Impact of metronomic trabectedin combined with low-dose cyclophosphamide on sarcoma microenvironment and correlation with clinical outcome: results from the TARMIC study.

Soft tissue sarcomas (STS) are diverse mesenchymal tumors with few therapeutic options in advanced stages. Trabectedin has global approval for treating STS patients resistant to anthracycline-based regimens. Recent pre-clinical data suggest that trabectedin's antitumor activity extends beyond tumor cells to influencing the tumor microenvironment (TME), especially affecting tumor-associated macrophages and their pro-tumoral functions. We present the phase I/II results evaluating a combination of metronomic trabectedin and low-dose cyclophosphamide on the TME in patients with advanced sarcomas. 50 patients participated: 20 in phase I and 30 in phase II. Changes in the TME were assessed in 28 patients using sequential tumor samples at baseline and day two of the cycle. Treatment notably decreased CD68 + CD163 + macrophages in biopsies from tumor lesions compared to pre-treatment samples in 9 of the 28 patients after 4 weeks. Baseline CD8 + T cell presence increased in 11 of these patients. In summary, up to 57% of patients exhibited a positive immunological response marked by reduced M2 macrophages or increased CD8 + T cells post-treatment. This positive shift in the TME correlated with improved clinical benefit and progression-free survival. This study offers the first prospective evidence of trabectedin's immunological effect in advanced STS patients, highlighting a relationship between TME modulation and patient outcomes.This study was registered with ClinicalTrial.gov, number NCT02406781.

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.

Percutaneous tumor ablation versus image guided robotic-assisted partial nephrectomy for cT1b renal cell carcinoma: a comparative matched-pair analysis (UroCCR 80).

BACKGROUND: Partial nephrectomy (PN) is the gold standard treatment for cT1b renal tumors. Percutaneous guided thermal ablation (TA) has proven oncologic efficacy with low morbidity for the treatment of small renal masses (<3 cm). Recently, 3D image-guided robot-assisted PN (3D-IGRAPN) has been described, and decreased perioperative morbidity compared to standard RAPN has been reported. Our objective was to compare two minimally invasive image-guided nephron-sparing procedures (TA vs. 3D-IGRAPN) for the treatment of cT1b renal cell carcinomas (4.1-7 cm). METHODS: Patients treated with TA and 3D-IGRAPN for cT1b renal cell carcinoma, prospectively included in the UroCCR database (NCT03293563), were pair-matched for tumor size, pathology, and RENAL score. The primary endpoint was the local recurrence rate between the two groups. Secondary endpoints included metastatic evolution, perioperative complications, decrease in renal function, and length of hospitalization. RESULTS: A total of 198 patients were included and matched into two groups of 72 patients. The local recurrence rate was significantly higher in the TA group than that in the 3D-IGRAPN group (4.2% vs. 15.2%, P=0.04). Metastatic evolution and perioperative outcomes such as major complications, eGFR decrease, and length of hospitalization did not differ significantly between the two groups. CONCLUSIONS: 3D-IGRAPN resulted in a significantly lower local recurrence rate and comparable rates of complications and metastatic evolution compared with thermal ablation.

A multicenter comparative matched-pair analysis of percutaneous tumor ablation and robotic-assisted partial nephrectomy of T1b renal cell carcinoma (AblatT1b study-UroCCR 80).

