Radiation oncologists at the Roberts Proton Therapy Center are conducting a Phase II clinical trial to ascertain the feasibility of proton therapy as an adjunct to surgery for WHO Grade I-III meningiomas and hemangiopericytomas.
This study seeks to assess the effect of proton therapy on rates of acute toxicity, fatigue and quality of life in the same population. The frequency of recurrence and long term toxicity will also be evaluated.
Surgery is the first-line therapy for the meningiomas, but the complexity of the lesions often precludes total resection, contributing to recurrence. The Simpson Criteria establish guidelines to measure the extent of surgery to predict probability of recurrence in meningeal tumors.
Simpson Grade I assigns a 9% risk of recurrence at 10 years to lesions having macroscopic gross total resection (GTR) with excision of the dura, sinus and bone. Simpson Grade IV, or subtotal resection, is associated with a 40% risk of recurrence at 10 years.
When GTR cannot be achieved, radiotherapy is often recommended. Retrospective reports suggest that post-operative radiation results in enhanced local control and substantial improvement in overall survival for patients with incomplete surgery and inoperable lesions.
However, standard photon radiotherapy (external beam radiation therapy or stereotactic radiosurgery) can expose significant normal brain tissue to the cumulative effects of radiation— and thus, increased risk of neurocognitive impairment. Higher doses of radiation to Grade II and III meningiomas are being investigated in an attempt to improve control rates.
At the Roberts Proton Therapy Center, radiation oncologists are assessing the application of proton radiotherapy to the treatment of meningiomas and brain cancers in a Phase II clinical trial. The objective of this trial is to assess the effect of proton therapy on quality of life and acute toxicity.
Proton radiotherapy is distinguished from standard photon therapy by its capacity to deliver high-dose-volume within an anatomical site while maintaining lower doses to surrounding normal tissues. Penn Medicine also offers pencil beam scanning for proton therapy. Pencil beam scanning allows for enhanced conformal dose around critical structures through modulation of dose in depth, while retaining the rapid dose fall-off from the Bragg-Peak effect.
Phase II Study
The phase II study will collect longitudinal data on fatigue and quality of life after proton therapy and gather toxicity data. Local control rates will also be evaluated.
Design: Thirty-eight patients will be enrolled in the phase II study. Patients from both the feasibility and phase II stages will be pooled for data analysis (a total of 50 patients), as the intended treatment is the same for both groups. Patients will be treated and followed for a minimum of 90 days from start of radiotherapy to determine acute toxicity. Patients will continue to be followed beyond 90 days for the late toxicity, fatigue, quality of life and progression-free and overall survival.
Objectives: Proton therapy at standard doses is not expected to improve clinical outcome but will likely reduce rates of acute toxicity, fatigue and poor quality of life. Most reports of fatigue and quality of life have been retrospective cross-sectional studies. Thus, fatigue and quality of life are not well understood for these patients.
Following radiotherapy, it is expected that fatigue will be most severe at 6 to 9 months and will gradually improve at 12 to 24 months. Quality of life outcomes may follow a similar pattern. Higher than standard doses of radiation may improve local control rates of Grade II and III meningiomas.
Endpoints: The endpoints for the Phase II study will include acute toxicity, late toxicity, fatigue, quality of life, cumulative total dose to normal brain tissue, progression-free survival and overall survival.
Detection of Vascular and Neuronal Changes and their Correlation to Neurocognitive Changes Following Proton and Photon Radiotherapy in Patients Receiving Skull Base and Brain Radiation
In addition to the Phase II study, a prospective neurocognitive trial is currently enrolling at Penn to study the use of proton therapy in patients treated with brain tumors and compare this to historical group of patients treated with photons. Patients receiving radiation therapy to the brain are eligible (as are a select group of family members not receiving radiation) to determine any neurocognitive effects of radiation and attempt to find imaging correlates to assist in radiation treatment planning in the future.
This study will collect longitudinal data on a series of neurocognitive tests as well as obtain magnetic resonance imaging (MRI) studies to estimate the degree of cognitive loss, if any, following radiotherapy using a prospective, longitudinal design beginning prior to radiotherapy (approximately baseline), and then approximately 1.5, 6, 12, and 24 months post completion of radiotherapy.
Design: Seventy patients will be enrolled and treated with radiation therapy to the brain or base of skull. They will then be followed over two years and obtain neurocognitive testing and MRI scans at specific time points over the course of 2 years. This will be done in conjunction to obtaining information regarding late toxicity.
Objectives: To determine if the decrease in overall low dose radiation with proton therapy to the brain has a meaningful impact on neurocognition and compare this to historical group of patients that received photon therapy as well as compared to normal control patients. In addition, we will attempt to correlate the changes noted with imaging correlates to assist in treatment planning for the future.
Endpoints: These include changes in neurocognition with an attempt to determine clinical and imaging correlates for memory decline.
Prospective participants and/or their physicians may contact Ellen Rash at 215-614-1786 for information about enrolling in these trials.
Among the largest and most respected programs in the world, Penn Radiation Oncology offers a variety of innovative treatment options to patients with cancer. In addition, as a national leader in basic science, translational research and clinical trials, Penn Radiation Oncology offers patients access to the latest treatment options–– including proton therapy––before they are widely available elsewhere.
Performing Proton Therapy for Meningiomas and Hemagiopericytomas at Penn Medicine
Michelle Alonso-Basanta, MD, PhD
Assistant Professor of Radiation Oncology
Goldie A. Kurtz, MD
Instructor of Radiation Oncology
Robert Lustig, MD
Professor of Clinical Radiation Oncology
Chief of Clinical Operations
Penn Radiation Oncology
Perelman Center for Advanced Medicine
3400 Civic Center Boulevard
Philadelphia, PA 19104