Family History Of Retinoblastoma Research Articles

Retinoblastoma in Turkey: survival and clinical characteristics 1981–2004

In this study, the authors aim to describe the survival and clinical characteristics of 141 retinoblastoma cases treated at Cerrahpasa Medical Faculty, University of Istanbul, Istanbul, Turkey, between 1981 and 2004. The authors retrospectively analyzed the clinical records of 141 children (177 eyes) diagnosed with retinoblastoma and treated between 1981 and 2004. Information on gender, laterality, age at diagnosis, presenting signs, spread of tumor, treatment modality, survival rate, and family history were collected. A total of 105 cases (74.5%) were unilateral and 36 cases (25.5%) were bilateral. The mean age overall at the time of diagnosis was 25 months; in unilateral cases, 29 months; and in bilateral cases, 16 months. The most common presenting signs were leukocoria (116 cases, 82%), strabismus (14 cases, 10%) and proptosis (11 cases, 8%). A total of 28 cases had orbital extension, nine patients had central nervous system invasion, and five cases exhibited bone marrow involvement. In total, 16 patients (11%) had a family history of retinoblastoma. One case developed a secondary neoplasm. The 3 year cumulative survival rate of 141 patients was 89.69% (unilateral, 90.74%; bilateral 87.35% P = 0.9371, P > 0.05, log rank test). The study's survival rate was similar to developed countries. The success in higher survival rates is based on the authors multidisciplinary team approach done by the same group and the support of the authors' clinic and government in sponsoring the medical insurance of all patients.

Lack of Efficacy of Dilated Screening for Retinoblastoma

To assess red reflex testing of the pharmacologically dilated pupil in screening for retinoblastoma. Children with a family history of retinoblastoma or a history of treated retinoblastoma who were admitted to our institution for examination using anesthesia during a 3-month period underwent red reflex testing of the pharmacologically dilated pupil in a masked fashion. Red reflexes were classified as normal (unremarkable), abnormal (in brightness or color), or absent (no reflex, black pupil). The results of the screenings were later compared with actual retinal findings. Red reflex testing of the dilated pupil failed to identify all 13 eyes that harbored retinoblastoma lesions (all 13 were classified as normal). The 3 eyes that were identified as having abnormal red reflexes had neither disease nor significant refractive error. Red reflex testing of the dilated pupil is a poor screening technique for retinoblastoma.

Sensitive multistep clinical molecular screening of 180 unrelated individuals with retinoblastoma detects 36 novel mutations in theRB1 gene

Retinoblastoma (RB) is a neoplasm of retinal origin caused by mutations in RB1, the retinoblastoma tumor suppressor gene. To facilitate genetics counseling and patient management, we adopted a multistep molecular screening assay for detecting RB1 mutations. This assay included DNA sequencing to identify mutations within coding exons and immediate flanking intronic regions, Southern blot analysis to characterize genomic rearrangements, and transcript analysis to characterize potential splicing mutations buried within introns. In a pilot investigation of 180 patients from North America, we identified germline RB1 mutations in 77 out of 85 bilateral RB patients (91%), 7 out of 10 familial unilateral (70%), and 6 out of 85 unilateral patients with no family history of RB (7%). Mutations included 36 novel alterations spanning the entire RB1 gene. Seven of these novel changes were missense or silent mutations. Sequence analysis predicted that, in five out of seven cases, the changes can cause aberrant splicing. This was confirmed by transcript analysis in four out of five cases. In addition, four intronic point mutations within nonconsensus sites activated cryptic splice sites. Without the transcript analysis, the significance of these 11 mutations would have remained undefined. In a separate investigation of a subset of unilateral RB tumors, we identified somatic biallelic RB1 gene inactivation in 34 out of 56 cases (61%) cases. In 14 tumors, only one of the two RB1 mutations could be detected, and in eight tumors, no mutations were detected. The absence of detectable RB1 mutations in eight bilateral cases and eight unilateral tumors suggests that alternative genetic mechanisms may underlie the development of RB in certain individuals.

