Search

Purpose: Hippocampal volume (HV) is an established predicting factor for neurocognitive function (NCF) in neurodegenerative disease. Whether the same phenomenon exists with hippocampal-avoidant whole brain radiation therapy is not known; therefore, we assessed the association of baseline HV with NCF among patients enrolled on RTOG 0933. Methods and Materials: Hippocampal volume and total brain volume were calculated from the radiation therapy plan. Hippocampal volume was correlated with baseline and 4-month NCF scores (Hopkins Verbal Learning Test–Revised [HVLT-R] Total Recall [TR], Immediate Recognition, and Delayed Recall [DR]) using Pearson correlation. Deterioration in NCF was defined per the primary endpoint of RTOG 0933(mean 4-month relative decline in HVLT-R DR). Comparisons between patients with deteriorated and nondeteriorated NCF were made using the Wilcoxon test. Results: Forty-two patients were evaluable. The median age was 56.5 years (range, 28-83 years), and 81% had a class II recursive partitioning analysis. The median total, right, and left HVs were 5.4 cm3 (range, 1.9-7.4 cm3), 2.8 cm3 (range, 0.9-4.0 cm3), and 2.7 cm3 (range, 1.0-3.7 cm3), respectively. The median total brain volume was 1343 cm3 (range, 1120.5-1738.8 cm3). For all measures of corrected HV, increasing HV was associated with higher baseline HVLT-R TR and DR scores (ρ: range, 0.35-0.40; P-value range, .009-.024) and 4-month TR and DR scores (ρ: range, 0.29-0.40; P-value range, .009-.04), with the exception of right HV and 4-month DR scores (ρ: 0.29; P = .059). There was no significant association between HV and NCF change between baseline and 4 months. Fourteen patients (33.3%) developed NCF deterioration per the primary endpoint of RTOG 0933. There was no significant difference in HV between patients with deteriorated and nondeteriorated NCF, although in all instances, patients with deteriorated NCF had numerically lower HV. Conclusions: Larger HV was positively associated with improved performance on baseline and 4-month HVLT-R TR and DR scores in patients with brain metastases undergoing hippocampal-avoidant whole brain radiation therapy but was not associated with a change in NCF.

Purpose: Randomized data show a survival benefit of stereotactic ablative body radiation therapy in selected patients with oligometastases (OM). Stereotactic magnetic resonance guided adaptive radiation therapy (SMART) may facilitate the delivery of ablative dose for OM lesions, especially those adjacent to historically dose-limiting organs at risk, where conventional approaches preclude ablative dosing. Methods and Materials: The RSSearch Registry was queried for OM patients (1-5 metastatic lesions) treated with SMART. Freedom from local progression (FFLP), freedom from distant progression (FFDP), progression-free survival (PFS), and overall survival (LS) were estimated using the Kaplan-Meier method. FFLP was evaluated using RECIST 1.1 criteria. Toxicity was evaluated using Common Terminology Criteria for Adverse Events version 4 criteria. Results: Ninety-six patients with 108 OM lesions were treated on a 0.35 T MR Linac at 2 institutions between 2018 and 2020. SMART was delivered to mostly abdominal or pelvic lymph nodes (48.1%), lung (18.5%), liver and intrahepatic bile ducts (16.7%), and adrenal gland (11.1%). The median prescribed radiation therapy dose was 48.5 Gy (range, 30-60 Gy) in 5 fractions (range, 3-15). The median biologically effective dose corrected using an alpha/beta value of 10 was 100 Gy10 (range, 48-180). No acute or late grade 3+ toxicities were observed with median 10 months (range, 3-25) follow-up. Estimated 1-year FFLP, FFDP, PFS, and OS were 92.3%, 41.1%, 39.3%, and 89.6%, respectively. Median FFDP and PFS were 8.9 months (95% confidence interval, 5.2-12.6 months) and 7.6 months (95% confidence interval, 4.5-10.6 months), respectively. Conclusions: To our knowledge, this represents the largest analysis of SMART using ablative dosing for non-bone OM. A median prescribed biologically effective dose of 100 Gy10 resulted in excellent early FFLP and no significant toxicity, likely facilitated by continuous intrafraction MR visualization, breath hold delivery, and online adaptive replanning. Additional prospective evaluation of dose-escalated SMART for OM is warranted.

