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ORIGINAL ARTICLE
Year : 2019  |  Volume : 15  |  Issue : 3  |  Page : 539-543

Adjuvant radiotherapy in carcinoma buccal mucosa; more conformal the best: Is it so?


1 Department of Radiation Oncology, M.S. Ramaiah Medical College, Bangaluru, Karnataka, India
2 Department of Medical Physics, Cancer Institute (WIA), Adyar, Chennai, Tamil Nadu, India

Date of Web Publication29-May-2019

Correspondence Address:
M G John Sebastian
Department of Radiation Oncology, M.S. Ramaiah Medical College, Bengaluru - 560 054, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.JCRT_101_17

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 > Abstract 


Introduction: Since 1980s, computerization has made improvements in radiation therapy delivery from conventional two-dimensional to three-dimensional conformal radiotherapy (2DCRT to 3DCRT) to intensity-modulated radiotherapy (IMRT) and its newer versions. This small study is aimed to compare the existing techniques for planning target volume (PTV) and organ at risk (OAR) dose distribution parameters in postoperative buccal mucosa cases.
Materials and Methods: Ten post operative cases of early stage carcinoma buccal mucosa in whom only post operative bed irradiation was indicated was enrolled and was planned with conventional, 3DCRT and IMRT techniques to get 95% PTV coverage and dose received by organs at risk were recorded and evaluated.
Results: Mean and standard deviation values for PTV 95% for IMRT, 3DCRT, and conventional plans were 96.4 ± 1.8, 95.1 ± 1.9, and 91 ± 2.7, respectively. Dose received by OARs was high in conventional technique when compared to the other two. Maximum dose received by 1 cc of brain (46.2 ± 7.9 and 60.8 ± 3.8) (priority was given for PTV coverage) and mean dose received by the same eye (13.6 ± 1.4 and 22 ± 2.4) were less in IMRT when compared to 3DCRT. However, maximum dose received by 1 cc of brainstem (29.7 ± 7.6 and 14.1 ± 9.5), optic chiasma (29.2 ± 4.2 and 12 ± 2.1), spinal cord (31.8 ± 3 and 20.9 ± 4.2), and the same-side optic nerve (22 ± 6.9 and 11.7 ± 9.4) and mean dose received by opposite-side parotid (8.7 ± 1.1 and 1.7 ± 0.4) and submandibular gland (18.6 ± 1.7 and 3.2 ± 0.9) were more with IMRT when compared to 3DCRT.
Conclusion: In postoperative cases of early-stage carcinoma buccal mucosa, it is good enough to treat with 3DCRT technique. Here, the target area will be well lateralized, and 3DCRT technique can give good target coverage and less dose to OARs, especially the only remaining major salivary glands.

Keywords: Buccal mucosa, intensity-modulated radiotherapy, parotid, three-dimensional conformal radiotherapy


How to cite this article:
Koushik A S, Sebastian M G, Janaki M G, Sathish S. Adjuvant radiotherapy in carcinoma buccal mucosa; more conformal the best: Is it so?. J Can Res Ther 2019;15:539-43

How to cite this URL:
Koushik A S, Sebastian M G, Janaki M G, Sathish S. Adjuvant radiotherapy in carcinoma buccal mucosa; more conformal the best: Is it so?. J Can Res Ther [serial online] 2019 [cited 2019 Aug 22];15:539-43. Available from: http://www.cancerjournal.net/text.asp?2019/15/3/539/244196




 > Introduction Top


Carcinoma of the oral cavity is the third most common malignancy in India with 77,003 new cases in 2012, and with 52,067 deaths, it accounts for the fifth most common cause of cancer-related deaths here.[1]

Buccal mucosa includes the membranous lining of the inner surface of the cheeks and lips from the line of contact of the opposing lips to the line of attachment of mucosa of the alveolar ridge (upper and lower) and pterygomandibular raphe.[2] The high incidence of carcinoma buccal mucosa in India is probably attributable to smoking and the usage of tobacco in its various forms.[3]

Cessation of smoking and tobacco usage is an important part in the management of oral cavity tumors. The preferred treatment modality for carcinoma buccal mucosa is resection of primary with ipsilateral or bilateral neck dissection followed by adjuvant treatment as indicated.

