Brachytherapy in the prevention of recurrence of conjunctival melanoma : Results of a case report in a University Hospital in Valladolid, Spain.

AIM: Describe the results of brachytherapy in the prevention of recurrences in conjunctival melanoma (CM) and describe a dosimetric protocol. METHODS: Retrospective and descriptive case report. Eleven consecutive patients with a confirmed histopathological diagnosis of CM treated with brachytherapy between 1992 and 2023 were reviewed. Demographic, clinical, and dosimetric characteristics as well as recurrences were recorded. Quantitative variables were represented by the mean, median, and standard deviation, and qualitative variables by frequency of distribution. RESULTS: Of a total of 27 patients diagnosed with CM, 11 who were treated with brachytherapy were included in the study (7 female; mean age at time of treatment: 59.4 years). Mean follow-up was 58.82 months (range 11-141 months). Of a total of 11 patients, 8 were treated with ruthenium-106 and 3 with iodine-125. Brachytherapy was performed in 6 patients as adjuvant therapy after biopsy-proven CM on histopathology and in the other 5 patients after recurrence. The mean dose was 85 Gy in all cases. Recurrences outside of the previously irradiated area were observed in 3 patients, metastases were diagnosed in 2 patients, and one case of an ocular adverse event was reported. CONCLUSION: Brachytherapy is an adjuvant treatment option in invasive conjunctival melanoma. In our case report, only one patient had an adverse effect. However, this topic requires further research. Furthermore, each case is unique and should be evaluated by experts in a multidisciplinary approach involving ophthalmologists, radiation oncologists, and physicists.

Uveal Melanoma Metastasis to the Contralateral Eye Structures: A Retrospective Comparative Analysis of 13 Consecutive Patients.

PURPOSE: To report uveal melanoma (UM) metastasis to the contralateral ocular and periocular structures. DESIGN: Retrospective study. PARTICIPANTS: Thirteen patients with UM metastasis to the contralateral ocular and periocular structures were included. METHODS: Clinical records were reviewed retrospectively. MAIN OUTCOME MEASURES: The development and time to onset of contralateral ocular and periocular metastasis, systemic metastasis, and death. RESULTS: Of the 13 000 treated UM patients, 13 patients were diagnosed with UM metastasis to the contralateral ocular and periocular structures. Mean patient age at primary UM diagnosis was 60 years (median, 60 years; range, 37-87 years). The primary uveal melanoma was in the choroid (n = 11) or ciliary body (n = 2) and was treated with brachytherapy (n = 11), proton beam radiotherapy (n = 1), or enucleation (n = 1). Systemic metastasis developed in 11 patients (85%) at a mean of 66 months (median, 34 months; range, 12-216 months) after diagnosis of the primary UM. All 11 patients (100%) showed liver metastasis and 8 patients (62%) also showed extrahepatic metastasis. The sites of metastasis to the contralateral ocular or periocular structures included the choroid in 4 patients (31%), the orbit in 7 patients (54%), and the eyelid in 2 patients (15%). One patient with eyelid metastasis demonstrated concurrent conjunctival nodule. Mean time to diagnosis of contralateral ocular or periocular metastasis was 94 months (median, 48 months; range, 9-375 months). Contralateral choroidal metastasis was multifocal in 3 of 4 patients (75%). Of 7 patients with orbital metastasis, 5 showed extraocular muscle involvement with restricted ocular motility. Treatment for contralateral choroidal metastasis included brachytherapy (n = 2), transpupillary thermotherapy (n = 1), and observation (n = 1). Treatment for contralateral periocular (orbit or eyelid) metastasis was excision (n = 5), external beam radiotherapy (n = 2), and observation (n = 2). Of 13 patients, death was documented in 11 patients at a mean of 17 months (median, 9 months; range, 3-54 months) as a result of systemic UM metastasis (n = 10) or unrelated cause (n = 1). CONCLUSIONS: Metastasis resulting from UM to the contralateral ocular and periocular structures is rare and generally occurs in patients with disseminated metastasis. Orbital tissue is the most common site of involvement, and these patients have short life expectancy.

Management of conjunctival melanoma with local excision and adjuvant brachytherapy.

