Molecular Epidemiology of ALK Rearrangements in Advanced Lung Adenocarcinoma in Latin America.

OBJECTIVE: Latin American countries are heterogeneous in terms of lung cancer incidence and exposure to potential carcinogens. We evaluated the frequency and clinical characteristics of ALK rearrangements (ALKr) in Latin America. METHODS: A total of 5,130 lung cancer patients from 10 Latin American countries were screened for inclusion. ALKr detection was performed by fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) to assess method variability. Demographic and clinicopathologic characteristics were analyzed. RESULTS: Among the 5,130 patients screened, 8.4% (n = 433) had nonevaluable FISH tests. Evaluable FISH analyses revealed positive ALKr in 6.8% (320/4,697) of the study population, which included patients from 9 countries. ALKr distribution for each country was: Mexico 7.6% (79/1,034), Colombia 4.1% (10/242), Argentina 6.0% (153/2,534), Costa Rica 9.5% (13/137), Panama 4.4% (5/114), Uruguay 5.4% (2/37), Chile 8.6% (16/185), Venezuela 8.9% (13/146), and Peru 10.8% (29/268). RT-PCR showed high positive (83.6%) and negative (99.7%) predictive values when compared to the gold standard FISH. In contrast, IHC only showed a high negative predictive value (94.6%). CONCLUSIONS: Although there is a clear country and continental variability in terms of ALKr frequency, this difference is not significant and the overall incidence of ALKr in Latin America does not differ from the rest of the world.

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.

Recommendations for detection, prioritization, and treatment of thoracic oncology patients during the COVID-19 pandemic: the THOCOoP cooperative group.

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.

Characteristics and long-term outcomes of advanced pleural mesothelioma in Latin America (MeSO-CLICaP).

BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive tumor, associated with poor prognosis. There is a lack of information about the clinical and pathological features related with survival in the Latin American population. METHODS: The MeSO-CLICaP registry identified 302 patients with advanced MPM diagnosed and treated between January 2008 and March 2016. The Cox model was applied to determine the variables associated with survival. A random forest tree model was built to predict the response to first-line chemotherapy among Latin American patients. RESULTS: The median age was 61.1 years (SD 10.6 years), 191 (63.2%) were men, 65.9% were ever smokers, and 38.7% had previous exposure to asbestos. A total of 237 (78.5%) had epithelioid tumors, and 188 (62.3%) and 114 (37.7%) cases had stage III or IV MPM, respectively. A total of 49 patients (16.2%) underwent pleurectomy, 57 (18.9%) received radiotherapy, and 279 patients received first-line platinum-based chemotherapy. The overall response rate to first-line chemotherapy was 40.4%, progression-free survival to first-line treatment was 5.7 months (95% CI 4.9-6.5), and 63 (20.8%) patients had pemetrexed maintenance. The median overall survival was 16.8 months (95% CI 13.0-20.5), and multivariate analysis found that stage (P = 0.013), and pleurodesis (P = 0.048), were independent prognostic factors for first-line overall survival. The model to predict response to first-line chemotherapy obtained a 0.98 area under the curve, a sensitivity of 93%, and a specificity of 95% for detecting responders and non-responders. CONCLUSION: This study identifies factors associated with clinical benefit from chemotherapy among advanced MPM Latin American patients, emphasizing the impact of histology and the clinical benefit of chemotherapy on outcomes.

EGFR exon 20 insertion in lung adenocarcinomas among Hispanics (geno1.2-CLICaP).

OBJECTIVES: Contrasting other EGFR mutations (EGFRm) in lung adenocarcinomas, insertions in exon 20 (exon20ins) are generally associated with resistance to targeted therapy, limiting therapeutic options and impoverishing the prognosis compared to other EGFRm. We sought to extensively characterize exon20ins from a large cohort of lung adenocarcinomas in Hispanic patients. MATERIALS AND METHODS: This was a region-wide, observational longitudinal cohort study to evaluate characteristics and outcomes of patients with exon20ins in lung adenocarcinoma, based on a secondary analysis of electronic records from the Geno1.2-CLICaP Platform and extended genotype testing. Patients from six Latin-American countries were included (Argentina, Colombia, Costa Rica, Ecuador, Panama, and Mexico). Data obtained included the molecular spectrum (extended genotyping for mutations in BRAF, NRAS, PIK3CA, Her2 and MEK1, as well as for EGFR amplification, ALK and PD-L1 protein expression), clinic-pathologic characteristics, prevalence and outcomes to therapeutic approach. RESULTS AND CONCLUSIONS: 4.005 patients diagnosed with stage III/IV lung adenocarcinoma from 2011 to 2016 were initially screened. Among these, 88 patients had a confirmed exon20 in. and were included; median age was 66-years, 62.5% were females, 64% were never smokers and 39% presented with brain metastases. The H773insH variant was the most frequent, making up 21.6% of cases. A common EGFRm was concomitantly found in 36.4% (del19/L858R), and 8% (G719X/L861Q/S768I) of cases. Five cases had additional mutations in PI3K, KRAS and MEK1, 26% had EGFR amplification and 81.7% had PD-L1 expression 1-50%. Overall response rate to first-line therapy was 28% and overall survival was 16.4 months. Prognosis was positively influenced by the concomitant presence of common EGFRm and response to first-line. Our results suggest that patients with EGFR exon20ins have similar clinical characteristics to those with common EGFRm but a poorer prognosis. Last, the mean PD-L1 expression in this population seems higher than for patients with common EGFRm.

