Quantitative diffusion-weighted MRI response assessment in rhabdomyosarcoma: an international retrospective study on behalf of the European paediatric Soft tissue sarcoma Study Group Imaging Committee.

OBJECTIVE: To investigate the feasibility of diffusion-weighted magnetic resonance imaging (DW-MRI) as a predictive imaging marker after neoadjuvant chemotherapy in patients with rhabdomyosarcoma. MATERIAL AND METHODS: We performed a multicenter retrospective study including pediatric, adolescent and young adult patients with rhabdomyosarcoma, Intergroup Rhabdomyosarcoma Study group III/IV, treated according to the European paediatric Soft tissue sarcoma Study Group (EpSSG) RMS2005 or MTS2008 studies. DW-MRI was performed according to institutional protocols. We performed two-dimensional single-slice tumor delineation. Areas of necrosis or hemorrhage were delineated to be excluded in the primary analysis. Mean, median and 5th and 95th apparent diffusion coefficient (ADC) were extracted. RESULTS: Of 134 included patients, 82 had measurable tumor at diagnosis and response and DW-MRI scans of adequate quality and were included in the analysis. Technical heterogeneity in scan acquisition protocols and scanners was observed. Mean ADC at diagnosis was 1.1 (95% confidence interval [CI]: 1.1-1.2) (all ADC expressed in * 10-3 mm2/s), versus 1.6 (1.5-1.6) at response assessment. The 5th percentile ADC was 0.8 (0.7-0.9) at diagnosis and 1.1 (1.0-1.2) at response. Absolute change in mean ADC after neoadjuvant chemotherapy was 0.4 (0.3-0.5). Exploratory analyses for association between ADC and clinical parameters showed a significant difference in mean ADC at diagnosis for alveolar versus embryonal histology. Landmark analysis at nine weeks after the date of diagnosis showed no significant association (hazard ratio 1.3 [0.6-3.2]) between the mean ADC change and event-free survival. CONCLUSION: A significant change in the 5th percentile and the mean ADC after chemotherapy was observed. Strong heterogeneity was identified in DW-MRI acquisition protocols between centers and in individual patients.

Volumetric histograms-based analysis of apparent diffusion coefficients and standard uptake values for the assessment of pediatric sarcoma at staging: preliminary results of a PET/MRI study.

PURPOSE: To assess the relationship between apparent diffusion coefficients (ADC) and standard uptake values (SUV) of pediatric sarcomas at staging by using volumetric histograms analyses. METHODS: Children with histologically proven sarcoma, referring to our tertiary center for a whole-body 18F-FDG PET/MRI for staging and including diffusion weighted imaging in the MRI protocol were investigated. Firstly, turbo inversion recovery magnitude (TIRM) and PET images were resliced and resampled according to the ADC maps. Regions of interests were drawn along tumor margins on TIRM images and then copied on PET and ADC datasets. Pixel-based SUVs and ADCs were collected from the entire volume of each lesion. Mean, median, skewness, and kurtosis of SUVs and ADCs values were computed, and the Pearson correlation coefficient was then applied (for the entire population and for histological subgroups with more than five patients). RESULTS: Thirteen patients met the inclusion criteria (six females; mean age 8.31 ± 6.03 years). Histology revealed nine rhabdomyosarcomas, three Ewing sarcomas, and one chondroblastic osteosarcoma. A significant negative correlation between ADCs' and SUVs' mean (rmean = - 0.501, P < 0.001), median (rmedian = - 0.519, P < 0,001), and skewness (rskewness = - 0.550, P < 0.001) emerged for the entire population and for rhabdomyosarcomas (rmean = - 0.541, P = 0.001, rmedian = - 0.597, P < 0.001, rskewness = - 0.568, P < 0.001), whereas a significant positive correlation was found for kurtosis (rkurtosis = 0.346, P < 0.001, and rkurtosis = 0.348, P < 0.001 for the entire population and for rhabdomyosarcomas, respectively). CONCLUSION: Our preliminary results demonstrate that, using volumetric histograms, simultaneously collected SUVs and ADCs are dependent biomarkers in pediatric FDG-avid sarcomas. Further studies, on a larger population, are necessary to confirm this evidence and assess its clinical implications.

Treatment of rhabdomyosarcoma in children and adolescent from four low health expenditures average rates countries.

