Cancer Research Building II

New Orleans, MD, United States

Cancer Research Building II

New Orleans, MD, United States
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Adding temozolomide (TMZ) to radiation for patients with newly-diagnosed anaplastic astrocytomas (AAs) is common clinical practice despite the lack of prospective studies demonstrating a survival advantage. Two retrospective studies, each with methodologic limitations, provide conflicting advice regarding treatment. This single-institution retrospective study was conducted to determine survival trends in patients with AA. All patients ≥18 years with newly-diagnosed AA treated at Johns Hopkins from 1995 to 2012 were included. As we incorporated TMZ into high-grade glioma treatment regimens in 2004, patients were divided into pre-2004 and post-2004 groups for analysis. Clinical, radiographic, and pathologic data were collected. Median overall survival (OS) was calculated using Kaplan–Meier estimates. A total of 196 patients were identified; 74 pre-2004 and 122 post-2004; mean age 47 ± 15 years; 57 % male; 87 % white, 69 % surgical debulking. Mean RT dose 5676 + 746 cGy; duration of concurrent chemoradiation 5.8 ± 0.8 weeks; and mean adjuvant chemotherapy 4.3 + 2.8 cycles. Baseline prognostic factors did not differ between groups. Chemotherapy was administered to 12 % of patients pre-2004 (TMZ = 1, procarbazine, lomustine and vincristine = 2, carmustine wafer = 6) and 94 % post-2004 (TMZ in all, p < 0.001). Median OS was 32 months (95 % CI 23–43). Survival was longer in the post-2004 cohort (37 mo, 24–64) than pre-2004 (27 mo, 19–40; HR 0.75, 0.53–1.06, p = 0.11). Multivariate analysis controlling for age, Karnofsky performance status, and extent of resection revealed a 36 % reduced risk of death (HR 0.64, 0.44–0.91, p = 0.015) in patients treated post-2004. This retrospective review found survival in newly diagnosed patients with AA improved with the addition of temozolomide to standard radiation. Until prospective randomized phase III data are available, these data support the practice of incorporating TMZ in the management of newly-diagnosed AA. © 2016, Springer Science+Business Media New York.


Mukherjee D.,Cancer Research Building II | Raza S.M.,Cancer Research Building II | Quinones-Hinojosa A.,Cancer Research Building II
British Journal of Neurosurgery | Year: 2010

A 37-year-old man who presented with difficulty breathing and nasal obstruction was found to have a large encephalocele, along with other, associated congenital anomalies. The etiology, epidemiology, classification, clinical presentation, imaging, and surgical approaches used for encaphaloceles are discussed. © 2010 The Neurosurgical Foundation.


Avendano J.,National Institute of Neurology and Neurosurgery | Quinones-Hinojosa A.,Cancer Research Building II
Spine | Year: 2012

Study Design. Observational cross-sectional study. Objective. Using data from the population-based cancer registries of the Surveillance, Epidemiology and End Results (SEER) program, we analyzed demographic features, tumor and treatment characteristics, as well as survival rates in patients with primary malignant astrocytomas of the spinal cord (PMASC). Summary of Background Data. PMASC is a rare neoplasm and is considered to carry the same dismal outcome as their cerebral counterparts. Our current knowledge is incomplete, and understanding the epidemiology, diagnosis, and optimal treatment still poses challenges. Methods. The SEER data from 1973 to 2007 were reviewed for pathologically confirmed primary anaplastic astrocytomas (AA) and glioblastomas of the spinal cord (C72.0). We compared the clinical features and outcomes of the cohort in uni- and multivariate fashion. Survival was calculated and compared using Kaplan-Meier curves and log-rank analysis. Results. Our search criteria retrieved 135 patients diagnosed with PMASC. The median survival for PMASC was 13 months with 1-, 2-, and 5-year survival rates of 51.8%, 32.2%, and 18.7%. Patient diagnosed with AA had a median survival time of 17 months versus 10 months in patients diagnosed with glioblastomas. Adult patients observed markedly prolonged survival compared with the pediatric group, with a 16-month versus 9-month median survival, respectively. Multivariate analysis revealed age at diagnosis, pediatric and adult age groups, sex, tumor histology, and extent of resection as significant predictors of survival. Interestingly, outcomes did not significantly change throughout the last decades or by receiving radiotherapy. Conclusion. Outcome for patients diagnosed with PMASC remains poor and presents an ongoing challenge for professionals in the field of neurospinal medicine and surgery. In our analyses of AA, adult patients, males, and patients undergoing radical resections were associated with increased survival. However, incidence of these lesions is low; hence, building strong collaborative, interdisciplinary, and multi-institutional study groups is necessary to define the optimal treatment of PMASC. © 2012 Lippincott Williams & Wilkins.


