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Dosimetric distribution to the tooth-bearing regions of the mandible following intensity-modulated radiation therapy for base of tongue cancer
Vol. 114 No. 2 August 2012
Dosimetric distribution to the tooth-bearing regions of the mandible following intensity-modulated radiation therapy for base of tongue cancer Heidi J. Hansen, DMD,a Beatrice Maritim, DMD,b George C. Bohle III, DDS,c Nancy Y. Lee, MD,d Joseph M. Huryn, DDS,e and Cherry L. Estilo, DMD,f New York, New York MEMORIAL SLOAN-KETTERING CANCER CENTER AND WEILL CORNELL MEDICAL COLLEGE/NEW YORK PRESBYTERIAN HOSPITAL
Objectives. Osteoradionecrosis is a significant complication following head and neck radiotherapy. The purpose of this study was to determine the intensity-modulated radiation therapy (IMRT) dosages delivered to the tooth-bearing regions of the mandible. Study Design. A total of 28 patients with base of tongue cancer with the following stages: T1-2/N2-3 (n ⫽ 10), T3-4/N2-3 (n ⫽ 10), and T1-4/N0 (n ⫽ 8), treated with IMRT, were included. Average mean and maximum doses were calculated for the anterior, premolar, and molar regions. Results. Lower doses were seen in anterior bone with smaller tumors. Large tumors, regardless of laterality, resulted in high doses to the entire mandible, with anterior bone receiving more than 6000 cGy. Conclusions. Tumor size is important in preradiation dental treatment planning. This information is important in planning preand postradiation dental extractions. Dosimetric analyses correlating mean and maximum point dose with clinical presentation and outcomes are needed to determine the best predictor of osteoradionecrosis risk. (Oral Surg Oral Med Oral Pathol Oral Radiol 2012;114:e50-e54)
Base of tongue (BOT) malignancies are frequently asymptomatic until reaching a large size (larger than 4 cm), and treatment therefore typically consists of primary radiotherapy with concurrent chemotherapy.1 Intensity-modulated radiation therapy (IMRT) is an effective modality in the treatment of head and neck cancer. IMRT generates dose distributions that sharply conform to tumor targets while minimizing dosages delivered to normal tissues. In the head and neck, sparing of normal structures, such as the parotid glands, This study was presented at the Multinational Association for Supportive Care in Cancer annual meeting in Athens, Greece, on June 24, 2011. a Fellow, Dental Service, Department of Surgery, Memorial SloanKettering Cancer Center, and Assistant Professor, Division of Oral & Maxillofacial Surgery & Dentistry, Department of Surgery, Weill Cornell Medical College/New York Presbyterian Hospital. b Fellow, Dental Service, Department of Surgery, Memorial SloanKettering Cancer Center. c Assistant, Attending, Dental Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center. d Associate Attending, Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center. e Chief, Dental Service, Department of Surgery, Memorial SloanKettering Cancer Center. f Associate Attending, Dental Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center. Received for publication Nov 9, 2011; returned for revision Jan 26, 2012; accepted for publication Jan 30, 2012. © 2012 Elsevier Inc. All rights reserved. 2212-4403/$ - see front matter doi:10.1016/j.oooo.2012.01.024
e50
has been shown to reduce the long-term hyposalivation caused by radiation-induced damage to salivary tissue.2,3 Osteoradionecrosis (ORN) is a significant and welldescribed complication following head and neck radiotherapy4-6; however, little is known about the rate of ORN in the IMRT era. ORN occurs more commonly in the mandible. This is thought to be because of its less abundant blood supply compared with that of the maxilla and also because it is often necessary to deliver high doses of radiation to tumors near the mandible. Typically, the risk of ORN is associated with mean doses of 5000 to 6000 cGy or higher (50-60 Gy).7 Because of IMRT’s complex multibeam delivery, clinicians planning postradiation dental extractions are often faced with difficulty determining the exact dose delivered to the bone surrounding the teeth. Although the mandible is routinely contoured as an avoidance structure because of its high risk of ORN, the exact amount of radiation delivered to the bone supporting the molars, premolars, and the anterior teeth has not been described. This is of particular importance, as this detailed information will help clinicians in planning for both pre- and postradiation dental extractions. The purpose of this study was to determine the amount of radiation delivered to these specific mandibular regions from 28 consecutive patients with BOT cancer treated with IMRT ⫾ chemotherapy at Memorial Sloan-Kettering Cancer Center (MSKCC).
