Orbital Tumor Recurrence Research Articles

High-Risk Histopathological Features of Retinoblastoma following Primary Enucleation: A Global Study of 1426 Patients from 5 Continents.

To evaluate high-risk histopathological features (HRHF) following primary enucleation of eyes with retinoblastoma (RB) and assess the patient outcomes across continents. Retrospective study of 1426 primarily enucleated RB eyes from five continents. Of all, 923 (65%) were from Asia (AS), 27 (2%) from Australia (AUS), 120 (8%) from Europe (EUR), 162 (11%) from North America (NA), and 194 (14%) from South America (SA). Based on the continent (AS vs. AUS vs. EUR vs. NA vs. SA), the histopathology features included massive choroidal invasion (31% vs. 7% vs. 13% vs. 19% vs. 27%, p=0.001), post-laminar optic nerve invasion (27% vs. 0% vs. 16% vs. 21% vs. 19%, p=0.0006), scleral infiltration (5% vs. 0% vs. 4% vs. 2% vs. 7%, p=0.13), and microscopic extrascleral infiltration (4% vs. 0% vs. <1% vs. <1% vs. 4%, p=0.68). Adjuvant chemotherapy with/without orbital radiotherapy was given in 761 (53%) patients. Based on Kaplan-Meier estimates in different continents (AS vs. AUS vs. EUR vs. NA vs. SA), the 6-year risk of orbital tumor recurrence was 5% vs. 2% vs. 0% vs. 0% vs. 12% (p<0.001), systemic metastasis was reported in 8% vs. 5% vs. 2% vs. 0% vs. 13% (p=0.001), and death in 10% vs. 3% vs. 2% vs. 0% vs. 11% (p<0.001) patients. There is a wide variation in the infiltrative histopathology features of RB across continents, resulting in variable outcomes. SA and AS had a higher risk of orbital tumor recurrence, systemic metastasis, and death compared to AUS, EUR, and NA.

Treatment Outcomes and Definition Inconsistencies in High-Risk Unilateral Retinoblastoma

PurposeTo compare the clinical outcomes of children with unilateral retinoblastoma (Rb) and high-risk histopathology features (HRHF) following upfront enucleation with/without adjuvant chemotherapy, and investigate cases locally considered non-HRHF but converted to a standardized HRHF definition. DesignRetrospective multinational clinical cohort study. MethodsChildren with Rb who presented to 21 centers from 12 countries between 2011-2020, and underwent primary enucleation were recruited. Centers retrieved clinical data and were asked to report detailed histopathology findings, as well as indicate cases defined locally as high-risk. For analysis, only unilateral cases with standardized HRHF, defined as retrolaminar optic nerve invasion, massive choroidal invasion, scleral invasion, anterior-segment involvement, and/or combined non-massive choroidal and prelaminar/laminar optic nerve invasion, were included. Main Outcome Measures included orbital tumor recurrence, systemic metastasis, survival and number and outcome of cases converted to standardized HRHF. ResultsA total of 600 children presenting to 14 centers in 9 countries were included. Of these, 505 (84.2%) were considered locally as HRHF and received adjuvant chemotherapy. After a median follow-up period of 39.2±1.6 months (range: 0.8-60.0 months), 36 (6.0%) had orbital tumor recurrence, 49 (8.2%) metastasis, and 72 (12.0%) children died. Children not receiving adjuvant chemotherapy were at significantly increased risk of orbital tumor recurrence, metastasis, and death (p ≤0.002). Of the study children, 63/600 (10.5%) were considered locally non-HRHF, but converted to standardized HRHF and included in the analysis. Of these, 6/63 (9.5%) had orbital tumor recurrence, 5/63 (7.9%) metastasis, and 6/63 (9.5%) children died. Isolated minor choroidal invasion with prelaminar/laminar optic nerve invasion was reported in 114 (19.0%) children, but considered locally as HRHF only in 68/114 (59.6%). Of these, 6/114 (5.3%) children developed metastasis and subsequently died, yielding a number needed to treat of 15. ConclusionBased on this multinational cohort of children with Rb, we recommend the use of adjuvant chemotherapy following upfront enucleation and diagnosis of HRHF. Variation exists worldwide among centers when defining HRHF, resulting in adverse patient outcomes, warranting standardization.

