The Role of KRAS Mutation in Colorectal Cancer-Associated Thrombosis.

Venous thromboembolic events (VTE) are common in patients with colorectal cancer (CRC) and represent a significant contributor to morbidity and mortality. Risk stratification is paramount in deciding the initiation of thromboprophylaxis and is calculated using scores that include tumor location, laboratory values, patient clinical characteristics, and tumor burden. Commonly used risk scores do not include the presence of molecular aberrations as a variable. This retrospective study aims to confirm the link between KRAS-activating mutations and the development of VTE in CRC. A total of 166 patients were included in this study. They were split into two cohorts based on KRAS mutational status. We evaluated the frequency and mean time to VTE development stratified by the presence of KRAS mutations. Patients with mutant KRAS had an odds ratio (OR) of 2.758 for VTE compared to KRAS wild-type patients, with an increased risk of thrombosis being maintained in KRAS mutant patients even after adjusting for other known VTE risk factors. Taking into account the results of this study, KRAS mutation represents an independent risk factor for VTE.

Systemic Neutrophil-to-Lymphocyte Ratio as a Prognostic Biomarker for Colon Cancer.

BACKGROUND AND AIM: Prior research linked a high preoperative neutrophil-to-lymphocyte ratio (NLR) to a worse prognosis in individuals with a variety of malignancies. This study aimed to establish the prognostic and predictive usefulness of preoperative NLR in colorectal cancer (CRC) patients and to identify an appropriate cut-off value for the NLR. We enrolled a total of 195 patients that underwent surgery for stage II and III colorectal cancer that required adjuvant chemotherapy as well as stage IV colorectal cancer patients treated with palliative intent. The mean NLR value was 3.42 +- 2.27. We used a receiver operating characteristic curve to estimate the optimum NLR cut-off value at 3. Patients with a NLR value above 3 were classified as high-NLR, while patients with a NLR below 3 were classified as low-NLR; Results Overall survival (OS) and progression-free survival (PFS) were significantly reduced in high-NLR patients. The overall response rate (ORR) was also lower in high-NLR patients. Conclusions Preoperative NLR is an accessible measurement that seems to have prognostic and predictive value in patients with colorectal cancer.

Restricted Mean Survival Time-Can It Be a New Tool in Assessing the Survival of Non-Small Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors?

BACKGROUND: Lung cancer (LC) is the first and most lethal cancer in the world; identifying new methods to treat it, such as immune checkpoint inhibitors (ICIs), is needed. ICIs treatment is very effective, but it comes bundled with a series of immune-related adverse events (irAEs). Restricted mean survival time (RMST) is an alternative tool for assessing the patients' survival when the proportional hazard assumption (PH) fails. METHODS: We included in this analytical cross-sectional observational survey patients with metastatic non-small-cell lung cancer (NSCLC), treated for at least 6 months with ICIs in the first- and second-line settings. Using RMST, we estimated the overall survival (OS) of patients by dividing them into two groups. A multivariate Cox regression analysis was performed to determine the impact of the prognostic factors on OS. RESULTS: Seventy-nine patients were included (68.4% men, mean age 63.8), and 34/79 (43%) presented irAEs. The OS RMST of the entire group was 30.91 months, with a survival median of 22 months. Thirty-two out of seventy-nine (40.5%) died before we ended our study. The OS RMST and death percentage favored the patients who presented irAEs (long-rank test, p = 0.036). The OS RMST of patients with irAEs was 35.7 months, with a number of deaths of 12/34 (35.29%), while the OS RMST of the patients without irAEs was 17 months, with a number of deaths of 20/45 (44.44%). The OS RMST by the line of treatment favored the first line of treatment. In this group, the presence of irAEs significantly impacted the survival of these patients (p = 0.0083). Moreover, patients that experienced low-grade irAEs had a better OS RMST. This result has to be cautiously regarded because of the small number of patients stratified according to the grades of irAEs. The prognostic factors for the survival were: the presence of irAEs, Eastern Cooperative Oncology Group (ECOG) performance status and the number of organs affected by metastasis. The risk of dying was 2.13 times higher for patients without irAEs than for the patients who presented irAEs, (CI) 95% of 1.03 to 4.39. Moreover, by increasing the ECOG performance status by one point, the risk of death increased by 2.28 times, with a CI 95% of 1.46 to 3.58, while the involvement of more metastatic organs was associated with a 1.60 times increase in the death risk, with a CI 95% of 1.09 to 2.36. Age and the type of tumor were not predictive for this analysis. CONCLUSIONS: The RMST is a new tool that helps researchers to better address the survival in studies with ICIs treatment where the PH fails, and the long-rank test is less efficient due to the existence of the long-term responses and delayed treatment effects. Patients with irAEs have a better prognosis than those without irAEs in the first-line settings. The ECOG performance status and the number of organs affected by metastasis must be considered when selecting patients for ICIs treatment.