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ORIGINAL ARTICLE Hansen et al. e51
high doses delivered to the entire mandible (Figure 3). Figure 4 depicts mandibular doses in patients with node-negative disease. Doses in patients without local metastasis appear to follow patterns similar to the other 2 groups of node-positive patients. Maximum point doses amounted to less than 1% of the total contoured mandibular volume (tooth-bearing bone) as calculated on dose volume curves generated by the MSKCC radiation treatment planning software. Mandibular volumes receiving more than 5500 cGy for different T-size tumors are depicted in Figure 5. The average volume percentage receiving more than 5500 cGy was calculated for each region (ipsi- and contralateral molars, premolars, and anterior teeth). It is evident that the mandibular volume percentages receiving more than 5500 cGy increase with increasing tumor size. Fig. 1. Example of the 5 contoured regions as drawn for each CT slice of the mandible.
MATERIAL AND METHODS After approval was obtained by the MSKCC institutional review board, 28 consecutive patients with BOT cancer were divided into 3 groups based on tumor size and nodal status: T1-2/N2-3 (n ⫽ 10), T3-4/N2-3 (n ⫽ 10), and T1-4/N0 (n ⫽ 8). All patients were seen before radiation therapy for a comprehensive dental evaluation and necessary treatment, including extractions, restorations, endodontic treatment, periodontal treatment, and, when necessary, radiation mouth guards. Patients were treated with platinum-based chemotherapy and IMRT to 7000 cGy. For each patient, using MSKCC radiation treatment planning software, the mandible in its entire height, from the alveolar crest to the inferior cortex, was manually contoured for the bone surrounding the right molars, left molars, right premolars, left premolars, and anterior teeth (canine to canine) (Figure 1). Cumulative dose-volume histograms were produced for each mandibular region in each patient and the average of the mean and the maximum point doses for each defined region were calculated. Regions were evaluated based on ipsi- or contralaterality to the primary tumor site. RESULTS The average mean and maximum point doses for the molars, premolars, and anterior teeth, both ipsilateral and contralateral to tumor sites for all 3 groups, are depicted in Table I. In general, compared with the molar regions, lower doses were seen for premolars and anterior teeth with smaller (T1-2) tumors (Figure 2). With larger (T3-4) disease, anterior teeth received an average of more than 6000 cGy (maximum point dose). Larger T3-4 tumors, regardless of laterality, resulted in
DISCUSSION This is the first article describing detailed dosimetry involving different tooth-bearing regions of the mandible in patients receiving IMRT for BOT cancer. Traditionally, with the use of conventional 2-dimensional radiotherapy in the treatment of oropharyngeal cancer, the areas of the mandible known to be at highest risk for ORN were the bilateral posterior areas. Initially, a radical approach to dental prophylaxis before radiation therapy was advocated, involving multiple prophylactic tooth extractions in areas of the jaws falling within the radiation fields.7 At MSKCC, our approach to dental extractions before radiation therapy has been more conservative, with the decision to prophylactically extract teeth based on multiple factors, such as dental and periodontal conditions, the patient’s approach to dental care, and the tumor stage and overall prognosis.8 Few studies have looked at detailed mandibular dosimetry with the use of conventional radiation therapy. Jereczek-Fossa et al.9 looked at mandibular radiation doses in patients treated with conventional radiotherapy for squamous cell carcinoma of the oropharynx by analyzing specific mandibular point doses. They concluded that point doses are not representative of whole mandibular dose, but that clearly, the highest doses given were in the posterior mandible. More recently, with the use of IMRT’s complex 3-dimensional dose delivery and target selection, it has been possible to spare healthy tissues.10,11 This has led to the assumption that only bone directly adjacent to tumor would be at highest risk of ORN; however, with a more complex dose delivery and tissue sparing favoring the major salivary glands, different dose gradients across the mandible are created. This makes determination of mandibular dosimetry and prediction of areas at highest risk for ORN difficult based on tumor site
ORAL AND MAXILLOFACIAL RADIOLOGY e52 Hansen et al.
