Successful long-term management of metastatic clear cell renal cell carcinoma with nivolumab: a case report and literature review.

In Colombia, renal cancer is a rare condition, with clear cell renal cell carcinoma (ccRCC) being the most prevalent neoplasm. In recent years, immune checkpoint inhibitors (ICI) have been proposed for the management of metastatic disease, as they have shown improved rates of response and long-term survival. Furthermore, they exhibit a favourable tolerance profile, and adverse events causing significant morbidity are infrequent. We report the case of a 61-year-old male patient initially diagnosed with early-stage ccRCC who underwent right nephrectomy in 2009. Six years later, disease recurrence with metastatic compromise was documented, which led to the resection of the L1 vertebral body followed by radiotherapy and maintenance treatment with sunitinib. Due to disease progression, treatment with sunitinib was discontinued. Subsequently, everolimus was initiated as second-line immunotherapy, which was later discontinued due to the appearance of new metastatic lesions. In 2017, the patient was referred to our institution, where a third-line pharmacological treatment with nivolumab was initiated. In 2022, complete remission by positron emission tomography-computed tomography (PET-CT) was evidenced, which has been sustained to date. This case demonstrates the efficacy and safety of ICI in patients with metastatic ccRCC. The case presented is relevant in that it describes the achievement of complete remission in a patient who did not respond to the first two lines of immunotherapy. Given the limited literature regarding the discontinuation of therapy after achieving sustained remission, further research is warranted to explore this topic.

Genotyping Squamous Cell Lung Carcinoma in Colombia (Geno1.1-CLICaP).

BACKGROUND: Lung 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. METHODS: The 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). RESULTS: A 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). CONCLUSIONS: The 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.

Systemic management of malignant meningiomas: A comparative survival and molecular marker analysis between Octreotide in combination with Everolimus and Sunitinib.

PURPOSE: To compare the effectiveness of octreotide/everolimus vs. sunitinib for the systemic treatment of recurrent aggressive meningiomas. METHODS: 31 patients with recurrent or refractory WHO II or WHO III meningiomas were examined in two reference centers in Colombia. Patients who had systemic treatment (sunitinib, everolimus/octreotide) and a complete follow-up were included. Overall survival (OS), progression-free survival (PFS) and toxicities were evaluated. Additionally, tissue samples were examined for PDGFRß and VEGFR2, their expression was correlated with outcomes. RESULTS: Twenty-two patients (72%) were female with a median age of 55 years (SD±15.3). The most prevalent histology was anaplastic meningioma in 20 patients (65%) with 48% of patients suffering from three previous relapses before the start of systemic treatment. A total of 14 patients received combination therapy with octreotide/everolimus, 11 received sunitinib and the remaining 6 received other second-line agents. Median OS was 37.3 months (95%CI 28.5-42.1) and the PFS during the treatment with everolimus/octreotide (EO) and sunitinib (Su) was 12.1 months (95%CI 9.2-21.1) and 9.1 months (95%CI 6.8-16.8); p = 0.43), respectively. The OS of the group treated with the EO→Su→Bev sequence (1st/2nd/3rd line) was 6.5 months longer than the Su→EO→Bev sequence (36.0 vs. 29.5 months) (p = 0.0001). When analyzing molecular markers, the positive PDGFRß and negative VEGFR2 expression were associated with longer survival both in OS and PFS. CONCLUSION: Sunitinib and octreotide/everolimus have similar efficacy and safety in the systemic management of refractory meningioma. VEGFR2 and PDGFRß expression are associated with better outcomes.

EGFR Amplification and Sensitizing Mutations Correlate with Survival in Lung Adenocarcinoma Patients Treated with Erlotinib (MutP-CLICaP).

