0
Clinical Sciences |

CyberKnife Radiosurgery for the Treatment of Intraocular and Periocular Lymphoma FREE

Carlos Bianciotto, MD; Carol L. Shields, MD; Sara E. Lally, MD; Jorge Freire, MD; Jerry A. Shields, MD
[+] Author Affiliations

Author Affiliations: Ocular Oncology Service (Drs Bianciotto, C. L. Shields, Lally, and J. A. Shields), Wills Eye Institute, Thomas Jefferson University, Philadelphia, Pennsylvania; and Capital Health Mercer CyberKnife Center, Trenton, New Jersey (Dr Freire).


Arch Ophthalmol. 2010;128(12):1561-1567. doi:10.1001/archophthalmol.2010.283.
Text Size: A A A
Published online

Objectives  To evaluate efficacy, patient tolerance, and adverse effects of CyberKnife radiosurgery for the treatment of intraocular and periocular lymphoma.

Methods  Retrospective case series of 13 patients who underwent CyberKnife radiosurgery was conducted.

Results  Fourteen eyes of 13 patients were included. The tissue location of the lymphoma was orbit (7 eyes), conjunctiva (3 eyes), choroid (2 eyes), and retina (2 eyes). The lymphoma type was classified as extranodal marginal zone B-cell lymphoma in 7 eyes (50%), diffuse large B-cell lymphoma in 3 eyes (21%), follicular lymphoma in 2 eyes (14%), and benign reactive lymphoid hyperplasia in 2 eyes (14%). The mean treatment dose was 1718 centigrays (cGy) (range, 1350-2250 cGy) given over a mean of 5 days (range, 3-5 days) with a mean dose rate of 320 cGy per fraction. Complete tumor resolution without local recurrence over a mean follow-up of 23 months was documented in all cases. Radiation-associated adverse effects included mild dry eye in 2 patients and cataract in 1 patient with conjunctival lymphoma. There was no radiation retinopathy or papillopathy, and visual acuity was preserved or improved in 13 eyes and decreased in 1 eye due to the presence of cataract.

Conclusions  CyberKnife radiosurgery is a well-tolerated technique for the treatment of intraocular and periocular lymphoma, allowing for local resolution of the lesions. An important benefit is that treatment was completed over 5 days.

Figures in this Article

The treatment of intraocular and periocular lymphoma varies according to specific tumor features such as size, shape, location, and grade of the lesion as well as the systemic status of the patient. Treatment options include surgical excision, chemotherapy, immunotherapy with rituximab for patients with positive CD 20 immunohistochemistry, or radiosurgery.130 For patients without systemic involvement, external beam radiotherapy (EBRT) is often used after histopathologic confirmation. Both primary intraocular lymphoma of the vitreous and retina and uveal lymphoma are treated with EBRT. Soft tissue periocular involvement with lymphoma also responds to EBRT. Local tumor control rates have been greater than 70% for retinovitreal lymphoma and greater than 92% for periocular lymphoma of the conjunctiva and orbit.2130 Standard EBRT is delivered over 20 days (4 weeks); requires complete immobilization, often with a frame or mask; and can lead to radiation adverse effects in the periocular region, including loss of vision or the eye.2130

The concept of stereotactic radiosurgery was first developed by Swedish neurosurgeon Lars Leksell in 1951 with the goal of providing nonsurgical ablation of tumors deep within the brain.3134 Initially considered an investigational device, radiosurgery has evolved to gain wide acceptance, becoming a routine procedure for the treatment of multiple disorders.3553 More recently, the advancement of image-guided radiosurgery has allowed for frameless treatment, often given over several sessions and at various extracranial sites.3553 In 1994, American neurosurgeon John Adler (who had previously trained with Leksell in Sweden) explored robotic technology and engineered the first robotic linear accelerator capable of precise radiosurgery delivery to targets as small as 5 mm. He called this robotically driven technique CyberKnife.3234

CyberKnife is an image-guided radiosurgical technique that uses a linear accelerator mounted on a robotic arm, delivering up to 1300 beams from a multidirectional perspective, limiting surface tissue damage.3234 It allows paramount conformal precision, thus limiting damage to surrounding healthy tissue. CyberKnife provides treatment with frameless comfortable delivery over 3 to 5 consecutive days in an outpatient setting.3234

In this report, we review the experience of a single institution with CyberKnife radiosurgery for the treatment of intraocular and periocular lymphoma. We explore treatment efficacy, patient tolerance, and adverse effects.

The medical records of all patients with intraocular or periocular lymphoma who were evaluated at the Ocular Oncology Service, Wills Eye Institute, Philadelphia, Pennsylvania, were reviewed. Patients who received CyberKnife radiosurgery were selected for further analysis. Institutional review board approval was obtained.

The data collected included age, race, sex, best-corrected Snellen visual acuity, initial ocular symptom, involved tissue (choroid, retina-vitreous, orbit, eyelid, or conjunctiva), and lymphoma type (extranodal marginal zone B-cell lymphoma [MALT], diffuse large B-cell, follicular, or benign reactive lymphoid hyperplasia). Imaging studies performed (magnetic resonance imaging, computed tomography, or ultrasound) were recorded. Maximum tumor dimensions were recorded in millimeters and measured from ophthalmoscopy and ultrasound for intraocular lesions, magnetic resonance imaging or computed tomography for orbital lesions, slitlamp evaluation for conjunctival lesions, and external examination for eyelid lesions. The location of the tumor was classified according to quadrant involved (superior, inferior, medial, or lateral), coronal location (intraocular, muscle involvement, lacrimal gland, orbital fat, or eyelid), and axial location (anterior, midorbit, posterior, or intraocular). Previous ocular treatments and procedures (pars plana vitrectomy, incisional biopsy, excisional biopsy, or fine-needle aspiration biopsy) were recorded. The systemic status of the patient at the first visit was also recorded. Follow-up visits were scheduled at 2, 6, 12, and 24 months and then on a yearly basis. Follow-up information included visual acuity, funduscopy, Hertel exophthalmometry, Ishihara color plates, Humphrey visual field, response to therapy with local tumor status (completely regressed, partially regressed, stable, or local recurrence), systemic outcome (alive without systemic involvement, alive with systemic involvement, or dead), and complications of therapy (dry eye syndrome [defined as the presence of superficial punctate keratitis on slitlamp examination, tear film break-up test of <10 seconds, or abnormal results of the Schirmer test], radiation retinopathy, radiation papillopathy, radiation cataract, or radiation glaucoma) and their management.

