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112 Adult brain tumors
116
Radiation Oncology, Biology, Physics Volume 32, Supplement 1 1:30-
3:00P.M.
111 RETINOBLASTOMA: GENETICS, DIAGNOSIS, TREATMENT AND SEQUELAE Edward C. Halperin, M.D. Professor and Vice-Chairman, Department of Radiation Oncology Duke University Medical Center, D~rham, NC
[here has been a conceptual breakthrough in our understanding of the molecular and genetic basis of the origins of human aeopLasia. Mutations in three broad categories of genes have been shown to contribute to the origins and progression of neoplasia in humans: the oncogenes, the tumor suppressor genes, and the mutator genes The retinoblastoma gene (RB1) is the best characterized tumor suppressor gene. It was first localized by Knudson and coworkers who observed an association between a deletion on the long arm of chromosome 13 and an inherited predisposition to retinoblastoma. The RB1 gene is composed of 27 exons encompassing more than 200 kilobases of genomic DNA. The product of the RB1 gene is a 105-107 kDa nuclear phosphoprotein which plays a part in regulating cellular DNA synthesis. Tumors arise, as predicted by Knudson's "two-hit" hypothesis, as a result of bi-allelic mutation of the RB1 gene. Inactivating mutations of the RB1 gene have been identified in various tumors, showing the RB1 gene product has an important role in regulating cell proliferation beyond its effect on retinoblasts. The RB1 gene was cloned and identified in 1986. Returning the RB1 gene to a retinoblastoma cell in culture reduces its tumorgenic potential. Retinoblastoma is the most common malignant intraocular tumor of childhood. The tumor consists of undifferentiated small anaplastic cells which may be round or polygonal. Both Flexner and Wintersteiner described the arrangement of the more differentiated malignant retinoblasioma cells in neuroepithelial rosettes which appear to represent an attempt to differentiate into photoreceptor cells. The tumor commonly presents with a white pupillary light reflex. The diagnosis is generally made based on physical examination, confirmatory photographs and diagnostic imaging studies and, in many cases, a supportive family history. The most widely used grouping system was proposed by A~gerncn Reese and Robert Ellsworth, The primary goal of retinoblastoma treatment is cure. It is reasonable to assert that a secondary goal of treatment is preservation of vision in the affected eye. Surgical options for therapy include enucleation, exenteration, photo coagulation, cryotherapy, and radioactive plaque application, External beam radiotherapy has a significant role to play in sight-preserving therapy. There has been a resurgence of interest in the use of systemic cytotoxic chemotherapy, either in addition to conventional surgical and radiotherapy techniques or as an alternative to them. The RB1 gene unequivocally is involved in carcinogenesis. Heritable retinoblastoma has an appreciable rate of second malignant neoplasm development - the cumulative mortality for all second tumors at 40 years of follow-up for bilateral retinoblastoma has been calculated to be 26%. Therapy choice may influence the risk and type of second malignant neoplasms. This refresher course will survey the genetic basis of retinoblastoma, techniques of diagnosis, forms of therapy, and the long-term consequences of cure of this fascinating childhood malignancy.
112 ADULT BRAIN TUMORS David A. Larson. M.D. Department of Radiation Oncology, Univ. of California, San Francisco, CA
Radiotherapy plays an important ro~e in the management of adults with brain tumors. This refresher course will focus on a wide variety of benign and malignant brain neoplasms and how contemporary radiotherapy affects survival. In each case the intent of radiation therapy is to destroy the neoplasm without affecting normal tissues. However, for many neoplasms serial post-treatment scans may show little change, and success is often measured more by absence of tumor progression than by scan normalization. Successful outcome after radiation therapy of brain tumors usually requires that (1) there is no tumor extension beyond the target volume, (2) adequate dose is delivered to the target volume, and (3) normal tissue tolerance doses are not exceeded. For some tumors it may be impossible to satisfy all three criteria. Three-dimensional treatment planning based on MRI or CT makes it possible to guarantee delivery of the full dose of radiation to gross tumor while minimizing the volume of normal tissue receiving high dose. Acceptable dose conformity can often be achieved with 2-4 static beams or arcs and are usually preferable to opposed lateral fields. Examples of planning solutions for a variety of tumor types, sizes, and anatomic location will be given. For some tumors, protocols involving substantial dose escalation require a large number of non-coplanar x-ray beams or particle therapy. Several concepts and techniques which relate to the treatment of brain tumors will be discussed, including conformal radiotherapy, brachytherapy, rad{osurgery, fractionated stereotactic radiotherapy, altered fracfionation, inverse treatment pIanning, re-irradiation and biologically effectwe dose (BED).
