Evolution of photodynamic therapy in the management of actinic keratosis: how effective and safe is it according to current evidence?

Introduction: Actinic keratosis is a premalignant dermatological condition characterized by the potential to progress to squamous cell carcinoma. To date, there is no treatment with an adequate benefit-risk balance. Photodynamic therapy is proposed as one of the most effective therapeutic tools. How...

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Autores:
Vargas, Laura
Londoño Serna, Andrés Felipe
Grisales Cano, Duvan Alejandro
Jaraba, Carlos
Ivan Peña
Bustillo, Max
Montenegro Salcedo, Zulmy Valeria
Tipo de recurso:
Article of investigation
Fecha de publicación:
2024
Institución:
Universidad de Ciencias Aplicadas y Ambientales U.D.C.A
Repositorio:
Repositorio Institucional UDCA
Idioma:
eng
OAI Identifier:
oai:repository.udca.edu.co:11158/6656
Acceso en línea:
https://repository.udca.edu.co/handle/11158/6656
https://doi.org/10.25176/rfmh.v24i4.6016
https://repository.udca.edu.co/
Palabra clave:
610 - Medicina y salud
Queratosis Actínica
Fototerapia
Terapéutica
Seguridad
Eficacia
Rights
openAccess
License
https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode.es
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dc.title.eng.fl_str_mv Evolution of photodynamic therapy in the management of actinic keratosis: how effective and safe is it according to current evidence?
dc.title.spa.fl_str_mv Evolución de la terapia fotodinámica en el manejo de la queratosis actínica: qué tan efectiva y segura es según la evidencia actual?
title Evolution of photodynamic therapy in the management of actinic keratosis: how effective and safe is it according to current evidence?
spellingShingle Evolution of photodynamic therapy in the management of actinic keratosis: how effective and safe is it according to current evidence?
610 - Medicina y salud
Queratosis Actínica
Fototerapia
Terapéutica
Seguridad
Eficacia
title_short Evolution of photodynamic therapy in the management of actinic keratosis: how effective and safe is it according to current evidence?
title_full Evolution of photodynamic therapy in the management of actinic keratosis: how effective and safe is it according to current evidence?
title_fullStr Evolution of photodynamic therapy in the management of actinic keratosis: how effective and safe is it according to current evidence?
title_full_unstemmed Evolution of photodynamic therapy in the management of actinic keratosis: how effective and safe is it according to current evidence?
title_sort Evolution of photodynamic therapy in the management of actinic keratosis: how effective and safe is it according to current evidence?
dc.creator.fl_str_mv Vargas, Laura
Londoño Serna, Andrés Felipe
Grisales Cano, Duvan Alejandro
Jaraba, Carlos
Ivan Peña
Bustillo, Max
Montenegro Salcedo, Zulmy Valeria
dc.contributor.author.none.fl_str_mv Vargas, Laura
Londoño Serna, Andrés Felipe
Grisales Cano, Duvan Alejandro
Jaraba, Carlos
Ivan Peña
Bustillo, Max
Montenegro Salcedo, Zulmy Valeria
dc.subject.ddc.none.fl_str_mv 610 - Medicina y salud
topic 610 - Medicina y salud
Queratosis Actínica
Fototerapia
Terapéutica
Seguridad
Eficacia
dc.subject.decs.none.fl_str_mv Queratosis Actínica
Fototerapia
Terapéutica
Seguridad
Eficacia
description Introduction: Actinic keratosis is a premalignant dermatological condition characterized by the potential to progress to squamous cell carcinoma. To date, there is no treatment with an adequate benefit-risk balance. Photodynamic therapy is proposed as one of the most effective therapeutic tools. However, there is still divergence regarding the quality of available evidence. The objective of this review is to analyze the most recent evidence on the therapeutic performance of photodynamic therapy in the management of actinic keratosis. A literature search was conducted in the PubMed, Scopus, and MEDLINE databases. Based on the most recent randomized controlled trial comparing, the use of dynamic phototherapy combined with aminolevulinic acid without incubation versus incubation for one hour; it was found that the intervention group had a higher percentage of lesion resolution compared to the control group (49.5% vs. 34.9%, p=0.002), as well as less pain in the intervention group (p=0.03). In addition, a similar trend was observed in other studies, suggesting that this therapy could be effective and beneficial in the management of actinic keratosis. Despite the limited and heterogeneous evidence regarding the use of dynamic phototherapy and its various combined regimens for the management of actinic keratosis, there is a clear trend towards potential benefits compared to other therapies.