BACKGROUND/OBJECTIVES: To evaluate the management of conjunctival melanoma with local excision and adjuvant brachytherapy. SUBJECTS/METHODS: Data of all patients who received local excision and adjuvant brachytherapy for conjunctival melanoma between 1999 and 2016 in a Dutch national referral centre were reviewed. A protocol with Sr-90 was used until 2012, a protocol with Ru-106 was used hereafter. Local recurrence, metastasis, survival, visual acuity and treatment complications were assessed. RESULTS: A total of 58 patients was identified: 32 patients were treated with Sr-90 and 26 with Ru-106. Mean follow-up time was 97.3 months (143.1 months after Sr-90, and 40.2 months after Ru-106). All lesions were epibulbar, the median tumour thickness was 0.9 mm. Local recurrence occurred in 13/58 cases (22%), with a 5-year recurrence rate of 21%. Local recurrence occurred equally often in both protocols, with 5-year recurrence rates of 19% (Sr-90) versus 23% (Ru-106) (p = 0.68). Metastasis developed in 3/58 cases (5%), with 2 cases after Sr-90, and 1 after Ru-106 (p = 1.00). The most reported complications were pain (29%), dry eyes (21%), symblepharon (9%), ptosis (12%) and cataract (9%). No severe corneal or scleral complications were observed. Median visual acuity was 1.00 pre-surgery, at the end of follow-up this was 1.00 (Sr-90) and 0.95 (Ru-106). CONCLUSION: Local excision with adjuvant brachytherapy provides good tumour control with excellent visual outcome and mild side effects in patients with limited conjunctival melanoma. Results after Sr-90 or Ru-106 were comparable; a choice for either treatment may be based on experience of the clinician and availability of materials.

Effects of radiation therapy on the meibomian glands and dry eye in patients with ocular adnexal mucosa-associated lymphoid tissue lymphoma.

BACKGROUND: Radiation therapy (RT) is the treatment of choice in patients with low-grade ocular adenexal mucosa-associated lymphoid tissue lymphoma (OAML) and many of them experience post-RT dry eye with varying severity. The purpose of the present study was to investigate ocular effects of RT on meibomian glands and dry eye by directly visualizing structural changes. Secondly, we focused on the comparison of two groups of patients according to tumor location and radiation technique. METHODS: Sixty-four eyes with OAML of conjunctiva, orbit, lacrimal gland, or lacrimal sac were grouped into conjunctival lymphoma and "orbital-type" lymphoma (i.e., orbit, lacrimal gland, and lacrimal sac). Subjects were investigated for morphological changes in meibomian glands by meiboscore grading system. Radiation technique was examined and Ocular Surface Disease Index (OSDI) questionnaire, Schirmer's test, tear film break-up time (TBUT), slit lamp examination of corneal surface and lid margin abnormality were conducted before and after RT. RESULTS: The increase in meiboscore was statistically significant over time after RT in both groups (P < 0.001). The extent of increase in meiboscore was significantly greater in the "orbital-type" lymphoma group than in the conjunctival lymphoma group (P < 0.001). The changes in OSDI, TBUT, corneal fluorescein staining score and lid margin abnormality score after RT were significantly different across two groups (P = 0.042, 0.001, 0.035 and 0.001, respectively). Schirmer's value decreased after RT in both groups. Dry eye symptoms were most severe right after RT in both groups, but a gradual resolution was noted in most patients with conjunctival lymphoma, whereas symptoms persisted in "orbital-type" lymphoma patients. The OSDI score and corneal fluorescein staining score were positively correlated with meiboscore in "orbital-type" patients at post-RT 6 months (r = 0.43, P = 0.04; r = 0.39, P = 0.03, respectively). CONCLUSIONS: Patients with OAML had different degrees of morphological changes in meibomian glands according to tumor location and radiation technique. "Orbital-type" lymphoma patients are more likely to experience severe injury to meibomian glands, which eventually leads to persistent dry eye. Patients with "orbital-type" lymphoma should be well informed of post-RT damage on meibomian glands and persistent dry eye.

Oncologic and visual outcomes after postoperative proton therapy of localized conjunctival melanomas.

