recent advances in management of lid tumors

1. Presented : Dr. Gunjan Chadha
Chairman : Dr. Neebha Passi
Convenor : Dr. Reena Gupta

2.  Eyelid malignancies represent between 5% and 10% of all skin cancers.
 The incidence of eyelid cancer is approximately 15 cases per 100,000 individuals per year
 The annual age-adjusted incidence of eyelid malignancies in Asia ranges from 3.1 to 6.5 per
million population.
 Extrapolating the Asian data, a rough estimate of the incidence of about 5000-6000 new cases
of eyelid malignancies in India every year.
 An average ophthalmologist is likely to see one case of eyelid malignancy in three years or
about 10 cases in an average practice life span.

3.  In America and Europe, the most common malignant tumor of the eyelid is
Basal cell carcinoma (BCC), accounting for 80–95% of all eyelid malignancies
Squamous cell carcinoma (SCC) (< 5%),
Sebaceous gland carcinoma (SGC) (1–3%)
Malignant melanoma (1%)
Miscellaneous tumors (< 1%) constitute the rest of eyelid malignancies

5. DETAILED
HISTORY
COMPLETE
LOCAL ND
OCULAR
EXAMINATIO
N
IMAGING
MODALITY
HISTOPATHO
LOGICAL
EXAMINATI
ON
TREATMENT

6. SURGICAL EXCISION
 The Standard treatment for all eyelid carcinomas is Surgical excision with negative margins
 Mohs micrographic surgery has become the most common method of managing both BCC and SCC.
 Typical surgical margins for BCC are 2-3 mm, whereas more aggressive carcinomas such as Seb Ca,
Merkel cell carcinoma, and melanoma require larger margins.
 In a study by Peters et al, local control of Merkel cell carcinoma was achieved by wide excision with 5-
mm margins
 Can present with both functional and aesthetic challenges during larger reconstruction

7. ADJUVANT THERAPY
 In cases of aggressive tumor types, local or perineural invasion, and lymphatic or distant
metastatic disease, adjuvant therapies - cryotherapy, radiation therapy, chemotherapy, and lymph
node dissection can be considered.
RADIATION THERAPY:
 In case of radiosensitive tumor – Merkel cell Carcinoma- radiation therapy forms an integral part.
 Some malignancies such as Seb Ca have been considered radio-resistant, but recent reports detail
its response to a dose of more than 55 Gy.
 Bet

8. CHEMOTHERAPY:
 Topical or localized chemotherapy can be useful in the setting of patients in whom surgery is
deferred or who have positive surgical margins in certain situations.
 Treatments include :
imiquimod 5% cream
mitomycin C eye drops
interferon alpha-2 B eye drops or injection
5-fluorouracil eye drops.
 Systemic chemotherapeutic agents are typically reserved for patients with metastatic disease.

9.  Synthetically derived imidazoquinoline amine, which is approved
for the treatment of genital warts, actinic keratosis, and superficial
basal cell carcinoma.
 Imiquimod is an “immune response modifier” that is being used in
cases where surgical excision is not possible.
 Periocular BCC lesions for which excision would cause significant
aesthetic and functional compromise are good candidates for topical
imiquimod cream.

10. MECHANISM OFACTION
Imiquimod, acting as an agonist of the toll-like receptor 7 (TLR7), enhances dendritic cell survival
and promotes the activation of tumor-specific T-lymphocytes thus, inducing secretion of several
cytokines, such as interferon-α, interleukin-6, and tumor necrosis factor-α.
Dosage:
The cream is applied 5 days/week for six weeks.
 It has been reported that imiquimod has a cure rate of 83% .
 An alternative in the treatment of elderly patients with major comorbidities and poor compliance

