Board Recommendations Research Articles

Good data relations key to Indigenous research sovereignty: A case study from Nunatsiavut.

Although researchers are committed to Indigenous data sovereignty in principle, they fall short in returning data and results to communities in which or with whom they conduct their research. This results in a misalignment in benefits of research toward researchers and settler institutions and away from Indigenous communities. To explore this, we conducted a case study analyzing the rate researchers returned data to Nunatsiavut, an autonomous area claimed by Inuit of Labrador, Canada. We assessed the data return rate for all research approved by the Nunatsiavut Government Research Advisory Committee between 2011 and 2021. In two-thirds of projects, researchers did not return the data they had collected. Based on our results and their contextualization with researchers and Nunatsiavut Research Centre staff members, we compiled recommendations for researchers, academia, government bodies, funding bodies, and Indigenous research governance boards. These recommendations aim to facilitate data return, thus putting data sovereignty into practice.

A qualitative study of providers’ perspectives on cross-institutional care coordination for pancreatic cancer: challenges and opportunities

BackgroundDespite calls for regionalizing pancreatic cancer (PC) care to high-volume centers (HVCs), many patients with PC elect to receive therapy closer to their home or at multiple institutions. In the context of cross-institutional PC care, the challenges associated with coordinating care are poorly understood.MethodsIn this qualitative study we conducted semi-structured interviews with oncology clinicians from a HVC (n = 9) and community-based hospitals (n = 11) to assess their perspectives related to coordinating the care of and treating PC patients across their respective institutions. Interviews were transcribed, coded, and analyzed using deductive and inductive approaches to identify themes related to cross-institutional coordination challenges and to note improvement opportunities.ResultsClinicians identified challenges associated with closed-loop communication due, in part, to not having access to a shared electronic health record. Challenges with patient co-management were attributed to patients receiving inconsistent recommendations from different clinicians. To address these challenges, participants suggested several improvement opportunities such as building rapport with clinicians across institutions and updating tumor board processes. The opportunity to update tumor board processes was reportedly multi-dimensional and could involve: (1) designating a tumor board coordinator; (2) documenting and disseminating tumor board recommendations; and (3) using teleconferencing to facilitate community-based clinician engagement during tumor board meetings.ConclusionsIn light of communication barriers and challenges associated with patient co-management, enabling the development of relationships among PC clinicians and improving the practices of multidisciplinary tumor boards could potentially foster cross-institutional coordination. Research examining how multidisciplinary tumor board coordinators and teleconferencing platforms could enhance cross-institutional communication and thereby improve patient outcomes is warranted.

Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy for the Treatment of Peritoneal Sarcomatosis.

(1) Background: Cytoreductive surgery (CRS) with HIPEC is considered the standard of care for selected patients with peritoneal carcinomatosis, but evidence-based treatment recommendations for the therapy of peritoneal sarcomatosis are scarce. (2) Methods: We retrospectively analyzed all adult patients treated with CRS and HIPEC for peritoneal sarcomatosis between 2017 and 2024. (3) Results: Ten patients with a median age of 46.1 years (range: 23-77 years) with metachronous (40%) or synchronous (60%) peritoneal sarcomatosis from six different tumor entities were treated according to tumor board recommendation using CRS and HIPEC with cisplatin and doxorubicin over 60 min at 42.0 °C. The length of stay in the intensive care unit and hospital was 1.24 (0.6-1.9 days) and 11.1 days (6-17 days), respectively. Complete cytoreduction was achieved in 90% of the patients, with a median PSI of 11.5. Postoperative complications occurred in five cases, but no surgical revisions were necessary, and no acute kidney damage was recorded. (4) Conclusions: CRS with HIPEC in the presence of peritoneal sarcomatosis could be safely performed in our collective. Whether this resulted in an oncological treatment benefit cannot be concluded in view of the heterogeneous and small collective. Therefore, larger and prospective studies are warranted.

