ABSTRACT
PURPOSE: To investigate the feasibility of a novel dedicated treatment planning solution, to automatically target multiple brain metastases with a single isocenter and multiple inversely-optimized dynamic conformal arcs (DCA), and to benchmark it against the well-established multiple isocenter DCA (MIDCA) and volumetric modulated arc therapy (VMAT) approaches. MATERIAL AND METHODS: Ten previously treated patients were randomly selected, each representing a variable number of lesions ranging between 1 to 8. The original MIDCA treatments were replanned with both VMAT and the novel brain metastases tool. The plans were compared by means of Paddick conformity (CI) and gradient index (GI), and the volumes receiving 10 Gy (V10) and 12 Gy (V12). RESULTS: The brain metastases software tool generated plans with similar CI (0.65 ± 0.08) as both established treatment techniques while improving the gradient (mean GI = 3.9 ± 1.4). The normal tissue exposure in terms of V10 (48.5 ± 35.9 cc) and V12 (36.3 ± 27.1 cc) compared similarly to the MIDCA technique and surpassed VMAT plans. CONCLUSIONS: The automated brain metastases planning algorithm software is an optimization of DCA radiosurgery by increasing delivery efficiency to the level of VMAT approaches. Improving dose gradients and normal tissue sparing over VMAT, revives DCA as the paradigm for linac-based stereotactic radiosurgery of multiple brain metastases.
Subject(s)
Brain Neoplasms/radiotherapy , Radiosurgery/methods , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy, Intensity-Modulated/methods , Algorithms , Automation , Benchmarking , Brain Neoplasms/pathology , Humans , Neoplasm Metastasis , Pattern Recognition, Automated , Radiation Dosage , Radiometry/methods , Radiotherapy Dosage , Radiotherapy, Conformal/methods , Random Allocation , SoftwareABSTRACT
BACKGROUND AND PURPOSE: Fludarabine, 9-beta-D-arabinofuranosyl-2-fluoroadenine, is an adenine nucleoside analogue that has significant activity in hematological malignancies and has shown promising activity in combination with radiation in preclinical solid tumor models. In this framework, we designed two phase I trials (one conducted at M.D. Anderson Cancer Center in Houston, and the other conducted in two Belgian hospitals) exploring concurrent fludarabine and radiotherapy in patients with intermediate to locally advanced head and neck squamous cell carcinomas (HNSCC). MATERIALS AND METHODS: Fludarabine was administered i.v. daily 3-4 h before the last 10 fractions of a standard radiation fractionation regimen (70 Gy in 7 weeks). The main objective of the trials was to determine the maximum tolerated dose (MTD) of fludarabine in this particular setting. Twenty-eight patients with stage T2-T4, any N, M0 were included in the study. Fludarabine doses started at 7.5 mg/m(2) per day (3 mg/m(2) per day in Houston) and increased by steps of 2.5 mg/m(2) per day (3 mg/m(2) per day in Houston). RESULTS: The addition of fludarabine at increasing doses to radiation did not result in increased intensity or duration of skin (18% grade 3 dermatitis) or mucosal (60% grade 3 mucositis) radiotoxicity compared to what was expected for radiation alone. At a daily dose of 17.5 mg/m(2), two patients out of five (40%) developed a grade 4 neutropenia, of whom one developed a neutropenic fever. This dose was set as the MTD. All patients developed a fludarabine dose-dependant lymphocytopenia. The plasma F-ara-A concentration peaked after the 30-min infusion in a dose-dependent fashion and reached an average peak concentration of approximately 2 microM for doses of 15 mg/m(2) and higher. CONCLUSIONS: This study demonstrates that fludarabine can be safely administered concurrently with radiation at a daily dose of 15 mg/m(2) during the final 2 weeks of radiotherapy. A phase II trial will be required to establish the potential role of concurrent fludarabine and radiotherapy in the treatment of moderately to locally advanced HNSCC.
