Higher aorta dose increased neutrophil-to-lymphocyte ratio resulting in poorer outcomes in stage II-III non-small cell lung cancer.

BACKGROUND: This study focused on the relationship between the neutrophil-to-lymphocyte ratio (NLR) and the dose of organs at risk in patients with stage II-III non-small cell lung cancer (NSCLC) receiving intensity-modulated radiotherapy. METHODS: The clinical characteristics and dosimetric parameters of 372 patients were collected retrospectively. A high NLR was defined as that ≥1.525. Survival analysis was conducted using the Kaplan-Meier and Cox regression analysis. Least absolute shrinkage and selection operator (LASSO) analysis was conducted to select appropriate dosimetric parameters. The risk factors of NLR were evaluated using univariate and multivariate logistic regression analyses. RESULTS: Patients with a high NLR had poorer progression-free survival (PFS) (p = 0.011) and overall survival (OS) (p = 0.061). A low NLR (<1.525) predicted better PFS (hazard ratio [HR] 0.676, 95% confidence interval [CI]: 0.508-0.900, p = 0.007) and OS (HR 0.664, 95% CI: 0.490-0.901, p = 0.009). The aorta dose differed between the low and high NLR groups (all <0.1) in the univariate analysis. An aorta V10 was confirmed as a significant risk factor for a high NLR (odds ratio [OR] 1.029, 95% CI: 1.011-1.048, p = 0.002). Receiving chemotherapy before (OR 0.428, 95% CI: 0.225-0.813, p = 0.010) and during (OR 0.491, 95% CI: 0.296-0.815, p = 0.006) radiotherapy were predictive factors of a low NLR. CONCLUSION: The aorta dose was significantly associated with a high NLR. Patients with stage II-III NSCLC with a high NLR had poorer prognosis. Receiving chemotherapy before and/or during radiotherapy predicted a low NLR.

Proton and Carbon Ion Radiation Therapy Decreased Severe Lymphopenia by Reducing Thoracic Vertebra and Aortic Doses in Non-Small Cell Lung Cancer Versus Intensity Modulated Radiation Therapy.

PURPOSE: Lymphopenia is a common adverse effect of radiation therapy (RT). Little is known about the difference in lymphopenia between intensity modulated (photon) radiation therapy (IMRT) and proton and carbon ion radiation therapy (PCIRT). This study aimed to investigate lymphopenia differences between IMRT and PCIRT in non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: Clinical and dosimetric parameters were collected from 343 patients who received definitive IMRT or PCIRT for NSCLC. Severe lymphopenia (SRL) was defined as an absolute lymphocyte count (ALC) ≤0.5 × 103 cells/µL. Overall survival (OS) was analyzed using the Kaplan-Meier method. Propensity score matching was performed between the IMRT and PCIRT groups. Least absolute shrinkage and selection operator analysis was used to select appropriate dosimetric parameters. Univariate and multivariate logistic regression analyses were conducted to identify the predictors of SRL. RESULTS: Compared with the IMRT group, the PCIRT group was less likely to develop SRL (P < .001). Compared with the non-SRL group, the SRL group showed significant association with poorer OS, with a median survival time of 29.2 versus 15.0 months (P = .046). IMRT was an independent risk factor of SRL (P = .004). A lower ALC before RT (P = .030) and larger planning target volume (PTV) (P = .002) were also significant independent risk factors for SRL. Moreover, the majority of dosimetric parameters of organs at risk in PCIRT were lower than those in IMRT (P < .001). Thoracic vertebra V5 (P = .002) and aorta V5 (P = .026) were identified as independent risk predictors of SRL after adding dosimetric parameters to the regression model. CONCLUSIONS: Compared with IMRT, PCIRT could reduce SRL incidence, possibly by limiting thoracic vertebra and aortic doses, and SRL was associated with poor outcomes in patients with NSCLC.

The KIR2DL2/HLA-C1C1 Gene Pairing Is Associated With an Increased Risk of SARS-CoV-2 Infection.

SARS-CoV-2 is the causative agent for the global COVID-19 pandemic; however, the interaction between virus and host is not well characterized. Natural killer cells play a key role in the early phase of the antiviral response, and their primary functions are dependent on signaling through the killer cell immunoglobulin-like receptor (KIR). This study measured the association between KIR/HLA class I ligand pairings and the occurrence and development of COVID-19. DNA of blood samples from 257 COVID-19 patients were extracted and used to detect KIR and HLA-C gene frequencies using single strain sequence-specific primer (SSP) PCR. The frequency of these genes was compared among 158 individuals with mild COVID-19, 99 with severe disease, and 98 healthy controls. The frequencies of KIR2DL2 (P=0.04, OR=1.707), KIR2DS3 (P=0.047, OR=1.679), HLA-C1C1 (P<0.001, OR=3.074) and the KIR2DL2/HLA-C1C1 pairing (P=0.038, OR=2.126) were significantly higher in the COVID-19 patients than the healthy controls. At the same time, the frequency of KIR2DL3+KIR2DL2-/HLA-C1+Others+ was lower in COVID-19 patients than in healthy individuals (P=0.004, OR=0.477). These results suggest that the protective effect of KIR2DL3 against SARS-CoV-2 infection is related to the absence of the KIR2DL2 gene. This study found no correlation between the frequencies of these genes and COVID-19 pathogenesis. Global statistical analysis revealed that the incidence of COVID-19 infection was higher in geographic regions with a high frequency of KIR2DL2. Together these results suggest that the KIR2DL2/HLA-C1C1 gene pairing may be a risk factor for SARS-CoV-2 infection.

Anti-ISI Demodulation Scheme and Its Experiment-Based Evaluation for Diffusion-Based Molecular Communication.

In diffusion-based molecular communication, the most common modulation technique is based on the concentration of information molecules. However, the random delay of molecules due to the channel with memory causes severe inter-symbol interference (ISI) among consecutive signals. In this paper, we propose a detection technique for demodulating signals, the increase detection algorithm (IDA), to improve the reliability of concentration-encoded diffusion-based molecular communication. The proposed IDA detects an increase (i.e., a relative concentration value) in molecule concentration to extract the information instead of detecting an absolute concentration value. To validate the availability of IDA, we establish a real physical tabletop test bed. And we evaluate the proposed demodulation technique using bit error rate (BER) and demonstrate by the tabletop molecular communication platform that the proposed IDA successfully minimizes and even isolates ISI, so that a lower BER is achieved than the common demodulation technique.