Incidence and risk factors for developing chemotherapy-induced neuropathic pain in 500 cancer patients: A file-based observational study.

OBJECTIVE: To define the incidence and risk factors for developing chemotherapy-induced neuropathic pain (CINP). METHODS: Retrospective, file-based analysis on cancer patients who received any type of conventional chemotherapy and for whom neurological evaluation was asked to reveal the extent of chemotherapy-induced peripheral neurotoxicity (CIPN) with or without CINP. CINP was assessed by means of the PI-NRS and Douleur Neuropathique-4 questionnaire. The total neuropathy score-clinical version graded the severity of CIPN. RESULTS: The medical files of 500 chemotherapy-treated cancer patients were reviewed. Any grade chronic CIPN was disclosed in 343 (68.6%) patients and CINP in 127 (37%) of them, corresponding to an overall percentage of 25.4% among all 500 included patients. The logistic regression analysis identified as independent predictors for CINP development the presence of uncomplicated diabetes (OR: 2.17; p = .039) and grade 2-3 chronic CIPN (OR: 1.61; p < .001) as also the administration of combined paclitaxel plus cisplatin (reference variable), compared to oxaliplatin (OR: 0.18; p = .001) and taxanes (OR: 0.16; p < .001). The increased severity of acute OXAIPN was associated with CINP (OR: 4.51; p < .001). OXA-treated patients with persistent CINP presented a worst likelihood to improve after chemotherapy discontinuation, than patients receiving combined paclitaxel plus cisplatin (OR: 50; p < .001). CONCLUSION: The incidence of CINP in our cohort was comparable to previous reports, with severities fluctuating upwards during chemotherapy and declined post-chemotherapy. Uncomplicated diabetes, the combined paclitaxel plus cisplatin treatment and the increased severity of acute oxaliplatin neurotoxicity mostly increase the risk for developing CINP. OXA-treated patients present less possibilities to recover from CINP after chemotherapy discontinuation, than other chemotherapies.

Prospectively assessing serum neurofilament light chain levels as a biomarker of paclitaxel-induced peripheral neurotoxicity in breast cancer patients.

Our aim was to assess the significance of measuring serum neurofilament light chain (sNfL) levels as a biomarker of paclitaxel-induced peripheral neurotoxicity (PIPN). We longitudinally measured sNfL in breast cancer patients, scheduled to receive the 12-weekly paclitaxel-based regimen. Patients were clinically examined by means of the Total Neuropathy Score-clinical version (TNSc), while sNfL were quantified, using the highly sensitive Simoa technique, before starting chemotherapy (baseline), after 2 (week 2) and 3 (week 3) weekly courses, and at the end of chemotherapy (week 12). Among 59 included patients (mean age: 53.1 ± 11.5 years), 33 (56%) developed grade 0-1 and 26 (44%) grade 2-3 PIPN at week 12. A significant longitudinal increase of sNfL levels from baseline to week-12 was determined, whereas patients with TNSc grade 2-3 PIPN had significantly increased sNfL levels at week 12, compared to those with grade 0-1. receiver-operated characteristics (ROC) analysis defined a value of NfL of >85 pg/mL at week 3 as the best discriminative determination to predict the development of grade 2-3 PIPN at week 12 (sensitivity 46.2%, specificity 84.8%). The logistic binary regression analysis revealed that age > 50 years and the cutoff of >85 pg/mL of sNfL levels at week 3 independently predicted the development of grade 2-3 PIPN at week 12 with a sensitivity of 46%, a specificity of 91%, and a positive and negative predictive values of 75% and 67%, respectively. sNfL levels seem to be a valuable biomarker of neuro-axonal injury in PIPN. An early increase of this biomarker after a 3-weekly chemotherapy course can be a predictive marker of final PIPN severity.

Incidence and characteristics of neurotoxicity in immune checkpoint inhibitors with focus on neuromuscular events: Experience beyond the clinical trials.