CyberKnife radiosurgery variables that were recorded included tumor volume measurements, total radiation dose in centigrays (cGy), number of fractions, number of beams, isodose, maximum dose, and conformality index. Complications, events during treatment, and patient comfort were also recorded.

Fourteen eyes from 13 patients underwent CyberKnife radiosurgery for treatment of biopsy-proven intraocular or periocular lymphoma between November 1, 2006, and September 30, 2009. The mean age of the patients was 68 years (median, 66; range, 46-91 years). One patient was Hispanic (8%) and the rest were white (92%). There were 5 men (38%) and 8 women (62%). The initial visual acuity and ocular symptoms are listed in Table 1.

Table Graphic Jump LocationTable 1. Findings in 14 Eyes With Intraocular or Periocular Lymphoma Treated With CyberKnife Radiosurgery

Seven patients (54%) had involvement of 1 intraocular or periocular structure (orbit in 5 patients [Figure 1], conjunctiva in 1 patient, and choroid in 1 patient); the remaining 6 (46%) had simultaneous involvement of more than 1 ocular structure (conjunctiva and orbit in 2 patients, retina and vitreous in 2 patients, eyelid and orbit in 1 patient, and conjunctiva and choroid in 1 patient). Six patients (46%) were diagnosed with MALT, 3 (23%) with diffuse large B-cell lymphoma, 2 (15%) with follicular lymphoma, and 2 (15%) with benign reactive lymphoid hyperplasia. Size and location of the lesions are described in detail in Table 1. Patient 3 had bilateral conjunctival involvement for which he underwent simultaneous treatment (Figure 2). All patients underwent both magnetic resonance imaging and computed tomography before the procedure (Figure 3), and 3 had additional B-scan ultrasound performed due to the intraocular location of the lymphoma (Figure 4). All patients had previous confirmation of the diagnosis by either fine-needle aspiration biopsy (patients 6, 9, and 11; Figure 5) or excisional biopsy (the remaining 10 patients). Ten patients (77%) had no systemic involvement at the initial visit. Of the remaining 3 patients (23%), 1 patient had involvement of the gastrointestinal tract (patient 6), 1 had brain lymphoma (patient 9), and 1 had multiorgan disease (patient 7).

Place holder to copy figure label and caption
Figure 1.

CyberKnife radiosurgery for the treatment of orbital lymphoma in a 79-year-old woman. A, Orbital lymphoma. B, Lymphoma shown on magnetic resonance imaging. C, Treatment with CyberKnife. Excellent clinical (D) and imaging (E) response, demonstrating marked resolution of the orbital tumor.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

CyberKnife radiosurgery for the treatment of bilateral conjunctival lymphoma in a 65-year-old man. A and B, Bilateral conjunctival lymphoma. C, Treatment with CyberKnife. D and E, Complete clinical regression.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.

CyberKnife radiosurgery for the treatment left upper eyelid lymphoma in a 69-year-old man. A, Left upper eyelid lymphoma. B, Lymphoma shown on computed tomography. C, Treatment with CyberKnife. Complete clinical (D) and imaging (magnetic resonance imaging) (E) tumor resolution.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 4.

CyberKnife radiosurgery for the treatment of primary retinal lymphoma in a 68-year-old man. A, Primary retinal lymphoma. B, Lymphoma shown on B-scan ultrasonography. C, Treatment with CyberKnife after fine-needle aspiration biopsy. Complete clinical (D) and ultrasonographic (E) resolution of the lymphoma.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 5.

CyberKnife radiosurgery for the treatment of choroidal lymphoma in a 59-year-old woman. A, Choroidal lymphoma. B, Lymphoma shown on ultrasonography. C, Treatment with CyberKnife. Excellent clinical (D) and ultrasonographic (E) response.

Graphic Jump Location

After a median follow-up of 23 months (mean, 23; range, 6-37 months), all patients had complete regression of the local lesions with no signs of local tumor recurrence. Systemic status of the patients at the last follow-up visit is shown in Table 1. Of the 2 patients with retina-vitreous lymphoma, 1 showed the presence of a stable systemic disease with brain involvement at the last visit, having received treatment to the brain with EBRT and systemic chemotherapy before the application of CyberKnife (patient 6), and the other (patient 9) developed brain involvement during follow-up and was treated with EBRT, with stable systemic status at date last seen. Patient 2 developed contralateral lacrimal gland lymphoma that was treated with excisional biopsy, and patient 7 died after developing multiorgan involvement that was treated with chemotherapy. One patient with orbital benign reactive lymphoid hyperplasia (patient 12) was found to have cervical lymph node involvement during the follow-up, with the pathology specimen showing MALT.

