Outcome of Treatment with Total Main Tumor Resection and Supraomohyoid Neck Dissection in Oral Squamous Cell Carcinoma

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1 ORIGINAL ARTICLE Outcome of Treatment with Total Main Tumor Resection and Supraomohyoid Neck Dissection in Oral Squamous Cell Carcinoma Gwo-An Liaw, 1 Ching-Yu Yen, 2,3 Wei-Fan Chiang, 2 Chin-Hai Lee, 2 Cheng Yang, 4 Chang-Ta Chiou, 5 Shyun-Yeu Liu 2,3 * Background/Purpose: Supraomohyoid neck dissection (SOHND) is commonly used to treat oral squamous cell carcinoma (OSCC) patients with clinical N0 or selected N1 status. The purpose of this study was to evaluate the clinical outcome of OSCC patients treated with SOHND. Methods: This retrospective study reviewed the clinical outcome of 257 patients (247 men, 10 women) with N0, N1 and N2a OSCC treated with wide excision of the main tumor and SOHND between 1992 and All patients were followed up for at least 5 years. Survival distributions were analyzed using Kaplan-Meier curves. N status was compared using χ 2 and log rank tests. Results: The neck failure rate was 20% for clinically false negative cases, 6.1% for clinically true negative cases, 21.8% for clinically false positive cases, and 40% for clinically true positive cases. The 3- and 5-year overall neck disease-free survival rates were 79.8% and 77.6%, respectively. The 3- and 5-year neck diseasefree survival rates were 86.7% and 84.2% for pathologic N0 cases, 56.9% and 56.9% for pathologic N1 cases, and 27.5% and 27.5% for pathologic N2 cases, respectively. Log rank test showed that the p value for difference in survival at 3 5 years was for pathologic N0 vs. N1 cases, < for pathologic N0 vs. N2 cases, and for pathologic N1 vs. N2 cases. Conclusion: This study showed that SOHND is effective for pathologic N0 OSCC, relatively effective for pathologic N1, and less effective for pathologic N2a. These findings also support that when SOHND is used to treat N2a OSCC, postoperative radiotherapy or radical neck dissection may be needed to improve the neck disease-free survival rate. [J Formos Med Assoc 2006;105(12): ] Key Words: oral squamous cell carcinoma, supraomohyoid neck dissection The incidence of regional lymph node metastasis in oral carcinoma varies from 6% to 85%. 1 For the oral cancer patient with regional lymph node metastasis, the survival rate is decreased to 50%. 2 Since the presence of neck lymph node metastasis is the most significant prognostic factors for oral squamous cell carcinoma (OSCC), 3 and no current imaging technique can unequivocally identify the presence of cervical metastatic lymph nodes, elective neck dissection is one of the standard treatment strategies. Due to the lack of occult metastasis in the five neck levels, there is no indication for comprehensive elective neck dissection in pathologic N0 cases. 4 The concept of 2006 Elsevier & Formosan Medical Association Department of Oral and Maxillofacial Surgery, Chi-Mei Hospital, Liouying, Tainan, 2 Department of Oral and Maxillofacial Surgery, and 4 Department of Plastic and Reconstructive Surgery, Chi-Mei Medical Center, Tainan, 3 School of Dentistry, Taipei Medical University, Taipei, and 5 Department of Oral and Maxillofacial Surgery, Chang Gung Memorial Hospital at Kaohsiung and Chang Gung University College of Medicine, Taoyuan, Taiwan. Received: April 10, 2006 Revised: June 1, 2006 Accepted: July 4, 2006 *Correspondence to: Dr Shyun-Yeu Liu, Department of Oral and Maxillofacial Surgery, Chi-Mei Medical Center, 901 Junghua Road, Yungkang, Tainan 710, Taiwan. lgan5433@yahoo.com.tw J Formos Med Assoc 2006 Vol 105 No

