Radiotherapy For Retinoblastoma Research Articles

RADT-30. RADIATION INDUCED MENINGIOMA IN BACKGROUND OF CHILDHOOD CRANIAL IRRADIATION: A CASE SERIES

Abstract BACKGROUND Cranial irradiation as part of prophylactic (PCI) or radical treatment for childhood malignancies can be associated with late consequences such as radiotherapy induced meningioma. METHODS We are reporting 5 such patients treated at our institute. RESULTS Case 1: 24y female received PCI for Acute Lymphoblastic Leukemia at the age of 2, and developed right frontal meningioma which was resected and pathology confirmed grade 2 atypical meningioma. It was treated with radiotherapy 60Gy/30fr and 2 year follow up scans remain stable. Case 2: 31y male received PCI as a child, and developed parieto-occipital meningioma which was excised multiple times. Pathology revealed Grade 2 atypical meningioma and was treated with radiotherapy 60Gy/30fr. Follow up scans 3.5 yrs later remain stable.Case3: 37y male received PCI at the age of 3, and developed multiple site meningiomas which were excised. Pathology showed likely Grade 2 meningioma. The sphenoid wing lesion progressed 2 years later, was re-excised and treated recently with radiotherapy 60Gy/30fr. Case 4: 52y female treated with radiotherapy for retinoblastoma at the age of 6-8 wks, developed left sphenoid wing meningioma which was resected and pathology revealed malignant meningioma. Radiotherapy 60Gy/30fr was recently completed.Case 5: 24y female treated with radiotherapy for medulloblastoma at the age of 5, developed meningiomas at multiple sites. Over the span of 10 years the frontal and clinoid lesions increased in size, and were treated with SRS/SRT recently. CONCLUSION All patients had background of cranial radiation and developed meningioma with latency period ranging 19 to 52 years. It is not possible to make an inference on gender, site of meningioma or craniaI dose correlation because of small number of cases and lack of data on dose. Further research is needed on how to prevent secondary malignancies in such patients and on standard of care for secondary meningiomas.

Surgical Outcomes in Radiation-induced Cataracts After External-beam Radiotherapy in Retinoblastoma.

Objectives:To investigate visual outcomes, surgical complications and tumor recurrence among children with retinoblastoma undergoing phacoemulsification and posterior chamber intraocular lens (PCIOL) implantation for radiation-induced cataract secondary to external beam radiotherapy.Materials and Methods:The medical records of all patients treated by phacoemulsification and PCIOL implantation for radiation-induced cataract after external beam radiotherapy for retinoblastoma at a single institution between 1980 and 2014 were reviewed retrospectively. The study included 6 eyes of 6 children (4 girls, 2 boys).Results:Four patients had bilateral and two patients had unilateral retinoblastoma. The median age at diagnosis of retinoblastoma was 28.3 months (range, 12-96 months). All patients received chemoreduction (OPEC protocol) and external beam radiotherapy with or without local ophthalmic therapies and developed radiation-induced cataracts. The median interval from retinoblastoma diagnosis to cataract surgery was 96.3 months (range, 73-122 months). Time interval between surgery and last retinoblastoma treatment was 67.2 months. Postoperative complications included iridocyclitis in 2 eyes and posterior capsule opacification in all eyes. The mean follow-up after surgery was 105.8 months (range, 59-120 months). Final visual acuity was better in all eyes than preoperative visual acuities.Conclusion:Phacoemulsification and PCIOL implantation is an effective method of managing radiation-induced cataracts in eyes with previously treated retinoblastoma. However, visual acuity was limited by the presence of primary macular tumor.