Adjuvant radiotherapy is indicated in high-risk features such as extracapsular nodal spread, positive and close margin, pT3 and above, N2 and above, N1 if the involved node is Level IV or V, perineural invasion, and vascular embolism [4],[5],[6],[7] Adjuvant radiotherapy is indicated only to tumor bed in pT3 cases if there is no other high-risk factors. Any margin <5 mm was considered as close margin and was considered for adjuvant radiotherapy to the tumor bed.

Radiation therapy has evolved from conventional to three-dimensional (3D) conformal to intensity-modulated radiotherapy (IMRT) over the past few decades. This happened as a part of attempts to increase target coverage and minimizing dose to organs at risk (OAR). The fluence-modulating property of IMRT gives it a theoretical advantage over three-dimensional conformal radiotherapy (3DCRT) which is also supported by recent trials.[8],[9] Although the superiority of IMRT over 3DCRT is clear in terms of target coverage and dose conformity, the use of multiple fields may result in undesirable doses to certain OAR which otherwise will get only minimal dose.[10],[11],[12] However, IMRT has its own limitations resulting from complex planning and delivery processes.


 > Materials and Methods Top


Ten patients of carcinoma buccal mucosa postwide local excision and modified radical neck dissection were accrued for the study. It was made sure that these patients required only postoperative bed irradiation. Hence, only patients with pathological node-negative status were included in the study.

Patients were positioned supine with head extended and shoulders retracted. A thermoplastic mask over the head-and-neck area was used for immobilization. Computed tomography (CT) of the head and neck with intravenous contrast was taken with 3 mm sections down to the infraclavicular region. CT is then transferred to the contouring station where the targets and OAR were marked. Clinical target volume included the postoperative bed and potential areas for microscopic disease spread. Since only pN0 cases were accrued for the study, nodal irradiation was not considered. A planning target volume (PTV) of 5 mm was given as per the institution protocol.

A conventional and a 3DCRT plan was created giving the first priority for target coverage with an aim to cover 100% of PTV with 95% of the prescribed dose with the help of ONCENTRA treatment planning system. Conventional plan was generated using anterolateral wedge pair technique [Figure 1]. 3DCRT plans were made with two parallel opposed oblique beams with field in field technique [Figure 2].
Figure 1: Conventional plan

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Figure 2: Three-dimensional conformal radiotherapy plan

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For IMRT plans, 7-9 fields isocentric technique using isotropic gantry angles were used [Figure 3]. Organs at risk were given constraints as per [Table 1], and inverse planning technique was used with MONACO treatment planning system. OAR was given constraints, and inverse planning technique was used with MONACO treatment planning system. Dose–volume histograms were calculated, and all comparative parameters were extracted for each plan and were analyzed.
Figure 3: Intensity-modulated radiotherapy plan

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Table 1: Intensity-modulated radiotherapy dose constraints

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Statistical methods

Dose received by OAR was significantly high in conventional planning when compared to the other two, and hence only 3DCRT and IMRT plans were considered for further evaluation. Data were statistically described in terms of mean ± standard deviation, median, and range. Comparison between the study plans was done using Mann–Whitney U-test for independent samples. P < 0.05 was considered statistically significant. All statistical calculations were done using computer programs SPSS (Statistical Package for the Social Science; SPSS Inc., Chicago, IL, USA) version 15 for Microsoft Windows.


 > Results Top


Between July 2014 and June 2015, ten patients of carcinoma buccal mucosa who underwent wide local excision, modified radical neck dissection, and reconstruction were accrued for the study. All the accrued patients had a pathological node-negative status, and hence neck irradiation was indicated. Pathological T3 status in eight and close margin in two patients were the indications of adjuvant radiotherapy. None of the patients received concurrent chemotherapy.

Three plans such as conventional, 3DCRT, and IMRT were made for each of the patients, and hence a total of thirty plans were made.

Conventional plans showed significantly high doses to OAR and hot spots at undesired area and were hence not considered for further analysis.

