{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T18:05:29Z","timestamp":1779905129530,"version":"3.53.1"},"reference-count":54,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,18]],"date-time":"2022-03-18T00:00:00Z","timestamp":1647561600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Novocure Ltd","award":["Not applicable"],"award-info":[{"award-number":["Not applicable"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Advanced hepatocellular carcinoma (HCC) is an aggressive disease associated with poor prognosis. Tumor Treating Fields (TTFields) therapy is a non-invasive, loco-regional treatment approved for glioblastoma and malignant pleural mesothelioma. HCC preclinical and abdominal simulation data, together with clinical results in other solid tumors, provide a rationale for investigating TTFields with sorafenib in this patient population. HEPANOVA was a phase II, single arm, historical control study in adults with advanced HCC (NCT03606590). Patients received TTFields (150 kHz) for \u226518 h\/day concomitant with sorafenib (400 mg BID). Imaging assessments occurred every 12 weeks until disease progression. The primary endpoint was the overall response rate (ORR). Safety was also evaluated. Patients (n = 27 enrolled; n = 21 evaluable) had a poor prognosis; &gt;50% were Child\u2013Turcotte\u2013Pugh class B and &gt;20% had a baseline Eastern Clinical Oncology Group performance status (ECOG PS) of 2. The ORR was higher, but not statistically significant, for TTFields\/sorafenib vs. historical controls: 9.5% vs. 4.5% (p = 0.24), respectively; all responses were partial. Among patients (n = 11) with \u226512 weeks of TTFields\/sorafenib, ORR was 18%. Common adverse events (AEs) were diarrhea (n = 15\/27, 56%) and asthenia (n = 11\/27, 40%). Overall, 19\/27 (70%) patients had TTFields-related skin AEs; none were serious. TTFields\/sorafenib improved response rates vs. historical controls in patients with advanced HCC, with no new safety concerns or related systemic toxicity.<\/jats:p>","DOI":"10.3390\/cancers14061568","type":"journal-article","created":{"date-parts":[[2022,3,20]],"date-time":"2022-03-20T21:25:00Z","timestamp":1647811500000},"page":"1568","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Tumor Treating Fields Concomitant with Sorafenib in Advanced Hepatocellular Cancer: Results of the HEPANOVA Phase II Study"],"prefix":"10.3390","volume":"14","author":[{"given":"Eleni","family":"Gkika","sequence":"first","affiliation":[{"name":"Department for Radiation Oncology, University Medical Centre Freiburg, Robert-Koch-Stra\u00dfe 3, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anca-Ligia","family":"Grosu","sequence":"additional","affiliation":[{"name":"Department for Radiation Oncology, University Medical Centre Freiburg, Robert-Koch-Stra\u00dfe 3, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Macarulla Mercade","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Vall d\u2019Hebr\u00f3n University Hospital and Vall d\u2019Hebr\u00f3n Institute of Oncology, 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Cubillo Graci\u00e1n","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Centro Integral Oncol\u00f3gico Clara Campal HM CIOCC, Hospital Universitario HM Sanchinarro, 28050 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas B.","family":"Brunner","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy, University Hospital Magdeburg, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Schulthei\u00df","sequence":"additional","affiliation":[{"name":"Department of Medicine II, University Hospital Freiburg, 79106 Freiberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Pazgan-Simon","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Hepatology, Wroclaw Medical University, 50-367 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Seufferlein","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University Hospital Ulm, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yann","family":"Touchefeu","sequence":"additional","affiliation":[{"name":"Nantes Universit\u00e9, CHU Nantes, Institut des Maladies de l\u2019Appareil Digestif (IMAD), H\u00e9pato-Gastroent\u00e9rologie, Inserm CIC 1413, F-44000 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/s41572-020-00240-3","article-title":"Hepatocellular carcinoma","volume":"7","author":"Llovet","year":"2021","journal-title":"Nat. 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