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Table I. Average mean and maximum doses for each contoured region in the 3 patient groups T1-2/N2-3
Ipsi M Ipsi P Contra M Contra P Anterior
T3-4/N2-3
T1-4/N0
Average max, cGy
Average mean, cGy
Average max, cGy
Average mean, cGy
Average max, cGy
Average mean, cGy
6558 5087 6123 4356 3767
4759 3261 4936 2738 2375
7233 6903 7353 6635 6311
6013 5329 5595 5110 4733
7086 6233 6694 5851 5254
5806 4024 4938 3545 2606
Ipsi, ipsilateral; Contra, contralateral; M, molar; P, premolar.
Fig. 2. Mean doses to each mandibular region based on tumor laterality for patients in the T1-2/N2-3 group. Two patients with midline tumors were not included (Ipsi, ipsilateral; Contra, contralateral; M, molar; P, premolar; A, anterior; mn, mean).
Fig. 3. Mean doses to each mandibular region based on tumor laterality for patients in the T3-4/N2-3 group. Two patients with midline tumors were not included (Ipsi, ipsilateral; Contra, contralateral; M, molar; P, premolar; A, anterior; mn, mean).
alone. Few studies have detailed the dosimetry delivered to the mandible with IMRT and none to our knowledge have contoured and examined different tooth-bearing areas of the mandibular bone. Parliament et al.12 examined whole mandibular IMRT doses in 23
patients and concluded that IMRT can have a dosesparing advantage compared with conventional radiotherapy if the mandible is contoured as an avoidance structure. Studer et al.13 examined dosimetry to whole mandibular bone in 73 patients and concluded that the
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ORIGINAL ARTICLE Hansen et al. e53
Fig. 4. Mean doses to each mandibular region based on tumor laterality for patients in the T1-4/N0 group. Two patients with midline tumors were not included (Ipsi, ipsilateral; Contra, contralateral; M, molar; P, premolar; A, anterior; mn, mean).
Fig. 5. Average volume % receiving ⬎ 5500 cGy by region for different tumor sizes (T1 through T4) (Ipsi, ipsilateral; Contra, contralateral; M, molar; P, premolar; Ant, anterior; mn, mean).
volume percentage receiving high doses was small compared with the full mandibular volume. Verdonck et al.14 examined 10 patients treated for oropharyngeal cancer with IMRT. They concluded that with maximized dose constraints in the anterior mandible it is possible to minimize anterior mandibular doses without reducing the planned target dose. None of these studies has given details regarding the radiation dose delivered to different regions of the mandible, however. The incidence of ORN in the era of IMRT has been described by Ben-David et al.15 They evaluated 176 patients who received parotid-sparing IMRT and had undergone a full dental evaluation before treatment; 17% of patients had dental extractions before radiother-
apy and 7% had postradiotherapy dental extractions. With a median follow-up of 34 months they saw no cases of ORN. Recently, Gomez et al.16 reported 2 cases of ORN from a group of 168 patients treated in our institution with IMRT for cancer of the oral cavity, oropharynx, nasopharynx, sinus, and hypopharynx. These patients were followed for a median of 37.4 months. The 2 reported cases of ORN were in patients who had surgery for floor-of-mouth cancers. We contoured the mandibles of 28 patients with different stages of BOT cancer treated with IMRT to determine whether tooth-bearing bone ipsi- and contralateral to tumor was radiated in a predictable fashion and whether tumor size and local metastasis were pre-
ORAL AND MAXILLOFACIAL RADIOLOGY e54 Hansen et al.