Screening for retinoblastoma: presenting signs as prognosticators of patient and ocular survival.

To correlate 3 common presenting signs of retinoblastoma with patient and ocular survival and to assess the efficacy of current pediatric screening practices for retinoblastoma. A retrospective study was conducted of 1831 retinoblastoma patients from our center (1914-June 2000). Patient survival (excluding deaths from other primary neoplasms) and ocular survival (presenting eyes) rates were calculated and analyzed using the Kaplan-Meier method. Leukocoria correlated with excellent patient survival (>86%, 5 years) but poor ocular survival in unilateral (4%, 5 years) and bilateral patients (29%, 5 years). A total of 308 (19%) of 1654 patients presented with strabismus: patient survival was excellent (90%, 5 years), and ocular survival was poor (17%, 5 years) yet better than leukocoria. Patients who had a family history of retinoblastoma and were clinically screened for retinal tumors from birth were diagnosed younger (8 months of age) and earlier (Reese Ellsworth group 1 = 26 [58%] of 45) and had better ocular survival than nonscreened patients with a family history. More patients were initially detected by family/friends (1315 [80%] of 1632) than pediatricians (123 [8%] of 1632) or ophthalmologists (156 [10%] of 1632). Most US children whose retinoblastoma is diagnosed initially present with leukocoria detected by a parent, despite routine pediatric screening for leukocoria via the red reflex test. Initial disease detection at the point of leukocoria or strabismus correlated with high patient survival rates and poor ocular survival rates for the presenting eye. Saving eyes and vision requires disease recognition before leukocoria, as demonstrated by the better ocular salvage rate among patients who had a positive family history and received clinical surveillance via early, routine dilated funduscopic examinations by an ophthalmologist.

Development of new retinoblastomas after 6 cycles of chemoreduction for retinoblastoma in 162 eyes of 106 consecutive patients.

To evaluate the occurrence of new retinoblastomas in patients treated with 6 cycles of chemoreduction. Prospective nonrandomized single-center case series. Ocular Oncology Service at Wills Eye Hospital of Thomas Jefferson University, Philadelphia, Pa, in conjunction with the Division of Oncology at The Children's Hospital of Philadelphia. A total of 162 eyes of 106 patients with retinoblastoma treated with 6 cycles of chemoreduction between January 1, 1995, and May 31, 2002. All patients received intravenous chemoreduction with vincristine sulfate, etoposide, and carboplatin, combined with focal treatment (cryotherapy or thermotherapy) to each retinal tumor. Development of new intraretinal retinoblastoma during or after treatment with chemoreduction. Recurrent subretinal tumor seeds or vitreous seeds were excluded from this analysis, and only primary new intraretinal tumors were included. Of 28 patients with unilateral retinoblastoma, new intraretinal tumor development was found during or after chemoreduction in 2 (9%) of the 23 patients with sporadic disease and 4 (80%) of the 5 patients with familial disease. The new tumor was located in the macula in none, between the macula and equator in 7 (54%), and between the equator and ora serrata in 6 (46%). Of the 78 patients with bilateral retinoblastoma, new tumor development was found during or after chemoreduction in 11 (19%) of the 57 patients with sporadic disease and 8 (38%) of the 21 patients with familial disease. The new tumor was macula in 2 (4%), between the macula and equator in 30 (55%), and between the equator and ora serrata in 23 (42%). Overall, according to Kaplan-Meier analysis, new tumor development occurred in 23% of patients by 1-year follow-up and 24% by 5-year follow-up. By multivariate analysis, the most important risk factors for the development of new tumors was younger age at presentation (median age, 2 months with new tumor vs 9 months without new tumor) and family history of retinoblastoma (12 [48%] of patients with new tumor vs 14 [17%] without new tumor). Children with retinoblastoma treated with chemoreduction should be followed for new intraretinal tumor development, as it peaks at a mean interval of 5 months after initiation of chemoreduction and affects 24% of patients by 5 years of follow-up. New tumors are most commonly found in those who develop disease as young infants and those with a family history of retinoblastoma.

