Organoids for functional precision medicine in advanced pancreatic cancer.

BACKGROUND: Patient-derived organoids (PDO) are promising tumor avatars that could enable ex vivo drug tests to personalize patients' treatment in the frame of functional precision oncology (FPM). Yet, clinical evidence remain scarce. This study aims to evaluate whether PDO can be implemented in clinical practice to benefit patients with advanced refractory pancreatic adenocarcinoma (PDAC). METHODS: During 2021-2022, 87 patients were prospectively enrolled in an IRB-approved protocol. Inclusion criteria were: histologically-confirmed PDAC, tumor site accessible. A panel of 25 approved antitumor therapies (chemogram) was tested and compared to patient responses to assess PDO predictive values and map the drug sensitivity landscape in PDAC. RESULTS: Fifty-four PDOs were generated from 87 pretreated patients (take-on rate 62%). The main PDO mutations were KRAS (96%), TP53 (88%) and CDKN2A/B (22%), with 91% concordance rate with their tumor of origin. The mean turnaround-time to chemogram was 6.8 weeks. In 91% of cases, ≥1 hit was identified (gemcitabine (n=20/54), docetaxel (n=18/54) and vinorelbine (n=17/54) with a median of 3 hits/patient [range:0-12]). Our cohort included 34 evaluable patients with full clinical follow-up. We report a chemogram sensitivity of 83.3% and specificity of 92.9%. The overall-response rate and progression-free survival were higher when patients received a "hit" treatment as compared to patients that received a "non-hit" drug (as part of routine management). Finally, we leveraged our PDO collection as a platform for drug validation and combo identification. We tested the anti-KRASG12D (MRTX1133), alone or combined, and identified a specific synergy with anti-EGFR therapies in KRASG12D variants. CONCLUSION: We report the largest prospective study aiming at implementing PDO-based FPM and identify very robust predictive values in this clinical setting. In a clinically relevant turnaround-time, we identify putative hits for 91% of patients, providing unexpected potential survival benefits in this very aggressive indication. While this remains to be confirmed in interventional precision oncology trials, PDO collection already provide powerful opportunities for drugs and combinatorial treatment development.

Polyetheretherketone Polymer Transpedicular Vertebral System to Treat Vertebral Compression Fracture: A Multicentre Pilot Study of Feasibility and Safety.

OBJECTIVES: To prospectively evaluate the feasibility and safety of a polyetheretherketone (PEEK) polymer transpedicular vertebral system to treat vertebral compression fracture (VCF). METHODS: Nine consecutive patients (4 men and 5 women; median age 59 [interquartile range: 58-64 years]) were included. The procedure duration, length of hospital stay, and complications were reported. Visual analog scale (VAS) and the Oswestry disability index (ODI) for pain and disability were assessed before and at 2, 6, and 12-month after the procedure. RESULTS: The procedure was technically feasible in all patients. The median procedural time was 64 minutes [45-94]. Only minor adverse events were reported (5 clinically asymptomatic cement leakages) but no severe complications. No post procedural adjacent fracture was reported during follow-up (median: 193 days [147-279]). The median VAS score decreased from 55 mm [50-70] before the procedure to 25 mm [5-30] at 2-month (P = .0003) and 30 mm [15-40] at 6-month follow-up (P = .14). The median ODI decreased from 23% [19-26] before the procedure to 12% [10-14] at 2-month (P = .03) and 12% [9-20] at 6-month follow-up (P = .47). CONCLUSIONS: Percutaneous transpedicular fixation of VCF by PEEK implants appears feasible and safe.

Defining textbook outcome for selective internal radiation therapy of hepatocellular carcinoma: an international expert study.

BACKGROUND: A textbook outcome (TO) is a composite indicator covering the entire intervention process in order to reflect the "ideal" intervention and be a surrogate for patient important outcomes. Selective internal radiation therapy (SIRT) is a complex multidisciplinary and multistep intervention facing the challenge of standardization. This expert opinion-based study aimed to define a TO for SIRT of hepatocellular carcinoma. METHODS: This study involved two steps: (1) the steering committee (4 interventional radiologists) first developed an extensive list of possible relevant items reflecting an optimal SIRT intervention based on a literature review and (2) then conducted an international and multidisciplinary survey which resulted in the final TO. This survey was online, from February to July 2021, and consisted three consecutive rounds with predefined settings. Experts were identified by contacting senior authors of randomized trials, large observational studies, or studies on quality improvement in SIRT. This study was strictly academic. RESULTS: A total of 50 items were included in the first round of the survey. A total of 29/40 experts (73%) responded, including 23 interventional radiologists (79%), three nuclear medicine physicians (10%), two hepatologists, and one oncologist, from 11 countries spanning three continents. The final TO consisted 11 parameters across six domains ("pre-intervention workup," "tumor targeting and dosimetry," "intervention," "post-90Y imaging," "length of hospital stay," and "complications"). Of these, all but one were applied in the institutions of > 80% of experts. CONCLUSIONS: This multidimensional indicator is a comprehensive standardization tool, suitable for routine care, clinical round, and research.

