Diego Tetzner Fernandes
IMPACTO DE UM VÍDEO EDUCATIVO SOBRE AS TOXICIDADES
DO TRATAMENTO RADIOTERÁPICO EM PACIENTES COM
CÂNCER DE CABEÇA E PESCOÇO E AVALIAÇÃO DE MÉTODOS DE
QUANTIFICAÇÃO DE CÉLULAS DENDRÍTICAS EM PACIENTES
HIV POSITIVOS COM CÂNCER DE CABEÇA E PESCOÇO
IMPACT OF AN EDUCATIONAL VIDEO ABOUT RADIOTHERAPY
TOXICITIES IN PATIENTS WITH HEAD AND NECK CANCER AND
EVALUATION OF QUANTIFICATION METHODS OF DENDRITIC
CELLS IN HIV POSITIVE PATIENTS WITH HEAD AND NECK
CANCER
Piracicaba/SP
2019
IMPACTO DE UM VÍDEO EDUCATIVO SOBRE AS TOXICIDADES
DO TRATAMENTO RADIOTERÁPICO EM PACIENTES COM
CÂNCER DE CABEÇA E PESCOÇO E AVALIAÇÃO DE MÉTODOS DE
QUANTIFICAÇÃO DE CÉLULAS DENDRÍTICAS EM PACIENTES
HIV POSITIVOS COM CÂNCER DE CABEÇA E PESCOÇO
IMPACT OF AN EDUCATIONAL VIDEO ABOUT RADIOTHERAPY
TOXICITIES IN PATIENTS WITH HEAD AND NECK CANCER AND
EVALUATION OF QUANTIFICATION METHODS OF DENDRITIC
CELLS IN HIV POSITIVE PATIENTS WITH HEAD AND NECK
CANCER
Tese apresentada à Faculdade de Odontologia de Piracicaba da Universidade Estadual de Campinas como parte dos requisitos exigidos para a obtenção do título de Doutor em Estomatopatologia na Área de Patologia.
Thesis presented to the Piracicaba Dental School of the University of Campinas in partial fulfillment of the requirements for the degree of Doctor in Oral Pathology and Oral Medicine in Oral Pathology area.
Orientador: Prof. Dr. Márcio Ajudarte Lopes
Coorientadora: Profa. Dra. Ana Carolina Prado Ribeiro e Silva
Este exemplar corresponde à versão final da tese defendida pelo aluno Diego Tetzner Fernandes, e orientado pelo Prof. Dr. Márcio Ajudarte Lopes.
Piracicaba/SP
2019
Dedico esta tese a todos os pacientes que de alguma forma passaram por meus
cuidados, os quais sempre serão a essência do propósito de todo meu trabalho e ambições. Sou
imensamente grato por todos os ensinamentos e confiança.
Aos meus pais, Carlos Alberto Neves Fernandes e Cristina Ap. Tetzner
Fernandes, e aos meus irmãos, Matheus Tetzner Fernandes e Ramon Fernandes Neto, por
todo amor, carinho e apoio. Não tenho palavras que mensurem a minha gratidão por todo
esforço que fizeram para que eu pudesse alcançar meus sonhos e objetivos.
À Anna Gabriella Camacho Presotto, pessoa que se tornou imprescindível em
minha caminhada. Obrigado por todo apoio, incentivo, ensinamentos e todo o amor concedido.
É incrível compartilhar a vida com você.
Ao meu amigo Pedro Augusto Bulhões Curioso. Obrigado por todos os momentos
compartilhados e por ter me ensinado tanto sobre a vida. Você sempre será lembrado com
carinho.
Agradeço a Deus por me proporcionar tantas conquistas e oportunidades, sempre
me cercando de pessoas maravilhosas em todos os momentos.
Ao meu orientador, Prof. Dr. Márcio Ajudarte Lopes, por ser meu Professor no
sentido mais completo da palavra. Sou muito grato pela confiança depositada em mim desde a
época da Graduação. Obrigado por todo o incentivo, oportunidades, amizade e, sobretudo, pela
imensa contribuição para o meu crescimento pessoal e profissional. Um dia espero conquistar
a admiração de um aluno da mesma maneira que conquistou a minha.
Agradeço aos meus avós Ramon Fernandes, Maria de Lourdes Neves
Fernandes e Yolanda Tetzner, que se foram durante este período do Doutorado. Obrigado por
O presente trabalho foi realizado com apoio da Coordenação de Aperfeiçoamento
de Pessoal de Nível Superior – Brasil (CAPES) – Código de Financiamento 001.
O presente trabalho foi realizado com apoio do Conselho Nacional de
Desenvolvimento Científico e Tecnológico (CNPq), processo nº 141063/2016-5.
À Universidade Estadual de Campinas (UNICAMP), na pessoa do Magnífico
Reitor, Prof. Dr. Marcelo Knobel e à Faculdade de Odontologia de Piracicaba –
UNICAMP, na pessoa do seu Diretor, Prof. Dr. Francisco Haiter Neto e Diretor Associado,
Prof. Dr. Flávio Henrique Baggio Aguiar.
À Profa. Dra. Karina Gonzales Silvério Ruiz, coordenadora geral dos programas
de Pós-graduação da Faculdade de Odontologia de Piracicaba da Universidade Estadual de
Campinas.
Ao Prof. Dr. Márcio Ajudarte Lopes, coordenador do programa de
Pós-graduação em Estomatopatologia da Faculdade de Odontologia de Piracicaba da Universidade
Estadual de Campinas.
Aos docentes das áreas de Semiologia e Patologia da Faculdade de Odontologia de
Piracicaba – UNICAMP, Prof. Dr. Márcio Ajudarte Lopes, Prof. Dr. Alan Roger dos
Santos Silva, Prof. Dr. Pablo Agustín Vargas, Prof. Dr. Oslei Paes de Almeida, Prof. Dr.
Edgard Graner, Prof. Dr. Ricardo Della Coletta, e Prof. Dr. Jacks Jorge Júnior, por todos
os ensinamentos a mim concedidos desde a graduação.
À toda equipe do Orocentro, particularmente Aparecida Campion, Daniele
Morelli, Rogério Elias de Andrade e Érika Graf Pedroso, pela prazerosa convivência e
amizade. Espero conquistar um ambiente de trabalho como este aonde quer que a vida me leve.
Meu carinho por esta clínica é tão especial graças a todas essas pessoas.
ensinamentos na área de radio-oncologia.
À toda equipe de Odontologia do Instituto do Câncer do Estado de São Paulo
(ICESP), na pessoa da coordenadora Dra. Thaís Bianca Brandão, pela respeitosa convivência
durante todo o período em que trabalhei com a pesquisa no hospital. Em especial, agradeço a
Prof. Dra. Ana Carolina Prado Ribeiro e Silva, pessoa que foi fundamental nas minhas
atividades de pesquisa do Doutorado. Obrigado por todo incentivo, ensinamentos e amizade.
Agradeço também a Dra. Karina Morais, por toda ajuda com a pesquisa e incentivo
profissional.
À Dra. Renata Markman, responsável pelo delineamento e início do projeto de
pesquisa realizado no ICESP. Obrigado pela amizade e todos os ensinamentos durante o período
da pós-graduação.
À Patrícia Vilas Boas, amiga da época de graduação, por sempre me receber de
portas abertas em seu apartamento em São Paulo todas as vezes que precisei.
Ao meu amigo Rodrigo Gustavo Paixão, obrigado por todas as palavras de
incentivo e por sempre estar presente mesmo diante da distância. Sua amizade representa mais
um presente que a FOP me proporcionou.
Ao Prof. Dr. Pedro Luiz Rosalen e a todos os membros do grupo de pesquisa de
produtos naturais e orgânicos vinculado à empresa BREYER & CIA. Obrigado pela
oportunidade e valiosos ensinamentos.
