Increasing the efficiency of the retinoblastoma brachytherapy protocol with ultrasonic hyperthermia and gold nanoparticles: a rabbit model.

PURPOSE: This study purposed to evaluate the efficacy of brachytherapy with the modality of ultrasonic hyperthermia in the presence of gold nanoparticles (GNPs) on an ocular retinoblastoma tumor in an animal model of the rabbit. MATERIALS AND METHODS: A retinoblastoma tumor was induced by the injection of the human cell line of Y79 in rabbit eyes (n = 41). After two weeks, tumor size reached a diameter of about 5-7 mm. Seven groups were involved: control, GNPs injection, hyperthermia, hyperthermia with GNPs injection, brachytherapy with I-125, a combination of hyperthermia and brachytherapy, and a combination of brachytherapy, hyperthermia and, GNPs. The tumor area was measured using B-mode ultrasound images on the zero-day and at the end of the third week. The groups were evaluated for a histopathological study of tumor necrosis. RESULTS: There was a significant difference between the relative area changes of tumor in the combination group with the other study groups (p < .05). The results of histopathologic studies confirmed the necrosis of living retinoblastoma cells. CONCLUSION: Combination therapy of brachytherapy and hyperthermia with GNPs reduces the relative size of the tumor. This method increases the necrosis percentage of retinoblastoma and significantly reduces the retinoblastoma mass in the rabbit eyes.

Outcomes of neonatal retinoblastoma in pre-chemotherapy and chemotherapy eras.

Purpose: To quantify outcomes for neonatal retinoblastoma patients treated during the pre-chemotherapy (1980-1994) and chemotherapy (1995-2018) eras. Methods: Retrospective review of retinoblastoma patients diagnosed within the first 28 days of life between 1/1/1980 and 11/30/2018. Student's t-test, Chi-square, and Fisher's exact test were performed to compare treatments and outcomes by era. Results: There were 68 patients with neonatal retinoblastoma (12% unilateral and 88% bilateral). According to era (pre-chemotherapy vs. chemotherapy), the number of treated patients was 26 (38%) vs. 42 (62%). Primary treatment was external beam radiotherapy (50% vs. 1%,P < 0.001), plaque radiotherapy (17% vs. 0%,P < 0.001), focal treatment (transpupillary thermotherapy or cryotherapy) only (21% vs. 14%,P= 0.33), intravenous chemotherapy (0% vs. 81%,P < 0.001), enucleation (10% vs. 4%,P= 0.26), or exenteration (2% vs. 0%,P= 0.37). Outcomes included tumor control (79% vs. 94%,P= 0.02), globe salvage (75% vs. 91%,P= 0.02), final gross visual acuity for salvaged eyes 20/200 or better (66% vs. 89%,P < 0.01), and death (19% vs. 0%,P < 0.01). Conclusion: Chemotherapy advancements for neonatal retinoblastoma have improved tumor control, globe salvage, visual acuity, and patient survival.

The clinical outcomes of proton beam radiation therapy for retinoblastomas that were resistant to chemotherapy and focal treatment.

PURPOSE: To evaluate the clinical results of proton beam radiation therapy (PBRT) for treatment of retinoblastoma. METHODS: Children with retinoblastoma who were treated with chemotherapy and focal treatment such as brachytherapy and thermotherapy but showed no response or developed recurrences later received PBRT. The PBRT strategy was designed to concentrate the radiation energy to the retinoblastoma and spare the surrounding healthy tissue or organs. RESULTS: There were three patients who received PBRT. The first patient received PBRT because of an initial lack of tumor regression with chemotherapy and brachytherapy. This patient showed regression after PBRT. The second patient who developed recurrence of retinoblastoma as diffuse infiltrating subretinal seeding was taken PBRT. After complete regression, there was recurrence of tumor and the eye was enucleated. The third patient had unilateral extensively advanced retinoblastoma. Initial chemotherapy failed and tumor recurred. The tumor responded to PBRT and regressed significantly. However, the eye developed sudden multiple recurrences, so we had to perform enucleation. CONCLUSIONS: PBRT for retinoblastoma was effective in cases of showing no response to other treatment modalities. However, it should be carefully applied when there was recurrence of diffuse infiltrating subretinal seeding or extensively advanced retinoblastoma initially.

