|Year : 2017 | Volume
| Issue : 2 | Page : 51-55
Effect of IMRT and three-dimensional conformal radiotherapy on oral Candida colonization: A comparative study
Jasmine Shanthi Kamath1, Raghavendra Kini2, Anup Kumar Shetty3, Vathsala Naik4
1 Department of Oral Medicine and Radiology, A B Shetty Memorial Institute of Dental Sciences, Nitte University, Mangalore, Karnataka, India
2 Department of Oral Medicine and Radiology, A. J. Institute of Dental Sciences, Mangalore, Karnataka, India
3 Department of Microbiology, Father Mullers Medical College and Hospital, Mangalore, Karnataka, India
4 Department of Oral Medicine and Radiology, BIDS, Bengaluru, Karnataka, India
|Date of Web Publication||26-Jul-2017|
Jasmine Shanthi Kamath
Department of Oral Medicine and Radiology, A B Shetty Memorial Institute of Dental Sciences, Nithyananda Nagar, Derlakatte, Mangalore, Karnataka
Source of Support: None, Conflict of Interest: None
Aim: To investigate oral candidiasis in patients with head and neck cancer before and after intensity-modulated radiation therapy and three-dimensional conformal radiotherapy (3D CRT) and to explore if there is an association with the type of radiotherapy used and the severity of candidiasis.
Materials and Methods: Patients who received radiation therapy (RT) for the treatment of head and neck cancer were divided into two groups: Group 1 consisted of patients (n = 20) who received Intensity modulated radiation therapy (IMRT) and Group 2 (n = 20) consisted of patients who received 3D CRT. Saliva from these patients was collected before and after radiotherapy and evaluated for Candida species using culture method.
Results: Significant increase of Candida albicans was seen in patients who underwent 3D CRT as compared to IMRT. Other species of Candida such as Candida tropicalis, Candida glabrata, and Candida krusei showed increase postradiotherapy in both groups, but the change was not significant.
Conclusion: Although candidiasis is seen regardless of the type of radiation therapy used, the oral environment is more stable after intensity-modulated radiation therapy as and when compared to 3D CRT. Salivary substitutes and good oral hygiene before, during, and after radiotherapy could be used to increase oral clearance and to decrease the chance of candidiasis.
Keywords: Candida, candidiasis, head and neck malignancy, intensity-modulated radiotherapy, radiotherapy, three-dimensional conformal radiotherapy
|How to cite this article:|
Kamath JS, Kini R, Shetty AK, Naik V. Effect of IMRT and three-dimensional conformal radiotherapy on oral Candida colonization: A comparative study. J Oral Res Rev 2017;9:51-5
|How to cite this URL:|
Kamath JS, Kini R, Shetty AK, Naik V. Effect of IMRT and three-dimensional conformal radiotherapy on oral Candida colonization: A comparative study. J Oral Res Rev [serial online] 2017 [cited 2018 Feb 21];9:51-5. Available from: http://www.jorr.org/text.asp?2017/9/2/51/211637
| Introduction|| |
Oral cancer is one of the leading causes of death in both the developed and the developing countries. With an estimated 16 million people affected worldwide by 2020, it is a multifactorial disease with multifaceted treatment strategies., One such treatment strategy is radiotherapy (RT). It could be the only treatment given or could be combined with surgery and chemotherapy. RT has seen advances from two-dimensional and three-dimensional conformal radiotherapy (3D CRT) to intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy. Although these newer modalities of RT are effective in eradicating or shrinking the tumor, they also negatively affect the surrounding structures around the tumor, including salivary glands, oral mucosa, teeth, and oral microflora.
This resident microflora plays an active role in the maintenance of the healthy state by contributing to the host defenses and preventing colonization by exogenous microorganisms. A disease or subsequent treatment for a condition can cause disruption of the resident oral microflora, causing growth of harmful organisms, removing the delicate balance, causing a normal commensal of the oral cavity to become pathogenic, and thus inducing a new diseased state. One such condition is candidiasis. This could be brought about by radiotherapy-induced xerostomia and mucosal morphological alterations, which encourages colonization of Candida leading to oral/pharyngeal candidiasis.,
The following study was done to investigate oral candidiasis in patients with head and neck cancer before and after receiving intensity-modulated radiation therapy and 3D CRT and to explore if candidiasis was more severe in patients undergoing IMRT or 3D CRT.
