RESUMO
O objei vo do presente trabalho é classifi -car o grau de mucosite oral de acordo com os parâmetros internacionais do Common Toxicity Criterion (CTC) em pacientes por-tadores de tumor de cabeça e pescoço submei dos à radioterapia e quimioterapia concomitantes, e caracterizar um perfi l dos pacientes em nosso meio, verifi cando os hábitos dos indivíduos, as caracterísi cas do tumor, o protocolo de tratamento e a intensidade desta reação aguda. Neste estudo foram avaliados 50 pacientes, sub-mei dos à radioterapia em megavoltagem com doses entre 66 a 70 Gy e quimiotera-pia com cisplai na ou carboplai na conco-mitante. Semanalmente foi avaliado o grau de mucosite de acordo com o CTC, uma escala ordinal que apresenta 4 graus. Ob-servou-se interrupção do tratamento por mucosite em 36% do total de pacientes e em 100% dos pacientes diabéi cos, o que nos permii u verifi car que esta patologia contribui para a gravidade da mucosite
DESCRITORES
Neoplasias de cabeça e pescoço Radioterapia
Quimioterapia Mucosite
Enfermagem oncológica
Mucositis in head and neck cancer patients
undergoing radiochemotherapy
*O
RIGINAL
A
R
TICLE
ABSTRACT
The objeci ve of present study was to clas-sify oral mucosii s according to the Com-mon Toxicity Criterion (CTC) internai onal parameters in head and neck tumor pa-i ents simultaneously treated with radio and chemotherapy, and characterize a pai ent profi le in our area, observing the individu-als’ habits, tumor characterisi cs, treatment protocol and acute reaci on intensity. Fit y pai ents undergoing simultaneous 66 to 70 Gy megavoltage radiotherapy and cisplai n/ carboplai n chemotherapy were evaluated in this study. Weekly evaluai ons of the de-gree of mucosii s were perfoemed accord-ing to CTC, a four-degree ordinal scale; 36% of all pai ents and 100% of those with diabe-tes disconi nued treatment due to mucosi-i s, showing that this pathology contributes to the severity of mucosii s.
DESCRIPTORS Head and neck neoplasms Radiotherapy
Drug therapy Mucosii s Oncologic nursing
RESUMEN
El trabajo objei vó clasifi car el grado de Mucosii s ora de acuerdo a parámetros internacionales del CTC en pacientes por-tadores de tumores de cabeza y cuello somei dos a radioterapia y quimioterapia concomitantes, y caracterizar un perfi l de pacientes en nuestro medio, verifi cando hábitos de los individuos, caracterísi cas del tumor, protocolo de tratamiento e in-tensidad de esta reacción aguda. Fueron evaluados 50 pacientes somei dos a ra-dioterapia en megavoltaje con dosis entre 66 y 70 G y quimioterapia con cisplai no o carboplai no concomitante. Se evaluó se-manalmente el grado de Mucosii s según el Common Toxicity Criterio – CTC, una es-cala ordinal que presenta cuatro grados. Se observó interrupción del tratamiento por Mucosii s en 36% del total de pacientes y en 100% de los pacientes diabéi cos, lo que nos permite verifi car que dicha patología potencia la gravedad de la mucosii s.
DESCRIPTORES Neoplasia de cabeza y cuello Radioterapia
Quimioterapia Mucosii s
Enfermería oncológica
Renata Cristina Schmidt Santos1, Rodrigo Souza Dias2, Adelmo José Giordani3, Roberto Araújo
Segreto4, Helena Regina Comodo Segreto5
MUCOSITE EM PACIENTES PORTADORES DE CÂNCER DE CABEÇA E PESCOÇO SUBMETIDOS À RADIOQUIMIOTERAPIA
MUCOSITIS EN PACIENTES PORTADORES DE CÁNCER DE CABEZA Y CUELLO SOMETIDOS A RADIOQUIMIOTERAPIA
* Taken from the thesis “Mucositis in head and neck cancer patients submitted to concomitant radio and chemotherapy”, Universidade Federal de São Paulo, 2009. 1RN. M.Sc. in Sciences, Universidade Federal de São Paulo. São Paulo, SP, Brazil. re_antena@yahoo.com.br 2 Assistant Physician. Ph.D. student,
Graduate Program in Radiotherapy, Oncology Department, Universidade Federal de São Paulo. São Paulo, SP, Brazil. rsdias@uninet.com.br 3 Physicist.