Background Survival of children with cancer in Eastern and Central Europe is 10-20% lower than in high income European countries. We evaluated outcome of children and adolescents with rhabdomyosarcoma (RMS) in Slovenia, Croatia, Slovakia and in Romania. Patients and methods We retrospectively analysed event-free survival (EFS) and overall survival (OS) for all patients treated in Slovenia and Croatia. Slovakia included patients from two centers, representing half of expected cases. Romania included patients from single institution, representing only 10% of expected patients. Joint database for analysis was established. Results One hundred seventy-eight children and adolescent with RMS diagnosed from January 2000 to December 2015 were included. Mean patient age at diagnosis was 7.7 years, one third was older than 10 years. Twenty-five percent had alveolar histology and 72% unfavorable location. Higher than expected proportion of patients had nodal involvement (24%) or metastatic disease (27%). All patients received systemic chemotherapy, 57% had radiotherapy and 63% surgery as local control. Kaplan- Meier estimates for 5-year EFS and OS were 50.7% and 59.6%, respectively. Five-year OS for patients with localised disease was 72% compared to 24% for metastatic disease. Conclusions Children with RMS treated in Eastern and Central Europe have inferior outcome compared to their counterparts treated in high income European countries. Active participation of low health expenditures average rates (LHEAR) countries in international clinical trials may improve outcome of paediatric oncology patients.

Radiologic Response Assessment in Pediatric Soft Tissue Sarcoma: Computed-Assisted Volume Evaluation.

OBJECTIVES: To compare 3 methods of dimensional assessment, with particular attention to a new software assisted method of volume calculation, in soft tissue sarcoma, and to investigate the interobserver agreement and the intermethod agreement in chemotherapy response classification and resultant clinical repercussions. STUDY DESIGN: We studied 34 pediatric patients with nonmetastatic soft tissue sarcoma who had undergone only diagnostic biopsy. Tumor size was measured both at diagnosis and after induction chemotherapy by 3 observers and using 3 measurement methods: maximum axis (1 diameter), estimated volume (3 diameters), and computed volume (software-assisted volume calculation). We used overall concordance correlation coefficient and Bland-Altman statistical methods to assess interobserver agreement and overall concordance correlation coefficient and the κ Cohen coefficient to assess intermethod agreement. RESULTS: According to overall concordance correlation coefficient, the interobserver agreement was very high for each method, with a slight superiority of the software assisted method; this agreement was not confirmed in Bland-Altman plots for maximum axis and estimated volume methods. According to kappa coefficients, the intermethod agreement in chemotherapy response evaluation was poor. CONCLUSIONS: Computed volume was the most accurate method in soft tissue sarcoma tumor size assessment. One- and 3-dimensional methods are not concordant in chemotherapy response classification. In particular, the maximum axis method underestimates chemotherapy response and can lead to switching the chemotherapy regimen erroneously.

Conservative strategy in infantile fibrosarcoma is possible: The European paediatric Soft tissue sarcoma Study Group experience.

BACKGROUND: Infantile fibrosarcoma (IFS) is a very rare disease occurring in young infants characterised by a high local aggressiveness but overall with a favourable survival. To try to reduce the total burden of therapy, the European pediatric Soft tissue sarcoma Study Group has developed conservative therapeutic recommendations according to initial resectability. MATERIAL AND METHODS: Between 2005 and 2012, children with localised IFS were prospectively registered. Initial surgery was suggested only if possible without mutilation. Patients with initial complete (IRS-group I/R0) or microscopic incomplete (group II/R1) resection had no further therapy. Patients with initial inoperable tumour (group III/R2) received first-line vincristine-actinomycin-D chemotherapy (VA). Delayed conservative surgery was planned after tumour reduction. Aggressive local therapy (mutilating surgery or external radiotherapy) was discouraged. RESULTS: A total of 50 infants (median age 1.4 months), were included in the study. ETV6-NTRK3 transcript was present in 87.2% of patients where investigation was performed. According to initial surgery, 11 patients were classified as group I, 8 as group II and 31 as group III. VA chemotherapy was first delivered to 25 children with IRS-III/R2 and one with IRS-II/R1 disease. Response rate to VA was 68.0%. Mutilating surgery was only performed in three cases. After a median follow-up of 4.7 years (range 1.9-9.0), 3-year event-free survival and overall survival were respectively 84.0% (95% confidence interval [CI] 70.5-91.7) and 94.0% (95% CI 82.5-98.0). CONCLUSIONS: Conservative therapy is possible in IFS as only three children required mutilating surgery, and alkylating or anthracycline based chemotherapy was avoided in 71.0% of patients needing chemotherapy. VA regimen should be first line therapy in order to reduce long term effects.