Increasing Annual Cancer Incidence in Patients Age 20-49 Years: A Real-Data Study.

PURPOSE: Data from population-based studies have shown an increased incidence of certain types of neoplasms in patients younger than 50 years (early-onset cancer [EOC]); however, little information is derived from other real-world data sources. In a nonpopulation registry, we analyzed changes in the incidence of several neoplasms in successive generations. METHODS: This cross-sectional study included all patients with a cancer diagnosis registered in one university hospital in Málaga, Spain, between 1998 and 2021, and 18 neoplasms were analyzed. For each neoplasm, the proportion of patients younger than 50 years and age 50 years and older (late-onset cancer [LOC]) of the total number of patients diagnosed each year was determined. In addition, the age limit was lowered to 45-40 years. Changes in these proportions between each year and the following year were assessed by calculating the annual percentage change (APC), and a final assessment of these changes was performed by determining the average APC (AAPC). RESULTS: Of the 24,596 patients, 5,466 (22.2%) had EOC, and 19,130 (77.8%) had LOC. The incidence of all tumors increased throughout the study period in both age groups. The AAPC increase was higher in patients with EOC than in those with LOC for the following neoplasms: head and neck (6.1% v 4.6%), colon (11.0% v 8.2%), testicular (16.3% v -13.1%), non-Hodgkin lymphoma (8.4% v 5.9%), rectum (16.1% v 6.8%), kidney (27.8% v 20.1%), and sarcoma (43.4% v 28.6%). This increase was confirmed in patients younger than 45 years and 40 years. CONCLUSION: Our results are consistent with the data published for most tumor sites analyzed. This global public health problem requires the utmost attention to decrease excess cancer in young patients.

Significance of clinical-immunological patterns and diagnostic yield of biopsies in microscopic polyangiitis and granulomatosis with polyangiitis.

BACKGROUND: Microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are the two major antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). OBJECTIVES: To characterize a homogenous AAV cohort and to assess the impact of clinicopathological profiles and ANCA serotypes on clinical presentation and prognosis. Clinical differences in GPA patients according to ANCA serotype and the diagnostic yield for vasculitis of biopsies in different territories were also investigated. RESULTS: This retrospective study (2000-2021) included 152 patients with AAV (77 MPA/75 GPA). MPA patients (96.1% myeloperoxidase [MPO]-ANCA and 2.6% proteinase 3 [PR3]-ANCA) presented more often with weight loss, myalgia, renal involvement, interstitial lung disease (ILD), cutaneous purpura, and peripheral nerve involvement. Patients with GPA (44% PR3-ANCA, 33.3% MPO, and 22.7% negative/atypical ANCA) presented more commonly with ear, nose, and throat and eye/orbital manifestations, more relapses, and higher survival than patients with MPA. GPA was the only independent risk factor for relapse. Poor survival predictors were older age at diagnosis and peripheral nerve involvement. ANCA serotypes differentiated clinical features in a lesser degree than clinical phenotypes. A mean of 1.5 biopsies were performed in 93.4% of patients in different territories. Overall, vasculitis was identified in 80.3% (97.3% in MPA and 61.8% in GPA) of patients. CONCLUSIONS: The identification of GPA presentations associated with MPO-ANCA and awareness of risk factors for relapse and mortality are important to guide proper therapeutic strategies in AAV patients. Biopsies of different affected territories should be pursued in difficult-to-diagnose patients based on their significant diagnostic yield.

An accessible deep learning tool for voxel-wise classification of brain malignancies from perfusion MRI.

Noninvasive differential diagnosis of brain tumors is currently based on the assessment of magnetic resonance imaging (MRI) coupled with dynamic susceptibility contrast (DSC). However, a definitive diagnosis often requires neurosurgical interventions that compromise patients' quality of life. We apply deep learning on DSC images from histology-confirmed patients with glioblastoma, metastasis, or lymphoma. The convolutional neural network trained on ∼50,000 voxels from 40 patients provides intratumor probability maps that yield clinical-grade diagnosis. Performance is tested in 400 additional cases and an external validation cohort of 128 patients. The tool reaches a three-way accuracy of 0.78, superior to the conventional MRI metrics cerebral blood volume (0.55) and percentage of signal recovery (0.59), showing high value as a support diagnostic tool. Our open-access software, Diagnosis In Susceptibility Contrast Enhancing Regions for Neuro-oncology (DISCERN), demonstrates its potential in aiding medical decisions for brain tumor diagnosis using standard-of-care MRI.

