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Background: The percutaneous treatment of calcified coronary lesions remains challenging and is associated with worse clinical outcomes. In addition, coronary artery calcification is associated with more frequent peri-procedural myocardial infarction., Study Design and Objectives: The ShOckwave ballooN or Atherectomy with Rotablation in calcified coronary artery lesions (SONAR) study is an investigator-initiated, prospective, randomized, international, multicenter, open label trial (NCT05208749) comparing a lesion preparation strategy with either shockwave intravascular lithotripsy (IVL) or rotational atherectomy (RA) before drug-eluting stent implantation in 170 patients with moderate to severe calcified coronary lesions. The primary endpoint is difference in the rate of peri-procedural myocardial infarction. Key secondary endpoints include rate of peri-procedural microvascular dysfunction, peri-procedural myocardial injury, descriptive study of IMR measurements in calcified lesions, technical and procedural success, interaction between OCT calcium score and primary endpoint, 30-day and 1-year major adverse clinical events., Conclusions: The SONAR trial is the first randomized controlled trial comparing the incidence of peri-procedural myocardial infarction between 2 contemporary calcium modification strategies (Shockwave IVL and RA) in patients with calcified coronary artery lesions. Furthermore, for the first time, the incidence of peri-procedural microvascular dysfunction after Shockwave IVL and RA will be evaluated and compared., Competing Interests: Declaration of competing interest JB reports research grants and speaking fees from Abbott Vascular and Biotronik AG, and consulting fees from Biotronik AG, Boston Scientific and Elixir. NMVM reports research grant support from Abbott Vascular, Medtronic, Boston Scientific, Daiichi Sankyo, Astra Zeneca and advisory fees from Abbott Vascular, Medtronic, Boston Scientific, Daiichi Sankyo, Amgen, Anteris, JenaValve, Siemens, and Teleflex. JD reports consulting fees from Topmedical and Boston Scientific., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Immune checkpoint inhibitors (ICI) are part of the current standard of care for metastatic clear-cell renal cell carcinoma (m-ccRCC). ICI can elicit diverse tumor response, including atypical responses such as pseudoprogression (psPD), mixed responses (MR) and late responses. We aimed to analyze the occurrence and prognostic impact of atypical responses in m-ccRCC patients treated with nivolumab., Materials and Methods: A retrospective analysis of m-ccRCC patients treated with nivolumab in first or subsequent therapy line between November 2012 and July 2022 was performed. All radiographic evaluations of eligible patients were analyzed using the iRECIST consensus guideline., Results: We assessed 247 baseline target lesions in 94 eligible patients. MR occurred in 11 (11.7%) patients: in 7 at first CT (computed tomography) evaluation (CT1) and in 4 at second CT evaluation (CT2). In 8 patients (73%), MR evolved to confirmed PD. In 3 patients (27%), MR evolved towards a partial response (PR) and was thus a psPD. psPD occurred in 8 (8.5%) patients: with psPD features at CT1 in 3 patients, with psPD features at CT2 in 2 patients, and with MR features at CT1 in 3 patients. psPD patients had similar progression-free survival and overall survival compared to patients displaying PR as best response without a phase of psPD. 76 patients were treated beyond immune unconfirmed progressive disease (iUPD) at any moment: 12 (16%) of them evolved towards PR or stable disease (SD). Treatment beyond immune confirmed PD (iCPD) in 20 patients did not lead to PR or SD., Conclusion: Atypical responses such as psPD and MR occurred in 8.5% and 11.7% of m-ccRCC patients treated with nivolumab at CT1 and CT2. Patients with psPD had favorable outcomes, while MR most often evolved to progression. Treatment with nivolumab beyond iCPD did not lead to tumor stabilization or regression., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Papillary renal cell carcinoma (papRCC) is a rare (10%-15%) subtype of renal cancer. Few prognostic biomarkers have been described in metastatic papRCC (m-papRCC) patients treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs). We aimed to study the prognostic impact of bone metastases (BM) on response rate, progression-free and overall survival (PFS and OS) in patients with m-papRCC treated with first agent VEGFR-TKIs., Patients and