Unraveling the role of local ablative therapies for patients with metastatic soft tissue sarcoma – A retrospective multicenter study of the Bavarian university hospitals

BackgroundLocal ablative therapies (LAT) are increasingly used in patients with metastatic soft tissue sarcoma (STS), yet evidence-based standards are lacking. This study aimed to assess the impact of LAT on survival of metastatic STS patients and to identify prognostic factors. MethodsIn this retrospective multicenter study, 246 STS patients with metastatic disease who underwent LAT on tumor board recommendation between 2017 and 2021 were analyzed. A mixed effects model was applied to evaluate multiple survival events per patient. ResultsMedian overall survival (OS) after first metastasis was 5.4 years with 1-, 2- and 5-year survival rates of 93.7, 81.7, and 53.1 %, respectively. A treatment-free interval ≥12 months and treatment of liver metastases were positively correlated with progression-free survival (PFS) after LAT (HR = 0.61, p = 0.00032 and HR = 0.52, p = 0.0081, respectively). A treatment-free interval ≥12 months and treatment of metastatic lesions in a single organ site other than lung and liver were positive prognostic factors for OS after first LAT (HR = 0.50, p = 0.028 and HR = 0.40, p = 0.026, respectively) while rare histotypes and LAT other than surgery and radiotherapy were negatively associated with OS after first LAT (HR = 2.56, p = 0.020 and HR = 3.87, p = 0.025). Additional systemic therapy was independently associated with a PFS benefit in patients ≤60 years with ≥4 metastatic lesions (for max. diameter of treated lesions ≤2 cm: HR = 0.32, p = 0.02 and >2 cm: HR = 0.20, p = 0.0011, respectively). ConclusionThis multicenter study conducted at six German university hospitals underlines the value of LAT in metastatic STS. The exceptionally high survival rates are likely to be associated with patient selection and treatment in specialized sarcoma centers.

Clinical management of oligometastatic cancer: Applying multidisciplinary tumor board recommendations in practice

AimsMultidisciplinary tumor boards (MDTs) are an integral part of ensuring high-quality, evidence-based and personalized cancer care. In this study, we aimed to evaluate the adherence to and implementation of MDT recommendations in patients with oligometastatic disease (OMD). MethodsWe screened all oncologic positron emission tomography (PET) scans conducted at a single comprehensive cancer center in 2020. Patients were included if they had evidence of imaging-based OMD from a solid organ malignancy on the index scans, had their OMD case discussed at an MDT, and were treated and followed up at the same center. A switch away from the MDT-recommended treatment modalities was classified as a major deviation; non-MDT-mandated adjustments to a recommended treatment modality were coded as minor deviation. Clinical data was obtained via chart review; statistical calculations were computed using the R software. ResultsAfter review of PET and/or concurrent brain scans, 787 cases of OMD were identified. Thereof, 347 (44.1 %) cases were discussed at MDT, of which 331 (42.1 %) were therapeutically managed and subsequently followed. The three most commonly recommended therapies were systemic therapy (35.6 %), multimodality treatment including definitive local therapy (17.8 %), and radiotherapy (13.9 %). A major deviation was recorded in 16.3 % of cases (most commonly: none of the MDT-recommended treatment modalities were performed: 19 (35.2 %); not all MDT-planned treatment modalities were performed: 12 (22.2 %); and additional treatment modality was performed: 11 (20.3 %). A minor deviation was found in 1.5 % of cases. On multivariable regression, number of distant metastases (n > 1) was associated with a major deviation (OR: 1.85; 95 % CI, 1.0–3.52). Major deviations were associated with a significantly worse OS (p = 0.0034). ConclusionsAdherence to and implementation of MDT recommendations in OMD patients was generally high (83.7%). Major deviations might be further reduced by more careful and elaborate discussions of OMD patient characteristics s and patient preferences.

Review of Pseudomonas aeruginosa and Klebsiella pneumoniae as venereal pathogens in horses.

Three bacteria extensively acknowledged as venereal pathogens with the potential to induce endometritis include Taylorella equigenitalis, the causative agent of contagious equine metritis (CEM), specific strains of Pseudomonas aeruginosa, and certain capsule types of Klebsiella pneumoniae. The United Kingdom's Horserace Betting Levy Board recommends pre-breeding screening for these bacteria in their International Codes of Practice and >20 000 samples are tested per annum in the United Kingdom alone. While the pathogenesis and regulatory importance of CEM are well established, an evaluation of the literature pertaining to venereal transmission of P. aeruginosa and K. pneumoniae was lacking. The aim of this review was to evaluate published literature and determine the significance of P. aeruginosa and K. pneumoniae as venereal pathogens in horses. Literature definitively demonstrating venereal transmission was not available. Instead, application of molecular typing methods suggested that common environmental sources of contamination, such as water, or fomites be considered as modes of transmission. The presence of organisms with pathogenic potential on a horse's external genitalia did not predict venereal transmission with resultant endometritis and reduced fertility. These findings may prompt further investigation using molecular technologies to confirm or exclude venereal spread and investigation of alternative mechanisms of transmission are indicated.