Radiation Oncology, Biology, Physics Volume 32, Supplement 1 1:30-
3:00P.M.
111 RETINOBLASTOMA: GENETICS, DIAGNOSIS, TREATMENT AND SEQUELAE Edward C. Halperin, M.D. Professor and Vice-Chairman, Department of Radiation Oncology Duke University Medical Center, D~rham, NC
[here has been a conceptual breakthrough in our understanding of the molecular and genetic basis of the origins of human aeopLasia. Mutations in three broad categories of genes have been shown to contribute to the origins and progression of neoplasia in humans: the oncogenes, the tumor suppressor genes, and the mutator genes The retinoblastoma gene (RB1) is the best characterized tumor suppressor gene. It was first localized by Knudson and coworkers who observed an association between a deletion on the long arm of chromosome 13 and an inherited predisposition to retinoblastoma. The RB1 gene is composed of 27 exons encompassing more than 200 kilobases of genomic DNA. The product of the RB1 gene is a 105-107 kDa nuclear phosphoprotein which plays a part in regulating cellular DNA synthesis. Tumors arise, as predicted by Knudson's "two-hit" hypothesis, as a result of bi-allelic mutation of the RB1 gene. Inactivating mutations of the RB1 gene have been identified in various tumors, showing the RB1 gene product has an important role in regulating cell proliferation beyond its effect on retinoblasts. The RB1 gene was cloned and identified in 1986. Returning the RB1 gene to a retinoblastoma cell in culture reduces its tumorgenic potential. Retinoblastoma is the most common malignant intraocular tumor of childhood. The tumor consists of undifferentiated small anaplastic cells which may be round or polygonal. Both Flexner and Wintersteiner described the arrangement of the more differentiated malignant retinoblasioma cells in neuroepithelial rosettes which appear to represent an attempt to differentiate into photoreceptor cells. The tumor commonly presents with a white pupillary light reflex. The diagnosis is generally made based on physical examination, confirmatory photographs and diagnostic imaging studies and, in many cases, a supportive family history. The most widely used grouping system was proposed by A~gerncn Reese and Robert Ellsworth, The primary goal of retinoblastoma treatment is cure. It is reasonable to assert that a secondary goal of treatment is preservation of vision in the affected eye. Surgical options for therapy include enucleation, exenteration, photo coagulation, cryotherapy, and radioactive plaque application, External beam radiotherapy has a significant role to play in sight-preserving therapy. There has been a resurgence of interest in the use of systemic cytotoxic chemotherapy, either in addition to conventional surgical and radiotherapy techniques or as an alternative to them. The RB1 gene unequivocally is involved in carcinogenesis. Heritable retinoblastoma has an appreciable rate of second malignant neoplasm development - the cumulative mortality for all second tumors at 40 years of follow-up for bilateral retinoblastoma has been calculated to be 26%. Therapy choice may influence the risk and type of second malignant neoplasms. This refresher course will survey the genetic basis of retinoblastoma, techniques of diagnosis, forms of therapy, and the long-term consequences of cure of this fascinating childhood malignancy.
112 ADULT BRAIN TUMORS David A. Larson. M.D. Department of Radiation Oncology, Univ. of California, San Francisco, CA
Radiotherapy plays an important ro~e in the management of adults with brain tumors. This refresher course will focus on a wide variety of benign and malignant brain neoplasms and how contemporary radiotherapy affects survival. In each case the intent of radiation therapy is to destroy the neoplasm without affecting normal tissues. However, for many neoplasms serial post-treatment scans may show little change, and success is often measured more by absence of tumor progression than by scan normalization. Successful outcome after radiation therapy of brain tumors usually requires that (1) there is no tumor extension beyond the target volume, (2) adequate dose is delivered to the target volume, and (3) normal tissue tolerance doses are not exceeded. For some tumors it may be impossible to satisfy all three criteria. Three-dimensional treatment planning based on MRI or CT makes it possible to guarantee delivery of the full dose of radiation to gross tumor while minimizing the volume of normal tissue receiving high dose. Acceptable dose conformity can often be achieved with 2-4 static beams or arcs and are usually preferable to opposed lateral fields. Examples of planning solutions for a variety of tumor types, sizes, and anatomic location will be given. For some tumors, protocols involving substantial dose escalation require a large number of non-coplanar x-ray beams or particle therapy. Several concepts and techniques which relate to the treatment of brain tumors will be discussed, including conformal radiotherapy, brachytherapy, rad{osurgery, fractionated stereotactic radiotherapy, altered fracfionation, inverse treatment pIanning, re-irradiation and biologically effectwe dose (BED).