Until recently, the treatment of lacrimal gland carcinoma almost always required removal of the eye. But for some patients with these tumors, globe-sparing surgery followed by radiation therapy can preserve vision and decrease ocular morbidity and facial disfigurement.
Carcinomas of the lacrimal gland, although rare, are associated with a high risk of recurrence, perineural invasion, and distant metastasis. About half of patients eventually die of their disease despite treatment.
Treatment for lacrimal gland carcinoma historically entailed orbital exenteration (removal of the eye and all orbital contents), usually followed by high-dose radiation therapy to address perineural invasion or close surgical margins. Surgeons were reluctant to preserve the eye because of concerns that the eye would be severely damaged by the radiation therapy.
In recent years, however, the routine use of orbital exenteration for lacrimal gland carcinoma has been called into question by efforts led by Bita Esmaeli, M.D., a professor of ophthalmology and the director of orbital oncology and ophthalmic plastic surgery at The University of Texas MD Anderson Cancer Center. Retrospective reports from MD Anderson and other centers found poor survival outcomes despite local control of the tumors in patients who underwent orbital exenteration. “Orbital exenteration has not shown any survival benefit,” Dr. Esmaeli said.
The globe-sparing approach
MD Anderson physicians led by Dr. Esmaeli and Steven Frank, M.D., an associate professor in the Department of Radiation Oncology and the medical director of the Proton Therapy Center, use a multidisciplinary globe-sparing approach to manage lacrimal gland carcinoma in selected patients while striving to preserve vision and cosmesis.
This approach involves globe-sparing surgery followed by high-dose adjuvant radiation therapy. Chemotherapy may be given along with radiation to patients with positive surgical margins or recurrent disease.
Dr. Frank said, “With exenteration, a functioning organ is removed because of an adjacent tumor. Our goal is to preserve the eye and its function through surgery and radiation therapy.”
The extent of surgery depends upon the tumor’s location in the lacrimal gland, which comprises the orbital lobe and the palpebral lobe, and the involvement of the orbital soft tissue. For most patients, a significant amount of the orbital lobe must be removed; some patients must also undergo resection of the palpebral part of the gland, which is closest to the eye. Dr. Esmaeli said, “To achieve the goal of resecting the lacrimal gland cancer but preserving the eye and functionally important tissues in the orbit as much as possible, the orbital surgeon must have experience with meticulous oncologic resection.”
The globe-sparing approach requires close collaboration among the orbital surgeon, medical oncologist, and radiation oncologist. This collaboration is especially important in radiation treatment planning, as the treatment field must cover the postoperative surgical bed and often must extend to the base of the skull, toward the brain stem, to prevent perineural invasion and disease recurrence.
Lacrimal Gland Carcinoma
Adenoid cystic carcinoma is the most common type of primary malignant epithelial tumor of the lacrimal gland (60%), followed by carcinoma ex pleomorphic adenoma (20%), de novo adenocarcinoma, and mucoepidermoid carcinoma. Of these tumors, adenoid cystic carcinoma has the most aggressive biology; perineural spread occurs in about 75% of patients. Adenoid cystic carcinoma tends to be diagnosed in younger patients than other subtypes of lacrimal gland carcinoma: the mean patient ages at diagnosis are 37 years and 56 years, respectively.
Symptoms of lacrimal gland carcinoma include globe displacement, vision problems, a palpable mass on the upper eyelid, and eye or periocular pain. Computed tomography and magnetic resonance imaging are necessary to determine the size and shape of the tumor and to estimate the involvement of surrounding tissue.
Innovations in radiation therapy
The majority of patients who undergo globe-sparing surgery for lacrimal gland carcinoma are now treated with intensity-modulated proton therapy. According to Dr. Frank, “Proton therapy is very effective because we can shape the radiation dose for the complex anatomy while minimizing the dose to the cornea and other optic structures.” Proton therapy also eliminates the exit radiation dose that occurs in photon therapy.
The first MD Anderson patient to receive globe-sparing surgery for lacrimal gland carcinoma was treated in 2007. The surgery was followed by intensity-modulated radiation therapy. Unfortunately, this patient, who received a radiation dose greater than 45 Gy to the cornea, developed severe corneal toxic effects that eventually necessitated enucleation. The patient has, however, remained disease free. Dr. Frank and his team of radiation oncologists were able to modify the isodose curves in subsequent patients to significantly reduce the risk of corneal toxicities.