Multidisciplinary Approach to Patent Foramen Ovale Closure for Cryptogenic Stroke: Brain-Heart Board Experience.

Patent foramen ovale (PFO) is present in approximately 25% of adult population. The prevalence of PFO is high in patients with cryptogenic stroke suggesting paradoxical embolism. PFO closure in carefully selected patients is an effective secondary preventive strategy in these patients. We report predictors of management recommendations by the multidisciplinary Board and their impact on outcomes. Brain-Heart Board comprises vascular and interventional neurology and cardiology subspecialties (structural, electrophysiology, and cardiac imaging). Adult patients referred to the Board for consideration of PFO closure between October 2017 to March 2021 were included in this retrospective cohort analysis. Demographics, comorbid conditions, risk of paradoxical embolism (RoPE) score, event frequencies (transient ischemic attack [TIA] or stroke, intracranial hemorrhage [ICH], post-PFO closure cardiac arrhythmias), and modified Rankin Scale (mRS) at 1 year were compared between the groups (PFO closure vs medical management). Multivariable logistic regression was used to identify factors associated with management recommendation and chi-square tests to test differences in outcomes for patients according to management. Two hundred seventy patients (229 stroke; 41 TIA) were discussed by the Board for PFO closure. 119 (44.0%) patients were recommended for PFO closure of which 117 (98.3%) had evidence of ischemic infarct on imaging. In univariate analysis, age was similar (50 ± 11.9 vs 52 ± 12.8, p = 0.17), but RoPE score was higher in closure as compared with the medical management group (6 [IQR 5-7] vs 5 [IQR 4-7], p < 0.05). In multivariable analysis, TIA as the index event was an independent predictor of Board recommendation against PFO closure (OR 0.05, 95% CI 0.01-0.19, p < 0.05). Event frequency was low in both cohorts (5.9% vs 4.8%, p > 0.05) and comprised cardiac arrhythmias (6 cases of atrial fibrillation and 1 ICH in closure group; 1 TIA and 1 recurrent stroke in medical management group). Excellent functional outcome (mRS 0-1) was similar in both cohorts (66.3% vs 70.7%, p > 0.05) at 1 year. Multidisciplinary Brain-Heart Board provides a clinical practice model of collaborative care to ensure proper patient selection for PFO closure. TIA as the index event is associated with recommendation of medical management by the multidisciplinary Brain-Heart Board.

A Tutorial for Enhancing Clarity and Transparency in Speech-Language-Hearing Sciences Intervention Research With the TIDieR.

The speech-language-hearing sciences (SLHS) field relies on rigorous research to inform clinical practice and improve outcomes for individuals with communication, swallowing, and hearing needs. However, a significant challenge in our field is the lack of accessibility, transparency, and reproducibility of this research. Such insufficiencies limit the generalizability and impact of study findings, particularly intervention research, as it becomes difficult to replicate and use the interventions in both clinical practice and research. In this tutorial, we highlight one particularly useful tool, the Template for Intervention Description and Replication (TIDieR; Hoffmann et al., 2014) checklist, which researchers can follow to improve reproducibility practices in SLHS. We provide an overview and guide on using the TIDieR checklist with a practical example of its implementation. Additionally, we discuss the potential benefits of increased transparency and reproducibility for SLHS, including improved clinical outcomes and increased confidence in the effectiveness of interventions. We also provide specific recommendations for scientists, journal reviewers, editors, and editorial boards as they seek to adopt, implement, and encourage using the TIDieR checklist.

