Improved outcomes in buccal squamous cell carcinoma

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1 ORIGINAL ARTICLE Improved outcomes in buccal squamous cell carcinoma Chun Shu Lin, MD, 1 * Yee Min Jen, MD, PhD, 1 Woei Yau Kao, MD, PhD, 2 Ching Liang Ho, MD, 2 Ming Shen Dai, MD, PhD, 2 Chia Lin Shih, DDS, 3 Jen Chan Cheng, DDS, 3 Ping Ying Chang, MD, 2 Wen Yen Huang, MD, 1 Yu Fu Su, MD 1 1 Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, 2 Department of Medical Oncology and Hematology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, 3 Department of Dentistry and Oral Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. Accepted 3 November 2011 Published online 20 January 2012 in Wiley Online Library (wileyonlinelibrary.com). DOI /hed ABSTRACT: Background. The treatment results of buccal squamous cell carcinoma before and after 2002 were compared. Methods. Two hundred forty-five patients with buccal cancer who underwent curative treatment were retrospectively reviewed. Results. The 5-year overall survival rate was 30.0% before 2002 and 53.5% after 2002 (p ¼.004). On multivariate analysis, T classification, surgical margins, and treatment modality significantly affected overall survival, and N classification and histologic grade had trends to affect it. Invasion depth had a trend to influence locoregional control. For patients with earlystage disease without adverse factors, the locoregional control was similar between surgery alone group and surgery þ radiotherapy group. Conclusion. The survival of patients with buccal cancer was improved after 2002, which represented the start of intensity-modulated radiotherapy (IMRT) in our institute. Ipsilateral neck alone irradiation was recommended for T1-2N0-1 and small T3N0 disease, and bilateral neck irradiation could be reserved for advanced disease. VC 2012 Wiley Periodicals, Inc. Head Neck 35: 65 71, 2013 KEY WORDS: buccal cancer, buccal squamous cell carcinoma, radiotherapy, intensity modulated radiotherapy, oral cancer Squamous cell carcinoma of the buccal mucosa is an aggressive cancer requiring multimodality treatment. 1,2 Wide excision of the tumor with ipsilateral neck dissection is the primary treatment modality. 3 5 Because of the high locoregional recurrence rate, postoperative radiotherapy (RT) has been recommended. 1,6 Conventional RT had been used for decades. However, conventional RT was associated with the risk of severe complication such as osteoradionecrosis. Irradiation of the ipsilateral neck alone was done for selected patients to spare the contralateral parotid gland. However, whether risk of recurrence at the unirradiated contralateral neck is increased remains to be studied. CT-based RT, including 3-dimensional conformal radiotherapy (3D conformal RT) and intensity-modulated radiotherapy (IMRT), results in better dosimetry than conventional RT through accurate contouring, multiple beams, and modified dose density. 7 However, the locoregional control rate in the era of CT-based RT for buccal cancer has not been reported. In the present study, we report our experience with CT-based RT for buccal cancer and compare results with patients treated with conventional RT. Failure pattern and safety of ipsilateral neck irradiation were also analyzed. In a previous article, we recommended routine use of postoperative RT for even those with early-stage (stage I II) disease without risk *Corresponding author: C. Lin, Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. chunshulin@gmail.com factors. 