Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 

 Table of Contents  
Year : 2012  |  Volume : 8  |  Issue : 6  |  Page : 67-71

The role of intensity modulated radiotherapy in advanced oral cavity carcinoma

1 Head and Neck Unit, Royal Marsden Hospital, SW3 6JJ; The Institute of Cancer Research, 237 Fulham Road, SW3 6JB, London, United Kingdom
2 Head and Neck Unit, Royal Marsden Hospital, SW3 6JJ, London, United Kingdom

Date of Web Publication24-Jan-2012

Correspondence Address:
S A Bhide
Head and Neck Unit, Royal Marsden Hospital, Downs Road, Sutton, SM2 5PT
United Kingdom
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-1482.92218

Rights and Permissions
 > Abstract 

It is increasingly being recognized that oral cavity cancer incidences are rising globally. Furthermore, these tumors represent a high risk group of tumors comparative to other head and neck tumor sub-sites and have a high preponderance of occult nodal metastases. Surgery alone leads to excellent outcomes in early stage disease. Advanced tumors require adjuvant radiotherapy with or without concomitant chemotherapy. Irradiation using 3D conformal radiotherapy results in high incidence of late radiation side-effects. Xersostomia and mandibular osteoradionecrosis result in most significant effects on patients' quality of life. Intensity modulated radiotherapy (IMRT) is an advanced approach to 3-D treatment planning and conformal therapy (3D-CRT). It optimizes the delivery of irradiation to irregularly-shaped volumes and has the ability to produce concavities in radiation treatment volumes and hence enables sparing of normal tissue while delivering adequate doses to the tumor volumes. In this manuscript, we discuss the advantages of IMRT based on review of published peer reviewed literature.

Keywords: Intensity modulated radiotherapy, oral cavity cancer, carcinoma

How to cite this article:
Bhide S A, Ahmed M, Newbold K, Harrington K J, Nutting C M. The role of intensity modulated radiotherapy in advanced oral cavity carcinoma. J Can Res Ther 2012;8, Suppl S2:67-71

How to cite this URL:
Bhide S A, Ahmed M, Newbold K, Harrington K J, Nutting C M. The role of intensity modulated radiotherapy in advanced oral cavity carcinoma. J Can Res Ther [serial online] 2012 [cited 2021 Nov 28];8:67-71. Available from: https://www.cancerjournal.net/text.asp?2012/8/6/67/92218

 > Introduction Top

Oral cavity cancer is the sixth most common cancer worldwide. [1] Incidences vary widely across geographical areas with the UK demonstrating a relatively low incidence of 3500 cases per year, [2] compared to parts of South East Asia where a third of all male cancers in India originate in the oral cavity. [3] Etiological factors for squamous cell oral cavity cancer (OCC) such as high tobacco and alcohol consumption, and betel quid chewing, may account for some of these geographical variations. [4] Recently infection with human papilloma virus has been identified as a causal factor for the rising incidence of oropharyngeal cancers in non-smokers. However, the relationship with oral cavity cancer is not yet established. [5]

It is increasingly being recognized that oral cavity cancer incidences are rising globally. Furthermor, these tumors represent a high risk group of tumors comparative to other head and neck tumor sub-sites and have a high preponderance of occult nodal metastases with an incidence of 20-40% on pathological examination of the clinically node-negative neck. [6],[7]

 > Treatment of Oral Cavity Cancers Top

External beam radiotherapy is used in the treatment of OCC, primarily in the post-operative setting but also as first definitive treatment when surgery is felt to be inappropriate. [8] In these early stage patients, risk stratification is based on thickness and grade of tumor. [9] Patients with oral tongue tumors or floor of mouth tumors with a clinically node-negative neck require surgical resection of the primary lesion and elective neck dissection at the very least. In 1972, a study by Lindberg demonstrated that the lymph node groups most frequently involved in patients with carcinoma of the oral cavity are the jugulodigastric and midjugular nodes (levels II and III). In patients with carcinoma of the floor of the mouth, anterior oral tongue, and buccal mucosa, the nodes most frequently involved are in the submandibular triangle (level I). Lindberg also noted that cancers frequently metastasize to both sides of the neck and can skip the submandibular and jugulodigastric nodes, metastasizing first to the midjugular region.

