SciELO - Scientific Electronic Library Online

 
vol.10 issue5 author indexsubject indexarticles search
Home Pagealphabetic serial listing  

My SciELO

Services on Demand

Article

Indicators

Related links

  • On index processCited by Google
  • Have no similar articlesSimilars in SciELO
  • On index processSimilars in Google

Share


Medicina Oral, Patología Oral y Cirugía Bucal (Ed. impresa)

Print version ISSN 1698-4447

Med. oral patol. oral cir. bucal (Ed.impr.) vol.10 no.5 Valencia Nov.-Dec. 2005

 

Measurement of secondary mucositis to oncohematologic treatment 
by means of different scale
Valoración de la mucositis secundaria a tratamiento oncohematológico mediante distintas escalas. 
Revisión

 

Fuensanta López Castaño (1), Ricardo E. Oñate Sánchez (2), Rocío Roldán Chicano (1), Mª Carmen Cabrerizo Merino (3)

(1) Odontólogo Prof. Colaborador
(2) Prof. Titular
(3) Prof. Asociado. U. Doc. P. Especiales Clínica Odontológica Universitaria Murcia

Address:
Dr. Ricardo E. Oñate Sánchez
Unidad Docente Pacientes Especiales
Clínica Odontológica Universitaria
Avda. Marqués de los Vélez S/N
30.008 MURCIA
Tlf. 968230061 Ext. 218
Email: reosan@um.es

Received: 11-05-2005  Accepted: 2-10-2005

López-Castaño F, Oñate-Sánchez RE, Roldán-Chicano R, Cabrerizo-Merino MC. Measurement of secondary mucositis to oncohematologic treatment by means of different scale. Med Oral Patol Oral Cir Bucal 2005;10:412-21.
© Medicina Oral S. L. C.I.F. B 96689336 - ISSN 1698-4447

ABSTRACT

Oral mucositis is the inflammation that takes place in the oral epithelium, as a result of antineoplastic treatments such as radiotherapy, chemotherapy or bone marrow transplant, being very frequent in these treatments for oncohematologic disease. The consequences of this inflammation, not only affect the quality of life of the patient, but can also suppose a limitation in the application of the treatment, as well as an increase in the hospital stay and therapeutic costs. A main obstacle for the study of the mucositis, has been the lack of a system adapted for its valuation by means of the oral examination. Methods developed to measure and quantify the changes produced in oral epithelium as a result of treatment of cancer can be very varied from more simple methods, such as general scales with four or five degrees of severity that link the mucositis to the state of oral health, to specific scales of treatment. In this last type of scale the type of antineoplastic treatment that gave rise to the mucositis is identified giving a global severity score for the mucositis.
The establishment of a common scale for the evaluation of mucositis is important, not only for clinical purposes but also for the investigation of the degree of toxicity of the different therapeutic regimes that give rise to the mucositis.

Key words: Mucositis, chemotherapy, x-ray, transplant of bone marrow, oncohematology, valuation, review.

 

RESUMEN

La mucositis oral es la inflamación que tiene lugar en el epitelio oral, a consecuencia de los tratamientos antineoplásicos tales como la radioterapia, la quimioterapia o el transplante de médula ósea, siendo muy frecuente en los tratamientos de los procesos oncohematológicos. Las consecuencias de esta inflamación, no sólo afectan a la calidad de vida del paciente, sino que además puede suponer una limitación en la aplicación del tratamiento, así como un aumento de la estancia hospitalaria y de los gastos terapéuticos. Un obstáculo principal a la hora de estudiar la mucositis, ha sido la falta de un sistema adecuado para su valoración mediante el examen oral. Los métodos desarrollados para medir y cuantificar los cambios producidos en el epitelio oral, como consecuencia del tratamiento del cáncer, van desde los más sencillos, tales como escalas generales con cuatro o cinco grados de severidad que permiten relacionar la mucositis con el estado de salud oral, hasta llegar a las escalas específicas de tratamiento, en las que se distingue el tipo de tratamiento antineoplásico que dio lugar a la mucositis, pasando por las escalas de múltiples variables, en las que se valoran distintos aspectos y se estudia su correspondencia con el estado de salud oral y su función, obteniendo una puntuación global de severidad de la mucositis; es importante el establecimiento de una escala común para la valoración de la mucositis, no sólo con fines clínicos sino también para la investigación del grado de toxicidad de los distintos regímenes terapéuticos que dan lugar a mucositis.