À psicóloga Nara dos Santos Zanetti, por todo apoio durante os momentos de
dificuldades pessoais e profissionais. Obrigado pela ajuda e orientações de como lidar com a
responsabilidade de trabalhar com pacientes oncológicos.
Ao Professor de Inglês, Jorge Valerio, por todos os ensinamentos, amizade e ajuda
para que eu conquistasse meus objetivos acadêmicos.
por todo acolhimento, oportunidades e valiosos ensinamentos.
A todas amizades que fiz durante o período em que passei em Pretoria, em especial
aos amigos Gregory Wall, Sofie Horsthuis, Nynke van der Wal, Daniel Castanheira,
Milehna Guarido, Jenny McEneaney, Jorge Armando, Lily Welborn, Paula Lerones,
Jonathan Du Toit, e Tumisso Dembola. Obrigado por todos os ensinamentos e experiências
inesquecíveis.
A todos os colegas e amigos que fazem ou fizeram parte do programa de
pós-graduação, em especial a Bruno Mariz, Carolina Carneiro, Celeste Sánchez, Débora
Pereira, Florence Juana, Iara Aquino, Isabel Schausltz, João Scarini, Juliana de Souza,
Karina Morais, Leonardo Reis, Luan César, Mariana Paglioni, Marisol Galvis, Maurício
Dourado, Natalia Palmier, Patrícia Fernandes, Pedro Curioso, Rachel Lamarck, Raísa
Sales, Renata Markman, Vinícius Torregrossa e Wagner Gomes, Agradeço pelos ótimos
momentos compartilhados, por toda ajuda e valiosa aprendizagem.
Aos meus irmãos de banda, Guilherme Bisca, André Abreu, Vitor Penteado e
Lucas Calheiros, amigos responsáveis pela realização de um sonho que venho vivenciando há
tantos anos. Obrigado pela amizade verdadeira e por todos os momentos de trabalho, conquistas
e diversão.
À Ana Maria Camacho Presotto, Odair Antonio Presotto e João Gabriel
Camacho Presotto, que me acolheram em sua família durante todo este período.
A todos os profissionais, familiares, amigos e demais pessoas que de alguma forma
contribuíram para a concretização destes trabalhos e conquistas.
Esta tese contemplou dois estudos distintos envolvendo pacientes com câncer de cabeça e
pescoço. O primeiro estudo verificou o impacto de um vídeo educativo na compreensão,
satisfação, qualidade de vida e estado emocional dos pacientes submetidos a radioterapia em
diferentes momentos do tratamento. Um vídeo educativo sobre a radioterapia e suas toxicidades
foi produzido e um ensaio clínico randomizado prospectivo foi realizado em dois grupos: grupo
controle, o qual recebeu informações verbais e escritas; e grupo experimental, o qual recebeu
as informações verbais, escritas e o vídeo. Questionários apropriados foram aplicados em 4
momentos distintos para avaliação da compreensão, ansiedade, depressão e qualidade de vida
dos pacientes. Durante um período de 3 anos, um total de 130 pacientes completaram o estudo.
Os resultados mostraram que o vídeo melhorou o entendimento do tratamento e seus efeitos
colaterais. Além disso, o grupo do vídeo relatou uma melhor conscientização sobre os cuidados
de saúde bucal durante o tratamento. Por outro lado, o vídeo não modificou os níveis de
ansiedade, depressão e a qualidade de vida dos pacientes. A osteoradionecrose e a cárie
relacionada à radiação foram os efeitos colaterais mais desconhecidos dos pacientes. Todos os
pacientes relataram boa aceitação e satisfação após a aplicação do vídeo. Sendo assim, uma
ferramenta audiovisual pode melhorar a compreensão dos pacientes sobre a radioterapia, e seu
uso conjunto às informações verbais e escritas em centros oncológicos deve ser encorajado.
Além disso, informações sobre osteorradionecrose e cáries relacionadas à radiação devem ser
reforçadas aos pacientes. O segundo estudo avaliou e propôs um novo método de quantificação
digital de células dendríticas (CDs) em carcinoma espinocelular ao compará-lo com um método
convencional de quantificação. Foram selecionados 26 casos de carcinoma espinocelular de
pacientes HIV positivos localizados em orofaringe, lábios e cavidade oral. Foram realizadas
reações de imunoistoquímica para os marcadores CD1a, CD83 e CD207, e as células positivas
foram digitalmente avaliadas utilizando um algoritmo de contagem de pixels. Um método de
quantificação convencional (método de área inespecífica; AI) e um novo método (método de
área específica; AE) foram executados, e a densidade de CDs positivas correspondentes às
regiões intra e peritumorais foram obtidas. O teste U de Mann-Whitney foi utilizado para
verificação da influência dos métodos de quantificação na contagem de células positivas de
acordo com as regiões avaliadas. Os dados foram submetidos à ANOVA e teste t de Student
para verificação da influência da localização do tumor, estágio, grau histológico e quantidade
de inflamação na contagem de densidade das CDs. Os métodos de quantificação celular
afetaram a contagem de CDs independentemente da região avaliada (P<0,05). Diferenças
significativas entre os métodos também foram observadas de acordo com as avaliações das
características do tumor. Em conclusão, o método de quantificação celular influencia os
resultados de densidade de CDs. Ao contrário do método convencional (método AI), o novo
método AE leva em consideração a variabilidade de tecido ou quantidade de inflamação a serem
avaliadas nas áreas de hotspots, melhorando a confiabilidade e a reprodutibilidade da
quantificação celular.
Palavras–chave: Neoplasias de Cabeça e Pescoço. Filmes e Vídeos educativos. Radioterapia. Contagem
This PhD thesis comprises two distinct studies involving patients with head and neck cancer.
The first study verified the impact of an educational video on the understanding, satisfaction,
quality of life, and emotional state of patients undergoing radiotherapy in different moments of
the treatment. A video about radiotherapy and its toxicities was produced and a prospective
randomized clinical trial was performed in two groups (control: received standard verbal and
written information; experimental: received standards information and video). Appropriated
questionnaires were applied in 4 different moments in order to evaluate patients’ understanding,
anxiety, depression, and quality of life. Over a three-year period, a total of 130 patients
completed the study. The video improved the understanding of the treatment and its side effects.
Also, the video group reported better awareness about oral health care during the treatment. On
the other hand, the educational video did not modify the patients’ anxiety, depression, and
quality of life levels. Osteoradionecrosis and radiation-related caries were the most patients’
unknown side effects. All patients reported a high acceptance and satisfaction about the video.
Hence, audio-visual tools may improve patients' understanding of radiotherapy and showed to
be a useful tool to be used in association with verbal and written information in cancer centers.
In addition, information about osteoradionecrosis and radiation-related caries must be
reinforced to the patients. The second study evaluated and proposed a novel digital dendritic
cells (DCs) quantification method in squamous cell carcinoma (SCC) comparing it with a
conventional quantification method. Twenty-six SCCs HIV-positive cases affecting the
oropharynx, lips and oral cavity were selected. Immunohistochemistry for CD1a, CD83, and
CD207 was performed and the positive cells were evaluated by automated examination using a
positive pixel count algorithm. A conventional quantification method (unspecific area method;
UA) and a novel method (specific area method; SA) were performed obtaining the
corresponding density of positive DCs for the intratumoral and peritumoral compartments. The
Mann-Whitney U test was used to verify the influence of the quantification methods on the
positive cell counting according to the evaluated regions. Data were subjected to the ANOVA
and Student’s t-test to verify the influence of the tumor location, stage, histological grade, and
amount of inflammation on the DCs density quantification. The cell quantification method
affected the DCs counting independently of the evaluated region (P-value <0.05). Significant
differences between methods were also observed according to the tumor features evaluations.