OBJECTIVE: Renal cell carcinomas represent the sixth- and tenth-most frequently diagnosed cancer in men and women. Recently, percutaneous-guided thermal ablations have proved to be as effective as partial nephrectomy and safer for treating small renal masses (i.e., < 3 cm). This study compared the perioperative and recurrence outcomes of percutaneous thermal ablation (TA) and robotic-assisted partial nephrectomy (RAPN) for the treatment of T1b renal cell carcinomas (4.1-7 cm). METHODS: Retrospective data from 11 centers on the national database, between 2010 and 2020, included 81 patients treated with thermal ablation (TA) and 308 patients treated with RAPN for T1b renal cell carcinoma, collected retrospectively and matched for tumor size, histology results, and the RENAL score. TA included cryoablation and microwave ablation. Endpoints compared the rate between the two groups: local recurrence, metastases, complications, renal function decrease, and length of hospitalization. RESULTS: After matching, 75 patients were included in each group; mean age was 76.6 (± 9) in the TA group and 61.1 (± 12) in the RAPN group, including 69.3% and 76% men respectively. The local recurrence (LR) rate was significantly higher in the TA group than in the PN group (14.6% vs 4%; p = 0.02). The LR rate was 20% (1/5) after microwave ablation, 11.1% (1/9) after radiofrequency ablation, and 14.7% (9/61) after cryoablation. The major complication rate (Clavien-Dindo ≥ 3) was higher following PN than after TA (5.3% vs 0%; p < 0.001). Metastases, eGFR decrease, and length of hospitalization did not differ significantly between the two groups. CONCLUSIONS: The local recurrence rate was significantly higher after thermal ablation; however, thermal ablation resulted in significantly lower rates of complications. Thermal ablation and robotic-assisted partial nephrectomy are effective treatments for T1b renal cancer; however, the local recurrence rate was higher after thermal ablation. KEY POINTS: • The local recurrence rate was significantly higher in the thermal ablation group than in the partial nephrectomy group. • The major complication rate (Clavien-Dindo ≥ 3) was higher following PN than after TA (5.3% vs. 0%; p < 0.001).

Radiofrequency ablation of lung metastases of colorectal cancer: could early radiomics analysis of the ablation zone help detect local tumor progression?

OBJECTIVES: To determine whether radiomics data can predict local tumor progression (LTP) following radiofrequency ablation (RFA) of colorectal cancer (CRC) lung metastases on the first revaluation chest CT. METHODS: This case-control single-center retrospective study included 95 distinct lung metastases treated by RFA (in 39 patients, median age: 63.1 years) with a contrast-enhanced CT-scan performed 3 months after RFA. Forty-eight radiomics features (RFs) were extracted from the 3D-segmentation of the ablation zone. Several supervised machine-learning algorithms were trained in 10-fold cross-validation on reproducible RFs to predict LTP, with/without denoising CT-scans. An unsupervised classification based on reproducible RFs was built with k-means algorithm. RESULTS: There were 20/95 (26.7%) relapses within a median delay of 10 months. The best model was a stepwise logistic regression on raw CT-scans. Its cross-validated performances were: AUROC = 0.72 (0.58-0.86), area under the Precision-Recall curve (AUPRC) = 0.44. Cross-validated balanced-accuracy, sensitivity and specificity were 0.59, 0.25 and 0.93, respectively, using p = 0.5 to dichotomize the model predicted probabilities (vs 0.71, 0.70 and 0.72, respectively using p = 0.188 according to Youden index). The unsupervised approach identified two clusters, which were not associated with LTP (p = 0.8211) but with the occurrence of per-RFA intra-alveolar hemorrhage, post-RFA cavitations and fistulizations (p = 0.0150). CONCLUSION: Predictive models using RFs from the post-RFA ablation zone on the first revaluation CT-scan of CRC lung metastases seemed moderately informative regarding the occurrence of LTP. ADVANCES IN KNOWLEDGE: Radiomics approach on interventional radiology data is feasible. However, patterns of heterogeneity detected with RFs on early re-evaluation CT-scans seem biased by different healing processes following benign RFA complications.

Pembrolizumab combined with low-dose cyclophosphamide and intra-tumoral injection of the toll-like receptor 4 agonist G100 in patients with advanced pretreated soft tissue sarcoma: results from the PEMBROSARC basket study.