Эффективность брахитерапии при ретинобластоме

Purpose. To assess the tumor control and complications of ruthenium 106 (Ru-106) and strontium 90 (Sr-90) plaques radiotherapy for retinoblastoma. Material and methods. The study included 60 children with retinoblastoma who were treated in the Ocular Oncology and Radiology Service at the S. Fyodorov Eye Microsurgery Federal State Institution with plague radiotherapy between 2006 and 2015. The mean patient age at the plaque treatment was 22 months (from 5 to 74 months). Prior this treatment the management of the retinoblastoma was carried out in one hundred tumors (92% of cases) and included various combinations of treatments such as systemic and/or local chemotherapy, external beam radiotherapy, laser coagulation, thermotherapy and cryotherapy. Five retinoblastomas (8%) were managed by plaque radiotherapy without any previous treatment. The Ru-106 plaques were used in 68.5% of cases (72 tumor foci) and the Sr-90 plaques – in 31.5% of cases (33 tumors). The mean doses to the tumor apex were 89 Gy for Ru-106 and 190 Gy for Sr-90 plaques, and to the tumor base were 348 Gy for Ru-106 and 757 Gy for Sr-90 plaques. Results. A complete tumor control was achieved in 87% of cases during a mean follow-up of 3.5 months. The failures after the plaque radiotherapy in 11% of cases were controlled with the thermotherapy and in 6% of cases with the repeated plaque radiotherapy. Radiation complications included nonproliferative retinopathy in 19% of cases, proliferative retinopathy – 4%, papillopathy – 11%, retinal detachment – 2%, vitreous hemorrhage – 18%, cataract – 3%, glaucoma and scleral necrosis – 0%. The mean follow-up period was 27 months (from 2 to 72 months). Conclusion. Plaque radiotherapy should be considered as an important and effective option for retinoblastoma, especially in resistant and recurrent tumors after a failure of other methods to achieve the tumor control. Complications such as radiation retinopathy and papillopathy, vitreous hemorrhage and retinal detachment should be anticipated, depending on the location, size of the tumor and previous treatment.

Upregulation of sodium iodide symporter (NIS) protein expression by an innate immunity component: Promising potential for targeting radiosensitive retinoblastoma

Retinoblastoma (RB), a malignant tumour of the eye arising from developing retina, is the most frequent primary intraocular malignancy of childhood. Its primary management with chemotherapy involves combination regimen of etoposide, vincristine and carboplatin and intra vitreal chemotherapy using melphalan when vitreous seeds develop. Radiotherapy is another effective mode in treating RB. We recently explored the notion if radiotherapy in RB can be mediated via Sodium Iodide Symporter (NIS), an intrinsic membrane glycoprotein which is a key regulator of iodide access to thyroid gland. Its expression has been exploited successfully for diagnostic imaging and molecular radionuclide-based therapy of thyroid cancer. We determined that NIS is expressed endogenously in RB tumour tissues, and in retinoblastoma cell lines Y79 and Weri-Rb-1, and therefore made an attempt to enhance the endogenously low expression of NIS protein in both Y79 and Weri-Rb-1 cells. Here we report about the potential of bovine lactoferrin (bLf) which is a known chemo preventive and emerging safe anti-cancer bio drug, as well as a natural transcriptional activator of genes, to enhance the endogenous expression of NIS in Y79 and Weri-Rb-1 cells. Real time PCR revealed that both cell lines express mRNA of lactoferrin receptors while flow cytometry and confocal microscopy showed the cells efficiently internalize bLf which upregulates NIS expression. These findings highlight an important step that could be taken towards the development of less harmful approaches for the treatment of RB by employing natural supplement bLf (with its clinically proven safe profile), and warrants further studies in future, focussing on enhancing NIS expression in RB cells and NIS functional assays in these cells.

Radiation-induced osteosarcomas after treatment for frontal gliomas: a report of two cases

Most radiation-induced osteosarcomas of the skull are reported to arise in the facial bone or paranasal sinus after radiotherapy for retinoblastoma and/or pituitary adenoma. Here we report two cases of radiation-induced osteosarcoma in the paranasal sinus after treatment for frontal glioma. Case 1 was a 56-year-old woman who underwent surgical resection of a left frontal tumor in October 1990. The histological diagnosis was a low-grade glioma, and radiotherapy of 54 Gy was administered. Sixteen years later, in September 2006, the patient noted an enlarging subcutaneous mass in the right frontal region. CT showed an osteolytic mass in the right frontal sinus. An open biopsy established the histopathological diagnosis of osteosarcoma, and the patient subsequently died of rapid tumor regrowth. Case 2 was a 58-year-old man who underwent partial removal of a bifrontal tumor in May 1996. The histological diagnosis was anaplastic oligoastrocytoma, and radiotherapy of 56 Gy was administered. Twelve years later, in March 2008, the patient was readmitted to our hospital for reasons of marked deterioration in general physical condition. Tumor recurrence was suspected in the left frontal lobe, and CT demonstrated an osteolytic mass in the left frontal and ethmoid sinus. A secondary operation was performed, and the pathological specimens were diagnosed as osteosarcoma. Radiotherapy was readministered, but the subject died of rapid tumor regrowth. From these clinicopathological findings, both cases were diagnosed as radiation-induced osteosarcoma. Radiation-induced osteosarcomas appeared 16 and 12 years after radiotherapy in cases 1 and 2, respectively. As the prognosis of radiation-induced osteosarcoma is poorer than that of primary osteo-sarcoma, careful attention is required for consideration of the long-term survival of patients with glioma.

