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Introducción: el desarrollo de nuevas tecnologías de diagnóstico molecular ha permitido la detección de numerosas alteraciones del genoma involucradas en el inicio y progresión del cáncer. Desempeña un rol importante la identificación de variantes de utilidad clínica o mutaciones accionables, entendidas como aquellas alteraciones puntuales que permiten guiar las decisiones terapéuticas con inhibidores dirigidos a estos blancos moleculares. El éxito de estos agentes ha llevado a un cambio de paradigma, a tal punto de reemplazar la quimioterapia convencional en un grupo selecto de pacientes que se benefician de terapia dirigida. La secuenciación de nueva generación (NGS, por sus siglas en inglés) es la base de las plataformas genómicas con las que se puede realizar un perfil genómico completo (CGP, por sus siglas en inglés), con el objetivo de identificar las mutaciones accionables sobre las cuales ejercerán su efecto los fármacos dirigidos, permitiendo así la medicina personalizada y oncología de precisión, sin embargo, la utilidad clínica de CGP en pacientes colombianos es desconocida. Objetivos: el objetivo principal de este estudio fue evaluar la utilidad clínica del perfil genómico integral en tumores sólidos durante la práctica clínica habitual en Colombia como recomendación de tratamiento.

Background Thymomas are a group of rare neoplasms of the anterior mediastinum. The objective of this study was to describe the demographics, clinical characteristics and treatment approaches in Latin America. Methods This was a retrospective multicenter cohort study including patients with histologically proven thymomas diagnosed between 1997 and 2018. Demographics, clinicopathological characteristics and therapeutic outcomes were collected locally and analyzed in a centralized manner. Results A total of 135 patients were included. Median age at diagnosis was 53 years old (19–84), 53.3% (n = 72) of patients were female and 87.4% had an ECOG performance score ranging from 0–1. A total of 47 patients (34.8%) had metastatic disease at diagnosis. Concurrent myasthenia gravis occurred in 21.5% of patients. Surgery was performed in 74 patients (54.8%), comprising 27 (20%) tumorectomies and 47 (34.8%) thymectomies. According to the Masaoka‐Koga system, overall survival (OS) at five‐years was 73.4%, 63.8% and 51%, at stages I–II, III–IVA and IVB, respectively (p = 0.005). Furthermore, patients with low lactate dehydrogenase (LDH) (≤373 IU/L) at baseline and myasthenia gravis concurrence showed significantly better OS (p = 0.001 and p = 0.008, respectively). In multivariate analysis, high LDH levels (HR 2.8 [95% confidence interval [CI]: 1.1–7.8]; p = 0.036) at baseline and not performing a surgical resection (HR 4.1 [95% CI: 1.3–12.7]; p = 0.016) were significantly associated with increased risk of death. Conclusions Our data provides the largest insight into the clinical characteristics and outcomes of patients with thymomas in Latin America. Survival in patients with thymomas continues to be very favorable, especially when subjected to adequate local control., Here, we report the largest analysis of clinical characteristics of thymomas and outcomes in Latin American patients. Out of 135 patients included in the study, 21.5% (n = 29) concurrently presented myasthenia gravis. Relapse‐free survival rates at five‐years were 58.5% for stage I–II, and 35.4% for stage III. Five‐year overall survival rates were 73.4%, 63.8% and 51%, at stages I–II, III–IVA and IVB, respectively.