publishDate 2024
dc.date.issued.none.fl_str_mv 2024
dc.date.accessioned.none.fl_str_mv 2025-09-25T15:11:34Z
dc.date.available.none.fl_str_mv 2025-09-25T15:11:34Z
dc.type.none.fl_str_mv Artículo de revista
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dc.identifier.citation.none.fl_str_mv Vargas Monroy LV, Londoño Serna AF, Grisales Cano DA , Jaraba Herazo CA, Peña Chamorro IA, Bustillo Orozco MJ, Montenegro Salcedo ZV, Ortega Sierra M. Evolution of photodynamic therapy in the management of actinic keratosis: How effective and safe is it according to current evidence?. Rev Fac Med Hum. 2024;24(4):190-195. https://doi.org/10.25176/rfmh.v24i4.6016
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dc.identifier.instname.none.fl_str_mv Universidad de Ciencias Aplicadas y Ambientales
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identifier_str_mv Vargas Monroy LV, Londoño Serna AF, Grisales Cano DA , Jaraba Herazo CA, Peña Chamorro IA, Bustillo Orozco MJ, Montenegro Salcedo ZV, Ortega Sierra M. Evolution of photodynamic therapy in the management of actinic keratosis: How effective and safe is it according to current evidence?. Rev Fac Med Hum. 2024;24(4):190-195. https://doi.org/10.25176/rfmh.v24i4.6016
18145469
Universidad de Ciencias Aplicadas y Ambientales
UDCA
url https://repository.udca.edu.co/handle/11158/6656
https://doi.org/10.25176/rfmh.v24i4.6016
https://repository.udca.edu.co/
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language eng
dc.relation.indexed.none.fl_str_mv LaReferencia
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dc.relation.citationvolume.none.fl_str_mv 24
dc.relation.ispartofjournal.none.fl_str_mv Revista de la Facultad de Medicina Humana
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spelling Vargas, Lauravirtual::884-1Londoño Serna, Andrés Felipevirtual::890-1Grisales Cano, Duvan Alejandrovirtual::891-1Jaraba, Carlosvirtual::892-1Ivan PeñaBustillo, Maxvirtual::893-1Montenegro Salcedo, Zulmy Valeriavirtual::894-12025-09-25T15:11:34Z2025-09-25T15:11:34Z2024Vargas Monroy LV, Londoño Serna AF, Grisales Cano DA , Jaraba Herazo CA, Peña Chamorro IA, Bustillo Orozco MJ, Montenegro Salcedo ZV, Ortega Sierra M. Evolution of photodynamic therapy in the management of actinic keratosis: How effective and safe is it according to current evidence?. Rev Fac Med Hum. 2024;24(4):190-195. https://doi.org/10.25176/rfmh.v24i4.6016https://repository.udca.edu.co/handle/11158/6656https://doi.org/10.25176/rfmh.v24i4.601618145469Universidad de Ciencias Aplicadas y AmbientalesUDCAhttps://repository.udca.edu.co/Introduction: Actinic keratosis is a premalignant dermatological condition characterized by the potential to progress to squamous cell carcinoma. To date, there is no treatment with an adequate benefit-risk balance. Photodynamic therapy is proposed as one of the most effective therapeutic tools. However, there is still divergence regarding the quality of available evidence. The objective of this review is to analyze the most recent evidence on the therapeutic performance of photodynamic therapy in the management of actinic keratosis. A literature search was conducted in the PubMed, Scopus, and MEDLINE databases. Based on the most recent randomized controlled trial comparing, the use of dynamic phototherapy combined with aminolevulinic acid without incubation versus incubation for one hour; it was found that the intervention group had a higher percentage of lesion resolution compared to the control group (49.5% vs. 34.9%, p=0.002), as well as less pain in the intervention group (p=0.03). In addition, a similar trend was observed in other studies, suggesting