Intravitreal Topotecan for Vitreous Seeds in Retinoblastoma: A Long-term Review of 91 Eyes.

PURPOSE: To study the long-term efficacy of intravitreal topotecan (IVT) for vitreous seeds in eyes with retinoblastoma and risk factors for their recurrence. DESIGN: Retrospective, non-comparative, interventional study. PARTICIPANTS: Ninety-one eyes of 90 patients with retinoblastoma treated between January 2013 and April 2019. METHODS: Patients with recurrent or refractory vitreous seeds after completion of intravenous or intra-arterial chemotherapy were treated with IVT (30 µg/0.15 ml) by the safety-enhanced technique. The injection was repeated every 4 weeks until the regression of seeds. Patients with a minimum follow-up of 12 months were included in the analysis. MAIN OUTCOME MEASURES: Primary outcome measures were vitreous seed regression and eye salvage. Secondary outcomes were risk factors for vitreous seed recurrence after treatment with IVT, vision salvage, and complications of IVT. RESULTS: The median age of the patients was 18 months, with most having group D (n = 58 [64%]) and group E (n = 26 [29%]) retinoblastoma. Vitreous seeds were refractory in 46 eyes (51%) and recurrent in 45 eyes (49%). A total of 317 IVT injections were administered, with the median being 3 injections. The median number of IVT injections required was 2.5 injections for dust, 3 injections for sphere, and 5 injections for cloud morphologic features. Recurrence of vitreous seeds after IVT was seen in 17 eyes (19%) at a mean follow-up of 7.9 months. At a mean follow-up 34 months, vitreous seed regression was achieved in 88 eyes (97%) and eye salvage was achieved in 77 eyes (85%). Older age (P = 0.018) and recurrence of retinal tumor (15/17 eyes; P < 0.01) significantly increased the risk of vitreous seed recurrence. Cataract was the most common complication seen in 17 eyes (9%). CONCLUSIONS: Intravitreal topotecan at an every 3- to 4-week regimen is effective against both refractory and recurrent vitreous seeds. The vitreous seed morphologic features correspond to the number of injections required for regression. Increasing age and recurrence of retinal tumor increase the risk of vitreous seed recurrence after treatment with IVT. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Does Multimodal Treatment Improve Eye and Life Salvage in Adenoid Cystic Carcinoma of the Lacrimal Gland?

PURPOSE: To evaluate the efficacy of multimodal treatment in adenoid cystic carcinoma (ACC) of the lacrimal gland. METHODS: A retrospective comparative case series of 40 consecutive patients with ACC of the lacrimal gland without systemic metastasis at the initial presentation and primarily managed by one of the 3 treatment protocols-surgery + external beam radiotherapy (EBRT) (group 1), surgery + EBRT + adjuvant chemotherapy (group 2), and neoadjuvant chemotherapy + surgery + EBRT + adjuvant chemotherapy (multimodal treatment) (group 3) at a tertiary care ocular oncology center. Local tumor control, eye salvage, and systemic metastasis were the primary outcome measures. RESULTS: The age ranged from 11 to 72 (mean ± SD, 36 ± 13; median, 36) years with 26 (65%) male and 14 (35%) female patients. Twelve (30%) patients belonged to group 1, 8 (20%) to group 2, and 20 (50%) to group 3. Primary surgery included tumor excision in 36 (90%) and orbital exenteration in 4 (10%). Chemotherapy composed of cisplatin + 5 fluorouracil (5FU) for 6 cycles in 28 (70%) patients. Extended-field stereotactic EBRT with a dose of 5,000-6,000 cGy included the entire pretreatment extent of the tumor with a 10-mm margin all around, superior orbital fissure, inferior orbital fissure, cavernous sinus, and temporal fossa. Mean duration of follow up after completion of treatment was 58 ± 26 (range, 29-180; median, 60) months. In all, local tumor recurrence occurred in 10 (25%) patients at a mean of 38 ± 23 (range, 12-120; median, 24) months. Local tumor recurrence was noted in 5 (42%) patients in group 1, 2 (25%) in group 2, and 3 (15%) in group 3. Overall, eye salvage was possible in 34 (85%) patients, with visual acuity >20/40 in 28 (82%). Systemic metastasis occurred in 10 (25%) patients at a mean of 53 ± 28 (range, 12-120; median, 43) months. Eight (67%) patients in group 1, 1 (13%) in group 2, and 1 (5%) in group 3 developed systemic metastasis. Six (15%) overall, 5 (42%) in group 1 and 1 (13%) in group 2, died with systemic metastasis. CONCLUSIONS: Multimodal treatment with sequential neoadjuvant chemotherapy, followed by surgery, extended-field stereotactic EBRT, and adjuvant chemotherapy seems relatively more effective in providing local tumor control and eye salvage and in minimizing the risk of systemic metastasis in ACC of the lacrimal gland.