Soft tissue sarcomas (STS) are heterogeneous mesenchymal tumors with limited therapeutic options in the advanced setting. Immune checkpoint inhibitors have been shown to have significant clinical activity in inflamed STS which are characterized by the presence of tertiary lymphoid structures (TLS). New strategies are needed to sensitize TLS-negative STS to immunotherapy. Engagement of the toll-Like Receptor 4 (TLR4) signal pathway contributes to the development of a favorable tumor microenvironment in solid tumors. G100 is a highly potent toll-like receptor 4 (TLR4) agonist. We hypothesized that intra-tumoral G100 would induce a robust local and potentially systemic anti-tumor immune response in the microenvironment of TLS-negative sarcoma, leading to improved response to PD1 inhibition. Twenty metastatic STS patients who had a superficial injectable lesion were treated with 50 mg of cyclophosphamide (CP) orally twice daily (1 week on and 1 week off), 200 mg of pembrolizumab intravenously on day 8 of a planned 21-day cycle and G100 20 µg one weekly intra-tumoral injection for at least 6 weeks and for a maximum of 12 weeks (1st injection one week before CP administration, ie. Day -7). Biopsies and blood were collected pre and post treatment. Of the 17 patients assessable for efficacy analysis, 2 were progression-free at 6 months, and the 6-month non-progression rate was 11.8% (95% CI: 1.5-36.4), indicating that the first endpoint of the study was not reached. In 8 patients, there was an increase in T-cell infiltration into tumor after treatment. The ratio CD8/Fox-P3 + CD4 on treatment decreased in 11 cases out of 14 suggesting a predominant induction of Treg. Soluble PDL1 levels at baseline were also with adverse outcome. G100 appears to modulate the tumor microenvironment with significant infiltration of T cells. However, clinical activity in combination with PD1 inhibition was limited and no clear correlation was observed between tumor shrinkage and increased inflammation. TLR4 stimulation might have both antitumor and pro-tumor consequences.Trial registration: This study was registered with ClinicalTrial.gov, number NCT02406781.

CIRSE Standards of Practice on Thermal Ablation of Bone Tumours.

BACKGROUND: Percutaneous thermal ablation is an effective, minimally invasive means of treating a variety of focal benign and malignant osseous lesions. To determine the role of ablation in individual cases, multidisciplinary team (MDT) discussion is required to assess the suitability and feasibility of a thermal ablative approach, to select the most appropriate technique and to set the goals of treatment i.e. curative or palliative. PURPOSE: This document will presume the indication for treatment is clear and approved by the MDT and will define the standards required for the performance of each modality. CIRSE Standards of Practice documents are not intended to impose a standard of clinical patient care, but recommend a reasonable approach to, and best practices for, the performance of thermal ablation of bone tumours. METHODS: The writing group was established by the CIRSE Standards of Practice Committee and consisted of five clinicians with internationally recognised expertise in thermal ablation of bone tumours. The writing group reviewed the existing literature on thermal ablation of bone tumours, performing a pragmatic evidence search using PubMed to search for publications in English and relating to human subjects from 2009 to 2019. Selected studies published in 2020 and 2021 during the course of writing these standards were subsequently included. The final recommendations were formulated through consensus. RESULTS: Recommendations were produced for the performance of thermal ablation of bone tumours taking into account the biologic behaviour of the tumour and the therapeutic intent of the procedure. Recommendations are provided based on lesion characteristics and thermal modality, for the use of tissue monitoring and protection, and for the appropriately timed application of adjunctive procedures such as osseus consolidation and transarterial embolisation. RESULTS: Percutaneous thermal ablation has an established role in the successful management of bone lesions, with both curative and palliative intent. This Standards of Practice document provides up-to-date recommendations for the safe performance of thermal ablation of bone tumours.

Sporadic Desmoid Tumours: Systematic Review with Reflection on the Role of Cryoablation.

Desmoid tumours (DT) are rare locally infiltrative soft-tissue tumours which do not metastasise. DT arise sporadically or are associated with familial syndromes, with different clinical and genetic patterns. In recent years there has been an increasing therapeutic role of cryoablation for the treatment of sporadic DT. Therefore, in this present review, we: (a) summarize all the main epidemiological, clinical, and therapeutic aspects of sporadic DT that are relevant to an interventional radiologists' practice; (b) present the results of a systematic review that has been conducted with the intent of highlighting the main clinical outcomes available thus far with cryoablation; and (c) discuss the current and future potential applications of cryoablation in this field. Five studies were included in the systematic review accounting for 146 patients. Only 18.5% patients received cryoablation as a first-line treatment. Overall, the volume of the DT undergoing cryoablation was very large (mean total DT volume of 237 cm3). Major complications were noted for 13.3-30% patients and following 2.4-6.7% interventional sessions. The rates of complete tumour response ranged between 0 and 43.3%. 1- and 3-year local progression-free survival rates were 85.1-85.8%, and 77.3-82.9%, respectively. Complete pain relief was reported in 40-66.7% symptomatic patients. In conclusion, cryoablation is currently proposed as a therapeutic strategy to very large DT, which is recognized to be associated with an increased procedure-related morbidity and reduced rates of complete tumour response. Proposing cryoablation as the first-line treatment may improve these clinical outcomes.

