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Brian Patrick O'Neill

Publications and source records attributed to Brian Patrick O'Neill.

12 recordsLinked to original sources
PubMed2006

Ocular manifestations and treatment of central nervous system lymphomas.

Intraocular primary central nervous system lymphoma (PCNSL), also called primary intraocular lymphoma (PIOL), is a subset of PCNSL in which lymphoma cells invade the subretinal pigment epithelial space and vitreous cavity with or without central nervous system involvement at the time of ocular diagnosis. The frequency of this rare condition has increased over the past years in immunosuppressed as well as immunocompetent patients. The authors review the current status of PIOL and elaborate on their group's experience with its diagnosis and treatment. The incidence of PIOL is increasing. There is evidence that chronic antigenic stimulation may result in the development of PIOL. Recent advancements in the diagnosis of PIOL include better handling of vitreous specimens for cytological studies, immunocytological investigation for lymphoid cells, flow cytometry, cytokine evaluation, and molecular analysis. Because PIOL has a nonspecific presentation, the differential diagnosis should include infectious and noninfectious causes presenting with vitreitis and/or subepithelial infiltration as well as paraneoplastic syndromes including CRMP-5 optic neuropathies. Given that therapy is long-term and has significant systemic and ocular complications, tissue diagnosis is important. Treatment of PIOL may include systemic chemotherapy in which high-dose methotrexate-based regimens are used as well as intraocular injections of methotrexate and rituximab (anti-CD20 antibody). Cranial and ocular external-beam radiotherapy is being used less often today. Further studies are needed to prevent the tumor formation in terms of eliminating antigenic load and inhibiting Bcell chemokines as well as to determine the optimal local and systemic chemotherapy and immunotherapy options in the management of PIOL.

Brain Neoplasms↗
PubMed2006

Whole-brain radiotherapy and high-dose methylprednisolone for elderly patients with primary central nervous system lymphoma: Results of North Central Cancer Treatment Group (NCCTG) 96-73-51.

PURPOSE: The aim of this study was to evaluate the efficacy, toxicity, and survival of whole-brain radiotherapy-treated (WBRT) and high-dose methylprednisolone (HDMP)-treated in elderly patients with primary central nervous system lymphoma (PCNSL). METHODS AND MATERIALS: Patients with PCNSL who were 70 years and older received 1 g of methylprednisolone daily for 5 days, 30 days after WBRT. Patients then received 1 g of methylprednisolone every 28 days until progression. The primary endpoint was overall survival (OS) at 6 months. Results were compared with those in patients on the previous North Central Cancer Treatment Group (NCCTG) trial who received pre-WBRT cytoxan, adriamycin, vincristine, prednisone (CHOP) and high-dose cytarabine (CHOP-WBRT). A planned interim analysis was performed. The current regimen would be considered inactive if survival was not improved from patients treated with CHOP-WBRT. RESULTS: Nineteen patients were accrued between 1998 and 2003. Median age was 76 years. Interim analysis revealed a 6-month survival of 33%, resulting in closure of the trial. Toxicity, OS, and event-free survival (EFS) were similar to those in patients more than 70 years of age who received CHOP-WBRT. The subgroup of patients who received HDMP had longer OS (12.1 vs. 7.0 months, p = 0.76) and EFS (11.7 vs. 4.0 months, p = 0.04) compared with the CHOP-WBRT patients alive 60 days after the start of treatment. CONCLUSIONS: Patients on-study long enough to receive HDMP had prolongation of OS and EFS compared to patients receiving CHOP-WBRT. Although the numbers of patients are too small for statistical conclusions, the HDMP regimen deserves further study.

Aged↗
PubMed2006

Delivery of chemotherapy and antibodies across the blood-brain barrier and the role of chemoprotection, in primary and metastatic brain tumors: report of the Eleventh Annual Blood-Brain Barrier Consortium meeting.

