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.

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.

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.

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.

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.

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.

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.

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.

Aqueous Deficient Dry Eye Syndrome Post Orbital Radiotherapy: A 10-Year Retrospective Study.

PURPOSE: Despite advances in orbital radiotherapy (XRT), a significant proportion of patients develop ophthalmic complication like dry eye syndrome (DES). The study evaluates the prevalence of aqueous deficient DES (ADDE) and lacrimal gland (LG) changes through histologic evaluation and ex-vivo expansion potential postorbital XRT. METHODS: With the approval of the institutional review board, medical records of patients who underwent orbital XRT as management protocol were reviewed for evidence of ADDE using DEWS (Dry Eye Workshop) 2007 criteria (n = 51). HuLG was harvested from three of these patients who underwent subsequent orbital exenteration and used for histological studies/ex-vivo culture. RESULTS: ADDE was noted in 47.07% of the patients, status postorbital XRT, with a prediction of nearly 50% developing it within 0.5 to 2.9 years. ADDE severity was grade 2 (18%), grade 3 (14%), and grade 4 (17%). Other comorbidities were radiation retinopathy (33.4%), radiation-induced cataract (24.9%), and radiation keratopathy (20.8%). Multivariate and univariate analysis showed that fraction of radiation and dose of radiation/fraction were significant risk factors; male gender and young age were protective factors. The post-XRT exenterated HuLG showed near-total effacement of histoarchitecture with intra/periductal and intra/interlobular fibrosis, loss of acini, and reduced secretory activity. The potential of the LG to expand and grow in culture was impaired with loss of stem cells as compared to normal HuLG. CONCLUSION: This study documents that orbital-XRT is associated with morphological and functional loss of lacrimal function in nearly 50% of the patients with a prediction of two-third developing ADDE by the end of 5 years. TRANSLATIONAL RELEVANCE: The study provides objective clinical evidence for DES development due to architectural/functional damage to the LG postorbital XRT. Based on recent findings that the LG can be cultured in-vitro, with preservation of stem cells and secretory potential, it would be logical to harvest a portion of LG before radiation, and expand and transplant it to rescue the damaged gland if indicated.

Orbital retinoblastoma: An update.

Orbital extension is a major cause of death in children with retinoblastoma in the developing countries. Delayed detection and inappropriate management contribute to poor outcome. Conventional treatment including primary orbital exenteration or chemotherapy or radiotherapy alone result in mortality as high as 70%. The recent understanding on the role of sequential multimodal therapy with a combination of high-dose chemotherapy, followed by appropriate surgery, radiotherapy, and additional adjuvant chemotherapy has helped dramatically improve life salvage.

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.

Choroidal Infiltration by Retinoblastoma: Predictive Clinical Features and Outcome.

PURPOSE: To identify the clinical features predictive of choroidal infiltration by retinoblastoma on histopathology and to report the outcome in these patients. METHODS: Retrospective study. RESULTS: Of the 403 patients who underwent primary enucleation for retinoblastoma, 113 patients had choroidal tumor infiltration and 290 patients had no choroidal tumor infiltration. There was a higher incidence of metastasis and related death in the choroidal tumor infiltration group compared to the no choroidal tumor infiltration group (4% vs 1%; P = .02). On multivariate analysis, the clinical features predictive of histopathologic massive choroidal infiltration included prolonged duration of symptoms for more than 6 months (hazard ratio [HR] = 3.04; P = .001) and secondary glaucoma (HR = 2.24; P = .005). CONCLUSIONS: In this study, the patients with retinoblastoma with prolonged duration of symptoms (> 6 months) had a three-fold greater risk and those with secondary glaucoma at presentation had a two-fold greater risk of massive choroidal tumor infiltration. [J Pediatr Ophthalmol Strabismus. 2016;53(6):349-356.].

Acute lymphoblastic leukemia as second primary tumor in a patient with retinoblastoma.

Second primary tumor (SPT) is defined as a second tumor that presents either simultaneously or after the diagnosis of an index tumor. Second primary malignancies are the leading cause of death in patients with heritable retinoblastoma (RB). Acute lymphoblastic leukemia (ALL), as SPT in RB patients, is extremely rare. To the best of our knowledge, only five cases of ALL as SPT in patients with RB has been documented in the literature. Herein, we report a case of a 6-year-old girl with bilateral RB, who developed ALL during the course of treatment of RB. This case highlights the importance of reviewing blood investigations regularly to diagnose leukemia as SPT in RB and also the necessity for proper counseling and lifelong follow-up in these patients.