Percutaneous osteoplasty in long bones: Current status and assessment of outcomes.

Osteoplasty is a minimally invasive imaging-guided intervention providing mechanical stabilization, bone consolidation and pain relief in oncologic patients presenting with non-osteoblastic bone metastases or with insufficiency fractures. The intervention relies on the injection of an acrylic substance (ie, polymethylmethacrylate; PMMA) into the target bone. PMMA is very resistant to axial compressive loads but much less to bending, torsional and shearing stresses. Accordingly, from a biomechanical standpoint osteoplasty is adapted for the palliative treatment of small painful lytic bone defects located in the epiphyseal region of long bones in patients with clear surgical contraindications; or for increasing the anchoring of the osteosynthesis material into the target bone. Although pain relief is rapid and effective following osteoplasty, secondary fractures have been reported in up to 8-9% of long bone tumors undergoing such intervention; and following such event, fixation with endomedullary osteosynthetic material (eg, nailing) is not practicable any more. Accordingly, careful patients' selection is critical and should happen with a multidisciplinary approach.

Single-Center Experience of Focal Thermo-Ablative Therapy After Pelvic Radiotherapy for In-Field Prostate Cancer Oligo-Recurrence.

PURPOSE: In-field prostate cancer (PCa) oligo-recurrence after pelvic radiotherapy is a challenging situation for which metastasis-directed treatments may be beneficial, but options for focal therapies are scarce. METHODS: We retrospectively reviewed data for patients with three or less in-field oligo-recurrent nodal, bone and/or locally recurrent (prostate, seminal vesicles, or prostatic bed) PCa lesions after radiation therapy, identified with molecular imaging (PET and/or MRI) and treated by focal ablative therapy (cryotherapy or radiofrequency) at the Institut Bergonié between 2012 and 2020. Chosen endpoints were the post-procedure PSA response (partially defined as a >50% reduction, complete as a PSA <0.05 ng/ml), progression-free survival (PFS) defined as either a biochemical relapse (defined as a rise >25% of the Nadir and above 2 ng/ml), radiological relapse (on any imaging technique), decision of treatment modification (hormonotherapy initiation or line change) or death, and tolerance. RESULTS: Forty-three patients were included. Diagnostic imaging was mostly 18F-Choline positron emission tomography/computerized tomography (PET/CT) (75.0%), prostate specific membrane antigen (PSMA) PET/CT (9.1%) or a combination of pelvic magnetic resonance imaging (MRI), CT, and 99 mTc-bone scintigraphy (11.4%). PSA response was observed in 41.9% patients (partial in 30.3%, complete in 11.6%). In the hormone-sensitive exclusive focal ablation group (n = 31), partial and complete PSA responses were 32.3 and 12.9% respectively. Early local control (absence of visible residual active target) on the post-procedure imaging was achieved with 87.5% success. After a median follow-up of 30 months (IQR 13.3-56.8), the median PFS was 9 months overall (95% CI, 6-17), and 17 months (95% CI, 11-NA) for PSA responders. Complications occurred in 11.4% patients, with only one grade IIIb Dindo-Clavien event (uretral stenosis requiring endoscopic uretrotomy). CONCLUSION: In PCa patients showing in-field oligo-recurrence after pelvic radiotherapy, focal ablative treatment is a feasible option, possibly delaying a systemic treatment initiation or modification. These invasive strategies should preferably be performed in expert centers and discussed along other available focal strategies in multi-disciplinary meetings.