Comparison between V95% (volume of PTV receiving 95% of the prescribed dose) and V107% (volume of PTV receiving ≥107% of prescribed dose) for 3DCRT and IMRT technique was done. Homogeneity index and conformity index were calculated for each case using the Radiation therapy Oncology Group equations [Table 2].[13]
Table 2: Dose-volume comparison for target volume coverage in intensity-modulated radiotherapy and three-dimensional conformal radiation therapy plans

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  • Homogeneity index = maximum isodose in the target ÷ reference isodose
  • Conformity index = volume of the reference isodose ÷ target volume.


For serial structures, maximum dose received by 1 cc volume was analyzed and found that it was within tolerable range [Figure 4]. Maximum dose to brain was high in 3DCRT plan but was not statistically significant. Maximum dose to brainstem, optic chiasma, bilateral optic nerves, and spinal cord was significantly less in 3DCRT plan [Table 3].
Figure 4: Comparison of dose received by serial structures (maximum dose)

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Table 3: Organs at risk dose comparison in intensity-modulated radiotherapy and three-dimensional conformal radiation therapy plans

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For parallel structures, the mean dose received was analyzed [Figure 5] and was found that ipsilateral eye received more dose in 3DCRT plan but was not statistically significant. Contralateral eyes and parotid and submandibular glands received statistically significant low dose when compared to IMRT plans [Table 3].
Figure 5: Comparison of dose received by parallel structures (mean dose)

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 > Discussion Top


Preferred initial modality of treatment in oral cavity malignancies is surgery followed by adjuvant treatment as per indication. All pN0 diseases, where adjuvant treatment is indicated, will receive radiotherapy only to tumor bed. Postoperative bed in buccal mucosa being well lateralized can be adequately covered without giving much dose to midline and opposite side structures.

We have accrued ten such cases of carcinoma buccal mucosa where only postoperative bed irradiation is indicated and made conventional, 3DCRT, and IMRT plans and assessed PTV coverage and dose to relevant OARs. We found that statistically significant low dose is received by brainstem, optic chiasma, spinal cord, same-side eye and optic nerve, and opposite-side parotid and submandibular gland in favor of 3DCRT.

The introduction of higher radiation delivery techniques in the form of IMRT was to increase the therapeutic window by giving maximum coverage to the PTV and reducing the dose to the OARs. For this, IMRT uses multiple beams and modulation of the fluence from each beam. This will reduce undesirable dose which are in close proximity to the target. In situations where the PTV is well lateralized and no OARs are abutting the PTV, the use of IMRT is questionable. In postoperative irradiation of carcinoma buccal mucosa, the PTV is well lateralized and adequate target coverage and sparing of OARs which are located along the midline and in the contralateral side can be easily achieved by two oblique beams as shown in [Figure 2].

A reduction in salivary function is a common toxicity and reduces the patient's quality of life. Xerostomia leads to multiple problems including poor dental hygiene, a propensity to oral infections, sleep disturbances, oral pain, and difficulty chewing and swallowing. Stimulated salivary production is largely derived from the parotid glands and resting (unstimulated) salivary production is from submandibular, sublingual, and numerous small oral salivary glands.[14] In carcinoma buccal mucosa cases, postoperative irradiation is hardly expected to spare ipsilateral parotid or submandibular glands since they may be already removed/damaged during surgery. Here comes the importance of achieving the least possible dose in the contralateral major salivary glands. Washington University researchers examined whole salivary flow. They found an exponential reduction in salivary flow of 0.04/Gy of mean parotid dose showing a dose–response relationship.[15] Hence even if IMRT is based on dose constraints, the lesser the dose to parotid, the lesser will be the xerostomia as per the dose–response relationship shown by this study, reiterating the need to reduce the dose for salivary glands. Most of the contemporary studies in head and neck including the PARSPORT trial which favors IMRT for sparing salivary gland are done on pharyngeal or laryngeal malignancies.[9] Role of IMRT in postoperative oral cavity cases is not studied widely. In buccal mucosa cases where one form of local treatment in the form of surgery has addressed the neck and a pN0 status is declared, postoperative nodal irradiation is not indicated, and in such cases, 3DCRT is good enough or scores better when compared to IMRT. In India, the incidence of carcinoma buccal mucosa is very high and complexity of treatment planning and cost of treatment are of important concerns. However, it is imperative to state that the superiority of IMRT is well documented in definitive treatment of other subsites of head and neck such as nasopharynx, oropharynx, and hypopharynx. Hence, it is essential to tailor treatment modality properly and select an appropriate technique for each particular subsite.