La activación de BIM es esencial para la apoptosis desencadenada por el inhibidor de la tirosina quinasa (TKI) del receptor del factor de crecimiento epidérmico (EGFR) en el cáncer de pulmón de células no pequeñas (CPCNP) con mutación de EGFR. Una deleción en el intrón dos del gen BIM da como resultado la generación de isoformas empalmadas alternativamente que alteran su respuesta apoptótica a los TKI, lo que confiere a las células de NSCLC una resistencia intrínseca a estos medicamentos. Los pacientes con ambas alteraciones tienen mala evolución clínica. El estudio actual tuvo como objetivo investigar la eficacia clínica y la tolerabilidad de EGFR-TKI más bevacizumab (Bev) versus EGFR-TKI solos como tratamiento de primera línea en pacientes con NSCLC avanzado con mutaciones de EGFR y deleciones BIM (BIMdel). MATERIALES Y MÉTODOS Se realizó un análisis retrospectivo. BIMdel se detectó mediante análisis de reacción en cadena de la polimerasa y secuenciación directa de ADN. La expresión de la proteína BIM se investigó mediante inmunohistoquímica y los niveles de ARNm de BIM mediante la reacción en cadena de la polimerasa con transcriptasa inversa. Se compararon las características clínicas, la supervivencia general, la supervivencia libre de progresión (PFS), la tasa de respuesta general (ORR) y los eventos adversos relacionados con el tratamiento entre ambos grupos. RESULTADOS Se incluyeron 33 pacientes; 15 recibieron EGFR-TKI y 18 recibieron EGFR-TKI más Bev. La mediana de edad fue de 63 años, con una mayoría de pacientes mujeres reclutadas. Todos los individuos incluidos tenían una puntuación de rendimiento del Grupo Oncológico Cooperativo del Este de 2 o menos. La adición de Bev resultó en un ORR significativamente más alto (94,4 % versus 40 %, P > 0,001). La mediana de SLP fue más larga con el uso de la terapia combinada (11,12 frente a 7,87 meses; P = 0,001). La mediana de supervivencia general tendió a ser más prolongada en los inhibidores de la tirosina quinasa con EGFR más Bev (30,9 frente a 25,4 meses; P = 0,06), pero no alcanzó significación estadística. La respuesta en términos de PFS parcial y completa, así como en general, se vio afectada favorablemente. CONCLUSIÓN Los EGFR-TKI más Bev confirieron una ORR y una SLP significativamente más altas en pacientes con NSCLC avanzado con mutación de EGFR y BIMdel. Se necesitan más estudios prospectivos para validar estos hallazgos. BIM activation is essential for epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI)–triggered apoptosis in EGFR-mutant non–small-cell lung cancer (NSCLC). A deletion in the intron two of the BIM gene results in generation of alternatively spliced isoforms that impairs their apoptotic response to TKIs, conferring the NSCLC cells intrinsic resistance to these medications. Patients with both alterations have poor clinical evolution. The current study aimed to investigate the clinical efficacy and tolerability of EGFR-TKIs plus bevacizumab (Bev) versus EGFR-TKIs alone as first-line treatment in advanced NSCLC patients with EGFR mutations and BIM deletions (BIMdel). MATERIALS AND METHODS A retrospective analysis was conducted. BIMdel was detected using polymerase chain reaction analysis and direct sequencing of DNA. BIM protein expression was investigated by immunohistochemistry, and BIM mRNA levels by reverse transcriptase-polymerase chain reaction. Clinical characteristics, overall survival, progression-free survival (PFS), overall response rate (ORR), and treatment-related adverse events were compared between both groups. RESULTS Thirty-three patients were included; 15 received EGFR-TKIs, and 18 received EGFR-TKIs plus Bev. The median age was 63 years, with a majority of recruited female patients. All included individuals had an Eastern Cooperative Oncology Group performance score of 2 or less. The addition of Bev resulted in a significantly higher ORR (94.4% v 40%, P > .001). Median PFS was longer with the use of the combination therapy (11.12 v 7.87 months; P = .001). Median overall survival tended to be longer in the EGFR-TKIs plus Bev (30.9 v 25.4 months; P = .06) but failed to reach statistical significance. Response in terms of both partial and complete as well as overall favorably affected PFS. CONCLUSION EGFR-TKIs plus Bev conferred a significantly higher ORR and PFS in advanced NSCLC patients with EGFR mutation and BIMdel. Further prospective studies are needed to validate these findings.

Background: In Colombia, the best strategy to establish indication for adjuvant chemotherapy in early breast cancer (EBC) remains unknown. This study aimed to identify the cost-utility of Oncotype DX™ (ODX) or Mammaprint™ (MMP) tests to establish the necessity of adjuvant chemotherapy. Methods: This study used an adapted decision-analytic model to compare cost and outcomes of care between ODX or MMP tests and routine care without ODX or MMP tests (adjuvant chemotherapy for all patients) over a 5-year time horizon from the perspective of the Colombian National Health System (NHS; payer). Inputs were obtained from national unit cost tariffs, published literature, and clinical trial database. The study population comprised women with hormone-receptor-positive (HR+), HER2-negative, lymph-node-negative (LN0) EBC with high-risk clinical criteria for recurrence. The outcome measures were discounted incremental cost-utility ratio (ICUR; 2021 United States dollar per quality-adjusted life-year [QALY] gained) and net monetary benefit (NMB).Probabilistic (PSA) and deterministic sensitivity analysis (DSA) were performed. Results: ODX increases QALYs by 0.05 and MMP by 0.03 with savings of $2,374 and $554 compared with the standard strategy, respectively, and were cost-saving in cost-utility plane. NMB for ODX was $2,203 and for MMP was $416. Both tests dominate the standard strategy. Sensitivity analysis revealed that with a threshold of 1 gross domestic product per capita, ODX will be cost-utility in 95.5% of the cases compared with 70.2% cases involving MMP.DSA showed that the variable with significant influence was the monthly cost of adjuvant chemotherapy. PSA revealed that ODX was a consistently superior strategy. Conclusions: Genomic profiling using ODX or MMP tests to define the need of adjuvant chemotherapy treatment in patients with HR+ and HER2− EBC is a cost-utility strategy that allows Colombian NHS to maintain budget.