Iodine 125 plaque radiotherapy as salvage treatment for retinoblastoma recurrence after chemoreduction in 84 tumors.

PURPOSE: To assess tumor control and complications of iodine 125 (I125) plaque radiotherapy for retinoblastoma recurrence after chemoreduction (CRD). DESIGN: Interventional retrospective case series. PARTICIPANTS: Children with retinoblastoma treated on the Oncology Service, Wills Eye Hospital, initially examined from July 1994 to April 2005. METHODS: Eighty-four retinoblastomas with solid recurrence after CRD were treated with custom designed I125 plaque radiotherapy. Eyes with vitreous or subretinal seed recurrence were excluded. The CRD regimen included vincristine, etoposide, and carboplatin for 6 cycles plus local consolidation with thermotherapy or cryotherapy. The only alternatives to plaque radiotherapy in these cases would have been external beam radiotherapy (EBRT), additional chemotherapy, or enucleation. MAIN OUTCOME MEASURES: Tumor control and radiation complications. RESULTS: Tumor control was achieved in 95% of eyes by 5 years follow-up. Of the 59 recurrent tumors after CRD alone, 56 (95%) were controlled with plaque radiotherapy. Of the 25 recurrent tumors after CRD and EBRT, 100% were controlled with plaque radiotherapy. Of the 3 failures after plaque radiotherapy, the median time to failure (tumor recurrence) was 4 months and all recurrences were detected within 1 year. There were no identifiable factors predictive of plaque radiotherapy failure. Using Kaplan-Meier analysis, radiation complications at 5 years included proliferative retinopathy (19%), nonproliferative maculopathy (24%), papillopathy (16%), transient mild vitreous hemorrhage (54%), cataract (43%), iris neovascularization (NVI; 8%), and glaucoma (4%). Nonresolving vitreous hemorrhage and scleral necrosis did not occur. Radiation complications showed minimal change at 10 and 15 years of follow-up. CONCLUSIONS: Iodine 125 plaque radiotherapy offers 95% tumor control for selected retinoblastomas that fail CRD. Complications such as radiation retinopathy and mild vitreous hemorrhage should be anticipated, depending on the location, size, and extent of the tumor.

[Use of ruthenuim 106 in retinoblastoma treatment]. / Vyuzití Ru106 pro lécbu retinoblastomu.

The Charles University Teaching Hospital in Prague - Motol started to treat patients with retinoblastoma by means of brachytherapy after obtaining the permission to use closed source of ionizing radiation in the beginning of the year 2003. The applicator containing ruthenium (106Ru) emitting mostly the beta radiation was chosen. Half-life is 369 days and the nominal activity of the source is 21.1 MBq. The applicator is placed in place for one to several days according to the prominence of the tumor and actual activity of the source. Duration of the application is calculated with a special program. In the year 2003, three patients with retinoblastoma were treated. In one case bilateral involvement was determined, and the brachytherapy was used for treatment of both eyes. The next patient was treated twice; one treatment followed the other with different localization of the applicator because of too large basis of the tumor. In 2003, altogether the brachytherapy was used for treatment of retinoblastoma five times. In all cases, the combined treatment (chemoreduction, teletherapy, transpupillary thermotherapy, or cryotherapy) was performed. One eyeball was enucleated because of severe post-radiation retinopathy, the second one for persisting tractional retinal detachment. In remaining cases no serious complications or progression of the malignancy were observed.

Causes of chemoreduction failure in retinoblastoma and analysis of associated factors leading to eventual treatment with external beam radiotherapy and enucleation.

