Shahzad Raza

Bio: Shahzad Raza is an academic researcher from University of Missouri–Kansas City. The author has contributed to research in topics: Medicine & Multiple myeloma. The author has an hindex of 20, co-authored 62 publications receiving 1306 citations. Previous affiliations of Shahzad Raza include University of Missouri & Brookdale University Hospital and Medical Center.

Antiangiogenic therapy using bevacizumab in recurrent high-grade glioma: impact on local control and patient survival.

Abstract: Object Antiangiogenic agents have recently shown impressive radiological responses in high-grade glioma. However, it is not clear if the responses are related to vascular changes or due to antitumoral effects. The authors report the mature results of a clinical study of bevacizumab-based treatment of recurrent high-grade gliomas. Methods Sixty-one patients with recurrent high-grade gliomas received treatment with bevacizumab at 10 mg/ kg every 2 weeks for 4 doses in an 8-week cycle along with either irinotecan or carboplatin. The choice of concomitant chemotherapeutic agent was based on the number of recurrences and prior chemotherapy. Results At a median follow-up of 7.5 months (range 1–19 months), 50 (82%) of 61 patients relapsed and 42 patients (70%) died of the disease. The median number of administered bevacizumab cycles was 2 (range 1–7 cycles). The median progression-free survival (PFS) and overall survival (OS) were 5 (95% confidence interval [CI] 2.3–7.7) and 9 (95% CI 7.6–10.4) months, respectiv...

A clinical trial of bevacizumab, temozolomide, and radiation for newly diagnosed glioblastoma.

Abstract: Object The presence of angiogenesis is a hallmark of glioblastoma (GBM). Vascular endothelial growth factor (VEGF), which drives angiogenesis, provides an additional target for conventional therapy. The authors conducted a prospective clinical trial to test the effectiveness of bevacizumab, an inhibitor of VEGF, in newly diagnosed GBM. Methods From 2006 through 2010, 51 eligible patients with newly diagnosed GBM were treated with involved-field radiation therapy and concomitant temozolomide (75 mg/m2 daily for 42 days) along with bevacizumab (10 mg/kg every 2 weeks), starting 29 days after surgery. This was followed by 6 cycles of adjuvant temozolomide therapy (150 mg/m2 on Days 1–7 of a 28-day cycle) with bevacizumab administered at 10 mg/kg on Days 8 and 22 of each 28-day cycle. Results The 6- and 12-month progression-free survival (PFS) rates were 85.1% and 51%, respectively. The 12- and 24-month overall survival (OS) rates were 85.1% and 42.5%, respectively. Grade III/IV toxicities were noted in 10 pa...

Feasibility of using bevacizumab with radiation therapy and temozolomide in newly diagnosed high-grade glioma.

Abstract: Introduction Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), has shown promise in the treatment of patients with recurrent high-grade glioma. The purpose of this study is to test the feasibility of using bevacizumab with chemoradiation in the primary management of high-grade glioma. Methods and Materials Fifteen patients with high-grade glioma were treated with involved field radiation therapy to a dose of 59.4 Gy at 1.8 Gy/fraction with bevacizumab 10 mg/kg on Days 14 and 28 and temozolomide 75 mg/m 2 . Subsequently, bevacizumab 10 mg/kg was continued every 2 weeks with temozolomide 150 mg/m 2 for 12 months. Changes in relative cerebral blood volume, perfusion-permeability index, and tumor volume measurement were measured to assess the therapeutic response. Immunohistochemistry for phosphorylated VEGF receptor 2 (pVEGFR2) was performed. Results Thirteen patients (86.6%) completed the planned bevacizumab and chemoradiation therapy. Four Grade III/IV nonhematologic toxicities were seen. Radiographic responses were noted in 13 of 14 assessable patients (92.8%). The pVEGFR2 staining was seen in 7 of 8 patients (87.5%) at the time of initial diagnosis. Six patients have experienced relapse, 3 at the primary site and 3 as diffuse disease. One patient showed loss of pVEGFR2 expression at relapse. One-year progression-free survival and overall survival rates were 59.3% and 86.7%, respectively. Conclusion Use of antiangiogenic therapy with radiation and temozolomide in the primary management of high-grade glioma is feasible. Perfusion imaging with relative cerebral blood volume, perfusion-permeability index, and pVEGFR2 expression may be used as a potential predictor of therapeutic response. Toxicities and patterns of relapse need to be monitored closely.