Treatment-refractory meningiomas have a dismal prognosis and limited treatment options. Meningiomas express high-densities of somatostatin receptors (SSTR), thus potentially susceptible to antitumorigenic effects of somatostatin analogues (SSA). Evidence for SSA in meningiomas is scarce, and it is unclear if published literature would either (1) support wider use of SSA, if (2) more evidence is desirable, or if (3) available evidence is sufficient to discard SSA. We addressed the need for more evidence with a systematic review and meta-analysis. We performed an individual patient data (IPD) meta-analysis. Main outcomes were toxicity, best radiological response, progression-free survival, and overall survival. We applied multivariable logistic regression models to estimate the effect of SSA on the probability of obtaining radiological disease control. The predictive performance was evaluated using area under the curve and Brier scores. We included 16 studies and compiled IPD from 8/9 of all previous cohorts. Quality of evidence was overall ranked "very low." Stable disease was reported in 58% of patients as best radiological response. Per 100mg increase in total SSA dosage, the odds ratios for obtaining radiological disease control was 1.42 (1.11 to 1.81, P = 0.005) and 1.44 (1.00 to 2.08, P = 0.05) for patients treated with SSA as monodrug therapy vs SSA in combination with everolimus, respectively. Low quality of evidence impeded exact quantification of treatment efficacy, and the association between response and treatment may represent reverse causality. Yet, the SSA treatment was well tolerated, and beneficial effect cannot be disqualified. A prospective trial without bias from inconsistent study designs is warranted to assess SSA therapy for well-defined meningioma subgroups.

Precision medicine has impacted the field of medical oncology by introducing personalized therapies, improving all measurable outcomes. This field, in turn, has expanded to obtaining and analyzing a vast and ever-increasing amount of genomic information. One technique currently applied is the liquid biopsy, which consists of detecting and isolating DNA and exosomes in cancer patients. Newly developed techniques have made it possible to use the liquid biopsy in a wide range of settings. However, challenges regarding the validation of its clinical utility exist because of a lack of standardization across different techniques and tumor types, confounder genomic information, lack of appropriate clinical trial designs, and a non-measured, and therefore not estimated, economic impact on population health. Nowadays, liquid biopsy is not routinely used, but ongoing research is increasing its popularity, and a new era in oncology is developing. Therefore, it is essential to have an in-depth understanding of the liquid biopsy technique. In this review, we summarize the leading techniques and liquid biopsy applications in cancer.

We present the case of a 73-year-old male patient with a history of tobacco use who presented with a central nervous system mass that was confirmed to be a lung adenocarcinoma metastasis. High PD-L1 expression as well as negativity to other targetable drivers led to initiation of pembrolizumab monotherapy and ablative stereotactic radiation therapy on oligo­residual disease, achieving a complete response after 2 years of therapy. Following discontinuation of systemic treatment, the patient developed widespread desquamative plaques. A skin biopsy revealed subepidermal blistering and eosinophilic infiltration in conjunction with C3 and IgG depositions on the basement membrane, detected by immunofluorescence. A diagnosis of bullous pemphigoid was obtained, and systemic corticosteroids were administered with lesion progression. Infliximab was also administered without meaningful clinical improvement. Metronomic cyclophosphamide achieved a complete resolution of skin lesions and up to this day the patient continues with tumor control and is free of dermatological findings. In conclusion, bullous pemphigoid is a very rare dermatological adverse effect related with pembrolizumab treatment. Only two cases, including this one, have been reported, especially with this medication for the treatment of non-small cell lung cancer. With more reported cases, management strategies can be optimized even in the steroid refractory setting.

During the last several years, multiple gene rearrangements with oncogenic potential have been described in NSCLC, identifying specific clinic-pathological subgroups of patients that benefit from a targeted therapeutic approach, including anaplastic lymphoma kinase (ALK), c-ros protooncogene 1 (ROS1) and, more recently, REarranged during Transfection (RET) and neurotrophic tyrosine receptor kinases (NTRK) genes. Despite initial impressive antitumor activity, the use of targeted therapies in oncogene-addicted NSCLC subgroups is invariably associated with the development of acquired resistance through multiple mechanisms that can include both on-target and off-target mechanisms. However, the process of acquired resistance is a rapidly evolving clinical scenario that constantly evolves under the selective pressure of tyrosine kinase inhibitors. The development of increasingly higher selective and potent inhibitors, traditionally used to overcome resistance to first generation inhibitors, is associated with the development of novel mechanisms of resistance that encompass complex resistance mutations, highly recalcitrant to available TKIs, and bypass track mechanisms. Herein, we provide a comprehensive overview on the therapeutic strategies for overcoming acquired resistance to tyrosine kinase inhibitors (TKIs) targeting the most well-established oncogenic gene fusions in advanced NSCLC, including ALK, ROS1, RET, and NTRK rearrangements.

Introducción: el cáncer de pulmón en quienes nunca han fumado es responsable de entre 17.000 y 26.000 muertes anuales en los Estados Unidos y también es la séptima causa principal de mortalidad por cáncer en este país. La incidencia de cáncer de pulmón en personas que nunca han fumado parece estar aumentando. El cáncer de pulmón (CP), es la principal causa de muerte por cáncer en todo el mundo, es una enfermedad compleja y muy heterogénea. Además, una parte de los pacientes con CP no ha fumado nunca, población que estamos comenzando a explorar de forma exhaustiva. Se han relacionado varios factores de riesgo con el CP en personas que nunca han fumado entre los cuales encontramos la exposición al radón, al humo del combustible doméstico, las infecciones por Mycobacterium tuberculosis y el virus del papiloma humano, resaltando el papel importante de estos factores en la carcinogénesis. La coinfección por VPH en el cáncer de pulmón favorece la inclusión de la oncoproteína E5 y, por tanto, altera la señalización mitogénica downstream de RAS, EGFR y proteína quinasa-C (PKC), y la activación constitutiva de AP-1, que a través de c-jun pueden promover la supervivencia de las células tumorales. Aún hace falta conocer la asociación entre el estado de infección por VPH y la respuesta terapéutica.