Visual acuity at the last visit remained stable in 5 eyes (36%), improved in 8 eyes (57%), and decreased in 1 eye (7%). The reason for the decreased vision in this eye with conjunctival involvement was the presence of posterior subcapsular radiation cataract. At the final visit, the visual field and color vision remained stable in 13 eyes and improved in 1 eye (patient 12). The radiation-associated adverse effects recorded at the last visit included dry eye syndrome in 2 patients (patients 3 and 8), which was treated with artificial tears in patient 3 and with punctal plug placement in patient 8, and cataract formation in patient 8, which was managed with cataract extraction. None of the patients developed skin erythema, radiation retinopathy, papillopathy, or glaucoma secondary to treatment during follow-up. Patient 10 reported tearing at the last follow-up visit, and patient 12 reported persistent diplopia.

CyberKnife radiosurgery variables for each patient are described in detail in Table 2. The median initial tumor volume was 14.55 mL, the median dose was 1750 cGy, the median number of treatment fractions was 5, the median number of beams was 133, the median isodose was 75 cGy, the median maximum dose was 2333.33 cGy, and the median conformality index was 1.4. Overall, treatment was well tolerated by all patients. Of 13 patients, 2 (patients 3 and 8) developed itching during treatment and 2 (patients 2 and 13) developed conjunctival erythema.

Table Graphic Jump LocationTable 2. CyberKnife Radiosurgery Parameters

Lymphoma is a multiorgan condition that can affect intraocular and periocular structures such as the choroid, retina, vitreous, conjunctiva, and orbit.120 Systemic non-Hodgkin lymphoma is estimated to affect 43 000 persons per year in the United States; ocular involvement is uncommon, representing approximately 2% of all extranodal lymphoma cases.120 Lymphoproliferative lesions include a wide range of diseases such as benign reactive lymphoid hyperplasia, atypical lymphoid hyperplasia, and lymphoma, based on varying degrees of histopathologic and immunophenotypic features.130

The approach to treatment of a lymphoid tumor of the eye and its adnexa includes an assessment of the patient's ocular and systemic status.130 If the patient shows no sign of systemic lymphoma after an evaluation by the oncologist, then the ocular tumor is addressed with complete excision plus cryotherapy if the mass is small and accessible (lymphoma of the conjunctiva or anterior orbit) or incisional biopsy and low-dose radiosurgery if the mass is large (posterior orbital tumors). In the case of choroidal or retinovitreal lymphoma, fine-needle aspiration biopsy followed by EBRT or chemotherapy is usually performed. If medical evaluation reveals systemic lymphoma, treatment of the ocular disease is secondary to systemic treatment (usually chemotherapy).130

The effectiveness of EBRT for the treatment of lymphoma of the eye and its adnexa has been widely documented.2130 In the ophthalmic literature, Kennerdell and associates21 described local tumor control of 95% at a mean follow-up of 7 years in 54 patients with orbital lymphoma treated with low-dose (24 Gy) EBRT. Similarly, Isobe and colleagues24 reported the use of moderate-dose EBRT (median tumor dose of 30.6 Gy) for the treatment of orbital lymphoma in 24 patients, with complete remission in 92% of the patients. The same authors30 described the use of EBRT in 15 patients with primary intraocular lymphoma with a control rate of 74% at 2 years. Local recurrence was found in only 1 of these patients.30 Uno and associates29 reported that 98% of 50 patients with MALT of the ocular adnexa had tumor control at 24 months. Berenbom et al25 described no cases of tumor recurrence in 7 patients with primary intraocular lymphoma treated with EBRT. Liao and associates27 described local disease control in all 20 patients with orbital lymphoma treated with EBRT after a mean follow-up of 4.7 years. In the present series, all 14 eyes showed complete resolution of lymphoma after CyberKnife radiosurgery with stability at a mean follow-up of 23 months. Since these are early results, longer follow-up is needed to assess the status of the lesions.

Adverse effects of conventional EBRT are well known.2130 In a series of 54 patients with orbital lymphoma treated with EBRT, Kennerdell and colleagues21 found that 33% of the patients treated with EBRT for orbital lymphoma developed chronic dry eye syndrome after a mean follow-up of 7 years. Similarly, Isobe and associates24 reported that after a median follow-up of 37 months, 13% of the patients developed cataract after use of moderate-dose EBRT for the treatment of orbital lymphoma. Berenbom and associates25 described dry eye syndrome and cataract in 57% and radiation retinopathy in 29% of patients after EBRT for the treatment of primary intraocular lymphoma. Liao and et al27 reported that 45% of patients developed dry eye syndrome and 35% had cataract after EBRT for the treatment of orbital lymphoma after a mean follow-up of 4.7 years. In the current series of 14 eyes with lymphoma treated with CyberKnife radiosurgery, the only adverse effects observed were mild dry eye syndrome in 2 eyes (14%) and cataract in 1 eye (7%) after a mean follow-up of 23 months (both patients had conjunctival involvement). To our knowledge, this is the largest series in the ophthalmic literature of lymphomatous lesions of the eye and adnexa treated with CyberKnife radiosurgery, and early results demonstrate relative safety. Longer follow-up is necessary to explore long-term adverse effects.

