Predictive factors and distribution of lymph node metastasis in lip cancer patients and their implications on the treatment of the neck

Predictive factors and distribution of lymph node metastasis in lip cancer patients and their implications on the treatment of the neck
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  Predictive factors and distribution of lymph nodemetastasis in lip cancer patients and theirimplications on the treatment of the neck Jose Guilherme Vartanian, Andre´ Lopes Carvalho,Manoel Jose´ de Arau´ jo Filho, Mituro Hattori Junior, Jose´ Magrin,Luiz Paulo Kowalski* Head and Neck Surgery and Otorhinolaryngology Department, Hospital do Caˆncer A.C. Camargo, Sa˜o Paulo,Brazil Received 11 July 2003; accepted 7 August 2003 Summary  The frequency of neck metastasis in lip cancer patients is low, however if present, it decreases survival rates, which reinforce the neck treatment as an impor-tant step in the management of these patients. This study evaluates the predictivefactors, the distribution of lymph node metastasis and their implications on the necktreatment. A retrospective analysis of lip cancer patients treated in our institutionfrom 1969 to 1999 was performed. A total of 617 patients were analysed. One hundredand seven patients (17.3%) were submitted to a neck dissection. T3/T4 tumours andcommissure involvement were significantly associated with the risk of neck metastasis( P  < 0.001 and  P  =0.004, respectively). No cases had levels IV and V involved with nodemetastasis, either clinically or pathologically. The results suggest that supraomohyoidneck dissection could be the option for the elective treatment in T3/T4 tumours andthose with commissure involvement, and the therapeutic option for patients withclinically positive necks. # 2003 Elsevier Ltd. All rights reserved. KEYWORDS Head and neck neoplasms;Lip cancer;Squamous cell carcinoma;Neck metastasis;Neck dissection Introduction Neck lymph node metastasis is the most sig-nificant prognostic factor in patients with squamouscell carcinoma of the head and neck. 1 Even thoughunusual, the occurrence of neck metastasis from lipcancer also decreases the patients overallsurvival. 2  4 Therefore, the management of the neckis a crucial step in the treatment of these patients.The standard treatment of regional lymph nodemetastasis in patients with head and neck cancerhas been the classical radical neck dissection.However, since its first description by Crile in1906, 5 several modifications have been introducedto decrease the morbidity of the procedure with-out jeopardizing the oncological results in selec-ted patients. Such procedures involve thepreservation of non-lymphatic structures (modified 1368-8375/$ - see front matter # 2003 Elsevier Ltd. All rights reserved.doi:10.1016/j.oraloncology.2003.08.007Oral Oncology (2004)  40  223–* Corresponding author. Tel.: +55-11-3272-5125; fax: +55-11-3277-6789. E-mail address: (L. Paulo Kowalski).  radical dissections) or the preservation of somegroups of lymph nodes (selective neck dissections).In lip cancer patients, some authors advocateneck dissection only in cases of palpable nodes, 3,6 while others recommend that patients with highrisk for occult neck metastasis should be submittedto an elective neck dissection. 7,8 In such cases, theselective neck dissection including levels I—III(supraomohyoid neck dissection) is the preferredoption. 4,7  10 Several reports in the literature havedescribed factors associated with the risk of occultneck metastasis from lip cancer, such as T stage,histologic degree of differentiation and commis-sure involvement, however the results are notuniform in all series. 3,4,11  13 Considering thedistribution of lymph node metastasis, recentreports have suggested the use of selective neckdissections as an option in selected patients withlimited neck disease. 4,8,14 The main objectives of this study are to analysethe predictive factors and the distribution of lymphnode metastasis in patients with squamous cell car-cinoma of the lip aiming to establish the rationalefor the use of selective neck dissection as elective(cN  ) or therapeutic (cN+) approach to the neck. Patients and methods A retrospective study was performed analysing aseries of consecutive lip cancer patients selectedfrom the hospital database, who were treated from1969 to 1999. The study was performed at a ter-tiary Cancer Centre—Hospital do Caˆncer A. C.Camargo, in Sa˜o Paulo, Brazil. The eligibility cri-teria included previously untreated patients withdiagnosis of squamous cell carcinoma of the lip,without a second primary tumour and submitted totreatment in the institution. A total of 617 eligiblepatients with lip squamous cell carcinoma wereevaluated at the institution in this period. Allmedical charts were reviewed and patients wererestaged according to the AJCC criteria. 