Post-therapeutic changes in the molecular profile of glioblastomas

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 2026-2026
Author(s):  
C. Horbinski ◽  
A. Mintz ◽  
J. Engh ◽  
F. Lieberman ◽  
R. L. Hamilton ◽  
...  
Keyword(s):  
Therapy Resistance ◽  
Primary Brain Tumor ◽  
External Beam Radiation ◽  
Molecular Profile ◽  
Genetic Profile ◽  
Low Grade ◽  
Beam Radiation ◽  
Molecular Alterations ◽  
Development Of Resistance ◽  
Formalin Fixed Paraffin Embedded

2026 Background: Glioblastoma multiforme is the most common and malignant primary brain tumor in adults. Despite aggressive surgery, radiation, and chemotherapy, average survival time after diagnosis is about 1 year. This may be partly due to development of resistance to adjuvant therapies. While the molecular alterations in pretreated glioblastomas have been the subject of much research in recent years, changes in their genetic profile after adjuvant therapy are largely unknown. Methods: Herein we describe a cohort of over 40 glioblastomas with characterization of key genetic loci (EGFR, p53, 1p, 19q, 9p, 10q, 17p) using fluorescence in situ hybridization, PCR-based loss of heterozygosity (LOH) analysis, and immunohistochemistry on formalin-fixed, paraffin-embedded tissues. Analyses were performed on tumor tissue obtained at initial diagnosis and at first recurrence. Treatment regimen during the interval consisted of external beam radiation therapy and temozolomide, an alkylating chemotherapeutic agent. Results: About 50% showed large increases or decreases in hyperploidy of chromosomes 1, 7, 9, and/or 19 after therapy. Over 70% showed changes in LOH patterns on 1p, 19q, 9p, 10q, and/or 17p. 24% of previously non-EGFR-amplified tumors acquired low-grade amplification (less than 10 copies/chromosome 7 CEP signal) after treatment, and 16% of EGFR-amplified tumors lost amplification after treatment. Conclusions: Our results suggest that the molecular profile of these tumors is dynamic and that certain key alterations, including acquisition of low-level EGFR amplification in previously EGFR-negative tumors, occurs in a subset of cases. Such alterations may contribute to therapy resistance as the glioma evolves in a changing microenvironment. No significant financial relationships to disclose.

Combined stereotactic split-course fractionated gamma knife radiosurgery and conventional radiation therapy for unfavorable gliomas: a phase I study

2000 ◽  
Vol 93 (supplement_3) ◽  
pp. 37-41 ◽  
Author(s):  
William F. Regine ◽  
Roy A. Patchell ◽  
James M. Strottmann ◽  
Ali Meigooni ◽  
Michael Sanders ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Disease Progression ◽  
Gamma Knife ◽  
Gamma Knife Radiosurgery ◽  
External Beam Radiation ◽  
Low Grade ◽  
Beam Radiation ◽  
Content Type ◽  
Group B ◽  
Fine Print

Object. This investigation was performed to determine the tolerance and toxicities of split-course fractionated gamma knife radiosurgery (FSRS) given in combination with conventional external-beam radiation therapy (CEBRT). Methods. Eighteen patients with previously unirradiated, gliomas treated between March 1995 and January 2000 form the substrate of this report. These included 11 patients with malignant gliomas, six with low-grade gliomas, and one with a recurrent glioma. They were stratified into three groups according to tumor volume (TV). Fifteen were treated using the initial FSRS dose schedule and form the subject of this report. Group A (four patients), had TV of 5 cm3 or less (7 Gy twice pre- and twice post-CEBRT); Group B (six patients), TV greater than 5 cm3 but less than or equal to 15 cm3 (7 Gy twice pre-CEBRT and once post-CEBRT); and Group C (five patients), TV greater than 15 cm3 but less than or equal to 30 cm3 (7 Gy once pre- and once post-CEBRT). All patients received CEBRT to 59.4 Gy in 1.8-Gy fractions. Dose escalation was planned, provided the level of toxicity was acceptable. All patients were able to complete CEBRT without interruption or experiencing disease progression. Unacceptable toxicity was observed in two Grade 4/Group B patients and two Grade 4/Group C patients. Eight patients required reoperation. In three (38%) there was necrosis without evidence of tumor. Neuroimaging studies were available for evaluation in 14 patients. Two had a partial (≥ 50%) reduction in volume and nine had a minor (> 20%) reduction in size. The median follow-up period was 15 months (range 9–60 months). Six patients remained alive for 3 to 60 months. Conclusions. The imaging responses and the ability of these patients with intracranial gliomas to complete therapy without interruption or experiencing disease progression is encouraging. Excessive toxicity derived from combined FSRS and CEBRT treatment, as evaluated thus far in this study, was seen in patients with Group B and C lesions at the 7-Gy dose level. Evaluation of this novel treatment strategy with dose modification is ongoing.