TRLS-04. EARLY INSIGHTS FROM PNOC027: PERSONALIZED TREATMENT APPROACHES BASED ON REAL-TIME DRUG SCREENING AND GENOMIC TESTING IN PEDIATRIC AND ADOLESCENT PATIENTS WITH RECURRENT MEDULLOBLASTOMA

Abstract BACKGROUND PNOC027, a clinical trial conducted by the Pediatric Neuro-Oncology Consortium (PNOC), explores a precision medicine strategy with up to four FDA-approved agents integrating real-time drug screening with whole exome DNA and RNA sequencing to guide personalized treatment approaches for children and young adults with relapsed medulloblastoma. METHODS Freshly isolated tumor cells from patients undergo high-throughput drug screening, evaluating responses to 232 clinically available compounds over 72 hours. In vitro drug responses are integrated with tumor genomic and transcriptomic data to predict drug combinations for each patient. Drugs are prioritized based on blood-brain barrier permeability, patient age, prior treatments, and other co-morbidities. Correlative studies include the collection of blood to assess circulating tumor DNA (ctDNA) before surgery and during treatment. Health-related quality of life (HRQOL) assessments will also be collected during therapy. RESULTS To date, nine patients have been enrolled. Eight of these have successfully completed real time drug screening with a median turnaround of 7 days from sample receipt. One patient was excluded due to ineligible (non-medulloblastoma) pathology after enrollment. Seven of these had whole exome sequencing, and six had RNA sequencing. Tumor board recommendations were rendered within 21 business days from the date of surgery. Among the diverse drug classes evaluated, histone deacetylase (HDAC) inhibitors, proteasome inhibitors, anthracyclines, DNA crosslinkers, and kinase inhibitors showed the most robust in vitro responses. Six patients received the recommended regimens, experiencing tolerable (grade 1/2) toxicities. Two patients succumbed to disease prior to therapy initiation, three exhibited disease progression while on therapy, and three remain on therapy. CONCLUSION PNOC027 demonstrates preliminary feasibility of real-time drug screening combined with DNA/RNA sequencing to inform targeted therapy selection in clinically relevant timeframes and with potential for disease response.

Acute and Long-Term Toxicity after Planned Intraoperative Boost and Whole Breast Irradiation in High-Risk Patients with Breast Cancer-Results from the Targeted Intraoperative Radiotherapy Boost Quality Registry (TARGIT BQR).

In the context of breast cancer treatment optimization, this study prospectively examines the feasibility and outcomes of utilizing intraoperative radiotherapy (IORT) as a boost in combination with standard external beam radiotherapy (EBRT) for high-risk patients. Different guidelines recommend such a tumor bed boost in addition to whole breast irradiation with EBRT for patients with risk factors for local breast cancer recurrence. The TARGIT BQR (NCT01440010) is a prospective, multicenter registry study aimed at ensuring the quality of clinical outcomes. It provides, for the first time, data from a large cohort with a detailed assessment of acute and long-term toxicity following an IORT boost using low-energy X-rays. Inclusion criteria encompassed tumors up to 3.5 cm in size and preoperative indications for a boost. The IORT boost, administered immediately after tumor resection, delivered a single dose of 20 Gy. EBRT and systemic therapy adhered to local tumor board recommendations. Follow-up for toxicity assessment (LENT SOMA criteria: fibrosis, teleangiectasia, retraction, pain, breast edema, lymphedema, hyperpigmentation, ulceration) took place before surgery, 6 weeks to 90 days after EBRT, 6 months after IORT, and then annually using standardized case report forms (CRFs). Between 2011 and 2020, 1133 patients from 10 centers were preoperatively enrolled. The planned IORT boost was conducted in 90%, and EBRT in 97% of cases. Median follow-up was 32 months (range 1-120, 20.4% dropped out), with a median age of 61 years (range 30-90). No acute grade 3 or 4 toxicities were observed. Acute side effects included erythema grade 1 or 2 in 4.4%, palpable seroma in 9.1%, punctured seroma in 0.3%, and wound healing disorders in 2.1%. Overall, chronic teleangiectasia of any grade occurred in 16.2%, fibrosis grade ≥ 2 in 14.3%, pain grade ≥ 2 in 3.4%, and hyperpigmentation in 1.1%. In conclusion, a tumor bed boost through IORT using low-energy X-rays is a swift and feasible method that demonstrates low rates in terms of acute or long-term toxicity profiles in combination with whole breast irradiation.

