Justus Adamson

PURPOSE: Stereotactic radiosurgery (SRS) is a highly effective therapy for newly diagnosed brain metastases. Prophylactic antiepileptic drugs are no longer routinely used in current SRS practice, owing to a perceived low overall frequency of new-onset seizures and potential side effects of medications. It is nonetheless desirable to prevent unwanted side effects following SRS. Risk factors for new-onset seizures after SRS have not been well established. As such, we aimed to characterize variables associated with increased seizure risk. METHODS AND MATERIALS: Patients treated with SRS for newly diagnosed brain metastases between 2013 and 2016 were retrospectively reviewed at a single institution. Data on baseline demographics, radiation parameters, and clinical courses were collected. RESULTS: The cohort consisted of 305 patients treated with SRS without prior seizure history. Median age and baseline Karnofsky Performance Scale score were 64 years (interquartile range, 55-70) and 80 (interquartile range, 80-90), respectively. Twenty-six (8.5%) patients developed new-onset seizures within 3 months of SRS. There was no association between new-onset seizures and median baseline Karnofsky Performance Scale score, prior resection, or prior whole brain radiation therapy. There were significant differences in the combined total irradiated volume (12.5 vs 3.7 cm3, P < .001), maximum single lesion volume (8.8 vs 2.8 cm3, P = .003), lesion diameter (3.2 vs 2.0 cm, P = .003), and number of lesions treated (3 vs 1, P = .018) between patients with and without new-onset seizures, respectively. On multivariate logistic regression, total irradiated volume (odds ratio, 1.09 for every 1-cm1 increase in total volume; confidence interval, 1.02-1.17; P = .016) and pre-SRS neurologic symptoms (odds ratio, 3.08; 95% confidence interval, 1.19-7.99; P = .020) were both significantly correlated with odds of seizures following SRS. CONCLUSIONS: Our data suggest that larger total treatment volume and the presence of focal neurologic deficits at presentation are associated with new-onset seizures within 3 months of SRS. High-risk patients undergoing SRS may benefit from counseling or prophylactic antiseizure therapy.

X-ray psoralen activated cancer therapy (X-PACT) is a new therapeutic approach that has been shown to induce tumor cell apoptosis and cytotoxicity in vitro, and slow tumor growth in BALB/c mice with syngeneic 4T1 tumors. X-PACT is accomplished by injection of co-incubated psoralen and phosphors; the phosphors emitUVto activate psoralen, and are activated by an external kV source. Here we describe application of a kVx-ray source mounted on board a medical linear accelerator for X-PACT in preparation for a phase I clinical trial of X-PACT for spontaneous tumors in pet dogs.We commissioned a 80 kVp beam at 50-80 cm from the source with varied blade settings to achieve rectangular collimated beams. Commissioning included dosimetry measurements, developing a formalism for absolute dose calculation in water, FLUKA Monte Carlo based planning and evaluation, and verification measurements. Dosimetry measurements includedAAPMTG-61 absolute dose calibration, depth dose curves, backscatter and collimator scatter factors, heel effect, and leakage. Reasonable agreement was achieved between measurement and Monte Carlo, and between calculated dose and verification measurements. Finally, we demonstrate the X-PACT treatment process for an example dog with a 3-5 cc left hip sarcoma located at a 2 cm depth. The absolute dose formalism indicated 21 pulses of 160 mAs were required to deliver the prescription dose of 0.6 Gy to 2.8 cm depth. The dose distribution was calculated with the Monte Carlo planning tool and visualized at 1 × 1 × 2mm3 spatial resolution. Adose enhancement in the hip bone of up to 4.5 Gy was observed. This work demonstrates that X-PACT is feasible utilizing diagnostic kV sources such as those mounted on a clinical linear accelerator, and reports commissioning and treatment planning data and formalism respectively.

In current standard radiation therapy process, patient anatomy is represented by the snapshot of computed tomography (CT) images at the simulation for treatment planning. The planned radiation dose distribution, obtained from either three-dimensional (3D) conformal radiation therapy (3DCRT) or intensity-modulated radiation therapy (IMRT) can have submillimeter precision through computer-based treatment planning. The improvement in the quality assurance of the treatment delivery system, as described in Chapter 15 in this book, can also achieve similar accuracy in geometry of the collimation components and <1%-2% on the radiation output. However, patient anatomy during the the treatment course is not static; the changes can be in the orders of centimeters. These deviations in patient anatomy from the time of initial simulation to the time of treatment delivery should be minimized or accounted for, to ensure that the optimal planned dose distribution is delivered to the patient.

AAPM TG-218 provides recommendations for standard IMRT pre-treatment QA without giving specifics for stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT). In light of this, our purpose is to report our experience with applying TG-218 recommendations to a large multicenter clinical SRS and SBRT program for a range of diverse clinical pre-treatment QA systems. Pre-treatment QA systems included Delta4 (Scandidos), Portal Dosimetry (Varian Medical Systems), ArcCHECK (SunNuclear), and SRS MapCHECK (SunNuclear). Plans were stratified by technique for each QA system, and included intracranial and extracranial IMRT and VMAT (total QA cases n=275). Gamma analysis was re-analyzed with spatial/dose criteria combinations ranging from 1 to 3 mm and 1% to 4%, and action and tolerance limits were calculated per plan type and compared to the "universal" TG-218 action limit of 90%. The analysis indicated that spatial tolerance criteria could be tightened to 1 mm while still maintaining an in-control QA process for all QA systems evaluated.