Advancing Beyond the Hippocampus to Preserve Cognition for Patients With Brain Metastases: Dosimetric Results From a Phase 2 Trial of Memory-Avoidance Whole Brain Radiation Therapy.

Purpose: Recent advances to preserve neurocognitive function in patients treated for brain metastases include stereotactic radiosurgery, hippocampal avoidance whole brain radiation therapy (WBRT), and memantine administration. The hippocampus, corpus callosum, fornix, and amygdala are key neurocognitive substructures with a low propensity for brain metastases. Herein, we report our preliminary experience using a "memory-avoidance" WBRT (MA-WBRT) approach that spares these substructures for patients with >15 brain metastases. Methods and Materials: Ten consecutive patients treated with MA-WBRT on a phase 2 clinical trial were reviewed. In each patient, the hippocampi, amygdalae, corpus callosum, and fornix were contoured. Patients were not eligible for MA-WBRT if they had metastases in these substructures. A memory-avoidance region was created using a 5-mm volumetric expansion around these substructures. Hotspots were avoided in the hypothalamus and pituitary gland. Coverage of brain metastases was prioritized over memory avoidance dose constraints. Dose constraints for these avoidance structures included a D100% ≤ 9 Gy and D0.03 cm3 ≤ 16 Gy (variation acceptable to 20 Gy). LINAC-based volumetric modulated arc therapy plans were generated for a prescription dose of 30 Gy in 10 fractions. Results: On average, the memory avoidance structure volume was 37.1 cm3 (range, 25.2-44.6 cm3), occupying 2.5% of the entire whole brain target volume. All treatment plans met the D100% dose constraint, and 8 of 10 plans met the D0.03 cm3 constraint, with priority given to tumor coverage for the remaining 2 cases. Target coverage (D98% > 25 Gy) and homogeneity (D2% ≤ 37.5 Gy) were achieved for all plans. Conclusions: Modern volumetric modulated arc therapy techniques allow for sparing of the hippocampus, amygdala, corpus callosum, and fornix with good target coverage and homogeneity. After enrollment is completed, quality of life and cognitive data will be evaluated to assess the efficacy of MA-WBRT to mitigate declines in quality of life and cognition after whole brain radiation.

Robust VMAT treatment planning for extremity soft tissue sarcomas.

Volumetric modulated arc therapy (VMAT) is a frequently employed and guideline-recommended radiotherapy (RT) modality for extremity soft tissue sarcomas (eSTS). Prior studies have demonstrated that significant tumor volume changes during treatment result in loss of target volume coverage with highly conformal techniques such as VMAT, but few solutions exist to these issues aside from adaptive replanning. Here, we describe a related but novel phenomenon in which relatively minor changes in surface volume contour (whether due to daily setup uncertainty, edema of peritumoral tissue, or progression or pseudo-progression of tumor volume itself) can result in unexpected subcutaneous hotspots. This phenomenon is of significant clinical concern given the known association between skin dose and major wound complications during preoperative RT for eSTS. By evaluating daily cone-beam CT (CBCT) images from thirteen eSTS patients treated with VMAT RT, we identify daily surface contour changes (range: 2 mm-15 mm, median: 8 mm) which are frequently below conventional adaptive replanning thresholds. When applied under experimental conditions, these external contour changes did not have major impacts on target volume coverage (range: 30.2%-91.2%, mean: 72.5%) but did result in unexpected hotspots of 125.8% on average (range: 110.0%-142.2%) in the subcutaneous tissues. To mitigate this issue, we develop a methodology for VMAT treatment planning using flash PTV and virtual bolus (VB) to produce robust treatment plans that are more resistant to target volume changes, surface contour changes, and setup uncertainties than conventional planning methods. With this methodology, robust plans were equivalent to standard plans at baseline, but, after incorporation of surface volume changes, both maintained target volume coverage (p < 0.001) and prevented development of subcutaneous hotspots (p < 0.001) better than standard plans. As such, this treatment planning methodology may facilitate development of robust VMAT treatment plans that minimize development of subcutaneous hotspots and preserve target volume coverage in the context of routine volumetric changes during preoperative RT.

