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array:24 [ "pii" => "S2173510719300175" "issn" => "21735107" "doi" => "10.1016/j.rxeng.2018.10.004" "estado" => "S300" "fechaPublicacion" => "2019-03-01" "aid" => "1102" "copyright" => "SERAM" "copyrightAnyo" => "2018" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Radiologia. 2019;61:134-42" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 7 "formatos" => array:2 [ "HTML" => 3 "PDF" => 4 ] ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0033833818302133" "issn" => "00338338" "doi" => "10.1016/j.rx.2018.10.009" "estado" => "S300" "fechaPublicacion" => "2019-03-01" "aid" => "1102" "copyright" => "SERAM" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Radiologia. 2019;61:134-42" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 2274 "formatos" => array:3 [ "EPUB" => 1 "HTML" => 1583 "PDF" => 690 ] ] "es" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Radiología en Imágenes</span>" "titulo" => "Inmunoterapia en oncología: un nuevo desafío radiológico" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "134" "paginaFinal" => "142" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Immunotherapy in oncology: a new challenge for radiologists" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0045" "etiqueta" => "Figura 9" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr9.jpeg" "Alto" => 1145 "Ancho" => 1733 "Tamanyo" => 157503 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Varón de 64 años, con melanoma y metástasis en el cuerpo vertebral de C7 intervenido, que realizó tratamiento completo con ipilimumab. Presenta dolor abdominal y hematoquecia en relación con colitis autoinmune perforada. Reconstrucción coronal. A) Tomografía computarizada (TC) de abdomen con ventana de pulmón con visualización de neumoperitoneo (flecha blanca). B) Imagen axial con ventana de partes blandas con engrosamiento, edema y realce de la pared del colon y líquido libre intraabdominal (flecha blanca). C) Imagen axial de TC de abdomen con ventana de pulmón con aire extraluminal en relación con neumoperitoneo (flecha blanca).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "A. Bustos Fiore, A. Banguero Gutiérrez, L. Guerrero Acosta, C. Segura Cros, R. Ramos de la Rosa" "autores" => array:5 [ 0 => array:2 [ "nombre" => "A." "apellidos" => "Bustos Fiore" ] 1 => array:2 [ "nombre" => "A. Banguero" "apellidos" => "Gutiérrez" ] 2 => array:2 [ "nombre" => "L. Guerrero" "apellidos" => "Acosta" ] 3 => array:2 [ "nombre" => "C." "apellidos" => "Segura Cros" ] 4 => array:2 [ "nombre" => "R." "apellidos" => "Ramos de la Rosa" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2173510719300175" "doi" => "10.1016/j.rxeng.2018.10.004" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173510719300175?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0033833818302133?idApp=UINPBA00004N" "url" => "/00338338/0000006100000002/v1_201903020656/S0033833818302133/v1_201903020656/es/main.assets" ] ] "itemSiguiente" => array:18 [ "pii" => "S2173510719300187" "issn" => "21735107" "doi" => "10.1016/j.rxeng.2018.06.001" "estado" => "S300" "fechaPublicacion" => "2019-03-01" "aid" => "1104" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Radiologia. 2019;61:143-52" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 18 "formatos" => array:2 [ "HTML" => 16 "PDF" => 2 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Report</span>" "titulo" => "Value of Posterior circulation ASPECTS and Pons-Midbrain Index on non-contrast CT and CT Angiography Source Images in patients with basilar artery occlusion recanalized after mechanical thrombectomy" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "143" "paginaFinal" => "152" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Valor de la escala ASPECTS de circulación posterior y del índice puente-mesencéfalo en imágenes de TC sin contraste y angiografía por TC en pacientes con oclusiones de la arteria basilar recanalizados tras trombectomía mecánica" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1612 "Ancho" => 2500 "Tamanyo" => 336750 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">ASPECTS (Alberta Stroke Program Early CT Score) scale (A, B and C) and pons-midbrain index (PMI) (D and E). On the pc-ASPECTS scale, we deducted one or two points depending on the territory affected: right or left thalamus, cerebellum or the territory of the posterior cerebral artery (one point); any part of the midbrain or pons (two points). A score of ten indicates a normal scan. On the PMI, we divided the pons and midbrain into two territories each (left and right). We assigned one point when 50% or less of the territory was affected and two points if more than 50% of the territory was affected. A score of zero indicated a normal scan.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "M.F. Werner, A. López-Rueda, F.X. Zarco, J. Blasco, L San Román, S. Amaro, E. Carrero, R. Valero, L. Oleaga, J.M. Macho, N. Bargalló" "autores" => array:11 [ 0 => array:2 [ "nombre" => "M.F." "apellidos" => "Werner" ] 1 => array:2 [ "nombre" => "A." "apellidos" => "López-Rueda" ] 2 => array:2 [ "nombre" => "F.X." "apellidos" => "Zarco" ] 3 => array:2 [ "nombre" => "J." "apellidos" => "Blasco" ] 4 => array:2 [ "nombre" => "L" "apellidos" => "San Román" ] 5 => array:2 [ "nombre" => "S." "apellidos" => "Amaro" ] 6 => array:2 [ "nombre" => "E." "apellidos" => "Carrero" ] 7 => array:2 [ "nombre" => "R." "apellidos" => "Valero" ] 8 => array:2 [ "nombre" => "L." "apellidos" => "Oleaga" ] 9 => array:2 [ "nombre" => "J.M." "apellidos" => "Macho" ] 10 => array:2 [ "nombre" => "N." "apellidos" => "Bargalló" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0033833818302157" "doi" => "10.1016/j.rx.2018.06.004" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0033833818302157?