Development of a Secure Web-Based Medical Imaging Analysis Platform: The AWESOMME Project.

Precision medicine research benefits from machine learning in the creation of robust models adapted to the processing of patient data. This applies both to pathology identification in images, i.e., annotation or segmentation, and to computer-aided diagnostic for classification or prediction. It comes with the strong need to exploit and visualize large volumes of images and associated medical data. The work carried out in this paper follows on from a main case study piloted in a cancer center. It proposes an analysis pipeline for patients with osteosarcoma through segmentation, feature extraction and application of a deep learning model to predict response to treatment. The main aim of the AWESOMME project is to leverage this work and implement the pipeline on an easy-to-access, secure web platform. The proposed WEB application is based on a three-component architecture: a data server, a heavy computation and authentication server and a medical imaging web-framework with a user interface. These existing components have been enhanced to meet the needs of security and traceability for the continuous production of expert data. It innovates by covering all steps of medical imaging processing (visualization and segmentation, feature extraction and aided diagnostic) and enables the test and use of machine learning models. The infrastructure is operational, deployed in internal production and is currently being installed in the hospital environment. The extension of the case study and user feedback enabled us to fine-tune functionalities and proved that AWESOMME is a modular solution capable to analyze medical data and share research algorithms with in-house clinicians.

Indeterminate pulmonary nodules in non-rhabdomyosarcoma soft tissue sarcoma: A study of the European paediatric Soft Tissue Sarcoma Study Group.

BACKGROUND: The aim of this study was to assess the clinical impact of indeterminate pulmonary nodules (no more than four pulmonary nodules of less than 5 mm or one nodule measuring between 5 and less than 10 mm by computed tomography [CT]) in children and adolescents with adult-type non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) at diagnosis. METHODS: Patients with NRSTS treated in 11 centers as part of the European paediatric Soft Tissue Sarcoma Study Group (EpSSG) were retrospectively assessed. Local radiologists, blinded to clinical information except for patients' age and tumor histotype, reviewed the chest CT at diagnosis and filled out a case report form. Because patients with or without indeterminate nodules in the EpSSG NRSTS 2005 study received the same type of treatment, event-free survival (EFS) and overall survival (OS) between groups by log-rank test were compared. RESULTS: Overall, 206 patients were examined: 109 (52.9%) were without any nodules, 78 (38%) had at least one indeterminate nodule, and 19 (9.2%) had nodules meeting the definition of metastases, which were then considered to be misclassified and were excluded from further analyses. Five-year EFS was 78.5% (95% CI, 69.4%-85.1%) for patients without nodules and 69.6% (95% CI, 57.9%-78.7%) for patients with indeterminate nodules (p = .135); 5-year OS was 87.4% (95% CI, 79.3%-92.5%) and 79.0% (95% CI, 67.5%-86.8%), respectively (p = .086). CONCLUSIONS: This study suggests that survival does not differ in otherwise nonmetastatic patients with indeterminate pulmonary nodules compared to nonmetastatic patients without pulmonary nodules. PLAIN LANGUAGE SUMMARY: Radiologists should be aware of the classification of indeterminate pulmonary nodules in non-rhabdomyosarcoma soft tissue sarcomas and use it in their reports. More than a third of patients with non-rhabdomyosarcoma soft tissue sarcoma can be affected by indeterminate pulmonary nodules. Indeterminate pulmonary nodules do not significantly affect the overall survival of pediatric patients with non-rhabdomyosarcoma soft tissue sarcoma.

Evolution of Patterns of Care and Outcomes in the Real-Life Setting for Patients with Metastatic GIST Treated in Three French Expert Centers over Three Decades.