PURPOSE: To evaluate the causes of chemoreduction failure in retinoblastoma and to analyze the associated factors for eventual treatment with external beam radiotherapy and enucleation. DESIGN: Prospective noncomparative case series. PARTICIPANTS: Seventy-one patients with 105 eyes with intraocular retinoblastoma that underwent chemoreduction therapy between October 1998 and January 2003. INTERVENTION: A 6-treatment cycle of chemoreduction therapy with vincristine, etoposide, and carboplatin was administered at monthly intervals. Unresponsive disease was defined as persistence of retinal tumors, vitreous seeds, or subretinal seeds after the second treatment cycle, with no appreciable sign of regression. Eyes with unresponsive disease were enucleated after the second treatment. Eyes that responded to chemoreduction therapy received focal treatment, including indirect laser photocoagulation, transpupillary thermotherapy, cryotherapy, and ruthenium 106 episcleral plaque radiotherapy after the second chemoreduction treatment, if necessary, to achieve complete tumor regression. Recurrence was defined as the regrowth of retinal tumors, vitreous or subretinal seeds after an initial favorable response, and regression. Recurrent retinal tumor, vitreous seeds, or subretinal seeds were treated with focal treatments and 2 to 3 additional chemoreduction treatments. When these methods failed or were not applicable, external beam radiotherapy and/or enucleation was administered. MAIN OUTCOME MEASURES: The use of external beam radiotherapy and enucleation for chemoreduction failure, which was defined as unresponsive or recurrent disease. RESULTS: The mean follow-up was 25.7 months (range: 6-49). Ten of 105 eyes (9.5%) with unresponsive disease were enucleated after the second treatment. Of the remaining 95 eyes, 42 (44.2%) developed recurrence after chemoreduction. Recurrent disease failing to be treated successfully by other methods was treated with external beam radiotherapy in 26 of 95 eyes (27.4%) and enucleation in 22 of 95 eyes (23.2%). External beam radiotherapy was successful in preventing enucleation in 20 of 26 eyes (76.9%). Overall, the globe salvage rate was 69.5%, ranging from 36.1% for Reese-Ellsworth group V disease to 87.0% for groups I to IV disease. Histopathologically, 29 of 31 enucleated eyes (93.5%) had poorly differentiated or moderately differentiated retinoblastoma. Using multivariate logistic regression analysis, factors predictive of eventual treatment with external beam radiotherapy were female gender (P = 0.010), presence of subretinal seeds (P = 0.023), and a greater number of chemoreduction treatments (P = 0.027). By multivariate analysis, the factors associated with the need for eventual treatment with enucleation were recurrence of retinal tumors (P = 0.004), presence of vitreous seeds (P = 0.008), greater tumor thickness (P = 0.015), presence of subretinal fluid (P = 0.040), and older patient age (P = 0.042). CONCLUSIONS: Chemoreduction failure in this article was defined as unresponsive or, more commonly, recurrent retinoblastoma. Older patient age, greater tumor thickness, presence of vitreous seeds and subretinal fluid at baseline, and retinal tumor recurrence after chemoreduction were factors associated with the need for enucleation.

[The organ-saving treatment of intraocular tumors (development trends)]. / Organosokhrannoe lechenie vnutriglaznykh opukholei (tendentsii razvitiia).

A trend towards an increase of malignant tumors observed during the recent 30-40 years, an unsatisfactory efficiency of enucleation as of a method applicable to treating such tumors and the designing of a modern technical basis stimulated a new trend in ophthalmooncology, i.e. organ-saving treatment. Outlined in the paper is an analysis of achievements of modern radiation treatment techniques and of local surgical extraction of tumors suggested both by Russian and foreign researchers; the methods are shown to be promising for future development.

Chemoreduction for retinoblastoma: analysis of tumor control and risks for recurrence in 457 tumors.

