Clinical trial NCT00832429
Conditions: Eyelid Sebaceous Gland Carcinoma
Sponsor: M.D. Anderson Cancer Center
Start date: 2009-02-25; Completion date: 2024-08-27
Enrollment: 20 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This phase II trial studies how well lymph node mapping works in finding disease that has spread from the place where it started to other places in the body in patients with sebaceous gland cancer of the eyelid. Lymph node mapping may help in planning surgery to remove cancer and affected lymph nodes.

Detailed description:
PRIMARY OBJECTIVES:

I. Identify the rate of SLN (sentinel lymph node) positivity for eyelid sebaceous gland carcinomas.

II. Identify the false negative events associated with SLN biopsy for sebaceous gland carcinomas.

SECONDARY OBJECTIVE:

I. Record any side effects associated with SLN biopsy for sebaceous gland carcinoma of the eyelid.

OUTLINE:

Patients receive technetium Tc 99m sulfur colloid intradermally (ID) and then undergo lymph node mapping and SLN biopsy.

After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for 4 years.

Arms: arm 1: Patients receive technetium Tc 99m sulfur colloid ID and then undergo lymph node mapping and SLN biopsy.
Interventions: intervention 1: Lymph Node Mapping intervention 2: Sentinel Lymph Node Biopsy intervention 3: Technetium Tc-99m Sulfur Colloid
Intervention descriptions: intervention 1: Undergo lymph node mapping intervention 2: Undergo SLN biopsy intervention 3: Given ID

Protocol documents:
Prot_SAP_000.pdf: 
 
 
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Protocol Title: Sentinel Lymph Node Localization and Biopsy for Sebaceous Gland Carcinoma 
of the Eyelid 
PI:  Dr Ryan Goepfert  
 
1.0 Objectives 
Primary Objectives: 
a) 
Identify the rate of SLN (sentinel lymph node) positivity for eyelid sebaceous gland 
carcinomas. 
b) 
Identify the false negative events associated with SLN biopsy for sebaceous gland 
carcinomas. 
Secondary Objective: 
Record any side effects associated with SLN biopsy for sebaceous gland carcinoma of the 
eyelid. 
2.0 Background 
Sebaceous gland carcinoma of the eyelid is a rare cancer with a tendency for regional nodal 
metastasis.  Clinically obvious regional nodal metastasis is detected in 10-20% of patients with 
sebaceous gland carcinoma of the eyelid according to most series. 
Sentinel lymph node mapping and selective lymphadenectomy is a technique that has been 
successful in identifying patients with cutaneous melanoma who have microscopic regional 
lymph node metastasis.  An early therapeutic lymph node dissection is subsequently performed 
in patients proven to harbor occult metastatic disease.  This technique is well characterized for 
cutaneous melanomas in most locations.  Our group has adapted SLN biopsy technique for 
conjunctival melanoma and eyelid sebaceous gland carcinoma.5,8-11,13  The potential survival 
benefit for patients with nodal metastasis treated with neck dissection followed by radiotherapy 
or systemic adjuvant therapy provides an important impetus for accurate assessment of nodal 
status in patients with eyelid sebaceous gland carcinoma. 
The primary objective of this study is to identify the rate of SLN positivity in patients with eyelid 
sebaceous gland carcinoma and to determine the false negative events for the same.  The SLN 
positivity rate refers to the number of patients who had a positive SLN on biopsy divided by the 
total number of patients.  The false negative events refer to recurrence in a lymphatic basin that 
was previously deemed to harbor a "negative" SLN within the first 3 years of follow-up. 
3.0 Patient Eligibility 
Inclusion Criteria: 
a)   
Participant must be 18 years of age or over. 
b)   
Possible or Suspicious sebaceous gland carcinoma of the eyelid. 


 
 
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c)   
A CXR (chest x-ray), liver enzymes, and a head and neck CT,a (SPECT/CT) or 
magnetic resonance imaging (MRI) , and an ultrasound negative for clinical evidence of   
 
metastasis. 
d)   
Patient provided written informed consent.  In the event that non-English   
 
speaking participants are eligible for this study, a short form (if applicable)  
 
 
or an ICD in their language, will be utilized and completed in accordance   
 
with the MDACC Policy for Consenting Non-English Speaking Participants. 
Exclusion Criteria: 
a) 
Pregnant or nursing females. 
 
