Effect of an electronic quality checklist on prescription patterns of prophylactic antiemetic and pain flare medications in the context of palliative radiotherapy for bone metastases.

PURPOSE: International guidelines are available to guide prescription of antiemetic and pain flare medications in patients receiving palliative radiotherapy for bone metastases, but prescription rates are quite variable. We hypothesized that a simple electronic quality checklist could increase the evidence-based use of these medications. MATERIALS AND METHODS: We implemented an electronic quality checklist item in our center for all patients treated with palliative radiotherapy for lumbar spine bone metastases. We retrospectively reviewed patients in the 6-month pre- and post-intervention. Patients were stratified according to if they were treated within a dedicated rapid palliative (RPAL) radiotherapy program or not. Chi-square tests were used to compare rates of antiemetic and pain flare medications pre- and post-intervention and RPAL vs not. RESULTS: A total of 375 patients were identified with 42 (11.2%) treated in dedicated RPAL program. The proportion of patients treated with prophylactic antiemetic and pain flare medications pre-intervention (n = 226) and post-intervention (n = 149) was respectively 34.1% vs 59.1% (p < 0.001) and 26.1% vs 43.0% (p = 0.01). Observed differences for antiemetic prescription rates were greater for patients who were not treated within a dedicated palliative radiotherapy program, but this was not the case for pain flare medications. CONCLUSIONS: Our data shows that a simple quality checklist item can have a significant effect on the evidence-based use of prophylactic antiemetic and pain flare medications in patients treated with palliative radiotherapy for bone metastases. We believe such strategies should be routinely included in other clinical pathways to improve the use of symptom control medications.

Time-lapse analysis of tangential migration in Sema6A and PlexinA2 knockouts.

In the developing cerebellum, granule cells migrate tangentially in the external granule cell layer and then radially and inward, across the molecular layer and Purkinje cell layer. We showed previously that the transmembrane semaphorin Sema6A and its receptor PlexinA2 control the ability of migrating granule cells to switch from one mode of migration to the other. In both Sema6A and PlexinA2 knockouts, a large number of granule cells remain in the molecular layer, a defect that is most likely due to abnormal nuclear translocation. We show here that the lack of Sema6A or PlexinA2 preferentially much more severely perturbs the migration of later-born granule cells than early-born ones. We also use a cerebellum slice model system and electroporation to perform time-lapse analysis of granule cell migration in wild-type mice, Sema6A and PlexinA2 knockouts. This study reveals that defects of tangential migration can be detected in bipolar granule cells before the initiation of radial migration. Our results also directly confirm that the absence of Sema6A does not perturb radial migration.

Evaluation of Unsolicited Feedback from Patients with Cancer and Their Families as a Strategy to Improve Cancer Care Delivery.

BACKGROUND: Unsolicited patient feedback (compliments and complaints) should allow the healthcare system to address and improve individual and overall patient, family, and staff experiences. We evaluated feedback at a tertiary cancer centre to identify potential areas for optimizing care delivery. METHODS: unsolicited feedback submitted to the Patient Relations Department, relating to the Divisions of Medical and Radiation Oncology, at the Ottawa Hospital, was analyzed. RESULTS: Of 580 individual reports submitted from 2016 to 2022, patient demographics were available for 97% (563/580). Median patient age was 65 years (range 17-101), and 53% (301/563) were female. The most common cancer types were breast (127/545, 23%) and gastrointestinal (119/545, 22%) malignancies, and most (64%, 311/486) patients had metastatic disease. Feedback was submitted mainly by patients (291/579, 50%), and predominantly negative (489/569, 86%). The main reasons for complaints included: communication (29%, 162/566) and attitude/conduct of care (28%, 159/566). While feedback rates were initially stable, an increase occurred from 2019 to 2021. CONCLUSIONS: Unsolicited feedback remains mostly negative, and relates to physician communication. If we are to drive meaningful changes in care delivery, more standardized means of assessing feedback and implementation strategies are needed. In addition, in an era of increased healthcare provider burnout, strategies to enhance formal positive feedback are also warranted.