Palabras clave: Mucositis, quimioterapia, radioterapia, transplante de médula ósea, , oncohematología, valoración, revisión.

 

INTRODUCTION

In hematologic neoplasms injuries in the oral cavity are frecuent. These injuries can be primary manifestations of the disease or secondary manifestations of the different treatments applied to these patients. Among the injuries produced by the cytostatic, the radiotherapy and the protocols of oncologyc treatment (chemotherapy and/or radiotherapy) administered to these patients the mucositis is the most important one.(Figure 1) (1, 2). Other alterations that appear in these treatments are the pain, dysgeusia, odinophagia and the subsequent dehydration and undernourishment (3). All them reduce the quality of life of the patient (2, 4). The alterations of the oral mucosa should be called stomatitis because the term mucositis can refer to any mucous membrane of the organism (1). However, there is a tacit agreement in international literature to use the term oral or buccal mucositis to refer to the alterations that the oncologycs treatments produces in the oral mucosa (1). This term, as explained by Köstler (2), arose at the end of the 80’s to define the inflammation in the oral cavity produced by the chemotherapy and radiotherapy because this inflammation is different from other oral injuries, denominated estomatitis, and with another one etiopathogenia. Nevertheless, according to other authors (5) the mucositis consists of an inflammation of the mucous that leads to an ulceration and rupture of the integrity of this one and that can affect to all gastrointestinal tract from the mouth to the anus. The oral mucositis represent a factor of significant risk for the sistemics infections particularly in the neutropenic state in which is the patient, (2, 3), since 20 - 50 % of septicemias in the inmunosupressed patients are originated in the mouth (6). In addition, the mucositis presence can have others consequences like the interruption of the antineoplastic treatment, (6) a limitation in the dose (3, 4, 7), the affectation of the quality of life (2, 4) or the failure of the same one (2), as well as an increase in the therapeutic costs (2, 4, 8) and the hospital stay (2, 9).

All factors previusly expouned explains the relevance of the oral mucositis in the oncologycs treatments.

EPIDEMIOLOGY

The incidence of the oral injuries can be modify according to the clinical pathology, the type of tretment applied and the buccal condition before the appearance of the disease (1, 2). However, the accumulation of factors provoke that 85% of the patients under oncologyc treatment with elevated doses of x-ray and/or mucotoxic chemotherapy develop complications in the oral cavity (1), which incidence are of the 40-90% and bigger in case of young patients and women (7).

The mucositis appears as much in patients under chemotherapy as in x-ray patients (9, 10), being more frequent in hematologics tumors that in solid tumors (9). This is due to the severity and duration of the myelosuppression which is are 2 or 3 times bigger in patients with hemophatology or in patients who are under bone marrow transplant (BMT) (11).

The severe mucositis is observed mainly in chemotherapy and x-ray simultaneous treatment. A 40% of the patients under conventional chemotherapy (12) and more than 70 % of the patients with bone marrow transplant develop oral complications derived from the treatment. (2, 6, 12). Around 18 - 20 % of the patients present mucositis in the first cycle of chemotherapy (4). In general, the patients of smaller age seem to have a bigger risk of mucositis induced by chemotherapy (9, 13). This is due to the greater mitotic rate (9, 12) and to the presence of a greater number of receptors for the epidermal growth factor in the young patients (9).

