NCAPH drives breast cancer progression and identifies a gene signature that predicts luminal a tumour recurrence.

BACKGROUND: Luminal A tumours generally have a favourable prognosis but possess the highest 10-year recurrence risk among breast cancers. Additionally, a quarter of the recurrence cases occur within 5 years post-diagnosis. Identifying such patients is crucial as long-term relapsers could benefit from extended hormone therapy, while early relapsers might require more aggressive treatment. METHODS: We conducted a study to explore non-structural chromosome maintenance condensin I complex subunit H's (NCAPH) role in luminal A breast cancer pathogenesis, both in vitro and in vivo, aiming to identify an intratumoural gene expression signature, with a focus on elevated NCAPH levels, as a potential marker for unfavourable progression. Our analysis included transgenic mouse models overexpressing NCAPH and a genetically diverse mouse cohort generated by backcrossing. A least absolute shrinkage and selection operator (LASSO) multivariate regression analysis was performed on transcripts associated with elevated intratumoural NCAPH levels. RESULTS: We found that NCAPH contributes to adverse luminal A breast cancer progression. The intratumoural gene expression signature associated with elevated NCAPH levels emerged as a potential risk identifier. Transgenic mice overexpressing NCAPH developed breast tumours with extended latency, and in Mouse Mammary Tumor Virus (MMTV)-NCAPHErbB2 double-transgenic mice, luminal tumours showed increased aggressiveness. High intratumoural Ncaph levels correlated with worse breast cancer outcome and subpar chemotherapy response. A 10-gene risk score, termed Gene Signature for Luminal A 10 (GSLA10), was derived from the LASSO analysis, correlating with adverse luminal A breast cancer progression. CONCLUSIONS: The GSLA10 signature outperformed the Oncotype DX signature in discerning tumours with unfavourable outcomes, previously categorised as luminal A by Prediction Analysis of Microarray 50 (PAM50) across three independent human cohorts. This new signature holds promise for identifying luminal A tumour patients with adverse prognosis, aiding in the development of personalised treatment strategies to significantly improve patient outcomes.

NCAPH Drives Breast Cancer Progression and Identifies a Gene Signature that Predicts Luminal A Tumor Recurrence.

Despite their generally favorable prognosis, luminal A tumors paradoxically pose the highest ten-year recurrence risk among breast cancers. From those that relapse, a quarter of them do it within five years after diagnosis. Identifying such patients is crucial, as long-term relapsers could benefit from extended hormone therapy, whereas early relapsers may require aggressive treatment. In this study, we demonstrate that NCAPH plays a role in the pathogenesis of luminal A breast cancer, contributing to its adverse progression in vitro and in vivo. Furthermore, we reveal that a signature of intratumoral gene expression, associated with elevated levels of NCAPH, serves as a potential marker to identify patients facing unfavorable progression of luminal A breast cancer. Indeed, transgenic mice overexpressing NCAPH generated breast tumors with long latency, and in MMTV-NCAPH/ErbB2+ double-transgenic mice, the luminal tumors formed were more aggressive. In addition, high intratumoral levels of Ncaph were associated with worse breast cancer evolution and poor response to chemotherapy in a cohort of genetically heterogeneous transgenic mice generated by backcrossing. In this cohort of mice, we identified a series of transcripts associated with elevated intratumoral levels of NCAPH, which were linked to adverse progression of breast cancer in both mice and humans. Utilizing the Least Absolute Shrinkage and Selection Operator (LASSO) multivariate regression analysis on this series of transcripts, we derived a ten-gene risk score. This score is defined by a gene signature (termed Gene Signature for Luminal A 10 or GSLA10) that correlates with unfavorable progression of luminal A breast cancer. The GSLA10 signature surpassed the Oncotype DX signature in discerning tumors with unfavorable outcomes (previously categorized as Luminal A by PAM50) across three independent human cohorts. This GSLA10 signature aids in identifying patients with Luminal A tumors displaying adverse prognosis, who could potentially benefit from personalized treatment strategies.

