Systemic Chemoreduction Research Articles

Combination of Brachytherapy and Intravitreal Chemotherapy in the Treatment of Retinoblastoma with Vitreous Seeding

Purpose: The aim of this study was to report the efficacy of combined intravitreal chemotherapy (IVC) and ruthenium-106 brachytherapy in retinoblastoma, either as first-line or second-line treatment, following systemic chemoreduction or intra-arterial chemotherapy. Methods: Retrospective data of 18 eyes from 18 patients treated with IVC and brachytherapy from August 2014 to December 2019 were collected. Results: The method described was our first-line therapy in 6 patients, whereas it was used as second-line treatment after chemoreduction in the remaining 12 patients. The eyes showed the following classification at initial presentation: 2 group B eyes, 3 group C eyes, and 13 group D eyes. The mean follow-up was 19.5 months (range 2–53 months). The mean patient age at brachytherapy was 34.0 months (range 15–83 months). The median prescribed dose at the tumour base and apex was 574.5 ± 306.7 Gy and 88.5 ± 12.2 Gy, respectively. The ocular retention rate was 66.7%. Six eyes had to be enucleated due to uncontrollable subretinal and recurrent vitreous seeding, tumour relapse, recurrence of a solid tumour elsewhere in the eye, and persistent vitreous bleeding with loss of tumour control. The mean number of intravitreal injections of melphalan was 5.0. Two patients received a simultaneous injection of topotecan for insufficient therapeutic response. With regard to radiogenic complications, we could observe temporary retinal and vitreous bleeding (27.8%), serous retinal detachment (44.4%), and radiogenic maculopathy and retinopathy (11.1%). None of the children showed metastatic disease during follow-up. Conclusion: Ruthenium-106 plaque therapy in combination with IVC is an effective local therapy with good tumour control rates even in advanced eyes. Overall, the analysed therapeutic approach shows an acceptable side-effect profile, especially when considering that external-beam radiation therapy and systemic polychemotherapy or at least the number of cycles needed, with their increased incidence of adverse events, can thus be avoided.

Новая методика органосохранного лечения ретинобластомы

Purpose. Elaboration of the new method of salvage retinoblastoma (RB) treatment, combining local and systemic chemotherapy. Material and methods. Salvage treatment using the new method was carried out in 71 children aged 2 months – 7 years on 102 eyes with RB in T1–T3 stages. At the Department of Pediatric Ophthalmopathology of SI «The Filatov Institute of Eye Diseases and Tissue Therapy of NAMS of Ukraine» the method of combined polychemotherapy (CPCT) was developed in 2010: primary IViC – injection of 0,01 µg (0,1 µg) Melphalan through pars plana; a course of CEV-protocol (drugs combination: Carboplatin + Etoposide Phosphate + Vincristine Sulfate) chemoreduction the next day after injection; monitoring the state of the tumor with repeated courses of SPHT every 3 weeks; addition of CPCT by focal destruction methods according to indications. In order to increase the ablasticity of IVi injections, we have developed the antireflux method of their implementation: to reduce IOP the diuretic injection is preliminarily performed in age-related dosage; puncture of the conjunctiva at the distance of 1–1,5 mm from the intended sclera puncture and its displacement above the IVi injection site; puncture of the sclera with obliquely perpendicular injection channel formation; IViC by cytostatic Melphalan in a volume of 0,1 ml in various dilutions depending on the indications; in repeated IViC – in different meridians; removing the needle with one-step tamponade of the injection site by cotton swab, antibiotic solution injecting under the conjunctiva with roller formation. Results. Ten-year experience of using the developed algorithm of salvage RB treatment by combined polychemotherapy, based on primary intravitreal melphalan chemotherapy (using the proposed antireflux injection method) with simultaneous systemic chemoreduction, proves its safety and effectivity – 77.5% regression of the tumors. Conclusion. Simultaneous action on the tumor of various cytostatics – one (melphalan) intraocular directly on the tumor and its vitreal clones, others – (carboplatin, etoposide, vincristine) – from the peripheral blood – creates the effect of «double blow» on RB cells. Key words: retinoblastoma, salvage treatment, combined polychemotherapy.

