Sunnybrook Health Sciences Centre Research Articles

Development and validation of a clinical prediction tool to estimate survival in community-dwelling adults living with dementia: a protocol

IntroductionA clinical prediction tool to estimate life expectancy in community-dwelling individuals living with dementia could inform healthcare decision-making and prompt future planning. An existing Ontario-based tool for community-dwelling elderly individuals does not perform well in people living with dementia specifically. This study seeks to develop and validate a clinical prediction tool to estimate survival in community-dwelling individuals living with dementia receiving home care in Ontario, Canada.Methods and analysisThis will be a population-level retrospective cohort study that will use data in linked healthcare administrative databases at ICES. Specifically, data that are routinely collected from regularly administered assessments for home care will be used. Community-dwelling individuals living with dementia receiving home care at any point between April 2010 and March 2020 will be included (N≈200 000). The model will be developed in the derivation cohort (N≈140 000), which includes individuals with a randomly selected home care assessment between 2010 and 2017. The outcome variable will be survival time from index assessment. The selection of predictor variables will be fully prespecified and literature/expert-informed. The model will be estimated using a Cox proportional hazards model. The model’s performance will be assessed in a temporally distinct validation cohort (N≈60 000), which includes individuals with an assessment between 2018 and 2020. Overall performance will be assessed using Nagelkerke’s R2, discrimination using the concordance statistic and calibration using the calibration curve. Overfitting will be assessed visually and statistically. Model performance will be assessed in the validation cohort and in prespecified subgroups.Ethics and disseminationThe study received research ethics board approval from the Sunnybrook Health Sciences Centre (SUN-6138). Abstracts of the project will be submitted to academic conferences, and a manuscript thereof will be submitted to a peer-reviewed journal for publication. The model will be disseminated on a publicly accessible website (www.projectbiglife.com).Trial registration numberNCT06266325(clinicaltrials.gov).

Exclusive Breastfeeding Rates Upon Hospital Discharge at a Tertiary Centre Prior to and During the COVID-19 Pandemic

This study aimed to describe exclusive breastfeeding (EBF) rates at discharge at Sunnybrook Health Sciences Centre and explore factors that contributed to changes in breastfeeding rates during the COVID-19 pandemic. Overall, 4762 patient charts were reviewed, 2000 from the pre-pandemic period, and 2762 from the lockdown period. Data was collected on EBF status at discharge, on maternal health history, and on infant characteristics. EBF rates fell from 75.8% to 73.85% from the pre-COVID-19 to COVID-19 period. During the pandemic, EBF was positively associated with BMI <30, spontaneous conception, and infants at risk of low blood sugar. Non-spontaneous conception was associated with lower EBF.

Transitioning Towards a Virtual Falls Prevention Program for Frail Seniors: Learning from the Experiences of Older Adults During the COVID-19 Pandemic.

The literature to date is unable to clearly characterize the appropriateness of virtual care for falls prevention services from the patient perspective. In response to COVID-19, the Falls Prevention Program (FPP) at Sunnybrook Health Sciences Centre was modified to include virtual components. We set out to uncover the experiences of this unique older-adult patient population to inform FPP quality improvement and appropriate incorporation of technology post-pandemic. FPP patients during the COVID-19 pandemic (February 2020 - February 2022) and their primary caregivers met inclusion criteria. Out of 18 eligible patients, 10 consented to participate in 20-minute, semi-structured telephone interviews conducted and transcribed by the first author. Inductive coding followed by theme generation occurred through collaborative analysis. The participants (n=10) were 60% female, mean age 84 years (SD 5.8), 60% living alone, and 70% university educated. We generated three main themes: 1) First Steps First, revealed a common desire for physical and mental support and the perceived essentials of a successful FPP highlighting the importance of program length and individualized attention; 2) Overcoming Obstacles, highlighted participants' experiences overcoming barriers with technology in the context of an isolating pandemic; and 3) Advancing Care Post-Pandemic, elaborated on the appropriateness of virtual care and delved into the importance of program personalization. The interviewed older adults revealed agreement on the FPP's necessity and the importance of increasing program length, one-on-one interaction, and program flexibility for unique patient needs. Incorporating virtual assessment prior to in-person exercises was largely favoured and should be considered as an appropriate use of technology post-pandemic.