The REthinking Clinical Trials Program Retreat 2023: Creating Partnerships to Optimize Quality Cancer Care.

Patients, families, healthcare providers and funders face multiple comparable treatment options without knowing which provides the best quality of care. As a step towards improving this, the REthinking Clinical Trials (REaCT) pragmatic trials program started in 2014 to break down many of the traditional barriers to performing clinical trials. However, until other innovative methodologies become widely used, the impact of this program will remain limited. These innovations include the incorporation of near equivalence analyses and the incorporation of artificial intelligence (AI) into clinical trial design. Near equivalence analyses allow for the comparison of different treatments (drug and non-drug) using quality of life, toxicity, cost-effectiveness, and pharmacokinetic/pharmacodynamic data. AI offers unique opportunities to maximize the information gleaned from clinical trials, reduces sample size estimates, and can potentially "rescue" poorly accruing trials. On 2 May 2023, the first REaCT international symposium took place to connect clinicians and scientists, set goals and identify future avenues for investigator-led clinical trials. Here, we summarize the topics presented at this meeting to promote sharing and support other similarly motivated groups to learn and share their experiences.

Cancer Center Staff Satisfaction: Descriptive Results of a Canadian Study.

Caring for cancer patients is generally considered very rewarding work, but it can also be stressful and demanding. Therefore, it is important for oncology healthcare professionals to feel satisfied with their work environment in order to provide the best care possible. An ethics-approved 61-item staff satisfaction survey was developed in-house to gain insights regarding workplace satisfaction among all staff at The Ottawa Hospital Cancer Center. Descriptive statistics were used to analyze the responses. A total of 478 individuals completed the online survey, with 75.1% women, 23.2% men, and 1.7% preferring not to say. This represented the vast majority (>75%) of cancer center staff. The approximate breakdown according to healthcare professional type was as follows: 21% nurses, 20% radiation therapists, 18% physicians, 13% clerical staff, and 28% other types of staff. Almost all (97.4%) generally enjoyed their work, with 60% stating "very much" and 37.4% stating "a little bit", and 93.3% found working with cancer patients rewarding. The overall satisfaction level at work was high, with 30.1% reporting "very satisfied" and 54.2% "somewhat satisfied". However, in terms of their work being stressful, 18.6% stated it was "very much" and 62.1% "a little bit". Also, in terms of their workload, 61.3% stated it was "very busy" and 10% stated it was "excessively busy". The most enjoyable aspects of work were listed as interactions with colleagues, interactions with patients, and learning new things. The least enjoyable aspects of work were excessive workload, a perceived unsupportive work environment, and technology problems. Levels of satisfaction and stress at work varied according to role at the cancer center. Most cancer center staff seem to enjoy their work and find it rewarding. However, the work environment can be challenging and stressful. Areas for improvement include managing workloads, ensuring staff feel supported, and improving the user-friendliness of technology.

Capturing the True Cost of Breast Cancer Treatment: Molecular Subtype and Stage-Specific per-Case Activity-Based Costing.

BACKGROUND: Breast cancer (BC) treatment is rapidly evolving with new and costly therapeutics. Existing costing models have a limited ability to capture current treatment costs. We used an Activity-Based Costing (ABC) method to determine a per-case cost for BC treatment by stage and molecular subtype. METHODS: ABC was used to proportionally integrate multidisciplinary evidence-based patient and provider treatment options for BC, yielding a per-case cost for the total duration of treatment by stage and molecular subtype. Diagnostic imaging, pathology, surgery, radiation therapy, systemic therapy, inpatient, emergency, home care and palliative care costs were included. RESULTS: BC treatment costs were higher than noted in previous studies and varied widely by molecular subtype. Cost increased exponentially with the stage of disease. The per-case cost for treatment (2023C$) for DCIS was C$ 14,505, and the mean costs for all subtypes were C$ 39,263, C$ 76,446, C$ 97,668 and C$ 370,398 for stage I, II, III and IV BC, respectively. Stage IV costs were as high as C$ 516,415 per case. When weighted by the proportion of molecular subtype in the population, case costs were C$ 31,749, C$ 66,758, C$ 111,368 and C$ 289,598 for stage I, II, III and IV BC, respectively. The magnitude of cost differential was up to 10.9 times for stage IV compared to stage I, 4.4 times for stage III compared to stage I and 35.6 times for stage IV compared to DCIS. CONCLUSION: The cost of BC treatment is rapidly escalating with novel therapies and increasing survival, resulting in an exponential increase in treatment costs for later-stage disease. We provide real-time, case-based costing for BC treatment which will allow for the assessment of health system economic impacts and an accurate understanding of the cost-effectiveness of screening.

