Perelman School of Medicine at the University of Pennsylvania

Clinical Research | Central Nervous System Cancers

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 protocol within the Service

Title: Proton Radiation for Chordomas and Chondrosarcomas

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

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.

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

Principal Investigator: Michelle Alonso-Basanta, M.D., Ph.D.
Coordinator: Tyler Brown
Office: (215) 615-5644
UPCC#: 08310

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.

Title: Circulating Tumor Markers for High Grade Glioma

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

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.

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

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

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.

Title: Pilot Study of Microvesicles: A Biomarker for Tumor Response/ Pseudoprogression in Glioblastoma

Principal Investigator: Robert Lustig, M.D.
Coordinator: Jerry Chen
Office: (215) 662-7449
UPCC#: 1231

Blood samples are used to estimate counts of extracellular vesicles (microvesicles), which are shed from tissues into the circulation. Microvesicles are membrane-derived, organelle-like structures that carry molecules, including miRNA and cytokines, for uptake by recipient cells, serving as a unique mechanism of intercellular trafficking of complex biological messages. Using volunteer and glioblastoma patient blood samples, this study will determine whether numbers of microvesicles, their increase/decrease over time and/or surface markers are biomarkers of glioblastoma patient outcome. Two clinically relevant 2D and 3D in vitro systems will be used to test the effect of changes on microvesicle production, characteristics, bioactivity, and cargo. The study will also explore the effect of therapeutic maneuvers on microvesicle production and bioactivity. Study participants must be older than 18, not pregnant or lactating, and able to undergo a standard course of external radiation to at least 60 Gy and be able to start a course of systemic temozolomide. This study will have minimum 50 patients; 30 patients with glioblastoma and 20 normal volunteers.

Title: Randomized Phase II Trial of Concurrent Bevacizumab and Re-Irradiation Versus Bevacizumab Alone as Treatment for Recurrent Glioblastoma.

Principal Investigator: Robert Lustig, M.D.
Coordinator: Susan Prendergast, RN
Office: (215) 662-4267
UPCC#: RTOG 1205

The primary objective of this study is to establish an improvement in overall survival in recurrent glioblastoma patients receiving bevacizumab and re-irradiation compared with patients receiving bevacizumab alone. To enroll, patients must have a histopathologically proven diagnosis of glioblastoma or variants (gliosarcoma, giant cell glioblastoma etc). Patients will be eligible if the original histology was lower-grade glioma and a subsequent diagnosis of glioblastoma or gliosarcoma is made. Enrolled patients are randomized to 1 of 2 treatment arms: In arm 1, patients receive bevacizumab intravenously (IV) over 30-90 minutes every 2 weeks and in arm 2, patients receive bevacizumab as in arm 1 and undergo radiation therapy using intensity-modulated radiation therapy (IMRT), 3-dimensional conformal radiation therapy (3D-CRT), or proton beam radiation therapy (RT) 5 days a week for 2 weeks. In both arms, courses with bevacizumab repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 2 months for 1 year, every 6 months for 1 year and then annually thereafter.

Title: Randomized Phase II Trial of Hypofractionated Dose-Escalated Photon IMRT or Proton Beam Therapy Versus Conventional Photon Irradiation With Concomitant and Adjuvant Temozolomide in Patients With Newly Diagnosed Glioblastoma

Principal Investigator: Robert Lustig, M.D.
Coordinator: Susan Prendergast, RN
Office: (215) 622-4267

The primary objective of this study is to determine if dose-escalated and -intensified photon IMRT or proton beam therapy (using a dose-per-fraction escalation with simultaneous integrated boost) with concomitant and adjuvant temozolomide improves overall survival, as compared to standard-dose photon irradiation with concomitant and adjuvant temozolomide. To enroll, patients must have a histologically proven diagnosis of glioblastoma (WHO grade IV) confirmed by central review prior to step 2 registration. Tumor tissue that is determined by central pathology review prior to step 2 registration to be of sufficient quantity for analysis of MGMT status. The tumor must be located in the supratentorial compartment only (any component involving the brain stem or cerebellum is not allowed).