Introducción: las mutaciones en el gen KRAS hacen parte de las alteraciones oncogénicas más frecuentes en pacientes con adenocarcinoma de pulmón abarcando alrededor del 30 % de esta población. Recientemente, en la Conferencia Mundial de Cáncer de Pulmón de 2019, el inhibidor específico de KRAS G12C AMG510 mostró resultados prometedores en el ensayo clínico de fase I, emergiendo como un tratamiento dirigido eficaz para aproximadamente el 10-12 % de los pacientes con NSCLC avanzado, con un impacto potencial relevante sobre su supervivencia y calidad de vida a largo plazo. En los colombianos, sin embargo, la frecuencia de las mutaciones de KRAS G12C no se ha estudiado y el pronóstico de los portadores de la mutación G12C aún no está claro. Objetivos: el diseño retrospectivo de este estudio tiene como objetivo evaluar la incidencia de este subtipo de mutación G12C del gen KRAS en muestras de pacientes colombianos con cáncer de pulmón de célula no pequeña EGFR y ALK negativos. La detección a nivel molecular de este subtipo de mutación es esencial para asignar el tratamiento personalizado basado en la oncología de precisión.

Atypical (WHO grade II) and malignant meningiomas (WHO Grade III) are a rare subset of primary intracranial tumors. Due to the high recurrence rate after surgical resection and radiotherapy, there has been a recent interest in exploring other systemic treatment options for these refractory tumors. Recent advances in molecular sequencing of tumors have elucidated new pathways and drug targets currently being studied. This article provides a thorough overview of novel investigational therapeutics, including targeted therapy, immunotherapy, and new technological modalities for atypical and malignant meningiomas. There is encouraging preclinical evidence regarding the efficacy of the emerging treatments discussed in this chapter. Several clinical trials are currently recruiting patients to translate targeted molecular therapy for recurrent and high-grade meningiomas.

Osimertinib is a third generation EGFR-TKI inhibitor approved in the first-line setting for patients with advanced non-small cell lung cancer (NSCLC). Additionally, it represents the treatment of choice in patients who present with T790M mutations and evidence of relapse of the disease. Effectiveness and safety of this drug have been studied in multiple clinical trials and observational studies, however, information regarding outcomes among Hispanic patients treated with Osimertinib is scarce. The objective of this study was to examine real-world effectiveness and safety of first-line Osimertinib in a cohort of Hispanic patients with NSCLC, emphasizing post-progression outcomes.This is a multicenter, multinational, retrospective cohort study of Hispanic patients treated with Osimertinib as first-line for EGFR-mutated NSCLC. Patients with a confirmed diagnosis of metastatic EGFR-mutated NSCLC who received Osimertinib (80mg/day until evidence of disease progression or presence of intolerable adverse effects) were identified and included. NGS was performed in tumor samples or liquid biopsies among patients who had disease progression. The primary outcome was progression-free survival, and the secondary outcome was post-progression survival.A total of 94 patients from Mexico, Argentina, Costa Rica, Colombia, Panama, Chile and the USA were included, with a median age of 59 years. Identified mutations included EGFR Exon 19 deletions and EGFR pL858R point mutations. Median progression-free survival (PFS) was 14.4 months (95%CI 12.4-18.2 months). Lung/pleura and lymph nodes were the most common sites of progression. Median post-progression survival was 7.73 months (95%CI 4.07 months-Not reached). Factors which negatively affected PFS included presence of liver metastases at diagnosis and a tumor mutational burden5 mut/Mb.Treatment with first line osimertinib represents an effective and safe option for Hispanic patients with metastatic NSCLC. Liver metastases and a higher tumor mutation burden were associated with a lower PFS. Despite effectiveness, different mechanisms of resistance were identified among the patients in this cohort, including mutations which can be targeted by other therapeutic options.

Galeno, médico de la línea hipocrática, nacido en Pérgamo en el siglo II después de Cristo, narraría en su estancia a Roma los casos de una enfermedad exantemática asociada a diarrea y fiebre que tomaría la vida de millones de ciudadanos del imperio romano. Esta enfermedad se diseminó por medio de los legionarios que, posteriormente a la campaña contra los Partos en oriente medio, marcharon de vuelta a la capital imperial para ver como una ola de muerte seguía su paso. El ímpetu de conquista militar perduraría en el espíritu de los emperadores, corregentes de ese entonces, llevando las tropas a la frontera germana y situando nuevamente a Galeno en el frente contra la plaga. En su regreso a Roma, posterior a la muerte del emperador Lucio Vero a manos de la enfermedad, Galeno se encargó de ser curador de la salud del hijo del emperador Marco Aurelio durante varios años, lo que le permitió continuar con sus estudios y su escritura, correspondiendo con su periodo de mayor productividad. La plaga Antonina, como se le conoció a este suceso, perduró por 23 años, tiempo durante el que se presentó en picos reincidentes y llevó el nombre de la dinastía de emperadores que vivieron durante su apogeo. Su impacto fue masivo en todas las áreas de la sociedad romana, con desenlaces fatales, debilitando la estructura misma del imperio y sembrando las bases para su colapso décadas más tarde.

