Citations 2
Incidence and clinical outcomes of perforations during mechanical thrombectomy for medium vessel occlusion in acute ischemic stroke: A retrospective, multicenter, and multinational study
Musmar, Basel , Salim, Hamza , Kobeissi, Hassan , Shaikh, Hamza , Khalife, Jane , Abdalkader, Mohamad , Klein, Piers , Heit, Jeremy J. , Regenhardt, Robert W. , Cancelliere, Nicole M , Amllay, Abdelaziz , Dusart, Anne , Bellante, Flavio, Rouchaud, Aymeric , Puri, Ajit S , Dyzmann, Christian , Kan, Peter , Colasurdo, Marco , Berge, Jérôme , Barreau, Xavier , Nedelcu, Simona , Henninger, Nils , Marotta, Thomas R. , Stapleton, Christopher J. , Rabinov, James D. , Dofuku, Shogo , Tan, Benjamin Yong‐Qiang , Salazar‐Marioni, Sergio , Capirossi, Carolina , Chervak, Lina , Adeeb, Nimer , Tjoumakaris, Stavropoula , Khandelwal, Priyank , Biswas, Arundhati , Clarençon, Frédéric , Elhorany, Mahmoud , Premat, Kévin , Valente, Iacopo , Filipe, João Pedro , Varela, Ricardo , Quintero‐Consuegra, Miguel , Gonzalez, Nestor R. , Möhlenbruch, Markus , Costalat, Vincent , Yedavalli, Vivek , Aziz, Yasmin , Stracke, Christian Paul , Kadirvel, Ramanathan , Hsieh, Cheng‐Yang , Liebeskind, David S. , Alexandre, Andrea , Tancredi, Illario , Faizy, Tobias D. , Lubicz, Boris , Patel, Aman B. , Guenego, Adrien , Musmar, Basel , Salim, Hamza , Kobeissi, Hassan , Klein, Piers , Nguyen, Thanh N , Regenhardt, Robert W , Bellante, Flavio , Forestier, Géraud , Marnat, Gaultier , Ota, Takahiro , Dofuku, Shogo , Yeo, Leonard Ll , Salazar-Marioni, Sergio , Jabbour, Pascal , Gonzalez, Nestor R , Möhlenbruch, Markus A , Jesser, Jessica , Aziz, Yasmin , Alexandru Radu, Răzvan , Faizy, Tobias D , Fahed, Robert , Liebeskind, David S. , Heit, Jeremy J , Yedavalli, Vivek S , Cancelliere, Nicole M , Rouchaud, Aymeric , Colasurdo, Marco , Henninger, Nils , Tan, Benjamin Yq , Alexandre, Andrea M , Varela, Ricardo , Dmytriw, Adam A. , Ghozy, Sherief , Siegler, James E. , Nguyen, Thanh N. , Bernstock, Joshua D. , Naamani, Kareem El , Meyer, Lukas , Forestier, Géraud , Saleme, Suzana , Mounayer, Charbel , Fiehler, Jens , Kühn, Anna Luisa , Sibon, Igor , Gopinathan, Anil , Martinez-Gutierrez, Juan Carlos , Sheth, Sunil A , Renieri, Leonardo , Mowla, Ashkan , Vagal, Achala , Cuellar, Hugo , Jabbour, Pascal , Khandelwal, Priyank , Pedicelli, Alessandro , Schiphorst, Adrien ter , Harker, Pablo , Gory, Benjamin , Hecker, Constantin , Killer-Oberpfalzer, Monika , Griessenauer, Christoph J. , Thomas, Ajith J , Radu, Răzvan Alexandru , Fahed, Robert , Weyland, Charlotte S. , Mendes Pereira, Vitor
European Stroke Journal | February 27, 2024 | Volume: 9 | Issue: 2 | Pages: 328-337
Abstract Background: Mechanical thrombectomy (MT) has revolutionized the treatment of acute ischemic stroke (AIS) due to large vessel occlusion (LVO), but its efficacy and safety in medium vessel occlusion (MeVO) remain less explored. This multicenter, retrospective study aims to investigate the incidence and clinical outcomes of vessel perforations (confirmed by extravasation during an angiographic series) during MT for AIS caused by MeVO. Methods: Data were collected from 37 academic centers across North America, Asia, and Europe between September 2017 and July 2021. A total of 1373 AIS patients with MeVO underwent MT. Baseline characteristics, procedural details, and clinical outcomes were analyzed. Results: The incidence of vessel perforation was 4.8% (66/1373). Notably, our analysis indicates variations in perforation rates across different arterial segments: 8.9% in M3 segments, 4.3% in M2 segments, and 8.3% in A2 segments (p = 0.612). Patients with perforation had significantly worse outcomes, with lower rates of favorable angiographic outcomes (TICI 2c-3: 23% vs 58.9%, p < 0.001; TICI 2b-3: 56.5% vs 88.3%, p < 0.001). Functional outcomes were also worse in the perforation group (mRS 0–1 at 3 months: 22.7% vs 36.6%, p = 0.031; mRS 0–2 at 3 months: 28.8% vs 53.9%, p < 0.001). Mortality was higher in the perforation group (30.3% vs 16.8%, p = 0.008). Conclusion: This study reveals that while the occurrence of vessel perforation in MT for AIS due to MeVO is relatively rare, it is associated with poor functional outcomes and higher mortality. The findings highlight the need for increased caution and specialized training in performing MT for MeVO. Further prospective research is required for risk mitigation strategies.
