Perelman School of Medicine at the University of Pennsylvania
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The Department of Radiation Oncology is in the new Perelman Center. Occupying approximately 80,000 square feet on the Concourse Level, the new treatment facilities includes the most advanced proton and conventional radiation treatment modalities available as well as public spaces designed for the highest levels of patient comfort.


Clinical Research- Central Nervous System

Strategic direction and overarching themes for the service

Clinical and translational research for tumors of the central nervous system in the department of Radiation Oncology at the University of Pennsylvania focuses on:

  • The impact of proton therapy for brain and base of skull tumors on neurocognitive function.

  • The use of multiple modalities for the treatment of brain metastases.

  • The use of circulating tumor cells as a marker for treatment response.

  • The use of proton therapy for dose escalation for meningiomas.

  • The use of novel investigational agents for the treatment and/or imaging of primary brain tumors.

Description of programs and protocols within the service

Title: Circulating Tumor Markers for High Grade Glioma

This study seeks to determine the pattern of circulating tumor cells (CTCs) before, during and after definitive radiotherapy and to determine the presence of Microvesicles in patients with high grade gliomas undergoing chemoradiation therapy.  Patients who are 18 years and older with a high grade glioma (grade III or IV) diagnosis are eligible to participate.  Little is known about the numbers, time course, and effect of these therapies on CTCs in high grade glioma patients. A better understanding of CTCs in this patient population will introduce a promising, non-invasive means to evaluate the biologic status of the primary brain tumor, with the potential to customize treatment.  CTCs are collected through multiple blood samples before, during and post-radiation treatment. The trial will also collect demographic, treatment, and CTC data over a two-year period.

Principal Investigator: Robert Lustig, M.D.
Coordinator: Dana Patsch, B.S.
Office: (215) 615-5645
UPCC: 09313

Title: Proton Radiation for Chordomas and Chondrosarcomas

This is a prospective study of patients undergoing proton radiation for chordomas and chondrosarcomas.  Patients who are 18 and older with a histologically confirmed diagnosis of chordoma or chondrosarcoma are able to participate. The goals of this study are: to assess acute and late toxicities, to compare the dose distribution to tumor and surrounding normal structures, to evaluate quality of life of subjects, and to monitor rates of local control and disease specific survival.  Subjects complete quality of life measures at baseline, weekly during treatment, and at each follow-up visit.

 Principal Investigator: Michelle Alonso-Basanta, M.D., Ph.D.
Coordinator: Susan Mazzoni, MPH
Office: (215) 300-1153
UPCC: 01310

Title: Feasibility and Phase II Study Using Proton Radiation for WHO Grade I-III Meningiomas and Hemangiopericytomas

This observational study follows patient treatment courses and records side effects as they receive proton therapy using a standard or escalating (if grade II and III) proton radiation dose for brain cancer to better understand the safety in this treatment modality. Patients eligible for this study include adults ages 18 and over who have a “meningioma” or “hemangiopericytoma” brain tumor, have a treating physician who believes that treatment with proton radiation therapy may be a good option, and have not had prior radiation to the brain.  Patients on study will be given two questionnaires every week while receiving radiation treatment, four questionnaires prior to start of radiation treatment (one time) and at each follow-up visit for up to five years after completion of treatment.

Principal Investigator: Robert Lustig, M.D.
Coordinator: Kristi M. Lelionis, M.S., CCRP
Office: (215) 615-3273
UPCC: 24309

Title: Detection of Vascular and Neuronal Changes Following Proton and/or Photon Radiotherapy in Patients Receiving Skull Base and/or Brain Radiation

This is a non-therapeutic study that employs the use of MRI Spectroscopy and a battery of neurocognitive tests to assist in estimating the degree of memory loss, if any, following radiotherapy to the base of skull or brain as measured by the neurocognitive battery testing.  Adults 18 years of age and older who are receiving radiation treatment (photon or proton) of at least 45 Gy for either benign or malignant tumors of the brain or base of skull are eligible to participate.  There is also a cohort of persons not receiving radiation who have not experienced brain injury to act as research controls.  The research procedures are performed at 5 time points:  Baseline before radiation and 4 follow ups at approximately 1.5 months, 6 months, 12 months & 24 months post-radiation.