1 This study also examine whether routine postoperative RT improves locoregional control of patients with early-stage carcinoma. MATERIALS AND METHODS Patients The database of patients who were diagnosed with malignant tumors of the buccal mucosa between 1983 and 2009 at our hospital was retrospectively reviewed. This analysis included only patients with squamous cell carcinoma who underwent planned definitive treatment. Patients with other histologic diagnosis were excluded, including verrucous carcinoma, acinic cell carcinoma, adenoid cystic carcinoma, adenocarcinoma, epimyoepithelial carcinoma, sarcoma, melanoma, and mucoepidermoid carcinoma. Patients with distant metastasis at presentation, synchronous cancers of the oral cavity, history of cancers, or definitive treatment outside our institute were all excluded. Two patients who underwent chemotherapy alone were excluded. This report focuses on the remaining 245 patients with M0 squamous cell carcinoma of the buccal mucosa and underwent treatment with a curative intent at our hospital. Institutional review board of Tri- Service General Hospital approved this study. There were 232 men and 13 women ranging in age from 22 to 94 years (median, 51 years). If the patient underwent surgery, pathologic stage was used; otherwise, clinical stage was applied. Disease in all patients was restaged using the staging criteria of the 2010 version of HEAD & NECK DOI /HED JANUARY

2 LIN ET AL. TABLE 1. Stage distribution of 245 patients with M0 squamous cell carcinoma of the buccal mucosa treated with a curative intent taken from the American Joint Committee on Cancer, N0 N1 N2 N3 Stage I (18%) T1 45 (18.4%) 6 (2.4%) 2 (0.8%) 0 (0%) Stage II (25%) T2 61 (24.9%) 5 (2.0%) 10 (4.1%) 0 (0%) Stage III (14%) T3 14 (5.7%) 9 (3.7%) 13 (5.3%) 1 (0.4%) Stage IV (43%) T4 31 (12.7%) 13 (5.3%) 32 (13.1%) 3 (1.2%) American Joint Committee on Cancer. 8 There were 45 patients (18%) with stage I disease, 61 (25%) with stage II, 34 (14%) with stage III, and 105 (43%) with stage IV (Table 1). Treatment modality included surgery alone (71 patients; 29%), surgery þ RT (81 patients; 33%), surgery þ adjuvant concurrent chemoradiotherapy (40 patients; 16%), definitive concurrent chemoradiotherapy (23 patients; 10%), and RT alone (30 patients; 12%). At the last follow-up, 137 patients (56%) were dead, 96 (39%) were alive, and 12 (5%) were lost to follow-up. The median follow-up time for all the patients alive was 40.1 months (range, months). Surgery The surgical procedure mainly included wide excision of the tumor with ipsilateral suprahyoid or supraomohyoid neck dissection for clinical N0 1 neck, ipsilateral radical or modified radical neck dissection for N2a 2b or N3 neck, and bilateral modified radical neck dissection for N2c disease. Block or marginal resection of the mandible or maxilla and resection of the parotid gland or submandibular gland were performed depending on tumor extension. Most cases required a flap reconstruction due to large defects after the surgery. A surgical margin of 5 mm was defined as a close margin. Among the 192 patients who underwent surgery, 61 patients had at least 1 positive node. Of the 61 patients, the condition of extranodal spreading was not described in the pathologic report of 18 patients. Most of these 18 patients were treated before Of the other 43 patients, 9 patients had extranodal spreading. Radiotherapy RT method included conventional RT (91 patients) and CT-based RT (83 patients). Radiation field of conventional RT included bilateral opposed parallel portals or ipsilateral anteroposterior opposed portals with or without wedge for the primary tumor or tumor bed and ipsilateral upper neck. 1 A single anteroposterior portal was used for the ipsilateral lower neck or bilateral neck in more advanced disease. Radiation dose was prescribed to the isocenter for conventional RT. Radiation field of CTbased RT, including 5 with 3D conformal RT before 2002 and 78 with IMRT after 2002, was contoured in the CT planning system. When the lower neck was treated with CT-based RT, a single anteroposterior portal was used for the first 7 patients. The lower neck was then contoured as part of IMRT planning thereafter. Radiation dose was prescribed to 90% isodose line for CT-based RT. The median dose was 60.0 gray (Gy; range, Gy) for patients with postoperative RT and 69.6 Gy (range, Gy) for definitive RT or concurrent chemoradiotherapy. The median dose to the lower neck was 49.3 Gy (range, Gy). The median interval between surgery and the start of RT was 44 days (range, days). The median RT