Artificial Intelligence-Guided Segmentation and Path Planning Software for Transthoracic Lung Biopsy.

PURPOSE: To validate the sensitivity and specificity of a 3-dimensional (3D) convolutional neural network (CNN) artificial intelligence (AI) software for lung lesion detection and to establish concordance between AI-generated needle paths and those used in actual biopsy procedures. MATERIALS AND METHODS: This was a retrospective study using computed tomography (CT) scans from 3 hospitals. Inclusion criteria were scans with 1-5 nodules of diameter ≥5 mm; exclusion criteria were poor-quality scans or those with nodules measuring <5mm in diameter. In the lesion detection phase, 2,147 nodules from 219 scans were used to develop and train the deep learning 3D-CNN to detect lesions. The 3D-CNN was validated with 235 scans (354 lesions) for sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) analysis. In the path planning phase, Bayesian optimization was used to propose possible needle trajectories for lesion biopsy while avoiding vital structures. Software-proposed needle trajectories were compared with actual biopsy path trajectories from intraprocedural CT scans in 150 patients, with a match defined as an angular deviation of <5° between the 2 trajectories. RESULTS: The model achieved an overall AUC of 97.4% (95% CI, 96.3%-98.2%) for lesion detection, with mean sensitivity of 93.5% and mean specificity of 93.2%. Among the software-proposed needle trajectories, 85.3% were feasible, with 82% matching actual paths and similar performance between supine and prone/oblique patient orientations (P = .311). The mean angular deviation between matching trajectories was 2.30° (SD ± 1.22); the mean path deviation was 2.94 mm (SD ± 1.60). CONCLUSIONS: Segmentation, lesion detection, and path planning for CT-guided lung biopsy using an AI-guided software showed promising results. Future integration with automated robotic systems may pave the way toward fully automated biopsy procedures.

Impact of catheter tip to hepatic vein ostium distance on the validity and prognostication of hepatic venous pressure gradient in cirrhosis.

Hepatic venous pressure gradient (HVPG) is an accurate measure of portal hypertension in cirrhosis. However, the effect of catheter tip distance from hepatic vein ostium (HVO) on HVPG is unknown. We performed a retrospective study on 228 patients with 307 HVPGs in our institution. The objectives of this study were to assess the effect of catheter position on the validity of HVPG and its prognostication in cirrhosis. In this study, free hepatic vein pressure (FHVP) was considered optimal when difference between FHVP and inferior vena cava pressure was ≤ 2 mmHg. HVPG progressively decreased (p < 0.001) when measured at increasing distance from HVO due to an increasing FHVP (p = 0.036) but an unchanged wedged hepatic vein pressure (p = 0.343). Catheter tip distance > 5 to ≤ 8 cm [odds ratio {OR} 0.16 (95% CI 0.05-0.47), p = 0.001] and > 8 cm [OR 0.14 (95% CI 0.04-0.47), p = 0.002] compared to ≤ 3 cm from HVO were independent predictors of not achieving optimal FHVP. Baseline HVPG ≥ 16 mmHg was strongly associated with deaths due to cirrhosis and liver transplantation for end-stage liver disease compared to HVPG < 16 mmHg when FHVP was optimal (p < 0.001) but not when it was suboptimal (p = 0.359). Our study showed that FHVP is spuriously elevated when measured at > 5 cm from HVO, resulting in inaccurately low HVPG.

The Role of Drug-Coated Balloon in Haemodialysis Arteriovenous Fistula Stenosis Management.

Arteriovenous fistula (AVF) stenosis is a common problem leading to dialysis access dysfunction. The conventional balloon (CB) is the most commonly used device during angioplasty but suffers from poor durability of results due to neointimal hyperplasia-mediated recurrence. The drug-coated balloon (DCB) is an adjunct to balloon angioplasty that reduces neointimal hyperplasia, thereby improving post-angioplasty patency. Despite the heterogeneity of DCB clinical trials to date, the evidence suggests that DCBs of different brands are not necessarily equal, and that patient selection, adequate lesion preparation and proper DCB procedural technique are important to realize the benefit of DCB angioplasty.

First-Line Systemic Therapies for Advanced Hepatocellular Carcinoma: A Systematic Review and Patient-Level Network Meta-Analysis.