Intermediate Molecular Phenotypes to Identify Genetic Markers of Anthracycline-Induced Cardiotoxicity Risk.

Cardiotoxicity due to anthracyclines (CDA) affects cancer patients, but we cannot predict who may suffer from this complication. CDA is a complex trait with a polygenic component that is mainly unidentified. We propose that levels of intermediate molecular phenotypes (IMPs) in the myocardium associated with histopathological damage could explain CDA susceptibility, so variants of genes encoding these IMPs could identify patients susceptible to this complication. Thus, a genetically heterogeneous cohort of mice (n = 165) generated by backcrossing were treated with doxorubicin and docetaxel. We quantified heart fibrosis using an Ariol slide scanner and intramyocardial levels of IMPs using multiplex bead arrays and QPCR. We identified quantitative trait loci linked to IMPs (ipQTLs) and cdaQTLs via linkage analysis. In three cancer patient cohorts, CDA was quantified using echocardiography or Cardiac Magnetic Resonance. CDA behaves as a complex trait in the mouse cohort. IMP levels in the myocardium were associated with CDA. ipQTLs integrated into genetic models with cdaQTLs account for more CDA phenotypic variation than that explained by cda-QTLs alone. Allelic forms of genes encoding IMPs associated with CDA in mice, including AKT1, MAPK14, MAPK8, STAT3, CAS3, and TP53, are genetic determinants of CDA in patients. Two genetic risk scores for pediatric patients (n = 71) and women with breast cancer (n = 420) were generated using machine-learning Least Absolute Shrinkage and Selection Operator (LASSO) regression. Thus, IMPs associated with heart damage identify genetic markers of CDA risk, thereby allowing more personalized patient management.

The relationship between PARP inhibitors with the relapse and leukemisation of lymphomas: a case report.

Background: Nowadays the poly-ADP ribose polymerase inhibitors (iPARPs) are the mainly treatment for the ovarian cancer and other solid tumours. However, given its recent use, long-term toxicity is still under study. The occurrence of acute leukaemias and myelodysplastic syndromes (MDS) secondarily to iPARPs is known (0.5-1%). Case Description: We present the case of a 78-year-old patient with a serous carcinoma of ovary in maintenance treatment with Niraparib after response to platinum. Along with the ovarian carcinoma the patient developed a diffuse large cell B lymphoma (DLBCL) five years ago, treated with R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisolone) with complete response. The patient was evaluated in the emergency due to constitutional syndrome, objectifying a bicytopenia (platelets 28,000/mcL, haemoglobin 9.6 g/dL). In the study of bicytopenia, a bone marrow infiltration by high-grade B lymphoma was diagnosed. Conclusions: The action of iPARPs on the selection of acquired mutations in clonal haematopoiesis maybe have been able to accelerate the process of relapse and leukemisation of the previous lymphoma. The association of treatment with iPARPs and the development of lymphomas is key for increasing knowledge of the safety profiles these drugs.

Efficacy and safety of PARP inhibitor in non-small cell lung cancer: a systematic review with meta-analysis.