2 G.A. Liaw, et al selective neck dissection (SND), which removes a selected group of lymph nodes with high risk occult metastasis, was introduced in the 1980s. A study of 501 patients undergoing 516 radical neck dissections by Shah in 1990 found that level I III lymph nodes had the greatest risk of nodal metastasis from primary OSCC. 5 Therefore, SOHND became the most widely used modality of SND SOHND has a neck recurrence and survival rate similar to that of modified radical neck dissection (MRND). As MRND has a higher postoperative morbidity rate, 1,8,11 SOHND is the most widely used treatment modality for OSCC patients with N0 and selected N1 status. 8,12,13 In this study, we evaluated the clinical outcome of OSCC patients treated with SOHND. surgical margin, and advanced primary tumor (T3 and T4). The neck radiation field included the lower neck and employed a radiation oncology protocol. However, the treatment procedure was decided on an individual basis and always after consultation with a radiation oncologist. Neck disease-free survival was defined as the interval between the date of the SOHND and the date of the last consultation or neck recurrence. Survival distributions were analyzed using Kaplan- Meier curves. The N status was compared using χ 2 and log rank tests. A p value less than 0.05 was considered statistically significant. Results Methods This retrospective study reviewed 328 surgically treated OSCC patients with clinical N0, N1 and selected N2a in levels I III treated at the oral and maxillofacial surgery department of Chi-Mei Medical Center in Taiwan between 1992 and The N stage was diagnosed based on physical examination and computed tomography or magnetic resonance imaging findings. Patients were excluded if they met any of the following criteria: recurrence or a second primary tumor; occurrence in association with a synchronous primary tumor outside the oral cavity; past history of head and neck cancer; previous radiation therapy to the head and neck. Patients with insufficient pathologic findings or with insufficient clinical followup data were also excluded. According to the methods of Hyam et al, 14 patients were divided into the following three age groups: younger than 40 years; years; older than 60 years. TNM status and clinical stages of oral cancer were determined according to the AJCC TNM staging system (5 th edition). The general protocol was to administer postoperative radiotherapy to patients undergoing elective neck dissection who had one or more lymph node metastases, extracapsular spread, perineural invasion, close A total of 257 OSCC patients (247 men, 10 women; mean age, 47 years; age range, years) who simultaneously received wide excision and SOHND were included. According to the methods of Hyam et al, these patients were divided into three age groups as follows: 45 (18%) patients aged younger than 40 years, 164 (63%) patients aged years, and 48 (19%) patients older than 60 years. The OSCC sites in these patients included 119 (46%) buccal mucosa, 63 (25%) tongue, 33 (13%) lower gingiva, and 42 (16%) other (Table 1). According to the AJCC TNM staging system, 64 (24.9%) cases were classified as T1, 97 (37.7%) Table 1. Distribution of sex, age and cancer site in 257 patients with oral squamous cell carcinoma Variable Category Patients, n (%) Sex Men 247 (96) Women 10 (4) Age, yr < (18) (63) > (19) Cancer site Buccal mucosa 119 (46) Tongue 63 (25) Lower gingiva 33 (13) Other sites 42 (16) 972 J Formos Med Assoc 2006 Vol 105 No 12

3 Supraomohyoid neck dissection as T2, 30 (11.7%) as T3 and 66 (25.7%) as T4. Pathology was classified as N0 in 202 (78.6%), N1 in 23 (8.9%), and N2 in 32 (12.5%) (Table 2). The 257 cases with SOHND included 162 (63%) clinical N0 cases and 95 (37%) clinical N+ cases (Figure 1). Among the 162 clinical N0 cases, 15 (9.3%) were clinically false negative cases (N1 = 9, N2 = 6), of which three (N1 = 1, N2 = 2) had recurrent neck cancer in the dissected neck with a neck failure rate of 20% (3/15). One (N2) of the three neck recurrence cases was found outside of the operative field of the SOHND. Among the 162 clinical N0 cases, 147 (90.7%) were true negative cases, of which nine had recurrent neck cancer in the dissected neck with a neck failure rate of 6.1% (9/147). All of the recurrences were within the area of the prior SOHND site. Among the 95 clinical N+ cases, 55 (57.9%) were clinically false positive, of which 12 had recurrent neck cancer with a neck failure rate of 21.8% (12/55). All of the recurrences were within the area of the prior SOHND site. Among the 95 N+ cases, 40 (42.1%) were clinically true positive cases (N1 = 14, N2 = 26), of which 16 (N1 = 4, N2 = 12) had recurrent neck cancer resulting in a neck failure rate of 40% (16/40) (Figure 1). Four of the 16 neck