Molecular Tumor Board Improves Outcomes for Hispanic Patients With Advanced Solid Tumors.

PURPOSE: Multidisciplinary molecular tumor boards (MTBs) decode complex genomic data into clinical recommendations. Although MTBs are well-established in the oncology practice in developed countries, this strategy needs to be better explored in developing countries. Herein, we describe the possible benefits and limitations of the first MTB established in Colombia. METHODS: Demographic, clinical, and genomic information was collected between August 2020 and November 2021. By mid-2020, an MTB strategy was created to discuss clinical cases with one or more genomic alterations identified by next-generation sequencing using an open-access virtual platform. We characterized the patient population as benefiting from the recommended treatment option. We assessed the benefits and access to available targeted therapies that have the potential to change clinical management by making recommendations to treating oncologists on the basis of genomic profiling. However, we did not assess the treatment oncologists' compliance with MTB recommendations because they were not intended to replace clinical judgment/standard of care. RESULTS: A total of 146 patients were included in the discussions of the MTB. The median age was 59 years, and 59.6% were women. Genomic results prompting a change in therapeutic decisions were obtained in 53.1% of patients (95% CI, 44.9 to 61.3). The most prevalent malignancy was non-small-cell lung cancer (51%). Other malignancies represented 60%, 50%, and 30% of patients with soft-tissue sarcomas, brain tumors, and breast cancer, respectively. CONCLUSION: Using an open-access virtual platform, MTBs were feasible in low- and middle-income countries on the basis of the capability to provide the benefits and access to available targeted therapies that are not standard of care. Furthermore, MTB recommendations were made available to the treating oncologist in different locations across Colombia, providing the option to modify clinical management in most of these patients.

Application of Comprehensive Genomic Profiling-Based Next-Generation Sequencing Assay to Improve Cancer Care in a Developing Country.

PURPOSE: Identifying actionable oncogenic mutations have changed the therapeutic landscape in different types of tumors. This study investigated the utility of comprehensive genomic profiling (CGP), a hybrid capture-based next-generation sequencing (NGS) assay, in clinical practice in a developing country. METHODS: In this retrospective cohort study, CGP was performed on clinical samples from patients with different solid tumors recruited between December 2016 and November 2020, using hybrid capture-based genomic profiling, at the individual treating physicians' request in the clinical care for therapy decisions. Kaplan-Meier survival curves were estimated to characterize the time-to-event variables. RESULTS: Patients median age was 61 years (range: 14-87 years), and 64.7% were female. The most common histological diagnosis was lung primary tumors, with 90 patients corresponding to 52.9% of the samples (95% CI 45.4-60.4%). Actionable mutations with FDA-approved medications for specific alterations correspondent to tumoral histology were identified in 58 cases (46.4%), whereas other alterations were detected in 47 different samples (37.6%). The median overall survival was 15.5 months (95% CI 11.7 months-NR). Patients who were subjected to genomic evaluation at diagnosis reached a median overall survival of 18.3 months (95% CI 14.9 months-NR) compared to 14.1 months (95% CI 11.1 months-NR) in patients who obtained genomic evaluation after tumor progression and during standard treatment (P = .7). CONCLUSION: CGP of different types of tumors identifies clinically relevant genomic alterations that have benefited from targeted therapy and improve cancer care in a developing country to guide personalized treatment to beneficial outcomes of cancer patients.