Somatic tissue testing in prostate cancer using the Oncomine V3 panel: A single-institution retrospective analysis.

e17002 Background: Approximately 20-30% of prostate cancer (PC) patients have a mutation in the homologous recombination repair or mismatch repair genes, 50% of which are somatic. These mutations have prognostic and predictive implications. Somatic tissue testing (STT) was implemented at Sunnybrook Health Sciences Centre using the Oncomine V3 panel, which includes 161 genes, but only four genes (BRCA1/2, ATM, PALB2) are reported due to funding restrictions. We describe our centre’s testing experience and the utility of reporting beyond these four genes. Methods: Sixty-two PC patients between May 1, 2021 - January 31, 2023 were included. Clinical characteristics were gathered via chart review. Somatic variants of genes of interest (GOI) within the Oncomine V3 panel were extracted by an annotation specialist. Results: STT was ordered at diagnosis in 69.4% of cases (n=42) vs. at progression in 27.4% (n=17), 3 cases were external and lacked clinical context. Tests were ordered in the locoregional disease setting in 46.8% (n=29), 37.1% (n=23) in the metastatic castrate-sensitive setting, 8.1% (n=5) in the metastatic castrate-resistant (CR) setting and 3.2% (n=2) in the non-metastatic CR setting. Tests were ordered by Urology or Pathology (reflex testing) in 64.5% (n=40), by Medical Oncology in 16% (n=10), by Radiation Oncology in 13% (n=8) and by others in 6.5% (n=4). Fifty-one samples (82.2%) were of the prostate and 11 (17.7%) were of metastatic sites. The median sample age was 8 days (range 0-5781). The median test turn-around time was 28.5 days (range 5-57). There were 378 variants within the GOI and meeting the limit of detection [1] , of which 63 (16.7%) were tier 1 or 2 and are listed by gene in the table. Eight of 63 variants (12.7%) were within the four funded genes whereas 55/63 (87.3%) were within unfunded genes of clinical significance. CDK12, FANCA, NBN (n=7, 11.2%) are investigated in poly (ADP-ribose) polymerase inhibitor trials and PMS2 deficiency (n=1, 1.6%) can select for immune checkpoint inhibitors. PIK3R1/PIK3CA/AKT1-mutated tumors (n=11, 17.7%) have shown response to AKT-inhibitors. SPOP-mutated tumors (n=6, 9.7%) are associated with prolonged response to androgen receptor blockade whereas PTEN/TP53/RB1-negative tumors (n=12, 19.4%) are associated with anti-androgen resistance and worse prognosis. Conclusions: The majority of STT variants identified were beyond the currently funded genes in Ontario, and many have important prognostic and predictive implications. This highlights that STT early in the disease course using expanded gene panels may help in delivering personalized PC care. [Table: see text]

Something to Chew on; Plate-Waste at an Ontario Veteran's Centre.

There is paucity of data assessing levels of food/beverage waste in long-term care (LTC) facilities, especially in Ontario. Observations in the Veteran's Centre (VC) at Sunnybrook Health Sciences Centre (Sunnybrook) indicated food/beverage waste may be high, potentially impacting sustainability efforts within our institution. Before proceeding with waste reduction efforts, we conducted a comprehensive 3-day waste-audit of food/beverage items provided to VC residents with the goal of understanding the extent of food/beverage waste at VC, items wasted, and any other factors that may inform future changes. Our results indicate that 28% of items served to residents were wasted. Lunch was the meal with greatest waste at 31% and waste of solid items was 12% higher than that of liquids. We observed a large variability in waste between residents and within each resident, with 15% of residents wasting >50% of items provided. This study provides a deeper insight into the magnitude of food/beverage waste in a LTC population and highlights the importance of considering individualized strategies to address waste to avoid negative impact on residents.

Machine Learning to Predict Outcomes of Fetal Cardiac Disease: A Pilot Study.