recurrences occurred outside the operative field of the SOHND and all were pathologic N2, with three in level IV and one in level V. Postoperative radiotherapy totaling at least 5000 cgy was given to the neck sites of 62 patients, including 56 with pathologic N+ and six with perineural invasion, close surgical margin, or advanced primary tumor (T3 and T4). Three patients discontinued radiation therapy because of intolerance. Table 2. Pathologic T and N status of 257 patients with oral squamous cell carcinoma T status T1 T2 T3 T4 Total, n (%) N status N (78.6) N (8.9) N (12.5) Total, n (%) 64 (24.9) 97 (37.7) 30 (11.7) 66 (25.7) cases with SOHND Clinical N0 162 (63%) Clinical N+ 95 (37%) Pathologic N+ (9.3%) N1=9 N2=6 Pathologic N (90.7%) 147 Pathologic N (57.9%) 55 Pathologic N+ (42.1%) N1=14 N2=26 Neck failure (3/15) N1=1 N2=2 Neck failure (9/147) Neck failure (12/55) Neck failure (16/40) N1=4 N2=12 Figure 1. Summary of the clinical outcome of 257 patients who underwent supraomohyoid neck dissection (SOHND). The 257 patients were divided into four groups based on pathologic findings. The clinically false negative group (n = 15) had occult positive lymph nodes and a neck failure rate of 20% (3/15). The clinically true negative group (n = 147) and clinically false positive group (n = 55) included patients whose lymph nodes were negative histologically and had neck failure rates of 6.1% (9/147) and 21.8% (12/55), respectively. The clinically true positive group (n = 40) consisted of patients whose SOHND had a neck failure rate of 40% (16/40). J Formos Med Assoc 2006 Vol 105 No

4 G.A. Liaw, et al Figure 2. Kaplan-Meier curve showing 3- and 5-year overall neck disease-free survival rates of 79.8% and 77.6%, respectively Survival function Censored Cumulative survival Duration (mo) Figure 3. Kaplan-Meier curves for patients with pathologic N0, N1 and N2 status (N0 vs. N1, p = ; N0 vs. N2, p = ; N1 vs. N2, p = ). Cumulative survival N2 N1 N0 N N0 N1 N2 translate N0 censored N1 censored N2 translate censored Duration (mo) The 3- and 5-year overall neck disease-free survival rates were 79.8% and 77.6%, respectively (Figure 2). The 3- and 5-year neck disease-free survival rates were 86.7% and 84.2% for pathologic N0 cases, 56.9% and 56.9% for pathologic N1 cases, and 27.5% and 27.5% for pathologic N2 cases (Figure 3, Table 3). Log rank test showed significant differences in overall disease-free survival rates of p = for pathologic N0 vs. N1 cases, < for pathologic N0 vs. N2 cases, and for pathologic N1 vs. N2 cases (Figure 3). Discussion The comprehensive removal of cervical lymph nodes, spinal accessory nerve, internal jugular vein, and the sternocleidomastoid muscle using radical neck dissection (RND) was systematically described by Crile in This operative procedure has significant long-term morbidity, including shoulder dysfunction, cosmetic deformity, cuta- neous paresthesia and chronic neck and shoulder pain syndrome. These morbidities are exacerbated 974 J Formos Med Assoc 2006 Vol 105 No 12

5 Supraomohyoid neck dissection Table 3. The 3- and 5-year neck disease-free survival rates according to pathologic N status* 3 years 5 years N0 86.7% (2.7%) 84.2% (3.1%) N1 56.9% (18.3%) 56.9% (18.3%) N2 27.5% (13.3%) 27.5% (13.3%) *Data presented as cumulative survival (standard error). when postoperative radiotherapy is added. Owing to the significant functional and esthetic morbidity associated with RND, Suarez 16 first introduced functional neck dissection (FND) in the early 1960s. FND preserved the spinal accessory nerve, internal jugular vein and the sternocleidomastoid muscle, resulting in less morbidity than RND, and the technique was designated as modified radical neck dissection (MRND) by American head and neck surgeons. 4 In the 1970s, studies revealed that lymphatic groups at risk for a particular primary site are predictable. 17 SND, introduced in the 1980s, removes a selected group of lymph nodes with high risk occult metastasis. The rationale for elective SOHND for OSCC is influenced by the pattern of spread of cancer to the neck, as described by Lindberg. 