Semiautomatic Cone-Beam Computed Tomography Virtual Hepatic Volumetry for Intra-Arterial Therapies.

PURPOSE: To evaluate a software simulating the perfused liver volume from virtual selected embolization points on proximal enhanced cone-beam computed tomography (CT) liver angiography data set using selective cone-beam CT as a reference standard. MATERIALS AND METHODS: Seventy-eight selective/proximal cone-beam CT couples in 46 patients referred for intra-arterial liver treatment at 2 recruiting centers were retrospectively included. A reference selective volume (RSV) was calculated from the selective cone-beam CT by manual segmentation and was used as a reference standard. The virtual perfusion volume (VPV) was then obtained using Liver ASSIST Virtual Parenchyma software on proximal cone-beam CT angiography using the same injection point as for selective cone-beam CT. RSV and VPV were then compared as absolute, relative, and signed volumetric errors (ABSErr, RVErr, and SVErr, respectively), whereas their spatial correspondence was assessed using the Dice similarity coefficient. RESULTS: The software was technically successful in automatically computing VPV in 74 of 78 (94.8%) cases. In the 74 analyzed couples, the median RSV was not significantly different from the median VPV (394 mL [196-640 mL] and 391 mL [192-620 mL], respectively; P = .435). The median ABSErr, RVErr, SVErr, and Dice similarity coefficient were 40.9 mL (19.9-97.7 mL), 12.8% (5%-22%), 9.9 mL (-49.0 to 40.4 mL), and 80% (76%-84%), respectively. No significant ABSErr, RVErr, SVErr, and Dice similarity coefficient differences were found between the 2 centers (P = .574, P = .612, P = .416, and P = .674, respectively). CONCLUSIONS: Perfusion hepatic volumes simulated on proximal enhanced cone-beam CT using the virtual parenchyma software are numerically and spatially similar to those manually obtained on selective cone-beam CT.

Intratumoral Immunotherapy: Is It Ready for Prime Time?

PURPOSE OF REVIEW: This review presents the rationale for intratumoral immunotherapy, technical considerations and safety. Clinical results from the latest trials are provided and discussed. RECENT FINDINGS: Intratumoral immunotherapy is feasible and safe in a wide range of cancer histologies and locations, including lung and liver. Studies mainly focused on multi-metastatic patients, with some positive trials such as T-VEC in melanoma, but evidence of clinical benefit is still lacking. Recent results showed improved outcomes in patients with a low tumor burden. Intratumoral immunotherapy can lower systemic toxicities and boost local and systemic immune responses. Several studies have proven the feasibility, repeatability, and safety of this approach, with some promising results in clinical trials. The clinical benefit might be improved in patients with a low tumor burden. Future clinical trials should focus on adequate timing of treatment delivery during the course of the disease, particularly in the neoadjuvant setting.

The PEARL Approach for CT-guided Lung Biopsy: Assessment of Complication Rate.

Background Percutaneous CT-guided biopsy of lung nodules is an established method with high diagnostic accuracy but a high rate of pneumothorax and chest tube insertion compared with endobronchial methods. Purpose To investigate the effect of a protocol combining patient positioning biopsy-side down, needle removal during expiration, autologous blood patch sealing, rapid rollover, and pleural patching (PEARL) on complication rate after percutaneous CT-guided lung biopsy, especially chest tube insertion. Materials and Methods In a secondary analysis of both prospectively and retrospectively acquired data from December 2019 to November 2020, consecutive participants underwent biopsy with use of the PEARL protocol (prospective data) and were compared with patients who underwent biopsy at the same tertiary cancer center according to the standard method without any additional techniques (controls, retrospective data). Patient demographics, lesion characteristics, intraprocedural data, complications, and histologic results were recorded and compared. Results One hundred patients in the control group (mean age ± standard deviation, 63 years ± 12; 61 men) and 100 participants in the PEARL group (mean age, 64 years ± 12; 48 men) were evaluated. No differences were found in patient and lesion characteristics. The emphysema rate was 47 of 100 patients (47%) in both groups. The rate of pneumothorax was 37 of 100 patients (37%) in the control group versus 16 of 100 (16%) in the PEARL group (P = .001). Of the pneumothoraxes that occurred, fewer were during the intervention in the PEARL group, with 21 of 37 onsets (57%) in the control group versus three of 16 onsets (19%) in the PEARL group (P < .001). A chest tube was inserted in 13 of 100 patients (13%) in the control group and only in one of 100 (1%) in the PEARL group (P = .002). Histologic findings were diagnostic in 94 of 100 patients (94%) in the control group and 95 of 100 (95%) in the PEARL group (P > .99). Conclusion During CT-guided percutaneous lung biopsy, a protocol of positioning biopsy-side down, needle removal during expiration, autologous blood patch sealing, rapid rollover, and pleural patching, or PEARL, reduced rates of pneumothorax and chest tube insertion. © RSNA, 2021.