MD, Coordinator of the Specialization Program in Medical Physics, Radiotherapy Sector, Oncology Department, Universidade Federal de São Paulo. São Paulo, SP, Brazil. adelmogiordani@ig.com.br 4 Associate Professor, Head of the Radiotherapy Sector, Oncology Department, Universidade Federal de
São Paulo. São Paulo, SP, Brazil. segreto.dmed@epm.br 5 Associate Professor, Coordinator of the Experimental Radiotherapy Laboratory, Oncology
Mucositis causes signifi cant pain,
chewing and swallowing diffi culties and is considered the most debilitating acute
reaction during head and neck cancer treatment.
INTRODUCTION
Head and neck cancer comprises all carcinomas
origi-nai ng in the muco-squamous epithelium, ranging from
the lips, oral and nasal cavii es, pharynx to the larynx and
middle ear. It is the third most prevalent tumor around the world and represents 7% of the 22.4 million people
diag-noses with cancer, excluding non-melanoma skin cancer(1).
With regard to Brazil, in 2010, about 14,120 new cases
of mouth cancer occurred. This fi gure corresponds to the
fit h most incident cancer among men and the seventh
among women(2).
The treatments used for this disease involve three
mo-dalii es: surgery, radiotherapy and chemotherapy, which
can be administered exclusively or concomitantly(3).
Head and neck cancer pai ents who receive
radio-therapy can develop reaci on of diff erent intensii es in
the mucosa. The associai on between radio and
chemo-therapy increases the incidence, severity and durai on of
oral mucosii s, especially when combinai ons of diff erent
drugs and hyperfraci onai on schedules are
used(4).
Mucosii s causes signifi cant pain,
chew-ing and swallowchew-ing diffi culi es and is
con-sidered the most debilitai ng acute reaci on
during head and neck cancer treatment(3).
The mechanism through which
muco-sii s occurs is based on the fact that oral
mucosii s presents high levels of mitoi c
aci vity and high cell turnover. Due to the
high degree of cell desquamai on, there is
a coni nuous need for cell muli plicai on to
recover the oral mucosa. Tissues with high
levels of mitoi c aci vity respond rapidly to the radiai on,
as the most sensii ve phases of the cell cycle are G2 and
mitosis. Thus, the mucosa is rapidly aff ected(5). The same
is true for chemotherapeui c drugs. These interfere in the
cell proliferai on and division process. The fact that the
mucous membranes are constantly renewed makes them
extremely sensii ve to the aci on of these drugs(5-6).
Among the methods used to assess the mucosii s
de-gree in clinical praci ce, it is important to highlight that
adequate mucosa assessment is needed before stari ng
head and neck radiotherapy and chemotherapy, as well as during treatment. A good assessment method needs
to consider the pai ent’s report, physical and nutrii onal
status and a detailed oral cavity inspeci on(5,7).
Among the diff erent mucosii s classifi cai on scales, an
analysis of 400 studies show that 43% use the scale of the
Nai onal Cancer Common Toxicity Criteria (NCI-CTC), 38%
use the World Health Organizai on (WHO) scale, 10% use
specifi c scales and 5% use scales by collaborai ng groups,
such as the scale the Radiai on Therapy Oncology Group
(RTOG) and the Eastern Cooperai ve Oncology Group
(ECOG)(5) use.