Introduction: Sorafenib was historically the standard of care for advanced hepatocellular carcinoma (aHCC) until it was superseded by the combination of atezolizumab and bevacizumab. Thereafter, several novel first-line combination therapies have demonstrated favorable outcomes. The efficacies of these treatments in relation to current and previous standards of care are unknown, necessitating an overarching evaluation. Methods: A systematic literature search was conducted on PubMed, EMBASE, Scopus, and the Cochrane Controlled Register of Trials for phase III randomized controlled trials investigating first-line systemic therapies for aHCC. Kaplan-Meier curves for overall survival (OS) and progression-free survival (PFS) were graphically reconstructed to retrieve individual patient-level data. Derived hazard ratios (HRs) for each study were pooled in a random-effects network meta-analysis (NMA). NMAs were also conducted using study-level HRs for various subgroups, according to viral etiology, Barcelona Clinic Liver Cancer (BCLC) staging, alpha-fetoprotein (AFP) levels, macrovascular invasion, and extrahepatic spread. Treatment strategies were ranked using p scores. Results: Among 4,321 articles identified, 12 trials and 9,589 patients were included for analysis. Only two therapies showed OS benefit over sorafenib: combined anti-programmed-death and anti-VEGF pathway inhibitor monoclonal antibodies (Anti-PD-(L)1/VEGF Ab), including atezolizumab-bevacizumab and sintilimab-bevacizumab biosimilar (HR = 0.63, 95% CI = 0.53-0.76) and tremelimumab-durvalumab (HR = 0.78, 95% CI = 0.66-0.92). Anti-PD-(L)1/VEGF Ab showed OS benefit over all other therapies except tremelimumab-durvalumab. Low heterogeneity (I2 = 0%) and inconsistency (Cochran's Q = 0.52, p = 0.773) was observed. p scores for OS ranked Anti-PD-(L)1/VEGF Ab as the best treatment in all subgroups, except hepatitis B where atezolizumab-cabozantinib ranked highest for both OS and PFS, as well as nonviral HCC and AFP ≥400 µg/L where tremelimumab-durvalumab ranked highest for OS. Conclusion: This NMA supports Anti-PD-(L)1/VEGF Ab as the first-line therapy for aHCC and demonstrates a comparable benefit for tremelimumab-durvalumab which also extends to certain subgroups. Results of the subgroup analysis may guide treatment according to baseline characteristics, while pending further studies.

A Randomized Phase 2 Trial of Nivolumab Versus Nivolumab-Ipilimumab Combination in EGFR-Mutant NSCLC.

Introduction: Although immune checkpoint inhibitors (ICIs) have dramatically improved outcomes for nononcogene-addicted NSCLC, monotherapy with programmed cell death protein-1 (PD1) inhibition has been associated with low efficacy in the EGFR-mutant setting. Given the potential for synergism with combination checkpoint blockade, we designed a trial to test the activity of combination nivolumab (N)-ipilimumab (NI) in EGFR-mutant NSCLC. Methods: This is a randomized phase 2 study (NCT03091491) of N versus NI combination in EGFR tyrosine kinase inhibitor (TKI)-resistant NSCLC, with crossover permitted on disease progression. The primary end point was the objective response rate, and the secondary end points included progression-free survival, overall survival, and safety of ICI after EGFR TKI. Results: Recruitment ceased owing to futility after 31 of 184 planned patients were treated. A total of 15 patients received N and 16 received NI combination. There were 16 patients (51.6%) who had programmed death-ligand (PDL1) 1 greater than or equal to 1%, and 15 (45.2%) harbored EGFR T790M. Five patients derived clinical benefits from ICI with one objective response (objective response rate 3.2%), and median progression-free survival was 1.22 months (95% confidence interval: 1.15-1.35) for the overall cohort. None of the four patients who crossed over achieved salvage response by NI. PDL1 and tumor mutational burden (TMB) were not able to predict ICI response. Rates of all grade immune-related adverse events were similar (80% versus 75%), with only two grade 3 events. Conclusions: Immune checkpoint inhibition is ineffective in EGFR TKI-resistant NSCLC. Whereas a small subgroup of EGFR-mutant NSCLC may be immunogenic and responsive to ICI, better biomarkers are needed to select appropriate patients.

Targeted Anterior Cervical Epidural Blood Patch in a Patient with Spontaneous Intracranial Hypotension.