In the ophthalmic literature, Hirschbein and associates35 described the use of CyberKnife radiosurgery for the treatment of orbital tumors, including 2 patients with conjunctival lymphoma and 3 with orbital lymphoma, resulting in complete resolution of the lesions after a mean follow-up of 8 months. In that small series, there were no cases of intraocular lymphoma (choroid or retina).35

The advantages of CyberKnife include, among others, patient comfort during frameless radiosurgery and the ability to fractionate the treatment dose.3234 Dose fractionation can enable the delivery of a higher total dose to the tumor while maintaining safe daily doses to surrounding critical structures. Fractionation of treatment is an important concept in radiation oncology because it takes advantage of the disparate biologies of healthy and neoplastic tissues, allowing preservation of the former and cell damage to the latter.3234 Fractionation allows time for healthy cells to recover, while tumor cells are generally less efficient in achieving repair between fractions. CyberKnife is usually fractionated over 5 days. Last, CyberKnife treatment allows for conformal fields that can be round or irregular so that the robotic machine can sculpt an unusually shaped area (nonisocentric planning) for radiosurgery treatment and avoid adjacent structures.3234

Conventional radiation therapy has proven to be effective for the treatment of ocular lymphoma. However, it uses a wide field of delivery with the risk of radiation-induced tissue injury to normal structures and even a risk for related secondary cancers.2130 This technique is well established and reliable, although some high-dose treatments may be limited by the radiation toxicity of healthy tissues near the target area. CyberKnife has the capacity to minimize irradiation of nearby critical structures through the use of multiple beams coming from different directions, with the intent to reduce collateral damage.3553 This capacity could be beneficial in the treatment of ocular lesions, in which radiation tolerance of the globe and optic nerve is considered. In a series of 49 patients with perioptic tumors (within 2 mm of the optic nerve) treated with CyberKnife radiosurgery, Adler and associates39 found that 94% of patients maintained or improved their visual field after a mean follow-up of 49 months. In a series of 16 patients with orbital tumors treated with CyberKnife, Hirschbein and associates35 found that all patients had stable or improved visual field after 8 months of follow-up. Romanelli and associates38 described the use of CyberKnife in 3 patients with optic nerve sheath meningiomas with improvement in the visual field in all patients after the procedure.

In summary, CyberKnife radiosurgery for the treatment of intraocular and periocular lymphoma in 14 eyes allowed for complete resolution without local recurrence. The 5-day frameless procedure was well tolerated by all patients. Radiation-associated adverse effects included mild dry eye syndrome in 2 eyes (14%) and cataract in 1 eye (7%). From these observations, it is evident that CyberKnife radiosurgery is a useful procedure for the treatment of intraocular and periocular lymphoma with minimal adverse effects. Further follow-up is warranted.

Correspondence: Carol L. Shields, MD, Ocular Oncology Service, Wills Eye Institute, 840 Walnut St, Ste 1440, Philadelphia, PA 19107 (carol.shields@shieldsoncology.com).

Submitted for Publication: February 9, 2010; final revision received March 11, 2010; accepted March 29, 2010.

Author Contributions: All authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Financial Disclosure: None reported.

