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Abstract accepted at SABCS 2023, poster presented at SABCS 2023 We report the efficacy of trastuzumab deruxtecan (T-DXd) in treating human epidermal growth factor receptor 2 (HER2) low, type ID leptomeningeal breast cancer (LMD) (with positive cerebrospinal fluid [CSF] cytology and hydrocephalus as the only abnormal imaging finding) and the diagnostic and monitoring utilization of a novel microfluidic platform called CNSide™. Breast cancer LMD is associated with poor prognosis, and effective treatments are lacking. Our case highlights two crucial aspects related to the treatment and monitoring of breast cancer LMD. First, T-DXd was chosen based on immunocytochemistry (IHC) data from CSF malignant cells and follow-up revealed effectiveness of T-DXd in treating HER2-low LMD. While the efficacy of T-DXd has been established in treating metastatic HER2-low breast cancer, our case represents, to our knowledge, the first demonstration of T-DXd's effectiveness in HER2-low breast cancer LMD. Second, since this is type 1D LMD with absence of unequivocal measurable radiological disease in both the central nervous system (CNS) and extra-CNS, we employed a novel microfluidic CSF assay to monitor disease response. This novel assay outperformed standard CSF cytology in our case. There is an urgent need to develop CSF tumor cell assessment tool that surpasses the capabilities of conventional CSF cytology. Article highlights T-DXd is highly efficacious in treating HER2 low, leptomeningeal breast cancer. CSF CNSide™ assay utilizes a microfluidic platform and an antibody capture method to capture tumor cells. It uses the same principles used for detecting circulating tumor cells in peripheral blood. CNSide™ assay has a sensitivity of 100% compared with standard CSF cytology which has a sensitivity of 50–60%. CNSide™ assay can be used for facilitating receptor status characterization and guiding treatment. Our case demonstrates efficacy of T-DXd in treating HER2 low leptomeningeal breast cancer and also highlights the clinical utility of CNSide™ assay. Our case aligns well with the emerging literature about the efficacy of T-DXd in treating metastatic HER2-low disease. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with brain tumors often experience changes in memory and other aspects of thinking. Many may also have difficulty with social cognition, affecting the abilities that facilitate social behavior and maintain social relationships; however, the data are limited. Whether treatments such as cranial radiation can impact social cognition is not well-studied. We sought to understand how radiation dose exposure to the amygdala–orbitofrontal network, which subserves social cognition and emotion recognition, impacted performance on an emotion recognition task. We found that radiation dose to the amygdala and associated structures was associated with performance on an emotion recognition task, including longer response times with increasing radiation doses. Radiation techniques that reduce the dose to the amygdala-orbitofrontal network may decrease side effects for patients receiving cranial radiation. Background: Although data are limited, difficulty in social cognition occurs in up to 83% of patients with brain tumors. It is unknown whether cranial radiation therapy (RT) dose to the amygdala–orbitofrontal network can impact social cognition. Methods: We prospectively enrolled 51 patients with low-grade and benign brain tumors planned for cranial RT. We assessed longitudinal changes on an emotion recognition task (ERT) that measures the ability to recognize emotional states by displaying faces expressing six basic emotions and their association with the RT dose to the amygdala–orbitofrontal network. ERT outcomes included the median time to choose a response (ERTOMDRT) or correct response (ERTOMDCRT) and total correct responses (ERTHH). Results: The RT dose to the amygdala–orbitofrontal network was significantly associated with longer median response times on the ERT. Increases in median response times occurred at lower doses than decreases in total correct responses. The medial orbitofrontal cortex was the most important variable on regression trees predicting change in the ERTOMDCRT. Discussion: This is, to our knowledge, the first study to show that off-target RT dose to the amygdala–orbitofrontal network is associated with performance on a social cognition task, a facet of cognition that has previously not been mechanistically studied after cranial RT. [ABSTRACT FROM AUTHOR]