Feasibility and results of an intraarterial chemotherapy program for the conservative treatment of retinoblastoma in Argentina.

The feasibility and results of intraarterial chemotherapy, also termed ophthalmic artery chemosurgery (OAC), for retinoblastoma in less developed countries have seldom been reported. A retrospective evaluation of a program of OAC in Argentina from 2010 to 2015. Ninety-seven eyes from 81 patients (61 bilateral) were analyzed. In 35 eyes, OAC was given as primary therapy and in 62 it was used for the treatment of tumors with partial response or those relapsing after systemic chemoreduction with focal therapy or external-beam radiotherapy. Twenty-two primarily treated eyes had group D and 13 groups B/C. A total of 400 procedures were carried out. Chemotherapy used included combinations of melphalan, carboplatin, and topotecan. There was no mortality associated with OAC. Toxicity included fever and neutropenia in five (1.25%), hypotension and bradycardia during anesthesia in two and femoral thrombosis in one, eyelid edema in nine, and neutropenia or thrombocytopenia in 28 cycles. With a median follow-up of 48.7 months (range 12-79), the 3-year probability of event-free survival (pEFS) (enucleation and/or radiotherapy were considered events) was comparable for patients who received first-line therapy and those treated at relapse (0.65 vs. 0.63, P=0.5). In the former, the pEFS was 0.91 and 0.43 for groups B/C and D, respectively (P=0.01). Two patients died of extraocular dissemination after refusal of enucleation. OAC was feasible with low toxicity. pEFS improved in all groups compared to the previous experience with systemic chemotherapy reducing the use of radiotherapy. The overall mortality associated with OAC is comparable to our previous experience with systemic chemoreduction.

Long-term outcomes of Group D retinoblastoma eyes during the intravitreal melphalan era.

To evaluate outcomes of Group D retinoblastoma (Rb) eyes during the intravitreal melphalan era. Retrospective chart review of patients diagnosed with Group D Rb from 2011 to 2016 was done. Overall, 76 Group D eyes of 68 patients were included; salvage therapy included systemic chemoreduction with vincristine, etoposide, and carboplatin with local consolidation, followed by intravitreal injection of melphalan for recurrent or persistent seeding. External beam radiation was not used as a treatment modality. Primary outcome measurement was globe salvage. Of 76 Group D eyes, 24 were enucleated primarily and 52 were treated with intent to salvage the globe. Systemic chemoreduction salvaged 25 of 52 eyes (48%). Tumor recurrences were diagnosed in 27 eyes (52%); five with massive retinal recurrences underwent enucleation and 22 were treated with intravitreal melphalan injection. Of the 22 injected eyes, 14 (64%) were salvaged and eight required enucleation primarily for retinal recurrences. Success in eradicating vitreous seeds was 100%. The Kaplan-Meier 3-year survival estimate for treated eyes is 76.5% (95% CI: 61.4-86.3). Median follow-up for the group of 76 Group D eyes was 29.5 months (SD 17.9 months). During a 6-year period that included the initiation of intravitreal melphalan at our institution, the salvage rate of treated Group D eyes was 75% (39/52 eyes). Intravitreal melphalan was utilized for ocular salvage in 42% (22/52 eyes). Systemic chemoreduction combined with intravitreal melphalan for seeding demonstrated a high overall salvage rate for Group D eyes in this cohort.

An international survey of classification and treatment choices for group D retinoblastoma.

