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This information is produced and provided by the National Cancer Institute (NCI). The information in this topic may have changed since it was written. For the most current information, contact the National Cancer Institute via the Internet web site at http://cancer.gov or call 1-800-4-CANCER.
Fortunately, cancer in children and adolescents is rare, although the overall incidence of childhood cancer has been slowly increasing since 1975.[1] Children and adolescents with cancer should be referred to medical centers that have a multidisciplinary team of cancer specialists with experience treating the cancers that occur during childhood and adolescence. This multidisciplinary team approach incorporates the skills of the following health care professionals and others to ensure that children receive treatment, supportive care, and rehabilitation that will achieve optimal survival and quality of life:
(Refer to the PDQ Supportive and Palliative Care summaries for specific information about supportive care for children and adolescents with cancer.)
Guidelines for pediatric cancer centers and their role in the treatment of pediatric patients with cancer have been outlined by the American Academy of Pediatrics.[2] At these pediatric cancer centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate in these trials is offered to most patients/families. Clinical trials for children and adolescents with cancer are generally designed to compare potentially better therapy with therapy that is currently accepted as standard. Most of the progress made in identifying curative therapies for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI Web site.
Dramatic improvements in survival have been achieved for children and adolescents with cancer.[1,3,4] Between 1975 and 2010, childhood cancer mortality has decreased by more than 50%.[1,3,4] Childhood and adolescent cancer survivors require close follow-up because cancer therapy side effects may persist or develop months or years after treatment. (Refer to the PDQ summary on Late Effects of Treatment for Childhood Cancer for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors.)
Retinoblastoma is a relatively uncommon tumor of childhood that arises in the retina and accounts for about 3% of the cancers occurring in children younger than 15 years. The estimated annual incidence in the United States is approximately 4 cases per 1 million children younger than 15 years. Although retinoblastoma may occur at any age, it most often occurs in younger children; the annual incidence is 10 to 14 cases per 1 million in children aged 0 to 4 years. Ninety-five percent of cases are diagnosed before age 5 years, and two-thirds of these cases occur before age 2 years. Older age is usually associated with more advanced disease and a poorer prognosis.[5]
Heritable and Nonheritable Forms of Retinoblastoma
Retinoblastoma is a tumor that occurs in heritable (25% to 30%) and nonheritable (70% to 75%) forms. Heritable disease is defined by the presence of a positive family history, multifocal retinoblastoma, or an identified germline mutation of the RB1 gene. This germline mutation may have been inherited from an affected progenitor (25%) or may have occurred in utero at the time of conception in patients with sporadic disease (75%). Heritable retinoblastoma may manifest as unilateral or bilateral disease. The penetrance of the RB1 mutation (laterality, age at diagnosis, and number of tumors) is probably dependent on concurrent genetic modifiers such as MDM2 and MDM4.[6,7] Approximately 85% of patients with unilateral retinoblastoma do not have the heritable form of the disease, whereas all children with bilateral disease are presumed to have the heritable form, even though only 25% have an affected parent. In heritable retinoblastoma, tumors tend to be diagnosed at a younger age than in the nonheritable form of the disease. Unilateral retinoblastoma in children younger than 1 year raises concern for heritable disease, whereas older children with a unilateral tumor are more likely to have the nonheritable form of the disease.[8,9]
Children with the heritable form of retinoblastoma may continue to develop new tumors for a few years after diagnosis and treatment; for this reason, they need to be examined frequently for the development of new tumors. It is recommended that they be examined every 2 to 4 months for at least 28 months.[10] The interval between exams is based on the age of the child (less frequent visits as the child ages) and the stability of the disease.
Early-in-life screening by fundus exams under general anesthesia at regular intervals, according to a schedule based on the absolute estimated risk, can improve prognosis in terms of globe sparing and use of less-intensive, ocular-salvage treatments in children with a positive family history of retinoblastoma.[11] Because a proportion of children who present with unilateral retinoblastoma will eventually develop disease in the opposite eye, periodic examinations of the unaffected eye are performed until the germline status of the RB1 gene is determined.
The parents and siblings of patients with retinoblastoma should have screening ophthalmic examinations to exclude an unknown familial disease. Siblings should continue to be screened until age 3 to 5 years or until it is confirmed that they do not have a genetic mutation.
Blood and/or tumor samples can be screened to determine if a patient with retinoblastoma has a mutation in the RB1 gene. Once the patient's genetic mutation has been identified, other family members can be screened directly for the mutation. The RB1 gene is located within the q14 band of chromosome 13. Exon by exon sequencing of the RB1 gene demonstrates germline mutation in 90% of patients with heritable retinoblastoma.[12,13,14] Although a positive finding with current technology confirms susceptibility, a negative finding cannot absolutely rule it out.[15] A multistep assay including 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 may need to be performed for a complete genetic evaluation of the RB1 gene.[15] In cases of somatic mosaicism or cytogenetic abnormalities, the mutations may not be easily detected, and more exhaustive techniques such as karyotyping, multiplex ligation-dependent probe amplification, fluorescence in situ hybridization, and methylation analysis of the RB1 promoter may be needed. The absence of detectable RB1 mutations in some patients may suggest that alternative genetic mechanisms may underlie the development of retinoblastoma.[16] In a report of 29 patients with clinical retinoblastoma and no evidence of a RB1 mutation, 15 demonstrated high levels of MYCN amplification. These patients had distinct, aggressive, histologic features and a median age at diagnosis of 4 months.[17]
Genetic counseling is an integral part of the management of patients with retinoblastoma and their families, regardless of clinical presentation;[18] counseling assists parents in understanding the genetic consequences of each form of retinoblastoma and in estimating the risk of disease in family members.[14,18] Genetic counseling, however, is not always straightforward. Families with retinoblastoma may have a founder mutation with embryonic mutagenesis causing genetic mosaicism of gametes.[19] A significant proportion (10%–18%) of children with retinoblastoma have somatic genetic mosaicism,[20,21] making the genetic story more complex and contributing to the difficulty of genetic counseling.[15]
(Refer to the PDQ summaries on Cancer Genetics Risk Assessment and Counseling and Cancer Genetics Overview for more information.)
Factors Influencing Mortality
The present challenge for those who treat retinoblastoma is to preserve life and to prevent the loss of an eye, blindness, and other serious effects of treatment that reduce the life span or the quality of life. With improvements in the diagnosis and management of retinoblastoma over the past several decades, metastatic retinoblastoma is observed less frequently in the United States and other developed nations. As a result, other causes of retinoblastoma-related mortality in the first decade of life, such as trilateral retinoblastoma and subsequent neoplasms (SNs), have become significant contributors to retinoblastoma-related mortality. In the United States, before the advent of chemoreduction as a means of treating bilateral (heritable) disease, trilateral retinoblastoma contributed to more than 50% of retinoblastoma-related mortality in the first decade after diagnosis.[22]
Trilateral retinoblastoma
Trilateral retinoblastoma is a well-recognized syndrome that occurs in 5% to 15% of patients with heritable retinoblastoma and is defined by the development of an intracranial midline neuroblastic tumor, which typically develops more than 20 months after the diagnosis of retinoblastoma.[23] Patients who are asymptomatic at the time of diagnosis with an intracranial tumor have a better outcome than patients who are symptomatic.
Given the poor prognosis of trilateral retinoblastoma and the short interval between the diagnosis of retinoblastoma and the occurrence of trilateral disease, routine neuroimaging could potentially detect the majority of cases within 2 years of first diagnosis. Although it is not clear whether early diagnosis can impact survival, screening with magnetic resonance imaging has been recommended as often as every 6 months for 5 years for those suspected of having heritable disease or those with unilateral disease and a positive family history.[23] Computed tomography scans are generally avoided for routine screening in these children because of the perceived risk of exposure to ionizing radiation.
Subsequent neoplasms (SNs)