Genomic Landscape of Primary Resistance to Osimertinib Among Hispanic Patients with EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC): Results of an Observational Longitudinal Cohort Study.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutations (EGFRm) represent one of the most common genomic alterations identified among patients with non-small cell lung cancer (NSCLC). Several targeted agents for patients with EGFRm have been proven safe and effective, including the third-generation tyrosine kinase inhibitor (TKI) osimertinib. Nonetheless, some patients will present with or develop EGFR-TKI resistance mechanisms. OBJECTIVE: We characterized the genomic landscape of primary resistance to osimertinib among Hispanic patients with EGFR-mutant NSCLC. METHODS: An observational longitudinal cohort study was conducted with two groups of patients, those with intrinsic resistance (cohort A) and those with long-term survival (cohort B). All patients were treated and followed between January 2018 and May 2022. All patients were assessed for Programmed Cell Death Ligand 1 (PD-L1) expression and Bcl-2-like protein 11 (BIM)/AXL mRNA expression before starting TKI. After 8 weeks of treatment, a liquid biopsy was performed to determine the presence of circulating free DNA (cfDNA), and next-generation sequencing (NGS) was used to identify mutations at the time of progression. In both cohorts, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated. RESULTS: We found a homogeneous distribution of EGFR-sensitizing mutations in both cohorts. For cohort A, exon 21 mutations were more common than exon 19 deletions (ex19dels) for cohort B (P = 0.0001). The reported ORR for osimertinib was 6.3% and 100% for cohorts A and B, respectively (P = 0.0001). PFS was significantly higher in cohort B (27.4 months vs. 3.1 months; P = 0.0001) and ex19del patients versus L858R (24.5 months, 95% confidence interval [CI] 18.2-NR), vs. 7.6 months, 95% CI 4.8-21.1; P = 0.001). OS was considerably lower for cohort A (20.1 months vs. 36.0 months; P = 0.0001) and was better for patients with ex19del, no brain metastasis, and low tumor mutation burden. At the time of progression, more mutations were found in cohort A, identifying off-target alterations more frequently, including TP53, RAS, and RB1. CONCLUSION: EGFR-independent alterations are common among patients with primary resistance to osimertinib and significantly impact PFS and OS. Our results suggest that among Hispanic patients, other variables associated with intrinsic resistance include the number of commutations, high levels AXL mRNA, and low levels of BIM mRNA, T790M de novo, EGFR p.L858R presence, and a high tumoral mutational burden.

STK11 and KEAP1 mutations in non-small cell lung cancer patients: Descriptive analysis and prognostic value among Hispanics (STRIKE registry-CLICaP).

BACKGROUND: Mutations in STK11 (STK11Mut) and, frequently co-occurring, KEAP1 mutations (KEAP1Mut) are associated with poor survival in metastatic Non-small Cell Lung Cancer (mNSCLC) patients treated with immunotherapy. However, there are limited data regarding the prognostic or predictive significance of these genomic alterations among Hispanics. METHODS: This retrospective study analyzed a cohort of Hispanic patients (N = 103) diagnosed with mNSCLC from the US and seven Latin American countries (LATAM) treated with immune checkpoint inhibitors (ICI) alone or in combination as first-line (Cohort A). All cases were treated in routine care between January 2016 and December 2021. The main objectives were to determine the association of mutations in STK11 or KEAP1 in these patients' tumors with overall (OS) and progression-free survival (PFS), presence of KRAS mutations, tumor mutational burden (TMB), and other relevant clinical variables. To compare outcomes with a STK11Wt/KEAP1Wt population, historical data from a cohort of Hispanic patients (N = 101) treated with first-line ICI was used, matching both groups by country of origin, gender, and Programed Death-ligand 1 (PD-L1) expression level (Cohort B). RESULTS: Most tumors had mutations only in STK11 or KEAP1 (45.6%) without KRAS co-mutation or any other genomic alteration. Besides, 35%, 8.7%, 6.8%, and 3.9% were KRASMut + STK11Mut, KRASMut + STK11Mut + KEAP1Mut, STK11Mut + KEAP1Mut, and KRASMut + KEAP1Mut, respectively. Based on KRAS status, STK11 alterations were associated with significantly lower PD-L1 expression among those with KRASWt (p = 0.023), whereas KEAP1 mutations were predominantly associated with lower PD-L1 expression among KRASMut cases (p = 0.047). Tumors with KRASMut + KEAP1Mut had significantly higher median TMB when compared to other tumors (p = 0.040). For Cohort A, median PFS was 4.9 months (95%CI 4.3-5.4), slightly longer in those with KEAP1mut 6.1 months versus STK11Mut 4.7 months (p = 0.38). In the same cohort, PD-L1 expression and TMB did not influence PFS. OS was significantly longer among patients with tumors with PD-L1 ≥ 50% (30.9 months), and different from those with PD-L1 1-49% (22.0 months), and PD-L1 < 1% (12.0 months) (p = 0.0001). When we compared the cohorts A and B, OS was significantly shorter for patients carrying STK1 [STK11Mut 14.2 months versus STK11Wt 27.0 months (p = 0.0001)] or KEAP1 [KEAP1Mut 12.0 months versus KEAP1Wt 24.4 months (p = 0.005)] mutations. PD-L1 expression significantly affected OS independently of the presence of mutations in STK11, KEAP1, or KRAS. TMB-H favored better OS. CONCLUSIONS: This is the first large Hispanic cohort to study the impact of STK11 and KEAP1 mutations in NSCLC patient treated with ICI. Our data suggest that mutations in the above-mentioned genes are associated with PD-L1 expression levels and poor OS.