A 45-year-old male was admitted with severe orthostatic headache secondary to spontaneous intracranial hypotension. He had the site of cerebrospinal fluid (CSF) leakage identified at the anterolateral aspect of the C7-T1 spinal level. He first underwent a conventional posterior-approach cervical epidural blood patch (EBP) which provided immediate relief to the patient's symptoms; however, his symptoms recurred two days later. To better target the anterolateral leakage site, we employed an anterior-approach EBP under computed tomography (CT) guidance. After this attempt, the patient experienced complete relief of his symptoms, and the headache eventually resolved.

Phantom and Animal Study of a Robot-Assisted, CT-Guided Targeting System using Image-Only Navigation for Stereotactic Needle Insertion without Positional Sensors.

PURPOSE: To evaluate the feasibility and accuracy of a robotic system to integrate and map computed tomography (CT) and robotic coordinates, followed by automatic trajectory execution by a robotic arm. The system was hypothesized to achieve a targeting error of <5 mm without significant influence from variations in angulation or depth. MATERIALS AND METHODS: An experimental study was conducted using a robotic system (Automated Needle Targeting device for CT [ANT-C]) for needle insertions into a phantom model on both moving patient table and moving gantry CT scanners. Eight spherical markers were registered as targets for 90 insertions at different trajectories. After a single ANT-C registration, the closed-loop software targeted multiple markers via the insertion of robotically aligned 18-gauge needles. Accuracy (distance from the needle tip to the target) was assessed by postinsertion CT scans. Similar procedures were repeated to guide 10 needle insertions into a porcine lung. A regression analysis was performed to test the effect of needle angulation and insertion depth on the accuracy of insertion. RESULTS: In the phantom model, all needle insertions (median trajectory depth, 64.8 mm; range, 46.1-153 mm) were successfully performed in single attempts. The overall accuracy was 1.36 mm ± 0.53, which did not differ between the 2 types of CT scanners (1.39 mm ± 0.54 [moving patient table CT] vs 1.33 mm ± 0.52 [moving gantry CT]; P = .54) and was not significantly affected by the needle angulation and insertion depth. The accuracy for the porcine model was 9.09 mm ± 4.21. CONCLUSIONS: Robot-assisted needle insertion using the ANT-C robotic device was feasible and accurate for targeting multiple markers in a phantom model.

Percutaneous Treatments for Persistent Bronchopleural and Alveolar-Pleural Fistulae.

Percutaneous glue embolization was investigated as a treatment for bronchopleural fistulae (BPFs) and alveolar-pleural fistulae (APFs) associated with persistent air leak. Seven consecutive patients with persistent air leak were treated with percutaneous glue embolization of the BPF/APF from both iatrogenic and spontaneous causes. Treatment was performed using direct n-butyl cyanoacrylate (nBCA) glue injection for discrete, visible fistulae (n = 4), fibrin glue spray for suspected tiny multifocal leaks (n = 2), or both (n = 1). The number of treatments required per patient was 1 (n = 3), 2 (n = 3), or 3 (n = 1). Technical success was achieved in all cases. Follow-up showed resolution of all air leaks, with mean chest tube removal at 7.1 days after the embolization. The follow-up duration ranged from 2 to 47 months. No significant procedure-related morbidity, mortality, or recurrence was encountered. Percutaneous treatment for persistent BPFs and APFs showed good efficacy in this small case series and warrants further investigation.

Recurrent Stenoses in Arteriovenous Fistula (AVF) for Dialysis Access: cuttIng ballooN angioplaSTy combined wITh paclitaxel drUg-coaTed balloon angioplasty, an observatIONal study (INSTITUTION Study).