In this study, we use the scale of the Nai onal Cancer
Common Toxicity Criteria (NCI-CTC), as a Portuguese ver-sion is available which was authorized by the Cancer
Ther-apy Evaluai on Program (CTEP), an NCI organ responsible
for publishing the table(8).
In view of the importance of mucosii s during
radio-therapy and chemoradio-therapy for head and neck tumor, this
study aims to classify the degree of mucosii s according to
internai onal CTC 2.0 parameters in pai ents submit ed to
concomitant radiotherapy and chemotherapy and to
ver-ify whether the individual characterisi cs of pai ents, the
disease and treatment infl uence the incidence and
sever-ity of the mucosii s.
LITERATURE REVIEW
In clinical terms, the installai on of mucosii s is
ob-served two weeks at er the start of radiotherapy. It starts
as an infl ammatory process of the mucosa,
predisposiion to opportunisi c infeci on
and, depending on its intensity, can evolve
to ulcerai on. Symptoms are pain and diffi
-culi es to eat, drink and talk. Consequences
include weight loss and worsening of the
pa-i ent’s general condii on(9).
Inii ally, mucosii s is characterized by
ep-ithelial cell deaths and absence of subsi
tu-i on by new cells. Capillary blood vessels
be-come hyperpermeable, leading to mucosal edema and decreased blood supply. These events determine the appearance of an
evo-lui onary clinical situai on with four phases:
whitening of the mucosa, erythema, pseudomembrane
and ulcerai on(7).
The most important risk factors determining greater
mucosal cell suscepi bility to radiotherapy and
chemo-therapy are: smoking, treatment type, age, chronic
illness-es like diabetillness-es(9).
A research accomplished in 1990(10) which involved 41
smokers who received hyperfraci onated radiotherapy for
head and neck tumor treatment, showed that pai ents
who stopped smoking before the start of treatment
pre-sented blander reaci ons. Pai ents were divided in four
groups: the fi rst included pai ents who had never smoked,
the second pai ents who had quit smoking before the
start of treatment, the third those who quit smoking
dur-ing treatment, but soon at er restarted, and the fourth
group with pai ents who had not quit smoking at any i me
during treatment. It was observed that the durai on of
mucosii s for pai ents in groups 1 and 2 was 13 weeks, in
On the other hand, a research that involved 115 head
and neck cancer pai ents submit ed to concomitant
radio-therapy and chemoradio-therapy and aimed to observe the
in-fl uence of cigaret es on tumor response to treatment and
survival did not demonstrate any diff erence between the
group of smokers and non-smokers regarding mucosii s
severity, although pai ents who smoked during treatment
showed a drop in survival rates(11).
Specifi cally concerning radiotherapy, some factors can
infl uence mucosii s severity, including total dose, treated
volume, fraci oning and treatment i me(12). One study(13)
confi rms high incidence levels of mucosii s in pai ents
who receive radiotherapy, with 97% for pai ents
receiv-ing radiotherapy in a conveni onal fraci oning schedule,
100% for pai ents with altered fraci oning (accelerated
or hyperfraci onated fraci oning) and 89% for pai ents
receiving conveni onal fraci oning radiotherapy and
che-motherapy at the same i me. This same study highlights
that accelerated radiotherapy schedules can infl uence
mucosii s severity: 53% of pai ents with degree 3 and 4
mucosii s were submit ed to radiotherapy with fraci
on-ing alterai ons, in comparison with 34% of pai ents who
received conveni onal fraci oning and 43 % for pai ents
treated with conveni onal fraci oning radiotherapy and
chemotherapy at the same i me(13). The incidence of
de-gree 3 and 4 mucosii s corresponded to 47% of pai ents
treated with accelerated or hyperfraci oning. In pai ents
who received 70Gy with a daily fraci on of 200 cGy for 7
weeks, the incidence level amounted to 25%(12-13).