11.  De Macedo et al - evaluated the efficacy of daily application of imiquimod cream to large
BCC eyelid lesions (up to 20 mm in diameter or 30 mm if involving the medial canthus)
without infiltration of deeper tissues on palpation. Treatment continued 5 days per week for 8-
16 weeks until the lesion became undetectable by slit lamp exam. Results indicated that 17 of
19 patients had complete clinical clearance at 3-month follow-up.
 In a study of 601 patients with histologically proven superficial basal-cell carcinoma,
topical imiquimod cream (once daily, 5 times a week, for 6 weeks) was superior, and topical
fluorouracil (twice daily for 4 weeks) was noninferior, to methylaminolevulinate photodynamic
therapy (2 sessions with an interval of 1 week ( Medscape)

12. 75-year-old woman with an infiltrative basal cell carcinoma (BCC) lesion on her right
cheek. A, Prior to treatment with imiquimod 3 times per week for 8 weeks. B, At the
end of the treatment period, showing marked erosion and crusting. C, After 5 years,
showing hypopigmentation and clinical resolution of her BCC lesion

13. ADVERSE EFFECTS:
 conjunctivitis
 keratitis
 foreign body sensation
 lacrimation
 decreased vision
 ectropion.
Of note, side effects resolved after treatment termination.
 The highest cure rates with imiquimod were after treatment for 12 weeks, with approximately
60% efficacy in the setting of 3 applications per week, 70% with 5 applications, and 76% with 7
applications

14. 5 Flouro Uracil:
 5-FU, with a 5% cream formulation is advised in the treatment of superficial BCC
 Dosage schedule: 2 daily applications for 2–4 weeks.
Photo Dynamic Thearapy:
 PDT with 5-aminolevulinic acid (ALA) or its methyl ester (methyl-5-amino-4-oxopentanoate,
MAL) can be effective for small and superficial BCC with a thickness not exceeding 2 mm.
 Successfully used for the treatment of periocular squamous papilloma, squamous cell
carcinoma, and basal cell carcinoma, with a response rate of 75% and with minimal damage to
surrounding tissues and excellent cosmetic outcome

15. ORBITAL INVOLVEMENT
 Until recently, an eyelid malignancy invading the orbit was considered an indication for
orbital exenteration (OE).
 OE is a radical, disfiguring and psychologically
 Traumatic surgical procedure often refused by patients

18.  Vismodegib is a hedgehog pathway inhibitor that was approved in 2012.
 Vismodegib is a drug indicated for the treatment of adults affected by mBCC and laBCC, who
have developed recurrence following surgery, or who are not candidates for radiotherapy.
MANUFACTURER : GENTECH
GENERIC NAME. : ERIVEDGE
DOSE : 150 MG (28 TAB)
Genentech has set the price of vismodegib at $7,500 for a
month's supply of once-daily capsules––or approximately
$250 per capsule

21. ERIVANCE BCC
To study efficacy and safety of drug a follow-up multicenter, phase
IIb trial that evaluated vismodegib therapy in two different
cohorts, unresectable laBCC and mBCC, with objective response
rate (ORR) as primary end point
The STEVIE (NCT01367665)
An open-label multicenter trial, which evaluated vismodegib
150 mg once daily in 1215 patients with laBCC or mBCC
for a median treatment duration of 86 months (range 0–44),
demonstrated similar safety results to ERIVANCE study

23. Clinical case report 1 of locally advanced BCC. Case report 1. Photo assessment: before vismodegib treatment (a); after 28 days of
vismodegib (b); partial clinical response at 6 months (c); onset of complete clinical response (d); ongoing clinical benefit (e). Radiological
assessment: basal cranial MRI performed in February 2017 before starting vismodegib (f), in June 2017 during vismodegib therapy (g) and
in May 2020 following 27 months of vismodegib treatment (h).