PURPOSE: To study the safety and efficacy of cutting balloon angioplasty (CBA) followed by paclitaxel drug-coated balloon (PCB) angioplasty for recurrent venous lesions in arteriovenous fistulas (AVFs). MATERIALS AND METHODS: We conducted a prospective single-arm cohort study of CBA followed by PCB angioplasty for recurrent AVF stenoses between September 2017 and April 2019. In total, 44 participants were recruited. Target lesions were included if they had recurred within 12 months post-angioplasty, were > = 0.5 cm upstream from the arteriovenous anastomosis, and did not involve the central veins. Up to two non-target lesions per circuit/participant with the same definition were allowed. Lesions were considered separate when there was an intervening 2-cm segment of normal vessel. Technical success was defined as complete lesion effacement on angioplasty. End-points of target and circuit patency were evaluated clinically at 3, 6, and 12 months post-procedure. RESULT: Technical success was 96% (42/44): Two participants were excluded from analysis due to the need for high-pressure balloon angioplasty as the target lesions did not efface with CBA. The median follow-up duration was 337.5 days. Mean stenosis pre- and post-angioplasty was 69.0% (51.6-84.8) and 20.8% (0-44.8), respectively. The target lesion primary, primary assisted and circuit patency for the entire study population (n = 42) were 61.6 ± 7.8%, 92.7 ± 4.0%, and 54.7 ± 7.9%, respectively, at 12 months. For participants without non-target lesions (n = 22), the rates were 77.3 ± 8.9%, 90.9 ± 6.1%, and 60.7 ± 11.0%, respectively, at 12 months. CONCLUSION: CBA followed by PCB angioplasty appears safe and feasible for treatment of recurrent venous lesions in dysfunctional AVFs.

Anastomosing Hemangioma on 68Ga-DOTATATE PET/CT: A Potential Pitfall.

ABSTRACT: Anastomosing hemangioma (AH) is a rare benign vascular lesion that primarily involves the genitourinary tract. Cases have also rarely been reported in other organs. AH is often discovered incidentally and resembles angiosarcoma histologically. On imaging, it may mimic other vascular lesions such as renal cell carcinoma and neuroendocrine tumors. We present a case of a 32-year-old woman with incidentally detected AH involving the kidneys, adrenal glands, liver, and retroperitoneum, initially presumed to be neuroendocrine tumors based on imaging findings on CT and 68Ga-DOTATATE PET scans.

SIroliMus coated angioPlasty versus plain balloon angioplasty in the tREatment of dialySis acceSs dysfunctION (IMPRESSION): study protocol for a randomized controlled trial.

BACKGROUND: Percutaneous transluminal angioplasty is the current standard treatment for arteriovenous fistula (AVF) stenosis. The mid- and long-term patency with plain balloon angioplasty (PBA) is however far from satisfactory. While paclitaxel-coated balloon angioplasty has been shown to be superior to PBA, concern over its safety profile has recently arisen after a reported possible increased mortality risk with a meta-analysis of large lower limb studies. An angioplasty balloon with a new type of drug coating, the sirolimus-coated balloon (SCB), has been proven to improve patency in the coronary arteries. However, its effect on AV access has yet to be studied. METHODS/DESIGN: This is an investigator-initiated, prospective, multicenter, double-blinded, randomized controlled clinical trial to assess the effectiveness of SCB compared to PBA in improving the patency of AVF after angioplasty. A total of 170 patients with mature AVF that requires PTA due to AVF dysfunction will be randomly assigned to treatment with a SCB or PBA at a 1:1 ratio, stratified by location of AVF and followed up for up to 1 year. The inclusion criteria include [1] adult patient aged 21 to 85 years who requires balloon angioplasty for dysfunctional arteriovenous fistula [2]; matured AVF, defined as being in use for at least 1 month prior to the angioplasty; and [3] successful angioplasty of the underlying stenosis with PBA, defined as less than 30% residual stenosis on digital subtraction angiography (DSA) and restoration of thrill in the AVF on clinical examination. The exclusion criteria include thrombosed or partially thrombosed access circuit at the time of treatment, presence of symptomatic or angiographically significant central vein stenosis that requires treatment with more than 30% residual stenosis post angioplasty, and existing stent placement within the AVF circuit. The primary endpoint of the study is access circuit primary patency at 6 months. The secondary endpoints are target lesion primary patency; access circuit-assisted primary patency; access circuit secondary patency at 3, 6, and 12 months; target lesion restenosis rate at 6 months; total number of interventions; complication rate; and cost-effectiveness. The trial is supported by Concept Medical. DISCUSSION: This study will evaluate the clinical efficacy and safety of SCB compared to PBA in the treatment of AVF stenosis in hemodialysis patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT04409912 . Registered on 1 June 2020.

Radioembolisation with Y90-resin microspheres followed by nivolumab for advanced hepatocellular carcinoma (CA 209-678): a single arm, single centre, phase 2 trial.