Choosing Wisely India: ten low-value or harmful practices that should be avoided in cancer care.

The Choosing Wisely India campaign was an initiative that was established to identify low-value or potentially harmful practices that are relevant to the Indian cancer health-care system. We undertook a multidisciplinary framework-driven consensus process to identify a list of low-value or harmful cancer practices that are frequently undertaken in India. A task force convened by the National Cancer Grid of India included Indian representatives from surgical, medical, and radiation oncology. Each specialty had representation from the private and public sectors. The task force included two representatives from national patient and patient advocacy groups. Of the ten practices that were identified, four are completely new recommendations, and six are revisions or adaptations from previous Choosing Wisely USA and Canada lists. Recommendations in the final list pertain to diagnosis and treatment (five practices), palliative care (two practices), imaging (two practices), and system-level delivery of care (two practices). Implementation of this list and reporting of concordance with its recommendations will facilitate the delivery of high-quality, value-based cancer care in India.

Asian expert recommendation on management of skin and mucosal effects of radiation, with or without the addition of cetuximab or chemotherapy, in treatment of head and neck squamous cell carcinoma.

With increasing numbers of patients with unresectable locoregionally advanced (LA) head and neck squamous cell carcinoma (HNSCC) receiving cetuximab/radiotherapy (RT), several guidelines on the early detection and management of skin-related toxicities have been developed. Considering the existing management guidelines for these treatment-induced conditions, clinical applicability and standardization of grading methods has remained a cause of concern globally, particularly in Asian countries. In this study, we attempted to collate the literature and clinical experience across Asian countries to compile a practical and implementable set of recommendations for Asian oncologists to manage skin- and mucosa-related toxicities arising from different types of radiation, with or without the addition of cetuximab or chemotherapy. In December 2013, an international panel of experts in the field of head and neck cancer management assembled for an Asia-Pacific head and neck cancer expert panel meeting in China. The compilation of discussion outcomes of this meeting and literature data ultimately led to the development of a set of recommendations for physicians with regards to the approach and management of dermatological conditions arising from RT, chemotherapy/RT and cetuximab/RT, and similarly for the approach and management of mucositis resulting from RT, with or without the addition of chemotherapy or cetuximab. These recommendations helped to adapt guidelines published in the literature or text books into bedside practice, and may also serve as a starting point for developing individual institutional side-effect management protocols with adequate training and education.

OPTIC NERVE INFILTRATION BY RETINOBLASTOMA: Predictive Clinical Features and Outcome.

PURPOSE: To identify the clinical features predictive of any optic nerve infiltration and postlaminar optic nerve infiltration by retinoblastoma on histopathology and to report the outcome (metastasis and death) in these patients. METHODS: Retrospective study. RESULTS: Of the 403 patients who underwent primary enucleation for retinoblastoma, 196 patients had optic nerve tumor infiltration (Group 1) and 207 patients had no evidence of optic nerve tumor infiltration (Group 2). Group 1 included patients with prelaminar (n = 47; 24%), laminar (n = 74; 38%), and postlaminar tumor infiltration with or without involving optic nerve transection (n = 74; 38%). Comparing Group 1 and Group 2, the patients in Group 1 had prolonged duration of symptoms (>6 months) (16% vs. 8%; P = 0.02) and were associated with no vision at presentation (23% vs. 10%; P = 0.01), higher rates of secondary glaucoma (42% vs. 12%; P < 0.0001), iris neovascularization (39% vs. 23%; P < 0.001), and larger tumors (mean tumor thickness, 12.8 mm vs. 12 mm; P = 0.0001). There was a higher prevalence of metastasis in Group 1 than in Group 2 (4% vs. 0%; P = 0.006). On multivariate analysis, clinical features predictive of any optic nerve tumor infiltration secondary glaucoma (hazard ratio = 5.38; P < 0.001) and those predictive of postlaminar optic nerve tumor infiltration included iris neovascularization (hazard ratio = 2.66; P = 0.001) and secondary glaucoma (hazard ratio = 3.13; P < 0.001). CONCLUSION: In this study, clinical features predictive of any optic nerve tumor infiltration included secondary glaucoma and those predictive of postlaminar optic nerve tumor infiltration included iris neovascularization and secondary glaucoma. Despite adjuvant treatment in those with postlaminar optic nerve tumor infiltration, metastasis occurred in 8% of patients.