Evaluation of OMOP CDM, i2b2 and ICGC ARGO for supporting data harmonization in a breast cancer use case of a multicentric European AI project.

OBJECTIVE: Observational research in cancer poses great challenges regarding adequate data sharing and consolidation based on a homogeneous data semantic base. Common Data Models (CDMs) can help consolidate health data repositories from different institutions minimizing loss of meaning by organizing data into a standard structure. This study aims to evaluate the performance of the Observational Medical Outcomes Partnership (OMOP) CDM, Informatics for Integrating Biology & the Bedside (i2b2) and International Cancer Genome Consortium, Accelerating Research in Genomic Oncology (ICGC ARGO) for representing non-imaging data in a breast cancer use case of EuCanImage. METHODS: We used ontologies to represent metamodels of OMOP, i2b2, and ICGC ARGO and variables used in a cancer use case of a European AI project. We selected four evaluation criteria for the CDMs adapted from previous research: content coverage, simplicity, integration, implementability. RESULTS: i2b2 and OMOP exhibited higher element completeness (100% each) than ICGC ARGO (58.1%), while the three achieved 100% domain completeness. ICGC ARGO normalizes only one of our variables with a standard terminology, while i2b2 and OMOP use standardized vocabularies for all of them. In terms of simplicity, ICGC ARGO and i2b2 proved to be simpler both in terms of ontological model (276 and 175 elements, respectively) and in the queries (7 and 20 lines of code, respectively), while OMOP required a much more complex ontological model (615 elements) and queries similar to those of i2b2 (20 lines). Regarding implementability, OMOP had the highest number of mentions in articles in PubMed (130) and Google Scholar (1,810), ICGC ARGO had the highest number of updates to the CDM since 2020 (4), and i2b2 is the model with more tools specifically developed for the CDM (26). CONCLUSION: ICGC ARGO proved to be rigid and very limited in the representation of oncologic concepts, while i2b2 and OMOP showed a very good performance. i2b2's lack of a common dictionary hinders its scalability, requiring sites that will share data to explicitly define a conceptual framework, and suggesting that OMOP and its Oncology extension could be the more suitable choice. Future research employing these CDMs with actual datasets is needed.

Texture Analysis of the Apparent Diffusion Coefficient Focused on Contrast-Enhancing Lesions in Predicting Survival for Bevacizumab-Treated Patients with Recurrent Glioblastoma.

PURPOSE: Glioblastoma often recurs after treatment. Bevacizumab increases progression-free survival in some patients with recurrent glioblastoma. Identifying pretreatment predictors of survival can help clinical decision making. Magnetic resonance texture analysis (MRTA) quantifies macroscopic tissue heterogeneity indirectly linked to microscopic tissue properties. We investigated the usefulness of MRTA in predicting survival in patients with recurrent glioblastoma treated with bevacizumab. METHODS: We evaluated retrospective longitudinal data from 33 patients (20 men; mean age 56 ± 13 years) who received bevacizumab on the first recurrence of glioblastoma. Volumes of contrast-enhancing lesions segmented on postcontrast T1-weighted sequences were co-registered on apparent diffusion coefficient maps to extract 107 radiomic features. To assess the performance of textural parameters in predicting progression-free survival and overall survival, we used receiver operating characteristic curves, univariate and multivariate regression analysis, and Kaplan-Meier plots. RESULTS: Longer progression-free survival (>6 months) and overall survival (>1 year) were associated with lower values of major axis length (MAL), a lower maximum 2D diameter row (m2Ddr), and higher skewness values. Longer progression-free survival was also associated with higher kurtosis, and longer overall survival with higher elongation values. The model combining MAL, m2Ddr, and skewness best predicted progression-free survival at 6 months (AUC 0.886, 100% sensitivity, 77.8% specificity, 50% PPV, 100% NPV), and the model combining m2Ddr, elongation, and skewness best predicted overall survival (AUC 0.895, 83.3% sensitivity, 85.2% specificity, 55.6% PPV, 95.8% NPV). CONCLUSIONS: Our preliminary analyses suggest that in patients with recurrent glioblastoma pretreatment, MRTA helps to predict survival after bevacizumab treatment.