| Materials and Methods|| |
Forty patients receiving radiotherapy for a head and/or neck malignancy were included in the study. Ethical approval for this study (AJEC/Rev/56/2012-13) was provided by the A. J. Ethics Committee of A. J. Institute of Medical Sciences, Mangalore, on 01 November 2012. Patients who had undergone radiotherapy in the past, patients under antibiotics or corticosteroids, and individuals having any other systemic illness predisposing to candidiasis were excluded from the study. Patients were divided into two groups. Group 1 consisted of 20 patients undergoing IMRT and Group 2 consisted of 20 patients undergoing 3D CRT [Figure 1]a.
|Figure 1: Photographs of the procedure. (a) Patient receiving radiotherapy for head and neck malignancy, (b) armamentarium for saliva collection, (c) streaking of saliva sample onto culture media, (d) incubator used for incubation of culture plates, (e) growth of Candida albicans on Sabouraud dextrose agar, (f) growth of Candida species on Candida CHROMagar|
Click here to view
After informing the patients regarding the nature of the study and after obtaining written consent, unstimulated whole saliva was collected from patients by asking them to spit into a sterile container once before the start of radiotherapy and once more after the completion of the radiation cycles [Figure 1]b. The patients were instructed to refrain from food and beverages for 1 h before collection of saliva. Saliva was collected twice. The specimen was immediately transported to microbiology laboratory for culture. A semiquantitative culture was done for the saliva specimen. A 4-mm nichrome loop, calibrated to deliver 10 μl of fluid, was used for streaking. The specimen was streaked on Sabouraud dextrose agar and Candida CHROMagar (Hi-Media Laboratories, Mumbai) [Figure 1]c. The culture media were incubated at 37°C for 24–48 h [Figure 1]d. After the incubation, the growth seen on the media was identified by Gram's staining, germ tube test, and colony color on CHROMagar. Species identification on CHROMagar was done as per the manufacturer's color chart [Figure 1]f. The colony count was done as <103, 103–104, 104–105, 105–106, and >106.
| Results|| |
Statistical Package for Social Sciences version 16.0 (Armonk, NY: IBM Corp). was used to analyze the data. Chi-square test was used to find the association of Candida growth between Group 1 and Group 2 participants. The mean age of the patients who were undergoing IMRT and 3D CRT was 45.2 and 54.2 years, respectively. Out of them, 55% females were undergoing IMRT and 65% males were undergoing 3D CRT. The most common malignancy for which the patients were undergoing IMRT was carcinoma of the oropharynx (20%) and for 3D CRT was carcinoma of the buccal mucosa (25%), followed by carcinoma of the tongue (20%) [Figure 2].
These patients received fractionated doses of radiation in-between 50.4 and 70 Gy, with a mean of 60.2 Gy and 62.7 Gy for IMRT and 3D CRT, respectively [Table 1].
The most common complication of radiation treatment observed was mucositis and xerostomia making collection of saliva extremely difficult in the postirradiation period.
Candida albicans increased in 15% and 35% of the patients after IMRT and 3D CRT, respectively [Table 2]. There were significantly increased isolates of C. albicans post 3D CRT as compared to IMRT group (P < 0.05). Candida tropicalis, Candida glabrata, and Candida krusei although were isolated post IMRT and 3D CRT did not show much difference in both the groups [Table 3], [Table 4], [Table 5].
|Table 2: Counts of Candida albicans in CFU/mL in patients undergoing intensity-modulated radiation therapy and three-dimensional conformal radiotherapy|
Click here to view
|Table 3: Counts of Candida tropicalis in CFU/mL in patients undergoing intensity-modulated radiation therapy and three-dimensional conformal radiotherapy|
Click here to view
|Table 4: Counts of Candida glabrata in CFU/mL in patients undergoing intensity-modulated radiation therapy and three-dimensional conformal radiotherapy|
Click here to view
|Table 5: Counts of Candida krusei in CFU/mL in patients undergoing intensity-modulated radiation therapy and three-dimensional conformal radiotherapy|
Click here to view
| Discussion|| |
The primary goal of RT is to destroy malignant cells and to prevent any harm befalling the normal surrounding tissues, including the high-risk organs. Technological advances of imaging, new and improved software and computer system, and advanced radiation delivery systems in the form of linear accelerators have enabled it to become a reality.
