Predictores radiológicos del volumen final del infarto cerebral en pacientes con obstrucción vascular proximal / Radiological predictors of final infarct volume in patients with proximal vascular occlusion

Introducción: Múltiples variables clínicas y radiológicas están involucradas en el pronóstico neurológico de los pacientes con accidente cerebrovascular (ACV) isquémico. Alrededor del 30% de los ACV isquémicos son causados por la obstrucción vascular proximal del circuito anterior; en estos casos, la utilidad de la trombólisis sistémica es limitada. La angiotomografía está indicada en los pacientes que pueden ser candidatos a tratamiento endovascular. Diferentes factores radiológicos como el grado de colaterales leptomeníngeas, o el largo, la densidad o la extensión del trombo, fueron descritos como predictores del pronóstico neurológico tras un ACV isquémico con compromiso vascular proximal. El volumen final del infarto cerebral se correlaciona con la mortalidad y el grado funcional a largo plazo de estos pacientes. El propósito de este estudio es determinar los mejores predictores radiológicos del volumen final del infarto cerebral en pacientes con ACV isquémico con compromiso proximal, utilizando angiotomografía. Materiales y métodos: Realizamos un estudio observacional retrospectivo. Incluimos pacientes adultos con ACV isquémico causado por la obstrucción de un vaso proximal, diagnosticados mediante angiotomografía en el período de junio de 2009 a diciembre de 2019. Medimos la densidad y el largo del trombo en la adquisición sin contraste, registramos el grado de colaterales leptomeníngeas y la extensión del trombo utilizando el clot burden score. Luego medimos el volumen final del infarto en una tomografía de control y analizamos el grado de correlación entre estos factores radiológicos en el volumen infartado. Resultados: Incluimos 54 pacientes con ACV isquémico por compromiso vascular proximal; 41 (75%) fueron mujeres. La mediana de edad fue de 82 años. Alrededor del 60% de los ACV comprometieron el hemisferio derecho y el vaso más afectado fue el segmento M1 de la arteria cerebral media (40,7%)...(AU)

Introduction: Various clinical and radiologic variables impact the neurologic prognosis of patients with ischemic cerebrovascular accidents. About 30% of ischemic cerebrovascular accidents are caused by proximal obstruction of the anterior circulation; in these cases, systemic thrombolysis is of limited usefulness. CT angiography is indicated in candidates for endovascular treatment. Various radiologic factors, including the grade of leptomeningeal collateral circulation, as well as the length, density, and extension of the thrombus, have been identified as predictors of neurologic prognosis after anterior ischemic cerebrovascular accidents due to proximal vascular obstruction. Final infarct volume correlations with mortality and long-term functional outcome in these patients. This study aimed to determine the best predictors of final infarct volume on CT angiography in patients with ischemic cerebral accidents due to proximal occlusion. Materials and methods: This retrospective observational study included adults with ischemic cerebrovascular accidents due to obstruction of the anterior circulation diagnosed by CT angiography in the period comprising June 2009 through December 2019. We measured the length and density of the thrombus in unenhanced CT images, and we used the clot burden score to record the grade of leptomeningeal collateral circulation and the extension of the thrombus. Then we measured the final infarct volume on follow-up CT and analyzed the correlations among these radiologic factors in the infarct volume. Results: We included 54 patients [mean age, 82 y; 41 (75%) women] with ischemic cerebrovascular accidents due to proximal occlusion. About 60% of the cerebrovascular accidents affected the right cerebral hemisphere, and the most commonly affected vessel was the M1 segment of the medial cerebral artery (40.7%)...(AU)

Radiological predictors of final infarct volume in patients with proximal vascular occlusion.

