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Hypertension as predictive factor for bevacizumab-containing first-line therapy in metastatic breast and colorectal cancer in BRECOL (GEICAM/2011-04) study.
No full textRetrospective data suggest an association between bevacizumab efficacy and the incidence of arterial hypertension (AHT). Additionally, epigenetic mechanisms have been related to AHT. This prospective observational study conducted by GEICAM Spanish Breast Cancer Research Group included metastatic breast (MBC) or colorectal (mCRC) cancer patients treated with bevacizumab-containing chemotherapy as first-line treatment. Blood pressure (BP) levels were measured (conventional and 24-h Holter monitoring) at baseline and up to cycle 3. Primary endpoint assessed BP levels increase as predictive factor for progression-free survival (PFS). Germline DNA methylation profile was explored in pre-treatment blood samples; principal component analysis was used to define an epigenetic predictive score for increased BP levels. From Oct-2012 to Jul-2016, 143 (78 MBC and 65 mCRC) patients were included. The incidence of AHT according to guidelines was neither predictive of PFS nor of best overall tumor response (BOR). No statistically significant association was observed with systolic BP nor diastolic BP increment for PFS or BOR. Grade 3 and 4 adverse events were observed in 37 and 5% of patients, respectively. We identified 27 sites which baseline methylation status was significantly associated to BP levels increase secondary to bevacizumab-containing chemotherapy. Neither the frequency of AHT nor the increase of BP levels were predictive of efficacy in MBC and mCRC patients treated with bevacizumab-containing chemotherapy. ClinicalTrials.gov Identifier: NCT01733628
Cardiovascular Considerations Before Cancer Therapy: Gaps in Evidence and JACC: CardioOncology Expert Panel Recommendations.
No full text20.500.12530/87857Baseline cardiovascular assessment before the initiation of potentially cardiotoxic cancer therapies is a key component of cardio-oncology, aiming to reduce cardiovascular complications and morbidity in patients and survivors. Recent clinical practice guidelines provide both general and cancer therapy-specific recommendations for baseline cardiovascular toxicity risk assessment and management, including the use of dedicated risk scores, cardiovascular imaging, and biomarker testing. However, the value of such interventions in altering disease trajectories has not been established, with many recommendations based on expert opinion or Level of Evidence: C, studies with a potential for high risk of bias. Advances in understanding underlying mechanisms of cardiotoxicity and the increased availability of genetic and immunologic profiling present new opportunities for personalized risk assessment. This paper evaluates the existing evidence on cardiovascular care of cancer patients before cardiotoxic cancer therapy and highlights gaps in evidence and priorities for future research
Standardizing Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer Treatment: Navigating Complexities and Charting the Path Forward.
No full text20.500.12530/87857The incorporation of hyperthermic intraperitoneal chemotherapy (HIPEC) into the treatment landscape for ovarian cancer has invoked a spectrum of emotions, ranging from enthusiastic anticipation to cautious skepticism [...]
Chromosomal breaks: another differential gap between early-onset and late-onset colorectal cancers
No full text20.500.12530/8789
Palbociclib and letrozole for hormone receptor-positive HER2-negative breast cancer with residual disease after neoadjuvant chemotherapy.
No full text20.500.12530/87871With the incorporation of cyclin-dependent kinase inhibitors in early breast cancer (BC), a better identification of biomarkers is needed. The PROMETEO II trial aimed to evaluate the antitumor activity of palbociclib plus letrozole and to identify response biomarkers in patients with operable HR+/HER2- BC and residual disease after neoadjuvant chemotherapy (NAC). The primary endpoint was the rate of complete cell cycle arrest (CCCA), centrally determined by Ki67 ≤ 2.7% at surgery. A comprehensive translational analysis was conducted. At surgery, the CCCA rate was 59.1%, with a 44.2% decrease in Ki67 from the end of NAC. Changes in intrinsic subtypes occurred in 48% of patients, with proliferation genes suppressed, and immune genes more upregulated in tumors with CCCA. Overall, 14% of tumors were classified as PD-L1+ after palbociclib. Nine patients experienced grade 3 adverse events (AEs). Palbociclib showed an anti-proliferative effect, with increased immune infiltration in residual tumors with CCCA.Trial registration: Palbociclib Plus Letrozole in Hormone Receptor Positive Residual Disease After Neoadjuvant Chemotherapy (PROMETEO II) ClinicalTrial.gov number NCT04130152. Study registration; October 17, 2019
Surprising and novel multivariate sequential patterns using odds ratio for temporal evolution in healthcare
No full textBackground Pattern mining techniques are helpful tools when extracting new knowledge in real practice, but the overwhelming number of patterns is still a limiting factor in the health-care domain. Current efforts concerning the definition of measures of interest for patterns are focused on reducing the number of patterns and quantifying their relevance (utility/usefulness). However, although the temporal dimension plays a key role in medical records, few efforts have been made to extract temporal knowledge about the patient's evolution from multivariate sequential patterns.Methods In this paper, we propose a method to extract a new type of patterns in the clinical domain called Jumping Diagnostic Odds Ratio Sequential Patterns (JDORSP). The aim of this method is to employ the odds ratio to identify a concise set of sequential patterns that represent a patient's state with a statistically significant protection factor (i.e., a pattern associated with patients that survive) and those extensions whose evolution suddenly changes the patient's clinical state, thus making the sequential patterns a statistically significant risk factor (i.e., a pattern associated with patients that do not survive), or vice versa.Results The results of our experiments highlight that our method reduces the number of sequential patterns obtained with state-of-the-art pattern reduction methods by over 95%. Only by achieving this drastic reduction can medical experts carry out a comprehensive clinical evaluation of the patterns that might be considered medical knowledge regarding the temporal evolution of the patients. We have evaluated the surprisingness and relevance of the sequential patterns with clinicians, and the most interesting fact is the high surprisingness of the extensions of the patterns that become a protection factor, that is, the patients that recover after several days of being at high risk of dying.Conclusions Our proposed method with which to extract JDORSP generates a set of interpretable multivariate sequential patterns with new knowledge regarding the temporal evolution of the patients. The number of patterns is greatly reduced when compared to those generated by other methods and measures of interest. An additional advantage of this method is that it does not require any parameters or thresholds, and that the reduced number of patterns allows a manual evaluation
New systemic treatment paradigms in resectable non-small cell lung cancer and variations in patient access across Europe.