Due to the widespread use of immune checkpoint inhibitors and the growing research efforts in this area, immune-mediated toxicity is well recognized. Nonetheless, few severe cases of oral or upper gastrointestinal tract mucosal involvement have been documented. Early recognition and prompt treatment are key to the adequate management of these patients. We present a male 93-year-old patient with an advanced head and neck tumor treated with nivolumab who developed severe oral ulcers. After discontinuation of nivolumab, he received initial steroid treatment without any significant improvement. Histopathologic analysis of the lesions revealed a pattern similar to graft versus host disease. Extrapolating the results of colchicine mouth washing in patients with active oral ulcers and Behçet’s disease, this strategy was implemented with concomitant metronomic cyclophosphamide, achieving complete ulcer resolution. Metagenomic oral bacterial sequencing during instauration of the lesions and highest extension revealed a significant decrease in microbiomic diversity and expansion of Haemophilus parainfluenzae similar to patients with active Behçet’s disease. In conclusion, oral ulcers associated with immune checkpoint inhibitors correspond to a difficult-to-treat entity that could physiopathologically be related to both graft versus host disease and Behçet’s disease.

Background: Mutations in STK11 (STK11(Mut)) and, frequently co-occurring, KEAP1 mutations (KEAP1(Mut)) 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 STK11(Wt)/KEAP1(Wt) 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 KRAS(Mut) + STK11(Mut), KRAS(Mut) + STK11(Mut) + KEAP1(Mut), STK11(Mut) + KEAP1(Mut), and KRAS(Mut) + KEAP1(Mut), respectively. Based on KRAS status, STK11 alterations were associated with significantly lower PD-L1 expression among those with KRAS(Wt) (p = 0.023), whereas KEAP1 mutations were predominantly associated with lower PD-L1 expression among KRAS(Mut) cases (p = 0.047). Tumors with KRAS(Mut) + KEAP1(Mut) 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 KEAP1(mut) 6.1 months versus STK11(Mut) 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 [STK11(Mut) 14.2 months versus STK11(Wt) 27.0 months (p = 0.0001)] or KEAP1 [KEAP1(Mut) 12.0 months versus KEAP1(Wt) 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.

Highlights • The identification of the KRAS G12C mutation in non-small cell lung cancer is relevant with new molecules being introduced for treatment. • The variation of mutation prevalence among different regions indicate that certain populations are more prone to develop KRAS G12C mutations among lung cancer than others. • Using genomic markers traditionally employed for the identification of individuals we managed to construct a model that was predictive for KRAS G12C mutational incidence, further indicating that appearance of KRAS G12C follows population substructures., Background The KRAS exon 2 p. G12C mutation in patients with lung adenocarcinoma has been increasing in relevance due to the development and effectiveness of new treatment medications. Studies around different populations indicate that regional variability between ethnic groups and ancestries could play an essential role in developing this molecular alteration within lung cancer. Methods In a prospective and retrospective cohort study on samples from lung adenocarcinoma from 1000 patients from different administrative regions in Colombia were tested for the KRAS p.G12C mutation. An analysis of STR populations markers was conducted to identify substructure contributions to mutation prevalence. Results Included were 979 patients with a national mean frequency for the KRAS exon 2 p.G12C mutation of 7.97% (95%CI 6.27–9.66%). Variation between regions was also identified with Antioquia reaching a positivity value of 12.7% (95%CI 9.1–16.3%) in contrast to other regions such as Bogota DC (Capital region) with 5.4% (2.7–8.2%) and Bolivar with 2.4% (95%CI 0–7.2%) (p-value = 0.00262). Furthermore, Short tandem repeat population substructures were found for eight markers that strongly yielded association with KRAS exon 2 p.G12C frequency reaching an adjusted R2 of 0.945 and a p-value of < 0.0001. Conclusions Widespread identification of KRAS exon 2 p.G12C mutations, especially in cases where NGS is not easily achieved is feasible at a population based level that can characterize regional and national patterns of mutation status. Furthermore, this type of mutation prevalence follows a population substructure pattern that can be easily determined by population and ancestral markers such as STR.