Shields  JAShields  CLScartozzi  R Survey of 1264 patients with orbital tumors and simulating lesions: the 2002 Montgomery Lecture, part 1. Ophthalmology 2004;111 (5) 997- 1008
PubMed
Demirci  HShields  CLShields  JAHonavar  SGMercado  GJTovilla  JC Orbital tumors in the older adult population. Ophthalmology 2002;109 (2) 243- 248
PubMed
Knowles  DM  IIJakobiec  FA Orbital lymphoid neoplasms: a clinicopathologic study of 60 patients. Cancer 1980;46 (3) 576- 589
PubMed
Knowles  DMJakobiec  FA McNally  LBurke  JS Lymphoid hyperplasia and malignant lymphoma occurring in the ocular adnexa (orbit, conjunctiva, and eyelids): a prospective multiparametric analysis of 108 cases during 1977 to 1987. Hum Pathol 1990;21 (9) 959- 973
PubMed
Cockerham  GCJakobiec  FA Lymphoproliferative disorders of the ocular adnexa. Int Ophthalmol Clin 1997;37 (4) 39- 59
PubMed
Coupland  SEKrause  LDelecluse  HJ  et al.  Lymphoproliferative lesions of the ocular adnexa: analysis of 112 cases. Ophthalmology 1998;105 (8) 1430- 1441
PubMed
Johnson  TETse  DTByrne  GE  Jr  et al.  Ocular-adnexal lymphoid tumors: a clinicopathologic and molecular genetic study of 77 patients. Ophthal Plast Reconstr Surg 1999;15 (3) 171- 179
PubMed
Sullivan  TJWhitehead  KWilliamson  R  et al.  Lymphoproliferative disease of the ocular adnexa: a clinical and pathologic study with statistical analysis of 69 patients. Ophthal Plast Reconstr Surg 2005;21 (3) 177- 188
PubMed
Jenkins  CRose  GEBunce  C  et al.  Histological features of ocular adnexal lymphoma (REAL classification) and their association with patient morbidity and survival. Br J Ophthalmol 2000;84 (8) 907- 913
PubMed
Fung  CYTarbell  NJLucarelli  MJ  et al.  Ocular adnexal lymphoma: clinical behavior of distinct World Health Organization classification subtypes. Int J Radiat Oncol Biol Phys 2003;57 (5) 1382- 1391
PubMed
White  WLFerry  JAHarris  NLGrove  AS  Jr Ocular adnexal lymphoma: a clinicopathologic study with identification of lymphomas of mucosa-associated lymphoid tissue type. Ophthalmology 1995;102 (12) 1994- 2006
PubMed
Jakobiec  FA McLean  IFont  RL Clinicopathologic characteristics of orbital lymphoid hyperplasia. Ophthalmology 1979;86 (5) 948- 966
PubMed
Knowles  DM  IIJakobiec  FA Ocular adnexal lymphoid neoplasms: clinical, histopathologic, electron microscopic, and immunologic characteristics. Hum Pathol 1982;13 (2) 148- 162
PubMed
Bairey  OKremer  IRakowsky  EHadar  HShaklai  M Orbital and adnexal involvement in systemic non-Hodgkin's lymphoma. Cancer 1994;73 (9) 2395- 2399
PubMed
Coupland  SEHummel  MStein  H Ocular adnexal lymphomas: five case presentations and a review of the literature. Surv Ophthalmol 2002;47 (5) 470- 490
PubMed
Sullivan  TJValenzuela  AA Imaging features of ocular adnexal lymphoproliferative disease. Eye (Lond) 2006;20 (10) 1189- 1195
PubMed
Jenkins  CRose  GEBunce  C  et al.  Clinical features associated with survival of patients with lymphoma of the ocular adnexa. Eye (Lond) 2003;17 (7) 809- 820
PubMed
Redfern  CHGuthrie  THBessudo  A  et al.  Phase II trial of idiotype vaccination in previously treated patients with indolent non-Hodgkin's lymphoma resulting in durable clinical responses. J Clin Oncol 2006;24 (19) 3107- 3112
PubMed
Plosker  GLFiggitt  DP Rituximab: a review of its use in non-Hodgkin's lymphoma and chronic lymphocytic leukaemia. Drugs 2003;63 (8) 803- 843
PubMed
Shields  CLShields  JACarvalho  CRundle  PSmith  AF Conjunctival lymphoid tumors: clinical analysis of 117 cases and relationship to systemic lymphoma. Ophthalmology 2001;108 (5) 979- 984
PubMed
Kennerdell  JSFlores  NEHartsock  RJ Low-dose radiotherapy for lymphoid lesions of the orbit and ocular adnexa. Ophthal Plast Reconstr Surg 1999;15 (2) 129- 133
PubMed
Chino  KTanyi  JAStea  B Stereotactic radiotherapy for unilateral orbital lymphoma and orbital pseudo-tumors: a planning study. Med Dosim 2009;34 (1) 57- 62
PubMed
Goyal  SCohler  ACamporeale  JNarra  VYue  NJ Intensity-modulated radiation therapy for orbital lymphoma. Radiat Med 2008;26 (10) 573- 581
PubMed
Isobe  KKagami  YHiguchi  K A multicenter phase II study of local radiation therapy for stage IEA mucosa-associated lymphoid tissue lymphomas: a preliminary report from the Japan Radiation Oncology Group (JAROG). Int J Radiat Oncol Biol Phys 2007;69 (4) 1181- 1186
Berenbom  ADavila  RMLin  HSHarbour  JW Treatment outcomes for primary intraocular lymphoma: implications for external beam radiotherapy. Eye (Lond) 2007;21 (9) 1198- 1201
PubMed
Matsuo  TYoshino  T Long-term follow-up results of observation or radiation for conjunctival malignant lymphoma. Ophthalmology 2004;111 (6) 1233- 1237
PubMed
Liao  SLKao  SCHou  PKChen  MS Results of radiotherapy for orbital and adnexal lymphoma. Orbit 2002;21 (2) 117- 123
PubMed
Esmaeli  BAhmadi  MAManning  J McLaughlin  PWGinsberg  L Clinical presentation and treatment of secondary orbital lymphoma. Ophthal Plast Reconstr Surg 2002;18 (4) 247- 253
PubMed
Uno  TIsobe  KShikama  N  et al.  Radiotherapy for extranodal, marginal zone, B-cell lymphoma of mucosa-associated lymphoid tissue originating in the ocular adnexa: a multiinstitutional, retrospective review of 50 patients. Cancer 2003;98 (4) 865- 871
Isobe  KEjima  YTokumaru  S  et al.  Treatment of primary intraocular lymphoma with radiation therapy: a multi-institutional survey in Japan. Leuk Lymphoma 2006;471800-1805
PubMed
Leksell  L The stereotaxic method and radiosurgery of the brain. Acta Chir Scand 1951;102 (4) 316- 319
PubMed
Andrews  DWBednarz  GEvans  JJDownes  B A review of 3 current radiosurgery systems. Surg Neurol 2006;66 (6) 559- 564
PubMed
Adler  JR  JrChang  SDMurphy  MJDoty  JGeis  PHancock  SL The CyberKnife: a frameless robotic system for radiosurgery. Stereotact Funct Neurosurg 1997;69 (1-4, pt 2) 124- 128
PubMed
Adler  JR  JrMurphy  MJChang  SDHancock  SL Image-guided robotic radiosurgery. Neurosurgery 1999;44 (6) 1299- 1307
PubMed
Hirschbein  MJCollins  SJean  WCChang  SDAdler  JR  Jr Treatment of intraorbital lesions using the Accuray CyberKnife system. Orbit 2008;27 (2) 97- 105
PubMed
Zorlu  FSelek  UKiratli  H Initial results of fractionated CyberKnife radiosurgery for uveal melanoma [published online ahead of print February 22, 2009]. J Neurooncol 2009;94 (1) 111- 117
PubMed
Muacevic  ANentwich  MWowra  BStaerk  SKampik  ASchaller  U Development of a streamlined, non-invasive robotic radiosurgery method for treatment of uveal melanoma. Technol Cancer Res Treat 2008;7 (5) 369- 374
PubMed
Romanelli  PWowra  BMuacevic  A Multisession CyberKnife radiosurgery for optic nerve sheath meningiomas. Neurosurg Focus 2007;23 (6) E11
PubMed10.3171/FOC-07/12/E11
Adler  JR  JrGibbs  ICPuataweepong  PChang  SD Visual field preservation after multisession CyberKnife radiosurgery for perioptic lesions. Neurosurgery 2006;59 (2) 244- 254
PubMed
Zytkovicz  ADaftari  IPhillips  TLChuang  CFVerhey  LPetti  PL Peripheral dose in ocular treatments with CyberKnife and Gamma Knife radiosurgery compared to proton radiotherapy [published online September 17, 2007]. Phys Med Biol 2007;52 (19) 5957- 5971
PubMed
On  AVHirschbein  MJWilliams  HJKaresh  JW CyberKnife radiosurgery and rituximab in the successful management of sclerosing idiopathic orbital inflammatory disease. Ophthal Plast Reconstr Surg 2006;22 (5) 395- 397
PubMed
Fariselli  LMarras  CDe Santis  MMarchetti  MMilanesi  IBroggi  G CyberKnife radiosurgery as a first treatment for idiopathic trigeminal neuralgia. Neurosurgery 2009;64(2 suppl)96- 101
PubMed
Murovic  JGibbs  IChang  SMobley  BPark  JAdler  J Foraminal nerve sheath tumors: intermediate followup after CyberKnife radiosurgery. Neurosurgery 2009;64(2 suppl)33- 43
Giller  CABerger  BDPistenmaa  DA  et al.  Robotically guided radiosurgery for children. Pediatr Blood Cancer 2005;45 (3) 304- 310
PubMed
Hara  WTran  PLi  G  et al.  CyberKnife for brain metastases of malignant melanoma and renal cell carcinoma. Neurosurgery 2009;64 (2) ((suppl)) A26- A32
PubMed
Colombo  FCasentini  LCavedon  CScalchi  PCora  SFrancescon  P CyberKnife radiosurgery for benign meningiomas: short-term results in 199 patients. Neurosurgery 2009;64 (2) ((suppl)) A7- A13
PubMed
Killory  BDKresl  JJWait  SDPonce  FAPorter  RWhite  Wl  Hypofractionated CyberKnife radiosurgery for perichiasmatic pituitary adenomas: early results. Neurosurgery 2009;64(2 suppl)19- 25
Adler  JR  JrChang  SD CyberKnife image-guided radiosurgery. Neurosurgery 2009;64 (2) ((suppl)) A1
PubMed
Sakamoto  GTBorchers  DJ  IIIXiao  FYang  HJChang  SDAdler  JR  Jr CyberKnife radiosurgery for trigeminal schwannomas. Neurosurgery 2009;64 (2) ((suppl)) A14- A18
PubMed
Wowra  BMuacevic  ATonn  JC Quality of radiosurgery for single brain metastasis with respect to treatment technology: a matched paired analysis [published online ahead of print February 1, 2009]. J Neurooncol 2009;94 (1) 69- 77
PubMed10.1007/s11060-009-9802-y
Gagnon  GJNasr  NMLiao  JJ  et al.  Treatment of spinal tumors using cyberknife fractionated stereotactic radiosurgery: pain and quality-of-life assessment after treatment in 200 patients. Neurosurgery 2009;64 (2) 297- 307
PubMed
Shimamoto  SInoue  TShiomi  H  et al.  CyberKnife stereotactic irradiation for metastatic brain tumors. Radiat Med 2002;20 (6) 299- 304
PubMed
Andrews  DWFaroozan  RYang  BP  et al.  Fractionated stereotactic radiotherapy for the treatment of optic nerve sheath meningiomas: preliminary observations of 33 optic nerves in 30 patients with historical comparison to observation with or without prior surgery. Neurosurgery 2002;51 (4) 890- 904
PubMed