Gastrointestinal stromal tumors (GIST) are rare mesenchymal tumors characterized by KIT or PDGFRA mutations. Over three decades, significant changes in drug discovery and loco-regional (LR) procedures have impacted treatment strategies. We assessed the evolution of treatment strategies for metastatic GIST patients treated in the three national coordinating centers of NetSarc, the French network of sarcoma referral centers endorsed by the National Institute of Cancers, from 1990 to 2018. The primary objective was to describe the clinical and biological profiles as well as the treatment modalities of patients with metastatic GIST in a real-life setting, including access to clinical trials and LR procedures in the metastatic setting. Secondary objectives were to assess (1) patients' outcome in terms of time to next treatment (TNT) for each line of systemic treatment, (2) patients' overall survival (OS), (3) evolution of patients' treatment modalities and OS according to treatment access: <2002 (pre-imatinib approval), 2002-2006 (pre-sunitinib approval), 2006-2014 (pre-regorafenib approval), post 2014, and (4) the impact of clinical trials and LR procedures on TNT and OS in the metastatic setting. 1038 patients with a diagnosis of GIST made in one of the three participating centers between 1990 and 2018 were included in the national prospective database. Among them, 492 patients presented metastasis, either synchronous or metachronous. The median number of therapy lines in the metastatic setting was 3 (range 0-15). More than half of the patients (55%) participated in a clinical trial during the course of their metastatic disease and half (51%) underwent additional LR procedures on metastatic sites. The median OS in the metastatic setting was 83.4 months (95%CI [72.7; 97.9]). The median TNT was 26.7 months (95%CI [23.4; 32.3]) in first-line, 10.2 months (95%CI [8.6; 11.8]) in second line, 6.7 months (95%CI [5.3; 8.5]) in third line, and 5.5 months (95%CI [4.3; 6.7]) in fourth line, respectively. There was no statistical difference in OS in the metastatic setting between the four therapeutic periods (log rank, p = 0.18). In multivariate analysis, age, AFIP Miettinen classification, mutational status, surgery of the primary tumor, participation in a clinical trial in the first line and LR procedure to metastatic sites were associated with longer TNT in the first line, whereas age, mitotic index, mutational status, surgery of the primary tumor and LR procedure to metastatic sites were associated with longer OS. This real-life study advocates for early reference of metastatic GIST patients to expert centers to orchestrate the best access to future innovative clinical trials together with LR strategies and further improve GIST patients' survival.

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.

Characterization of Breast Tumors from MR Images Using Radiomics and Machine Learning Approaches.

Determining histological subtypes, such as invasive ductal and invasive lobular carcinomas (IDCs and ILCs) and immunohistochemical markers, such as estrogen response (ER), progesterone response (PR), and the HER2 protein status is important in planning breast cancer treatment. MRI-based radiomic analysis is emerging as a non-invasive substitute for biopsy to determine these signatures. We explore the effectiveness of radiomics-based and CNN (convolutional neural network)-based classification models to this end. T1-weighted dynamic contrast-enhanced, contrast-subtracted T1, and T2-weighted MR images of 429 breast cancer tumors from 323 patients are used. Various combinations of input data and classification schemes are applied for ER+ vs. ER-, PR+ vs. PR-, HER2+ vs. HER2-, and IDC vs. ILC classification tasks. The best results were obtained for the ER+ vs. ER- and IDC vs. ILC classification tasks, with their respective AUCs reaching 0.78 and 0.73 on test data. The results with multi-contrast input data were generally better than the mono-contrast alone. The radiomics and CNN-based approaches generally exhibited comparable results. ER and IDC/ILC classification results were promising. PR and HER2 classifications need further investigation through a larger dataset. Better results by using multi-contrast data might indicate that multi-parametric quantitative MRI could be used to achieve more reliable classifiers.

Radiomics combined with transcriptomics to predict response to immunotherapy from patients treated with PD-1/PD-L1 inhibitors for advanced NSCLC.