period was 57 days (range, days). One hundred twelve patients underwent postoperative RT to the bilateral neck, including 45 with N0, 21 with N1, 44 with N2, and 2 with N3 disease. Sixty-two patients underwent postoperative RT to the ipsilateral neck only, including 45 with N0, 6 with N1, 9 with N2a b, and 2 with N3 disease. Regarding patients with early-stage carcinoma, 57 underwent surgery alone, 42 had surgery þ RT, and the remaining 7 patients underwent RT alone. Postoperative RT was used when adverse histologic factors were noted. The adverse histologic factors included T3 4 disease, positive or close surgical margins, muscle and bone invasion, skin invasion, extranodal spreading, lymphovascular space invasion, and high-grade tumors. Buccal cancer itself was considered a poor prognostic factor and postoperative RT was optimal for patients in the early-stage without other risk factors. For patients in the early-stage without other risk factors, 48 patients underwent surgery alone and 30 patients underwent surgery þ RT. Chemotherapy Chemotherapy that consisted of cisplatin 80 to 100 mg/ m 2 /day on days 1, 22, and 43 during the course of RT has been the standard regimen After the year 2007, weekly chemotherapy with cisplatin 30 to 40 mg/m 2 during the course of RT was another treatment option in our hospital. For high-risk patients, adjuvant chemotherapy was given monthly for 3 cycles afterward. 12 Cisplatin 80 mg/m 2 /day was administered on day 1 and fluorouracil 1000 mg/m 2 on days 1 to 4 as a 96-hour continuous infusion for every cycle of adjuvant chemotherapy. Regarding the 139 patients with stage III to IV carcinoma, 14 patients had surgery alone, 24 had RT alone, 46 had surgery þ postoperative RT, 33 had surgery þ postoperative concurrent chemoradiotherapy, and 22 had concurrent chemoradiotherapy alone. Statistical analysis All statistical analysis was performed using SPSS 16.0 software. The survival and follow-up times were calculated from the date of pathologic diagnosis to death or last follow-up. Survival and locoregional control curves were computed using the Kaplan Meier method and 66 HEAD & NECK DOI /HED JANUARY 2013

3 BUCCAL SQUAMOUS CELL CARCINOMA FIGURE 1. Overall survival curves for all patients. The 5-year survival rate was 60.4% for patients with stage I, 67.2% for stage II, 42.7% for stage III, and 23.7% stage IV disease (p <.001). prognostic factors were evaluated using the log rank test. The significance of various factors was further analyzed using the Cox regression model. An a error of 0.05 was chosen for statistical significance. RESULTS Survival and locoregional control The 5-year overall survival rate for all patients was 44.1%, and 60.4%, 67.2%, 42.7%, and 23.7% for patients with stage I, II, III, and IV, respectively (p <.001; Figure 1). The 5-year disease-free survival rate for all patients was 38.1%, and 59.3%, 45.9%, 42.3%, and 22.4% for patients with stage I, II, III, and IV, respectively (p <.001). Most patients died of locoregional recurrences. The 5-year locoregional control rate for all patients was 40.4%, and 59.3%, 47.9%, 44.2%, and 26.1% patients with stage I, II, III, and IV, respectively (p <.001; Figure 2). The 5-year probability of distant metastasis for all patients was 13.3%, and 7.3%, 5.6%, 16.3%, and 21.5% for patients with stage I, II, III, and IV, respectively (p ¼.009). The following factors were analyzed for locoregional control and survival: sex, age, TNM stage and classifications, histologic grade, surgical margins, invasion depth, skin invasion, lymphovascular space invasion, extranodal spreading, treatment modality, RT period, RT method, and the interval between surgery and the start of RT. The significant factors in the univariate analysis were further analyzed with multivariate analysis. Univariate analysis indicated that advanced TNM staging group (p <.001), advanced T classification (p <.001), advanced N classification (p <.001), positive surgical margins (p <.001), deep invasion depth (p <.001), skin invasion (p <.001), lymphovascular