Rehabilitation of severe dentofacial deformity after early radiotherapy of retinoblastoma: a case report.

BACKGROUND: Retinoblastoma is an intraocular cancer of infancy and childhood, which has been treated with radiation therapy and chemotherapy. Radiation on growing patients can cause deterioration in maxillofacial growth and development that leads to severe skeletal discrepancies between the maxilla and mandible, and dental problems such as crossbite, openbite, and hypodontia. CASE PRESENTATION: We present the case of a 19-year-old Korean man with chewing disability and dentofacial deformities. He had undergone enucleation of the right eye and radiation therapy of the left eye due to retinoblastoma 100 days after birth. Subsequently, he received cancer therapy for the secondary nasopharyngeal cancer at the age of 11 years. He was diagnosed with severe skeletal deformity including sagittal, transverse, and vertical growth deficiency of the maxilla and midface, and with class III malocclusion, severe anterior and posterior crossbite, posterior openbite, multiple missing upper incisors, right premolars, and second molars, and impaction of the lower right second molars. To restore impaired functions and esthetics of the jaw and dentition, the orthodontic treatment combined with two jaw surgery was performed. At the end of surgical orthodontics, dental implants were placed for prosthetic treatment of missing teeth. Additional plastic surgery for zygoma elevation was done with calvarial bone graft followed by fat graft. Facial esthetics and occlusal functions of patient were favorably enhanced with the improvement of skeletal discrepancy and the rehabilitation of maxillary dentition by prosthetic work. At the 2-year follow-up, the skeletal and dental relationships and implant prosthetics were well maintained. CONCLUSION: In an adult patient with dentofacial deformities caused by early cancer therapy in the head and neck area, interdisciplinary interventions including additional plastic surgery of zygoma depression and prosthetic work of missing teeth as well as surgical-orthodontic treatment could establish favorable facial esthetics and oral rehabilitation.

Retinoblastoma seeds: impact on American Joint Committee on Cancer clinical staging.

AIM: To investigate whether the American Joint Committee on Cancer (AJCC) clinical category cT2b needs to be subclassified by the type and distribution of retinoblastoma (RB) seeding. METHODS: Multicentre, international registry-based data were collected from RB centres enrolled between January 2001 and December 2013. 1054 RB eyes with vitreous or subretinal seeds from 18 ophthalmic oncology centres, in 13 countries within six continents were analysed. Local treatment failure was defined as the use of secondary enucleation or external beam radiation therapy (EBRT) and was estimated with the Kaplan-Meier method. RESULTS: Clinical category cT2b included 1054 eyes. Median age at presentation was 16.0 months. Of these, 428 (40.6%) eyes were salvaged, and 430 (40.8%) were treated with primary and 196 (18.6%) with secondary enucleation. Of the 592 eyes that had complete data for globe salvage analysis, the distribution of seeds was focal in 143 (24.2%) and diffuse in 449 (75.8%). The 5-year Kaplan-Meier cumulative globe-salvage (without EBRT) was 78% and 49% for eyes with focal and diffuse RB seeding, respectively. Cox proportional hazards regression analysis confirmed a higher local treatment failure risk with diffuse seeds as compared with focal seeds (hazard rate: 2.8; p<0.001). There was insufficient evidence to prove or disprove an association between vitreous seed type and local treatment failure risk(p=0.06). CONCLUSION: This international, multicentre, registry-based analysis of RB eyes affirmed that eyes with diffuse intraocular distribution of RB seeds at diagnosis had a higher risk of local treatment failure when compared with focal seeds. Subclassification of AJCC RB category cT2b into focal vs diffuse seeds will improve prognostication for eye salvage.

Ruthenium plaque radiotherapy in the current era of retinoblastoma treatment.