scholarly journals A case of primary mucosa-associated lymphoid tissue lymphoma of the prostate

Rare Tumors ◽  
2009 ◽  
Vol 1 (2) ◽  
pp. 169-170
Author(s):  
Noriko Koga ◽  
Masanori Noguchi ◽  
Fukuko Moriya ◽  
Kouichi Ohshima ◽  
Nobuyuki Yoshitake ◽  
...  
Keyword(s):  
B Cell ◽  
Lymphoid Tissue ◽  
Marginal Zone ◽  
Specific Antigen ◽  
Bone Marrow Aspiration ◽  
External Beam Radiation ◽  
Low Grade ◽  
Beam Radiation ◽  
Malt Type Lymphoma ◽  
Immunohistochemical Studies

We report a case of primary mucosa-associated lymphoid tissue (MALT) lymphoma of the prostate. A 67-year-old man presented with urinary obstruction and an elevated prostate-specific antigen (PSA) level. A physical examination revealed mild prostate enlargement and no lymphadenopathy. A needle biopsy and immunohistochemical studies of the prostate were performed, which revealed marginal zone B-cell MALT-type lymphoma. A bone marrow aspiration and biopsy did not show involvement by lymphoma. Magnetic resonance imaging (MRI) of the abdomen and the pelvis revealed no lymphadenopathy or ascites. There was no involvement of other sites by lymphoma. The patient was diagnosed and staged as extranodal marginal zone B-cell MALT-type lymphoma of the prostate, low grade and stage I. The patient received external beam radiation therapy to the prostate with a total dose of 3600cGy in 22 fractions, and became free of disease within the following 15 months.

scholarly journals Intratumoural Heterogeneity Underlies Distinct Therapy Responses and Treatment Resistance in Glioblastoma

Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 190 ◽  
Author(s):  
Seçkin Akgül ◽  
Ann-Marie Patch ◽  
Rochelle C.J. D’Souza ◽  
Pamela Mukhopadhyay ◽  
Katia Nones ◽  
...  
Keyword(s):  
Targeted Therapies ◽  
Dynamic Environment ◽  
Treatment Resistance ◽  
Therapy Resistance ◽  
Disease Recurrence ◽  
Therapeutic Interventions ◽  
Molecular Profile ◽  
Molecular Alterations ◽  
Pathologic Features ◽  
Intratumoural Heterogeneity

Glioblastomas are the most common and lethal neoplasms of the central nervous system. Neighbouring glioma cells maintain extreme degrees of genetic and phenotypic variation that form intratumoural heterogeneity. This genetic diversity allows the most adaptive tumour clones to develop treatment resistance, ultimately leading to disease recurrence. We aimed to model this phenomenon and test the effectiveness of several targeted therapeutic interventions to overcome therapy resistance. Heterogeneous tumour masses were first deconstructed into single tumour cells, which were expanded independently as single-cell clones. Single nucleotide polymorphism arrays, whole-genome and RNA sequencing, and CpG methylation analysis validated the unique molecular profile of each tumour clone, which displayed distinct pathologic features, including cell morphology, growth rate, and resistance to temozolomide and ionizing radiation. We also identified variable sensitivities to AURK, CDK, and EGFR inhibitors which were consistent with the heterogeneous molecular alterations that each clone harboured. These targeted therapies effectively eliminated the temozolomide- and/or irradiation-resistant clones and also parental polyclonal cells. Our findings indicate that polyclonal tumours create a dynamic environment that consists of diverse tumour elements and treatment responses. Designing targeted therapies based on a range of molecular profiles can be a more effective strategy to eradicate treatment resistance, recurrence, and metastasis.

Secondary gliosarcoma after diagnosis of glioblastoma: clinical experience with 30 consecutive patients

2010 ◽  
Vol 112 (5) ◽  
pp. 990-996 ◽  
Author(s):  
Seunggu J. Han ◽  
Isaac Yang ◽  
Jose J. Otero ◽  
Brian J. Ahn ◽  
Tarik Tihan ◽  
...  
Keyword(s):  
Malignant Glioma ◽  
Retrospective Chart Review ◽  
High Grade Glioma ◽  
External Beam Radiation ◽  
Molecular Profile ◽  
External Beam ◽  
Beam Radiation ◽  
Additional Chemotherapy ◽  
Radiotherapy Alone ◽  
Neurological Surgery