To determine which IIRC scheme was used by retinoblastoma centers worldwide and the percentage of D eyes treated primarily with enucleation versus globe salvaging therapies as well as to correlate trends in treatment choice to IIRC version used and geographic region. An anonymized electronic survey was offered to 115 physicians at 39 retinoblastoma centers worldwide asking about IIRC classification schemes and treatment patterns used between 2008 and 2012. Participants were asked to record which version of the IIRC was used for classification, how many group D eyes were diagnosed, and how many eyes were treated with enucleation versus globe salvaging therapies. Averages of eyes per treatment modality were calculated and stratified by both IIRC version and geographic region. Statistical significance was determined by Chi-square, ANOVA and Kruskal-Wallis tests using Prism. The survey was completed by 29% of physicians invited to participate. Totally 1807 D eyes were diagnosed. Regarding IIRC system, 27% of centers used the Children's Hospital of Los Angeles (CHLA) version, 33% used the Children's Oncology Group (COG) version, 23% used the Philadelphia version, and 17% were unsure. The rate for primary enucleation varied between 0 and 100% and the mean was 29%. By IIRC version, primary enucleation rates were: Philadelphia, 8%; COG, 34%; and CHLA, 37%. By geographic region, primary enucleation rates were: Latin America, 57%; Asia, 40%; Europe, 36%; Africa, 10%, US, 8%; and Middle East, 8%. However, systemic chemoreduction was used more often than enucleation in all regions except Latin America with a mean of 57% per center (P<0.0001). Worldwide there is no consensus on which IIRC version is used, systemic chemoreduction was the most frequently used initial treatment during the study period followed by enucleation and primary treatment modality, especially enucleation, varied greatly with regards to IIRC version used and geographic region.

Treatment Outcomes of Focal Laser Consolidation during Chemoreduction for Group B Retinoblastoma

To evaluate the ocular treatment outcomes of focal laser consolidation during systemic chemoreduction for Group B tumors in the posterior fundus. Single-institution retrospective chart review from 1995 to2016. Patients with Group B retinoblastoma with at least 1 tumor in the posterior fundus. Evaluation of tumor response to chemotherapy and laser consolidation. Change in the tumor size with treatment, and the association of timing of laser consolidation to the horizontal and vertical diameter of the final chorioretinal scar. Forty Group B eyes (22 right eyes and 18 left eyes) were included in the analysis. Mean age at diagnosis was 6.4 months (range 0-24 months). Of the 40 eyes, 35 were treated with both systemic chemotherapy and laser, 4 with chemotherapy only, and 1 eye with laser without chemotherapy. Mean age at initial laser treatment was 7.7 months (standard deviation 5.9 months) and mean number of laser sessions was 6 (standard deviation 5 sessions). The overall globe salvage rate was 95% (38/40 eyes). Mean horizontal and vertical diameters of the tumors in this group showed statistically significant decreases from diagnosis to all subsequent visits (P= 0.0024). The median percent reductions in the horizontal and vertical diameters of the tumors treated with both chemotherapy and laser from diagnosis to the final visit were 13% and 14%, respectively; the overall scar area showed a 13% decrease. For tumors receiving chemotherapy prior to laser therapy, the median reduction in tumor area was 18% from diagnosis to the final examination. Small tumors were found to have a 52% increase in final scar size from diagnosis, whereas larger tumors demonstrated a 37% decrease. The overall success in treating Group B tumors with chemotherapy and laser was very favorable when considering scar size and globe salvage rates. The size of the chorioretinal scar at the end of treatment was on average 13% smaller than the original tumor size, with greater reductions being noted when chemotherapy preceded laser treatment and when the tumor size at diagnosis was greater than 4.5 mm. A small subset of perifoveal lesions was treated successfully with chemotherapy, alone without laser consolidation.

Clinical outcome and regression patterns of retinoblastoma treated with systemic chemoreduction and focal therapy: A prospective study.