space invasion (p <.001), extranodal spreading (p <.001), treatment modality (p <.001; Figure 3), prolonged RT period (p <.001), and conventional RT method (p ¼.004; Figure 4) were all significantly associated with poor overall survival and locoregional control (Table 2). Figure 4 showed that CT-based RT patients had significantly better 5-year overall survival (53.5% vs 30.0%; p ¼.004) and locoregional control (40.5% vs 30.0%; p ¼.019) than conventional RT patients. Histologic grade significantly affected overall survival (p ¼.017) but not locoregional control. Fifty-three patients (22%) did not undergo curative surgery, only definitive RT with/without chemotherapy was used. For patients who had radical surgery, 12 patients had positive margins, 37 had close margins, and 143 had free margins. The 5-year locoregional control was 16.4% for patients who did not undergo surgery, 11.1% for patients with positive margins, 65.2% for patients with close margins, and 46.4% for patients with free margins (p <.001). On multivariate analysis, T classification (p <.001), surgical margins (p ¼.022), and treatment modality (p ¼.039) significantly affected overall survival (Table 3). There was a trend toward worse overall survival for advanced N classification (p ¼.052) and poor histologic grade (p ¼.060). Only invasion depth (p ¼.051) had a trend to affect locoregional control. Regarding patients with early-stage carcinoma, the 5- year locoregional control rate was 56.6% for the surgery alone group compared to 51.0% for the surgery þ RT group (p ¼.568). For patients with early-stage carcinoma without adverse histologic factors, the locoregional control was 54.4% for the surgery alone group and 44.0% for the surgery þ RT group (p ¼.931). Regarding patients with locally advanced-stage carcinoma, postoperative concurrent chemoradiotherapy was compared to postoperative RT. The use of chemotherapy is not associated with better locoregional control and survival. Failure pattern One hundred thirty patients had locoregional failure, including 29 residual tumors, 63 local recurrences only, 13 ipsilateral neck recurrences only, 10 local plus ipsilateral neck recurrences, 3 contralateral neck recurrences, 1 FIGURE 2. Locoregional control curves for all patients. The 5- year locoregional control rate was 59.3% for patients with stage I, 47.9% for stage II, 44.2% for stage III, and 26.1% for stage IV disease (p <.001). HEAD & NECK DOI /HED JANUARY

4 LIN ET AL. DISCUSSION We update our experience using conventional RT for buccal cancer and compare results to patients treated with CT-based RT. CT-based RT patients had significantly better overall survival and locoregional control than conventional RT patients in univariate analysis, but not in multivariate analysis. We believe that CT-based RT may improve treatment outcome, but the effect was influenced by combined modality treatment in the era of CT-based RT. The improvement may be the results of better delineation of treatment target. Rusthoven et al 13 evaluated 6759 patients with stage III to IVb head and neck cancer treated with RT as the primary local treatment modality. Patients treated after 1998 had a 7.6% and 6.1% absolute improvement in overall and cause-specific survival, respectively, compared with patients treated before This benefit in survival was limited to tumors of the oral cavity, oropharynx, and hypopharynx. We conclude that the treatment outcome of patients with stage III to IVb head and neck squamous cell carcinoma treated with primary RT has improved with time due to improved treatment strategy. Studer et al 14 analyzed 28, 20, and 30 patients with oral cavity cancer who underwent postoperative IMRT, postoperative 3-D conformal RT, and surgery FIGURE 3. Locoregional control and survival curves for patients who underwent different treatment modalities. S, surgery; RT, radiotherapy; chemo, chemotherapy. (A) The 5-year overall survival rate was 59.7% for the S þ RT group, 55.9% for the S group, 35.0% for the S þ RT þ chemo group, 19.9% for the RT þ chemo