Chemoreduction with topotecan and vincristine: Quantifying tumor response in bilateral retinoblastoma patients.

BACKGROUND: Evaluate the efficacy of two courses of vincristine and topotecan (VT) neoadjuvant intravenous chemotherapy in reducing retinoblastoma tumor volumes. METHODS: Twenty-seven patients with previously untreated, bilateral advanced retinoblastoma who were enrolled on a prospective treatment protocol (NCT00186888). Patients underwent high-resolution ophthalmic imaging at diagnosis and were reimaged following treatment with two cycles of VT. Tumor height and diameter were measured before and after treatment, and tumor volumes were calculated. Statistical methods for dependent samples were used. RESULTS: Imaging was completed for 75 tumors in 23 patients (43 eyes). After two cycles of VT, median decrease in tumor height was 47% and median decrease in tumor diameter was 22%. Median decrease in estimated tumor volume was 74%. Sixty-one of 75 tumors demonstrated >50% reduction in tumor volume. Distance from the optic nerve (=0 vs >0), age (<4 vs >4 months), macular location (within vs outside), and time (pre- and posttreatment) were found significantly associated with log-transformed tumor volume adjusting for the repeated effect of patient eye using generalized estimating equations to estimate the parameters of a generalized linear model (P < .0001 [ ß : 1.95, CI: 1.53-2.36], P = .0031 [ ß : 1.49, CI: 0.57-2.41], P < .0001 [ ß : .94, CI: 0.54-1.35], and P < .0001 [ ß : 1.43, CI: 1.15-1.71]). CONCLUSION: Chemoreduction was achieved in all patients and most retinoblastoma tumors following two cycles of VT. Reduction in tumor dimensions was comparable to that reported with platinum-based chemotherapy. Tumor location, distance from the optic nerve, and age at diagnosis were significant predictors of treatment response.

Postoperative Echography for Optimization of Radiation Dosimetry in Patients with Uveal Melanoma Treated with Plaque Brachytherapy.

PURPOSE: (1) To describe the technique of postoperative echography to confirm the intended treatment dose to the tumor apex in patients with uveal melanoma treated with plaque brachytherapy. (2) To describe the local tumor control rate and visual outcomes with the brachytherapy strategies used at our institution. DESIGN: Retrospective review. SUBJECTS: Three hundred seventy-two consecutive patients with uveal melanoma (small, medium, and large) treated with plaque brachytherapy at the University of Iowa from August 2008 to February 2019. METHODS: Patient demographics and tumor characteristics were recorded for each patient. Patients with posterior tumors treated with plaque brachytherapy (n = 355) underwent intraoperative ultrasound to confirm plaque placement, and additional postoperative ultrasound on day 1 to 3 postplaque insertion. In cases where intratumor/episcleral plaque edema or hemorrhage shifted the dose to the prescription point to < 85 Gray (Gy), the duration of plaque brachytherapy was increased to compensate. Statistical analysis was performed to compare variables associated with the need for plaque adjustment. MAIN OUTCOMES MEASURES: Variables associated with plaque dose needing to be recalculated, local tumor control, and visual acuity outcomes. RESULTS: In 31 (8.3%) cases, postoperative echography showed that the tumor apex had shifted outside the 85 Gy isodose curve, requiring adjustment of the duration of brachytherapy (28 cases) or repositioning of the plaque (3 cases). Collaborative Ocular Melanoma Study tumor size was significantly associated with need to adjust the plaque prescription dose (P = 0.03), with large tumors having the highest rate of adjustment. Tumor thickness was larger in cases requiring plaque adjustment compared with those that were not adjusted (median 4.9 mm vs. 3.0 mm, P < 0.01). Local tumor control was 99% (95% confidence interval, 97%-100%) at 5 years and 99% (95% confidence interval, 97%-100%) at 10 years. The percentage of patients who had experienced a visual acuity decline of ≥ 3 lines of vision or had < 20/200 acuity was 14.9% at 1 year after brachytherapy, 35.3% at 3 years, and 51.6% at 5 years. CONCLUSIONS: Postoperative ultrasound performed on postoperative day 1 to 3 after plaque insertion for patients undergoing brachytherapy for uveal melanoma may result in improved local tumor control, particularly in the setting of thicker or larger tumors. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Intravitreal Carboplatin as Salvage Treatment for Progressive Vitreous Disease in Retinoblastoma: A Phase I Clinical Trial.

