New Targeted Therapies and Immunotherapies for Locally Advanced Periocular Malignant Tumours: Towards a New ‘Eye-Sparing’ Paradigm?

Abstract

The management of periocular skin malignant tumours is challenging. Surgery remains the mainstay of treatment for localised eyelid cancers. For more locally advanced cancers, especially those invading the orbit, orbital exenteration has long been considered the gold standard; however, it is a highly disfiguring and traumatic surgery. The last two decades have been marked by the emergence of a new paradigm shift towards the use of ‘eye-sparing’ strategies. In the early 2000s, the first step consisted of performing wide conservative eyelid and orbital excisions. Multiple flaps and grafts were needed, as well as adjuvant radiotherapy in selected cases. Although being incredibly attractive, several limitations such as the inability to treat the more posteriorly located orbital lesions, as well as unbearable diplopia, eye pain and even secondary eye loss were identified. Therefore, surgeons should distinguish ‘eye-sparing’ from ‘sight-sparing’ strategies. The second step emerged over the last decade and was based on the development of targeted therapies and immunotherapies. Their advantages include their potential ability to treat almost all tumours, regardless of their locations, without performing complex surgeries. However, several limitations have been reported, including their side effects, the appearance of primary or secondary resistances, their price and the lack of consensus on treatment regimen and exact duration. The aim of this article was to review the evolution of the management of locally advanced periocular malignant tumours over the last three decades and highlight the new paradigm shift towards the use of ‘eye-sparing’ strategies.

Recurrence Following Globe Sparing Excision for Basal Cell Carcinoma with Anterior Orbital Invasion

“…10 However, complete response rates vary from 29-67%, and its use is hampered by side effects that include muscle spasms, alopecia, dysgeusia, dysosmia, and weight loss. [11][12][13] Globe-sparing excision with the option for perioperative vismodegib or radiotherapy provides a reasonable alternative to exenteration for achieving definitive local tumor control. However, clinicians must remain vigilant for recurrence, which can remain radiologically silent for years before presenting with deep and aggressive disease.…”

Orbital/Periorbital Plexiform Neurofibromas: Classification and Surgical Strategies for a Better Outcome

“…Although there is a surgical classification based on orbital soft tissue, bony involvement, and blindness, there is no further consensus concerning surgical management for OPPN. 2 Similar to periocular skin tumor, 5 classifying OPPN based on its depth as OPPN-A or OPPN-AP is useful for deciding on surgical strategies. The Whitaker classification comprises four categories: category I, no refinements or surgical revisions advisable or necessary; category II, soft-tissue or lesser bone contouring revision was advisable; category III, major osteotomies or bone graft repositioning advisable (not as extensive as the original procedure); category IV, major craniofacial procedure advisable (duplicating or exceeding the original procedure).…”

Small but Challenging Conjunctival Melanoma: New Insights, Paradigms and Future Perspectives

“…As stated above, OE is a disfiguring surgical procedure, which is often refused by patients, its ability to reduce the metastatic spread having failed to be demonstrated. As for other locally advanced periocular malignancies, the last decade has been marked by the emergence of new eye-sparing strategies to avoid OE [ 98 ].…”

“…Although attractive, the enthusiasm aroused by conservative surgery followed by radiotherapy should be tempered because: data are currently scarce and are only based on retrospective studies; about one third of patients will experience tumour recurrence requiring revision surgeries +/− radiotherapy; complications are common (sicca syndrome, cataract, secondary glaucoma, corneal ulcer) and may impair patient’s quality of life [ 62 , 73 ]; although the globe is preserved, several patients will progressively lose their vision (secondary glaucoma, limbal cell deficiency); therefore, a distinction should be made between eye-sparing and sight-sparing strategies [ 98 ]; about 20% of patients will ultimately undergo secondary OE with possible delays in socket wound healing and orbital implant osseointegration failure due to previous radiotherapy [ 62 , 105 ]; not all CMs are eligible for conservative surgery. …”

“…although the globe is preserved, several patients will progressively lose their vision (secondary glaucoma, limbal cell deficiency); therefore, a distinction should be made between eye-sparing and sight-sparing strategies [ 98 ];…”