Retinoblastoma in Taiwan: Survival and Clinical Characteristics 1978–2000

Purpose: Few estimates of the survival rates ofwas retinoblastoma have been reported from the Asia region. In this study, we aim to describe the survival and clinical characteristics of 96 retinoblastoma cases treated at Chang Gung Medical Center, Taipei, between 1978 and 2000. Methods: We retrospectively analyzed the clinical records of 96 children (116 eyes) diagnosed with retinoblastoma and treated between 1978 and 2000. Information on sex, laterality, age at diagnosis, presenting signs, spread of tumor, treatment modality, survival rate, and family history were collected. Results: Seventy-six (79.2%) cases were unilateral and 20 (20.8%) were bilateral. The mean age overall at the time of diagnosis was 24.7 months; in unilateral cases, 27.1 months; and in bilateral cases, 15.6 months. The most common presenting signs were leukocoria (75 cases, 78.1.0%), buphthalmos (34 cases, 35.4%), proptosis (16 cases, 16.7%), and strabismus (12 cases, 12.5%). Forty-two eyes had orbital extension, 27 patients had central nervous system invasion, 16 cases exhibited bone marrow involvement, and 3 cases had liver metastasis. Three (3.1%) patients had a family history of retinoblastoma. None of the cases developed a secondary neoplasm. The 3-year cumulative survival rate of the 96 patients was 64.41% (unilateral, 71.97%; bilateral 40.01%). Conclusions: The mortality was much higher than that in reports on Western and Japanese patients. Delayed diagnosis with frequent extraocular spread at the time of diagnosis caused the low survival rate. Fewer familial cases were encountered in our study than in other studies.

Clinicopathologic study of retinoblastoma including MIB-1, p53, and CD99 immunohistochemistry.

Retinoblastoma is the most common intraocular tumor of childhood and has served as a model for the understanding or tumorigenesis. This study retrospectively examines the clinicopathologic features of 19 retinoblastomas and defines the MIB-1 (cell proliferation marker), p53 (tumor suppression gene), and CD99 (HBA71 or MIC2 antibody) immunoreactivity in 10 selected cases. Nineteen patients (11 boys), ranging in age from 6 to 47 months (mean, 20 months), were included for study. Clinical presentations included: leukocoria (n = 12), strabismus (n = 6), apparent decreased visual acuity (n = 5), and proptosis (n = 1). Five patients had bilateral tumors and one neoplasm arose in a patient with a known family history of retinoblastoma. All tumors were histologically characterized by a proliferation of small cells with high nuclear-to-cytoplasmic ratios. Commonly encountered histologic features included necrosis (n = 17, 89%), calcification (n = 16, 84%), fleurettes (n = 14, 74%), and Flexner-Wintersteiner rosettes (n = 11, 58%). Retinal involvement was noted in 18 tumors (95%) and optic nerve invasion in six cases (32%). The surgical optic nerve margin was positive in one case. Mitosis counts were evaluable in 18 cases and ranged from 1 to 42 mitotic figures/10 high power field (mean, 13 mitotic figures/10 high power field). Ten tumors were evaluated with MIB-1, p53, and CD99 antibodies by paraffin immunohistochemistry. MIB-1 labeling indices ranged from 31.4 to 77.1 (mean, 49.4). p53 immunostaining was observed in six tumors; less than 10% of tumor cells were noted to be p53 positive in each case. CD99 positivity was demonstrable focally in three tumors. Adjuvant chemotherapy and/or radiation therapy was administered in six patients. Tumor recurrence was not observed in any of the patients with a mean follow-up of 8.9 years. Only one patient died (20 years after enucleation) because of metastatic osteosarcoma. (1) Fleurettes and Flexner-Wintersteiner rosettes are variable findings in retinoblastoma. (2) Retinoblastomas are characterized by marked cell proliferation as evidenced by generally high mitosis counts and extremely high MIB-1 labeling indices, but this does not appear to adversely impact on prognosis. (3) Unlike peripheral primitive neuroectodermal tumors, most retinoblastomas do not stain positively with antibody to CD99. (4) Limited p53 immunostaining was present in 60% of tumors studied. (5) Enucleation with negative optic nerve margin is potentially curative in patients with retinoblastoma.