PURPOSE: To evaluate individual tumor control following chemoreduction for retinoblastoma. METHODS: Prospective nonrandomized single-center case series of 457 retinoblastomas managed with six cycles of chemoreduction (vincristine, etoposide, and carboplatin). The tumors were then managed with chemoreduction alone (group A) or chemoreduction combined with thermotherapy (group B), cryotherapy (group C), or both thermotherapy and cryotherapy (group D). The main outcome measure was development of tumor recurrence. RESULTS: Of 457 retinoblastomas, 63 (14%) were in group A, 256 (56%) in group B, 127 (28%) in group C, and 11 (2%) in group D. The tumor was located in the macula in 33 (52%) of group A, 109 (43%) of group B, 3 (2%) of group C, and 1 (9%) of group D. Using Kaplan-Meier analysis, recurrence of the individual retinoblastoma at 7 years was found in 45% of group A and in 18% of combined groups B, C, and D. Treatment of the 93 tumor recurrences included thermotherapy, cryotherapy, or plaque radiotherapy in 62 cases (67%) and external beam radiotherapy or enucleation in 31 cases (33%). Risk factors predictive of tumor recurrence by multivariate analysis included macular tumor location for all groups and, additionally, female sex for group A and increasing tumor thickness for groups B, C, and D. CONCLUSIONS: Chemoreduction alone or combined with cryotherapy and/or thermotherapy is effective for treatment of retinoblastoma, but tumor recurrence is greatest for those located in the macula and those with greater thickness. Globe salvage is usually achieved despite tumor recurrence.

[New strategies in the management of retinoblastoma]. / Nouvelles stratégies dans le traitement du rétinoblastome.

It was rare that a child survived retinoblastoma at the beginning of the twentieth century. Today the survival rate is in the order of 95% in reference centers, with new strategies improving prognosis step by step. Systematic enucleation used to be the starting point of any true and structured management, until the advent of radiotherapy made it possible not only to save lives but also to retain some useful vision. Early diagnosis has enabled focal therapies such as photocoagulation, cryocoagulation, and radioactive applicators to open up a new era of targeted tumor treatment. However, the onset of nonocular tumors secondary to radiotherapy, the resistance of certain tumors to irradiation, and unsightly cosmetic consequences all justify research into alternative therapeutic strategies. New types of chemotherapy have shown spectacular results and are currently under study: chemoreduction to make large tumors more manageable and enable less aggressive treatment of tumors located in delicate sites, thermochemotherapy using the effect of heat on plasma membrane permeability to antimitotics, and chemotherapy associated with cyclosporine to reduce the multidrug resistance of certain tumors. The aim is to avoid primary enucleation and external beam radiation as far as possible. The future may lie in local chemotherapy, hyperthermia, and dynamic phototherapy, accelerated proton beam radiotherapy also has promising prospects.

Plaque radiotherapy for retinoblastoma: long-term tumor control and treatment complications in 208 tumors.

OBJECTIVE: To evaluate the clinical factors predictive for tumor recurrence and treatment complications in a large series of children who underwent plaque radiotherapy for retinoblastoma. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: The participants included 141 children with retinoblastoma who were managed on the Oncology Service at Wills Eye Hospital with plaque radiotherapy between July 1976 and June 1999. MAIN OUTCOME MEASURES: Tumor recurrence and treatment complications. RESULTS: There were 208 tumors managed with plaque radiotherapy. The mean patient age at plaque treatment was 19 months. Prior treatment to the retinoblastoma of concern was delivered to 148 tumors (71%) and included various combinations of treatments such as intravenous chemoreduction, external beam radiotherapy, laser photocoagulation, thermotherapy, and cryotherapy. For 72 retinoblastomas (35%), more than one therapeutic method had failed to achieve tumor control before the use of plaque radiotherapy. Of the 208 retinoblastomas managed with plaque radiotherapy, Kaplan-Meier estimates of tumor control were 83% at 1 year and 79% at 5 years. Of the 60 tumors treated only with plaque radiotherapy (primary treatment), recurrence at 1 year was 12%. Of the 148 tumors treated after failure of other methods (secondary treatment), specific Kaplan-Meier estimates of tumor recurrence at 1 year was detected in 8% of tumors previously treated with chemoreduction, 25% of tumors previously treated with external beam radiotherapy, 34% tumors previously treated with both chemoreduction and external beam radiotherapy, and 8% of tumors previously treated with laser photocoagulation, thermotherapy, or cryotherapy (methods other than chemoreduction and external beam radiotherapy). Using multivariable analysis, the risks for tumor recurrence included the presence of tumor seeds in the vitreous, presence of subretinal tumor seeds, and increasing patient age. Using Kaplan-Meier estimates, radiation complications at 5 years of follow-up included nonproliferative retinopathy in 27%, proliferative retinopathy in 15%, maculopathy in 25%, papillopathy in 26%, cataract in 31%, glaucoma in 11%, and scleral necrosis in 0%. CONCLUSIONS: Plaque radiotherapy for retinoblastoma provides tumor control in 79% of cases at 5 years of follow-up. It is particularly useful for those tumors that fail treatment with chemoreduction, laser photocoagulation, thermotherapy, and cryotherapy. Tumors in young patients without vitreous or subretinal seeding show the best long-term control.