Thus, the positive cell quantification method influences the DCs density results. Unlike the
conventional method (UA method), the novel SA method avoids non-target areas included in
the hotspots improving the reliability and reproducibility of the cell quantification.
Keywords: Head and Neck Neoplasms. Instructional Films and Videos. Radiotherapy. Cell
1 Introdução ... 13
2 Artigos
2.1 Artigo:
The impact of an educational video about radiotherapy and its toxicities in head
and neck cancer patients. Evaluation of patients’ understanding, anxiety, depression, and
quality of life.
... 17
2.2 Artigo:
Different methods of cell quantification can lead to different results: a comparison
of digital methods using a pilot study of dendritic cells in HIV-positive patients.
... 38
3 Discussão ... 54
4 Conclusão ... 58
Referências ... 59
Apêndice 1
-Resultados estatísticos complementares (Valores de P) – Artigo 1
... 64
Anexos
Anexo 1
-Escala de Ansiedade e Depressão (HAD)
... 65
Anexo 2
-Questionário de qualidade de vida da Universidade de Washington
... 66
Anexo 3
-Questionário de entendimento da Radioterapia (Pré-RT)
... 69
Anexo 4
-Questionário de entendimento da Radioterapia (Pós-RT)
... 70
Anexo 5
-Certificados de aprovação do comitê de ética
... 71
Anexo 6
-Comprovante de submissão do artigo
... 74
1 Introdução
Câncer de cabeça e pescoço (CCP) é um termo utilizado para descrever um grupo
diverso de tumores malignos que afetam a boca, faringe, laringe, cavidade nasal e seios
paranasais (Syrigos et al., 2009). Este tipo de doença representa cerca 4% de todos os tumores
malignos que acometem o ser humano, sendo frequentemente diagnosticados em estágios
avançados (Bray et al., 2018). No Brasil, para o ano de 2018, foram estimados 14.700 novos
casos de câncer somente em cavidade oral (INCA, 2018).
O tratamento do CCP é multidisciplinar e depende de vários fatores, como a localização,
o estadiamento clínico e o grau de diferenciação tumoral (Shah and Gil, 2009). A radioterapia
(RT) é utilizada como uma das principais formas de tratamento e pode ser associada ao
tratamento cirúrgico e/ou quimioterápico, especialmente em pacientes que apresentem tumores
em estágios avançados (Shah and Gil, 2009). No entanto, o uso da radiação ionizante para
eliminar as células cancerígenas também causa alterações nos tecidos normais inseridos no
campo de radiação (Rosales et al., 2009). Estes efeitos colaterais indesejáveis, que em diversas
situações podem prejudicar o tratamento oncológico, são classificados como efeitos agudos e
crônicos. Os efeitos colaterais agudos começam a surgir entre o fim da primeira à terceira
semana de RT (dose cumulativa de 10-30Gy) e podem persistir por algumas semanas após o
término do tratamento. As toxicidades mais comuns são lesões de mucosite, hipossalivação,
disgeusia, disfagia, candidíase e outras infecções oportunistas. Após o término da RT, alguns
efeitos colaterais são considerados crônicos ou tardios, como hipossalivação, cáries
relacionadas à radiação, osteorradionecrose e trismo (Brody et al., 2013; Ray-Chaudhuri et al.,
2013)
Além de inúmeras dúvidas e desafios que os pacientes e seus familiares precisam
enfrentar diante do diagnóstico de uma doença tão estigmatizante como o câncer, surgem
incertezas quanto ao prognóstico e dificuldades de compreensão da doença que podem
prejudicar o tratamento. Grande parte dos pacientes iniciam o tratamento radioterápico após
serem submetidos a procedimentos cirúrgicos, apresentando sequelas físicas e psicológicas
(Bennenbroek et al., 2003; Chen et al., 2013). Portanto, devido ao potencial estresse envolvido
desde o diagnóstico até a reabilitação, a maioria dos pacientes deseja saber o máximo de
informações possível sobre sua doença e tratamento (Knox et al., 2002; Bennenbroek et al.,
2003; Lamb et al., 2011; Chen et al., 2013). Geralmente, os pacientes oncológicos passam por
consultas prévias ao início da RT nas quais recebem esclarecimento a respeito da RT, além de
orientações e recomendações sobre o tratamento. No entanto, a RT é tecnicamente complexa e
gera dificuldade de compreensão da linguagem e conteúdo das informações fornecidas pela
equipe multidisciplinar (Fallowfield and Jenkins, 1999; Knox et al., 2002; Dunn et al., 2004;
Hahn et al., 2005). Com isso, grande parte dos pacientes têm dificuldade de absorver e assimilar
a grande quantidade de informações (Matsuyama et al., 2013) e muitos relatam insatisfação
com relação às informações recebidas (van der Meulen et al., 2013).
O uso de métodos audiovisuais tem demonstrado ser uma opção interessante para
melhora na retenção de informações e satisfação dos pacientes (Knox et al., 2002; Bennenbroek
et al., 2003; Dunn et al., 2004; Hahn et al., 2005; Koss et al., 2018). A efetividade de vídeos
educativos sobre efeitos colaterais de tratamentos pode ser encontrada em diferentes áreas da
medicina, mostrando uma melhora na adesão ao tratamento e prevenção de complicações
relacionadas à não aderência das recomendações (Hahn et al., 2005; Williams et al., 2017;
Dawdy et al., 2018). Apesar dos resultados promissores, a literatura ainda carece de dados
sólidos sobre a utilização desta ferramenta na área de CCP (D’Souza et al., 2017).
Em 2013, nosso grupo de pesquisa publicou um estudo indicando que o uso de um
vídeo educacional em pacientes com CCP tratados com RT pode melhorar a compreensão dos
pacientes sobre o tratamento e seus efeitos colaterais, além de reduzir dúvidas e o medo antes
do tratamento (González-Arriagada et al., 2013). No entanto, devido a diversas limitações do
estudo anterior, os autores enfatizaram a necessidade de um novo estudo com uma amostra
maior de pacientes, incluindo outras análises em diferentes momentos do tratamento. Com isso,
o objetivo do estudo do primeiro artigo foi verificar se um vídeo educativo com foco na
apresentação e manejo das toxicidades da RT em CCP pode contribuir com a melhora da
compreensão, satisfação, estado emocional e qualidade de vida dos pacientes em diferentes
momentos do tratamento.
Os pacientes infectados com o vírus da imunodeficiência humana (HIV), associados à
síndrome de imunodeficiência adquirida (AIDS), possuem um maior risco de desenvolvimento
de malignidades em comparação com pacientes não infectados. O sarcoma de Kaposi e o
Linfoma não-Hodgkin de células B são exemplos de neoplasias comumente associadas ao
HIV/AIDS, consideradas neoplasias relacionadas a esta condição (Bunn and van Heerden,
2012). Por outro lado, com o advento da Terapia Antirretroviral Altamente Ativa (HAART), a
expectativa de vida de pacientes infectados com o HIV vem aumentando, e consequentemente,
novos desafios clínicos passaram a ser associados a este grupo de pacientes, como o
desenvolvimento de neoplasias malignas que anteriormente não eram associados à AIDS (Bunn
and van Heerden, 2012; Mourad et al., 2013; Grew et al., 2014; Thrift and Chiao, 2018). Neste
contexto, a incidência de CCP aumentou acentuadamente desde o uso generalizado da HAART
(Gillison, 2009; Picard et al., 2018; Thrift and Chiao, 2018). No entanto, o manejo mais
adequado do CCP em pacientes HIV positivos é desconhecido devido à escassez de dados e
estudos relacionados a esta condição (Grew et al., 2014). Durante os eventos da carcinogênese,
foram observadas alterações nos fatores imunológicos do hospedeiro. Com isso, o estudo dessas
interações complexas é necessário para uma melhor compreensão de tais malignidades
(Bennaceur et al., 2008).