INTRODUCTION: conjunctival melanomas have high local relapse rates. Oncologic and visual outcomes can be improved with proton therapy and no-touch surgery. MATERIAL AND METHODS: a monocentric retrospective study of consecutive patients treated with surgery and proton therapy for conjunctival melanoma was conducted. Proton therapy was performed to a total dose of 45 Grays physical dose delivered in eight fractions over two weeks. RESULTS: Ninety-two patients were included. The mean age was 63-year-old. 65.2% of patients had primary acquired melanosis. The mean tumor thickness and diameter was 2.5 mm and 7.0 mm respectively. The clinical stage was T1 in 71.6% of cases, with a quadrangular involvement of more than 90° in 69% of cases. Conjunctival melanomas were of epithelioid cell-type in 40% of cases. Mean follow-up was 4.7 years. Five-year local failure rate was 33.2%. Of 25 local recurrences, 14 were marginal/out-of-field, 4 in-field, others were undetermined. First surgery at expert center resulted in 24.3% of local failure at 5 years versus 38.7% if performed elsewhere (p = 0.41). Salvage exenteration was performed in 13 patients. Tumor stage and quadrangular involvement were significant factors for local failure. Five-year progression-free survival and cause-specific death rates were 61.5 and 3.6%. Stage and epithelioid type were associated with poorer progression-free survival. Trophic toxicity occurred in 22.9% of patients and was treated locally, with grafts in 7 patients. Glaucoma and cataract occurred in 13 and 22 patients respectively. Prognostic factors for visual deterioration were age, tumor extent (multifocality, quadrangular involvement > 180°) and cryotherapy. CONCLUSIONS: 5-year local failure rate after postoperative proton therapy for conjunctival melanoma was of 33.2%. Radiation-induced complications were overall manageable.

Proton radiotherapy in advanced malignant melanoma of the conjunctiva.

BACKGROUND: The management of conjunctival melanoma is challenging and frequently ends in exenteration. The aim of this retrospective study was to evaluate the long-term results of proton beam radiation with regard to various clinical parameters. METHODS: Eighty-nine patients with extended conjunctival melanoma (≥T2) and multifocal bulbar located tumors (T1c/d) were treated consecutively with proton radiotherapy (dose 45 Gy). The following parameters were assessed: TNM stage, tumor origin, local recurrence, performance of exenteration, occurrence of metastases, overall survival, and potential complications. A time-to-event analysis was preformed to the primary endpoints: relapse, metastasis, exenteration, and death by use of Kaplan-Meier cumulative survival estimates and Cox proportional hazards regression that provides hazard ratios and 95% confidence intervals. RESULTS: The median follow-up time was 4.2 years (max. 21.7 years). Local recurrence and metastatic disease occurred in 33% and 16% of patients, respectively. Exenteration-free survival and overall survival tended to be worse in T3 melanoma. No association between tumor origin and local recurrence, metastatic disease, or overall survival was observed. Main complications after proton radiotherapy were sicca-syndrome (30%), secondary glaucoma (11%), and limbal stem cell deficiency (8%). CONCLUSIONS: In summary, proton radiotherapy in conjunctival melanoma is an effective alternative to exenteration, with a 5-year cumulative probability of eye preservation of 69%.

Radiation treatment to a postresection primary mucoepidermoid carcinoma (MEC) of the conjunctiva with positive margins at the Tenon's fascia-A case study.

The primary occurrence of mucoepidermoid carcinoma (MEC) of the conjunctiva is extremely rare, aggressive, and easily mistaken for squamous cell carcinoma. With fewer than 50 cases reported in the literature, there is no consensus on the most effective treatment. Radiation is an alternative to enucleation or orbital exenteration with the potential of eye preservation. We investigated several radiation approaches for a case with postresection positive margins at Tenon's fascia, and reported the patient's clinical course during the treatment and for a short time thereafter. An otherwise healthy 64-year-old male presented with MEC extending to the deep margin at the Tenon's fascia. Plans for 4 different radiation therapy treatment modalities (Intensity Modulated Radiation Therapy [IMRT], Volumetric Modulated Radiation Therapy [VMAT], double scattering (DS) proton, and reverse eye plaque low dose rate [LDR] ) were created and compared based on tumor coverage and normal tissue doses. The planning target volume (PTV) was too large and nonuniform for an eye plaque application. Using the largest plaque available (22 mm), the calculated minimum dose to the PTV was 57% while the dose to the skin was 1000% of the prescription. The proton plan completely spared the contralateral ocular structures and reduced the max doses to the ipsilateral macula and optic nerve, but was not clinically available at the time of treatment. The IMRT and VMAT plans produced similar dose distributions to each other, but VMAT further minimized dose to the ipsilateral eye. Due to the uniqueness of this case, a thorough study of the available radiation treatment options was deemed necessary. All of the external beam treatment techniques produced acceptable plans with VMAT producing the best available plan in this case. The patient was treated with the VMAT plan with a prescription of 6600 cGy in 30 fractions. At 5 months post-treatment, the patient is recovering from expected acute responses to radiation with follow ups scheduled.