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173510719300187?idApp=UINPBA00004N" "url" => "/21735107/0000006100000002/v1_201903140618/S2173510719300187/v1_201903140618/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S2173510718300715" "issn" => "21735107" "doi" => "10.1016/j.rxeng.2018.02.008" "estado" => "S300" "fechaPublicacion" => "2019-03-01" "aid" => "1075" "copyright" => "SERAM" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Radiologia. 2019;61:124-33" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 3 "formatos" => array:2 [ "HTML" => 1 "PDF" => 2 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Update in Radiology</span>" "titulo" => "Vascular malformations and tumors. Part 2: Low-flow lesions" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "124" "paginaFinal" => "133" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Malformaciones vasculares y tumores de partes blandas. Parte 2: lesiones de bajo flujo" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0045" "etiqueta" => "Figure 9" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr9.jpeg" "Alto" => 698 "Ancho" => 1750 "Tamanyo" => 113661 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">17-Year-old female with Surge–Weber syndrome. Susceptibility weighted image (a) shows atrophy and cortical mineralization involving the sulcus of the right parietal-temporal occipital convexity (arrows), reflecting low vascular malformations in the pia mater. Marked right calvarial thickening is seen on axial T2-weighted (b) and coronal T1-weighted (c) images. Facial capillary malformation was present on clinical exam.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "L. Flors, K.D. Hagspiel, A.W. Park, P.T. Norton, C. Leiva-Salinas" "autores" => array:5 [ 0 => array:2 [ "nombre" => "L." "apellidos" => "Flors" ] 1 => array:2 [ "nombre" => "K.D." "apellidos" => "Hagspiel" ] 2 => array:2 [ "nombre" => "A.W." "apellidos" => "Park" ] 3 => array:2 [ "nombre" => "P.T." "apellidos" => "Norton" ] 4 => array:2 [ "nombre" => "C." "apellidos" => "Leiva-Salinas" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0033833818301486" "doi" => "10.1016/j.rx.2018.02.012" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0033833818301486?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173510718300715?idApp=UINPBA00004N" "url" => "/21735107/0000006100000002/v1_201903140618/S2173510718300715/v1_201903140618/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Radiology through images</span>" "titulo" => "Immunotherapy in oncology: A new challenge for radiologists" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "134" "paginaFinal" => "142" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "A. Bustos Fiore, A. Banguero Gutiérrez, L. Guerrero Acosta, C. Segura Cros, R. Ramos de la Rosa" "autores" => array:5 [ 0 => array:4 [ "nombre" => "A." "apellidos" => "Bustos Fiore" "email" => array:2 [ 0 => "arianabustos@hotmail.com" 1 => "ariana.bustos@quironsalud.es" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "A." "apellidos" => "Banguero Gutiérrez" ] 2 => array:2 [ "nombre" => "L." "apellidos" => "Guerrero Acosta" ] 3 => array:2 [ "nombre" => "C." "apellidos" => "Segura Cros" ] 4 => array:2 [ "nombre" => "R." "apellidos" => "Ramos de la Rosa" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Hospital Universitario Quirón Dexeus, Barcelona, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Inmunoterapia en oncología: un nuevo desafío radiológico" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 929 "Ancho" => 1587 "Tamanyo" => 81896 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">The PD-1 immunosuppression mechanism as a target for cancer therapy. PD-1 is expressed on the surface of effector T-cells after activation and its ligand PD-L1 is expressed in the tumour cell. PD-1 to PD-L1 binding gives an inhibitory signal in through SHP2 phosphatases, which reduces cytokine production and T-cell proliferation, thereby allowing tumour cells to evade the host's immune response. Anti-PD-1 and PD-L1 antibodies prevent this binding and block the immune inhibition by the tumour, inducing an immune response against the tumour.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Unlike conventional cancer treatments that fight tumour cells using surgery, radiation and cytotoxic chemotherapy, immunotherapy uses the passive and active immune response to treat the cancer. There are two modes of treatment: passive immunotherapy, which is already an established therapy in some types of cancer, and active immunotherapy, which is an emerging treatment. A good response to cytotoxic chemotherapy is characterised by a rapid reduction in tumour size and lack of appearance of new lesions. In contrast, with active immunotherapy there may be an initial delay in the response to treatment (slow reduction in tumour size), the appearance of new lesions or an increase in total tumour load without this necessarily indicating tumour progression. It can also cause undesired activation of autoimmunity and give rise to a wide variety of toxic effects that must be recognised and treated immediately. The objective of this work is to evaluate the radiological patterns of response to treatment using immune-related response criteria and to describe the associated adverse effects.