INTRODUCTION: Various clinical and radiologic variables impact the neurologic prognosis of patients with ischemic cerebrovascular accidents. About 30% of ischemic cerebrovascular accidents are caused by proximal obstruction of the anterior circulation; in these cases, systemic thrombolysis is of limited usefulness. CT angiography is indicated in candidates for endovascular treatment. Various radiologic factors, including the grade of leptomeningeal collateral circulation, as well as the length, density, and extension of the thrombus, have been identified as predictors of neurologic prognosis after anterior ischemic cerebrovascular accidents due to proximal vascular obstruction. Final infarct volume correlations with mortality and long-term functional outcome in these patients. This study aimed to determine the best predictors of final infarct volume on CT angiography in patients with ischemic cerebral accidents due to proximal occlusion. MATERIALS AND METHODS: This retrospective observational study included adults with ischemic cerebrovascular accidents due to obstruction of the anterior circulation diagnosed by CT angiography in the period comprising June 2009 through December 2019. We measured the length and density of the thrombus in unenhanced CT images, and we used the clot burden score to record the grade of leptomeningeal collateral circulation and the extension of the thrombus. Then we measured the final infarct volume on follow-up CT and analyzed the correlations among these radiologic factors in the infarct volume. RESULTS: We included 54 patients [mean age, 82 y; 41 (75%) women] with ischemic cerebrovascular accidents due to proximal occlusion. About 60% of the cerebrovascular accidents affected the right cerebral hemisphere, and the most commonly affected vessel was the M1 segment of the medial cerebral artery (40.7%). Final infarct volume correlated with the grade of leptomeningeal collateral circulation (p=0.03) and with the clot burden score (p=0.01). Neither the length nor the density of the thrombus correlated with final infarct volume. CONCLUSION: The final infarct volume can be estimated on the initial CT angiogram. Nevertheless, we found no useful predictive factors in unenhanced CT images. The best independent radiologic predictors of the final infarct volume are the grade of collateral circulation and the clot burden score, especially in patients who did not undergo mechanical thrombectomy, because mechanical thrombectomy improves outcomes. These factors are important for decision making in the management of patients with ischemic cerebrovascular accidents due to proximal occlusion.

Leptomeningeal metastasis from solid tumours: EANO-ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up

These joint European Association of Neuro-Oncology (EANO)­European Society for Medical Oncology (ESMO) recommendations for the diagnosis and treatment of leptomeningeal metastasis (LM) from solid tumours provide an update of the first joint EANO­ESMO guideline1 and complement the EANO­ESMO guideline on brain metastasis from solid tumours.2 LM is defined as the spread of tumour cells within the leptomeninges and the subarachnoid space. The present recommendations address LM from extra-central nervous system (CNS) solid tumours, but do not address LM from primary brain tumours, lymphoma or leukaemia. The recommendations cover diagnosis, treatment and follow-up, but do not cover the differential diagnosis, treatment-related adverse events (AEs) or supportive or palliative care in detail. The authors propose diagnostic criteria and assign levels of certainty to the diagnosis of LM in order to provide guidance regarding when to treat versus when to intensify diagnostic efforts and which patients to include in clinical trials. The authors also provide a pragmatic treatment algorithm based on LM subtypes. Supporting evidence for this guideline focuses on LM-specific data with reference to the EANO­ESMO guideline on brain metastasis from solid tumours2 when LM-specific data are not available. Given the low level of evidence available, recommendations are often based on expert opinion and consensus rather than on evidence from informative clinical trials. Still, these EANO­ESMO multidisciplinary recommendations serve as a valuable source of information for physicians and other health care providers, as well as for patients and relatives.

Phase I, first-in-human study of MSC-1 (AZD0171), a humanized anti-leukemia inhibitory factor monoclonal antibody, for advanced solid tumors.

BACKGROUND: Activation of leukemia inhibitory factor (LIF) is linked to an immunosuppressive tumor microenvironment (TME), with a strong association between LIF expression and tumor-associated macrophages (TAMs). MSC-1 (AZD0171) is a humanized monoclonal antibody that binds with high affinity to LIF, promoting antitumor inflammation through TAM modulation and cancer stem cell inhibition, slowing tumor growth. In this phase I, first-in-human, open-label, dose-escalation study, MSC-1 monotherapy was assessed in patients with advanced, unresectable solid tumors. MATERIALS AND METHODS: Using accelerated-titration dose escalation followed by a 3 + 3 design, MSC-1 doses of 75-1500 mg were administered intravenously every 3 weeks (Q3W) until progression or unmanageable toxicity. Additional patients were enrolled in selected cohorts to further evaluate safety, pharmacokinetics (PK), and pharmacodynamics after escalation to the next dose had been approved. The primary objective was characterizing safety and determining the recommended phase II dose (RP2D). Evaluating antitumor activity and progression-free survival (PFS) by RECIST v1.1, PK and immunogenicity were secondary objectives. Exploratory objectives included pharmacodynamic effects on circulating LIF and TME immune markers. RESULTS: Forty-one patients received treatment. MSC-1 monotherapy was safe and well tolerated at all doses, with no dose-limiting toxicities. The maximum tolerated dose was not reached and the RP2D was determined to be 1500 mg Q3W. Almost half of the patients had treatment-related adverse events (TRAEs), with no apparent trends across doses; no patients withdrew due to TRAEs. There were no objective responses; 23.7% had stable disease for ≥2 consecutive tumor assessments. Median PFS was 5.9 weeks; 23.7% had PFS >16 weeks. On-treatment changes in circulating LIF and TME signal transducers and activators of transcription 3 signaling, M1:M2 macrophage populations, and CD8+ T-cell infiltration were consistent with the hypothesized mechanism of action. CONCLUSIONS: MSC-1 was very well tolerated across doses, with prolonged PFS in some patients. Biomarker and preclinical data suggest potential synergy with checkpoint inhibitors.

