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.

An international phase II trial and immune profiling of SBRT and atezolizumab in advanced pretreated colorectal cancer.

BACKGROUND: Immuno-radiotherapy may improve outcomes for patients with advanced solid tumors, although optimized combination modalities remain unclear. Here, we report the colorectal (CRC) cohort analysis from the SABR-PDL1 trial that evaluated the PD-L1 inhibitor atezolizumab in combination with stereotactic body radiation therapy (SBRT) in advanced cancer patients. METHODS: Eligible patients received atezolizumab 1200 mg every 3 weeks until progression or unmanageable toxicity, together with ablative SBRT delivered concurrently with the 2nd cycle (recommended dose of 45 Gy in 3 fractions, adapted upon normal tissue tolerance constraint). SBRT was delivered to at least one tumor site, with at least one additional measurable lesion being kept from the radiation field. The primary efficacy endpoint was one-year progression-free survival (PFS) rate from the start of atezolizumab. Sequential tumor biopsies were collected for deep multi-feature immune profiling. RESULTS: Sixty pretreated (median of 2 prior lines) advanced CRC patients (38 men [63%]; median age, 59 years [range, 20-81 years]; 77% with liver metastases) were enrolled in five centers (France: n = 4, Spain: n = 1) from 11/2016 to 04/2019. All but one (98%) received atezolizumab and 54/60 (90%) received SBRT. The most frequently irradiated site was lung (n = 30/54; 56.3%). Treatment-related G3 (no G4-5) toxicity was observed in 3 (5%) patients. Median OS and PFS were respectively 8.4 [95%CI:5.9-11.6] and 1.4 months [95%CI:1.2-2.6], including five (9%) patients with PFS > 1 year (median time to progression: 19.2 months, including 2/5 MMR-proficient). Best overall responses consisted of stable disease (n = 38; 64%), partial (n = 3; 5%) and complete response (n = 1; 2%). Immune-centric multiplex IHC and RNAseq showed that SBRT redirected immune cells towards tumor lesions, even in the case of radio-induced lymphopenia. Baseline tumor PD-L1 and IRF1 nuclear expression (both in CD3 + T cells and in CD68 + cells) were higher in responding patients. Upregulation of genes that encode for proteins known to increase T and B cell trafficking to tumors (CCL19, CXCL9), migration (MACF1) and tumor cell killing (GZMB) correlated with responses. CONCLUSIONS: This study provides new data on the feasibility, efficacy, and immune context of tumors that may help identifying advanced CRC patients most likely to respond to immuno-radiotherapy. TRIAL REGISTRATION: EudraCT N°: 2015-005464-42; Clinicaltrial.gov number: NCT02992912.

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.

Emerging and Evolving Concepts in Cancer Immunotherapy Imaging.

Criteria based on measurements of lesion diameter at CT have guided treatment with historical therapies due to the strong association between tumor size and survival. Clinical experience with immune checkpoint modulators shows that editing immune system function can be effective in various solid tumors. Equally, novel immune-related phenomena accompany this novel therapeutic paradigm. These effects of immunotherapy challenge the association of tumor size with response or progression and include risks and adverse events that present new demands for imaging to guide treatment decisions. Emerging and evolving approaches to immunotherapy highlight further key issues for imaging evaluation, such as dissociated response following local administration of immune checkpoint modulators, pseudoprogression due to immune infiltration in the tumor environment, and premature death due to hyperprogression. Research that may offer tools for radiologists to meet these challenges is reviewed. Different modalities are discussed, including immuno-PET, as well as new applications of CT, MRI, and fluorodeoxyglucose PET, such as radiomics and imaging of hematopoietic tissues or anthropometric characteristics. Multilevel integration of imaging and other biomarkers may improve clinical guidance for immunotherapies and provide theranostic opportunities.

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.

Sequence analyses of relapsed or refractory diffuse large B-cell lymphomas unravel three genetic subgroups of patients and the GNA13 mutant as poor prognostic biomarker, results of LNH-EP1 study.