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">1</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Molecular mechanisms of action of immunotherapy agents</span><p id="par0010" class="elsevierStylePara elsevierViewall">Its development is based on the concept of immune surveillance, which is the immune system's ability to detect tumour cells and develop a response capable of destroying them. However, the body is not capable of generating a sufficiently large antitumour response, which allows the cells to grow and metastasise. Immunotherapy's objective is to enhance the immune system, enabling it to generate a more effective response. This can be achieved in two ways:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">•</span><p id="par0015" class="elsevierStylePara elsevierViewall">Passive immunotherapy: this is based on the administration of preformed monoclonal antibodies that act directly on the known cancer proteins associated with that tumour; the disadvantage is that resistance may develop.</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">•</span><p id="par0020" class="elsevierStylePara elsevierViewall">Active immunotherapy: various forms exist such as cytokines, biochemical therapy and immunomodulatory therapy with monoclonal antibodies. This last technique, which we will focus on, uses drugs that act to block immune checkpoints, allowing T-cell-mediated activation of the immune system. The available agents are: cytotoxic T-lymphocyte antigen-4 inhibitors, anti-CTLA-4 (ipilimumab), programmed cell death protein-1 inhibitors, anti-PD-1 (nivolumab and pembrolizumab) and programmed cell death ligand-1 inhibitors, anti-PD-L1 (atezolizumab and durvalumab). The mechanisms of action of these drugs are shown in <a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1 and 2</a>.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia></li></ul></p><p id="par0025" class="elsevierStylePara elsevierViewall">It should be noted that immunotherapy enhances the immune system so that it generates a more effective response.</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Clinical applications</span><p id="par0030" class="elsevierStylePara elsevierViewall">These new therapies are used to treat advanced treatment-resistant cancer or recurrent disease that does not respond to conventional treatment.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">2</span></a> They are indicated for the treatment of advanced melanoma, non-small cell lung carcinoma, renal cell carcinoma, urothelial carcinoma and squamous cell carcinoma of the head and neck. Their use also extends to some haematological cancers such as treatment-resistant Hodgkin's lymphoma.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">3</span></a> They can be used as monotherapy, although combinations already authorised include anti-PD-1/anti-CTLA-4 for advanced melanoma and anti-PD-1/first-line chemotherapy for non-small cell lung carcinoma.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">2</span></a></p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">New treatment response patterns</span><p id="par0035" class="elsevierStylePara elsevierViewall">In tumours treated with cytotoxic chemotherapy, the RECIST (Response Evaluation Criteria In Solid Tumors) 1.1 criteria are used, and a response is considered favourable if there is a decrease in tumour size a few weeks after the start of treatment. In contrast, tumour growth or the presence of new lesions is considered disease progression and tumour stability after the end of treatment is often transitory and is also an indication of failure. With active immunotherapy, these criteria are of no use and response criteria relating to immunity have been proposed. These include new measurable lesions within the “total tumour load” compared with respect to the baseline. “Total tumour load” is calculated using bidirectional measurements, the sum of products of diameters (SPD) of all target lesions (5 lesions per organ), up to a maximum of 10 visceral and 5 cutaneous lesions. In subsequent follow-up, new lesions are added to the total tumour load and are not systematically interpreted as disease progression, avoiding treatment withdrawal (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">4</span></a> The concept of “pseudoprogression” has been introduced—an initial increase in total tumour load that later falls at subsequent follow-ups and that is due to peritumoural oedema, lymphocytic infiltrate or persistence of tumour growth due to an initial delay in the response to treatment.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">5</span></a> It is also worth highlighting that “pseudoprogression” appears at approximately 12 weeks from the start of treatment and occurs in only a small number of patients (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>). For most patients, new or growing lesions represent true progression (<a class="elsevierStyleCrossRef" href="#fig0025">Fig. 5</a>).<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">6</span></a> Another manifestation is “hyperprogression”, characterised by rapid disease progression after administering these drugs due to an acceleration in the growth kinetics of the tumour cells. This is described in some 29% of patients and is associated with shorter survival periods.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">7</span></a> The “abscopal” effect is a rare phenomenon observed in patients treated with immunomodulatory agents who are also receiving radiotherapy; it refers to the shrinkage of tumours away from the site receiving radiotherapy. It has been reported in melanoma, lymphoma and renal cell cancer and it has been postulated that the radiotherapy triggers an increase in the systemic immune response.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">8</span></a></p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><elsevierMultimedia ident="fig0025"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">These “immune-related response criteria” (IrRC) have limitations: bidirectional measurements take longer and give rise to greater intra- and interobserver variability than unidirectional measurements. It is difficult to compare studies evaluated with RECIST 1.1 and then IrRC during the treatment of patients who receive first-line cytotoxic chemotherapy followed by immunotherapy.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">9</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Several radiological investigations have focussed on this point with the aim of unifying strategies, and the results point towards an “immune-related RECIST 1.1” as a practical way to help compare tumour responses. Another line of investigation is seeking to incorporate additional markers that could optimise the response assessment such as tumour density measured in Hounsfield units (HU), volume or metabolic activity.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">10</span></a> In one study,<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">11</span></a> although an objective response appeared much earlier, the mean time until the complete response criteria were met in patients who achieved this was thirty months, with a range from three to seventy months (<a class="elsevierStyleCrossRef" href="#fig0030">Fig. 6</a>).</p><elsevierMultimedia ident="fig0030"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">It should be noted that one of the key points of the IrRC criteria is the need to assess the response during and after the end of treatment, with two consecutive studies separated by at least four weeks.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Adverse effects</span><p id="par0055" class="elsevierStylePara elsevierViewall">A large number of autoimmune adverse effects are described below (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). These can present in asymptomatic patients and are detected in radiological follow-up, and therefore must be diagnosed and, depending on their severity, a decision made on whether to suspend the treatment.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">12</span></a> In melanoma, some of these adverse effects have been associated with clinical benefit and are considered a marker of response to treatment.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">9</span></a> Moreover, there is evidence that these patients had more disease-free time and longer survival.<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">13</span></a> It is worth noting that, although the adverse effects are treated with high doses of corticosteroids, these do not appear to alter the duration of the tumour response.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">14</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Pulmonary and mediastinal disorders</span><p id="par0060" class="elsevierStylePara elsevierViewall">Pneumonitis: pneumonitis due to these drugs is rare, but potentially fatal. The figures for pneumonitis are higher in lung cancer and renal cell carcinoma than in melanoma. Its radiological presentation is non-specific, but diffuse ground-glass opacity, diffuse or patchy consolidations, traction bronchiectasis, loss of lung volume, pleural effusion and even a pattern simulating lymphangitis carcinomatosa may be observed.<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">15</span></a> In patients treated with nivolumab, pneumonitis presents at 2.6 months (mean; range of 0.5–11.5 months) and the patterns of presentation in descending order of frequency are: cryptogenic organising pneumonia, nonspecific interstitial pneumonia, hypersensitivity pneumonitis, acute interstitial pneumonia and distress. The treatment for autoimmune pneumonitis is suspension of the treatment and administration of oral or intravenous corticosteroids, and in patients who do not respond, immune suppressors (mycophenolate mofetil, cyclophosphamide or infliximab) must be administered. Up to 30% of patients can restart treatment once their clinical picture resolves, and, of these, pneumonitis recurs in 25–28%. Autoimmune pneumonitis has also been found to recur with the same radiological pattern without reintroduction of the immunotherapy when corticosteroid treatment is suspended, in which case the pneumonitis is considered to be caused by a baseline autoimmune mechanism. However, this could also be due to the long half-life of nivolumab, estimated at 27 days, with a time to complete elimination from tissues of up to four months (<a class="elsevierStyleCrossRefs" href="#fig0035">Figs. 7 and 8</a>).<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">16</span></a></p><elsevierMultimedia ident="fig0035"></elsevierMultimedia><elsevierMultimedia ident="fig0040"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">Sarcoidosis-like syndrome: observed in 5–7% of patients with melanoma who receive treatment with ipilimumab. Patients are often asymptomatic and computed tomography (CT) shows bilateral hilar and mediastinal lymphadenopathy and opacities in the lungs with a peribronchial distribution which normally remit spontaneously. The differential diagnosis must be performed with disease progression or metastatic disease,<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">3</span></a> confirmed using a biopsy to differentiate between the two possibilities where necessary.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Gastrointestinal disorders</span><p id="par0070" class="elsevierStylePara elsevierViewall">Colitis: this is one of the adverse effects most commonly associated with the use of ipilimumab, its frequency and severity depending on the dose. CT assesses the extent of the compromised bowel, thickening of the wall, distension and vascular ingurgitation of the mesenteric vessels. The most serious complication is perforation, which occurs in less than 1% of cases and has a mortality rate of 5% (<a class="elsevierStyleCrossRef" href="#fig0045">Fig. 9</a>).<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">17</span></a> Autoimmune colitis usually affects the descending colon, with two different patterns having been described:<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">•</span><p id="par0075" class="elsevierStylePara elsevierViewall">Diffuse colitis with mild wall thickening, which tends to present with watery diarrhoea and responds to treatment with corticosteroids.</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">•</span><p id="par0080" class="elsevierStylePara elsevierViewall">Segmental colitis associated with diverticulosis, which presents with diarrhoea and haematochezia and requires treatment with corticosteroids and antibiotics.</p></li></ul></p><elsevierMultimedia ident="fig0045"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">Pneumatosis intestinalis and bowel perforation: pneumatosis intestinalis is characterised by the presence of subserosal air, submucosal air or air in the wall of the intestine, and bowel perforation by the presence of air in the peritoneum. It is important to bear in mind that these two conditions, which are normally serious pathologies, can manifest in cancer patients treated with these therapies. The average time between the start of treatment and the perforation or pneumatosis is generally 1–13 months. Up to 70% are diagnosed in follow-up studies in asymptomatic patients. Air bubbles may be present in the mesenteric vein and portal vein and tend to be factors for poor prognosis. Treatment is conservative and the immunological treatment must be suspended.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">18</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Hepatitis: this is rare and detected due to elevated enzyme levels; its radiological manifestations are steatosis, hepatomegaly, oedema and periportal lymphadenopathy.<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">12,14</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">Pancreatitis: this can manifest as asymptomatic enzyme elevation or as necrotising pancreatitis. CT allows early detection of acute pancreatitis in symptomatic patients with ambiguous biochemistry results, as enzymes can be normal in up to 46% of cases. It is important to highlight that this clinical picture can be reversed by suspending the treatment and that it has a tendency to recur in up to 44% of cases (<a class="elsevierStyleCrossRef" href="#fig0050">Fig. 10</a>).<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">19</span></a></p><elsevierMultimedia ident="fig0050"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Endocrine disorders</span><p id="par0100" class="elsevierStylePara elsevierViewall">These are observed in up to 22% of patients treated with ipilimumab or nivolumab. The most common are thyroiditis and adrenal gland dysfunction, and the least common hypophysitis (<a class="elsevierStyleCrossRef" href="#fig0055">Fig. 11</a>).<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">9</span></a></p><elsevierMultimedia ident="fig0055"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Other disorders</span><p id="par0105" class="elsevierStylePara elsevierViewall">There are also neurological and musculoskeletal disorders that are associated with the treatment. In some cases, increased density of the retroperitoneal fat and that in the perirenal space has been described, which suggests infiltration by lymphocytes.</p><p id="par0110" class="elsevierStylePara elsevierViewall">It should be noted that patients who present adverse effects during the course of treatment have more disease-free time and longer survival.</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conclusion</span><p id="par0115" class="elsevierStylePara elsevierViewall">Imaging plays a fundamental role in early detection, monitoring and recurrence in cancer patients. Immunotherapy is a challenge from a radiological point of view in terms of both the assessment of response to treatment and the correct detection of associated adverse effects. This presents an opportunity for radiology; taking advantage of it will depend on the ability of radiologists to assess the effects of these new emerging therapies incorporating knowledge from various disciplines.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">20</span></a></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Authorship</span><p id="par0120" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">1.</span><p id="par0125" class="elsevierStylePara elsevierViewall">Responsible for the integrity of the study: ABF and ABG.</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">2.</span><p id="par0130" class="elsevierStylePara elsevierViewall">Study conception: ABF, ABG and LGA.</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">3.</span><p id="par0135" class="elsevierStylePara elsevierViewall">Study design ABF, ABG and CSC.</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">4.</span><p id="par0140" class="elsevierStylePara elsevierViewall">Data collection: ABF, ABG and RRR.</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">5.</span><p id="par0145" class="elsevierStylePara elsevierViewall">Data analysis and interpretation: ABF and CSC.</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">6.</span><p id="par0150" class="elsevierStylePara elsevierViewall">Statistical processing: N/A.</p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">7.</span><p id="par0155" class="elsevierStylePara elsevierViewall">Literature search: ABF, ABG and LGA.</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">8.</span><p id="par0160" class="elsevierStylePara elsevierViewall">Drafting of the article: ABF and ABG.</p></li><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">9.</span><p id="par0165" class="elsevierStylePara elsevierViewall">Critical review of the manuscript with intellectually relevant contributions: ABF, ABG and LGA.</p></li><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">10.</span><p id="par0170" class="elsevierStylePara elsevierViewall">Approval of the final version: ABF, ABG, RRR, CSC and LGA.</p></li><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">11.</span><p id="par0175" class="elsevierStylePara elsevierViewall">All authors have read and approved the final version of the article.</p></li></ul></p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conflicts of interest</span><p id="par0180" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres1163672" "titulo" => "Abstract" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1089246" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1163671" "titulo" => "Resumen" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "abst0015" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1089247" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Molecular mechanisms of action of immunotherapy agents" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Clinical applications" ] ] ] 6 => array:2 [ "identificador" => "sec0020" "titulo" => "New treatment response patterns" ] 7 => array:3 [ "identificador" => "sec0025" "titulo" => "Adverse effects" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0030" "titulo" => "Pulmonary and mediastinal disorders" ] 1 => array:2 [ "identificador" => "sec0035" "titulo" => "Gastrointestinal disorders" ] 2 => array:2 [ "identificador" => "sec0040" "titulo" => "Endocrine disorders" ] 3 => array:2 [ "identificador" => "sec0045" "titulo" => "Other disorders" ] ] ] 8 => array:2 [ "identificador" => "sec0050" "titulo" => "Conclusion" ] 9 => array:2 [ "identificador" => "sec0055" "titulo" => "Authorship" ] 10 => array:2 [ "identificador" => "sec0060" "titulo" => "Conflicts of interest" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-03-28" "fechaAceptado" => "2018-10-21" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1089246" "palabras" => array:5 [ 0 => "Imaging in oncology" 1 => "Directed molecular therapy" 2 => "Immunotherapy" 3 => "Criteria for immune response" 4 => "Adverse events" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1089247" "palabras" => array:5 [ 0 => "Imagen en oncología" 1 => "Terapia molecular dirigida" 2 => "Inmunoterapia" 3 => "Criterios de respuesta inmunológica" 4 => "Eventos adversos" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">In patients with oncologic disease, immunotherapy has become established as an alternative or complementary therapy to traditional treatment options (surgery, radiotherapy, and chemotherapy). Currently available immunotherapy modes can be divided into two types: passive and active. The active type strengthens the immune system's response to tumour cells by activating both humoral immunity and cell-mediated immunity, using the adaptive response. This article aims to analyse the radiologic patterns of the response to immunotherapy through immune-response-related criteria and to describe the main adverse effects associated with this treatment approach.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conclusion</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Imaging tests play a fundamental role in the follow-up of oncologic patients and in the assessment of their response to treatment. Immunotherapy represents a challenge for radiologists both in the evaluation of the response to immunotherapy and in the detection of the adverse effects associated with this treatment approach.</p></span>" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Objetivo</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">La inmunoterapia en oncología se ha establecido como una terapia alternativa o complementaria al tratamiento tradicional (cirugía, radioterapia y quimioterapia). La inmunoterapia disponible actualmente se divide en dos categorías: pasiva y activa. La respuesta activa refuerza el sistema inmune para responder frente a las células tumorales activando tanto la inmunidad humoral como la celular, utilizando la respuesta adaptativa. El objetivo de este trabajo es valorar los patrones radiológicos de respuesta al tratamiento inmunológico mediante los criterios de respuesta relacionados con la inmunidad (<span class="elsevierStyleItalic">immune related response criteria</span> [irRC]) y describir los principales efectos adversos asociados.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusión</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Las pruebas de imagen tienen un papel fundamental en el seguimiento y valoración de la respuesta al tratamiento en pacientes oncológicos. La inmunoterapia es un desafío en el enfoque radiológico tanto para la valoración de la respuesta al tratamiento como para la correcta detección de los efectos adversos asociados.</p></span>" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "abst0015" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusión" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Bustos Fiore A, Banguero Gutiérrez A, Guerrero Acosta L, Segura Cros C, Ramos de la Rosa R. Inmunoterapia en oncología: un nuevo desafío radiológico. Radiología. 2019;61:134–142.</p>" ] ] "multimedia" => array:12 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 944 "Ancho" => 1584 "Tamanyo" => 66926 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Molecular mechanisms inhibiting immunity by tumours and their blocking with anti-CTLA-4 antibodies. The interaction between CTLA-4 and its ligand (B7) in the antigen-presenting cell inhibits the immune response of T-cells against the tumour, which enables the tumour cells to escape immune attack. Anti-CTLA-4 antibodies such as ipilimumab block the interaction between CTLA-4 and its ligand (B7), thereby blocking the immune inhibition of the T-cells and activating the immune response against the cancer.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 929 "Ancho" => 1587 "Tamanyo" => 81896 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">The PD-1 immunosuppression mechanism as a target for cancer therapy. PD-1 is expressed on the surface of effector T-cells after activation and its ligand PD-L1 is expressed in the tumour cell. PD-1 to PD-L1 binding gives an inhibitory signal in through SHP2 phosphatases, which reduces cytokine production and T-cell proliferation, thereby allowing tumour cells to evade the host's immune response. Anti-PD-1 and PD-L1 antibodies prevent this binding and block the immune inhibition by the tumour, inducing an immune response against the tumour.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1475 "Ancho" => 2076 "Tamanyo" => 217907 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Immune-related response criteria (IrRC).</p>" ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1878 "Ancho" => 1133 "Tamanyo" => 251562 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">72-Year-old male with large-cell neuroendocrine lung cancer in “pseudoprogression”. (A) Axial computed tomography (CT) image of the neck showing right paratracheal adenopathic conglomerate masses after 6 cycles of nivolumab (white arrow). (B) Axial CT image of the neck with adenopathic conglomerate masses that have slightly increased in size after 9 treatment cycles with nivolumab (white arrow). (C) Axial CT image of the neck with adenopathic conglomerate masses that have significantly decreased in size after 15 treatment cycles with nivolumab (white arrow).</p>" ] ] 4 => array:7 [ "identificador" => "fig0025" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 1375 "Ancho" => 1733 "Tamanyo" => 290469 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">58-Year-old male with small cell lung cancer in tumour progression. (A and B) Axial computed tomography (CT) images of the thorax with a mediastinal window prior to the start of treatment. It shows a mass in the right lower lobe (asterisk), pleural effusion, right-sided pleural thickening and a soft tissue mass encompassing the anterior costal arches (white arrows). (C and D) Axial CT images of the thorax with a mediastinal window after the 1st cycle of atezolizumab with an increase in the size of the mass located in the right lower lobe (asterisk), in pleural effusion, in the right-sided pleural thickening and in the soft tissue mass encompassing the anterior costal arches (white arrows).</p>" ] ] 5 => array:7 [ "identificador" => "fig0030" "etiqueta" => "Figure 6" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr6.jpeg" "Alto" => 1273 "Ancho" => 1733 "Tamanyo" => 222382 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">63-Year-old male with stage IV lung adenocarcinoma in complete metabolic response. (A and B) Axial positron emission tomography–computed tomography (PET–CT) images with lymphadenopathies in an aortopulmonary window and abdominal CT with a splenic focal lesion associated with metastasis prior to the start of treatment with nivolumab (white arrows). (C and D) Axial PET–CT images with a decrease in the size of the lymphadenopathies in the aortopulmonary window and in the splenic focal lesion without metabolic activity after 28 cycles of nivolumab (white arrows).</p>" ] ] 6 => array:7 [ "identificador" => "fig0035" "etiqueta" => "Figure 7" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr7.jpeg" "Alto" => 1263 "Ancho" => 1733 "Tamanyo" => 363118 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">63-Year-old male with lung adenocarcinoma with bone and brain metastases and clinical symptoms of dyspnoea and fever associated with autoimmune pneumonitis after 18 cycles of nivolumab. (A and B) Axial computed tomography (CT) image and coronal reconstruction of the thorax with a pulmonary window with bilateral areas of ground-glass opacity and thickening of the bronchial walls in the LLL with adjacent patchy areas of consolidation (black arrows). (C and D) Axial CT image and coronal reconstruction of the thorax with a pulmonary window showing an increase in the bilateral areas of ground-glass opacity and in the thickening of the bronchial walls in the LLL with adjacent patchy areas of consolidation (black arrows) associated with radiological deterioration after 15 days of treatment with corticosteroids, unfavourable evolution and death.</p>" ] ] 7 => array:7 [ "identificador" => "fig0040" "etiqueta" => "Figure 8" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr8.jpeg" "Alto" => 701 "Ancho" => 1733 "Tamanyo" => 179990 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">55-Year-old male with lung adenocarcinoma lung metastases presenting cough and dyspnoea associated with autoimmune pneumonitis after 8 cycles of nivolumab. (A and B) axial computed tomography (CT) image and coronal reconstruction of the thorax with a pulmonary window with bilateral areas of ground-glass opacity (white arrows) and right-sided pleural effusion (asterisk).</p>" ] ] 8 => array:7 [ "identificador" => "fig0045" "etiqueta" => "Figure 9" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr9.jpeg" "Alto" => 1145 "Ancho" => 1733 "Tamanyo" => 157503 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">64-Year-old male with melanoma and metastasis in the C7 vertebral body, treated surgically, who completed treatment with ipilimumab. He presented abdominal pain and haematochezia associated with autoimmune colitis with perforation. Coronal reconstruction. (A) Computed tomography (CT) of the abdomen with a pulmonary window showing pneumoperitoneum (white arrow). (B) Axial image with a window on soft tissues with thickening, oedema and enhancement of the bowel wall and intra-abdominal free fluid (white arrow). (C) Axial CT image of the abdomen with a pulmonary window with extraluminal air associated with pneumoperitoneum (white arrow).</p>" ] ] 9 => array:7 [ "identificador" => "fig0050" "etiqueta" => "Figure 10" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr10.jpeg" "Alto" => 1506 "Ancho" => 2500 "Tamanyo" => 253398 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">61-Year-old male with right orbital adenocarcinoma of lacrimal gland origin and metastatic lymphadenopathies with epigastric pain and amylase elevation associated with autoimmune pancreatitis after 6 cycles of nivolumab. (A) Axial positron emission tomography-computed tomography (PET–CT) images with oedema of the tail of the pancreas and increased metabolic activity (white arrows). (B and C) Axial PET–CT images two months later with the same symptomatology, showing oedema of the head and body of the pancreas and increased metabolic activity associated with recurrent autoimmune pancreatitis (white arrows).</p>" ] ] 10 => array:7 [ "identificador" => "fig0055" "etiqueta" => "Figure 11" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr11.jpeg" "Alto" => 1455 "Ancho" => 1733 "Tamanyo" => 249270 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">55-Year-old male with lung adenocarcinoma and lung metastases with hypothyroidism associated with autoimmune thyroiditis after 5 cycles of nivolumab. (A) Axial computed tomography (CT) image of the thorax with a mediastinal window showing oedema and diffuse reduction in thyroid gland density (white arrows). (B) Axial CT image of the thorax with a mediastinal window three months earlier showing normal thyroid gland characteristics (white arrows).</p>" ] ] 11 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pulmonary/mediastinal \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pneumonitis, sarcoidosis-like syndrome \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gastrointestinal \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Colitis, pneumatosis, bowel perforation, hepatitis, pancreatitis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Endocrine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Thyroiditis, adrenal gland dysfunction \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Neurological \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Autoimmune hypophysitis, aseptic meningitis, arachnoiditis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Musculoskeletal \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Myositis, arthritis, abdominal fasciitis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Skin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Maculopapular exanthema, vitiligo \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Miscellaneous \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Opacities in the retroperitoneal fat and fat in the perirenal space \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1986198.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Adverse effects of immunotherapy.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:20 [ 0 => array:3 [ "identificador" => "bib0105" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cancer immunotherapy: imaging assessment of novel treatment response patterns and immune related adverse events" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "J. 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