The Development of Young Children With Retinoblastoma

To assess the health and development of children with retinoblastoma (RB), or cancer of the retina, and to determine if they are at greater risk for developmental delays than normal children. Specific aims were to determine if type of RB (unilateral vs bilateral), family history, and number of treatment types affected mental and motor development. Descriptive study based on medical record review and pediatric, psychological, and visual evaluations. Major referral center for patients with RB and early intervention program in a voluntary urban hospital. Fifty-four children younger than 41 months with RB who attend an ophthalmology oncology clinic were recruited for study. Measures included demographic variables such as social class and race/ethnicity, and medical factors such as age at diagnosis (<18 months vs >18 months), type of RB (unilateral or bilateral), family history of RB, and number and types of treatments. All children received a pediatric examination that assessed physical growth and health; a behavioral test of visual acuity using Teller acuity cards; and the Bayley Scales of Infant Development II, a standardized test of mental and motor development. Children found to have delays were referred to intervention services to treat their specific areas of weakness. Three quarters of the children had had 1 eye enucleated; 51 of 54 had normal vision in at least 1 eye, and the other 3 had partial vision in 1 eye. Except for the RB, 46 children were largely normal in growth and health, and 8 had medical diagnoses that were unrelated to RB or its treatment. The average mental and motor development scores were in the normal range (91.4 +/- 16.3, and 91.1 +/- 13.4) and not significantly lower than the normal population. Twenty-six children were referred for early intervention services, and 21 of 26 were referred for services to improve their visuomotor coordination. Demographic variables were not associated with medical variables or outcome. Children with bilateral RB, in which both eyes are affected, performed significantly less well in motor development, received many more types of treatments, and were more likely to be referred for visuomotor therapy than children with unilateral RB. Children with RB generally function normally in terms of physical health and mental and motor development. However, they are more likely to show delays in visuomotor integration. Early developmental evaluations may improve the visuomotor development of children with visual impairment due to RB.