Combined local treatments for vertebral metastases with limited epidural extension.

OBJECTIVES: Vertebral metastases with limited epidural extension (VMLEE) are frequently encountered in cancer patients; they can cause severe and debilitating symptoms including pain and neurological impairment and are usually treated by radiotherapy. In this study, we mainly evaluated the safety of combined local treatments (CLT), associating radiofrequency ablation (RFA) with vertebroplasty and radiotherapy (RT) to treat VMLEE. Also, we aimed to evaluate the short-term efficacy of CLT on bone metastases palliation and long-term prevention of skeletal-related events. METHODS: We retrospectively reviewed treatment complications, pain palliation, and skeletal complications after combined local treatments (CLT) for vertebral metastasis with limited epidural extension (VMLEE). RESULTS: Eighteen consecutive patients had CLT for 24 VMLEE, between June 2016 and January 2021. No major post-treatment complication was recorded. Nine patients had pain before the initiation of CLT. One month after CLT, only 3 patients had residual pain with a significant decrease of visual analogue scale (VAS), from 7.3 ± 2.4 to 2 ± 0 (p = .008), as well as the mean morphine milligram equivalent dose from 196.6 ± 135.7 to 38.5 ± 26, p = .008. Mean follow-up was 16.7 ± 11.5 months. Only one vertebra showed an increase of a preexisting vertebral fracture. Nine VMLEE had evidence of residual disease, including 2 which resulted in spinal cord compression (2, 11 months). CONCLUSION: CLT was safe and effective for pain palliation and long-term prevention of skeletal-related events for treatment of patients with VMLEE. The effectiveness of this combined treatment on tumor control and epidural involvement on the long term needs further investigation.

Thermal ablation in the management of oligometastatic colorectal cancer.

PURPOSE: To review available evidence on thermal ablation of oligometastatic colorectal cancer. METHODS: Technical and cancer specific considerations for percutaneous image-guided thermal ablation of oligometastatic colorectal metastases in the liver and lung were reviewed. Ablation outcomes are compared to surgical and radiation therapy literature. RESULTS: The application of thermal ablation varies widely based on tumor burden, technical expertise, and local cancer triage algorithms. Ablation can be performed in combination or in lieu of other cancer treatments. For surgically non-resectable liver metastases, a randomized trial has demonstrated the superiority of thermal ablation combined with chemotherapy compared to systemic chemotherapy alone in term of progression-free survival and overall survival (OS), with 5-, and 8-year OS of 43.1% and 35.9% in the combined arm vs. 30.3% and 8.9% in the chemotherapy alone arm. As ablation techniques and technology improve, the role of percutaneous thermal ablation may expand even into surgically resectable disease. Many of the prognostic factors for better OS after local treatment of lung metastases are the same for surgery and thermal ablation, including size and number of metastases, disease-free interval, complete resection/ablation, negative carcinoembryonic antigen, neoadjuvant chemotherapy, and controlled extra-pulmonary metastases. When matched for these factors, thermal ablation for lung and liver metastases appears to provide equivalent overall survival as surgery, in the range of 50% at 5 years. Thermal ablation has limitations that should be respected to optimize patient outcomes and minimize complications including targets that are well-visualized by image guidance, measure <3cm in diameter, and be located at least 3mm distance from prominent vasculature or major bronchi. CONCLUSIONS: The routine incorporation of image-guided thermal ablation into the therapeutic armamentarium for the treatment of oligometastatic colorectal cancer can provide long survival and even cure.

Consensus Guidelines for the Definition of Time-to-Event End Points in Image-guided Tumor Ablation: Results of the SIO and DATECAN Initiative.