Dr. Frank uses several special proton delivery techniques to minimize the radiation dose to avoid damaging the cornea, optic nerve, optic chiasm, and other critical structures. For example, Dr. Frank uses a combination of active scanning and passive scattering radiation to minimize the radiation dose to the optic nerve. However, the target area still receives an appropriate radiation dose (54–60 Gy) for treating microscopic and gross residual disease.
Dr. Frank also uses a custom-made mold to ensure immobilization for patients during proton therapy. The mold, which includes a head and shoulder structure and a mask with a bite block, prevents movement greater than 1 mm. Patients typically undergo 15-minute proton treatment sessions 5 days a week for 6 weeks.
The use of precisely targeted radiation therapy has helped minimize the toxic effects of radiation. All patients treated with the globe-sparing approach have experienced dry eye syndrome, which was expected since the lacrimal gland was removed and the lacrimal fossa was irradiated. One patient also experienced mild radiation retinopathy, and one patient (described above) experienced severe corneal and conjunctival damage, which required enucleation.
“We are one of the first centers to use this multidisciplinary globe-sparing approach,” Dr. Esmaeli said. “We carefully select our patients and have been closely observing our patients treated with this approach to learn about the local control rates and also the ocular toxicity associated with this multimodality treatment strategy.”
The decision to undergo globe-sparing treatment for lacrimal gland carcinoma is made by the orbital surgeon, the radiation oncologist, the medical oncologist, and the patient. Dr. Esmaeli stressed the importance of counseling patients preoperatively: “Patients should understand the inherently higher risk of local-regional recurrence with globe-sparing surgery and the ocular side effects of radiation therapy. Having said that, with a median follow-up time of over 2 years, none of our first 11 lacrimal gland carcinoma patients treated with a globe-sparing approach has experienced a local or regional recurrence.”
Some patients are not good candidates for globe-sparing surgery and are still best treated by exenteration. Indications for exenteration include large tumor size, extensive infiltration of other critical orbital structures, recurrence after previous globe-sparing treatment, high histologic grade, and patient preference for a more radical surgery to potentially lower the risk of local recurrence.
Expanding the use of globe-sparing treatment
Drs. Esmaeli and Frank said that they also use the globe-sparing approach for other orbital cancers. Dr. Esmaeli said, “We are pushing the frontiers in surgical resection and radiation treatment of orbital cancers with the goal of preserving visual function and cosmesis whenever possible for all cancers that occur in the orbit and periorbital region.”
For more information, contact Dr. Bita Esmaeli at 713-792-4457 or Dr. Steven Frank at 713-563-3601.
OncoLog, April 2015, Volume 60, Issue 4
MD Anderson’s Orbital Oncology and Ophthalmic Plastic Surgery Program
The orbital oncology and ophthalmic plastic surgery program in the Department of Plastic Surgery at MD Anderson specializes in surgical treatment of tumors of the orbit, eyelid, conjunctiva, eye, and ocular adnexal structures as well as reconstructive surgery in the periocular region. It is the only dedicated orbital surgery and ophthalmic plastic surgery program based at a comprehensive cancer center in the United States. The primary goals of this program are eliminating ocular and orbital cancers while preserving the eye and vision and restoring function and cosmesis in the periocular region.
The orbital surgeons work closely with surgeons from other disciplines such as plastic surgery, head and neck surgery, skull base surgery, and neurosurgery and with radiation oncologists and medical oncologists to develop multidisciplinary treatments for orbital and ocular cancers.
The orbital oncology and ophthalmic plastic surgery program is led by Dr. Bita Esmaeli, who pioneered the sentinel lymph node biopsy technique for eyelid and ocular adnexal cancers. Dr. Esmaeli is also the principal investigator for a tissue banking study for uveal melanoma and the co-chair of The Cancer Genome Atlas working group for uveal melanoma.
The orbital oncology and ophthalmic plastic surgery program is currently conducting several clinical trials. Two of these trials aim to detect low-volume metastatic disease through sentinel lymph node biopsy: GSP00-106 for patients with conjunctival and eyelid melanoma and 2008-0266 for patients with sebaceous gland carcinoma of the eyelid. A trial of in vivo confocal microscopy of pigmented conjunctival lesions (2010-0330) is comparing imaging studies between participants with conjunctival melanoma and those with healthy eyes for differences that might lead to earlier diagnosis of these lesions.
For more information about MD Anderson’s orbital oncology and ophthalmic plastic surgery program, visit Orbital Oncology and Ophthalmic Plastic Surgery.