Patients with heritable retinoblastoma have a markedly increased frequency of SNs.[24,25] There may be an association between type of RB1 mutation and incidence of SNs, with complete loss of RB1 activity having a higher incidence of SNs.[26] The cumulative incidence was reported to be 26% (± 10%) in nonirradiated patients and 58% (± 10%) in irradiated patients by 50 years after diagnosis of retinoblastoma—a rate of about 1% per year.[27] However, more recent studies analyzing cohorts of patients treated with more advanced radiation planning and delivery technology have reported the rates to be about 9.4% in nonirradiated patients and about 30.4% in irradiated patients.[28] The most common SN is osteosarcoma, followed by soft tissue sarcoma and melanoma; these malignancies may occur inside or outside of the radiation field, although most are radiation-induced. The carcinogenic effect of radiation therapy is associated with the dose delivered, particularly for subsequent sarcomas, where a step-wise increase is apparent at all dose categories. In irradiated patients, two-thirds of SNs occur within irradiated tissue, and one-third occur outside the radiation field.[27,28,29]
The risk of SNs also appears to be dependent on the patient's age at the time the external-beam radiation therapy is given, especially in children younger than 12 months, and the histopathologic types of SNs may be influenced by age.[28,30,31] These data support a genetic predisposition to soft tissue sarcomas, in addition to the risk of osteosarcoma.[29]
There is no evidence of an increased incidence of acute myeloid leukemia in children with heritable retinoblastoma.[32]; [33][Level of evidence: 3iiiA] Of 245 patients, all of whom received etoposide, only one patient had acute promyelocytic leukemia after 79 months.[32]
With the increase in survival of patients with heritable retinoblastoma, it has become apparent that they are also at risk of developing epithelial cancers late in adulthood. A marked increase in mortality from lung, bladder, and other epithelial cancers has been described.[34,35]
Survival from SNs is certainly suboptimal and varies widely across studies.[25,34,36,37,38,39] However, with advances in therapy, it is essential that all SNs be treated with curative intent.[40] Those who survive SNs are at a sevenfold increased risk for developing another SN.[41] The risk further increases threefold when patients are treated with radiation therapy for their retinoblastoma.[42] Retinoblastoma survivors with bilateral disease and an inherited germline mutation are at a slightly higher risk of a SN than those without an inherited mutation; this increase appears to be most significant for melanoma.[43]
There is no clear increase in SNs in patients without a germline retinoblastoma mutation beyond that associated with the treatment.[27,39]
Late Effects from Retinoblastoma Therapy
Orbital growth is somewhat diminished after enucleation; however, the impact of enucleation on orbital volume may be less after placement of an orbital implant.[44]
Patients with retinoblastoma demonstrate a variety of long-term visual field defects after treatment for their intraocular disease. These defects are related to tumor size, location, and treatment method.[45] One study of visual acuity after treatment with systemic chemotherapy and focal ophthalmic therapy was conducted in 54 eyes in 40 children. After a mean follow-up of 68 months, 27 eyes (50%) had a final visual acuity of 20/40 or better, and 36 eyes (67%) had final visual acuity of 20/200 or better. The clinical factors that predicted visual acuity of 20/40 or better were a tumor margin at least 3 mm from the foveola and optic disc and an absence of subretinal fluid.[46]
Because systemic carboplatin is now commonly used in the treatment of retinoblastoma (refer to the Intraocular Retinoblastoma and Extraocular Retinoblastoma sections of this summary for more information), concern has been raised about hearing loss related to therapy. While an analysis of 164 children treated with six cycles of carboplatin-containing therapy (18.6 mg/kg per cycle) showed no loss of hearing among children who had a normal initial audiogram,[47] another series documented hearing loss in 17% of patients.[48] Age younger than 6 months at the time of treatment and higher carboplatin systemic exposures appear to correlate with an increased risk of ototoxicity.[48,49]
Retinoblastoma is composed mainly of undifferentiated anaplastic cells that arise from the retina. Histology shows similarity to neuroblastoma and medulloblastoma, including aggregation around blood vessels, necrosis, calcification, and Flexner-Wintersteiner rosettes. Retinoblastomas are characterized by marked cell proliferation, as evidenced by high mitosis counts, extremely high MIB-1 labeling indices, and strong diffuse nuclear immunoreactivity for CRX, a useful marker to discriminate retinoblastoma from other malignant small round cell tumors.[1,2]
Cavitary Retinoblastoma
Cavitary retinoblastoma, a rare variant of retinoblastoma, has ophthalmoscopically visible lucent cavities within the tumor. The cavitary spaces appear hollow on ultrasonography and hypofluorescent on angiography. Histopathologically, the cavitary spaces have been shown to represent areas of photoreceptor differentiation.[3] These tumors have been associated with minimal visible tumor response to chemotherapy, which is thought to be a sign of tumor differentiation.[4]
Although there are several staging systems available for retinoblastoma,[1] for the purpose of treatment, retinoblastoma is categorized into intraocular and extraocular disease. Overall assessment of retinoblastoma extension is documented by staging systems; the intraocular extension, which is relevant for ocular salvage, is documented by grouping systems.
Intraocular retinoblastoma is localized to the eye and may be confined to the retina or may extend to involve other structures such as the choroid, ciliary body, anterior chamber, and optic nerve head. Intraocular retinoblastoma, however, does not extend beyond the eye into the tissues around the eye or to other parts of the body.
Extraocular (metastatic) retinoblastoma has extended beyond the eye. It may be confined to the tissues around the eye (orbital retinoblastoma), or it may have spread to the central nervous system, bone marrow, or lymph nodes (metastatic retinoblastoma).
Staging Systems
AJCC Staging System
Several staging systems have been proposed over the years. The AJCC clinical and pathological classifications represent a consensus opinion around which a common language is used.
Clinical classification system
Pathologic classification system
International Retinoblastoma Staging System
A simplified staging system, the International Retinoblastoma Staging System, has been proposed by an international consortium of ophthalmologists and pediatric oncologists.[2]
Grouping Systems
Grouping systems are relevant for assessment of intraocular disease extension and are helpful predictors of ocular salvage.
Reese-Ellsworth Classification for Intraocular Tumors
Reese and Ellsworth developed a classification system for intraocular retinoblastoma that has been shown to have prognostic significance for maintenance of sight and control of local disease at a time when surgery and external-beam radiation therapy (EBRT) were the primary treatment options.
Group I: very favorable for maintenance of sight
Group II: favorable for maintenance of sight
Group III: possible for maintenance of sight
Group IV: unfavorable for maintenance of sight
Group V: very unfavorable for maintenance of sight
International Classification of Retinoblastoma
There is a new grouping system for retinoblastoma, which may offer greater precision in stratifying risk for newer therapies. The International Classification of Retinoblastoma that is used in the current Children's Oncology Group treatment studies and in some institutional studies has been shown to assist in predicting those who are likely to be cured without the need for enucleation or EBRT.[3,4,5,6] The International Classification of Retinoblastoma was able to predict high-risk histopathology in a study of over 500 patients with retinoblastoma. Histopathologic evidence of high-risk disease was noted in 17% of Group D and 24% of Group E eyes in this study. Such predication can be helpful in counseling parents regarding the need for postoperative systemic therapy.[7]
Treatment planning by a multidisciplinary team of cancer specialists, including a pediatric oncologist, ophthalmologist, and radiation oncologist, who have experience treating ocular tumors of childhood is required to optimize treatment outcomes.[1] Evaluation at specialized treatment centers is highly suggested before the initiation of treatment in order to improve the likelihood of ocular salvage.
The goals of therapy are threefold:
The type of treatment required depends on both the extent of the disease within the eye and whether the disease has spread beyond the eye, either to the brain or to the rest of the body.[2] Eyes with glaucoma and those in which glaucoma resulted in buphthalmia are significantly associated with high-risk pathology and the occurrence of microscopically residual tumor.[3] Enucleation is reserved for patients with advanced unilateral intraocular disease with no hope for useful vision in the affected eye. Subsequent risk of extraocular recurrence may be increased in the presence of high-risk histopathologic features such as massive choroid invasion, scleral invasion, and optic nerve invasion.[4,5,6]; [7][Level of evidence: 3iiDi]
Routine bone marrow biopsy and lumbar puncture are not indicated, except when there is a high level of suspicion that the tumor has spread beyond the globe.[8,9,10]
It is not uncommon for patients with retinoblastoma to have extensive disease within one eye at diagnosis, with either massive tumors involving more than one-half of the retina, multiple tumors diffusely involving the retina, or obvious seeding of the vitreous. For those with bilateral disease, systemic therapy may be used to treat the more severe eye.[11,12]
Metastasis from retinoblastoma generally develops within 1 year of diagnosis. If there is no metastatic disease by 5 years after treatment, the patient is generally considered cured.[13]
Treatment of retinoblastoma is individualized and considers the age of the patient, laterality, potential for vision, and intraocular tumor burden. When selecting a treatment option, cure of the disease, preservation of sight, and prevention of late effects should be considered.[1]