Neonatal neoplasms

Purpose: To describe neoplasms diagnosed in children ≤ 28 days of age along with their treatment, associated congenital anomalies, and the long-term consequences of the diagnoses and treatments. Methods and Materials: Utilizing autopsy records, a computerized tumor registry, and medical records, we identified patients and stillborns at Duke University Medical Center (DUMC) diagnosed with neoplasms at ≤ 28 days of age between 1930 and 1998. Results: Twenty-three neonates with neoplasms were identified. There were 7 males (30%) and 16 females (70%). Follow-up of survivors ranged from 4 months to 27 years (mean 9 years). The 20 patients identified via the computerized registry system for 1980–1998 constitute 2% (20/925) of all neoplasms seen in patients ≤ 16 years of age over this same time period at DUMC. The histologic diagnoses were teratoma/germ cell tumor ( n = 8, 35%), neuroblastoma ( n = 5, 22%), retinoblastoma ( n = 4, 17%), primary central nervous system (CNS) tumor ( n = 3, 13%), and one case each of rhabdomyosarcoma, glossal glial choristoma, and hemangioma in the setting of Kasabach-Merritt Syndrome. Of the eight teratoma/germ cell tumor patients, 6 were female (75%) and 2 male (25%). There was one malignant germ cell tumor, 2 immature teratomas, and 5 teratomas. Two of the seven patients with immature teratomas or teratoma were long-term survivors following surgery. The one patient with malignant germ cell tumor, treated with surgery and chemotherapy, died. Associated anomalies were imperforate anus, congenital absence of a limb, left ventricular hypertrophy, fusion or absence of toes, coarctation of the aorta, and pulmonary valve dysplasia. Of the five children with neuroblastoma, 4 were female. INSS Stages were 1 ( n = 1), 2A ( n = 1), 3 ( n = 1), and 4S ( n = 2). Two were treated with surgery + chemotherapy + radiotherapy; two with surgery + chemotherapy; and one with surgery alone. Four children are long-term survivors. Associated congenital anomalies and medical problems were ventricular septal defect, seizure disorder, and Fanconi’s anemia. A child with a dumbbell neuroblastoma, treated with surgery and chemotherapy, is paraplegic. Of the four children with retinoblastoma, two were female. Two had trilateral disease and two bilateral. Three of the four had a family history of retinoblastoma. The two children with trilateral retinoblastoma died after therapy with surgery, craniospinal and orbital irradiation, and chemotherapy. Two children with bilateral disease are long-term survivors: one treated with radiotherapy + chemotherapy and one with radiotherapy alone. They have marked orbital bone growth abnormalities. The three patients with CNS tumors were female. The histologies were glioblastoma multiforme, anaplastic astrocytoma, and malignant mixed oligodendroglioma. Two of the patients are long-term survivors after surgery + chemotherapy. Six children received eight courses of radiation therapy: 2 for Stage 4S neuroblastoma with respiratory compromise from an enlarging liver and 4 for retinoblastoma. The two infants with trilateral retinoblastoma received two courses of irradiation each: one of the treatment of intraocular tumor and a second, at an older age, for the pineal tumor. The most serious complication of anesthesia was a case of enterobacter cloacae sepsis in the central venous access line used for repetitively administering the anesthetic. Conclusion: The most common neonatal neoplasm histologic diagnoses are teratoma/germ cell tumor, neuroblastoma, and retinoblastoma. Neonatal neoplasms may be associated with congenital anomalies. Radiation therapy is administered infrequently in a population highly susceptible to late ill effects. When radiotherapy is required, anesthesia may be repetitively administered to aid in reproducible treatment.

Incidence and survival characteristics of retinoblastoma in Singapore from 1968-1995.

To describe the incidence and survival of 69 Singapore residents with retinoblastoma in all Singapore hospitals from 1968-1995. Data of all Singapore residents diagnosed with retinoblastoma from 1968-1995 were collected by the Singapore Cancer Registry based on notifications from physicians, pathology records, hospital discharge records, and death certificates. The medical records of 46 patients were traced, and information on laterality of tumor, spread of tumor, mode of treatment, and family history of retinoblastoma was obtained. Time trends and survival characteristics of the cohort were described. The incidence rate of retinoblastoma was 2.4 per 1 million for children <9 years and 11.1 per 1 million for children <5 years. The incidence of retinoblastoma has been almost uniform over time from 1968-1995, except for an apparent increase in 1988-1992. The 3-year survival rate for retinoblastoma was 83%. Survival rates were higher in children <2 years because children who present at a younger age may have tumors diagnosed at earlier stages of the disease. There was no difference in survival rates for sex, race, laterality, family history of retinoblastoma, treatment, or year of diagnosis. Retinoblastoma is the most common eye cancer in children that may cause blindness or death. The incidence rates of retinoblastoma in Singapore have remained fairly stable over 28 years, and the survival rate is higher in younger children. This study will be helpful in monitoring future disease patterns in Asian populations.

Observations on 17 patients with retinocytoma.

