European value-based healthcare benchmarking: moving from theory to practice.

BACKGROUND: Value-based healthcare (VBHC) is a conceptual framework to improve the value of healthcare by health, care-process and economic outcomes. Benchmarking should provide useful information to identify best practices and therefore a good instrument to improve quality across healthcare organizations. This paper aims to provide a proof-of-concept of the feasibility of an international VBHC benchmarking in breast cancer, with the ultimate aim of being used to share best practices with a data-driven approach among healthcare organizations from different health systems. METHODS: In the VOICE community-a European healthcare centre cluster intending to address VBHC from theory to practice-information on patient-reported, clinical-related, care-process-related and economic-related outcomes were collected. Patient archetypes were identified using clustering techniques and an indicator set following a modified Delphi was defined. Benchmarking was performed using regression models controlling for patient archetypes and socio-demographic characteristics. RESULTS: Six hundred and ninety patients from six healthcare centres were included. A set of 50 health, care-process and economic indicators was distilled for benchmarking. Statistically significant differences across sites have been found in most health outcomes, half of the care-process indicators, and all economic indicators, allowing for identifying the best and worst performers. CONCLUSIONS: To the best of our knowledge, this is the first international experience providing evidence to be used with VBHC benchmarking intention. Differences in indicators across healthcare centres should be used to identify best practices and improve healthcare quality following further research. Applied methods might help to move forward with VBHC benchmarking in other medical conditions.

Machine learning identifies experimental brain metastasis subtypes based on their influence on neural circuits.

A high percentage of patients with brain metastases frequently develop neurocognitive symptoms; however, understanding how brain metastasis co-opts the function of neuronal circuits beyond a tumor mass effect remains unknown. We report a comprehensive multidimensional modeling of brain functional analyses in the context of brain metastasis. By testing different preclinical models of brain metastasis from various primary sources and oncogenic profiles, we dissociated the heterogeneous impact on local field potential oscillatory activity from cortical and hippocampal areas that we detected from the homogeneous inter-model tumor size or glial response. In contrast, we report a potential underlying molecular program responsible for impairing neuronal crosstalk by scoring the transcriptomic and mutational profiles in a model-specific manner. Additionally, measurement of various brain activity readouts matched with machine learning strategies confirmed model-specific alterations that could help predict the presence and subtype of metastasis.

Protocol to generate murine organotypic brain cultures for drug screening and evaluation of anti-metastatic efficacy.

Organotypic brain cultures are short-term assays that phenotypically and functionally recapitulate brain metastatic cells in vivo. Here, we present a protocol to generate murine organotypic brain cultures for drug screening. We describe steps for sectioning of murine brains and plating of organotypic cultures. We then detail evaluation of the anti-metastatic effect of chemical compounds through bioluminescence imaging before and after drug treatment. Combined with downstream applications, this protocol allows comprehensive characterizations of both cancer cells and the tumor-associated microenvironment. For complete details on the use and execution of this protocol, please refer to Zhu et al. (2022).1.

Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism.

Whole-brain radiotherapy (WBRT) is the treatment backbone for many patients with brain metastasis; however, its efficacy in preventing disease progression and the associated toxicity have questioned the clinical impact of this approach and emphasized the need for alternative treatments. Given the limited therapeutic options available for these patients and the poor understanding of the molecular mechanisms underlying the resistance of metastatic lesions to WBRT, we sought to uncover actionable targets and biomarkers that could help to refine patient selection. Through an unbiased analysis of experimental in vivo models of brain metastasis resistant to WBRT, we identified activation of the S100A9-RAGE-NF-κB-JunB pathway in brain metastases as a potential mediator of resistance in this organ. Targeting this pathway genetically or pharmacologically was sufficient to revert the WBRT resistance and increase therapeutic benefits in vivo at lower doses of radiation. In patients with primary melanoma, lung or breast adenocarcinoma developing brain metastasis, endogenous S100A9 levels in brain lesions correlated with clinical response to WBRT and underscored the potential of S100A9 levels in the blood as a noninvasive biomarker. Collectively, we provide a molecular framework to personalize WBRT and improve its efficacy through combination with a radiosensitizer that balances therapeutic benefit and toxicity.

Tratamiento conservador del adenosarcoma mülleriano de cérvix uterino / Conservative treatment of a müllerian adenosarcoma of the uterine cervix

El adenosarcoma mülleriano de cérvix es un tumor muy poco frecuente que aparece generalmente en mujeres jóvenes, como un pólipo cervical sangrante, con tendencia a la recurrencia local debido a su bajo potencial de malignidad. No está claro cuál es su tratamiento óptimo, pero en casos seleccionados se puede realizar tratamiento conservador para preservar la fertilidad de la mujer, destacando la importancia del seguimiento clínico prolongado. Presentamos el caso de un adenosarcoma mülleriano de cérvix en una mujer de 19 años tratada con una conización extensa (AU)

Müllerian adenosarcoma of the cervix is a rare tumor that usually presents in young women as a bleeding cervical polyp. There is a tendency for local recurrence due to their low malignant potential. The optimal therapy for these tumors is uncertain but conservative treatment can be provided in selected patients to preserve female fertility. Long-term follow-up is of paramount importance. We present the case of a 19-year-old girl who was diagnosed with a Müllerian adenosarcoma of the uterine cervix treated with a wide cervical conization (AU)

Primeros resultados de la disección del ganglio centinela en los carcinomas epidermoides vulvares / First results in the sentinel lymph node procedure in vulvar squamous cell carcinoma

Objetivos: Conocer nuestros primeros resultados en la disección selectiva del ganglio centinela en el cáncer de vulva, en cuanto a tasa de detección del ganglio, casos de falsos negativos y su relación con la recidiva tumoral o no. Material y métodos: Estudio retrospectivo de los primeros 9 casos de ganglio centinela en carcinomas epidermoides vulvares, realizado entre junio de 2004 y diciembre de 2007. Resultados: Se detectó el ganglio centinela en 8 de las 9 pacientes; la tasa de detección fue del 88,8%. No hubo ningún caso de falso negativo, por lo que el valor predictivo negativo de la técnica fue del 100%. Solamente una paciente con ganglio centinela negativo ha fallecido por cáncer de vulva; esta mujer estaba afectada por anemia de Fanconi. Conclusiones: La técnica del ganglio centinela en los carcinomas epidermoides vulvares es factible y puede ser una alternativa a la linfadenectomía inguinofemoral convencional (AU)

Objective: The aim was to analyse our first results in the sentinel lymph node procedure in vulvar cancer, as regards the detection rate, false negative cases and relation with cancer recurrence or not. Material and methods: Retrospective study of first 9 cases of sentinel lymph node detection in vulvar squamous cell carcinoma, between June 2004 and December 2007. Results: We identified the sentinel node in 8 out of 9 patients (88% detection rate). There were no false negative cases, giving a negative predictive value of 100 %. Only one patient with a negative sentinel node died of vulvar cancer. She also had Fanconi anaemia. Conclusions: Sentinel lymph node detection in patients with squamous cell carcinoma of the vulva is feasible, and can be an alternative to conventional inguinofemoral lymphadenectomy (AU)