As células dendríticas (CDs) possuem um papel fundamental na regulação das respostas
imunológicas, incluindo a imunidade antitumoral. Elas constituem uma população heterogênea
de células, onde as células imaturas possuem alta atividade fagocitária e as células maduras
uma alta capacidade de produção de citocinas. Tais condições mantêm um equilíbrio entre
imunidade inata e adquirida (Banchereau & Steinman, 1998). As principais populações de CDs
no epitélio da mucosa são as células de Langerhans (CLs). As CLs podem ter um papel
importante no curso de uma infecção pelo HIV, incluindo a provável captação inicial do vírus,
transmissão para os gânglios linfáticos e subsequente transferência para as células T (Lombardi
et al., 1993). Ao provocar imunossupressão, o HIV provoca uma resposta imune defeituosa à
infecção por vírus, podendo explicar assim, as taxas aumentadas de displasia e câncer em
pacientes HIV positivos (Sobhani et al., 2004). Estudos prévios mostraram uma baixa densidade
de CLs em carcinomas espinocelular (CECs) de pele (Galan and Ko, 2007), colo uterino
(Zimmermmann et al., 2012) e mucosa anal (Cruz et al., 2012). Embora não haja uma relação
clara entre a contagem de células T CD4, a carga viral do HIV e a densidade de CLs (Nandwani
et al., 1996), alguns estudos sugerem que as alterações imunológicas associadas à infecção pelo
HIV são fatores predisponentes para o desenvolvimento de CEC (Cruz et al., 2012;
Zimmermmann et al., 2012).
No entanto, não há estudos sobre a densidade de CDs em pacientes HIV positivos com
CCP. Além disso, novas ferramentas digitais na área da patologia tem melhorado e facilitado o
processo de quantificação celular por meio de análises de imunoistoquímica. A avaliação
automatizada envolvendo um algoritmo de contagem de pixels vêm substituindo os antigos
métodos de contagem manual, o que permite a exploração do uso da associação de diferentes
ferramentas digitais. Entretanto, os métodos convencionais de quantificação celular em CEC
não consideram a variabilidade da apresentação morfológica do tumor ou a quantidade de
inflamação nas áreas selecionadas avaliadas. Normalmente, uma área de 1 mm² selecionada de
um CEC bem ou moderadamente diferenciado tem uma quantidade diferente de tecido tumoral
quando comparada com uma área de mesmo tamanho de um CEC pouco diferenciado. De
maneira semelhante, essa variabilidade também pode ocorrer em regiões com quantidades
diferentes de inflamação, podendo afetar a avaliação de células imunes, como CDs. Nos
métodos convencionais, a quantificação celular é efetuada em toda região da área selecionada.
Portanto, áreas que não fazem parte da finalidade da avaliação, como regiões de fibrose, podem
ser erroneamente consideradas. Sendo assim, a reprodutibilidade dos estudos é afetada.
Uma grande variabilidade de valores tem sido observada em trabalhos que investigam
a densidade de CDs (Zimmermmann et al., 2012; Gondak et al., 2012, 2014; Jardim et al.,
2018), o que dificulta o uso da literatura científica como referência para novos estudos. Assim,
o objetivo do estudo apresentado no segundo artigo foi avaliar e propor um novo método de
quantificação de CDs em CEC, comparando-o com um método convencional a fim de verificar
se o método de quantificação influencia os resultados finais obtidos.
2.1 Artigo
*
The impact of an educational video about radiotherapy and its toxicities in head and neck cancer patients. Evaluation of patients’ understanding, anxiety, depression, and quality of life.
Diego Tetzner Fernandes DDS, MsC(a); Renata Lucena Markman DDS, PhD(a); Ana Carolina Prado-
Ribeiro DDS, PhD(a,b); Karina Morais DDS, PhD(b); Juliana Ono Tonaki(b); Thaís Bianca Brandão DDS,
PhD(b); Cesar Rivera DDS, PhD(c); Alan Roger Santos-Silva DDS, PhD(a); Márcio Ajudarte Lopes DDS,
PhD(a)
(a) Oral Diagnosis Department, Piracicaba Dental School, University of Campinas – UNICAMP, Piracicaba, São Paulo, Brazil.
(b) Dental Oncology Service, Instituto do Câncer do Estado de São Paulo, ICESP-FMUSP, São Paulo, Brazil.
(c) Oral Pathology and Medicine Research Group, Department of Basic Biomedical Sciences, Faculty of Health Sciences, Universidad de Talca, Chile.
Corresponding Author:
Prof. Dr. Márcio Ajudarte Lopes
Faculdade de Odontologia de Piracicaba - UNICAMP Departamento de Diagnóstico Oral - Semiologia Av. Limeira, 901 CEP 13.414-903
Piracicaba - São Paulo – Brasil Tel.: +55 19 21065320
E-mail: malopes@fop.unicamp.br
________________
ORCID of each author:
Diego Tetzner Fernandes: https://orcid.org/0000-0003-4437-8497 Renata Lucena Markman:
Ana Carolina Prado Ribeiro: https://orcid.org/0000-0002-0127-7998 Karina Morais:
Thaís Bianca Brandão: https://orcid.org/0000-0001-9128-3138 Cesar Rivera:
Alan Roger Santos-Silva: https://orcid.org/0000-0003-2040-6617 Marcio Ajudarte Lopes: https://orcid.org/0000-0001-6677-0065
Acknowledgments
The authors would like to gratefully acknowledge the financial support of the National Council for Scientific and Technological Development – CNPq, Brazil (process number 141063/2016-5).
The authors state that there are no funding sources that supported the current work. The authors have no conflicts of interest related to this study.
ABSTRACT
Purpose Head and neck radiotherapy can cause several toxicities and its management has important
treatment implications. Proper information about treatment is crucial to assist patients by preparing them and enhancing their ability to manage their illness. Thus, this study aimed to verify the impact of an educational video on the improvement of the patient’s understanding, satisfaction, quality of life, and the influence on their emotional state in different moments of the treatment.
Methods A 10-min video about head and neck radiotherapy and its toxicities was produced. A
prospective randomized clinical trial was performed in two groups: the control (n=65), which received standard verbal and written information, and the experimental group (n=65), which received standards information and the video. Appropriated questionnaires (HADS, UW-QOLv4, IRTU, and Post-RTU) were applied in 4 different moments in order to evaluate patients’ understanding, anxiety, depression, and quality of life.
Results The video improved the understanding of treatment and its side effects. Also, the video group
reported better awareness about oral health care during the treatment. Osteoradionecrosis and radiation-related caries were the most patients’ unknown side effects. On the other hand, the educational video did not modify the patients’ anxiety, depression, and quality of life. All patients reported a high satisfaction about the video.
Conclusions Audio-visual tools may improve patients' understanding of radiotherapy and showed to be
a useful tool to be used in association with verbal and written information in cancer centers. In addition, information about osteoradionecrosis and radiation-related caries must be reinforced to the patients.
INTRODUCTION
Head and neck (HN) cancer represents almost 4% of all malignancies, being frequently diagnosed at advanced stages and treated with radical therapies [1]. Radiotherapy (RT) is one of the main treatment options for HN cancer and it is commonly associated with surgery or chemotherapy [2]. Conventional HN RT generally involves high doses of radiation in fractionated daily doses, which lead to important toxicities in all tissues included in the radiation field [3–8]. Oral Mucositis, xerostomia, dermatitis, disgeusia, and candidiasis are examples of acute toxicities that occur during treatment. Also, chronic side effects such as xerostomia, radiation-related caries, and osteoradionecrosis, will certainly interfere with patients' lives. All these side effects may play a fundamental role in patient’s therapy, prognosis, and quality of life [3–9].
