[1] Kalavrezos N, Bhandari R. Current trends and future perspectives in the
surgicalmanagement of oral cancer. Oral Oncol 2010;46:429–432.
[2] Kernohan MD, Clark JR, Gao K, et al. Predicting the prognosisof oral squamous cell
carcinoma
2010;136:1235–1239.
after
first
recurrence.
Arch
Otolaryngol
HeadNeck
Surg
[3] Huang TY, Hsu LP, Wen YH, et al. Predictors of locore-gional recurrence in early stage
oral cavity cancer with free surgical margins. Oral Oncol 2010;46:49–55.
[4] Bernier J, Domenge C, Ozsahin M, et al. Postoperative irradiation with or without
10
concomitant chemotherapy forlocally advanced head and neck cancer. N Engl J Med
11
2004;350:1945–1952.
12
[5] Cooper JS, Pajak TF, Forastiere AA, et al. Postoperative concurrent radiotherapy and
13
chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J
14
Med 2004;350:1937–1944.
15
[6] Bernier J, Cooper JS, Pajak TF, et al. Defining risk levels in locally advanced head and
16
neck cancers: a comparativeanalysis of concurrent postoperative radiation plus
17
chemotherapy trials of theEORTC (#22931) and RTOG (# 9501). Head Neck
18
2005;27:843–850.
19
[7] Sutton DN, Brown JS, Rogers SN, et al. The prognostic implications of the surgical
20
margin in oral squamous cell carcinoma. Int J Oral Maxillofac Surg. 2003
21
Feb;32(1):30-34.
22
[8] Bessell A, Glenny AM, Furness S, et al. Interventions for the treatment of oral and
23
oropharyngeal cancers: surgical treatment. Cochrane Database Syst Rev. 2011 Sep
24
7;(9):CD006205.
25
[9] Dixit S, Vyas RK, Toparani RB, et al. Surgery versus surgery and postoperative
26
radiotherapy in squamous cell carcinoma of the buccal mucosa: a comparative study.
27
Ann Surg Oncol. 1998 Sep;5(6):502-510.
15
[10] Hinni ML, Ferlito A, Brandwein-Gensler MS, et al. Surgical margins in head and neck
cancer: a contemporary review. Head Neck. 2013 Sep;35(9):1362-1370.
[11] Meier JD, Oliver DA, Varvares MA. Surgical margin determination in head and neck
oncology: current clinical practice. The results of an International American Head and
Neck Society Member Survey. Head Neck. 2005 Nov;27(11):952-958.
[12] Nason RW, Binahmed A, Pathak KA, et al. What is the adequate margin of surgical
resection in oral cancer? Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009
May;107(5):625-629.
[13] Wong LS, McMahon J, Devine J, et al. Influence of close resection margins on local
10
recurrence and disease-specific survival in oral and oropharyngeal carcinoma. Br J Oral
11
Maxillofac Surg. 2012 Mar;50(2):102-108.
12
[14] Ch'ng S, Corbett-Burns S, Stanton N, et al. Close margin alone does not warrant
13
postoperative adjuvant radiotherapy in oral squamous cell carcinoma. Cancer. 2013 Jul
14
1;119(13):2427-2437.
15
[15] Weijers M, Snow GB, Bezemer DP, et al. The status of the deep surgical margins in
16
tongue and floor of mouth squamous cell carcinoma and risk of local recurrence; an
17
analysis of 68 patients. Int J Oral Maxillofac Surg. 2004 Mar;33(2):146-149.
18
19
20
21
[16] Loree TR, Strong EW. Significance of positive margins in oral cavity squamous
carcinoma. Am J Surg. 1990 Oct;160(4):410-414.
[17] Liao CT, Chang JT, Wang HM, et al. Analysis of risk factors of predictive local tumor
control in oral cavity cancer. Ann Surg Oncol. 2008 Mar;15(3):915-922.
22
[18] Hicks WL Jr, North JH Jr, Loree TR, Maamoun S, Mullins A, Orner JB, Bakamjian
23
VY, Shedd DP. Surgery as a single modality therapy for squamous cell carcinoma of
24
the oral tongue. Am J Otolaryngol. 1998 Jan-Feb;19(1):24-28.
25
26
27
[19] Binahmed A, Nason RW, Abdoh AA. The clinical significance of the positive surgical
margin in oral cancer. Oral Oncol. 2007 Sep;43(8):780-784.
[20] Kademani D, Bell RB, Bagheri S, et al. Prognostic factors in intraoral squamous cell
16
carcinoma: the influence of histologic grade. J Oral Maxillofac Surg. 2005
Nov;63(11):1599-1605.