Neoadjuvant Systemic Chemotherapy in the Management of Extensive Eyelid Sebaceous Gland Carcinoma: A study of 10 Cases.

PURPOSE: To report the efficacy of neoadjuvant systemic chemotherapy in the management of eyelid sebaceous gland carcinoma (SGC). METHODS: Retrospective study of 10 patients that received neoadjuvant systemic chemotherapy (Cisplatin/Carboplatin and 5-Fluorouracil) for eyelid SGC. RESULTS: The mean age at presentation of eyelid SGC was 58 years (median, 55 years; range, 45 to 72 years). There were 6 females and 4 males. The mean tumor basal diameter was 36 mm (median, 31 mm, range, 20 to 65 mm), with orbital tumor extension in 9 cases. On the basis of TNM Classification, the tumors were classified as T3 (n = 10), N1 (n = 6), and M1 (n = 2). The mean number of cycles of neoadjuvant systemic chemotherapy per patient was 3 (median, 3; range, 3 to 4). The mean percentage reduction of tumor basal diameter after neoadjuvant chemotherapy was 74% (median, 80%; range, 30% to 100%). None of them had any major systemic side-effects of neoadjuvant chemotherapy. Postchemotherapy, surgical treatment for residual tumor was performed in 7 cases. Five cases underwent excision biopsy and 2 cases with residual orbital component underwent eyelid-sparing orbital exenteration. No tumor recurrence was noted in any of the 7 cases at a mean follow-up period of 18 months (median, 14 months; range, 3 to 63 months). One patient died due to systemic metastasis. CONCLUSION: Neoadjuvant systemic chemotherapy is effective and safe in the management of eyelid sebaceous gland carcinoma.

Management and outcome of retinoblastoma with vitreous seeds.

PURPOSE: To report the treatment response of retinoblastoma with vitreous seeds to high-dose chemotherapy coupled with periocular carboplatin. DESIGN: Retrospective, interventional case series. PARTICIPANTS: Consecutive patients with retinoblastoma with vitreous seeds managed over 10 years at a comprehensive ocular oncology center and followed up for at least 12 months after the completion of treatment were included in this study. Institutional review board approval was obtained. INTERVENTION: High-dose chemotherapy with a combination of vincristine, etoposide, and carboplatin in patients with focal vitreous seeds and additional concurrent periocular carboplatin in patients with diffuse vitreous seeds. MAIN OUTCOME MEASURES: Tumor regression, vitreous seed regression, and eye salvage. RESULTS: After excluding the better eye of bilateral cases, 101 eyes of 101 patients were part of the final analysis. All the patients belonged to Reese-Ellsworth group VB, but on the International Classification of Retinoblastoma (ICRB), 21 were group C, 40 were group D, and 40 were group E. The mean basal diameter of the largest tumor was 11.8 ± 4.7 mm. Mean tumor thickness was 7.5 ± 4.0 mm. Vitreous seeds were focal in 21 eyes and diffuse in 80 eyes. Chemotherapy cycles ranged from 6 to 12 (median, 6). Seventy-three eyes with diffuse vitreous seeds received a 15-mg posterior sub-Tenon carboplatin injection (range, 1-13 mg; median, 6 mg). Follow-up duration ranged from 13.4 to 129.2 months (median, 48 months). External beam radiotherapy (EBRT) was necessary in 33 eyes with residual tumor, vitreous seeds, or both. In all, 20 eyes (95%) with ICRB group C retinoblastoma, 34 eyes (85%) with group D retinoblastoma, and 23 eyes (57.5%) with group E retinoblastoma were salvaged. Of 77 eyes that were salvaged, 74 (96%) had visual acuity of 20/200 or better. Twenty-four of 33 chemotherapy failures (73%) regressed with EBRT. None of the patients demonstrated second malignant neoplasm or systemic metastasis. Factors predicting tumor regression and eye salvage were bilateral retinoblastoma and absence of subretinal fluid. Factors predicting vitreous seed regression were absence of subretinal fluid and subretinal seeds. CONCLUSIONS: Intensive management with primary high-dose chemotherapy and concurrent periocular carboplatin, and EBRT selectively in chemotherapy failures, provides gratifying outcome in retinoblastoma with vitreous seeds.