PURPOSE: To determine the safety and toxicity profile of intravitreal carboplatin as salvage treatment for retinoblastoma with vitreous disease. DESIGN: Single-institution, interventional prospective clinical trial. PARTICIPANTS: Patients with progressive or recurrent vitreous seeds after completion of primary treatment for intraocular retinoblastoma. METHODS: Eligible eyes received an intravitreal injection of carboplatin every 14 to 21 days with simultaneous focal therapy (laser, thermotherapy, and brachytherapy) provided at the discretion of the ocular oncologist. The evaluation with examination under anesthesia, ultrasound biomicroscopy, and electroretinography (ERG) were performed before each injection to assess for tumor response and drug-related toxicity. A serious adverse event resulted in dose recalculation and ultimately early closure of the study. MAIN OUTCOME MEASURES: Regression pattern of vitreous disease and incidence of dose-limiting toxicities. RESULTS: Four patients were enrolled at an initial dose of 0.3 mg. Complete regression of vitreous seeds was noted in all patients after 5, 2, 2, and 1 injections (respectively). Two patients developed recurrent vitreous disease at 3 and 25 months after complete regression and ultimately required enucleation. A serious adverse event occurred in 1 patient who developed acute vision loss with extinguished ERG response 72 hours after the second injection; ultimately, this eye developed a cataract and required enucleation. After temporary suspension and dose modification, 3 patients were enrolled at an injection dose of 3 µg and treated with a total of 5, 2, and 1 injections, respectively. Complete regression of vitreous disease was not achieved in any patient though ERG amplitudes remained stable. After removal from protocol, all 3 patients had a complete response to intravitreal melphalan. Concern for dose escalation and further toxicity in the setting of an effective and safe alternative (melphalan) led to the termination of the study. CONCLUSIONS: Intravitreal carboplatin may be effective in treating progressive vitreous seeding at higher doses, but permanent retinal toxicity was observed. Other alternative agents should be considered. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Iodine-125 Episcleral Plaque Brachytherapy for AJCC T4 Posterior Uveal Melanoma: Clinical Outcomes in 158 Patients.

BACKGROUND/AIMS: The aim of this study is to report the burden of ocular morbidity following iodine-125 episcleral plaque brachytherapy (EPBT) in the treatment of American Joint Committee on Cancer (AJCC) T4-staged posterior uveal melanoma (PUM). METHODS: Clinical records of patients with T4-staged PUM treated with 125I EPBT were analyzed for incidence of treatment failure and radiation-induced complications. RESULTS: Cumulative incidence of local treatment failure was 9% (95% CI 5-15%) at 5 years and was associated with decreased tumor height (HR = 0.78; p = 0.01). Cumulative incidence of enucleation at 5 years was 21% and was correlated with worsening baseline visual acuity (HR = 1.42; p = 0.05). Increasing patient age was associated with higher rates of vitreous hemorrhage (HR = 1.03; p = 0.02) and cataract surgery (HR = 1.05; p < 0.001). Increased tumor height was associated with higher rates of neovascular glaucoma (HR = 1.16; p = 0.03) and vitreous hemorrhage (HR = 1.23; p < 0.001). CONCLUSION: 125I EPBT is an effective treatment for T4-staged PUM and achieves high rates of local control. Treatment failure appears to be more common among minimally elevated tumors. Other causes of ocular morbidity were associated with increasing tumor height, patient age, and baseline visual acuity.

Uveal metastases in the mid-southeastern United States: a single-institution experience.

PURPOSE: To report the clinical features of uveal metastases in a geographic region associated with high tobacco use. METHODS: Medical records from all patients diagnosed with uveal metastasis at a single tertiary referral center between 2000 and 2017 were retrospectively reviewed. The clinical features and the primary tumor site associated with each metastatic lesion were recorded. RESULTS: Ninety-nine uveal metastatic tumors were identified in 85 eyes of 74 patients (34 males). Median age at diagnosis was 62 years. Median tumor diameter was 11.6 mm and median height was 3.1 mm. Carcinoma of the lung was the most common primary tumor occurring in 37 patients (50%) followed by breast in 16 patients (21%). Among females, metastatic lesions originated from the lung in 18 patients and from the breast in 16 patients. Median survival following intraocular metastasis was 9 months for patients with a primary lung malignancy and 36 months for patients with breast cancer (log-rank test, P=0.002). CONCLUSION: Intraocular metastasis is more frequently observed in patients with carcinomas of the lung rather than breast at our treatment center. Both regional and global changes in cancer epidemiology most likely account for the findings in this study.

Spatiotemporal Patterns of Tumor Occurrence in Children with Intraocular Retinoblastoma.

PURPOSE: To accurately map the retinal area covered by tumor in a prospectively enrolled cohort of children diagnosed with retinoblastoma. METHODS: Orbital MRI in 106 consecutive retinoblastoma patients (44 bilateral) was analyzed. For MRI-visible tumors, the polar angle and angle of eccentricity of points defining tumor perimeter on the retina were determined by triangulation from images in three orthogonal planes. The centroid of the mapped area was calculated to approximate tumor origin, and the location and cumulative tumor burden were analyzed in relation to mutation type (germline vs. somatic), tumor area, and patient age at diagnosis. Location of small tumors undetected by MRI was approximated with fundoscopic images. RESULTS: Mapping was successful for 129 tumors in 91 eyes from 67 patients (39 bilateral, 43 germline mutation). Cumulative tumor burden was highest within the macula and posterior pole and was asymmetrically higher within the inferonasal periphery. Tumor incidence was lowest in the superotemporal periphery. Tumor location varied with age at diagnosis in a complex pattern. Tumor location was concentrated in the macula and superonasal periphery in patients <5.6 months, in the inferotemporal quadrant of the posterior pole in patients 5.6-8.8 months, in the inferonasal quadrant in patients 8.8-13.2 months, and in the nasal and superotemporal periphery in patients >13.2 months. The distribution of MRI-invisible tumors was consistent with the asymmetry of mapped tumors. CONCLUSIONS: MRI-based mapping revealed a previously unrecognized pattern of retinoblastoma localization that evolves with age at diagnosis. The structured spatiotemporal distribution of tumors may provide valuable clues about cellular or molecular events associated with tumorigenesis in the developing retina.