Immune checkpoint inhibitors (ICIs) are associated with various neurological adverse events (NAEs). We herein explored the incidence and clinical phenotype of immune-related NAEs in cancer patients. Medical records of ICI-treated cancer patients were reviewed between the years 2010 and 2018, with an aim to characterize immuno-related NAEs. A total of 1185 ICIs-treated patients were identified, 63.7% of which were males and 36.3% were females, with a mean age of 63.4 ± 7.3 years. Twenty-four from the overall ICIs-treated patients (2%) developed NAEs. No differences were identified in terms of age, sex, tumor type and class of ICIs between the patients who developed NAEs and those who did not. The median number of cycles of ICI treatment before NAEs onset were 4.5 (1-10), and the median time was 102 days. Peripheral nervous system (PNS) involvement was present in 14 patients (58.4%) and central nervous system (CNS) involvement in 10 (33.3%), including 2 patients with aseptic meningitis and polyradicular involvement. Amongst PNS complications, there were five (20.8%) with axonal sensory neuropathies, four (16.7%) with Guillain-Barre-like syndromes, and four (16.7%) with myositis and/or myasthenic syndromes. The majority of patients with PNS-related NAEs (n = 11; 78.6%) improved after ICIs discontinuation and treatment with immune-modulating therapies. The time to neuromuscular toxicities onset was significantly shorter, compared to CNS NAEs (median 70 vs 119 days, P = .037). Immune-related NAEs mostly present with neuromuscular complications. Discontinuation of ICIs and appropriate treatment should be commenced early throughout the process, in order to maximize a favorable outcome.

Myasthenia Gravis Induced by Immune Checkpoint Inhibitors: An Emerging Neurotoxicity in Neuro-Oncology Practice: Case Series.

Immunotherapy with immune checkpoint inhibitors (ICIs) have been reported to induce de novo or exacerbate pre-existing Myasthenia Gravis (MG). We present a single center case series of patients who developed an immune-related myasthenia gravis (irMG) related with ICIs. We performed a retrospective chart review of the electronic medical records between 1 September 2017 and 2022. We report the clinical features, presentation forms, diagnostic workflows, general management and outcomes of six patients who received ICIs for different solid organ malignancies and developed an irMG frequently overlapping with immune-related myocarditis and/or myositis. The aim of the article is to describe the clinical features, treatment and outcomes of this challenging and potentially life-threating syndrome, comparing our data with those described in the literature. Differences between irMG and classic MG are highlighted.

Late effects of cancer treatment: consequences for long-term brain cancer survivors.

Late adverse effects of cancer treatments represent a significant source of morbidity and also financial hardship among brain tumor patients. These effects can be produced by direct neurologic damage of the tumor and its removal, and/or by complementary treatments such as chemotherapy and radiotherapy, either alone or combined. Notably, young adults are the critical population that faces major consequences because the early onset of the disease may affect their development and socioeconomic status. The spectrum of these late adverse effects is large and involves multiple domains. In this review we classify the main long-term adverse effects into 4 sections: CNS complications, peripheral nervous system complications, secondary neoplasms, and Economic impact. In addition, CNS main complications are divided into nonfocal and focal symptoms. Owing to all the secondary effects mentioned, it is essential for physicians to have a high level of clinical suspicion to prevent and provide early intervention to minimize their impact.

Vagus nerve stimulation as a potential modulator of periictal psychotic episodes: A report of four cases.

Drug resistant epilepsy (DRE) has been associated with a high incidence of psychotic disorders. Patients can develop psychosis after starting a new antiseizure medication, after undergoing resective surgery, or after implantation of a vagus nerve stimulation (VNS) system. The aim of this study was to investigate the modulation effect of VNS on psychotic episodes in DRE patients with a pre-existing history of periictal psychotic episodes (PPE). We retrospectively report the outcome of four patients from a single tertiary center with PPE prior to implantation. None of the implanted patients developed de novo PPE after VNS therapy. Regarding seizure outcome, all patients demonstrated a response to VNS with two who experienced who status epilepticus and three patients wtih a change in semiology with after VNS implantation. PPE disappeared in all the study patients, two of them at 6 months post-implantation and in the others after 2 and 3 years, respectively. 18F-FDG-PET results showed hypermetabolism in both anterior insular and medial frontal lobes which disappeared in the 18F -FDG-PET 4 years post-implantation. Based on the results of this series of cases we suggest that VNS therapy may be useful to modulatet PPE in patients with DRE, though effectiveness may be time-dependent.

Perilesional edema in brain metastases as predictive factor of response to systemic therapy in non-small cell lung cancer patients: a preliminary study.