Déficit de Fructosa -1,6 Bisfosfatasa: Causa de Hipoglicemia Severa en Adultos Jóvenes

Resumen La deficiencia de fructosa-1,6-bisfosfatasa (deficiencia de FBPasa) es un defecto metabólico congénito poco común que afecta la gluconeogénesis. Es una enfermedad genética autosómica recesiva. El paciente se presenta con hipoglucemia en ayunas y acidosis metabólica, y puede tener hiperventilación, apnea y cetosis. Aunque la enfermedad puede ser fatal en el período neonatal, el tratamiento adecuado puede producir un pronóstico excelente. A continuación, presentamos una paciente de 21 años con déficit de fructosa-1,6-bisfosfatasa, quien presentó cuadro gastroenteritis viral que provocó descompensación de su patológica de base, la paciente presentó evolución satisfactoria al manejo con cristaloides y dextrosa endovenosa. Se expone este caso porque es una entidad de baja frecuencia, con escasos reportes en adultos y con adecuada respuesta al tratamiento dietario.

Abstract Fructose-1,6-bisphosphatase deficiency (FBPase deficiency) is a rare congenital metabolic defect affecting gluconeogenesis. It is an autosomal recessive genetic disease. The patient presents with fasting hypoglycemia and metabolic acidosis, and may have hyperventilation, apnea, hypoglycemia, and ketosis. Although the disease can be fatal in the neonatal period, appropriate treatment can produce an excellent prognosis. Here we present the case of a 21-year-old patient with fructose-1,6-bisphosphatase deficiency, who presented with viral gastroenteritis that caused decompensation of her underlying pathology, the patient presented satisfactory evolution with crystalloids and intravenous dextrose. This case is presented because of its low frequency, with few reports in adults and with adequate response to dietary treatment.

Malnutrition in paediatric patients with leukaemia and lymphoma: a retrospective cohort study.

INTRODUCTION: Paediatric cancer is a potentially curable disease and its prognosis has been linked to several factors, such as nutritional status. The impact of malnutrition on these patients, either by overnutrition or undernutrition, varies and its relationship with outcomes is inconsistent. This study was conducted in order to determine the frequency of malnutrition in children with haematolymphoid malignancies at the time of diagnosis, as well as during treatment and to also investigate its relationship with the development of infections and death. MATERIALS AND METHODS: A retrospective cohort study of 191 children with a recent diagnosis of a haematolymphoid malignancy. The risks and nutritional classification were determined using anthropometry, follow-ups were conducted for up to 24 months and the presentation and frequency of infections and/or death were also recorded. Bivariate and multivariate analyses were conducted using binomial logistic regressions, for death and infection outcomes during follow-up. Survival analysis was conducted for various factors and types of cancer. RESULTS: 83.7% of children had a sufficient nutritional classification at diagnosis, 6.8% had malnutrition by undernutrition and 9.4% by overnutrition. 83.8% had at least one infectious complication during follow-up and 47.1% had ≥ 3. This percentage increased to 69.2% when configuring it in the malnutrition by undernutrition group. 18.3% of patients died. When configuring the mortality, the percentage was greater in patients with Acute Myeloid Leukaemia (AML) (57.1%) and malnutrition by undernutrition (30.7%). The multivariate analysis for the outcome of death, only showed a statistically significant variable (AML odds ratio = 26.52; confidence interval = 1.09-643.24; p = 0.04). CONCLUSION: No statistically significant relationship was found between the nutritional status of children with haematolymphoid neoplasms, and outcomes such as infections or death. The differences in the results obtained in these investigations may be related to the varied nutritional status definitions and the ways of measuring them, thus limiting comparisons between them.