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dictors for amount and distribution of dose. Our results indicate that tumor size is an important predictor of mandibular dose with large (T3-4) tumors showing similarly high mean doses across the entire mandible. Treatment of smaller tumors appears to result in lower doses to the anterior regions compared with the premolar and molar regions and lower contralateral compared with ipsilateral doses. In all the patients in the study, maximum point doses represented a small volume percentage (1%) of the total mandibular volumes calculated. For this reason, determination of maximum point dosage is less important with regard to predicting ORN risk than calculation of volumes receiving doses above the threshold known to be associated with a high risk of ORN (5500 cGy). In our small group of patients, no significant difference in mandibular dose was seen between patients with cervical nodal metastasis or without, indicating that nodal involvement is a less accurate predictor of mandibular dose compared with tumor size. With our findings in mind, dental evaluation and treatment planning before radiation therapy must take several factors into consideration, including tumor laterality, tumor size, and presence or absence of local metastasis. These considerations are in addition to dental factors routinely addressed, which include the patient’s approach to dental care and maintenance, along with current dental and periodontal status. With large T3-4 BOT disease, the entire mandible should be considered to be potentially in the field of radiation, and all mandibular teeth, irrespective of the laterality of the tumor, should be evaluated regarding their long-term prognosis. This is in contrast to the era of conventional 2-dimensional radiotherapy when the anterior mandible was thought to be spared from high doses of radiation and was, therefore, not at risk for ORN. Good communication with the treating radiation oncologist is essential to determine the extent of dental intervention necessary before radiation therapy. In the era of IMRT, further dosimetric analyses correlating with clinical outcomes are needed to determine whether the maximum point dose or the mean dose is a better predictor of the risk of developing ORN. This project is under way.
2. Lee N, Puri DR, Blanco AI, Chao KS. Intensity-modulated radiation therapy in head and neck cancers: an update. Head Neck 2007;29:387-400. 3. Eisbruch A. Radiotherapy: IMRT reduces xerostomia and potentially improves QOL. Nat Rev Clin Oncol 2009;6:567-8. 4. Marx RE. Osteoradionecrosis: a new concept of its pathophysiology. J Oral Maxillofac Surg 1983;41:283-8. 5. Marx RE, Johnson RP. Studies in the radiobiology of osteoradionecrosis and their clinical significance. Oral Surg Oral Med Oral Pathol 1987;64:379-90. 6. Sciubba JJ, Goldenberg D. Oral complications of radiotherapy. Lancet Oncol 2006;7:175-83. 7. Wahl MJ. Osteoradionecrosis prevention myths. Int J Radiat Oncol Biol Phys 2006;64:661-9. 8. Sulaiman F, Huryn JM, Zlotolow IM. Dental extractions in the irradiated head and neck patient: a retrospective analysis of Memorial Sloan-Kettering Cancer Center protocols, criteria, and end results. J Oral Maxillofac Surg 2003;61:1123-31. 9. Jereczek-Fossa BA, Garibaldi C, Catalano G, D’Onofrio A, De Pas T, Bocci C, et al. Analysis of mandibular dose distribution in radiotherapy for oropharyngeal cancer: dosimetric and clinical results in 18 patients. Radiother Oncol 2003;66:49-56. 10. Lee NY, Terezakis SA. Intensity-modulated radiation therapy. J Surg Oncol 2008;97:691-6. 11. Eisbruch A. Clinical aspects of IMRT for head-and-neck cancer. Med Dosim 2002;27:99-104. 12. Parliament M, Alidrisi M, Munroe M, Wolfaardt J, Scrimger R, Thompson H, et al. Implications of radiation dosimetry of the mandible in patients with carcinomas of the oral cavity and nasopharynx treated with intensity modulated radiation therapy. Int J Oral Maxillofac Surg 2005;34:114-21. 13. Studer G, Studer SP, Zwahlen RA, Huguenin P, Grätz KW, Lütolf UM, Glanzmann C. Osteoradionecrosis of the mandible: minimized risk profile following intensity-modulated radiation therapy (IMRT). Strahlenther Onkol 2006;182:283-8. 14. Verdonck HW, de Jong JM, Granzier ME, Nieman FH, de Baat C, Stoelinga PJ. Intensity-modulated radiation therapy for oropharyngeal cancer: radiation dosage constraint at the anterior mandible. Oral Oncol 2009;45:511-4. 15. 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. 16. Gomez DR, Estilo CL, Wolden SL, Zelefsky MJ, Kraus DH, Wong RJ, et al. Correlation of osteoradionecrosis and dental events with dosimetric parameters in intensity-modulated radiation therapy for head-and-neck cancer. Int J Radiat Oncol Biol Phys 2011;81:e207-13.