Purpose: Accurate dose calculation is important in both target and low dose normal tissue regions for brain stereotactic radiosurgery (SRS). In this study, we aim to evaluate the dosimetric accuracy of the two advanced dose calculation algorithms for brain SRS. Methods: Retrospective clinical case study and phantom study were performed. For the clinical study, 138 SRS patient plans (443 targets) were generated using BrainLab Elements Voxel Monte Carlo (VMC). To evaluate the dose calculation accuracy, the plans were exported into Eclipse and recalculated with Acuros XB (AXB) algorithm with identical beam parameters. The calculated dose at the target center (Dref), dose to 95% target volume (D95), and the average dose to target (Dmean) were compared. Also, the distance from the skull was analyzed. For the phantom study, a cylindrical phantom and a head phantom were used, and the delivered dose was measured by an ion chamber and EBT3 film, respectively, at various locations. The measurement was compared with the calculated doses from VMC and AXB. Results: In clinical cases, VMC dose calculations tended to be higher than AXB. It was found that the difference in Dref showed > 5% in some cases for smaller volumes < 0.3 cm3. Dmean and D95 differences were also higher for small targets. No obvious trend was found between the dose difference and the distance from the skull. In phantom studies, VMC dose was also higher than AXB for smaller targets, and VMC showed better agreement with the measurements than AXB for both point dose and high dose spread. Conclusion: The two advanced calculation algorithms were extensively compared. For brain SRS, AXB sometimes calculates a noticeable lower target dose for small targets than VMC, and VMC tends to have a slightly closer agreement with measurements than AXB. [ABSTRACT FROM AUTHOR]

Objectives: Head and neck cancer is a common malignancy frequently treated with chemotherapy and radiotherapy. Studies have shown an increased risk of stroke with the receipt of radiotherapy, but data on stroke-related mortality are limited, particularly in the modern era. Evaluating stroke mortality related to radiotherapy is vital given the curative nature of head and neck cancer treatment and the need to understand the risk of severe stroke in this population. Methods: We analyzed the risk of stroke death among 122,362 patients (83,651 patients who received radiation and 38,711 patients who did not) with squamous cell carcinoma of the head and neck (HNSCC) diagnosed between 1973 and 2015 in the SEER database. Patients in radiation vs. no radiation groups were matched using propensity scores. Our primary hypothesis was that radiotherapy would increase the hazard of death from stroke. We also examined other factors impacting the hazard of stroke death, including whether radiotherapy was performed during the modern era when IMRT and modern stroke care were available as well as increased HPV-mediated cancers of the head and neck. We hypothesized that the hazard of stroke death would be less in the modern era. Results: There was an increased hazard of stroke-related death in the group receiving radiation therapy (HR 1.203, p = 0.006); however, this was a very small absolute increase, and the cumulative incidence function of stroke death was significantly reduced in the modern era (p < 0.001), cohorts with chemotherapy (p=0.003), males (p=0.002), younger cohorts (p<0.001) and subsites other than nasopharynx (p=0.025). Conclusions: While radiotherapy for head and neck cancer increases the hazard of stroke death, this is reduced in the modern era and remains a very small absolute risk. [ABSTRACT FROM AUTHOR]