Introduction: In this study, we aim to build radiomics and multiomics models based on transcriptomics and radiomics to predict the response from patients treated with the PD-L1 inhibitor. Materials and methods: One hundred and ninety-five patients treated with PD-1/PD-L1 inhibitors were included. For all patients, 342 radiomic features were extracted from pretreatment computed tomography scans. The training set was built with 110 patients treated at the Léon Bérard Cancer Center. An independent validation cohort was built with the 85 patients treated in Dijon. The two sets were dichotomized into two classes, patients with disease control and those considered non-responders, in order to predict the disease control at 3 months. Various models were trained with different feature selection methods, and different classifiers were evaluated to build the models. In a second exploratory step, we used transcriptomics to enrich the database and develop a multiomic signature of response to immunotherapy in a 54-patient subgroup. Finally, we considered the HOT/COLD status. We first trained a radiomic model to predict the HOT/COLD status and then prototyped a hybrid model integrating radiomics and the HOT/COLD status to predict the response to immunotherapy. Results: Radiomic signature for 3 months' progression-free survival (PFS) classification: The most predictive model had an area under the receiver operating characteristic curve (AUROC) of 0.94 on the training set and 0.65 on the external validation set. This model was obtained with the t-test selection method and with a support vector machine (SVM) classifier. Multiomic signature for PFS classification: The most predictive model had an AUROC of 0.95 on the training set and 0.99 on the validation set. Radiomic model to predict the HOT/COLD status: the most predictive model had an AUROC of 0.93 on the training set and 0.86 on the validation set. HOT/COLD radiomic hybrid model for PFS classification: the most predictive model had an AUROC of 0.93 on the training set and 0.90 on the validation set. Conclusion: In conclusion, radiomics could be used to predict the response to immunotherapy in non-small-cell lung cancer patients. The use of transcriptomics or the HOT/COLD status, together with radiomics, may improve the working of the prediction models.

Prognostic Factors for Local Recurrence after Cryoablation of Desmoid Tumors.

PURPOSE: To determine the risk factors for local of adult patients treated for desmoid tumors by cryoablation. MATERIALS AND METHODS: Eighty-four patients treated for nonabdominopelvic desmoid tumors by cryoablation from July 2012 to July 2020 were included in a retrospective study. The population was composed of 64 women (76.19%) and 20 men (23.81%), aged from 16 to 75 years (median, 35 years ± 14.25). Each patient underwent preprocedural gadolinium-enhanced magnetic resonance imaging and was followed up to 36 months with the same technique. Clinical features, such as tumor size and previous treatment, epidemiological features, and the technical parameters of cryoablation, were studied. RESULTS: Local relapse was found in 19 (22.62%) of 84 patients. The 12-, 24-, and 36-month progression-free survival rates were 89% (95% confidence interval [CI], 79-94), 74% (95% CI, 60-83), and 68% (95% CI, 53-79), respectively. In univariate analysis, significant prognostic factors associated with local recurrence were non-abdominal wall location (P = .042), debulking strategy (P = .0105), risk of visceral injury (P = .034) or peripheral nerve injury during cryoablation (P = .033), previous radiation therapy (P = .043), and treatment before 2016 (P = .008). In multivariate analysis, abdominal wall tumors displayed the best outcome, whereas the neck and trunk showed a high rate of recurrence (hazard ratio, 7.307 [95% CI, 1.396-38.261]). CONCLUSIONS: The local recurrence of desmoid tumors after cryoablation depends on a number of prognostic factors, in particular, a non-abdominal wall location of the tumor and previous local treatment such as surgery or radiation therapy.

Efficacy and Safety of Adjuvant Radiotherapy in Re-excised Soft-tissue Sarcoma After Unplanned Resection.

INTRODUCTION: The objective of this study was to evaluate the efficacy and safety of adjuvant radiotherapy (aRT) in patients with soft-tissue sarcoma (STS) re-excised after unplanned tumor resection (UPR). MATERIALS AND METHODS: From 2000 to 2015, we retrospectively evaluated patients with STS of limb or trunk who underwent post-UPR re-excision in our expert center and received or not aRT. RESULTS: Median follow-up was 121 months (IQR 94-165). Among the 145 patients, 37 were not treated with aRT (no-RT) and 108 received aRT with a median radiation dose of 50 Gy (IQR 50-60). At 10 years, patients in the aRT and no-RT groups showed a cumulative incidence of local failure (10y-LF) of 14.7% and 37.7%, and a local recurrence-free survival (10y-LRFS) of 61.3% and 45.8%, respectively. Multivariate analysis identified aRT and age ≥70 years as independent predictors of both LF and LRFS, while grade 3 and deep-seated tumor were independent predictors of LRFS. In overall population, 10-year distant metastasis-free survival (10y-DMFS) and overall survival (10y-OS) were 63.7% and 69.4%. In multivariate analyses, age ≥70 years, grade 3, and deep-seated lesion were associated with shorter DMFS and OS. Acute severe adverse events were not significantly increased in aRT group (14.8% vs. 18.1%, P = .85) but dramatically increased if radiation dose exceeded 50 Gy (risk ratio 2.96 compared to ≤50 Gy, P = .04). CONCLUSION: In STS patients re-excised after UPR, 50 Gy aRT was safe and associated with reduced LF and longer LRFS. It seems to be beneficial even in absence of residual disease or in absence of initial adverse prognostic factors.