4.0 Pretreatment Evaluation 
Patients who meet the inclusion criteria are evaluated in the Ophthalmology Clinic with a 
complete ophthalmologic examination.  The tumor size, location and extent are 
characterized.  The pathology slides are reviewed by the pathology department at M.D. 
Anderson and the diagnosis of eyelid sebaceous gland carcinoma is confirmed.  A CXR, a 
CT or MRI of head and neck or a SPECT /CT scan and an ultrasound of regional nodes are 
obtained to establish lack of clinically identifiable metastatic disease.  The patient's ability to 
undergo surgery under general anesthesia will also be evaluated/assessed at this time.  The 
eligible patients then undergo preoperative lymphoscintigraphy. 
NOTE:  A serum/blood pregnancy test (i.e., 10cc’s) will be obtained, within 7 days prior to 
SLN mapping and biopsy, for all female patients of child-bearing potential, unless previously 
ordered as part of standard of care prior to surgery.  A negative pregnancy test will be 
verified on all female patients of child-bearing potential prior to any SLN mapping and 
biopsy.  If beta hcg is outside normal range, a 2nd test will be obtained.  If beta hcg is out of 
range a second time, a gynecologic consult will be obtained. 
Women of child-bearing potential (WOCBP) include any female who has experienced 
menarche and who has not undergone successful surgical sterilization (hysterectomy, 
bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal [defined as 
amenorrhea  12 consecutive months; or women on hormone replacement therapy (HRT) 
with documented serum follicle stimulating hormone (FSH) level  35mIU/mL].  Even women 
who are using oral, implanted or injectable contraceptive hormones or mechanical products 
such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to 
prevent pregnancy or practicing abstinence or where partner is sterile (e.g., vasectomy), 
should be considered to be of child bearing potential. 
5.0 Methodology and Treatment Plan 
Within 24 hours prior to planned surgery, patients will be injected with 0.3-0.4 mci of Tc99m-
sulfur colloid in 0.15-0.2 cc volume intradermally in 2-4 spots around the eyelid sebaceous 
gland carcinoma.  Multiple standard of care images of the head and neck including 
SPECT/CT will be obtained in the Nuclear Medicine Department following standard of care 


 
 
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protocols at MD Anderson Cancer Center..  At this point transmission images of the head 
and neck region will be performed. 
Intra-operative Mapping and Sentinel Node Biopsy 
On the day of  surgery, 0.15-0.2 cc (0.3-0.4 mCi) of Tc99m-Sulfur colloid will be injected 
intradermally around the primary lesion approximately one hour prior to the procedure, only 
if it has been more than 24 hours since the prior injection of Tc99m-sulfur colloid.  
Intraoperative lymphatic mapping and SLN identification are performed based on the 
localization of the radioactive colloid in regional lymph nodes.  The hand-held gamma probe 
is used to localize the SLN transcutaneously before a small skin incision is made over the 
corresponding nodal basin(s), and identification of a SLN is attempted.  An SLN is defined 
as one that collects radiolabeled colloid (at least twice background) within a regional nodal 
basin.  The maximal ex-vivo counts per second are recorded for each SLN.  The SLN 
harvest is considered to be complete when radiotracer uptake in the draining nodal basin(s) 
is less than twice background.  All patients will undergo wide local excision of the eyelid 
sebaceous gland carcinoma if needed during the same anesthesia session. 
The intradermal injection of Tc99m-Sulfur colloid as well as resection of the eyelid tumor will 
be done by the PI.  The intraoperative localization of SLN will be performed by a surgeon 
from Surgical Oncology or from Head & Neck Surgery. 
Excised SLNs are analyzed following the same methodology as in other anatomic locations.  
Briefly, the SLNs are breadloafed at 2 mm interval.  Formalin-fixed, paraffin-embedded and 
serially sections at 4-µm intervals are obtained.  Initially, one hematoxilin and eosin (H&E) 
stained slide is examined by routine microscopy.  If a metastasis is identified, the diagnosis 
is rendered.  In the report, the size (two dimensions) of the largest metastatic focus, the 
localization of metastasis (subscapular, intraparenchymal or both) and the presence or 
absence of the extracapsular extension will be included.  If metastasis is not identified in the 
initial H&E section, a serial level will be obtained and another H&E-stained slide will be 
examined, along with an immunohistochemical study performed on paraffin-embedded 
sections.  The immunohistochemical study will include  a pan-keratin cocktail (containing 
antibodies against high and low molecular-weight keratins), as well as antisera against 
epithelial membrane antigen (EMA).  The combination of immunohistochemical studies is 
performed in order to expand the sensitivity of sebaceous carcinoma metastases detection 
method in SLNs. 
6.0 Evaluation During Study 
An ophthalmologic exam to check for recurrence of the eyelid tumor is undertaken every 
three months (+/- 6 weeks) during the first year and every 6 months (+/- 6 weeks) during 
years 2-5.  A CXR will be performed 1 year (+/- 6 weeks) after removal of the primary tumor.  
A head and neck CT or MRI or a SPECT /CT scan is done once every 6 months (+/- 6 
weeks) during the first year and then once a year (+/- 6 weeks), thereafter and as needed.  
An ultrasound of regional nodes will be repeated 1 year (+/- 6 weeks) after removal of 
primary tumor. 