15 The group of patients that were submitted to anelective (N0) or therapeutic (N+) neck dissection ora salvage neck dissection in previously untreatedneck by surgery or radiation were evaluated todetermine the metastatic lymph node distribution.The lymph nodes were dissected by the pathologistprior to fixation and lymph nodes were classifiedinto levels I—V according to the Memorial SloanKettering Cancer Center classification. 16 A descriptive analysis of the anatomical distribu-tion of metastatic lymph nodes and their corre-lation with the clinical and pathological statuswere performed. The Chi-square test and Fischer’sexact test were utilized to analyse the associationof demographic, clinical and pathological variableswith neck metastasis. Results Six hundred and seventeen patients with lip can-cer were analysed. There were 507 males (82.2%).Ages ranged from 13 to 93 years (median, 61years). The tumours were sited at the lower lip in593 cases (96.1%); upper lip in 8 (1,3%) and com-missure in 12 (1.9%). The commissure was involvedin 105 cases (17.0%). The majority of patients werediagnosed at early stages (T1/T2 in 81.0% of cases).Regarding the clinical N stage, there were clinicallynegative necks (cN0) in 79.0% of patients (Table 1).A subgroup of 63 patients that showed patho-logical neck metastasis were analysed to evaluatethe predictive factors for lymph node dissemina-tion. This subgroup included 44 patients with neckmetastasis detected in the neck dissection speci-men (36 therapeutic dissections; eight electivedissections) and 16 had exclusively neck recur-rences at a previously untreated neck. These eightpatients electively treated and the 16 patientswith neck recurrences, were also considered aspatients with occult neck disease. Patients withcombined local and regional recurrences were notincluded in this subset because the neck metastasiscould result from the primary or recurrent tumour.The T stage distribution in this group were: T1 in 17of cases (27%); T2, 19 (30.2%); T3, 14 (22.2%); T4,11 (17.5%); and Tx in 2 cases (3.2%). There were 26cN0 patients (41.2%); 19 N1 (30.2%); and 18 N2 Table 1  Clinical characteristics of the 617 patientswith lip squamous cell carcinomaClinical characteristics No. (%)Gender Male 507 (82.2%)Female 110 (17.8%)Age (years) Range (Median) 13—93 (61)Site of origin Upper lip 8 (1.3%)Lower lip 593 (96.1%)Comissure 12 (1.9%)Clinical T stage T1 329 (53.3%)t2 171 (27.7%)t3 76 (12.3%)t4 36 (5.8%)tx 5 (0.8%)Clinical N stage N0 487 (79.0%)n1 62 (10.0%)N2 62 (10.0%)N3 6 (1.0%) 224 J. G. Vartanian et al.  (28.6%). Among the variables studied (gender,tumour subsite, T stage and tumour degree), T3and T4 stage and commissure involvement weresignificantly associated with the risk of neck meta-stasis ( P  < 0.001 and  P  =0.004, respectively)(Table 2). When considering patients with occultneck disease, the risk for occult neck metastasiswere 23.3% for T3/T4 tumour patients and 15.4% forpatients with commissure involvement (Table 3).One hundred and seven patients (17.3%) weresubmitted to a neck dissection. The indication wastherapeutic (cN+) in 83 patients (77.6%), and elec-tive (cN0) in 24 patients (22.4%). A unilateral orbilateral selective (supraomohyoid) neck dissectionwas performed in 80 patients (74.8%), an unilateralor bilateral radical (or modified radical) neck dis-section in 23 patients (21.5%), and a combinedselective and radical dissection in four patients(3.7%). Regarding the cN+ patients, only 36 (43.4%)confirmed to be pathologically involved (pN+),indicating a high frequency of false positive rate of the preoperative evaluation. In the group of cN0patients, eight (33.3%) presented occult neckmetastasis (pN+). The most frequent levels of metastatic spread were levels I and II. None of thecases presented levels IV and V involved, neitherclinical nor pathological (Table 4). Adjuvant radio-therapy was performed in 26 of 44 cases (59.5%)regardless the type of neck dissection.The follow-up period ranged from 2 days to 26.6years, with a median of 62.2 months. Regionalrecurrences were detected in three of 107 neckdissected patients (2.8%), being two cases at thecontra lateral non-dissected neck side and only onecase (0.9%) in the ipsilateral dissected field. Allthree patients were submitted to surgical resection Table 2  Risk for neck