A Retrospective Study of 291 Patients With Head and Neck Sarcomas: Treatment, Outcomes, and Prognostic Factors.

AIMS: Sarcomas constitute a group of rare malignant neoplasms, commonly subcategorized into soft tissue sarcomas (STS) and bone sarcomas. This study aims to describe the treatment modalities and outcome of head and neck sarcoma (HNS) patients in western Denmark and to identify prognostic factors for overall survival and recurrence in HNS patients. MATERIALS AND METHODS: The Aarhus sarcoma registry, The National Danish Sarcoma Database, and the Danish National Pathology Registry were used to identify HNS adult patients diagnosed between 1979 and 2022. RESULTS: Altogether, 291 patients were included in this study. The prevalent histological subtypes were undifferentiated pleomorphic sarcoma (16%; 48/291) and leiomyosarcoma (15%; 44/291) for STS patients (n = 230) and chondrosarcoma (10%; 28/291) and osteosarcoma (7%; 19/291) for bone sarcoma patients (n = 61). Surgery with curative intent was performed in 71% (164/230) and 70% (43/61) of STS and bone sarcoma patients, respectively. Clear resection was achieved in 59% (97/164) of STS patients and 44% (19/43) of bone sarcoma patients. Eighty-nine patients relapsed (STS n = 66, bone sarcoma n = 23) after a median time of 2.7/5.5 years for STS/bone sarcoma patients. The five-year overall survival rates were 45% for STS patients and 66% for bone sarcoma patients. The following factors were significantly, negatively associated with overall survival in STS patients: Age (hazard ratio (HR)) = 1.02, p < 0.001), tumour size ≥5 cm (HR = 1.75, p = 0.003), metastatic disease (HR = 3.17, p < 0.001), high grade tumour (HR = 2.24, p = 0.004), previous cancer (HR = 2.84, p < 0.001), and high Aarhus composite biomarker score (ACBS) (HR = 4.56, p = 0.001). For relapse in STS patients, higher tumour grade (HR = 3.19, p = 0.014), intralesional margins (HR = 2.84, p < 0.001), ≥2 previous cancers (HR = 3.00, p = 0.004), and high ACBS (HR = 3.29, p = 0.047), were negatively associated. For bone sarcomas only higher age (HR = 1.02, p = 0.049) and intralesional margins (HR = 2.91, p = 0.042) were significant negative factors for overall survival. CONCLUSION: Multiple prognostic factors for overall survival and relapse were identified, especially for STS patients.

Severity and 1-month outcome of SARS-CoV-2 infection in patients with solid cancers: a Danish nationwide cohort study.

BACKGROUND: Cancer patients are vulnerable to infections, are older and often have comorbidities in comparison to the general population, which increases the risk for severe outcomes related to COVID-19 diagnosis. METHODS: This study is a prospective, nationwide study in patients with solid cancer and SARS-CoV-2 infection included between 10 March to 15 June 2020. Patient's baseline characteristics were collected. The study's primary outcome was overall survival within 30 days of verified SARS-CoV-2 infection. Secondary outcomes were hospital admission, admission to an ICU, and need for supplemental oxygen. RESULTS: A total of 112 patients with a cancer diagnosis and verified SARS-CoV-2 infection were identified. After one month of follow up, hospitalization was required for 54% (n = 61) and 21% of the patients had died and 14 of the 23 deceased cancer patients were ≥70 years. Most patients were classified with mild COVID-19 symptoms (66%, n = 74); however, 48% (n = 23) of the ≥70-year-olds patients were classified with severe or critical COVID-19 symptoms. Among the total study population, 61% (n = 68) had comorbidities and comorbidity were more frequently observed among the deceased (91%, n = 21) and older cancer patients (≥70 years, 81%, n = 39). CONCLUSIONS: Acknowledging the low sample size in this study, our work shows that age and comorbidities, but not recent cytotoxic therapy, are associated with adverse outcomes of SARS-CoV-2 infection for patients with solid cancer. Particularly, patients with progressive disease seem to be at greater risk of a fatal outcome from COVID-19.HighlightsAge, performance status, and comorbidities are strong predictors of adverse outcome in cancer patients with SARS-CoV-2 infection.Patients with progressive cancer disease seem to be at greater risk of a fatal outcome from COVID-19.Recent cytotoxic therapy, however, did not seem to be associated with increased risk for adverse outcomes of SARS-CoV-2 infection for patients with solid cancer.

Radiation-Induced Sarcoma: A Retrospective Population-Based Study Over 34 Years in a Single Institution.