There is currently no consensus regarding preferred clinical outcome measures following image-guided tumor ablation or clear definitions of oncologic end points. This consensus document proposes standardized definitions for a broad range of oncologic outcome measures with recommendations on how to uniformly document, analyze, and report outcomes. The initiative was coordinated by the Society of Interventional Oncology in collaboration with the Definition for the Assessment of Time-to-Event End Points in Cancer Trials, or DATECAN, group. According to predefined criteria, based on experience with clinical trials, an international panel of 62 experts convened. Recommendations were developed using the validated three-step modified Delphi consensus method. Consensus was reached on when to assess outcomes per patient, per session, or per tumor; on starting and ending time and survival time definitions; and on time-to-event end points. Although no consensus was reached on the preferred classification system to report complications, quality of life, and health economics issues, the panel did agree on using the most recent version of a validated patient-reported outcome questionnaire. This article provides a framework of key opinion leader recommendations with the intent to facilitate a clear interpretation of results and standardize worldwide communication. Widespread adoption will improve reproducibility, allow for accurate comparisons, and avoid misinterpretations in the field of interventional oncology research. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Liddell in this issue.

Using prostate contrast retention (PCR) as the procedural endpoint in prostatic artery embolization for benign prostatic hyperplasia.

OBJECTIVES: The failure rate following prostate artery embolization (PAE) is around 20%, which may in part result from inadequate embolization. Prostate contrast retention (PCR) adequacy on immediate post-embolization cone-beam CT may provide better assessment of embolization completeness than arterial contrast stasis seen on fluoroscopy alone. The aim of this study was to evaluate outcomes of PAE using PCR adequacy as the procedural endpoint. METHODS: A retrospective cohort study of all PAE cases using this technique at a single large volume center was conducted. Following initial embolization of the main prostatic arteries, if PCR was inadequate, additional embolization was performed. Technical success (adequate PCR) was defined as > 75% global prostate gland contrast staining. Clinical success was determined in accordance to CIRSE standards of practice. RESULTS: One hundred sixty-five patients (mean age 68 ± 8.4 years) underwent PAE from June 2017 to March 2019. Technical and clinical success rates were 98.8% and 96.4% respectively. Clinical success rate was significantly higher in patients with adequate PCR. International Prostate Symptom Scores (IPSS) and Quality of Life (QoL) scores significantly improved at 1-, 3-, 6-, and 12-month follow-up when compared to baseline. Prostate volume (PV) and post-voiding residual bladder volume were significantly reduced at 3, 6, and 12 months in comparison to baseline. Mild (Clavien-Dindo grade I/II) and moderate (grade III) complication rates were 12.1% and 3.6% respectively. CONCLUSIONS: By using PCR adequacy as a guide to determine the procedure endpoint for PAE, it may be possible to achieve more complete embolization and thus higher clinical success rates. KEY POINTS: • By using PCR adequacy as a guide to determine the procedure endpoint for PAE, it may be possible to achieve more complete embolization and thus higher clinical success rates.

Risk factors for local tumor progression after RFA of pulmonary metastases: a matched case-control study.

OBJECTIVES: Curative treatment of oligometastatic pulmonary disease aims at eradication of all metastases. Radiofrequency ablation (RFA) has been shown to be an efficient method and the frequency of local tumor progression (LTP) should be minimized. The objective of this study was to determine the morphological and treatment-related risk factors for LTP after RFA of pulmonary metastases. MATERIALS AND METHODS: All patients treated with RFA for pulmonary metastases from 2002 to 2014 were reviewed. All LTPs from 2011 to 2014 were individually matched on the basis of tumor size, number, and histology. In total, 48 LTPs and 112 controls were blindly analyzed for morphological factors including vicinity of bronchus and vessels as well as treatment-related factors such as the size of the ablation zone and ablation margins. RESULTS: In the simple regression analysis, the significant predictive variables were ≤ 5-mm distance to a large bronchus (OR = 4.94; p = 0.0095) or large vessel (OR = 7.09; p < 0.001), minimal ablation margin (≤ 5 mm (OR = 42.67; p < 0.001), and a central-peripheral ablation offset/ablation zone size > 0.36 (OR = 13.83; p = 0.013). In the multiple regression model, only a minimal ablation margin ≤ 5 mm remained a significant risk factor for LTP. CONCLUSION: Only the minimal ablation margin remains significant in the multiple regression analysis; the other factors are presumably surrogates of an insufficient ablation margin. Improvement of lung RFA outcomes can probably be obtained by immediate post RFA evaluation of ablation margins to ensure a minimal ablation margin of at least 5 mm. KEY POINTS: • A distance < 5 mm to a bronchus or vessel of over 3 mm diameter is associated with insufficient ablation margin and thus risk factors for local tumor progression after pulmonary radiofrequency ablation. • A minimal ablation margin of > 5 mm after pulmonary RFA is associated with significantly less local tumor progression and should be looked for at the end of treatment session before needle removal in order to decrease local tumor progression. • Tumor location, pleural contact, occurrence of intra-alveolar hemorrhage, pulmonary atelectasis, and pneumothorax are not associated with an increased risk of local tumor progression.