ESMO recommendations on the use of circulating tumour DNA assays for patients with cancer: a report from the ESMO Precision Medicine Working Group.

Circulating tumour DNA (ctDNA) assays conducted on plasma are rapidly developing a strong evidence base for use in patients with cancer. The European Society for Medical Oncology convened an expert working group to review the analytical and clinical validity and utility of ctDNA assays. For patients with advanced cancer, validated and adequately sensitive ctDNA assays have utility in identifying actionable mutations to direct targeted therapy, and may be used in routine clinical practice, provided the limitations of the assays are taken into account. Tissue-based testing remains the preferred test for many cancer patients, due to limitations of ctDNA assays detecting fusion events and copy number changes, although ctDNA assays may be routinely used when faster results will be clinically important, or when tissue biopsies are not possible or inappropriate. Reflex tumour testing should be considered following a non-informative ctDNA result, due to false-negative results with ctDNA testing. In patients treated for early-stage cancers, detection of molecular residual disease or molecular relapse, has high evidence of clinical validity in anticipating future relapse in many cancers. Molecular residual disease/molecular relapse detection cannot be recommended in routine clinical practice, as currently there is no evidence for clinical utility in directing treatment. Additional potential applications of ctDNA assays, under research development and not recommended for routine practice, include identifying patients not responding to therapy with early dynamic changes in ctDNA levels, monitoring therapy for the development of resistance mutations before clinical progression, and in screening asymptomatic people for cancer. Recommendations for reporting of results, future development of ctDNA assays and future clinical research are made.

Cambios en el examen clínico objetivo y estructurado (ECOE) de las facultades de Medicina durante la COVID-19. Experiencia de una ECOE de casos-clínicos computarizados simulados (ECOE-CCS) conjunta / Changes in the Objective Structured Clinical Examination (OSCE) of University Schools of Medicine during COVID-19. Experience with a computer-based case simulation OSCE (CCS-OSCE)

Antecedentes y objetivos La pandemia de la COVID-19 ha obligado a completar los estudios universitarios online. La Conferencia Nacional de Decanos de Facultades de Medicina coordina una prueba de evaluación de competencias clínicas objetiva y estructurada (ECOE) de 20 estaciones presenciales a los estudiantes de sexto del grado. Como consecuencia de la pandemia se ha diseñado una ECOE sustitutoria con casos-clínicos computarizados simulados (ECOE-CCS). El objetivo del artículo es describir la elaboración, la ejecución y el desarrollo de la prueba. Materiales y métodos Estudio descriptivo de la ECOE-CCS conjunta desde su gestación en abril 2020 hasta su ejecución en junio 2020. Resultados La ECOE-CCS evaluó las competencias de anamnesis, exploración, juicio clínico, aspectos éticos, relaciones interprofesionales, prevención y promoción de la salud. No se evaluaron habilidades técnicas ni de comunicación. La ECOE-CCS consistió en 10 estaciones de 12 minutos de duración, con un número de preguntas de seis a 21 (media: 1,1 minutos/pregunta). En la ECOE-CCS se utilizó la plataforma virtual del campus de cada una de las 16 facultades de Medicina que participaron, con un total de 2.829 estudiantes de sexto curso. Se realizó de una forma conjunta en dos fechas de junio del 2020. Conclusiones La experiencia de la ECOE-CCS permitió llevar a cabo una integración y el trabajo interdisciplinar de las diferentes facultades de Medicina. La ECOE-CCS realizada podría asemejarse al Step 3 CCS de la United States Medical Licensing Examination (AU)