Although knowledge of molecular biology and cellular physiology has advanced at a rapid pace, much remains to be learned about delivering chemotherapy and antibodies across the blood-brain barrier (BBB) for the diagnosis and treatment of central nervous system (CNS) disease. A meeting, partially funded by an NIH R13 grant, was convened to discuss the state of the science, current knowledge gaps, and future directions in the delivery of drugs and proteins to the CNS, for the treatment of primary and metastatic brain tumors. Meeting topics included CNS metastases and the BBB, and chemoprotection and chemoenhancement in CNS disorders. The discussions regarding CNS metastases generated possibilities of chemoprotection as a means not only to decrease treatment-related toxicity but also to increase chemotherapy dose intensity. The increasing incidence of sanctuary brain metastasis from breast cancer, in part due to the difficulty of monoclonal antibodies (mAbs) such as herceptin to cross the BBB, was one of the most salient "take home" messages of the meeting.

Animals↗
PubMed2006

International study on low-grade primary central nervous system lymphoma.

OBJECTIVE: The aim of this study was to characterize the clinical presentation, course, and outcome of low-grade primary central nervous system lymphoma. METHODS: Cases were assessed in a retrospective series collected from 18 cancer centers in 5 countries. RESULTS: Forty patients (18 men, 22 women; median age, 60 years [range, 19-78]) were identified. Involvement of a cerebral hemisphere or deeper brain structures was seen in 37 patients, only leptomeningeal involvement in 2 patients, and spinal cord disease in 1 patient. Chemotherapy/radiotherapy was conducted in 15 patients, radiotherapy alone in 12, chemotherapy alone in 10, and tumor resection alone in 2, whereas 1 patient received no treatment. The median progression-free, disease-specific, and overall survival were 61.5 (range, 0-204), 130 (range, 1-204), and 79 (range, 1-204) months, respectively. Only age 60 years or older was associated with shorter progression-free (p = 0.009), disease-specific (p = 0.015), and overall survival (p = 0.001) in multivariate analysis. INTERPRETATION: Low-grade primary central nervous system lymphoma differs from the high-grade subtype in its pathological, clinical, and radiological features. It has a better long-term outcome than primary central nervous system lymphoma in general with age 60 years or older adversely affecting survival.

Age Factors↗
PubMed2005

Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma.

Standardized guidelines for the baseline evaluation and response assessment of primary CNS lymphoma (PCNSL) are critical to ensure comparability among clinical trials for newly diagnosed patients. The relative rarity of this tumor precludes rapid completion of large-scale phase III trials and, therefore, our reliance on the results of well-designed phase II trials is critical. To formulate this recommendation, an international group of experts representing hematologic oncology, medical oncology, neuro-oncology, neurology, radiation oncology, neurosurgery, and ophthalmology met to review current standards of reporting and to formulate a consensus opinion regarding minimum baseline evaluation and common standards for assessing response to therapy. The response guidelines were based on the results of neuroimaging, corticosteroid use, ophthalmologic examination, and CSF cytology. A critical issue that requires additional study is the optimal method to assess the neurocognitive impact of therapy and address the quality of life of PCNSL survivors. We hope that these guidelines will improve communication among investigators and comparability among clinical trials in a way that will allow us to develop better therapies for patients.

Central Nervous System Neoplasms↗
PubMed2005

Primary CNS lymphoma of T-cell origin: a descriptive analysis from the international primary CNS lymphoma collaborative group.