Neumonitis por docetaxel, discusión de un caso / Interstitial pneumonitis due to docetaxel

Resumen La neumonitis intersticial por docetaxel es un evento infrecuente, pero con alto potencial de mortalidad y puede ser potencialmente reversible con el uso de esteroides sistémicos; se considera importante en el diagnóstico diferencial del paciente bajo quimioterapia con síntomas respiratorios. A continuación, se presenta un caso de neumonitis fatal por docetaxel en un paciente con carcinoma de próstata avanzado. Paciente de 80 años de edad con historia de cáncer de próstata de 15 años de evolución, en progresión ósea y ganglionar, y que inició manejo con docetaxel. Después de la aplicación del tercer ciclo presenta disnea de esfuerzos, fiebre, tos seca y deterioro general. Se realizó diagnóstico de neumonitis por docetaxel y se descartaron otras entidades. La neumonitis intersticial por docetaxel es una entidad rara. Los pilares del tratamiento son la suspensión del medicamento, el soporte ventilatorio y el uso de glucocorticoides sistémicos.

Abstract Interstitial pneumonitis due to docetaxel is an infrequent event but with a high mortality potential; it can be potentially reversible with the use of systemic steroids and is considered important in the differential diagnosis of the patient undergoing chemotherapy with respiratory symptoms. We present a case of fatal pneumonitis due to docetaxel in a patient with advanced prostate carcinoma. An 80-year-old patient with a history of prostate cancer of15 years of evolution, with disease progression in bones and lymph nodes, in whom treatment with Docetaxel was started, after the application of the third cycle, he presented with dyspnea on exertion, fever, dry cough and general deterioration. A diagnosis of pneumonitis due to docetaxel was made, discarding other entities. Interstitial pneumonitis due to docetaxel is a rare entity. The pillars of the treatment are the suspension of the medication, the ventilatory support and the use of systemic glucocorticoids.

Neumonía y neumotórax espontáneo por tuberculosis / Pneumonia and spontaneous pneumothorax due to tuberculosis

La neumonía por tuberculosis es un diagnóstico difícil de hacer, dado que no es considerado un germen común y su presentación clínica suele ser más subaguda o crónica, no obstante en el trabajo realizado por Vélez et al, en la ciudad de Medellín, se encontró que hasta 2.9% de las neumonías estudiadas fueron por tuberculosis, lo cual no es un porcentaje despreciable. A continuación presentamos dos casos de neumonía por tuberculosis de difícil diagnóstico, llamativos dada la evolución y presentación inusual y con los cuales queremos nuevamente llamar la atención como diagnóstico diferencial en pacientes que no responden al tratamiento de neumonía. (Acta Med Colomb 2016; 41: 62-66).

Tuberculosis pneumonia is difficult to diagnose, since it is not considered a common germ and its clinical presentation is often more subacute or chronic; however, in the work of Vélez et al. in the city of Medellin, it was found that up to 2.9% of pneumonias studied were caused by tuberculosis which is not a negligible percentage. Two cases of tuberculosis pneumonia difficult to diagnose are presented, which are striking given the evolution and unusual presentation and with which we again call attention as a differential diagnosis in patients who do not respond to treatment of pneumonia. (Acta Med Colomb 2016; 41: 62-66).