Plexin-A2 and its ligand, Sema6A, control nucleus-centrosome coupling in migrating granule cells.

During their migration, cerebellar granule cells switch from a tangential to a radial mode of migration. We have previously demonstrated that this involves the transmembrane semaphorin Sema6A. We show here that plexin-A2 is the receptor that controls Sema6A function in migrating granule cells. In plexin-A2-deficient (Plxna2(-/-)) mice, which were generated by homologous recombination, many granule cells remained in the molecular layer, as we saw in Sema6a mutants. A similar phenotype was observed in mutant mice that were generated by mutagenesis with N-ethyl-N-nitrosourea and had a single amino-acid substitution in the semaphorin domain of plexin-A2. We found that this mutation abolished the ability of Sema6A to bind to plexin-A2. Mouse chimera studies further suggested that plexin-A2 acts in a cell-autonomous manner. We also provide genetic evidence for a ligand-receptor relationship between Sema6A and plexin-A2 in this system. Using time-lapse video microscopy, we found that centrosome-nucleus coupling and coordinated motility were strongly perturbed in Sema6a(-/-) and Plxna2(-/-) granule cells. This suggests that semaphorin-plexin signaling modulates cell migration by controlling centrosome positioning.

Cancer Clinic Redesign: Opportunities for Resource Optimization.

Ambulatory cancer centers face a fluctuating patient demand and deploy specialized personnel who have variable availability. This undermines operational stability through the misalignment of resources to patient needs, resulting in overscheduled clinics, budget deficits, and wait times exceeding provincial targets. We describe the deployment of a Learning Health System framework for operational improvements within the entire ambulatory center. Known methods of value stream mapping, operations research and statistical process control were applied to achieve organizational high performance that is data-informed, agile and adaptive. We transitioned from a fixed template model by an individual physician to a caseload management by disease site model that is realigned quarterly. We adapted a block schedule model for the ambulatory oncology clinic to align the regional demand for specialized services with optimized human and physical resources. We demonstrated an improved utilization of clinical space, increased weekly consistency and improved distribution of activity across the workweek. The increased value, represented as the ratio of monthly encounters per nursing worked hours, and the increased percentage of services delivered by full-time nurses were benefits realized in our cancer system. The creation of a data-informed demand capacity model enables the application of predictive analytics and business intelligence tools that will further enhance clinical responsiveness.

Matrix-binding vascular endothelial growth factor (VEGF) isoforms guide granule cell migration in the cerebellum via VEGF receptor Flk1.

Vascular endothelial growth factor (VEGF) regulates angiogenesis, but also has important, yet poorly characterized roles in neuronal wiring. Using several genetic and in vitro approaches, we discovered a novel role for VEGF in the control of cerebellar granule cell (GC) migration from the external granule cell layer (EGL) toward the Purkinje cell layer (PCL). GCs express the VEGF receptor Flk1, and are chemoattracted by VEGF, whose levels are higher in the PCL than EGL. Lowering VEGF levels in mice in vivo or ectopic VEGF expression in the EGL ex vivo perturbs GC migration. Using GC-specific Flk1 knock-out mice, we provide for the first time in vivo evidence for a direct chemoattractive effect of VEGF on neurons via Flk1 signaling. Finally, using knock-in mice expressing single VEGF isoforms, we show that pericellular deposition of matrix-bound VEGF isoforms around PC dendrites is necessary for proper GC migration in vivo. These findings identify a previously unknown role for VEGF in neuronal migration.

