Unique brain injury patterns after proton vs photon radiotherapy for WHO grade 2-3 gliomas.

BACKGROUND: Central nervous system (CNS) injury following brain-directed radiotherapy remains a major challenge. Proton radiotherapy (PRT) minimizes radiation to healthy brain, potentially limiting sequelae. We characterized CNS radiotoxicity, including radiation-induced leukoencephalopathy (RIL), brain tissue necrosis (TN), and cerebral microbleeds (CMB), in glioma patients treated with PRT or photons (XRT). PATIENTS AND METHODS: Thirty-four patients (19 male; median age 39.6 years) with WHO grade 2-3 gliomas treated with partial cranial radiotherapy (XRT [n = 17] vs PRT[n = 17]) were identified and matched by demographic/clinical criteria. Radiotoxicity was assessed longitudinally for 3 years post-radiotherapy via serial analysis of T2/FLAIR- (for RIL), contrast-enhanced T1- (for TN), and susceptibility (for CMB)-weighted MRI sequences. RIL was rated at whole-brain and hemispheric levels using a novel Fazekas scale-informed scoring system. RESULTS: The scoring system proved reliable (ICC > 0.85). Both groups developed moderate-to-severe RIL (62%[XRT]; 71%[PRT]) within 3 years; however, XRT was associated with persistent RIL increases in the contralesional hemisphere, whereas contralesional hemispheric RIL plateaued with PRT at 1-year post-radiotherapy (t = 2.180; P = .037). TN rates were greater with PRT (6%[XRT] vs 18%[PRT]; P = ns). CMB prevalence (76%[XRT]; 71%[PRT]) and burden (mean #CMB: 4.0[XRT]; 4.2[PRT]) were similar; however, XRT correlated with greater contralesional hemispheric CMB burden (27%[XRT]; 17%[PRT]; X2 = 4.986; P = .026), whereas PRT-specific CMB clustered at the radiation field margin (X2 = 14.7; P = .002). CONCLUSIONS: CNS radiotoxicity is common and progressive in glioma patients. Injury patterns suggest radiation modality-specificity as RIL, TN, and CMB exhibit unique spatiotemporal differences following XRT vs PRT, likely reflecting underlying dosimetric and radiobiological differences. Familiarity with such injury patterns is essential to improve patient management. Prospective studies are needed to validate these findings and assess their impacts on neurocognitive function.

Brain volume loss after cranial irradiation: a controlled comparison study between photon vs proton radiotherapy for WHO grade 2-3 gliomas.

PURPOSE: Radiation therapy (RT) is an integral treatment component in patients with glioma but associated with neurotoxicity. Proton RT (PRT), as compared with photon RT (XRT), reduces excess radiation to nontarget tissue. We used a retrospective method to evaluate brain imaging metrics of neurotoxicity after treatment with PRT and XRT for glioma. METHODS: We analyzed brain volume change in thirty-four patients with WHO grade 2-3 gliomas treated with either PRT (n = 17) or XRT (n = 17). Both groups were carefully matched by demographic/clinical criteria and assessed longitudinally for two years post-radiotherapy. Brain volume change was measured as ventricular volume expansion in the tumor free hemisphere (contralateral to RT target) as a proxy indicator of brain volume loss. We further assessed the impact of volumetric changes on cognition in PRT patients, who completed neuropsychological testing as part of an outcome study. RESULTS: We found significant ventricular volume increases in the contralesional hemisphere in both groups at two years post-RT (F(1, 31) = 18.45, p < 0.000, partial η2 = 0.373), with greater volume change observed in XRT (26.55%) vs. PRT (12.03%) (M = 12.03%, SD = 16.26; F(1,31) = 4.26, p = 0.048, partial η2 = 0.121). Although, there was no group-level change on any cognitive test in PRT treated patients, individual changes on cognitive screening, working memory, processing speed and visual memory tasks correlated with contralesional brain volume loss. CONCLUSION: This study suggests progressive brain volume loss following cranial irradiation, with greater severity after XRT vs. PRT. Radiation-induced brain volume loss appears to be associated with measurable cognitive changes on an individual level. Prospective studies are warranted to validate these findings and their impacts on long-term cognitive function and quality of life. An improved understanding of the structural and functional consequences of cranial radiation is essential to develop neuroprotective strategies.