18 It is well documented that if the levels I III lymph nodes with the highest risk of metastasis are shown to have no metastasis after removal by SOHND, the likelihood of level IV or V lymph node metastasis is extremely low. The factors influencing neck disease-free survival rates after SOHND include incomplete SOHND, histopathology and radiotherapy. 13 The histopathologic factor is micrometastasis beyond the pathologic slicing detected nodes. 19 Previously reported neck failure in histopathologic N0 necks is therefore likely to be related to the varying diligence of the pathologist in the assessment of the operative specimen. The radiotherapeutic factor is discontinuation of radiotherapy. In the present study, the neck failure rate was 20% for clinically false negative cases, 6.1% for clinically true negative cases, 21.8% for clinically false positive cases, and 40% for clinically true positive cases. In 1972, Fletcher 20 reported that 5000 rads by radiotherapy was sufficient to control subclinical disease in the neck. The neck failure rates of clinically false negative and true positive groups in this study were obviously higher than those of other studies. 9,21 Moreover, the high neck failure rates in this study might be attributable to rejection or intolerance of radiotherapy in some cases resulting in discontinuation of radiotherapy. Increases in the overall neck failure rate were also observed. However, the neck failure rates for clinically true negative and false positive groups in this study were similar to those of other studies. 9,21 There- fore, SOHND may be an accurate procedure for selective OSCC cases. Despite the effective staging and therapeutic procedure for clinical N0 cases, 8,21 the use of SOHND as a therapeutic procedure for clinical N+ cases remains very controversial. RND or MRND are commonly used surgical procedures for the treatment of the N+ neck. However, the trend toward minimizing tissue loss from an extirpative procedure with preservation of function has resulted in an increasing interest in the use of various modifications of RND. When using a more selective surgical procedure in selected N+ patients, regional control achieved a comparable result to that of MRND. 8,22,23 Kolli et al 3 reported that SOHND in patients with pathologically positive nodes in the neck was inadequate for regional control without postoperative radiation therapy. In the absence of factors that violate the fascial compartments of the neck or disrupt lymphatic flow, such as massive adenopathy or gross extracapsular spread, the rationale behind this procedure remains viable. 22 Medina and Byers 8 suggested that SOHND is primarily indicated for patients with T2, T3, and T4N0, and selected N1 OSCC. Spiro et al 9 reported that therapeutic SOHND in conjunction with postoperative ra- diation therapy is highly effective in controlling N1, N2a and N2b. Jeroen et al 23 found that SOHND is inadequate for clinically positive neck disease due to the higher risk of metastases in level IV; therefore, MRND was recommended for such cases. In the present study, the 3- and 5-year neck disease-free survival rates were 86.7% and J Formos Med Assoc 2006 Vol 105 No

6 G.A. Liaw, et al 84.2% for N0 cases, 56.9% and 56.9% for N1 cases, and 27.5% and 27.5% for N2 cases. No neck recurrence was found between 3 and 5 years in N1 and N2 cases in this study, resulting in identical 3- and 5-year neck disease-free survival rates. The results of this study indicate that SOHND is therapeutic for patients with pathologically uninvolved neck. The lack of significant difference in the 3- and 5-year neck disease-free survival rates between N0 and N1 cases suggests that SOHND may be utilized in OSCC patients with clinical N0 and N1 necks. Johnson et al 24 found that if multiple positive nodes and/or extracapsular extension were present, most recurrences were in the dissected field. Thus, when SOHND is used for OSCC patients with clinical N2 neck, combined radiotherapy or RND is indeed needed. The predictive value of neck node involvement on recurrence and survival in OSCC is well known, but whether this predictive value on survival holds in patients with occult metastases or micrometastases is unclear. 