An international epidemiological analysis of young patients with non-small cell lung cancer (AduJov-CLICaP).

BACKGROUND: A proportion of patients with NSCLC is diagnosed at 40 years or younger. These patients tend to be never-smokers, usually present with stage IV adenocarcinoma, and have somatic genomic alterations. Few studies have documented and analyzed epidemiological characteristics of this population. MATERIALS AND METHODS: We performed an international epidemiological analysis of 389 young patients with NSCLC. Data was collected from centers participating in the Latin American Consortium for Lung Cancer Research (AduJov-CLICaP). Patients were identified and data was retrospectively collected from different Latin American countries and Canada (Argentina=6, Canada=19, Colombia=29, Costa Rica=9, Mexico=219, Nicaragua=2, Panama=19, Perú=76 and Venezuela=10). The period of study was from 2012 to 2017. Inclusion criteria were: age 40 years or less and a histologically confirmed NSCLC. Clinical data was obtained, and EGFR mutation status and EML4-ALK translocation were collected. RESULTS: NSCLC patients aged 40 years or less accounted for approximately 4% of the total NSCLC population. Female patients accounted for 54.5%, while median age was of 37 years. Adenocarcinoma accounted for 86.1% (n=335/389), 72.5% (n=282/389; unknown=5) of patients were non-smokers, and 90.3% (n=351/389) had stage IV disease. Site of metastasis was obtained from 260/351 (unknown=91) stage IV patients (lung metastasis=40.0%, CNS metastasis=35.7%, and bone metastasis=31.5%). OS for the total population was 17.3 months (95%CI=13.9-20.7). OS for EGFRm(+)=31.4months (95%CI=11.6-51.3), EGFRm(-)=14.5months (95%CI=11.0-17.9) (p=0.005). OS for alk(+)=9.8months (95%CI=3.1-16.5) and alk(-)=5.6months (95%CI=3.9-7.3) (p=0.315). CONCLUSIONS: Patients aged 40 years or less account for a small but important proportion of NSCLC cases. Younger patients may have different characteristics compared to the older population. EGFRm and EML4-alk translocation frequency is higher than that of the general population.

EGFR Mutations in Latinos From the United States and Latin America.

PURPOSE: Epidermal growth factor receptor (EGFR) mutations confer sensitivity to EGFR tyrosine kinase inhibitors in patients with advanced non-small-cell lung cancer (NSCLC). There are limited and conflicting reports on the frequency of EGFR mutations in Latinos. PATIENTS AND METHODS: Samples from 642 patients with NSCLC from seven institutions in the United States and Latin America were assessed for EGFR mutations (exons 18 to 21) at Clinical Laboratory Improvement Amendments-certified central laboratories. RESULTS: EGFR mutation analysis was successfully performed in 480 (75%) of 642 patients; 90 (19%) were Latinos, 318 (66%) were non-Latino whites, 35 (7%) were non-Latino Asians, 30 (6%) were non-Latino blacks, and seven (2%) were of other races or ethnicities. EGFR mutations were found in 21 (23%) of 90 Latinos with varying frequencies according to the country of origin; Latinos from Peru (37%), followed by the United States (23%), Mexico (18%), Venezuela (10%), and Bolivia (8%). In never-smoker Latinos and Latinos with adenocarcinoma histology, EGFR mutation frequencies were 38% and 30%, respectively. There was a significant difference in the frequency of EGFR mutations among the different racial and ethnic subgroups analyzed (P < .001), with non-Latino Asians having the highest frequency (57%) followed by Latinos (23%), non-Latino whites (19%), and non-Latino blacks (10%). There was no difference between Latinos (23%) and non-Latinos (22%; P = .78) and Latinos and non-Latino whites (P = .37). Patients from Peru had an overall higher frequency of mutations (37%) than all other Latinos (17%), but this difference only exhibited a trend toward significance (P = .058). CONCLUSION: There was no significant difference between the frequency of EGFR mutations in NSCLC in Latinos and non-Latinos.

Tratamiento del cáncer de laringe experiencia en el Instituto Oncológico Doctor Luis Razetti / Laryngeal cancer treatment experience in the Oncology Institute Doctor Luis Razetti