Background: Amplification of EGFR and its active mutant EGFRvIII are common in glioblastoma (GB). While EGFR and EGFRvIII play critical roles in pathogenesis, targeted therapy with EGFR-tyrosine kinase inhibitors (TKIs) or antibodies has shown limited efficacy. To improve the likelihood of effectiveness, we targeted adult patients with recurrent GB enriched for simultaneous EGFR amplification and EGFRvIII mutation, with osimertinib/bevacizumab at doses described for non-small cell lung cancer (NSCLC). Methods: We retrospectively explored whether previously described EGFRvIII mutation in association with EGFR gene amplification could predict response to osimertinib/bevacizumab combination in a subset of 15 patients treated at recurrence. The resistance pattern in a subgroup of subjects is described using a commercial NGS panel in liquid biopsy.Results: There were ten males (66.7%), and the median patient’s age was 56 years (range 38-70 years). After their initial diagnosis, 12 patients underwent partial (26.7%) or total resection (53.3%). Subsequently, all cases received IMRT and concurrent and adjuvant temozolomide (TMZ; the median number of cycles 9, range 6-12). The median follow-up after recurrence was 17.1 months (95% CI 12.3-22.6). All patients received osimertinib/bevacizumab as a second-line intervention with a median progression-free survival (PFS) of 5.1 months (95% CI 2.8-7.3) and overall survival (OS) of 9.0 months (95% CI 3.9-14.0). The PFS6 was 46.7%, and the overall response rate (ORR) was 13.3%. After exposure to the osimertinib/bevacizumab combination, the main secondary alterations were MET amplification, STAT3, IGF1R, PTEN, and PDGFR.Conclusions: While the osimertinib/bevacizumab combination was marginally effective in most GB patients with simultaneous EGFR amplification plus EGFRvIII mutation, a subgroup experienced a long-lasting meaningful benefit. The findings of this brief cohort justify the continuation of the research in a clinical trial. The pattern of resistance after exposure to osimertinib/bevacizumab includes known mechanisms in the regulation of EGFR, findings that contribute to the understanding and targeting in a stepwise rational this pathway.

Las cardiopatías congénitas son alteraciones de la forma y la función del corazón y corresponden a la segunda anomalía congénita más frecuente en el mundo. En Colombia, se registra una prevalencia de 15,7 por 10000 recién nacidos con predominio masculino, y con una mortalidad prenatal de 2,7%, y posnatal del 2,5% durante el primer año de vida. Reportamos un recién nacido de sexo femenino, sin antecedentes prenatales de importancia, con único hallazgo en ecografías de tamización compatible con una arteria umbilical única, quien, por un estado fetal insatisfactorio a las 39 semanas, nace por cesárea. Dada mala adaptación neonatal e hipoxia asociada se realizaron estudios de extensión evidenciando retorno pulmonar anómalo, inicialmente sospechado como hallazgo único y aislado. Exploración clínica adicional evidenció hipoplasia de músculos de la masticación, sugestiva de una alteración en la embriogénesis del primer arco faríngeo. Reclasificando esta anomalía como sindrómica, se sospechó de un trastorno por deleción de 22q11.2. Durante su estancia hospitalaria fallece. En el estudio de autopsia se evidencia un retorno pulmonar anómalo incompleto, el cual es una entidad bastante rara correspondiendo del 0,5 al 3% de las cardiopatías congénitas, de las cuales los parciales corresponden a menos del 0.7% de las mismas.

BackgroundLung cancer is a public health problem, and squamous cell carcinoma (SCC) is the second most prevalent subtype of this neoplasm. Compared to other subtypes, including adenocarcinoma, SCC is less well understood in terms of molecular pathogenesis, limiting therapeutic options among targeted agents approved for other disease subgroups. In this study, we sought to characterize the SCC genomic profile using a validated Next Generation Sequencing (NGS) platform.MethodsThe comprehensive NGS assay (TruSight Tumor 170) was used in order to target the full coding regions of 170 cancer-related genes on SCC samples. PD-L1 expression in tumor cells (TCs) was assessed using clone 22C3 (Dako). Clinical outcomes were correlated with molecular profile, including progression free survival (PFS), overall response rate (ORR), and overall survival (OS).ResultsA total of 26 samples were included, median age was 67 years (r, 33–83) and 53.8% were men. Tobacco consumption was identified in all subjects (mean 34-year package). For first-line treatment 80.8% of patients received cisplatin or carboplatin plus gemcitabine. In terms of molecular profile, we identified a high prevalence of inactivating mutations in TP53 (61.5%), PIK3CA (34.6%), MLL2 (34.6%), KEAP1 (38.4%), and NOTCH1 (26.9%). PD-L1 expression ranged from negative, 1, 2–49, and ≥50% in 23.1, 38.5, 26.9, and 11.5%, respectively. Interestingly, the genetic alterations did not have an effect in PFS, OS or ORR in this study. However, PDL1 expression was higher among those who had mutations in TP53 (p = 0.037) and greater expression of PDL1 was related to PIK3CA alterations (p = 0.05).ConclusionsThe genomic profile of SCC encompasses important genes including TP53, PIK3CA and KEAP1. TP53 mutations could be associated with PDL1 expression, generating hypothesis regarding specific treatment options.