BACKGROUND: The significance of upfront systemic therapies as an alternative to whole brain radiotherapy (WBRT) for multiple brain metastases (BM) is debatable. Our purpose is to investigate if peritumoral edema could predict the intracranial response to systemic chemotherapy (chemo) in patients with advanced non-squamous non-small cell lung cancer (non-SQ-NSCLC) and synchronous multiple BM. METHODS: In this observational cohort study, we evaluated the outcome of 28 patients with multiple BM (≥3) treated with chemo based on cisplatin/carboplatin plus pemetrexed (chemo, group A, n=17) or WBRT plus subsequent chemo (group B, n=11). The intracranial response, assessed by the response assessment neuro-oncology (RANO) BM criteria, was correlated with the degree of BM-associated edema estimated by the maximum diameter ratio among fluid attenuated inversion recovery (FLAIR) and gadolinium-enhanced T1WI (T1Gd) per each BM at the baseline brain magnetic resonance imaging (MRI). RESULTS: No differences were observed in baseline characteristics between both groups, except for the number of patients under steroid treatment that was clearly superior in group B (P=0.007). Median OS was similar between groups. Regarding FLAIR/T1Gd ratio (F/Gd), patients treated with chemo alone exhibited significantly higher values (P=0.001) in those who developed intracranial progression disease (PD) (2.80±0.32 mm), compared with those who achieved partial response (PR) (1.30±0.11 mm) or stable disease (SD) (1.35±0.09 mm). In patients treated with WBRT, F/Gd ratio was not predictive of response. CONCLUSIONS: Peritumoral edema estimated by F/Gd ratio appears a promising predictive tool to identify oligosymptomatic patients with multiple BM in whom WBRT can be postponed.

Gossypol Treatment Restores Insufficient Apoptotic Function of DFF40/CAD in Human Glioblastoma Cells.

Glioblastoma (GBM) is a highly aggressive brain tumor and almost all patients die because of relapses. GBM-derived cells undergo cell death without nuclear fragmentation upon treatment with different apoptotic agents. Nuclear dismantling determines the point-of-no-return in the apoptotic process. DFF40/CAD is the main endonuclease implicated in apoptotic nuclear disassembly. To be properly activated, DFF40/CAD should reside in the cytosol. However, the endonuclease is poorly expressed in the cytosol and remains cumulated in the nucleus of GBM cells. Here, by employing commercial and non-commercial patient-derived GBM cells, we demonstrate that the natural terpenoid aldehyde gossypol prompts DFF40/CAD-dependent nuclear fragmentation. A comparative analysis between gossypol- and staurosporine-treated cells evidenced that levels of neither caspase activation nor DNA damage were correlated with the ability of each compound to induce nuclear fragmentation. Deconvoluted confocal images revealed that DFF40/CAD was almost completely excluded from the nucleus early after the staurosporine challenge. However, gossypol-treated cells maintained DFF40/CAD in the nucleus for longer times, shaping a ribbon-like structure piercing the nuclear fragments and building a network of bridged masses of compacted chromatin. Therefore, GBM cells can fragment their nuclei if treated with the adequate insult, making the cell death process irreversible.

Defining a Standardized Information Model for Multi-Source Representation of Breast Cancer Data.

This work aims to define a standardized information model for representation of multiple data sources in breast cancer. A set of data elements has been identified using ICHOM Breast Cancer as the minimum data set and adapting it to the needs of Hospital Universitario 12 de Octubre. With this, an information model has been defined according to ISO 13606 and SNOMED CT standards.

Perspectiva histórica de los estudios con mayor impacto en el tratamiento de los gliomas / Historical perspective of the studies with the greatest impact on the treatment of gliomas

Históricamente, los avances en el área de conocimiento de la neurooncología y las mejoras en la supervivencia de los pacientes con tumores cerebrales han sido relativamente escasos. Uno de los principales puntos de inflexión puede establecerse a partir de 2005, cuando se constata el hasta entonces potencial papel terapéutico de los citostáticos en estos tumores, cambiando consiguientemente el estándar de tratamiento. Hasta esa fecha, sólo la radioterapia y la cirugía se consideraban tratamientos realmente eficaces. Este cambio ha contribuido al desarrollo de nuevas terapias sistémicas y a profundizar en el estudio de la gliomagénesis. Los avances en los campos básicos del conocimiento de los tumores cerebrales han ayudado a mejorar el diseño y los resultados de los nuevos ensayos clínicos, al mismo tiempo que los resultados clínicos retroalimentan y ofrecen nuevos datos para seguir avanzando en la comprensión de estos tumores. Sin embargo, estos esperanzadores avances abren nuevas cuestiones aún no resueltas y ofrecen un enfoque crítico a la interpretación de estudios pasados. La presente revisión principalmente actualiza los resultados de los ensayos que cambiaron o modificaron la práctica clínica del tratamiento y el manejo de los gliomas. Se excluyen trabajos relevantes de investigación básica que aún no han tenido traslación en la implementación de cambios en el tratamiento de estos pacientes