that this therapy could be effective and beneficial in the management of actinic keratosis. Despite the limited and heterogeneous evidence regarding the use of dynamic phototherapy and its various combined regimens for the management of actinic keratosis, there is a clear trend towards potential benefits compared to other therapies.Introducción:La queratosis actínica consiste en una entidad patológica dermatológicapremaligna, caracterizada por tener el potencial de progresar a carcinoma escamocelular. A la fecha, no existe un tratamiento con un adecuado balance benecio-riesgo. La terapia fotodinámica se postula como una de las herramientas terapéuticas más ecaces. No obstante, aún existe divergencia en cuanto a la calidad de la evidencia disponible. El objetivo de esta revisión consiste en analizar la evidencia más reciente sobre la evolución del rendimiento terapéutico de la terapia fotodinámica en el manejo de la queratosis actínica. Se realizó una búsqueda bibliográca en las bases de datos PubMed, Scopus, y MEDLINE. Con base en el ensayo controlado aleatorizado más reciente, donde compararon el uso de fototerapia dinámica combinado con ácido aminolevulínico sin incubación versus con incubación de una hora, se evidenció que el grupo intervención tuvo mayor porcentaje de resolución de lesiones comparado al grupo control (49,5 % versus 34,9 %, p=0,002), así como menor dolor en el grupo intervención (p=0,03); adicional a la tendencia similar en los otros estudios, se encuentra que esta terapia podría ser ecaz y beneciosa en el manejo de la queratosis actínica. A pesar de que la evidencia sobre el uso de fototerapia dinámica y sus distintos esquemas combinados, para el manejo de la queratosis actínica es limitada y heterogénea, existe una marcada tendencia sobre un potencial benecio, comparado a otras terapiasIncluye referencias bibliográficasapplication/pdfenghttps://creativecommons.org/licenses/by-nc-sa/4.0/legalcode.eshttps://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/openAccessAtribución-NoComercial-CompartirIgual 4.0 Internacional (CC BY-NC-SA 4.0)http://purl.org/coar/access_right/c_abf2https://revistas.urp.edu.pe/index.php/RFMH/article/view/6016/10886610 - Medicina y saludQueratosis ActínicaFototerapiaTerapéuticaSeguridadEficaciaEvolution of photodynamic therapy in the management of actinic keratosis: how effective and safe is it according to current evidence?Evolución de la terapia fotodinámica en el manejo de la queratosis actínica: qué tan efectiva y segura es según la evidencia actual?Artículo de revistahttp://purl.org/coar/resource_type/c_2df8fbb1info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionTexthttp://purl.org/redcol/resource_type/ARThttp://purl.org/coar/version/c_970fb48d4fbd8a85LaReferencia(2024)64124Revista de la Facultad de Medicina 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jecuta públicamente en forma digital la Obra o cualquier Obra Derivada u Obra Colectiva, Usted debe mantener intacta toda la información de derecho de autor de la Obra y proporcionar, de forma razonable según el medio o manera que Usted esté utilizando: (i) el nombre del Autor Original si está provisto (o seudónimo, si fuere aplicable), y/o (ii) el nombre de la parte o las partes que el Autor Original y/o el Licenciante hubieren designado para la atribución (v.g., un instituto patrocinador, editorial, publicación) en la información de los derechos de autor del Licenciante, términos de servicios o de otras formas razonables; el título de la Obra si está provisto; en la medida de lo razonablemente factible y, si está provisto, el Identificador Uniforme de Recursos (Uniform Resource Identifier) que el Licenciante especifica para ser asociado con la Obra, salvo que tal URI no se refiera a la nota sobre los derechos de autor o a la información sobre el licenciamiento de la Obra; y en el caso de una Obra Derivada, atribuir el crédito identificando el uso de la Obra en la Obra Derivada (v.g., "Traducción Francesa de la Obra del Autor Original," o "Guión Cinematográfico basado en la Obra original del Autor Original"). Tal crédito puede ser implementado de cualquier forma razonable; en el caso, sin embargo, de Obras Derivadas u Obras Colectivas, tal crédito aparecerá, como mínimo, donde aparece el crédito de cualquier otro autor comparable y de una manera, al menos, tan destacada como el crédito de otro autor comparable.</li>
      <li>
        Para evitar toda confusión, el Licenciante aclara que, cuando la obra es una composición musical:
        <ol type="i">
          <li>Regalías por interpretación y ejecución bajo licencias generales. El Licenciante se reserva el derecho exclusivo de autorizar la ejecución pública o la ejecución pública digital de la obra y de recolectar, sea individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, SAYCO), las regalías por la ejecución pública o por la ejecución pública digital de la obra (por ejemplo Webcast) licenciada bajo licencias generales, si la interpretación o ejecución de la obra está primordialmente orientada por o dirigida a la obtención de una ventaja comercial o una compensación monetaria privada.</li>
          <li>Regalías por Fonogramas. El Licenciante se reserva el derecho exclusivo de recolectar, individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, los consagrados por la SAYCO), una agencia de derechos musicales o algún agente designado, las regalías por cualquier fonograma que Usted cree a partir de la obra (“versión cover”) y distribuya, en los términos del régimen de derechos de autor, si la creación o distribución de esa versión cover está primordialmente destinada o dirigida a obtener una ventaja comercial o una compensación monetaria privada.</li>
        </ol>
      </li>
      <li>Gestión de Derechos de Autor sobre Interpretaciones y Ejecuciones Digitales (WebCasting). Para evitar toda confusión, el Licenciante aclara que, cuando la obra sea un fonograma, el Licenciante se reserva el derecho exclusivo de autorizar la ejecución pública digital de la obra (por ejemplo, webcast) y de recolectar, individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, ACINPRO), las regalías por la ejecución pública digital de la obra (por ejemplo, webcast), sujeta a las disposiciones aplicables del régimen de Derecho de Autor, si esta ejecución pública digital está primordialmente dirigida a obtener una ventaja comercial o una compensación monetaria privada.</li>
    </ol>
  </li>
  <br/>
  <li>
    Representaciones, Garantías y Limitaciones de Responsabilidad.
    <p>A MENOS QUE LAS PARTES LO ACORDARAN DE OTRA FORMA POR ESCRITO, EL LICENCIANTE OFRECE LA OBRA (EN EL ESTADO EN EL QUE SE ENCUENTRA) “TAL CUAL”, SIN BRINDAR GARANTÍAS DE CLASE ALGUNA RESPECTO DE LA OBRA, YA SEA EXPRESA, IMPLÍCITA, LEGAL O CUALQUIERA OTRA, INCLUYENDO, SIN LIMITARSE A ELLAS, GARANTÍAS DE TITULARIDAD, COMERCIABILIDAD, ADAPTABILIDAD O ADECUACIÓN A PROPÓSITO DETERMINADO, AUSENCIA DE INFRACCIÓN, DE AUSENCIA DE DEFECTOS LATENTES O DE OTRO TIPO, O LA PRESENCIA O AUSENCIA DE ERRORES, SEAN O NO DESCUBRIBLES (PUEDAN O NO SER ESTOS DESCUBIERTOS). ALGUNAS JURISDICCIONES NO PERMITEN LA EXCLUSIÓN DE GARANTÍAS IMPLÍCITAS, EN CUYO CASO ESTA EXCLUSIÓN PUEDE NO APLICARSE A USTED.</p>
  </li>
  <br/>
  <li>
    Limitación de responsabilidad.