No full text20.500.12530/87909The treatment landscape of resectable early-stage non-small cell lung cancer (NSCLC) is set to change significantly due to encouraging results from randomized trials evaluating neoadjuvant and adjuvant immunotherapy, as well as adjuvant targeted therapy. As of January 2024, marketing authorization has been granted for four new indications in Europe, and regulatory approvals for other study regimens are expected. Because cost-effectiveness and reimbursement criteria for novel treatments often differ between European countries, access to emerging developments may lead to inequalities due to variations in recommended and available lung cancer care throughout Europe. This Series paper (i) highlights the clinical studies reshaping the treatment landscape in resectable early-stage NSCLC, (ii) compares and contrasts approaches taken by the European Medicines Agency (EMA) for drug approval to that taken by the United States Food and Drug Administration (FDA), and (iii) evaluates the differences in access to emerging treatments from an availability perspective across European countries
Superior semicircular canal dehiscence in relation with the superior petrosal sinus: our experience, surgical management and systematic review of literature.
No full text20.500.12530/87858Most of Superior Semicircular Canal Dehiscence (SSCD) are located in the apical region of the SSC. However, in a small number of cases, it may be situated in the medial wall, causing the SSC to contact with the superior petrosal sinus (SPS). The aim of this study is to describe four patients with SSCD involving the superior petrosal sinus (SSCD-SPS) and to perform a review of the literature. Observational retrospective study of patients diagnosed of SSCD-SPS in a tertiary referral center. A systematic review was made, identifying 7 articles in the literature. Clinical presentation, complementary test (pure-tone audiometry, PTA; vestibular evoked myogenic potential, VEMP; computed tomography, CT), therapeutic management and outcomes were reported. Four new cases of SSCD-SPS are reported, in three of them a transmastoid plugging was performed. 54 patients with SSCD-SPS (57 dehiscences) were reported in the literature. The most frequent symptoms were aural pressure (57.41%) and vertigo provoked by pressure/Valsalva (55.55%). Conductive hearing loss was the most common finding in PTA (47.37%). Abnormally low thresholds were observed in 59.46% of reported VEMP. Transmastoid approach was used in ten cases, middle fossa approach in four, round window reinforcement in one, and occlusion of the SPS using coils in two. Within SSCD, we have encountered a rare subtype characterized by its medial wall location in close proximity to the SPS. This subgroup needs special consideration as it has shown its own distinct characteristics. Regarding therapeutic management, we advocate a transmastoid approach
Socioeconomic Patterns in the Frequency of Doctor Visits in Germany and Spain in Subjects With and Without Chronic Diseases.
No full textThe objective of universal health care systems is to achieve equality in the use of health services at the same level of care need. This study evaluates the relationship of socioeconomic position with the frequency of doctor visits in subjects with and without chronic diseases in Germany and Spain. The dependent variables included number of consultations and if a medical consultation occurred. The socioeconomic factors were income and education. The magnitude of the relationship between socioeconomic position and medical consultation frequency was estimated by calculating the percentage ratio using binomial regression and by calculating the difference in consultations by analysis of the covariance, in the case of number of visits. Statistically significant findings according to education were not observed. The percentage ratio in the medical consultations among those with lower and higher income was 1.03 (95% confidence interval [CI] 1.01-2.88) in Germany and 1.11 (95% CI 1.03-1.20) in Spain among subjects with any of the studied chronic conditions. Also, in Germany the difference in the average number of consultations comparing lower income subjects with higher was 3.98 (95% CI 2.40-5.57) in those with chronic conditions. In both countries, there were no differences in the frequency of doctor visits according to education. However, a pro-inequality trend exists in favor of subjects with lower income
Role of VV ECMO tracheal surgery and carinal resection: Two case reports.
No full text20.500.12530/87909The aim of this study is to describe the anaesthesia management of two patients undergoing carinal resection under veno-venous extracorporeal membrane oxygenation (VV ECMO). In both cases, anaesthesia was induced and then maintained with inhalational agents during pneumonectomy and mediastinoscopy (respectively). Then the jugular and femoral veins were cannulated and VV ECMO was started after heparinization. One of the patients presented bleeding during surgery, which was treated with low-dose vasopressors (norepinephrine) and transfusion of platelets, fresh frozen plasma, and concentrated red blood cells. During VV ECMO, anaesthesia was maintained with target-controlled infusion of propofol. VV ECMO can be expected to improve surgical conditions in tracheal surgery; however, it is still a novel technique in this context. In selected patients, it would guarantee ventilatory support during carinal resection, but it is essential to carefully plan anaesthesia maintenance and prepare for VV ECMO-related complications. This technique should only be used in tertiary centres with experience in VV ECMO management