Object Gliosarcoma can arise secondarily, after conventional adjuvant treatment of high-grade glioma. The current literature on the occurrence of secondary gliosarcoma (SGS) after glioblastoma multiforme (GBM) is limited, with only 12 reported cases. The authors present a large series of histologically confirmed SGSs, with follow-up to describe the clinical and radiological presentation, pathological diagnosis, and treatment outcomes. Methods Gliosarcoma cases were identified using the University of California, San Francisco's Departments of Neurological Surgery and Neuropathology databases. Through a retrospective chart review, cases of gliosarcoma were considered SGS if the following inclusion criteria were met: 1) the patient had a previously diagnosed intracranial malignant glioma that did not have gliosarcoma components; and 2) the histopathological tissue diagnosis of the recurrence confirmed gliosarcoma according to the most current WHO criteria. Extensive review of clinical, surgical, and pathology notes was performed to gather clinical and pathological data on these cases. Results Thirty consecutive patients in whom SGS had been diagnosed between 1996 and 2008 were included in the analysis. All patients had previously received a diagnosis of malignant glioma. For the initial malignant glioma, all patients underwent resection, and 25 patients received both external-beam radiation and chemotherapy. Three patients received radiotherapy alone, 1 patient was treated with chemotherapy alone, and 1 patient's tumor rapidly recurred as gliosarcoma, requiring surgical intervention prior to initiation of adjuvant therapy. The median time from diagnosis of the initial tumor to diagnosis of gliosarcoma was 8.5 months (range 0.5–25 months). All but 1 patient (who only had a biopsy) underwent a second operation for gliosarcoma; 8 patients went on to receive radiotherapy (4 had brachytherapy, 3 had external-beam radiation, and 1 had Gamma Knife surgery); and 14 patients received additional chemotherapy. The median length of survival from the time of gliosarcoma diagnosis was 4.4 months (range 0.7–46 months). The median survival from the time of the original GBM diagnosis was 12.6 months (range 5.7–47.4 months). Patients who had received concurrent and adjuvant temozolomide for GBM had worse outcomes than those who had not (4.3 and 10.5 months, respectively; p = 0.045). There was no difference in time to diagnosis of gliosarcoma in these 2 groups (8 and 8.5 months; p = 0.387). Two patients who had not received radiation therapy for GBM had an anecdotally very prolonged survival (20.9 and 46.4 months). Conclusions The data underscore the difficulty associated with management of this disease. The strikingly poor survival of patients with SGS who had previously received combined radiation and temozolomide chemotherapy for GBM may reflect a unique molecular profile of GBM that eventually recurs as SGS. Further work will be required, controlling for multiple prognostic factors with larger numbers of patients.

Sclerosing Epithelioid Fibrosarcoma of the Cecum: A Radiation-Associated Tumor in a Previously Unreported Site

2007 ◽  
Vol 131 (12) ◽  
pp. 1825-1828 ◽  
Author(s):  
Jared C. Frattini ◽  
Julie Ann Sosa ◽  
Susanne Carmack ◽  
Marie E. Robert
Keyword(s):  
Ionizing Radiation ◽  
Nuclear Reactor ◽  
Soft Tissues ◽  
Atomic Bomb ◽  
External Beam Radiation ◽  
Low Grade ◽  
Beam Radiation ◽  
Sclerosing Epithelioid Fibrosarcoma ◽  
First Case ◽  
Radiation Induced

Abstract Data from the nuclear reactor explosion in Chernobyl and the atomic bomb detonations in Hiroshima and Nagasaki demonstrated an association between ionizing radiation and tumoriogenesis. There is a significant association between external beam radiation and radiation-induced sarcoma. Sclerosing epithelioid fibrosarcoma is a rare form of malignant fibrosarcoma that is low grade and indolent with distinct immunohistopathologic characteristics that usually occurs in the soft tissues of the extremities. A 62-year-old man from Kiev who aided in the cleanup at Chernobyl presented with crampy abdominal pain, nausea, and vomiting. His workup revealed a cecal mass, and the final pathology from his laparotomy confirmed sclerosing epithelioid fibrosarcoma with metastasis to the liver. In addition to a review of the literature, we report the first case of sclerosing epithelioid fibrosarcoma arising from the large bowel. Exposure to ionizing radiation from Chernobyl could have played a role in the development of his tumor.

scholarly journals Priming radioimmunotherapy with external beam radiation in patients with relapsed low grade non-Hodgkin lymphoma

2017 ◽  
Vol 8 (4) ◽  
pp. 129-138 ◽  
Author(s):  
Yazan Abuodeh ◽  
Kamran Ahmed ◽  
Michelle Echevarria ◽  
Arash Naghavi ◽  
G. Daniel Grass ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Low Dose ◽  
Univariate Analysis ◽  
External Beam Radiation ◽  
Anatomical Location ◽  
Low Grade ◽  
External Beam ◽  
Beam Radiation ◽  
Non Hodgkin Lymphoma ◽  
Significant Difference