PubMed | Cancer Research Building II and Saint Agnes Hospital
Type: Journal Article | Journal: Journal of neuro-oncology | Year: 2016

Adding temozolomide (TMZ) to radiation for patients with newly-diagnosed anaplastic astrocytomas (AAs) is common clinical practice despite the lack of prospective studies demonstrating a survival advantage. Two retrospective studies, each with methodologic limitations, provide conflicting advice regarding treatment. This single-institution retrospective study was conducted to determine survival trends in patients with AA. All patients18years with newly-diagnosed AA treated at Johns Hopkins from 1995 to 2012 were included. As we incorporated TMZ into high-grade glioma treatment regimens in 2004, patients were divided into pre-2004 and post-2004 groups for analysis. Clinical, radiographic, and pathologic data were collected. Median overall survival (OS) was calculated using Kaplan-Meier estimates. A total of 196 patients were identified; 74 pre-2004 and 122 post-2004; mean age 4715years; 57% male; 87% white, 69% surgical debulking. Mean RT dose 5676+746cGy; duration of concurrent chemoradiation 5.80.8weeks; and mean adjuvant chemotherapy 4.3+2.8 cycles. Baseline prognostic factors did not differ between groups. Chemotherapy was administered to 12% of patients pre-2004 (TMZ=1, procarbazine, lomustine and vincristine=2, carmustine wafer=6) and 94% post-2004 (TMZ in all, p<0.001). Median OS was 32months (95% CI 23-43). Survival was longer in the post-2004 cohort (37 mo, 24-64) than pre-2004 (27 mo, 19-40; HR 0.75, 0.53-1.06, p=0.11). Multivariate analysis controlling for age, Karnofsky performance status, and extent of resection revealed a 36% reduced risk of death (HR 0.64, 0.44-0.91, p=0.015) in patients treated post-2004. This retrospective review found survival in newly diagnosed patients with AA improved with the addition of temozolomide to standard radiation. Until prospective randomized phase III data are available, these data support the practice of incorporating TMZ in the management of newly-diagnosed AA.


Hyung S.-W.,Korea University | Lee M.Y.,Pohang University of Science and Technology | Lee M.Y.,Korea Institute of Science and Technology | Yu J.-H.,Cancer Research Institute | And 15 more authors.
Molecular and Cellular Proteomics | Year: 2011

Prediction of the responses to neoadjuvant chemotherapy (NACT) can improve the treatment of patients with advanced breast cancer. Genes and proteins predictive of chemoresistance have been extensively studied in breast cancer tissues. However, noninvasive serum biomarkers capable of such prediction have been rarely exploited. Here, we performed profiling of N-glycosylated proteins in serum from fifteen advanced breast cancer patients (ten patients sensitive to and five patients resistant to NACT) to discover serum biomarkers of chemoresistance using a label-free liquid chromatography-tandem MS method. By performing a series of statistical analyses of the proteomic data, we selected thirteen biomarker candidates and tested their differential serum levels by Western blotting in 13 independent samples (eight patients sensitive to and five patients resistant to NACT). Among the candidates, we then selected the final set of six potential serum biomarkers (AHSG, APOB, C3, C9, CP, and ORM1) whose differential expression was confirmed in the independent samples. Finally, we demonstrated that a multivariate classification model using the six proteins could predict responses to NACT and further predict relapse-free survival of patients. In summary, global N-glycoproteome profile in serum revealed a protein pattern predictive of the responses to NACT, which can be further validated in large clinical studies. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.