[Current therapy aspects of intraocular tumors]. / Aktuelle Therapieaspekte intraokularer Tumoren.

The most frequent primary intraocular malignancies are uveal melanoma in adults and retinoblastoma in children. Genetic findings in uveal melanoma now allow a better risk-prediction with regard to metastatic disease. New treatment modalities like endo-resection, trans-scleral resection, proton beam irradiation and trans-pupillary thermotherapy are now being established in clinical routine. Management of retinoblastoma has changed during the last years considerably. In hereditary retinoblastoma external beam radiotherapy (EBR) results in a sixfold increased risk for the development of secondary, non ocular malignant tumors in these patients. New treatment regimens based on systemic chemotherapy were developed to replace EBR. In combination with chemotherapy there has been a continuing trend toward more conservative focal treatment for retinoblastoma. Indications and first results of these new treatment modalities are presented.

Exposure of primary orbital implants in postenucleation retinoblastoma patients.

PURPOSE: To determine significant factors influencing the exposure of primary orbital implants in patients with retinoblastoma. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: One hundred nine consecutive patients (110 sockets) who had undergone enucleation for retinoblastoma from January 1993 to December 1997. METHODS: Two patients with recurrence of orbital retinoblastoma were excluded from further analysis, leaving 107 patients (108 sockets). The parameters analyzed included the patient's age; gender; ocular diagnosis; surgeon; type, covering, and size of the implant; the use of chemotherapy or radiotherapy; and the timing of these treatments in relation to enucleation. Study patients were divided into two main groups: the "treated group"-patients who had undergone adjuvant external beam radiotherapy or chemotherapy, and the "untreated group"-patients had undergone enucleation with or without cryotherapy, laser thermotherapy, or brachytherapy to the index or fellow eye. The following additional parameters were noted in the patients with exposed implants: time to exposure from date of enucleation and treatment of exposure. MAIN OUTCOME MEASURE: Exposure of orbital implants. RESULTS: There were two exposures caused by orbital recurrence of retinoblastoma. The rate of nontumor recurrence exposure was 28% (30 of 108). The median time to exposure was 136 days (range, 1-630 days). There were 18 exposures (35%,18 of 51) in the treated group, with a 34% exposure rate (13 of 38) in the chemotherapy group. The exposure rate was 21% (12 of 57) in the untreated group. The rates of exposure according to implant were: Vicryl mesh-wrapped hydroxyapatite (2 of 18, 11%), Medpor (8 of 13, 53%), plain polymethylmethacrylate (PMMA) (4 of 50, 8%), Mersilene-wrapped PMMA (9 of 17, 53%) and Castroviejo (7 of 10, 70%). Eight of the exposures (27%) were managed conservatively; the remainder required surgical repair. CONCLUSIONS: Results suggested that implant type and covering (P = 0.000) had a highly significant effect on the rate of exposure in postenucleation retinoblastoma patients. There was no statistical evidence that age, gender, ocular diagnosis, surgeon, size of the implant, or radiotherapy had an effect on implant exposure. There was an increased rate of exposure in the chemotherapy group, although this did not achieve statistical significance (P = 0.058), but a detrimental effect could not be excluded.