Background: The aim of this study was to evaluate the outcomes of priming salvage radioimmunotherapy (RIT) with a low dose of external beam radiotherapy (EBRT) in patients with relapsed low grade non-Hodgkin lymphoma (LG-NHL). Methods: Patients who received salvage RIT with or without 2 × 2 Gy EBRT between March 2009 and February 2013 were retrospectively reviewed at a single institution. Planning target volume (PTV) for EBRT was created by adding a 1–2 cm expansion to the gross tumor volume depending on the anatomical location. Kaplan−Meier method via log-rank was employed to analyze the endpoints freedom from progression (FFP) and overall survival (OS). Results: We identified 22 patients who received salvage RIT without chemotherapy with a median follow up of 34 months. Of these, 9 (41%) patients were treated with EBRT immediately prior to RIT, and 13 (59%) received salvage RIT alone. Median FFP was not reached in patients who underwent combination treatment, while it was 9 months for patients treated with RIT alone ( p = 0.02). OS for all patients at 36 months was 80.3% with no significant difference between the two groups ( p = 0.88). On univariate analysis, the addition of EBRT was associated with improved FFP [hazard ratio (HR) = 4.17; 95% confidence interval (CI), 1.24–19.1; p = 0.02)]. No long term toxicities were reported in both groups. Conclusions: RIT outcomes and effects were improved with addition of low-dose EBRT immediately prior to it, in the treatment of relapsed LG-NHL with no additional toxicity. This study is hypothesis-generating and the findings should be validated in prospective studies.

scholarly journals Multimodal Imaging and Clinicopathologic Correlation in Primary Uveal Lymphoma

2016 ◽  
Vol 7 (1) ◽  
pp. 39-43
Author(s):  
Brandon Erickson ◽  
Dimosthenis Mantopoulos ◽  
Lynn Schoenfield ◽  
Colleen M. Cebulla
Keyword(s):  
Retinal Detachment ◽  
Multimodal Imaging ◽  
Radiation Treatment ◽  
B Cell Lymphoma ◽  
Needle Aspiration ◽  
Good Prognosis ◽  
External Beam Radiation ◽  
Low Grade ◽  
Beam Radiation ◽  
Primary Uveal Lymphoma

Purpose: We report a rare case of primary uveal lymphoma and characterize it using histopathology and multimodal imaging. Patient and Methods: A 41-year-old male presented with a 2-year history of increasingly blurry vision in his right eye and no systemic symptoms. Examination revealed a retinal detachment and mass lesion in the right eye. Radiologic and histologic testing was performed. Results: Multimodal imaging localized the lesion to the choroid, and fine needle aspiration biopsy diagnosed the lesion as a low-grade B-cell lymphoma. The patient was treated with external beam radiation, resulting in regression of the mass and resolution of the retinal detachment. Conclusions: Primary uveal lymphoma is a rare, usually indolent tumor that carries a good prognosis. In this case, we show that primary uveal lymphoma has distinct findings via histopathology and multimodal imaging, and that imaging after radiation treatment documents disease regression.

Survival after stereotactic biopsy and irradiation of cerebral nonanaplastic, nonpilocytic astrocytoma

1995 ◽  
Vol 82 (4) ◽  
pp. 523-529 ◽  
Author(s):  
L. Dade Lunsford ◽  
Salvador Somaza ◽  
Douglas Kondziolka ◽  
John C. Flickinger
Keyword(s):  
Radiation Therapy ◽  
Median Survival ◽  
Stereotactic Biopsy ◽  
External Beam Radiation ◽  
Low Grade ◽  
Beam Radiation ◽  
Initial Management ◽  
Content Type ◽  
Colloidal Phosphorus ◽  
Fine Print

✓ The authors investigated the outcome of stereotactic biopsy and radiotherapy in 35 consecutive adult patients with nonanaplastic, nonpilocytic astrocytomas who were diagnosed between 1982 and 1992. The median patient age at presentation was 32 years. All received fractionated external-beam radiation therapy (median dose 56 Gy) as the initial management strategy. Additional treatment in two patients included intracavitary irradiation with colloidal phosphorus-32. Six patients (17%) had documented tumor progression during the follow-up interval and died. Three others died of causes unrelated to their tumor. Median survival after stereotactic biopsy and irradiation was 118 months (9.8 years). Median survival from the time of onset of neurological symptoms was 148 months (12.3 years). Only three patients required delayed cytoreductive surgery. The outcome of brain astrocytomas, although improved because of earlier diagnosis and therapy, does not substantiate this tumor as having benign behavior; early recognition with neuroimaging, immediate histological diagnosis via stereotactic biopsy, and initial fractionated radiation therapy may provide the potential for longer survival for patients with low-grade astrocytomas. The majority of such surviving patients have a satisfactory quality of life, which is manifested by prolonged normal functional and employment status. The survival data reported in this prospective Phase I–II clinical trial suggest that stereotactic biopsy and radiation therapy are appropriate initial management strategies for astrocytomas.

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