Retinoblastoma Outcomes Based on the 8th Edition American Joint Committee on Cancer Pathological Classification in 1411 Patients

PurposeTo evaluate the outcomes of retinoblastoma (RB) based on the 8th edition of the American Joint Committee on Cancer (AJCC) pathological classification in a global cohort of patients. DesignRetrospective, multicentre, intercontinental collaborative study Participants1411 patients Intervention(s)Primary enucleation with/without adjuvant chemotherapy/radiotherapy Main outcomes(s)Orbital tumor recurrence, tumor-related metastasis, tumor-related death ResultsBased on the 8th edition AJCC pathological classification, 645 (46%) eyes belonged to pT1, 164 (11%) to pT2, 493 (35%) to pT3, and 109 (8%) to pT4 categories. At a mean follow-up of 38 months (median, 35 months; <1-149 months), orbital tumor recurrence was seen in 8 (1%), 5 (3%), 22 (4%) and 25 (23%) of pT1, pT2, pT3, and pT4 (p<0.001) categories, respectively; tumor-related metastasis was seen in 7 (1%), 5 (3%), 40 (8%), and 46 (43%) of pT1, pT2, pT3, and pT4 (p<0.001) categories, respectively; tumor-related death was seen in 12 (2%), 7 (4%), 64 (13%), and 64 (59%) of pT1, pT2, pT3, and pT4 (p<0.001) categories, respectively. Multivariate Cox proportional hazards analysis of outcomes revealed pT category and adjuvant therapy as independent predictors of outcomes. Categories pT3b (p=0.005), pT3c (p<0.001), pT3d (p<0.001), and pT4 (p<0.001) had a greater hazard for orbital recurrence; categories pT2a (p=0.015), pT3a (p<0.001), pT3b (p<0.001), pT3c (p<0.001), pT3d (p<0.001) and pT4 (p<0.001) had a greater hazard for tumor-related metastasis; and categories pT2a (p=0.068), pT2b (p=0.004), pT3a (p<0.001), pT3b (p<0.001), pT3c (p<0.001), pT3d (p<0.001) and pT4 (p<0.001) had a greater hazard for tumor-related death when compared to the pT1 category. Patients who did not receive adjuvant therapy had greater hazards of orbital tumor recurrence in categories pT3b (p=0.005), pT3c (p=0.003), and pT4 (p=0.002); greater hazards of tumor-related metastasis in categories pT3a (p=0.001), pT3b (p=0.01), pT3c (p=0.001), and pT4 (p=0.007); and tumor-related death in categories pT3a (p<0.001), pT3b (p=0.009), pT3c (p=0.018), and pT4 (p<0.001) when compared to those who received adjuvant therapy. ConclusionThe 8th edition AJCC pathological classification predicts outcomes in patients undergoing primary enucleation for RB, and adjuvant therapy is associated with a lower risk of orbital recurrence, tumor-related metastasis, and tumor-related death in the pT3 and pT4 categories.

Safety and Efficacy of Intravitreal Chemotherapy (Melphalan) to Treat Vitreous Seeds in Retinoblastoma

Background: Active vitreous seeds in eyes with retinoblastoma (Rb) adversely affects the treatment outcome. This study aimed to investigate the safety and efficacy of intravitreal melphalan chemotherapy (IViC) as a treatment for recurrent and refractory vitreous seeds in patients with Rb. Methods: We used a retrospective non-comparative study of patients with intraocular Rb who had vitreous seeds and were treated by IViC (20–30 μg of melphalan) using the safety-enhanced anti-reflux technique. Tumor response, ocular toxicity, demographics, clinical features, and survival were analyzed. Results: In total, 27 eyes were treated with 108 injections for recurrent (16 eyes) or refractory (11 eyes) vitreous seeds after failed systemic chemotherapy. A total of 15 (56%) were males, and 20 (74%) had bilateral disease. At diagnosis, the majority (n = 21) of the injected eyes were group D, and n = 6 were group C. Vitreous seeds showed complete regression in 21 (78%) eyes; 100% (n = 10) for eyes with focal seeds; 65% (n = 11/17 eyes) for eyes with diffuse seeds (p = 0.04); 7 (64%) eyes with refractory seeds; and 14 (87%) eyes with recurrent seeds showed complete response (p = 0.37). In total, 16 (59%) eyes developed side effects: retinal toxicity (48%), pupillary synechiae (15%), cataracts (30%), iris atrophy (7%), and retinal and optic atrophy (4%). Only one child was lost to follow-up whose family refused enucleation and none developed orbital tumor recurrence or distant metastasis. Conclusion: IViC with melphalan is effective (more for focal than diffuse seeding) and a relatively safe treatment modality for Rb that can improve the outcomes of eye salvage procedures. However, unexpected toxicity can occur even with the standard dose of 20–30 μg.