REFERENCES
Cherry L. Estilo, DMD Dental Service Department of Surgery Memorial Sloan-Kettering Cancer Center New York, NY 10065 [email protected]
1. Setton J, Caria N, Romanyshyn J, Koutcher L, Wolden SL, Zelefsky MJ, et al. Intensity-modulated radiotherapy in the treatment of oropharyngeal cancer: an update of the Memorial SloanKettering Cancer Center experience. Int J Radiat Oncol Biol Phys 2012;82:291-8.
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Dosimetric distribution to the tooth-bearing regions of the mandible following intensity-modulated radiation therapy for base of tongue cancer Heidi J. Hansen, DMD,a Beatrice Maritim, DMD,b George C. Bohle III, DDS,c Nancy Y. Lee, MD,d Joseph M. Huryn, DDS,e and Cherry L. Estilo, DMD,f New York, New York MEMORIAL SLOAN-KETTERING CANCER CENTER AND WEILL CORNELL MEDICAL COLLEGE/NEW YORK PRESBYTERIAN HOSPITAL
Objectives. Osteoradionecrosis is a significant complication following head and neck radiotherapy. The purpose of this study was to determine the intensity-modulated radiation therapy (IMRT) dosages delivered to the tooth-bearing regions of the mandible. Study Design. A total of 28 patients with base of tongue cancer with the following stages: T1-2/N2-3 (n ⫽ 10), T3-4/N2-3 (n ⫽ 10), and T1-4/N0 (n ⫽ 8), treated with IMRT, were included. Average mean and maximum doses were calculated for the anterior, premolar, and molar regions. Results. Lower doses were seen in anterior bone with smaller tumors. Large tumors, regardless of laterality, resulted in high doses to the entire mandible, with anterior bone receiving more than 6000 cGy. Conclusions. Tumor size is important in preradiation dental treatment planning. This information is important in planning preand postradiation dental extractions. Dosimetric analyses correlating mean and maximum point dose with clinical presentation and outcomes are needed to determine the best predictor of osteoradionecrosis risk. (Oral Surg Oral Med Oral Pathol Oral Radiol 2012;114:e50-e54)
Base of tongue (BOT) malignancies are frequently asymptomatic until reaching a large size (larger than 4 cm), and treatment therefore typically consists of primary radiotherapy with concurrent chemotherapy.1 Intensity-modulated radiation therapy (IMRT) is an effective modality in the treatment of head and neck cancer. IMRT generates dose distributions that sharply conform to tumor targets while minimizing dosages delivered to normal tissues. In the head and neck, sparing of normal structures, such as the parotid glands, This study was presented at the Multinational Association for Supportive Care in Cancer annual meeting in Athens, Greece, on June 24, 2011. a Fellow, Dental Service, Department of Surgery, Memorial SloanKettering Cancer Center, and Assistant Professor, Division of Oral & Maxillofacial Surgery & Dentistry, Department of Surgery, Weill Cornell Medical College/New York Presbyterian Hospital. b Fellow, Dental Service, Department of Surgery, Memorial SloanKettering Cancer Center. c