Characteristics and outcomes of thymomas in Latin America: Results from over 10 years of experience (CLICaP-LATimus).

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.

Efficacy and Safety of Nivolumab in Previously Treated Patients With Non-Small-cell Lung Cancer: Real World Experience in Argentina.

BACKGROUND: Nivolumab was the first anti-programmed cell death 1 drug approved in Argentina for non-small-cell lung cancer treatment in the second-line setting. MATERIALS AND METHODS: The present study was a multicenter, observational, retrospective study of patients with progression to stage IV NSCLC during platinum-based chemotherapy who had received nivolumab monotherapy in a drug-expanded access program in Argentina. RESULTS: The data from 109 patients were assessed retrospectively for safety and clinical outcomes. The follow-up period was 8.83 months (interquartile range, 3.4-12.67); 57.8% were men, 29.4% were current smokers, and 78.0% had a diagnosis of nonsquamous cell cancer. The median number of chemotherapy lines before nivolumab was 2 (range, 1-4). Also, 59.6% had received radiotherapy and 89% had received platinum-based chemotherapy. The drug-related toxicity rate was 78.9%, the grade 2-3 toxicity rate was 28.4%, and 33.9% of patients had required corticosteroids. The treatment response was evaluated in 104 patients. The best response was a complete response in 2 (2%), partial response in 28 (27%), stable disease in 33 (32%), and progressive disease in 41 (39%). Univariate analysis revealed that the absence of corticosteroid use (P = .034), toxicity grade 1-3 (P = .0025), and performance status of ≤ 1 (P = .049) were associated with longer disease-free survival, performance status of ≤ 1 (P < .001), and toxicity grade 1-3 (P = .001) were associated with longer overall survival. On multivariate Cox regression analysis, toxicity grade 1-3 (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.24-0.81; P = .008) and age ≤ 50 years (HR, 0.28; 95% CI, 0.13-0.61; P = .001) were associated with longer progression-free survival and corticosteroid use was associated with shorter progression-free survival (HR, 2.06; 95% CI, 1.22-3.48; P = .007). CONCLUSIONS: The use of nivolumab in the real world setting in patients with heavily pretreated NSCLC was well tolerated and showed promising clinical efficacy. The performance status, use of corticosteroids, and immune-mediated toxicity seem to be the conditions that can affect the clinical outcomes.

Immunotherapy at any line of treatment improves survival in patients with advanced metastatic non-small cell lung cancer (NSCLC) compared with chemotherapy (Quijote-CLICaP).

BACKGROUND: To compare survival outcomes of patients with advanced or metastatic non-small cell lung cancer (NSCLC) who received immunotherapy as first-, second- or beyond line, versus matched patients receiving standard chemotherapy with special characterization of hyperprogressors. METHODS: A retrospective cohort study of 296 patients with unresectable/metastatic NSCLC treated with either, first-, second-, third- or fourth-line of immunotherapy was conducted. A matched comparison with a historical cohort of first-line chemotherapy and a random forest tree analysis to characterize hyperprogressors was conducted. RESULTS: Median age was 64 years (range 34-90), 40.2% of patients were female. A total of 91.2% of patients had an Eastern Cooperative Oncology Group (ECOG) performance score ≤ 1. Immunotherapy as first-line was given to 39 patients (13.7%), second-line to 140 (48.8%), and as third-line and beyond to 108 (37.6%). Median overall survival was 12.7 months (95% CI 9.67-14 months) and progression-free survival (PFS) of 4.27 months (95% CI 3.97-5.0). Factors associated with increased survival included treatment with immunotherapy as first-line (P < 0.001), type of response (P < 0.001) and PD-L1 status (P = 0.0039). Compared with the historical cohort, immunotherapy proved to be superior in terms of OS (P = 0.05) but not PFS (P = 0.2). A total of 44 hyperprogressors were documented (19.8%, [95% CI 14.5-25.1%]). Leukocyte count over 5.300 cells/dL was present in both hyperprogressors and long-term responders. CONCLUSIONS: Patients who receive immune-checkpoint inhibitors as part of their treatment for NSCLC have better overall survival (OS) compared with matched patients treated with standard chemotherapy, regardless of the line of treatment.

Real-World Treatment Patterns, Survival, and Prediction of CNS Progression in ALK-Positive Non-Small-Cell Lung Cancer Patients Treated with First-Line Crizotinib in Latin America Oncology Practices.