Evaluation of biometric formulas in the calculation of intraocular lens according to axial length and type of the lens.

To compare the accuracy of the modern biometric formulas in cataract surgery according to axial length and lens type. It is a Cross-sectional design from 365 patients who underwent cataract surgery. The SRK/T, Hoffer Q, Haigis, and Holladay I formulas were extracted from the IOLMaster 500 biometer. Barret formulas and the Kane were obtained from the online calculator. Patients are classified according to axial length (AL) into three groups: AL ≤ 22 mm, 22 < AL < 25 mm, and AL ≥ 25 mm. In addition, implanted intraocular lenses are classified as Monofocal, extended focus, and Multifocal. There are no significant differences between the formulas. In short, the Kane formula was more accurate than the other biometric formulas. Kane and SRK/T were the most accurate in monofocal lenses, with the lowest residual refractive error. The Holladay I formula obtained the lowest mean absolute error with the highest number of eyes with minimum residual ± 0.5Dp in the multifocal lenses in the 22 < AL < 25 mm eyes. In the long AL eyes, SRK/T and Kane's obtained the lowest mean absolute error and the best percentage of eyes with ± 0.5Dp of residual refractive error. There are no significant differences between the formulas. However Kane's formula has shown high accuracy, especially in short and long eyes with monofocal lenses.

Comparison of Iris-Claw Phakic Lens Implant versus Corneal Laser Techniques in High Myopia: A Five-Year Follow-Up Study.

Background. This study aimed to compare the efficacy and safety of Femto-LASIK, PRK, and Artiflex/Artisan phakic lens implantation in the surgical correction of myopia at different moments of postoperative follow-up; to propose a linear predictive model of visual acuity without correction at five years of refractive procedures; and to evaluate its validity. Methods. A retrospective observational analysis was performed. Patients were clinically reviewed after three months, one year, two years, and five years. Univariate and bivariate analyses and a multivariate linear regression model were performed. Results. Six hundred seventy-nine eyes were analyzed: 18.9% Artiflex, 2.8% Artisan, 42.3% Femto-LASIK, and 36.1% PRK. There were significant differences in effectiveness and safety after five years when comparing Artiflex/Artisan versus PRK and Femto-LASIK (p < 0.01). The linear regression model explained 30.32% of the patients' visual acuity variability after five years. Conclusions. PRK surgery, Femto-Lasik, and Artiflex/Artisan type phakic lens implantation are effective, safe, and predictable techniques with stable refractive results. Phakic lenses magnify myopic patients who improve their UCVA and BCVA. Concerning phakic lens implantation, corneal endothelial cells remain stable. The predictive model calculated that surgery with a phakic lens increased the UCVA result at five years, and surgery with PRK slightly decreased the long-term results.

Bilateral vocal fold paralysis after COVID-19 infection. Another neuro-invasive manifestation? Case series / Parálisis bilateral de cuerdas vocales tras infección por COVID-19. ¿Una manifestación neuroinvasiva? Serie de casos

Abstract The agent that causes the coronavirus disease (COVID-19), associated with the severe acute respiratory syndrome (SARS-CoV-2), produces a spectrum of symptoms that mainly affect the respiratory system, the central nervous system (CNS), the regulation of hemostasis and the immune system. Bilateral vocal fold paralysis (BVFP) is a condition of unknown incidence among infected patients, either because it is short-lived or because of the difficulty in establishing a direct cause to the virus. Viral infection has been described in the literature as a cause of BVFP and there is the suspicion that a proportion of the idiopathic cases are due to undiagnosed viral infections. Although the neurotropic mechanisms for SARS-CoV-2 remain unclear, there is strong evidence to ensure its neuroinvasive potential. The most frequent etiologies of BVFP are trauma, neoplasm, and neurological, but a viral origin should not be ruled out. Causality between COVID-19 and BVFP is plausible and will require further study in the short and long term. We present a case series that support and discuss the hypothesis under consideration.

