Three-dimensional Radiologic Assessment of Chemotherapy Response in Ewing Sarcoma Can Be Used to Predict Clinical Outcome

Aghighi, Maryam; Boe, Justin; Rosenberg, Jarrett; Eyben, Rie von; Gawande, Rakhee; Petit, Philippe; Sethi, Tarsheen; Sharib, Jeremy M.; Marina, Neyssa; DuBois, Steven G.; Daldrup-Link, Heike E.

doi:10.1148/radiol.2016151301

Cited by 44 publications

(39 citation statements)

References 66 publications

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“…Given that 8 cm estimates a tumor larger than 200 mL but is not associated with inferior local tumor control may indicate maximum tumor dimension measurements are an inadequate prognostic variable with contemporary treatment. In fact, Aghighi et al (14) demonstrated that 3-dimensional tumor measurements for ES significantly correlated with clinical outcomes compared with 1- or 2-dimensional measurements, in which the correlation was weaker or not significant.…”

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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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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“…Since HisRes has been identified as a prognostic factor, image‐based response might well correlate with HisRes . Previously published reports on imaging based tumor response cited only limited numbers of patients and focused more on response during late induction chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

The relation of radiological tumor volume response to histological response and outcome in patients with localized Ewing Sarcoma

et al. 2019

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Background Magnetic resonance imaging (MRI) is the modality of choice for local staging and response evaluation of Ewing sarcoma (EwS). Aim of this study was to determine the relevance of tumor volume response (TVR) in relation to histological response (HisRes) and survival, in order to evaluate if early modification of chemotherapy might be indicated in patients with inadequate TVR. Methods Three dimensional (3D)‐tumor volume data at diagnosis, during early induction phase (1‐3 courses of chemotherapy; n = 195) and/or late induction phase (4‐6 courses; n = 175) from 241 localized patients were retrospectively analyzed. A distinction was made between adequate response (reduction ≥67%) and inadequate response (reduction <67% or progression). Correlations between TVR, HisRes, event free survival (EFS), and overall survival (OS) were analyzed using chi‐square tests, log‐rank tests, and the Cox‐regression model. Results Early adequate TVR, noted in 41% of patients, did not correlate with EFS (P = 0.92) or OS (P = 0.38). During late induction phase 62% of patients showed an adequate TVR. EFS for patients with late adequate TVR was better (78%) than for those with inadequate late TVR (61%) (P = 0.01); OS was 80% and 69% (P = 0.26), respectively. No correlation was found between TVR and HisRes. Multivariate analysis showed that poor HisRes, pelvic location and late inadequate TVR were associated with poor outcome. Conclusions Early inadequate TVR does not predict adverse outcome; therefore, changing the treatment to second line chemotherapy is not indicated in case of inadequate early TVR. Late adequate TVR and good HisRes correlate with better EFS; patients with late inadequate TVR might benefit from augmented therapy.

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“…At the time of the RECIST update in 2009 (RECIST 1.1), the lack of rigorous clinical validation and of widespread access to these newer imaging approaches prevented their implementation and adoption. However, in recent years, a number of publications have demonstrated the high reproducibility and interobserver reliability of volume measurements using semiautomated tumor segmentation technique implemented in commercially available15, 16, 17, 18 or in‐house software 19. The estimated ellipsoidal volume has been suggested as an approximation for software‐calculated actual volume to overcome limitations related to software availability and has shown good correlation to actual volume 15, 18.…”

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confidence: 99%

“…However, in recent years, a number of publications have demonstrated the high reproducibility and interobserver reliability of volume measurements using semiautomated tumor segmentation technique implemented in commercially available15, 16, 17, 18 or in‐house software 19. The estimated ellipsoidal volume has been suggested as an approximation for software‐calculated actual volume to overcome limitations related to software availability and has shown good correlation to actual volume 15, 18. Moreover, for a number of cancers 3D assessments enable to capture finer changes in tumor size,17, 18 and better correlates to long‐term clinical outcome, such as OS,2, 18, 21 compared to 1D measurements.…”

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confidence: 99%

“…The estimated ellipsoidal volume has been suggested as an approximation for software‐calculated actual volume to overcome limitations related to software availability and has shown good correlation to actual volume 15, 18. Moreover, for a number of cancers 3D assessments enable to capture finer changes in tumor size,17, 18 and better correlates to long‐term clinical outcome, such as OS,2, 18, 21 compared to 1D measurements. Such results were supported by Schiavon et al .,15 showing that ellipsoidal volume provides a satisfactory approximation for the actual volume of liver metastases in imatinib‐treated GIST.…”

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confidence: 99%

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Pharmacometric Modeling of Liver Metastases' Diameter, Volume, and Density and Their Relation to Clinical Outcome in Imatinib‐Treated Patients With Gastrointestinal Stromal Tumors

Schindler

Krishnan

Mathijssen

et al. 2017

CPT Pharmacom & Syst Pharma

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Three‐dimensional and density‐based tumor metrics have been suggested to better discriminate tumor response to treatment than unidimensional metrics, particularly for tumors exhibiting nonuniform size changes. In the developed pharmacometric modeling framework based on data from 77 imatinib‐treated gastrointestinal patients, the time‐courses of liver metastases' maximum transaxial diameters, software‐calculated actual volumes (Vactual) and calculated ellipsoidal volumes were characterized by logistic growth models, in which imatinib induced a linear dose‐dependent size reduction. An indirect response model best described the reduction in density. Substantial interindividual variability in the drug effect of all response assessments and additional interlesion variability in the drug effect on density were identified. The predictive ability of longitudinal tumor unidimensional and three‐dimensional size and density on overall survival (OS) and progression‐free survival (PFS) were compared using parametric time‐to‐event models. Death hazard increased with increasing Vactual. This framework may guide early clinical interventions based on three‐dimensional tumor responses to enhance benefits for patients with gastrointestinal stromal tumors (GIST).

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Three-dimensional Radiologic Assessment of Chemotherapy Response in Ewing Sarcoma Can Be Used to Predict Clinical Outcome

Cited by 44 publications

References 66 publications

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

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

The relation of radiological tumor volume response to histological response and outcome in patients with localized Ewing Sarcoma

Pharmacometric Modeling of Liver Metastases' Diameter, Volume, and Density and Their Relation to Clinical Outcome in Imatinib‐Treated Patients With Gastrointestinal Stromal Tumors

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