Supra-omohyoid neck dissection (dissection of nodal compartments level I to III) offers similar rates of locoregional control and survival as a modified radical neck dissection. [10] Most surgical groups advocate the use of an extended supra-omohyoid dissection in oral tongue tumors and deem it compulsory for the node positive patient due to the risk of skip metastasis to nodal compartment level IV while some groups will recommend the extended supra-omohyoid dissection for floor of mouth tumors in addition to tongue tumors. [11] Tumors approaching the midline require dissection of the contralateral neck. Post-operative radiotherapy is administered in selected high risk groups. [12]

 > Radiotherapy for Oral Cavity Cancers Top

Stage III and IV tumors of the oral cavity generally require bilateral oral cavity and neck irradiation following surgery. The acute toxicity from bilateral oral cavity irradiation is severe, and the majority of patients develop grade 2/3 oral mucositis and dysphagia. However, these acute effects are self-limiting and it is the permanent nature of the late effects which become more problematic. Sixty-six percent of patients with stage III disease and 58% patients with stage IV undergoing appropriate surgical management and post-operative radiotherapy will survive five years or longer and are deemed cured beyond this point. They are therefore susceptible to lifelong consequences of irradiation.

 > Intensity Modulated Radiotherapy Top

Intensity modulated radiotherapy (IMRT) is an advanced approach to 3-D treatment planning and conformal therapy (3D-CRT). It optimizes the delivery of irradiation to irregularly-shaped volumes and has the ability to produce concavities in radiation treatment volumes. Typically for head and neck cancer the clinical target volume 1 (CTV1), which includes the primary tumor and the involved nodes receives a higher radiation dose as compared to the clinical target volume 2 (CTV2). The different doses to CTV1 and 2 can be delivered simultaneously, while sparing the parotid salivary glands and the spinal cord. In the head and neck region, IMRT has a number of potential advantages: (i) it allows for greater sparing of normal structures such as salivary glands, esophagus, optic nerves, brain stem, and spinal cord; [13],[14] (ii) it allows treatment to be delivered in a single treatment phase without the requirement for matching additional fields to provide tumor boosts and eliminates the need for electron fields to the posterior (level II, V) neck nodes; (iii) it offers the possibility of simultaneously delivering higher radiation doses to regions of gross disease and lower doses to areas of microscopic disease, the so-called simultaneous integrated boost (SIB-IMRT). [15]

Salivary sparing

The most common late effect of bilateral oral cavity irradiation is xerostomia which can affect dentition, speech, swallowing and mastication. Radiation for squamous cell OCC requires high doses in the region of 66-70 Gy for radical treatment and 60Gy in the post-operative setting. These dose levels far exceed the tolerance doses of salivary tissue, resulting in a high incidence of xerostomia for this group of patients. Eisbruch et al. (1999) were able to demonstrate substantial preservation of flow rates for unstimulated saliva with a mean threshold dose to the parotid at <24Gy, and <26Gy for stimulated saliva. [16] Stimulated salivary flow recovered over a period of approximately 12 months. Unilateral parotid dose levels above these values saw virtually no recovery of salivary flow, confirming that the parotid gland behaves as a parallel organ exhibiting a threshold effect. Partial volume thresholds also displayed a threshold effect and the volume of parotid tissue able to receive 30Gy (V 30 ) was 45%. Nutting et al were able to demonstrate a 50% reduction in subjective xerostomia rates with IMRT compared to the conventionally treated patients by maintaining a mean dose to the contralateral parotid gland of 26Gy. [17] Parotid-sparing IMRT for oropharyngeal tumors was achieved in most cases by sparing the contralateral parotid gland where the contra-lateral parapharyngeal space (upper part of level II) and parotid gland were judged to be at very low risk of harboring occult metastases. Further sparing of salivary gland tissue was achieved by applying a dose constraint to the anterior oral cavity and sparing this structure in the optimization process. Contra lateral parotid, sub-mandibular glands and oral cavity can be spared when treating well lateralized tumors (buccal mucosa, retro-molar trigone, lateral alveolar ridge) of the oral cavity. Sparing the contra lateral organs at risk is difficult when treating mid-line tumors of the oral cavity in order to deliver adequate doses to the bilateral parapharyngeal spaces and lymph node levels Ib and II. Ahmed et al in a planning study demonstrated that parotid sparing is achievable in the treatment of advanced squamous cell OCC, particularly in patients who have not undergone surgery, but also in post-operative patients where the superior border of delineation can be lowered to below the hard palate with the use of a bite block and providing the neck is maintained in a neutral position, [Figure 1]. [18] In addition, Miah et al have demonstrated that the incidence of late grade II xerostomia can be reduced by sparing bi-lateral superficial parotid glands, while delivering adequate doses to the parapharyngeal spaces and level II lymph nodes in tumors of the oropharynx. [19]
Figure 1: Parotid sparing (glands outlined in purple) that can be achieved using IMRT (B) compared to 3D-CRT (A)