BACKGROUND: Non-small cell lung cancer (NSCLC) has undergone a major change in the last decade in terms of survival and prognosis due to the introduction of new drugs in the last 10 years. One of the drugs with the most promising preliminary results in NSCLC are PARP inhibitors (iPARPs), whose clinical trials have very heterogeneous results. The use of iPARPs in NSCLC may lead to increased survival in several selected patients, and their use may become a standard in the coming years. However, there is currently controversy about the efficacy and safety of these drugs in NSCLC. Therefore, future studies are needed to evaluate their role in these tumours. The aim of this review is to evaluate the efficacy and safety of iPARPs in the treatment of NSCLC. METHODS: We performed a systematic review with meta-analysis using the different clinical trials (PubMed, COCHRANE, Science Direct, EMBASE and the clinical trial registry) that evaluated the efficacy and safety of iPARP in NSCLC by PRISMA criteria. The primary endpoint was to evaluate the efficacy of iPARPs in the treatment of NSCLC through overall and progression-free survival (OS and PFS). Two authors independently reviewed the articles and abstracts (A.O.H. and J.R.R.), with subsequent confirmation by a third independent reviewer (E.B.M.). The heterogeneity of the included studies in the meta-analysis was assessed by using the I2 statistic. RESULTS: A total of 14 articles were included for analysis (2,651 patients). A total of 1,503 patients were randomised in iPARP arms and 1,148 patients were included in control arms. Three clinical trials were conducted in localised or locally advanced NSCLC and 11 in advanced or metastatic stages. The global OS of the meta-analysis showed a hazard ratio (HR) of 0.85 [95% confidence interval (CI): 0.74-0.97] with a heterogeneity (I2) of 0% (P=0.84). PFS showed a HR of 0.93 (95% CI: 0.74-1.17) with an I2=51% (P=0.07). The overall adverse event rate (grade 1-5) was similar in both iPARP and placebo arms. CONCLUSIONS: iPARPs are a future promising in the treatment of NSCLC in terms of efficacy and safety. Proper patient selection [homologous recombination deficiency (HRD) positive] is key for future clinical trials. The studies conducted to date open a new approach for a novel treatment modality in NSCLC.

Randomized phase 3 noninferiority trial of radiotherapy and cisplatin vs radiotherapy and cetuximab after docetaxel-cisplatin-fluorouracil induction chemotherapy in patients with locally advanced unresectable head and neck cancer.

OBJECTIVES: Concurrent chemoradiotherapy is the standard treatment for patients with unresectable, locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN); induction chemotherapy (ICT) may provide survival benefits in some patients. This study aimed to demonstrate the noninferiority of concomitant cetuximab plus radiotherapy (cet+RT) vs cisplatin plus radiotherapy (cis+RT) in patients with unresectable LA-SCCHN who were responsive to ICT. MATERIALS AND METHODS: This randomized, open-label, phase 3 trial studied patients with unresectable LA-SCCHN who received 3 cycles of ICT (docetaxel, cisplatin, and 5-fluorouracil; TPF) followed by cis+RT (standard arm) or cet+RT (experimental arm). The primary endpoint was noninferiority of the experimental arm vs the standard arm in terms of overall survival (OS), based on a hazard ratio (HR) of < 1.3. Secondary endpoints included progression-free survival, overall response, safety, and quality of life (QOL). RESULTS: Between July 15, 2008, and July 5, 2013, 519 patients were recruited and started ICT; 407 patients received post-ICT treatment (cis+RT, n = 205; cet+RT, n = 202). At a median follow-up of 43.9 (cis+RT) and 41.1 (cet+RT) months, median OS was 63.6 and 42.9 months with cis+RT and cet+RT, respectively (HR [90% CI] = 1.106 [0.888-1.378], P =.4492). There were no differences in progression-free survival, overall response rates, or adverse event rates between groups. There was greater late neurotoxicity with cis+RT than cet+RT (P =.0058). Several QOL dimensions improved with cet+RT vs cis+RT (physical functioning, P =.0287; appetite loss, P =.0248; social contact, P =.0153). CONCLUSION: Noninferiority of cet+RT over cis+RT was not demonstrated.

Epidemiological Study of Prostate Cancer in the Province of Salamanca (2006-2015)

Objectives: Knowing the incidence of prostate cancer in Salamanca and its evolution, as well as the age at diagnosis and its evolution. In addition, analyzing the mortality from prostate cancer in the province of Salamanca. Methods: Descriptive and analytical, longitudinal and retrospective observational study. From the collection of data from the Pathological Anatomy service and the Clinical Documentation service of the Hospital Complex of Salamanca a database was developed for the calculation of incidence rates. The information collected on mortality was obtained through the National Institute of Statistics. For regression analysis, segmented “jointpoint” models were developed. Results: 2676 males diagnosed with prostate cancer were recorded in the province of Salamanca (period 2006-2015). The risk of prostate cancer up to age 74 in 2006 was 6.23%, almost double in 2010. The evolution of mortality rates adjusted to the European population in the province of Salamanca during the period 2006-2015 showed a slight decrease. Conclusions: In general, Prostate cancer incidence rates increased progressively over the years studied, similar to Spain’s overall rates. These rates increased as age progressed. In general, our incidence rates were lower than those reported by the provinces of northern Spain (except Vizcaya) and higher than those recorded by the provinces of southern Spain. In Europe, our rate was surpassed by countries in northern and western Europe and lower than countries in southern and eastern Europe, and part of central Europe. Countries like U.S.A had rates higher than ours, while Canada accounted for a similar rate. On the other hand, mortality rates remained stable during the middle of the study period, suffering from then on a non-statistically significant anual decrease (AU)

