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Objectives To investigate whether whole-body diffusion-weighted imaging (WB-DWI) alone is adequate for detecting metastases in melanoma patients, or if standard WB contrast-enhanced magnetic resonance imaging (WB-ceMRI) is required. Methods Seventy-one WB-DWI studies were performed quarterly along with whole-body MRI including contrast-enhanced sequences (WB-ceMRI) in 19 patients with advanced melanoma. The reference standard was biopsy, other imaging investigations, or changes observed on follow-up. Findings of metastasis in separate WB-DWI and WB-DWI + WB-ceMRI readings were compared using κ statistics. Additionally, the distribution of findings was examined and calculated per body region (brain, neck, chest, abdomen, liver, pelvis, subcutaneous tissues, bones) and diagnostic accuracy (DA), sensitivity, specificity, negative predictive value, and positive predictive value were calculated per patient. Results The eight examinations that were positive by the reference standard contained a total of 14 metastatic findings. With almost perfect agreement between techniques (κ = 85 %, 95 % CI 70–100 %) for detection of examinations with metastatic findings, and complete agreement in extracranial metastasis detection, 10 metastases were detected using WB-DWI and 13 using WB-DWI + WB-ceMRI. WB-DWI and WB-DWI + WB-MRI had equivalent per patient DA (79 %). Conclusions WB-DWI without additional WB-ceMRI sequences is promising for the detection of extracranial metastases in melanoma patients, but contrast-enhanced MRI is required for evaluating the brain. Key Points • Whole-body (WB) magnetic resonance imaging (MRI) is increasingly used for oncological disease assessment. • WB diffusion-weighted MRI detects extracranial metastases in melanoma patients. • Contrast-enhanced MRI is only required for detecting brain metastases. • WB-DWI is inferior to low-dose CT for detecting lung metastases.

Objectives Solitary plasmacytoma (SP) is characterized by a single mass of clonal plasma cells. Definitive RT can result in long-term local control of the SP. Due to the small number of patients and narrow range of doses, phase III randomized trials are lacking. The aim of this study is to further support the potential use of RT for the treatment of SP. Methods Clinical data of all patients treated for SP at our Institution between 1992 and 2018 were reviewed. A total of 42 consecutive patients were analyzed. Results The median follow-up was 84.8 months. Radiation dose did not differ significantly as a function of sex, type of SP (solitary bone plasmacytoma or as extramedullary plasmacytoma), tumor size; conversely differs significantly as a function of age ( p  = 0.04). The 5y-OS and 10y-OS were, respectively, 96 and 91%. Local recurrences developed in 21.4% of patients (9/42). 16 patients progressed to MM (38.1%). The 5y-progression to MM free survival (PMFS) and the 10y-PMFS were, respectively, 68.6 and 61.9%. Conclusions Our data confirm that good results are achievable with RT to treat SP, but they don’t allow defining a dose–effect correlation; therefore, it remains uncertain which is the most effective dose and whether lower doses can guarantee adequate disease control.

IntroductionEwing sarcoma is a rare paediatric cancer. Currently, there is no way of accurately predicting these patients’ survival at diagnosis. Disease type (ie, localised disease, lung/pleuropulmonary metastases and other metastases) is used to guide treatment decisions, with metastatic patients generally having worse outcomes than localised disease patients. However, not all patients fit this trend. An accurate prognostic model could be used to guide treatment decisions in clinical practice to avoid patients being incorrectly under or overtreated.Methods and analysisThis study aims to develop and internally validate prognostic models in newly diagnosed Ewing sarcoma patients, using the EE2012 clinical trial data set. The models will incorporate prognostic factors, identified from a literature review, to predict patients’ probability of event-free survival at clinically important time points. Three models will be developed, for comparison of their performance and stability, using different methods of model selection and penalisation for overfitting (full model or backwards selection applying uniform shrinkage; and lasso variable selection). The models will be internally validated using bootstrapping to give optimism-adjusted performance statistics (calibration and discrimination) and model stability results. Patient and clinical user groups will be asked to determine risk thresholds to guide treatment decisions in clinical practice based on the model. Decision curve analyses will examine clinical utility at these thresholds.Ethics and disseminationThis study is a secondary analysis of EE2012 clinical trial data. The EE2012 trial received ethical approval from the competent authorities (UK ethics reference approval number 12/NW/0827). This study is covered by the trial ethics in place. The results from this study will be published in peer-reviewed journals to act as a benchmark for future studies.Trial registration numberEudraCT number 2012-002107-17. ISRCTN number 92192408.

