Neutrophil-to-Lymphocyte Ratio Is a Major Prognostic Factor in Non-small Cell Lung Carcinoma Patients Undergoing First Line Immunotherapy With Pembrolizumab.

BACKGROUND/AIM: Lung cancer is one of the most common malignant neoplastic diseases and by far the leading cause of cancer death worldwide. Recently, immune checkpoint inhibitors (ICIs) have received increasing attention for playing a crucial role in non-small cell lung cancer (NSCLC). Biomarkers, such as programmed cell death-ligand 1 (PD-L1) and tumor mutational burden (TMB), seemed to be helpful in selecting patients who are more likely to benefit from ICI treatment: however, their role has not yet been fully clarified. PATIENTS AND METHODS: In this retrospective study, we evaluated the relationship between pre-treatment peripheral blood neutrophil-to-lymphocyte ratio (NLR) and survival in 252 patients suffering from advanced NSCLC who had received pembrolizumab as their first-line immunotherapy. RESULTS: Compared to their NLR low counterparts who had a median overall survival (OS) of 34.8 months, patients with NLRs above 4.8 had a median OS of 7.6 months (HR=3.26, 95%Cl=2.3-4.6, p-value<0.0000001). In multivariate Cox regression analysis, alongside other variables, such as metastatic sites, age, and sex, NLR and PD-L1 predicted progression-free survival and OS; furthermore, a very high NLR - over 10 - seemed to forecast a very dismal prognosis in patients undergoing immunotherapy, with sudden deaths in the days immediately following therapy (median OS=3.8 months). CONCLUSION: NLR acts as a valuable and reliable prognostic factor in non-small cell lung carcinoma patients undergoing first line immunotherapy with pembrolizumab. Additional investigation is necessary to fully elucidate the underlying biological rationale, which can be found in myeloid derived suppressor cells, a heterogeneous population of cells with neutrophil-like immunophenotypic features.

FOLFIRINOX or nab-paclitaxel plus gemcitabine in metastatic pancreatic adenocarcinoma: an observational study.

Aim: Comparison of first-line FOLFIRINOX (FFN) and nab-paclitaxel plus gemcitabine (NabGem) in patients with metastatic pancreatic ductal adenocarcinoma. Patients & methods: The authors analyzed data from 160 patients with metastatic pancreatic adenocarcinoma receiving first-line FFN (n = 43) or NabGem (n = 117). Results: FFN and NabGem were similar in median progression-free survival (24.43 vs 26.28 weeks; hazard ratio [HR]: 0.88) and medial overall survival (47.43 vs 42.86 weeks; HR: 0.90). Of the 43 patients receiving FFN, 26 (60.4%) were treated with second-line NabGem; 14/117 (12.0%) patients receiving NabGem received second-line FFN (p < 0.0001). In the FFN → NabGem and NabGem → FFN groups, median overall survival was 51.2 and 71.6 weeks (HR: 0.69; p = 0.15). In patients receiving NabGem, second-line FFN, compared with FOLFOX/CAPOX or FOLFIRI, improved median progression-free survival 2 (25.6 vs 12.1 weeks; HR: 0.47; p = 0.0067) and median overall survival 2 (39.0 vs 19.14 weeks; HR: 0.49; p = 0.032). Conclusion: First-line FFN and NabGem promote similar clinical outcomes. Second-line FFN should be considered after NabGem.

Use of FOLFIRINOX or Nab-Paclitaxel Plus Gemcitabine for the Treatment of Locally Advanced Pancreatic Adenocarcinoma: A Single Institution Observational Study.

Patients with locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC) do not present distant metastases but are not eligible for surgery upfront. Chemotherapy regimens, such as FOLFIRINOX (FFN) or nab-paclitaxel plus gemcitabine (GemNab) in combination with loco-regional treatments are generally used in this setting. However, the best treatment choice is unknown. We retrospectively analyzed the information of 225 patients with stage II-III PDAC treated at our institution between October 2011 and December 2020. A total of 94 patients with LA PDAC who are non-eligible for surgery upfront received neoadjuvant FFN or GemNab. Of the 67 patients receiving FFN, 28 (41.8%) underwent surgery after neoadjuvant therapy. Of the 27 patients treated with GemNab, 6 (22.2%) became eligible for resection. The median overall survival (OS) was 85.1 weeks and 54.3 weeks in the FFN and GemNab groups, respectively (HR = 0.54, p = 0.0109). The median OS was 189.7 weeks and 76.4 weeks in the resected and unresected cohorts, respectively (HR = 0.25, p < 0.0001). Neutropenia (37.3%), anemia (6.0%), and diarrhea (6.0%) in the FFN group and neutropenia (22.2%) and thrombocytopenia (18.5%) in the GemNab groups were the most frequent grade 3-4 side effects. Higher rates of thrombocytosis (p < 0.0001) and peripheral edema (p < 0.0001) were observed in the GemNab group. Our results suggest that the use of FFN is associated with more favorable clinical outcomes than GemNab for patients with LA PDAC. Future randomized and controlled clinical trials are needed to further elucidate the role of these regimens and loco-regional treatments in this setting.

Outcomes of congenital cytomegalovirus disease following maternal primary and non-primary infection.

BACKGROUND: Natural history and long term prognosis of congenital cytomegalovirus (CMV) disease according to maternal primary versus non-primary infection are not clearly documented. OBJECTIVE: To investigate clinical, laboratory and neuroimaging features at onset and long term outcome of congenitally CMV-infected patients born to mothers with non-primary infection compared with a group of patients born to mothers with primary infection. STUDY DESIGN: Consecutive neonates born from 2002 to 2015 were considered eligible for the study. Patients underwent clinical, laboratory and instrumental investigation, and audiologic and neurodevelopmental evaluation at diagnosis and during the follow up. RESULTS: A cohort of 158 congenitally infected children was analyzed. Ninety-three were born to mothers with primary CMV infection (Group 1) and 65 to mothers with a non-primary infection (Group 2). Eighty-eight infants had a symptomatic congenital CMV disease: 49 (46.2%) in Group 1 and 39 (60%) in Group 2. Maternal and demographic characteristics of patients of Group 1 and Group 2 were comparable, with the exception of prematurity and a 1-min Apgar score less than 7, which were more frequent in Group 2 compared to Group 1. Prevalence of neuroimaging findings did not significantly differ between the two groups. An impaired neurodevelopmental outcome was observed in 23.7% of patients of Group 1 and in 24.6% cases of Group 2. Similarly, the frequency of hearing loss did not differ between the two groups (25.8% versus 26.2%, respectively). CONCLUSIONS: Neurodevelopmental and hearing sequelae are not affected by the type of maternal CMV infection. Preventing strategies should be developed for both primary and non-primary infections.