    <p>A MENOS QUE LO EXIJA EXPRESAMENTE LA LEY APLICABLE, EL LICENCIANTE NO SERÁ RESPONSABLE ANTE USTED POR DAÑO ALGUNO, SEA POR RESPONSABILIDAD EXTRACONTRACTUAL, PRECONTRACTUAL O CONTRACTUAL, OBJETIVA O SUBJETIVA, SE TRATE DE DAÑOS MORALES O PATRIMONIALES, DIRECTOS O INDIRECTOS, PREVISTOS O IMPREVISTOS PRODUCIDOS POR EL USO DE ESTA LICENCIA O DE LA OBRA, AUN CUANDO EL LICENCIANTE HAYA SIDO ADVERTIDO DE LA POSIBILIDAD DE DICHOS DAÑOS. ALGUNAS LEYES NO PERMITEN LA EXCLUSIÓN DE CIERTA RESPONSABILIDAD, EN CUYO CASO ESTA EXCLUSIÓN PUEDE NO APLICARSE A USTED.</p>
  </li>
  <br/>
  <li>
    Término.
    <ol type="a">
      <li>Esta Licencia y los derechos otorgados en virtud de ella terminarán automáticamente si Usted infringe alguna condición establecida en ella. Sin embargo, los individuos o entidades que han recibido Obras Derivadas o Colectivas de Usted de conformidad con esta Licencia, no verán terminadas sus licencias, siempre que estos individuos o entidades sigan cumpliendo íntegramente las condiciones de estas licencias. Las Secciones 1, 2, 5, 6, 7, y 8 subsistirán a cualquier terminación de esta Licencia.</li>
      <li>Sujeta a las condiciones y términos anteriores, la licencia otorgada aquí es perpetua (durante el período de vigencia de los derechos de autor de la obra). No obstante lo anterior, el Licenciante se reserva el derecho a publicar y/o estrenar la Obra bajo condiciones de licencia diferentes o a dejar de distribuirla en los términos de esta Licencia en cualquier momento; en el entendido, sin embargo, que esa elección no servirá para revocar esta licencia o que deba ser otorgada , bajo los términos de esta licencia), y esta licencia continuará en pleno vigor y efecto a menos que sea terminada como se expresa atrás. La Licencia revocada continuará siendo plenamente vigente y efectiva si no se le da término en las condiciones indicadas anteriormente.</li>
    </ol>
  </li>
  <br/>
  <li>
    Varios.
    <ol type="a">
      <li>Cada vez que Usted distribuya o ponga a disposición pública la Obra o una Obra Colectiva, el Licenciante ofrecerá al destinatario una licencia en los mismos términos y condiciones que la licencia otorgada a Usted bajo esta Licencia.</li>
      <li>Si alguna disposición de esta Licencia resulta invalidada o no exigible, según la legislación vigente, esto no afectará ni la validez ni la aplicabilidad del resto de condiciones de esta Licencia y, sin acción adicional por parte de los sujetos de este acuerdo, aquélla se entenderá reformada lo mínimo necesario para hacer que dicha disposición sea válida y exigible.</li>
      <li>Ningún término o disposición de esta Licencia se estimará renunciada y ninguna violación de ella será consentida a menos que esa renuncia o consentimiento sea otorgado por escrito y firmado por la parte que renuncie o consienta.</li>
      <li>Esta Licencia refleja el acuerdo pleno entre las partes respecto a la Obra aquí licenciada. No hay arreglos, acuerdos o declaraciones respecto a la Obra que no estén especificados en este documento. El Licenciante no se verá limitado por ninguna disposición adicional que pueda surgir en alguna comunicación emanada de Usted. Esta Licencia no puede ser modificada sin el consentimiento mutuo por escrito del Licenciante y Usted.</li>
    </ol>
  </li>
  <br/>
</ol>