Molecular diagnostics play an increasing role in the diagnosis of Ewing sarcoma. The type of molecular testing used in clinical practice has been poorly described. To describe patterns of translocation testing for newly diagnosed Ewing sarcoma. Children's Oncology Group (COG) trial AEWS1221 was a phase III randomized trial enrolling patients with newly diagnosed metastatic Ewing sarcoma from 2014 to 2019. Patients were required to have a histologic diagnosis of Ewing sarcoma, but translocation testing was not required. Sites provided types and results of any molecular diagnostics performed. Data from 305 enrolled patients were available. The most common type of molecular testing was fluorescence in situ hybridization (FISH) performed on the primary tumor (236 of 305 patients; 77.4%), with positive testing for an EWSR1 or FUS translocation in 211 (89.4%). Reverse transcription-polymerase chain reaction (RT-PCR) on the primary tumor was performed in 61 of 305 patients (20%), with positive results in 48 of 61 patients (78.7%). Next-generation sequencing was reported in 7 patients for the primary tumor and in 3 patients for metastatic sites. For all types of testing on either primary or metastatic tumor, 16 of 305 patients (5.2%) had no reported translocation testing. When evaluating all results from all testing, 44 of 305 patients (14.4%) lacked documentation of an abnormality consistent with a molecular diagnosis of Ewing sarcoma. COG sites enrolling in a Ewing sarcoma trial have high rates of testing by FISH or PCR. A small proportion of patients have no translocation testing on either primary or metastatic sites. Next-generation sequencing techniques are not yet commonly used in this context.

Objective To compare whole-body MRI (WB-MRI) and axial skeleton MRI (AS-MRI) in detecting and measuring bone metastases in patients with prostate cancer (PCa). Methods WB-MRI and AS-MRI examinations were performed in 60 patients with PCa at high risk of metastases. Two radiologists separately categorised the AS-MRI and WB-MRI as negative or positive for metastases, and measured focal metastases using the “Response evaluation criteria in solid tumours” (RECIST) criteria transposed to bone. One radiologist reviewed all examinations 2 months later. Inter- and intraobserver agreements in establishing the presence/absence of metastases were calculated. Bland-Altman plots were used to assess measurement agreement between AS-MRI and WB-MRI. Results Strong to perfect inter- and intraobserver agreements were found between AS-MRI and WB-MRI in defining the presence/absence of bone metastases. There were no patients with isolated “peripheral” metastases at WB-MRI, missed at AS-MRI. There was no difference in lesion count between the two radiologists. AS-MRI and WB-MRI provided statistically equivalent RECIST values for one radiologist and slightly lower values at AS-MRI for the other. Conclusions In our series of PCa patients, AS-MRI and WB-MRI were equivalent in determining the presence/absence of bone metastases and provided similar evaluation of the metastatic burden.

Objective The objective of this study was to evaluate whether the average apparent diffusion coefficient (ADC) or the minimum ADC is more useful for evaluating the chemotherapeutic response of osteosarcoma. Materials and methods Twenty-two patients with osteosarcoma were examined in this study. Diffusion-weighted (DW) and magnetic resonance (MR) images were performed for all patients before and after chemotherapy. The pre- and post-chemotherapy values were obtained both in the average and minimum ADC. The pre-chemotherapy values of the average ADC and minimum ADC respectively were compared with the post-chemotherapy values. In addition, the ADC ratios ([ADC post - ADC pre ] / ADC pre ) were calculated using the average ADC and the minimum ADC. Twenty-two patients with osteosarcomas were divided into two groups, those with a good response to chemotherapy (≥ 90% tumor necrosis, n  = 7) and those with a poor response (< 90% tumor necrosis, n  = 15). The average ADC ratio and the minimum ADC ratio of the two groups were compared. Results With both the average ADC and the minimum ADC, post-chemotherapy values were significantly higher than pre-chemotherapy values ( P  < 0.05). The patients with a good response had a significantly higher minimum ADC ratio than those with a poor response (1.01 ± 0.22 and 0.55 ± 0.29 respectively, P  < 0.05). However, with regard to the average ADC ratio, no significant difference was observed between the two groups (0.66 ± 0.18 and 0.46 ± 0.31 respectively, P  = 0.19). Conclusion The minimum ADC is useful for evaluating the chemotherapeutic response of osteosarcoma.

Sarcomas are malignant soft tissue and bone tumours affecting adults, adolescents and children. They represent a morphologically heterogeneous class of tumours and some entities lack defining histopathological features. Therefore, the diagnosis of sarcomas is burdened with a high inter-observer variability and misclassification rate. Here, we demonstrate classification of soft tissue and bone tumours using a machine learning classifier algorithm based on array-generated DNA methylation data. This sarcoma classifier is trained using a dataset of 1077 methylation profiles from comprehensively pre-characterized cases comprising 62 tumour methylation classes constituting a broad range of soft tissue and bone sarcoma subtypes across the entire age spectrum. The performance is validated in a cohort of 428 sarcomatous tumours, of which 322 cases were classified by the sarcoma classifier. Our results demonstrate the potential of the DNA methylation-based sarcoma classification for research and future diagnostic applications. Sarcomas are morphologically heterogeneous tumours rendering their classification challenging. Here the authors developed a classifier using DNA methylation data from several soft tissue and bone sarcoma subtypes, which has the potential to improve classification for research and clinical purposes.