Figures

Place holder to copy figure label and caption
Figure 1.

CyberKnife radiosurgery for the treatment of orbital lymphoma in a 79-year-old woman. A, Orbital lymphoma. B, Lymphoma shown on magnetic resonance imaging. C, Treatment with CyberKnife. Excellent clinical (D) and imaging (E) response, demonstrating marked resolution of the orbital tumor.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

CyberKnife radiosurgery for the treatment of bilateral conjunctival lymphoma in a 65-year-old man. A and B, Bilateral conjunctival lymphoma. C, Treatment with CyberKnife. D and E, Complete clinical regression.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.

CyberKnife radiosurgery for the treatment left upper eyelid lymphoma in a 69-year-old man. A, Left upper eyelid lymphoma. B, Lymphoma shown on computed tomography. C, Treatment with CyberKnife. Complete clinical (D) and imaging (magnetic resonance imaging) (E) tumor resolution.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 4.

CyberKnife radiosurgery for the treatment of primary retinal lymphoma in a 68-year-old man. A, Primary retinal lymphoma. B, Lymphoma shown on B-scan ultrasonography. C, Treatment with CyberKnife after fine-needle aspiration biopsy. Complete clinical (D) and ultrasonographic (E) resolution of the lymphoma.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 5.

CyberKnife radiosurgery for the treatment of choroidal lymphoma in a 59-year-old woman. A, Choroidal lymphoma. B, Lymphoma shown on ultrasonography. C, Treatment with CyberKnife. Excellent clinical (D) and ultrasonographic (E) response.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. Findings in 14 Eyes With Intraocular or Periocular Lymphoma Treated With CyberKnife Radiosurgery
Table Graphic Jump LocationTable 2. CyberKnife Radiosurgery Parameters