Radiomics complements clinical, radiological, and technical features to assess local control of colorectal cancer lung metastases treated with radiofrequency ablation.

OBJECTIVES: Radiofrequency ablation (RFA) of lung metastases of colorectal origin can improve patient survival and quality of life. Our aim was to identify pre- and per-RFA features predicting local control of lung metastases following RFA. METHODS: This case-control single-center retrospective study included 119 lung metastases treated with RFA in 48 patients (median age: 60 years). Clinical, technical, and radiological data before and on early CT scan (at 48 h) were retrieved. After CT scan preprocessing, 64 radiomics features were extracted from pre-RFA and early control CT scans. Log-rank tests were used to detect categorical variables correlating with post-RFA local tumor progression-free survival (LTPFS). Radiomics prognostic scores (RPS) were developed on reproducible radiomics features using Monte-Carlo cross-validated LASSO Cox regressions. RESULTS: Twenty-six of 119 (21.8%) nodules demonstrated local progression (median delay: 11.2 months). In univariate analysis, four non-radiomics variables correlated with post-RFA-LTPFS: nodule size (> 15 mm, p < 0.001), chosen electrode (with difference between covered array and nodule diameter < 20 mm or non-expandable electrode, p = 0.03), per-RFA intra-alveolar hemorrhage (IAH, p = 0.002), and nodule location into the ablation zone (not seen or in contact with borders, p = 0.005). The highest prognostic performance was reached with the multivariate model including a RPS built on 4 radiomics features from pre-RFA and early revaluation CT scans (cross-validated concordance index= 0.74) in which this RPS remained an independent predictor (cross-validated HR = 3.49, 95% confidence interval = [1.76 - 6.96]). CONCLUSIONS: Technical, radiological, and radiomics features of the lung metastases before RFA and of the ablation zone at 48 h can help discriminate nodules at risk of local progression that could benefit from complementary local procedure. KEY POINTS: • The highest prognostic performance to predict post-RFA LTPFS was reached with a parsimonious model including a radiomics score built with 4 radiomics features. • Nodule size, difference between electrode diameter, use of non-expandable electrode, per-RFA hemorrhage, and a tumor not seen or in contact with the ablation zone borders at 48-h CT were correlated with post-RFA LTPFS.

Cryoablation for Palliation of Painful Bone Metastases: The MOTION Multicenter Study.

Purpose: To assess the clinical effectiveness of cryoablation for palliation of painful bone metastases. Materials and Methods: MOTION (Multicenter Study of Cryoablation for Palliation of Painful Bone Metastases) (ClinicalTrials.gov NCT02511678) was a multicenter, prospective, single-arm study of adults with metastatic bone disease who were not candidates for or had not benefited from standard therapy, that took place from February 2016 to March 2018. At baseline, participants rated their pain using the Brief Pain Inventory-Short Form (reference range from 0 to 10 points); those with moderate to severe pain, who had at least one metastatic candidate tumor for ablation, were included. The primary effectiveness endpoint was change in pain score from baseline to week 8. Participants were followed for 24 weeks after treatment. Statistical analyses included descriptive statistics and logistic regression to evaluate changes in pain score over the postprocedure follow-up period. Results: A total of 66 participants (mean age, 60.8 years ± 14.3 [standard deviation]; 35 [53.0%] men) were enrolled and received cryoablation; 65 completed follow-up. Mean change in pain score from baseline to week 8 was -2.61 points (95% CI: -3.45, -1.78). Mean pain scores improved by 2 points at week 1 and reached clinically meaningful levels (more than a 2-point decrease) after week 8; scores continued to improve throughout follow-up. Quality of life improved, opioid doses were stabilized, and functional status was maintained over 6 months. Serious adverse events occurred in three participants. Conclusion: Cryoablation of metastatic bone tumors provided rapid and durable pain palliation, improved quality of life, and offered an alternative to opioids for pain control.Keywords: Ablation Techniques, Metastases, Pain Management, Radiation Therapy/OncologySupplemental material is available for this article.© RSNA, 2021.