Las conexiones de la enfermedad de Alzheimer: ¿Dónde están? Análisis desde la Proteómica cuantitativa: [revisión] / The Alzheimer’s connection: where is it? Insights from Quantitative Proteomics: [review]

En el presente artículo se presentan los conceptos básicos que definen la patología de la enfermedad de Alzheimer (EA) y los métodos fundamentales utilizados en Neuroproteómica para su estudio. De igual manera, se discuten algunos resultados en el análisis de esta enfermedad y su relación con el genotipo APOE4 de APOE, el gen que codifica la Apolipoproteína E (ApoE). Finalmente se hacen algunas consideraciones generales sobre la EA, cómo evitar su progresión y se discute brevemente el futuro de la investigación en esta área.

Síndrome de Doege-Potter. Tumor fibroso de pleura irresecable asociado a hipoglucemia / Doege-Potter syndrome. An inoperable fibrous tumor of the pleura associated with hypoglycemia

Mujer de 47 años con antecedente de un tumor fibroso de la pleura previamente resecado en dos ocasiones en seguimiento clínico, fue hospitalizada por cuadro de pérdida de la conciencia. Se documentó hipoglucemia refractaria y progresión de su enfermedad que se consideró irresecable. La hipoglucemia se mantenía a pesar de altos flujos de dextrosa intravenosa. Se inició manejo con esteroides a altas dosis con lo cual se logró controlar.

Conceptos básicos de modelación matemática y simulación computacional de sistemas biológicos. Una herramienta útil para la docena y la investigación / Basic mathematical modulation and simulation concepts of biological systems: a useful teaching and research tool

La investigación de tipo experimental en seres vivos afronta en la actualidad como mayores obstáculos, los problemas éticos implícitos a la manipulación de los tejidos y problemas técnicos inhertes a las complejas interacciones que se desarrollan en y entre sus subsistemas y a las diversas formas en que son moduladas sus respuestas por factores extrínsecos.

Registro de la experiencia inicial con el stent XT, un dispositivo radiopaco y flexible: resultados angiográficos y evaluación técnica

El stent XT es un nuevo dispositivo expandible con balón, formado por múltiples módulos adheridos a una columna longitudinal radiopaca. Este stent cabe dentro de los clasificados como espiralados o "coils" debido a su configuración, apariencia y comportamiento físico. Viene acompañado de una herramienta especialmente diseñada para facilitar el montaje del stent sobre el balón. El objetivo de este estudio es evaluar la técnica de implantación y los resultados inmediatos del uso de este stent en la circulación coronaria. Las longitudes disponibles son 6, 11, 15 y 19 mm, y se recomienda su uso en vasos menores de 4,0 mm de diámetro. Desde diciembre/96 hasta mayo/97 se implantaron 87 stents en 63 pacientes consecutivos (edad media 59 mas menos 12 años; 50 pacientes -79 por ciento- de sexo masculino). La indicación clínica fue angina inestable en 40 pacientes, angina estable en 11, infarto agudo de miocardio en 3 e isquemia silente en 9. La implantanción del stent fue electiva en 71 lesiones (80 por ciento) y por disección o resultado subóptimo en 16 (20 por ciento). Treinta y tres lesiones se encontraban en la descendente anterior, 20 en la circunfleja, 32 en la coronaria derecha y 2 en puentes de safena. Se obtuvo éxito angiográfico inicial en todas las lesiones (100 por ciento). No obstante, en 10 lesiones (12 por ciento) se presentó ruptura del balón durante la implantación del stent, 4 de ellos requiriendo otro stent para lograr un buen resultado. No se presentaron migraciones de stent ni complicaciones mayores (muerte, IM, cirugía urgente). En un caso el stent montado no logró atravesar el sitio de la lesión requirió la implantación de otro dispositivo. Cada intervencionista evaluó la facilidad de montaje, posicionamiento en la arteria, implantación, radiopacidad, navegabilidad, respecto de ramas y forma arterial, para describir un índice de comportamiento del stent. Dicho índice fue excelente en 76 stents, aceptable en 10 y pobre en uno. En conclusión, el stent XT es un dispositivo seguro de fácil empleo y manejo, con flexibilidad y radiopacidad destacables. En nuestra experiencia se obtuvieron buenos resultados clínicos y angiográficos