Cancer surgery during the COVID-19 pandemic: The experience of a comprehensive cancer center performing preoperative screening by RT-PCR and chest CT scan.

BACKGROUND AND OBJECTIVES: During the worldwide pandemic of coronavirus disease 2019 (COVID-19), oncological procedures considered to be urgent could not be delayed, and a specific procedure was required to continue surgical activity. The objective was to assess the efficacy of our preoperative screening algorithm. METHODS: This observational retrospective study was performed between the 25th of March and the 12th of May 2020 in a comprehensive cancer center in France. Patients undergoing elective oncologic surgery were tested by preoperative nasopharyngeal reverse-transcription polymerase chain reaction (RT-PCR) that could be associated with a chest computerized tomography (CT) scan. RESULTS: Of the 510 screening tests (in 477 patients), only 5% (15/477) were positive for COVID-19 in 24 patients (18 RT-PCR+ and 7 CT scan+/RT-PCR-). Four patients were ultimately false positives based on the CT scan. In total, only 4.2% (20/477) of the patients were COVID-19+. The positivity rate decreased with time after the containment measures were implemented (from 7.4% to 0.8%). In the COVID-19+ group, 20% of the patients had postoperative pulmonary complications, whereas this was the case for 5% of the patients in the COVID-19 group. CONCLUSIONS: Maintaining secure surgical activity is achievable and paramount in oncology care, even during the COVID-19 pandemic, with appropriate screening based on preoperative RT-PCR.

Percutaneous lung and liver CT-guided ablation on swine model using microwave ablation to determine ablation size for clinical practice.

PURPOSE: Microwave ablation (MWA) provides an effective treatment of lung and liver tumors but suffers from a lack of reproducibility of ablation size among currently available technologies. In-vitro evaluations are far removed from clinical practices because of uninfused tissue. This study is in-vivo preclinical testing of a new MWA system on swine lungs and liver. MATERIALS AND METHODS: All ablations were performed under CT guidance and multiple algorithms were tested with a power of 50, 75, and 100 W for durations of 3, 5, 8, 10, and 15 min. A 3 D-evaluation of the ablation zone was carried out using enhanced-CT. The sphericity index, coefficients of variation, and energy efficiency (which corresponds to the volume yield according to the power supplied) were calculated. RESULTS: Fifty liver and 48 lung ablations were performed in 17 swine. The sphericity index varies from 0.50 to 0.80 for liver ablations and from 0.40 to 0.69 for lung ablations. The coefficient of variation was below 15% for 4/5 and 4/8 protocols for lung and liver ablations, respectively. The energy efficiency seems to decrease with the duration of the ablation from 0.60 × 10-3 cm3/J (75 W, 3 min) to 0.26 × 10-3 cm3/J (100 W, 15 min) in the liver and from 0.57 × 10-3 cm3/J (50 W, 10 min) to 0.42 × 10-3 cm3/J (100 W, 12 min) in the lungs. CONCLUSION: A shorter treatment time provides the best energy efficiency, and the best reproducibility is obtained for a 10 min treatment duration. The system tested provides an interesting reproducibility in both lung and liver measurements. Our results may help interventional radiologists in the optimal selection of treatment parameters.

Image-guided Percutaneous Fixation with Internal Cemented Screws of Impending Femoral Neck Pathologic Fractures in Patients with Metastatic Cancer: Safety, Efficacy, and Durability.

