Prognostic Factors and Markers in Non-Small Cell Lung Cancer: Recent Progress and Future Challenges.

Lung cancer is a highly aggressive neoplasm and, despite the development of recent therapies, tumor progression and recurrence following the initial response remains unsolved. Several questions remain unanswered about non-small cell lung cancer (NSCLC): (1) Which patients will actually benefit from therapy? (2) What are the predictive factors of response to MAbs and TKIs? (3) What are the best combination strategies with conventional treatments or new antineoplastic drugs? To answer these questions, an integrative literature review was carried out, searching articles in PUBMED, NCBI-PMC, Google Academic, and others. Here, we will examine the molecular genetics of lung cancer, emphasizing NSCLC, and delineate the primary categories of inhibitors based on their molecular targets, alongside the main treatment alternatives depending on the type of acquired resistance. We highlighted new therapies based on epigenetic information and a single-cell approach as a potential source of new biomarkers. The current and future of NSCLC management hinges upon genotyping correct prognostic markers, as well as on the evolution of precision medicine, which guarantees a tailored drug combination with precise targeting.

Clinical Utility of Universal Germline Genetic Testing for Patients With Breast Cancer.

Importance: National Comprehensive Cancer Network guidelines currently recommend germline testing for high-risk genes in selected patients with breast cancer. The clinical utility of recommending testing all patients with breast cancer with multigene panels is currently under consideration. Objective: To examine the implications of universal testing of patients with breast cancer with respect to clinical decision-making. Design, Setting, and Participants: Patients from a previously reported cohort were assessed as in-criteria or out-of-criteria according to the 2017 guidelines and underwent testing with a multigene germline panel between 2017 to 2018. Patients were women and men aged 18 to 90 years, with a new and/or previous diagnosis of breast cancer who had not undergone either single or multigene testing. Clinicians from 20 community and academic sites documented patient clinical information and changes to clinical recommendations made according to test findings. Association between prevalence of pathogenic or likely pathogenic germline variants and previously unreported clinical features, including scores generated by the BRCAPRO statistical model, was determined. Data were analyzed from April 2020 to May 2022. Exposure: New and/or previous diagnosis of breast cancer. Main Outcomes and Measures: Disease management recommendations that were changed as a result of genetic testing results are reported. Results: Clinicians were asked to assess changes to clinical management as a result of germline genetic testing for 952 patients. Informative clinician-reported recommendations were provided for 939 (467 in-criteria and 472 out-of-criteria) of the patients with breast cancer (936 [99.7%] female; 702 [74.8%] White; mean [SD] age at initial diagnosis, 57.6 [11.5] years). One or more changes were reported for 31 of 37 (83.8%) in-criteria patients and 23 of 34 (67.6%) out-of-criteria patients with a pathogenic or likely pathogenic variant. Recommendations were changed as a result of testing results for 14 of 22 (63.6%) out-of-criteria patients who had a variant in a breast cancer predisposition gene. Clinicians considered testing beneficial for two-thirds of patients with pathogenic or likely pathogenic variants and for one-third of patients with either negative results or variants of uncertain significance. There was no difference in variant rate between patients meeting the BRCAPRO threshold (≥10%) and those who did not (P = .86, Fisher exact test). No changes to clinical recommendations were made for most patients with negative results (345 of 349 patients [98.9%]) or variants of uncertain significance (492 of 509 patients [96.7%]). Conclusions and Relevance: In this cohort study, germline genetic testing was used by clinicians to direct treatment for most out-of-criteria patients with breast cancer with pathogenic or likely pathogenic germline variants, including those with moderate-risk variants. Universal germline testing informs clinical decision-making and provides access to targeted treatments and clinical trials for all patients with breast cancer.

Caracterización de la infección urinaria y resistencia antimicrobiana en receptores de trasplante renal de un centro colombiano / Characterization of Urinary Tract Infection and Antimicrobial Resistance in Kidney Transplant Recipients from a Colombian Tertiary Center