PURPOSE: To describe the demographic and tumor related characteristics and outcomes for patients with primary T-cell CNS lymphoma (TPCNSL). PATIENTS AND METHODS: A retrospective series of patients with TPCNSL was compiled from twelve cancer centers in seven countries. RESULTS: We identified 45 patients with a median age of 60 years (range, 3 to 84 years). Twenty (44%) had Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1. Twenty-six (58%) had involvement of a cerebral hemisphere and sixteen (36%) had lesions of deeper sites in the brain. Serum lactate dehydrogenase was elevated in 7 (32%) of 22 patients, and CSF protein was elevated in 19 of 24 patients (79%) with available data. The median disease-specific survival (DSS) was 25 months (95% CI, 11 to 38 months). The 2- and 5-year DSS were 51% (95% CI, 35% to 66%) and 17% (95% CI, 6% to 34%), respectively. Univariate and multivariate analyses were conducted for age (</= 60 v > 60 years), PS (0 or 1 v 2, 3, or 4), involvement of deep structures of the CNS (no v yes), and methotrexate (MTX) use in the primary treatment (yes v no). Only PS and MTX use were significantly associated with better outcome with hazard ratios of 0.2 (95% CI, 0.1 to 0.4) and 0.4 (95% CI, 0.2 to 0.8), respectively. CONCLUSION: This is the largest series ever assembled of TPCNSL. The presentation and outcome appear similar to that of B cell PCNSL. PS 0 or 1 and administration of MTX are associated with better survival.

Adolescent↗
PubMed2004

High-dose intravenous methotrexate followed by autologous stem cell transplantation as a potentially effective therapy for neurolymphomatosis.

BACKGROUND: Neurolymphomatosis (NL) is a rare neurologic manifestation of systemic lymphoma characterized by lymphomatous infiltration of the peripheral nervous system. The diagnosis of NL is difficult and requires a multidisciplinary approach for obtaining an adequate biopsy specimen of the suspected nerve. The prognosis of patients with NL has been poor because adequate penetration of chemotherapy into the nervous system is difficult. METHODS: The authors presented the case of a 37-year-old man who was treated for Ann Arbor Stage IVB diffuse large B-cell lymphoma. The patient developed disease recurrence in the sciatic nerve without systemic involvement. RESULTS: The patient achieved a clinical response after receipt of high-dose intravenous methotrexate followed by high-dose chemotherapy and autologous stem cell transplant. CONCLUSIONS: The authors reported this case to highlight the effectiveness of this regimen in a rare and fatal disorder. In the current study they also reviewed the literature regarding the diagnosis, prognosis, and treatment of NL.

Adult↗
PubMed2004

Brain metastases.

BACKGROUND: Systemic cancer is the second most common cause of death for adults in the United States. Twenty percent of these patients develop neurologic symptoms sometime during their illness. An apparent increase in the incidence of both systemic cancers and resulting brain metastases are posing an increasing challenge to health care providers. Neurologic complications lead to significant morbidity and mortality in these patients. Therefore, it is important to understand the current concepts of diagnosis and treatment of patients with brain metastases. REVIEW SUMMARY: This review summarizes the epidemiology, clinical features, pathophysiology, and diagnostic evaluation of brain metastases. The section on current treatments is presented from the perspective of the three most common primary tumor locations along with the treatment approach to other metastatic tumors. This review includes a thorough evaluation of the literature, highlights controversies over treatment options, and provides insight into novel approaches currently under investigation. Clinical studies needed for further study are also discussed. CONCLUSIONS: A clearer understanding of the pathophysiology of metastatic tumors and advances in diagnostic technology have paved the road to a better approach to treatment of brain metastases. Although no curative treatments are available to date, significant improvement in a patient's quality of life and life expectancy can be achieved with the available therapy. A better understanding of different primary cancers leading to brain metastases leads to a more effective treatment. More studies are needed to critically analyze the clear benefit of these treatment options in selected patients.

Brain Neoplasms↗
PubMed2004

Immunomodulatory treatment trial for paraneoplastic neurological disorders.