As for age, young pai ents concomitantly submit ed to
radiotherapy and chemotherapy are more prone to
mu-cosii s development due to the high mitoi c aci vity of the
epithelial cells. On the other hand, elderly would be less
prone to mucosii s due to their low mitoi c aci vity. With
regard to elderly pai ents submit ed to chemotherapy,
however, the physiological decline of the kidney funci on
can contribute to the development of mucosii s at more
advanced ages if no dose adjustment is made according
to the capacity of the pai ent’s kidney funci on. When the
kidney funci on decreases, excrei on i me for the drug
in-creases, so that it remains in the body longer and, hence,
can cause more damage. The relai on between the cell
replicai on rate and the severity of damage the ionizing
radiai on causes suggests that, the higher the age, the
lesser the severity of the reaci ons(14). Another study(15)
suggested that oral mucosa cell reparai on is impaired
with aging, contribui ng to the development of more
se-vere mucosii s.
With regard to diabetes, as this disease entails
sys-temic repercussions, it can infl uence mucosii s severity.
Research shows that type I and II diabetes pai ents are at
greater risk of developing gingivii s and periodontal
dis-ease due to the impaired healing and metalloproteinase
enzymes’ rapid degradai on of the collagen(16).
METHOD
An observai onal cohort study was developed
be-tween January and December 2006 at a teaching hospital
in São Paulo City. Approval from the hospital’s Insi tui
on-al Review Board was obtained under process 0365/05.
Out of 175 head and neck cancer pai ents forwarded
to the Radiotherapy Sector, 50 complied with the
inclu-sion criteria. Twenty-one of these were submit ed to
sur-gery, followed by radiotherapy and adjuvant chemothera-py, while 29 only received concomitant radiotherapy and chemotherapy.
The inclusion criteria in this study were: Pai ents over
18 years of age, diagnosed with head and neck cancer with histological evidence, in the following primary sites: oral cavity, oropharynx, hypopharynx, larynx and maxillary
sinus, submit ed to concomitant radiotherapy and
chemo-therapy, who signed the informed consent term.
The following exclusion criteria were adopted:
Pa-i ents with enhanced trismus, making tge adequate
in-speci on of the oral cavity and oropharynx impossible;
pai ents submit ed to another chemotherapy protocol,
pai ents previously submit ed to radiotherapy and/or
che-motherapy and pai ents who did not conclude the inii ally
proposed treatment.
Pai ents were submit ed to radiotherapy with
oppos-ing parallel cervicofacial fi elds, with the total dose ranging
between 66 and 70 Gy, in fraci ons of 2gy/day em
apa-relho de megavoltagem. They received chemotherapy
withReceberam quimioterapia com cisplai na na dose 30
mg/m2 of cisplai n per week or weekly carboplai n,
calcu-lated according to the plasma concentrai on curve.
The nurse interviewed the pai ents on the treatment
planning day. On this occasion, the fi rst mucosa
assess-ment took place, repeated every week during the eni re
treatment. The radiotherapist assessed the degree of
mu-cosii s, followed by the nurse.
For the interview, a form was prepared with general
informai on, a history with individual aspects for each
pa-i ent, disease and treatment characterisi cs.
The criterion adopted to assess the degree of
muco-sii s was the Common Toxicity Criterion – CTC, which is a
four-degree ordinal scale: Grade 0-no change; Grade 1-er-ythema of the mucosa; Grade 2-patchy
pseudomembra-nous reaci on (patches generally = 1.5 cm in diameter and
non-coni guous); Grade 3-confl uent pseudomembranous
reaci on (coni guous patches generally > 1.5 in diameter);
Grade 4-necrosis or deep ulcerai on; may include
bleed-ing not induced by minor trauma or abrasion(8). According
to the evolui on of the oral mucosii s during treatment,
therapeui c measures were taken, depending on the
The parameters for individual clinical characterisi cs of
the disease, of the mucosii s (global incidence of diff erent
grades, incidence per anatomic region, grades according to weeks of treatment) and main complaints reported by
the pai ents were submit ed to descripi ve analysis.