Resumen El agente causal de la enfermedad por coronavirus (COVID-19), asociado a síndrome respiratorio agudo grave (SARS-CoV-2), genera un espectro de síntomas que afectan fundamentalmente el sistema respiratorio, el sistema nervioso central (SNC), la regulación hemostásica y el sistema inmune. La parálisis bilateral de cuerdas vocales (PBCV) es una entidad cuya incidencia en infectados se desconoce, bien porque no se presentan durante el tiempo suficiente o por la dificultad de establecer una causalidad directa con el virus. La infección vírica, como causa de PBCV, está descrita en la literatura y se sospecha que una parte de los casos idiopáticos corresponden a infecciones víricas no diagnosticadas. Aunque los mecanismos neurotrópicos no están completamente aclarados para el SARS-CoV-2, existen indicios sólidos para asegurar su potencial neuroinvasivo. Las causas traumáticas, neoplásicas y neurológicas son las etiologías más comunes de PBCV, sin que se pueda descartar el origen vírico. Es plausible una causalidad entre el COVID-19 y la PBCV, que requerirá mayores estudios a corto y largo plazo. Presentamos una serie de casos que sostienen y discuten la hipótesis en consideración.

Stent-retriever alone versus combined use of stent-retriever and contact aspiration technique for middle cerebral artery M2 occlusions: a propensity score analysis.

BACKGROUND: The optimal endovascular treatment (EVT) technique for middle cerebral artery (MCA) M2 segment occlusions remains unknown. We aim to analyze whether reperfusion rate, procedure times, procedure-related complications, and clinical outcome differed between patients with isolated M2 occlusions who underwent stent-retriever (SR) alone versus combined SR and contact aspiration (CA) as a front-line EVT. METHODS: Patients who underwent EVT for isolated MCA-M2 occlusion were recruited from the prospectively ongoing ROSSETTI registry. Patients were divided regarding the EVT approach into SR alone versus SR+CA and propensity score matching was used to achieve baseline balance. Demographic, procedural, safety, and clinical outcomes were compared between groups. Multivariable logistic regression analysis was performed to identify independent predictors of first-pass effect (FPE) and 90-day modified Rankin scale (mRS) 0-2. RESULTS: 214 patients underwent EVT for M2 occlusion, 125 treated with SR alone and 89 with SR+CA. Propensity score matchnig analysis selected 134 matched patients. The rates of FPE (42% vs 40%, p=1.000) and 90-day mRS 0-2 (60% vs 51%, p=0.281) were comparable between groups. Patients treated with SR alone had lower need of rescue therapy (p=0.006), faster times to reperfusion (p<0.001), and lower procedure-related complications (p=0.031). Higher initial Alberta Stroke Program Early CT Score was an independent predictor of FPE. Age, baseline National Institutes of Health Stroke Scale score, and procedure duration were significant predictors of good clinical outcome at 3 months. CONCLUSIONS: As front-line modality in M2 occlusions, the SR alone approach results in similar rates of reperfusion and good clinical outcomes to combined SR+CA and might be advantageous due to faster reperfusion times and fewer adverse events.

Ability of final PET/CT to predict response to first-line treatment in real patients with classical Hodgkin lymphoma.

Up to 25% of patients with classical Hodgkin lymphoma (cHL) and a negative interim PET/CT will progress. Unfortunately, there are few published studies on the predictive value of PET/CT performed after finishing treatment. The objective of our study was to assess the role of the final PET/CT (fPET/CT) in predicting progression in a retrospective series of patients treated in the last 10 years with a homogeneous protocol (ABVD + / - radiotherapy). We reviewed a cohort of 227 patients with newly diagnosed cHL. fPET/CT was performed on 212 patients (93%). In patients with a positive fPET, progression-free survival at 60 months was 17% (94% if fPET was negative, p = 0.000). The positive and negative predictive values for the fPET were 76% and 94%, respectively (Fisher's exact test, p = 0.000). In the subgroup of patients with advanced-stage cHL, progression-free survival at 60 months was 91% with negative fPET and 0% with positive fPET (p = 0.000). However, fPET was negative in 19 of the 29 patients with a positive interim PET/CT (only 2 showed progression). In conclusion, fPET is a useful tool to predict treatment failure in patients with newly diagnosed cHL, especially advanced-stage disease.