BACKGROUND: Two major treatment modalities for retinoblastoma, intraarterial chemotherapy (IAC) and intravitreal chemotherapy (IVitC), have superseded external beam radiotherapy for eye salvage. In this new setting our objectives were to evaluate the indications for plaque radiotherapy, complications, and recurrence rates. METHODS: Retrospective detailed review of patient's charts was performed for all subjects treated with plaque radiotherapy for retinoblastoma between January 2015 and December 2020. RESULTS: A total of 12 eyes of 12 patients were included. Mean age at plaque insertion was 45 months (median 29, range 17-150). The treatment dose was 40 Gy to the tumor apex. The indication for plaque radiotherapy was salvage therapy in 11 eyes (92%) and primary treatment in one eye (8%). At last follow-up from plaque insertion (mean 36 months, range 3-67), four (33%) patients had visual acuity better than 0.5 LogMAR and four (33%) had visual acuity worse than 1.0 LogMAR. Radiation-related complications were: one (8%) vitreous haemorrhage, two (16%) non-proliferative radiation retinopathy and one (8%) cataract. Recurrence was detected in four (33%) patients at a mean of 7.8 months (median 5, range 1-20) post-plaque. Globe salvage rate was 75%, as three eyes required enucleation, one to treat recurrence of the tumor treated with plaque and two to treat recurrence of other tumors. CONCLUSIONS: In the current era of retinoblastoma management, a role for plaque radiotherapy remains for salvage or primary treatment in eyes with localised active tumor, providing tumor control in 66%. Close observation is recommended to both detect recurrence and radiation-related complications.

Measured, calculated, and egs_brachy I-125 dose distributions in a gold plaque for retinoblastoma treatment.

BACKGROUND: This study measured and calculated dose distributions around a unique gold plaque for whole-eye radiotherapy (to treat retinoblastoma). The applicator consists of a pericorneal ring attached to the four extraocular muscles and four legs, each loaded with I-125 seeds. They are inserted beneath the conjunctiva in-between each pair of muscles and attached anteriorly to the ring. The applicator was designed in such a way that the dose is directed toward the middle of the eye while sparing surrounding tissues. PURPOSE: (I) To compare the measured and calculated data obtained by thermoluminescent dosimeters (TLDs) in a solid-water phantom, a Gafchromic film in a solid-water phantom, the treatment planning systems, and Monte Carlo simulations; (II) to use Monte Carlo simulations for the determination of the dose to the organs at risk by taking the gold shielding and the anisotropy into account. METHODS: The dose around the applicator was measured using TLDs and Gafchromic EBT2 film in eye-shaped solid-water phantoms. Dose calculations were performed with the TheraPlan Plus and BrachyVision planning system and Monte Carlo simulations with egs_brachy code. A computer-aided design drawing of the applicator was created and used to create the input file for the Monte Carlo simulations. RESULTS: Monte Carlo calculated dose to the optic nerve is 64.8% of the central dose in the eye, whereas the planned dose is 93.7%. The Monte Carlo lens dose varies from 72.0% to 86.1%, whereas the planned dose varies from 73.0% to 84.3%. Monte Carlo-calculated dose to the bony orbit is 11.3%, whereas the planned dose is as high as 54.7% compared to the dose in the center region of the eye. CONCLUSIONS: The measured and Monte Carlo-simulated dose distributions matched well, whereas planned dose distributions showed discrepancies in some areas of the eye and outside of the eye due to their ignorance of the shielding effects of the plaque.

Episcleral Iodine-125 radioactive plaque brachytherapy as a salvage treatment for retinoblastoma in the era of intraarterial chemotherapy.

BACKGROUND: Retinoblastoma shows high rates of recurrence after initial chemotherapy (systemic or intraarterial). Our aim was to evaluate the effectiveness of iodine-125 radioactive plaque brachytherapy as a salvage treatment with globe-preserving attributes after initial chemotherapy in patients with intraocular retinoblastoma. METHODS: The effect of brachytherapy was investigated retrospectively in 17 eyes of 17 patients who were followed up due to retinoblastoma between May 2012 and June 2018 and who received iodine-125 radioactive plaque brachytherapy as a salvage treatment after systemic or intra-arterial chemotherapy. The regression, ocular toxicity, and enucleation rates were evaluated at the end of the follow-up period. RESULTS: The tumor locations were post equator, macular, anterior to the equator, and peripapillary in 5, 3, 7, and 2 patients, respectively. Regression was initially and rapidly observed in 17 of the 17 eyes that underwent brachytherapy. Enucleation was performed in 5 (29.42%) of these patients due to recurrence with diffuse tumor involvement, and 4 of the tumors were located anterior to the equator. In 12 (70.58%) patients, the eyes were protected from enucleation following local brachytherapy. CONCLUSIONS: Radioactive plaque brachytherapy can be applied as an effective salvage therapy with successful results in retinoblastoma patients who have received initial systemic or intra-arterial chemotherapy. Post equator-located solitary tumors have the highest success rate.

Monte Carlo simulation of tilted contact plaque brachytherapy placement for juxtapapillary retinoblastoma.