Strowd R.E.,III | Strowd R.E.,Cancer Research Building II | Grossman S.A.,Johns Hopkins
Current Treatment Options in Oncology | Year: 2015

Central nervous system gliomas are the most common primary brain tumor, and these are most often high-grade gliomas. Standard therapy includes a combination of surgery, radiation, and chemotherapy which provides a modest increase in survival, but virtually, no patients are cured, the overall prognosis remains poor, and new therapies are desperately needed. Tumor metabolism is a well-recognized but understudied therapeutic approach to treating cancers. Dietary and nondietary modulation of glucose homeostasis and the incorporation of dietary supplements and other natural substances are potentially important interventions to affect cancer cell growth, palliate symptoms, reduce treatment-associated side effects, and improve the quality and quantity of life in patients with cancer. These approaches are highly desired by patients. However, they can be financially burdensome, associated with toxicities, and have, on occasion, reduced the efficacy of proven therapies and negatively impacted patient outcomes. The lack of rigorous scientific data evaluating almost all diet and supplement-based therapies currently limits their incorporation into standard oncologic practice. Rigorous studies are needed to document and improve these potentially useful approaches in patients with brain and other malignancies. © 2015, Springer Science+Business Media New York.


Pendleton C.,Cancer Research Building II | Zaidi H.A.,Cancer Research Building II | Pradilla G.,Cancer Research Building II | Cohen-Gadol A.A.,Clarian Neuroscience Institute | Quinones-Hinojosa A.,Cancer Research Building II
Nature Reviews Endocrinology | Year: 2010

Background. This case study illustrates Harvey Cushing's pioneering work in pituitary transplantation in the early 20th century and the essential relationship between laboratory research and clinical practice. In 1911, a 48 year-old man presented at Johns Hopkins Hospital with bitemporal hemianopsia, hypothermia, hypersomnolence, decreased libido, polydypsia and polyuria.Investigation. A review of the Johns Hopkins Hospital surgical records from 1896-1912 on a patient with hypopituitarism secondary to a suprasellar mass, in whom the first documented pituitary gland transplantation was performed.Diagnosis. A diagnosis of hypopituitarism was made. Postmortem examination revealed a cystic cavity lined with squamous epithelium.Management. The patient was treated with whole-gland pituitary extract, which improved his symptoms only temporarily. Cushing transplanted a pituitary gland obtained from a spontaneously aborted fetus into the cerebral cortex of the patient, who showed marked improvement of his somnolence and confusion, whereas his polyuria and polydypsia persisted. A recurrence of symptoms after 6 weeks prompted Cushing to attempt a second transplant of a fetal pituitary gland, without improvement. The patient resumed hormonal supplementation with whole-gland pituitary extract, but died a month after the second transplant from respiratory complications. © 2010 Macmillan Publishers Limited. All rights reserved.


Grossman R.,Neuro Oncology Surgical Outcomes Research Laboratory | Mukherjee D.,Neuro Oncology Surgical Outcomes Research Laboratory | Chaichana K.L.,Neuro Oncology Surgical Outcomes Research Laboratory | Salvatori R.,Johns Hopkins University | And 5 more authors.
Clinical Endocrinology | Year: 2010

Background Preoperative determinants of surgical risk in elderly patients with pituitary tumour are not fully defined. The aim of this study was to quantify operative risk for these patients. Design and methods We performed a retrospective analysis of the Nationwide Inpatient Sample (1998-2005), a database containing discharge information from a stratified, random sample of 20% of all non-federal hospitals in 37 states. Patients >65 years old who underwent pituitary tumour resection were identified by ICD-9 coding. Primary outcome was inpatient death. Other outcomes included post-operative complications, length of stay (LOS) and total charges. Results A total of 8400 patients (53·7% male) were identified. Mean age was 72·2. Mean co-morbidity score was 5·3. A majority were white (82·0%) admitted to academic hospitals (69·5%) for elective procedures (55·7%). Inpatient mortality was 3·8%. The most common complication was fluid and electrolyte abnormalities (14·3%). Mean LOS was 8·5 days. In multivariate analysis, patients >80 years old had 30% greater odds of death, relative to 65-69 year old counterparts. Each complication increased LOS by an average of at least 4 days. These associations were statistically significant (P-values <0·05). Conclusions New clinically relevant risk stratification information is now available to assist clinicians in operative decision-making for elderly patients with pituitary tumour considering operative intervention. © 2010 Blackwell Publishing Ltd.