Historically, advances in our knowledge of neuro-oncology and improvements in the survival of patients with brain tumours have been relatively scarce. One of the main turning points can be established from 2005 onwards, when the potential therapeutic role of cytostatics in these tumours was confirmed, thus changing the standard of treatment. Up until that date, only radiation therapy and surgery were considered truly effective treatments. This shift has contributed to the development of new systemic therapies and to an in-depth study of gliomagenesis. Advances in the knowledge of the basic fields of brain tumours have helped improve the design and results of new clinical trials, while clinical outcomes provide feedback and new data to further the understanding of these tumours. However, these promising advances open up new unresolved questions and offer a critical approach to the interpretation of past studies. This review mainly updates the results of trials that changed or modified the clinical practice of the treatment and management of gliomas. Commenting on relevant basic research papers that have not yet been translated into the implementation of changes in the treatment of these patients is excluded

Comunicación de valores críticos: resultados de una encuesta realizada por la comision de la calidad extraanalítica de la SEQC / Critical values reporting: results of a Spanish laboratories survey

Introducción. La detección y comunicación de valores críticos es una de las funciones del laboratorio que más repercusión tiene sobre la seguridad del paciente. La Comisión de la Calidad Extraanalítica de la SECQ ha realizado unas encuestas para conocer la situación de los laboratorios españoles. Material y métodos. Se enviaron dos encuestas a 728 laboratorios participantes en el Programa de Garantía Externa de la Calidad de Bioquímica suero, para conocer diferentes aspectos relacionados con la comunicación de los mismos y el límite establecido para diferentes magnitudes, diferenciando entre consulta externa y hospitalización. Resultados. La mayoría de los laboratorios encuestados tienen definidos valores críticos (81,5 %) y es el facultativo del laboratorio quien los notifica (87,3 %) telefónicamente (91,1 %) al médico responsable del paciente (86,6 %). Un 58 % de laboratorios comprueba que el aviso se ha recibido, un 54,8 % no ha definido el plazo de entrega y el 87,9 % no utiliza un indicador para controlar este proceso. Resultados. Las medianas obtenidas para la mayoría de constituyentes no difieren según el origen de los pacientes, siendo parecidas para consulta externa y hospitalización. Sin embargo, se encuentran diferencias en el nivel bajo del calcio y en el nivel alto de la creatinina, la glucosa y la urea. Conclusiones. Se observa una falta de estandarización y consenso en el tratamiento de estos valores. Debido a que su detección implica una actuación médica urgente, consideramos necesario que los laboratorios en colaboración con los clínicos desarrollen estrategias adecuadas para el establecimiento y notificación de estos valores (AU)

Introduction. Detection and reporting of critical values have great implications on patient safety. The SEQC Committee for the extra-analytical quality assessment has carried out a survey in order to evaluate these in Spanish laboratories. Material and methods. Two surveys were distributed among 728 participants registered in the External Quality Assessment Scheme (clinical chemistry, serum). Participants were asked to provide information regarding reporting of critical values and their decision limits. Outpatient and in-patient reporting were considered separately. Results. Most laboratories (81.5 %) had their critical values already defined; physicians assumed the responsibility of notifying critical results in 87.3 % of cases; critical results were mainly informed by telephone (91.1 %); 58 % of laboratories further verified that such notifications were received; delivery time was not taken into account in 54.8 % of laboratories; 87.9 % did not employ any indicator to track this process. Results. Median values obtained for most constituents did not differ and were similar for outpatient and hospital settings. Nevertheless, differences were found for the lower calcium critical value and for high critical values for creatinine, glucose and urea. Conclusions. Handling of critical values lacks standardization and a consensus among Spanish laboratories. Suitable strategies should be developed between laboratories and clinicians in order to correctly define and set up critical values, as their detection requires urgent medical action (AU)