BACKGROUND: The 106-Ruthenium contact plaque applicator is utilized for the treatment of intraocular tumor within a thickness of less than 6 mm. If anything obstructs the placement of the plaque applicator, the treatment is generally difficult because the applicator has to be temporarily located just on the opposite side of the retinal tumor. Furthermore, the plaque applicator edge of approximately 1 mm does not contain 106Ru, estimating the delivered radiation dose for eccentric tumor is challenging because the lateral dose profile is inadequately provided by the manufacture's certification. This study aims to simulate tumor coverage of the tilted applicator placement for treating an infant with juxtapapillary retinoblastoma and to achieve the effective treatment. CASE PRESENTATION: We present an infant with retinoblastoma whose tumor involved macular and was invading just temporal side of the optic disc. Additionally, posterior staphyloma was induced by a series of previous treatments, making it more difficult to treat the standard plaque placement. Thus, the applicator type of CCA was intentionally tilted to the eyeball and the distance between the posterior edge of the applicator and the eyeball had to be then equal to or more than 2 mm based on the dose distribution of the applicator calculated using Monte Carlo simulation to minimize damage to surrounding tissues while covering the tumor. It was then comparable to the certification and previous reports. Based on the acquired dose distribution, the optimal placement of the applicator was derived from varying the distance between the applicator's edge and the eyeball, and the distance was then determined to be 2 mm. In this case, the minimum dose rate in the tumor was 25.5 mGy/min, and the time required to deliver the prescribed dose was 26.2 h. Therefore, the tilted 106Ru plaque applicator placement could deliver the required dose for the treatment. The physical examination revealed no active tumor as a result of the treatment. CONCLUSIONS: Optimizing the placement of the 106Ru plaque applicator, it was possible to guarantee that the prescribed dose will be delivered to the tumor even if the standard placement is not possible for the juxtapapillary tumor.

Primary laser therapy as monotherapy for discrete retinoblastoma.

BACKGROUND/AIM: Laser photocoagulation is less invasive than chemotherapy (systemic, intra-arterial or periocular) and brachytherapy. We studied the safety and efficacy of laser as primary monotherapy for discrete retinoblastoma with well-defined borders and attached retina. METHODS: A single-institution retrospective non-comparative review (2004-2018) of discrete retinoblastoma tumours managed with primary laser (532 or 810 nm wavelength, 0.5-1 s duration and power titrated until desired tumour whitening). Efficacy was evaluated by tumour long-term stability avoiding non-laser therapies. Safety was evaluated by frequency of laser-related complications and uncontrollable tumour progression. RESULTS: Eligible were 112 tumours in 55 eyes of 44 patients. Laser monotherapy (median 2 sessions) achieved initial remission in 95/112 (85%) tumour. Initial encircling only laser photocoagulation was associated with tumour progression (9/11, one tumour had vitreous seeding) compared with direct or combined photocoagulation techniques (0/94 and 0/7 tumours, respectively, p<0.001). Direct laser had no vitreous seeding, haemorrhage or injury to vital structures. Tumour recurrences developed in 52/112 (46%) tumour but repeat laser achieved long-term stability, except five tumour recurrences that required invasive therapy. Receiver operating characteristic analysis identified threshold largest basal diameter of 3 disc diameters (DD) for successful laser monotherapy, where 92/106 (87%) of tumours ≤3 DD and 0/6>3 DD achieved long-term stability with laser monotherapy (p<0.001). Overall, 35/55 (64%) eyes and 24/44 (55%) patients achieved long-term stability with laser monotherapy. No eye was enucleated for uncontrollable tumour progression. CONCLUSIONS: Discrete retinoblastoma ≤3 DD can be effectively and safely managed with laser monotherapy, sparing a significant proportion of patients/eyes from more invasive therapies.

Effect of Photobiomodulation on Restoration of Ionization Radiation-Induced Thyroid Dysfunction Through p53 and Retinoblastoma Signaling.