24. Dosage:
 150 mg PO qDay
 Continue until disease progression or unacceptable toxicity
Adverse Effects:
Muscle spasms , alopecia , and dysgeusia , weight loss, fatigue, diarrhea, decreased appetite
Limitations:
 The cost of vismodegib can be inhibitory for patients at approximately $7,500 per month.
 The inhibitory action of vismodegib on smoothened does not change the underlying mutation in
patched homologue 1, which is believed to be the driver of BCC formation.
 upon discontinuation of the medication, the underlying drive for proliferation is uninhibited

25.  Sonidegib binds to and inhibits SMO, a transmembrane protein involved in Hedgehog signal transduction.
 Indicated for adults with locally advanced basal cell carcinoma that has recurred following surgery or radiation
therapy, or those who are not candidates for surgery or radiation therapy
Dosage:
 200 mg PO qDay
 Continue treatment until disease progression or unacceptable toxicity
Adverse effect :
 Increased serum creatinine (92%)
 Increased serum creatine kinase (61%)
 Muscle spasms (54%)
 Alopecia (53%)
 Hyperglycemia

26. Checkpoint Inhibitor
 Cemiplimab - Recombinant human immunoglobulin G4 monoclonal antibody binds to PD-1 and
blocks its interaction with PD-L1 and PD-L2
 In 2021, it was fully approved for patients with locally advanced BCC and metastatic BCC
(mBCC).
Approved for :
 Squamous cell skin cancer
 Basal cell carcinoma
 Non-small cell lung cancer

27.  is an antibody that attaches to a molecule called PD-1,
which is present on the surface of T-cells – the primary
immune cells involved in killing cancer cells.
 In healthy tissues, PD-1 acts as a brake that keeps T cells
from creating an immune reaction that gets out of control.
 However, cancers can hijack this safety mechanism and
prevent T cells from doing their job – killing the cancer
cells.
 cancer cells or other cells within the tumor mass display on
their surface molecules called PD-L1 or PD-L2.
 PD-L1 or PD-L2 interact with PD-1 on T cells, the T cells
become inactive and do not attack the cancer cells.
 Cemiplimab binds to the PD-1 molecules on T cells in such
a way that prevents the interaction between PD-1 and PD-
L1/PD-L2, and allows the T cells to be active and attack the
cancer cells.

28.  phase II, nonrandomized, open-label trial, Study
1620.
 Patients (n=112) with locally advanced or
metastatic BCC (mBCC) whose BCC had
progressed on HHI or who were not
candidates for HHI therapy received
cemiplimab until disease progression,
unacceptable toxicity, or completion of planned
treatment.

29. Dosage:
 intravenous infusion, or I.V. over 30 minutes every three weeks (1mg/ml )
 Treatment should be continued until disease progression or unacceptable toxicity.
ADVERSE EFFECTS:
chest pain
Cough
breathing problems
swelling,
nausea and vomiting
changes in appetite or weight
easy bruising or bleeding

31.  Epidermal growth factor receptor, also known as HER1 or
ErbB1, is an extracellular transmembrane receptor kinase that
can be activated via the binding of multiple ligands such as
EGF, epiregulin, and transforming growth factor-α.
 The effects of EGFR activation within keratinocytes are
antiapoptotic, including increased cellular
proliferation/migration and blockage of cellular
differentiation and severe epidermal disorganization and
invasion
 Squamous cell carcinoma has been characterized by
overexpression of EGFR, noted in 78% of cutaneous SCC
cells and 62% of actinic keratoses.

32.  Cetuximab, a chimeric mouse-human IgG1 monoclonal antibody, which competitively inhibits
EGF binding to its receptor.
 Other drugs:
 Erlotinib, -which reduces the autophosphorylation of the EGFR, causes cell cycle arrest at the
G1 phase.
 Gefitinib
 El-Sawy et al have reported both clinical and radiologic tumor response to EGFR inhibitors
in 3 patients (2 with cetuximab, 1 with erlotinib) with locally advanced cutaneous SCC of the
periocular skin with orbital extension.

35.  The gold standard treatment of eyelid carcinomas is surgical resection with clear margins.
 The management of unresectable eyelid or periocular carcinoma has recently evolved from
exenteration and high dose radiation therapy, both of which can lead to disfigurement and
significant patient morbidity.
 The development of targeted drug therapy and immunotherapy against specific genetic
mutations in cutaneous malignancies allows for the destruction of specific cancer cells and less
systemic toxicity – is the ray of hope