La infección del tracto urinario (ITU) es una de las principales complicaciones postrasplante renal, los datos a nivel nacional en ese grupo poblacional son limitados. Objetivos caracterizar la microbiología de las ITU presentadas en receptores de trasplante renal (TxR) en un centro colombiano durante el periodo 2017­2019, los factores relacionados con la resistencia antimicrobiana y el impacto de la ITU en la función del injerto renal. Métodos estudio de corte transversal ejecutado mediante el análisis de la base de datos de ingresos hospitalarios por urgencias de pacientes receptores de TxR con sospecha clínica de ITU en una institución de cuarto nivel en Bogotá, Colombia. El análisis de datos se ejecutó en STATA 13.0. Resultados La ITU causó 12,69% de visitas a urgencias en pacientes trasplantados. Los microorganismos aislados fueron: Escherichia coli 52,22%, Klebsiella pneumoniae 16,67%, Pseudomonas aeruginosa 4,44%, Salmonella spp 4,44%, Proteus mirabilis 3,33%, Serratia marcescens 2,22%, Klebsiella oxytoca 2,22%, Citrobacter koseri 1,11%, Enterobacter cloacae 1,11%, otros 2,22%; El urocultivo fue negativo en 10% de los casos. El 28,39% (n:23) de gérmenes aislados fue multisensible mientras que el 71,60% (n:58) expresó algún tipo de patrón de resistencia distribuido así: 68,96% productor de betalactamasa de espectro extendido (BLEE), 15,52% productor de carbapenemasas, 12,06% productor de betalactamasa tipo IRT, 3,45% fue catalogado como multirresistente. 17,78% de los pacientes presentó criterios de urosepsis, no se registró ningún caso de mortalidad asociada a la ITU. La creatinina sérica tuvo un incremento promedio de 0,46 mg/dl durante el episodio de ITU (p: <0,0001) y el antecedente de diabetes mellitus se relacionó con la ITU causada por gérmenes resistentes (p: 0,008). Conclusiones La ITU es una causa frecuente de atención en urgencias para pacientes receptores de TxR; la Escherichia coli es el microorganismo causal más frecuente y cerca del 70% de los gérmenes aislados presentó algún patrón de resistencia antimicrobiana.

Urinary tract infection (UTI) is one of the most common complications after kidney transplantation (KTx). This study aims to characterize the microbiology of UTIs presented in KTx recipients in a Colombian tertiary center during the period 2017­2019, factors related with antimicrobial resistance and the impact of UTI on kidney graft function. Methods A cross-sectional retrospective single center study were made through the institutional database analysis of hospital admissions to the emergency room of KTx recipients with clinical suspicion of UTI. Data analysis was run on STATA 13.0. Results UTI caused 12.69% of visits to the emergency room in transplant patients during the study period. The isolated microorganisms were Escherichia coli 52.22%, Klebsiella pneumoniae 16.67%, Pseudomonas aeruginosa 4.44%, Salmonella spp 4.44%, Proteus mirabilis 3.33%, Serratia marcescens 2.22%, Klebsiella oxytoca 2.22%, Citrobacter koseroi 1.11%, others 2.22%; Urine culture was negative in 10% of cases. 28.39% (n: 23) of isolated germs were multisensitive while 71.60% (n: 58) expressed some type of resistance pattern distributed as follows: 68.96% extended spectrum beta-lactamase (ESBL) producers, 15.52% carbapenemases producers, 12.06% IRT-type beta-lactamase producers, 3.45% was classified as multi-resistant. 17.78% of patients presented criteria for urosepsis, there was no cases of mortality due to UTI. Serum creatinine had an average increase of 0.46 mg/dl during the UTI episode (p: <0.0001) and a history of diabetes mellitus was related with UTI caused by resistant germs (p: 0.008). Conclusion UTI is a frequent cause of emergency care for KTx recipients. E. coli is the most common causative microorganism and about 70% of isolated germs showed some pattern of antimicrobial resistance.

Capacidad Vesical como Pronóstico de Trasplante Renal / Bladder Capacity as a Renal Transplant Prognosis