High-grade glioma before and after treatment with radiation and Avastin: Initial observations

Abstract: We evaluate the effects of adjuvant treatment with the angiogenesis inhibitor Avastin (bevacizumab) on pathological tissue specimens of high-grade glioma. Tissue from five patients before and after treatment with Avastin was subjected to histological evaluation and compared to four control cases of glioma before and after similar treatment protocols not including bevacizumab. Clinical and radiographic data were reviewed. Histological analysis focused on microvessel density and vascular morphology, and expression patterns of vascular endothelial growth factor–A (VEGF-A) and the hematopoietic stem cell, mesenchymal, and cell motility markers CD34, smooth muscle actin, D2-40, and fascin. All patients with a decrease in microvessel density had a radiographic response, whereas no response was seen in the patients with increased microvessel density. Vascular morphology showed apparent “normalization” after Avastin treatment in two cases, with thin-walled and evenly distributed vessels. VEGF-A expression in tumor cells was increased in two cases and decreased in three and did not correlate with treatment response. There was a trend toward a relative increase of CD34, smooth muscle actin, D2-40, and fascin immunostaining following treatment with Avastin. Specimens from four patients with recurrent malignant gliomas before and after adjuvant treatment (not including bevacizumab) had features dissimilar from our study cases. We conclude that a change in vascular morphology can be observed following anti-angiogenic treatment. There seems to be no correlation between VEGF-A expression and clinical parameters. While the phenomena we describe may not be specific to Avastin, they demonstrate the potential of tissue-based analysis for the discovery of clinically relevant treatment response biomarkers.

Insight into Sweet's syndrome and associated-malignancy: a review of the current literature.

Abstract: Sweet's syndrome (acute febrile neutrophilic dermatosis) is an infrequent skin disease characterized by sudden onset of fever, leucocytosis and erythematous plaques or nodules infiltrated by neutrophils. There are three main clinical settings in which Sweet's syndrome has been described: classical or idiopathic Sweet's syndrome, malignancy-associated Sweet's syndrome and drug-induced Sweet's syndrome. Classical Sweet's is often preceded by an upper respiratory tract infection and may be associated with inflammatory bowel disease and pregnancy. Approximately 21% of patients have an associated malignancy, most commonly hematological disease. The syndrome may occur as a paraneoplastic accompaniment to established cancer or may be a first sign of malignancy or its recurrence. The incidence is said to be increasing in recent years due to the frequent use of growth factors in cancer patients. Several anticancer agents including all-trans-retinoic acid proteosome inhibitors, hypomethylating agents, tyrosine kinase inhibitors and lenalidomide are potential harbingers of Sweet's syndrome. Unfortunately, little is known about the pathophysiology of Sweet's syndrome and there are no established guidelines for treatment of malignancy-associated Sweet's syndrome. Systemic corticosteroids are the mainstay of treatment. Sweet's syndrome caused by anticancer agents sometimes involves withdrawal or temporary discontinuation of anticancer agents, use of systemic corticosteroids and/or rechallenge with either with the same anticancer agents or different agents. This report provides insights into the pathophysiology, clinical presentation, diagnostic work, differential diagnosis and management of malignancy-associated Sweet's syndrome published in reported cases.

Malignant Gliomas in Adults

Abstract: Approximately 5% of patients with malignant gliomas have a family history of gliomas. Some of these familial cases are associated with rare genetic syndromes, such as neurofibromatosis types 1 and 2, the Li−Fraumeni syndrome (germ-line p53 mutations associated with an increased risk of several cancers), and Turcot’s syndrome (intestinal polyposis and brain tumors). 10 However, most familial cases have

Updated Response Assessment Criteria for High-Grade Gliomas: Response Assessment in Neuro-Oncology Working Group

Abstract: Currently, the most widely used criteria for assessing response to therapy in high-grade gliomas are based on two-dimensional tumor measurements on computed tomography (CT) or magnetic resonance imaging (MRI), in conjunction with clinical assessment and corticosteroid dose (the Macdonald Criteria). It is increasingly apparent that there are significant limitations to these criteria, which only address the contrast-enhancing component of the tumor. For example, chemoradiotherapy for newly diagnosed glioblastomas results in transient increase in tumor enhancement (pseudoprogression) in 20% to 30% of patients, which is difficult to differentiate from true tumor progression. Antiangiogenic agents produce high radiographic response rates, as defined by a rapid decrease in contrast enhancement on CT/MRI that occurs within days of initiation of treatment and that is partly a result of reduced vascular permeability to contrast agents rather than a true antitumor effect. In addition, a subset of patients treated with antiangiogenic agents develop tumor recurrence characterized by an increase in the nonenhancing component depicted on T2-weighted/fluid-attenuated inversion recovery sequences. The recognition that contrast enhancement is nonspecific and may not always be a true surrogate of tumor response and the need to account for the nonenhancing component of the tumor mandate that new criteria be developed and validated to permit accurate assessment of the efficacy of novel therapies. The Response Assessment in Neuro-Oncology Working Group is an international effort to develop new standardized response criteria for clinical trials in brain tumors. In this proposal, we present the recommendations for updated response criteria for high-grade gliomas.

The somatic genomic landscape of glioblastoma

Abstract: We describe the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer.