Cell-Free Circulating Tumor DNA Improves Standard Genotyping of Non-Small-Cell Lung Cancer and Increases Detection of Targetable Alterations in a Selected Hispanic Cohort.

BACKGROUND: Several studies have shown that the non-small-cell lung cancer (NSCLC) genomic background among Hispanics differs from other populations. The finding of low-frequency genomic alterations in cell-free DNA (cfDNA) can increase diagnostic accuracy and could improve treatment in NSCLC. METHODS: Data from 54 Hispanic patients with advanced NSCLC with high clinical suspicion for ALK, EGFR, and ROS1 mutations were collected (including young age, female sex, and non-smokers). cfDNA was extracted from plasma and analyzed using a commercial next-generation sequencing test (Guardant360) which detects genomic alterations in 74 genes. RESULTS: The median age was 56 years (range 31-83). Most patients were female (661.1%) and never smokers (72.3%). Among the patients included, 96% (52/54) had cfDNA detectable alterations with a mean number of 3.37 cfDNA alterations per test (range 1-10). cfDNA was able to detect some genomic alterations previously undetected by tissue biopsy. Among patients with insufficient or unavailable tissue to perform testing, mutations in EGFR and ALK which led to a change in therapy were determined using cfDNA in 28.8 and 3.8% of cases, respectively. Among patients with cfDNA alterations, 46.1% (n = 24) were switched to a targeted therapy with a median progression-free survival of 11.1 months (95% CI 7.6-14.6) and an overall survival of 40.3 months (95% CI 27.1-53.6). Concurrent genetic mutations with TP53 and KRAS negatively impacted the prognosis. CONCLUSIONS: In a selected population of NSCLC Hispanic patients, comprehensive cfDNA analysis allowed a treatment change in 46.1% of the cases. Guardant360 allows the identification of genomic alterations to improve treatment selection and increase prognosis.

Focal-to-bilateral tonic-clonic seizures and High-grade CMV-infection are poor survival predictors in Tumor-related Epilepsy Adult-type diffuse gliomas-A single-center study and literature review.

Introduction: Previous studies have reported a correlation between a high-grade CMV-infection and an unfavorable prognosis in glioblastoma (GB). Coversely, epilepsy has been associated with a more favorable outcome in GB patients. Despites epilepsy and CMV share similar molecular mechanisms in GB tumoral microenvironment, the correlation between Tumor-Related-Epilepsy (TRE) and CMVinfection remains unexplored. The aim of our study is to examine the correlation between the dregree of CMV infection and seizure types on the survival of TRE Adult-type-diffuse-glioma. To achieve this objective, we conducted a comprehensive literature review to assess our results regarding previous publications. Methods: We conducted a retrospective-observational study on TRE Adult-type-diffuse-gliomas treated at a single center in Mexico from 2010 to 2018. Tumor tissue and cDNA were analyzed by immunochemistry (IHC) for CMV (IE and LA antigens) at the Karolinska Institute in Sweden, and RT-PCR for CMV-gB in Torreon Mexico, respectively. Bivariate analysis (X2-test) was performed to evaluate the association between subtypes of Adult-type-diffuse-glioma (IDH-mut grade 4 astrocytoma vs. IDH-wt glioblastoma) and the following variables: type of hemispheric involvement (mesial vs. neocortical involvement), degree of CMV infection (<25%vs. >25% infected-tumoral cells) and seizure types [Focal awareness, focal impaired awareness, and FBTCS]. Kaplan Meier and Cox analyses were performed to determine the risk, p < 0.05 was considered statistically significant. Results: Sixty patients with TRE Adult type diffuse gliomas were included (80% IDH-wt glioblastoma and 20% IDH-mut grade 4astrocytomas). The mean age was 61.5 SD ± 18.4, and 57% were male. Fifty percent of the patients presented with mesial involvement of the hemysphere. Seizure types included focal awareness (15%), focal impaired awareness (43.3%), and FBTCS (41.7%). Ninety percent of cases were treated with Levetiracetam and 33.3% presented Engel-IA postoperative seizure control. More than 90% of samples were positive for CMV-immunohistochemistry (IHC). However, all cDNA analyzed by RT-PCR return negative results. The median of overall survival (OS) was 15 months. High-grade CMV-IE infection (14 vs. 25 months, p<0.001), mesial involvement (12 vs. 18 months, p<0.001), and FBTCS were associated with worse OS (9 vs.18 months for non-FBTCS). Multivariate analysis demonstrated that high-grade CMV infection (HR = 3.689, p=0.002) and FBTCS (HR=7.007, p<0.001) were independent unfavorable survival factors. Conclusions: CMV induces a proinflammatory tumoral microenvironment that contributes to the developmet of epilepsy. Tumor progression could be associated not only with a higher degree of CMV infection but also to epileptogenesis, resulting in a seizure phenotype chracterized by FBTCS and poor survival outcomes. This study represents the first survival analysis in Latin America to include a representative sample of TRE Adult-type diffuse gliomas considering CMV-infection-degree and distinguishing features (such as FBTCS) that might have potential clinical relevance in this group of patients. Further prospective studies are required to validate these results.

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.

Rare association between penile squamous cell carcinoma and parathyroid related peptide (PTH-rP) secretion.

We report on a rare case of an adult with severe hypercalcemia secondary to the ectopic secretion of parathyroid-related peptide (PTH-rP) from a penile squamous cell cancer (PC). A patient of 47 years old was admitted with warty lesions and areas of ulceration covered by purulent material in a large area of the groin, scrotum and penis. Laboratory tests revealed severe hypercalcemia and elevation of PTH-rP; the biopsy reported PC. Hypercalcemia was successfully treated with zoledronic acid, however, the tumor displayed aggressive behavior, which resulted in a poor prognosis for the patient.

Rare association between penile squamous cell carcinoma and parathyroid related peptide (PTH-rP) secretion / Associação rara entre carcinoma de células escamosas do pênis e secreção de peptídeo relacionado ao paratormônio (PTH-rP)

We report on a rare case of an adult with severe hypercalcemia secondary to the ectopic secretion of parathyroid-related peptide (PTH-rP) from a penile squamous cell cancer (PC). A patient of 47 years old was admitted with warty lesions and areas of ulceration covered by purulent material in a large area of the groin, scrotum and penis. Laboratory tests revealed severe hypercalcemia and elevation of PTH-rP; the biopsy reported PC. Hypercalcemia was successfully treated with zoledronic acid, however, the tumor displayed aggressive behavior, which resulted in a poor prognosis for the patient.

Relatamos um caso raro em um adulto com hipercalcemia grave secundária à secreção ectópica de peptídeo relacionado ao paratormônio (PTH-rP) de um carcinoma de células escamosas do pênis (CP). Um paciente de 47 anos foi admitido com lesões verrucosas e áreas de ulceração cobertas por material purulento em uma grande área da virilha, escroto e pênis. Os testes laboratoriais revelaram hipercalcemia grave e elevação do PTH-rP; a biópsia mostrou um CP. A hipercalcemia foi tratada de forma bem-sucedida com ácido zoledrônico. Entretanto, o tumor apresentava um comportamento agressivo, resultando em um prognóstico ruim para o paciente.