Epiphyseal-sparing biological reconstruction of bone sarcoma in children: Focus on articular function and growth.

INTRODUCTION: Epiphyseal preservation surgery and biological reconstruction after resection of metaphyseal bone sarcoma in children is a surgical challenge which can only be justified if future joint function is maintained. HYPOTHESIS: The main hypothesis of this work was that long-term function was maintained. The secondary hypotheses were that local control of the disease and growth restoration were achieved, at the cost of an acceptable number of complications. MATERIAL AND METHOD: This was a retrospective study of 14 children with a median age of 8 years [2-14] at the time of surgery. The tumors (Ewing's sarcoma or osteosarcoma) were mostly situated at the knee (n=9) and hip (n=3). The reconstruction used an induced membrane (n=7) or an allograft (n=7). We studied joint function, mechanisms contributing to loss of growth, surgical complications and survival at the last follow-up. RESULTS: At the median follow-up of 76 months [24-130], 9 out of 14 patients required revision for non-union, and 4 of them required a second revision. At the last follow-up, 82% of the length had been restored, due to 3 bone lengthenings and 7 contralateral epiphysiodeses. Preserved joint function was excellent with an average modified MSTS score of 28.3/30 [24-30]. No local recurrence was reported. DISCUSSION: Our experience of epiphyseal preservation allows local control of the disease and very good function but at the cost of a cumbersome surgical program (12 out of 14 patients were reoperated on, with an average of 1.2 interventions per patient). The main difficulty is the growth management, most often by complex programs of alternating bone lengthening and shortening. LEVEL OF EVIDENCE: IV, retrospective study.

Small-Cell Lung Cancer Transformation as a Mechanism of Resistance to Pralsetinib in RET-Rearranged Lung Adenocarcinoma: A Case Report.

The majority of resistance to Rearranged during transfection (RET)-specific tyrosine kinase inhibitors (TKI) described in RET-rearranged non-small cell lung cancer (NSCLC) patients are driven by RET-independent mechanisms. We provide the first case report of a RET-rearranged lung adenocarcinoma (LUAD) transformation into small-cell lung cancer (SCLC) as a mechanism of acquired resistance to pralsetinib. A 43-year-old patient presented with a RET-rearranged LUAD revealed by pleural effusion. After 14 months of response to pralsetinib, biopsy of a progressive pleural lesion found a phenotypic transformation into SCLC. Molecular analysis identified the same RET fusion and TP53 mutation in both primary adenocarcinoma and recurrence as SCLC. The patient achieved partial response after switch to carboplatin and etoposide chemotherapy and presented with progression disease after 6 months. Histological transformation could be a mechanism of resistance to RET-TKIs and rebiopsy should be considered to adapt subsequent treatment.

Prognostic factors of the synovial sarcoma of the extremities: imaging does matter.

