Therapeutic drug monitoring to personalize dosing of imatinib, sunitinib, and pazopanib:A mixed methods study on barriers and facilitators

Background:Personalized dosing based on measurement of individual drug levels and adjusting the dose accordingly can improve efficacy and decrease unnecessary toxicity of oncological treatment. For imatinib, sunitinib, and pazopanib, this therapeutic drug monitoring (TDM)-guided dosing is, however, not routinely used, despite accumulating evidence favoring individualized dosing. Therefore, we aimed to identify and quantify (potential) barriers and facilitators in TDM-guided dosing for imatinib, sunitinib, and pazopanib. Methods: We performed a mixed methods study among all stakeholders involved: patients, healthcare professionals (HCPs), pharmaceutical companies, and health insurance companies. During the first qualitative part of this study, we performed semi-structured individual interviews and one focus group interview to identify all (potential) barriers and facilitators, and during the second quantitative part of this study, we used a web-based survey to quantify these findings. The interviews addressed the six domains of the implementation of change model of Grol and Wensing: (1) the innovation itself; (2) the HCP; (3) the patient; (4) social context; (5) organizational context; and (6) finances, law, and governance. Results: In the qualitative study, we interviewed 20 patients, 18 HCPs and 10 representatives of pharmaceutical and health insurance companies and identified 72 barriers and 90 facilitators. In the quantitative study, the survey was responded by 66 HCPs and 58 patients. Important barriers were on the domain of the HCP, such as a lack of experience with TDM (36.4%), on the domain of the patient, such as lack of awareness of TDM (39.7%), and the processing time for measurement and interpretation of the TDM result (40.9%) (organizational domain). Important facilitators were education of HCPs (95.5%), education of patients (87.9%) and facilitating an overview of when and where TDM measurements are being performed (86.4%). Conclusion: We identified and quantified important barriers and facilitators for the implementation of TDM-guided dosing for imatinib, sunitinib, and pazopanib. Based on our results, the implementation strategy should mainly focus on educating both HCPs and patients and on the organizational aspect of TDM.</p

A qualitative research on co-creating care pathways for Sarcoma and GIST by stimulating reflection

Introduction: Care Pathway Management intends to enhance the quality of care by restructuring care services. As recipients of care, patients have relevant experiential knowledge on the provision of care, but they are rarely involved in Care Pathway Management due to various barriers. This study aims to acquire insights into how patients can be meaningfully involved in Care Pathway Management. Methods: A case study was cond

Genetic Differences in Female House Mice in Aggressive Response to Sex Steroid Hormone Treatment

Male mice, genetically selected for aggression, characterized by short attack latency (SAL) or long attack latency (LAL), differ on several testosterone (T)-related parameters during ontogeny and adult age. The variation in aggressive behavior at adult age may be due to differences in degree of androgenization prenatally. When exposed to T at prenatal, neonatal, and/or adult age, nonlactating females also display intraspecific fighting behavior. In the present study, we investigated in females of the SAL and LAL selection lines, whether the differentiation of aggression involves processes similar to ones seen in males. Therefore, we injected females with testosterone propionate (TP) or vehicle on the day of birth, treated them after ovariectomy at adult age with T, estradiol (E), or vehicle, and tested their aggressive response. We found that neonatally vehicle-treated SAL females show a higher aggressive response to chronic T treatment at adult age than LAL females receiving the same treatment. Females of both selection lines treated with vehicle or E as adults were not aggressive. Neonatal TP treatment did not influence the adult T sensitivity and difference between selection lines in response to T at adult age. However, neonatally TP-treated SAL females showed aggressive behavior when treated with E at adult age, whereas LAL females failed to do so. These results suggest a genetic difference in susceptibility to T and E, which plays a major role prenatally, in organizing the development of sex steroid-dependent neural systems.

What Is a Sarcoma 'Specialist Center'? Multidisciplinary Research Finds an Answer

The management of sarcomas in specialist centers delivers significant benefits. In much of the world, specialists are not available, and the development of expertise is identified as a major need. However, the terms 'specialist' or 'expert' center are rarely defined. Our objective is to offer a definition for patient advocates and a tool for healthcare providers to underpin improving the care of people with sarcoma. SPAGN developed a discussion paper for a workshop at the SPAGN 2023 Conference, attended by 75 delegates. A presentation to the Connective Tissue Oncology Society (CTOS) and further discussion led to this paper. Core Principles were identified that underlie specialist sarcoma care. The primary Principle is the multi-disciplinary team discussing every patient, at first diagnosis and during treatment. Principles for optimal sarcoma management include accurate diagnosis followed by safe, high-quality treatment, with curative intent. These Principles are supplemented by Features describing areas of healthcare, professional involvement, and service provision and identifying further research and development needs. These allow for variations because of national or local policies and budgets. We propose the term 'Sarcoma Intelligent Specialist Network' to recognize expertise wherever it is found in the world. This provides a base for further discussion and local refinement

Epithelioid hemangioendothelioma, an ultra-rare cancer : a consensus paper from the community of experts

Epithelioid hemangioendothelioma (EHE) is an ultra-rare, translocated, vascular sarcoma. EHE clinical behavior is variable, ranging from that of a low-grade malignancy to that of a high-grade sarcoma and it is marked by a high propensity for systemic involvement. No active systemic agents are currently approved specifically for EHE, which is typically refractory to the antitumor drugs used in sarcomas. The degree of uncertainty in selecting the most appropriate therapy for EHE patients and the lack of guidelines on the clinical management of the disease make the adoption of new treatments inconsistent across the world, resulting in suboptimal outcomes for many EHE patients. To address the shortcoming, a global consensus meeting was organized in December 2020 under the umbrella of the European Society for Medical Oncology (ESMO) involving >80 experts from several disciplines from Europe, North America and Asia, together with a patient representative from the EHE Group, a global, disease-specific patient advocacy group, and Sarcoma Patient EuroNet (SPAEN). The meeting was aimed at defining, by consensus, evidence-based best practices for the optimal approach to primary and metastatic EHE. The consensus achieved during that meeting is the subject of the present publication