metastasis among the 617 casesVariables N0 neck N+ neck  P  Gender Male 451 56 (12.4) 0.142Female 103 7 (6.8)Commissure Not involved 454 43 (9.5) 0.004Involved 86 19 (22.1)T stage T1/T2 465 37 (7.9)  < 0.001T3/T4 86 24 (27.9) Table 3  Risk of occult neck metastasis in cN0 patients by T stage and commissure involvementOccult metastasisNo Yes  P  N(%) N(%)cT stage T1/T2 358 (95.7) 16 (4.3)T3/T4 23 (76.7) 7 (23.3)  < 0.001Commissure No 341 (95.5) 16 (4.5)Yes 33 (84.6) 6 (15.4) 0.005 Table 4  Distribution of lymph node metastasis and the association with clinical diagnosis of lymph nodes suspectedto be metastaticpN level [N (%)]0 I II I/II I/III I/II/III TotalcN level 0 16 (66.7) 6 (25.0) 2 (8.3) 24I 41 (60.3) 19 (27.9) 4 (5.9) 3 (4.4) 1 (1.5) 68I/II 6 (42.9) 3 (21.4) 2 (14.3) 2 (14.3) 1 (7.1) 14I/III 1 (100.0) 1Total 63 28 8 5 1 2 107 Predictive factors and distribution of lymph node metastasis in lip cancer patients 225  as a salvage treatment of their regional recur-rences. Most patients were submitted to a selec-tive neck dissection, however, none presentedregional recurrences at the ipsilateral neck sidebeyond the dissection field.In the group of 107 patients submitted to a neckdissection, the 5-year disease specific survivalrates were 90.6% and 74.6% for patients withpathologically negative and positive necks, respec-tively ( P  =0.086). Discussion Lip cancer patients usually have a good prog-nosis, possibly as a result of early diagnosis due tothe location of the tumour, and also due to thelower rate of regional lymph node metastasis. 3,4 However, when regional lymph node metastasis isdetected, there is a significant decrease in theoverall survival rates. 2  4,11,17 Such negative impacton the prognosis is well established in most sites of head and neck squamous cell carcinoma. 1,18 It has been reported the low accuracy of clinicaland methods for the detection of regional meta-stasis. 14,18 Other methods have been described tobetter staging patients with head and neck cancer,as ultrasound-guided fine needle aspiration cytol-ogy 19 and sentinel lymph node biopsy, 12,18 but suchtools are not worldwide available or accepted andthe results are still debatable. Therefore, the mostaccurate method to detect regional lymph nodemetastasis is the selective neck dissection. 21 A selective neck dissection has been consideredthe standard elective surgical treatment of theneck in head and neck cancer patients with a highrisk for occult neck metastasis ( > 20%). Based onstudies about the patterns of lymph node spread bythe site of the primary tumor 1 and the low fre-quency of isolated level V involvement in oral cav-ity and lip cancer patients, 20 the selectivedissection including levels I—III (supraomohyoid) has been considered the best option. 1,4,7  10,17 In lip cancer patients, most authors agree that anelective supraomohyoid neck dissection is indi-cated in high-risk patients, 4,7,8 however, con-troversies still exist regarding which are thepatients at high risk for occult neck metastasis.Several series have analysed factors associatedwith neck dissemination such as the size of theprimary tumour, histopathologic grade, recurrenttumour, subsite of srcin (lower lip and commis-sure), tumour thickness and perineuralinvasion. 3,4,11  13 De Visscher et al. 11 described thatincreasing tumour thickness, infiltrative invasionpattern and perineural infiltration were significantrisk factors for regional metastasis. In our study,these variables were not analysed due to the ret-rospective nature of the study with the lack of information in several charts, but all can be iden-tified in the pathological analysis of the specimen.For clinical purposes, it would be more significantto establish a model of risk factors including onlyvariables that could be assessed prior to the surgicalprocedure.Regarding the variables studied, our resultsshowed that T3 and T4 tumours and tumours invol-ving commissure were associated with higher ratesof neck metastasis, 22.3% and 18.1%, respectively(Table 2). When we excluded cN+ patients andanalysed just patients with occult neck metastasis(8 cN0/pN+ and 16 exclusively neck recurrences),the risk for such dissemination were seen in 23.3and 15.4% of the cases, respectively (Table 3). Inthe group of patients with neck recurrences alone,we also excluded patients that were submitted toradiotherapy as an adjuvant treatment of theirprimary tumour. Therefore, our results suggest thatthe elective neck treatment should be considered inthe group of patients with T3 and T4 tumours,mainly in those with commissure involvement.As