Immunohistochemical Assessment of the P53 Protein as a Predictor of Non-Small Cell Lung Cancer Response to Immunotherapy.

BACKGROUND: Determining predictive biomarkers for immune checkpoint inhibitors (ICIs) is a current challenge in oncology. Previous studies on non-small cell lung cancer (NSCLC) have shown how TP53 gene mutations are correlated with different responses to ICIs. Strong and diffuse immuno-expression of p53 by immunohistochemistry (IHC) is interpreted as a likely indicator of a TP53 gene mutation. We aimed to assess the p53 protein expression via IHC in NSCLC as a predictive biomarker of the response to ICIs. METHODS: This was a retrospective hospital-based study of patients with NSCLC treated with Nivolumab in the University Hospital of Salamanca. All diagnostic biopsies were studied via IHC (measuring p53 protein expression, peroxidase anti-peroxidase immunohistochemistry technique using Leica BOND Polymer development kits). Survival analysis was performed by subgroups of expression of p53 and other factors using the Kaplan-Meier estimator and Cox proportional-hazards model. RESULTS: Seventy-three patients were included (59 men and 14 women). The median age was 68 (44-84) years. Thirty-six biopsies were adenocarcinoma, 34 were squamous, and three were undifferentiated. In 41 biopsies (56.2%), the cellular expression of p53 was <5% (Group A), and in 32 biopsies (43.8%), the expression was ≥5% (Group B). In the general analysis, no differences were observed in overall survival (OS) (A: 12 months vs B: 20 months; p = 0.070) or progression-free survival (PFS) (A: 4 m vs B: 7 m; p = 0.064). Significant differences were observed in adenocarcinomas for both OS (A: 8 m vs B: median not reached; p = 0.002) and PFS (A: 3 m vs 8 m; p = 0.013). No differences in PFS and OS were observed in squamous cell carcinoma. Significant differences were observed in OS in the PD-L1 negative group (0% expression) (A: 13 m vs B: 39 m; p = 0.024), but not in PFS (A: 3 m vs B: 7 m; p = 0.70). No differences were observed in the PD-L1 positive group. CONCLUSIONS: A trend toward a greater response to ICIs was observed in the PFS and OS of patients with high expression of p53 by IHC (TP53 mutation), especially in the PD-L1 negative adenocarcinoma subgroup. These results will make it possible to make future modifications to the clinical guidelines of NSCLC according to the expression of p53.

Influence of DNA Mismatch Repair (MMR) System in Survival and Response to Immune Checkpoint Inhibitors (ICIs) in Non-Small Cell Lung Cancer (NSCLC): Retrospective Analysis.

Mutations in the mismatch repair (MMR) system predict the response to immune checkpoint inhibitors (ICIs) like colon or gastric cancer. However, the MMR system's involvement in non-small cell lung cancer (NSCLC) remains unknown. Addressing this issue will improve clinical guidelines in the case of mutations in the main genes of the MMR system (MLH1, MSH2, MSH6, and PMS2). This work retrospectively assessed the role that these gene mutations play in the response to and survival of ICIs in NSCLC. Patients with NSCLC treated with nivolumab as the second-line treatment in the University Hospital of Salamanca were enrolled in this study. Survival and response analyses were performed according to groups of MMR system gene expression (MMR expression present or deficiency) and other subgroups, such as toxicity. There was a statistically significant relationship between the best response obtained and the expression of the MMR system (p = 0.045). The presence of toxicity grade ≥ 3 was associated with the deficiency expression of MMR (dMMR/MSI-H) group (p = 0.022; odds ratio = 10.167, 95% confidence interval (CI) 1.669-61.919). A trend towards greater survival and response to ICIs was observed in NSCLC and dMMR. Assessing the genes in the MMR system involved in NSCLC is key to obtaining personalized immunotherapy treatments.