Since the diagnosis, cancer patients are likely to have sentiments of anxiety, susceptibility, and helplessness related to the uncertain clinical course of the disease and treatment [10]. HN cancer patients undergoing RT often arrive at the first consultation after surgical treatment with physical and psychological sequelae, uncertainty, anxiety, depression, stress, shame, guilt, changes in facial appearance, and self-esteem [11, 12]. Therefore, the whole process since diagnosis to rehabilitation is stressful for patients and their relatives [13–15]. This can be particularly relevant in the context of Public Hospitals in Latin-America, where most of the patients are poorly educated with many social issues related to a developing country. Thus, most of the patients want as much information as possible about their disease and treatment [11, 12, 16, 17].
Usually, patients go through a pre-RT visit with the multidisciplinary team aiming to solve doubts about the therapy, understand the treatment process and receive recommendations. However, RT is technically complex and patients are often unaware of what to expect with the treatment. Due to the difficulty in understanding the language and the content of the provided information [13, 16, 18, 19], most of the patients are not able to absorb the amount of information [20] and many of them are unsatisfied with the information received prior to treatment [21].
Different methods have been suggested to improve the medical information provided to patients, but the most used in clinical practice consists of verbal and written materials. However, their effectiveness is reduced [22]. Although the understanding of cancer and treatment has been associated
with the level of education and employment status, it has been shown that the use of an educational video could improve the understanding of the patients [23–28]. The use of audio-visual methods has been demonstrated to be a low-cost option associated with an improvement in the information retention [12, 16, 26] and patient satisfaction [12, 13, 18, 29, 30]. The effectiveness of educational videos about collateral effects in medical treatments can be found in different medical fields, showing an improvement in treatment adherence and prevention of complications related to non-compliance of recommendations [18, 25, 27]. However, besides some studies presented no significant results and others showed good improvement of patients’ understanding [13, 23], the literature still lacks solid data in the HN cancer field [31].
In 2013, our research group published a study indicating that the use of an educational video in HN cancer patients treated with RT may improve the patients’ understanding about the treatment, its side effects, and may reduce the doubts and fear before therapy [23]. However, due to several limitations presented in this previous study, the authors highlighted the necessity of a next study with a higher number of patients, including other analysis in different treatment moments. Therefore, the aim of the present study is to verify if an educational video focused on the HN cancer RT toxicities and their management contributes to the improvement of the patient’s understanding, satisfaction, quality of life, and the influence in their emotional state in different moments of the treatment.
METHODS
A prospective longitudinal randomized clinical trial study was conducted at São Paulo State Cancer Institute (ICESP), São Paulo, Brazil. The study was approved by the National Human Research Ethics Committee (CAAE: 51237015.5.0000.0065). Sample size calculation was performed to ensure that the number of cases assessed was sufficient to extract relevant and accurate information. Considering a confidence level of 95% (α= 0.05) and a power of 80% (1-β = 0.80), a number of 65 patients per group was established.
The inclusion criteria were contemplated by patients diagnosed with HN cancer and treated for the first time with RT (curative dose; 50-70 Gy); the participants had to be over the age of 18, be able to understand the applied questionnaires and complete all the survey period with a stable self-awareness.
All patients who did not meet the inclusion criteria over the whole survey period were excluded. All participants have signed the consent form and the study was conducted between January 2016 and November 2018.
The patients were divided into two groups: a control group, without any modification of the current hospital protocol, in which patients received verbal and written information about the RT, its toxicities, and recommendations; and an interventional group (video group), where patients watched an educational video after the hospital standard protocol. After the video presentation, the patients’ personal opinion about the new tool was recorded. All patients were accompanied by relatives or friends during all survey process. Once participants had concluded the study, demographics and clinicopathological data were collected using the Hospital electronic medical record system (Tasy, Java version; product #NOCTN306, Koninklijke Philips N.V., 2004 - 2017).
Video
A 10-min video was produced by a professional audiovisual company according to a script developed by the multidisciplinary oncology team; the video was produced with a clear narrative, subtitles, short videos, and pictures. The video was shown on a 21-inch monitor with speakers, using a low light room in the Hospital. The key content of the educational video involved: a clear and simple overview of what is radiation and how does it treat cancer; explanation of the need for a planning computed tomography scan, the confection and use of the mask and intraoral stent (when appropriated); reinforcement of the need for dental evaluation before the treatment beginning; examples of all the possible toxicities; and recommendations about oral hygiene, bad habits suspension, general care, and proper diet.
Questionnaires
The questionnaires were applied equally for both groups in four different phases. A pre-treatment phase, during the patient’s first consultation after the establishment of the pre-treatment; the second week of RT, comprising the beginning of the oral toxicities effects (2-10 Gy); the fifth week of the RT, comprising the manifestation and intensification of all toxicities (40-50 Gy); and the
post-treatment phase, 30 days after the end of the RT. The questionnaires types applied in each post-treatment phase is illustrated in Table 1.
Table 1: Types of questionnaires applied according to the treatment phases.
Phases Questionnaires
HADS UW-QOL IRTU Post-RTU
Pre-treatment x X x
Second week of RT x X x
Fifth week of RT x X
30 days post-treatment x X x
HADS: Hospital Anxiety and Depression Scale; UW-QOL: University of
Washington Quality of Life Questionnaire v.4; IRTU: Initial Radiotherapy Understanding Questionnaire; Post-RTU: Post-radiotherapy Understanding Questionnaire.
Hospital Anxiety and Depression Scale (HADS) and University of Washington Quality of Life Questionnaire (UW-QOLv4)
The HADS is a 14-item questionnaire used to assess the severity of anxiety and depression symptoms. Seven items assess anxiety, and the other 7 items assess depression. Each item has four possible responses (scored 0–3), and the anxiety (HADS-A) and depression (HADS-D) subscales feature independent measures [32, 33]. The averages of the subscales were obtained for each group.
The UW-QOLv4 comprised 15 items: 12 disease-specific questions (pain, appearance, activity, recreation, swallowing, chewing, speech, shoulder mobility, taste, saliva, mood, and anxiety) and three general questions. The items were scored on a scale ranging from 0 (worst) to 100 (best) using a Likert-type scale. In the present study, a UW-QOLv4 composite score from 0 to 100 was obtained by averaging the scores of the disease-specific items [34, 35].
Initial Radiotherapy Understanding (IRTU) and Post-Radiotherapy Understanding (Post-RTU) Questionnaires
Both questionnaires were developed and used by González-Arriagada et al., [23] in a previous study. The IRTU questionnaire comprises of 14 items where the understanding of the patients was determined by the first 10 questions and the other 4 questions intend to determine doubts about the therapy and anxiety level. The Post-RTU questionnaire comprises of 11 items and was formulated
according to the IRTU questionnaire questions; the first 6 questions were related to the understanding of the therapy and the remaining questions were applied to determine the satisfaction of the received information and fear. There was only one correct answer for each question to determine the patients’ understanding (“yes” or “no” answers).
Analysis
The results were tabulated and analyzed with the SAS software (The SAS System, 9.4. SAS Institute Inc., Cary, NC, USA, 2012). All data included in this study were tested regarding normality using the Shapiro-Wilk test and the asymmetry and kurtosis coefficients. Mixed linear generalized models of rank-based analysis of variance (ANOVA-R) were adjusted aiming to test the effects of groups and phases through the methodology of an experiment with repeated measures. Also, rank-based multiple comparisons of averages based on Student’s t-test was obtained. The significance level was fixed at 5% for all statistical tests.
