Scientific letter
Complete tumor response after concomitant treatment with lenvatinib and radioembolization with Ytrio-90 of advanced stage hepatocarcinoma
Respuesta tumoral completa tras el tratamiento concomitante con lenvatinib y radioembolización con Ytrio-90 de un hepatocarcinoma en estadio avanzado
Belén Martínez Benitoa,
, Víctor González Pintora, Lourdes del Campo del Valb, Luisa García-Bueya
Corresponding author
a Servicio de Aparato Digestivo, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), Madrid, Spain
b Servicio de Radiodiagnóstico, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid (UAM), Madrid, Spain
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array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Lourdes" "apellidos" => "del Campo del Val" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "Luisa" "apellidos" => "García-Buey" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Aparato Digestivo, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Radiodiagnóstico, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid (UAM), Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Respuesta tumoral completa tras el tratamiento concomitante con lenvatinib y radioembolización con Ytrio-90 de un hepatocarcinoma en estadio avanzado" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1387 "Ancho" => 1605 "Tamanyo" => 316736 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(a) Multimodal CT image with intravenous contrast (June 2022): arterial (A), portal (P) and late (T) phases. Tumour thrombus in the right posterior portal branch with uptake and lavage; (b) SPECT-CT axial section image (September 2022). The radiopharmaceutical is deposited at the site of the tumour thrombus; (c) Multimodal contrast-enhanced CT image post-radioembolisation (December 2022). Arterial (A), portal (P) and late (T) phases. Absence of uptake of the tumour thrombus. Small areas of infarction in liver segment 7.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Hepatocellular carcinoma (HCC) is the most common primary liver cancer and one of the main causes of death in patients with liver cirrhosis. Patients with normal liver function and good functional status who have HCC with vascular or extrahepatic invasion are classified as advanced stage (stage C) according to the Barcelona Clinic Liver Cancer (BCLC) staging system. In recent years, there have been significant advances in treatment, with either the combination atezolizumab-bevacizumab or tremelimumab-durvalumab currently considered the first-line drugs of choice. If these are contraindicated or not available, lenvatinib, sorafenib or durvalumab would be indicated.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> There are also ongoing studies assessing the utility of locoregional therapies, such as transarterial radioembolisation (TARE) using Yttrium-90 spheres in this context.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We present here the case of a female patient in whom systemic treatment with lenvatinib was combined with TARE with Yttrium-90 for the treatment of advanced-stage HCC due to the presence of portal vein tumour thrombosis.</p><p id="par0015" class="elsevierStylePara elsevierViewall">This was a 67-year-old woman with a history of polymyalgia rheumatica, liver cirrhosis with portal hypertension, Child-Pugh A, due to autoimmune hepatitis and hepatitis C virus, treated and in sustained virological response. She was diagnosed with HCC in segment 7 and treated by radiofrequency ablation in 2018.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Years later, an increase in alpha-fetoprotein to 80 ng/mL was detected. Computed tomography (CT) detected a 10-mm pseudonodular area with arterial enhancement and early lavage consistent with HCC in liver segment 6; ablative treatment with microwaves was performed in March 2022. Given the persistent rise of alpha-fetoprotein to 674 ng/mL, a repeat CT scan was performed. A post-ablation cystic cavity was observed in segment 6 and, adjacent to it, a thrombus in the posterior branches of the right portal vein, with uptake in the arterial phase and lavage in the portal and late phases, consistent with intravascular tumour (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>a). In view of these findings: hepatocellular carcinoma with vascular invasion in a patient in excellent general condition and preserved liver function, consistent with BCLC-stage C,<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> and given that the history of autoimmune diseases contraindicated the use of atezolizumab-bevacizumab, she was started on systemic treatment with lenvatinib in June 2022.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,4</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Despite treatment, alpha-fetoprotein continued rising to 1,975 ng/mL. It was decided to perform TARE of the tumour thrombus using Yttrium-90 micro-spheres in September 2022, achieving technical success (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>b). The follow-up CT scan in December 2022 showed atrophy of the posterior segments of the right lobe of the liver and necrosis of the portal vein tumour thrombosis, which had completely lost its arterial vascularisation, suggesting a response to TARE according to the modified response evaluation criteria in solid tumours (m-RECIST) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>c). Alpha-fetoprotein levels decreased to 4 ng/mL and the patient remained asymptomatic, continuing on lenvatinib. After a year of follow-up, we were able to confirm a sustained tumour response and normal liver function.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Lenvatinib is a receptor tyrosine kinase inhibitor used in the systemic treatment of advanced-stage HCC when either the combination atezolizumab-bevacizumab or tremelimumab-durvalumab is contraindicated.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,4</span></a> TARE with Yttrium-90 is a locoregional treatment applied to HCC in all stages. In portal vein tumour thrombosis, radioembolisation with Yttrium-90 micro-spheres enables deep infiltration into the tumour without causing ischaemia of the adjacent liver parenchyma, which means TARE has an adequate safety profile.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Currently, the evidence supporting the use of radioembolisation in HCC is primarily based on cohort studies.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> However, the available randomised clinical trials comparing the efficacy of sorafenib with that of TARE (SARAH and SIRveNIB), and the SORAMIC trial, which compares sorafenib with the combination of sorafenib and TARE, have not been able to demonstrate its superiority over sorafenib in terms of overall survival, despite showing that TARE has a better tumour response rate and tolerance.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">More studies are warranted to evaluate the benefit of TARE in selected patient subgroups, such as those with portal vein tumour thrombosis.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,5</span></a> Studies need to take into account the radiation dose delivered to the tumour, as this determines the effectiveness of the technique,<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> and determine the duration of the tumour response.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Ethical responsibilities</span><p id="par0040" class="elsevierStylePara elsevierViewall">All ethical procedures have been implemented. The privacy rights of the subjects have been respected.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Funding</span><p id="par0045" class="elsevierStylePara elsevierViewall">No financial support has been received for the conduct of the research or for the preparation of the article.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Authors</span><p id="par0050" class="elsevierStylePara elsevierViewall">Belén Martínez Benito: authorship of the manuscript.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Luisa García-Buey: conception of the manuscript, supervision of the drafting of the manuscript, diagnosis and treatment of the patients included.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Other authors: diagnosis and treatment of the patients included.</p><p id="par0065" class="elsevierStylePara elsevierViewall">All authors approved the final version of the manuscript.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Ethical responsibilities" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Funding" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Authors" ] 3 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1387 "Ancho" => 1605 "Tamanyo" => 316736 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(a) Multimodal CT image with intravenous contrast (June 2022): arterial (A), portal (P) and late (T) phases. Tumour thrombus in the right posterior portal branch with uptake and lavage; (b) SPECT-CT axial section image (September 2022). The radiopharmaceutical is deposited at the site of the tumour thrombus; (c) Multimodal contrast-enhanced CT image post-radioembolisation (December 2022). Arterial (A), portal (P) and late (T) phases. Absence of uptake of the tumour thrombus. Small areas of infarction in liver segment 7.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "[1]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diagnóstico y tratamiento del carcinoma hepatocelular. Actualización del documento de consenso de la AEEH, AEC, SEOM, SERAM, SERVEI y SETH" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Reig" 1 => "A. 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