Single-Isocenter Multitarget Stereotactic Radiosurgery Is Safe and Effective in the Treatment of Multiple Brain Metastases.

PURPOSE: Multiple studies have reported favorable outcomes for stereotactic radiosurgery (SRS) in the treatment of limited brain metastases. An obstacle of SRS in the management of numerous metastases is the longer treatment time using traditional radiosurgery. Single-isocenter multitarget (SIMT) SRS is a novel technique that permits rapid therapy delivery to multiple metastases. There is a lack of clinical evidence regarding its efficacy and safety. We report the outcomes of patients treated with this technique. METHODS AND MATERIALS: We reviewed the records of patients with intact or resected brain metastases treated with SRS in 1 to 5 fractions using SIMT technique at our institution, with at least 1 available follow-up brain magnetic resonance imaging. Survival, disease control, and toxicity were evaluated using Cox regression, logistic regression, and Kaplan-Meier analysis. RESULTS: We identified 173 patients with 1014 brain metastases. Median follow up was 12.7 months. Median beam-on time was 4.1 minutes. The median dose to the brain was 219.4 cGy. Median overall survival and freedom from intracranial progression were 13.2 and 6.3 months, respectively. Overall survival did not differ between patients treated with greater than or less than 4 lesions (hazard ratio, 1.03; 95% confidence interval 0.66-1.61; P = .91). Actuarial 1- and 2-year local control were 99.0% and 95.1%, respectively. Rates of grade 2 and grade 3 or higher radionecrosis were 1.4% and 0.9%, respectively. CONCLUSIONS: SIMT radiosurgery delivered in 1 to 5 fractions offers excellent local control and acceptable toxicity in the treatment of multiple intact and postoperative brain metastases. This technique should be evaluated prospectively.

Dosimetric evaluation between megavoltage cone-beam computed tomography and body mass index for intracranial, thoracic, and pelvic localization.

The aim of this study was to evaluate radiation dose for organs at risk (OAR) within the cranium, thorax, and pelvis from megavoltage cone-beam computed tomography (MV-CBCT). Using a clinical treatment planning system, CBCT doses were calculated from 60 patient datasets using 27.4 × 27.4 cm(2) field size and 200° arc length. The body mass indices (BMIs) for these patients range from 17.2-48.4 kg/m(2). A total of 60 CBCT plans were created and calculated with heterogeneity corrections, with monitor units (MU) that varied from 8, 4, and 2 MU per plan. The isocenters of these plans were placed at defined anatomical structures. The maximum dose, dose to the isocenter, and mean dose to the selected critical organs were analyzed. The study found that maximum and isocenter doses were weakly associated with BMI, but linearly associated with the total MU. Average maximum/isocenter doses in the cranium were 10.0 (± 0.18)/7.0 (± 0.08) cGy, 5.0 (± 0.09)/3.5 (± 0.05) cGy, and 2.5 (± .04)/1.8 (± 0.05) cGy for 8, 4, and 2 MU, respectively. Similar trends but slightly larger maximum/isocenter doses were found in the thoracic and pelvic regions. For the cranial region, the average mean doses with a total of 8 MU to the eye, lens, and brain were 9.7 (± 0.12) cGy, 9.1 (± 0.16) cGy, and 7.2 (± 0.10) cGy, respectively. For the thoracic region, the average mean doses to the lung, heart, and spinal cord were 6.6 (± 0.05) cGy, 6.9 (± 1.2) cGy, and 4.7 (± 0.8) cGy, respectively. For the pelvic region, the average mean dose to the femoral heads was 6.4 (± 1.1) cGy. The MV-CBCT doses were linearly associated with the total MU but weakly dependent on patients' BMIs. Daily MV-CBCT has a cumulative effect on the total body dose and critical organs, which should be carefully considered for clinical impacts.