Near of 50 % of all the head and neck cancer are treated with single radiotherapy or combinated with chemotherapy and surgery (10). The oral mucositis induced by the radiotherapy in head and neck go forward giving rise to the appearance of ulcers or pseudomembranes in 80% of the treated patients (14) and 15 % of the patients who receive dose of x-ray discharges in the buccal cavity and the pharingic zone must been hospitalized by the complications derived from the treatment (9).Therefore the duration and reduction of severity of oral mucositis and its sequels in patients who have been put under BMT can have a significant impact in the morbidity and mortality an also in the cost of the necessary cares. (8)

MEASUREMENT OF THE MUCOSITIS

Whereas the pain and the functional incapacities are potentially important by their clinical and research implications the quantification of these variables can suposse an important challenge. A main obstacle for the investigation of the mucositis has been the lack of a definitive system to appropriately measure mucositis through the oral examination. In the last 30 years have been developed different models to document and to quantify the changes in epithelial tissue of the oral cavity and the alterations of their function, during and after the cancer treatment. These methods vary from the simple ones with 3 or 4 degrees of toxicity to the “toxicity scales” with detailed and specific register of the events and changes that take place measured in different anatomical regions in the oral cavity. Nevertheless, there are some practical considerations that must been adressed at the time of selecting scales, such as: who will register the changes, how the mucositis is due to be measure, how often will be made the mesurement and under what clinical conditions? (9). In the classifications of scales usually it is possible differentiate in “general” scales of valuation of the mucositis and “multiple variable” mucositis rating scales . The first ones usually are composed by 4 or 5 variables and allow to relate the mucositis and the global state of the mouth. The second type of scales, however, values different variables and their correspondence with the state of oral status and function and the obtained scores are added to obtain a global valuation of the severity of the mucositis (13). To this classification we must add the “specific scales” in which the type is different from conducted treatment that gives rise to the mucositis.

At the moment the scales available are:

1. General scales:

1.1. Scale of the Institute of Investigation of Cancer Fred Hutchinson (FHCRC)
1.2. Scale of Lindquist/Hickey.
1.3. Scale of the World-wide Organization of the Health (the WHO).

2. Multiple variable rating scale:

2.1. Scale of Beck.
2.2. Scale of Eilers.
2.3. Scale of Walsh

3. Specific scales of treatment:

3.1. Scale of the Western for Consortium Cancer Nursing Research (WCCNR)
3.2. Scale of the National Institute of the Cancer.
3.3. Scale of the Radiation Therapy Oncology Group/European for Organization Research and Treatment of Cancer. (RTOG/EORTC).
3.4. Oral Mucositis Rating Scale (OMRS)
3.5. Index of Mucositis Oral (IMO)
3.6. Scale of Spijkervet.

Of all the systems of measurement that are considered valid, the system of the WHO and the NCI scale are the most used.

1. General Scales:

An advantage of this type of scales is its simplicity, which favors its handling fast and easily. Examples of general scales are the scale of the WHO composed of 5 degrees (0 - 4 of normal to severe) (1, 2, 6, 9, 14), the scale of 4 degrees, (0 - 3 of normal to severe), developed by Lindquist and Hickey (16) and the scale of the Institute of investigation of the Cancer Fred Hutchinson (13). These scales are reflected in table 1.

1.1. Scale of the Institute of Investigation of Cancer Fred Hutchinson (FHCRC):

The Institute of Investigation of the Cancer Fred Hutchinson (13) makes a valuation of the of the mucositis severity in 5 degrees: no, mild, moderate, severe, and life-threatening. This scale, although simple, lacks of clarity and objective criteria to clarify each phase of the mucositis, for example the difference between slight and moderate or moderate and severe must be detailed to avoid any mistake at the time of valuing the mucositis and be clasified in one section or another.

1.2. Scale of Lindquist /Hickey:

The scale of Lindquist and Hickey (16), clasify the mucositis according to four variables, the degree of erythema, the degree of ulceration, the patient capacity to eat as well as the existence or not of pain.