 > Conclusion Top


Use of IMRT in carcinoma buccal mucosa is limited to cases where there is infratemporal fossa involvement or neck node irradiation is indicated. In well-lateralized treatment targets as in here, the use of IMRT will result in more doses to opposite-side structures. Avoiding such unnecessary overdosing is very essential in case of postoperative buccal mucosa cases where preservation of opposite side salivary glands is of utmost importance. In addition, the complexity of planning and delivery associated withIMRT can also be avoided.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC Cancer Base No. 11. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://www.globocan.iarc.fr. [Last accessed on 2016 Jun 01].  Back to cited text no. 1
    
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Halperin EC, Perez CA, Brady LW. Principles and Practice of Radiation Oncology. 6th ed. Philadelphia: Wolters Kluwer, Lippincott Williams & Wilkins; 2013.  Back to cited text no. 2
    
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National Cancer Registry Programme: Consolidated Report of Hospital Based Registries; 1994-1998 (Internet). Available from: http://www. ncdirindia.org/ncrp/Old_Reports/Five_Years_consolidated_HBCR_report_1994_98.pdf. [Last accessed on 2017 Jan 28].  Back to cited text no. 3
    
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Cooper JS, Pajak TF, Forastiere AA, Jacobs J, Campbell BH, Saxman SB, et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 2004;350:1937-44.  Back to cited text no. 4
    
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Bernier J, Domenge C, Ozsahin M, Matuszewska K, Lefèbvre JL, Greiner RH, et al. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 2004;350:1945-52.  Back to cited text no. 5
    
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Bernier J, Cooper JS, Pajak TF, van Glabbeke M, Bourhis J, Forastiere A, et al. Defining risk levels in locally advanced head and neck cancers: A comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501). Head Neck 2005;27:843-50.  Back to cited text no. 6
    
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Cooper JS, Zhang Q, Pajak TF, Forastiere AA, Jacobs J, Saxman SB, et al. Long-term follow-up of the RTOG 9501/intergroup phase III trial: Postoperative concurrent radiation therapy and chemotherapy in high-risk squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 2012;84:1198-205.  Back to cited text no. 7
    
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Buettner F, Miah AB, Gulliford SL, Hall E, Harrington KJ, Webb S, et al. Novel approaches to improve the therapeutic index of head and neck radiotherapy: An analysis of data from the PARSPORT randomised phase III trial. Radiother Oncol 2012;103:82-7.  Back to cited text no. 8
    
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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.  Back to cited text no. 9
    
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Binhu J, Supe S, Pawar Y. Intensity modulated radiotherapy (IMRT) the white, black and grey: A clinical perspective. Rep Pract Oncol Radiother 2009;14:95-103.  Back to cited text no. 10
    
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Rosenthal DI, Chambers MS, Fuller CD, Rebueno NC, Garcia J, Kies MS, et al. Beam path toxicities to non-target structures during intensity-modulated radiation therapy for head and neck cancer. Int J Radiat Oncol Biol Phys 2008;72:747-55.  Back to cited text no. 11
    
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Peszynska-Piorun M, Malicki J, Golusinski W. Doses in organs at risk during head and neck radiotherapy using IMRT and 3D-CRT. Radiol Oncol 2012;46:328-36.  Back to cited text no. 12
    
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Huchet A, Caudry M, Belkacémi Y, Trouette R, Vendrely V, Causse N, et al. Volume-effect and radiotherapy [II]. Part II: Volume-effect and normal tissue. Cancer Radiother 2003;7:353-62.  Back to cited text no. 13
    
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Dawes C, Wood CM. The contribution of oral minor mucous gland secretions to the volume of whole saliva in man. Arch Oral Biol 1973;18:337-42.  Back to cited text no. 14
    
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Blanco AI, Chao KS, El Naqa I, Franklin GE, Zakarian K, Vicic M, et al. Dose-volume modeling of salivary function in patients with head-and-neck cancer receiving radiotherapy. Int J Radiat Oncol Biol Phys 2005;62:1055-69.  Back to cited text no. 15
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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