The association between socioeconomic position and tumour size, grade, stage, and mortality in Danish sarcoma patients - A national, observational study from 2000 to 2013.

Background: Survival in sarcoma patients depends on a range of prognostic factors. An association between cancer survival and socioeconomic position is known for several other cancers. We therefore examined the relations between three socioeconomic factors and risk of presenting with known tumour related prognostic factors, and the overall mortality of the different socioeconomic and prognostic factors in 1919 patients diagnosed with sarcoma in Denmark 2000-2013.Material and methods: Patients with sarcoma in extremities or trunk wall aged 30 years or more at diagnosis were identified in the Danish Sarcoma Registry and linked on an individual level to Danish national registries. We obtained data on educational level, disposable income and cohabitation status. Odds ratios (ORs) were estimated for the association between the socioeconomic factors and grade, stage and tumour size. Hazard ratios (HRs) were estimated using Cox proportional hazard models.Results: In adjusted analyses, educational level, income and cohabitation status were not associated with high grade or dissiminated stage at time of diagnosis. However, living alone was statistically significantly associated with having a large soft tissue sarcoma (≥5 cm) at time of diagnosis (OR 1.51; CI1.12-2.03). The overall mortality was statistically significantly increased in the group of patients with ≤10 years of education (HR 1.27; CI 1.02-1.57), in patients with the 20% lowest income (HR 1.30; CI 1.00-1.67) and nearly in patients living alone (HR 1.16; CI 0.99-1.36).Conclusion: In this nationwide, multicentre, population-based study, soft tissue sarcoma patients living alone had greater risk of having a large tumour at time of diagnosis. Soft tissue and bone sarcoma patients with a short education, low income, or living alone, had a higher mortality. This might indicate that the social differences in mortality might be related to treatment aspects and the biology of the disease rather that the diagnostic process.

Use of Healthcare Services Two Years before Diagnosis in Danish Sarcoma Patients, 2000-2013.

BACKGROUND: Sarcoma is a rare type of cancer with nonspecific symptoms and uncertain aetiology. Thus, timely diagnosis of sarcomas is a clinical challenge. The aim of this study was to investigate the use of healthcare services 24 months preceding a sarcoma diagnosis compared to a matched cohort. MATERIALS AND METHODS: The study was a retrospective, population-based, matched cohort registry-study. Patients with sarcoma in Denmark in 2000-2013 were identified in the Danish Sarcoma Registry (n = 2167) and matched 1 : 10 on gender, age, and listed general practice. Using a binomial regression model, incidence rate ratios were calculated for face-to-face contacts in general practice, inpatient and outpatient visits, surgery, paraclinical examinations, and diagnostic imaging. Analyses were stratified for sarcoma subtypes, grade, stage, gender, and presence of comorbidity. RESULTS: The sarcoma patients had significantly increased incidence rate ratios in use of healthcare services compared to the matched cohort a year before their diagnoses. An increase in consultation rates was seen 11 months before diagnosis for inpatient visits, 9 months before diagnosis in general practice and outpatient visits, 8 months before diagnosis for paraclinical examinations, and 4 and 3 months before diagnosis for diagnostic imaging and surgery, respectively. There were no clinical significant differences in length of increased consultation rates between sarcoma type, stage, and grade. Sarcoma patients with comorbidity had persistently higher consultation rates compared to patients without comorbidity. CONCLUSIONS: The use of healthcare services among sarcoma patients increased several months before diagnosis in all healthcare sectors. The results reveal a diagnostic time window and a potential to refer, diagnose, and treat sarcoma patients in a timelier manner.

The impact of comorbidity on mortality in Danish sarcoma patients from 2000-2013: A nationwide population-based multicentre study.

INTRODUCTION: Sarcoma is a rare type of cancer. The incidence increases with age and elderly patients may have comorbidity that affects the prognosis. The aim of this study was to describe the type and prevalence of comorbidity in a nationwide population-based study in Denmark from 2000-2013 and to analyse the impact of the different comorbidities on mortality. MATERIAL AND METHODS: The Danish Sarcoma Registry is a national clinical database containing all patients with sarcoma in the extremities or trunk wall from 2000 and onwards. By linking data to other registries, we were able to get patient information on an individual level including date and cause of death as well as the comorbidity type up to 10 years prior to the sarcoma diagnosis. Based on diseases in the Charlson Comorbidity Index, we pooled the patients into six categories: no comorbidity, cardiopulmonary disease, gastrointestinal disease, neurovascular disease, malignant neoplasms, and miscellaneous (diabetes, renal and connective tissue diseases). 2167 patients were included. RESULTS: The prevalence of comorbidity was 20%. For patients with localized disease, comorbidity increased the disease-specific mortality significantly (HR 1.70 (95% CI 1.36-2.13)). For patients with metastatic disease at the time of diagnosis, comorbidity did not affect the disease-specific mortality (HR 1.05 (95% CI 0.78-1.42)). The presence of another cancer diagnosis within 10 years prior to the sarcoma diagnosis was the only significant independent prognostic factor of disease-specific mortality with an increase of 66% in mortality rate compared to patients with no comorbidity (HR 1,66 (95% CI 1.22-2.25)). CONCLUSION: Comorbidity is a strong independent prognostic factor of mortality in patients with localized disease. This study emphasizes the need for optimizing the general health of comorbid patients in order to achieve a survival benefit from treatment of patients with localized disease, as this is potentially modifiable.