group, and 3.5% for the RT group (p <.001). (B) The 5- year locoregional control rate was 47.4% for the S þ RT group, 50.4% for the S group, 38.5% for the S þ RT þ chemo group, 21.3% for the RT þ chemo group, and 14.4% for the RT group (p <.001). supraclavicular nodal recurrence, and 11 second primary cancers within the oral cavity. Of the 112 patients who had bilateral neck RT, no patient had contralateral neck recurrence. Of the 62 patients receiving ipsilateral neck only RT, only 1 patient (1.6%) who had N3 disease had contralateral neck recurrence. Seventy-one patients underwent surgery alone, including 61 with N0, 6 with N1, and 4 with N2a disease, and 2 patients (2.8%) had contralateral neck recurrence. These 2 patients were diagnosed with T1N0 and T4N2a buccal cancers, respectively. FIGURE 4. Survival and locoregional control curves for patients who had radiotherapy as part of their treatment modality. (A) The 5-year overall survival rate was 53.5% for 3-dimensional conformal radiotherapy (3-D conformal RT) and intensity modulated radiation therapy (IMRT), and 30.0% for conventional RT patients (p ¼.004). (B) The 5-year locoregional control rate was 40.5% for 3-D conformal RT and IMRT, and 30.0% for conventional RT patients (p ¼.019). 68 HEAD & NECK DOI /HED JANUARY 2013

5 BUCCAL SQUAMOUS CELL CARCINOMA TABLE 2. Patient characteristics and significant prognostic factors identified by univariate analysis. Factor (no. of patients, %) 5-y locoregional control rate 5-y overall survival rate Staging groups I (45, 18) 59.3% 60.4% II (61, 25) 47.9% 67.2% III (34, 14) 44.2% 42.7% IV (105, 43) 26.1% p < % p <.001 T classification T1 (53, 22) 62.0% 61.5% T2 (76, 31) 50.9% 68.1% T3 (37, 15) 21.1% 24.4% T4 (79, 32) 23.8% p < % p <.001 N classification N0 (151, 62) 47.6% 56.0% N1 (33, 13) 41.0% 27.7% N2 (57, 23) 20.5% 22.2% N3 (4, 2) 25.0% p < % p <.001 Surgical margins Free (143, 58) 46.4% 57.7% Close (37, 15) 65.2% 56.1% Positive (12, 5) 11.1% 8.3% No surgery (53, 22) 16.4% p < % p <.001 Invasion depth Mucosa þ submucosa (68, 28) 56.7% 66.6% Muscle þ bone (177, 72) 33.7% p < % p <.001 Skin invasion No (207, 84) 44.8% 49.2% Yes (38, 16) 16.3% p < % p <.001 Lymphovascular space invasion No (146, 60) 55.7% 64.3% Yes (9, 4) 0% 0% Not available (90, 36) 16.8% p < % p <.001 Extranodal spreading in pnþ patients No (34, 56) 50.4% 52.5% Yes (9, 15) 44.4% 0% Not available (18, 29) 10.0% p ¼ % p <.001 Histologic grade Grade 1 (91, 37) 39.8% 50.1% Grade 2 (121, 49) 41.1% 44.2% Grade 3 (33, 14) 41.9% p ¼ % p ¼.017 Treatment modality S (71, 29) 50.4% 55.9% RT (30, 12) 14.4% 3.5% S þ RT (81, 33) 47.4% 59.7% Concurrent chemoradiotherapy (23, 10) 21.3% 19.9% S þ concurrent chemoradiotherapy (40, 16) 38.5% p < % p <.001 RT method Conventional RT (91, 52) 30.0% 30.0% CT-based RT (83, 48) 40.5% p ¼ % p ¼.004 RT period <6 wk (33, 19) 22.7% 25.6% 6 8 wk (53, 30) 54.2% 59.0% 8 10 wk (40, 23) 38.7% 46.2% >10 wk (48, 28) 22.6% p < % p <.001 Abbreviations: S, surgery alone; RT, radiotherapy alone; Conventional RT, conventional radiotherapy; CT-based RT, CT-based radiotherapy. alone, respectively. Patients treated with postoperative IMRT showed the highest local control rate among the 3 groups. However, there were potential biases that need to be considered in this analysis. Improving staging and better selection of patients through preoperative medical and anesthesiologic workup, better surgical technique and postoperative care, different strategy of chemotherapy, 10,11 and better supportive care during and after RT were all the possible factors that could improve treatment outcome in the era of CT-based RT. CT-based RT may be 1 of these factors, but probably not the only one. The wide use of whole body positron emission tomography preoperatively improved staging in our hospital since Goerres et al 17 noticed that whole body positron emission tomography provided relevant additional HEAD & NECK DOI /HED JANUARY