Addition of intracranial aspiration to balloon guide catheter does not improve outcomes in large vessel occlusion anterior circulation stent retriever based thrombectomy for acute stroke.

BACKGROUND: Balloon guide catheter (BGC) in stent retriever based thrombectomy (BGC+SR) for patients with large vessel occlusion strokes (LVOS) improves outcomes. It is conceivable that the addition of a large bore distal access catheter (DAC) to BGC+SR leads to higher efficacy. We aimed to investigate whether the combined BGC+DAC+SR approach improves angiographic and clinical outcomes compared with BGC+SR alone for thrombectomy in anterior circulation LVOS. METHODS: Consecutive patients with anterior circulation LVOS from June 2019 to November 2020 were recruited from the ROSSETTI registry. Demographic, clinical, angiographic, and outcome data were compared between patients treated with BGC+SR alone versus BGC+DAC+SR. The primary outcome was first pass effect (FPE) rate, defined as near complete/complete revascularization (modified Thrombolysis in Cerebral Infarction (mTICI) 2c-3) after single device pass. RESULTS: We included 401 patients (BGC+SR alone, 273 (66.6%) patients). Patients treated with BGC+SR alone were older (median age 79 (IQR 68-85) vs 73.5 (65-82) years; p=0.033) and had shorter procedural times (puncture to revascularization 24 (14-46) vs 37 (24.5-63.5) min, p<0.001) than the BGC+DAC+SR group. Both approaches had a similar FPE rate (52% in BGC+SR alone vs 46.9% in BGC+DAC+SR, p=0.337). Although the BGC+SR alone group showed higher rates for final successful reperfusion (mTICI ≥2b (86.8% vs 74.2%, p=0.002) and excellent reperfusion, mTICI ≥2 c (76.2% vs 55.5%, p<0.001)), there were no significant differences in 24 hour National Institutes of Health Stroke Scale score or rates of good functional outcome (modified Rankin Scale score of 0-2) at 3 months across these techniques. CONCLUSIONS: Our data showed that addition of distal intracranial aspiration catheters to BGC+SR based thrombectomy in patients with acute anterior circulation LVO did not provide higher rates of FPE or improved clinical outcomes.

Evaluation of a new nomogram for Ferrara ring segment implantation in keratoconus.

AIM: To evaluate the short-term clinical outcomes of Ferrara rings in keratoconus using an optimized nomogram developed after several years of research and retrospective analysis of clinical data. METHODS: This prospective longitudinal non-comparative clinical trial evaluated 88 eyes of 88 patients (age 18-62y) with keratoconus diagnosis from two Spanish centers. Ferrara ring segment (AJL Ophthalmic) implantation was performed in all cases, using the mechanical procedure in 25 eyes (28.4%) and a femtosecond laser-assisted procedure in 63 eyes (71.6%). The ring segments implanted in each case were selected using a new optimized nomogram that considered variables such as anterior corneal asphericity and astigmatism or the discrepancy among astigmatism and coma orientations. Visual, refractive, corneal topographic, aberrometric, and pachymetric changes after surgery were evaluated during a 3-month follow-up. RESULTS: The implants induced a significant refractive change as well as an improvement in uncorrected (UDVA) and corrected distance visual acuity (CDVA; P<0.001). Postoperative CDVA of 0.10 logMAR or better was achieved in 28.4% and 46.5% of eyes, respectively. Two eyes (2.3%) lost two or more lines of CDVA whereas a total of 53.5% of eyes gained lines of CDVA. A significant central anterior and posterior corneal flattening was induced (P≤0.003), with a significant reduction of anterior (P<0.001) and posterior corneal astigmatisms (P=0.048), and a change in anterior asphericity (P<0.001). Total primary coma (6 mm pupil) change was also statistically significant (preoperative 3.66±3.04 µm vs postoperative 2.33±2.26 µm, P<0.001). No significant differences were found in the effect of ring segments between cases implanted using the mechanical and femtosecond techniques (P≥0.101). CONCLUSION: The implantation of Ferrara rings based on the nomogram evaluated is safe and effective for promoting a visual rehabilitation in keratoconus, with a relevant control of primary coma aberration.

Lower Survival and Increased Circulating Suppressor Cells in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma with Deficit of Vitamin D Levels Using R-GDP Plus Lenalidomide (R2-GDP): Results from the R2-GDP-GOTEL Trial.

