Background: Use of exosomes as biomarkers in non‐small cell lung cancer (NSCLC) is an intriguing approach in the liquid‐biopsy era. Exosomes are nano‐sized vesicles with membrane‐bound proteins that reflect their originating cell. Prognostic biomarkers are needed to improve patient selection for optimal treatment. We here evaluate exosomes by protein phenotyping as a prognostic biomarker in NSCLC.Methods: Exosomes from plasma of 276 NSCLC patients were phenotyped using the Extracellular Vesicle Array; 49 antibodies captured the proteins on the exosomes, and a cocktail of biotin‐conjugated antibodies binding the general exosome markers CD9, CD81 and CD63 was used to visualise the captured exosomes. For each individual membrane‐bound protein, results were analysed based on presence, in a concentration‐dependent manner, and correlated to overall survival (OS).Results: The 49 proteins attached to the exosomal membrane were evaluated. NY‐ESO‐1, EGFR, PLAP, EpCam and Alix had a significant concentration‐dependent impact on inferior OS. Due to multiple testing, NY‐ESO‐1 was the only marker that maintained a significant impact on inferior survival (hazard rate (HR) 1.78 95% (1.78–2.44); p = 0.0001) after Bonferroni correction. Results were adjusted for clinico‐pathological characteristics, stage, histology, age, sex and performance status.Conclusion: We illustrate the promising aspects associated with the use of exosomal membrane‐bound proteins as a biomarker and demonstrate that they are a strong prognostic biomarker in NSCLC.

Previous studies of soft tissue sarcoma (STS) have identified a number of possible prognostic factors; however, the majority of these include highly selected populations, with unclear validation of data and insufficient statistical methods. We identified prognostic factors in a validated, population-based 30-year series of STS treated at a single institution, using an advanced statistical approach. Between 1979 and 2008, 922 adult patients from western Denmark were treated at the Aarhus Sarcoma Center for non-metastatic STS in the extremities or trunk. The endpoints were local recurrence (LR) and disease-specific mortality (DSM). Prognostic factors were analyzed using a proportional hazard model, including continuous variables as cubic splines. Directed acyclic graphs were used to depict the causal structure. The 5-year LR was 16% and the 5-year DSM was 24%. Important prognostic factors for both LR and DSM were age, duration of symptoms, tumor size, grade, margin, and radiotherapy, while anatomical location (upper, lower extremity, trunk) was prognostic for DSM. In this population-based series of adult, non-metastatic STS, we included directed acyclic graphs, cubic splines, and a competing risk model in order to minimize bias, and demonstrated that these statistical methods are feasible. Using these statistical methods on a large, validated dataset, we excluded depth as a prognostic factor and established that age, duration of symptoms, size, grade, margin, and radiotherapy were important prognostic factors for both local recurrence and disease-specific mortality.

Background: Inflammation-scores based on general inflammation markers are suggested as prognostic markers of overall survival (OS) in lung cancer. However, whether these inflammation-scores improves the prognostication performed by well-established prognostic markers is unsettled. In a large register-based lung cancer patient cohort, nine different inflammation-scores were compared, and their ability to optimize the prognostication of OS was evaluated. Methods: Lung cancer patients diagnosed from 2009–2018 in The Central Denmark Region were identified in the Danish Lung Cancer Registry. Pre-treatment inflammation markers were extracted from the clinical laboratory information system. Prognostication of OS was evaluated by Cox proportional hazard models. Comparison of the inflammation-scores and their added value to established prognostic markers were assessed by Akaike's information criteria and Harrel's C-index. Results: In total, 5,320 patients with non-small cell lung cancer (NSCLC) and 890 patients with small cell lung cancer (SCLC) were identified. In NSCLC, the Aarhus composite biomarker score (ACBS), including albumin, C-reactive protein, neutrophil count, lymphocyte count and haemoglobin, and the neutrophil-lymphocyte-ratio (NLR) were superior. Furthermore, they improved the prognostication of OS significantly (p <0.0001) (ACBS: HR: 2.24 (95%CI: 1.97–2.54); NLR: HR: 1.58 (95%CI: 1.47 – 1.69)). In SCLC, three scores were equally superior and improved the prognostication of OS p < 0.0001): neutrophil–lymphocyte-ratio (HR:1.62 (95%CI: 1.38–1.90)), modified Glasgow Prognostic Score (mGPS) (HR:1.70 (95%CI: 1.55–1.86) and the Combined NLR and GPS (CNG) (HR:2.10 (95%CI: 1.77–2.49). Conclusions: The ACBS was the optimal score in NSCLC, whereas neutrophil–lymphocyte-ratio, mGPS and CNG were equally superior in SCLC. Additionally, these inflammation-scores all optimised the prognostication of OS and added value to well-established prognostic markers.

