Association of PD-L1 expression with driver gene mutations and clinicopathological characteristics in non-small cell lung cancer: A real-world study of 10 441 patients.

BACKGROUND: Programmed death ligand-1 (PD-L1) expression is a well-known predictive biomarker of response to immune checkpoint blockade in non-small cell lung cancer (NSCLC). However, there is limited evidence of the relationship between PD-L1 expression, clinicopathological features, and their association with major driver mutations in NSCLC patients in Latin America. METHODS: This retrospective study included patients from Argentina with advanced NSCLC, and centralized evaluation of PD-L1 expression concurrently with genomic alterations in the driver genes EGFR, ALK, ROS1, BRAF, and/or KRAS G12C in FFPE tissue samples. RESULTS: A total of 10 441 patients with advanced NSCLC were analyzed. Adenocarcinoma was the most frequent histological subtype (71.1%). PD-L1 expression was categorized as PD-L1 negative (45.1%), PD-L1 positive low-expression 1%-49% (32.3%), and PD-L1 positive high-expression ≥50% (22.6%). Notably, current smokers and males were more likely to have tumors with PD-L1 tumor proportion score (TPS) ≥50% and ≥ 80% expression, respectively (p < 0.001 and p = 0.013). Tumors with non-adenocarcinoma histology had a significantly higher median PD-L1 expression (p < 0.001). Additionally, PD-L1 in distant nodes was more likely ≥50% (OR 1.60 [95% CI: 1.14-2.25, p < 0.01]). In the multivariate analysis, EGFR-positive tumors were more commonly associated with PD-L1 low expression (OR 0.62 [95% CI: 0.51-0.75], p < 0.01), while ALK-positive tumors had a significant risk of being PD-L1 positive (OR 1.81 [95% CI: 1.30-2.52], p < 0.01). CONCLUSIONS: PD-L1 expression was associated with well-defined clinicopathological and genomic features. These findings provide a comprehensive view of the expression of PD-L1 in patients with advanced NSCLC in a large Latin American cohort.

Cáncer de primario desconocido / Cancer of unknown primary site

Consideramos un tumor de origen desconocido cuando a pesar de exhaustivos estudios no es posible determinar el origen de una neoplasia que se presenta metastásica. Esta presentación puede representar entre el 2 al 9 % de las neoplasias. La sobrevida a 5 años es del 11%. La sobrevida al año es menor al 15% y del 5-10% a los 5 años. Ciertas características clínicas a saber sexo masculino, múltiples metástasis cerebrales, compromiso pleural/pulmonar, compromiso hepático, compromiso adrenal e histología de adenocarcinoma son indicadores de mal pronóstico mientras que la presencia de ganglios linfáticos e histología de neuroendocrino se asocian con largos sobrevividores. Para llegar a un diagnóstico diferencial es fundamental contar con una metodología de búsqueda del primario así como un detallado trabajo de los anatomopatólogos. De acuerdo a la localización los tratamientos son una combinación de cirugía, radioterapia y quimioterapia.

Clinicians should consider a carcinoma of unknown primary site when after performing an exhaustive physical examination with a complete history, chest radiographs and abdominopelvic tomography, it is not possible to identify the origin of a metastatic malignancy. Metastatic cancer with no obvious primary site, accounts for about 2 to 6% in the USA, and for 2 to 9% in the rest of the world. About 58% of all carcinomas of unknown primry site are adenocarcinomas. The most frequent symptoms include anorexia, fatigue, weakness, weight loss and a poorly clinical state. Signs are related to the compromised metastatic places of origin. Until recently these patients attracted little attention, since prognosis was believed to be uniformly por regardless of treatment, however effective therapy is now available for many types of advanced cancer due to the development of new drugs and new procedures. The authors describe the methodology to seek the primary site, the pathology, staging and treatment. Optimal therapy depends on the recognition of the localiation with a combination of surgery, radiotherapy and chemotherapy.