Hypnosis instead of general anaesthesia in paediatric radiotherapy: report of three cases.

PURPOSE: This report proposes hypnosis as a valid alternative to general anaesthesia for immobilisation and set-up in certain cases in paediatric radiotherapy. METHODS: We report three cases of children who underwent radiotherapy in 1994 and were treated using hypnosis for set-up during irradiation. The first and the second were two cases of macroscopic resection of cerebellar medulloblastoma in which craniospinal irradiation was necessary, while the third patient suffered of an endorbitary relapse of retinoblastoma previously treated with bilateral enucleation, radiotherapy and chemotherapy; in this last situation the child needed radiation as palliative therapy. Hypnosis was used during treatment to obtain the indispensable immobility. Hypnotic conditioning was obtained by our expert psychotherapist while the induction during every single treatment was made by the clinician, whose voice was presented to the children during the conditioning. RESULTS: Every single fraction of the radiation therapy was delivered in hypnosis and without the need for narcosis. CONCLUSIONS: Hypnosis may be useful in particular situations to prepare paediatric cancer patients during irradiation, when lack of child collaboration might necessitate the use of general anaesthesia and when anaesthesia itself is not possible.

Combined chemoreduction and adjuvant treatment for intraocular retinoblastoma.

OBJECTIVE: The purpose of the study is to investigate chemoreduction and adjuvant treatment (AT) for retinoblastoma and its effect on complete retinal tumor control, vitreous seed control, and subretinal seed control. DESIGN: The study design was a prospective, nonrandomized clinical trial. PARTICIPANTS: There were 130 intraocular retinoblastomas in 52 eyes of 32 consecutive patients observed for at least 1 year after initiation of treatment. INTERVENTION: Treatment with chemoreduction using vincristine, etoposide, and carboplatin (VEC) and adjuvant treatment (+ AT) (cryotherapy, laser photocoagulation, thermotherapy, chemothermotherapy, plaque radiation therapy, or external beam radiation therapy) were assessed. MAIN OUTCOME MEASURES: The effect of chemoreduction for 6 cycles (VEC x 6) versus fewer than 6 cycles (VEC x <6) on retinoblastoma control was analyzed. Furthermore, the impact of adjuvant treatment (+ AT) versus no adjuvant treatment (no AT) on retinoblastoma control was analyzed. RESULTS: Retinal tumors showed favorable initial regression with chemoreduction. Adjuvant treatment was applied to 93% of the retinal tumors after chemoreduction and only 2% recurred over the mean follow-up of 17 months (range 13-27 months). Vitreous seeds and subretinal seeds showed initial regression and often complete disappearance with chemoreduction. In those eyes with seeds before treatment, the addition of AT to VEC for 6 cycles decreased the vitreous seed recurrence from 75% to 0% (P = 0.04) and also decreased the subretinal seed recurrence from 67% to 0% (P = 0.003). More important, when considering that enucleation or external beam radiation therapy was the only other treatment option for these 52 eyes, the authors were successful in avoiding these methods in 42% of cases. Of the 36 eyes classified as Reese-Ellsworth group 5, there was 78% ocular salvage, and external beam radiation therapy was avoided in 25% of these eyes. There was a 100% ocular salvage in the group 5 eyes that received VEC for 6 cycles + AT to retinal tumors and seeds. CONCLUSIONS: Chemoreduction and AT to intraocular retinoblastoma and its seeds provides good retinal tumor control, even in eyes with advanced disease. Chemoreduction alone generally is not adequate to achieve complete tumor seed control. Cautious follow-up of affected patients is recommended because the risk for recurrent vitreous and subretinal seeds is substantial and proper treatment is critical for salvaging the eye.

External beam radiation for retinoblastoma: results, patterns of failure, and a proposal for treatment guidelines.