Adenoid cystic carcinoma of the lacrimal gland: role of nuclear survivin (BIRC5) as a prognostic marker.

AIMS: This study aimed to evaluate the expression of nuclear survivin in adenoid cystic carcinoma (ACC) of the lacrimal gland and to determine if this expression is associated with histopathological features, markers of apoptosis and proliferation or clinical outcomes. METHODS AND RESULTS: Immunohistochemical staining for survivin, p53, Ki-67 and Bcl-2 was analyzed in 55 cases of ACC of lacrimal gland. Thirty-one cases (56.3%) expressed nuclear survivin. All cases expressed p53, Ki-67 and Bcl-2. Eleven cases (35.5%) had a high nuclear survivin score (NS-SCORE) and 20 cases (64.5%) had a low NS-SCORE. Cases with a high NS-SCORE had a shorter progression-free survival (PFS) (P < 0.0001), higher expression of Ki-67 (P < 0.005) and a solid tumour pattern >30% (P < 0.005). CONCLUSION: Nuclear expression of survivin impacts prognosis significantly and is thus a promising prognostic marker in ACC of the lacrimal gland.

Plaque brachytherapy - Radiating positivity.

Background: Plaque brachytherapy is an evolving, yet effective globe and vision-sparing modality for the treatment of intraocular tumors by transscleral irradiation of the tumor base with a radioactive implant. The American Brachytherapy Society (ABS) along with the collaboration of the international multicenter Ophthalmic Oncology Task Force (OOTF) was assembled to reach a consensus regarding establishing practice guidelines and setting standards of care for intraocular tumors. The advent of plaque brachytherapy has revolutionized the outcomes of intraocular tumors, thus ensuring globe salvage, reducing morbidity and mortality, and avoiding cosmetic disfigurement. A well-planned dosimetry for plaque brachytherapy results in achieving local tumor control and excellent prognosis. Purpose: This technique provides the advantage of focal radiation, thus eliminating the damage to the adjacent structures, minimal periorbital tissue damage, absence of cosmetic disfigurement owing to lack of retarded bone growth as seen in external beam radiotherapy. Thus, it reduces the risk of metastasis, and with the recent advances, it provides a shorter duration of treatment. Synopsis: : In this video, we shall display the concept of plaque brachytherapy, the various types of plaques available, different radiations sources, planning dosimetry and calculations, target disease spectrum, surgical placement, and post-radiation outcomes in terms of local tumor control and prognosis. Highlights: This video highlights the history, basic principles and techniques of plaque brachytherapy and provides an understanding of its applications in the world of ocular oncology. Video link: https://youtu.be/7PX0mDQETRY.

Metastatic retinoblastoma at presentation: Clinical presentation, treatment, and outcomes.

The aim of this study was to retrospectively determine clinical features, treatment outcomes, and overall survival in four patients with metastatic retinoblastoma at presentation. The mean age at diagnosis was 63 months (range: 24-108 months). Three patients had overt orbital disease of at least one eye and one patient had microscopic orbital disease with scleral infiltration on histopathology. Metastatic sites included regional lymph nodes (RLN) (n = 4), bone marrow (BM) (n = 2), and cerebrospinal fluid (CSF) (n = 1). The most common sites of RLN were ipsilateral preauricular nodes (two patients) and contralateral parotid gland involvement (one patient). The treatment administered included primary enucleation (n = 1), high-dose intravenous chemotherapy (n = 4), secondary enucleation (n = 2), orbital external beam radiotherapy (n = 3), and intrathecal chemotherapy (n = 1). High-risk features included massive choroidal and microscopic scleral infiltration in the eye that underwent primary enucleation. At a mean follow-up of 33 months (range, 4-68 months), one patient with CSF involvement deceased in 4 months. The remaining three patients were alive and disease-free at the last mean follow-up period of 43 months (range, 18-68 months). The results of our study showed that RLN and BM metastasis respond well to treatment while CSF metastasis is associated with poor prognosis.

Brachytherapy training in India: Results from the GEC-ESTRO-India survey.

