Response to chemotherapy estimates by FDG PET is an important prognostic factor in patients with Ewing sarcoma

Raciborska, Anna; Bilska, Katarzyna; Drabko, Katarzyna; Michalak, Elżbieta; Chaber, Radosław; Pogorzała, Monika; Połczyńska, Katarzyna; Sobol, Grazyna; Wieczorek, Maria; Muszyńska-Rosłan, Katarzyna; Rychłowska-Pruszyńska, Magdalena; Rodríguez‐Galindo, Carlos; Dziuk, Mirosław

doi:10.1007/s12094-015-1351-6

Cited by 59 publications

(30 citation statements)

References 30 publications

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“…The strength of this study was the homogeneity of treatment, including the duration of neoadjuvant chemotherapy, the surgical team and pathological assessment, all important determinants of EFS that could be confounding factors in assessing the predictive value of FDG PET. The concordance between a good histological response (>90 % tumour necrosis in OS patients and Picci II/III necrosis in EWS patients) and SUV1 (<6) in this study was very robust, confirming the findings in smaller series [15, 16, 32, 33], and is in contrast with the findings of a study performed in America [31]. Differences in patient characteristics (age), treatment and histological examination assessment could explain these conflicting results.…”

Section: Discussionsupporting

confidence: 88%

“…SUV2 seems exclusively useful in EWS patients. In our study SUV2 was able to predict histological response, as shown in a paediatric series [32], and might be used for example by surgeons to plan a local treatment approach. Furthermore, a good metabolic response was associated with best survival in EWS patients (80 % 3-year EFS in patients with a reduction in SUV2 of ≥55 %, in contrast to 20 % in patients with a poor metabolic response).…”

Section: Discussionmentioning

confidence: 70%

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The role of FDG PET/CT in patients treated with neoadjuvant chemotherapy for localized bone sarcomas

Palmerini

Colangeli

Nanni³

et al. 2016

Eur J Nucl Med Mol Imaging

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PurposeThe histological response to neoadjuvant chemotherapy is an important prognostic factor in patients with osteosarcoma (OS) and Ewing sarcoma (EWS). The aim of this study was to assess baseline primary tumour FDG uptake on PET/CT, and serum values of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH), to establish whether these factors are correlated with tumour necrosis and prognosis.MethodsPatients treated between 2009 and 2014 for localized EWS and OS, who underwent FDG PET/CT as part of their staging work-up, were included. The relationships between primary tumour SUVmax at baseline (SUV1), SUVmax after induction chemotherapy (SUV2), metabolic response calculated as [(SUV1 − SUV2)/SUV1)] × 100, LDH and ALP and tumour response/survival were analysed. A good response (GR) was defined as tumour necrosis >90 % in patients with OS, and grade II-III Picci necrosis (persitence of microscopic foci only or no viable tumor) in patients with Ewing sarcoma.ResultsThe study included 77 patients, 45 with EWS and 32 with OS. A good histological response was achieved in 53 % of EWS patients, and 41 % of OS patients. The 3-year event-free survival (EFS) was 57 % in EWS patients and 48 % OS patients. The median SUV1 was 5.6 (range 0 – 17) in EWS patients and 7.9 (range 0 – 24) in OS patients (p = 0.006). In EWS patients the GR rate was 30 % in those with a high SUV1 (≥6) and 72 % in those with a lower SUV1 (p = 0.0004), and in OS patients the GR rate was 29 % in those with SUV1 ≥6 and 64 % in those with a lower SUV1 (p = 0.05). In the univariate analysis the 3-year EFS was significantly better in patients with a low ALP level (59 %) than in those with a high ALP level (22 %, p = 0.02) and in patients with a low LDH level (62 %) than in those with a high LDH level (37 %, p = 0.004). In EWS patients the 3-year EFS was 37 % in those with a high SUV1 and 75 % in those with a low SUV1 (p = 0.004), and in OS patients the 3-year EFS was 32 % in those with a high SUV1 and 66 % in those with a low SUV1 (p = 0.1). Histology, age and gender were not associated with survival. In the multivariate analysis, SUV1 was the only independent pretreatment prognostic factor to retain statistical significance (p = 0.017). SUV2 was assessed in 25 EWS patients: the median SUV2 was 1.9 (range 1 – 8). The GR rate was 20 % in patients with a high SUV2, and 67 % in those with a low SUV2 (p = 0.02). A good metabolic response (SUV reduction of ≥55 %) was associated with a 3-year EFS of 80 % and a poor metabolic response with a 3-year EFS of 20 % (p = 0.05). In the OS patients the median SUV2 was 2.7 (range 0 – 4.5). Neither SUV2 nor the metabolic response was associated with outcome in OS patients.ConclusionFDG PET/CT is a useful and noninvasive tool for identifying patients who are more likely to be resistant to chemotherapy. If this finding is confirmed in a larger series, SUV1, SUV2 and metabolic response could be proposed as factors for stratifying EWS patients to identify those with high-grade localized bone EWS who would benefit from ri...