1.3. Scale used by the WHO:

In 1979, the WHO defined the state of the mucositis injuries according to the severity of the same ones thus establishing degrees of 0 - 4. As in the scale of Lindquist and Hickey, it is not only valued the presence of erythema and ulceraction but also the capacity to eat that displayed by the patient. This scale has been used in multiple studies. (1, 2, 6, 9, 14, 15)

While these general scales provide a general and global vision of the oral status, they are vague to measure relating the types and the extension of the injuries in the weave, specially in terms of damage extension. For example a moderate area of 1 cm2 of erythema in the left yugal mucosa will obtain the same score that a moderate erythema that involves all the mucosa of the mouth; There are big difference between both situations in the pain suffered by the patient and his capacity to eat. Besides, there exist others factors that can determine subjective complaints as well as the functional capacity which is not related with the state of the oral cavity, and its combination might concern the capacity of these scales to provide an unequivocal valuation of the tissue damage of the epithelial tissue (13).

2. Multiple variable scales:

The scales of multiple variables provide a more detailed and precise score in the valuation of the oral cavity. Most of these scales were adapted from previous scales used to value the oral state in conjunction with the valuation of the patient, related to the protocols of care (13). Within this type of scales, we can find the following ones: Scale of Beck, scale of Eilers and the scale of Walsh.

2.1. Scale of Beck:

The scale of Beck (17) is composed by 8 categories. Of these eight categories the observer is in charge of evaluate the lip, tongue, mucosa, gingiva, saliva, dentition, and the capacity to speak. However, the valuation of the capacity to swallow is realized by the patient reason why it presents a subjective component (13).

2.2. Scale of Eilers:

Guide of oral valuation developed by Eilers ET to. (18) It consists of eight categories: voice, swallowing, lips, the capacity to speak, saliva, mucous membrans, gingiva and dentition, which are valued using a score of 1(normal) to 3 (definitively compromised). These more detailed scales have a minor time of clinical experience and frequently need the training of experts specialized in the oral cavity to obtain homogeneity and agreement among the different professionals in charge of the mucositis valuation. (9)

2.3. Scale of Walsh:

The scale presented/displayed by Walsh ET to. (19) It scale has more variables appropiate for the mucosa valuation and is, in general, simpler although still it combines subjective and functional variables.

This type of multiple variable scales of manifold has been used to measure a wide amount of oral changes, of mucosa characteristics, of saliva and amount of flow and also the aptitude to swallow as well as to express the quality and the effectiveness of the oral hygiene. Besides its usefulness to determine when to change or to alter the care of the patient these scales reveals several factors whose capacity to value the damage of the tissue produced by the cancer therapy must be considered. Nevertheless, many of the variables present some difficulty at the time of valuation the damaged produced and providing a score according to it, for example, how much mucous area is necessary to be involved with an erythema of a given severity to determine the score for each area?, or how to determine the volume and consistency of the saliva through the simple visual observation?. Other factors exist, like drugs administered to the patient or to let pass the air through the mouth that can significantly to alter the salivary function and to provoke the sensation of oral dryness. The swallowing can be compromised by factors nonrelated to the oral state of the cavity, like the toxicities of the gastrointestinal therapy, pharyngeal disease or loss of the general appetite. The relation of severity of pain with the swallowing can be affected additionally by other aspects like psychological factors, the use of analgesic for other pain problems and the presence of other systemic complications (13).

3. Specific scales of treatment:

Recently has been described different scales specifically focused in the oral changes induced by the chemotherapy, the radiotherapy or the regimes of preparation of the bone marrow transplant. Some examples of these scales can be observed in table 2.

3.1. Scale of the Western for Consortium Cancer Nursing Research (WCCNR):

The Western for Consortium Cancer Nursing Research (WCCNR) (20) has developed a system to evaluate the mucositis induced by chemotherapy which is essentially a combination of the general scales and multiple variables scales. It uses a scale of 4 points for each section characterized by a detailed description for each one of the characteristics that tend to happen jointly with increase of the severity degree. The authors consider that the advantages of this system are their low complexity (compared with scales of multiple variables) and the fact that the description for each stage has been selected to describe technical and very intuitively the general progression of the estomatitis induced by the chemotherapy.