Methods: A multicentric, retrospective analysis of patient records was conducted. BM were detected by computed tomography and/or bone scintigraphy. The International Metastatic RCC Database Consortium (IMDC) score was calculated at start of first agent VEGFR-TKI treatment., Results: Forty-nine patients were included. Best objective response was partial response in 20%, stable disease in 60% and early progressive disease in 20% of patients. Median PFS (mPFS) was 6.0 months and median OS (mOS) 14.0 months after start of first agent VEGFR-TKI. The IMDC score correlated with mOS: 77.5 months in good, 17.0 months in intermediate and 8.0 months in poor risk patients (P = 0.002). Patients with BM had a poorer outcome compared to patients without BM: mPFS was 4.0 vs. 7.0 months (P = 0.006) and mOS 7.5 vs. 19.0 months (P = 0.002). On bivariate analysis, the presence of BM was independently associated with PFS (P = 0.02) and OS (P = 0.049), independent of the IMDC risk groups., Conclusion: In m-papRCC patients treated with first agent VEGFR-TKIs, the presence of BM is an unfavorable prognostic factor, associated with shorter PFS and OS., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to assess the 2-year clinical outcomes of the Firehawk stent (Shanghai MicroPort Medical Group, Shanghai, China), a novel abluminal groove-filled biodegradable-polymer sirolimus-eluting coronary stent, compared with XIENCE (Abbott Vascular, Santa Clara, California), a durable-polymer everolimus-eluting coronary stent., Background: The long-term outcomes of the Firehawk stent have not been evaluated beyond 1 year in a randomized all-comers clinical trial., Methods: The TARGET All Comers study is a prospective, multicenter, all-comers, randomized, noninferiority trial conducted in Europe. A total of 1,653 patients were randomly assigned to undergo implantation of either the Firehawk or the XIENCE stent. The primary endpoint was target lesion failure, a composite of cardiac death, target vessel myocardial infarction, or ischemia-driven target lesion revascularization., Results: At 2-year follow-up, the incidence of target lesion failure was 8.7% in the Firehawk group versus 8.6% in the XIENCE group (p = 0.92). The event rates of individual components of the primary endpoint were comparable for the 2 groups. Landmark analyses between 1- and 2-year follow-up revealed no statistically significant difference of TLF for the Firehawk versus the XIENCE stent. Beyond 1 year, very late definite or probable stent thrombosis occurred in 3 patients (0.4%) in the Firehawk group and in 7 patients (0.9%) in the XIENCE group (p = 0.34)., Conclusions: The 2-year follow-up of the TARGET All Comers study confirms comparable safety and efficacy profiles of the Firehawk and XIENCE stents., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The FIREHAWK is a drug-eluting stent with a fully biodegradable sirolimus-containing polymer coating localised to recessed abluminal grooves on the stent surface. We investigated clinical outcomes with this targeted, low-dose, biodegradable polymer, sirolimus-eluting stent compared with XIENCE durable polymer, everolimus-eluting stents in an all-comers population., Methods: The TARGET All Comers study was a prospective, multicentre, open-label randomised non-inferiority trial done at 21 centres in ten European countries. Patients with symptomatic or asymptomatic coronary artery disease and objective evidence of myocardial ischaemia who qualified for percutaneous coronary intervention were randomised 1:1 to undergo implantation of a FIREHAWK or XIENCE. Randomisation was web-based, with random block allocation and stratification by centre and ST elevation myocardial infarction. Outcome assessors were masked to treatment allocation, but treating physicians and patients were not. The primary endpoint was target lesion failure at 12 months, a composite of cardiac death, target vessel myocardial infarction, or ischaemia-driven target lesion revascularisation. The control event rate for XIENCE was assumed to be 7%, the non-inferiority margin was 3.5%, and the primary analysis was in the intention-to-treat population, censoring patients who did not have either an event before 365 days or contact beyond 365 days. Late lumen loss was the primary endpoint of an angiographic substudy designed to investigate the non-inferiority of the FIREHAWK compared with the XIENCE stent. This trial is registered with ClinicalTrials.gov, number NCT02520180., Findings: From Dec 17, 2015, to Oct 14, 2016, 1653 patients were randomly assigned to implantation of the FIREHAWK (n=823) or XIENCE (n=830). 