shown in Table 4, we did not have levels IV orV lymph nodes with metastasis, neither clinicallynor pathologically. In the group of 107 patientssubmitted to neck dissection, 17 recurrences weredetected in the follow-up period, most of thembeing local recurrences. Only three patients pre-sented regional recurrences, two at the contralateral non-dissected neck side, and just one in theipsilateral dissected field (0.9%).Kowalski et al. 8 studying 212 patients submittedto a supraomohyoid neck dissection, suggests thatthis selective dissection could be sufficient as thetherapeutic option in lip cancer patients clinicallystaged as N1 at level I. Byers et al. 10 evaluated thepatterns of regional failure in patients submitted toselective neck dissections, including oral and oro-pharyngeal cancer patients submitted to a suprao-mohyoid dissection, and showed 5.6% and 35.7% of recurrences in N1 patients submitted to a suprao-mohyoid dissection with and without adjuvantradiatherapy, respectively. Gooris et al. 4 reporteda prospective series of 44 patients with lower lipcancer submitted to a supraomohyoid neck dissec-tion followed by radiotherapy when indicated, andshowed four neck recurrences (9%), all within thedissection field.Elective supraomohyoid neck dissection (levelsI—III) should be indicated in high-risk patients (T3/T4 lip cancers, mainly in those with commissureinvolvement). Also, this selective neck dissectioncould be the therapeutic option in patients with226 J. G. Vartanian et al.  clinically positive neck (at levels I or II), followedby adjuvant radiotherapy when indicated. A radicalcomprehensive dissection (classical or modified)should be performed only for patients with exten-sive N2 or N3 metastasis. References 1. Shah J. Patterns of cervical lymph node metastasis fromsquamous carcinomas of the upper aerodigestive tract . Am J Surg  1990; 160 :282—286.2. Baker SR. Current management of cancer of the lip . Oncol-ogy (Huntingt)  1990; Sep 4 (9):107—120.3. Zitsch RP, Lee BW, Smith RB. Cervical lymph node metas-tases and squamous cell carcinoma of the lip . Head Neck 1999; 21 :447—453.4. Gooris PJJ, Vermey A, Visscher JGAM, Burlage FR, Rooden-burg JLN. Supraomohyoid neck dissection in the manage-ment of cervical lymph node metastases of squamous cellcarcinoma of the lower lip . Head Neck  2002; 24 :678—683.5. Crile G. Excision of cancer of the head and neck with spe-cial reference to the plan of dissection based on 132 oper-ations . JAMA  1906; 47 :1780—1786.6. Califano L, Zupi A, Massari PS, Giardino C. Lymph nodemetastasis in squamous cell carcinoma of the lip. A retro-spective analysis of 105 cases . Int J Oral Maxillofac Surg 1994; Dec 23 (6 Pt 1):351—355.7. Medina JE, Byers RM. Supraomohyoid neck dissection:rationale, indications, and surgical technique . Head Neck 1989; 11 :111—122.8. Kowalski LP, Magrin J, Waksman G, Santo GF, Lopes ME, dePaula RP, et al. Supraomohyoid neck dissection in thetreatment of head and neck tumours—survival results in212 cases . Arch Otolaryngol Head Neck Surg  1993; 119 :958—963.9. Spiro DS, Spiro HS, Shah J, Sessions RB, Strong EW. Criticalassessment of supraomohyoid neck dissection . Am J Surg 1988; 156 :287—290.10. Byers RM, Clayman GL, Mcgill D, Andrews T, Kare RP,Roberts DB, et al. Selective neck dissections for squamouscarcinoma of the upper aerodigestive tract: patterns of regional failure . Head Neck  1999; 21 :499—505.11. 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Registro dos exames de pec¸as ciru´rgicas: esva-ziamento cervical . Rev Paul Me´d   1957; 51 :387—391.17. Robbins KT, Medina JE, Wolfe GT, Levine PA, Sessions RB,Pruet CW. Standardizing neck dissection terminology . ArchOtolaryngol Head Neck Surg  1991; 117 :601—605.18. Shoaib T, Soutar DS, MacDonald DG, Camilleri JG, DunawayDJ, Gray HW, et al. The accuracy of head and neck carci-noma sentinel lymph node biopsy in the clinically N0 neck .Cancer   2001; 91 :2077—2083.19. Van-den-Brekel MWM, Casteligins JA, Stel HV, Luth WJ,Valk J, van der Waal I, et al. Occult metastatic neckdisease: detection with ultrasound and ultrasound-guidedfine needle aspiration cytology . Radiology   1991; 180 :457—461.20. Davidson BJ, Kulkarny V, Delacure MD, Shah JP. Posteriortriangle metastasis of squamous cell carcinoma of theupper aerodigestive tract . Am J Surg  1993; 166 :395—398.21. Kowalski LP, Medina J. Nodal metastases—predictivefactors . Otolaryngol Clin North Am  1998; 31 (4):621—637. Predictive factors and distribution of lymph node metastasis in lip cancer patients 227
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