Purpose: Hippocampal neural stem-cell injury during whole-brain radiotherapy (WBRT) may play a role in memory decline. Intensity-modulated radiotherapy can be used to avoid conformally the hippocampal neural stem-cell compartment during WBRT (HA-WBRT). RTOG 0933 was a single-arm phase II study of HA-WBRT for brain metastases with prespecified comparison with a historical control of patients treated with WBRT without hippocampal avoidance. Patients and Methods: Eligible adult patients with brain metastases received HA-WBRT to 30 Gy in 10 fractions. Standardized cognitive function and quality-of-life (QOL) assessments were performed at baseline and 2, 4, and 6 months. The primary end point was the Hopkins Verbal Learning Test–Revised Delayed Recall (HVLT-R DR) at 4 months. The historical control demonstrated a 30% mean relative decline in HVLT-R DR from baseline to 4 months. To detect a mean relative decline ≤ 15% in HVLT-R DR after HA-WBRT, 51 analyzable patients were required to ensure 80% statistical power with α = 0.05. Results: Of 113 patients accrued from March 2011 through November 2012, 42 patients were analyzable at 4 months. Mean relative decline in HVLT-R DR from baseline to 4 months was 7.0% (95% CI, −4.7% to 18.7%), significantly lower in comparison with the historical control (P < .001). No decline in QOL scores was observed. Two grade 3 toxicities and no grade 4 to 5 toxicities were reported. Median survival was 6.8 months. Conclusion: Conformal avoidance of the hippocampus during WBRT is associated with preservation of memory and QOL as compared with historical series.

Objectives: This study compares the dosimetry and efficiency of two modern radiosurgery (SRS) modalities for multiple brain metastases (Gamma Knife and LINAC-based RapidArc/volumetric modulated arc therapy), with a special focus on the comparison of low dose spread. Methods: Six patients with three or four small brain metastases were used in this study. The size of targets varied from 0.1 ~ 10.5 cc. SRS doses were prescribed according to size of lesions. SRS plans were made using both Gamma Knife® Perfexion and a single-isocenter, multiple non-coplanar RapidArc®. Dosimetric parameters analyzed included RTOG conformity index (CI), gradient index (GI), 12 Gy isodose volume (V12Gy) for each target, and the dose “spread” (Dspread) for each plan. Dspread reflects SRS plan’s capability of confining radiation to within the local vicinity of the lesion and to not spread out to the surrounding normal brain tissues. Each plan has a dose (Dspread), such that once dose decreases below Dspread (on total tissue DVH), isodose volume starts increasing dramatically. Dspread is defined as that dose when volume increase first exceeds 20 cc per 0.1 Gy dose decrease. Results: RapidArc SRS has smaller CI (1.19 ±0.14 vs. 1.50 ± 0.16, p<0.001) and larger GI (4.77 ± 1.49 vs. 3.65 ± 0.98, p <0.01). V12Gy results were comparable (2.73 ± 1.38 cc vs. 3.06 ± 2.20 cc, p = 0.58). Moderate to lower dose spread, V6, V4.5, and V3, were also equivalent. Gamma Knife plans achieved better very low dose spread (≤3 Gy) and also had slightly smaller Dspread, 1.9 Gy vs 2.5 Gy. Total treatment time for Gamma Knife is estimated between 60~100 min. Gamma Knife treatments are between 3~5 times longer compared to RapidArc treatment techniques. Conclusion: Dosimetric parameters reflecting prescription dose conformality (CI), dose fall off (GI), radiation necrosis indicator (V12Gy), and dose spread (Dspread) were compared between Gamma Knife SRS and RapidArc SRS for multi-mets. RapidArc plans have smaller CI but larger GI. V12Gy are comparable. Gamma Knife appears better at reducing only very low dose spread (<3Gy). The treatment time of RapidArc SRS is significantly reduced compared to Gamma Knife SRS.

Introduction: Tumor Treating Fields (TTFields; antimitotic treatment) delivers low-intensity, intermediate-frequency, alternating electric fields through skin-applied transducer arrays. TTFields (200 kHz) was FDA-approved in glioblastoma (GBM), based on the phase 3 EF-11 (recurrent GBM, rGBM) and EF-14 (newly diagnosed GBM, ndGBM) trials. The most common TTFields-related adverse event (AE) in both trials was array-associated skin irritation. We now report on TTFields-related AEs in the real-world, clinical practice setting. Methods: Unsolicited, post-marketing surveillance data from TTFields-treated patients (October 2011–February 2019) were retrospectively analyzed using MedDRA v21.1 preferred terms, stratified by region (US, EMEA [Europe, Middle East, Africa], Japan), diagnosis (ndGBM, rGBM, anaplastic astrocytoma/oligodendroglioma, other brain tumors), and age (< 18 [pediatric], 18–64 [adults], ≥ 65 [elderly]; years of age). Results: Of 11,029 patients, 53% were diagnosed with ndGBM and 39% were diagnosed with rGBM at any line of disease recurrence. Most were adults (73%), 26% were elderly, and the male-to-female ratio was ~ 2:1 (close to published ratios of typical GBM populations). The most commonly reported TTFields-related AE was array-associated skin reaction, occurring in patients with ndGBM (38%), rGBM (29%), anaplastic astrocytoma/oligodendroglioma (38%), and other brain tumors (31%); as well as 37% of pediatric, 34% of adult, and 36% of elderly patients. Most skin AEs were mild/moderate and manageable. Other TTFields-related AEs in patients with ndGBM/rGBM included under-array heat sensation (warmth; 11%, 10%, respectively) and electric sensation (tingling; 11%, 9%, respectively), and headache (7%, 6%, respectively). Conclusions: This TTFields safety surveillance analysis in > 11,000 patients revealed no new safety concerns, with a favorable safety profile comparable with published TTFields/GBM trials. The safety profile remained consistent among subgroups, suggesting feasibility in multiple populations, including elderly patients. Graphic