Advances in molecular profiling of newly diagnosed diffuse large B-cell lymphoma (DLBCL) have recently refine genetic subgroups. Genetic subgroups remain undetermined at the time of relapse or refractory (RR) disease. This study aims to decipher genetic subgroups and search for prognostic molecular biomarkers in patients with RR-DLBCL. From 2015 to 2021, targeted next-generation sequencing analyses of germline-matched tumor samples and fresh tissue from RR-DLBCL patients were performed. Unsupervised clustering of somatic mutations was performed and correlations with patient outcome were sought. A number of 120 patients with RR-DLBCL were included in LNH-EP1 study and a molecular tumor landscape was successfully analyzed in 87% of patients (104/120 tumor samples). The median age was 67.5 years (range 27.4-87.4), median number of previous treatments was 2 (range 1-9). The most frequently mutated genes were TP53 (n = 53 mutations; 42% of samples), CREBBP (n = 39; 32%), BCL2 (n = 86; 31%), KMT2D (n = 39; 28%) and PIM1 (n = 54; 22%). Unsupervised clustering separated three genetic subgroups entitled BST (enriched in BCL2, SOCS1, and TNFRSF14 mutations); TKS (enriched in TP53, KMT2D, and STAT6 mutations); and PCM (enriched in PIM1, CD79B, and MYD88 mutations). Median overall survival (OS) was 11.0 (95% confidence interval [CI]: 8.1-12.6) months. OS was not significantly different between the three genetic subgroups. GNA13 mutant was significantly associated with an increased risk of death (hazard ratio: 6.6 [95% CI: 2.1-20.6]; p = .0011) and shorter OS (p = .0340). At the time of relapse or refractory disease, three genetic subgroups of DLBCL patients were delineated, which could help advance precision molecular medicine programs.

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.

Post-Radiation Grade 3 Neuroendocrine Carcinoma: A New Entity?

BACKGROUND: Cancer survivors have a 14% increased risk of developing a malignancy compared with the general population. Second radiation-induced malignancies with different histologies have been described in different organs. Based on individual observations, we hypothesized that neuroendocrine carcinoma (NEC) could arise in irradiated organs. METHODS: In a retrospective analysis of Gustave Roussy database of NEC patients (small cell lung cancer excluded) diagnosed as a second cancer, we looked for the frequency of grade 3 NEC that arose in patients who had received previous radiation therapy for a first cancer. Radiation therapy for the first cancer, dose, location of radiation therapy, pathological characteristics, overall survival, and response to treatment of secondary NEC were analyzed. RESULTS: From January 1995 to December 2017, 847 cases of NEC were seen at Gustave Roussy. Among them, 95 (11.2%) patients had a history of previous malignancy of which 36 (4%) had been treated with radiation therapy. Out of these 36 patients, 12 (1.4% of all NEC patients) developed a NEC within the previous irradiated organ (median dose of 50 Gy, range 36-67.5). Most frequent first cancers were breast cancer (n = 4) and Hodgkin lymphoma (n = 3). NEC arose within a median time of 21.7 years (range 5.1-36.4) from radiation in the thorax (n = 5), digestive tract (n = 3), and other sites. Five large cell NEC, 3 small cell NEC, 1 mixed neuroendocrine neoplasm and 3 not otherwise specified NEC were diagnosed. Ten patients had stage IV disease at diagnosis; median overall survival was 37.8 months (95% CI [17.6 to NA]). Three patients (25%) achieved complete response with multimodal treatment. CONCLUSIONS: NEC can arise from previously irradiated organs and may have a better outcome in this setting. Other risk factors should be investigated to explain the high rate of previous cancer in this population of neuroendocrine neoplasm.

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.

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.

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.

Association of metastatic pattern and molecular status in stage IV non-small cell lung cancer adenocarcinoma.