Assessment of Repeatability, Reproducibility, and Performances of T2 Mapping-Based Radiomics Features: A Comparative Study.

BACKGROUND: Magnetic resonance imaging (MRI)-based radiomics features (RFs) quantify tumors radiological phenotypes but are sensitive to postprocessing parameters, including the intensity harmonization technique (IHT), while mappings enable objective quantitative assessment. PURPOSE: To investigate whether T2 mapping could improve repeatability, reproducibility, and performances of radiomics compared to conventional T2-weighted imaging (T2WI). STUDY TYPE: Prospective. SUBJECTS: Twenty-six healthy adults. FIELD STRENGTH/SEQUENCE: Respiratory-trigged radial turbo spin echo (TSE) multiecho T2 mapping (prototype) and conventional TSE T2WI of the abdomen were acquired twice at 1.5 T. ASSESSMENT: T2 maps were reconstructed using a two-parameter exponential fitting model. Volumes-of-interest (VOIs) were manually drawn in six tissues: liver, kidney, pancreas, muscle, bone, and spleen. After co-registration, conventional T2WIs were processed with two IHTs (standardization [std] and histogram-matching [HM]) resulting in four paired input image types: initial T2WI, T2WIstd , T2WIHM , and T2-map. VOIs were propagated to extract 45 RFs from MRI-1 and MRI-2 of each image type (LIFEx, v5.10). STATISTICAL TESTS: Influence of the input data type on RF values was evaluated with analysis of variance. RFs test-retest repeatability and reproducibility over multiple segmentations were evaluated with intra-class correlation coefficient (ICC). Correlations between k-means clusters and the six tissues depending on the RFs dataset were investigated with adjusted-Rand-index (ARI). RESULTS: About 41 of 45 (91.1%) RFs were significantly influenced by the input image type (P values < 0.05), which was the most influential factor on repeatability of RFs (P-value < 0.05). Repeatability ICCs from T2-map displayed intermediate values between the initial T2WI (range: 0.407-0.736) and the T2WIHM (range: 0.724-0.817). The number of RFs with interobserver and intraobserver reproducibility ICCs ≥ 0.90 was 37/45 (82.2%) for T2WIHM , 33/45 (73.3%) for T2WIstd , 31/45 (68.9%) for T2 map, and 25/45 (55.6%) for the initial T2WI. T2 map provided the best tissue discrimination (ARI = 0.414 vs. 0.157 with T2WIHM ). DATA CONCLUSION: T2 mapping provided RFs with moderate to substantial repeatability and reproducibility ICCs, along with the most preserved discriminative information. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: 1.

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.

Intensity harmonization techniques influence radiomics features and radiomics-based predictions in sarcoma patients.

Intensity harmonization techniques (IHT) are mandatory to homogenize multicentric MRIs before any quantitative analysis because signal intensities (SI) do not have standardized units. Radiomics combine quantification of tumors' radiological phenotype with machine-learning to improve predictive models, such as metastastic-relapse-free survival (MFS) for sarcoma patients. We post-processed the initial T2-weighted-imaging of 70 sarcoma patients by using 5 IHTs and extracting 45 radiomics features (RFs), namely: classical standardization (IHTstd), standardization per adipose tissue SIs (IHTfat), histogram-matching with a patient histogram (IHTHM.1), with the average histogram of the population (IHTHM.All) and plus ComBat method (IHTHM.All.C), which provided 5 radiomics datasets in addition to the original radiomics dataset without IHT (No-IHT). We found that using IHTs significantly influenced all RFs values (p-values: < 0.0001-0.02). Unsupervised clustering performed on each radiomics dataset showed that only clusters from the No-IHT, IHTstd, IHTHM.All, and IHTHM.All.C datasets significantly correlated with MFS in multivariate Cox models (p = 0.02, 0.007, 0.004 and 0.02, respectively). We built radiomics-based supervised models to predict metastatic relapse at 2-years with a training set of 50 patients. The models performances varied markedly depending on the IHT in the validation set (range of AUROC from 0.688 with IHTstd to 0.823 with IHTHM.1). Hence, the use of intensity harmonization and the related technique should be carefully detailed in radiomics post-processing pipelines as it can profoundly affect the reproducibility of analyses.