AIMS: About a half of all cancer patients receive radiotherapy as part of their oncological treatment. Because of the carcinogenic effect of ionising radiation, there is a rare, but definite, risk of developing secondary malignancies, including sarcomas. The aim of this retrospective study was to describe the prevalence, patient and tumour characteristics, as well as prognosis and outcome, of patients with radiation-induced sarcomas (RIS) in a cohort of patients treated in the Sarcoma Centre at Aarhus University Hospital over a period of 34 years. MATERIALS AND METHODS: All patients who fulfilled the criteria for RIS and were treated for RIS in the period 1979-2013 were included. Patient data were retrieved from the Aarhus Sarcoma Registry and the National Danish Sarcoma Database, crosschecked with the National Register of Pathology and validated using the patients' medical records. The primary end point was the effect of surgery and treatment intent on overall survival. Overall survival is reported using the Kaplan-Meier estimates and compared using the Log-rank test. Descriptive statistics are presented for patients, tumours and treatment characteristics. RESULTS: Of 2845 patients diagnosed with sarcoma between 1979 and 2013, 64 (2%) were diagnosed with RIS. The median interval from the original malignancy was 11 years. The most common histological type was undifferentiated pleomorphic sarcoma (33%). Curative treatment was intended for 45 patients. Fifty patients underwent surgery, of whom 80% had microscopically radical resection (R0). The 5-year overall survival for the whole cohort was 32%. Patients who underwent surgery had a significantly better overall survival compared with patients who were not treated with surgery. In the univariate Cox proportional hazard analyses, no metastases at diagnosis, surgery and R0 resection were favourable prognostics factors of survival. CONCLUSION: This study showed that RIS patients are unique in their epidemiology and tumour characteristics. They have a poor prognosis and need special research investigating new intensive treatment strategies to improve the outcome.

Serum Biomarkers as Prognostic Factors for Metastatic Sarcoma.

AIMS: To investigate the prognostic value of combining inflammatory biomarkers in a prognostic index (Aarhus composite biomarker score: ACBS), adjusted for known confounders, including comorbidity, in patients with metastatic sarcoma. MATERIALS AND METHODS: All patients diagnosed with metastatic sarcoma from 1993 until 2008 were extracted from the Aarhus sarcoma database. The levels of serum albumin, C-reactive protein, serum sodium, haemoglobin, neutrophils and lymphocytes were collected. ACBS as well as the neutrophil to lymphocyte ratio (NLR), Glasgow prognostic score (GPS) and a combined score of GPS and NLR known as CNG were calculated. The prognostic importance of the biomarkers on disease-specific mortality was analysed. Adjustments were made for age, comorbidity, histological type and site of metastasis using the Cox proportional hazard model. Harrell's concordance index (C-index) was used to evaluate whether the ACBS adds prognostic information to already known prognostic factors. The data were validated using the bootstrapping method. RESULTS: In total, 265 patients with metastatic sarcoma were included. The 2-year disease-specific mortality was 74% (95% confidence interval 68-80) and 79% (95% confidence interval 68-88) for soft-tissue sarcoma and bone sarcoma, respectively. Comorbidity was present in 21% of soft-tissue sarcoma patients and 13% of the bone sarcoma patients. All six biomarkers were independent prognostic factors. The various scoring systems (NLR, GPS, CNG and ACBS) combining more than one biomarker were also prognostic for disease-specific mortality. CONCLUSION: The biomarker scoring systems are independent prognostic factors for adult patients with metastatic sarcoma. However, a modified ACBS was superior to all the other scoring systems in predicting outcome.

Solitary Fibrous Tumour: A Single Institution Retrospective Study and Further Validation of a Prognostic Risk Assessment System.

AIMS: Solitary fibrous tumour (SFT) is a rare mesenchymal-derived neoplasm that can arise in any anatomical location in the body. SFT rarely metastasises, but aggressive behaviour is seen in a minority of cases, and relapses can occur several years after treatment. It would be a clinical advantage if high-risk patients could be identified before treatment. MATERIALS AND METHODS: We retrospectively analysed a population-based cohort of SFT to describe treatment, outcome, prognostic factors and to further validate a previously published risk assessment tool (D-score) based on age, tumour size and mitotic index. Seventy-two patients diagnosed with SFT in the Central, North and Southern Denmark regions between 1979 and 2013 were included in the study. RESULTS: For patients with localised disease at the time of diagnosis (n = 64) the 5 and 10 year overall survival was 86% (95% confidence interval 74-92) and 65% (95% confidence interval 50-78), respectively. Seventeen of 62 patients (27%) who were in remission after radical treatment developed recurrence with either local or distant disease. The 5 year recurrence-free survival was 83% (95% confidence interval 70-90) and the 10 year was 69% (95% confidence interval 53-81). The 5 year local recurrence-free survival was 96% (95% confidence interval 86-99) and the 10 year was 92% (95% confidence interval 76-96). The median time to both overall recurrence and local recurrence was 4.3 years. Metastatic or inoperable SFT had a poor prognosis with a median overall survival of 8.4 months (range 3.6-26.4) and a 5 year overall survival of 11% (95% confidence interval 2-30). A further validation of a risk assessment tool (D-score) confirmed that patients classified as high-risk had a significantly decreased overall survival, with a hazard ratio of 3.7 (95% confidence interval 1.1-12.3). CONCLUSIONS: This study showed that our management and outcome were comparable with other published studies describing SFT and confirmed the value of the D-score as a risk assessment tool. Because of late recurrences, long-term (e.g. 10 years) follow-up for moderate- and high-risk patients is recommended.

Exosomal proteins as prognostic biomarkers in non-small cell lung cancer.

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.