Acute esophageal necrosis induced by immune checkpoint inhibitors.

A 73-year-old male with a history of chronic obstructive pulmonary disease and stage IV lung adenocarcinoma, being treated with the PD-1 inhibitor nivolumab, presented to the Emergency Room with a two-day history of coffee ground emesis and melena. On examination, he was tachycardic (130 per minute) and hypotensive (95/55 mmHg). Laboratory studies revealed anemia (6.9 g/dl), leukocytosis and hyper-lactatemia (lactate 6.3 mmol/l). Esophagogastroduodenoscopy was performed which showed diffuse circumferential blackish, necrotic-appearing mucosa of the first third of the esophagus. These findings were consistent with a diagnosis of acute esophageal necrosis (AEN). A biopsy of the esophageal mucosa demonstrated fragments of necrotic tissue with predominant lymphocyte infiltration. He was managed with a strict restriction of oral intake, total parenteral nutrition, double-dose proton pump inhibitors and broad-spectrum antibiotics (piperacillin/tazobactam). Despite the measures adopted, the patient presented a progressive clinical deterioration and died of multiple organ failure 12 days after admission.

Immune System Disorders, Cancer and Viral Infections: A New Treatment Opportunity for the Immune Checkpoint Inhibitors.

The relationship between viral infections and cancer is well known and has been established for decades. Multiple tumours are generated from alterations secondary to viral infections 2 resulting from a dysregulation of the immune system in many cases. Certain causal relationships, such as that between the Epstein-Barr virus (EBV) in nasopharyngeal cancer or hepatitis C and B viruses in hepatocarcinoma, have been clearly established, and their implications for the prognosis and treatment of solid tumours are currently unknown. Multiple studies have evaluated the role that these infections may have in the treatment of solid tumours using immunotherapy. A possible relationship between viral infections and an increased response to immune checkpoint inhibitors (ICIs) has been established at a theoretical level in solid neoplasms, such as EBV-positive cavum cancer and human papillomavirus (HPV)-positive and oropharyngeal cancer. These could yield a greater response associated with the activation of the immune system secondary to viral infection, the consequence of which is an increase in survival in these patients. That is why the objective of this review is to assess the different studies or clinical trials carried out in patients with solid tumours secondary to viral infections and their relationship to the response to ICIs.

Multimodal physical exercise and functional rehabilitation program in oncological patients with asthenia. study protocol.

BACKGROUND: The increase in the survival of oncology patients include multiple side effects as cancer-related asthenia and dyspnea, which represents a serious health problem. An implementation of the conventional clinical practice, developed through multimodal physical exercise and functional rehabilitation program intervention, may be useful in controlling dyspnoea. This study aims to evaluate the effects of a multimodal exercise and functional rehabilitation program on fatigue, pain, functional capacity, and quality of life in cancer patients with cancer-related asthenia. METHODS: This is a protocol for an experimental, prospective, randomised study using a parallel, fixed assignment scheme, with an experimental group and a control group in patients from the oncology hospitalisation unit at the Salamanca University Hospital Complex in Spain, using consecutive sampling to select 50 participants with oncological asthenia who are hospitalised at the time of inclusion. After the baseline evaluation, the participants will be randomised into two groups. Both groups will receive standard clinical practice care and the normal health education program at discharge, but in addition, the participants assigned to the experimental group will also complete a multimodal exercise and functional rehabilitation program lasting one month. The primary outcomes will be basic activities of daily living (Barthel Index) and degree of asthenia (FACT-An scale). Additionally, physical performance will be evaluated with the Short Physical Performance Battery (SPPB), as will the attention and executive functions (Trail-Making Test), fear/avoidance of movement (TAMPA scale), pain (VAS scale), and body composition (waist, hip, brachial, thigh, wrist, and ankle circumferences). DISCUSSION: The results of this study may be translated to clinical practice, incorporating a specific autonomy recovery programme into comprehensive rehabilitation programmes of care for cancer patients with asthenia. The current study addresses to improve the conventional clinical practice by proposing a multimodal physical exercise and functional rehabilitation program intervention, which will be implemented by an interdisciplinary team, to try to improve the autonomy of cancer patients with cancer-related asthenia. TRIAL REGISTRATION: ClinicalTrials.gov; ID: NCT04761289. (February 18, 2021).  https://clinicaltrials.gov/ct2/show/ NCT04761289.