A new coronavirus, named severe acute respiratory syndrome-coronavirus-2 by the WHO, has rapidly spread around the world since its first reported case in late December of 2019 from Wuhan, the People's Republic of China. As of mid-April 2020, this virus has affected more than 180 countries and territories, infecting more than 1,650,000 individuals and causing over 100,000 deaths. With approximately 20 million new cases globally per year, cancer affects a substantial portion of the population. Individuals affected by cancer are more susceptible to infections owing to coexisting chronic diseases (cardiovascular, pulmonary, and diabetes), overall poor health status, and systemic immunosuppressive states caused by both cancer and the anticancer treatment. As a consequence, patients with malignancies, especially those with lung cancer who develop coronavirus disease 2019, experience more difficult outcomes. A recent multicenter study carried out by the Hubei Anti-Cancer Association has also documented that patients with lung cancer had an increased risk of death, intensive care unit requirement, risk of presenting severe or critical symptoms, and use of invasive mechanical ventilation. Here, we present two representative cases of patients with lung cancer and coronavirus disease 2019 without respiratory compromise and with atypical and severe skin manifestations-findings that could be influenced by the long-term use of anti-programmed cell death protein 1 antibody.

The world currently faces a pandemic due to SARS-CoV-2. Relevant information has emerged regarding the higher risk of poor outcomes in lung cancer patients. As such, lung cancer patients must be prioritized in terms of prevention, detection and treatment. On May 7th, 45 experts in thoracic cancers from 11 different countries were invited to participate. A core panel of experts regarding thoracic oncology care amidst the pandemic gathered virtually, and a total of 60 initial recommendations were drafted based on available evidence, 2 questions were deleted due to conflicting evidence. By May 16th, 44 experts had agreed to participate, and voted on each of the 58 recommendation using a Delphi panel on a live voting event. Consensus was reached regarding the recommendations (>66 % strongly agree/agree) for 56 questions. Strong consensus (>80 % strongly agree/agree) was reached for 44 questions. Patients with lung cancer represent a particularly vulnerable population during this time. Special care must be taken to maintain treatment while avoiding exposure.

Background The intestinal microbiota is an important factor in modulating immune‐mediated tumor cell destruction. Alterations in the microbiome composition have been linked to reduced efficacy of immune checkpoint inhibitor (ICI) therapies. Therefore, antibiotic treatment (ATB), which modifies the diversity of the gut bacteria populations, could lead to a reduced efficacy of ICI treatments. Methods This was a retrospective cohort study. Patients with advanced non‐small cell lung cancer (NSCLC) treated with anti‐programmed cell death ligand‐1 (PD‐L1) alone, or in combination in three different countries in Latin America were included. After identification, patients were placed into three groups: Non‐ATB exposed (no‐ATB), exposed within 30 days of the first dose of ICI (pre‐ICI ATB) and patients receiving ATB concomitantly with ICI (ICI‐ATB). Progression‐free survival (PFS), overall survival (OS) and response rates to treatment with ICI were assessed. Results A total of 140 patients were included, of which 32 patients (23%) received ATB treatment. The most common ATB types were fluoroquinolones and B‐lactams. No differences in survival according to antibiotic type were identified. Median OS in patients not exposed to ATB was 40.6 months (95% CI: 32–67.7), compared with 20.3 months (95% CI: 12.1‐non‐reached [NR]) for patients with pre‐ICI ATB treatment and 24.7 months (95% CI: 13‐NR) for patients treated with ATB concomitantly with ICI. There were no significant differences in terms of PFS, or response rates across all treatment groups. Conclusions Antibiotic treatment was associated with reduced OS in Hispanic patients with NSCLC treated with ICIs., Antibiotic treatment has been shown to deter outcomes in patients treated with immune checkpoint inhibitors. The effect of antibiotics is studied for the first time in Latin American patients undergoing ICI therapy. Patients treated with antibiotics prior or during ICI therapy had a significantly shorter overall survival.

Precision oncology is the field that places emphasis on the diagnosis and treatment of tumors that harbor specific genomic alterations susceptible to inhibition or modulation. Although most alterations are only present in a minority of patients, a substantial effect on survival can be observed in this subgroup. Mass genome sequencing has led to the identification of a specific driver in the translocations of the tropomyosin receptor kinase family (NTRK) in a subset of rare tumors both in children and in adults, and to the development and investigation of Larotrectinib. This medication was granted approval by the US Food and Drug Administration for NTRK-positive tumors, regardless of histology or age group, as such, larotrectinib was the first in its kind to be approved under the premise that molecular pattern is more important than histology in terms of therapeutic approach. It yielded significant results in disease control with good tolerability across a wide range of diseases including rare pediatric tumors, salivary gland tumors, gliomas, soft-tissue sarcomas, and thyroid carcinomas. In addition, and by taking different approaches in clinical trial design and conducting allocation based on biomarkers, the effects of target therapies can be isolated and quantified. Moreover, and considering developing nations and resource-limited settings, precision oncology could offer a tool to reduce cancer-related disability and hospital costs. In addition, developing nations also present patients with rare tumors that lack a chance of treatment, outside of clinical trials. This, in turn, offers the possibility for international collaboration, and contributes to employment, education, and health service provisions. The reviews of this paper are available via the supplemental material section.