Systematic review of sarcomas radiomics studies: Bridging the gap between concepts and clinical applications?

OBJECTIVES: Sarcomas are a model for intra- and inter-tumoral heterogeneities making them particularly suitable for radiomics analyses. Our purposes were to review the aims, methods and results of radiomics studies involving sarcomas METHODS: Pubmed and Web of Sciences databases were searched for radiomics or textural studies involving bone, soft-tissues and visceral sarcomas until June 2020. Two radiologists evaluated their objectives, results and quality of their methods, imaging pre-processing and machine-learning workflow helped by the items of the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2), Image Biomarker Standardization Initiative (IBSI) and 'Radiomics Quality Score' (RQS). Statistical analyses included inter-reader agreements, correlations between methodological assessments, scientometrics indices, and their changes over years, and between RQS, number of patients and models performance. RESULTS: Fifty-two studies were included involving: soft-tissue sarcomas (29/52, 55.8 %), bone sarcomas (15/52, 28.8 %), gynecological sarcomas (6/52, 11.5 %) and mixed sarcomas (2/52, 3.8 %), mostly imaged with MRI (36/52, 69.2 %), for a total of distinct patients. Median RQS was 4.5 (28.4 % of the maximum, range: -7 - 17). Performances of predictive models and number of patients negatively correlated (p = 0.027). None of the studies detailed all the items from the IBSI guidelines. There was a significant increase in studies' impact factors since the establishing of the RQS in 2017 (p = 0.038). CONCLUSION: Although showing promising results, further efforts are needed to make sarcoma radiomics studies reproducible with an acceptable level of evidence. A better knowledge of the RQS and IBSI reporting guidelines could improve the quality of sarcoma radiomics studies and accelerate clinical applications.

Is percutaneous image-guided renal tumour ablation ready for prime time?

In the last few decades, thermal ablation (TA) techniques have been increasingly applied to treat small localised renal cell carcinomas. Despite this trend, there is still an underuse of TA compared to surgery and a substantial lack of high-quality evidence derived from large, prospective, randomised controlled trials comparing the long-term oncologic outcomes of TA and surgery. Therefore, in this narrative review, we assess published guidelines and recent literature concerning the diagnosis and management of kidney-confined renal cell carcinoma to understand whether percutaneous image-guided TA is ready to be proposed as a first-line treatment.

Complications Following Percutaneous Image-guided Radiofrequency Ablation of Bone Tumors: A 10-year Dual-Center Experience.

Background Percutaneous radiofrequency ablation (RFA) is effective in the management of bone tumors. However, knowledge of the complication rate and risk factors for complications of RFA is lacking. Purpose To report the complication rate and risk factors of bone tumor RFA. Materials and Methods This retrospective study reviewed complications in consecutive patients who underwent RFA of primary or metastatic bone tumors from January 2008 to April 2018. Complications were categorized into major (grade 3 or 4, severe or life-threatening) or minor (grade 1 or 2, mild or moderate) according to Common Terminology Criteria for Adverse Events. Univariable and multivariable regression analyses were performed to identify variables associated with complications of RFA. Results A total of 169 patients (median age, 63 years; interquartile range, 55-73 years; 85 men) with 217 tumors were evaluated. The total complication rate was 30.0% (65 of 217; 95% confidence interval [CI]: 23.8%, 36.0%). The major complication rate was 2.3% (five of 217; 95% CI: 0.8%, 5.3%), with secondary fracture being the most frequent event (1.8% [four of 217]). The minor complication rate was 27.7% (60 of 217; 95% CI: 21.7%, 33.6%), with immediate postoperative pain being the most frequent event (18.0% [39 of 217]). Risk factors for all complications included tumor size greater than 3 cm (adjusted odds ratio [AOR], 2.4 [95% CI: 1.2, 4.5]; P = .03) and previous radiation therapy (AOR, 3.8 [95% CI: 2.0, 7.4]; P = .02). The only risk factor for minor complications was previous radiation therapy (AOR, 2.2 [95% CI: 1.0, 4.7]; P = .04). Conclusion Bone tumor radiofrequency ablation is safe, with a low rate of major complications mainly consistent with secondary fractures. Risk factors for complications are tumor size greater than 3 cm and previous radiation therapy. © RSNA, 2020 Online supplemental material is available for this article.