Paraneoplastic neurological disorders are devastating remote effects of malignancy. Despite compelling evidence of an autoimmune pathogenesis, empiric immunomodulatory treatment of these disorders is often ineffective. However, very few systematic studies have been conducted, and the treatment of patients without active malignancy has not been addressed. We conducted a prospective open-label treatment study of plasma exchange plus conventional cancer chemotherapy (10 patients) or plasma exchange plus continuous oral cyclophosphamide (10 patients). All patients had progressive symptoms and at least moderate disability at enrollment (mean Rankin score, 3.4). Patients who had experienced symptoms for more than 12 months were excluded (mean duration of symptoms at enrollment, 3.6 months). The primary outcome measure was change in quantitative disability measures (Rankin and Barthel scores) after 6 months of treatment; a positive response was defined as stability or improvement in disability. Overall, 50% of patients had a positive response at 6 months (6 patients had improved by at least 1 Rankin grade). Patients with good outcome tended to be those with less disability at time of enrollment. Hematologic toxicity was common among those receiving cyclophosphamide. Aggressive immunosuppression early in the clinical course should be considered in patients who have paraneoplastic neurological disorders, even when there is no evidence of active malignancy.

Adjuvants, Immunologic↗
PubMed2003

A comparison of surgical resection and stereotactic radiosurgery in the treatment of solitary brain metastases.

PURPOSE: To determine whether neurosurgery (NS) or stereotactic radiosurgery (RS) provided better local tumor control and enhanced patient survival. METHODS AND MATERIALS: Retrospective review of all solitary brain metastases (SBM) patients newly diagnosed at Mayo Clinic Rochester between 1991 and 1999. Eligible patients satisfied tumor size and SBM site criteria to qualify for both NS and RS. RESULTS: There were no significant differences between 74 NS and 23 RS patients in terms of baseline characteristics (age, gender, systemic disease type, systemic disease status, signs/symptoms at SBM presentation) or percent of patients who received whole brain radiotherapy. Median follow-up for alive patients was 20 months (range 0-106 months). There was no significant difference in patient survival (p = 0.15); the 1-year survival rate was 56% for the RS patients and 62% for the NS patients. Multivariate Cox regression analysis found that a significant prognostic factor for survival was a performance score of 0 or 1. There was a significant (p = 0.020) difference in local tumor control between NS and RS for solitary brain metastasis; none of the RS group had local recurrence compared to 19 (58%) of the NS group. CONCLUSION: The need for a Phase III study comparing these two techniques appears to be supported by the data from this study.

Aged↗
PubMed2002

The continuing increase in the incidence of primary central nervous system non-Hodgkin lymphoma: a surveillance, epidemiology, and end results analysis.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is an extranodal form of non-Hodgkin lymphoma arising in the craniospinal axis. The incidence of PCNSL appears to be increasing. METHODS: PCNSL incidence data from 1973-1997 were obtained from the nine Surveillance, Epidemiology and End Results (SEER) registries. To limit the influence of the human immunodeficiency virus on incidence rates, data of never-married males and females and persons of unknown marital status were excluded. As a surrogate for new technology, SEER data were reviewed by dates of diagnosis (surrogate for imaging) and compared with glioma incidence (surrogate for stereotactic neurosurgery and improved diagnostic neuropathology). Age-adjusted incidence rates were estimated and compared for the period prior to computed tomography (CT) (1973-1984) and the magnetic resonance imaging (MRI) period (1985-1997). The estimated annual percent change was calculated based on linear regression analyses using SEER*STAT. RESULTS: The incidence of PCNSL appears to be increasing in all SEER registries examined. All age groups demonstrated an increase over time. This increase was observed both in the CT era as well as in the MRI era. PCNSL age-adjusted incidence (0.15 to 0.48, a 3-fold increase) outpaced that of systemic lymphoma (14.1 to 18.5, a 33% increase) for the same registries over the same time periods. The rate of increase has begun to slow since 1985; the estimated annual percent change for PCNSL was three-fold higher during the period 1973-1985 compared with 1986-1997. CONCLUSION: The incidence rate of PCNSL continues to rise. The increase is evident in all age groups and in both genders. Data from the current study suggest that improved diagnostic tools, such as CT or MRI, cannot explain this increase.

Adult↗