Purpose:To prospectively study the clinical outcome and regression patterns of early retinoblastoma (Groups A and B) after systemic chemotherapy and focal consolidation in Indian children.Materials and Methods:Group A eyes were treated with focal therapy (transpupillary thermotherapy/cryotherapy) and Group B with systemic chemoreduction and focal therapy. Outcome measures were efficacy and safety of treatment, risk factors for treatment failure, regression patterns, and factors predictive of regression patterns.Results:Of 119 eyes (216 tumors), 14 (11.8%) were Group A and 105 (88.2%) were Group B eyes. The mean follow-up was 22.6 months. Tumor control was achieved in 111/119 eyes (93.3% overall, 100% Group A, 92.4% Group B). Eight Group B eyes (6.7%) had treatment failure. No serious systemic side-effects were noted. Risk factors for failure included larger tumors (P = 0.001) and proximity to posterior pole (P = 0.014). Regression patterns were Type 4 (50.2%), Type 3 (31.7%), Type 1 (11.1%), and Type 2 (7%). Factors predictive of Type 4 regression were smaller tumors, anterior location, younger age; Type 3 regression was associated with larger tumors, macular location, and older age.Conclusions:Systemic chemoreduction and focal therapy provided effective tumor control in Indian children. Factors predictive of regression patterns included age, tumor size and its location, and the modality of treatment.

Second primary osteosarcomas in patients with retinoblastoma.

Second primary malignancies have become the leading cause of death in retinoblastoma survivors. Although osteosarcoma is the most common second malignancy, little is known about its clinical and therapeutic features. We retrospectively reviewed a database of patients with retinoblastoma and osteosarcoma occurring as a second malignancy between 1964 and 2010 at the National Cancer Center Hospital of Japan. Among 857 patients with retinoblastoma registered in the database, 10 (1.1%) developed osteosarcoma as a second malignancy. The median age at the onset of retinoblastoma was 3 months, being bilateral in nine patients and unilateral in one. Systemic chemoreduction was performed in three patients and intra-arterial chemotherapy in six; all patients received external beam radiotherapy. The median age at the onset of second primary osteosarcoma was 11.2 years; four were radiation-related and six were located in an extremity. Among five patients treated at our institute, four patients with tumors on an extremity were treated by wide resection with neoadjuvant and adjuvant chemotherapy. Three of these four patients (75%) were good responders to high-dose methotrexate-based multi-agent chemotherapy and survived with no evidence of disease (median follow-up period, 17.3 years). One patient whose temporal bone was affected underwent radiotherapy with chemotherapy but died after local recurrence. The clinical outcomes of second primary osteosarcoma in an extremity occurring in retinoblastoma survivors may be more favorable than those of conventional osteosarcoma. Early diagnosis of radiation-related osteosarcoma arising in the craniofacial region should be made at a stage where complete resection is possible.

Multidisciplinary management of retinoblastoma: Experience in 37 eyes

ObjectiveTo report the results of the multidisciplinary management of patients with retinoblastoma, including survival, enucleation rate, and systemic chemoreduction success. MethodsA retrospective study was conducted on 27 patients (37 eyes) diagnosed with retinoblastoma, and treated by a multidisciplinary team in San Juan de Dios Hospital. Demographic information, clinical characterization, survival, local and systemic treatments were included in the analysis. Patients treated with intra-arterial chemotherapy (IAC) were also reviewed. ResultsThe study included 14 male patients (52%). The median of age at presentation was 8 months (0.16–90). The median follow-up time was 33±21 months. The diagnosis was made in 10 (37%) cases after 15 months old, with a median of 35 months (24–90). 17 (63%) patients had unilateral retinoblastoma, and 10 (37%) bilateral retinoblastoma. Leukocoria, isolated or associated with other signs, was the most frequent reason for referral (63%). Global enucleation rate was 57% (n=21), being the primary treatment in 15 (55%) patients. Enucleation rate in unilateral retinoblastoma was 76.5%, and for bilateral retinoblastoma, it was 60% for one eye and 10% for both. Systemic chemotherapy was prescribed in 17 (63%) patients, with a mean number of cycles of 5.3±2.1. The overall success of chemoreduction and focal therapy in order to avoid external radiotherapy and/or enucleation was 68%. Three patients were treated with IAC as a salvage therapy, controlling the tumor in 2 patients at 6 months of follow-up. These are the first cases reported in Chile. Survival rate was 100%. ConclusionMultidisciplinary management of retinoblastoma led to a survival rate and morbidity comparable with international reports.