3.2. Scale of the National Institute of the Cancer (NCI - CTC):

The National Institute of the Cancer, presented in 1998 (21) an update of CTC (Common Toxicity Criteria) in which the mucosities is differentiated in mucositis due to radiation, mucositis due to chemotherapics, and the mucositis derived from the bone marrow transplant and it is classifies according to the zone of appearance as showed in table 2. This scale is one of the most used together with the WHO (2, 9, 22, 23, 24).

3.3. Oral Mucositis Scale Rating (ORMS):

The Oral Mucositis Scale Rating (25) was designed as an instrument to quantify the kind and severity of the different changes that took place in the mucosa associated to the transplant of bone marrow (TMO), such as atrophies, erythema, ulceration, hiperkeratosis...) by means of a scale from 0 to 3 (normal to severe). Later this scale was used to design the Oral Mucositis Index (OMI). A slightly modified form was used by Kolbinson ET to. (26) to describe the earlier oral changes post- BMT.

3.4. Index of Mucositis Oral (OMI):

In 1992 Schubert et all. (25) made a study in 188 patients before the transplant of bone marrow and up to 42 days after this one. In that study the OMRS was used to develop a new specific index that would measure the severe mucositis after the transplant and it was denominated oral index of mucositis (OMI). It was composed by 34 ítems with the purpose of measuring the number of oral complications that appear in patients who have been transplanted, specifically, erythema, ulceration, atrophy, edema, and other parameters. While this scale is useful when providing data for the statistical analyses, its use was restricted to the dental trained professionals due to the degree of specialized experience and knowledge necessary to evaluate the parameters. McGuire ET to. (27) working closely with Schubert successfully shortened the OMI in a version of 20 - items to be valued by nondental professionals without specific training in the field. (5) Both OMI versions of 34 and 20 items are inadequate to measures an objective data that is the epithelial weave of the mucosa (Example: erythema and ulceration). Then it would have to be used an additional instruments in order to measure subjective and functional elements of the weave injury like the pain and the nutritional deterioration,. (5)

3.5. Scale of Spijkervet:

The scale of Spijkervet (28), in which the values showed in table 2 are applied, differ from the OMRS scale in the use of quantitative determinants for some variables and qualitative determinants for others variables. All of them are added at the end to achieve to a global score. Variables have been selected according to the clinical descriptors related with changes on the oral mucosa that tends to be noticed in patients who have undergone BMT like atrophy, erythema, pseudomembranes liquenoides lesions, ulceration, hiperkeratosis, and edema. The variables of atrophy, erythema, liquenoides lesions hiperkeratosis, and edema were valued in a scale of 0 to 3 (0, normality /no change; 1, slight; 2, moderate; 3, severe).

In these punctuations, each variable was defined according to a descriptive criteria. For example, the rank for the erythema or the red coloration that vary from 0 to 3 and that represents the transition from a normal red coloration to the severe erythema and that is equivalent to the color of fresh arterial blood. The changes of ulceration and pseudomembrane were valued through a scale based on the implied surface area, (0: None; 1: > 0 but smaller or equal to 1cm2; 2: > 1 cm2 but smaller or equal to 2 cm2; 3: > 2 cm2). The oral cavity is divided in seven anatomical areas with subareas that include the lips (top and low), labial mucosa (top and low) mucous buccal (right and left), dorsum and borde of tongue, floor of mouth, soft and hard palate, and gingiva.

3.7. Scale RTOG/EORTC:

The scale of the Radiation Therapy Oncology Group/European Organization Research and Treatment of Cancer (RTOG/EORTC), (29) establishes the existence of 5 mucositis degrees based on the intensity of the affectation, from the abscence of changes with respect to the basal situation (Degree 0) to the appearance of ulceration and/or necrosis (Degree 4). (30, 31)