The search of prognostic factors is a priority in diffuse large B-cell lymphoma (DLBCL) due to its aggressiveness. We have recently found that the level of circulating MDSCs is a good marker of survival in a translational study based on a trial (EudraCT Number: 2014-001620-29), using lenalidomide combined with R-GDP (rituximab plus gemcitabine, cisplatin, and dexamethasone). Since Vitamin D is a known immunomodulator, we have studied blood levels of these cell populations comparing patients with deficit of vitamin D levels (<15 ng/mL with those with normal levels >15 ng/mL. Mann-Whitney U test was used to compare cells distributions between groups, Wilcoxon test to compare cells distribution at different times and Spearman test to measure the association between cell populations. Patients with vitamin D deficit maintained the increased level of immune suppressor cells, whereas we observed a depletion of all immune suppressor cells in patients with normal vitamin D levels. In conclusion, we have confirmed the importance of vitamin D in the response to treatment in R/R DLBCL, suggesting that vitamin D deficit may be involved in the immune deficit of these patients, and thus, vitamin D supplementation in these patients may help to obtain a better response, warranting further investigation.

Significant Decrease in Annual Cancer Diagnoses in Spain during the COVID-19 Pandemic: A Real-Data Study.

The COVID-19 pandemic has caused a profound change in health organizations at both the primary and hospital care levels. This cross-sectional study aims to investigate the impact of the COVID-19 pandemic in the annual rate of new cancer diagnosis in two university-affiliated hospitals. This study includes all the patients with a pathological diagnosis of cancer attended in two hospitals in Málaga (Spain) during the first year of pandemic. This study population was compared with the patients diagnosed during the previous year 2019. To analyze whether the possible differences in the annual rate of diagnoses were due to the pandemic or to other causes, the patients diagnosed during 2018 and 2017 were also compared. There were 2340 new cancer diagnosis compared to 2825 patients in 2019 which represented a decrease of -17.2% (p = 0.0001). Differences in the number of cancer patients diagnosed between 2018 and 2019 (2840 new cases; 0.5% increase) or 2017 and 2019 (2909 new cases; 3% increase) were not statistically significant. The highest number of patients lost from diagnosis in 2020 was in breast cancer (-26.1%), colorectal neoplasms (-16.9%), and head and neck tumors (-19.8%). The study of incidence rates throughout the first year of the COVID-19 pandemic shows that the diagnosis of new cancer patients has been significantly impaired. Health systems must take the necessary measures to restore pre-pandemic diagnostic procedures and to recover lost patients who have not been diagnosed.

Percutaneous cryoablation of chondroblastoma and osteoblastoma in pediatric patients.

BACKGROUND: To review the safety and efficacy of percutaneous cryoablation for the treatment of chondroblastoma and osteoblastoma in the pediatric and adolescent population. MATERIALS AND METHODS: A retrospective review from 2016 to 2020 was performed to evaluate clinical and imaging response to percutaneous cryoablation in 11 symptomatic patients with diagnosis of chondroblastoma and osteoblastoma treated from two pediatric hospitals with at least 12-month follow-up. Technical success (correct needle placement and potential full coverage of the tumor with the planned ablation zone) and clinical success (relief of the symptoms) were evaluated. The primary objective was to alleviate pain related to the lesion(s). Immediate and late complications were recorded. Patients were followed in clinic and with imaging studies such as MRI or CT for a minimum of 6 months. RESULTS: A total of 11 patients were included (mean 14 years, age range 9-17; male n = 8). Diagnoses were osteoblastoma (n = 4) and chondroblastoma (n = 7). Locations were proximal humerus (n = 1), femur condyle (n = 1), and proximal femur (n = 1) tibia (n = 3), acetabulum (n = 3), thoracic vertebra (n = 1) and lumbar vertebra (n = 1). Cryoablation was technically successful in all patients. Clinical success (cessation of pain) was achieved in all patients. No signs of recurrence were observed on imaging follow-up in any of the patients. One of the patients developed periprocedural right L2-L3 transient radiculopathy as major immediate complication. CONCLUSIONS: Percutaneous image-guided cryoablation can be considered potentially safe and effective treatment for chondroblastoma and osteoblastoma in children and adolescents.