El cáncer de laringe representa un 20%-25% de los carcinomas de cabeza y cuello. Actualmente su tratamiento incluye diversas modalidades, desde cirugía para enfermedad localizada hasta esquemas concurrentes de quimioterapia y radioterapia para estadios avanzados. Evaluar los resultados del tratamiento del carcinoma laríngeo en nuestra institución en el período 2000-2009; por lo que se realizó un estudio retrospectivo analítico basado en las historias clínicas de pacientes con diagnóstico histopatológico de carcinoma laríngeo, en estadios precoces y avanzados no metastásicos. El objetivo primario del estudio es evaluar la supervivencia global, según el estadiaje y/o las modalidades terapéuticas. Los objetivos secundarios incluyen supervivencia libre de enfermedad y supervivencia libre de laringectomía. Un total de 187 pacientes, la sobrevida global fue significativamente mayor en estadios precoces comparado a estadios avanzados (P=0,023). La sobrevida global en estadios avanzados no presentó diferencias estadísticamente significativas independientemente de la modalidad de tratamiento aplicado. La sobrevida libre de laringectomía y libre de enfermedad muestra una tendencia preliminar a favor del tratamiento concurrente definitivo en estadios avanzados. La sobrevida global y libre de enfermedad en estadios precoces no presentó variación de acuerdo a la modalidad del tratamiento definitivo (P=0,086). La radioterapia ofrece una eficacia comparable a la cirugía en estadios precoces, el tratamiento multimodal de estadios avanzados permite una mayor sobrevida libre de laringectomía y libre de enfermedad sin impacto aparente en la sobrevida global en relación con la cirugía radical.

The laryngeal cancer accounts for 20%- 25% of all the head and neck carcinomas. The current treatment includes various forms ranging from surgery for localized disease to concurrent schemes chemotherapy and radiotherapy for the advanced stages. The purpose of this study is to evaluate the results of the treatment of laryngeal carcinoma at our institution in the period 2000-2009. For what was done a retrospective study based on medical records of patients with histopathological diagnosis of laryngeal carcinoma, stage early and in advanced non-metastatic. The primary objective is to evaluate overall survival, according to the staging and or therapeutic modalities we used. The secondary end points included disease free survival, laringectomy free survival. For a total of 187 patients, the overall survival was significantly higher in early stages compared to advanced stages (P=0.023). The global survival in advanced stages did not differ statistically significant regardless of the type of treatment we applied. The free laringectomy survival and the disease free survival show atrend in favor of the preliminary final concurrent treatment in the advanced stages. The overall survival and disease free survival in early stages did not present variation according to the definitive treatment modality (P= 0.086). Radiotherapy offers comparable efficacy to surgery in early stages, multimodal treatment for advanced stages allows greater laringectomy free survival and disease free survival without apparent impact on overall free survival in relation to the radical surgery.

Tratamiento adyuvante en cáncer de colon: nuestra experiencia / Adjuvant treatment for colon cancer: our experience

El cáncer de colon es uno de los tumores más frecuentes en nuestro país. Posterior a cirugía, la quimioterapia adyuvante ha mostrado beneficios para los pacientes de alto riesgo y ganglios positivos, por lo que es considerada estándar. De este estudio, es evaluar la experiencia de nuestra institución en lo que a esta modalidad de tratamiento se refiere durante cinco años. De manera preliminar, se evaluaron un total de 118 pacientes. La distribución por género fue igual. Los tumores de colon izquierdo ocuparon el mayor porcentaje (45,76%), la histología más frecuente fue adenocarcinoma. En cuanto al TNM, el T más frecuente fue el T3 (53.1%) y el N el NO (46,9%). El 63,2% de pacientes recibió quimioterapia adyuvante, siendo los esquemas más utilizados, Folfox 4 62,5% seguido de Xelos 18,1% y Capecitabina 13,9. El 66,7% presentó eventos adversos. siendo las más frecuentes diarreas, nauseas, vómitos, y neuropatía periférica, todos G1/2 en la mayoría de los casos. No hubo muerte asociada al tratamiento. El 100% de los pacientes tuvieron seguimiento y para el año 2009 el 55,93% se encontraban vivos. La sobrevida global fue mayor en el grupo que recibió adyuvancia sin llegar a significancia estadística (P=0,098) ya que hasta la fecha no se ha alcanzado la mediana de sobrevida global. La sobrevida libre de enfermedad, fue mayor en el grupo que recibió quimioterapia, alcanzado significancia estadística (P=0,045).

Colon cancer is one of the most common tumors in our country. Following surgery, adjuvant chemotherapy has shown benefit for patients at high risk and node-positive, so it is considered standard modality. The aim of this study is to evaluate the experience of our institution as far as this treatment modality, referred for five years. Preliminary we evaluated total of 118 patients, the gender distribution was equal. Left colon tumors, occupied the highest percentage (45.76%) and the most common histology was adenocarcinoma. With regard to TNM, T3 was the most frequent (53.1%) and N0 also (46.9%). Of the sample assessed, 63.2% received adjuvant che motherapy, being the most widely used schemes, Folfox 4 62.5 %, Xelox18.1% and Capecitabine 13.9%. 66.7% of patients had adverse events, being the most frequent diarrhea, nausea, vomiting, and peripheral neuropathy, all G1/2 in most cases. There were no treatment-related deaths. 100% of patients had follow-up, for the year 2009, 55.93% of them were alive. The OS was greater in the group that received adjuvant treatment with regard to that it did not receive it, without statistics significant (P=0.098) since up to the date there has not been reached the median of global survival. Similar results were obtained with regard to the DFS, being this major in the group that received chemotherapy, versus the group that did not receive it, reached significant statistics (P=0.045).