The Impact of Capital Structure on Performance in SMEs: The Saudi Parallel Financial Market

This study aims to analyse the effect of corporate capital structure on the financial performance of small and medium enterprises (SMEs). Despite the importance of SMEs for economic growth and technology advancements and the vital role of capital structure on financial performance, there is a scarcity of studies that investigate SMEs. This study focuses on SMEs that were listed in the Saudi Parallel Market (Nomu) for the period of 2017–2022. To the best of our knowledge, this is the first study that examines this relationship for Saudi SMEs. Our research utilises secondary data and employs descriptive statistics and Pooled OLS regression analyses. This study finds that the firm’s capital structure impacts its financial performance. In particular, we find that there is a positive significant relationship between total debt and return on equity. However, when we distinguish between long-term and short-term debt, we find that positive effect is mainly attributed to long-term rather than short-term debt. This study employs several robust tests. Based on the findings of this study, the authors provide several practical recommendations for corporate boards, executives, decision-makers, and regulators whose interest is the growth and sustainable performance of SMEs. KEYWORDS corporate finance, financial performance, leverage, Nomu exchange, Saudi firms, shareholder’s equity

Corporate Governance and Firm Performance: A Cross-Country Analysis in South Korea

Purpose: The aim of the study was to examine the corporate governance and firm performance: a cross-country analysis. Methodology: This study adopted a desk methodology. A desk study research design is commonly known as secondary data collection. This is basically collecting data from existing resources preferably because of its low cost advantage as compared to a field research. Our current study looked into already published studies and reports as the data was easily accessed through online journals and libraries. Findings: Financial regulations in Germany impact market liquidity through a complex interplay of factors. While they enhance stability and investor protection, compliance costs and altered trading dynamics may initially hinder liquidity. However, regulatory initiatives driving innovation and global harmonization can ultimately foster a more efficient market environment, benefiting both domestic and international Unique Contribution to Theory, Practice and Policy: Agency theory, stewardship theory &amp; institutional theory may be used to anchor future studies on the corporate governance and firm performance: a cross-country analysis. The study should provide practical recommendations for firms and corporate boards to enhance their corporate governance practices based on empirical findings. The study should inform policymakers and regulatory authorities about the implications of corporate governance regulations on firm performance and market competitiveness.

Impact of Foreign Direct Investment (FDI) on Economic Growth: A Study of Brazil

Purpose: The aim of the study was to investigate the impact of foreign direct investment (FDI) on economic growth: a study of Brazil&#x0D; Methodology: This study adopted a desk methodology. A desk study research design is commonly known as secondary data collection. This is basically collecting data from existing resources preferably because of its low cost advantage as compared to a field research. Our current study looked into already published studies and reports as the data was easily accessed through online journals and libraries.&#x0D; Findings: The study on Foreign Direct Investment (FDI) and economic growth in Brazil found a positive relationship between FDI inflows and GDP growth. FDI contributes to capital accumulation, technology transfer, and sectoral diversification, enhancing competitiveness. However, the impact varies across regions and industries, with disparities in spillover effects. Targeted policies are needed to maximize FDI benefits and promote inclusive growth, addressing regional disparities and socio-economic inequalities.&#x0D; Unique Contribution to Theory, Practice and Policy: Dependency theory, modernization theory &amp; institutional theory may be used to anchor future studies on the impact of foreign direct investment (FDI) on economic growth: a study of Brazil. The study should provide practical recommendations for firms and corporate boards to enhance their corporate governance practices based on empirical findings. The study should inform policymakers and regulatory authorities about the implications of corporate governance regulations on firm performance and market competitiveness.

Incidental finding of leukaemia in circulating tumour DNA— the importance of a molecular tumour board

As the use of liquid biopsies are increasing across multiple indications in cancer medicine, the detection of incidental findings on circulating tumour DNA is of increasing importance. We report the finding of leukaemia detected in a patient who underwent plasma-based circulating tumour DNA next generation screening as part of a screening liquid biopsy study. A BRAF V600E mutation detected was deemed pathogenic following discussion at a molecular tumour board, and recommendation of further investigations led to the diagnosis of an occult haematological malignancy. We report the importance of molecular tumour board discussion and recommendations in the identification of incidental, pathogenic findings on circulating tumour DNA.