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 70%

The role of FDG PET/CT in patients treated with neoadjuvant chemotherapy for localized bone sarcomas

Palmerini

Colangeli

Nanni³

et al. 2016

Eur J Nucl Med Mol Imaging

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“…A surrogate metric to determine whether treatment intensification is warranted in patients undergoing RT is needed. Many studies demonstrate tumors with minimal metabolic changes on [ 18 F]fluorodeoxyglucose positron emission tomography ( 18 F-FDG PET) following neo-adjuvant therapy are associated with a higher risk of progression (21-23). None of these reports discuss the association of local tumor control with 18 F-FDG PET, so it is unclear whether 18 F-FDG PET has a role in determining high-risk RT cases.…”

Section: Discussionmentioning

confidence: 99%

Identification of Patients With Localized Ewing Sarcoma at Higher Risk for Local Failure: A Report From the Children's Oncology Group

Ahmed

Randall

DuBois

et al. 2017

International Journal of Radiation Oncology*Biology*Physics

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Purpose To identify clinical and treatment variables associated with a higher risk of local failure in Ewing sarcoma patients treated on recent Children's Oncology Group protocols. Methods and Materials Data for 956 patients treated with ifosfamide and etoposide–based chemotherapy on INT-0091, INT-0154, and AEWS0031 were analyzed. Local treatment modalities were defined as surgery, definitive radiation therapy (RT), or surgery plus radiation (S+RT). Five-year cumulative incidence of local failure was determined. Results The local failure rate for the entire cohort was 7.3%, with a 3.9% rate for surgery, 15.3% for RT (P<.01), and 6.6% for S+RT (P = .12). The local failure incidence was 5.4% for extremity tumors, 13.2% for pelvis tumors (P<.01), 5.3% for axial non-spine tumors (P = .90), 9.1% for extraskeletal tumors (P=.08), and 3.6% for spine tumors (P = .49). The incidence of local failure was 14.8% for extremity tumors and 22.4% for pelvis tumors treated with RT, compared with 3.7% for extremity tumors and 3.9% for pelvis tumors treated with surgery (P≤01). There was no difference in local failure incidence by local treatment modality for axial non-spine, spine, and extraskeletal tumors. The local failure incidence was 11.9% in patients aged ≥18 years versus 6.7% in patients aged <18 years (P = .02). Age ≥18 years (hazard ratio 1.9, P = .04) and treatment with RT (hazard ratio 2.40, P<.01) remained independent prognostic factors for higher local failure incidence on multivariate analysis. Tumor size (

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“…While mutations in the STAG2 , CDKN2A , and TP53 genes can be found in about 20% of Ewing's sarcoma cases, their prognostic significance remains controversial . Moreover, the prognostic and predictive utility of 18F‐fluorodeoxyglucose positron emission tomography in Ewing's sarcoma has been reported.…”

Section: Research Directions In Ewing's Sarcomamentioning

confidence: 99%

Current Status of Proteomics in Ewing's Sarcoma

Kondo

2018

Proteomics Clinical Apps

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Ewing's sarcoma is an extremely rare mesenchymal malignancy of the bone, which predominantly occurs in children and young adolescents. Ewing's sarcoma is characterized by chromosomal translocations resulting in the formation of chimeric fusions between the EWS gene and transcription factors of the ETS family, such as EWS-FLI-1. The clinical outcome of Ewing's sarcoma remains poor, and novel therapeutic approaches are required. Proteomic analyses have been applied to identify the functions of the fusion gene product, and a novel mechanism of EWS-FLI-1 turnover has been proposed. Furthermore, proteomics has revealed the regulation of IL-6 secretion by EWS-FLI-1, which may promote malignant behavior in tumor cells. In addition, proteomic approaches have been used to assess the effects of unique genes and drugs on Ewing's sarcoma and to determine specific biomarker candidates for the prediction of drug resistance and recurrence. By identifying the proteins relevant to the molecular backgrounds of clinical characters of Ewing's sarcoma, we can understand the biology of Ewing's sarcoma and develop clinical applications. Fundamental research systems such as tumor cell and tissue biobanks and databases are required to make effective use of the limited clinical materials and promote research into Ewing's sarcoma.

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Response to chemotherapy estimates by FDG PET is an important prognostic factor in patients with Ewing sarcoma

Abstract: (18)F-FDG PET demonstrates high diagnostic accuracy for response to initial chemotherapy in patients with ES and it correlates with outcome. The role of FDG PET in predicting response and outcome should be further investigated.

Cited by 59 publications

References 30 publications

The role of FDG PET/CT in patients treated with neoadjuvant chemotherapy for localized bone sarcomas

The role of FDG PET/CT in patients treated with neoadjuvant chemotherapy for localized bone sarcomas

Identification of Patients With Localized Ewing Sarcoma at Higher Risk for Local Failure: A Report From the Children's Oncology Group

Current Status of Proteomics in Ewing's Sarcoma

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