The parameters for the reaci on of the mucosa
accord-ing to individual clinical characterisi cs were submit ed to
infereni al analysis. For the infereni al analysis, the
pa-i ents were grouped as follows: pai ents whose treatment
was not suspended because of the mucosii s (grades 0,
1 and 2*) and pai ents whose treatment was suspended
because of the mucosii s (grades 2** and 3). The
treat-ment suspension criterion adopted for grade 2 pai ents
was reported dysphagia and odynophagia, compromising
nutrii on and the presence of non-confl uent but patchy
pseudomembranous reaci on.
The stai si cal tests used were: Fisher’s exact test (P)
and chi-square (x2).
For all tests, the rejeci on level of the null hypothesis
was set at 0.05 or 5% (p < 0.05), marking signifi cant rai os
with an asterisk and non-signifi cant ones with (NS).
RESULTS
In this study, 45 (90%) pai ents were male and 5 (10%)
female. The mean age was 58 years, 39 (78%) pai ents
were white and 11 (22%) black. Fourty (80%) pai ents
in-dicated they had quit smoking before the start of
treat-ment, while 8 (16%) admit ed they had not quit smoking
and only 2 (4%) affi rmed they had never smoked. Only 15
(30%) pai ents were hypertensive and 3 (6%) diabei c.
As for the primary site, 10 pai ents suff ered from oral
cavity cancer, 32 oropharyngeal, 4 hypopharyngeal, 3 la-ryngeal and 1 maxillary sinus cancer.
A predominance of grade 1 and 2 mucosii s was
ob-served (68%) (Picture 1), with higher incidence levels in the oropharyngeal region (51%) (Picture 2), between the third and sixth week of treatment (Picture 3).
Of all pai ents, 86% had their treatment interrupted
at some i me, in 36% of treatment due to mucosii s. The
mean interrupi on i me was 5.9 days.
The main complaints the pai ents reported at er the
start of treatment were loss of taste (41%) and xerostomia (29%) (Picture 4).
Picture 3 – Grade of mucositis according to treatment weeks
Picture 4 – Main patient complaints
Picture 2 – Incidence of mucositis according to topography
40 35 30 25 20 15 10 5 0
Grade 0 Grade 1 Grade 2 Grade 3
patients
(%)
16%
30%
38%
16%
25
20
15
10
5
0 Gg
Number
of
reactions
HP LJM RJM Orof Tg Reaction site
Grade 3 Grade 2 Grade 1
18 16 14 12 10 8 6 4 2 0
1º
Number
of
patients
Weeks
2º 3º 4º 5º 6º 7º 8º 9º 10º
Grade 1 Grade 2 Grade 3
45 40 35 30 25 20 15 10 5 0
Loss of taste
Patients
(%)
Odynophagia/ Dysphagia
Xerostomia Lack of appetite 41%
19%
29%
11%
The analysis of pai ents’ individual clinical
characteris-i cs, disease and treatment characterisi cs showed that
DISCUSSION
Mucosii s is quite a common complicai on in head
and neck cancer pai ents treated with chemotherapy and
radiotherapy. It is associated with discomfort and intake
and swallowing diffi culty, and its consequences can range
from treatment interrupi on to nasogastric probe use and
hospitalizai on(9).
In this research, the predominance of grade 1 (30%)
and 2 (38%) mucosii s was observed, with the oropharynx
as the main site. This is due to the fact that most pai ents
in the sample presented oropharyngeal and oral cavity tumors. In literature, we found a study of head and neck
cancer pai ents submit ed to diff erent treatment types:
concomitant radiotherapy and chemotherapy, conveni al
or hyperfraci onated radiotherapy, or chemotherapy only.