CONCLUSIONS

There are several oncologic treatments to which patients are someted and also are multiple and diverse the protocols and the toxicities derived. Therefore it is not easy to establish a scale of valuation of the mucositis. However we have different methods each one with its advantages and disadvantages but valid to all and each one of the clinical situations of the patients suitable for been used according to the conditions and considering different issues like the type of treatment that has given rise to the mucositis, who will make the measurements, what we want to measure, or with what aims we made the mucositis valuation. The general scales offer a simple and easily handling method even by nontrained personnel for a brief valuation of the mucositis but its main disadvantage is the lack of specificity. These scales could be used to evaluate the presence or absence of mucositis as well as its degree. On the other hand the multiple variable scales provide a more precise and detailed valuation of a greater number of oral changes derived from the mucositis and it precise of more trained personnel. Consequently they can be applied to those cases in which the objective is to measure the extension and location of the mucositis. If it was tried to measure the mucositis derived from a certain oncologic treatment it is possible to employ the specific scales in which are differentiated the oral changes induced by each one of the antineoplastics treatme

REFERENCES

1. Puyal M, Jiménez C, Chimenos E, López J, Juliá, A. Protocolo de estudio y tratamiento de la Mucositis bucal en los pacientes con hemopatías malignas. Med. Oral 2003; 8: 10-8        [ Links ]

2. Köstler WJ, Hejna M, Wenzel C, Zielinski CC. Oral Mucositis Complicating Chemotherapy and/or Radiotherapy: Options for Prevention and Treatment. CA Cancer J Clin 2001; 51: 290-315         [ Links ]

3. Porock D. Factors influencing the severity of radiation skin and oral mucosal reactions: development of a conceptual framework. Eur J Cancer Care (Engl) 2002; 1: 33-43.         [ Links ]

4. Dodd MJ, Dibble S, Miaskowski C, Paul S, Cho M, MacPhail L, et al.: A comparison of the affective state and quality of life of chemotherapy patients who do and do not develop chemotherapy-induced oral mucositis. J Pain Sym Manag 2001; 21: 498-505.         [ Links ]

5. McGuire DB. Mucosal tissue injury in cancer therapy. More than muscositis and mouthwash. Cancer Pract 2002; 10: 179-91.         [ Links ]

6. Awidi A, Homsi U, Kakail RI, Mubarak A, Hassan A, Kelta M, et al. Double-blind, placebo-controlled cross-over study of oral pilocarpine for the prevention of chemotherapy-induced oral mucositis in adult patients with cancer. Eur J Cancer 2001; 37: 2010-4.         [ Links ]

7. Sonis ST. Mucositis as a biological process: a new hypothesis for the development of chemotherapy-induced stomatotoxicity. Oral Oncol 1998; 34: 39-43.         [ Links ]

8. Gabriel DA, Shea T, Olajida O, Serody JS, Comeau T The effect of oral mucositis on morbidity and mortality in bone marrow transplant. Semin Oncol 2003; 30 (6 Suppl 18): 76-83.         [ Links ]

9. Pico JL, Ávila-Garavito A, Naccache P. Mucositis : Its Occurrence, Consequences, and Treatment in the Oncology Setting. Oncologist 1998; 3: 446-51.         [ Links ]

10. Caribé-Gomes F, Chimenos-Küstner E, López López J, Finestres-Zubeldia F, Guix-Melcior B. Manejo odontológico de las complicaciones de la radioterapia y quimioterapia en el cáncer oral. Med Oral 2003; 8: 178-87.         [ Links ]

11. McGuire DB, Altomonte V, Peterson DE, Wingard JR, Jones RJ, Grochow LB. Patterns of mucositis and pain in patients receiving preparative chemotherapy and bone marrow transplantation. Oncol Nurs Forum 1993; 20: 1493-502.         [ Links ]

12. Wojtaszek CA. Management of chemotherapy induced stomatitis. Clin J Oncol Nurs 2000; 4: 263-9.         [ Links ]

13. Schubert MM. Measurement of oral tissue damage and mucositis pain. En: Chapman CR, Foley KH, eds. Current and Emerging Issues on Cancer Pain: Research and Practice. New York: Raven Press; 1993. p. 247-65.         [ Links ]

14. Stokman MA, Spijkervet FK, Wymenga AN, Burlage FR, Timens W, Roodenburg JL, et al. Quantification of oral mucositis due to radiotherapy by determining viability and maturation of epithelial cells. J Oral Pathol Med 2002; 31: 153-7.         [ Links ]