Manejo multidisciplinario en retinoblastoma: experiencia en 37 ojos

ObjectiveTo report the results of the multidisciplinary management of patients with retinoblastoma, including survival, enucleation rate, and systemic chemoreduction success. MethodsA retrospective study was conducted on 27 patients (37 eyes) diagnosed with retinoblastoma, and treated by a multidisciplinary team in San Juan de Dios Hospital. Demographic information, clinical characterization, survival, local and systemic treatments were included in the analysis. Patients treated with intra-arterial chemotherapy (IAC) were also reviewed. ResultsThe study included14 male patients (52%). The median of age at presentation was 8 months (0.16-90). The median follow-up time was 33 ± 21 months. The diagnosis was made in 10 (37%) cases after 15 months old, with a median of 35 months (24-90). 17 (63%) patients had unilateral retinoblastoma, and 10 (37%) bilateral retinoblastoma. Leukocoria, isolated or associated with other signs, was the most frequent reason for referral (63%). Global enucleation rate was 57% (n=21), being the primary treatment in 15 (55%) patients. Enucleation rate in unilateral retinoblastoma was 76.5%, and for bilateral retinoblastoma, it was 60% for one eye and 10% for both. Systemic chemotherapy was prescribed in 17 (63%) patients, with a mean number of cycles of 5.3 ± 2.1. The overall success of chemoreduction and focal therapy in order to avoid external radiotherapy and/or enucleation was 68%. Three patients were treated with IAC as a salvage therapy, controlling the tumor in 2 patients at 6 months of follow-up. These are the first cases reported in Chile. Survival rate was 100%. ConclusionMultidisciplinary management of retinoblastoma led to a survival rate and morbidity comparable with international reports.

Low-Dose Chemoreduction for Infants Diagnosed with Retinoblastoma before 6 Months of Age

Aim: The purpose of this study was to evaluate the outcomes of infants diagnosed with retinoblastoma before 6 months of age, including the need for chemoreduction (CRD). In this age group, dosage of CRD was reduced due to its potential for toxicity. Methods: This is a retrospective review from 2000 to 2009 that includes 126 eyes of 72 infants (18 unilateral, 54 bilateral). Systemic CRD was administered when local modalities failed or were considered inadequate. Primary outcome measures were the need for CRD and globe salvage. Results: Of the 72 infants diagnosed before 6 months of age, 48 (67%) ultimately required CRD for globe salvage, 40 (56%) patients before 6 months of age. Globe salvage was achieved in 62% (78/126) of eyes overall and in 93% (68/73) of eyes with Group A-C disease. No patient was hospitalized for CRD-related illness; survival was 100%. The mean follow-up was 52.9 months (range 1-148 months). Conclusion: Utilizing a combination of focal modalities and reduced-dose CRD, children diagnosed with retinoblastoma before 6 months of age attain globe salvage rates comparable to those of older age groups. Two thirds of the infants ultimately required CRD for globe salvage. Bilateral disease as well as Group D and E classification in at least one eye at presentation increased the chance of requiring CRD (p < 0.0001 and p < 0.016, respectively).

Factors predictive of long-term visual outcomes of Group D eyes treated with chemoreduction and low-dose IMRT salvage: The Children's Hospital Los Angeles experience

AimTo evaluate clinical factors predictive of visual outcomes in Group D retinoblastoma eyes.MethodsRetrospective chart review of patients with Group D retinoblastoma from January 2000 to December 2009. All patients were...