[21] McMahon JD, Devine JC, Hetherington J, et al. Involved surgical margins in oral and
oropharyngeal carcinoma-an anatomical problem? Br J Oral Maxillofac Surg. 2011
Apr;49(3):172-175.
[22] McMahon J, O'Brien CJ, Pathak I, et al. Influence of condition of surgical margins on
local recurrence and disease-specific survival in oral and oropharyngeal cancer. Br J
Oral Maxillofac Surg. 2003 Aug;41(4):224-231.
[23] Brandwein-Gensler M, Teixeira MS, Lewis CM, et al. Oral squamous cell carcinoma:
10
histologic risk assessment, but not margin status, is strongly predictive of local
11
disease-free and overall survival. Am J Surg Pathol. 2005 Feb;29(2):167-178.
12
[24] Solomon J, Hinther A, Matthews TW, et al. The impact of close surgical margins on
13
recurrence in oral squamous cell carcinoma. J Otolaryngol Head Neck Surg. 2021 Feb
14
12;50(1):9.
15
[25] Kurita H, Nakanishi Y, Nishizawa R, et al. Impact of different surgical margin
16
conditions on local recurrence of oral squamous cell carcinoma. Oral Oncol. 2010
17
Nov;46(11):814-817.
18
[26] Yang TL, Wang CP, Ko JY, et ak. Association of tumor satellite distance with
19
prognosis and contralateral neck recurrence of tongue squamous cell carcinoma. Head
20
Neck. 2008 May;30(5):631-638.
21
[27] Byers RM, Bland KI, Borlase B, Luna M. The prognostic and therapeutic value of
22
frozen section determinations in the surgical treatment of squamous carcinoma of the
23
head and neck. Am J Surg. 1978 Oct;136(4):525-528.
24
[28] Slootweg PJ, Hordijk GJ, Schade Y, et al. Treatment failure and margin status in head
25
and neck cancer. A critical view on the potential value of molecular pathology. Oral
26
Oncol. 2002 Jul;38(5):500-503.
27
[29] Chen TY, Emrich LJ, Driscoll DL. The clinical significance of pathological findings in
17
surgically resected margins of the primary tumor in head and neck carcinoma. Int J
Radiat Oncol Biol Phys. 1987 Jun;13(6):833-837.
[30] Hamman J, Howe CL, Borgstrom M, et al. Impact of Close Margins in Head and Neck
Mucosal Squamous Cell Carcinoma: A Systematic Review. Laryngoscope. 2022
Feb;132(2):307-321.
[31] Fives C, Feeley L, O'Leary G, Sheahan P. Importance of lymphovascular invasion and
invasive front on survival in floor of mouth cancer. Head Neck. 2016 Apr;38 Suppl
1:E1528-1534.
10
[32] Jones HB, Sykes A, Bayman N, et al. The impact of lymphovascular invasion on
survival in oral carcinoma. Oral Oncol. 2009 Jan;45(1):10-15.
11
[33] Tai SK, Li WY, Chu PY, et al. Risks and clinical implications of perineural invasion in
12
T1-2 oral tongue squamous cell carcinoma. Head Neck. 2012 Jul;34(7):994-1001.
13
[34] Chen TC, Wang CP, Ko JY, et al. The impact of perineural invasion and/or
14
lymphovascular invasion on the survival of early-stage oral squamous cell carcinoma
15
patients. Ann Surg Oncol. 2013 Jul;20(7):2388-2395.
16
[35] Huang S, Zhu Y, Cai H, et al. Impact of lymphovascular invasion in oral squamous
17
cell carcinoma: A meta-analysis. Oral Surg Oral Med Oral Pathol Oral Radiol. 2021
18
Mar;131(3):319-328.e1.
19
[36] Hasegawa T, Tanakura M, Takeda D, et al. Risk factors associated with distant
20
metastasis in patients with oral squamous cell carcinoma. Otolaryngol Head Neck Surg.
21
2015;152(6):1053-1060.
22
[37] Hasegawa T, Shibuya Y, Takeda D, et al. Prognosis of oral squamous cell carcinoma
23
patients with level IV/V metastasis: An observational study. J Craniomaxillofac Surg.
24
2017;45(1):145-149.
25
[38] Yanamoto S, Denda Y, Ota Y, et al. Postoperative adjuvant therapy for patients with
26
loco-regionally advanced oral squamous cell carcinoma who are at high risk of
27
recurrence. Int J Oral Maxillofac Surg. 2020 Jul;49(7):848-853.