Background: Inflammation may contribute to cognitive difficulties in patients with breast cancer. We tested 2 hypotheses: inflammation is elevated in patients with breast cancer vs noncancer control participants and inflammation in patients is associated with worse attention and processing speed over the course of chemotherapy.Methods: Serum cytokines (interleukin [IL]-4, 6, 8, 10; tumor necrosis factor [TNF]-α) and soluble receptors [sTNFRI, II]) were measured in 519 females with breast cancer before and after chemotherapy and 338 females without cancer serving as control participants. Attention and processing speed were measured by Rapid Visual Processing (RVP), Backward Counting (BCT), and Trail Making-A (TMT-A) tests. Linear regression models examined patient vs control cytokines and receptor levels, adjusting for covariates. Linear regression models also examined relationships between patient cytokines and receptor levels and test performance, adjusting for age, body mass index, anxiety, depression, cognitive reserve, and chemotherapy duration. Statistical tests were 2-sided (α = .05).Results: sTNFRI and sTNFRII increased over time in patients relative to controls, whereas IL-4, IL-6, and IL-10 decreased. Prechemotherapy, higher IL-8 associated with worse BCT (β = 0.610, SE = 0.241, P = .01); higher IL-4 (β = -1.098, SE = 0.516, P = .03) and IL-10 (β = -0.835, SE = 0.414, P = .04) associated with better TMT-A. Postchemotherapy, higher IL-8 (β = 0.841, SE = 0.260, P = .001), sTNFRI (β = 6.638, SE = 2.208, P = .003), and sTNFRII (β = 0.913, SE = 0.455, P = .045) associated with worse BCT; higher sTNFRII also associated with worse RVP (β = -1.316, SE = 0.587, P = .03). At prechemotherapy, higher IL-4 predicted RVP improvement over time (β = 0.820, SE = 0.336, P = .02); higher sTNFRI predicted worse BCT over time (β = 5.566, SE = 2.367, P = .02). Longitudinally, increases in IL-4 associated with BCT improvement (β = -0.564, SE = 0.253, P = .03).Conclusions: Generally, worse attention and processing speed were associated with higher inflammatory cytokines and receptors and lower anti-inflammatory cytokines in patients; future confirmatory studies are needed. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 42-year-old African-American woman who was diagnosed with AIDS 11 years before the abrupt onset of numbness and heaviness in her left lower limb. The patient was expected to have an idiopathic transverse myelitis. She underwent extensive laboratory evaluation for causes of longitudinally extensive myelopathies and the brain lesions.

Introduction: Radiation-induced cognitive decline (RICD) occurs in 50%-90% of adult patients 6 months post-treatment. In patients with low-grade and benign tumours with long expected survival, this is of paramount importance. Despite advances in radiation therapy (RT) treatment delivery, better understanding of structures important for RICD is necessary to improve cognitive outcomes. We hypothesise that RT may affect network topology and microstructural integrity on MRI prior to any gross anatomical or apparent cognitive changes. In this longitudinal cohort study, we aim to determine the effects of RT on brain structural and functional integrity and cognition., Methods and Analysis: This study will enroll patients with benign and low-grade brain tumours receiving partial brain radiotherapy. Patients will receive either hypofractionated (>2 Gy/fraction) or conventionally fractionated (1.8-2 Gy/fraction) RT. All participants will be followed for 12 months, with MRIs conducted pre-RT and 6-month and 12 month post-RT, along with a battery of neurocognitive tests and questionnaires. The study was initiated in late 2018 and will continue enrolling through 2024 with final follow-ups completing in 2025. The neurocognitive battery assesses visual and verbal memory, attention, executive function, processing speed and emotional cognition. MRI protocols incorporate diffusion tensor imaging and resting state fMRI to assess structural connectivity and functional connectivity, respectively. We will estimate the association between radiation dose, imaging metrics and cognitive outcomes., Ethics and Dissemination: This study has been approved by the Research Subjects Review Board at the University of Rochester (STUDY00001512: Cognitive changes in patients receiving partial brain radiation). All results will be published in peer-reviewed journals and at scientific conferences., Trial Registration Number: ClinicalTrials.gov NCT04390906., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Inflammation may contribute to cognitive difficulties in patients with breast cancer. We tested 2 hypotheses: inflammation is elevated in patients with breast cancer vs noncancer control participants and inflammation in patients is associated with worse attention and processing speed over the course of chemotherapy., Methods: Serum cytokines (interleukin [IL]-4, 6, 8, 10; tumor necrosis factor [TNF]-α) and soluble receptors [sTNFRI, II]) were measured in 519 females with breast cancer before and after chemotherapy and 338 females without cancer serving as control participants. Attention and processing speed were measured by Rapid Visual Processing (RVP), Backward Counting (BCT), and Trail Making-A (TMT-A) tests. Linear regression models examined patient vs control cytokines and receptor levels, adjusting for covariates. Linear regression models also examined relationships between patient cytokines and receptor levels and test performance, adjusting for age, body mass index, anxiety, depression, cognitive reserve, and chemotherapy duration. Statistical tests were 2-sided (α = .05)., Results: sTNFRI and sTNFRII increased over time in patients relative to controls, whereas IL-4, IL-6, and IL-10 decreased. Prechemotherapy, higher IL-8 associated with worse BCT (β = 0.610, SE = 0.241, P = .01); higher IL-4 (β = -1.098, SE = 0.516, P = .03) and IL-10 (β = -0.835, SE = 0.414, P = .04) associated with better TMT-A. Postchemotherapy, higher IL-8 (β = 0.841, SE = 0.260, P = .001), sTNFRI (β = 6.638, SE = 2.208, P = .003), and sTNFRII (β = 0.913, SE = 0.455, P = .045) associated with worse BCT; higher sTNFRII also associated with worse RVP (β = -1.316, SE = 0.587, P = .03). At prechemotherapy, higher IL-4 predicted RVP improvement over time (β = 0.820, SE = 0.336, P = .02); higher sTNFRI predicted worse BCT over time (β = 5.566, SE = 2.367, P = .02). Longitudinally, increases in IL-4 associated with BCT improvement (β = -0.564, SE = 0.253, P = .03)., Conclusions: Generally, worse attention and processing speed were associated with higher inflammatory cytokines and receptors and lower anti-inflammatory cytokines in patients; future confirmatory studies are needed., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Advances in cancer treatments have led to substantially improved survival for patients with cancer. However, many patients experience changes in cognition as a side effect of both cancer and cancer treatment. This occurs with both central nervous system (CNS) tumors and non-CNS tumors and in both children and adults. Studies of patients with non-CNS cancer have shown that cancer-related cognitive impairment (CRCI), which can include changes in memory, executive function, attention, and processing speed, occurs in up to 30% of patients prior to any treatment and in up to 75% of patients during treatment. A subset of patients with non-CNS and CNS cancer appear to be at higher risk for CRCI, so much research has gone into identifying who is vulnerable. Risk factors for CRCI in adults include cognitive reserve, age, genetic factors, and ethnicity; risk factors for children include genetic factors, female sex, younger age at diagnosis, chemotherapy dose, and both dose and field size for radiation. Although the field has made substantial strides in understanding and treating CRCI, more research is still needed to improve outcomes for both pediatric and adult cancer survivors.

Object: In select patient populations, hyperglycemia has been shown to increase the risk of surgical site infection (SSI), whereas stringent glucose control has improved outcomes. To date, no study has focused on whether SSIs in patients with brain tumors undergoing resection are associated with hyperglycemia., Methods: The authors performed a retrospective chart review of patients who underwent a craniotomy after receiving a diagnosis of brain tumor. From 2001 to 2008, 2485 patients underwent a craniotomy for tumor resection at the Brain Tumor & Neuro-Oncology Center at the Cleveland Clinic. Fifty-seven of these patients (2.3%) developed SSIs postoperatively. A matched case-control study design was used, with 57 patients who developed SSIs after craniotomy (cases) matched with 57 patients who did not develop SSIs (controls). The results were analyzed using both univariate and multivariate conditional logistic regression., Results: Glucose level was not a significant factor in postoperative SSI (p = 0.83) after adjusting for duration of surgery and adherence to antibiotic prophylaxis. However, duration of surgery was significantly associated with postoperative SSI (p = 0.047)., Conclusions: For patients who undergo craniotomy for definitive resection of a brain tumor, duration of surgery described more variation in the model to predict SSI than blood glucose levels.