Impact of chemoreduction for conservative therapy for retinoblastoma in Argentina

Few studies were reported from developing countries regarding patient outcome and ocular survival in children with bilateral retinoblastoma treated with chemoreduction compared to external beam radiotherapy (EBRT). We undertook a retrospective study of three treatment eras: (1) (1988-1995) n = 68 when EBRT was used as primary conservative therapy; (2) (1995-2003) n = 46 when carboplatin-based systemic chemoreduction was introduced and (3) (2003-2009) (n = 83) when additional periocular chemotherapy was added for advanced tumors and pre-enucleation chemotherapy was given for those with massive buphthalmia. The probability of 5-year disease-free survival was 0.94 (95% confidence interval [CI] 0.91-0.98%) without significant differences among the three eras. Chemoreduction reduced the use of EBRT from 84.6% to 68.7% in eras 1 and 3, respectively (P = 0.008), which was more evident in cases with less advanced disease. Chemoreduction also significantly improved the 5-year probability of preservation of eyes with advanced disease from 0.13 (95% CI 0.04-0.27) during era 1 to 0.49 (95% CI 0.34-0.62) in era 3 (P < 0.0001). Chemoreduction was not associated with changes in the probability of extraocular relapse, which was reduced after the introduction of pre-enucleation chemotherapy. Second malignancies occurred in nine cases, acute myeloid leukemia being the most fatal one. Trilateral retinoblastoma occurred in three cases and all of them had been exposed to chemotherapy. Chemoreduction reduced the need for EBRT in eyes with less advanced disease and improved the preservation of eyes with advanced disease while its effects on secondary malignancies or trilateral disease remain unclear.

Incidence of Pineal Gland Cyst and Pineoblastoma in Children With Retinoblastoma During the Chemoreduction Era

To report on the frequency of cysts and tumors of the pineal gland in patients with retinoblastoma. Observational retrospective case control study. Institutional. study population: Four hundred eight patients treated for retinoblastoma from January 2000 to January 2012 at Wills Eye Institute, Philadelphia, Pennsylvania, USA. Magnetic resonance imaging (MRI) features of the pineal gland were evaluated in all patients with retinoblastoma. Characteristics of patients with pineal cysts and pineoblastoma were reviewed. Comparison of frequency of pineal gland cyst and pineoblastoma in children managed with systemic chemoreduction vs other methods. Of 408 patients, treatment included systemic chemoreduction in 252 (62%) and nonchemoreduction methods in 156 (38%). Overall, 34 patients (8%) manifested pineal gland cyst and 4 (1%) showed pineoblastoma. Of all 408 patients, comparison (chemoreduction vs nonchemoreduction) revealed pineal cyst (20/252 vs 14/156, P = .7) and pineoblastoma (1/252 vs 3/156, P = .1). The pineal cyst (n = 34) (mean diameter 4 mm) was asymptomatic (n = 34), followed conservatively (n = 34), and with minimal enlargement (n = 2, 9%) but without progression to pineoblastoma. The cyst was found in 22 germline and 12 nongermline patients (P = .15). Among the 4 patients with pineoblastoma, all had germline mutation and 2 had family history of retinoblastoma. Among all patients with family history of retinoblastoma (n = 45), 2 (4%) developed pineoblastoma. The pineoblastoma was asymptomatic in 2 patients and symptomatic with vomiting and headache in 2 patients. The mean interval from date of retinoblastoma detection to pineal cyst was 2 months (median 2, range 0-8 months) and to pineoblastoma was 27 months (median 28, range 7-46 months). Management included aggressive chemotherapy and radiotherapy, with 2 survivors. Pineal gland cyst was incidentally detected in 8% of retinoblastoma patients, causing no symptoms, and without progression to pineoblastoma. Pineoblastoma was detected in 1% of patients and fewer patients who received systemic chemotherapy developed pineoblastoma, possibly indicating a systemic protective effect.