IMRT is a new and advanced technique of delivering the needed radiation in a precise manner. This high-precision radiation therapy uses computer-controlled linear accelerator (linac) that delivers the dose to the tumor or specific areas that lie within the tumor.
Compared with 3D-CRT, IMRT has better flexibility in confining the dose to complex-shaped regions, which is made possible due to varying strength of the beam, thus, in IMRT, there is varying intensity within the beam.,
Pow et al., Kam et al., and Nutting et al. in their randomized clinical trial have proven IMRT to be effective in sparing salivary glands, with decreased incidence of xerostomia and noticeable improvements in quality of life (QOL).,,, Eisbruch et al. in their observations of patients over 2 years suggested that a long-term clinical benefit was seen from the sparing of major salivary glands, resulting in improvements in xerostomia in patients undergoing IMRT. Chao et al. in a prospective clinical study showed that objective and subjective improvement was seen, in xerostomia and QOL scores in patients with head and neck cancers receiving IMRT.
The patients in our study who were diagnosed with carcinoma of oropharynx were treated with IMRT as IMRT yields exceptional treatment outcomes in such cases as concluded by a study by May et al. Similar findings were also seen by Chao et al.
Conventional fractionation was followed in case of 3D CRT with a daily dose of 2 Gy per day and 1.80 Gy per day in case of IMRT as seen to be a normal protocol followed in majority of the cases.
Coming to candidiasis, patients undergoing radiotherapy for head and neck malignancies are at a risk of developing oral candidiasis, as was seen in all our patients. This was in line with most of the studies conducted by Chen and Webster., Silverman et al., Belazi et al., Dahiya et al., Jham and da Silva Freire, and Bakki et al., which showed significant increase in oral candidiasis posttreatment. Radiotherapy-induced xerostomia, decreased pH, buffering capacity, and decreased oral clearance are the major causes cited for oral candidiasis in post-RT patients.,,,,,
C. albicans was the predominant species that was increased in both the groups. While comparing the two groups, it was seen that there was a statistically significant increase (P < 0.05) in the 3D CRT group than in the IMRT group. This could be due to parotid sparing in patients undergoing IMRT and more precise delivery of radiation to the malignant region, thus decreasing the cause for xerostomia and its consequences and hence the severity of candidiasis., Although isolations of nonalbicans species were observed, there were no significant differences between the two groups.
| Conclusion|| |
Intensity-modulated radiation therapy creates a more stable environment in the oral cavity as compared to any other form of radiotherapy with decreased severity of candidiasis. Nevertheless, salivary substitutes and good oral hygiene before, during, and after radiotherapy could be used to increase oral clearance and to decrease the chance of candidiasis, thus improving the QOL.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
World Health Organization. The Global Burden of Disease: 2004 Update. Geneva: World Health Organization; 2008.
Dubal M, Nayak A, Suragimath A, Sande A, Kandagal S. Analysis of smoking habits in patients with varying grades of smoker's palate in South Western region of Maharashtra. J Oral Res Rev 2015;7:12-5. [Full text]
Danaraddi S, Koneru A, Hunasgi S, Ramalu S, Vanishree M. Natural ways to prevent and treat oral cancer. J Oral Res Rev 2014;6:34-9. [Full text]
Baskar R, Lee KA, Yeo R, Yeoh KW. Cancer and radiation therapy: Current advances and future directions. Int J Med Sci 2012;9:193-9.
Akpan A, Morgan R. Oral candidiasis. Postgrad Med J 2002;78:455-9.
Williams D, Lewis M. Pathogenesis and treatment of oral candidosis. J Oral Microbiol 2011;3:5771.
Elith C, Dempsey SE, Findlay N, Warren-Forward HM. An introduction to the intensity-modulated radiation therapy (IMRT) techniques, tomotherapy, and VMAT. J Med Imaging Radiat Sci 2011;42:37-43.
Chui CS, Chan MF, Yorke E, Spirou S, Ling CC. Delivery of intensity-modulated radiation therapy with a conventional multileaf collimator: Comparison of dynamic and segmental methods. Med Phys 2001;28:2441-9.