A Validated Prognostic Biomarker Score for Adult Patients with Nonmetastatic Soft Tissue Sarcomas of the Trunk and Extremities.

BACKGROUND: The prognostic value of serum biomarkers in soft tissue sarcoma (STS) is limited, and its clinical applicability is compromised by a common inability to adjust for important confounders. The aim of this study was to determine the prognostic value of pretreatment biomarkers on disease-specific survival (DSS) adjusted for confounders. METHODS: The study included 818 patients with localized STS. Pretreatment levels of albumin, C-reactive protein, hemoglobin, neutrophils, and lymphocytes were tested individually and combined in prognostic scores: neutrophil/lymphocyte ratio (NLR), Glasgow Prognostic Score (GPS), and Aarhus Composite Biomarker Score (ACBS) which includes all five biomarkers. Patients were randomly split into a test cohort and a validation cohort. The prognostic value of biomarkers on DSS was estimated using crude and adjusted Cox proportional hazard models. The different biomarker scores were compared using Akaike's information criteria. RESULTS: In the test cohort of 403 patients, all biomarkers except lymphocyte count were significant prognostic factors for DSS also after adjusting for confounders. NLR, GPS, and ACBS were independently associated with decreased survival; however, ACBS was significantly superior to NLR (P=.02) and GPS (P=.002). These findings were validated in the randomly assigned validation cohort of 415 patients. In the pooled data of 818 patients, the ACBS performed better than GPS and NLR. ACBS 2 was independently associated with decreased DSS compared to ACBS 0, hazard ratio 2.3[95% confidence interval: 1.5-3.5], P<.001. CONCLUSION: Patients with abnormal values in more than one serum biomarkers had a significant additional risk of dying compared to patients with only one abnormal value. ACBS was validated as an independent prognostic factor that is superior to both NLR and GPS.

A prognostic profile of hypoxia-induced genes for localised high-grade soft tissue sarcoma.

BACKGROUND: For decades, tumour hypoxia has been pursued as a cancer treatment target. However, prognostic and predictive biomarkers are essential for the use of this target in the clinic. This study investigates the prognostic value of a hypoxia-induced gene profile in localised soft tissue sarcoma (STS). METHODS: The hypoxia-induced gene quantification was performed by real-time quantitative PCR (RT-qPCR) of formalin-fixed, paraffin-embedded tissue samples. The gene expression cut-points were determined in a test cohort of 55 STS patients and used to allocate each patient into a more or a less hypoxic group. The cut-points found in the test cohort were applied to a cohort of 77 STS patients for validation. RESULTS: For patients with localised high-grade STS treated with surgery with or without postoperative radiation therapy, the prognostic value of the hypoxia-induced gene profile was proved in the test cohort and confirmed in the validation cohort. After adjustment for confounders, the hazard ratio (HR) was 3.2 (95% CI: 1.5; 7.0) for patients with more hypoxic tumours compared with patients with less hypoxic tumours regarding disease-specific survival. Moreover, for the development of metastatic disease, the HR was 2.61 (95% CI: 1.27; 5.33). CONCLUSIONS: The hypoxia-induced gene profile is a validated independent prognostic marker that may help identify STS patients needing more aggressive or different adjuvant treatment.

The Prognostic Value of Serum Biomarkers in Localized Bone Sarcoma.

OBJECTIVE: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Characteristics of 64 sarcoma patients referred to a sarcoma center after unplanned excision.

BACKGROUND AND METHODS: Unplanned excision of sarcoma before referral to specialist centers can affect prognosis and surgical outcome. The diagnostic pathway of these patients is uncertain and needs to be reviewed. We aimed to describe patient and tumor characteristics, initial symptoms, initial and final diagnosis, and explore reasons for unplanned excision in this patient group. From a previous study on 258 sarcoma patients, we identified 64 patients referred after surgery. Medical records were reviewed. RESULTS: The majority were soft tissue sarcomas, most often with thoracic location. Leiomyosarcoma was the most frequent final diagnosis, lipoma, and fibroma/dermatofibroma the most frequent initial diagnoses. Fifty percent were superficial small tumors, and 60.9% had not received diagnostic imaging before surgery. Fifty percent were referred from public surgical departments, and 1/3 from private specialists. Twenty-three patients had initial presence of alarm symptoms registered before surgery, the remaining 2/3 fell outside referral criteria or alarm symptoms were not discovered. CONCLUSIONS: Patients referred after unplanned excision often have small superficial tumors and the majority fall outside of defined referral criteria. Referral criteria are not a guarantee for detection of all sarcomas and surgeons should always be aware of the possibility of malignancy when removing a tumor.