Repeat surgery of recurrent glioma for molecularly informed treatment in the age of precision oncology: A risk–benefit analysis

PurposeSurgery for recurrent glioma provides cytoreduction and tissue for molecularly informed treatment. With mostly heavily pretreated patients involved, it is unclear whether the benefits of repeat surgery outweigh its potential risks.MethodsPatients receiving surgery for recurrent glioma WHO grade 2–4 with the goal of tissue sampling for targeted therapies were analyzed retrospectively. Complication rates (surgical, neurological) were compared to our institutional glioma surgery cohort. Tissue molecular diagnostic yield, targeted therapies and post-surgical survival rates were analyzed.ResultsBetween 2017 and 2022, tumor board recommendation for targeted therapy through molecular diagnostics was made for 180 patients. Of these, 70 patients (38%) underwent repeat surgery. IDH-wildtype glioblastoma was diagnosed in 48 patients (69%), followed by IDH-mutant astrocytoma (n = 13; 19%) and oligodendroglioma (n = 9; 13%). Gross total resection (GTR) was achieved in 50 patients (71%). Tissue was processed for next-generation sequencing in 64 cases (91%), and for DNA methylation analysis in 58 cases (83%), while immunohistochemistry for mTOR phosphorylation was performed in 24 cases (34%). Targeted therapy was recommended in 35 (50%) and commenced in 21 (30%) cases. Postoperatively, 7 patients (11%) required revision surgery, compared to 7% (p = 0.519) and 6% (p = 0.359) of our reference cohorts of patients undergoing first and second craniotomy, respectively. Non-resolving neurological deterioration was documented in 6 cases (10% vs. 8%, p = 0.612, after first and 4%, p = 0.519, after second craniotomy). Median survival after repeat surgery was 399 days in all patients and 348 days in GBM patients after repeat GTR.ConclusionSurgery for recurrent glioma provides relevant molecular diagnostic information with a direct consequence for targeted therapy under a reasonable risk of postoperative complications. With satisfactory postoperative survival it can therefore complement a multi-modal glioma therapy approach.

Risk-benefit analysis of surgical treatment strategies for cystic craniopharyngioma in children and adolescents.

Treatment strategies for craniopharyngiomas are still under debate particularly for the young population. We here present tumor control and functional outcome data after surgical treatment focusing on stereotactic and microsurgical procedures for cystic craniopharyngiomas in children and adolescents. From our prospective institutional database, we identified all consecutive patients less than 18 years of age who were surgically treated for newly-diagnosed cystic craniopharyngioma between, 2000 and, 2022. Treatment decisions in favor of stereotactic treatment (STX) or microsurgery were made interdisciplinary. STX included aspiration and/or implantation of an internal shunt catheter for permanent cyst drainage. Microsurgery aimed for safe maximal tumor resections. Study endpoints were time to tumor recurrence (TTR) and functional outcome including ophthalmological/perimetric, endocrinological, and body-mass index (BMI) data. 29 patients (median age 9.9 yrs, range 4-18 years) were analyzed. According to our interdisciplinary tumor board recommendation, 9 patients underwent stereotactic treatment, 10 patients microsurgical resection, and 10 patients the combination of both. Significant volume reduction was particularly achieved in the stereotactic (p=0.0019) and combined subgroups (p<0.001). Improvement of preoperative visual deficits was always achieved independent of the applied treatment modality. Microsurgery and the combinational treatment were associated with higher rates of postoperative endocrinological dysfunction (p<0.0001) including hypothalamic obesity (median BMI increase from 17.9kg/m2 to 24.1kg/m2, p=0.019). Median follow-up for all patients was 93.9 months (range 3.2-321.5 months). Recurrent tumors were seen in 48.3% and particularly concerned patients after initial combination of surgery and STX (p=0.004). In here, TTR was 35.1 ± 46.9 months. Additional radiation therapy was found indicated in 4 patients to achieve long-lasting tumor control. In children and adolescents suffering from predominantly cystic craniopharyngiomas, stereotactic and microsurgical procedures can improve clinical symptoms at low procedural risk. Microsurgery, however, bears a higher risk of postoperative endocrine dysfunction. A risk-adapted surgical treatment concept may have to be applied repeatedly in order to achieve long-term tumor control even without additional irradiation.

Application of a 21-Gene Recurrence Score in a Swiss Single-Center Breast Cancer Population: A Comparative Analysis of Treatment Administration before and after TAILORx.