Objective: This study aimed to investigate whether photobiomodulation (PBM) restores normal thyroid follicular cells affected by ionizing radiation, and to determine the mechanism of PBM on thyroid function. Background: Despite diverse applications of PBM to medical therapy, there has been no evidence of its involvement with thyroid function. Methods: A light emission diode (850 nm) array was used at 2, 5, and 10 J/cm2 for in vitro analysis in human thyroid N-Thy-3.1 cells, and at 120 J/cm2 for in vivo analysis in C58BL6 mice. Cell survival and proliferation were evaluated through clonogenic and MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide] assays. Cell cycle was measured using flow cytometry. Cell cycle markers, such as p53, retinoblastoma (Rb), and E2F1, were investigated by western blot analysis. In vitro levels of cyclic adenosine monophosphate (cAMP) and thyroglobulin (TG) and in vivo levels of cAMP, TG, thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) were measured using enzyme-linked immunosorbent assay. Results: A lethal dose for N-Thy-3.1 cells was 6 Gy. PBM at 2 J/cm2 was the most effective for causing cell cycle arrest by ionizing radiation. PBM regulated p53, Rb, and cAMP expression levels in vitro. PBM restored proliferation by regulating Rb and p53 in ionizing radiated thyroid follicular tissues. PBM also recovered cAMP, TG, and thyroid function marker expression (TSH, T3, and T4) by ionizing radiation in vivo. Conclusions: PBM restored ionizing radiation-induced thyroid follicular cell dysfunction by increasing cAMP proliferation and expression. PBM is effective for ionizing radiation-induced hypothyroidism by complementing cell proliferation and cAMP, presenting a novel method for clinical application.

The role for intra-arterial chemotherapy for refractory retinoblastoma: a systematic review.

BACKGROUND: Intra-arterial chemotherapy is a new retinoblastoma treatment associated with high rates of globe salvage that has been widely adopted for primary treatment of retinoblastoma but is less frequently used as secondary treatment for refractory retinoblastoma. This systematic review aims to summarize the reported outcomes of intra-arterial chemotherapy for refractory retinoblastoma. METHODS: We conducted a systematic review of studies published on PubMed, Medline, and Embase from 2011 to 2021 reporting globe salvage rates following intra-arterial chemotherapy for secondary treatment of refractory retinoblastoma. RESULTS: Our search yielded 316 studies, and 24 met inclusion criteria. The 24 included studies were comprised of 1366 patients and 1757 eyes. Among these, 1184 (67%) eyes received secondary indication treatment, and globe salvage was achieved for 776 of these 1184 eyes (64%). Sixteen studies reported cannulation success rates from 71.8 to 100%. Pooled analysis of subjects revealed 21 patients (2.6%) with metastatic disease and 26 deaths (3%) during study follow-up periods (7-74 months). The most common ocular complications were vitreous hemorrhage (13.2%), loss of eyelashes (12.7%), and periocular edema (10.5%). The most common systemic complications were nausea/vomiting (20.5%), neutropenia (14.1%), fever (8.2%), and bronchospasm (6.2%). CONCLUSIONS: Intra-arterial chemotherapy is associated with high rates of globe salvage and low rates of serious complications in patients with refractory retinoblastoma. Unfortunately, current literature is predominantly comprised of retrospective case studies, and further high-quality evidence is necessary to inform clinical practice.

Applications of iodine-125 plaque radiotherapy for residual or recurrent retinoblastoma.

OBJECTIVE: To determine the role of iodine-125 plaque radiotherapy (IPR) as a secondary treatment for localized (solitary or multiple) residual (partially regressed) or recurrent (regrowth after ≥6 months stability) retinoblastoma in the era of systemic and/or regional chemotherapy. DESIGN: A single-institute retrospective, noncomparative, interventional case series managed between July 2014 and June 2019. PARTICIPANTS: Thirteen consecutive eyes of 12 patients with 14 residual or recurrent retinoblastoma tumors treated with IPR. Patients who had to follow up <1 year post-IPR were excluded except for those who had enucleation. METHODS: Data collected included pre-IPR treatments, tumor characteristics at IPR, and post-IPR anatomical outcome (local tumor control and globe salvage) and functional outcome (radiation complications). RESULTS: Local tumor control was achievable in 12 of 14 tumors. Local recurrences were observed in 2 of 5 tumors that exhibited fish-flesh regression after IPR (p = 0.04). Globe salvage was possible in 11 eyes (12 tumors). Only 2 eyes were legally blind and the remaining 9 eyes had vision >20/125. Radiation-induced complications included radiation retinopathy (4/11), radiation papillopathy (1/11), diffuse vitreous hemorrhage (4/11). Eyes with fish-flesh-regressed tumours tended to show more complications, but were statistically insignificant (p = 0.09, Fisher exact test). There was no association of time to IPR (early <6 months vs late >6 months) with occurrence of tumor recurrence or complications (p > 0.05). CONCLUSION: IPR offers satisfactory local tumor control and globe salvage in localized recurrent/residual retinoblastoma. Fish-flesh tumor regression after IPR should be closely monitored for further recurrences.