Pow EH, Kwong DL, McMillan AS, Wong MC, Sham JS, Leung LH, et al.
Xerostomia and quality of life after intensity-modulated radiotherapy vs. conventional radiotherapy for early-stage nasopharyngeal carcinoma: Initial report on a randomized controlled clinical trial. Int J Radiat Oncol Biol Phys 2006;66:981-91.
Kam MK, Leung SF, Zee B, Chau RM, Suen JJ, Mo F, et al.
Prospective randomized study of intensity-modulated radiotherapy on salivary gland function in early-stage nasopharyngeal carcinoma patients. J Clin Oncol 2007;25:4873-9.
Nutting CM, Morden JP, Harrington KJ, Urbano TG, Bhide SA, Clark C, et al.
Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): A phase 3 multicentre randomised controlled trial. Lancet Oncol 2011;12:127-36.
Bjordal K, Kaasa S, Mastekaasa A. Quality of life in patients treated for head and neck cancer: A follow-up study 7 to 11 years after radiotherapy. Int J Radiat Oncol Biol Phys 1994;28:847-56.
Eisbruch A, Kim HM, Terrell JE, Marsh LH, Dawson LA, Ship JA. Xerostomia and its predictors following parotid-sparing irradiation of head-and-neck cancer. Int J Radiat Oncol Biol Phys 2001;50:695-704.
Chao KS, Deasy JO, Markman J, Haynie J, Perez CA, Purdy JA, et al.
Aprospective study of salivary function sparing in patients with head-and-neck cancers receiving intensity-modulated or three-dimensional radiation therapy: Initial results. Int J Radiat Oncol Biol Phys 2001;49:907-16.
May JT, Rao N, Sabater RD, Boutrid H, Caudell JJ, Merchant F, et al.
Intensity-modulated radiation therapy as primary treatment for oropharyngeal squamous cell carcinoma. Head Neck 2013;35:1796-800.
Chao KS, Majhail N, Huang CJ, Simpson JR, Perez CA, Haughey B, et al.
Intensity-modulated radiation therapy reduces late salivary toxicity without compromising tumor control in patients with oropharyngeal carcinoma: A comparison with conventional techniques. Radiother Oncol 2001;61:275-80.
Studer G, Huguenin PU, Davis JB, Kunz G, Lütolf UM, Glanzmann C. IMRT using simultaneously integrated boost (SIB) in head and neck cancer patients. Radiat Oncol 2006;1:7.
Chen TY, Webster JH. Oral monilia study on patients with head and neck cancer during radiotherapy. Cancer 1974;34:246-9.
Silverman S Jr., Luangjarmekorn L, Greenspan D. Occurrence of oral Candida
in irradiated head and neck cancer patients. J Oral Med 1984;39:194-6.
Belazi M, Velegraki A, Koussidou-Eremondi T, Andreadis D, Hini S, Arsenis G, et al.
isolates in patients undergoing radiotherapy for head and neck cancer: Prevalence, azole susceptibility profiles and response to antifungal treatment. Oral Microbiol Immunol 2004;19:347-51.
Dahiya MC, Redding SW, Dahiya RS, Eng TY, Kirkpatrick WR, Coco BJ, et al.
Oropharyngeal candidiasis caused by non-albicans yeast in patients receiving external beam radiotherapy for head-and-neck cancer. Int J Radiat Oncol Biol Phys 2003;57:79-83.
Jham BC, da Silva Freire AR. Oral complications of radiotherapy in the head and neck. Braz J Otorhinolaryngol 2006;72:704-8.
Bakki SR, Kantheti LP, Kuruba KK, Poosarla C, Baddam VR, Mulakaluri RR. Candidal carriage, isolation and species variation in patients undergoing radiotherapy and chemotherapy for head and neck tumours. J Dr NTR Univ Health Sci 2014;3:28-34.
Eisbruch A, Ten Haken RK, Kim HM, Marsh LH, Ship JA. Dose, volume, and function relationships in parotid salivary glands following conformal and intensity-modulated irradiation of head and neck cancer. Int J Radiat Oncol Biol Phys 1999;45:577-87.
Torres SR, Peixoto CB, Caldas DM, Silva EB, Akiti T, Nucci M, et al.
Relationship between salivary flow rates and Candida
counts in subjects with xerostomia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002;93:149-54.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]