Different combinations of the following approaches may be applied to the individual patient depending on whether the patient has unilateral or bilateral disease.
Treatment options for the involved eye include the following:
Multiagent chemotherapy is generally used, although carboplatin as a single agent causes shrinkage of retinoblastoma tumors.[15]; [16][Level of evidence: 3iiiDiii] Most standard regimens incorporate vincristine, carboplatin, and etoposide, although a two-drug regimen without etoposide may also be effective for early intraocular stages.[1,11,14,17,18,19] The success rate of these trials varies from center to center, but overall, the rate is highest for discrete tumors without vitreous seeding. Local tumor recurrence is not uncommon in the first few years after treatment [20] and can often be successfully treated with focal therapy.[8] Among patients with heritable disease, younger patients and those with a positive family history are more likely to form new tumors. Chemotherapy may treat small, previously undetected lesions by slowing their growth, and this may improve overall salvage with focal therapy.[21]
There are data suggesting that the use of systemic chemotherapy may decrease the risk of development of trilateral retinoblastoma.[22]
Small body and ocular size may pose technical limitations to its use in very young patients. Intravenous chemotherapy has been used in neonates and young infants to postpone intra-arterial chemotherapy. One or several cycles of single-agent carboplatin have been used to bridge the time until the child is aged 3 months and weighs 6 kg.[36][Level of evidence: 3iiiDi]
In a recent report of 81 patients with heritable retinoblastoma, intra-arterial chemotherapy was able to eliminate ophthalmoscopically undetectable tumors present at diagnosis in the majority of patients.[37][Level of evidence: 3iiDi]
This treatment is not without complications in some cases.[23,30,38,39] Retinal and choroidal vasculopathy may occur in 10% to 20% of patients.[32,40]
Unilateral Disease
Standard treatment options
Because unilateral disease is usually massive and there is often no expectation that useful vision can be preserved, up-front surgery (enucleation) is usually recommended. Careful examination of the enucleated specimen by an experienced pathologist is necessary to determine whether high-risk features for metastatic disease are present. These features include anterior chamber seeding, choroidal involvement, tumor beyond the lamina cribrosa, or scleral and extrascleral extension.[19,46,47,48] Systemic adjuvant therapy with vincristine, doxorubicin, and cyclophosphamide or with vincristine, carboplatin, and etoposide has been used in patients with certain high-risk features assessed by pathologic review after enucleation to prevent the development of metastatic disease,[19,49,50,51,52]; [53][Level of evidence: 2A] with the suggestion of success compared with historical controls.[54][Level of evidence: 3iiDiii]
Patients with unilateral disease may also be offered chemotherapy and aggressive focal treatments in an attempt to save the eye and preserve vision.[1] Ocular salvage rates correlate with intraocular stage. In selected children with unilateral disease, Reese-Ellsworth (R-E) Group correlated with successful systemic chemoreduction; 11% of children classified as having R-E Group II or III disease, 60% of children having R-E Group IV disease, and 100% of children having R-E Group V disease required enucleation or EBRT within 5 years of treatment.[55] Caution must be exerted with extended systemic chemotherapy and delayed enucleation when tumor control does not appear to be possible. Pre-enucleation chemotherapy for eyes with advanced intraocular disease may result in downstaging and underestimate the pathological evidence of extraretinal and extraocular disease, thus increasing the risk of dissemination.[56]
The delivery of chemotherapy via ophthalmic artery cannulation as initial treatment for advanced unilateral retinoblastoma appears to be more effective than systemic chemoreduction. In the setting of a multidisciplinary, state-of-the-art center, intra-arterial chemotherapy may result in ocular salvage rates in excess of 80% for patients with advanced intraocular unilateral retinoblastoma.[27]; [23,28][Level of evidence: 3iiiDii]; [25][Level of evidence: 3iiiDiv]
Because a proportion of children who present with unilateral retinoblastoma will eventually develop disease in the opposite eye, these children are candidates for genetic counseling and testing and periodic examinations of the unaffected eye, regardless of the treatment they received. Asynchronous bilateral disease occurs most frequently in patients with affected parents and in children diagnosed during the first months of life. Pre-enucleation magnetic resonance imaging has low sensitivity and specificity for the detection of high-risk pathology.[57] As discussed, genetic counseling and testing at the time of diagnosis is the key to defining risk and planning follow-up.
Bilateral Disease
The management of bilateral disease depends on the extent of the disease in each eye. Systemic therapy is generally chosen based on the eye with more extensive disease. Treatment modality options described for unilateral disease may be applied to one or both affected eyes in patients with bilateral disease. Chemoreduction (systemic or intra-arterial) coupled with aggressive focal treatments and very close monitoring is usually the treatment of choice, with the goal of ocular and vision preservation and the delay or avoidance of EBRT and enucleation.
Intraocular tumor burden is usually asymmetric. Treatment is dictated by the most advanced eye. While up-front enucleation of an advanced eye and risk-adapted adjuvant chemotherapy may be required, a more conservative approach using primary chemoreduction with close follow-up for response and focal treatment (e.g., cryotherapy or laser therapy) may be indicated. EBRT is now reserved for patients whose eyes do not respond adequately to primary systemic or intra-arterial chemotherapy and focal consolidation.
A number of large centers in Europe and North America have published trial results that used systemic chemotherapy in conjunction with aggressive focal consolidation for patients with bilateral disease.[1,18,20,21,58,59,60,61,62,63] Chemotherapy may shrink the tumors (chemoreduction), allowing greater efficacy of subsequent focal therapy.[1] Treatment strategies often differ in terms of chemotherapy regimens and local control measures.
Centers using the R-E Classification for Intraocular Tumors have demonstrated that the goal to save eyes may be achievable for tumors that are R-E Group IV or lower. The backbone of the chemoreduction protocols has generally been carboplatin, etoposide, and vincristine (CEV); using this regimen in combination with aggressive focal treatments, enucleation or EBRT may be avoided in R-E Groups I, II, and III eyes.[1,11] Tumors associated with massive vitreous or subretinal seeds have proven problematic.[64] Local control is often transient in patients with vitreous seeding or very large tumors (R-E Group V), and more than one-half of patients may eventually need EBRT and/or enucleation.[1,11] In one study, the addition of high-dose cyclosporine A (a modulator of p-glycoprotein) to the CEV regimen resulted in improved ocular salvage rates.[60]
The International Classification of Retinoblastoma grouping system may be better than the R-E Classification for Intraocular Tumors at predicting success of treatment with systemic chemotherapy in combination with local control. The combinations of carboplatin and etoposide (CE) [65] or CEV [66,67] in conjunction with local control have resulted in ocular salvage rates above 90% for early intraocular disease (Groups A and B eyes), 70% to 90% for Group C eyes, and 40% to 50% for Group D eyes.[65,67,68]; [65][Level of evidence: 3iiDiv] However, for patients with advanced intraocular disease (typically Group D eyes), EBRT is frequently required for ocular salvage.[65]; [66][Level of evidence: 3iiDiii]
For patients with large intraocular tumor burden or with subretinal or vitreous seeds (Groups C and D eyes), the use of periocular chemotherapy, usually in combination with systemic therapy, has been explored.[43,69] In one study, systemic chemoreduction, subtenon carboplatin, and local consolidation resulted in ocular salvage of 47% of Group D eyes. An additional 35% of eyes were salvaged with intensity-modulated radiation therapy.[70][Level of evidence: 2Div] The impact of this approach on ocular salvage is not well defined.
The treatment recommendation for Group E eyes is up-front enucleation. The use of prolonged systemic chemotherapy for Group E eyes to avoid or delay enucleation has been associated with lower disease-specific survival (P < .001).[56][Level of evidence: 3iiiB]
Delivery of chemotherapy via ophthalmic artery cannulation has also been shown to be feasible and effective in patients with bilateral disease, in both the up-front and salvage settings.[23,28,35][Level of evidence: 3iiDii] However, this treatment should only be performed in an experienced center with a state-of-the-art treatment infrastructure and a dedicated multidisciplinary team.
The unresolved issues are long-term tumor control and the consequences of chemotherapy. Most of these patients are exposed to etoposide, which has been associated with secondary leukemia in patients without predisposition to cancer, but at modest rates when compared with the risks associated with EBRT in heritable retinoblastoma.