Specific autonomy recovery programme in a comprehensive rehabilitation on functionality and respiratory parameters in oncological patients with dyspnoea. Study protocol.

BACKGROUND: Survival in cancer patients has increased exponentially in recent years, with multiple side effects caused by treatments. Cancer-related asthenia and dyspnea are among them, which represent a serious health problem, with considerable limitations and reduced quality of life. An implementation of the conventional clinical practice, developed through physical exercise, may be useful in controlling dyspnoea. This study aims to compare the effects of a comprehensive rehabilitation implementing a programme of multimodal physical exercise with a specific autonomy recovery programme, versus an isolated intervention using the physical exercise programme alone, on the functionality, physical performance and respiratory parameters in oncologycal patients with dyspnea. METHODS: This is a protocol por an experimental, prospective, randomized, parallel-controlled clinical trial, with two arms design of fixed assignment with an experimental and control groups. It will conduct in the Oncology Hospitalisation Unit at the University Hospital Complex of Salamanca, using consecutive sampling to select 50 participants with oncological dyspnoea who are hospitalised at the time of inclusion. After baseline assessment, participants will be randomised into the groups. Experimental group will complete Comprehensive Rehabilitation with the autonomy recovery and the multimodal exercise programmes, and in the control group, only the multimodal exercise programme will be carried out. The primary outcomes will be basic activities of daily living (Barthel Index) and degree of dyspnoea (MRC scale). Additionally, physical performance will be evaluated with the Short Physical Performance Battery (SPPB), as will the oxygen saturation in the blood using pulse oximetry, fear/avoidance of movement with the Tampa Scale of Kinesiophobia (TSK), and the quality of life of the oncology patient (ECOG performance scale). DISCUSSION: The results of this study may be translated to clinical practice, incorporating a specific autonomy recovery programme into comprehensive rehabilitation programmes of care for cancer patients with dyspnoea. Increase in the survival of patients with cancer includes multiple side effects as cancer-related asthenia and dyspnea, which represents a serious health problem. The current study addresses to improve the conventional clinical practice by proposing an integral, rehabilitative approach, to implement education and training for oncology patients with dyspnea to increase their quality of life. TRIAL REGISTRATION: ClinicalTrials.gov; ID: NCT04766593 . (February 23, 2021).

Impacto de un programa de rehabilitación integral funcional en la calidad de vida del paciente oncológico con disnea / Impact of a comprehensive functional rehabilitation programme on the quality of life of the oncological patient with dyspnoea

Antecedentes: La disnea constituye una de las principales causas de pérdida de funcionalidad en el paciente con cáncer. Las medidas farmacológicas consiguen una reducción del síntoma, pero sin generalizar esa mejora a la funcionalidad. Proponemos la inclusión de un programa de rehabilitación integral funcional. El objetivo del estudio fue comprobar la eficacia del programa en la mejora tanto de los niveles de autonomía como de disnea en pacientes con cáncer.MétodosEstudio experimental, prospectivo, longitudinal, aleatorizado mediante un esquema paralelo de asignación fija con grupo experimental y grupo control. El grupo de intervención, además del tratamiento clínico convencional realizado en el grupo control, recibió el Programa de Rehabilitación Funcional. Los resultados principales a medir fueron la funcionalidad (Barthel), los niveles de disnea (MRC) y la CVRS (Euro-QOL). Enmascaramiento con simple ciego, pero análisis estadístico realizado por personal ajeno al estudio.ResultadosMuestra final de 113 individuos, 52 en el grupo control y 61 en el experimental, procedentes de la Unidad de Oncología del Complejo Hospitalario Universitario de Salamanca. A nivel descriptivo buen balanceo entre grupos en edad, género y diagnóstico. Diferencias estadísticamente significativas entre los miembros de ambos grupos en los niveles de funcionalidad (p = 0,000), en los niveles de disnea (p = 0,001) y en los los sub-ítems pertenecientes al cuestionario Euro-QOL, salvo en el sub-ítem relacionado con el dolor (p = 0,311). No se observan efectos adversos importantes o efectos secundarios. (AU)

