner corner of the eye using a thin needle (29G). Chlonisol was administered at the maximum tolerated dose of 20 mg/kg or at the lower dose of 15 mg/kg intraperitoneally 24 hours after tumor transplantation. RESULTS: In mice with Ehrlich carcinoma, sarcoma 37, lymphosarcoma LIO-1 and melanoma B16 transplanted under the skin of the lower eyelid, a single intraperitoneal injection of chlonisol at the dose of 20 or 15 mg/kg caused significant inhibition of tumor growth reaching 100%. Chlonisol significantly increased overall survival in animals with Ehrlich carcinoma (log rank test, p=0.0464), sarcoma 37 (log rank test, p<0.0001), lymphosarcoma LIO-1 (log rank test, p=0.0122) and B16 melanoma (log rank test, p<0.0001); the proportion of animals that were fully healed was 25, 78, 67 and 25%, respectively. CONCLUSION: Chlonisol has a pronounced antitumor effect in mice with Ehrlich carcinoma, sarcoma 37, lymphosarcoma LIO-1 and B16 melanoma transplanted into the eyelid.

Establishment and Characterization of a Novel Human Ocular Adnexal Sebaceous Carcinoma Cell Line.

Purpose: Sebaceous carcinoma (SC) is a malignant eyelid tumor of the ocular adnexa that is primarily treated via surgical excision. Few therapies exist in advanced cases, and medical therapy is limited because of our incomplete understanding of SC biology. Herein, we describe a technique to culture human ocular adnexal SC for use as an in vitro model. Methods: Human ocular adnexal SC tumor cells were isolated from a patient undergoing orbital exenteration surgery and named Bascom Palmer 50 (BP50). They were cultured in Dulbecco's modified Eagle medium/nutrient mixture F-12 supplemented with 10% fetal bovine serum and antibiotics and were maintained at 37°C in humidified 5% CO2. The cells were characterized by immunohistochemistry, exome sequencing, and short tandem repeats analysis. In vitro drug screening against mitomycin-C (MMC) was performed using a cell viability assay. Results: BP50 grew past 40 passages with a doubling time of 52.3 hours. Immunocytochemical staining revealed expression of SC-associated markers adipophilin, epithelial membrane antigen, p53, and androgen receptor. Whole exome sequencing showed a significant carryover in somatic mutations between the tumor tissue and corresponding cell line, revealing genetic markers consistent with SC. MMC affected cell viability in a dose-dependent manner. Conclusions: BP50 displays characteristics of ocular adnexal SC and therefore may facilitate improved understanding of SC biology and the high throughput assessment of novel therapeutic compounds and new drug combinatorial approaches targeted for this disease. Translational Relevance: Drug screening with MMC against these cells shows in vitro evidence to support its continued clinical use in SC.

To compare intralesional and oral propranolol for treating periorbital and eyelid capillary hemangiomas.

Purpose: A pilot randomized control trial to compare the efficacy and side effects of intralesional and oral propranolol in periorbital and eyelid capillary hemangiomas. Methods: Twenty patients were prospectively randomized to two groups of ten each. Group 1 was initiated on oral propranolol 1 mg/kg/day titrated to final dose of 3 mg/kg/day over 1 week which was continued for 6 months and then tapered over 1 week; Group 2 received 3 doses of direct intralesional propranolol hydrochloride 1 mg/ml; 0.2 ml/cm 4-6 weeks apart. Hemangioma area and corneal astigmatism were measured. Results: Within each group at 6 months there was a significant reduction in area (group 1: 83.48 ± 11.67%,P= 0.0019; group 2: 67.78 ± 21.71%,P= 0.0019) and improvement in astigmatism (pre, post: group 1: 2.98D @ 179.8°, 1.13D @ 179.8°,P= 0.0045; group 2: 1.62D @ 90.16°, 0.75D @ 179.9°,P= 0.0001). There was no difference in area reduction (P = 0.056), change in appearance (P = 0.085), ptosis (P = 0.23) and side effects (lethargy, poor feeding;P= 0.171) between the two groups. Conclusion: Efficacy and side effects with intralesional propranolol are comparable to oral propranolol for periorbital and eyelid lesions.

Primary multifocal anaplastic large cell lymphoma with eyelid involvement: a case report / Linfoma anaplásico de grandes células primário multifocal com envolvimento de pálpebra: relato de caso

ABSTRACT Ocular adnexal involvement in CD30+ lymphoproliferative disorders is rare. We report the case of a 73-year-old woman with a relapsing primary cutaneous anaplastic large cell lymphoma on her eyelid. A systemic extension study excluded extracutaneous involvement. Systemic chemotherapy resulted in an optimal response, with complete regression of the cutaneous lesions. There has been no recurrence during the 2 years of follow-up.

RESUMO O acometimento ocular adicional nos distúrbios linfoproliferativos CD30+ é raro. Relatamos o caso de uma mulher de 73 anos com linfoma de grandes células anaplásicas primárias recidivantes em sua pálpebra. A avaliação sistêmica excluiu envolvimento extracutâneo. A quimioterapia sistémica resultou em uma resposta ótima, com regressão completa das lesões cutáneas. Não houve recidiva durante 2 anos de acompanhamento.

Primary multifocal anaplastic large cell lymphoma with eyelid involvement: a case report.

Ocular adnexal involvement in CD30+ lymphoproliferative disorders is rare. We report the case of a 73-year-old woman with a relapsing primary cutaneous anaplastic large cell lymphoma on her eyelid. A systemic extension study excluded extracutaneous involvement. Systemic chemotherapy resulted in an optimal response, with complete regression of the cutaneous lesions. There has been no recurrence during the 2 years of follow-up.

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

PURPOSE: 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. DESIGN: Retrospective case series. METHODS: Background, treatment, and outcome data were retrospectively collected from the medical records of all patients with locally advanced and metastatic orbital or periocular BCC treated with vismodegib in 2012-2017 at 2 tertiary medical centers. RESULTS: 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 9 months, with follow-up of 26 months (range 9-60 months) overall and 17 months 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 16 months, and 3 who stopped treatment had a recurrence 8 months 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). CONCLUSIONS: 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.

Topical timolol treatment for periocular infantile haemangioma in the developing world.

Infantile haemangioma is a relatively common benign tumour which often does not require treatment. We present a case of a segmental infantile haemangioma with periocular involvement impacting on early visual development which was successfully treated with topical timolol maleate 0.5% drops in the developing world.