References

Shields  JAShields  CLScartozzi  R Survey of 1264 patients with orbital tumors and simulating lesions: the 2002 Montgomery Lecture, part 1. Ophthalmology 2004;111 (5) 997- 1008
PubMed
Demirci  HShields  CLShields  JAHonavar  SGMercado  GJTovilla  JC Orbital tumors in the older adult population. Ophthalmology 2002;109 (2) 243- 248
PubMed
Knowles  DM  IIJakobiec  FA Orbital lymphoid neoplasms: a clinicopathologic study of 60 patients. Cancer 1980;46 (3) 576- 589
PubMed
Knowles  DMJakobiec  FA McNally  LBurke  JS Lymphoid hyperplasia and malignant lymphoma occurring in the ocular adnexa (orbit, conjunctiva, and eyelids): a prospective multiparametric analysis of 108 cases during 1977 to 1987. Hum Pathol 1990;21 (9) 959- 973
PubMed
Cockerham  GCJakobiec  FA Lymphoproliferative disorders of the ocular adnexa. Int Ophthalmol Clin 1997;37 (4) 39- 59
PubMed
Coupland  SEKrause  LDelecluse  HJ  et al.  Lymphoproliferative lesions of the ocular adnexa: analysis of 112 cases. Ophthalmology 1998;105 (8) 1430- 1441
PubMed
Johnson  TETse  DTByrne  GE  Jr  et al.  Ocular-adnexal lymphoid tumors: a clinicopathologic and molecular genetic study of 77 patients. Ophthal Plast Reconstr Surg 1999;15 (3) 171- 179
PubMed
Sullivan  TJWhitehead  KWilliamson  R  et al.  Lymphoproliferative disease of the ocular adnexa: a clinical and pathologic study with statistical analysis of 69 patients. Ophthal Plast Reconstr Surg 2005;21 (3) 177- 188
PubMed
Jenkins  CRose  GEBunce  C  et al.  Histological features of ocular adnexal lymphoma (REAL classification) and their association with patient morbidity and survival. Br J Ophthalmol 2000;84 (8) 907- 913
PubMed
Fung  CYTarbell  NJLucarelli  MJ  et al.  Ocular adnexal lymphoma: clinical behavior of distinct World Health Organization classification subtypes. Int J Radiat Oncol Biol Phys 2003;57 (5) 1382- 1391
PubMed
White  WLFerry  JAHarris  NLGrove  AS  Jr Ocular adnexal lymphoma: a clinicopathologic study with identification of lymphomas of mucosa-associated lymphoid tissue type. Ophthalmology 1995;102 (12) 1994- 2006
PubMed
Jakobiec  FA McLean  IFont  RL Clinicopathologic characteristics of orbital lymphoid hyperplasia. Ophthalmology 1979;86 (5) 948- 966
PubMed
Knowles  DM  IIJakobiec  FA Ocular adnexal lymphoid neoplasms: clinical, histopathologic, electron microscopic, and immunologic characteristics. Hum Pathol 1982;13 (2) 148- 162
PubMed
Bairey  OKremer  IRakowsky  EHadar  HShaklai  M Orbital and adnexal involvement in systemic non-Hodgkin's lymphoma. Cancer 1994;73 (9) 2395- 2399
PubMed
Coupland  SEHummel  MStein  H Ocular adnexal lymphomas: five case presentations and a review of the literature. Surv Ophthalmol 2002;47 (5) 470- 490
PubMed
Sullivan  TJValenzuela  AA Imaging features of ocular adnexal lymphoproliferative disease. Eye (Lond) 2006;20 (10) 1189- 1195
PubMed
Jenkins  CRose  GEBunce  C  et al.  Clinical features associated with survival of patients with lymphoma of the ocular adnexa. Eye (Lond) 2003;17 (7) 809- 820
PubMed
Redfern  CHGuthrie  THBessudo  A  et al.  Phase II trial of idiotype vaccination in previously treated patients with indolent non-Hodgkin's lymphoma resulting in durable clinical responses. J Clin Oncol 2006;24 (19) 3107- 3112
PubMed
Plosker  GLFiggitt  DP Rituximab: a review of its use in non-Hodgkin's lymphoma and chronic lymphocytic leukaemia. Drugs 2003;63 (8) 803- 843
PubMed
Shields  CLShields  JACarvalho  CRundle  PSmith  AF Conjunctival lymphoid tumors: clinical analysis of 117 cases and relationship to systemic lymphoma. Ophthalmology 2001;108 (5) 979- 984
PubMed
Kennerdell  JSFlores  NEHartsock  RJ Low-dose radiotherapy for lymphoid lesions of the orbit and ocular adnexa. Ophthal Plast Reconstr Surg 1999;15 (2) 129- 133
PubMed
Chino  KTanyi  JAStea  B Stereotactic radiotherapy for unilateral orbital lymphoma and orbital pseudo-tumors: a planning study. Med Dosim 2009;34 (1) 57- 62
PubMed
Goyal  SCohler  ACamporeale  JNarra  VYue  NJ Intensity-modulated radiation therapy for orbital lymphoma. Radiat Med 2008;26 (10) 573- 581
PubMed
Isobe  KKagami  YHiguchi  K A multicenter phase II study of local radiation therapy for stage IEA mucosa-associated lymphoid tissue lymphomas: a preliminary report from the Japan Radiation Oncology Group (JAROG). Int J Radiat Oncol Biol Phys 2007;69 (4) 1181- 1186
Berenbom  ADavila  RMLin  HSHarbour  JW Treatment outcomes for primary intraocular lymphoma: implications for external beam radiotherapy. Eye (Lond) 2007;21 (9) 1198- 1201
PubMed
Matsuo  TYoshino  T Long-term follow-up results of observation or radiation for conjunctival malignant lymphoma. Ophthalmology 2004;111 (6) 1233- 1237
PubMed
Liao  SLKao  SCHou  PKChen  MS Results of radiotherapy for orbital and adnexal lymphoma. Orbit 2002;21 (2) 117- 123
PubMed