BACKGROUND: Therapeutic synergism between radiotherapy and immune checkpoint blockade has been observed in preclinical models of hepatocellular carcinoma. We aimed to study the safety and efficacy of sequential radioembolisation with yttrium-90-resin microspheres (Y90-radioembolisation) followed by nivolumab in patients with advanced hepatocellular carcinoma. METHODS: Patients with Child-Pugh A cirrhosis and advanced hepatocellular carcinoma not suitable for curative surgery were treated with Y90-radioembolisation followed by intravenous nivolumab 240 mg 21 days after Y90-radioembolisation and every 2 weeks thereafter. The primary endpoint, assessed in the per-protocol population, was the objective response rate, determined by RECIST version 1.1, defined as the proportion of patients with a confirmed complete or partial response observed for lesions both within and outside the Y90-radioembolisation field. This study is registered with ClinicalTrials.gov, NCT03033446 and has been completed. FINDINGS: 40 patients were enrolled, of whom 36 received Y90-radioembolisation followed by nivolumab. One (3%) patient had a complete response and ten (28%) had a partial response; the objective response rate was 30·6% (95% CI 16·4-48·1). The most common treatment-related adverse events of any grade were pruritus (18 [50%] of 36 patients) and maculopapular rash (13 [36%]). Two (6%) patients experienced grade 3-4 treatment-related adverse events: one patient had a grade 3 increase in alanine aminotransferase levels, grade 3 bilirubin increase, and grade 4 increase in aspartate aminotransferase levels, while the other had a grade 3 maculopapular rash. Five (14%) patients had a treatment-related serious adverse event (Steven-Johnson syndrome, hepatitis E infection, fever, liver abscesses, and ascites). INTERPRETATION: Y90-radioembolisation followed by nivolumab resulted in an encouraging objective response rate in patients with advanced hepatocellular carcinoma, although the activity observed was not as high as the study was powered for. This strategy should be further evaluated in patients with Barcelona Clinic Liver Clinic (BCLC) stage B hepatocellular carcinoma that is ineligible or refractory to transarterial chemoembolisation and patients with BCLC C disease without extrahepatic spread. FUNDING: National Medical Research Council Singapore, Bristol-Myers Squibb, Sirtex.

Drug Coated Balloons for Dysfunctional Haemodialysis Venous Access: A Patient Level Meta-Analysis of Randomised Controlled Trials.

OBJECTIVE: To perform an individual patient data level meta-analysis of randomised controlled trials comparing drug coated balloon angioplasty (DCB) against conventional percutaneous transluminal angioplasty (PTA) in the treatment of dysfunctional haemodialysis venous access. METHODS: A search was conducted from inception to 13 November 2020. Kaplan-Meier curves comparing DCB with PTA by target lesion primary patency (TLPP) and access circuit primary patency (ACPP) were graphically reconstructed to retrieve patient level data. One stage meta-analyses with Cox models with random effects shared frailties were conducted to determine hazard ratios (HRs). Dynamic restricted mean survival times (RMST) were conducted in view of violation of the proportional hazards assumption. Conventional two stage meta-analyses and network meta-analyses under random effects Frequentist models were conducted to determine overall and comparative outcomes of paclitaxel concentrations used. Where outliers were consistently detected through outlier and influence analyses, sensitivity analyses excluding those studies were conducted. RESULTS: Among 10 RCTs (1 207 patients), HRs across all models favoured DCB (one stage shared frailty HR 0.62, 95% CI 0.53 - 0.73, p < .001; two stage random effects HR 0.60, 95% CI 0.42 - 0.86, p = .018, I2 = 65%) for TLPP. Evidence of time varying effects (p = .005) was found. TLPP RMST was + 3.54 months (25.0%) longer in DCB treated patients compared with PTA (p = .001) at three years. TLPP at six months, one year, and two years was 75.3% vs. 58.1%, 51.1% vs. 37.1%, and 31.4% vs. 26.0% for DCB and PTA, respectively. The P-Scores within the Frequentist network meta-analysis suggest that higher concentrations of paclitaxel were associated with better TLPP and ACPP. Among six RCTs (854 patients), the one stage model favoured DCB (shared frailty HR 0.72, 95% CI 0.60 - 0.87, p < .001) for ACPP. Conversely, the two stage random effects model demonstrated no significant difference (HR 0.76, 95% CI 0.35 - 1.67, p = .41, I2 = 81%). Sensitivity analysis excluding outliers significantly favoured DCB (HR 0.61, 95% CI 0.41 - 0.91, p = .027, I2 = 62%). CONCLUSION: Overall evidence suggests that DCB is favoured over PTA in TLPP and ACPP.