RESULTS
Clinicopathological and demographic findings
A total of 130 patients (65 per group) completed the study. Seventy-one patients were excluded during the survey period due to complications related to cancer or the treatment such as RT absences or discontinuation, change to palliative protocol, limitations to answer the questionnaires, or death. The clinicopathological data details are presented in Table 2. Despite the randomization of the study, the groups presented an excellent homogeneity. All patients were over 40 years old and were mainly between the sixth and seventh decades of life (mean age of 59.1 years, with a male predominance [89%]). The majority of the patients had a poor educational level (70% presenting less than high school education) and presented marked history of tobacco (95%) and alcohol consumption (85%). All of the patients were diagnosed with HN squamous cell carcinoma, and the most common tumor location was the Oropharynx (42%). Also, 89% of the patients presented advanced stage disease (stages III and IV). The patients received RT exclusively (12%) or associated with surgery (15%) and/or chemotherapy
(73%). The total dose received by the patients ranged from 50 to 70 Gy, fractioned in daily doses of 200 or 250 cGy (Table 2).
Table 2: Mean ± Standard deviation of age at first consultation and frequency of categorical demographics and clinicopathological data.
Control group (n=65) Video group (n=65) Total (n=130)
Age 59.1 ±7.9 59.1 ±7.8 59.1 ±7.8 40–49 7 (11%) 8 (12%) 15 (12%) 50–59 23 (35%) 24 (37%) 47 (36%) 60–69 29 (45%) 27 (42%) 56 (43%) >70 6 (9%) 6 (9%) 12 (9%) Gender Male 61 (94%) 55 (85%) 116 (89%) Female 4 (6%) 10 (15%) 14 (11%) Educational level 0 - non-educated 4 (6%) 2 (3%) 6 (5%) 1 - basic education 40 (62%) 45 (69%) 85 (65%) 2 - high school 14 (22%) 15 (23%) 29 (22%) 3 - college 7 (11%) 3 (5%) 10 (8%)
Tobacco use history
Yes 61 (94%) 62 (95%) 123 (95%)
Deny 4 (6%) 3 (5%) 7 (5%)
Alcohol abuse history
Yes 52 (80%) 58 (89%) 110 (85%) Deny 13 (20%) 7 (11%) 20 (15%) Location Oral cavity 20 (31%) 17 (26%) 37 (28%) Oropharynx 28 (43%) 27 (42%) 55 (42%) Larynx 12 (18%) 14 (22%) 26 (20%) Other location 5 (8%) 7 (11%) 12 (9%) Tumor Stage (SCC) I 2 (3%) 1 (2%) 3 (2%) II 5 (8%) 7 (11%) 12 (9%) III 12 (18%) 11 (17%) 23 (18%) IV 46 (71%) 46 (71%) 92 (71%) Treatment RT 5 (8%) 10 (15%) 15 (12%) RT+Surg 11 (17%) 9 (14%) 20 (15%) RT + CT 41 (63%) 37 (57%) 78 (60%) RT+Surg+CT 8 (12%) 9 (14%) 17 (13%)
Total dose of radiation
<6.000 3 (5%) 1 (2%) 4 (3%)
6.000–7.000 62 (95%) 64 (98%) 126 (97%)
n number of patients; RT: radiotherapy; Surg: surgery; CT: chemotherapy; Tumor Stage - According to 7th
Hospital Anxiety and Depression Scale and University of Washington Quality of Life Questionnaire results.
The Anxiety and Depression scores were treated separately and no difference was found between the studied groups (HADS-A, P=0.1832; HADS-D, P=0.2641). The same occurred for the UW-QOL scores (P=0.5148). However, the treatment phases influenced both questionnaires results (HADS and UW-QOL; Figure 1). The results revealed that the patients showed more anxious before the beginning of the RT and in the fifth week of the treatment. The level of depression was higher in the fifth week of RT. Regarding the UW-QOL, all evaluated phases were affected and the worst quality of life was presented in the fifth week of treatment (Figure 1).
Figure 1: Mean ± Standard deviation of Anxiety (A), Depression (B) and Quality of Life (C) scores according to phases. P value obtained from ANOVA-R. Means followed by the same letter are not significantly different (P<0.05; t-test applied on ranks). HADS: Hospital Anxiety and Depression Scale; UW-QOL: University of Washington Quality of Life Questionnaire v.4. Pre-RT: Pre-radiotherapy phase; Week 2: Second week of radiotherapy; Week 5: Fifth week of radiotherapy; Post-RT: 30 days after the final of the radiotherapy.
Findings of Radiotherapy understanding questionnaires.
All the patients in the video group showed high acceptance and satisfaction after the video presentation and reported that they would recommend the video use for the next patients. A general understanding of radiotherapy and its toxicities was evaluated by the percentage of right answers presented in the first 10 questions of the IRTU questionnaires, and the first 6 questions on the Post-RTU questionnaire (Table 3). The video group showed a better understanding in all phases. However, the
difference between the groups was statistically significant only in the second week of RT (89%, video group; 77% control group; P=0.0024; Table 3).
Table 3: General correct answers percentage about radiotherapy knowledge according to phase.
P value for IRTU and Post-RTU questionnaires was respectively obtained from ANOVA-R
and Student t-test. Means followed by the same letter are not significantly different (P<0.05; t-test applied on ranks).
Questionnaire Phase Group Correct answers percentage P value
IRTU Pre-RT Control 69 c 0.0024 Video 73 cb Week 2 Control 77 b Video 89 a
Post-RTU Post-RT Control 78 0.1173
Video 86
Pre-RT: Pre-radiotherapy phase; Post-RT: Post-radiotherapy phase.
The understanding of the patients according to each question and phase is illustrated in the Tables 4 and 5. As the general score quantification presented, in most of the questions, patients of the video group showed a better understanding compared to the control group. However, the difference between the groups was statistically significant only for question #3 (P=<.0001), which was about the need of dental evaluation (examination of the mouth) before RT in edentulous patients. The most unknown toxicities Pre-RT were the osteoradionecrosis (56%, question #10), which was displayed to the patients as a possibility of bone healing problem after tooth extraction, followed by the caries susceptibility in patients undergo RT (radiation-related caries; 43%, question #4; Table 5). The majority of the patients showed a significant improvement of the understanding in the second week of the treatment (8/10 questions; Table 4).
There was no difference between the two groups regarding the questions verifying doubts about the treatment, fear, and anxiety level. However, the patients reported being less scarred (P=0.0018) and less anxious in the second week of the treatment (P=<0.0001). About 57% of the patients reported that they did not know someone (friend or relative) who has been treated by RT.
Control Video Control Video 1. Do you know why you will do radiotherapy?
Yes 83% 85% 86% 95%
0.9986 0.0448
No 17% 15% 14% 5%
2. Do you know if there are complications (mouth, teeth, bone, skin) associated with radiotherapy?
Yes 77% 74% 85% 94%
0.1443 0.0012
No 23% 26% 15% 6%
3. Do you think that dental evaluation (examination of the mouth and teeth) before radiotherapy is needed only in patients who have teeth?