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.

A Multicenter, International Collaborative Study for American Joint Committee on Cancer Staging of Retinoblastoma: Part II: Treatment Success and Globe Salvage.

PURPOSE: To evaluate the ability of the American Joint Committee on Cancer (AJCC) 8th edition to predict local tumor control and globe salvage for children with retinoblastoma (RB). DESIGN: International, multicenter, registry-based retrospective case series. PARTICIPANTS: A total of 2854 eyes of 2097 patients from 18 ophthalmic oncology centers from 13 countries over 6 continents. METHODS: International, multicenter, registry-based data were pooled from patients enrolled between January 2001 and December 2013. All RB eyes with adequate records to allow tumor staging by the AJCC 8th edition criteria and follow-up to ascertain treatment outcomes were included. MAIN OUTCOME MEASURES: Globe-salvage rates were estimated by AJCC clinical (cTNMH) categories and tumor laterality. Local treatment failure was defined as use of enucleation or external beam radiation therapy (EBRT), with or without plaque brachytherapy or intra-arterial chemotherapy (IAC). RESULTS: Unilateral RB occurred in 1340 eyes (47%). Among the 2854 eyes, tumor categories were cT1 to cT4 in 696 eyes (24%), 1334 eyes (47%), 802 eyes (28%), and 22 eyes (1%), respectively. Of these, 1275 eyes (45%) were salvaged, and 1179 eyes (41%) and 400 eyes (14%) underwent primary and secondary enucleation, respectively. The 2- and 5-year Kaplan-Meier cumulative globe-salvage rates without the use of EBRT by cTNMH categories were 97% and 96% for category cT1a tumors, 94% and 88% for cT1b tumors, 68% and 60% for cT2a tumors, 66% and 57% for cT2b tumors, and 32% and 25% for cT3 tumors, respectively. Risk of local treatment failure increased with increasing cT category (P < 0.001). Cox proportional hazards regression analysis confirmed a higher risk of local treatment failure in categories cT1b (hazard ratio [HR], 3.5; P = 0.004), cT2a (HR, 15.1; P < 0.001), cT2b (HR, 16.4; P < 0.001), and cT3 (HR, 45.0; P < 0.001) compared with category cT1a. Use of plaque brachytherapy and IAC improved local tumor control in categories cT1a (P = 0.031) and cT1b (P < 0.001). CONCLUSIONS: Multicenter, international, internet-based data sharing validated the 8th edition AJCC RB staging to predict globe-salvage in a large, heterogeneous, real-world patient population with RB.

Retinoblastoma in Infancy with Subsequent Bladder Leiomyosarcoma in Adulthood: Genomic Considerations.

Hereditary retinoblastoma is attributed to germline mutation in an RB1 tumor suppressor gene followed by somatic mutation in the other allele. This report details a case of leiomyosarcoma of the bladder in a 24-year-old man with a history of retinoblastoma treated by enucleation and radiotherapy in infancy. Leiomyosarcoma is the most common secondary soft tissue malignancy in retinoblastoma survivors; however, leiomyosarcoma of the bladder in retinoblastoma survivors is very rare. Survivors of hereditary retinoblastoma should be monitored closely for secondary malignancies, and there should be an increased suspicion of malignancy. Furthermore, tumors can occur outside the field of radiation.

The role of external beam radiation therapy for retinoblastoma after failure of combined chemoreduction and focal consolidation therapy.

Purpose: To study the role of external beam radiation therapy (EBRT) for the treatment of retinoblastoma eyes that were not cured by combined systemic chemotherapy and focal consolidation therapy.Methods and Materials: A retrospective case series of 28 eyes for 24 retinoblastoma patients treated by EBRT after the failure of tumor controlled by chemotherapy and focal therapy. The main outcome measures included: international intraocular retinoblastoma classification stage (IIRC) and Reese Ellsworth (RE) stage, tumor seeding, treatment modalities, eye salvage, and survival.Results: The median age at diagnosis was 11 months. There were 14 (58%) males and 20 (83%) bilateral cases. All eyes were treated initially by systemic chemotherapy (range; 6-8 cycles). The dose of radiation used for all eyes was 45 Gray (Gy).The mean follow-up was 75months, and the overall eye salvage rate after EBRT was 13 (46%) eyes: 67% (2/3) for IIRC group B, 71% (5/7) for group C, and 33% (6/18) for group D eyes. Vitreous seeds and tumor stage migration during management by chemotherapy were the most important significant predictive factors for tumor control (p = .001 and 0.033, respectively).Conclusion: Eyes with retinoblastoma that failed chemotherapy followed by focal therapy were controlled with EBRT. However, the presence of vitreous seeds, stage migration during the course of chemotherapy, as well as good vision in the other eye may not justify the known risks of EBRT.