Background and objectives The COVID-19 pandemic has forced universities to move the completion of university studies online. Spain's National Conference of Medical School Deans coordinates an objective, structured clinical competency assessment called the Objective Structured Clinical Examination (OSCE), which consists of 20 face-to-face test sections for students in their sixth year of study. As a result of the pandemic, a computer-based case simulation OSCE (CCS-OSCE) has been designed. The objective of this article is to describe the creation, administration, and development of the test. Materials and methods This work is a descriptive study of the CCS-OSCE from its planning stages in April 2020 to its administration in June 2020. Results The CCS-OSCE evaluated the competences of anamnesis, exploration, clinical judgment, ethical aspects, interprofessional relations, prevention, and health promotion. No technical or communication skills were evaluated. The CCS-OSCE consisted of ten test sections, each of which had a 12-minutes time limit and ranged from six to 21 questions (mean: 1.1 minutes/question). The CCS-OSCE used the virtual campus platform of each of the 16 participating medical schools, which had a total of 2,829 students in their sixth year of study. It was jointly held on two dates in June 2020. Conclusions The CCS-OSCE made it possible to bring together the various medical schools and carry out interdisciplinary work. The CCS-OSCE conducted may be similar to Step 3 of the United States Medical Licensing Examination (AU)

Changes in the Objective Structured Clinical Examination (OSCE) of University Schools of Medicine during COVID-19. Experience with a computer-based case simulation OSCE (CCS-OSCE).

BACKGROUND AND OBJECTIVES: The COVID-19 pandemic has forced universities to move the completion of university studies online. Spain's National Conference of Medical School Deans coordinates an objective, structured clinical competency assessment called the Objective Structured Clinical Examination (OSCE), which consists of 20 face-to-face test sections for students in their sixth year of study. As a result of the pandemic, a computer-based case simulation OSCE (CCS-OSCE) has been designed. The objective of this article is to describe the creation, administration, and development of the test. MATERIALS AND METHODS: This work is a descriptive study of the CCS-OSCE from its planning stages in April 2020 to its administration in June 2020. RESULTS: The CCS-OSCE evaluated the competences of anamnesis, exploration, clinical judgment, ethical aspects, interprofessional relations, prevention, and health promotion. No technical or communication skills were evaluated. The CCS-OSCE consisted of ten test sections, each of which had a 12-min time limit and ranged from six to 21 questions (mean: 1.1 min/question). The CCS-OSCE used the virtual campus platform of each of the 16 participating medical schools, which had a total of 2829 students in their sixth year of study. It was jointly held on two dates in June 2020. CONCLUSIONS: The CCS-OSCE made it possible to bring together the various medical schools and carry out interdisciplinary work. The CCS-OSCE conducted may be similar to Step 3 of the United States Medical Licensing Examination.

Oral cancer awareness in North-Western Spain: a population-based study.

BACKGROUND: An early diagnosis depends greatly on patient awareness. Thus, the aim of this study was to investigate general awareness of oral cancer and knowledge about its risk factors, signs and symptoms. MATERIAL AND METHODS: Cross-sectional population-based survey of randomly selected respondents conducted from March 1, 2015 to 30 June 2016. RESULTS: A total of 5,727 people entered the survey (response rate: 53%). When asked what cancers participants had heard about, 20.3% mentioned oral cancer. Regarding risk factors, tobacco was mentioned by 55.3% of the sample (n=3,169), followed by alcohol (12.5%; n=708), poor oral hygiene (10.8%; n=618), diet (6.5%; n=377), and genetics (4.5%; n=248). CONCLUSIONS: General population has low awareness of oral cancer with poor knowledge of risk factors and main alarm signs. In addition, individuals in the risk group scored lower values in the main variables analysed; even those highly educated showed insufficient awareness and knowledge of oral cancer. In these circumstances, there is clear need for educational interventions tailored to the target audience and aimed at increasing knowledge and awareness of oral cancer to promote primary prevention of oral cancer and minimising the time interval of patients with symptomatic oral cancer in their path to treatment.

[Changes in the Objective Structured Clinical Examination (OSCE) of University Schools of Medicine during COVID-19. Experience with a computer-based case simulation OSCE (CCS-OSCE)]. / Cambios en el examen clínico objetivo y estructurado (ECOE) de las facultades de Medicina durante la COVID-19. Experiencia de una ECOE de casos-clínicos computarizados simulados (ECOE-CCS) conjunta.