Multicenter Study of Metastatic Lung Tumors Targeted by Interventional Cryoablation Evaluation (SOLSTICE).

OBJECTIVE: To assess the safety and local recurrence-free survival in patients after cryoablation for treatment of pulmonary metastases. METHODS: This multicenter, prospective, single-arm, phase 2 study included 128 patients with 224 lung metastases treated with percutaneous cryoablation, with 12 and 24 months of follow-up. The patients were enrolled on the basis of the outlined key inclusion criteria, which include one to six metastases from extrapulmonary cancers with a maximal diameter of 3.5 cm. Time to progression of the index tumor(s), metastatic disease, and overall survival rates were estimated using the Kaplan-Meier method. Complications were captured for 30 days after the procedure, and changes in performance status and quality of life were also evaluated. RESULTS: Median size of metastases was 1.0 plus or minus 0.6 cm (0.2-4.5) with a median number of tumors of 1.0 plus or minus 1.2 cm (one to six). Local recurrence-free response (local tumor efficacy) of the treated tumor was 172 of 202 (85.1%) at 12 months and 139 of 180 (77.2%) at 24 months after the initial treatment. After a second cryoablation treatment for recurrent tumor, secondary local recurrence-free response (local tumor efficacy) was 184 of 202 (91.1%) at 12 months and 152 of 180 (84.4%) at 24 months. Kaplan-Meier estimates of 12- and 24-month overall survival rates were 97.6% (95% confidence interval: 92.6-99.2) and 86.6% (95% confidence interval: 78.7-91.7), respectively. Rate of pneumothorax that required pleural catheter placement was 26% (44/169). There were eight grade 3 complication events in 169 procedures (4.7%) and one (0.6%) grade 4 event. CONCLUSION: Percutaneous cryoablation is a safe and effective treatment for pulmonary metastases.

Magnetic resonance imaging assessment of chemotherapy-related adipocytic maturation in myxoid/round cell liposarcomas: specificity and prognostic value.

OBJECTIVE: To investigate the specificity, clinical implication and prognostic value of MRI adipocytic maturation (MAM) in myxoid/round cells liposarcomas (MRC-LPS) treated with neoadjuvant chemotherapy (NAC). METHODS: Of the 89 patients diagnosed with MRC-LPS at our sarcoma reference center between 2008 and 2018, 28 were included as they were treated with NAC, surgery and radiotherapy. All patients underwent contrast-enhanced MRIs at baseline and late evaluation. A control cohort of 13 high-grade pleomorphic and dedifferentiated LPS with same inclusion criteria was used to evaluate the specificity of MAM in MRC-LPS. Two radiologists analyzed the occurrence of MAM, changes in the tumor architecture, shape and surrounding tissues during NAC. Pathological features of tumor samples were reviewed and correlated with MRI. Metastatic relapse-free survival was estimated with Kaplan-Meier curves and Cox models. Associations between prognostic T1-based delta-radiomics features and MAM were investigated with Student t-test. RESULTS: MAM was more frequent in MRC-LPS (p = 0.045) and not specific of any type of chemotherapy (p = 0.7). Regarding MRC-LPS, 14 out of 28 patients (50%) demonstrated MAM. Eight patients showed metastatic relapses. MAM was not associated with metastatic relapse-free survival (p = 0.9). MAM correlated strongly with the percentage of histological adipocytic differentiation on surgical specimen (p < 0.001), which still expressed the tumor marker NY-ESO-1. None of the prognostic T1-based delta-radiomics features was associated with MAM. CONCLUSION: MAM seems a neutral event during NAC. ADVANCES IN KNOWLEDGE: MAM predominated in MRC-LPS and was not specific of a type of chemotherapy. Occurrence of MAM was not associated with better patients' metastasis free survival.