In patients with cavitary retinoblastoma, minimal visual response is seen after intravenous chemotherapy and/or intra-arterial chemotherapy. Despite the blunted clinical response, cavitary retinoblastoma has a favorable long-term outcome with stable tumor regression and globe salvage. Aggressive or prolonged chemotherapy or adjunctive therapies are generally not necessary. In a retrospective series of 26 cavitary retinoblastomas that were treated with intravenous chemoreduction and/or intra-arterial chemotherapy, the mean reduction in tumor base was 22% and mean reduction in tumor thickness was 29%. Despite minimal reduction, tumor recurrence was noted in only one eye, globe salvage was achieved in 22 eyes, and there were no cases of metastasis or death during 49 months (range, 6–189 months) of follow-up.[71]
Treatment Options Under Clinical Evaluation
Studies are planned for a variety of patient groups. The International Classification of Retinoblastoma is being utilized for these trials.
Information about ongoing clinical trials is available from the NCI Web site.
Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with intraocular retinoblastoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
In developed countries, few patients with retinoblastoma present with extraocular disease. Extraocular disease may be localized to the soft tissues surrounding the eye or to the optic nerve beyond the margin of resection. However, further extension may occur into the brain and meninges with subsequent seeding of the spinal fluid, and as distant metastatic disease involving the lungs, bones, and bone marrow.
Standard Treatment Options
Orbital and locoregional retinoblastoma
Orbital retinoblastoma occurs as a result of progression of the tumor through the emissary vessels and sclera. For this reason, transscleral disease is considered to be extraocular and should be treated as such. Orbital retinoblastoma is isolated in 60% to 70% of cases. Treatment includes systemic chemotherapy and radiation therapy; with this approach, 60% to 85% of patients can be cured. Because most recurrences occur in the central nervous system (CNS), regimens using drugs with well-documented CNS penetration are recommended. Different chemotherapy regimens have proven to be effective, including vincristine, cyclophosphamide, and doxorubicin and platinum- and epipodophyllotoxin-based regimens, or a combination of both.[1,2,3] For patients with macroscopic orbital disease, it is recommended that surgery be delayed until response to chemotherapy is achieved (usually two or three courses of treatment). Patients then undergo enucleation and receive an additional four to six courses of chemotherapy. Next, local control is consolidated with orbital irradiation (40 Gy to 45 Gy). Using this approach, orbital exenteration is not indicated.[3] Patients with isolated involvement of the optic nerve at the transsection level receive similar systemic treatment, and irradiation includes the entire orbit (36 Gy) with 10 Gy boost to the chiasm (total 46 Gy).[2]
Central nervous system disease
Intracranial dissemination occurs by direct extension through the optic nerve and its prognosis is dismal. Treatment for these patients includes platinum-based intensive systemic chemotherapy and CNS-directed therapy. Although intrathecal chemotherapy has been traditionally used, there is no preclinical or clinical evidence to support its use. Although the use of irradiation in these patients is controversial, responses have been observed with craniospinal irradiation using 25 Gy to 35 Gy to the entire craniospinal axis and a boost (10 Gy) to sites of measurable disease. Therapeutic intensification with high-dose, marrow-ablative chemotherapy and autologous hematopoietic progenitor cell rescue has been explored, but its role is not yet clear.[4][Level of evidence: 3iiA]
Trilateral retinoblastoma is usually associated with a pineal lesion with a cystic appearance that can be misleading or, less commonly, as a suprasellar lesion.[5] In patients with the heritable form of retinoblastoma, CNS disease is less likely the result of metastatic or regional spread than a primary intracranial focus, such as a pineal tumor. The prognosis for patients with trilateral retinoblastoma is very poor; most patients die of disseminated neuraxis disease in less than 9 months. While pineoblastomas occurring in older patients are sensitive to radiation therapy, current strategies are directed towards avoiding irradiation by using intensive chemotherapy followed by consolidation with myeloablative chemotherapy and autologous hematopoietic progenitor cell rescue, an approach similar to those being used in the treatment of brain tumors in infants.[6]
Because of the poor prognosis of trilateral retinoblastoma, screening neuroimaging is a common practice. Routine baseline brain magnetic resonance imaging (MRI) is recommended at diagnosis because it may detect trilateral retinoblastoma at a subclinical stage. In a small series of patients, the 5-year overall survival was 67% for those detected at baseline, compared with 11% for the group with a delayed diagnosis.[5] The value of screening with MRI for those suspected of having heritable disease or those with unilateral disease and a positive family history is under discussion. It has been recommended as often as every 6 months for up to 5 years. Given the short interval between the diagnosis of retinoblastoma and the occurrence of trilateral retinoblastoma, routine screening might detect the majority of cases within 2 years. However, it is not clear whether screening by neuroimaging improves survival.[7] Computed tomography scans should be avoided for routine screening in these children because of the perceived risk of exposure to ionizing radiation.
Extracranial metastatic retinoblastoma
Hematogenous metastases may develop in the bones, bone marrow, and less frequently, in the liver. Although long-term survivors have been reported with conventional chemotherapy, these reports should be considered anecdotal; metastatic retinoblastoma is not curable with conventional chemotherapy. In recent years, however, studies of small series of patients have shown that metastatic retinoblastoma can be cured using high-dose, marrow-ablative chemotherapy and autologous hematopoietic stem cell rescue.[8,9,10,11,12,13,14]; [15][Level of evidence: 3iiA]
Two reports suggest that there may be a role for intensive multimodality therapy with autologous stem cell rescue for patients with metastatic retinoblastoma.[4,15][Level of evidence: 3iiA] A few responses were noted in CNS (including trilateral) and systemic metastases.
The following is an example of national and/or institutional clinical trial that is currently being conducted. Information about ongoing clinical trials is available from the NCI Web site.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with extraocular retinoblastoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
The prognosis for a patient with recurrent or progressive retinoblastoma depends on the site and extent of the recurrence or progression and previous treatment. Metastasis in retinoblastoma generally occurs within 1 year of diagnosis.[1] New intraocular tumors can arise in patients with the heritable form of disease whose eyes have been treated with focal measures only, since every cell in the retina carries the RB1 mutation; this is not technically recurrence. Even with prior treatment consisting of chemoreduction and focal measures in very young patients with heritable retinoblastoma, surveillance may detect new tumors at an early stage and additional focal therapy, including plaque brachytherapy, can be successful in eradicating tumor.[2,3,4,5,6] When the recurrence or progression of retinoblastoma is confined to the eye and is small, the prognosis for sight and survival may be excellent with local therapy only.[7][Level of evidence: 3iiDiv] If the recurrence or progression is confined to the eye but is extensive, the prognosis for sight is poor; however, survival remains excellent. Intra-arterial chemotherapy into the ophthalmic artery has been effective in patients who relapse after systemic chemotherapy and radiation therapy.[8] Recurrence in the orbit after enucleation is treated with aggressive chemotherapy in addition to local radiation therapy because of the high risk of metastatic disease.[9][Level of evidence: 3iiA] If the recurrence or progression is extraocular, the chance of survival is poor, with death usually occurring within 6 months.[1] In this circumstance, the treatment depends on many factors, including individual patient considerations. Clinical trials may be appropriate to consider.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent retinoblastoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
This summary was comprehensively reviewed.
This summary is written and maintained by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ NCI's Comprehensive Cancer Database pages.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of retinoblastoma. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
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This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
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For more information, U.S. residents may call the National Cancer Institute's (NCI's) Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237) Monday through Friday from 8:00 a.m. to 8:00 p.m., Eastern Time. A trained Cancer Information Specialist is available to answer your questions.
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Helpless (Hoa-cha)
Drama, Suspense/Thriller
Mun-ho and Seon-yeong are a couple engaged to be married who pull over at a rest stop on their way to meeting Mun-ho's parents. When Mun-ho returns to the car with coffee, he finds the car door flung open in the pouring rain with the engine still running - his fiancée is nowhere to be found. Frantic after discovering her apartment emptied out and that her previous workplaces don't even exist, Mun-ho enlists his cousin and former police detective, Jong-geun, to help him find her. As they delve deeper, they discover that piecing together the shards of this woman's puzzle produces a horrifying picture.
Cast: Seon-gyun Lee, Duek-mun Choi, Byeol Kim, Min-hie Kim, Seong-ha Jo
Produced by:
Directed by: Young-Joo Byun
Written by: Young-Joo Byun
Running time: 1hr 57min
Opens: May 11, 2012 Limited
|Theaters for Today
Pick a day
on this day.