Prediction of outcomes following a prenatal diagnosis of congenital heart disease (CHD) is challenging. Machine learning (ML) algorithms may be used to reduce clinical uncertainty and improve prognostic accuracy. We performed a pilot study to train ML algorithms to predict postnatal outcomes based on clinical data. Specific objectives were to predict (1) in utero or neonatal death, (2) high-acuity neonatal care and (3) favorable outcomes. We included all fetuses with cardiac disease at Sunnybrook Health Sciences Centre, Toronto, Canada, from 2012 to 2021. Prediction models were created using the XgBoost algorithm (tree-based) with fivefold cross-validation. Among 211 cases of fetal cardiac disease, 61 were excluded (39 terminations, 21 lost to follow-up, 1 isolated arrhythmia), leaving a cohort of 150 fetuses. Fifteen (10%) demised (10 neonates) and 65 (48%) of live births required high acuity neonatal care. Of those with clinical follow-up, 60/87 (69%) had a favorable outcome. Prediction models for fetal or neonatal death, high acuity neonatal care and favorable outcome had AUCs of 0.76, 0.84 and 0.73, respectively. The most important predictors for death were the presence of non-cardiac abnormalities combined with more severe CHD. High acuity of postnatal care was predicted by anti Ro antibody and more severe CHD. Favorable outcome was most predicted by no right heart disease combined with genetic abnormalities, and maternal medications. Prediction models using ML provide good discrimination of key prenatal and postnatal outcomes among fetuses with congenital heart disease.

Retrospective Analysis of the Integration of Palliative Care Into the Care of Stroke Patients Admitted to a Regional Stroke Center.

Background: Palliative care (PC) aims to enhance the quality of life for patients when confronted with serious illness. As stroke inflicts high morbidity and mortality, the integration of PC within acute stroke care remains an important aspect of quality inpatient care. However, there is a tendency to offer PC to stroke patients only when death appears imminent. We aim to understand why this may be by examining stroke patients admitted to a regional stroke centre who subsequently died and their provision of PC. Methods: We conducted a retrospective single-centre cohort study of patients who died during admission to the regional stroke centre at Sunnybrook Health Sciences Centre (SHSC) in Toronto, Ontario, Canada. Baseline demographics were assessed using means, standard deviations (SD), medians, interquartile ranges (IQR), and proportions. Descriptive statistics, univariate, and multivariate analyses were performed to ascertain relationships between collected variables. Results: Univariate modeling demonstrated that older age, being female, no stroke diagnosis at admission to hospital, ischemic stroke, and comorbidities of cancer or dementia were associated with a higher incidence of palliative medicine consultation (PMC), while admission from an acute care hospital and a Glasgow Coma Scale (GCS) coma classification were associated with a lower incidence of PMC. The multivariate model identified the GCS coma-related category as the only significant factor associated with a higher incidence of death but was non-significantly related to a lower incidence of PMC. Conclusion: These results highlight continued missed opportunities for PC in stroke patients and underscore the need to better optimize PMC.

Knowledge-based planning for Gamma Knife.

Current methods for Gamma Knife (GK) treatment planning utilizes either manual forward planning, where planners manually place shots in a tumor to achieve a desired dose distribution, or inverse planning, whereby the dose delivered to a tumor is optimized for multiple objectives based on established metrics. For other treatment modalities like IMRT and VMAT, there has been a recent push to develop knowledge-based planning (KBP) pipelines to address the limitations presented by forward and inverse planning. However, no complete KBP pipeline has been created forGK. To develop a novel (KBP) pipeline, using inverse optimization (IO) with 3D dose predictions for GK. Data were obtained for 349 patients from Sunnybrook Health Sciences Centre. A 3D dose prediction model was trained using 322 patients, based on a previously published deep learning methodology, and dose predictions were generated for the remaining 27 out-of-sample patients. A generalized IO model was developed to learn objective function weights from dose predictions. These weights were then used in an inverse planning model to generate deliverable treatment plans. A dose mimicking (DM) model was also implemented for comparison. The quality of the resulting plans was compared to their clinical counterparts using standard GK quality metrics. The performance of the models was also characterized with respect to the dosepredictions. Across all quality metrics, plans generated using the IO pipeline performed at least as well as or better than the respective clinical plans. The average conformity and gradient indices of IO plans was 0.737 0.158 and 3.356 1.030 respectively, compared to 0.713 0.124 and 3.452 1.123 for the clinical plans. IO plans also performed better than DM plans for five of the six quality metrics. Plans generated using IO also have average treatment times comparable to that of clinical plans. With regards to the dose predictions, predictions with higher conformity tend to result in higher quality KBP plans. Plans resulting from an IO KBP pipeline are, on average, of equal or superior quality compared to those obtained through manual planning. The results demonstrate the potential for the use of KBP to generate GK treatment with minimal humanintervention.