Long-term evaluation of outcomes and survival of patients treated for retinoblastoma

PurposeThe purpose of our study was to assess long-term outcomes of patients suffering from retinoblastoma who underwent systemic chemotherapy using vincristine, etoposide, and carboplatin (VEC protocol) followed by other local treatments. Material and methodsA retrospective review of patients diagnosed with retinoblastoma from 1997 to 2012 in the Department of Ophthalmology and Ocular Oncology of the University Hospital in Krakow was performed. A total of 58 eyes of 42 patients were analyzed. The main outcome measures were survival rate of the patient, final visual acuity, preservation of affected eyeball, intraocular relapse, extraocular orbital tumor recurrence, and occurrence of other neoplasms. ResultsThe overall survival rate was 97.6%. The majority of eyes (67.2%) had retinoblastomas of group V in the Reese-Ellsworth Classification (REC). Ocular preservation was achieved in 41.4% eyes. Of the 24 preserved eyes, 41.7% had a final visual acuity of 6/12 or better, 12.5% had visual acuity worse than 6/12 but better than 6/60, and 45.8% had visual acuity of 6/60 or worse. Three patients (7.1%) experienced orbital recurrence of retinoblastoma and one patient (2.4%) developed a second malignancy (chronic myeloid leukemia associated with the Philadelphia chromosome). ConclusionsRetinoblastomas, especially in Reese-Ellsworth group V (RE group V), not only impair vision, but may lead to metastases and death. Early diagnosis and prompt treatment are essential to salvage the eye and vision, and to avoid metastases. Long-term follow-up of retinoblastoma survivors is important to identify late effects associated with treatment and the occurrence of second malignancies.

Unilateral unifocal advanced intraocular retinoblastoma: is reasonable to adopt intra‐arterial chemotherapy as single therapeutic choice?

AbstractPurposeTo report the outcome of 30 naive unilateral unifocal retinoblastoma cases treated with intra‐arterial chemotherapy alone.MethodsFrom 2008 to 2019, 192 eyes affected with retinoblastoma have been treated with intra‐arterial chemotherapy (IAC). 100 out of 192 (52%) eyes were naive advanced unilateral unifocal retinoblastoma (Group B‐E). 30 out of 100 (30%) received intra‐arterial chemotherapy alone. All patients underwent genetic testing at diagnosis. MR was performed at diagnosis, during treatment (when necessary), 3 months after last infusion and annually to evaluate eyeball growth.ResultsTumor control and globe salvage was achieved in 100% of the reported cases (follow‐up ranged from 11 years to 9 months). New tumors or relapse have not been detected. No further local or systemic therapies were necessary. Procedure complications and local and systemic effects are reported. No intraocular or orbital tumor recurrence or metastatic disease have been observed observed.ConclusionsThe outcome will be correlated to genetic analysis, doses and drugs used (alone or in combination) and number of infusions received.