Cost-Utility Analysis of Radiation Treatment Modalities for Intermediate-Risk Prostate Cancer.

INTRODUCTION: Variable costs of different radiation treatment modalities have played an important factor in selecting the most appropriate treatment for patients with intermediate-risk prostate cancer. METHODS: Analysis using a Markov model was conducted to simulate 20-year disease trajectory, quality-adjusted life years (QALYs) and health system costs of a cohort of intermediate-risk prostate cancer patients with mean age of 60 years. Clinical outcomes on toxicity and disease recurrence were measured and a probabilistic sensitivity analysis was performed, varying input parameters simultaneously according to their distributions. RESULTS: Among the six radiation treatment modalities, including conventionally fractionated intensity-modulated radiation therapy (IMRT), hypofractionated IMRT, IMRT combined with high-dose-rate (HDR) brachytherapy, HDR brachytherapy monotherapy, low-dose-rate brachytherapy monotherapy, and stereotactic body radiotherapy (SBRT), SBRT was found to be more cost-effective when compared with LDR-b and other treatment modalities, resulting in an incremental cost-utility ratio of $2985 per QALY. CONCLUSIONS: Stereotactic body radiotherapy is the most cost-effective radiation treatment modality in treatment of intermediate-risk prostate cancer, while treatment toxicity and cost data are the key drivers of the cost-utility. Further work is required with long-term follow-up for SBRT.

Convergent evidence identifying MAP/microtubule affinity-regulating kinase 1 (MARK1) as a susceptibility gene for autism.

Autism spectrum disorders (ASDs) are common, heritable, but genetically heterogeneous neurodevelopmental conditions. We recently defined a susceptibility locus for ASDs on chromosome 1q41-q42. High-resolution single-nucleotide polymorphisms (126 SNPs) genotyping across the chromosome 1q41-q42 region, followed by a MARK1 (microtubule affinity-regulating kinase 1)-tagged-SNP association study in 276 families with autism from the Autism Genetic Research Exchange, showed that several SNPs within the MARK1 gene were significantly associated with ASDs by transmission disequilibrium tests. Haplotype rs12740310*C-rs3737296*G-rs12410279*A was overtransmitted (P(corrected)= 0.0016), with a relative risk for autism of 1.8 in homozygous carriers. Furthermore, ASD-associated SNP rs12410279 modulates the level of transcription of MARK1. We found that MARK1 was overexpressed in the prefrontal cortex (BA46) but not in cerebellar granule cells, on postmortem brain tissues from patients. MARK1 displayed an accelerated evolution along the lineage leading to humans, suggesting possible involvement of this gene in cognition. MARK1 encodes a kinase-regulating microtubule-dependent transport in axons and dendrites. Both overexpression and silencing of MARK1 resulted in significantly shorter dendrite length in mouse neocortical neurons and modified dendritic transport speed. As expected for a gene encoding a key polarity determinant Par-1 protein kinase, MARK1 is involved in axon-dendrite specification. Thus, MARK1 overexpression in humans may be responsible for subtle changes in dendritic functioning.

The Capital Investment Strategy for Radiation therapy in Ontario: A Framework to Ensure Access to Radiation Therapy.

PURPOSE: Ontario Health (Cancer Care Ontario), formerly known as CCO, is the provincial governmental agency in Ontario, Canada responsible for developing radiation therapy-specific capital investment strategies, updated every 5 years, to ensure equitable access and to gain the highest value from these investments in infrastructure. These plans are informed by the changing landscape of health care delivery, technologic advancements affecting radiation therapy care, patient desire for care closer to home, and expected increases in utilization of radiation therapy services. In this article, we describe the development, model, and final recommendations of CCO's fifth radiation therapy capital investment strategy. METHODS AND MATERIALS: A panel of multidisciplinary provincial experts, in combination with 2 patient and family advisors, developed planning principles to guide the development of a patient-centered strategy. Adaption of the previously used model for radiation therapy planning was used. RESULTS: The development of the capital investment strategy took place from fall 2017 to fall 2018. The model included 3 main factors: patient demand (including utilization targets), machine throughput, and machine demand and supply. The final recommendation is for an investment of 26 new radiation therapy machines in the province by 2028. CONCLUSIONS: The strategy plans for continued province-wide access to quality radiation therapy care and ensures machines are added to the system at the right place and in the right time. Ongoing data collection throughout this period is necessary to ensure the strategy achieves its goals and to allow for planning of future strategies.