Case Report: Primary Conjunctival Non-Hodgkin Marginal Zone Lymphoma.

SIGNIFICANCE: Ophthalmic manifestations of non-Hodgkin lymphoma are rare, and the diagnosis can be delayed because of nonspecific symptoms and a tendency to mimic the appearance of other ocular diseases. Suspicious presentations will require confirmation of the lymphoma through surgical biopsy. PURPOSE: The purpose of this study was to present an isolated conjunctival non-Hodgkin marginal zone lymphoma without systemic involvement, which was successfully managed with external beam radiation. CASE REPORT: A 49-year-old man reported a red, temporal bulbar conjunctival growth on the left eye for several weeks, which was initially treated as a nodular episcleritis. When the condition did not resolve, a subsequent biopsy diagnosed a low-grade non-Hodgkin marginal zone lymphoma; further testing found no systemic involvement. No intraocular involvement was noted, and B-scan ultrasound and magnetic resonance imaging did not demonstrate any uveal or orbital extension. A trial of doxycycline did not lead to regression, and the isolated lesion was observed. Because of possible slow growth, the lesion was eventually treated with external beam radiation, which resulted in significant tumor regression. Four years after the radiotherapy, the tumor has not recurred, and there has been no systemic involvement. CONCLUSIONS: This case of a low-grade extranodal marginal zone lymphoma on the temporal conjunctiva represents a less common variation of the classic fornix-based presentation. It is not unusual for conjunctival lymphomas to masquerade as another clinical entity, sometimes making the initial diagnosis challenging. If a patient does not respond as expected to conventional therapy, a biopsy to rule out malignancy should be considered.

Superficial radiotherapy as a treatment alternative for recurrent conjunctival squamous cell carcinoma: a case study.

This case study discusses the use of superficial radiotherapy (SXRT) in the treatment of recurrent conjunctival squamous cell carcinoma (SCC). Conjunctival SCC is often an aggressive cancer, with surgery the current standard of care. There is currently limited literature on alternative treatment options to treat conjunctival SCC recurrences that enable ocular function preservation. Furthermore, the use of SXRT in this setting is not well-reported. Technical feasibility, practical limitations and potential side effects of SXRT (in comparison to other treatment options) are discussed in this case study. This case describes a 62 years old male with limited treatment options following multiple recurrences of conjunctival SCC. He was prescribed a therapeutic SXRT dose of 48.4 Gy in 22 fractions (5 fractions/week). At 6-month follow-up, there was no evidence of residual or recurrent disease, or any significant objective or patient reported treatment induced side effects. This case study provides preliminary evidence for the potential application of SXRT for conjunctival SCC. The benefits reported in this case study warrant further investigation of the applicability of SXRT in a larger patient cohort, with the potential to provide patients with a less invasive treatment alternative for recurrent conjunctival SCC.

Meibomian Gland Dysfunction Associated With Periocular Radiotherapy.