Health literacy of patients eligible for cochlear implants

Background Hearing loss is known to be an independent risk factor for inadequate health literacy. The objective of this study was to assess the level of health literacy among patients undergoing cochlear implantation to determine areas for improvement in delivery of patient information. Methods A cross-sectional survey was conducted at the otology-neurotology clinic at Sunnybrook Health Sciences Centre. Patients eligible for cochlear implantation completed two health literacy screening tools: The Short Test of Functional Health Literacy in Adults (S-TOFHLA) and Brief Health Literacy Screen (BHLS). Results Thirty seven patients were included (41% female, 59% male, mean age: 55 years). Most patients had adequate health literacy through BHLS (76%) and S-TOFHLA (98%) scoring. Over 80% of patients were not able to correctly recount all the operative risks associated with cochlear implant surgery and one third of patients did not correctly recount any risks associated with a cochlear implant surgery. Female sex was associated with higher scores (p=0.03) and low income (<$35,000) was associated with lower scores (p=0.05). Conclusion Patients eligible for cochlear implants have adequate health literacy, but most are not able to recount operative risks. Educational tools are required to improve patient retention, understand, and perioperative health information delivery.

Human Epidermal Growth Factor Receptor 2-Low Breast Cancer Brain Metastases: An Opportunity for Targeted Systemic Therapies in a High-Need Patient Population.

Trastuzumab deruxtecan is a new treatment option for patients with advanced human epidermal growth factor receptor 2 (HER2)-low breast cancer (BC). Although HER2-low status has been characterized in early and advanced BC, it has yet to be fully characterized in brain metastases (BrM). Patients who underwent surgery for BC BrM at Sunnybrook Health Sciences Centre and for whom HER2 status was available on resected BrM were studied. Estrogen receptor, progesterone receptor, and HER2 status were assessed on the basis of ASCO/College of American Pathologists (CAP) guidelines. HER2-zero was defined as immunohistochemistry (IHC) 0; HER2-low was defined as IHC 1+ or IHC 2+ with fluorescence in situ hybridization (FISH)-negative status. HER2-positive (HER2+) was defined as IHC 3+ or IHC 2+ with positive FISH. Clinicopathologic features were recorded. We also assessed the prognostic association between extent of HER2 expression and (1) brain-specific progression-free survival (bsPFS), as well as (2) overall survival (OS). In this retrospective cohort of 102 patients with resected BC BrM, 53% (n = 54) were HER2+, 29.4% (n = 30) were HER2-low, and 17.6% (n = 18) had HER2-zero status. Among BrM that were triple-negative on the basis of ASCO/CAP guidelines, 63.6% (n = 14/22) were reclassified as being HER2-low. Sixty percent (n = 15/25) of BrM that were hormone receptor-positive/HER2-negative (HR+/HER2-) were reclassified as being HER2-low. In total, 51 patients had matched primary breast and BrM tissue available; results of HER2 status when categorized as HER2-zero, HER2-low, and HER2+ were concordant in 82.3% (n = 42/51) of cases (Cohen's kappa, 0.58; P = .07). There was no significant association between HER2-zero, HER2-low, and HER2+ status in BrM and either bsPFS or OS. Among patients with surgically resected BrM, a high proportion of those with metastatic triple-negative BC and HR+/HER2- disease have HER2-low BrM with potential to benefit from HER2-targeted therapy.

Cannabinoid Use and Obstructive Sleep Apnea: A Retrospective Cohort Study.