Mitigating Radiotoxicity in the Central Nervous System: Role of Proton Therapy.

OPINION STATEMENT: Central nervous system (CNS) radiotoxicity remains a challenge in neuro-oncology. Dose distribution advantages of protons over photons have prompted increased use of brain-directed proton therapy. While well-recognized among pediatric populations, the benefit of proton therapy among adults with CNS malignancies remains controversial. We herein discuss the role of protons in mitigating late CNS radiotoxicities in adult patients. Despite limited clinical trials, evidence suggests toxicity profile advantages of protons over conventional radiotherapy, including retention of neurocognitive function and brain volume. Modelling studies predict superior dose conformality of protons versus state-of-the-art photon techniques reduces late radiogenic vasculopathies, endocrinopathies, and malignancies. Conversely, potentially higher brain tissue necrosis rates following proton therapy highlight a need to resolve uncertainties surrounding the impact of variable biological effectiveness of protons on dose distribution. Clinical trials comparing best photon and particle-based therapy are underway to establish whether protons substantially improve long-term treatment-related outcomes in adults with CNS malignancies.

Feasibility and Acceptance of Direct-to-Home Tele-neuropsychology Services during the COVID-19 Pandemic.

OBJECTIVE: Neuropsychological assessment via video conferencing has been proposed during the COVID-19 pandemic. Existing literature has demonstrated feasibility and acceptance of neuropsychological measures administered by videoconference, although few studies have examined feasibility and patient acceptance of TNP visits directly to patients' homes (DTH-TNP). METHODS: We modified a previously published patient satisfaction survey for DTH-TNP and developed a clinician feasibility survey to examine experiences during DTH-TNP. RESULTS: Seventy-two patients (age range: preschool-geriatric) evaluated by DTH-TNP for cognitive problems at an academic medical center responded to voluntary surveys between April 20, 2020, and August 19, 2020, and 100% indicated satisfaction. Fifty-nine percent of patients reported limitations (e.g., technological concern) during the appointment. 134 clinician surveys were collected and indicated that clinicians achieved the goal of their appointment in 90% of encounters. CONCLUSIONS: These qualitative data suggest that patients and clinicians found DTH-TNP to be satisfactory during the COVID-19 pandemic, while also recognizing limitations of the practice. These results are limited in that voluntary surveys are subject to bias. They support the growing body of literature suggesting that DTH-TNP provides a valuable service, though additional research to establish reliability and validity is needed.

The development and implementation of teleneuropsychology in an academic lifespan neuropsychology center: Lessons learned from the COVID-19 pandemic.

INTRODUCTION: Teleneuropsychology (TNP) became a critical means for providing care during the COVID-19 pandemic and may continue as an option for delivery of neuropsychological services. To understand how patient characteristics impact clinician decisions and service models, this study examines practice patterns within a lifespan outpatient neuropsychology center before, during and post-pandemic. METHODS: Patient volume, demographics, and characteristics were compared across four, 3-month time intervals in 2019-2020. Two baseline intervals when the center was physically open (PO) were compared to one interval when the center was physically closed (PC) (all evaluations were conducted via direct-to-home TNP) and a fourth interval when the center was physically reopened (RO) and evaluations were conducted in one of the three modalities: in-person, virtual only or hybrid (both virtual/in-person). RESULTS: A total of 1,459 total neuropsychological evaluations were conducted with a 64.6% reduction during PC. At RO, the number of evaluations returned to pre-COVID baseline during which in-person (72.4%) evaluations were conducted at a higher rate than hybrid (7.1%) or virtual only (20.4%). Across the lifespan, mean number of appointments to complete evaluations was significantly greater during PC (p< .001) than at other time intervals, and during RO, hybrid evaluations required significantly more appointments (p < .001) than in-person and virtual. The majority of evaluations were conducted with adult patients (71.4%). For adult patients, neurodegenerative/memory disorders received TNP evaluations at a higher rate during PC and RO. Pediatric patients were significantly older during PC (p < .001); neurodevelopmental referrals received more hybrid and virtual evaluations. CONCLUSIONS: Results indicate that patient characteristics, especially age and referral categories, impact the feasibility of TNP. Data from the RO period suggest that in-person evaluations not surprisingly remain the mainstay; however, for adult patients, and especially older adults with neurodegenerative/memory disorders, TNP may provide an important option for delivery of neuropsychological evaluations.