Assistant, Attending, Dental Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center. d Associate Attending, Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center. e Chief, Dental Service, Department of Surgery, Memorial SloanKettering Cancer Center. f Associate Attending, Dental Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center. Received for publication Nov 9, 2011; returned for revision Jan 26, 2012; accepted for publication Jan 30, 2012. © 2012 Elsevier Inc. All rights reserved. 2212-4403/$ - see front matter doi:10.1016/j.oooo.2012.01.024
e50
has been shown to reduce the long-term hyposalivation caused by radiation-induced damage to salivary tissue.2,3 Osteoradionecrosis (ORN) is a significant and welldescribed complication following head and neck radiotherapy4-6; however, little is known about the rate of ORN in the IMRT era. ORN occurs more commonly in the mandible. This is thought to be because of its less abundant blood supply compared with that of the maxilla and also because it is often necessary to deliver high doses of radiation to tumors near the mandible. Typically, the risk of ORN is associated with mean doses of 5000 to 6000 cGy or higher (50-60 Gy).7 Because of IMRT’s complex multibeam delivery, clinicians planning postradiation dental extractions are often faced with difficulty determining the exact dose delivered to the bone surrounding the teeth. Although the mandible is routinely contoured as an avoidance structure because of its high risk of ORN, the exact amount of radiation delivered to the bone supporting the molars, premolars, and the anterior teeth has not been described. This is of particular importance, as this detailed information will help clinicians in planning for both pre- and postradiation dental extractions. The purpose of this study was to determine the amount of radiation delivered to these specific mandibular regions from 28 consecutive patients with BOT cancer treated with IMRT ⫾ chemotherapy at Memorial Sloan-Kettering Cancer Center (MSKCC).
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ORIGINAL ARTICLE Hansen et al. e51
high doses delivered to the entire mandible (Figure 3). Figure 4 depicts mandibular doses in patients with node-negative disease. Doses in patients without local metastasis appear to follow patterns similar to the other 2 groups of node-positive patients. Maximum point doses amounted to less than 1% of the total contoured mandibular volume (tooth-bearing bone) as calculated on dose volume curves generated by the MSKCC radiation treatment planning software. Mandibular volumes receiving more than 5500 cGy for different T-size tumors are depicted in Figure 5. The average volume percentage receiving more than 5500 cGy was calculated for each region (ipsi- and contralateral molars, premolars, and anterior teeth). It is evident that the mandibular volume percentages receiving more than 5500 cGy increase with increasing tumor size. Fig. 1. Example of the 5 contoured regions as drawn for each CT slice of the mandible.