Click here to view

Six studies investigating the use of IMRT in OCC have been published to date. Chen et al performed a non-randomized retrospective comparison of patients treated with IMRT vs. 3D-CRT. [20] The rates of grade 2 xerostomia at two years were 36% vs. 82% respectively. The grade 2 xersotomia was 29% as reported by Gomez et al. [21] The other studies failed to report the rates of xerostomia. Parotid dose levels are not the only factor to influence xerostomia rates, particularly subjective xerostomia scores. The parotid glands along with the sub-mandibular gland represent the major salivary glands and produce the bulk of saliva. The minor salivary glands which are scattered throughout the oral cavity produce less than 10% of the total saliva volume but crucially contribute more than 70% of total mucins. [22] Mucins serve as mucosal lubricants. Their molecular structure binds water effectively thus maintaining the mucosal membranes in a state of hydration. [23] The need to spare the mucin-producing minor and submandibular salivary glands became apparent after the realization that parotid-sparing alone achieves modest patient-reported gains in xerostomia. [24],[25] Hence, most IMRT OP studies have since defined a cost function for oral-cavity sparing in their optimization process. As an at risk structure a dose constraint of 30Gy or less is applied. As this structure is part of the target volume for OCC, this dose constraint cannot be applied in IMRT planning of these patients. This may have significant implications on subjective xerostomia scores and highlights the need to assess not only salivary flow rates but also QOL measurements or subjective xerostomia scores.

 > Osteoradionecrosis of Mandible Top

A more problematic late effect of radiation is osteoradionecrosis (ORN). Osteoradionecrosis, a process of bone and soft tissue necrosis, arising as a result of radiation-induced hypocellularity, hypoxia and hypovascularity, results in an area of non-healing bone. ORN can lead to pain, infection and sequestration of bone and, in extreme cases, the development of fistulae. [26] ORN is the most severe complication of bone irradiation, most commonly affecting the body of the mandible which may be a result of the relatively poor vascularity of this region. [27] Spontaneous ORN is dose dependent (> 60 Gy) and relates to the volume of mandible within the treatment field. [28],[29] Trauma-related ORN can occur at lower doses. Reuther et al were able to demonstrate a significant correlation between radiation dose and extent of ORN. Most ORN lesions measuring 2 cm or more occurred at doses of 60 Gy or higher. At this dose level, there was also a preponderance of smaller ORN lesions. Below 60 Gy most lesions were < 2 cm in size. [30] A similar study demonstrated increasing incidences of ORN with increased doses of radiotherapy. Few cases of ORN were observed below 50Gy. [31] A more recent study by Lee et al found that the risk of ORN either traumatic or spontaneous correlated to the mandible receiving a radiation dose of BED equivalent 102.6 Gy (2) or higher. In their series of 198 patients, 45% of which were OCC cases and the remainder OP cases, the overall ORN rates were 6.6%. They observed no cases of ORN in patients receiving doses below this threshold. Hence, they concluded that radiation to the mandible at doses of 54Gy or higher (at conventional fractionation) was a risk factor for the development of ORN. [32] Conventional planning frequently causes hot-spots within parts of the mandible outside the target volume (mandible PRV), and the greater the size of the areas of high dose, the greater the subsequent risk of ORN.Other studies have defined 'the delivery of >95% of the total radiation dose to the whole bone diameter' as a risk factor and also the presence of teeth in the high dose area. [33] The incidence of severe osteoradionecrosis after treatment for head and neck cancer is 5-15% depending on the dose to the mandible and factors such dental hygiene. [33],[34] Studies have demonstrated that the dose to the mandible can be minimized without affecting the dose to the target volumes. [33],[35]