OBJECTIVES: Synovial sarcomas (SS) of the extremities are rare soft tissue sarcomas that are more common in young adults. We deciphered the imaging phenotype of SS with the aim to determine if imaging could provide an incremental value to currently known prognostic factors (PF)-age and histological grade-to predict long-term overall survival (OS). METHODS: This retrospective multicenter study included consecutive pediatric and adult patients with synovial sarcomas of the extremities from December 2002 to August 2020. Inclusion criteria were (i) a follow-up greater than 5 years and (ii) available pre-therapeutic MRI. A subset analysis included MRI and CT-scan. Clinical, pathological, and imaging variables were collected in all patients. The primary endpoint was to evaluate the association of these variables with OS using univariate and multivariate Cox regressions. RESULTS: Out of 428 patients screened for eligibility, 98 patients (mean age: 37.1 ± 15.2 years) were included (MRI: n = 98/98, CT scan: n = 34/98; 35%). The median OS was 75.25 months (IQR = 55.50-109.12) and thirty-six patients (n = 36/98;37%) died during follow-up. The recurrence rate was 12.2% (n =12/98). SS lesions were mostly grade 2 (57/98; 58%). On MRI, SS had a mean long-axis diameter of 67.5 ± 38.3 mm. On CT scan, 44% (15/34) were calcified. Grade (hazard ratio [HR] = 2.71; 95%CI = 1.30-5.66; p = 0.008), size of the lesions evaluated on MRI (HR = 1.02; 95% CI = 1.01-1.03; p < 0.001), and calcifications on CT scan (HR = 0.10; 95% CI = 0.02-0.50; p = 0.005) were independent PF of OS. CONCLUSIONS: This study demonstrated that imaging biomarkers can be used to predict long-term outcome in patients with SS. Strikingly, the presence of calcifications on CT scan is associated with favorable outcome and provides an incremental value over existing PF such as age, grade, and size. KEY POINTS: • Beyond its diagnostic value, MRI is a pre-operative prognostic tool in synovial sarcomas of the extremities since the size of the lesion is an important prognostic factor. • Calcifications on CT scans are independently and significantly associated with prolonged overall survival.

Expanding the molecular spectrum of tenosynovial giant cell tumors.

Background: While great advances in clinical and pathological description of tenosynovial giant cell tumors (TGCT) have been made, TGCT molecular heterogeneity represents an ongoing challenge. The canonical oncogenic fusion CSF1::COL6A3 is not systematically observed, suggesting that other oncogenic mechanisms are involved in tumorigenesis. This study aims to explore by RNA sequencing a retrospective series of tumors diagnosed as TGCT, in order to provide a better description of their molecular landscape and to correlate molecular features with clinical data. Methods: We analyzed clinicopathological data and performed whole-exome RNA sequencing on 41 TGCT samples. Results: RNAseq analysis showed significant higher CSF1 and CSF1-R expression than a control panel of 2642 solid tumors. RNA sequencing revealed fusion transcripts in 14 patients including 6 not involving CSF1 and some previously unreported fusions. Unsupervised clustering on the expression profiles issued from this series suggested two distinct subgroups: one composed of various molecular subtypes including CSF1 and FN1 rearranged samples and one composed of four tumors harboring an HMGA2::NCOR2 fusion, suggesting distinct tumor entities. Overall, 15 patients received at least one systemic anti-CSF1R treatment and clinical improvement was observed in 11 patients, including patients from both clusters. Discussion: This study reported molecular heterogeneity in TGCT, contrasting with the clinical and pathological homogeneity and the ubiquitous high CSF1 and CSF1R expression levels. Whether molecular diversity may impact the efficacy of systemic treatments needs to be further investigated.

Prediction of lipomatous soft tissue malignancy on MRI: comparison between machine learning applied to radiomics and deep learning.

OBJECTIVES: Malignancy of lipomatous soft-tissue tumours diagnosis is suspected on magnetic resonance imaging (MRI) and requires a biopsy. The aim of this study is to compare the performances of MRI radiomic machine learning (ML) analysis with deep learning (DL) to predict malignancy in patients with lipomas oratypical lipomatous tumours. METHODS: Cohort include 145 patients affected by lipomatous soft tissue tumours with histology and fat-suppressed gadolinium contrast-enhanced T1-weighted MRI pulse sequence. Images were collected between 2010 and 2019 over 78 centres with non-uniform protocols (three different magnetic field strengths (1.0, 1.5 and 3.0 T) on 16 MR systems commercialised by four vendors (General Electric, Siemens, Philips, Toshiba)). Two approaches have been compared: (i) ML from radiomic features with and without batch correction; and (ii) DL from images. Performances were assessed using 10 cross-validation folds from a test set and next in external validation data. RESULTS: The best DL model was obtained using ResNet50 (resulting into an area under the curve (AUC) of 0.87 ± 0.11 (95% CI 0.65-1). For ML/radiomics, performances reached AUCs equal to 0.83 ± 0.12 (95% CI 0.59-1) and 0.99 ± 0.02 (95% CI 0.95-1) on test cohort using gradient boosting without and with batch effect correction, respectively. On the external cohort, the AUC of the gradient boosting model was equal to 0.80 and for an optimised decision threshold sensitivity and specificity were equal to 100% and 32% respectively. CONCLUSIONS: In this context of limited observations, batch-effect corrected ML/radiomics approaches outperformed DL-based models.