Purpose: Compared with computed tomography, magnetic resonance (MR) image guidance offers significant advantages for radiation therapy (RT) that may be particularly beneficial for reirradiation (reRT). However, clinical outcomes of MR-guided reRT are not well described in the published literature. Methods and Materials: We performed a single-institution retrospective safety and efficacy analysis of reRT patients treated on the MRIdian Linac to targets within the abdomen or pelvis using continuous intrafraction MR-based motion management with automatic beam triggering. Fiducial markers were not used. Results: We evaluated 11 patients who received prior RT to a median of 50 Gy (range, 30-58.8 Gy) in 25 fractions (range, 5-28 fractions). The median interval to reRT was 26.8 months. The most frequently retreated sites were nodal metastases (36.4%) and pancreatic cancer (27.3%). The median reRT dose was 40 Gy (range, 25-54 Gy) in 6 fractions (range, 5-36 fractions); ultrahypofractionation (63.6%) was more common than hyperfractionation (36.4%). Daily on-table adaptive replanning was used for 3 patients (27.3%). With a median of 14 months’ follow-up from reRT completion (range, 6-32 months), the median and 1-year freedom from local progression were 29 months and 88.9%, respectively, and the median and 1-year overall survival were 17.5 months and 70.0%, respectively. One patient (9.1%) experienced acute grade 2 toxic effects; there were no acute or late treatment-related toxic effects of grade 3 or greater. Conclusions: Magnetic resonance–guided reRT appeared to be feasible and may facilitate safe dose escalation. Additional follow-up is needed to better assess long-term efficacy and late toxic effects. Prospective evaluation of this novel treatment strategy is warranted.

Purpose: Postoperative radiation therapy (RT) is commonly used for World Health Organization grade II-III intracranial ependymoma. Clinicians generally aim to begin RT ≤5 weeks after surgery, but postoperative recovery and need for second look surgery can delay the initiation of adjuvant therapy. On ACNS 0831, patients were required to enroll ≤8 weeks after initial surgery and begin adjuvant therapy within 3 weeks after enrollment. The purpose of this study was to determine the optimal timing of RT after surgery. Methods and Materials: The National Cancer Database was queried for patients (aged 1-39 years) with localized World Health Organization grade II-III intracranial ependymoma treated with surgery and postoperative RT. Overall survival (OS) curves were plotted based on RT timing (≤5 weeks, 5-8 weeks, and >8 weeks after surgery) and were compared by log-rank test. Factors associated with OS were identified by multivariate analysis. After 2009, complete data were available on whether patients underwent gross total resection or subtotal resection. Planned subset analysis was performed to examine the effect of RT timing on OS in patients with known extent of resection. Results: In the final analytical data set of 1043 patients, no difference in 3-year OS was observed in patients who initiated RT ≤5 weeks, 5 to 8 weeks, and >8 weeks after surgery (89.8% vs 89.1% vs 88.4%; P = .796). On multivariate analysis, grade III tumors (hazard ratio, 2.752; 95% confidence interval, 1.969-3.846, P < .001) and subtotal resection (hazard ratio, 2.253; 95% confidence interval, 1.405-3.611, P < .001) were significantly associated with reduced OS. Timing of RT, total RT dose, age, and other factors were not significant. These findings were affirmed in the subset of patients treated between 2010 and 2016, when extent of resection was routinely recorded. Conclusions: Delayed postoperative RT was not associated with inferior survival in patients with intracranial ependymoma. Delayed RT initiation may be acceptable in patients who require longer postoperative recovery or referral to an appropriate RT center, but should be minimized whenever practical.

Purpose: NRG Oncology's RTOG 0933 demonstrated benefits to memory preservation after hippocampal avoidant whole-brain radiation therapy (HA-WBRT), the avoidance of radiation dose to the hippocampus (using intensity modulated radiation planning and delivery techniques) during WBRT, supporting the hypothesis of hippocampal radiosensitivity and associated memory specificity. However, some patients demonstrated cognitive decline, suggesting mechanisms outside hippocampal radiosensitivity play a role. White matter injury (WMI) has been implicated in radiation therapy–induced neurocognitive decline. This secondary analysis explored the relationship between pretreatment WMI and memory after HA-WBRT. Methods and Materials: Volumetric analysis of metastatic disease burden and disease-unrelated WMI was conducted on the pretreatment magnetic resonance image. Correlational analyses were performed examining the relationship between pretreatment WMI and Hopkins Verbal Learning Test-Revised (HVLT-R) outcomes at baseline and 4 months after HA-WBRT. Results: In the study, 113 patients received HA-WBRT. Of 113 patients, 33 underwent pretreatment and 4-month posttreatment HVLT testing and pretreatment postcontrast volumetric T1 and axial T2/fluid-attenuated inversion recovery magnetic resonance imaging. Correlation was found between larger volumes of pretreatment WMI and decline in HVLT-R recognition (r = 0.54, P