C-Reactive Protein Pretreatment-Level Evaluation for Ewing’s Sarcoma Prognosis Assessment—A 15-Year Retrospective Single-Centre Study

Abstract

Background: A pathological/inflamed cellular microenvironment state is an additional risk factor for any cancer type. The importance of a chronic inflammation state in most diffuse types of tumour has already been analysed, except for in Ewing’s sarcoma. It is a highly malignant blue round cell tumour, with 90% of cases occurring in patients aged between 5 and 25 years. Worldwide, 2.9 out of 1,000,000 children per year are affected by this malignancy. The aim of this retrospective study was to analyse the role of C-reactive protein (CRP) as a prognostic factor for Ewing’s sarcomas. Methods: This retrospective study at Klinikum rechts der Isar included 82 patients with a confirmed Ewing’s sarcoma diagnosis treated between 2004 and 2019. Preoperative CRP determination was assessed in mg/dL with a normal value established as below 0.5 mg/dL. Disease-free survival time was calculated as the time between the initial diagnosis and an event such as local recurrence or metastasis. Follow-up status was described as death of disease (DOD), no evidence of disease (NED) or alive with disease (AWD). The exclusion criteria of this study included insufficient laboratory values and a lack of information regarding the follow-up status or non-oncological resection. Results: Serum CRP levels were significantly different in patients with a poorer prognosis (DOD) and in patients who presented distant metastasis (p = 0.0016 and p = 0.009, respectively), whereas CRP levels were not significantly different in patients with local recurrence (p = 0.02). The optimal breakpoint that predicted prognosis was 0.5 mg/dL, with a sensitivity of 0.76 and a specificity of 0.74 (AUC 0.81). Univariate CRP analysis level >0.5 mg/dL revealed a hazard ratio of 9.5 (95% CI 3.5–25.5). Conclusions: In Ewing’s sarcoma cases, we consider a CRP pretreatment value >0.5 mg/dL as a sensitive prognostic risk factor indication for distant metastasis and poor prognosis. Further research with more data is required to determine more sensitive cutoff levels.

C-reactive Protein Pretreatment-Level Evaluation with Histopathological Correlation for Chondrosarcoma Prognosis Assessment—a 15-Year Retrospective Single-Centre Study

“…The relevance of CRP levels in Ewing Sarcoma patients were already demonstrate in our 2022 study [8]. CRP level >0.5 mg/dL revealed an 8.3 HR (95% CI 3-22.7).…”

“…Over the last decade, there has been a renewed emphasis on the clinical utility of serum CRP, extending beyond inflammation to encompass the prediction and diagnosis of various conditions, notably cardiovascular diseases and malignancies. Elevated serum CRP levels have been observed in patients with numerous malignancies, highlighting a close association between inflammation and cancer [6][7][8][9][10]. The term "tumor CRP" is commonly used but actually until now unexplained.…”

TCR-transgenic T cells and YB-1-based oncolytic virotherapy improve survival in a preclinical Ewing sarcoma xenograft mouse model

“…Cellular immunotherapy approaches have to address a multitude of obstacles: physical barriers, low to absent MHC class I expression, immunosuppressive innate cells of myelomonocytic origin, cancerassociated fibroblast-like tumor cells, chemo-and cytokines as well non-classical MHCs in the TME preventing an impactful T cell attack (8,(50)(51)(52)(53)(54). They additionally have to include properties to revert immunosuppressive systemic factors, such as fibroblastic/ myeloid-derived suppressor cells, chronic inflammation or tumorderived extracellular vesicles hampering proper antigen presentation and activation of DC to enable formation of antitumor T cell immunity (1,2,55).…”

The Prognostic Value of the Serum Level of C-Reactive Protein for Survival of Children with Ewing’s Sarcoma

“…The prognostic value of CRP has also been evaluated in patients affected by bone and soft tissue sarcomas, without differentiating the various histotypes that have distinct treatments and prognoses [12][13][14][15]. The only studies that analyzed CRP in patients with Ewing's sarcoma had important limitations [13,[16][17][18][19]. Nakamura et al analyzed patients without rule out the presence of inflammatory conditions [13].…”

“…Xu et al only analyzed patients with vertebral or sacral Ewing's sarcoma, which are usually associated with worse prognosis [17]. Recently, two other studies analyzed the possible association between pathological CRP and prognosis in patients with Ewing's sarcoma, but the authors did not analyze tumor size, other inflammatory biomarkers, and did not consider the subgroup analysis of localized patients and metastatic patients [18,19].…”