OBJECTIVE: This study describes the real-world characteristics, treatment sequencing, and outcomes among Hispanic patients with locally advanced/metastatic ALK-positive non-small-cell lung cancer (NSCLC) treated with crizotinib. METHODS: A retrospective patient review was conducted for several centers in Latin America. Clinicians identified ALK-positive NSCLC patients who received crizotinib and reported their clinical characteristics, treatments, and survival. Overall survival and progression-free survival (PFS) were described. A Random Forest Tree (RFT) model was constructed to predict brain progression. RESULTS: A total of 73 patients were included; median age at diagnosis was 58 years, 60.3% were female, and 93.2% had adenocarcinoma. Eighty-nine percent of patients were never smokers/former smokers, 71.1% had ≥2 sites of metastasis, and 20.5% had brain metastases at diagnosis. The median PFS on first-line crizotinib was 7.07 months (95% CI 3.77-12.37) and the overall response rate was 52%. Of those who discontinued crizotinib, 55.9% progressed in the central nervous system (CNS). The RFT model reached a sensitivity of 100% and a specificity of 88% for prediction of CNS progression. CONCLUSIONS: The overall response rate and the PFS observed in Hispanic patients with ALK-positive NSCLC treated with first-line crizotinib were similar to those in previous reports. An RFT model is helpful in predicting CNS progression and can help clinicians tailor treatments in a resource-limited practice.

Eficacia de los inhibidores de ALK en dos casos con evaluación positiva por inmunohistoquímica y negativa por FISH / Efficacy of ALK inhibitors in two cases with positive evaluation by immunohistochemistry and negative by FISH

En el carcinoma de pulmón de células no pequeñas (CPCNP), la activación de ALK se produce por la formación de genes de fusión. El perfil clínico donde ocurre con más frecuencia corresponde a pacientes jóvenes, mayormente mujeres, no fumadores, histología de adenocarcinoma y ausencia de mutaciones de EGFR y KRAS. Su presencia se describe en el 3-10% de los CPCNP. La importancia de la determinación de ALK radica en que identifica un subgrupo de pacientes con un comportamiento biológico diferente, en los cuales el tratamiento con inhibidores específicos, como el crizotinib, ceritinib o alectinib, es más eficaz que los convencionales. Las alteraciones moleculares de ALK pueden identificarse por hibridación in situ (ISH), por inmunohistoquímica (IHQ) y por RT-PCR, aunque el FISH es el procedimiento diagnóstico de referencia a nivel clínico. Se examinaron 308 casos de CPCNP y se compararon los resultados por FISH e IHQ. De los 8 (3%) identificados con expresión positiva, sólo 6 presentaron el rearreglo de ALK. Se presentan dos casos clínicos con ALK positivo por IHC y FISH negativo, uno presentó respuesta al tratamiento dirigido y otro no. A pesar de que el FISH es el gold standard, se acepta el uso de IHQ ya sea para definir conducta como único test o para screening y ulterior confirmación por FISH en los casos positivos. Estos dos casos con distinta respuesta al tratamiento con IHQ positiva pero FISH negativo, indican la ausencia de pautas, requiriendo de más conocimiento en el futuro para optimizar las conductas médicas (AU)

In non-small cell lung cancer, ALK activation is produced by gene fusion. The clinical scenario where this type of tumor appears more frequently is in young, female patients, without smoking history, adenocarcinoma histology and with no EGFR or KRAS mutation. It is described as 3 to 10% of non- small cell lung cancer cases. The importance of ALK determinations lies in the identification of a subgroup of patients with a different biological behavior and sensible tumor to target therapy with ALK inhibitors. Molecular alterations of ALK can be determined by in situ hybridization, immunohistochemistry (IHC) and RT-PCR, FISH is the reference diagnostic procedure in clinical applications. Were evaluated 308 cases of non-small cell lung cancer, and FISH and IHC results were compared. Eight (3%) cases presented positive expression, but only 6 of them presented ALK rearrangements. These two clinical cases of patients with IHC positive but FISH negative for ALK are presented, observing good clinical response in only one of them. Although FISH is considered the gold standard technique, IHC use is accepted for treatment decisions as a lone procedure or as screening with FISH confirmation in positive cases. These two particular cases express the absence of guidelines in this infrequent scenario, needing more knowledge in the future in order to take better medical decisions (AU)