Pharmacodynamic effects of regorafenib in metastatic colorectal carcinoma (mCRC).
Wong, Andrea Li Ann , Lim, Robert, Soh, Inho, Titin, Christina, Soong, Richie Chuan Teck, Pang, Brendan, Sapari, Nur Sabrina, Wang, Ting Ting, Zee, Ying Kiat, Chuah, Benjamin, Jeffers, Michael , Lathia, Chetan, Trnkova, Zuzana Jirakova , Wilhelm, Scott M., Sinha, Arvind Kumar , Gopinathan, Anil , Tan, Chee‐Seng , Soh, I Peng Thomas, Venkatesh, Sudhakar K. , Soong, Richie Chuan Teck, Goh, Boon Cher
Journal of Clinical Oncology | March 11, 2020 | Volume: 31 | Issue: 15_suppl | Pages: e14507-e14507
10.1200/jco.2013.31.15_suppl.e14507
e14507 Background: Regorafenib, an oral multikinase inhibitor of VEGFR2/3, PDGFRb, KIT, FGFR, RET, RAF and TIE2, is efficacious in refractory mCRC but its mechanism of action is unclear and predictive biomarkers are lacking. Methods: We assessed tumor and circulatory biomarkers in a phase 2 study of regorafenib in refractory mCRC patients. Regorafenib was administered orally at 160mg/d for 3 out of 4 weeks. Post cycle 2 response was assessed by RECIST 1.1. Subjects were scheduled for FDG PET-CT scans (pre + D15) and paired core needle tumor biopsies for IHC analysis (pre + D21) in cycle 1. Archival tumor mutations were evaluated using Sequenom MassARRAY OncoCarta Panel V1.0 assay. Results: 35 patients were treated; 49% received > 4 prior therapies and 43% had prior bevacizumab. Median PFS was 3.45 mths (95% CI: 3.40-3.49), ORR was 3% and disease control rate [DCR] (PR + SD at 8 wks) was 57%. Early PET responses (EORTC criteria) were seen in 49%, but did not predict for DCR (p=1.0). Fatigue, hand foot skin reaction (HFSR), voice change and diarrhea occurred in > 30% of subjects. Grade 3-5 toxicities occurred in 46%, the commonest being HFSR and rash (17% each). Median relative dose intensity was 92%; 43% required > 1 dose reduction, 60% required > 1 dose interruption. KRAS (29%), BRAF (9%), EGFR (9%), NRAS (6%) KIT (3%), PIK3CA (3%), PDGFRA (3%) and CDK (3%) mutations were detected in archival tumors. None predicted for ORR or DCR; PFS was identical in KRAS mutant vs wt patients (3.45 mths, p=0.39) and similar in BRAF mutant vs wt patients (3.48 vs 3.45 mths, p=0.10). The patient with the longest PFS (12.6 mths) had a BRAF mutation. Amongst the 10 paired tumor samples available, IHC markers upregulated in >50% cases were pMEK, pERK, pJun and pJNK, whilst those downregulated/ unchanged in >50% were pKIT, pVEGFR2, CD31 [vascular endothelial cells (ECs)] and podoplanin (lymphatic ECs). The greatest change was observed in podoplanin expression, corresponding to a 60% reduction in lymphatic vessel density. Conclusions: FDG-PET responses in cycle 1 did not predict for regorafenib clinical benefit in mCRC patients. Targeting lymphatic/vascular ECs in the tumor microenvironment may be a more significant antitumor mechanism of regorafenib than MAP kinase pathway inhibition. Clinical trial information: NCT01189903.