Alternated intra‐arterial and intravitreal chemotherapy: successes and failures of advanced intraocular retinoblastoma treated without systemic chemotherapy

PurposeTo report the efficacy of combined intravitreal chemotherapy (IViC) and intra‐arterial chemotherapy (IAC) for the treatment of advanced stage retinoblastoma.MethodsThe medical records of twenty patients affected by unilateral advanced retinoblastoma (Reese‐Ellsworth stage Vb/D of ABC classification). After clinical and ophthalmoscopic evaluation, they underwent MRI to exclude local and CNS dissemination. The IAC was given to treat retinal masses and intravitreal injections to treat vitreous seeding. Patients had received two cycles (six infusions) of IAC, and from six up to ten melphalan injections into the vitreous, with an interval of 7–10 days between them.ResultsAll patients underwent to bimonthly MRI examination, during treatment and every 3 months for 1 year after last injection, to exclude orbital dissemination. Successful control (57.8%) of tumor masses and vitreous seeds was achieved in all cases at 12 up to 60 months follow‐up. No permanent complications have been reported. Transient omplications disappeared throughout the months. No intraocular or orbital tumor recurrence or retinoblastoma metastases were observed.ConclusionsSequential IAC and intravitreal melphalan for advanced retinoblastoma is a good tool to provide retinal and vitreous seed control.

High-Resolution Magnetic Resonance Imaging Can Reliably Detect Orbital Tumor Recurrence after Enucleation in Children with Retinoblastoma

Orbital tumor recurrence is a rare but serious complication in children with retinoblastoma, leading to a high risk of metastasis and death. Therefore, we assume that these recurrences have to be detected and treated as early as possible. Preliminary studies used magnetic resonance imaging (MRI) to evaluate postsurgical findings in the orbit. In this study, we assessed the diagnostic accuracy of high-resolution MRI to detect orbital tumor recurrence in children with retinoblastoma in a large study cohort. Consecutive retrospective study (2007-2013) assessing MRI findings after enucleation. A total of 103 MRI examinations of 55 orbits (50 children, 27 male/23 female, mean age 16.3±12.4 months) with a median time of 8 months (range, 0-93) after enucleation for retinoblastoma. High-resolution MRI using orbital surface coils was performed on 1.5 Tesla MRI systems to assess abnormal orbital findings. Five European experts in retinoblastoma imaging evaluated the MRI examinations regarding the presence of abnormal orbital gadolinium enhancement and judged them as "definitive tumor," "suspicious of tumor," "postsurgical condition/scar formation," or "without pathologic findings." The findings were correlated to histopathology (if available), MRI, and clinical follow-up. Abnormal orbital enhancement was a common finding after enucleation (100% in the first 3 months after enucleation, 64.3% >3 years after enucleation). All histopathologically confirmed tumor recurrences (3 of 55 orbits, 5.5%) were correctly judged as "definitive tumor" in MRI. Two orbits from 2 children rated as "suspicious of tumor" received intravenous chemotherapy without histopathologic confirmation; further follow-up (67 and 47 months) revealed no sign of tumor recurrence. In 90.2%, no tumor was suspected on MRI, which was clinically confirmed during follow-up (median follow-up after enucleation, 45 months; range, 8-126). High-resolution MRI with orbital surface coils may reliably distinguish between common postsurgical contrast enhancement and orbital tumor recurrence, and therefore may be a useful tool to evaluate orbital tumor recurrence after enucleation in children with retinoblastoma. We recommend high-resolution MRI as a potential screening tool for the orbit in children with retinoblastoma to exclude tumor recurrence, especially in high-risk patients within the critical first 2 years after enucleation.

Alternated intra-arterial and intravitreal chemotherapy for advanced intraocular retinoblastoma: preliminary successful results without systemic chemotherapy.

To describe the efficacy of intravitreal chemotherapy (IViC) preceded by intra-arterial chemotherapy (IAC) for the treatment of advanced stage retinoblastoma. This non-comparative interventional case series retrospectively reviewed the medical records of six patients who presented within months of each other with unilateral retinoblastoma, Reese-Ellsworth stage Vb/D of ABC classification in the affected eye. After clinical and ophthalmoscopic evaluation, they underwent MRI to exclude local and CNS dissemination. The IAC was given to treat retinal masses and intravitreal injections to treat vitreous seeding. Patients had received two cycles (six infusions) of IAC, and from six up to ten melphalan injections into the vitreous, with an interval of 7-10 days between them. From one to four intravitreal injections were performed for partial remission or consolidation. No permanent complications of procedures have been reported. All patients underwent to bimonthly MRI examination, during treatment and every 3 months for 1 year after last injection, to exclude orbital dissemination. Successful control (100 %) of tumor masses and vitreous seeds was achieved in all cases at 12 months follow-up. Complications were posterior lens opacity, acute ischemic papillitis, partial CVR thrombosis, hypotonia (case 1), partial vitreous hemorrhage (case 4). No complications appeared in cases 2, 3, 5, and 6. No intraocular or orbital tumor recurrence or retinoblastoma metastases (follow-up range, 12-33 months) were observed. Sequential IAC and intravitreal melphalan for advanced retinoblastoma allowed to provide retinal and vitreous seed control.