In patients with hormone receptor positive, human epidermal receptor 2 negative (HR+/HER2-) negative breast cancer (BC), the TAILORx study showed the benefit of adding chemotherapy (CHT) to endocrine therapy (ET) in a subgroup of patients under 50 years with an intermediate Oncotype DX recurrence score (RS 11-25). The aim of the present study was to determine if the TAILORx findings, including the changes in the RS categories, impacted CHT use in the intermediate RS (11-25) group in daily practice, as well as to identify the main factors for CHT decisions. We conducted a retrospective study on 326 BC patients (59% node-negative), of which 165 had a BC diagnosis before TAILORx (Cohort A) and 161 after TAILORx publication (Cohort B). Changes in the RS categories led to shifts in patient population distribution, thereby leading to a 40% drop in the low RS (from 60% to 20%), which represented a doubling in the intermediate RS (from 30% to 60%) and an increase of 5% in the high RS (from 8-10% to 15%). The overall CHT recommendation and application did not differ significantly between cohort B when compared with A (19% vs. 22%, resp., p = 0.763). In the intermediate RS (11-25), CHT use decreased by 5%, while in the high-risk RS category (>25), there was an increase of 13%. The tumor board recommended CHT for 90% of the patients according to the new RS guidelines in cohort A and for 85% in cohort B. The decision for CHT recommendation was based on age (OR 0.93, 95% CI 0.08-0.97, p = 0.001), nodal stage (OR 4.77, 95% CI 2.03-11.22, p < 0.001), and RS categories (RS 11-25 vs. RS 0-10: OR 0.06 (95% CI 0.02-0.17), p < 0.001; RS > 26 vs. RS 11-25: OR 618.18 95% CI 91.64-4169.91, p < 0.001), but did not depend on the cohort. In conclusion, while the tumor board recommendation for CHT decreased in the intermediate RS category, there was an increase being reported in the high RS category, thus leading to overall minor changes in CHT application. As expected, among the younger women with intermediate RS and unfavorable histopathological factors, CHT use increased.

Determinants Affecting the Clinical Implementation of a Molecularly Informed Molecular Tumor Board Recommendation: Experience from a Tertiary Cancer Center.

Molecular Tumor Boards (MTBs) converge state-of-the-art next-generation sequencing (NGS) methods with the expertise of an interdisciplinary team consisting of clinicians, pathologists, human geneticists, and molecular biologists to provide molecularly informed guidance in clinical decision making to the treating physician. In the present study, we particularly focused on elucidating the factors impacting on the clinical translation of MTB recommendations, utilizing data generated from gene panel mediated comprehensive genomic profiling (CGP) of 554 patients at the MTB of the Comprehensive Cancer Center Erlangen, Germany, during the years 2016 to 2020. A subgroup analysis of cases with available follow-up data (n = 332) revealed 139 cases with a molecularly informed MTB recommendation, which was successfully implemented in the clinic in 44 (31.7%) of these cases. Here, the molecularly matched treatment was applied in 45.4% (n = 20/44) of cases for ≥6 months and in 25% (n = 11/44) of cases for 12 months or longer (median time to treatment failure, TTF: 5 months, min: 1 month, max: 38 months, ongoing at data cut-off). In general, recommendations were preferentially implemented in the clinic when of high (i.e., tier 1) clinical evidence level. In particular, this was the case for MTB recommendations suggesting the application of PARP, PIK3CA, and IDH1/2 inhibitors. The main reason for non-compliance to the MTB recommendation was either the application of non-matched treatment modalities (n = 30)/stable disease (n = 7), or deteriorating patient condition (n = 22)/death of patient (n = 9). In summary, this study provides an insight into the factors affecting the clinical implementation of molecularly informed MTB recommendations, and careful considerations of these factors may guide future processes of clinical decision making.

Development of an Online Training to Engage Home Visitors as Research Stakeholders

Abstract: Background: Home visiting (HV) has demonstrated positive impacts across family well-being domains. Home visitors receive training in HV model requirements as well as to develop knowledge and various skills. Despite growth in HV research, we are not aware of existing training or required competencies in research design, research methods, or dissemination of research findings for home visitors. Objectives: Via ongoing collaboration with an Advisory Board of key HV stakeholders, we developed a three-module online training that incorporated examples from HV research and practice to address the gap in research training for home visitors and to promote home visitors' engagement as research stakeholders. Methods: A convenience sample of home visitors ( n = 176) was surveyed on research knowledge, research self-efficacy, and priority training topics, with results used to create a beta version of the training completed by six home visitors. Home visitor feedback on the beta version, coupled with Advisory Board recommendations, led to creation of the final online training. Forty home visitors viewed the final training and completed pre- and post-training surveys to assess changes in research knowledge and self-efficacy. Twelve home visitors also completed a semi-structured qualitative interview. Home visitors demonstrated improvements in research knowledge and self-efficacy and found the training easy to understand and useful. Conclusions: Guidance from stakeholders led to development of an online training that was effective in improving home visitors' research knowledge and self-efficacy. This training can be used by HV researchers and practitioners as a tool to promote home visitors' active engagement as stakeholders in research.