65 patients in the FIREHAWK group and 66 in the XIENCE group had insufficient follow-up data and were excluded from the analyses. At 12 months, target lesion failure occurred in 46 (6·1%) of 758 patients in the FIREHAWK group and in 45 (5·9%) of 764 patients in the XIENCE group (difference 0·2%, 90% CI -1·9 to 2·2, p non-inferiority =0·004, 95% CI -2·2 to 2·6, p superiority =0·88). There were no differences in ischaemia-driven revascularisation or stent thrombosis rates at 12 months. 176 patients were included in the angiographic substudy, in which in-stent late lumen loss was 0·17 mm (SD 0·48) in the FIREHAWK group and 0·11 mm (0·52) in the XIENCE group (p=0·48), with an absolute difference of 0·05 mm (95% CI -0·09 to 0·18, p non-inferiority =0·024)., Interpretation: In a broad all-comers population of patients requiring stent implantation for myocardial ischaemia, the FIREHAWK was non-inferior to the XIENCE as assessed with the primary endpoint of target lesion failure at 12 months and in-stent late lumen loss at 13 months. The FIREHAWK is a safe and effective alternative stent to treat patients with ischaemic coronary artery disease in clinical practice., Funding: Shanghai Microport Medical., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: This study aims to investigate the use of chemotherapy with or without bevacizumab in older patients with metastatic colorectal cancer (mCRC) in current daily practice and to identify predictive parameters for treatment-related outcomes., Patients and Methods: This is a Belgian multi-centre, observational cohort study. Patients≥70years old with mCRC considered suitable for first-line chemotherapy were eligible for inclusion. At baseline geriatric screening and assessment was performed. Treatment choice was at the discretion of the investigator. Treatment duration, Progression Free Survival (PFS) and safety were recorded., Results: Between August 2011 and July 2013, 252 patients with mCRC were included of which 50.8% were treated with bevacizumab. Median treatment duration was 5.5months and median PFS was 8.9months. Approximately 50% of patients experienced severe adverse events, most frequently diarrhea. In multivariate analysis, baseline Eastern Cooperative Oncology Group (ECOG)-performance status (PS) was predictive for treatment duration (p=0.0047), PFS (p<0.0001) and severe toxicity and baseline nutritional status for PFS (p=0.0007). In patients with a good ECOG-PS, nutritional status was predictive for PFS., Conclusions: In current daily practice in Belgium, half of older patients with colorectal cancer treated with chemotherapy also receive bevacizumab. Nearly half of older patients presented with severe toxicity during treatment. Baseline nutritional status is a predictive marker for PFS. Patients with a baseline ECOG-PS≥2 have shorter PFS and higher risk of severe toxicity and should therefore be treated with caution., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: To evaluate capecitabine-docetaxel (XT), with trastuzumab (H) in human epidermal growth factor receptor 2 (HER2)-positive disease, in inoperable locally advanced breast cancer (LABC)., Patients and Methods: Patients received up to six neoadjuvant 21-day cycles of capecitabine 900 mg/m(2) twice daily, days 1-14, plus docetaxel 36 mg/m(2), days 1 and 8. Patients with HER2-positive disease also received trastuzumab 6 mg/kg every 3 weeks. The primary end point was pathologic complete response (pCR) rate, evaluated separately in HER2-negative and HER2-positive cohorts. Secondary end points included clinical response rates and tolerability., Results: The pCR rate was 15% [95% confidence interval (CI) 7-28] in 53 patients receiving XT and 40% (95% CI 26-55) in 50 patients receiving HXT. After neoadjuvant therapy, 50 patients receiving XT and 45 receiving HXT underwent surgery. No unexpected toxicity was observed: the most common grade ≥3 adverse events were diarrhea/mucositis (30% and 20%, respectively) and grade 3 hand-foot syndrome (11% and 6%, respectively). Disease-free survival and overall survival were similar with XT and HXT after median follow-up of 22 months in the XT cohort and 21 months in the HXT cohort., Conclusion: Neoadjuvant XT (HXT in HER2-positive disease) is highly effective in inoperable LABC, demonstrating pCR rates of 15% and 40%, respectively. This non-anthracycline-containing regimen offers obvious benefits in early disease, where avoidance of long-term cardiotoxicity is particularly important.