Background To assess prognostic and predictive effects of clinical and biochemical factors in our published randomized study of a weekly low dose (metronomic arm) versus a conventional dosage of zoledronic acid (conventional arm) in breast cancer patients with bone metastases. Methods Treatment outcome of 60 patients with bone metastases were used to assess impacts of following potential prognostic factors, estrogen receptor status, lymph node status, 2 year-disease free interval (DFI), numbers of chemotherapy regimens administered, interventions, and serum levels of VEGF, N-telopeptide of type I collagen (NTx), CEA, and CA 15-3. Results In univariate analyses, patients pretreated with 2 or fewer chemotherapy regimens, ER-positive tumors, 3 or fewer lymph nodes, DFI of more than 2 years, serum VEGF of less than 500 pg/mL after 3 months of intervention, serum CEA and CA 15-3 of less than ULN, and baseline serum NTx of less than 18 nM BCE had significantly longer progression free survival (PFS). The multivariate analysis showed that ER positivity (hazard ratio [HR], 0.295; 95% confidence interval [CI], 0.141-0.618; P = 0.001), serum VEGF of less than 500 pg/mL after 3 months of intervention (HR, 2.220; 95% CI, 1.136-4.338; P = 0.020), baseline serum NTx of less than 18 nM BCE (HR, 2.842; 95% CI, 1.458-5.539; P = 0.001), and 2 or fewer chemotherapy regimens received (HR, 7.803; 95% CI, 2.884-21.112; P = 0.000) were associated with a better PFS. When evaluating the predictive effect of the biochemical factors, an interaction between NTx and zoledronic acid intervention was shown (P = 0.005). The HR of weekly low dose versus a conventional dosage of zoledronic acid was estimated to be 2.309 (99% CI, 1.067-5.012) in patients with baseline serum NTx of more than 18 nM BCE, indicating a superiority of weekly low dose of zoledronic acid. Conclusions ER, serum VEGF level after intervention, and numbers of chemotherapy regimens administered are prognostic but not predictive factors in breast cancer patients with bone metastases. Patients with baseline serum NTx of more than 18 nM BCE might benefit more from weekly low-dose of zoledronic acid. Trial registration ClinicalTrials.gov unique identifier: ClinicalTrials.gov: NCT00524849

Due to their rarity and diversity, sarcomas are difficult to diagnose. Consequently, there is an urgent demand for a novel diagnostic test for these cancers. In this study, we investigated serum miRNA profiles from 1002 patients with bone and soft tissue tumors representing more than 43 histological subtypes, including sarcomas, intermediate tumors, and benign tumors, to determine whether serum miRNA profiles could be used to specifically detect sarcomas. Circulating serum miRNA profiles in sarcoma patients were clearly distinct from those in patients with other types of tumors. Using the serum levels of seven miRNAs, we developed a molecular detector, Index VI, that could distinguish sarcoma patients from benign and healthy controls with remarkably high sensitivity (90%) and specificity (95%), regardless of histological subtype. Index VI provides an approach to the early and precise detection of sarcomas, potentially leading to curative treatment and longer survival. Sarcomas are rare malignant tumours of bone and soft tissue whose diagnosis remain difficult. Here, the authors analyse serum samples from over 1000 patients and using separate discovery, training and validation cohorts, identify and validate a 7-microRNA index that distinguishes malignant sarcomas from benign disease.

Bone is the most frequent site for metastasis for many cancers, notably for tumours originating in the breast and the prostate. Tumour cells can escape from the primary tumour site and colonize the bone microenvironment. Within the bone, these disseminated tumour cells, as well as those arising in the context of multiple myeloma, may assume a state of dormancy, remaining quiescent for years before resuming proliferation and causing overt metastasis, which causes bone destruction via activation of osteoclast-mediated osteolysis. This structural damage can lead to considerable morbidity, including pain, fractures and impaired quality of life. Although treatment of bone metastases and myeloma bone disease is rarely curative, disease control is often possible for many years through the use of systemic anticancer treatments on a background of multidisciplinary supportive care. This care should include bone-targeted agents to inhibit tumour-associated osteolysis and prevent skeletal morbidity as well as use of appropriate local treatments such as radiation therapy, orthopaedic surgery and specialist palliative care to minimize the impact of metastatic bone disease on physical functioning. In this Primer, we provide an overview of the clinical features, the pathophysiology and the specific treatment approaches to prevent and treat bone metastases from solid tumours as well as myeloma bone disease. The majority of individuals with cancer, notably those with breast or prostate cancer, will develop bone metastases. In this Primer, Coleman and colleagues discuss the epidemiology, pathophysiology and diagnosis of metastatic bone disease and highlight the specific treatment strategies to prevent disease progression and to manage skeletal morbidities.