subset: commoncrawl


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Faith Has Its Reasons
from R.C. Sproul Sep 04, 2015 Category: ArticlesChristians from every theological tradition have for centuries confessed their faith by reciting the Apostles' Creed. Elsewhere I have taught on the actual content of this creed, but if there is one aspect of this confession that we often fail to reflect on, it is the creed's opening words... Keep Reading
An Interview with Dr. Michael Horton (pt. 2)
from Burk Parsons Dec 01, 2009 Category: ArticlesThis is part two of my interview with Michael Horton. You can read the first part here. Keep Reading
An Interview with Dr. Michael Horton
from Burk Parsons Nov 30, 2009 Category: ArticlesMike Horton is a husband, a father, and a pastor. He's also a professor, an editor, and a prolific author. From reading his long list of academic credentials you might get the impression that he's an ivory-tower theologian with no time or concern for people. I recently had the opportunity to interview Mike. Keep Reading
Looking up to Heroes
from R.C. Sproul Nov 29, 2009 Category: ArticlesWhen I was a boy I thought like a boy. I behaved like a boy. I understood like a boy. I was deeply impressed by heroes. Mostly, they were figures from the sports world. There was Doak Walker, Charlie "Choo Choo" Justice, Sammy Baugh, Bob Waterfield, Felix "Doc" Blanchard, Johnny Lujack. I hoarded and traded baseball cards. Keep Reading
Give a Reformation Trust Book Set
from Karisa Schlehr Nov 28, 2009 Category: Reformation TrustWhat's better than giving someone a book for Christmas? Giving multiple books at a discounted price. Enjoy these book sets from Reformation Trust and grow in your knowledge of the deep truths of Scripture. Keep Reading
You Can Still Make an Impact in 2009
from John Petersen Nov 26, 2009 Category: Ministry NewsIn just a few weeks Ligonier must close the books on 2009 with what we fervently pray is a balanced ministry budget. We have a large hurdle to clear toward that goal: the $1,787,151 we need to receive by December 31 to meet our year-end obligations. Keep Reading
True Gratitude
from Karisa Schlehr Nov 26, 2009 Category: R.C. SproulOne of the grand traditions of America is our tradition of taking one day out of the year and setting it apart as a special holiday--a holy day--a day to commemorate the benevolent providence of God. It was originally called Thanksgiving. The idea of Thanksgiving day has its roots in our own history, in the bitter struggle that the original founding fathers of this country had with the elements. Keep Reading
The Gift of Knowledge
from Karisa Schlehr Nov 25, 2009 Category: Ligonier ResourcesThe Bible, philosophy, apologetics, and theology can be rather intimidating areas of study for most people. Yes, they are very important to learn but where do you even start? R.C. Sproul has produced what we refer to as Overview Series. In these four resources, he provides a thorough, yet easy to understand examination of each of these topics. Start knowing what you believe and why you believe it. Keep Reading
Tabletalk 2010: The First Six Months
from Chris Donato Nov 24, 2009 Category: Tabletalk MagazineFor more than thirty years, Tabletalk has existed as a magazine for the church. So it strives to help explain important, biblical doctrines and events that shape the church while encouraging people to reflect the image of Christ in both word and deed. We are proud to follow that same trajectory in 2010--dealing with issues that challenge, exhort, and encourage God's people. Keep Reading
Of Origins and Twitter Posts
from Chris Larson Nov 24, 2009 Category: Ministry NewsToday marks 150 years since Charles Darwin's book, On the Origin of Species, was published. At our Twitter account every hour, we'll be highlighting 24 resources that discuss evolution, creation, atheism, and subjects related to cosmology and science -- all from a biblical worldview. Keep Reading
Social Darwinism
from Gene Edward Veith Nov 23, 2009 Category: Tabletalk MagazineCharles Darwin's theory of evolution was never just about biology. Nor were its consequences just about religion. Rather, the origins and effects of Darwinism were largely cultural and moral. Darwin's Origin of Species was published in 1859, which was at the height of the Industrial Revolution and the Capitalist Revolution. Keep Reading


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NBA free agents (* -- indicates restricted free agent, with team allowed to match outside offers to retain player):
Best of who is left: Alexis Ajinca, Gilbert Arenas, Keith Bogans, Erick Dampier, Francisco Elson, Melvin Ely, Kryrlo Fesenko, Eddie House, Jamario Moon, James Posey, Joe Smith, Etan Thomas.
ATLANTA HAWKS: Hilton Armstrong, Jason Collins (signed with Hawks), Jamal Crawford (signed with Trail Blazers), Josh Powell (committed overseas for season), Etan Thomas, Damien Wilkins (signed with Pistons).
BOSTON CELTICS: Carlos Arroyo, Glen Davis (re-signed, traded to Magic), Troy Murphy (signed with Lakers), Sasha Pavlovic (signed with Celtics), Von Wafer (signed with Magic), Delonte West (signed with Mavericks), Jeff Green (signed with Celtics, failed physical, contract voided).
CHARLOTTE BOBCATS: Kwame Brown (signed with Warriors), Melvin Ely, Dominic McGuire (signed with Warriors), Joel Przybilla (expected to retire), Garrett Temple (committed overseas for season), Dante Cunningham (signed with Grizzlies).
CHICAGO BULLS: Keith Bogans, Rasual Butler (signed with Raptors), John Lucas III (signed with Bulls), Jannero Pargo (signed with Hawks), Brian Scalabrine (signed with Bulls), Kurt Thomas (signed with Trail Blazers).
CLEVELAND CAVALIERS: Baron Davis (signed with Knicks), Manny Harris, Anthony Parker (signed with Cavaliers).
DALLAS MAVERICKS: J.J. Barea (signed with Timberwolves), Caron Butler (signed with Clippers), Brian Cardinal (signed with Mavericks), Tyson Chandler (signed with Knicks), Andy Rautins, DeShawn Stevenson (signed with Nets), Peja Stojakovic (retired).
DENVER NUGGETS: Nene (signed with Nuggets), Kenyon Martin (committed overseas for season), J.R. Smith (committed overseas for season), Arron Afflalo (signed with Nuggets), Wilson Chandler* (committed overseas for season), Gary Forbes (signed with Raptors).
DETROIT PISTONS: Richard Hamilton (signed with Bulls), Tracy McGrady (signed with Hawks), Tayshaun Prince (signed with Pistons), DaJuan Summers (signed with Hornets), Chris Wilcox (signed with Celtics), Jonas Jerebko (signed with Pistons), Kareem Rush, Rodney Stuckey (signed with Pistons), Jake Voskuhl.
GOLDEN STATE WARRIORS: Acie Law, Vladimir Radmanovic (signed with Hawks), Al Thornton, Reggie Williams (signed with Bobcats).
HOUSTON ROCKETS: Chuck Hayes (signed with Kings), Jeremy Lin (signed with Knicks), Yao Ming (retired).
INDIANA PACERS: Mike Dunleavy (signed with Bucks), T.J. Ford (signed with Spurs), Jeff Foster (signed with Pacers), Solomon Jones (signed with Clippers), Josh McRoberts (signed with Lakers), James Posey.
LOS ANGELES CLIPPERS: Jamario Moon, Craig Smith (signed with Trail Blazers), DeAndre Jordan (signed offer sheet with Warriors, retained by Clippers).
LOS ANGELES LAKERS: Shannon Brown (signed with Suns), Theo Ratliff, Joe Smith.
MEMPHIS GRIZZLIES: Shane Battier (signed with Heat), Leon Powe, Marc Gasol (signed with Grizzlies), Hamed Haddadi (signed with Grizzlies), Brian Skinner.
MIAMI HEAT: Mike Bibby (signed with Knicks), Erick Dampier, Eddie House, Juwan Howard (signed with Heat), James Jones (signed with Heat), Jamaal Magloire (signed with Raptors), Mario Chalmers (signed with Heat).
MILWAUKEE BUCKS: Earl Boykins, Chris Douglas-Roberts (committed overseas for season), Michael Redd (signed with Suns), Luc Richard Mbah a Moute (signed with Nuggets, offer matched by Bucks).
MINNESOTA TIMBERWOLVES: Sebastian Telfair (signed with Suns), Bonzi Wells.
NEW JERSEY NETS: Dan Gadzuric (committed overseas for season), Kris Humphries (signed with Nets), Travis Outlaw (signed with Kings), Ime Udoka, Ben Uzoh, Sasha Vujacic (committed overseas for season), Mario West (committed overseas for season), Brandan Wright (signed with Mavericks).
NEW ORLEANS HORNETS: David Andersen, Marcus Banks, Aaron Gray (signed with Raptors), Willie Green (signed with Hawks), Carl Landry (signed with Hornets), D.J. Mbenga, Jason Smith (signed with Hornets), David West (signed with Pacers), Marco Belinelli (signed with Hornets).
NEW YORK KNICKS: Chauncey Billups (signed by Clippers), Anthony Carter (signed with Raptors), Jared Jeffries (signed with Knicks), Roger Mason (signed with Wizards), Shawne Williams (signed with Nets), Shelden Williams (signed with Nets), Derrick Brown (signed with Bobcats).
OKLAHOMA CITY THUNDER: Daequan Cook (signed with Thunder), Nate Robinson (signed with Warriors).
ORLANDO MAGIC: Malik Allen, Gilbert Arenas, Earl Clark (signed with Magic), Jason Richardson (signed with Magic).
PHILADELPHIA 76ERS: Tony Battie (signed with 76ers), Antonio Daniels, Jason Kapono (signed with Lakers), Darius Songaila (committed overseas for season), Spencer Hawes (signed with 76ers), Thaddeus Young (signed with 76ers).
PHOENIX SUNS: Vince Carter (signed with Mavericks), Grant Hill (signed with Suns), Mikael Pietrus (signed with Celtics), Aaron Brooks* (committed overseas for season).
PORTLAND TRAIL BLAZERS: Earl Barron, Patrick Mills*, Greg Oden (signed with Trail Blazers), Brandon Roy.
SACRAMENTO KINGS: Samuel Dalembert (signed with Rockets), Marquis Daniels (signed with Celtics), Darnell Jackson, Pooh Jeter (committed overseas for season), Marcus Thornton (signed with Kings).
SAN ANTONIO SPURS: Antonio McDyess (retired), Steve Novak (signed with Knicks), Chris Quinn (committed overseas for season).
TORONTO RAPTORS: Alexis Ajinca, Joey Dorsey (committed overseas for season), Reggie Evans (signed with Clippers), Julian Wright, Sonny Weems* (committed overseas for season).
UTAH JAZZ: Francisco Elson, Kyrylo Fesenko, Andrei Kirilenko (committed overseas for season), Ronnie Price (signed with Suns), Earl Watson (signed with Jazz).
WASHINGTON WIZARDS: Mardy Collins, Maurice Evans (signed with Wizards), Josh Howard (signed with Jazz), Mustafa Shakur (committed overseas for season), Yi Jianlian (signed with Mavericks), Othyus Jeffers*, Larry Owens*, Hamady Ndiaye (signed with Wizards), Nick Young (signed with Wizards).
-- Ira WindermanCopyright © 2015, Sun Sentinel