18
[39] Okura M, Yanamoto S, Umeda M, et al; Japan Oral Oncology Group. Prognostic and
staging implications of mandibular canal invasion in lower gingival squamous cell
carcinoma. Cancer Med. 2016;5(12):3378-3385.
[40] Shibuya Y, Ohtsuki Y, Hirai C, et al. Oral squamous cell carcinoma with microscopic
extracapsular spread in the cervical lymph nodes. Int J Oral Maxillofac Surg.
2014;43(4):387-392.
[41] Hamilton SN, Arshad O, Kwok J, et al. Documentation and incidence of late effects
and screening recommendations for adolescent and young adult head and neck cancer
survivors treated with radiotherapy. Support Care Cancer. 2019 Jul;27(7):2609-2616
10
[42] Reuther T, Schuster T, Mende U, Kübler A. Osteoradionecrosis of the jaws as a side
11
effect of radiotherapy of head and neck tumour patients--a report of a thirty year
12
retrospective review. Int J Oral Maxillofac Surg. 2003 Jun;32(3):289-295.
13
[43] Brown JS, Blackburn TK, Woolgar JA, et al. A comparison of outcomes for patients
14
with oral squamous cell carcinoma at intermediate risk of recurrence treated by surgery
15
alone or with post-operative radiotherapy. Oral Oncol. 2007 Sep;43(8):764-773.
16
[44] Moergel M, Meurer P, Ingel K, et al. Effectiveness of postoperative radiotherapy in
17
patients with small oral and oropharyngeal squamous cell carcinoma and concomitant
18
ipsilateral singular cervical lymph node metastasis (pN1) : A meta-analysis.
19
Strahlenther Onkol. 2011 Jun;187(6):337-343.
20
[45] Ampil FL, Caldito G, Ghali GE, Nathan CO. Postoperative radiotherapy for insecure
21
or positive surgical margins in head and neck cancer. J Oral Maxillofac Surg. 2003
22
Apr;61(4):425-429.
23
[46] Barry CP, Wong D, Clark JR, et al. Postoperative radiotherapy for patients with oral
24
squamous cell carcinoma with intermediate risk of recurrence: A case match study.
25
Head Neck. 2017 Jul;39(7):1399-1404.
26
[47] Liu T, Chua B, Batstone M. Postoperative Radiotherapy for Oral Squamous Cell
27
Carcinoma With Histologic Risk Factors: Are We Over-Treating? J Oral Maxillofac
19
Surg. 2018 Jul;76(7):1565-1570.
[48] Jang JY, Choi N, Ko YH, et al. Differential Impact of Close Surgical Margin on Local
Recurrence According to Primary Tumor Size in Oral Squamous Cell Carcinoma. Ann
Surg Oncol. 2017 Jun;24(6):1698-1706.
20
FIGURE CAPTIONS
Table 1. Characteristics of patients in pN- and pN+ groups
Table 2. Characteristics of patients according to LC and DSS in pN- and pN+ groups
Table 3. Results of multivariate Cox proportional hazards analysis of predictors of disease
specific survival (DSS) in pN- patients
Table 4. Results of multivariate Cox proportional hazards analysis of predictors of disease
specific survival (DSS) in pN+ patients
Figure 1. Cumulative local control rates and disease specific survival rates of pN- groups.
Figure 2. Cumulative local control rates and disease specific survival rates of pN+ groups.
10
11
Figure 3. Cumulative local control rates, regional control rates, disease specific survival
rates, and distant metastasis control rates of the close margin cases in pN- groups.
12
Figure 4. Cumulative local control rates, regional control rates, disease specific survival
13
rates, and distant metastasis control rates of the positive margin cases in pN-
14
groups.
15
16
Figure 5. Cumulative local control rates, regional control rates, disease specific survival
rates, and distant metastasis control rates of the close margin cases in pN+ groups.
17
Figure 6. Cumulative local control rates, regional control rates, disease specific survival
18
rates, and distant metastasis control rates of the positive margin cases in pN+
19
groups.
20
21
FIGURE LEGENDS
22
Figure 1. The 3-year cumulative LC rates for the negative margin, CM, and PM pN- group
23
were 93.8%, 83.0%, and 72.2%, respectively. Negative margin was associated
24
with a better LC rate than CM and PM (P < 0.05). The 3-year cumulative DSS
25
rates for the negative margin, CM, and PM of pN- group were 96.8%, 90.8%, and
26
91.4%, respectively. Negative margin was associated with a better DSS rate than
27
CM (P < 0.05).