The effect of chemotherapy in metastatic bone sarcomas is poor and the condition is invariably fatal. Therefore, new treatment modalities are intensely needed. Pazopanib is a selective multitargeted tyrosine kinase inhibitor that has proven to be effective in the treatment of metastatic soft tissue sarcomas. The objective of this study was to evaluate the off-label use of pazopanib in patients with metastatic bone sarcomas who failed standard chemotherapy. All patients with metastatic bone sarcomas treated with pazopanib between October 1st, 2011 and October 1st, 2017 at the Department of Oncology, Aarhus University Hospital were evaluated. Demographics, treatment, and survival outcomes were collected and analyzed. Nineteen patients were identified. The median age was 38 years (range 18-62). Most of the patients (50%) were diagnosed with osteosarcoma. All patients had documented disease progression at the time of initiating pazopanib treatment. The median overall survival was 11 months. Median progression free survival was 5.4 months. Out of 19 patients, 13 (68%) had either partial response or stable disease. In five patients, the dose of pazopanib was reduced because of toxicity. Off-label use of pazopanib is effective in the treatment of metastatic bone sarcomas of different histologies. Pazopanib was well tolerated in the treatment of patients with refractory bone sarcomas. Studies examining the effect of pazopanib alone or in combination with chemotherapy or other targeted therapies are needed.

Certain biomarkers such as the C-reactive protein, serum albumin, and the neutrophils to lymphocyte ratio are of prognostic significance regarding survival in different types of cancers. Data from sarcoma patients are sparse and mainly derived from soft tissue sarcoma and/or metastatic cases. Adjusting for confounders such as comorbidity and age is an essential safeguard against erroneous conclusions regarding the possible prognostic value of these biomarkers. The aim of this study was to assess the prognostic value of a battery of pretreatment biomarkers in the serum of patients with localized bone sarcomas and to adjust for potential confounders. All patients diagnosed with localized intermediate and high-grade bone sarcoma during 1994 to 2008 were extracted from the Aarhus Sarcoma Registry. The serum levels of albumin, C-reactive protein, hemoglobin, neutrophils, lymphocytes, and sodium were collected from the patient records. The prognostic values of overall and disease-specific mortality were tested for each individual biomarker as well as for the Glasgow prognostic score (GPS) and for a new composite score incorporating five biomarkers (Aarhus composite biomarker score: ACBS). Adjustments were made for comorbidity as well as other possible prognostic factors, such as size, histological type, margin, chemotherapy, and soft tissue extension, using the Cox proportional hazard model. A total of 172 patients with high- or intermediate-grade localized bone sarcoma were included. Of these patients, 63 were diagnosed with chondrosarcoma and 109 patients with Ewing/osteosarcoma. The median age was 55 years for chondrosarcoma and 19 years for Ewing/osteosarcoma patients. The overall 5-year mortality was 31% [95% confidence interval (CI): 21-44] and 41% (95% CI: 33-51), whereas the 5-year disease-specific mortality was 21% (95% CI: 12-34) and 39% (95% CI: 31-49) for chondrosarcoma and Ewing/osteosarcoma, respectively. Comorbidities were present in 12% of the Ewing/osteosarcoma patients and in 24% of the chondrosarcoma patients. After adjustment for comorbidity and other confounders, it was found that elevated levels of CRP, low hemoglobin, low sodium, high GPS, and high ACBS were associated with increased overall mortality. Furthermore, elevated levels of CRP, low hemoglobin, high GPS, and high ACBS were associated with increased disease-specific mortality. Elevated levels of CRP, low hemoglobin, high GPS, and high ACBS were all independent prognostic factors for both overall and disease-specific mortality. ACBS is a new three-level score of five biomarkers, but its value has to be confirmed in an independent data set.