Introducción La capacidad vesical pre trasplante renal, ha demostrado tener un impacto significativo en el pronóstico, la calidad de vida y complicaciones urológicas en los pacientes. Métodos Estimar la correlación de Pearson que existe entre la capacidad vesical pre- trasplante (CVPRE) comparado con el tiempo de duración de Terapia de reemplazo renal (TRR); como factor pronóstico. Método Se realizó una base de datos de pacientes con Trasplante Renal realizados por un Grupo Trasplante, de una sola institución, en los últimos 7 años, desde el 2010 hasta el año 2018. Se tomaron datos del estudio pre trasplante por parte del servicio de Urología y controles mensuales pos trasplante, hasta la fecha. Se tomaron en cuenta datos como: Tiempo de diagnóstico de ERC estadio final, tiempo y tipo de terapia de reemplazo renal, capacidad vesical y función renal pre-trasplante versus función renal y capacidad vesical pos-trasplante y complicaciones urológicas pos-trasplante. Con esos datos, se realizó el cruce de variables, utilizando el Coeficiente de correlación de Pearson, expresando resultados con valores entre 1, para mostrar correlación y significancia estadística en la práctica clínica. Resultados Entre los años 2010 hasta mayo de 2018, se llevaron a cabo 203 Trasplantes renales, se tabularon 114 pacientes cuyos datos se encontraban completos. La Correlación Pearson fue de: −0,3 entre tiempo de TRR y CVPRE; −0,14 entre CVPRE y creatinina pos TR; 0,09 entre CVPRE y RVU; de 0,14 entre CVPRE e IVU; esas 2 últimas, complicaciones urológicas pos-trasplante renal. Conclusiones Existe correlación inversa entre el tiempo de TRR y Capacidad vesical pre- trasplante, lo cual influye en el pronóstico del paciente trasplantado renal, en términos de función renal pos-trasplante y complicaciones urológicas dadas por RVU e IVU.

Introduction The bladder capacity has demonstrated to have an important impact in prognosis, quality of life and urological complications in patients. Objective Estimate the Pearson correlation that exists between pre-transplant bladder capacity compared to the duration of renal replacement therapy (RRT); as a prognosis factor. Methods A database of Kidney Transplantation patients performed by a Transplant Group, from a single institution, during the last 7 years, from 2010 to 2018, was made. Data from the pretransplant study carried out by the Urology Service and from the post-transplant monthly controls, to date were also analyzed. Data such as: Time of CKD final stage diagnosis, time and type of renal replacement therapy, bladder capacity and pretransplant renal function versus post-transplant renal function and bladder capacity and post-transplant urological complications, were also taken into consideration. With these data, a variable crossing was carried out, using the Pearson Correlation Coefficient, expressing results with values ranging between −1 and 1, to show correlation and statistical significance in clinical practice. Results 203 kidney transplants carried out between years 2010 to May 2018; of these 114 patients, whose data were complete, were tabulated. The Pearson Correlation was: −0.3 between RRT and PTBC time; −0.14 between PTBC and creatinine after TR; 0.09 between PTBC and RVU; of 0.14 between PTBC and IVU; the last 2 were urological complications after kidney transplant. Conclusions There is an inverse correlation between RRT Time and bladder capacity before transplantation, which influences the prognosis of the renal transplant patient, in terms of post-transplant renal function and urological complications due to VUR and UTI.

Underdiagnosis of Hereditary Breast Cancer: Are Genetic Testing Guidelines a Tool or an Obstacle?

PURPOSE: An estimated 10% of breast and ovarian cancers result from hereditary causes. Current testing guidelines for germ line susceptibility genes in patients with breast carcinoma were developed to identify carriers of BRCA1/ 2 variants and have evolved in the panel-testing era. We evaluated the capability of the National Comprehensive Cancer Network (NCCN) guidelines to identify patients with breast cancer with pathogenic variants in expanded panel testing. METHODS: An institutional review board-approved multicenter prospective registry was initiated with 20 community and academic sites experienced in cancer genetic testing and counseling. Eligibility criteria included patients with a previously or newly diagnosed breast cancer who had not undergone either single- or multigene testing. Consecutive patients 18 to 90 years of age were consented and underwent an 80-gene panel test. Health Insurance Portability and Accountability Act-compliant electronic case report forms collected information on patient demographics, diagnoses, phenotypes, and test results. RESULTS: More than 1,000 patients were enrolled, and data records for 959 patients were analyzed; 49.95% met NCCN criteria, and 50.05% did not. Overall, 8.65% of patients had a pathogenic/likely pathogenic (P/LP) variant. Of patients who met NCCN guidelines with test results, 9.39% had a P/LP variant. Of patients who did not meet guidelines, 7.9% had a P/LP variant. The difference in positive results between these groups was not statistically significant (Fisher's exact test P = .4241). CONCLUSION: Our results indicate that nearly half of patients with breast cancer with a P/LP variant with clinically actionable and/or management guidelines in development are missed by current testing guidelines. We recommend that all patients with a diagnosis of breast cancer undergo expanded panel testing.