Prediction of Histologic Neoadjuvant Chemotherapy Response in Osteosarcoma Using Pretherapeutic MRI Radiomics.

Histologic response to chemotherapy for osteosarcoma is one of the most important prognostic factors for survival, but assessment occurs after surgery. Although tumor imaging is used for surgical planning and follow-up, it lacks predictive value. Therefore, a radiomics model was developed to predict the response to neoadjuvant chemotherapy based on pretreatment T1-weighted contrast-enhanced MRI. A total of 176 patients (median age, 20 years [range, 5-71 years]; 107 male patients) with osteosarcoma treated with neoadjuvant chemotherapy and surgery between January 2007 and December 2018 in three different centers in France (Centre Léon Bérard in Lyon, Centre Hospitalier Universitaire de Nantes in Nantes, and Hôpital Cochin in Paris) were retrospectively analyzed. Various models were trained from different configurations of the data sets. Two different methods of feature selection were tested with and without ComBat harmonization (ReliefF and t test) to select the most relevant features, and two different classifiers were used to build the models (an artificial neural network and a support vector machine). Sixteen radiomics models were built using the different combinations of feature selection and classifier applied on the various data sets. The most predictive model had an area under the receiver operating characteristic curve of 0.95, a sensitivity of 91%, and a specificity 92% in the training set; respective values in the validation set were 0.97, 91%, and 92%. In conclusion, MRI-based radiomics may be useful to stratify patients receiving neoadjuvant chemotherapy for osteosarcomas. Keywords: MRI, Skeletal-Axial, Oncology, Radiomics, Osteosarcoma, Pediatrics Supplemental material is available for this article. © RSNA, 2022.

Long-term outcomes after definitive radiotherapy with modern techniques for unresectable soft tissue sarcoma.

INTRODUCTION: The use of definitive radiotherapy (dRT) in unresectable soft-tissue sarcomas (STS) is still controversial and recent data are scarce. We report clinical results of this therapeutic option. METHODS: We retrospectively included STS patients treated between 2009 and 2020, with dRT for unresectable or with a measurable residual disease after R2 surgery. Response rate, local failure (LF), progression-free survival (PFS) and overall survival (OS) were evaluated. RESULTS: 116 patients with localized/locally advanced STS were treated from 2009 to 2020, with a median age of 71 years (range 18-92). Most tumors were deep-seated (96.6%), grade 2-3 (85.1%), located in the trunk or extremities (74.2%). Helical tomotherapy, volumetric modulated arc therapy, or stereotactic radiotherapy was performed in 39.7%, 19% and 8.6% of patients, respectively. The median equivalent dose in 2 Gy fractions (EQD2) was 60 Gy (IQR 52-65). At first follow-up, 66 (58.9%) and 25 (22%) patients had stable disease and partial response. After a median follow-up of 54.8 months (IQR 40.3-95.4), 3-year LF, PFS and OS were 43.2%, 16.6% and 34%, respectively. Median OS was 21.4 months (95%CI 14-26). The multivariate analysis identified grade 3 and AJCC T3-T4 stage to be associated with both shorter PFS and OS (all p < 0.001). Macroscopically incomplete resection and EQD2 ≥ 64 Gy were associated with better OS (p = 0.016 and p = 0.007). Acute and late severe adverse events occurred in 24 (19.7%) and 5 (4.3%) patients. CONCLUSION: In unresectable STS patients, definitive modern radiotherapy is a safe and effective treatment yielding long term control in selected patients.

Percutaneous Core Needle Biopsy Can Efficiently and Safely Diagnose Most Primary Bone Tumors.

