Prognostic value of the modified systemic inflammation score in non-small-cell lung cancer with brain metastasis

Abstract

Background Brain metastases (BM) from non-small-cell lung cancer (NSCLC) is the most common brain malignancy. Systemic inflammation biomarkers have recently been evaluated as prognosis indicators in several tumors. The combination of these markers has not been evaluated in NSCLC with BM yet. Here, we explored the predictive value of pretreatment inflammatory biomarkers and established a novel, clinically applicable prognostic index for NSCLC patients with BM. Methods A retrospective investigation of 951 NSCLC patients newly diagnosed with BM at Sun Yat-sen University Cancer Center was conducted. We randomly divided patients into a training cohort (n = 674) or validation cohort (n = 277). Receiver operating characteristic (ROC) curve analysis was carried out to obtain the optimal cut-off values of pretreatment systemic inflammatory indexes. The associations between serum biomarkers and overall survival (OS) were analyzed by Kaplan–Meier curves and Cox proportional models. The resulting prediction model has been externally verified through the validation cohort. Results The optimal cut-off value of the neutrophil–lymphocyte ratio (NLR) in predicting OS was 4.71, while the clinical standard of 40 mg/L was chosen as the optimal cut-off value of albumin. Univariate and multivariate analyses revealed that patients receiving local treatment, chemotherapy, a NLR < 4.71 and albumin ≥ 40 mg/l independently predicted improved survival. We combined the two inflammatory indexes (NLR and albumin level) to establish the modified systemic inflammation score (mSIS) which divides patients into low risk, medium risk or high-risk groups. The 1-year OS rates of three groups were 59.7%, 40.5% and 29.4%, respectively in the training cohort. The same result was verified in the validation cohort with the 1-year OS rates 69.7%, 47.0% and 7.7%, respectively. The mSIS exhibited better discrimination power than the American Joint Committee on Cancer’s (AJCC) 7th T + N staging system in the training cohort (Harrell’s concordance index (C-index): 0.744 vs 0.502, P < 0.05), and the discrimination was also superior to that of AJCC’s 7th T + N staging system in the validation cohort (C-index: 0.724 vs 0.527, P < 0.05). The 1-year and 2-year OS rates of the AUC also exhibited superior survival predictive ability to that of the AJCC’s 7th T + N staging system in NSCLC patients with BM. Conclusion The pretreatment mSIS may be an independent prognostic factor for OS in NSCLC patients with BM and warrants further research.

Exploring the Molecular Tumor Microenvironment and Translational Biomarkers in Brain Metastases of Non-Small-Cell Lung Cancer

“…Diving deeper into the prognostic potential of immune parameters, several groups uncovered that the neutrophil-lymphocyte ratio (NLR) and serum albumin levels served as independent harbingers of enhanced survival in NSCLC patients with brain metastasis [139]. When NLR and albumin metrics were integrated to conceive the modified systemic inflammation score (mSIS), it outperformed the discriminative capability of the AJCC's seventh T + N staging system [140]. In parallel, another research contingent identified the prognostic relevance of the prognostic nutritional index (PNI) and systemic immune inflammation index (SII) for NSCLC patients manifesting brain metastases [141].…”

Vaccination against SARS-CoV-2 in adults with a diagnosis of cancer: a short review

“…Already early on in the pandemic and long before vaccines were available, it became clear that patients with a diagnosis of cancer are at significantly higher risk of becoming infected with SARS-CoV-2 [1]. In an analysis of electronic health record (EHR) data from the USA, patients with active cancer (diagnosis of cancer within the last year) were found to be even more receptive to an infection than the overall population of patients with a diagnosis of cancer [1].…”

“…Already early on in the pandemic and long before vaccines were available, it became clear that patients with a diagnosis of cancer are at significantly higher risk of becoming infected with SARS-CoV-2 [1]. In an analysis of electronic health record (EHR) data from the USA, patients with active cancer (diagnosis of cancer within the last year) were found to be even more receptive to an infection than the overall population of patients with a diagnosis of cancer [1]. In fact, adjusted odds of an infection (adjustment for gender, age, race, coronavirus disease 2019 risk factors, cancer treatments, transplantation, stay in a nursing home) were higher for patients with non-Hodgkin lymphoma, lung cancer, breast cancer, colorectal cancer, and prostate cancer, while patients with leukemia (adjusted odds ratio [aOR] 12.16) appeared to be at the highest risk of an infection compared to patients without cancer.…”

“…In fact, adjusted odds of an infection (adjustment for gender, age, race, coronavirus disease 2019 risk factors, cancer treatments, transplantation, stay in a nursing home) were higher for patients with non-Hodgkin lymphoma, lung cancer, breast cancer, colorectal cancer, and prostate cancer, while patients with leukemia (adjusted odds ratio [aOR] 12.16) appeared to be at the highest risk of an infection compared to patients without cancer. The higher vulnerability of patients with an active cancer diagnosis furthermore extends to having a severe disease course resulting in a higher likelihood of hospitalization and mortality [1]. Various mechanisms may be responsible for this observation, including but not limited to higher expression of ACE2 (angiotensin-converting enzyme 2) in various types of cancer (therefore making the entry into the cell easier for the virus), cancer's immune evasion mechanisms (e.g., lower number and response of T-cells), higher likelihood of cytokine storm (due to higher levels of IL-6 in patients with cancer), and/or bone marrow suppression by chemotherapy [2].…”

“…The data presented above demonstrate the even higher vulnerability of patients with hematologic cancer compared to patients with solid cancer during the COVID-19 pandemic. Patients with hematologic cancer not only bear a higher risk of infection [1], but also have a lower chance of seroconversion even after multiple vaccinations [9,12], with a tendency to lower antibody response [15,19] and higher risk of break-through infection [20] compared to patients with solid cancer. Due to the central role of B-cells in the immune system's reaction to a COVID-19 infection, but also in building immunity after vaccination [21], patients with hematologic cancer receiving B-cell-depleting therapy (anti-CD20 therapy, BTKi) appear to be the most vulnerable of cancer patients [6,15,19].…”