Cancer, cognition, and COVID: delivering direct-to-home teleneuropsychology services to neuro-oncology patients.

BACKGROUND: The COVID-19 pandemic induced rapid adoption of telemedicine services for neuro-oncology patients at an increased risk of infection. Neuropsychological assessment is important to neuro-oncology care yet challenging to complete outside of a structured testing environment. Teleneuropsychology (TNP) has been explored in limited populations and proven feasible and reliable. Conducting TNP visits directly to patients' home (DTH) had minimal prior study. METHODS: We used two voluntary surveys to examine acceptance (patients) and feasibility (providers) of DTH-TNP at two regionally diverse medical institutions providing neuropsychological services to neuro-oncology patients from April to September 2020. RESULTS: A total of 119 patients were scheduled during the study period, 79 of whom completed neuropsychological testing via DTH-TNP. Neuropsychology providers completed surveys on 68 of these encounters (86%). In 98% of cases, neuropsychologists were able to achieve or partially achieve the individually defined goals of their assessment. Common problems reported included patient dysregulation (16%) and slow/unreliable internet (15%). Of the 52 patients who responded, 98% were satisfied with the DTH-TNP experience, and 92% would recommend the virtual visit to others. All respondents felt understood by the examiner (100%) and the majority denied technical difficulties (90%), communication challenges (94%), or privacy concerns (98%). Patients reported reduced risk of infection and saved travel time as favorable aspects of DTH-TNP. CONCLUSIONS: These preliminary results suggest neuro-oncology patients find DTH-TNP acceptable and neuropsychologists find it a feasible practice, while also recognizing its limitations. Results suggest that further study of DTH-TNP (eg, reliability, validity) for neuro-oncology patients is warranted.

Mobile Intervention to Improve Sleep and Functional Health of Veterans With Insomnia: Randomized Controlled Trial.

BACKGROUND: Insomnia is a prevalent and debilitating disorder among veterans. Cognitive behavioral therapy for insomnia (CBTI) can be effective for treating insomnia, although many cannot access this care. Technology-based solutions and lifestyle changes, such as physical activity (PA), offer affordable and accessible self-management alternatives to in-person CBTI. OBJECTIVE: This study aims to extend and replicate prior pilot work to examine whether the use of a mobile app for CBTI (cognitive behavioral therapy for insomnia coach app [CBT-i Coach]) improves subjective and objective sleep outcomes. This study also aims to investigate whether the use of the CBT-i Coach app with adjunctive PA improves sleep outcomes more than CBT-i Coach alone. METHODS: A total of 33 veterans (mean age 37.61 years, SD 9.35 years) reporting chronic insomnia were randomized to use either the CBT-i Coach app alone or the CBT-i Coach app with a PA intervention over 6 weeks, with outcome measures of objective and subjective sleep at pre- and posttreatment. RESULTS: Although the PA manipulation was unsuccessful, both groups of veterans using the CBT-i Coach app showed significant improvement from baseline to postintervention on insomnia (P<.001), sleep quality (P<.001), and functional sleep outcomes (P=.002). Improvements in subjective sleep outcomes were similar in those with and without posttraumatic stress disorder and mild-to-moderate sleep apnea. We also observed a significant but modest increase in objective sleep efficiency (P=.02). CONCLUSIONS: These findings suggest that the use of a mobile app-delivered CBTI is feasible and beneficial for improving sleep outcomes in veterans with insomnia, including those with comorbid conditions such as posttraumatic stress disorder or mild-to-moderate sleep apnea. TRIAL REGISTRATION: ClinicalTrials.gov NCT03305354; https://clinicaltrials.gov/ct2/show/NCT03305354.