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Moderator: ADGO BOD
To kick of the season, I'm running a 1 round match Saturday April 09 at Redan. With current tournaments on the ADGO calendar and my work schedule this is the only date available. Signup from 9-9:45AM, then get everyone playing by 10AM. Tag cost is $15 again this year.
Wookie wrote:I do have to apologize, I did not want the tags to be yellow. We just did that a few years ago. I was trying to get GOLD instead but I guess they didn't pay attention nor did they send me a color proof. I guess I need to be more specific and should have learned after last year when I said green and they sent a very different shade of green.
Rich Meade wrote:noob question...
What are the tags for?
Return to Atlanta Bag Tag Challenge
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Items: 0
Aerosoles Shoes for WomenEvery pair of Aerosoles offers superior core comfort and support from its design technology: diamond flex soles pattern, foam footbed & soft cushioned insole. Explore the stylish affordable Aerosoles shoes women love! Find the perfect fit & price made for you.
Save on our selection of colors, fabrics, sizes & styles of Aerosoles comfortable shoes for women online at Boscov�s Department Store!


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HILLSDALE - The 2014-15 season is young, but Hillsdale College men's basketball coach John Tharp likes what he sees so far from his Chargers.Hillsdale College is 5-1 overall so far (3-1 GLIAC). The Chargers are averaging 68.5 ppg. and giving up 62.2 ppg.Defensively, the Chargers are out-rebounding their opponents, 42.5-39. They are shooting 44 percent overall from the field and holding their opponents to 40 percent shooting.With finals out of the way, the Chargers will...
HILLSDALE — Being referred to as "a regular" when it comes to ringing bells for the Hillsdale Salvation Army makes Tom Osbourne swell with pride.
HILLSDALE — With flakes of snow providing a dusting of cover on building rooftops Wednesday morning, work began to clean ground for two new sled runs at Lewis Emery Park.The sledding areas tucked back in the east corner of the...
HILLSDALE — Robots will be calling Hillsdale High School home after the first of the year.The school recently received two grants – the FIRST Robotics Competition Robotics Grant and a Michigan Department of Education...
If you are a commercial property owner, investor, or manager, you tend to have a lot on your plate when it comes to maintenance.
By Melissa CrawleyMore Content Now
I first fell in love with felt Advent calendars about six years ago when I saw a Christmas tree with 25 superbly decorated pockets at Pottery Barn.
WEEK IN RELIGIONAn evangelical Muslim preacher is being investigated by Pakistani police for allegedly making blasphemous comments about Islam in a viral video that began circulating earlier this month.
A visual step-by-step that will teach you how to glaze a holiday ham from start to finish.
Tis the season to be jolly�and get fat. Fend off holiday weight gain with our practical tips.
And then there were five.The finale of�Survivor's 29th season...
- Events Calendar


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[VIDEO] Beyonce' Releases Visual for "Drunk In Love" Featuring Hubby Jay-Z
For those who aren't in the know, Beyonce shocked the world this past week when she released a surprise album entitled "Beyonce". The video went straight to itunes, and is set to debut at #1 this week with over 800,000 copies sold in just 3 days, THAT's BANANAS!
Earlier today, King Bey released the visual to "Drunk In Love" featuring her husband, Jay-Z who happens to be coming to Buffalo, NY early in 2014 with his Magna Carta Holy Grail Tour


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Fred V
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Meet Bouchon—the wine lover's stool. Its mushroom-esque seat is made from regenerated cork (sustainably harvested from living trees) while its muselet-shaped base is constructed from sturdy steel. Designed for Domitalia by Foico Orlandini and Andrea Radice, this barstool combines playfulness and practicality to form a perfect perch for sipping your Sauvingon blanc.
Seat: regenerated cork. Base: steel. Indoor use only.
This product has no reviews yet. Be the first to review this product. Write a review
Enjoy 10% off your first order*


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Summer 2012 Issue
This IssueThis is our Summer 2012 issue. Feel free to read these articles and share them with your friends and loved ones. Thank you for your interest in UNH!
About This PublicationCharger Connection is a production of the the University of New Haven Office of Undergraduate Admissions to help parents and counselors of future college students with their college search and selection process.


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Paul Schrier And Jason Narvy On 20 Years Of 'Mighty Morphin Power Rangers' [SDCC]
San Diego Comic-Con comes but once a year, but when it does it brings good cheer I usually do my best to track down anyone I can who is involved with the Power Rangers. What can I say? Tokusatsu, original or localized, is just my jam like that


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Furthermore, we are now allowing you to post your World of Logs parses if you feel stuck with respect to your DPS. Please note you must follow the criteria listed here:
- The parse must be from a 10 or 25 man raid (non-heroic is fine). 5-mans and target dummies are not welcome.
- In line with this, you must be max level (85). We're not about to look over a log from a level 70 Sunwell run.
- Your profile MUST work. If you tend to change specs/log out in PVP gear please create a character profile through Wowhead or a similar site. That way if your issue is related to your gear, help can be provided.
- You must give a few sentences regarding what you think your problem is. Are you moving a lot due to fight mechanics? Do you perform some vital secondary role that may impact your DPS? (kiting, etc). We can't help you if you don't help us.
Please note that this thread is no exception to how the rest of our forums work regarding the fact that no one is obligated to help you. Do not bump, repost, or cry about it.


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Call (888) 784-1722 Mon-Sat 8:30-5:00 PST
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Green-fed Earthworm Castings, Cold Water Kelp Meal, Wild-Caught Fish Bone Meal, Soybean Meal and a plethora of rich organic nutrients. Formulated from a fine selection of composted organic materials. Our blend is packed full of the organic materials that help your plants become established. We only use Forest Humus, Fir Bark, Peat Moss, Worm Castings, Alfalfa Meal, Kelp Meal, Soybean Meal, Fish Meal, Fish Bone Meal, MicroActive™ Seaweed Extract, Aloe Vera, Yucca Extract and Oyster Shell & Dolomite Limes. We have also included Probiotic® beneficial soil Microbes plus both Ecto and Endo Mycorrhizae.
Home Grown® Vegetable Garden Planting Mix creates the perfect soil conditions to promote plant health and abundant vegetables and herbs. Home Grown® can be used for many projects in the garden: amendment for planting trees, shrubs, bare root planting & flowers.
I used this planting mix to plant veggies and flowers in pots on my deck. Everything is doing great and I think this soil works much better than an ordinary potting mix. Would highly recommend.Review by Debbie (on 5/8/13)
I used this mix in a smartpot for herbs. My herbs grew quickly and looked great. I would definitely use this mix again.Review by Kim (on 12/18/12)


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Visit USD
The University of San Diego is a special place that we encourage you to experience in person. Visitors use a variety of words to describe our campus: gorgeous, surprising, pristine, impressive. We could go on and on about the 16th century Spanish Renaissance architecture, the near–perfect southern California climate, the sky–scraping Immaculata Chapel, and our state–of–the–art facilities. But you really have to see the USD campus to believe it. So please come and visit. Take a tour, visit a class, talk to the students. It is the buzz of life and pride through campus that best exemplifies the passions of USD's diverse, community–minded, and talented student body. We love visitors, and we'd love to welcome you to campus.
Virtual Tour
Let current students lead you on a virtual tour of campus and discover what USD has to offer.
Campus Tours
A USD Student Ambassador will lead you through campus as they share stories of their own experience as a Torero.
Maps & Directions
By air, land or sea, there is always a way to get to USD.
Hotel Information
Making a short stay of your trip? San Diego offers great options close to USD, downtown, and the beaches.
Upcoming Events
We invite you to join us at an upcoming Admissions event. Learn about USD and how you can become a valuable part of our community.
USD on the Road
The USD Admissions team travels all over the world to meet promising prospective students. Find out when we'll be at a school or city near you.
Campus Security
In compliance with the Jeanne Clery Disclosure of Campus Security Policy and Campus Crime Statistics Act, the Annual Security and Fire Safety Report is available for viewing at http://www.sandiego.edu/safety/documents/annualreport.pdf.
This report includes statistics for the previous three years concerning reported crimes that occurred on-campus, in certain off-campus buildings or properties, and on nearby public property. A print copy of this report may also be obtained at the USD Department of Public of Safety.


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Customer Reviews
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"Bright faux-leather business card holder"
By Gina
Comments: Just received this as a gift, and had to post a review. I love it!! My mom knows me too well. I love bright colors, so she gave me one of each color :) Plus, it arrived beautifully gift wrapped. I have to recommend memorablegifts.com to my colleagues !
"good college grad gift or for a new job"
By sf buyer
Comments: adorable. personalization looked perfect and was done really well.