A biopsy is a prerequisite for the diagnosis and evaluation of musculoskeletal tumors. It is considered that surgical biopsy provides a more reliable diagnosis because it can obtain more tumor material for pathological analysis. However, it is often associated with a significant complication rate. Imaging-guided percutaneous core needle biopsy (PCNB) is now widely used as an alternative to surgical biopsy; it appears to be minimally invasive, possibly with lower complication rates. This study evaluates the diagnostic yield of the preferred use of PCNB in a referral center, its accuracy, and its complication rate. The data relating to the biopsy and the histological analysis were extracted from the database of a bone tumor reference center where PCNB of bone tumors was discussed as a first-line option. 196 bone tumors were biopsied percutaneously between 2016 and 2020. They were located in the axial skeleton in 21.4% (42) of cases, in the lower limb in 58.7% (115), and in the upper limb in 19.9% (39) cases. We obtained a diagnosis yield of 84.7% and a diagnosis accuracy of 91.7%. The overall complication rate of the percutaneous biopsies observed was 1.0% (n = 2), consisting of two hematomas. PCNB performed in a referral center is a safe, precise procedure, with a very low complication rate, and which avoids the need for first-line open surgical biopsy. The consultation between pathologist, radiologist, and clinician in an expert reference center makes this technique an effective choice as a first-line diagnosis tool.

Impact of histological subtype on radiological and pathological response after neoadjuvant radiotherapy in soft tissue sarcoma.

BACKGROUND: Evaluation of response to neoadjuvant radiotherapy (NART) does not consider soft tissue sarcoma (STS) heterogeneity. We aimed to investigate radiological and pathological response of 4 major histotypes. METHODS: Extremity or trunk STS patients who received 50 Gy NART between 2009 and 2020 were retrospectively included. Relative variation in tumor size (RVTS) and pathological response were reported in the overall population and in undifferentiated pleomorphic sarcoma (UPS), myxofibrosarcoma (MFS), myxoid liposarcoma (MLS) and synovial sarcoma (SS) patients to identify response modalities of each histotype. RESULTS: Among the 121 included patients, 49, 19, 13 and 11 presented UPS, MFS, MLS and SS. Median RVTS were 0% (IQR -18-+18), +8% (IQR 0-+24), -12% (IQR -20-3) and -11% (IQR -15-9), respectively (p = 0.001). Median viable cells were 10%, 60%, 20% and 70% (p = 0.007). In overall population, pathological complete response and median necrosis were 27.7% and 10% without significant correlation to histotype (p = 0.18 and 0.06). Nineteen (38.8%) UPS specimens presented cysts that were emptied during the sampling process and distorted the microscopic response evaluation. Infiltrative growth pattern was observed in 28% and 38.9% UPS and MFS patients. Five (38.5%) MLS presented mature adipocytes without proven prognostic value. Cysts were observed in 36% of SS specimens. In the absence of initial tumor limits, the great viable cellularity of SS may be overestimated by their nodular aspect. CONCLUSION: After NART, we highlighted disparate response of UPS, frequent progression of MFS, and confirmed MLS and SS radiosensitivity. Response must be interpreted with caution and consider the histotype-specific patterns.

Association between Body Mass Index and Survival Outcome in Metastatic Cancer Patients Treated by Immunotherapy: Analysis of a French Retrospective Cohort.

The response to immunotherapy has been little investigated in overweight and obese cancer patients. We evaluated the relationships between BMI, toxicity, and survival in patients treated by immunotherapy for metastatic cancer. We included metastatic cancer patients treated by immunotherapy between January 2017 and June 2020 at the Centre Léon Bérard. In total, 272 patients were included: 64% men and 36% women, with a median age of 61.4 years. BMI ≥ 25 in 34.2% and 50% had non-small cell lung cancer (n = 136). Most received monotherapy, with nivolumab in 41.9% and pembrolizumab in 37.9%. Toxicity, mostly dysthyroiditis, occurred in 41%. Median overall survival (OS), estimated by Kaplan-Meier analysis, was significantly longer for patients with a BMI ≥ 25 than for those with a BMI < 25 (24.8 versus 13.7 months HR = 0.63; 95% CI 0.44-0.92, p = 0.015), and for patients experiencing toxicity than for those without toxicity (NR versus 7.8 months, HR = 0.22; 95% CI 0.15-0.33, p < 0.001). Adjusted OS was associated with toxicity, and the occurrence of toxicity was associated with sex and histological features but not with BMI. Thus, being overweight and experiencing toxicity was associated with longer overall survival in patients treated by immunotherapy. More attention should be paid to body composition in the care of cancer patients.