Obstructive sleep apnea (OSA) is a sleep disorder with no widely accepted pharmacological therapy. Cannabinoids have been suggested to reduce OSA severity in small human studies. The purpose of this retrospective cohort study was to explore the association of self-reported cannabis use on OSA severity and sleep parameters in a large cohort of adults undergoing in-laboratory polysomnography. Sleep and medication data were collected for all consecutive adults who completed diagnostic polysomnography at Sunnybrook Health Sciences Centre from 2010 to 2022. Multivariable linear regression models were employed that adjusted for age, sex, and BMI (minimally adjusted model), as well as medication and comorbidity data (maximally adjusted model). An exploratory subgroup analysis was additionally run in patients with moderate to severe OSA. Of 6,958 individuals (mean age 54.7 ± 16.3, BMI 29.1 ± 6.8, 51.0% female), 71 reported cannabis use. In our minimally adjusted models, cannabis use predicted a reduced respiratory disturbance index (RDI) (β: -4.8 [95% CI: -9.4, -0.2]; p = 0.042); this association became nonsignificant in the fully adjusted models. In an exploratory analysis of patients with moderate to severe OSA (n = 613), cannabis use (n = 7) predicted increased stage N3 sleep (β: 33.5 [95% CI: 15.6, 51.4]; p < 0.001) and decreased REM sleep (β: 16.0 [95% CI: 0.3, 31.7]; p = 0.046). Self-reported cannabis use was not associated with OSA severity after adjusting for confounders. In an exploratory subgroup analysis of patients with moderate to severe OSA, cannabis use impacted sleep architecture. Future studies should further explore these findings.

Lymph node yield: Impact on oncologic outcomes in oral cavity cancer.

Lymph node metastases are associated with poor prognosis in oral cavity squamous cell carcinoma (OCSCC). In other cancers, clinical guidelines on the number of lymph nodes removed during primary surgery, lymph node yield (LNY), exist. Here, we evaluated the prognostic capacity of LNY on regional failure, locoregional recurrence, and disease-free survival (DFS) in patients with OCSCC treated by primary neck surgery. This retrospective cohort study took place at Sunnybrook Health Sciences Centre in Toronto, Canada and involved a chart review of all adult patients with treatment-naive OCSCC undergoing primary neck dissection. For each outcome, we first used the maximally selected rank statistics and an optimism-corrected concordance to identify an optimal threshold of LNY. We then used a multivariable Cox proportional hazards model to assess the association between high LNY (>threshold) and each outcome. Among the 579 patients with OCSCC receiving primary neck dissection, 61.7% (n = 357) were male with a mean age of 62.9 years (standard deviation: 13.1) at cancer diagnosis. When adjusting for sociodemographic and clinical factors, LNY >15 was significantly associated with improved DFS (adjusted HR [aHR]: 0.73, 95% CI: 0.54-0.98), locoregional recurrence (aHR: 0.68, 95% CI: 0.49-0.95), and regional failure (aHR: 0.61, 95% CI: 0.39-0.93). Our study findings suggested high LNY to be a strong independent predictor of various patient-level quality of surgical care metrics. The optimal LNY we found (15) was lower than the conventionally recommended (18), which calls for further research to establish validity in practice.

The Impact of Out-of-Hospital Time and Prehospital Intubation on Return of Spontaneous Circulation following Resuscitative Thoracotomy in Traumatic Cardiac Arrest