Background Prophylactic image-guided procedures performed by interventional radiologists for impending pathologic fractures are becoming more pertinent, as patients with metastatic cancer have extended overall survival because of advanced therapies. Purpose To evaluate the efficacy, safety, and palliative durability of collimated-beam CT-guided percutaneous fixation with internal cemented screws (FICS) for impending pathologic fractures of the femoral neck. Materials and Methods This single-institute retrospective study examined all patients with metastatic cancer treated between February 2010 and October 2019 with collimated-beam CT-guided percutaneous FICS procedures for preventive consolidation of impending femoral neck pathologic fractures. The short-term palliative efficacy was assessed through comparison of visual analog scale (VAS) scores before and 1 month after FICS. A review of cross-section imaging and clinic reports identified any procedural complications. Long-term consolidation efficacy was defined as the absence of any screw dislodgement or development of a pathologic fracture at completion of the study. The Wilcoxon test was used for the mean comparison of paired nonparametric variables. Results Sixty-one consecutive patients (mean age, 59 years ± 11 [standard deviation]; 35 women) underwent preventive FICS for consolidation of impending pathologic femoral neck fracture with a mean follow-up of 533 days ± 689. Two patients died of cancer within the first month. Complications were limited to three self-resolving hematomas. The mean VAS score decreased 1 month after FICS from 4.2 ± 3.2 to 1.8 ± 2.0 (P < .001). The long-term consolidation efficacy was 92% (54 of 59 patients), with three of 59 patients (5%) subsequently developing fractures despite FICS and an additional two of 59 patients (3%) with durable FICS undergoing definitive total hip arthroplasty surgery because of local tumor progression. Conclusion Percutaneous fixation with internal cemented screws as performed by the interventional radiologist is a safe nonsurgical treatment that provides an effective palliative result and durable prevention for impending pathologic fractures of the femoral neck. © RSNA, 2020 Online supplemental material is available for this article.

Treatment intensification with hepatic arterial infusion chemotherapy in patients with liver-only colorectal metastases still unresectable after systemic induction chemotherapy - a randomized phase II study -- SULTAN UCGI 30/PRODIGE 53 (NCT03164655)- study protocol.

BACKGROUND: Approximately 40% of colorectal cancer patients will develop colorectal liver metastases (CRLM). The most effective approach to increase long-term survival is CRLM complete resection. Unfortunately, only 10-15% of CRLM are initially considered resectable. The objective response rates (ORR) after current first-line systemic chemotherapy (sys-CT) regimens range from 40 to 80% and complete resection rates (CRR) range from 25 to 50% in patients with initially unresectable CRLM. When CRLM patients are not amenable to complete resection after induction of sys-CT, ORRs obtained with second-line sys-CT are much lower (between 10 and 30%) and consequently CRRs are also low (< 10%). Hepatic arterial infusion (HAI) oxaliplatin may represent a salvage therapy in patients with CRLM unresectable after one or more sys-CT regimens with ORRs and CRRs up to 60 and 30%, respectively. This study is designed to evaluate the efficacy of an intensification strategy based on HAI oxaliplatin combined with sys-CT as a salvage treatment in patients with CRLM unresectable after at least 2 months of first-line induction sys-CT. OBJECTIVES AND ENDPOINTS OF THE PHASE II STUDY: Our main objective is to investigate the efficacy, in term of CRR (R0-R1), of treatment intensification in patients with liver-only CRLM not amenable to curative-intent resection (and/or ablation) after at least 2 months of induction sys-CT. Patients will receive either HAI oxaliplatin plus systemic FOLFIRI plus targeted therapy (i.e. anti-EGFR antibody or bevacizumab) or conventional sys-CT plus targeted therapy (i.e. anti-EGFR or antiangiogenic antibody). Secondary objectives are to compare: progression-free survival, overall survival, objective response rate, depth of response, feasibility of delivering HAI oxaliplatin including HAI catheter-related complications, and toxicity (NCI-CTCAE v4.0). METHODS: This study is a multicenter, randomized, comparative phase II trial (power, 80%; two-sided alpha-risk, 5%). Patients will be randomly assigned in a 1:1 ratio to receive HAI oxaliplatin combined with systemic FOLFIRI plus targeted therapy (experimental arm) or the best sys-CT plus targeted therapy on the basis of their first-line prior sys-CT history and current guidelines (control arm). One hundred forty patients are required to account for non-evaluable patients. TRIAL REGISTRATION: ClinicalTrials.gov, (NCT03164655). Trial registration date: 11th May 2017.

Robotic assistance in interventional radiology: dream or reality?

KEY POINTS: • Robotic assistance in medicine has been a revolution.• The use of robots has naturally extended to interventional radiology for percutaneous and endovascular interventions.• The guidance is mainly performed with a remote (computer or joystick) allowing the operator and his team not to be exposed to X-rays.

CT guidance assisted by electromagnetic navigation system for percutaneous fixation by internal cemented screws (FICS).