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Radcliff, KY (April 1, 2011) - U.S. Cavalry, the world's leading multi-channel distributor for Military, Law Enforcement and Homeland Security personnel is now taking pre-orders for the blueprint of the next generation of Tactical Response Uniform! The TRU Xtreme: MOLLE Xtreme Tactical Response Uniform from TRU-SPEC® brings the Tactical Response Uniform into the 21st Century. For additional technical details, check out our interactive microsite with product views, specifications and video by visiting: http://www.uscav.com/mollextreme/
The TRU Xtreme: MOLLE Xtreme Tactical Response Uniform from TRU-SPEC® is based on the Army Combat Uniform (ACU) with improvements geared for tactical teams and combat troops in the field. TRU-SPEC took feedback from soldiers on the drawbacks of the ACU and sought to improve them. Common stress points like elbow and shirt pockets are reinforced with extra stitching and bartacks. Hook-and-loop fabric that also sees heavy use has extra stitching as well. SuperFabric® external elbow and knee pockets are secured with hook-and-loop closures and makes the addition of elbow pads and knee pads quick and easy. Additional features that are an improvement over the traditional ACU include 50/50 Nylon/Cotton Ripstop fabric, No Melt, No Drip Flame Protection, articulated elbows and knees and slanted, bellowed chest pockets with inverted pleat hook-and-loop closures.
Although all are improvements over the standard ACU, the standout feature of the TRU Xtreme: MOLLE Xtreme Tactical Response Uniform is the addition of Mil-Spec MOLLE webbing over the entire uniform. This simple but revolutionary concept has resulted in the most customizable, operator-friendly uniform ever created. The Xtreme MOLLE webbing allows the operator to add pouches, gear and accessories where they need it. Bulky vests, harness systems and backpacks are now things of the past. Configure the uniform to match the mission.
The TRU Xtreme: MOLLE Xtreme Tactical Response Uniform is initially being offered in MULTICAM®, the pattern currently being worn by out troops fighting in Afghanistan. After extensive military field testing, the TRU Xtreme: MOLLE Xtreme Tactical Response Uniform is currently under consideration for adoption in the Afghanistan theater.
The TRU Xtreme: MOLLE Xtreme Tactical Response Uniform from TRU-SPEC – The blueprint for the modern tactical response uniform is available for pre-order exclusively at U.S. Cavalry.
About U.S. Cavalry: U.S. Cavalry, headquartered in Radcliff, Kentucky, has served professionals for 35 years by delivering the world's finest equipment, services and training. The company serves its customers through managed accounts, retail stores, mail order catalogs and web site. For more information, log-on to our web site at www.uscav.com or call 800.777.7172 today.
About TRU-SPEC: Since 1950, TRU-SPEC has been one of the leading suppliers of personal equipment, material and uniforms. To the many thousands of police, firefighters, EMTs and military personnel who use and depend on our products daily, TRU-SPEC has become synonymous with quality, innovation and service. Please visit www.uscav.com/truspec for the full line of TRU-SPEC products.


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industrial waste recycling Companies in Nova Scotia
NISKAE Inc.
based in Lachine, QUEBEC (CANADA)
Specialized in wastewater treatment and recycling, NISKAE was created to answer the constantly growing need of industrial companies, to respect the rules and regulations in terms of rejecting used water. With a rapid return on investment, within a year, Niskae is offering ecological and cost saving solutions.
Eldan Recycling A/S
based in Faaborg, DENMARK
Eldan Recycling A/S is one of the leading suppliers of equipment to the recycling and waste handling industries. We design and manufacture the equipment in-house at the production facility in Faaborg, Denmark. The main field of expertise is solutions for recycling of tyre, cable, aluminium (UBCs) and WEEE (Waste Electronic and Electric Equipment). We also supply waste ...
econ industries GmbH
based in Starnberg, GERMANY
Hazardous and industrial waste technologies are our profession. The VacuDry units - a thermal desorption process working with high temperature and lowest vacuum - are state-of-the-art for treating mercury, hydrocarbon, PCB, solvent polluted sludge and soils. We also offer solidification units to stabilise inorganic ashes, dust and sludge as well as sterilising systems ...
OZONATOR Industries Limited
based in Regina, SASKATCHEWAN (CANADA)
OZONATOR Industries Ltd., the manufacturer and world distributor of the OZONATOR NG Technology - the most sustainable technology available for the sterilization of medical and bio-hazardous waste. The OZONATOR sterilization technology is based on ozone and does not use heat, steam, chemicals, microwaves or radiation to sterilize waste to 6log10 (99.9999%) reduction. The ...
Go Green Industrial Supply
based in Maple Ridge, BRITISH COLUMBIA (CANADA)
Go Green Water Recycling (a division of Go Green Industrial) was created to provide an efficient solution to recycling and reclaiming waste water runoff produced by industry. We are deeply committed to preserving and maintaining our environment, not just locally, but globally. We researched the waste water systems that were in use in multiple worldwide locations and ...
Liquid Waste Technology LLC (LWT LLC)
based in New Richmond, WISCONSIN (USA)
Liquid Waste Technology (LWT) specializes in the design and manufacture of custom dredging system solutions for the dredging industry. LWT builds high quality computer and remote controlled portable dredges uniquely equipped for a variety of applications including: Dewatering Projects, Wastewater Lagoon Dredging, Water Treatment Plant Maintenance, Mine Tailings, Canal ...
Epcon Industrial Systems, LP
based in The Woodlands, TEXAS (USA)
Epcon Industrial Systems specializes in custom designing and manufacturing of Regenerative Thermal Oxidizers (RTO`s); Recuperative Thermal Oxidizers; Direct Fired Afterburners; Industrial Furnaces; Industrial Ovens and Speciality Finishing Systems.
Oxford Instruments Industrial Analysis
based in Abingdon, UNITED KINGDOM
Oxford Instruments designs, supplies and supports high-technology tools and systems with a focus on research and industrial applications. Innovation has been the driving force behind Oxford Instruments` growth and success for over 50 years, and its strategy is to effect the successful commercialisation of these ideas by bringing them to market in a timely and ...
Macpresse Europa S.R.L
based in Vernate, ITALY
Macpresse International is an Italian company headquartered in Vernate (Milan). Macpresse has been designing and installing recovery facilities for recycling secondary scrap materials for over 40 years. Macpresse provides scrap-handling solutions in the following sectors: recovery of first/secondary materials, processing of municipal solid waste (MSW) and industrial ...
Erdwich Zerkleinerungssysteme GmbH
based in Kaufering, GERMANY
Shredding systems & refrigerator recycling. With 1-, 2-, and 3-shaft machines, Erdwich offers here a vast range of disintegrators. As part of complete systems for processing refrigerators, hospital waste, paper, wood, synthetic materials, rejects, domestic and industrial waste etc. these machines will convince you by there precision and reliability in the hard industrial ...


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When last we checked in to Haven , things were bad. One of the main characters lay dead. A secondary character was revealed to be a serial killer. Would Audrey and Duke -- unaware of what happened -- More »
" Magic Hour (Part Two) " didn't quite have the same finesse that part one had, but we needed to find out what happened last week, didn't we? Audrey seemed to grow up a little since her trip to Colora More »
I've said it before, and I'll say it again, Haven , has the best recaps of any series I watch. "Magic Hour (Part 2)" started off with a handy recap of last week's episode that made it easy to jump r More »
Haven "Magic Hour (Part 2)" Season 3 Episode 8 airs on Friday Nov 9, 2012 at 10pm on Syfy. Show Summary : Based on the novella "The Colorado Kid" from renowned author Stephen King, "Haven" is a Syfy More »
Of all the weird things in Haven , that bizarre, disappearing, memory-erasing barn is one of the weirdest. Does it come back in "Magic Hour," part 2? Find out when the episode airs on Friday, November More »


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Near Wolf Creek, Ore. -- The remains of an unidentified body were found Saturday afternoon near the 8100 block of Lower Graves Creek Road.
Oregon State Police Criminal Investigations Division, the OSP Forensic Services Division and State Medical Examiner's Office, are working to identify the body as well as a cause of death.
Investigators are unable to confirm if the remains are of a male or female.
Copyright KOBI-TV. All rights reserved unless otherwise stated. This material may not be published, broadcast, rewritten, or redistributed without written permission.