BACKGROUND AND OBJECTIVES: The COVID-19 pandemic has forced universities to move the completion of university studies online. Spain's National Conference of Medical School Deans coordinates an objective, structured clinical competency assessment called the Objective Structured Clinical Examination (OSCE), which consists of 20 face-to-face test sections for students in their sixth year of study. As a result of the pandemic, a computer-based case simulation OSCE (CCS-OSCE) has been designed. The objective of this article is to describe the creation, administration, and development of the test. MATERIALS AND METHODS: This work is a descriptive study of the CCS-OSCE from its planning stages in April 2020 to its administration in June 2020. RESULTS: The CCS-OSCE evaluated the competences of anamnesis, exploration, clinical judgment, ethical aspects, interprofessional relations, prevention, and health promotion. No technical or communication skills were evaluated. The CCS-OSCE consisted of ten test sections, each of which had a 12-minutes time limit and ranged from six to 21 questions (mean: 1.1 minutes/question). The CCS-OSCE used the virtual campus platform of each of the 16 participating medical schools, which had a total of 2,829 students in their sixth year of study. It was jointly held on two dates in June 2020. CONCLUSIONS: The CCS-OSCE made it possible to bring together the various medical schools and carry out interdisciplinary work. The CCS-OSCE conducted may be similar to Step 3 of the United States Medical Licensing Examination.

Delay-induced resonance suppresses damping-induced unpredictability.

Combined effects of the damping and forcing in the underdamped time-delayed Duffing oscillator are considered in this paper. We analyse the generation of a certain damping-induced unpredictability due to the gradual suppression of interwell oscillations. We find the minimal amount of the forcing amplitude and the right forcing frequency to revert the effect of the dissipation, so that the interwell oscillations can be restored, for different time delay values. This is achieved by using the delay-induced resonance, in which the time delay replaces one of the two periodic forcings present in the vibrational resonance. A discussion in terms of the time delay of the critical values of the forcing for which the delay-induced resonance can tame the dissipation effect is finally carried out. This article is part of the theme issue 'Vibrational and stochastic resonance in driven nonlinear systems (part 1)'.

Transient chaos under coordinate transformations in relativistic systems.

We use the Hénon-Heiles system as a paradigmatic model for chaotic scattering to study the Lorentz factor effects on its transient chaotic dynamics. In particular, we focus on how time dilation occurs within the scattering region by measuring the time with a clock attached to the particle. We observe that the several events of time dilation that the particle undergoes exhibit sensitivity to the initial conditions. However, the structure of the singularities appearing in the escape time function remains invariant under coordinate transformations. This occurs because the singularities are closely related to the chaotic saddle. We then demonstrate using a Cantor-like set approach that the fractal dimension of the escape time function is relativistic invariant. In order to verify this result, we compute by means of the uncertainty dimension algorithm the fractal dimensions of the escape time functions as measured with an inertial frame and a frame comoving with the particle. We conclude that, from a mathematical point of view, chaotic transient phenomena are equally predictable in any reference frame and that transient chaos is coordinate invariant.

Clinical development of therapies targeting TGFß: current knowledge and future perspectives.

Transforming growth factor beta (TGFß) is a pleiotropic cytokine that plays a key role in both physiologic and pathologic conditions, including cancer. Importantly, TGFß can exhibit both tumor-suppressive and oncogenic functions. In normal epithelial cells TGFß acts as an antiproliferative and differentiating factor, whereas in advanced tumors TGFß can act as an oncogenic factor by creating an immune-suppressive tumor microenvironment, and inducing cancer cell proliferation, angiogenesis, invasion, tumor progression, and metastatic spread. A wealth of preclinical findings have demonstrated that targeting TGFß is a promising means of exerting antitumor activity. Based on this rationale, several classes of TGFß inhibitors have been developed and tested in clinical trials, namely, monoclonal, neutralizing, and bifunctional antibodies; antisense oligonucleotides; TGFß-related vaccines; and receptor kinase inhibitors. It is now >15 years since the first clinical trial testing an anti-TGFß agent was engaged. Despite the promising preclinical studies, translation of the basic understanding of the TGFß oncogenic response into the clinical setting has been slow and challenging. Here, we review the conclusions and status of all the completed and ongoing clinical trials that test compounds that inhibit the TGFß pathway, and discuss the challenges that have arisen during their clinical development. With none of the TGFß inhibitors evaluated in clinical trials approved for cancer therapy, clinical development for TGFß blockade therapy is primarily oriented toward TGFß inhibitor combinations. Immune checkpoint inhibitors are considered candidates, albeit with efficacy anticipated to be restricted to specific populations. In this context, we describe current efforts in the search for biomarkers for selecting the appropriate cancer patients who are likely to benefit from anti-TGFß therapies. The knowledge accumulated during the last 15 years of clinical research in the context of the TGFß pathway is crucial to design better, innovative, and more successful trials.