Functional Precision Medicine Vs Genomics Vs Clinical Experience: Feasibility Results from the Multicentric, Prospective, Randomized Controlled Exalt-2 Trial

Background Aggressive hematological malignancies have a dismal prognosis in the relapsed/refractory setting representing an unmet medical need. Despite the advance of numerous novel therapeutics to clinical routine, treatment selection at advanced disease stages typically is challenging because of chemoresistance, cumulative toxicity, patient-specific factors, and a lack of evidence-based protocols in heavily pretreated patients. Precision medicine approaches promise to extend the number of candidate drugs beyond the standard of care, ultimately providing a treatment rationale in situations where evidence-based treatment options are scarce. We have previously shown that single-cell functional precision medicine (scFPM) is clinically feasible and efficacious in patients with aggressive hematological cancers who exceeded all standard therapy lines (Snijder et al. Lancet Haematology 2017, Kornauth et al, Cancer Discovery 2022). Inspired by this proof of concept, we launched a multicentric, prospective, randomized controlled trial to assess if genetic, or functional precision medicine-guided therapy may improve patient outcomes compared to best clinical experience-guided therapy (NCT04470947). Methods EXALT-2 is a multicentric, prospective, randomized controlled trial in five academic hospitals in Austria (Vienna, Graz, Innsbruck, Linz, and Salzburg). The study aims to enroll 150 patients with aggressive hematological malignancies in a relapsed/refractory setting with an overall good performance status (ECOG ≤ 1). After inclusion, a real-time tumor-containing biopsy is obtained to confirm relapse and collect viable tumor samples from each patient. Tumor cells are subjected to single-cell functional precision medicine (scFPM) and comprehensive genomic profiling (CGP) assays. Importantly, scFPM testing comprises flow cytometry- and/or imaging-based high-throughput drug screening. Depending on the randomization arm, therapy is suggested by the multicentric, multidisciplinary EXALT-2 tumor board, which consists of at least 2 hematology specialists, a pathologist, a molecular biologist, and a pharmacist. The EXALT-2 board gives a treatment recommendation either based on i) scFPM or ii) CGP results, or iii) without any precision medicine support (Physicians' Choice, PC). If precision medicine assays fail or do not yield a treatment recommendation, a cross-over between study arms is allowed. An overview of the study design is shown in Figure 1A. Results Feasibility results are available for the first 55 included patients. Of these, 54 patients (98%) underwent real-time biopsy and were randomized with an equal distribution across study arms. 42 patients (76%) received a therapy suggestion from the EXALT-2 tumor board. The majority of these patients suffered from aggressive lymphoma . Finally, 39 patients (71% of the total, 92% of patients with a board recommendation) received treatment. 10 patients were classified as early drop-outs due to death or progression within the first 28 days of board-recommended therapy according to the study protocol. 29 patients (53% of total, 69% of patients with a board recommendation) continued on study and are available for further evaluation. Precision medicine assays were technically feasible in most instances (flow cytometry-based scFPM: 80% of tests; microscopy-based scFPM: 52% of tests; CGP: 86% of tests) and identified actionable hits in 100%, 100%, and 78%, respectively. The median time to report was shorter for scFPM than CGP testing (7 vs. 19 days, p&amp;lt;0.0001; Figure 1B). CGP identified a median of 1 (0-5) druggable genetic targets. In 60% of the patients (12 out of 20) with complete work-up, we observed a substantial overlap between genetic and functional (within the top 10 drug hits) results. Conclusions Our results provide further evidence that either genetic-based or functional precision medicine can be efficiently and safely implemented in clinical routine. scFPM and CGP aid to identify a rationale for innovative treatment options in a heavily pretreated cohort. Treatment recommendations can be translated to clinical application in the majority of these patients.