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You are here
Check Up Event - Safe Kids Rhode Island - 7/1/2014 - 11:00AM-2:00PM
Did you know that 3 out of 4 car seats are not used correctly? Is yours one? We can help! Come and have your car seat installation checked by one of our CPS certified technicians. This event is free and no appointment needed.
Tuesday, July 1, 2014 - 11:00am to 2:00pm
WhereKohl's Seekonk
1 Commerce Way
Seekonk, MA


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Snap 'N Soar - Kid Powered Planes
Own the sky with these kid-powered airplanes!
Fly miniature jet style planes safely indoors and outside in just a snap.
Load your plane onto the handheld charger and simply snap your wrist for jet style, free flying fun as far as 30 feet. Adjustable flight surfaces allow you to perform amazing loop and stunts easily. Includes 1 launcher and 3 jet style planes. No batteries required. Recommended for ages 8 and up. Warning Choking Hazard - Small parts.
Measurements: 4" L x 4.5" W x 1" H
Weight: 2 lbs.
Snap 'N Soar - Kid Powered Planes
Reviewed by 1 customer
- Breaks To Easily
- Doesn't Last
Best Uses
- To Cheap For Kids
Comments about Snap 'N Soar - Kid Powered Planes:
It was broke after one use. Would have been better if it was made stronger.
- Was this a gift?:
- Yes
Snap 'N Soar - Kid Powered Planes
Our innovative products will provide you and your family with years of enjoyment. And with the Brookstone Protection Plus service and replacement plans, you'll have the added peace of mind knowing that if the unexpected does happen, we will simply repair or replace your covered product. Our enhanced coverage goes above and beyond the manufacturer's warranty, saving you time and money.
- 2-Year Extended Replacement Plan $4.99
- 3-Year Extended Replacement Plan $8.99
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By Jerry O'Brien
Proctor, Minn.
The 41st annual Silver 1000 at the Proctor Speedway is a long running special event which
started out as a Late Model Special back in 1973 and the Modifieds were added in 2000. This 41st
version had three races instead of two as the biggest race was against Mom Nature as officials
hustled to get the event in the books. The "Grand Daddy Of 'Em All" drew 29 Modifieds and 30
Late Models as heavy rains and severe thunderstorm warnings plagued the area….except for the
City of Proctor and the Proctor Speedway. Though ominous clouds and a few sprinkles loomed,
the race went on and it was a good one. Weather concerns no doubt kept a number of traveling
racers and fans from making the trip which kept the car count on the low side. A pretty good
crowd did show to see the two division program.


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365-Day Returns... Hassle-Free!
Main Content
Order as many items as you like with our $4.99 flat rate shipping.
This item ships within two business days.
Order as many items as you like with our $4.99 flat rate shipping.
Need it faster?
The rivalry you have with other SEC teams runs deep – but that's what makes the Southeastern Conference the best athletic conference in the nation! It just goes to show how dedicated every SEC fan base is. Boast that pride with the SEC Helmets tee. This lightweight shirt features an SEC logo on the left chest, with each team's helmet on the back surrounding another SEC logo.
- 100% Pre-shrunk cotton
- Imported
- Lightweight ribbed T-shirt
- Officially licensed SEC tee
- Screen print graphics
Shop early for holidays and birthdays with our 365 Day No-Hassle Return Policy! Because we stand behind the quality of our products, you can return any item in original condition for up to a full year from the purchase date. We want you and your gift recipients to love what you ordered, but if not, we make returns easy for you.
Special event items are produced by manufacturers only after the outcome of a game or event. These are advanced sale items and will ship immediately after they are received in our warehouse.
Manufacturer direct items are shipped directly from the manufacturer. These items are not available for international or expedited shipping.
Customized items can be personalized with options such as your name, your favorite number, and/or designs. Some options may be limited by league rules.


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Not really. Every now and then someone will ask about ideas for making things at their home shop they can sell and make a buck or three.
The other day a nice lady called and asked if I did window guards. I explained that I don't do window guards because people die when there is a fire and there are guards on the windows.
"No. Not that kind" she said. "I want a window guard for my dogs to see out of our privacy fence."
"I can do that" I said.
2" X 2" X 1/8" inch angle outside frame. Inside measurements are 8" X 16". They are attached with six lag screws into the horizontal rails of the fence. I added a 2" X 2" cedar rail for the bottom or top not supported by the fence rail 2" X 4". The 2 X 2 was attached to the pickets with stainless screws before I cut out the hole.
Installed this way they window grill is secure. You can shake the fence and not shake the grill.
Pricing: For the guy working out of the garage I would suggest $50.00 each for the grill and at least $50.00 for the installation. A regular business would have to have more of course because employees are involved. I used a cordless drill, cordless impact, and of course a cordless sawsall for the install. This particular client paid more than what I suggest and she had me do three of them at her house.
She loves them. Her dogs love them too. Love makes the world go around.
Results 1 to 10 of 17
11-06-2010, 08:21 PM #1Senior Member
- Join Date
- Sep 2006
- Posts
- 316
Pup peepholes for sale or rent.....
ya know, ive always liked your work, sir.... and again, im diggin the job.... nice lines, sirwelder_one
nothing fancy, just a few hot glue guns for metal
Hey harv,
Now, that is what I call unique & quite marketable. Nice job, well executed, & looks to be profitable..... that's how it's supposed to be. You did good...... matter of fact, I'm gonna copy it...with your permission.
Denny* Complete welding, machine, & fab shop *
* Mobile unit *
* Finally retired *
* A man's word is his honor..... without honor, there is nothing. *
* Words are like bullets..... once they leave your muzzle, you cannot get them back. *
* I have no reservation to kill nor hesitation to die for the U.S. Constitution & the American Flag. *
* Age is a state of mind..... at my age, you cannot fathom what is in my mind. *
11-06-2010, 10:02 PM #4Senior Member
- Join Date
- Sep 2006
- Posts
- 316
I've got an antique tire roller (the iron rings around wooden wagon wheels are called tires). I rolled the pieces of quarter inch bar stock into three foot circles. They worked out perfect for giving me arcs that matched in the panels.
I wish I was an artist. Because if I was an artist I would form the quarter inch bar stock into images of dog breeds. That way I could charge twice as much!
I do recommend the fastening method I used. I thought a lot about it and believe the fasteners being in shear makes the connnection a lot stronger over time because wood and metal like to separate over time.
I think it's great that you want to do it too.
Excellent idea!!!! The mounting is VERY well thought out, you cannot see any fasteners which is good.
RudyT-4 Paraplegic, Runnin' the Pedal With my elbow, now trying to get used to a momentary switch.......
Journeyman Millwright, Local 1102, Detroit, Michigan (Disabled)
Syncrowave 200
Coolmate 1
11-07-2010, 06:55 AM #6Senior Member
- Join Date
- Sep 2006
- Posts
- 316
For those who didn't get it Rudy is a paraplegic. That means he can't feel anything below his injury. He could have a dingleberry land on his leg for instance and not know it until he smelled burning flesh. Or he could move into a hot piece of metal and get severely burned and not know it was happening. The same thing goes for machinery.
Rudy must have a real love for welding to expose himself to the potential of serious injury. He is to be congratulated for his passion but I hope he is taking care to protect himself.
When I see someone like Rudy I guess I appreciate it more than others. That's because I had a friend who was a super quad and he still did work even though the risk was greater for him than someone who could feel their legs and belly.
I'll never forget the panhandler who hit me up for a dollar at a gas station one morning. I gave him a buck in a moment of weakness and so I guess he thought that paid for some conversation. He asked me what I did. When I told him that I was a weldor he said he went to school for that but didn't like all the burns from the hot sparks.
Thank you Rudy for doing instead of quitting. And if you have a situation where you need some brainstorming to overcome a situation, well, we're here.
11-07-2010, 06:58 AM #7Senior Member
- Join Date
- Sep 2006
- Posts
- 316
11-07-2010, 07:12 AM #8welder_one
nothing fancy, just a few hot glue guns for metal
11-07-2010, 10:59 AM #9Senior Member
- Join Date
- Sep 2007
- Location
- Medford MA
- Posts
- 544
very nice work - looks great!


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After staying home with his two sons for a year and his daughter since her infancy, Tim Myers knows all about being a stay-at-home parent. He knows the most effective cleaning products, which snacks to buy, and has developed a "housemaid's knee." He has experienced first-hand the profound influence fathers have on their children, along with the challenges of being a committed parent. By recounting personal experiences, offering honest, sincere opinions, and including quizzes for fatherly-preparedness, Tim Myers emphasizes the importance of fatherly contribution and influence in the home. He shows fathers that they are not only vital to home life, but that fatherhood also brings great joy into men's lives, not to mention a surprising amount of plain old fun. In addition, Myers details the essential role of fathers, and the very real (and sometimes frustrating) transition into taking an active role in home life.
Tim J. Myers is a writer, songwriter, storyteller, and senior lecturer at Santa Clara University in Silicon Valley. He is a widely published writer for adults and children. His book Glad to Be Dad: A Call to Fatherhood made #5 on Amazon's "Hot New Releases in Fatherhood" list, was featured on the Parents Magazine site, quoted on Disney's BabyZone site, won the Ben Franklin Digital Award, and has gotten excellent reviews.
Length: 60 minutes, with Q&A after
For more information and to register for this program, please contact Youth Services at 1-408-615-2916.
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