Title: Phase I/II Trial of Pre-Operative Image Guided Intensity Modulated Proton Radiation Therapy (IMPT) or Photon (IMRT) with Simultaneously Integrated Boost to the High Risk Margin for Retroperitoneal Sarcomas

Principal Investigator: William Levin, M.D.
Coordinator: Dana Patsch
Office: (215) 615-5645
UPCC#: 4214

This is a Phase I/II study of pre-operative image guided IMPT (IG-IMPT) or IMRT with simultaneously integrated boost (SIB) to the high risk margin of retroperitoneal sarcoma. The phase I portion of this study will evaluate up to four dose levels of IGIMPT or IMRT with simultaneously integrated boost (SIB) to the high risk margin of retroperitoneal sarcoma. Once the maximum tolerated dose (MTD) is determined (Phase I), participants will be accrued to the Phase II treatment using the combination of IG-IMPT or IMRT with SIB to determine if there is a sufficient signal, with respect to local recurrence, to warrant pursuing a large phase IIR or phase III trial.

Title: Retreatment of Recurrent Tumors Using Proton Radiotherapy

Principal Investigator: John P. Plastaras, M.D., Ph.D.
Coordinator: Kristi Lelionis, MS, CCRP
Office: (215) 615-3273
UPCC#: 23309

The purpose of this study is to determine the feasibility of using proton radiotherapy for reirradiation of recurrent malignancies. The primary outcomes are feasibility and acute toxicity. The study is infeasible if patient cannot be given treatment. Patient is unable to tolerate 15% treatment. patient is unable to complete all of his/her treatments within 10 days of estimated date of treatment completion. Acuite Toxicity is defined as any grade 4 toxicity observed within 90 days from the initiation of radiotherapy that is felt to be directly related to their proton treatment. Toxicities will be graded by NCI CTC Version 4.0. Patients will be stratified by treatment site (Head and Neck, Thorax, Abdomen, Pelvis, Extremities) and by treatment volume (low volume, high volume) for a total of 10 strata. This study will be done in two phases. In the first phase, feasibility will be established using the primary objectives set below. The second phase will begin no earlier than 90 days after the last patient in the initial phase has completed treatment in each strata and once feasibility has been verified.

Title: Prospective Follow-Up of Outcomes in Patients Receiving Photodynamic Therapy for Neoplastic Diseases

Principal Investigator: Charles Simone, M.D.
Coordinator: Ashley Feriozzi
Office: (215) 615-3272
UPCC#: 06911

This is an observational study for subjects who are age 18 or older and will undergo Photodynamic Therapy (PDT) for a diagnosis of neoplastic disease under the direction of a Penn physician. The purpose of this study is to learn and understand more about how PDT works. To do this we need to study the experiences of patients who undergo PDT and examine things like tumor type, other medical conditions, other therapies and treatment results.

There are no interventions being performed and only medical record data will be collected. We will collect your name, medical record number, date of birth, date of initiation of specific therapies such as surgery, radiation or PDT. This information will not be disclosed to others outside of the study team. The entire study is anticipated to take 10 years. Asubject will be in the study until they inform us that they no longer wish to participate.

Title: RADVAX: A Stratified Phase I Trial of Pembrolizumab with Hypofractionated Radiotherapy in Patients with Advanced and Metastatic Cancers

Principal Investigator: Amit Maity, M.D. Ph.D.
Coordinator: Tyler Brown
Office: (215) 615-5644
UPCC#: 40914

Phase I clinical trial of hypofractionated radiotherapy to an isolated index lesion in combination with the PD-1 inhibitor, Pembrolizumab in patients with metastatic cancers who have failed anti-PD-1 therapy (melanoma and NSCLC) and patients with metastatic cancers who have have progressed after at least one regimen of systemic therapy (breast, pancreas, and other).

Publications from the Service Members

Michelle Alonso-Basanta, M.D., Ph.D.
Jay F. Dorsey, M.D., Ph.D.
Yi Fan, M.D. Ph.D.
Christine Hill-Kayser, M.D.
Goldie Kurtz, M.D.
Robert Lustig, M.D.

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