Principal Investigator:  Michelle Alonso-Basanta, M.D., Ph.D.
Coordinator: Sue Prendergast, RN
Office: (215) 301-2650
UPCC: 08310

Title A Clinical Study Conducted in Multiple Centers Comparing Veliparib and Whole Brain Radiation Therapy (WBRT) Versus Placebo and WBRT in Subjects With Brain Metastases From Non-Small Cell Lung Cancer (NSCLC)

The purpose of this trial is to study the investigational drug veliparib (ABT-888) in subjects with brain metastases that developed as a result of having Non-Small Cell Lung Cancer (NSCLC).  PARP is a naturally occurring protein made by the body that may help cancer cells overcome injury or damage caused by radiation, making these treatments less effective.  Veliparib blocks the activity of PARP.  This blocking activity may prevent the cancer cell from repairing itself and continuing growing.  Veliparib, when given together with whole brain radiation treatment (WBRT), may make WBRT work better by stopping the cancer cell from healing and growing.  Patients who are 18 years of age and older who have a diagnosis of non-small cell lung cancer with brain metastases are eligible to participate.  This study also involves neurocognitive testing. Patients will be tested before radiation treatment begins and at monthly intervals post-radiation to measure their cognitive abilities. Additionally, patients have the option of giving blood for research purposes to measure how the drug is absorbed and removed from the body.

Principal Investigator: Michelle Alonso-Basanta, M.D.
Coordinator: Dana Patsch, B.S.
Office: (215) 615-5645
UPCC: 27312

Relevant Publications

 

Detection of brain tumor cells in the peripheral blood by a telomerase promoter-based assay.

Macarthur KM, Kao GD, Chandrasekaran S, Alonso-Basanta M, Chapman C, Lustig RA, Wileyto EP, Hahn SM, Dorsey JF.

Cancer Res. 2014 Apr 15;74(8):2152-9. doi: 10.1158/0008-5472.CAN-13-0813. Epub 2014 Feb 13.  PMID:24525740

 

Gamma Knife radiosurgery to four or more brain metastases in patients without prior intracranial radiation or surgery.

Ojerholm E, Lee JY, Kolker J, Lustig R, Dorsey JF, Alonso-Basanta M.

Cancer Med. 2014 Jun;3(3):565-71. doi: 10.1002/cam4.206. Epub 2014 Feb 10.  PMID:24510602

 

A phase I study of nelfinavir concurrent with temozolomide and radiotherapy in patients with glioblastoma multiforme.

Alonso-Basanta M, Fang P, Maity A, Hahn SM, Lustig RA, Dorsey JF.

J Neurooncol. 2014 Jan;116(2):365-72. doi: 10.1007/s11060-013-1303-3. Epub 2013 Nov 6.  PMID:24194293

 

Selective targeting of brain tumors with gold nanoparticle-induced radiosensitization.

Joh DY, Sun L, Stangl M, Al Zaki A, Murty S, Santoiemma PP, Davis JJ, Baumann BC, Alonso-Basanta M, Bhang D, Kao GD, Tsourkas A, Dorsey JF.

PLoS One. 2013 Apr 30;8(4):e62425. doi: 10.1371/journal.pone.0062425. Print 2013.  PMID: 23638079

 

Modulation of CCAAT/enhancer binding protein homologous protein (CHOP)-dependent DR5 expression by nelfinavir sensitizes glioblastoma multiforme cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).

Tian X, Ye J, Alonso-Basanta M, Hahn SM, Koumenis C, Dorsey JF.

J Biol Chem. 2011 Aug 19;286(33):29408-16. doi: 10.1074/jbc.M110.197665. Epub 2011 Jun 22. PMID: 21697087

 

Acute Toxicity Profile of Patients with Low-grade Gliomas and Meningiomas Receiving Proton Therapy.

Maquilan G, Grover S, Alonso-Basanta M, Lustig RA.

Am J Clin Oncol. 2013 Feb 5. [Epub ahead of print] PMID: 23388559

 

Profilin-1 phosphorylation directs angiocrine expression and glioblastoma progression through HIF-1α accumulation.

Fan Y, Potdar AA, Gong Y, Eswarappa SM, Donnola S, Lathia JD, Hambardzumyan D, Rich JN, Fox PL.

Nat Cell Biol. 2014 May;16(5):445-56. doi: 10.1038/ncb2954. Epub 2014 Apr 20. PMID: 24747440



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