Avelumab plus standard-of-care chemoradiotherapy versus chemoradiotherapy alone in patients with locally advanced squamous cell carcinoma of the head and neck: a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial.

BACKGROUND: Chemoradiotherapy is the standard of care for unresected locally advanced squamous cell carcinoma of the head and neck. We aimed to assess if addition of avelumab (anti-PD-L1) to chemoradiotherapy could improve treatment outcomes for this patient population. METHODS: In this randomised, double-blind, placebo-controlled, phase 3 study, patients were recruited from 196 hospitals and cancer treatment centres in 22 countries. Patients aged 18 years or older, with histologically confirmed, previously untreated, locally advanced squamous cell carcinoma of the oropharynx, hypopharynx, larynx, or oral cavity (unselected for PD-L1 status), an Eastern Cooperative Oncology Group performance status score of 0 or 1, and who could receive chemoradiotherapy were eligible. Patients were randomly assigned (1:1) centrally by means of stratified block randomisation with block size four (stratified by human papillomavirus status, tumour stage, and nodal stage, and done by an interactive response technology system) to receive 10 mg/kg avelumab intravenously every 2 weeks plus chemoradiotherapy (100 mg/m2 cisplatin every 3 weeks plus intensity-modulated radiotherapy with standard fractionation of 70 Gy [35 fractions during 7 weeks]; avelumab group) or placebo plus chemoradiotherapy (placebo group). This was preceded by a single 10 mg/kg avelumab or placebo lead-in dose given 7 days previously and followed by 10 mg/kg avelumab or placebo every 2 weeks maintenance therapy for up to 12 months. The primary endpoint was progression-free survival by investigator assessment per modified Response Evaluation Criteria in Solid Tumors, version 1.1, in all randomly assigned patients. Adverse events were assessed in patients who received at least one dose of avelumab or placebo. This trial is registered with ClinicalTrials.gov, NCT02952586. Enrolment is no longer ongoing, and the trial has been discontinued. FINDINGS: Between Dec 12, 2016, and Jan 29, 2019, from 907 patients screened, 697 patients were randomly assigned to the avelumab group (n=350) or the placebo group (n=347). Median follow-up for progression-free survival was 14·6 months (IQR 8·5-19·6) in the avelumab group and 14·8 months (11·6-18·8) in the placebo group. Median progression-free survival was not reached (95% CI 16·9 months-not estimable) in the avelumab group and not reached (23·0 months-not estimable) in the placebo group (stratified hazard ratio 1·21 [95% CI 0·93-1·57] favouring the placebo group; one-sided p=0·92). The most common grade 3 or worse treatment-related adverse events were neutropenia (57 [16%] of 348 patients in the avelumab group vs 52 [15%] of 344 patients in the placebo group), mucosal inflammation (50 [14%] vs 45 [13%]), dysphagia (49 [14%] vs 47 [14%]), and anaemia (41 [12%] vs 44 [13%]). Serious treatment-related adverse events occurred in 124 (36%) patients in the avelumab group and in 109 (32%) patients in the placebo group. Treatment-related deaths occurred in two (1%) patients in the avelumab group (due to general disorders and site conditions, and vascular rupture) and one (<1%) in the placebo group (due to acute respiratory failure). INTERPRETATION: The primary objective of prolonging progression-free survival with avelumab plus chemoradiotherapy followed by avelumab maintenance in patients with locally advanced squamous cell carcinoma of the head and neck was not met. These findings may help inform the design of future trials investigating the combination of immune checkpoint inhibitors plus CRT. FUNDING: Pfizer and Merck KGaA, Darmstadt, Germany.

Balloon guide catheter improvements in thrombectomy outcomes persist despite advances in intracranial aspiration technology.