Real-World Data on Clinical Outcomes of Patients with Liver Cancer: A Prospective Validation of the National Cancer Centre Singapore Consensus Guidelines for the Management of Hepatocellular Carcinoma.

INTRODUCTION: Real-world management of patients with hepatocellular carcinoma (HCC) is crucially challenging in the current rapidly evolving clinical environment which includes the need for respecting patient preferences and autonomy. In this context, regional/national treatment guidelines nuanced to local demographics have increasing importance in guiding disease management. We report here real-world data on clinical outcomes in HCC from a validation of the Consensus Guidelines for HCC at the National Cancer Centre Singapore (NCCS). METHOD: We evaluated the NCCS guidelines using prospectively collected real-world data, comparing the efficacy of treatment received using overall survival (OS) and progression-free survival (PFS). Treatment outcomes were also independently evaluated against 2 external sets of guidelines, the Barcelona Clinic Liver Cancer (BCLC) and Hong Kong Liver Cancer (HKLC). RESULTS: Overall treatment compliance to the NCCS guidelines was 79.2%. Superior median OS was observed in patients receiving treatment compliant with NCCS guidelines for early (nonestimable vs. 23.5 months p < 0.0001), locally advanced (28.1 vs. 22.2 months p = 0.0216) and locally advanced with macrovascular invasion (10.3 vs. 3.3 months p = 0.0013) but not for metastatic HCC (8.1 vs. 6.8 months p = 0.6300), but PFS was similar. Better clinical outcomes were seen in BCLC C patients who received treatment compliant with NCCS guidelines than in patients with treatment only allowed by BCLC guidelines (median OS 14.2 vs. 7.4 months p = 0.0002; median PFS 6.1 vs. 4.0 months p = 0.0286). Clinical outcomes were, however, similar for patients across all HKLC stages receiving NCCS-recommended treatment regardless of whether their treatment was allowed by HKLC. CONCLUSION: The high overall compliance rate and satisfactory clinical outcomes of patients managed according to the NCCS guidelines confirm its validity. This validation using real-world data considers patient and treating clinician preferences, thus providing a realistic analysis of the usefulness of the NCCS guidelines when applied in the clinics.

Integrative Profiling of T790M-Negative EGFR-Mutated NSCLC Reveals Pervasive Lineage Transition and Therapeutic Opportunities.

PURPOSE: Despite the established role of EGFR tyrosine kinase inhibitors (TKIs) in EGFR-mutated NSCLC, drug resistance inevitably ensues, with a paucity of treatment options especially in EGFR T790M-negative resistance. EXPERIMENTAL DESIGN: We performed whole-exome and transcriptome analysis of 59 patients with first- and second-generation EGFR TKI-resistant metastatic EGFR-mutated NSCLC to characterize and compare molecular alterations mediating resistance in T790M-positive (T790M+) and -negative (T790M-) disease. RESULTS: Transcriptomic analysis revealed ubiquitous loss of adenocarcinoma lineage gene expression in T790M- tumors, orthogonally validated using multiplex IHC. There was enrichment of genomic features such as TP53 alterations, 3q chromosomal amplifications, whole-genome doubling and nonaging mutational signatures in T790M- tumors. Almost half of resistant tumors were further classified as immunehot, with clinical outcomes conditional on immune cell-infiltration state and T790M status. Finally, using a Bayesian statistical approach, we explored how T790M- and T790M+ disease might be predicted using comprehensive genomic and transcriptomic profiles of treatment-naïve patients. CONCLUSIONS: Our results illustrate the interplay between genetic alterations, cell lineage plasticity, and immune microenvironment in shaping divergent TKI resistance and outcome trajectories in EGFR-mutated NSCLC. Genomic and transcriptomic profiling may facilitate the design of bespoke therapeutic approaches tailored to a tumor's adaptive potential.