Introduction Resuscitative thoracotomy (RT) is a critical procedure performed in certain trauma patients in extremis, with extremely low survival rates. Currently, there is a paucity of data pertaining to prehospital variables and their predictive role in survival outcomes in traumatic cardiac arrest (TCA) patients requiring RT. The aim of the study was to determine the impact of prehospital intubation and out-of-hospital time (OOHT) on return of spontaneous circulation (ROSC) and survival in TCA requiring RT. Methods This was a retrospective cohort study of trauma patients presenting to two level-1 trauma centers, St. Michael’s Hospital and Sunnybrook Health Sciences Center, in Toronto, Canada (January 1, 2005-December 31, 2020). Our exposures of interest were any prehospital intubation attempt and OOHT. Primary and secondary outcome measures were ROSC post-RT and survival to hospital discharge, respectively, and data analysis was performed using univariate logistic regression. Results A total of 195 patients were included, of which 86% were male, and the mean age was 33 years. ROSC and survival to hospital discharge were achieved in 30% and 5% of patients, respectively. Of those who survived to discharge, 89% sustained penetrating trauma. There was no association between OOHT and ROSC (OR = 1.00, 95% CI 0.97–1.03) or survival (OR = 0.99, 95% CI 0.94–1.05). The odds of ROSC were lower in penetrating trauma in the presence of any prehospital intubation attempt (OR = 0.39, 95% CI 0.19–0.82, p = 0.01). ROSC was less likely among all patients with no prehospital signs of life (SOL) compared to those who had prehospital SOL (OR = 0.30, 95% CI 0.13–0.69, p < 0.01). Conclusions There was a significant association between prehospital intubation and lower likelihoods of ROSC in the penetrating TCA population requiring RT, as well as with the absence of prehospital SOL in all patients. OOHT did not appear to significantly impact ROSC or survival.

TILE pilot trial study protocol: Tinzaparin Lead-in to Prevent the Post-Thrombotic syndrome study protocol

IntroductionThe post-thrombotic syndrome (PTS) is a form of chronic venous insufficiency due to a prior ipsilateral deep venous thrombosis (DVT). This is a frequent complication that develops in 20%–50% of...

P11.63.B VALIDATING THE NEUROLOGIC ASSESSMENT IN NEURO-ONCOLOGY (NANO) SCALE IN CLINICAL PRACTICE: A MULTI-CENTER PROSPECTIVE STUDY IN PATIENTS WITH GLIOBLASTOMA

Abstract BACKGROUND The neurologic assessment in neuro-oncology (NANO) scale was developed as a standardized metric to objectively measure neurologic function in patients with brain tumors and complement radiographic assessment in defining overall outcomes. The scale has been incorporated in clinical trials, however, real-world use of the NANO scale to drive clinical decision-making and the predictive value of the NANO scale to determine overall survival remains unclear in glioblastoma. MATERIAL AND METHODS We report on an ongoing multi-center study of prospective NANO score collection to evaluate neurologic function in patients with glioblastoma, seen at Dana-Farber Cancer Institute (DFCI) and Sunnybrook Health Sciences Center (SHSC). Patient demographics, tumor histology, molecular status, treatment history, and progression dates are being captured. NANO score, Karnofsky performance status (KPS) and corticosteroid dose are collected at prespecified time points (prior to start of therapy, and during each subsequent MRI visit). Changes in the NANO score will be correlated to overall survival and subgroup analyses will be performed for specific domains of the NANO scale. Statistical analyses including descriptive data analysis and generalized linear models will be performed using R (version 3.4.3). RESULTS Since June 2020, 145 patients have been enrolled in this study across the two sites including 90 (62%) with ≥2 follow-up visits. 129 patients had baseline post-operative NANOs captured, with 45 (35%) patients having no deficits in any NANO domain at baseline. All patients with intact baseline NANO had a KPS of 80 or above. Adaptation to a virtual platform for NANO (vNANO) allowed for improved recruitment and follow-up of patients. Validation of vNANO is being performed in a subset of this population. Our interim analysis will be presented at the 2023 EANO meeting. CONCLUSION Evaluation of neurologic function by NANO is feasible in both an in-person and virtual framework in a prospective multi-center study in patients with glioblastoma. NANO is able to objectively track neurologic function throughout disease course in glioblastoma. Integration of vNANO may allow for reduced clinical visits and improve access to specialized care for patients in geographically remote locations.

Facilitators and barriers in oncology clinical practice influencing nurses' completion of GRASP Workload Measurement System to ensure patient-centred care.