BACKGROUND: First-pass effect (FPE) has been established as a key metric for technical success and strongly correlates with better clinical outcomes. Most data supporting improved outcomes with the use of a balloon guide catheter (BGC) predate the advent of last-generation large-bore intracranial aspiration catheters. We aim to evaluate the impact of BGC in FPE and clinical outcomes in a large cohort of patients treated with contemporary technology. METHODS: Patients were recruited from the prospectively ongoing ROSSETTI registry. This registry includes all consecutive patients with anterior circulation large-vessel occlusion (LVO) from 10 comprehensive stroke centers in Spain. Demographic, clinical, angiographic, and clinical outcome data were compared between BGC and non-BGC groups. FPE was defined as the achievement of mTICI2c-3 after a single device pass. RESULTS: 426 patients were included out of which 271 (63.62%) used BCG. BGC-treated patients had higher FPE rate (45.8% vs 27.7%; P<0.001), higher final mTICI ≥2 c recanalization rate (76.8% vs 50.3%, respectively; P<0.001), shorter procedural time [median (IQR), 30 (19-58) vs 43 (33-71) min; P<0.001], higher NIHSS difference from admission to 24 hours [median (IQR), 8 (2-12) vs 3 (0-10); P=0.001], and lower mortality rate (17.6% vs 29.8%, P=0.026) compared with non-BGC patients. BGC use was an independent predictor of FPE (OR 2.197, 95% CI 1.436 to 3.361; P<0.001), and excellent clinical outcome at 3 months (OR 0.34, 95% CI 0.17 to 0.68; P=0.002). CONCLUSIONS: Our results support the benefit of BGC use on angiographic and clinical outcomes in anterior circulation LVO ischemic stroke remain significant even when considering recent improvements in intracranial aspiration technology.

Proposal and validation of a method to classify genetic subtypes of diffuse large B cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease whose prognosis is associated with clinical features, cell-of-origin and genetic aberrations. Recent integrative, multi-omic analyses had led to identifying overlapping genetic DLBCL subtypes. We used targeted massive sequencing to analyze 84 diagnostic samples from a multicenter cohort of patients with DLBCL treated with rituximab-containing therapies and a median follow-up of 6 years. The most frequently mutated genes were IGLL5 (43%), KMT2D (33.3%), CREBBP (28.6%), PIM1 (26.2%), and CARD11 (22.6%). Mutations in CD79B were associated with a higher risk of relapse after treatment, whereas patients with mutations in CD79B, ETS1, and CD58 had a significantly shorter survival. Based on the new genetic DLBCL classifications, we tested and validated a simplified method to classify samples in five genetic subtypes analyzing the mutational status of 26 genes and BCL2 and BCL6 translocations. We propose a two-step genetic DLBCL classifier (2-S), integrating the most significant features from previous algorithms, to classify the samples as N12-S, EZB2-S, MCD2-S, BN22-S, and ST22-S groups. We determined its sensitivity and specificity, compared with the other established algorithms, and evaluated its clinical impact. The results showed that ST22-S is the group with the best clinical outcome and N12-S, the more aggressive one. EZB2-S identified a subgroup with a worse prognosis among GCB-DLBLC cases.

Defining a Standard Set of Health Outcomes for Patients With Squamous Cell Carcinoma of the Head and Neck in Spain.

PURPOSE: A systematic, standardized collection of health outcomes during patient treatment and follow-up, relevant from the perspective of all stakeholders, is a crucial step toward effective and efficient disease management. This project aimed to define a standard set of health outcomes for patients with squamous cell carcinoma of the head and neck (SCCHN). METHODS: The project was led and coordinated by a scientific committee (SC). It comprised: (1) a literature review (to identify variables used during SCCHN management); (2) 1st-SC meeting (to select the variables for presentation during nominal groups-NG); (3) five NG (n=42 experts) and four interviews with patients (to reach consensus on the variables for inclusion); and (4) final-SC meeting (to review the results of NG ensuring consensus on the variables where consensus was not reached). RESULTS: Experts agreed to include the following variables in the standard set: treatment-related (treatment intent and type, response to treatment, treatment toxicity/complication, treatment completion), degree of health (performance status, patient-reported health status, pain, dysphonia, feeding and speech limitations, body image alteration, tracheotomy), survival (overall and progression-free survival, cause of death), nutritional (weight, nutritional intervention), other variables (smoking status, alcohol consumption, patient satisfaction with aftermath care, employment status), and case-mix variables (demographic, tumor-related, clinical and nutritional factors). CONCLUSIONS: This project may pave the way to standardizing the collection of health outcomes in SCCHN and promote the incorporation of patients' perspective in its management. The information provided through the systematic compilation of this standard set may define strategies to achieve high-quality, patient-centered care.