2 Whether early treatment of occult neck disease results in better survival remains controversial. By contrast, the type of therapeutic approach used to control regional lymphatic spread in the neck plays an essential role in prognosis. For the clinical N0 neck, a waitand-see approach or immediate elective SOHND is indicated. Fakih et al 25 found no significant difference in survival rate between the two strategies. On the other hand, Kligerman et al 26 reported a significantly decreased regional recurrence rate and improved 3-year survival with elective SOHND in a series of 67 patients with T1N0 and T2N0 oral cancers. In the present study, SOHND was our general protocol for the clinical N0 neck, except for patients with old age or medical compromise, who were treated using the wait-andsee strategy. References 1. Brazilian Head and Neck Cancer Study Group. Results of a prospective trial on elective modified radical classical versus supraomohyoid neck dissection in the management of oral squamous carcinoma. Am J Surg 1998;176: Leemans CR, Tiwari R, Nauta JJ, et al. Recurrence at the primary site in head and neck cancer and the significance of neck lymph node metastases as a prognostic factor. Cancer 1994;73: Kolli VR, Datta RV, Orner JB, et al. The role of supraomohyoid neck dissection in patients with positive nodes. Arch Otolaryngol Head Neck Surg 2000;126: Ferlito A. Evolution in the philosophy of neck dissection. Acta Otolaryngol 2001;121: Shah JP. The patterns of cervical lymph node metastasis from squamous carcinoma of the upper aerodigestive tract. Am J Surg 1990;160: Byers RM, Wolf PF, Ballantyne AJ. Rationale for elective neck dissection. Head Neck 1988;10: Pitman KT, Johnson JT, Myers EN. Effectiveness of selective neck dissection for management of the clinically negative neck. Arch Otolaryngol Head Neck Surg 1997;123: Medina JE, Byers RM. Supraomohyoid neck dissection: rationale, indications, and surgical technique. Head Neck 1989;11: Spiro RH, Morgan GJ, Strong EW, et al. Supraomohyoid neck dissection. Am J Surg 1996;172: Davidson J, Khan Y, Gilbert R, et al. Is selective neck dissection sufficient treatment for the N0/pN+ neck? J Otolaryngol 1997;26: Majoufre C, Faucher A, Laroche C, et al. Supraomohyoid neck dissection in cancer of the oral cavity. Am J Surg 1999;178: Hughes CJ, Gallo O, Spiro RH, et al. Management of occult neck metastases in oral cavity squamous carcinoma. Am J Surg 1993;166: Byers RM. Modified neck dissection. A study of 967 cases from 1970 to Am J Surg 1985;150: Hyam DM, Conway RC, Sathiyaseelan Y, et al. Tongue cancer: do patients younger than 40 do worse? Australian Dental Journal 2003;48: Crile G. Excision of cancer of the head and neck with special reference to the plan of dissection based on 132 patients. JAMA 1906;47: Suarez O. El problema de las metastasis linfaticas yalejadas del cancer de laringe e hipofaringe. Rev Otorrinolaringol 1963;23: Byers RM, Wolf PF, Ballantyns AJ. Rationale for elective modified neck dissection. Head Neck 1988;10: Lindberg R. Distribution of cervical lymph node metastases from squamous cell carcinoma of the upper respiratory and digestive tracts. Cancer 1972;29: Saka SM, Mcdonald DG. Sampling of jugulo-digastric lymph nodes in oral cancer. Br J Cancer 1987;55: Fletcher GH. Elective irradiation of subclinical disease in cancers of the head and neck. Cancer 1972;29: J Formos Med Assoc 2006 Vol 105 No 12

7 Supraomohyoid neck dissection 21. Spiro JD, Spiro RH, Shah JP, et al. Critical assessment of supraomohyoid neck dissection. Am J Surg 1988;156: Traynor SJ, Cohen JI, Gray J, et al. Selective neck dissection and the management of the node-positive neck. Am J Surg 1996;172: Kerrebijn JD, Freeman JL, Irish JC, et al. Supraomohyoid neck dissection. Is it diagnostic or therapeutic? Head Neck 1999;21: Johnson JT, Barnes L, Myers EN, et al. The extracapsular spread of tumors in cervical node metastasis. Arch Otolaryngol 1981;107: Fakih AR, Rao RS, Patel AR. Prophylactic neck dissection in squamous cell carcinoma of oral tongue: a prospective randomized study. Seminars Surg Oncol 1989;5: Kligerman J, Lima RA, Soares JR, et al. Supraomohyoid neck dissection in the treatment of T1/T2 squamous cell carcinoma of the oral cavity. Am J Surg 1994;168: J Formos Med Assoc 2006 Vol 105 No