Craniofacial second primary tumors in patients with germline retinoblastoma previously treated with external beam radiotherapy: A retrospective institutional analysis.

BACKGROUND: The long-term survival of germline retinoblastoma patients is decreased due to the risk of second primary tumors (SPTs) that occur years after the diagnosis of retinoblastoma. This risk is related to genetic predisposition and other factors, such as the treatment of retinoblastoma by external beam radiotherapy (EBRT). PROCEDURE: We studied the incidence, risk factors, and prognosis of specific craniofacial SPTs developed within the margins of radiation field in a cohort of 209 patients with germline retinoblastoma treated with EBRT at our institution between 1977 and 2010. Clinical characteristics, survival, incidence, and histology of craniofacial SPTs were recorded. RESULTS: Fifty-three of the 209 patients developed 60 distinct craniofacial SPTs in irradiated field with a median time from EBRT of 16.9 years (4-35) and a median follow-up of 24.8 years (5.3-40). Osteosarcoma (33.3%) and undifferentiated sarcoma (23.3%) were the more prevalent histological entities. Benign tumors (16.7%) also occurred. The cumulative incidence of craniofacial SPTs reached 32.6% at 35 years after EBRT, and the median survival after diagnosis was five years. In our series, irradiation under 12 months of age, bilateral EBRT, or previous treatment of retinoblastoma with chemotherapy did not significantly increase the risk of craniofacial SPTs. CONCLUSIONS: This work presents a strong argument to avoid EBRT in the management of retinoblastoma and emphasizes the high risk and poor prognosis of specific craniofacial SPTs. This study also points to the question of the need and benefits of special programs for early detection of craniofacial SPTs in survivors of irradiated germline retinoblastoma.

Paediatric proton therapy.

Proton beam therapy is a highly conformal form of radiation therapy, which currently represents an important therapeutic component in multidisciplinary management in paediatric oncology. The precise adjustability of protons results in a reduction of radiation-related long-term side-effects and secondary malignancy induction, which is of particular importance for the quality of life. Proton irradiation has been shown to offer significant advantages over conventional photon-based radiotherapy, although the biological effectiveness of both irradiation modalities is comparable. This review evaluates current data from clinical and dosimetric studies on the treatment of tumours of the central nervous system, soft tissue and bone sarcomas of the head and neck region, paraspinal or pelvic region, and retinoblastoma. To date, the clinical results of irradiating childhood tumours with high-precision proton therapy are promising both with regard to tumour cure and the reduction of adverse events. Modern proton therapy techniques such as pencil beam scanning and intensity modulation are increasingly established modern facilities. However, further investigations with larger patient cohorts and longer follow-up periods are required, in order to be able to have clear evidence on clinical benefits.

Episcleral brachytherapy for retinoblastoma.

BACKGROUND/AIMS: To report visual outcomes, survival outcomes and complications following episcleral brachytherapy (EB) for retinoblastoma. METHODS: Retrospective review of retinoblastoma cases treated with EB in a single institution. Survival outcomes were analysed using the Kaplan-Meier method. RESULTS: Eleven tumours of 11 eyes were treated with either iodine-125 or ruthenium-106 EB with a mean apical dose of 44 Gy. The tumours were classified as group B in 5 (46%), C in 3 (27%) or D in 3 (27%) eyes, respectively. Mean follow-up time was 75.4 months. EB served as primary treatment in 3 eyes (27%) and secondary treatment in 8 eyes (73%). Final visual acuity was better than 20/200 in 70% of cases. Globe preservation was achieved in 9 (82%) eyes. Local recurrence occurred in 18% of cases at a mean onset of 17.4 months after EB. Two group D tumours that recurred after secondary EB underwent enucleation. Mean onset of radiation retinopathy was 17.4 months following EB. No metastatic or fatal events were recorded. Kaplan-Meier analysis showed recurrence-free survival and ocular survival of 80% and overall survival of 100% at 5 years after EB. CONCLUSION: EB is an effective primary or secondary treatment modality for selected retinoblastoma eyes (groups B and C). Advanced group D tumours may represent a risk factor for local recurrence. Visually significant complications such as radiation retinopathy should be anticipated.