Background: Dyspnoea is one of leading causes of loss of autonomy in patients with advanced-stage cancer. Pharmacological measures achieve a reduction of the symptom, but without generalizing this improvement to functionality. We propose the inclusion of a comprehensive functional rehabilitation programme. The purpose is to test the efficacy of an integral respiratory rehabilitation programme to improve autonomy levels and relieve cancer-related dyspnoea.MethodsExperimental design, prospective, longitudinal, randomized study based on a parallel fixed allocation scheme using an experimental group and a control group. The intervention group participated in comprehensive functional rehabilitation, while the control group only received standard drug treatment. Single blind masking, but statistical analysis was performed by non-study personnel.ResultsFinal sample of 113 individuals, 52 in the control group and 61 in the experimental group, from the Oncology Unit of the University Hospital Complex of Salamanca. Statistically significant differences (are observed) between the members of both groups in the levels of functionality (p = .000), in the levels of dyspnoea (p =.001) and in the sub-items of the Euro-QOL questionnaire, except in the sub-item related to pain (p = .311). No major adverse effects or side effects are observed. (AU)

Resistance to Immune Checkpoint Inhibitors Secondary to Myeloid-Derived Suppressor Cells: A New Therapeutic Targeting of Haematological Malignancies.

Myeloid-derived suppressor cells (MDSCs) are a set of immature myeloid lineage cells that include macrophages, granulocytes, and dendritic cell precursors. This subpopulation has been described in relation to the tumour processes at different levels, including resistance to immunotherapy, such as immune checkpoint inhibitors (ICIs). Currently, multiple studies at the preclinical and clinical levels seek to use this cell population for the treatment of different haematological neoplasms, together with ICIs. This review addresses the different points in ongoing studies of MDSCs and ICIs in haematological malignancies and their future significance in routine clinical practice.

Response to Treatment with an Anti-Interleukin-6 Receptor Antibody (Tocilizumab) in a Patient with Hemophagocytic Syndrome Secondary to Immune Checkpoint Inhibitors.

Background. Immunotherapy represents one of the fundamental treatments in the management of some types of cancer, especially malignant melanoma. Toxicity derived from increased immune system activity can manifest in multiple organs and systems. We present a case of hematological toxicity, manifested as hemophagocytic syndrome (HPS), which was successfully treated with an anti-interleukin-6 antibody (tocilizumab). Case Report. This case presents a 75-year-old woman diagnosed with metastatic choroidal melanoma, refractory to several lines of treatment. After the failure of the previous lines, ipilimumab was started. After the third dose, she developed grade 2 thrombocytopenia and anemia accompanied by elevated levels of ferritin, triglycerides, and decreased fibrinogen. Hemophagocytosis was observed in the bone marrow biopsy, and a PET-CT showed splenomegaly with increased metabolism. Treatment was based on high doses of corticosteroids and tocilizumab. Four days after the start of treatment, progressive clinical and analytical improvement was observed, achieving total remission of the condition. Discussion. HPS induced by immunotherapy is due to an immunorelated cytokine storm syndrome (CSS). The administration of the anti-interleukin-6 receptor antibody drug acted on this cytokine cascade, leading to stabilization and subsequent remission. For this reason, the use of tocilizumab should be part of the immunotherapy-induced HPS treatment algorithm.