The presented results were very close to those found in
this study, in which 83% of pai ents presented some grade
of mucosii s; the moderate grade predominated in 35%(17).
In another study of head and neck cancer pai ents
sub-mit ed to diff erent treatment modes, however, 91% of
pai ents developed some grade of mucosii s, but grade 3
(60%) predominated(18).
Higher mucosii s incidence levels were found between
the third and sixth weeks of treatment, with a
predomi-Table 1- Interrupted (IT) and non-interrupted (NIT) treatment
due to mucositis classifi ed according to CTC 2.0 - São Paulo – 2005/2006
Grade 2* non-interrupted treatment (NIT); Grade 2 ** interrupted treatment (IT)
NIT Grade 0.1 and 2*
N (%)
IT Grade 2** e 3
N (%)
Total N (%) P
Age range
Up to 60years More than 60 years
Gender Female Male Race Black White Hypertension Yes No Diabetes Yes No Smoking Smoker Former smoker Non smoker Staging II III IVA IVB Surgery Yes No 21 (67.7) 13 (68.4) 3 (60) 31 (68.9) 7 (63.6) 27 (69.2) 10 (66.7) 24 (68.6) 0 34 (72.3) 7 (77.8) 25 (64.1) 2 (100) 4 (100) 6 (60) 19 (63.3) 5 (83.3) 19 (73.1) 15 (62.5) 10 (32.2) 6 (31.5) 2 (40) 14 (31.1) 4 (36.3) 12 (30.8) 5 (33.3) 11 (31.4) 3 (100) 13 (27.7) 2 (22.2) 14 (35.9) 0 0 4 (40) 11 (36.7) 1 (16.7) 7 (26.9) 9 (37.5) 31 (100) 19 (100) 5 (100) 45 (100) 11 (100) 39 (100) 15 (100) 35 (100%) 3 (100) 47 (100) 9 (100) 39 (100) 2 (100) 4 (100) 10 (100) 30 (100) 6 (100) 26 (100) 24 (100) 0.96 (NS) 0.60 (NS) 0.49 (NS) 0.57 (NS) 0.02* 0.44 (NS) 0.37 (NS) 0.54 (NS)
nance of grade 1 and 2 reaci ons. Another study shows
higher incidence levels of mucosii s between the third
and seventh week of treatment, with a predominance of
grade 3, when pai ents were treated with concomitant
radiotherapy and chemotherapy, but with altered
frac-i onai on; which could jusi fy the higher incidence level
of grade 3(18). Another factor is that, in the present study,
some pai ents’ treatment was interrupted when they
suf-fered from grade 2 mucosii s, which did not permit the
evolui on of toxicity. In literature, we found studies that
affi rm that, at er one or two weeks of radiotherapy, oral
erythema can be verifi ed. At er the second week, with
about 20 Gy, edema can be verifi ed; the erythema is no
longer that visible due to the pressure exerted on the
cap-illary vessels; this is provoked by the accumulai on of
ex-travascular liquid. At er 3 weeks, with about 30Gy,
vascu-lar permeability is enhanced, contribui ng to increase the
edema(19-20). Based on these studies, it is perceived that
the signs become more evident as from the third week,
without ignoring individual variai ons in responses.
As for individual clinical factors, our results showed
that age was not an important factor for mucosii s
sever-ity. Some authors meni on that that the chance of
muco-sii s decreases with age. This is supposedly due to the low
rate of cell replicai on in elderly pai ents, as cells with high
mitoi c aci vity are more sensii ve to radiotherapy and
chemotherapy. It should be highlighted that the mean age
of the study pari cipants was lower (57.52 years) in
com-parison with the literature (61.3 and 60.7 years)(9,17).
Regarding smoking, this factor showed no stai si cal
signifi cance, probably due to the low incidence level of
smokers in our sample. The results showed that (16%)
ad-mit ed smoking during treatment, and only two had their
treatment interrupted because of the mucosii s. Research
is found in the literature with diverging results; while
some did not observe infl uence from smoking on
mucosi-i s, others affi rmed that smoking exerted infl uence when
the irradiated volume was smaller(10-11). It should be taken
into account that, in these studies, pai ents were
submit-ted to diff erent treatments.