PURPOSE: To investigate the influence of periocular radiotherapy on meibomian glands. METHODS: We evaluated 28 patients (40 eyes) who received radiotherapy (RT group) for conjunctival or orbital lymphoma and 30 age-matched control subjects (60 eyes). Subjects underwent slit-lamp examination of the eyelids, Schirmer test, meibography, and evaluation of tear film breakup time (TBUT), Ocular Surface Disease Index (OSDI) scores, meibomian glands evaluation (meiboscore, meibum expressibility, and lid margin abnormality scores), and tear film lipid layer thickness using an ocular surface interferometer. These parameters were compared between subjects in the RT and control groups. RESULTS: Meiboscores as well as meibum expressibility and OSDI scores in the RT group were significantly higher compared with those in the control group (1.6 ± 0.9 vs. 0.4 ± 0.6, 1.6 ± 1.0 vs. 0.2 ± 0.4, and 48.1 ± 21.4 vs. 6.2 ± 4.4, respectively, P < 0.001, all), whereas the Schirmer value (9.2 ± 5.1 vs. 12.3 ± 5.2, P = 0.004), TBUT (4.2 ± 2.5 vs. 6.4 ± 2.6, P = 0.001), and lipid layer thickness (61.0 ± 29.3 vs. 85.2 ± 20.0, P < 0.001) in the RT group were lower compared with those in the control group. The percentage of meibomian gland dropout was significantly correlated with age (P = 0.025) and total radiation dose (P = 0.012), regardless of the target location of irradiation. Even low-dose irradiated eyes (<30 Gy) exhibited significantly higher meiboscores (P < 0.001) and shorter TBUT (P = 0.005) compared with control eyes. CONCLUSIONS: Eyes that received periocular radiotherapy exhibited relatively high tear film instability induced by meibomian gland dysfunction, contributing to the high severity of dry eye symptoms.

Recurrent Conjunctival Myofibrosarcoma Managed With Triple Application of Episcleral Brachytherapy.

PURPOSE: To report a case of recurrent conjunctival myofibrosarcoma treated with wide surgical excision, cryotherapy, and triple sequential applications of episcleral brachytherapy. METHODS: A single case of recurrent conjunctival myofibrosarcoma. RESULTS: A 54-year-old man with a history of a renal transplant presented with a recurrent conjunctival tumor. Histopathologic diagnosis was established through immunohistochemistry. In total, 3 iodine radiation episcleral plaques were used over a period of 49 weeks. After cicatricial ectropion repair and cataract surgery, visual acuity was 20/20 at 4.5-year follow-up without evidence of recurrence or radiation retinopathy. CONCLUSIONS: Myofibrosarcoma is a rare mesenchymal tumor that can present as ocular surface tumor. Final histopathologic diagnosis can be challenging, and immunohistochemistry is important for evaluation. Myofibrosarcoma should be considered in the clinical differential diagnosis of atypical ocular surface lesions and the histopathologic differential diagnosis of ocular spindle neoplasms.

Electron beam radiotherapy for the management of recurrent extensive ocular surface squamous neoplasia with orbital extension.

Recurrent extensive ocular surface squamous neoplasia (OSSN) with orbital invasion can be successfully managed with external radiotherapy using electrons resulting in eye and vision salvage. We report a case of right eye recurrent OSSN in an immunocompetent adult Indian male, with extensive orbital involvement. The patient had two previous surgical excisions with recurrent disease. At this stage, conventionally exenteration is considered the treatment modality. However, he was treated with 5040 cGy radiotherapy (15eV electrons) resulting in complete disease regression. At the end of 3 years follow-up, the patient was disease free, maintained a vision of 20/25, with mild dry eye, well-managed with topical lubricants. Extensive OSSN with orbital invasion does not always need exenteration. External beam electron radiotherapy provides a noninvasive cure with organ and vision salvage and should be considered in extensive OSSN not amenable to simple excision biopsies. Long-term studies to evaluate the effect of radiation on such eyes are suggested.

The treatment of carcinoma in situ and squamous cell carcinoma of the conjunctiva with fractionated strontium-90 radiation in a population with a high prevalence of HIV.

BACKGROUND: This study explores the safety and efficacy of strontium 90 (Sr-90) brachytherapy as the sole adjuvant therapy for carcinoma in situ (CIS) and squamous cell carcinoma (SCC) of the conjunctiva in a high HIV prevalent area. METHODS: This is a retrospective case review of patients treated with 60 Gray Sr-90 brachytherapy in four divided doses after resection with a 2 mm margin and histological confirmation. Cryotherapy or alcohol debridement was not performed at the time of excision due to limited resources. Two plaque sizes, 8.5 mm and 18 mm, were used. RESULTS: Sixty-nine patients were treated and had a median follow-up of 27 months (range 6-127). Thirty-three (47.8%) were HIV-positive. CIS was present in 40.6% and SCC in 59.4%. The surgical margins were positive in 39 (56.5%). Twenty patients (29.0%) were treated with the 18 mm plaque and 49 (71.0%) with the 8.5 mm plaque. Eight (11.6%) patients developed a recurrence at a median of 5 months (range 2-40). Recurrences only occurred in patients treated with the 8.5 mm plaque (p=0.094). There was no significant effect of HIV status, positive margins or staging on the number of recurrences. Treatment side effects were a dry eye in five patients which was successfully managed with topical lubricants, and induced astigmatism of 1 dioptre of cylinder in one patient. CONCLUSIONS: Sr-90 brachytherapy is safe and effective in preventing recurrences in ocular surface squamous neoplasia in a high HIV prevalent setting. The 18 mm plaque size is superior to the 8.5 mm plaque size.