Dopamine Receptors and the Kidney: An Overview of Health- and Pharmacological-Targeted Implications.

The dopaminergic system can adapt to the different physiological or pathological situations to which the kidneys are subjected throughout life, maintaining homeostasis of natriuresis, extracellular volume, and blood pressure levels. The role of renal dopamine receptor dysfunction is clearly established in the pathogenesis of essential hypertension. Its associations with other pathological states such as insulin resistance and redox balance have also been associated with dysfunction of the dopaminergic system. The different dopamine receptors (D1-D5) show a protective effect against hypertension and kidney disorders. It is essential to take into account the various interactions of the dopaminergic system with other elements, such as adrenergic receptors. The approach to therapeutic strategies for essential hypertension must go through the blocking of those elements that lead to renal vasoconstriction or the restoration of the normal functioning of dopamine receptors. D1-like receptors are fundamental in this role, and new therapeutic efforts should be directed to the restoration of their functioning in many patients. More studies will be needed to allow the development of drugs that can be targeted to renal dopamine receptors in the treatment of hypertension.

Impact of a comprehensive functional rehabilitation programme on the quality of life of the oncological patient with dyspnoea. / Impacto de un programa de rehabilitación integral funcional en la calidad de vida del paciente oncológico con disnea.

BACKGROUND: Dyspnoea is one of leading causes of loss of autonomy in patients with advanced-stage cancer. Pharmacological measures achieve a reduction of the symptom, but without generalizing this improvement to functionality. We propose the inclusion of a comprehensive functional rehabilitation programme. The purpose is to test the efficacy of an integral respiratory rehabilitation programme to improve autonomy levels and relieve cancer-related dyspnoea. METHODS: Experimental design, prospective, longitudinal, randomized study based on a parallel fixed allocation scheme using an experimental group and a control group. The intervention group participated in comprehensive functional rehabilitation, while the control group only received standard drug treatment. Single blind masking, but statistical analysis was performed by non-study personnel. RESULTS: Final sample of 113 individuals, 52 in the control group and 61 in the experimental group, from the Oncology Unit of the University Hospital Complex of Salamanca. Statistically significant differences (are observed) between the members of both groups in the levels of functionality (p = .000), in the levels of dyspnoea (p =.001) and in the sub-items of the Euro-QOL questionnaire, except in the sub-item related to pain (p = .311). No major adverse effects or side effects are observed. CONCLUSION: Non-pharmacological interventions using a comprehensive functional rehabilitation programme improve functionality and relieve dyspnoea in cancer patients.

Study of Chemotherapy-Induced Cognitive Impairment in Women with Breast Cancer.

BACKGROUND: Oncology patients experience a large number of symptoms and, those referring to cognitive performance has an ever-increasing importance in clinical practice, due to the increase in survival rates and interest in the patient's quality of life. The studies reviewed showed that chemotherapy-related cognitive impairment might occur in 15 and 50% of oncology patients. The main objective of this research was to study the impact of chemotherapy on the cognitive function of patients with locoregional breast cancer. METHOD: Analytical, prospective, longitudinal study using three measures, unifactorial intrasubject design, non-probability, and random selection sampling. The sample comprised women newly diagnosed with locoregional breast cancer in stages I, II, IIIA who received chemotherapy at the University Hospital of Salamanca (Complejo Asistencial Universitario de Salamanca), randomly selected for three years. Semi-structured interviews were conducted, and anxiety and depression (Hospital Anxiety and Depression scale, HAD); quality of life (QLQ-BR23 scale) and the following cognitive variables were assessed-processing speed, attention, memory, and executive functions (subtests of the Wechsler Intelligence Scale and the Trail Making Test). RESULTS: The final sample size included 151 participants; 23 were excluded. A decline in cognitive performance was observed in patients, which did not completely recover two months after chemotherapy was completed. Additionally, worse cognitive performance was observed in patients with anxious or depressive symptoms. There was a negative impact on the quality of life. CONCLUSION: Chemotherapy had an impact on the cognitive performance of oncology patients in most cognitive domains studied.