Alternating intra‐arterial and intravitreal chemotherapy for advanced intraocular retinoblastoma: First successful results without systemic chemotherapy

AbstractPurpose Background: To describe the efficacy of intra‐arterial chemotherapy combined with intravitreal chemotherapy for the treatment of advanced stage retinoblastomaMethods The Authors report the medical records of four patients who presented with unilateral retinoblastoma, (Reese‐Ellsworth stage Vb/ group D of ABC Classification in the affected eye). They underwent clinical and ophthalmoscopic evaluation and MRI to exclude local and CNS dissemination. All 4 patients received 2 cycles (six infusions) of intrarterial chemotherapy (4‐5 mg of melphalan/0.3‐0.4 mg of topotecan), and from 7 up to 9 melphalan injections into the vitreous (10‐30μg in 0.05 mL).Results Successful control of tumor masses and vitreous seeds was achieved in all cases at long‐term (&gt; 6 months) follow‐up. Tumor control was 100% in all cases. Complications included: posterior lens opacities, acute ischemic papillitis, transient hypotonia, vitreous hemorrhage. There were no cases of orbital tumor recurrence or metastasis (follow‐up range, 6 – 12 months).Conclusion Sequential intra‐arterial chemotherapy and intravitreal melphalan for advanced retinoblastoma allowed to provide retinal and vitreous seed control

Need for Lacrimal Bypass Surgery after Medial Canthal Tumor Resection: Survey of Current Practices

Objective: No ideal monitoring period exists before conjunctivodacryocystorhinostomy (CDCR) after excision of medial canthal tumors. This study seeks to define current clinical practices via a survey of oculoplastic and orbital surgeons. Methods: An online survey of medial canthal tumor management was offered via email to ASPORS members. Tumors included: basal cell carcinoma (BCC), squamous cell carcinoma (SCC), sebaceous cell carcinoma (SebC), melanoma (M), keratoacanthoma (KAC), and other adnexal cancers. Results: 87 members responded. Most surgeons follow patients at intervals no longer than 3-6 months, with monthly exams initially for SebC (17%) and M (20%). > 85% of surgeons follow asymptomatic patients for >12 months before release, with many observing >60-month periods for BCC (29%), SCC (36%), SebC (57%), M (68%), and KAC (23%). 92% of respondents defer CDCR; the majority wait >12 months for all tumors before CDCR. A majority (53%) reported at least 75% of patients developing symptomatic epiphora requiring CDCR. The majority of surgeons (73%) do not perform ancillary testing before CDCR, and 53% perform pre-operative imaging. However, 14% have experienced local or orbital tumor recurrence following CDCR. Conclusions: SebC and M follow-up intervals trend shorter, while most respondents follow these tumors post-excision > 5 years. > 25% of surgeons follow all tumors for > 60 months. CDCR is delayed for > 12 months by > 75% of surgeons for all tumors. 8% perform CDCR at the time of excision, and 14% reported local/orbital recurrence following CDCR with 52% obtaining pre-CDCR imaging. These results support extended follow-up before CDCR combined with appropriate imaging/testing to minimize morbidity/mortality.

