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.

Survival analyses of the ZeOxaNMulti trial: Follow-up randomized, double-blinded, placebo-controlled trial of oral PMA-zeolite to prevent chemotherapy-induced side effects, especially peripheral neuropathy.

Following the previously published results of the clinical randomized ZeOxaNMulti trial, we evaluated the potential of the tested product PMA-ZEO (Multizeo Med) in the prevention of chemotherapy-induced side effects (especially peripheral neuropathy) within a 30-month follow-up analysis. The aim was to determine the disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS) in a study-population suffering from colorectal cancer that was previously enrolled in the ZeOxaNMulti trial from April 2015 to October 2018. The participants of the study were randomized to receive either PMA-ZEO or placebo while undergoing oxaliplatin-based chemotherapy. A total of 104 patients (pts) (51% of participants randomized to the PMA-ZEO group and 49% to the placebo group), out of a total of 120 pts included in the ZeOxaNMulti trial in 2015, were followed up until March 2021 and were included in the follow-up analysis. According to the chemotherapy line, 44.2% of patients received chemotherapy in an adjuvant setting, and 55.8% of patients received chemotherapy as first-line treatment. The statistical analysis for DFS, PFS, and OS was performed by comparison of the end results with data from the PMA-ZEO/placebo-intervention start point. The analysis of OS did not show statistically significant differences in the first-line chemotherapy patients randomized to PMA-ZEO than among the placebo group (p = 0.1) over the whole period of follow-up (30 months). However, focusing on the PMA-ZEO supplementation time point (7 months), a positive and statistically significant trend (p = 0.004) was documented in the OS analysis for the first-line chemotherapy patients with increasing months of PMA-ZEO treatment compared to the placebo group. Furthermore, borderline statistical significance was reached for PFS at the PMA-ZEO supplementation time point (7 months) in the first-line chemotherapy patients (p = 0.05) for cancer progression events. After stratification of the first-line chemotherapy patients, statistically relevant trends for OS for age, comorbidities, and oxaliplatin dosage (cycles) were also determined. The overall results for DFS (adjuvant patients), PFS (first-line chemotherapy patients), and OS (adjuvant and first-line chemotherapy patients) were generally slightly better in the PMA-ZEO group than in the placebo group, even though no statistically significant results were obtained between the groups within the follow-up period until 2021 (30 months). Based on this follow-up analysis, protective effects of PMA-zeolite supplementation can be deduced. A positive trend and more importantly, significant results in PFS and OS for specific patient groups during and/or after PMA-ZEO treatment were determined, which supports the use of PMA-ZEO as an oncological supportive therapy.

Stocky/Packed Pancreas: A Case of Focal Drug-Induced Acute Pancreatitis Mimicking Cancer.

Drug-induced acute pancreatitis (DIP) is a recognised but underreported entity in the literature. Immunotherapy drugs have been described as one possible emerging cause, although the pathogenic mechanism is still largely unclear. To date, only a few cases have been reported, even if in recent times there is an over-increasing awareness of this pathologic entity. The imaging-based diagnosis of DIP can be difficult to establish, representing a real challenge for a radiologist, especially when the inflammatory disease appears as a focal mass suspicious for a malignancy. Case report: We herein report the case of a 71-year-old man with a known history of partially responsive lung adenocarcinoma subtype with high programmed cell death ligand 1 (PD-L1) expression, who underwent positron emission tomography (PET)/computed tomography (CT) imaging follow-up after one year of immunotherapy. The exam revealed a stocky/packed lesion in the pancreatic body, with increased 18F-fluorodeoxyglucose (FDG) accumulation highly suggestive of pancreatic cancer, which finally was proven to be a DIP induced by immunotherapy. Conclusion: Distinguishing between focal DIP and pancreatic neoplasm is, therefore, crucial for timely therapeutic management and prognostic stratification. A deep knowledge of possible imaging pitfalls coupled with a comprehensive clinical and laboratory assessment is pivotal to avoid any delays in diagnosis.

Folinic acid in colorectal cancer: esquire or fellow knight? Real-world results from a mono institutional, retrospective study.

The stock of therapeutic weapons available in metastatic colorectal cancer (mCRC) has been progressively grown over the years, with improving both survival and patients' clinical outcome: notwithstanding advances in the knowledge of mCRC biology, as well as advances in treatment, fluoropyrimidine antimetabolite drugs have been for 30 years the mainstay of chemotherapy protocols for this malignancy. 5-Fluorouracil (5FU) seems to act differently depending on administration method: elastomer-mediated continuous infusion better inhibits Thymidylate Synthase (TS), an enzyme playing a pivotal role in DNA synthetic pathway. TS overexpression is an acknowledged poor prognosis predicting factor. The simultaneous combination of 5FU and folinate salt synergistically strengthens fluorouracil cytotoxic effect. In our experience, levofolinate and 5FU together in continuous infusion prolong progression free survival of patients suffering from mCRC, moreover decreasing death risk and showing a clear clinical benefit for patients, irrespective of RAS mutational status, primitive tumor side and metastases surgery.