Hospital administrators have a great interest in obtaining a valid and reliable nursing workload measurement to help determine the hours of care needed per patient; one such method available is the GRASP Workload Measurement System. At Sunnybrook Health Sciences Centre, nurses' GRASP compliance and accuracy varies and often does not meet the target of 90%. The target assists the organization in estimating ongoing nursing workload and patients' care needs, while ensuring the provision of safe and appropriate care that is fiscally responsible. The objective of the quality initiative reported in this paper was to identify the facilitators and barriers that influence nurses' completion of GRASP. The quality improvement project was conducted using a mixed-method design with a sample of 28 nurses working in oncology acute care and palliative care inpatient units. The Theoretical Domain Framework (TDF), often used in behaviour change studies, was used in designing the questionnaire survey and interview questions that listed pertinent and measurable factors that may influence nurses' GRASP completion. Facilitators included: nurses' knowledge about the role GRASP has in funding and staffing levels, job responsibility, and perception of GRASP as a potential tool to organize work. Barriers identified by nurses included insufficient GRASP knowledge, limited access to workstations and computers, GRASP tool elements not capturing the complexity of the nursing work, time constraints, increased patients' acuity, and care demands. In addition to the Theoretical Domain Framework, the Normalization Process Theory was used to guide the implementation and evaluation of the recommendations to enhance nurses' GRASP compliance and adherence practice.

HER2-LOW BREAST CANCER BRAIN METASTASES: INCIDENCE AND TREATMENT IMPLICATIONS

Abstract Brain metastases (BrM) are a major cause of morbidity and mortality among women with breast cancer (BC). Central nervous system (CNS)-penetrating systemic therapies for patients with HER2-negative BrM are lacking; given CNS activity of trastuzumab deruxtecan, efficacy for patients with HER2-low BrM is of interest. METHODS: A retrospective study of two cohorts of consecutive patients who underwent surgery for BC BrM at Sunnybrook Health Sciences Centre were identified. BrM subtype was assessed based on 2018 ASCO/CAP guidelines. HER2-zero was defined as immunohistochemistry (IHC) 0; HER2-low was defined as IHC 1+ or 2+ and fluorescence in situ hybridization (FISH) negative status. HER2-positive was defined as IHC 3+ or IHC 2+ with positive FISH. We also assessed the prognostic association between extent of HER2 expression and i) brain-specific progression free survival (bsPFS), as well as ii) overall survival (OS). RESULTS: Out of 137 patients with resected BrM, tissue for HER2 assessment was available in 74.5% (n=102) of cases. In this cohort, the median age at BrM diagnosis was 53.5 (range, 32- 85). 68.6% (n=70) had extracranial disease. 53% (n=54) of the BrM were HER2-positive; 29.4% (n=30) were HER2-low and 17.6% (n=18) had HER2-zero status. Among BrM that were triple negative based on ASCO/CAP guidelines, 14 out of 22 cases (63.6%) were re-classified as being HER2-low. 15/25 (60%) BrM that were hormone receptor positive/HER2 negative (HR+/HER2-) based on ASCO/CAP guidelines were re-classified as being HER2-low. There was no significant association between the extent of HER2 expression (HER2-zero, HER2-low versus HER2-positive status) in BrM and either bsPFS or OS. CONCLUSION: Among patients with surgically resected BrM, a high proportion of those with metastatic TNBC and HR+/HER2-negative disease have “HER2-low” BrM with potential to benefit from HER2-targeted therapy.

Improving hand therapy delivery during care transitions in multisystem trauma patients

High-quality hand therapy is critical to maximising functional capacity and optimising overall outcomes following hand injuries. Therapy delivery requires clear communication between surgeons and occupational therapists. At Sunnybrook Health Sciences...

The impact of COVID-19 on the experiences of patients and their family caregivers with medical assistance in dying in hospital