The study by Ahmed et al assessed the volumes of mandible exposed to high doses represented by the V50, 55, 60. IMRT was able to reduce, not only the dose maxima to the mandible PRV, to significantly lower values than those seen in conventional planning but also the volumes of mandible receiving 50, 55 and 60 Gy. Furthermore, in the IMRT plans a rim of mandible along the buccal cortex was spared from the high isodose curves of 95% to 100, [Figure 2]. [18] Based on the data from the above studies, one would anticipate this dosimetric advantage seen with IMRT to translate into a clinical advantage, with a potential to reduce the risk of ORN. This clinical benefit was not conclusively demonstrated in the RTOG-022 IMRT study which demonstrated ORN rates of 6%. [36] Similarly studies of IMRT for OCC have demonstrated the risk of late ORN of around 5%. [21],[37] Two studies in OP cancer have demonstrated substantial benefit with IMRT for the prevention of ORN. The first of these studies reviewed all patients treated with parotid sparing IMRT in prospective studies at a single institution. The patients adhered to a strict dental policy of dental evaluation, patient education and radiation guards for dental metal work. So far not a single case of ORN has been identified. [35] Similarly Studer et al demonstrated a low ORN incidence of 1.3% with parotid sparing IMRT. [33] Both studies used an oral cavity dose constraint as the majority of tumors were oropharyngeal in origin. However, the latter study group also included 18 OCC patients. A subsequent study by this group compared 58 IMRT treated OCC patients with 33 historical controls (treated with 3DCRT). Patients treated with definitive RT alone demonstrated higher locoregional recurrence rates with IMRT, than those treated with 3DCRT while patients receiving combined modality treatment with surgery and IMRT demonstrated the best local control rates. Once more an oral cavity dose constraint was used and no cases of ORN after 22 months have been described. This is not strictly possible in the treatment of OCC where the oral cavity is the principal target volume and more compromise local control. Other risk factors for ORN aside from the volume of irradiated mandible, and dose maxima to the mandible, need to be considered. The importance of dental care is undoubtedly a contributory factor. This will impact on the risk of dental caries and minimize the requirement for dental extractions. IMRT may also diminish this risk due to improved saliva flow. In the planning study described above, the parotid sparing potential of IMRT for OCC has been demonstrated. The sparing of minor salivary tissue was not attempted due to the 'at risk' tumor volume. The extent to which these varying factors bear an impact on ORN is difficult to define but it is likely that a combination of mandible sparing, salivary tissue sparing and exemplary dental care all contribute to the lowered ORN rates seen in these clinical studies.
Figure 2: Relative mandibular sparing (outer rim) that can be achieved with IMRT compared to 3D-CRT

Click here to view

Predictably, the mandibular-sparing potential of IMRT diminishes in patients who require a rim resection or segmental mandiblectomy. One would expect to see even less of a benefit in patients with alveolar tumors where the bulk of the mandible (most of which will be reconstructed) is encompassed within PTV1. There is evidence of higher rates of ORN in T4 tumors. [30],[31] This is felt to be due to a combination of factors including the type of surgery, the high radiation dose in adjacent mandible and hypoxia in the surgical bed. Lee's study which demonstrated radiation BED to be a risk factor for ORN showed that the most significant risk factor for ORN was in fact previous mandibular surgery. [32] Hence although it is technically more difficult to spare the mandible in these patients, mandible sparing is more likely to be necessary. The other key risk factor for ORN in these patients is the addition of chemotherapy to their radiation treatment. Increasingly chemoradiation is being used in patients with positive margins or with evidence of extracapsular spread. [38] Patients not suitable for surgery receive chemoradiation as definitive treatment unless contra-indicated. Studies have demonstrated higher ORN incidences in this group of patients with one study from the University of Chicago demonstrating an ORN incidence of 18.4% in patients with advanced OCC receiving chemoradiation. Some patients in this study had received IMRT but the majority had been treated with older radiation techniques. [39]