6 LIN ET AL. TABLE 3. Prognostic factors identified by multivariate Cox regression analyses. Factor p value Overall survival T classification <.001 Surgical margins.022 Treatment modality.039 N classification.052 Histologic grade.060 Locoregional control Invasion depth.051 information to a standard clinical staging procedure in patients with oral cavity cancer. Liao et al 16 also reported that combined evaluation of pathologic node status and maximal standard uptake value at the primary and regional lymph nodes may improve prognostic stratification in oral cavity cancers. Recognition of the lymphatic spreading pattern improved recent surgical technique and may improve postoperative care. Bernier et al 10 and Cooper et al 11 reported that postoperative concurrent chemoradiotherapy is more efficacious than RT alone in patients with locally advanced head and neck cancer. Incorporation of high-dose chemotherapy during RT has been widely used in our hospital since 2004 and weekly chemotherapy since However, the use of chemotherapy with postoperative RT was not associated with better outcomes in our study. There were only 33 patients in the surgery þ postoperative concurrent chemoradiotherapy group and 46 patients in the surgery þ postoperative RT group. Because of relatively few patients in this retrospective study, this issue should be further examined. In this study, there was another potential bias that needs to be mentioned. Pathologic stage was used for patients who underwent surgery, and clinical stage was applied for patients with medically inoperable or unresectable disease. More information was used for the treatment plan for patients who had surgery. This may result in better treatment outcomes for surgery, surgery þ RT, and surgery þ concurrent chemoradiotherapy groups than RT and concurrent chemoradiotherapy groups under stage-to-stage comparison. On multivariate analysis, T classification, surgical margins, and treatment modality significantly affected overall survival, and N classification and histologic grade had trends to affect it. Invasion depth had a trend to affect locoregional control. Huang et al 22 studied 172 patients with buccal cancer and he concluded that stage and histologic grade are the most important prognostic factors affecting survival rate. Jing et al 23 analyzed the prognostic factors for 45 patients with buccal cancer with negative surgical margins. T classification and tumor thickness were the predictors for cervical lymph node metastasis, and T classification and recurrence were predictive factors for survival. Diaz et al 24 reviewed 250 patients with buccal cancer and showed that muscle invasion, Stensen s duct involvement, and extranodal spreading were all associated with decreased survival. He stated that buccal cancer is a highly aggressive form of oral cavity cancer, with a tendency to recur locoregionally. Liao et al 5 studied 232 patients with squamous cell carcinoma of the buccal mucosa treated with radical surgery with or without neck dissection. Both pathologic nodal status and cell differentiation were the significant prognostic factors of diseasefree survival. It seems that histologic grade and invasion depth are as important as TNM stage and surgical margin, and should be part of decision-making for adjuvant therapy. The 5-year locoregional control rate for all patients in this study was 40.4%, which seems relatively lower than other series. 25,26 However, only 58% of patients had free margins after radical surgery in this study. For patients with free margins, the 5-year locoregional control was 46.4%. For patients who had close margins and received adequate adjuvant therapy, the 5-year locoregional control increases to 65.2% that was comparable to patients with free margins. Chiou et al 25 analyzed 110 patients with buccal mucosa carcinoma in which only 6 patients had positive surgical margins. All the 110 patients received surgery with/without adjuvant therapy. The 3-year locoregional control for the 110 patients was 73% and for close margins 71%. Lin et al 26 reviewed 145 patients with buccal cancers. All these patients underwent radical surgery with free margins. Postoperative