Randomized Controlled Trial Comparing Drug-coated Balloon Angioplasty versus Conventional Balloon Angioplasty for Treating Below-the-Knee Arteries in Critical Limb Ischemia: The SINGA-PACLI Trial.

Background There is a paucity of randomized trials demonstrating superior efficacy of drug-coated balloon angioplasty (DCBA) compared with conventional percutaneous transluminal angioplasty (PTA) for below-the-knee arterial disease in patients with -critical limb ischemia. Purpose To compare DCBA versus PTA for below-the-knee lesions in participants with critical limb ischemia through 12 months. Materials and Methods In this prospective, randomized, two-center, double-blind superiority study, participants with critical limb ischemia with rest pain or tissue loss with atherosclerotic disease in the native below-the-knee arteries were randomly assigned (in a one-to-one ratio) to DCBA or PTA after stratification for diabetes and renal failure between November 2013 and October 2017. The primary efficacy end point was angiographic primary patency at 6 months analyzed on an intention-to-treat basis. Secondary end points through 12 months were composed of major adverse events including death and major amputations, wound healing, limb salvage, clinically driven target-lesion revascularization, and amputation-free survival. Primary and binary secondary end points, analyzed by using generalized-linear model and time-to-event analyses, were estimated with Kaplan-Meier survival curves and hazard ratios (Cox regression). Results Seventy participants (mean age, 61 years ± 10 [standard deviation]; 43 men) in the DCBA group and 68 (mean age, 64 years ± 10; 50 men) in the PTA group were evaluated. The percentage of patients with angiographic primary patency at 6 months was 43% (30 of 70) in the DCBA group and 38% (26 of 68) in the PTA group (P = .48). Through 12 months, the percentage of deaths was similar: 21% in the DCBA group and 16% in the PTA group (P = .43). Amputation-free survival rate assessed with Kaplan-Meier curves differed through 12 months: 59% (41 of 70) in the DCBA group compared with 78% (53 of 68) in the PTA group (P = .01). Conclusion In participants with critical limb ischemia, the drug-coated balloon angioplasty group and the conventional percutaneous transluminal angioplasty group had similar primary patency rates at 6 months after treatment of below-the-knee arteries. Amputation-free survival rates through 12 months were higher in the percutaneous transluminal angioplasty group. © RSNA, 2021 Online supplemental material is available for this article.

Individualized Molecular Profiling for Allocation to Clinical Trials Singapore Study-An Asian Tertiary Cancer Center Experience.

PURPOSE: Precision oncology has transformed the management of advanced cancers through implementation of advanced molecular profiling technologies to identify increasingly defined subsets of patients and match them to appropriate therapy. We report outcomes of a prospective molecular profiling study in a high-volume Asian tertiary cancer center. PATIENTS AND METHODS: Patients with advanced cancer were enrolled onto a prospective protocol for genomic profiling, the Individualized Molecular Profiling for Allocation to Clinical Trials Singapore study, at the National Cancer Center Singapore. Primary objective was to identify molecular biomarkers in patient's tumors for allocation to clinical trials. The study commenced in February 2012 and is ongoing, with the results of all patients who underwent multiplex next-generation sequencing (NGS) testing until December 2018 presented here. The results were discussed at a molecular tumor board where recommendations for allocation to biomarker-directed trials or targeted therapies were made. RESULTS: One thousand fifteen patients were enrolled with a median age of 58 years (range 20-83 years). Most common tumor types were lung adenocarcinoma (26%), colorectal cancer (15%), and breast cancer (12%). A total of 1,064 NGS assays were performed, on fresh tumor tissue for 369 (35%) and archival tumor tissue for 687 (65%) assays. TP53 (39%) alterations were most common, followed by EGFR (21%), KRAS (14%), and PIK3CA (10%). Of 405 NGS assays with potentially actionable alterations, 111 (27%) were allocated to a clinical trial after molecular tumor board and 20 (4.9%) were enrolled on a molecularly matched clinical trial. Gene fusions were detected in 23 of 311 (7%) patients tested, including rare fusions in new tumor types and known fusions in rare tumors. CONCLUSION: Individualized Molecular Profiling for Allocation to Clinical Trials Singapore demonstrates the feasibility of a prospective broad molecular profiling program in an Asian tertiary cancer center, with the ability to develop and adapt to a dynamic landscape of precision oncology.