MATERIAL AND METHODS After approval was obtained by the MSKCC institutional review board, 28 consecutive patients with BOT cancer were divided into 3 groups based on tumor size and nodal status: T1-2/N2-3 (n ⫽ 10), T3-4/N2-3 (n ⫽ 10), and T1-4/N0 (n ⫽ 8). All patients were seen before radiation therapy for a comprehensive dental evaluation and necessary treatment, including extractions, restorations, endodontic treatment, periodontal treatment, and, when necessary, radiation mouth guards. Patients were treated with platinum-based chemotherapy and IMRT to 7000 cGy. For each patient, using MSKCC radiation treatment planning software, the mandible in its entire height, from the alveolar crest to the inferior cortex, was manually contoured for the bone surrounding the right molars, left molars, right premolars, left premolars, and anterior teeth (canine to canine) (Figure 1). Cumulative dose-volume histograms were produced for each mandibular region in each patient and the average of the mean and the maximum point doses for each defined region were calculated. Regions were evaluated based on ipsi- or contralaterality to the primary tumor site. RESULTS The average mean and maximum point doses for the molars, premolars, and anterior teeth, both ipsilateral and contralateral to tumor sites for all 3 groups, are depicted in Table I. In general, compared with the molar regions, lower doses were seen for premolars and anterior teeth with smaller (T1-2) tumors (Figure 2). With larger (T3-4) disease, anterior teeth received an average of more than 6000 cGy (maximum point dose). Larger T3-4 tumors, regardless of laterality, resulted in
DISCUSSION This is the first article describing detailed dosimetry involving different tooth-bearing regions of the mandible in patients receiving IMRT for BOT cancer. Traditionally, with the use of conventional 2-dimensional radiotherapy in the treatment of oropharyngeal cancer, the areas of the mandible known to be at highest risk for ORN were the bilateral posterior areas. Initially, a radical approach to dental prophylaxis before radiation therapy was advocated, involving multiple prophylactic tooth extractions in areas of the jaws falling within the radiation fields.7 At MSKCC, our approach to dental extractions before radiation therapy has been more conservative, with the decision to prophylactically extract teeth based on multiple factors, such as dental and periodontal conditions, the patient’s approach to dental care, and the tumor stage and overall prognosis.8 Few studies have looked at detailed mandibular dosimetry with the use of conventional radiation therapy. Jereczek-Fossa et al.9 looked at mandibular radiation doses in patients treated with conventional radiotherapy for squamous cell carcinoma of the oropharynx by analyzing specific mandibular point doses. They concluded that point doses are not representative of whole mandibular dose, but that clearly, the highest doses given were in the posterior mandible. More recently, with the use of IMRT’s complex 3-dimensional dose delivery and target selection, it has been possible to spare healthy tissues.10,11 This has led to the assumption that only bone directly adjacent to tumor would be at highest risk of ORN; however, with a more complex dose delivery and tissue sparing favoring the major salivary glands, different dose gradients across the mandible are created. This makes determination of mandibular dosimetry and prediction of areas at highest risk for ORN difficult based on tumor site
ORAL AND MAXILLOFACIAL RADIOLOGY e52 Hansen et al.
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Table I. Average mean and maximum doses for each contoured region in the 3 patient groups T1-2/N2-3
Ipsi M Ipsi P Contra M Contra P Anterior
T3-4/N2-3
T1-4/N0
Average max, cGy
Average mean, cGy
Average max, cGy
Average mean, cGy
Average max, cGy
Average mean, cGy
6558 5087 6123 4356 3767
4759 3261 4936 2738 2375
7233 6903 7353 6635 6311
6013 5329 5595 5110 4733
7086 6233 6694 5851 5254
5806 4024 4938 3545 2606
Ipsi, ipsilateral; Contra, contralateral; M, molar; P, premolar.
Fig. 2. Mean doses to each mandibular region based on tumor laterality for patients in the T1-2/N2-3 group. Two patients with midline tumors were not included (Ipsi, ipsilateral; Contra, contralateral; M, molar; P, premolar; A, anterior; mn, mean).
Fig. 3. Mean doses to each mandibular region based on tumor laterality for patients in the T3-4/N2-3 group. Two patients with midline tumors were not included (Ipsi, ipsilateral; Contra, contralateral; M, molar; P, premolar; A, anterior; mn, mean).
alone. Few studies have detailed the dosimetry delivered to the mandible with IMRT and none to our knowledge have contoured and examined different tooth-bearing areas of the mandibular bone. Parliament et al.12 examined whole mandibular IMRT doses in 23
patients and concluded that IMRT can have a dosesparing advantage compared with conventional radiotherapy if the mandible is contoured as an avoidance structure. Studer et al.13 examined dosimetry to whole mandibular bone in 73 patients and concluded that the
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ORIGINAL ARTICLE Hansen et al. e53
Fig. 4. Mean doses to each mandibular region based on tumor laterality for patients in the T1-4/N0 group. Two patients with midline tumors were not included (Ipsi, ipsilateral; Contra, contralateral; M, molar; P, premolar; A, anterior; mn, mean).