 
 
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A study participant's inability to comply with study policies and procedures, including the 
inability to comply with recommended follow up visits and testing, will be withdrawn from the 
study by the study PI. 
7.0 Evaluation of Side Effects 
There are no significant ocular toxicity expected from SLN biopsy in the periocular region.8-
11  One potential side effect of the SLN biopsy for periocular tumors is the likelihood of 
involvement of the preauricular (parotid) lymph nodes and the risk of damage to the facial 
nerve during the dissection and biopsy.  In our experience so far, in over 40 patients, there 
have been no cases of permanent facial nerve paralysis, although 3 patients with ocular 
tumors have had mild, temporary marginal mandibular nerve paresis, which resolved 
spontaneously after three weeks.  This risk will be discussed with each patient prior to 
sentinel node biopsy.  If facial nerve weakness occurs, the patient will be promptly evaluated 
by the ophthalmologist for protection of the corneal surface and consideration will be given 
to periocular reconstructive surgery, if the paresis or palsy is not improved after several 
months of observation. 
8.0 Number of Patients 
This study will be conducted at M.D. Anderson Cancer Center only.  Given the rare nature of 
eyelid sebaceous gland carcinoma, we estimate that accrual will be about 8-10 participants 
a year.  Our goal is to enroll 20 patients in this study.  All will be enrolled at M.D. Anderson 
only. 
9.0 Statistical Considerations 
The rate of SLN positivity and the false negative events will be reported using descriptive 
statistics.  Given the rare nature of this cancer, a total patient number of 20 is likely the 
maximum number that we can feasibly accrue in a few years.  The estimated rate of 
positivity for SLN is about 15% and the estimated rate of false negative events is 8%.  
Based on these assumptions, the widths of 95% binomial confidence intervals based on 20 
patients would be:  5%: 0.25; 10%: 0.30; 15%: 0.35; 20%: 0.38. 
10. Data Analysis 
Data analysis will be done at the end of patient accrual and follow up. 
 
11.0 References 
1. Esmaeli B, Wang X, Youssef A, et al. Patterns of regional and distant metastasis in 
patients with conjunctival melanoma: Experience at a cancer center over four decades. 
Ophthalmology 2001: 108: 2102-2105. 
2. Chao AN, Shields CL, Krema H, et al. Outcome of Patients with Periocular Sebaceous 
Gland Carcinoma with and without Conjunctival Intraepithelial Invasion. Ophthalmology 
2001; 1877-1883. 


 
 
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3. Gershenwald J, Tsent C, Thompson W, et al. Improved sentinel lymph node localization 
in patients with primary melanoma with the use of radiolabeled colloid. Surgery 1998; 124: 
203-210 . 
4. Bostick P, Essner R, Sarantou R, et all. Intraoperative lymphatic mapping for early-stage 
melanoma of the head and neck. American Journal of Surgery 1997; 174: 536-539. 
5. Esmaeli B. Sentinel Lymph Node Mapping for Patients with cutaneous and conjunctival 
malignant melanoma. Ophthal Plast Reconstr Surg 2000; 16:170-172. 
6. Morton DL, Wen D, Wong JH, et al. Technical details for intraoperative lymphatic mapping 
for early stage melanoma. Arch Surg 1992: 127: 392-399. 
7.Yu LL, Flotte TJ, Tanabe KK, et al.  Detection of microscopic melanoma metastases in 
sentinel lymph node.  Cancer 1999; 86: 617-627. 
8.Esmaeli B, Eicher S, Delpassand E.  Sentinel lymph node biopsy for conjunctival 
melanoma. Ophthal Plast Reconstr Surg 2000; 17: 436-442. 
9.Esmaeli B, Reifler D, Prieto VG, et al.  Conjunctival melanoma with a positive sentinel 
lymph node.  Arch Ophthalmol 2003; 121:1779-1783. 
10.Amato M, Esmaeli B, Ahmadi MA, et al.  Feasibility of preoperative lymphoscintigraphy 
for identification of sentinel lymph nodes in patients with conjunctival and periocular skin 
malignancies.  Ophthal Plast Reconstr Surg 2003; 19: 102-106. 
11.Nijhawan N, Ross MI, Diba R, et al. Experience with sentinel lymph node biopsy for 
eyelid and conjunctival malignancies at a cancer center.  Ophthal Plast Reconstr Surg, in 
press. 
12.Cochran AJ.  Surgical pathology remains pivotal in the evaluation of "sentinel" lymph 
nodes (editorial).  Am J Surg Pathol 1999; 23: 1169-1172. 
13. Ho VH, Ross MI, Prieto VG, et al.  Sentinel lymph node biopsy for sebaceous cell 
carcinoma and melanoma of the ocular adnexa.  Arch of Otolaryngology/Head and Neck 
Surgery; 133:820-6, 2007. 
14. Husain A, Blumenschein G, Esmaeli B. Treatment and outcomes for metastatic 
sebaceous cell carcinoma of the eyelid. Int J Dermatol; 47(3):276-9, 2008. 
 
 
 
 
 
 
 


 
 
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