PURPOSE: To evaluate electromagnetic navigation system (ENS) for percutaneous fixation by internal cemented screw (FICS) under CT guidance. BACKGROUND: FICS is a recently developed modality that consists in inserting screws, under imaging guidance, into bone through a minimal skin incision. FICS recently showed good efficacy for the palliation or prevention of pathologic fractures of the pelvic ring and femoral neck. MATERIALS AND METHODS: In this single-center retrospective study, we reviewed all consecutive cancer patients treated with percutaneous FICS under ENS-assisted CT guidance for the prevention or palliation of pelvic or femoral neck fractures. The primary endpoint was technical success. Secondary endpoints were screw placement accuracy (defined by proximal deviation p, distal deviation d, and angle deviation θ), radiation dose exposure, number of CT acquisitions, duration of procedures, and complications. RESULTS: Mean duration of FICS procedures was 111 ± 51 min. Mean post-procedure hospitalization length was 2.1 days. Technical success was achieved in 48 cases (96%) with a total of 76 screws inserted. Mean distance p, mean distance d, and mean angle θ were respectively 8.0 ± 4.5 mm, 7.5 ± 4.4 mm, and 5.4 ± 2°. Angle θ accuracy was higher for screws with a craniocaudal angulation of less than 20° (4.4° vs 6.4°, p = 0.02). The mean number of CT acquisitions during procedures was 6.4 ± 3.0. The mean dose length product was 1524 ± 953 mGy cm and the mean dose area product was 12 ± 8 Gy cm2. Five complications occurred in 4 patients. CONCLUSION: CT guidance assisted by ENS is an effective approach for percutaneous FICS. KEY POINTS: • ENS-assisted CT enables screw insertion in the pelvic ring and femoral neck, with a wide range of trajectories, even when a significant craniocaudal angulation is required. • ENS-assisted CT can be used as an alternative to CBCT guidance for percutaneous fixation by internal cemented screw. • ENS-assisted CT provides high technical success rate with excellent placement accuracy.

Safety and Efficacy of Multilevel Thoracolumbar Vertebroplasty in the Simultaneous Treatment of Six or More Pathologic Compression Fractures.

PURPOSE: To assess the safety and efficacy of multilevel thoracolumbar vertebroplasty in the simultaneous treatment of ≥ 6 painful pathologic compression fractures. MATERIALS AND METHODS: Retrospective review was conducted of 50 consecutive patients treated with vertebroplasty for ≥ 6 pathologic compression fractures in a single session for pain palliation at a tertiary single cancer center from 2015 to 2019. Outcomes measured included procedural safety according to Common Terminology Criteria for Adverse Events (CTCAE), change in 4-week postprocedure back pain by numeric rating scale (NRS), comparison of daily opioid medication consumption, and development of skeletal-related events. RESULTS: A total of 397 pathologic compression fractures were treated during 50 sessions (mean, 7.9 per patient ± 1.5). Mean procedure duration was 162 minutes ± 35, mean postoperative hospitalization duration was 1.6 days ± 0.9, and mean follow-up duration was 401 days ± 297. Seven complications were recorded, including 1 case of symptomatic polymethyl methacrylate pulmonary embolism. No major complications (CTCAE grade 4/5) were reported. NRS pain score was significantly decreased (5.0 ± 1.8 vs 1.7 ± 1.4; P < .0001), with a mean score decrease of 3.3 points (66%). Opioid agent use decreased significantly (76 mg/24 h ± 42 vs 45 mg/24 h ± 37; P = .0003), with a mean decrease of 30 mg/24 h (39%). Skeletal-related events occurred in 7 patients (14%). CONCLUSIONS: Multilevel vertebroplasty for ≥ 6 pathologic compression fractures is safe and provides significant palliative benefit when performed simultaneously.

Lung microwave ablation - an in vivo swine tumor model experiment to evaluate ablation zones.

PURPOSE: To evaluate microwave ablation (MWA) algorithms, comparing pulsed and continuous mode in an in vivo lung tumor mimic model. MATERIALS AND METHODS: A total of 43 lung tumor-mimic models of 1, 2 or 3 cm were created in 11 pigs through an intra-pulmonary injection of contrast-enriched minced muscle. Tumors were ablated under fluoroscopic and 3D-CBCT-guidance using a single microwave antenna. Continuous (CM) and pulsed mode (PM) were used. According to tumor size, 3 different algorithms for both continuous and pulsed mode were used. The ablation zones were measured using post-procedural 3D-CBCT and on pathologic specimens. RESULTS: Two radiologists measured the ablation zones on CBCT and they significantly correlated with macroscopic and microscopic pathological findings: r = 0.75 and 0.74 respectively (p < 0.0001) (inter-observer correlation r = 0.9). For 1, 2 and 3 cm tumors mimics lesions (TMLs), mean maximal and transverse ablation diameters were 3.6 [Formula: see text] 0.3 × 2.2 [Formula: see text] 0.3 cm; 4.1 [Formula: see text] 0.5 × 2.6 [Formula: see text] 0.3 cm and 4.8 [Formula: see text] 0.3 × 3.2 [Formula: see text] 0.3 cm respectively using CM; And, 3.0 [Formula: see text] 0.2 × 2.1 [Formula: see text] 0.2 cm; 4.0 [Formula: see text] 0.4 × 2.7 [Formula: see text] 0.4 cm and 4.6 [Formula: see text] 0.4 × 3.2 [Formula: see text] 0.4 cm respectively for PM, without any significant difference except for 1 cm TMLs treated by PM ablation which were significantly smaller (p = 0.009) The sphericity index was 1.6, 1.6, 1.5 and 1.4, 1.5, 1.4 at 1, 2 and 3 cm for CM and PM respectively, p = 0.07, 0.14 and 0.13 for 1, 2 and 3 cm tumors mimics. CONCLUSION: Microwave ablation for 1-3 cm lung tumors were successfully realized but with a moderate reproducibility rate, using either CM or PM. Immediate post ablation CBCT can accurately evaluate ablation zones.

