Biomedical subjects

Marilena Cesari

Publications and source records attributed to Marilena Cesari.

4 recordsLinked to original sources

PubMed2026

Circulating IGF2BP3 enables risk stratification and predicts treatment response in Ewing sarcoma.

Ewing sarcoma (EWS), the second most common pediatric bone tumor, presents with a markedly heterogeneous clinical spectrum and optimal risk stratification is therefore crucial for improving treatment outcomes. The RNA-binding protein IGF2BP3 is a critical oncogenic driver of EWS malignancy. This study evaluates the clinical utility of circulating IGF2BP3 as a biomarker to predict treatment response and risk of disease progression in patients with EWS. Plasma samples from 60 patients with EWS diagnosed and treated at the IRCCS Rizzoli Orthopedic Institute (Bologna, Italy) were collected at diagnosis before treatment initiation and/or after induction chemotherapy. For 51 of these patients, blood was collected at diagnosis, prior to any treatments. For 25 patients, blood samples were available at diagnosis and before surgical intervention, allowing longitudinal analysis in the same patient. For 9 patients, blood was collected only after preoperative chemotherapy, before surgical intervention. Circulating IGF2BP3 levels were quantified using a highly specific and sensitive ELISA assay. Plasma samples from healthy donors served as controls. IGF2BP3 plasma levels were correlated with IGF2BP3 tumor tissue expression, established clinical risk factors, and cumulative incidence of relapse using univariable and multivariable analyses. Plasma IGF2BP3 levels were significantly elevated in patients with EWS compared with healthy controls, with a subset of patients (22/51, 43.2%) exhibiting clinically relevant concentrations. Circulating IGF2BP3 levels reflected tumor expression of the molecule and provided additional prognostic information beyond standard clinicopathologic features. The prognostic impact of circulating IGF2BP3 was primarily observed in patients with localized disease, in whom elevated levels were identified as a significant adverse prognostic factor for disease-specific survival (hazard ratio, 10.63; 95% CI, 1.27-88.62; P = 0.029). Longitudinal monitoring demonstrated that persistence of IGF2BP3 in plasma after induction chemotherapy was a strong predictor of poor clinical outcomes. Circulating IGF2BP3 represents a valuable biomarker for early risk stratification in EWS, particularly in patients with localized disease. Although this is single-marker assay, the expression of the molecule may impact on the fate of many mRNAs. We present an accurate, simple, cost-effective and easy clinical applicable tool to support risk-adapted therapeutic interventions. The limited number of employed patients warrants the need of larger cohorts for validation.

Humans↗

PubMed2006

Influence of local recurrence on survival in patients with extremity osteosarcoma treated with neoadjuvant chemotherapy: the experience of a single institution with 44 patients.

BACKGROUND: Risk factors for local recurrence (LR) after osteosarcoma, such as surgical margins and histologic response to preoperative treatment, have been well documented, whereas the outcome for patients who locally recur has not been well established yet. METHODS: Retrospective analysis of the management and outcome of 44 patients who developed LR after treatment of osteosarcoma of the extremities with neoadjuvant chemotherapy was performed in a single institution between 1983 and 1999. RESULTS: In 24 patients (54.5%), LR was the first sign of recurrence; in 8 patients (18.2%) LR followed systemic recurrence and in 12 patients (27.3%), the 2 events, local and systemic recurrence, were concurrent. Of the 44 patients, 26 with local recurrences were free of disease, but only 5 were long-term event-free survivors, and 39 patients developed further recurrences: 37 died of the tumor and 2 were alive with uncontrolled disease at the time of last follow-up. The 5-year disease-free survival rate after the last recurrence was 15.9%; it was 25.9% for patients who achieved remission and 0% for the others. The only prognostic factor identified for post-LR disease-free survival was the presence of systemic recurrence at the time of diagnosis of LR or before (5-year postrecurrence event-free survival rate of 29.1% for patients without metastases at the time of local recurrence vs. 0% for those with metastases; P = .02). CONCLUSIONS: These results confirm that patients with osteosarcoma of the extremities who develop LR are at a very significantly high risk of developing metastatic disease and dying of the tumor.

Adolescent↗

PubMed2006

Late relapse in osteosarcoma.

The aim of this study was to identify predictive factors of late relapse in nonmetastatic osteosarcoma patients treated at the Rizzoli Institute from 1983 to 1997. Clinical features of patients who had late (>4 y of follow-up) or earlier recurrence were compared. Late relapse was reported in 24 (3.7%) of the 648 patients who entered the studies. A surgical complete remission was achieved in 19 (79%) patients. The 5-year probability of postrelapse survival was 65% for the complete remission patients (48% in the entire group), which was significantly better than that of the patients (5-year postrelapse survival 20%) with an early relapse. Sex, site, and size of the tumor, histologic subtype, alkaline phosphatase and lactate dehydrogenase serum levels, type of surgery, and histologic response did not significantly differ between patients with late or early relapse. No clinical predictive factors of late relapse were identified and a prolonged follow-up is recommended for all patients.

Adolescent↗

PubMed2005

Prospective evaluation of renal function in pediatric and adult patients treated with high-dose ifosfamide, cisplatin and high-dose methotrexate.

We investigated the renal function of pediatric and adult patients who had been submitted to chemotherapy with high-dose methotrexate (MTX), cisplatin and high-dose ifosfamide (IFO). We observed 43 osteosarcoma patients aged 4--34 years (median 16 years). The median received cumulative doses of MTX, cisplatin and IFO were 60.1 g/m, 598 mg/m and 73.5 g/m. Renal function was assessed by measurement of creatinine clearance, renal threshold for phosphate (Tmp/GFR), urinary alpha1-microglobulin (A1M):creatinine ratio, urinary albumin:creatinine ratio, 24-h glycosuria and proteinuria. The median interval between chemotherapy completion and first renal function assessment was 2 months (range 2--4 months); assessments were then performed at a median interval of 16 months (range 9--49 months). A significant decrease of TmP/GFR was observed only in the pediatric group (under 18 years): the percentage of patients with TmP/GFR<1 mmol/l increased from 21% (six of 28) at the end of treatment to 46% (13 of 28) at the late assessment. Glycosuria in 10 (67%) of 15 adults and 21 (75%) of pediatric patients was detected with an increased incidence compared to the early post-chemotherapy assessment (13% adults and 29% children). A significant increase of the albumin:creatinine ratio and A1M:creatinine ratio was observed only in adults. Overall, 21 patients had a reduced glomerular function at the latest evaluation, associated with glycosuria in 15 patients (71%), proteinuria in 14 (67%) and TmP/GFR<1 mmol/l in 11 (52%). We conclude that strict monitoring of renal function should be recommended in pediatric and adult patients after chemotherapy with high-dose MTX, cisplatin and high-dose IFO.

Acute Kidney Injury↗