People would rather see a physician than a dentist when experiencing a long-standing oral ulceration. A population-based study in Spain.

BACKGROUND: Primary care physicians have been reported to be the first choice for patients with oral ulcerations. This study investigates the health-seeking behaviour of lay public in Galicia (North-western Spain) if experiencing a long-standing oral ulceration. MATERIAL AND METHODS: Cross-sectional population-based survey of randomly selected respondents conducted from March 1, 2015 to 30 June 2016. RESULTS: A total of 5,727 pedestrians entered the study (response rate: 53%), mostly in the 45-64 age group (30.2%; n=1,728), 47.7% of them (n=2,729) were males. Most participants (42.1%; n=2,411) reported to visit their dentist once a year and had secondary or compulsory education as their highest educational achievement (28.18%, n=1,614; 28%, n=1,600 respectively). When questioned what they would do if they had a wound/ulceration lasting longer than 3 weeks, most participants answered they would go to see their primary care physician (62.8%; n=3,597) and less than one quarter of the sample (23.8%; n=1,371) would seek consultation with their dentist. CONCLUSIONS: General Galician population would seek professional consultation about a long-standing oral ulceration, relying mostly on primary care physicians. Those neglecting these lesions are elderly, less-schooled people and unaware of oral cancer.

Strategies of analgesic treatment after cesarean delivery. Current state and new alternatives. / Estrategias de tratamiento analgésico tras cesárea. Estado actual y nuevas alternativas.

The number of caesarean sections performed worldwide is increasing, and with it, the need for the optimal analgesia strategies. Deficient postoperative analgesia increases the need for opioids, delays recovery, and is associated with chronic pain and postpartum depression. It is essential to find good postoperative pain control strategies that facilitate early mobility, early recovery, and early hospital discharge with minimal side effects on the mother and infant. Multimodal analgesia based on neuroaxial anaesthesia with morphine in combination with non-opioids such as non-steroidal anti-inflammatory drugs and paracetamol, gives the best post-caesarean analgesia outcome, and allows anaesthesiologists to reserve opioids, corticoids, gabapentin, magnesium or ketamine for situations where neuroaxial anaesthesia cannot be performed, for high-risk patients, or when pain is difficult to control. Peripheral nerve block techniques can also be added, such as transverse abdominis plane block, erector spinae block, or continuous wound infiltration.

How liquid biopsies can change clinical practice in oncology.

Cell-free DNA fragments are shed into the bloodstream by tumor cells. The analysis of circulating tumor DNA (ctDNA), commonly known as liquid biopsy, can be exploited for a variety of clinical applications. ctDNA is being used to genotype solid cancers non-invasively, to track tumor dynamics and to detect the emergence of drug resistance. In a few settings, liquid biopsies have already entered clinical practice. For example, ctDNA is used to guide treatment in a subset of lung cancers. In this review, we discuss how recent improvements in the sensitivity and accuracy of ctDNA analyses have led to unprecedented advances in this research field. We further consider what is required for the routine deployment of liquid biopsies in the clinical diagnostic space. We pinpoint technical hurdles that liquid biopsies have yet to overcome, including preanalytical and analytical challenges. We foresee how liquid biopsies will transform clinical practice: by complementing (or replacing) imaging to monitor treatment response and by detecting minimal residual disease after surgery with curative intent.

Cerebrospinal fluid cell-free tumour DNA as a liquid biopsy for primary brain tumours and central nervous system metastases.

Challenges in obtaining tissue specimens from patients with brain tumours limit the diagnosis and molecular characterisation and impair the development of better therapeutic approaches. The analysis of cell-free tumour DNA in plasma (considered a liquid biopsy) has facilitated the characterisation of extra-cranial tumours. However, cell-free tumour DNA in plasma is limited in quantity and may not reliably capture the landscape of genomic alterations of brain tumours. Here, we review recent work assessing the relevance of cell-free tumour DNA from cerebrospinal fluid in the characterisation of brain cancer. We focus on the advances in the use of the cerebrospinal fluid as a source of cell-free tumour DNA to facilitate diagnosis, reveal actionable genomic alterations, monitor responses to therapy, and capture tumour heterogeneity in patients with primary brain tumours and brain and leptomeningeal metastases. Profiling cerebrospinal fluid cell-free tumour DNA provides the opportunity to precisely acquire and monitor genomic information in real time and guide precision therapies.