NBTXR3, a first-in-class radioenhancer hafnium oxide nanoparticle, plus radiotherapy versus radiotherapy alone in patients with locally advanced soft-tissue sarcoma (Act.In.Sarc): a multicentre, phase 2-3, randomised, controlled trial.

BACKGROUND: Pathological complete response to preoperative treatment in adults with soft-tissue sarcoma can be achieved in only a few patients receiving radiotherapy. This phase 2-3 trial evaluated the safety and efficacy of the hafnium oxide (HfO2) nanoparticle NBTXR3 activated by radiotherapy versus radiotherapy alone as a pre-operative treatment in patients with locally advanced soft-tissue sarcoma. METHODS: Act.In.Sarc is a phase 2-3 randomised, multicentre, international trial. Adults (aged ≥18 years) with locally advanced soft-tissue sarcoma of the extremity or trunk wall, of any histological grade, and requiring preoperative radiotherapy were included. Patients had to have a WHO performance status of 0-2 and a life expectancy of at least 6 months. Patients were randomly assigned (1:1) by an interactive web response system to receive either NBTXR3 (volume corresponding to 10% of baseline tumour volume at a fixed concentration of 53·3 g/L) as a single intratumoural administration before preoperative external-beam radiotherapy (50 Gy in 25 fractions) or radiotherapy alone, followed by surgery. Randomisation was stratified by histological subtype (myxoid liposarcoma vs others). This was an open-label study. The primary endpoint was the proportion of patients with a pathological complete response, assessed by a central pathology review board following European Organisation for Research and Treatment of Cancer guidelines in the intention-to-treat population full analysis set. Safety analyses were done in all patients who received at least one puncture and injection of NBTXR3 or at least one dose of radiotherapy. This study is registered with ClinicalTrials.gov, number NCT02379845, and is ongoing for long-term follow-up, but recruitment is complete. FINDINGS: Between March 3, 2015, and Nov 21, 2017, 180 eligible patients were enrolled and randomly assigned and 179 started treatment: 89 in the NBTXR3 plus radiotherapy group and 90 in the radiotherapy alone group. Two patients in the NBTXR3 group and one patient in the radiotherapy group were excluded from the efficacy analysis because they were subsequently discovered to be ineligible; thus, a total of 176 patients were analysed for the primary endpoint in the intention-to-treat full analysis set (87 in the NBTXR3 group and 89 in the radiotherapy alone group). A pathological complete response was noted in 14 (16%) of 87 patients in the NBTXR3 group and seven (8%) of 89 in the radiotherapy alone group (p=0·044). In both treatment groups, the most common grade 3-4 treatment-emergent adverse event was postoperative wound complication (eight [9%] of 89 patients in the NBTXR3 group and eight [9%] of 90 in the radiotherapy alone group). The most common grade 3-4 adverse events related to NBTXR3 administration were injection site pain (four [4%] of 89) and hypotension (four [4%]) and the most common grade 3-4 radiotherapy-related adverse event was radiation skin injury in both groups (five [6%] of 89 in the NBTXR3 group and four [4%] of 90 in the radiotherapy alone group). The most common treatment-emergent grade 3-4 adverse event related to NBTXR3 was hypotension (six [7%] of 89 patients). Serious adverse events were observed in 35 (39%) of 89 patients in the NBTXR3 group and 27 (30%) of 90 patients in the radiotherapy alone group. No treatment-related deaths occurred. INTERPRETATION: This trial validates the mode of action of this new class of radioenhancer, which potentially opens a large field of clinical applications in soft-tissue sarcoma and possibly other cancers. FUNDING: Nanobiotix SA.