INTRODUCTION: Brachytherapy (BT) is integral in treatment of gynecological malignancies and is also an option for many other cancers. Data on training and proficiency levels of early career oncologists is limited. Like other continents a survey was conducted for early career oncologists in India. METHODS AND MATERIALS: An online survey was conducted from November 2019 to February 2020, through Association of Radiation Oncologists of India (AROI) for early career radiation oncologists expected to be within 6 years of training. The survey used a 22 item questionnaire that was also used for European survey. Responses to individual statements were recorded on a 1-5 Likert-type scale. Descriptive statistics were used to describe proportions. RESULTS: One-hundred twenty-four (17%) of 700 recipients responded to the survey. Majority of the respondents (88%) stated that being able to perform BT at the end of their training was important. Two-thirds of the respondents (81/124) had performed >10 intracavitary procedure and 22.5% had performed >10 intracavitary-interstitial implants. Many respondents had not performed nongynecological procedure- breast (64%), prostate(82%), gastro-intestinal (47%). Respondents predicted that in next 10 years, the role of BT is likely to increase. Lack of dedicated curriculum and training was perceived as the greatest barriers to achieving independence in BT (58%). Respondents suggested that BT training should be prioritized during conferences (73%) and online teaching modules (56%), along with development of BT skills labs (65%). CONCLUSION: This survey identified a lack of proficiency in gynecological intracavitary-interstitial brachytherapy and non-gynecological brachytherapy, despite BT training being regarded as highly important. Dedicated programs, including standardized curriculum and assessment need to be developed for training early- career radiation oncologists in BT.

A Multi-centric retrospective study into the epidemiological distribution of breast cancer patients in India.

BACKGROUND: A multicentric private hospital-based retrospective study was conducted to understand the epidemiology of breast cancer in terms of demographics and clinical characteristics (staging and hormone receptor status) at the time of diagnosis. METHODS: The data for 5,688 female breast cancer patients were collected from the hospital and clinical records of four study centres. All statistical analysis was performed using Microsoft Excel 2016 and R software. Survival was estimated by the Kaplan-Meier method and compared by the log-rank test. A P value of <.05 was considered statistically significant. RESULTS: The mean and median age of the study population was 52.6 (± 12.4) years and 53.0 (range 51-54 across the four centers) years, respectively. About 68% of patients were in the age category of 41 65 years, 17.6% were <40 years old among whom 23.4% of patients reported a positive family history. Most of the patients (66.3%) were diagnosed at an early stage (Stage I and II). The 3-year OS probability was 100%, 97.5%, 94.1%, and 74.7% for TNM Stages I, II, III, and IV, respectively. The 3-year RFS was 95.7%, 95.5%, 84.5%, and 49% for TNM Stages I, II, III, and IV, respectively. CONCLUSION: The present study highlights the epidemiological distribution of breast cancer patients. It emphasizes the importance of disease awareness among the urban and educated female population as most patients were diagnosed at earlier stages and demonstrated higher OS and RFS than reported in government registries.

Brachytherapy in India: Learning from the past and looking into the future.

India has a longstanding tradition in the practice of brachytherapy and has actively contributed to the scientific literature by conducting prospective studies, clinical audits, developing innovative techniques, and performing randomized studies. Indian investigators have also contributed to international collaborative research, education, training programs along with guideline development for brachytherapy in cervix and head and neck cancers. The present article summarizes the key contributions to scientific literature, current infrastructure, skill set for brachytherapy, existing challenges, and strategy to further strengthen brachytherapy practice in the next decade.

Ocular oncology practice guidelines during COVID-19 pandemic-An expert consensus.

The outbreak of rapidly spreading COVID-19 pandemic in December 2019 has witnessed a major transformation in the health care system worldwide. This has led to the re-organization of the specialty services for the effective utilization of available resources and ensuring the safety of patients and healthcare workers. Suspension of oncology services will have major implications on cancer care due to delayed diagnosis and treatment leading to irreversible adverse consequences. Therefore various oncology organizations have called for a continuation of cancer care during this crisis with diligence. The COVID-19 pandemic has forced the clinicians to transform the components of care from screening to outpatient care and primary management. The purpose of this article is to establish guidelines and recommendations for ocular oncology in the management of ocular tumors set by a multidisciplinary team of experts including ocular, medical and radiation oncologists, and pathologists. As the pandemic is evolving fast, it will require constant updates and reformation of health strategies and guidelines for safe and quality health care.

Primary orbital low-grade fibromyxoid sarcoma - A case report.