Yes 82% 17% 75% 20%
<.0001 0.7619
No 18% 83% 25% 80%
4. Do you think that the patient who will undergo radiotherapy is more likely to get caries?
Yes 57% 57% 69% 80%
0.4186 0.0030
No 43% 43% 31% 20%
5. Do you think that radiotherapy can burn the skin?
Yes 82% 78% 86% 95%
0.7594 0.0028
No 18% 22% 14% 5%
6. Do you think that you can get ulcers in the mouth because of the radiation?
Yes 85% 86% 95% 98%
0.2692 0.0023
No 15% 14% 5% 2%
7. Do you think that thrush can appear during radiotherapy?
Yes 69% 71% 82% 94%
0.1378 0.0003
No 31% 29% 18% 6%
8. Do you think that you can lose the taste of food due to radiotherapy?
Yes 82% 78% 94% 91%
0.5999 0.0021
No 18% 22% 6% 9%
9. Do you think that you can stay with dry mouth or without saliva because of the radiotherapy?
Yes 89% 80% 88% 94%
0.8817 0.0912
No 11% 20% 12% 6%
10. Can radiotherapy impair bone healing if you need to remove the teeth?
Yes 46% 43% 62% 72%
0.3212 <.0001
No 54% 57% 38% 28%
11. Still have doubts about the radiotherapy treatment?
Yes 15% 17% 8% 11%
0.5441 0.0609
No 85% 83% 92% 89%
12. Do you feel afraid or scared to do radiotherapy treatment?
Yes 25% 29% 14% 11%
0.7448 0.0018
No 75% 71% 86% 89%
13. How would you define the level of anxiety you have before radiotherapy?
(a) Very anxious 28% 35% 12% 8%
0.8648 <.0001
(b) Anxious 28% 18% 15% 17%
(c) A little anxious 23% 29% 23% 32%
(d) Not anxious 22% 17% 49% 43%
14. Do you know someone (friend or relative) who had radiotherapy treatment?
Yes 45% 43% 43% 43%
0.9193 0.8586
No 55% 57% 57% 57%
Regarding the Post-RTU questionnaire, there was no different in the understanding of the patients between the groups (P>0.05). However, some important information was observed: seven patients (11%) in the control group and two (3%) in the video group reported that they did not know why they had received the RT. Thirty-eight percent (25 patients) in the control group and 20% (13 patients) in the video group reported that they did not have any complication caused by RT (P=0.0638), although all the patients presented toxicities. Three (5%) patients in the control group and 4 (6%) in the video group answered that they presented complications that were not previously informed, and 3 (5%) patients in the control group affirmed that the dental evaluation before RT was not necessary. About 36% (46 patients) of the patients still showed unfamiliarity about the osteoradionecrosis topic saying that they did not know if extraction should be avoided in the future, after the RT (question #6). The majority of the patients (94,5%) reported that the information received before treatment was enough to be prepared for it and 23% reported that they thought to quit RT. Finally, although it was not statistically significant, more patients in the video group reported being more worried about taking care of their oral health during RT (86%, video group; 78%, control group; P=0.5425; Table 5).
Table 5: Post-radiotherapy Understanding Questionnaire percentage results in control and video group. P values obtained from ANOVA-R based on a generalized linear mixed model (GLMM).
Post-radiotherapy Understanding Questionnaire Control Video P value
1. Do you know why you did the radiotherapy?
Yes 89% 97%
0.9702
No 11% 3%
2. Did you have any complications caused by radiotherapy?
Yes 62% 80%
0.0638
No 38% 20%
3. Were there some complications during radiotherapy that you were not informed of?
Yes 5% 6%
0.6042
No 95% 94%
4. Do you think that dental evaluation before radiotherapy was necessary?
Yes 95% 100%
0.9803
No 5% 0%
5. Do you think that the patient who underwent radiotherapy is more likely to get caries?
Yes 68% 82%
0.3239
No 32% 18%
6. Do you know if extractions should be avoided in the future in patients who were treated with radiotherapy?
Yes 62% 66%
0.7773
No 38% 34%
7. Do you think that the information received prior to radiotherapy were enough to prepare you for treatment?
Yes 95% 94%
0.7634
No 5% 6%
8. Did you feel afraid or scared before radiotherapy?
Yes 42% 42%
0.6287
No 58% 58%
9. Did you think about quitting radiotherapy?
Yes 23% 23%
0.6374
No 77% 77%
10. Did you feel more worried about taking care of your oral health during the radiotherapy?
Yes 78% 86%
0.5425
No 22% 14%
11. Would you include some other information before the radiotherapy?
Yes 9% 11%
0.6801
Educational level and understanding grade
The educational level only affected the general understanding of RT between the groups in the Post-RT phase (P= 0.0245). The results showed an understanding improvement of the less educated patients (up to basic education) in the video group, presented a correct answers average of 88%, while the control group presented 75%. The patients’ educational level did not affect the majority of the variables studied (P>0.05).
DISCUSSION
Diagnosis and treatment of cancer are known to be inevitably distressing to patients and their relatives [10, 13–15]. Studies show that providing comprehensive and relevant information about the treatment can assist patients by preparing them and enhancing their ability to manage their illness and its side effects [31, 36]. Hence, it is crucial that the multidisciplinary team possess resources to provide information to patients in the most comprehensive manner, especially when disease management is complex as is in HN cancer [31].
Audio-visual tools can provide a multi-channel message through non-verbal and representational communication, showing to be effective in several aspects in diverse fields of medicine [18, 25, 27]. Also, educational videos are time efficient in the outpatient setting, being easy and inexpensive to incorporate into busy health care settings [12, 13, 16, 26]. Therefore, aiming to better justify the implementation of this tool in cancer centers, the current study is an improvement and continuation of a seminal study of an educational video in HN cancer patients treated with RT [23]. Different from the studies found in the literature [23, 24, 26, 28, 30, 37, 38], the patient’s understanding, quality of life and emotional state distress were evaluated in different moments of the treatment.
The clinicopathological and demographic findings of the participants in the present study were consistent with the classical HN cancer patient profile [1, 2]. Besides the unfavorable clinical profile, emotional factors such as depression and anxiety are common findings that may influence treatment side effects and the expectations of recovery after RT [11, 23]. However, corroborating the previous study [23], no statistical differences were found between the video and control groups when anxiety was evaluated by the understanding questionnaire. Moreover, according to the specific questionnaires
evaluated, the educational video did not influence the patients’ anxiety, depression, and quality of life. Nevertheless, the results of the different treatment phases showed that patients presented the highest level of anxiety before the beginning of the treatment. This result can be expected since the patients are in a vulnerable situation before an unknown procedure. In the second week of RT, known for the beginning of the RT toxicities manifestation, the patients showed a depression level increase and a worsening of the quality of life compared to the Pre-RT phase. On the other hand, the patients reported feeling less scared after having known the treatment routine.
In the fifth week, the patients presented the worst levels of depression and quality of life compared to the other phases evaluated. This can be explained by the peak of the toxicities manifestations usually presented in this phase, which remain until the end of the RT. Hence, is important to highlight this data to bring the attention of the multi-professional team to providing patients' adequate psychological support in this treatment moment.
Thirty days after the end of the treatment, a considerable recovery of the acute toxicities is frequently noted. Therefore, this phase showed a decrease in the anxiety and depression levels and also an improvement of quality of life compared to the previous phase. However, the anxiety and depression levels were similar to those presented in the second week of treatment, and the quality of life remained with worse results compared to the Pre-RT and Week 2 phases. These findings can be explained by the fact that the patients still remained worried about the uncertainties of the treatment results, the need for routine exams, and the presence of the chronic RT toxicities. A previous study [15] reported that high HADS scores can also be related to the presence of a feeding tube, speech and swallowing problems, less social contacts, a passive style of coping, and non-expression of emotions. Corroborating the present results, Haisfield-Wolfe et al. [39] reported that mild to moderate depression may continue for three to six years after diagnosis.
Another factor which could potentially influence the patients’ knowledge about the treatment is their educational level [23]. HN cancer patients commonly have a low educational level, and many patients are not able to read, which can difficult communication with them. Dunn et al. [13] stated that the association of educational methods may achieve better results in patients’ knowledge and
satisfaction. Also, it has been reported that a video is a useful educational tool for the undereducated population [24] and it can be helpful and better than booklets as a complementary educational tool [22].