Concerning diabetes, although a small number of
pa-i ents in our sample (6%) presented the disease, 100% had
their treatment interrupted due to the severity of the
mu-cosii s, as evidenced by the stai si cal signifi cance. In
lit-erature, we found a research that observed that oral
cav-ity and oropharyngeal cancer pai ents who were diabei cs
and submit ed to radiotherapy with altered fraci oning
were at greater risk of developing grade 3 and 4
muco-sii s(17). Furthermore, studies were observed in which the
authors affi rm that, as a systemic disease, diabetes can
in-fl uence mucosii s severity, and that this pathology should
be taken into account in pai ents receiving head and neck
irradiai on(21).
According to the literature, type 1 and 2 diabetes
peri-odontal disease. This is due to impaired healing at er
rap-id collagen degradai on by metalloproteinase enzymes.
In addii on, the infl ammatory process is accelerated,
which hampers healing, enhances monocyte response, induces high levels of glycosylated proteins, increases
the advanced glycai on end products (AGEs) in i ssues
and decreases the chemotaxis of neutrophils(16,21-22).
Thus, based on the above informai on and the present
study results, we believe that diabei c pai ents
submit-ted to radiotherapy and chemotherapy, treatments that
induce infl ammai on, can present predisposii on to the
development of more severe mucosii s, due to factors
sensii zing the oral mucosa.
CONCLUSION
When analyzed on the whole, the present study data
show that head and neck cancer pai ents submit ed to
con-comitant radiotherapy and chemotherapy predominantly
present grade 1 and 2 mucosii s between the third and
sixth week of treatment. Among individual pai ent, disease
and treatment characterisi cs, only diabetes enhanced the
development of severe mucosii s. Therefore, we believe
that diabei c pai ents can benefi ts from more frequent
monitoring during treatment, including specifi c orientai on
and care, such as glucose and medicai on control. It is
im-portant for nurses to heed these parameters, considering that, in view of their presence at the radiotherapy and che-motherapy sectors, they can collaborate to enhance
treat-ment and improve pai ents’ quality of life.
REFERENCES
1. Parkin DM, Bray F, Ferlay J, Pisani P. Esi mai ng the world
can-cer burden: Globocan 2000. Int J Cancan-cer. 2001;94(2):153-6.
2. Brasil. Ministério da Saúde; Insi tuto Nacional do Câncer
(INCA). Incidência de câncer no Brasil: esi mai va 2010
[Inter-net]. Rio de Janeiro: INCA; 2009. [citado 2009 set. 15].
Dis-ponível em: ht p://www.inca.gov.br/esi mai va/2010/esi
ma-i va20091201.pdf
3. Rose-Ped AM, Bellm LA, Epstein JB, Troi A, Gwede C, Fuchs
HJ. Complicai ons of radiai on therapy for head and neck
can-cers: the pai ent’s perspeci ve. Cancer Nurs.
2002;25(6):461-7; quiz 468-9.
4. Denham JW, Peters LJ, Johansen J, Poulsen M, Lamb DS,
Hind-ley A, et al. Do acute mucosal reaci ons lead to consequeni al
late reaci ons in pai ents with head and neck câncer?
Radio-ther Oncol. 1999;52(2):157-64.
5. Sonis ST, Eli ng LS, Keefe D, Peterson DE, Schubert M,
Hau-er-Jensen M, et al., Perspeci ves on cancer therapy-induced
mucosal injury: pathogenesis, measurement,
epidemiol-ogy, and consequences for pai ents. Cancer. 2004;100(9
Sup-pl):1995-2025.