An 18-year-old female presented with rapidly progressive proptosis of the left eye for one month and grade II relative afferent pupillary defect. Orbital imaging showed a well-defined homogenous extraconal mass in close relation to the lateral rectus muscle and extending up to the superior orbital fissure, associated with bony erosion. An incisional biopsy was performed, with the histopathology demonstrating stellate to spindle-shaped tumor cells (fibroblasts) embedded in a richly myxoid matrix. A diagnosis of low-grade fibromyxoid sarcoma (LGFS) was made. The patient was treated by stereotactic external beam radiotherapy. Here, we report a case of LGFS which, to the best of our knowledge, is the first at an orbital location.

Eye salvage in diffuse anterior retinoblastoma using systemic chemotherapy with periocular and intravitreal topotecan.

Diffuse anterior retinoblastoma is an infrequent presentation in which the tumor is confined to the anterior segment, and there is no retinal mass. An 18-month-old Asian Indian boy presented with white spots in the left eye. There were extensive anterior segment seeds without a retinal tumor. Fine-needle aspiration biopsy confirmed the diagnosis of retinoblastoma, and the patient received intravenous chemotherapy with a combination of vincristine-carboplatin-etoposide, periocular topotecan, and intravitreal topotecan to achieve complete tumor regression.

Intravitreal topotecan in the management of refractory and recurrent vitreous seeds in retinoblastoma.

BACKGROUND/AIM: To evaluate the efficacy of intravitreal topotecan for refractory or recurrent vitreous seeds in retinoblastoma. METHODS: Intravitreal injection of topotecan hydrochloride (30 µg/0.15 mL) was provided every 3 weeks by the safety enhanced technique. RESULTS: The study included 17 consecutive patients with retinoblastoma with refractory or recurrent vitreous seeds. Five eyes (29%) belonged to International Classification of Retinoblastoma group C and 12 eyes (71%) belonged to group D. Primary treatment included triple drug intravenous chemotherapy for a mean of 10 cycles (median, 9 cycles; range, 6-18 cycles). Fifteen patients (88%) had undergone 56 periocular carboplatin injections with a mean of 4 injections (median, 3 injections; range, 1-8 injections), concurrent with intravenous chemotherapy. A total of 53 intravitreal topotecan injections were performed in 17 eyes of 17 consecutive patients with refractory or recurrent vitreous seeds with a mean of 3 injections (median, 3 injections; range, 2-6 injections). Complete regression of vitreous seeds was achieved in 17 of 17 eyes (100%). At a mean follow-up of 23.8 months (median, 24 months; range, 15.1-34.1 months), one eye (6%) with a recurrent retinal tumour needed enucleation, and the rest of the 16 eyes (94%) maintained complete regression. Final visual acuity could be reliably assessed in all 16 eyes (100%), of whom 12 eyes (75%) had visual acuity ≥20/200. None of the patients developed ocular or systemic complications. CONCLUSION: Three-weekly intravitreal topotecan appears effective and safe in controlling focal or diffuse refractory or recurrent vitreous seeds in retinoblastoma.

Ocular Surface Squamous Neoplasia in Papillon-Lefèvre Syndrome: Outcome at Long-Term Follow-Up of 12 Years.

PURPOSE: To discuss the association between ocular surface squamous neoplasia (OSSN) and Papillon-Lefèvre syndrome (PLS) and present the long-term outcome in a patient with these diseases. METHODS: Case report. RESULTS: A 14-year-old boy presented with a raised pigmented mass lesion at the limbus in the right eye, which was clinically suggestive of OSSN. He also had palmoplantar hyperkeratosis and periodontosis suggestive of PLS. Excision biopsy of the lesion confirmed the diagnosis of OSSN. He was free of tumor recurrence for 2 years and was lost to follow-up thereafter. Seven years later, the patient presented with diffuse tumor recurrence with orbital extension in the right eye, regional lymph node metastasis, and ipsilateral parotid gland infiltration. The patient underwent exenteration of the right orbital contents, right parotidectomy, and radical neck dissection followed by concomitant external beam radiotherapy and systemic chemotherapy. Eleven years from initial presentation, the patient was detected to have OSSN in the contralateral eye and was managed by wide excision biopsy and adjuvant cryotherapy. One year after detection of OSSN in the left eye, the patient was found to have systemic metastases to the lungs and brain. The patient died of the disease within 3 months of detection of systemic metastasis. CONCLUSIONS: OSSN in PLS is associated with poor prognosis.