Our previous study stated that the video was particularly useful in patients with a low educational level [23]. According to the present findings, the less educated patients had a better understanding of the information received only after treatment (Post-RT phase). It is important to mention that the previous study was performed in a small local hospital with no standardized RT information protocols while the present survey was conducted in one of the largest cancer hospitals of Latin America, using the video as a complementary method, without changes in the hospital routine protocols. Curiously, in both studies, a few patients stated that they did not know why they would be receiving RT, and others reported that they did not have any complication caused by RT, although all of the patients presented some toxicities during treatment. Even though these patients appeared to present a good self-awareness, these results can be explained by several reasons such as the state of confusion of the patients after therapy, low educational level, difficulties of understanding, and the questions not being well or clearly formulated [23].
Despite the educational level, our results showed that the majority of patients showed a significant improvement in the understanding during the treatment progression. This can be expected as the patients have suffered side effects and the information are usually reinforced during treatment. Matsuyama et al. [20] also stated that patients may learn about RT during their treatment course, and reinforced the importance of an educational tool application at the initial consultation as in this time the patients are asked to sign the informed consent for treatment. Similar than the previous study [23] osteoradionecrosis and radiation-related caries were the most unknown side effects associated with RT in the IRTU and Post-RTU questionnaire. González-Arriagada et al. [23] mentioned that it probably happened because the patients were not so interested in the late effects during the treatment and also because of the high proportion of edentulous patients. However, these are the most important consequences of HN RT, and it is crucial that the patients comprehend those implications to prevent future problems such as osteonecrosis of the jaw.
The literature has emphasized that the improvement of the understanding about cancer and its therapy can help the patients to make decisions and obtain better results with medical treatments [23,
24, 31]. The use of images with verbal communication might be the best and cost-effective way of giving pre-treatment information, obtaining good results and patients' acceptance. In the present study, despite the educational video did not modify patients’ anxiety, depression, and quality of life, the video group demonstrated a better understanding about their treatment and its side effects, high acceptance and satisfaction after the video presentation. Also, the video group showed to be more awareness about the necessity of oral evaluation before the beginning of the treatment (regardless of the presence of teeth) and the about oral health care during RT.
Thus, the present study demonstrated that an audio-visual tool may improve patients' understanding of RT and showed to be a useful tool to be used in conjunction with verbal and written information in cancer centers. In addition, information about osteoradionecrosis and radiation-related caries must be reinforced to patients.
REFERENCES
1. Bray F, Ferlay J, Soerjomataram I, et al (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424.
2. Shah JP, Gil Z (2009) Current concepts in management of oral cancer-surgery. Oral Oncol 45:394–401.
3. Rosales AC de MN, Esteves SCB, Jorge J, et al (2009) Dental needs in Brazilian patients subjected to head and neck radiotherapy. Braz Dent J 20:74–7.
4. Ohrn KE, Sjödén PO, Wahlin YB, Elf M (2001) Oral health and quality of life among patients with head and neck cancer or haematological malignancies. Support Care Cancer 9:528–38. 5. Specht L (2002) Oral complications in the head and neck radiation patient. Introduction and
scope of the problem. Support Care Cancer 10:36–9.
6. Tao Y, Daly-Schveitzer N, Lusinchi A, Bourhis J (2010) Advances in radiotherapy of head and neck cancers. Curr Opin Oncol 22:194–9.
8. Moroney LB, Helios J, Ward EC, et al (2017) Patterns of dysphagia and acute toxicities in patients with head and neck cancer undergoing helical IMRT ± concurrent chemotherapy. Oral Oncol 64:1–8.
9. Guchelaar HJ, Vermes A, Meerwaldt JH (1997) Radiation-induced xerostomia: pathophysiology, clinical course and supportive treatment. Support Care Cancer 5:281–8. 10. Llewellyn CD, McGurk M, Weinman J (2007) The relationship between the Patient Generated
Index (PGI) and measures of HR-QoL following diagnosis with head and neck cancer: are illness and treatment perceptions determinants of judgment-based outcomes? Br J Health Psychol 12:421–37.
11. Chen S-C, Lai Y-H, Liao C-T, et al (2013) Supportive care needs in newly diagnosed oral cavity cancer patients receiving radiation therapy. Psychooncology 22:1220–8.
12. Bennenbroek FTC, Buunk BP, Stiegelis HE, et al (2003) Audiotaped social comparison information for cancer patients undergoing radiotherapy: differential effects of procedural, emotional and coping information. Psychooncology 12:567–79.
13. Dunn J, Steginga SK, Rose P, et al (2004) Evaluating patient education materials about radiation therapy. Patient Educ Couns 52:325–332.
14. Lee C-Y, Lee Y, Wang L-J, et al (2017) Depression, anxiety, quality of life, and predictors of depressive disorders in caregivers of patients with head and neck cancer: A six-month follow-up study. J Psychosom Res 100:29–34.
15. Verdonck-de Leeuw IM, Eerenstein SE, Van der Linden MH, et al (2007) Distress in spouses and patients after treatment for head and neck cancer. Laryngoscope 117:238–41.
16. Knox R, Butow PN, Devine R, Tattersall MHN (2002) Audiotapes of oncology consultations: only for the first consultation? Ann Oncol Off J Eur Soc Med Oncol 13:622–7.
17. Lamb B, Green JSA, Vincent C, Sevdalis N (2011) Decision making in surgical oncology. Surg Oncol 20:163–8.
18. Hahn CA, Fish LJ, Dunn RH, Halperin EC (2005) Prospective trial of a video educational tool for radiation oncology patients. Am J Clin Oncol 28:609–12.
Eur J Cancer 35:1592–7.
20. Matsuyama RK, Lyckholm LJ, Molisani A, Moghanaki D (2013) The value of an educational video before consultation with a radiation oncologist. J Cancer Educ 28:306–313.
21. van der Meulen IC, de Leeuw JRJ, Gamel CJ, Hafsteinsdóttir TB (2013) Educational intervention for patients with head and neck cancer in the discharge phase. Eur J Oncol Nurs 17:220–227. 22. Butow P, Brindle E, McConnell D, et al (1998) Information booklets about cancer: factors
influencing patient satisfaction and utilization. Patient Educ Couns 33:129–41.
23. González-Arriagada WA, de Andrade MAC, Ramos LMA, et al (2013) Evaluation of an educational video to improve the understanding of radiotherapy side effects in head and neck cancer patients. Support Care Cancer 21:2007–2015.
24. Bouton ME, Shirah GR, Nodora J, et al (2012) Implementation of educational video improves patient understanding of basic breast cancer concepts in an undereducated county hospital population. J Surg Oncol 105:48–54.
25. Dawdy K, Bonin K, Russell S, et al (2018) Developing and Evaluating Multimedia Patient Education Tools to Better Prepare Prostate-Cancer Patients for Radiotherapy Treatment (Randomized Study). J Cancer Educ 33:551–556.
26. Koss TS, Macci Bires A, Cline TW, Mason DL (2018) Evaluation of an Educational Video: What to Expect on the First Day of Chemotherapy. Crit Care Nurs Q 41:142–160.
27. Williams K, Blencowe J, Ind M, Willis D (2017) Meeting radiation therapy patients informational needs through educational videos augmented by 3D visualisation software. J Med Radiat Sci 64:35–40.
28. Nathoo D (2017) Video Material as an Effective Educational Tool to Address Informational and Educational Needs of Cancer Patients Undergoing Radiation Therapy. J Cancer Educ 32:219– 227.
29. Thomas R, Thornton H, Mackay J (1999) Patient information materials in oncology: are they needed and do they work? Clin Oncol (R Coll Radiol) 11:225–31.
30. Du W, Mood D, Gadgeel S, Simon MS (2009) An educational video to increase clinical trials enrollment among breast cancer patients. Breast Cancer Res Treat 117:339–47.