To study the clinical features and natural history of 17 patients with retinocytoma. A retrospective case series. Tertiary referral center. Data on 17 patients with retinocytoma were reviewed for clinical features. The natural history of retinocytoma and its risk for malignant transformation were also evaluated. Among 920 consecutive patients who had retinoblastoma, retinocytoma, or both, we identified 24 tumors in 17 patients (1.8%) with clinical features compatible with retinocytoma. The median age at diagnosis was 15 years (range, 4-45 years). Of the 24 tumors, the retinocytoma was bilateral in 3 cases (13%) and the family history of retinoblastoma was positive in 3 cases (13%). Seventeen (71%) of the tumors were extramacular in location, and 7 (29%) were located in the macular area. Ophthalmoscopic features characteristic of retinocytoma included the presence of a translucent retinal mass in 21 (88%), calcification in 15 (63%), and retinal pigment epithelial alteration in 13 (54%) of the 24 tumors. A combination of all 3 features was observed in 8 (33%) of the 24 tumors. In 13 (54%) of the tumors, a zone of chorioretinal atrophy could be observed. In 1 patient, subtle tumor regression was documented photographically. Only 1 retinocytoma (4%) underwent malignant transformation into retinoblastoma. At the last follow-up visit, none of the patients had developed a pineoblastoma or another second malignant neoplasm. Retinocytoma is a rare benign retinal tumor that has characteristic clinical features. The areas of chorioretinal atrophy were suggestive of tumor regression. In our series, the risk for malignant transformation of retinocytoma into retinoblastoma was 4%; therefore, patients with a presumed diagnosis of retinocytoma should be closely observed.

Client advocacy and collaboration with insurance and laboratory testing agencies: a case study illustrating genetic counselor roles.

AbstractGenetic counseling and the many roles a genetic counselor must assume to provide quality genetic health care are becoming increasingly complex, especially when the genetic condition is rare, and DNA testing is costly and not yet routinely used. A case study of a couple with a family history of retinoblastoma and their pursuit of DNA testing for prenatal diagnosis is presented. The case study illustrates the instrumental role of the genetic counselor in advocating for clients for genetic services such as DNA testing and in educating insurance companies in the nature and importance of such services to achieve improved client health care outcomes.

Familial retinoblastoma: where and when?

To determine when patients with a family history of retinoblastoma and previously normal eye exam develop intraocular disease, and where the new retinoblastoma tumors occur. A retrospective chart review of retinoblastoma patients. Sixty-two percent of the first eyes (eyes having a previously normal examination) were diagnosed with retinoblastoma by 6 months of age, 90% by 12 months and 100% by 28 months. For the second eye, 27% were identified by 6 months, 64% by 12 months, 91% by 30 months and 100% by 44 months. The younger the age at initial diagnosis of retinoblastoma, the greater the likelihood that tumors will initially be found in the posterior pole. Macular tumors were diagnosed very early (mean 4 months) and once a retinoblastoma focus had appeared in one eye no new tumors developed in the macula of either eye. The timing, location, and number of new retinoblastoma tumors follows a predictable pattern.

Retinoblastoma: Problems and Perspectives from India

This study examined the salient clinical and epidemiological characteristics of retinoblastoma (RB) in India, thereby highlighting the problems encountered there. The epidemiological characteristics of 296 patients with RB over 8 years were evaluated using hospital records and postal follow-ups. Unilateral disease was seen in 61.8% of patients. The overall median age at presentation was 3.5 years (3.5 years for unilateral RB and 1.0 years for bilateral RB). The male/female ratio was 1.4:1. The median duration of symptomatic disease was 8 months. Consanguineous marriage was seen in 17% and family history of RB was noted in 1.7% cases. Also, 2 % had a history of other malignancy in the family. Associated congenital malformation was seen in 10.5% of cases. A second malignancy was seen in 0.67% of cases at a mean duration of 4.5 years after completion of therapy. A predominance of advanced-stage disease (74.5% had Reese-Ellsworth group TV and V disease) was seen in our series. Only 43.6% of patients had disease localized to the globe without any infiltration/invasion. The majority of cases had advanced-stage disease at presentation and came from the underprivileged class of society. Patients with bilateral RB presented much earlier than those with unilateral disease. In patients with unilateral RB, higher age at presentation as well as advanced disease may be related to much delay in seeking medical attention. In view of the advanced stage at presentation, there also exist a possibility of difference in the biology of the tumor seen in these patients.

Retinoblastoma in Turkey: diagnosis and clinical characteristics.