Regression patterns in treated retinoblastoma with chemotherapy plus focal adjuvant therapy

The aim of this study was evaluation of the regression patterns after 3, 6, and 8 months of treatment. A total of 100 retinoblastoma tumors (57 eyes of 35 patients) were treated with 6 (n = 8) or 8 (n = 92) cycles of systemic chemoreduction and tumor consolidation (transpupillary thermotherapy [TTT] or cryotherapy) during this prospective study. After 3 months of treatment, type 3 was the predominant pattern (n = 57%, 57%), while after 6 and 8 months of treatment the tumors regressed to type 4 most often (44% and 52%, respectively). Smaller tumors and the peripheral tumors were likely to regress to type 4, whereas larger tumors and those nearer to fovea were more likely to become type 1 pattern. Tumors consolidated with cryotherapy mostly showed type 4 regression (3rd month: 40%, 6th month: 90%, and 8th month: 87.5%). Whereas, those treated with TTT rather regressed to type 3 after 3 months (57.9%) and to type 4 after 6 and 8 months of treatment (51.4% and 59.5%, respectively). Recurrence of the tumor was 40% in our cases with defined correlation with tumor location, size, and subretinal seeds. We conclude that regression patterns of tumors in patients undergoing systemic chemoreduction with focal adjuvant treatments predominantly changed over time and their changes are dependent on tumor size, location, and type of treatment. It appears that subretinal seeds, tumor size, and location of tumors are the most important factors predicting tumor recurrence.

Intra‐arterial chemotherapy is more effective than sequential periocular and intravenous chemotherapy as salvage treatment for relapsed retinoblastoma

Treatment of eyes with retinoblastoma failing systemic chemoreduction and external beam radiotherapy is seldom efficacious. This study compares the efficacy and toxicity of intra-arterial ophthalmic artery chemotherapy (IAO) to our historical cohort of sequential periocular and systemic chemotherapy in such patients. Eighteen eyes (15 consecutive patients) were retrospectively evaluated. Eight eyes received IAO for a median of four cycles (range: 2-9) including melphalan alone (n = 3) or after topotecan and carboplatin (n = 4) or topotecan and carboplatin without melphalan (n = 1). Ten eyes received a median of two cycles (range: 1-3) of periocular topotecan (n = 9) or carboplatin (n = 1) followed by intravenous topotecan and cyclophosphamide in three patients if at least stable disease was achieved. Both groups were comparable for disease extension and prior therapy. No extraocular dissemination or second malignancy occurred and all patients are alive. The probability of enucleation-free eye survival at 12 months was 0.87 (95% CI: 0.42-0.97) for the IAO group, compared to 0.1 (95% CI: 0.06-0.35) for the periocular group (P < 0.01). Ocular toxicity was mild and similar in both groups (mostly mild orbital edema). Systemic toxicity was low for IAO and periocular injection, but children who received sequentially intravenous chemotherapy (n = 12 cycles) had five episodes of grade 4 neutropenia, three of which resulted in hospitalizations. No case in the IAO group presented these complications. IAO is significantly superior to sequential periocular-intravenous topotecan-containing regimens in eyes with relapsed intraocular retinoblastoma with a more favorable toxicity profile.

Long‐term outcomes of Group D eyes in bilateral retinoblastoma patients treated with chemoreduction and low‐dose IMRT salvage

To evaluate outcomes of Group D eyes of bilateral retinoblastoma patients treated with primary chemoreduction and external beam radiation as salvage. Retrospective chart review of patients diagnosed with bilateral retinoblastoma and designated Group D in at least one eye from January 1, 2000 to December 31, 2009. Overall, 62 Group D eyes of 49 patients were included; 13 had bilateral Group D disease. Primary chemoreduction with vincristine, etoposide, and carboplatin with local consolidation was administered, followed by external beam radiation in the form of intensity-modulated radiation therapy (IMRT) as salvage for recurrent tumor. Primary outcome measure was globe salvage. Of 62 Group D eyes, 7 were enucleated primarily; 55 were treated with systemic chemoreduction, and local therapy. Chemoreduction cured 26 of 55 eyes (47%). Recurrences were found in 29 eyes; 5 underwent enucleation and 24 were treated with IMRT at a dose of 24 Gy (2 eyes) or 36 Gy (22 eyes). Of the 24 irradiated eyes, 19 (79%) were salvaged and 5 required enucleation. Final visual acuity ranged from 20/20 to light perception with 10 eyes having 20/80 or better visual acuity. Average follow-up was 54.2 months. Kaplan-Meier estimates of eye survival of Group D eyes in bilateral patients at 12 months is 82% (95% confidence interval [CI] 70.1-89.7%); at 60 months eye survival is estimated to be 68% (95% confidence interval [CI] 55.4-82.8%). Systemic treatment for retinoblastoma demonstrated a high rate of globe preservation with acceptable complications and many eyes retaining functional vision.