15. Plevova P. Prevention and treatment of chemotherapy- and radiotherapy-induced oral mucositis: a review. Oral Oncol 1999; 35: 453-70.         [ Links ]

16. Lindquist SF, Hickey AJ, Drane JB. Effect of oral hygiene on stomatitis in patients receiving cancer chemotherapy. J Prosthet Dent 1978; 40: 312-4.         [ Links ]

17. Beck S. Impact of a systematic oral care protocol on stomatitis after chemotherapy. Cancer Nurs 1979; 2: 185-199.         [ Links ]

18. Eilers J, Berger AM, Petersen MC. Development, testing, and application of the oral assessment guide. Oncol Nurs Forum 1988; 15: 325-30.         [ Links ]

19. Walsh LJ, Hill G, Seymour G, Roberts A. A scoring system for the quantitative evaluation of oral mucositis during bone marrow transplantation. Spec Care Dentist 1990; 10: 190-5.         [ Links ]

20. Western Consortium for Cancer Nursing Research. Development of a staging system for chemotherapy-induced stomatitis. Cancer Nurs 1991; 14: 6-12.         [ Links ]

21. Cancer Therapy Evaluation Program: Common Toxicity Criteria Version 2.0. DCTD, NCI, NIH, DHHS 1998. Disponible en: http://ctep.cancer.gov/forms/CTCv20_4-30-992.pdf         [ Links ]

22. Epstein JB, Gorsky M, Guglietta A, Le N, Sonis ST. The correlation between epidermal growth factor levels in saliva and the severity of oral mucositis during oropharyngeal radiation therapy. Cancer 2000; 89: 2258-65.         [ Links ]

23. Dazzi C, Cariello A, Giovanis P, Monti M, Vertogen B, Leoni M, et al. Prophylaxis with GM-CSF mouthwashes does not reduce frequency and duration of severe oral mucositis in patients with solid tumors undergoing high-dose chemotherapy with autologous peripheral blood stem cell transplantation rescue: a double blind, randomized, placebo-controlled study. Ann Oncol 2003; 14: 559-63.         [ Links ]

24. Trotti A, Byhardt R, Stetz J, Gwede C, Corn B, Fu K, et al. Common toxicity criteria: version 2.0. an improved reference for grading the acute effects of cancer treatment: impact on radiotherapy. Int J Radiat Oncol Biol Phys 2000 1; 47: 13-47.         [ Links ]

25. Schubert MM, Williams BE, Lloid ME, Donaldson G, Chapko MK. Clinical assessment scale for the rating of oral mucosal changes associated with bone marrow transplantation. Development of an oral mucositis index. Cancer 1992 15; 69: 2469-77.         [ Links ]

26. Kolbinson DA, Schubert MM, Flournoy N, Truelove EL. Early oral changes following bone marrow transplantation. Oral Surg Oral Med Oral Pathol 1988; 66: 130-8.         [ Links ]

27. McGuire DB, Peterson DE, Muller S, Owen DC, Slemmons MF, Schubert MM. The 20 item Oral Mucositis Index: reliability and validity in bone marrow and stem cell transplant patients. Cancer Invest. 2002; 20: 893-903.         [ Links ]

28. Spijkervet FKL, van Saene HKF, Panders AK, Vermey A, Mehta DM. Scoring irradiation mucositis in head and neck cancer patients. J Oral Pathol Med 1989; 18: 167-71.         [ Links ]

29. Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys 1995; 30: 1341-6.         [ Links ]

30. Montero Luis A, Hervás A , Morera R, Ramos A. Toxicidad sobre piel y mucosas: tratamientos de soporte. Oncología 2004; 27: 402-7        [ Links ]

31. Johnson JT. Prevention of radiation-induced mucositis. Curr Oncol Rep 2001; 3: 56-8.         [ Links ]

Creative Commons License All the contents of this journal, except where otherwise noted, is licensed under a Creative Commons Attribution License