The Prognostic Value of Neutrophil-to-Lymphocyte Ratio in Patients with Metastatic Renal Cell Carcinoma.

BACKGROUND: Metastatic renal cell carcinoma (mRCC) is an aggressive cancer characterised by an increased recurrence rate and an inadequate response to treatment. This study aimed to investigate the importance of the neutrophil-to-lymphocyte ratio (NLR) as a prognostic marker for long-term survival in patients with mRCC. METHODS: We retrospectively analysed data from 74 patients with mRCC treated at our medical centre with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). We evaluated the predictive value of NLR for overall survival (OS) in these patients. RESULTS: The median OS was 5.1 months in the higher NLR group (≥3) and 13.3 months in the lower NLR group (<3) (p < 0.0001). There was no significant difference in the OS between the TKI and ICI therapies in the low NLR group (12.9 vs. 13.6 months, p = 0.411) or in the high NLR group (4.7 vs. 5.5 months, p = 0.32). Both univariate and multivariate analyses revealed that a higher NLR was an independent prognostic factor of long-term survival in patients with mRCC treated with first-line therapy. CONCLUSIONS: This retrospective study showed that adding NLR to other Memorial Sloan Kettering Cancer Center (MSKCC) and International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) variables might improve the prognostic and predictive power of these models.

Correlation Between Pretreatment Neutrophil-to-Lymphocyte Ratio and Programmed Death-Ligand 1 Expression as Prognostic Markers in Non-Small Cell Lung Cancer.

Background The neutrophil-to-lymphocyte ratio (NLR) at baseline treatment is an important marker of systemic inflammation, which is correlated with survival benefits in lung, breast, ovarian, bladder, and colorectal cancer. Programmed death-ligand 1 (PD-L1) expression is a biomarker with discording results regarding survival benefits in lung cancer. In our research, we studied the relationship between these two markers in patients with lung cancer. Methods Patients with stage I, II, III, and IV lung cancer (n = 80) were included in this retrospective study. The NLR baseline was recorded before the initiation of treatment. The NLR cut-off value was 4. PD-L1 expression was determined by immunohistochemical staining. Univariate and multivariate survival analyses were conducted to test their prognostic value. Results NLR proved to be a significant prognostic factor for progression-free survival (PFS) (p=0.002, Log Rank) with a mean PFS of 27.7 months for low NLR patients and 12.8 months for high NLR patients. It was also significant for overall survival (OS) (p=0.007, Log Rank) with a mean OS of 52 months for low NLR patients and 41.6 months for high NLR patients. The prognostic impact of PD-L1 expression on PFS and OS was not statistically significant with a mean PFS of 23.1 months for PD-L1-negative patients and 15.8 months for PD-L1-positive patients (p=0.422, Log Rank). Mean OS was 49 months for PD-L1-negative patients while for PD-L1-positive patients, it was 43.3 months (p=0.550 Log Rank). Regarding the correlation between PD-L1 expression and NLR value, PFS mean survival times were 13.1 months for PD-L1(+)/NLR>4, 15.1 months for PD-L1(-)/NLR>4, 16.4 months for PD-L1(+)/NLR<4 and 27.8 months for PD-L1(-)/NLR<4. This correlation between PFS and the combined PD-L1 and NLR prognostic factor was statistically relevant (p=0.04). For OS, the PD-L1/NLR combined prognostic factor was not statistically relevant (p=0.055). A mean PFS time of 27.8 months was reported for PD-L1(-)/NLR<4 group patients while for the other groups, the mean PFS was 14.9 months (p=0.045). In univariate analysis, the elevated NLR was significantly associated with a decreased PFS time (HR=2.31, 95% CI =1.323- 4.051, p=0.03) as well as OS (HR=3.555, 95% CI=1.310- 9.652, p=0.013). In multivariate analysis, NLR remained statistically significant for PFS (HR=2.160, 95% CI=1.148- 4.062, p=0.013) and OS (HR=4.364, 95% CI=1.474- 12.921, p=0.008) after adjusting for the factors of age, gender, tumor stage, lymph node stage, clinical stage, histology, and PD-L1 expression. PD-L1 expression was not a valid prognostic factor for progression or death in either univariate or multivariate analysis. We also stratified the disease control rate (DCR) depending on PD-L1/NLR combined factor expression. In the PD-L1(-)/NLR<4 group, we had the highest number of partial responses (PRs) and only one complete response (CR) compared to the other groups (p=0.006). Conclusions As the number of patients is limited in the present analysis, it is hypothesized that these two markers can be useful in dividing patients into two prognostic groups: the good prognostic group reunites PD-L1(+)/NLR<4 and PD-L1(-)/NLR<4 and the poor prognostic group reunites PD-L1(+)/NLR>4 and PD-L1(-)/NLR>4.