BACKGROUND: Patients with recurrent high grade glioma (rHGG) have a poor prognosis with limited treatment options, especially those refractory to bevacizumab. A phase II multi-center trial was performed to determine the overall survival (OS) of hypofractioned radiation with concurrent bevacizumab (BEV) and temozolomide (TMZ) followed by maintenance BEV and TMZ in patients with rHGG. METHODS: Inclusion criteria were recurrent anaplastic glioma (AG) or glioblastoma (GBM) with patients stratified into 4 groups based on histologic grade and prior exposure to bevacizumab (Bev). Treatment consisted of hypofractionated radiation at 1.8 Gy for 25 fractions (45Gy total dose) concurrent with bevacizumab 10mg/kg every 2 weeks and temozolomide 75mg/m2 daily followed by adjuvant treatment cycles (8 week cycles) of bevacizumab 10mg/kg every 2 weeks and temozolomide 50mg/m2 daily for 6 weeks. Primary endpoint was overall survival (OS). RESULTS: Fifty-four patients were treated (37 men, 17 women). Median age was 49 (range 21-72). Of the 54 patients, 31 were Bev exposed GBM, 7 were Bev naïve GBM, 6 were Bev exposed AG, and 3 were Bev naïve AG. OS for Bev exposed GBM was 7.5 months, 15.0 months for Bev naïve GBM, and 5.0 months for Bev exposed AG. All Bev naïve AG patients are still living. Median OS for all patients with prior Bev exposure was 7.5 months. Grade 3 and 4 toxicities included lymphopenia (grade 3, n=4; grade 4, n=1) and thrombocytopenia (grade 3, n=1; grade 4, n =1). CONCLUSION: The combination of hypofractionated reirradiation, bevacizumab, and temozolomide was relatively safe and showed modest activity in recurrent high-grade glioma patients, including those with progressive disease while on bevacizumab.
BACKGROUND
The use of Tumor Treating Fields (TTFields) following resection and chemoradiation has increased survival in patients with Glioblastoma. Randomized data provide strong rationale for planning TTFields transducer array placement to maximize TTFields dose at the tumor in a patient-specific manner. Here we present a case demonstrating the use of numerical simulations for patient-specific TTFields treatment planning for a spinal tumor.
METHODS
Treatment planning was performed for a 48 year old patient following T10-L1 laminectomy, gross total resection, and postoperative chemoradiation for an anaplastic astrocytoma of the spinal cord. An MRI at 3 weeks following chemoradiation showed tumor recurrence. Based on the post-chemoradiation MRI, a patient-specific model was created. The model was created by modifying a realistic computational phantom of a healthy female. To mimic the laminectomy, the lamina in T10-L1 was removed, and the region assigned electric conductivity similar to that of muscle. A virtual mass was introduced into the spinal cord. Virtual transducer arrays were placed on the model at multiple positions, and delivery of TTFields simulated. The dose delivered by different transducer array layouts was calculated, and the layouts that yielded maximal dose to the tumor and spine identified.
RESULTS
Transducer array layouts, in which the arrays were placed on the back of the patient with one array above the tumor and one array below the tumor, yielded the highest doses at the tumor site. Such layouts yielded TTFields doses of over 3.4mW/cm3 which is well above the threshold dose of 1.1 mW/cm3 reported previously [Ballo et al Red Jour 2019].
CONCLUSIONS
These data represent the first ever study on utilizing numerical simulations in order to plan treatment for a spinal tumor in a patient-specific manner. This is an important milestone in the developing a framework for TTFields dosimetry and treatment planning.
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