RT was done for all patients. The 5-year locoregional control was 69%. We believe that the locoregional control rate for patients who had adequate surgery and adjuvant therapy in our institute was not lower than other series. Three of 245 patients developed contralateral neck recurrence in this study. The contralateral neck recurrence rate was 1.6% for patients who underwent postoperative ipsilateral neck alone irradiation, 0% after postoperative bilateral neck irradiation, and 2.8% after surgery alone. The contralateral neck recurrence rate is relatively low in patients with buccal cancer who had adequate locoregional treatment. After adequate surgery and neck dissection, ipsilateral neck alone irradiation could be considered for selected patients, including T1 2N0 1 and small T3N0 disease. Bilateral neck irradiation may be reserved for more advanced disease. Lin et al 26 reviewed 145 patients with buccal cancer who underwent radical surgery and postoperative RT with or without chemotherapy. One hundred twenty patients underwent unilateral neck irradiation. Locoregional control did not differ between patients undergoing unilateral or bilateral neck treatments, and the contralateral neck failure rate was 2.1%. Liao et al 27 studied 913 patients with oral cavity cancer and the 5-year contralateral neck recurrence was 7%. Gonzalez Garcia et al 28 reviewed 315 patients with oral cavity cancer treated by surgery with or without postoperative RT. Eighteen patients (5.69%) developed contralateral neck recurrence. Vergeer et al 29 included 123 patients with well-lateralized oral and oropharyngeal cancer. The postoperative RT field encompassed the ipsilateral neck and primary site. Contralateral neck metastases developed in 7 patients (6%). The number of lymph node metastases was the only significant prognostic factor with regard to contralateral neck control. Borderline significance was found for extranodal spreading. Squamous cell carcinoma of the buccal mucosa is a cancer associated with a low rate of contralateral neck recurrence, high rate of locoregional recurrence, and poor 70 HEAD & NECK DOI /HED JANUARY 2013

7 BUCCAL SQUAMOUS CELL CARCINOMA survival. 1,24,30 Even for early-stage disease, the local recurrence incidence is up to 41% in our previous report and we recommended postoperative RT. 1 In this study, the locoregional control for patients with early-stage carcinoma without adverse histologic factors is comparable between the surgery alone group and the surgery þ RT group. Sieczka et al 30 analyzed 104 patients with buccal cancer and tried to find the association between T classification and local control. After surgical resection with negative margins for T1 2 disease, the local failure rate was 40%. Strome et al 6 included 31 patients with earlystage buccal cancer disease. Eighty percent of evaluable patients had locoregional recurrence in 5 years. The locoregional control for patients with early-stage buccal cancer was poor, and adjuvant treatment should still be considered. We recommend detailed examination of the pathologic sections to find adverse factors, and those patients with risk factors should undergo postoperative RT. In conclusion, squamous cell carcinoma of the buccal mucosa is associated with a low rate of contralateral neck recurrence, high rate of locoregional recurrence, and poor survival. However, the survival was improved in the CTbased RT era. We recommend ipsilateral neck alone irradiation for T1 2N0 1 and small T3N0 disease, and bilateral neck irradiation could be reserved for advanced disease. After detailed pathologic examination, postoperative RT could be omitted for early-stage disease without adverse histologic factors. Postoperative RT could eliminate the adverse effect of close margins and improve locoregional control. Histologic grade and invasion depth are as important as TNM stage and surgical margins, and should be part of decision-making for adjuvant therapy. REFERENCES 1. Lin CS, Jen YM, Cheng MF, et al. 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