Intraoperative high-dose rate of radioactive phosphorus 32 brachytherapy for diffuse recalcitrant conjunctival neoplasms: a retrospective case series and report of toxicity.

IMPORTANCE: Adjunct treatments for conjunctival malignancies are needed when standard therapy provides limited benefits or fails. OBJECTIVE: To describe the results of patients with diffuse conjunctival neoplasms treated with radioactive phosphorus 32 (32P)-impregnated flexible film. DESIGN, SETTING, AND PARTICIPANTS: This retrospective case series between January 1, 2010, and January 1, 2013, was conducted at Memorial Sloan-Kettering Cancer Center, a tertiary referral center. The study was conducted on 7 eyes of 6 patients treated for diffuse conjunctival squamous cell carcinoma, sebaceous carcinoma, or lymphoma that had recurrent or residual disease after primary treatment. INTERVENTIONS: Patients underwent mapping biopsies and detailed conjunctival drawings to delineate the pathologic extent of the disease. The brachytherapy film used for treatment was the RIC Conformal Source Model 100 (RIC-100, RI Consultants). The RIC-100 is a flexible, thin (approximately 0.5-mm) film made of a polymer chemically bound to 32P. The radioactive 32P film was placed intraoperatively, allowed to stay in place until the prescription dose was reached, and then removed. The median dose at the prescription point (1 mm from the surface of the film) was 15 Gy (range, 5-17 Gy). MAIN OUTCOMES AND MEASURES: Patients were tested for best-corrected visual acuity, recurrence-free survival, and adverse events scored by using the Adult Comorbidity Evaluation-27 scale. RESULTS: Between 2010 and 2013, 7 eyes of 6 patients were treated. The median age of patients was 70 years. All patients had a recurrent or persistent neoplasm. Four patients with squamous cell carcinoma, 1 with sebaceous carcinoma, and 1 with metachronous bilateral lymphomas were treated. The median treatment time was 19 minutes (range, 10-52 minutes). The median follow-up was 24.9 months (range, 3.1-38.2 months). Recurrence-free survival 24 months after brachytherapy was 75% (95% CI, 19-89.1). Two moderate adverse events and 1 severe adverse event occurred. Visual acuity was stable or improved in 5 of the 7 eyes (ie, better than 20/70 in the 5 patients who retained their treated eye). CONCLUSIONS AND RELEVANCE: Our results show the use of an intraoperative high-dose rate of 32P brachytherapy in selected cases of recalcitrant diffuse conjunctival neoplasms. This technique offers a novel adjunct in the treatment of these cancers. Further follow-up and study are warranted.

More than meets the eye: the 'pink salmon patch'.

Ocular adnexal lymphomas account for 1-2% of all non-Hodgkin's lymphomas. Conjunctiva is the primary site of involvement in one-third of cases. We present a case of a 47-year-old Hispanic woman who presented with left eye itching and irritation associated with a painless pink mass. Physical examination revealed the presence of a 'pink salmon-patch' involving her left medial conjunctiva. Orbital CT showed a subcentimeter left preseptal soft tissue density. Biopsy revealed a dense subepithelial lymphoid infiltrate comprised predominantly of B cells that did not coexpress CD5 or CD43. These findings were consistent with B-cell marginal zone lymphoma. Further staging assessment did not reveal disseminated disease. She had stage 1E extranodal marginal zone lymphoma as per Ann Arbor staging system. She received external beam radiotherapy to her left eye with complete resolution of the lymphoma in 2 months and continues to remain tumour free at 8-month follow-up. She will be followed up closely for development of any local (unilateral or contralateral eye) or systemic recurrence in the long run.