Raza S.M.,Johns Hopkins Neuro Oncology Surgical Outcomes Research Laboratory | Recinos P.F.,Johns Hopkins Neuro Oncology Surgical Outcomes Research Laboratory | Avendano J.,Johns Hopkins Neuro Oncology Surgical Outcomes Research Laboratory | Adams H.,Johns Hopkins Neuro Oncology Surgical Outcomes Research Laboratory | And 3 more authors.
Minimally Invasive Neurosurgery | Year: 2011

Background: The surgical management of deep intra-axial lesions still requires microsurgical approaches that utilize retraction of deep white matter to obtain adequate visualization. We report our experience with a new tubular retractor system, designed specifically for intracranial applications, linked with frameless neuronavigation for a cohort of intraventricular and deep intra-axial tumors. Methods: The ViewSite Brain Access System (Vycor, Inc) was used in a series of 9 adult and pediatric patients with a variety of pathologies. Histological diagnoses either resected or biopsied with the system included: colloid cyst, DNET, papillary pineal tumor, anaplastic astrocytoma, toxoplasmosis and lymphoma. The locations of the lesions approached include: lateral ventricle, basal ganglia, pulvinar/posterior thalamus and insular cortex. Post-operative imaging was assessed to determine extent of resection and extent of white matter damage along the surgical trajectory (based on TFLAIR and diffusion restriction/ADC signal). Results: Satisfactory resection or biopsy was obtained in all patients. Radiographic analysis demonstrated evidence of white matter damage along the surgical trajectory in one patient. None of the patients experienced neurological deficits as a result of white matter retraction/manipulation. Conclusion: Based on a retrospective review of our experience, we feel that this accesss system, when used in conjunction with frameless neuronavigational systems, provides adequate visualization for tumor resection while permitting the use of standard microsurgical techniques through minimally invasive craniotomies. Our initial data indicate that this system may minimize white matter injury, but further studies are necessary. © Georg Thieme Verlag KG Stuttgart - New York.


Tran N.P.,Cancer Research Building II | Hung C.-F.,Cancer Research Building II | Roden R.,Cancer Research Building II | Wu T.-C.,Cancer Research Building II
Recent Results in Cancer Research | Year: 2014

Human papillomavirus (HPV), the most common sexually transmitted virus, and its associated diseases continue to cause significant morbidity and mortality in over 600 million infected individuals. Major progress has been made with preventative vaccines, and clinical data have emerged regarding the efficacy and cross-reactivity of the two FDA approved L1 virus like particle (VLP)-based vaccines. However, the cost of the approved vaccines currently limits their widespread use in developing countries which carry the greatest burden of HPV-associated diseases. Furthermore, the licensed preventive HPV vaccines only contain two high-risk types of HPV (HPV-16 and HPV-18) which can protect only up to 75 % of all cervical cancers. Thus, second generation preventative vaccine candidates hope to address the issues of cost and broaden protection through the use of more multivalent L1-VLPs, vaccine formulations, or alternative antigens such as L1 capsomers, L2 capsid proteins, and chimeric VLPs. Preventative vaccines are crucial to controlling the transmission of HPV, but there are already hundreds of millions of infected individuals who have HPV-associated lesions that are silently progressing toward malignancy. This raises the need for therapeutic HPV vaccines that can trigger T cell killing of established HPV lesions, including HPV-transformed tumor cells. In order to stimulate such antitumor immune responses, therapeutic vaccine candidates deliver HPV antigens in vivo by employing various bacterial, viral, protein, peptide, dendritic cell, and DNA-based vectors. This book chapter will review the commercially available preventive vaccines, present second generation candidates, and discuss the progress of developing therapeutic HPV vaccines. © 2014 Springer-Verlag Berlin Heidelberg.

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