Sarcopenia and serum biomarkers of oxidative stress after a 6-month physical activity intervention in women with metastatic breast cancer: results from the ABLE feasibility trial.

PURPOSE: Sarcopenia has been identified as an important prognostic factor for patients with cancer. This study aimed at exploring the potential associations between a 6-month physical activity intervention and muscle characteristics, sarcopenia, oxidative stress and toxicities in patients with metastatic breast cancer. METHODS: Women newly diagnosed with metastatic breast cancer (N = 49) participated in an unsupervised, personalized, 6-month physical activity intervention with activity tracker. Computerized tomography images at the third lumbar vertebra were analysed at baseline, three months and six months to assess sarcopenia (muscle mass index < 40 cm2/m2) and muscle quality (poor if muscle attenuation < 37.8 Hounsfield Units). Oxidative markers included plasma antioxidant enzymes (catalase, glutathione peroxidase and superoxide dismutase activities), prooxidant enzymes (NADPH oxidase and myeloperoxidase activities) and oxidative stress damage markers (advanced oxidation protein products, malondialdehyde (MDA) and DNA oxidation. RESULTS: At baseline 53% (mean age 55 years (SD 10.41)) were sarcopenic and 75% had poor muscle quality. Muscle cross sectional area, skeletal muscle radiodensity, lean body mass remained constant over the six months (p = 0.75, p = 0.07 and p = 0.75 respectively), but differed significantly between sarcopenic and non-sarcopenic patients at baseline and 6-months. Sarcopenic patients at baseline were more likely to have an increase of MDA (p = 0.02) at 6 months. Being sarcopenic during at least one moment during the 6-month study was associated with a higher risk of developing severe toxicities (grade > 2) (p = 0.02). CONCLUSIONS: This study suggests potential benefits of physical activity for maintenance of muscle mass. Sarcopenia can alter many parameters and disturb the pro and antioxidant balance.

CRYODESMO-O1: A prospective, open phase II study of cryoablation in desmoid tumour patients progressing after medical treatment.

BACKGROUND: Desmoid tumours (DTs) are rare tumours originating from musculoaponeurotic structures. Although benign, they may be locally aggressive, leading to pain and disability. European Society for Medical Oncology (ESMO) guidelines recommend frontline watchful waiting and medical treatment in progressing tumours. Cryoablation is an interventional radiology technique that is suitable for DT patients (pts) on the basis of repeated cycles of freezing, leading to cell death. METHODS: CRYODESMO-01 (ClinicalTrials.gov Identifier: NCT02476305) is a prospective, open-label, non-randomised, non-comparative, multicenter study assessing cryoablation in non-abdominopelvic progressing DT. Inclusion criteria were: pts ≥18 y.o., confirmed DT accessible to cryoablation (≥90% destruction), measurable lesion conforming to modified response evaluation criteria in solid tumours (mRECIST), progressive disease after ≥2 lines of medical therapy or with functional symptoms/pain, adequate biological parameters, informed consent, and affiliation to a medical insurance scheme. The primary end-point was the non-progression rate at 12 months; secondary end-points included safety, quality of life (QoL), assessment of pain and functional status. FINDINGS: 50 pts were enrolled (78% female) from four French centres and all were treated. The mean age was 41 y.o. (19-73). The median number of prior treatments was 2.00 [1-4] including non-steroidal anti-inflammatory drugs (NSAIDs), hormone therapy, chemotherapy, and anti-angiogenics. Tumour location included limbs (36%), trunk (60%), and cervical area (4%). The median tumour largest diameter was 89 mm. The rate of non-progressing disease at +12 months was 86% [confidence level (CI) 95% 73-94%]. Median PFS was not reached at a median follow-up of 31 months. Grade 1 and 2 toxicity occurred in 32.8% and 44.5% of patients, grade 3-4 in 22% and no Grade 5 toxicity was observed. Cryoablation significantly improved functional status and pain scores. INTERPRETATION: Cryoablation demonstrated feasibility in progressive DT pts. The study met is primary end-point with 86% of non-progressive disease at +12 months, with reduced pain, better functional status, and encouraging long-term disease control.