 > Treatment Outcomes Top

IMRT plans have steep dose gradients on account of the attempt to spare the organs at risk. The sharp dose gradients increase the likelihood of a geographical miss and the possibility of reduced loco-regional controls. Chen et al, in a non-randomized retrospective comparison of patients treated with IMRT vs. 3D-CRT showed equivalent outcomes. [20] The five other studies that used IMRT for OCC demonstrated equivalent if not superior outcomes for IMRT when compared to historical controls. [21],[37],[40],[41],[42]

 > Conclusion Top

IMRT of advanced oral cavity tumors offers the potential to reduce the risks of xerostomia and ORN through parotid and mandibular sparing. This can be performed without compromising on target volume coverage and hence treatment outcomes.

 > References Top

1.Moore SR, Johnson NW, Pierce AM, Wilson DF. The epidemiology of mouth cancer: A review of global incidence. Oral Dis 2000;6:65-74.  Back to cited text no. 1
2.Campaign TC. CRC Cancer Stats, Oral UK. London: CRC; 2000.  Back to cited text no. 2
3.Sunny L, Yeole BB, Hakama M, Shiri R, Sastry PS, Mathews S, et al. Oral cancers in Mumbai, India: A fifteen years perspective with respect to incidence trend and cumulative risk. Asian Pac J Cancer Prev 2004;5:294-300.  Back to cited text no. 3
4.IARC. Tobacco Habits other than Smoking; Betel-quid and Areca-nut Chewing, and Some Related Nitrosamines. Lyon: International Agency for Research on Cancer; 1985.  Back to cited text no. 4
5.Pintos J, Black MJ, Sadeghi N, Ghadirian P, Zeitouni AG, Viscidi RP, et al. Human papillomavirus infection and oral cancer: A case-control study in Montreal, Canada. Oral Oncol 2008;44:242-50.  Back to cited text no. 5
6.Walvekar RR, Chaukar DA, Deshpande MS, Pai PS, Chaturvedi P, Kakade A, et al. Squamous cell carcinoma of the gingivobuccal complex: Predictors of locoregional failure in stage III-IV cancers. Oral Oncol 2009;45:135-40.  Back to cited text no. 6
7.Woolgar JA, Scott J. Prediction of cervical lymph node metastasis in squamous cell carcinoma of the tongue/floor of mouth. Head Neck 1995;17:463-72.  Back to cited text no. 7
8.Kademani D, Bell RB, Bagheri S, Holmgren E, Dierks E, Potter B, et al. Prognostic factors in intraoral squamous cell carcinoma: The influence of histologic grade. J Oral Maxillofac Surg 2005;63:1599-605.  Back to cited text no. 8
9.Spiro RH, Huvos AG, Wong GY, Spiro JD, Gnecco CA, Strong EW. Predictive value of tumor thickness in squamous carcinoma confined to the tongue and floor of the mouth. Am J Surg 1986;152:345-50.  Back to cited text no. 9
10.Results of a prospective trial on elective modified radical classical versus supraomohyoid neck dissection in the management of oral squamous carcinoma. Brazilian Head and Neck Cancer Study Group. Am J Surg 1998;176:422-7.  Back to cited text no. 10
11.Shah JP, Candela FC, Poddar AK. The patterns of cervical lymph node metastases from squamous carcinoma of the oral cavity. Cancer 1990;66:109-13.  Back to cited text no. 11
12.Peters LJ, Goepfert H, Ang KK, Byers RM, Maor MH, Guillamondegui O, et al. Evaluation of the dose for postoperative radiation therapy of head and neck cancer: First report of a prospective randomized trial. Int J Radiat Oncol Biol Phys 1993;26:3-11.  Back to cited text no. 12
13.Chao KS, Deasy JO, Markman J, Haynie J, Perez CA, Purdy JA, et al. A prospective 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.  Back to cited text no. 13
14.Eisbruch A, Marsh LH, Martel MK, Ship JA, Ten Haken R, Pu AT, et al. Comprehensive irradiation of head and neck cancer using conformal multisegmental fields: Assessment of target coverage and noninvolved tissue sparing. Int J Radiat Oncol Biol Phys 1998;41:559-68.  Back to cited text no. 14
15.Butler EB, Teh BS, Grant WH 3rd, Uhl BM, Kuppersmith RB, Chiu JK, et al. Smart (simultaneous modulated accelerated radiation therapy) boost: A new accelerated fractionation schedule for the treatment of head and neck cancer with intensity modulated radiotherapy. Int J Radiat Oncol Biol Phys 1999;45:21-32.  Back to cited text no. 15
16.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.  Back to cited text no. 16
17.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. 17
18.Ahmed M, Hansen VN, Harrington KJ, Nutting CM. Reducing the risk of xerostomia and mandibular osteoradionecrosis: The potential benefits of intensity modulated radiotherapy in advanced oral cavity carcinoma. Med Dosim 2009;34:217-24.  Back to cited text no. 18
19.Miah AB, Bhide SA, MT GU, al e. Bilateral superficial lobe parotid sparing IMRT: Treating base of tongue tumours: Similar outcomes to unilateral whole parotid gland sparing. Radiother Oncol 2009;90 (suppl 2):S11.  Back to cited text no. 19