Retinoblastoma (RB) is the most frequent malignant intraocular tumor in childhood. Six hundred and thirty-six cases with 831 RB-affected eyes were diagnosed and treated in our specialist center between 1963-1994. The diagnosis was made by histopathologic examination in 617 cases and clinically in 19 cases. Four hundred and forty-one (69.3%) cases were unilateral and 195 (30.7%) were bilateral. Two hundred and sixty-eight (42.1%) were females and 368 (57.9%) were males. The youngest patient was 20 days old and the oldest was 16 years old at the time of diagnosis (mean: 2.2 years). In thirty-four (5.3%) cases, a family history of RB was present. Ten of these cases were unilateral and 24 were bilateral. The most frequent presenting signs were leukocoria (394 cases, 61.9%), buphthalmos (92 cases, 14.5%), and strabismus (68 cases, 10.7%). The referring initial diagnoses were correct in 519 (81.6%) cases and false-negative in 117 (18.4%) cases. The most frequent initial false-negative diagnoses of the referring physicians were buphthalmos (43 cases, 6.8%), endophthalmitis (37 cases, 5.8%), and retinal detachment (12 cases, 1.9%). Apart from these 636 cases, there were 29 false-positive RB diagnoses during the same study period for which enucleation was performed. False-positive diagnoses included endophthalmitis (9 cases), retinal dysplasia (6 cases), retinal detachment (5 cases), vitreous hemorrhage (4 cases), Coats' disease (4 cases), and toxocariasis (one case). Ancillary testing for metastasis was carried out in all cases with newly diagnosed retinoblastoma. Five hundred and ninety-eight (72%) eyes had intraocular disease and 233 (28%) had extraocular spread. Of these 233 RBS, 58 had systemic disease. Fifty-two out of 58 tumors showing systemic involvement had either optic nerve or extrascleral extension at the histopathologic examination of enucleation material. The remaining six eyes had intraocular Class IV-V RB.

Asynchronous bilateral retinoblastoma: the St. Jude Children's Research Hospital experience.

Between May 1962 and July 1993, 172 children presented at the St. Jude Children's Research Hospital for evaluation and/or treatment of retinoblastoma (RB). Of these, 65 presented with bilateral disease, while 107 had unilateral tumors. Of these 107 patients, nine subsequently developed RB in the unaffected eye. Initial age at diagnosis of these nine patients ranged from 3 weeks to 24 months (median = 2 months); five of the nine had a family history of RB at the time of initial diagnosis and one patient, without a family history of RB, presented with unilateral multiple tumors indicating inheritance of a germinal mutation and increased risk of RB development in the companion eye. Time to development of companion eye RB was 1-61 months postinitial diagnosis. Treatment of the initial eye included enucleation (n = 4), chemotherapy (n = 3), irradiation (n = 7), or a combination of these three modalities. Reese-Ellsworth grouping of the companion eye disease included I A (n = 7), III A (n = 1), and IV A (n = 1). Treatment of the second affected eye included irradiation in seven patients, cryotherapy in four, and chemotherapy in three. No companion eye has required enucleation to date. At last followup, 14/18 eyes remain intact. There have been no cases of metastatic dissemination; however, one patient has developed a second malignant neoplasm outside the field of irradiation. Eight of the nine patients remain alive. This experience reinforces the need for close follow-up of patients diagnosed with unilateral RB, especially those with a family history of RB and those with unilateral multiple tumors.

Second malignant neoplasms in children with retinoblastoma: the St. Jude Children's Research Hospital experience.

A retrospective review of 172 children with primary diagnosis of retinoblastoma (RB) was completed at St. Jude Children's Research Hospital to evaluate the incidence of second malignant neoplasm (SMN) development. Sixty-five patients presented with bilateral RB and 107 with unilateral RB. During follow-up, which ranged from 6 to 340 months (median = 170 months), 6 children (3.5%) developed SMN. All patients who developed SMN presented with bilateral disease (n = 5) or asynchronous bilateral disease (n = 1); two patients had a family history of RB. All had received irradiation. Four patients developed osteogenic sarcoma within this irradiated volume, one developed a basal cell carcinoma in the temporal region (within the irradiation field), and one was diagnosed with a lower extremity Ewing's sarcoma. Time to development of SMN ranged from 125 to 194 months post-irradiation. Initial irradiation total dose ranged between 32 and 45.76 Gy. Three patients were treated with anterior field irradiation and three received lens-sparing techniques (anterior/lateral n = 2, lateral n = 1). At last follow-up, 4/6 patients had died of SMN. The crude incidence is 3.5% with an estimation of risk using the density method of 24% at 20 years for SMN development. The specifics of the treatment associated with these second malignancies and the possible reasons for the reported incidence of SMN will be discussed.