BackgroundThe COVID-19 pandemic and its containment measures have drastically impacted end-of-life and grief experiences globally, including those related to medical assistance in dying (MAiD). No known qualitative studies to date have examined the MAiD experience during the pandemic. This qualitative study aimed to understand how the pandemic impacted the MAiD experience in hospital of persons requesting MAiD (patients) and their loved ones (caregivers) in Canada.MethodsSemi-structured interviews were conducted with patients who requested MAiD and their caregivers between April 2020 and May 2021. Participants were recruited during the first year of the pandemic from the University Health Network and Sunnybrook Health Sciences Centre in Toronto, Canada. Patients and caregivers were interviewed about their experience following the MAiD request. Six months following patient death, bereaved caregivers were interviewed to explore their bereavement experience. Interviews were audio-recorded, transcribed verbatim, and de-identified. Transcripts were analyzed using reflexive thematic analysis.ResultsInterviews were conducted with 7 patients (mean [SD] age, 73 [12] years; 5 [63%] women) and 23 caregivers (mean [SD] age, 59 [11] years; 14 [61%] women). Fourteen caregivers were interviewed at the time of MAiD request and 13 bereaved caregivers were interviewed post-MAiD. Four themes were generated with respect to the impact of COVID-19 and its containment measures on the MAiD experience in hospital: (1) accelerating the MAiD decision; (2) compromising family understanding and coping; (3) disrupting MAiD delivery; and (4) appreciating rule flexibility.ConclusionsFindings highlight the tension between respecting pandemic restrictions and prioritizing control over the dying circumstances central to MAiD, and the resulting impact on patient and family suffering. There is a need for healthcare institutions to recognize the relational dimensions of the MAiD experience, particularly in the isolating context of the pandemic. Findings may inform strategies to better support those requesting MAiD and their families during the pandemic and beyond.

HER2-low breast cancer brain metastases: Incidence and treatment implications.

2035 Background: Brain metastases (BrM) are a major cause of morbidity and mortality among women with breast cancer (BC). Central nervous system (CNS)-penetrating systemic therapies for patients with HER2-negative BrM are lacking; this is particularly problematic for patients with triple negative disease (TNBC) who have a high likelihood of developing BrM. Given CNS activity of trastuzumab deruxtecan, efficacy for patients with HER2-low BrM is of interest. Methods: A retrospective study of two cohorts of patients who underwent surgery for BC BrM at Sunnybrook Health Sciences Centre between 1999-2013 and 2008-2018 were identified. Estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 (HER2) status were assessed based on 2018 ASCO/CAP guidelines. HER2-zero was defined as immunohistochemistry (IHC) 0; HER2-low was defined as IHC 1+ or IHC 2+ with fluorescence in situ hybridization (FISH) negative status. HER2-positive was defined as IHC 3+ or IHC 2+ with positive FISH. Clinicopathological features were recorded. We also assessed the prognostic association between extent of HER2 expression and i) brain-specific progression free survival (bsPFS), as well as ii) overall survival (OS). Results: Out of 137 patients with resected BrM, tissue for HER2 assessment was available in 74.5% (n=102) of cases. In this cohort, the median age at BrM diagnosis was 53.5 (range, 32-85). 18.6% (n=19) had leptomeningeal disease and 68.6% (n=70) had extracranial disease. 53% (n=54) of the BrM were HER2-positive; 29.4% (n=30) were HER2-low and 17.6% (n=18) had HER2-zero status. Among BrM that were triple negative based on ASCO/CAP guidelines, 14 out of 22 cases (63.6%) were re-classified as being HER2-low. 15/25 (60%) BrM that were hormone receptor positive/HER2 negative (HR+/HER2-) based on ASCO/CAP guidelines were re-classified as being HER2-low. In total, 51 patients had matched primary breast and BrM tissue available; results of HER2 status when categorized as HER2-zero, HER2-low and HER2-positive were concordant in 82.3% (n= 42/51) of cases (Cohen’s kappa 0.58, p=0.0719). In 7 cases, the primary breast tissue was HER2-zero whereas the BrM was either HER2-low (n=5) or HER2-positive (n=2). In only one case (2%), expression of HER2 was lower in the BrM (HER2-low) compared to the primary BC (HER2-positive). Median time from primary BC to the development of BrM was 35 months (IQR, 14-69) in the overall cohort; patients with HER2-zero BrM had a numerically longer time to development of BrM (45.8 months), compared to those with HER2-low (35 months) and HER2-positive (35 months) BrM (p=0.948). There was no significant association between HER2-zero, HER2-low and HER2-positive status in BrM and either bsPFS or OS. Conclusions: Among patients with surgically resected BrM, a high proportion of those with metastatic TNBC and HR+/HER2-negative disease have “HER2-low” BrM with potential to benefit from HER2-targeted therapy.