20.Chen WC, Hwang TZ, Wang WH, Lu CH, Chen CC, Chen CM, et al. Comparison between conventional and intensity-modulated post-operative radiotherapy for stage III and IV oral cavity cancer in terms of treatment results and toxicity. Oral Oncol 2009;45:505-10.  Back to cited text no. 20
21.Gomez DR, Zhung JE, Gomez J, Chan K, Wu AJ, Wolden SL, et al. Intensity-modulated radiotherapy in postoperative treatment of oral cavity cancers. Int J Radiat Oncol Biol Phys 2009;73:1096-103.  Back to cited text no. 21
22.Milne RW, Dawes C. The relative contributions of different salivary glands to the blood group activity of whole saliva in humans. Vox Sang 1973;25:298-307.  Back to cited text no. 22
23.Tabak LA. In defense of the oral cavity: Structure, biosynthesis, and function of salivary mucins. Annu Rev Physiol 1995;57:547-64.  Back to cited text no. 23
24.Eisbruch A. Reducing xerostomia by IMRT: What may, and may not, be achieved. J Clin Oncol 2007;25:4863-4.  Back to cited text no. 24
25.Murdoch-Kinch CA, Kim HM, Vineberg KA, Ship JA, Eisbruch A. Dose-effect relationships for the submandibular salivary glands and implications for their sparing by intensity modulated radiotherapy. Int J Radiat Oncol Biol Phys 2008;72:373-82.  Back to cited text no. 25
26.Store G, Boysen M. Mandibular osteoradionecrosis: Clinical behaviour and diagnostic aspects. Clin Otolaryngol Allied Sci 2000;25:378-84.  Back to cited text no. 26
27.Bras J, de Jonge HK, van Merkesteyn JP. Osteoradionecrosis of the mandible: Pathogenesis. Am J Otolaryngol 1990;11:244-50.  Back to cited text no. 27
28.Glanzmann C, Gratz KW. Radionecrosis of the mandibula: A retrospective analysis of the incidence and risk factors. Radiother Oncol 1995;36:94-100.  Back to cited text no. 28
29.Marx RE, Johnson RP. Studies in the radiobiology of osteoradionecrosis and their clinical significance. Oral Surg Oral Med Oral Pathol 1987;64:379-90.  Back to cited text no. 29
30.Reuther T, Schuster T, Mende U, Kubler A. Osteoradionecrosis of the jaws as a side effect of radiotherapy of head and neck tumour patients-a report of a thirty year retrospective review. Int J Oral Maxillofac Surg 2003;32:289-95.  Back to cited text no. 30
31.Curi MM, Dib LL. Osteoradionecrosis of the jaws: A retrospective study of the background factors and treatment in 104 cases. J Oral Maxillofac Surg 1997;55:540-4; discussion 5-6.  Back to cited text no. 31
32.Lee IJ, Koom WS, Lee CG, Kim YB, Yoo SW, Keum KC, et al. Risk factors and dose-effect relationship for mandibular osteoradionecrosis in oral and oropharyngeal cancer patients. Int J Radiat Oncol Biol Phys 2009;75:1084-91.  Back to cited text no. 32
33.Studer G, Studer SP, Zwahlen RA, Huguenin P, Gratz KW, Lutolf UM, et al. Osteoradionecrosis of the mandible: Minimized risk profile following intensity-modulated radiation therapy (IMRT). Strahlenther Onkol 2006;182:283-8.  Back to cited text no. 33
34.Mendenhall WM. Mandibular osteoradionecrosis. J Clin Oncol 2004;22:4867-8.  Back to cited text no. 34
35.Ben-David MA, Diamante M, Radawski JD, Vineberg KA, Stroup C, Murdoch-Kinch CA, et al. Lack of osteoradionecrosis of the mandible after intensity-modulated radiotherapy for head and neck cancer: Likely contributions of both dental care and improved dose distributions. Int J Radiat Oncol Biol Phys 2007;68:396-402.  Back to cited text no. 35
36.Eisbruch AH, Garden A, et al. Phase II Multi-institutional Study of IMRT for Oropharyngeal Cancer (RTOG 00-22): Int J Radiat Oncol Biol Phys 2006;66 Supplement.  Back to cited text no. 36
37.Daly ME, Le QT, Kozak MM, Maxim PG, Murphy JD, Hsu A, et al. Intensity-Modulated Radiotherapy for Oral Cavity Squamous Cell Carcinoma: Patterns of Failure and Predictors of Local Control. Int J Radiat Oncol Biol Phys 2010.  Back to cited text no. 37
38.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. 38
39.Stenson KM, Kunnavakkam R, Cohen EE, Portugal LD, Blair E, Haraf DJ, et al. Chemoradiation for patients with advanced oral cavity cancer. Laryngoscope 2010;120:93-9.  Back to cited text no. 39
40.Studer G, Zwahlen RA, Graetz KW, Davis BJ, Glanzmann C. IMRT in oral cavity cancer. Radiat Oncol 2007;2:16.  Back to cited text no. 40
41.Hsieh CH, Kuo YS, Liao LJ, Hu KY, Lin SC, Wu LJ, et al. Image-guided intensity modulated radiotherapy with helical tomotherapy for postoperative treatment of high-risk oral cavity cancer. BMC Cancer 2011;11:37.  Back to cited text no. 41
42.Yao M, Chang K, Funk GF, Lu H, Tan H, Wacha J, et al. The failure patterns of oral cavity squamous cell carcinoma after intensity-modulated radiotherapy-the university of iowa experience. Int J Radiat Oncol Biol Phys 2007;67:1332-41.  Back to cited text no. 42