Clinical Specialist Radiation Therapist in Palliative Radiation Therapy: Report of an Orientation, Training, and Support Program.

INTRODUCTION: A clinical specialist radiation therapist (CSRT) position in palliative radiation therapy (RT) was created at our institution. Herein, we report the details of the CSRT's orientation, training, and support program. METHODS: We performed an audit and needs assessment of palliative RT services at our centre. This identified opportunities for improvement that could be facilitated by the CSRT. We defined the CSRT job description including priority responsibilities: (1) optimizing palliative RT services for outpatients and developing a rapid access palliative RT program, (2) optimizing palliative RT services for inpatients at our institution, (3) improving links to community physicians and hospitals caring for patients with advanced cancers. We formed a core resource team to provide ongoing support and to design and implement the orientation and training program. The program involved training in clerical and administrative systems as well as treatment planning and physics training relevant to palliative RT. Clinical placements at several hospitals were arranged in both inpatient and outpatient settings. The CSRT worked with radiation and medical oncologists, palliative care specialists, nurse practitioners, hospitalists, and social workers. RESULTS: Through clinical placements and self-directed learning, the CSRT gained knowledge and competencies in patient care coordination, history taking and physical examination, clinical oncology practice including the evidence-based use of palliative RT and symptom control measures, treatment planning, communication, patient advocacy, and advance care planning. We provided practice resources including office space and a planning station, educational opportunities including workshops in palliative and psychosocial care, and research opportunities including methodologic and research ethics training. DISCUSSION: To our knowledge, this is the first detailed report of its kind for an advanced practice radiation therapy role. We hope our report will inform the design and implementation of programs elsewhere to help prepare individuals for similar roles in palliative RT. CONCLUSION: The CSRT in palliative RT at our institution underwent a comprehensive orientation and training program. Institutions with similar CSRT positions are encouraged to report the details of their own programs.

The somatostatin 2A receptor is enriched in migrating neurons during rat and human brain development and stimulates migration and axonal outgrowth.

The neuropeptide somatostatin has been suggested to play an important role during neuronal development in addition to its established modulatory impact on neuroendocrine, motor and cognitive functions in adults. Although six somatostatin G protein-coupled receptors have been discovered, little is known about their distribution and function in the developing mammalian brain. In this study, we have first characterized the developmental expression of the somatostatin receptor sst2A, the subtype found most prominently in the adult rat and human nervous system. In the rat, the sst2A receptor expression appears as early as E12 and is restricted to post-mitotic neuronal populations leaving the ventricular zone. From E12 on, migrating neuronal populations immunopositive for the receptor were observed in numerous developing regions including the cerebral cortex, hippocampus and ganglionic eminences. Intense but transient immunoreactive signals were detected in the deep part of the external granular layer of the cerebellum, the rostral migratory stream and in tyrosine hydroxylase- and serotonin- positive neurons and axons. Activation of the sst2A receptor in vitro in rat cerebellar microexplants and primary hippocampal neurons revealed stimulatory effects on neuronal migration and axonal growth, respectively. In the human cortex, receptor immunoreactivity was located in the preplate at early development stages (8 gestational weeks) and was enriched to the outer part of the germinal zone at later stages. In the cerebellum, the deep part of the external granular layer was strongly immunoreactive at 19 gestational weeks, similar to the finding in rodents. In addition, migrating granule cells in the internal granular layer were also receptor-positive. Together, theses results strongly suggest that the somatostatin sst2A receptor participates in the development and maturation of specific neuronal populations during rat and human brain ontogenesis.