Poster 046: Maxillary Cancer Treatment Under the CT-Navigation System

Poster 046: Maxillary Cancer Treatment Under the CT-Navigation System

Risk of Soft Tissue Sarcomas by Individual Subtype in Survivors of Hereditary Retinoblastoma

Survivors of hereditary retinoblastoma have an increased risk for second malignancies, especially soft tissue sarcomas. However, the risks of individual histologic subtypes of soft tissue sarcomas have not been evaluated. We estimated the risk for six subtypes of soft tissue sarcomas (fibrosarcoma, liposarcoma, histiocytoma, leiomyosarcoma, rhabdomyosarcoma, and others) in a cohort of 963 one-year survivors of hereditary retinoblastoma among patients diagnosed at two US institutions from 1914 through 1984. We calculated standardized incidence ratios (SIRs) for specific subtypes of soft tissue sarcomas by comparison with population data from the Connecticut Tumor Registry or from National Cancer Institute Surveillance, Epidemiology, and End Results database. We also calculated the cumulative risk for all soft tissue sarcomas combined. We observed 69 soft tissue sarcomas in 68 patients with hereditary retinoblastoma. Risks were elevated for soft tissue sarcomas overall (SIR = 184, 95% confidence interval [CI] = 143 to 233) and for individual subtypes. Leiomyosarcoma was the most frequent subtype (SIR = 390, 95% CI = 247 to 585), with 78% of leiomyosarcomas diagnosed 30 or more years after the retinoblastoma diagnosis (SIR = 435, 95% CI = 258 to 687). Among patients treated with radiotherapy for retinoblastoma, we found statistically significantly increased risks of soft tissue sarcomas in the field of radiation. Irradiated patients also had increased risks of soft tissue sarcomas, especially leiomyosarcomas, outside the field of radiation, and risks of soft tissue sarcomas were increased in nonirradiated patients as well, indicating a genetic predisposition to soft tissue sarcomas independent of radiation. The cumulative risk for any soft tissue sarcoma 50 years after radiotherapy for retinoblastoma was 13.1% (95% CI = 9.7% to 17.0%). Long-term follow-up of a cohort of survivors of hereditary retinoblastoma revealed a statistically significant excess of leiomyosarcoma and other soft tissue sarcomas that persists decades after the retinoblastoma diagnosis. Retinoblastoma survivors should undergo regular medical surveillance for sarcomas in their adult years.

Uncommon presentation of pediatric ruptured intracranial aneurysm after radiotherapy for retinoblastoma. Case report

Objective Radiation-induced intracranial aneurysms are a rare entity with high mortality. Their pathogenesis is still in debate. Their unique anatomy and behavior should be considered when deciding the proper management. A background of radiation, uncommon anatomic aspects, age of presentation, and location guide us to suspect a radiation-induced etiology. We report the case of a pediatric patient with a ruptured intracranial aneurysm, who previously received radiation therapy to the orbits. We aim to contribute to the literature of this uncommon condition and stress the importance of its prompt diagnosis and treatment. Case Description A 12-year-old boy, who received radiation therapy for recurrent bilateral retinoblastomas at age 4 months, suddenly developed severe headache associated with nausea and vomiting. A computed tomography scan revealed subarachnoid hemorrhage. A 4-vessel cerebral angiogram revealed a 2-mm aneurysm in the right A1 segment. The aneurysm was clipped successfully with excellent outcome. After 3 years of follow-up, the patient remains neurologically intact and asymptomatic. A new computed tomography angiogram revealed no new aneurysms. Conclusion Vascular abnormalities develop after radiation injury to the brain. Aneurysm formation after radiation therapy has been previously reported, probably secondary to endothelial injury. In this case, early presentation, unusual anatomy, location, and small size at rupture, in contrast with saccular aneurysms, suggest a radiation-induced etiology.

Prophylactic radiotherapy in retinoblastoma – is it really new?

Prophylactic radiotherapy in retinoblastoma – is it really new?