BACKGROUND: Non-small cell lung cancer (NSCLC) has a 5-year survival of 5-16%. Epidermal growth factor receptor (EGFR) mutations, in most cases, confer sensitivity to EGFR tyrosine kinase inhibitor (TKI) therapy. Nonetheless, it is still unclear why clinical outcomes vary among patients with identical EGFR mutations. The amplification of the EGFR gene (EGFRamp) may play a significant role. OBJECTIVE: Compare the complete (CR) and partial response (PR) rates, overall survival (OS), and progression-free survival (PFS) in Hispanic patients with lung adenocarcinoma treated with erlotinib with EGFR mutations (L858R or exon 19 deletion [Del19]) with and without concomitant EGFRamp. PATIENTS AND METHODS: Seventy-two EGFR-positive lung adenocarcinoma patients of Hispanic origin, who underwent first-line treatment with erlotinib, were evaluated for EGFRamp by fluorescence in situ hybridization (FISH). The clinical outcomes were analyzed according to EGFR mutations and EGFRamp status. RESULTS: 30.6% of samples showed EGFRamp, more frequently present in patients with Del19 (p = 0.05). Patients with EGFRamp had a longer PFS (in months) [(28.5, 95% CI 22.3-34.6) vs. (11.0, 95% CI 8.2-16.7); p = 0.002] and OS [(37.8, 95% CI 30.9-44.7) vs. (27.1, 95% CI 12.8-41.3); p = 0.009] than those without. EGFRamp significantly influenced the response to erlotinib (p = 0.0001). EGFRamp+/Del19 had a longer OS, 37.8 (95% CI 31.0-44.6), compared to EGFRamp+/L8585R, 27.5 (95% CI 12.4-42.5) (p < 0.001) and longer PFS (p = 0.043). CONCLUSION: Among Hispanic patients, EGFRamp was present in 30% of patients with EGFR mutations. EGFR mutations and EGFRamp are associated with better OS, PFS, CR, and PR to erlotinib and, hence, could aid in the correct selection of patients that benefit from EGFR TKI treatment.

Survival Outcomes According to TIMP1 and EGFR Expression in Heavily Treated Patients with Advanced Non-small Cell Lung Cancer who Received Biweekly Irinotecan Plus Bevacizumab.

BACKGROUND: Heavily treated patients with non-small cell lung cancer (NSCLC) have few treatment options, while irinotecan and bevacizumab have proven synergistic action in preclinical studies. PATIENTS AND METHODS: A total of 49 patients with heavily treated NSCLC were enrolled from 2011-2014 and treated with irinotecan and bevacizumab. Treatment response along with mutational status of epidermal growth factor receptor (EGFR), and tissue inhibitor of metalloproteinases-1 (TIMP1) and EGFR expression were evaluated. Progression-free (PFS) and overall (OS) survival were monitored. RESULTS: Median follow-up was 13.2 months. Twenty-three patients had received three or more prior therapy lines. Overall response rate was 32% [95% confidence interval (CI)=22%-39%] and 26% of patients achieved stable disease. Median PFS was 4.4 (95% CI=2.8-8.3) months and median OS 18.0 (95% CI=16.2-30.7) months. Nine patients harboring EGFR mutations had a long-lasting partial response. A shorter OS was found in patients with a higher TIMP1 expression (p=0.006). CONCLUSION: Irinotecan combined with bevacizumab had favorable antitumor activity in heavily pretreated patients with NSCLC. These results suggest this is a reasonable strategy, particularly for patients with low TIMP1 expression.

Caracterización clínica y radiológica del compromiso pulmonar por toxoplasmosis aguda diseminada en nueve pacientes inmunocompetentes / Clinical and radiological characterization of the pulmonary commitment for acute toxoplasmosis disseminated in nine immunocompetents patients

La toxoplasmosis aguda en el individuo inmunocompetente generalmente tiene un comportamiento benigno y autolimitado. Sin embargo, en pacientes provenientes de área selvática se han presentado casos severos de compromiso visceral, el más frecuente de ellos, el pulmonar. Se realizó la descripción clínica y radiológica de nueve individuos miembros de las fuerzas militares de Colombia, con toxoplasmosis aguda y compromiso pulmonar. El 55% de los casos presentó disnea clase funcional II/IV; 33% clase funcional III/IV y tan sólo 1/9 pacientes presentó clase funcional IV/IV. La imagen radiológica más común fue la consolidación pulmonar unifocal o multifocal (66%), y en menor frecuencia la presencia de infiltrados reticulares, reticulonodulares y derrame pleural. La totalidad de los pacientes evolucionaron en forma satisfactoria, dos de ellos con necesidad de soporte con ventilación mecánica no invasiva.

Descripción de un brote epidémico de toxoplasmosis aguda en pacientes inmunocompetentes miembros de las fuerzas militares de Colombia durante operaciones de selva / Description of an epidemic outbreak of acute toxoplasmosis in immunocompetent patients from Colombian Armed Forces during jungle operations