Trilateral retinoblastoma-incidence and outcome: A decade of experience

Purpose : This report examines the incidence and outcome of trilateral retinoblastoma in children treated for retinoblastoma. A group of patients who are at highest risk for the development of trilateral retinoblastoma is defined. Methods and Materials : Between 1979 and 1990, 117 children were treated with external beam radiation therapy for retinoblastoma, ( 97 117 , bilateral). Median follow-up time was 68 months. The median age at diagnosis was 7 months. Results : Six cases of trilateral retinoblastoma were identified. The incidence of trilateral retinoblastoma in children with bilateral retinoblastoma was 6% ( 6 97 ) and 10% in those with a family history of retinoblastoma. The median age at diagnosis of RB in the children with trilateral retinoblastoma, was 3 months, younger than the median age of the entire retinoblastoma group. In all cases, the pineal region was excluded from the radiotherapy fields. Treatment for the trilateral retinoblastoma consisted of craniospinal axis radiation therapy and chemotherapy in three patients, chemotherapy alone in two, and no treatment in one. All patients died from this disease. Overall, of the 117 children treated at our institution for retinoblastoma with a median follow-up of 68 months, 12 have died. Trilateral retinoblastoma was the major cause of death, accounting for 50% ( 6 12 ) of deaths. Conclusion : Trilateral retinoblastoma is a major and under-appreciated cause of mortality in the first 5 years after the diagnosis of bilateral retinoblastoma. A more aggressive approach toward screening a defined population of childhood retinoblastoma survivors may be warranted.

Recurrence of unilateral retinoblastoma following radiation therapy.

A retrospective analysis of 65 unilateral retinoblastoma patients treated initially with external beam radiation, revealed that 25 eyes (38.5%) developed local recurrence of retinoblastoma. The mean age at diagnosis was 1.8 years for patients who developed recurrences vs. 0.9 years for those who did not. Ninety-six percent of the recurrences occurred less than two years from the age at diagnosis; the amount of time from the end of external beam radiation treatment until a tumor recurred was independent of the age at diagnosis. The initial largest basal diameter was 10.7 DD for tumors which later recurred and 5.9 DD for tumors that were cured. Sixty-nine percent of eyes in groups III-V had tumor recurrence, and 10% of eyes in groups I-II had recurrence. All but one eye (24 eyes) that developed recurrence were enucleated. Family history of retinoblastoma, location of the tumor, gender, and laterality did not significantly correlate with the mean age of initial diagnosis for tumors that recurred or the mean time of onset for recurrence.

Current Management of Retinoblastoma

The recommended management of retinoblastoma based on personal experience with the assessment and treatment of more than 450 children with this intraocular malignant lesion is presented. Although retinoblastoma is usually managed by enucleation, the treatment of each case must be individualized; in an increasing number of children, the techniques of irradiation, photocoagulation, or cryotherapy are being used. In some patients, a combination of these techniques is necessary. Chemotherapy is often used to prevent distant metastatic involvement, although its effectiveness as a prophylactic treatment has not been clearly established. Because metastatic retinoblastoma is often fatal, intense chemotherapy is recommended in this setting. The prognosis for vision and life in patients with retinoblastoma has improved considerably during the past century, primarily because of earlier recognition of the tumor and use of modern therapeutic methods. All children of parents with a family history of retinoblastoma should be examined by a qualified ophthalmologist immediately after birth in order to detect and treat this condition as early as possible.