Feasibility of removable balloon implant for simultaneous magnetic nanoparticle heating and HDR brachytherapy of brain tumor resection cavities

Abstract

Aim: Hyperthermia (HT) has been shown to improve clinical response to radiation therapy (RT) for cancer. Synergism is dramatically enhanced if HT and RT are combined simultaneously, but appropriate technology to apply treatments together does not exist. This study investigates the feasibility of delivering HT with RT to a 5-10mm annular rim of at-risk tissue around a tumor resection cavity using a temporary thermobrachytherapy (TBT) balloon implant. Methods: A balloon catheter was designed to deliver radiation from High Dose Rate (HDR) brachytherapy concurrent with HT delivered by filling the balloon with magnetic nanoparticles (MNP) and immersing it in a radiofrequency magnetic field. Temperature distributions in brain around the TBT balloon were simulated with temperature dependent brain blood perfusion using numerical modeling. A magnetic induction system was constructed and used to produce rapid heating (>0.2 C/s) of MNPfilled balloons in brain tissue-equivalent phantoms by absorbing 0.5 W/ml from a 5.7 kA/m field at 133 kHz. Results: Simulated treatment plans demonstrate the ability to heat at-risk tissue around a brain tumor resection cavity between 40-48 C for 2-5cm diameter balloons. Experimental thermal dosimetry verifies the expected rapid and spherically symmetric heating of brain phantom around the MNP-filled balloon at a magnetic field strength that has proven safe in previous clinical studies. Conclusions: These preclinical results demonstrate the feasibility of using a TBT balloon to deliver heat simultaneously with HDR brachytherapy to tumor bed around a brain tumor resection cavity, with significantly improved uniformity of heating over previous multi-catheter interstitial approaches. Considered along with results of previous clinical thermobrachytherapy trials, this new capability is expected to improve both survival and quality of life in patients with glioblastoma multiforme.

Evaluation of a Balloon Implant for Simultaneous Magnetic Nanoparticle Hyperthermia and High-Dose-Rate Brachytherapy of Brain Tumor Resection Cavities

“…As shown in Figure 1A, multiple catheters are housed within a flexible sheath, which extends from inside the balloon to ports outside the skull: a central lumen allows the insertion of a catheter through which an HDR brachytherapy source travels to the balloon center; a second lumen allows the insertion of a fiber optic probe into the outer balloon to monitor the nanofluid temperature during heating; and two additional lumens are used to fill the inner and outer balloons. Further details of the TBT implant design are reported in reference [41].…”

“…The assembled phantom was positioned at the center of the RF coil to surround the nanofluid with a uniform magnetic field. Field homogeneity within the coil has been reported previously [41]. The pre-programmed power sequence Job #1 (Table 2) was used to reach a peak temperature of 34 °C inside the nanofluid, starting from room temperature at 20 °C, i.e., a temperature increase of ΔT = 14 °C.…”

“…Combining thermal therapy (40)(41)(42)(43)(44)(45)(46)(47)(48) • C for 15-60 min) with radiation therapy enhances radiation response [6][7][8][9][10] and improves clinical outcomes [11][12][13][14][15]. One randomized clinical trial in primary GBM demonstrated a statistically significant doubling of 2-year survival (31% vs. 15%, p = 0.02) by adding two 30 min interstitial microwave hyperthermia sessions to an interstitial iodine-125 ( 125 I) brachytherapy boost, following the then standard partial brain external beam radiotherapy (EBRT) with 59.4 Gy in 33 fractions and oral hydroxyurea as a radiosensitizer [16].…”

“…After decades of investigation of fundamentally imperfect percutaneous catheterbased treatments not well matched to the task of treating a large annular tumor margin surrounding a resection cavity at depth in sensitive normal brain, the development of a novel treatment approach was initiated. Stauffer et al [41] describe the design and early testing of a novel dual-wall balloon implant intended for the simultaneous delivery of heat and radiation doses applied uniformly to the resection cavity wall and falling off within 5-10 mm of the tumor margin in order to minimize complications in surrounding brain. The current effort presents a thorough evaluation of two different size and style thermobrachytherapy (TBT) balloon implant devices manufactured according to that design.…”