OBJECTIVES: The aim of our study was to investigate the association between driver oncogene alterations and metastatic patterns on imaging assessment, in a large cohort of metastatic lung adenocarcinoma patients. METHODS: From January 2010 to May 2017, 550 patients with stage IV lung adenocarcinoma with molecular analysis were studied retrospectively including 135 EGFR-mutated, 81 ALK-rearrangement, 47 BRAF-mutated, 141 KRAS-mutated, and 146 negative tumors for these 4 mutations (4N). After review of the complete imaging report by two radiologists (junior and senior) to identify metastatic sites, univariate correlation analyzes were performed. RESULTS: We found differences in metastatic tropism depending on the molecular alteration type when compared with the non-mutated 4N group: in the EGFR group, pleural metastases were more frequent (32% versus 20%; p = 0.021), and adrenal and node metastases less common (6% versus 23%; p < 0.001 and 11% versus 23%; p = 0.011). In the ALK group, there were more brain and lung metastases (respectively 42% versus 29%; p = 0.043 and 37% versus 24%; p = 0.037). In the BRAF group, pleural and pericardial metastases were more common (respectively 47% versus 20%; p < 0.001 and 11% versus 3%; p = 0.04) and bone metastases were rarer (21% versus 42%; p = 0.011). Lymphangitis was more frequent in EGFR, ALK, and BRAF groups (respectively 6%, 7%, and 15% versus 1%); p = 0.016; p = 0.009; and p < 0.001. CONCLUSION: The application of these correlations between molecular status and metastatic tropism in clinical practice may lead to earlier and more accurate identification of patients for targeted therapy. KEY POINTS: • Bone and brain metastasis are the most common organs involved in lung adenocarcinoma but the relative incidence of each metastatic site depends on the molecular alteration. • EGFR-mutated tumors preferentially spread to the pleura and less commonly to adrenals, ALK-rearrangement tumors usually spread to the brain and the lungs, whereas BRAF-mutated tumors are unlikely to spread to bones and have a serous (pericardial ad pleural) tropism. • These correlations could help in the clinical management of patients with metastatic lung adenocarcinoma.

National dose reference levels in computed tomography-guided interventional procedures-a proposal.

OBJECTIVES: To establish national reference levels (RLs) in interventional procedures under CT guidance as required by the 2013/59/Euratom European Directive. METHODS: Seventeen categories of interventional procedures in thoracic, abdominopelvic, and osteoarticular specialties (percutaneous infiltration, vertebroplasty, biopsy, drainage, tumor destruction) were analyzed. Total dose length product (DLP), number of helical acquisitions (NH), and total DLP for helical, sequential, or fluoroscopic acquisitions were recorded for 10 to 20 patients per procedure at each center. RLs were calculated as the 3rd quartiles of the distributions and target values for optimization process (TVOs) as the median. RLs and TVOs were compared with previously published studies. RESULTS: Results on 5001 procedures from 49 centers confirmed the great variability in patient dose for the same category of procedures. RLs were proposed for the DLPs and NHs in the seventeen categories. RLs in terms of DLP and NH were 375 mGy.cm and 2 NH for spinal or peri-spinal infiltration, 1630 mGy.cm and 3 NH for vertebroplasty, 845 mGy.cm and 4 NH for biopsy, 1950 mGy.cm and 8 NH for destruction of tumors, and 1090 mGy.cm and 5 NH for drainage. DLP and NH increased with the complexity of procedures. CONCLUSIONS: This study was the first nationwide multicentric survey to propose RLs for interventional procedures under CT guidance. Heterogeneity of practice in centers were found with different levels of patient doses for the same procedure. The proposed RLs will allow imaging departments to benchmark their practice with others and optimize their protocols. KEY POINTS: • National reference levels are proposed for 17 categories of interventional procedures under CT guidance. • Reference levels are useful for benchmarking practices and optimizing protocols. • Reference levels are proposed for dose length product and the number of helical acquisitions.

Correction to: National dose reference levels in computed tomography-guided interventional procedures-a proposal.

The original version of this article, published on 02 May 2020, unfortunately contained a mistake.