Esmaeli  BAhmadi  MAManning  J McLaughlin  PWGinsberg  L Clinical presentation and treatment of secondary orbital lymphoma. Ophthal Plast Reconstr Surg 2002;18 (4) 247- 253
PubMed
Uno  TIsobe  KShikama  N  et al.  Radiotherapy for extranodal, marginal zone, B-cell lymphoma of mucosa-associated lymphoid tissue originating in the ocular adnexa: a multiinstitutional, retrospective review of 50 patients. Cancer 2003;98 (4) 865- 871
Isobe  KEjima  YTokumaru  S  et al.  Treatment of primary intraocular lymphoma with radiation therapy: a multi-institutional survey in Japan. Leuk Lymphoma 2006;471800-1805
PubMed
Leksell  L The stereotaxic method and radiosurgery of the brain. Acta Chir Scand 1951;102 (4) 316- 319
PubMed
Andrews  DWBednarz  GEvans  JJDownes  B A review of 3 current radiosurgery systems. Surg Neurol 2006;66 (6) 559- 564
PubMed
Adler  JR  JrChang  SDMurphy  MJDoty  JGeis  PHancock  SL The CyberKnife: a frameless robotic system for radiosurgery. Stereotact Funct Neurosurg 1997;69 (1-4, pt 2) 124- 128
PubMed
Adler  JR  JrMurphy  MJChang  SDHancock  SL Image-guided robotic radiosurgery. Neurosurgery 1999;44 (6) 1299- 1307
PubMed
Hirschbein  MJCollins  SJean  WCChang  SDAdler  JR  Jr Treatment of intraorbital lesions using the Accuray CyberKnife system. Orbit 2008;27 (2) 97- 105
PubMed
Zorlu  FSelek  UKiratli  H Initial results of fractionated CyberKnife radiosurgery for uveal melanoma [published online ahead of print February 22, 2009]. J Neurooncol 2009;94 (1) 111- 117
PubMed
Muacevic  ANentwich  MWowra  BStaerk  SKampik  ASchaller  U Development of a streamlined, non-invasive robotic radiosurgery method for treatment of uveal melanoma. Technol Cancer Res Treat 2008;7 (5) 369- 374
PubMed
Romanelli  PWowra  BMuacevic  A Multisession CyberKnife radiosurgery for optic nerve sheath meningiomas. Neurosurg Focus 2007;23 (6) E11
PubMed10.3171/FOC-07/12/E11
Adler  JR  JrGibbs  ICPuataweepong  PChang  SD Visual field preservation after multisession CyberKnife radiosurgery for perioptic lesions. Neurosurgery 2006;59 (2) 244- 254
PubMed
Zytkovicz  ADaftari  IPhillips  TLChuang  CFVerhey  LPetti  PL Peripheral dose in ocular treatments with CyberKnife and Gamma Knife radiosurgery compared to proton radiotherapy [published online September 17, 2007]. Phys Med Biol 2007;52 (19) 5957- 5971
PubMed
On  AVHirschbein  MJWilliams  HJKaresh  JW CyberKnife radiosurgery and rituximab in the successful management of sclerosing idiopathic orbital inflammatory disease. Ophthal Plast Reconstr Surg 2006;22 (5) 395- 397
PubMed
Fariselli  LMarras  CDe Santis  MMarchetti  MMilanesi  IBroggi  G CyberKnife radiosurgery as a first treatment for idiopathic trigeminal neuralgia. Neurosurgery 2009;64(2 suppl)96- 101
PubMed
Murovic  JGibbs  IChang  SMobley  BPark  JAdler  J Foraminal nerve sheath tumors: intermediate followup after CyberKnife radiosurgery. Neurosurgery 2009;64(2 suppl)33- 43
Giller  CABerger  BDPistenmaa  DA  et al.  Robotically guided radiosurgery for children. Pediatr Blood Cancer 2005;45 (3) 304- 310
PubMed
Hara  WTran  PLi  G  et al.  CyberKnife for brain metastases of malignant melanoma and renal cell carcinoma. Neurosurgery 2009;64 (2) ((suppl)) A26- A32
PubMed
Colombo  FCasentini  LCavedon  CScalchi  PCora  SFrancescon  P CyberKnife radiosurgery for benign meningiomas: short-term results in 199 patients. Neurosurgery 2009;64 (2) ((suppl)) A7- A13
PubMed
Killory  BDKresl  JJWait  SDPonce  FAPorter  RWhite  Wl  Hypofractionated CyberKnife radiosurgery for perichiasmatic pituitary adenomas: early results. Neurosurgery 2009;64(2 suppl)19- 25
Adler  JR  JrChang  SD CyberKnife image-guided radiosurgery. Neurosurgery 2009;64 (2) ((suppl)) A1
PubMed
Sakamoto  GTBorchers  DJ  IIIXiao  FYang  HJChang  SDAdler  JR  Jr CyberKnife radiosurgery for trigeminal schwannomas. Neurosurgery 2009;64 (2) ((suppl)) A14- A18
PubMed
Wowra  BMuacevic  ATonn  JC Quality of radiosurgery for single brain metastasis with respect to treatment technology: a matched paired analysis [published online ahead of print February 1, 2009]. J Neurooncol 2009;94 (1) 69- 77
PubMed10.1007/s11060-009-9802-y
Gagnon  GJNasr  NMLiao  JJ  et al.  Treatment of spinal tumors using cyberknife fractionated stereotactic radiosurgery: pain and quality-of-life assessment after treatment in 200 patients. Neurosurgery 2009;64 (2) 297- 307
PubMed
Shimamoto  SInoue  TShiomi  H  et al.  CyberKnife stereotactic irradiation for metastatic brain tumors. Radiat Med 2002;20 (6) 299- 304
PubMed
Andrews  DWFaroozan  RYang  BP  et al.  Fractionated stereotactic radiotherapy for the treatment of optic nerve sheath meningiomas: preliminary observations of 33 optic nerves in 30 patients with historical comparison to observation with or without prior surgery. Neurosurgery 2002;51 (4) 890- 904
PubMed

Correspondence

CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Topics
PubMed Articles