6. Sawada NO, Nicolussi AC, Okino L, Cardozo FMC, Zago MMF.
Quality of life evaluai on in cancer pai ents to submit ed to
chemotherapy. Rev Esc Enferm USP [Internet]. 2009 [cited
2009 Sept 15];43(3):581-7. Available from: ht p://www.scielo.
br/pdf/reeusp/v43n3/en_a12v43n3.pdf
7. Naidu MUR, Ramana GV, Rani PU, Mohan IK, Suman A, Roy P. Chemotherapy-induced and/or therapy-induced oral
mucosii s-complicai ng the treatment of cancer. Neoplasia.
2004;6(5):423-31.
8. Saad ED, Hoff PM, Carnelós RP, Katz A, Novis YAS,
Pietro-cola M, et al. Critérios comuns de toxicidade do Insi tuto
Nacional de Câncer dos Estados Unidos. Rev Bras Cancerol. 2002;48(10):63-96.
9. Porock D. Factors infl uencing the severity of radiai on skin and
oral mucosal reaci ons: development of a conceptual
frame-work. Eur J Cancer Care. 2002;11(1):33-43.
10. Rugg T, Saunders MI, Dische S. Smoking and mucosal
re-aci ons to radiotherapy. Br J Radiol. 1990;63(751):554-6.
Browman GP, Wong G, Hodson I, Sathya J, Russeli R,
Mcal-pine L, et al., Infl uence of cigaret e smoking on the effi cacy
of radiai on therapy in head and neck cancer. N Engl J Med.
1993;328(3):159-63.
11. Mani ni G, Manfrida S, Francesco C, Giammarino D, Petrone
A, Vitucci P, et al. Impacto of dose and volume on radiai
on-induced mucosii s. Rays. 2005;30(2):137-44.
12. Troi A, Bellm LA, Epstein JB, Frame D, Fuchs HJ, Gwede CG,
et al. Mucosii s incidence, severity and associated outcomes
in pai ents with head and neck cancer receiving
radiother-apy with or without chemotherradiother-apy: a systemai c literature
review. Radiother Oncol. 2003;66(3):253-62.
13. Porock D, Nikolei S, Cameron F. The relai onship between
factors that impair wound healing and the severity of acute
radiai on skin and mucosal toxicii es in head and neck
can-cer. Cancer Nurs. 2004;27(1):71-8.
14. Gelman RS, Taylor SG. Cyclophosphamide, methotrexate,
and 5-fl uorouracil chemotherapy in women more than 65
years old with advanced breast cancer: the eliminai on of
age trends in toxicity by using doses based on creai nine
19. Baker DG. The radiobiological basis for i ssue reaci ons in
the oral cavity following therapeui c x-irradiai on: a review.
Arch Otolaryngol. 1982;108(1):21-4.
20. Barasch A, Peterson DE. Risk factors for ulcerai ve oral
mu-cosii s in cancer pai ents: unanswered quesi ons. Oral
On-col. 2003;39(2):91-100.
21. Soell M, Hassan M, Miliauskaite A, Haikel Y, Selimovic D. The
oral cavity of elderly pai ents in diabetes. Diabetes Metab.
2007;33 Suppl 1:S10-8.
15. Ryan ME, Carnu O, Kamer A. The infl uence of diabetes on
the periodontal i ssues. J Am Dent Assoc. 2003;134(Spec
No):30S-40S.
16. Vera-Lionch M, Oster G, Hagiwara M, Sonis S. Oral
mucosi-i s in pai ents undergoing radiai on treatment for head and
neck carcinoma. Cancer. 2006;106(2):329-36.
17. Eli ng LS, Cooksley CD, Chambers MS, Garden AS. Risk,
out-comes, and costs of radiai oninduced oral mucosii s among
pai ents with head-and-neck malignancies. Int J Radiat
On-col Biol Phys. 2007;68(4):1110-20.
18. Aziz L, Ebenfelt A. Mucosal secrei on changes during