Fig. 5. Average volume % receiving ⬎ 5500 cGy by region for different tumor sizes (T1 through T4) (Ipsi, ipsilateral; Contra, contralateral; M, molar; P, premolar; Ant, anterior; mn, mean).
volume percentage receiving high doses was small compared with the full mandibular volume. Verdonck et al.14 examined 10 patients treated for oropharyngeal cancer with IMRT. They concluded that with maximized dose constraints in the anterior mandible it is possible to minimize anterior mandibular doses without reducing the planned target dose. None of these studies has given details regarding the radiation dose delivered to different regions of the mandible, however. The incidence of ORN in the era of IMRT has been described by Ben-David et al.15 They evaluated 176 patients who received parotid-sparing IMRT and had undergone a full dental evaluation before treatment; 17% of patients had dental extractions before radiother-
apy and 7% had postradiotherapy dental extractions. With a median follow-up of 34 months they saw no cases of ORN. Recently, Gomez et al.16 reported 2 cases of ORN from a group of 168 patients treated in our institution with IMRT for cancer of the oral cavity, oropharynx, nasopharynx, sinus, and hypopharynx. These patients were followed for a median of 37.4 months. The 2 reported cases of ORN were in patients who had surgery for floor-of-mouth cancers. We contoured the mandibles of 28 patients with different stages of BOT cancer treated with IMRT to determine whether tooth-bearing bone ipsi- and contralateral to tumor was radiated in a predictable fashion and whether tumor size and local metastasis were pre-
ORAL AND MAXILLOFACIAL RADIOLOGY e54 Hansen et al.
OOOO August 2012
dictors for amount and distribution of dose. Our results indicate that tumor size is an important predictor of mandibular dose with large (T3-4) tumors showing similarly high mean doses across the entire mandible. Treatment of smaller tumors appears to result in lower doses to the anterior regions compared with the premolar and molar regions and lower contralateral compared with ipsilateral doses. In all the patients in the study, maximum point doses represented a small volume percentage (1%) of the total mandibular volumes calculated. For this reason, determination of maximum point dosage is less important with regard to predicting ORN risk than calculation of volumes receiving doses above the threshold known to be associated with a high risk of ORN (5500 cGy). In our small group of patients, no significant difference in mandibular dose was seen between patients with cervical nodal metastasis or without, indicating that nodal involvement is a less accurate predictor of mandibular dose compared with tumor size. With our findings in mind, dental evaluation and treatment planning before radiation therapy must take several factors into consideration, including tumor laterality, tumor size, and presence or absence of local metastasis. These considerations are in addition to dental factors routinely addressed, which include the patient’s approach to dental care and maintenance, along with current dental and periodontal status. With large T3-4 BOT disease, the entire mandible should be considered to be potentially in the field of radiation, and all mandibular teeth, irrespective of the laterality of the tumor, should be evaluated regarding their long-term prognosis. This is in contrast to the era of conventional 2-dimensional radiotherapy when the anterior mandible was thought to be spared from high doses of radiation and was, therefore, not at risk for ORN. Good communication with the treating radiation oncologist is essential to determine the extent of dental intervention necessary before radiation therapy. In the era of IMRT, further dosimetric analyses correlating with clinical outcomes are needed to determine whether the maximum point dose or the mean dose is a better predictor of the risk of developing ORN. This project is under way.
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REFERENCES
Cherry L. Estilo, DMD Dental Service Department of Surgery Memorial Sloan-Kettering Cancer Center New York, NY 10065 [email protected]
1. Setton J, Caria N, Romanyshyn J, Koutcher L, Wolden SL, Zelefsky MJ, et al. Intensity-modulated radiotherapy in the treatment of oropharyngeal cancer: an update of the Memorial SloanKettering Cancer Center experience. Int J Radiat Oncol Biol Phys 2012;82:291-8.
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