Desarrollo de un perfil de genes implicados en la angiogénesis tumoral con valor predictivo de respuesta a la quimioterapua en el cáncer de ovario avanzado

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid. Facultad de Medicina, Departamento de Anatomía Patológica. Fecha de lectura: 1 de Febrero de 201

On-line breath analysis of volatile organic compounds as a method for colorectal cancer detection

Background: Analysis of exhaled volatile organic compounds (VOCs) in breath is an emerging approach for cancer diagnosis, but little is known about its potential use as a biomarker for colorectal cancer (CRC). We investigated whether a combination of VOCs could distinct CRC patients from healthy volunteers. Methods: In a pilot study, we prospectively analyzed breath exhalations of 38 CRC patient and 43 healthy controls all scheduled for colonoscopy, older than 50 in the average-risk category. The samples were ionized and analyzed using a Secondary ElectroSpray Ionization (SESI) coupled with a Time-of-Flight Mass Spectrometer (SESI-MS). After a minimum of 2 hours fasting, volunteers deeply exhaled into the system. Each test requires three soft exhalations and takes less than ten minutes. No breath condensate or collection are required and VOCs masses are detected in real time, also allowing for a spirometric profile to be analyzed along with the VOCs. A new sampling system precludes ambient air from entering the system, so background contamination is reduced by an overall factor of ten. Potential confounding variables from the patient or the environment that could interfere with results were analyzed. Results: 255 VOCs, with masses ranging from 30 to 431 Dalton have been identified in the exhaled breath. Using a classification technique based on the ROC curve for each VOC, a set of 9 biomarkers discriminating the presence of CRC from healthy volunteers was obtained, showing an average recognition rate of 81.94%, a sensitivity of 87.04% and specificity of 76.85%. Conclusions: A combination of cualitative and cuantitative analysis of VOCs in the exhaled breath could be a powerful diagnostic tool for average-risk CRC population. These results should be taken with precaution, as many endogenous or exogenous contaminants could interfere as confounding variables. On-line analysis with SESI-MS is less time-consuming and doesn’t need sample preparation. We are recruiting in a new pilot study including breath cleaning procedures and spirometric analysis incorporated into the postprocessing algorithms, to better control for confounding variables

Genetic polymorphisms of SCN9A are associated with oxaliplatin-induced neuropathy

BACKGROUND: Oxaliplatin is a chemotherapy agent active against digestive tumors. Peripheral neuropathy is one of the most important dose-limiting toxicity of this drug. It occurs in around 60-80% of the patients, and 15% of them develop severe neuropathy. The pathophysiology of oxaliplatin neurotoxicity remains unclear. SCN9A is a gene codifying for a subtype sodium channel (type IX, subunit α) and mutations in this gene are involved in neuropathic perception. In this study we investigated whether SCN9A genetic variants were associated with risk of neurotoxicity in patients diagnosed of cancer on treatment with oxaliplatin. METHODS: Blood samples from 94 patients diagnosed of digestive cancer that had received oxaliplatin in adjuvant or metastatic setting were obtained from three hospitals in Madrid. These patients were classified into two groups: "cases" developed oxaliplatin-induced grade 3-4 neuropathy (n = 48), and "controls" (n = 46) had no neuropathy or grade 1. The neuropathy was evaluated by an expert neurologist and included a clinical examination and classification according to validated neurological scales: National Cancer Institute Common Toxicity Criteria (NCI-CTC), Oxaliplatin-Specific Neurotoxicity Scale (OSNS) and Total Neuropathy score (TNS). Genotyping was performed for 3 SCN9A missense polymorphisms: rs6746030 (R1150W), rs74401238 (R1110Q) and rs41268673 (P610T), and associations between genotypes and neuropathy were evaluated. RESULTS: We found that SCN9A rs6746030 was associated with protection for severe neuropathy (OR = 0.39, 95% CI = 0.16-0.96; p = 0.041). Multivariate analysis adjusting for diabetes provided similar results (p = 0.036). No significant differences in neuropathy risk were detected for rs74401238 and rs41268673. CONCLUSION: SCN9A rs6746030 was associated with protection for severe oxaliplatin-induced peripheral neuropathy. The validation of this exploratory study is ongoing in an independent series.For all the patients who accepted to participate in this investigation. Funding This work was supported by projects from the“Spanish Ministry of Economy and Competiveness”(grant number SAF2015-64850-R) and from Carlos III Health Institute project: PI12/02824S

Epidemiological analysis of SARS-CoV-2 virus infection in patients with solid tumors: The experience of Infanta Sofía University Hospital (HUIS)

Background The global SARS-CoV-2 outbreak has significantly affected hospital assistance to cancer patients. Diagnostic and treatment paradigms have been challenged with an urgent need for patient protection. In the abscence of data to balance clinical decissions we aimed to analyze HUIS experience during the peak of the outbreak. Methods Cancer pts atended at HUIS since February 24th to April 24th were collected. Clinical management was adapted according to evolving international consensus. All PCR+ COVID-19 pts have been included in a database. Oncological and COVID-19 diseases characteristics as well as cancer management have been collected. The main objective of this analysis was to know the risk of SARS-CoV-2 infection, hospitalization rate and mortality of cancer patientes in our center during the outbreak and to identify potential predictive factors. Results Overall, 853 cancer pts had been attended at our department during this period of time. Twenty-six pts (3.05%) were hospitalized with confirmed COVID-19 diagnosis. Underlying solid tumors were the following: breast (256, 30.01%), GI (312, 36.8%), lung (100, 11.72%) and others (185, 21.47%). 322 pts (37.75%) had metastatic cancer and 531 (62.25%) had early stage diseases. 395 pts (46.31%) were treated with antineoplastic agents: 62,63% received treatment as adjuvant therapy, 18. 92% as first line (or maintenance) treatment in advanced diseases and 12.81% second or following lines of treatment in advaced diseases. 10 pts (32.26%) with COVID-19 died. Futher analysis regarding clinical, laboratory and hospital risk factors – such as diagnostic procedures, type and length of treatments, number of hospital visits, etc will be reported in the final presentation. Conclusions COVID-19 hospitalization rate was 3.05%, and mortality rate was 32.26%. Adequate testing and protective measures are mandatory to warrant an optimal managment of cancer pts during the global SARS-CoV-2 outbreak.Sin financiación18.274 JCR (2019) Q1, 9/244 Oncology1.039 SJR (2019) Q1, 483/2754 Medicine (miscellaneous)No data IDR 2019UE

A multicenter clinical registry with associated biological samples of gynecological cancer patients: Pilot study of the Spanish Ovarian Cancer Research Group (GEICO 81-T)

Sin financiación32.976 JCR (2020) Q1, 7/242 Oncology7.954 SJR (2020) Q1, 2/129 HematologyNo data IDR 2020UE