La toxoplasmosis es una de las infecciones oportunistas más frecuentes en los pacientes infectados con el virus de inmunodeficiencia humana (VIH), mientras que, en los pacientes inmunocompetentes, la infección es sintomática sólo en 10% a 20% de los casos, generalmente con un comportamiento benigno y autolimitado. En la última década se han informado casos graves de compromiso visceral por toxoplasmosis aguda en pacientes inmunocompetentes. En este artículo se presenta un brote epidémico causado por Toxoplasma gondii en personal militar durante el desarrollo de operaciones de selva en el área general de La Macarena, Meta, Colombia. Los 18 casos reportados se confirmaron mediante inmunofluorescencia indirecta (IFI) de anticuerpos IgG anti-toxoplasma, al obtener títulos iguales o superiores a 1:1.024 (valor negativo inferior a 1:16). Los síntomas más importantes en estos pacientes fueron fiebre prolongada, adenopatías y compromiso pulmonar y gastrointestinal. Un paciente desarrolló compromiso miopericárdico grave. Todos los pacientes se recuperaron después de tratamiento con pirimetamina/sulfodaxina y clindamicina durante tres semanas. Una hipótesis para la presentación del brote epidémico es el consumo de agua contaminada con ooquistes y, probablemente, la seriedad del compromiso puede atribuirse a una cepa silvestre del parásito, tal como se ha descrito en otros casos reportados en la literatura, aunque en nuestro caso en particular, no se pudo realizar el aislamiento y tipificación de las cepas involucradas.

Toxoplasmosis is a common opportunistic infection in patients infected with HIV/AIDS while in immunocompetent patients this infection causes symptoms only in 10% to 20% of the cases, generally with a benign and autoresolutive course. In the last decade some severe cases with visceral involvement has been reported in immunocompetent patients, though they were isolated or recovered during years. We present the first Colombian report of an epidemic outbreak caused by Toxoplasma gondii in military personnel deployed to rural areas located at La Macarena, Meta, Colombia. All 18 cases were confirmed by IgG indirect immunofluorescence (IFI) with titers higher than 1:1,024 (normal range: 1:16). Their main symptoms were fever, adenopathies and pulmonary and gastrointestinal compromise. One patient developed severe myocardial compromise. All the patients recovered after treatment with pyrimetamine/sulfadoxine and clyndamicin for 3 weeks. A possible hypothesis for this outbreak was the consumption of contaminated water with oocysts, and probably the severity of the compromise could be elicited by a “wild” strain of the parasite as it is reported in the literature. Unfortunately, it was impossible to isolate and identify the specific strain.

A propósito de la etiología bacteriana de epoc y asma. Infección por chlamydia pneumoniae y enfermedad pulmonar crónica: ¿relación causal o epifenómeno? / A propósito da etiología bacteriana de epoc e asma. Infecção por chlamydia pneumoniae e doença pulmonar crônica: ¿relação causal ou epifenómeno? / In reference to the bacteriologic ethiology of copd and asthma. Chlamydia pneumoniae infection and chronic lung disease: causative relationship or epiphenomenum?

Chlamydia pneumoniae es una bacteria intracelular involucrada en el desarrollo de infecciones respiratorias agudas y en la fisiopatología de enfermedades pulmonares crónicas, concretamente en la enfermedad pulmonar obstructiva crónica y en el asma del adulto, entidades en cuyas exacerbaciones también parece estar implicada. En la actualidad se esgrimen diversas hipótesis para explicar la relación entre la infección respiratoria por Chlamydia pneumoniae y las patologías pulmonares crónicas, pero existe controversia acerca de si simplemente se trata de un epifenómeno. A continuación se describen los principales hallazgos que sugieren el papel etiológico de la infección por esta bacteria en la enfermedad pulmonar crónica y aunque no se conocen estudios sobre este tema en Colombia, se auguran futuras líneas de investigación al respecto...

Chlamydia pneumoniae is an intracellular bacteria involved in the development of acute respiratory infections and in the physiopathology of chronic lung illnesses, specifically in COPD and adult asthma where it seems to play a role in their exacerbations. At the present time, there are diverse hypothesis being proposed to explain the relationship between the respiratory infections due to Chlamydia pneumoniae and chronic lung diseases but there is controversy as to whether this is simply an epiphenomenon. Here we describe the principal observations, which strongly suggest the etiologic role of this bacterial infection in the genesis of chronic obstructive lung diseases. Although we don't know about any trials on this topic in our country, its importance ensures future investigation on this field...

Chlamydia pneumoniae é uma bactéria intracelular associada no desenvolvimento de infecções respiratórias agudas e na fisiopatologia de doenças pulmonares crônicas, concretamente na doença pulmonar obstructiva crônica e no asma do adulto, entidades em cujas exacerbações também parece estar implicada. Na atualidade se esgrimem diversas hipóteses para explicar a relação entre a infecção respiratória por Chlamydia pneumoniae e as patologias pulmonares crônicas, mas existe controvérsia a respeito de se simplesmente trata-se de um epifenômeno. A seguir se descrevem os principais achados que sugerem o papel etiológico da infecção por esta bactéria na doença pulmonar crônica e ainda que não se conheçam estudos sobre este tema em Colômbia, auguram-se futuras linhas de investigação ao respeito...