  [Figure 1], [Figure 2]

This article has been cited by
1 Oral cancer: Current role of radiotherapy and chemotherapy18
Huang, S.-H., OæSullivan, B.
Medicina Oral, Patologia Oral y Cirugia Bucal. 2013; 18(2): e233-e240
2 Comparison of survival rates between patients treated with conventional radiotherapy and helical tomotherapy for head and neck cancer
Kong, M., Hong, S.E., Choi, J., Kim, Y.
Radiation Oncology Journal. 2013; 31(1): 1-11
3 Influence of the modulation factor on the treatment plan quality and execution time in Tomotherapy in head and neck cancer: In-phantom study
Ryczkowski, A., Piotrowski, T.
Journal of Cancer Research and Therapeutics. 2013; 9(4): 618-623
4 Dental status, dental rehabilitation procedures, demographic and oncological data as potential risk factors for infected osteoradionecrosis of the lower jaw after radiotherapy for oral neoplasms: A retrospective evaluation
Niewald, M., Fleckenstein, J., Mang, K., (...), Spitzer, W.J., Rübe, C.
Radiation Oncology. 2013; 8(1): 227
5 The first special issue.... of many more to come!
Murthy, V.
Journal of Cancer Research and Therapeutics. 2012; 8(sup 2): 53-54
6 Document Interleukin-6 as a therapy target in oral squamous carcinoma
Culig, Z.
Expert Opinion on Therapeutic Targets. 2012; 17(1): 53-59


Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  >Abstract>Introduction>Treatment of Ora...>Radiotherapy for...>Intensity Modula...>Osteoradionecros...>Treatment Outcomes>Conclusion>Article Figures
  In this article

 Article Access Statistics
    PDF Downloaded444    
    Comments [Add]    
    Cited by others 6    

Recommend this journal