Comparing TIMP-1 and Hsp70 in Blood and Saliva as Potential Prognostic Markers in HNSCC.

(1) Background: Currently, there is no clinically used liquid biomarker in head and neck squamous cell carcinoma (HNSCC) patients. One reason could be the limited shedding of tumor material in early disease stages. Molecular diagnostics assessing both blood and especially saliva could potentially improve the accuracy of biomarkers. In this prospective study, two markers, tissue inhibitor of metalloprotease-1 (TIMP-1) and heat shock protein 70 (Hsp70), were analyzed in HNSCC patients. The purpose of the study was to evaluate differences between saliva and serum as sample material. Further, their prognostic and predictive value and usefulness for early detection was assessed. (2) Methods: A total of 73 HNSCC patients were prospectively monitored by collecting blood and saliva before, during, and after therapy, as well as in the follow-up period between 2018 and 2021. In total, 212 serum and 194 saliva samples were collected. A control group consisting of 40 subjects (15 patients with local infections in the head and neck area and 25 without infections) were examined as well. The collected samples were evaluated for the two proteins by using an enzyme-linked immunosorbent assay (ELISA). (3) RESULTS: The TIMP-1 concentration correlated significantly in blood and saliva, whereas the Hsp70 concentration did not. Saliva TIMP-1 was significantly higher in tumor patients compared to the control group (p = 0.013). High pretreatment TIMP-1 saliva levels were associated with significantly poorer disease-free survival (DFS) (p = 0.02). A high saliva TIMP-1/Hsp70 ratio was significantly associated with poorer DFS (HR: 1.4; 95% CI: 1.04-1.88; p = 0.026) and a high TIMP-1 serum concentration was significantly associated with poorer PFS (HR: 1.9; 95% CI: 1.2, 2.8; p = 0.003) and poorer overall survival (OS) (HR: 2.9; 95% CI: 1.4, 5.9; p = 0.003) in the Cox proportional hazards model. The saliva TIMP-1 to Hsp70 ratio was significantly higher at the time of recurrence (p = 0.015). Conclusion: TIMP-1 in serum is a promising prognostic marker for HNSCC. Saliva TIMP-1 and the saliva TIMP-1 to Hsp70 ratio provides additional information on the disease-free survival.

Trends in age- and sex-specific lung cancer mortality in Europe and Northern America: Analysis of vital registration data from the WHO Mortality Database between 2000 and 2017.

BACKGROUND: In the context of new targeted therapies and immunotherapy as well as screening modalities for lung cancer patients, detailed mortality trends in Europe and Northern America are unknown. METHODS: Time-trend analysis using vital registration data of Northern America and Europe from the WHO Mortality Database (years 2000/2017). To assess improvements in lung cancer mortality, we performed a population-averaged Poisson autoregressive analysis. The average annual percent change (AAPC) was used as a summary measure of overall and country-specific trends in mortality. Second, we studied time trends of lung cancer incidence and smoking prevalence rates. FINDINGS: In the total population of 872·5 million people between 2015 and 2017, the average annual age-standardised mortality from lung cancer was 54·6 deaths per 100 000, with substantial differences across countries. Lung cancer was reported as the primary cause of death in 5·4 cases per 100 deaths. The age-standardised mortality rate decreased constantly (AAPC -1·5%) between 2000 and 2017. While mortality in men dropped annually by an average of -2·3%, mortality in women decreased by an average of -0·3%. This slight decline was driven exclusively by the USA. In contrast, 21 out of 31 countries registered a significant increase in female lung cancer mortality between 2000 and 2017, with Spain (AAPC 4·1%) and France (AAPC 3·6%) leading the list. INTERPRETATION: Despite overall decreases in lung cancer mortality trends, female mortality remained unchanged or increased significantly in all countries except the USA. National mortality outcomes reflect variabilities in tobacco control, screening, therapeutic advances, and access to health care.

Circulating Tumor DNA Profiling of a Diffuse Large B Cell Lymphoma Patient with Secondary Acute Myeloid Leukemia.

Diffuse large B cell lymphomas (DLBCL) are the most common neoplasia of the lymphatic system. Circulating cell-free DNA released from tumor cells (ctDNA) has been studied in many tumor entities and successfully used to monitor treatment and follow up. Studies of ctDNA in DLBCL so far have mainly focused on tracking mutations in peripheral blood initially detected by next-generation sequencing (NGS) of tumor tissue from one lymphoma manifestation site. This approach, however, cannot capture the mutational heterogeneity of different tumor sites in its entirety. In this case report, we present repetitive targeted next-generation sequencing combined with digital PCR out of peripheral blood of a patient with DLBCL relapse. By combining both detection methods, we were able to detect a new dominant clone of ctDNA correlating with the development of secondary therapy-related acute myeloid leukemia (t-AML) during the course of observation. Conclusively, our case report reinforces the diagnostic importance of ctDNA in DLBCL as well as the importance of repeated ctDNA sequencing combined with focused digital PCR assays to display the dynamic mutational landscape during the clinical course.

Preinfection laboratory parameters may predict COVID-19 severity in tumor patients.

BACKGROUND: Infection with SARS-CoV-2 leads to COVID-19, the course of which is highly variable and depends on numerous patient-specific risk factors. Patients with tumor diseases are considered to be more susceptible to severe COVID-19; however, they also represent a heterogeneous group of individuals with variable risk. Identifying specific risk factors for a severe course of COVID-19 in patients with cancer is of great importance. METHODS: Patients diagnosed with solid tumors or hematological malignancies and PCR-confirmed SARS-CoV-2 infection were included into the multicentric ADHOK (Arbeitsgemeinschaft der Hämatologen und Onkologen im Krankenhaus e.V.) coronavirus tumor registry. Detailed information about the patients' cancer disease, treatment, and laboratory parameters prior to infection, was collected retrospectively. The outcome of the SARS-CoV-2 infection was graded according to the WHO. RESULTS: A total of 195 patients (68% with solid neoplasms and 32% with hematological malignancies) were included in the registry. Overall, the course of the SARS-CoV-2 infection varied greatly, as 69% of all patients were either asymptomatic or encountered a mild to moderate course, while 23% of the cohort died from COVID-19. In multivariable analysis, preinfection laboratory parameters (determined at least 10 days and a median of 21 days before the first documentation of SARS-CoV-2 infection) significantly correlated with severe course of the disease. Out of these, the absolute neutrophil count prior to infection showed the strongest association with COVID-19-related death. CONCLUSION: The course of COVID-19 in patients with tumor diseases is highly variable. Preinfection laboratory parameters may aid to identify patients at risk for severe COVID-19 at an early stage prior to infection with the virus. German Clinical Trials Register identification: DRKS00023012.