Mortality From Second Tumors Among Long-Term Survivors of Retinoblastoma

Children diagnosed with retinoblastoma, a rare cancer of the eye, tend to develop and die of second primary cancers in childhood and adolescence, but few investigations have followed patients into adulthood. Retinoblastoma is frequently caused by inherited mutations of the RB1 tumor suppressor gene. Most patients with germline (hereditary) mutations have bilateral disease. We sought to quantify the mortality from second malignancies among long-term survivors of retinoblastoma and to identify factors that predispose to these deaths. A retrospective cohort study examined mortality among 1603 patients enrolled at 1 year after diagnosis of retinoblastoma during the period 1914-1984. Data on demography, family history, and retinoblastoma treatment were collected by medical chart review and questionnaire interview. Number of deaths, by cause, was compared with the corresponding expected figure based on U.S. mortality data for the general population for 1925-1990. Follow-up was complete for 1458 patients (91%) for a median of 17 years after retinoblastoma diagnosis. A total of 305 deaths occurred, 167 of them from retinoblastoma. There were 96 deaths from second primary tumors (relative risk [RR] = 30), 21 from other known causes (RR = 1.0), and 21 from ill-defined or unknown causes. Statistically significant excess mortality was found for second primary cancers of bone, connective tissue, and malignant melanoma and benign and malignant neoplasms of brain and meninges. Among 919 children with bilateral retinoblastoma, 90 deaths from second primary tumors occurred (RR = 60). Deaths from second tumors were more frequent among females (RR = 39) than males (RR = 22) (P = .007). The cumulative probability of death from second primary neoplasms was 26% at 40 years after bilateral retinoblastoma diagnosis, and additional cancer deaths occurred thereafter. Radiotherapy for retinoblastoma further increased the risk of mortality from second neoplasms. An excess of mortality from a second cancer, not seen in prior studies, was found among the 684 children with unilateral disease (RR = 3.1; 95% confidence interval = 1.0-7.3). These findings implicate germinal mutations in the retinoblastoma gene in second cancer mortality. Radiotherapy treatment for retinoblastoma appears to further enhance the inborn susceptibility to development of a second cancer. Patients with retinoblastoma, particularly bilateral retinoblastoma, should have careful follow-up, and interventions should be developed to reduce mortality from a second cancer.

Radiotherapy in retinoblastoma: Indications, techniques, results and future considerations

Radiotherapy in retinoblastoma: Indications, techniques, results and future considerations

Visual results and ocular complications following radiotherapy for retinoblastoma.

Between 1956 and 1974, 28 children with retinoblastoma have been irradiated with the linear accelerator at the Stanford University Medical Center. Twenty-seven children (96%) have been cured of their tumor, with follow-up ranging from 2 1/2 to 21 years. In these survivors, 50 eyes were affected. Twelve were treated by primary enucleation and 38 were irradiated. Sixteen of the 38 irradiated eyes (42%) were ultimately enucleated for recurrent tumor, neovascular glaucoma, or inability to observe the tumor through opaque media. Thus, 22 (58%) irradiated eyes were saved. Of these, five eyes had visual acuity of 20/40 or better, five had 20/50 to 20/100, nine had 20/200 to hand motion, and three had light perception or no light perception. Radiation therapy can sterilize the tumor and maintain useful vision in many children with retinoblastoma.

Osteogenic sarcoma developing after radiotherapy for retinoblastoma

Osteogenic sarcoma developing after radiotherapy for retinoblastoma

TUMORS FOLLOWING RADIATION ABOUT THE EYE

Cases of malignant and benign tumors following radiation for retinoblastoma are discussed. A survey of 170 patients given radiotherapy for retinoblastoma showed development of secondary tumors in 9 (5.3%). All the patients but 1 received the substantial radiation dose generally recommended in the past 20 yr, the notable exception being a patient who developed a basal cell carcinoma following a dose that was of the order of 1/6 the usual dose. In 8 cases of malignant tumor reported following radiation for retinoblastoma after intervals ranging from 5 1/2 to 29 yr after treatment, the onset of a new disease was heralded by the appearance of a mass in or near the radiated areas. Most were subcutaneous, but one of these lay behind the eye and resulted in exophthalmos. A subcutaneous mass was the presenting complaint in 7 of 10 cases. An additional 9 patients with malignant tumor following radiation for retinoblastoma ranged in age from 7 to 30 yr; 8 of these were 16 yr old or younger. The interval between initial treatment and postradiation neoplasm ranged from 4 to 26 hr. In all but 1 case, the postradiation neoplasm occurred within 18 yr. The average interval of appearance formore » osteosarcoma was 6.5 yr; for rhabdomyosarcoma, fibrosarcoma, mesenchymoma, and undifferentiated sarcoma, 12 yr; for chondrosarcoma, 9 yr; and for carcinoma, 15 yr. Three additional adult cases are repprted concerning skin lesions that occurred following radiation in the area of the eye. (TCO)« less