Bilateral orbital vasculature alterations after systemic chemotherapy and external beam radiation therapy treatment of advanced retinoblastoma: implications for intraarterial chemotherapy management.

The purpose of this study was to report significant alterations in orbital vasculature after combined systemic chemoreduction with consolidating external beam radiotherapy treatment in a case of advanced retinoblastoma and to discuss implications for intraarterial melphalan rescue chemotherapy. We studied the case of a 22-month-old child who had been treated recently with intraarterial melphalan perfusion after multimodal therapy for advanced intraocular retinoblastoma. Orbital angiography of both eyes, performed before the intraarterial melphalan injection, documented an atypical attenuated orbital vasculature. The right ophthalmic artery angiogram showed loss of a normal dominant central retinal artery. Instead, multiple dysplastic angiogenic vessels from the ophthalmic artery were found to supply the retina. A single long ciliary artery was noted with collateral vessels supplying the anterior globe. The left ophthalmic artery angiogram showed a stenotic artery with minimal anterograde flow. Orbital vasculature may be impacted by combined systemic chemotherapy and external beam radiation therapy. These changes need to be considered in the use of intraarterial melphalan for the treatment of patients with advanced retinoblastoma.

13qdel syndrome and corpus callosum agenesis in two identical twins

Abstract Purpose We report two (twin A and twin B) cases of unilateral retinoblastoma in identical female twins with 13q deletion syndrome. Family history for retinoblastoma was negative. Karyotypic analyses (peripheral lymphocytes) of the brother and their parents showed no abnormalities. Methods Twin A has demonstrated unilateral, multifocal retinoblastoma (left eye), diagnosed at the age of 5 months, which was recalcitrant to systemic chemoreduction, than treated with intraarterial chemotherapy. Twin B has demonstrated unilateral unifocal retinoblastoma (right eye) at 9 months of age, successfully treated with brachytherapy. Both had prominent eyebrows, broad nasal bridge, large, prominent, low – set ears, bulbous tipped nose, large mouth, and thin upper lip. MRI revealed ventricles dilatation associated with corpus callosum agenesis. DNA analysis was performed with polymorphic microsatellite markers to confirm monozygosity. Single‐stranded conformation polymorphism and Southern blot analysis of the retinoblastoma gene were performed. Results Molecular genetic analyses confirmed monozygosity. Conclusion We describe two cases of 13q deletion syndrome in bicorial identical twins.

Ophthalmic Vasculature Alterations Following Systemic Chemotherapy and Periocular Carboplatin Treatment of Advanced Retinoblastoma

The purpose of this study was to report significant alterations in orbital vasculature following combined systemic chemoreduction/laser ablation and periocular carboplatin treatment and to discuss treatment implications in two cases of advanced retinoblastoma. Assessment of orbital and ophthalmic vasculature was done following nine cycles of systemic chemotherapy. Intra-arterial chemotherapy was provided 6 months following completion of systemic chemoreduction, when the tumor was clearly active and progressive. Orbital angiography of both eyes, performed prior to the intra-arterial melphalan injection, documented sclerosis of the ophthalmic artery vasculature with delayed transit time, decreased choroidal blush, and anomalous vessels in the eye receiving periocular carboplatin injections. The orbital vasculature in the contralateral eye was not affected. Orbital and ophthalmic vascular alterations may occur with the use of combined systemic chemotherapy and periocular carboplatin. Systemic chemotherapy and focal transpupillary laser tumor ablation, alone, did not appear to impact the orbital and ophthalmic vascular supply. Impaired vascular supply may have significant influence on the impact of the efficacy of standard and future experimental therapeutic options.