Intravitreal Melphalan for Refractory or Recurrent Vitreous Seeding From Retinoblastoma

To evaluate the efficacy and complications of intravitreal chemotherapy for viable vitreous seeding from retinoblastoma. Intravitreal injection of melphalan (8-50 μg in 0.05 mL) followed by injection site cryotherapy. Among 12 treated cases, success with control of vitreous seeds was achieved in 10 of 12 cases at immediate follow-up (0-3 months), 8 of 10 cases at short-term follow-up (3-6 months), and 6 of 10 cases at long-term (>6 months) follow-up. Among those 8 cases that received an 8- to 10-μg dose, control was achieved in 6 of 8 cases at immediate follow-up, 5 of 7 cases at short-term follow-up, and 3 of 7 cases at long-term follow-up. Complications with the 8- to 10-μg dose were minor and included preretinal hemorrhage and retinal vasculitis with retinal pigment epithelial alterations. Of those 4 that received a 50-μg dose, immediate, short-term, and long-term control was 100%, but complications of cataract, vitreous hemorrhage, subretinal hemorrhage, severe hypotonia, and phthisis lead to enucleation in 2 cases. There was no case of orbital tumor recurrence or retinoblastoma metastasis (follow-up range, 8-66 months). Intravitreal melphalan for recurrent vitreous seeds from retinoblastoma appears to provide vitreous seed control in some patients. A high dose (50 μg) of melphalan is toxic and should be avoided.

Medulloepithelioma of the optic disc

A 6-year-old boy with a history of an amblyopic, occasionally red left eye was found to have a solid white mass overlying the optic disc on dilated ocular fundus examination. Transvitreal endoincisional biopsy of the mass yielded neoplastic tissue consistent with intraocular medulloepithelioma. The eye was removed subsequently because of concern that the tumor may invade the retrobulbar optic nerve. Histopathologic and immunohistochemical analysis of the tumor confirmed nonteratoid medulloepithelioma of the optic disc. The child has been followed up for over 36 months without any signs of orbital tumor recurrence or metastasis.

Eosinophilic granuloma of the orbit: Report of two cases

We present clinical, radiological, and histopathological findings and treatment results of two infants with orbital eosinophilic granuloma. Both patients presented at 1 year of age with unilateral proptosis, periorbital edema, and a superotemporally located, ill-defined orbital mass on computed tomographic (CT) imaging, with bone erosion in one patient. After subtotal excision, histopathological examination revealed eosinophilic granuloma, and the proptosis resolved with no sign of orbital tumor recurrence or systemic involvement at 12 and 23 months follow-up. Eosinophilic granuloma is a rare childhood orbital tumor that may or may not present with osteolytic change.

Influence of Coralline Hydroxyapatite Used as an Ocular Implant on the Dose Distribution of External Beam Photon Radiation Therapy

Coralline hydroxyapatite spheres are used as buried integrated ocular implants after enucleation or evisceration surgery. Because such implants are used after surgery for intraocular malignancy and because some patients may require postoperative radiation therapy for orbital tumor recurrence, the radiation attenuation characteristics of the implant are of interest. The authors evaluated the attenuation and scattering properties of coralline hydroxyapatite implants using a 4 MV photon beam and film dosimetry. Optical density analyses indicate that coralline hydroxyapatite implants have no significant influence on the attenuation or scattering properties of the photon beam. As such, there is no basis for concern that such implants might adversely affect external beam photon irradiation.

Fine Needle Aspiration Biopsy in the Diagnosis of Intraocular Cancer: Cytologic-Histologic Correlations

Fine needle aspiration biopsy was used as an investigational procedure in the evaluation of 71 eyes harboring a suspected intraocular malignancy between January 8, 1981, and January 21, 1983. Twenty-seven of these 71 biopsies were performed prior to any treatment as a diagnostic procedure and the others were performed following enucleation or tumor excision to provide specimens for cytologic-histologic correlation. The histologic findings confirmed the cytologic diagnosis of malignancy or benignancy in 94.3% of the 53 cases in which a corresponding tissue specimen was available for histologic evaluation. None of the eight eyes with a cytologically confirmed diagnosis of malignancy that were managed conservatively following the biopsy has experienced visual loss attributable to the biopsy. There have been no instances of documented needle tract seeding by tumor cells or orbital tumor recurrence to date in the 27 cases in which diagnostic fine needle aspiration biopsy had been performed prior to treatment.