PURPOSE: To analyze treatment results and patterns of failure following external beam radiation for retinoblastoma and propose treatment guidelines according to specific clinical variables. METHODS AND MATERIALS: We analyzed 27 patients (34 eyes) with retinoblastoma who received external beam radiation as initial treatment at Hahnemann University Hospital from October 1980 to December 1991 and have been followed for at least 1 year. Of the 34 eyes, 14 were Groups I-II (Reese-Ellsworth classification), 7 were Group III, and 13 were Groups IV-V. Doses ranged from 34.5-49.5 Gy (mean 44.3 Gy, median 45 Gy) in 1.5-2.0 Gy fractions generally delivered through anterior and lateral wedged pair fields. RESULTS: At a mean follow up of 35.2 months (range 12-93 months), local tumor control was obtained in 44% (15 out of 34) of eyes with external beam radiation alone. Salvage therapy (plaque brachytherapy, cryotherapy, and/or photocoagulation) controlled an additional 10 eyes (29.5%), so that overall ocular survival has been 73.5%. Local tumor control with external beam radiotherapy alone was obtained in 78.5% (11 out of 14) of eyes in Groups I-II, but in only 20% (4 out of 20) of eyes in Groups III-V. A total of 67 existing tumors were identified prior to treatment in the 34 treated eyes and local control with external beam radiation alone was obtained in 87% (46 out of 53) of tumors measuring 15 mm or less and in 50% (7 out of 14) of tumors measuring more than 15 mm. When analyzing patterns of failure in the 19 eyes that relapsed, a total of 28 failure sites were identified and consisted of progression of vitreous seeds in seven instances (25% of failure sites) recurrences from previously existing tumors in 10 instances (36% of failure sites) and development of new tumors in previously uninvolved retina in 11 instances (39% of failure sites). CONCLUSIONS: 1) We find that external beam radiation to a dose of 45 Gy in fractions of 1.5 to 2.0 Gy provides adequate tumor control in retinoblastoma eyes Groups I-II (Reese-Ellsworth classification) or tumors measuring 15 mm in diameter or less. Eyes in more advanced group staging or containing tumors larger than the 15 mm seem to require higher radiation doses. We propose treatment guidelines for external beam radiation of retinoblastoma that specifically take into account the important clinical variables of tumor stage and patient age. 2) External beam radiation does not prevent the appearance of new tumors in clinically uninvolved retina. Therefore, the traditional belief that external beam radiation can treat the retina "prophylactically" should be seriously questioned. Due to this finding and their significant less morbidity, focal treatment modalities (plaque brachytherapy, photocoagulation, and/or cryotherapy), when clinically feasible, should be considered the treatment of choice for intraocular retinoblastoma. External beam radiation should be considered only when focal treatment modalities are not clinically indicated.

Conservative treatment of retinoblastoma. The use of plaque brachytherapy.

Retinoblastoma is the most common intraocular malignancy in childhood. The tumor arises from multipotential retinal cells. Treatment options include enucleation, external beam radiotherapy, episcleral plaque radiotherapy, photocoagulation, cryotherapy or a combination of these modalities. In retinoblastoma 10% have a positive family history and of the remaining 90%, 35% represent germinal chromosomal mutations while 65% represent somatic chromosomal mutations. Therefore, approximately 40% of all retinoblastomas are hereditary and are transmitted as a highly penetrant autosomal dominant trait. In the Wills Eye/Hahnemann University experience an analysis of 400 consecutive patients, 103 tumors in 103 eyes were treated with solitary plaque radiotherapy. Tumor regression was observed in all patients initially. After 40 months mean follow-up, persistent regression was observed in 89 cases (87%) and recurrences in 13 cases (13%). Of the 13 recurrences, five were in the group treated primarily (5/31) and eight in the group treated after failing other modalities (8/72). Plaque brachytherapy is an important tool in the management of retinoblastoma. Our preliminary data suggest that plaque brachytherapy is an effective treatment modality for primary treatment as well as after failure using other modalities.