The COVID-19 pandemic caused a change in our society and put health systems in crisis worldwide. Different risk factors and comorbidities have been found that increase the risk of mortality when acquiring this infection. The use of alternative devices to the cigarette like the electronic cigarettes, the vapers have been studied widely and generators of great controversy since it has been discovered that they also produce different pulmonary affections. When developing the SARS-CoV2 infection, different theories have been generated about the greater predisposition to a worse prognosis of people who use electronic cigarettes; however, the information on this continues in discovery. A group of experts made up of oncologists, infectologists, pulmonologists, and epidemiologists met to review the literature and then generate theories about the impact of electronic cigarettes on SARS-CoV2 infection.

PROPÓSITO En medio de una pandemia mundial, la evidencia sugiere que, al igual que otras infecciones virales respiratorias graves, los pacientes con cáncer tienen un mayor riesgo de infectarse por COVID-19 y tienen un pronóstico más precario. MÉTODOS Hemos modelado la mortalidad y el requerimiento de la unidad de cuidados intensivos (UCI) para la atención de pacientes con cáncer infectados por COVID-19 en América Latina. Se construyó un modelo dinámico de Markov multiestatal. Las probabilidades de transición se estimaron sobre la base de informes publicados para la probabilidad acumulada de complicaciones. Los valores del número reproductivo básico (R0) se modelaron con R utilizando el paquete EpiEstim. Las estimaciones de los días de necesidad de UCI y la mortalidad absoluta se calcularon imputando el número de casos acumulados en el modelo de Markov. RESULTADOS El tiempo medio estimado de necesidad de UCI fue de 12,7 días, el tiempo medio hasta la mortalidad fue de 16,3 días después de la infección y el tiempo medio hasta el episodio grave fue de 8,1 días. La ocupación máxima de la UCI para pacientes con cáncer se calculó a los 16 días después de la infección. El análisis de sensibilidad determinista reveló un intervalo de mortalidad entre el 18,5% y el 30,4%. Con la tendencia de incidencia real, se esperaría que América Latina perdiera aproximadamente 111,725 pacientes con cáncer por SARS-CoV-2 (rango, 87,116-143,154 pacientes) para el día 60 desde el inicio del brote. Las pérdidas calculadas varían entre el 1% y el 17,6% de todos los pacientes con cáncer de la región. CONCLUSIÓN Los casos relacionados con el cáncer y las muertes atribuibles al SARS-CoV-2 ejercerán una gran presión sobre los sistemas de salud en América Latina. La implementación temprana de intervenciones sobre la base de datos proporcionados por modelos de enfermedades podría mitigar tanto las infecciones como las muertes entre los pacientes con cáncer. PURPOSE In the midst of a global pandemic, evidence suggests that similar to other severe respiratory viral infections, patients with cancer are at higher risk of becoming infected by COVID-19 and have a poorer prognosis. METHODS We have modeled the mortality and the intensive care unit (ICU) requirement for the care of patients with cancer infected with COVID-19 in Latin America. A dynamic multistate Markov model was constructed. Transition probabilities were estimated on the basis of published reports for cumulative probability of complications. Basic reproductive number (R0) values were modeled with R using the EpiEstim package. Estimations of days of ICU requirement and absolute mortality were calculated by imputing number of cumulative cases in the Markov model. RESULTS Estimated median time of ICU requirement was 12.7 days, median time to mortality was 16.3 days after infection, and median time to severe event was 8.1 days. Peak ICU occupancy for patients with cancer was calculated at 16 days after infection. Deterministic sensitivity analysis revealed an interval for mortality between 18.5% and 30.4%. With the actual incidence tendency, Latin America would be expected to lose approximately 111,725 patients with cancer to SARS-CoV-2 (range, 87,116-143,154 patients) by the 60th day since the start of the outbreak. Losses calculated vary between , 1% to 17.6% of all patients with cancer in the region. CONCLUSION Cancer-related cases and deaths attributable to SARS-CoV-2 will put a great strain on health care systems in Latin America. Early implementation of interventions on the basis of data given by disease modeling could mitigate both infections and deaths among patients with cancer.

Objectives: The objectives of this study are to evaluate the relationship between authorship networking, socioeconomic factors, and scientific productivity across Latin America. Methods: In a bibliometric analysis of cancer-related Latin-American publications, the relationship between authorship network indicators, sociodemographic factors, and number of peer-reviewed indexed publications per country was explored. A systematic review of the literature for cancer publications between 2000 and 2018 using the Scopus database limited to Latin-American authors was used for the construction of coauthorship and publication networks and their respective metrics. Sociodemographic variables including percentage of invested gross domestic product in research, population, and cancer incidence were also estimated. Multiple linear regression models were constructed to determine the relationship between productivity and the aforementioned variables. Results: A total of 8,528 articles across nine countries were included. Brazil was the most productive nation with 41.8% of identified references followed by Mexico (16.6%) and Argentina (12.9%). Latin America experienced a 9% growth in number of publications across the studied time frame. After analyzing networking and sociodemographic variables, number of authors in a collaboration network and percentage of invested gross domestic product were associated with high productivity yielding a multiple regression model with an R2 value of 0.983. Conclusions: This study indicates that extensive authorship networking and a high investment in research strongly predict cancer-related productivity. (C) 2020 Elsevier Inc. All rights reserved.