21
Figure 2. The 3-year cumulative LC rates for the negative margin, CM, and PM of pN+
group were 83.4%, 68.8% and 51.8%, respectively. Negative margin was
associated with a better LC rate than CM and PM (P < 0.05). CM was associated
with a better LC rate than PM (P < 0.05). The 3-year cumulative DSS rates for
the negative margin, CM, and PM of pN+ group were 63.1%, 53.0%, and 48.2%,
respectively. Negative margin was associated with a better DSS rate than PM (P
< 0.05).
10
11
12
13
14
15
16
Figure 3. In pN- groups, the S only group was associated with a better LC rate than the S
+ RT/CCRT groups (P < 0.05).
Figure 4. In pN- groups, the S only group was associated with better RC, DM, and DSS
rates than the S + RT/CCRT groups (P < 0.05).
Figure 5. In pN+ groups, there were no significant differences between S only and S +
RT/CCRT groups.
Figure 6. In pN- groups, there were significant differences between S onlyl and S +
RT/CCRT groups.
Table 1. Characteristics of patients in pN- and pN+ groups
Variables
Number of patients (%)
pN -
pN +
1488 (69.4)
657 (30.6)
Male
824 (55.4)
393 (56.3)
Female
664 (44.6)
264 (43.7)
15–99
15–96
66.4 ± 14.1
66.1 ± 14.1
1060 (71.2)
452 (68.8)
319 (21.4)
148 (22.5)
81 (5.4)
45 (6.9)
15 (1.0)
6 (0.9)
Unknown
13 (0.9)
6 (0.9)
Tongue
730 (49.1)
303 (46.1)
Buccal
147 (9.9)
62 (9.4)
Maxillary gingiva
184 (12.4)
79 (12.0)
Mandibular gingiva
306 (20.6)
150 (22.8)
Oral floor
121 (8.1)
63 (9.6)
496 (33.3)
62 (9.4)
505 (33.9)
224 (34.1)
166 (11.2)
102 (15.5)
4a/b
321 (21.6)
269 (40.9)
ENE -
496 (33.3)
379 (57.7)
ENE +
278 (42.3)
992 (66.7)
0 (0)
496 (33.3)
0 (0)
0 (0)
291 (44.3)
More than 2
0 (0)
366 (55.7)
992 (66.7)
0 (0)
Number of patients
Sex
Age
Range (Years)
Mean ± SD
Performance status
Subsite
T classification
Status of positive lymph metastasis
Nonexcuted neck dissection on first surgery
Number of pathological lymph node metastases
Nonexcuted neck dissection on first surgery
Surgical margins
Negative
1257 (84.5)
529 (80.5)
Close margins
171 (11.5)
88 (13.4)
60 (4.0)
40 (6.1)
Well differentiated
859 (57.7)
306 (46.6)
Moderately differentiated
560 (37.6)
286 (43.5)
Poorly differentiated
51 (3.4)
63 (9.6)
Unknown
18 (1.2)
2 (0.3)
No
863 (58.0)
211 (32.1)
Yes
216 (14.5)
246 (37.4)
Unknown
409 (27.5)
200 (30.4)
No
1034 (69.5)
334 (50.8)
Yes
114 (7.7)
151 (23.0)
Unknown
340 (22.8)
172 (26.2)
No
1443 (97.0)
391 (59.5)
Yes
45 (3.0)
266 (40.5)
1320 (88.7)
362 (55.1)
Death of local failure
42 (2.8)
66 (10.0)
Death of regional failure
5 (0.3)
64 (9.7)
Death of distant metastasis
16 (1.1)
79 (12.0)
Death of other disease
83 (5.6)
50 (7.6)
Tumor-bearing survival
22 (1.5)
36 (5.5)
Positive margins
Histological differentiation
Lymphovascular space invasion
Neural Invasion
Postoperative adjuvant therapy
Treatment outcome
Survival
Table 2. Characteristics of patients according to LC and DSS in pN- and pN+ groups
Variables
pN 3 year LC
P value
(%)
pN +
3 year DSS
P value
(%)
3 year LC
P value
(%)
3 year DSS
P value
(%)
Sex
Male
93.0
Female
90.2
0.006 *
96.2
0.293 *
95.6
80.8
0.066 *
77.5
59.1
0.562 *
63.5
Age
> 70
88.0
< 69
94.8
< 0.001 *
94.2
< 0.001 *
97.4
74.0
< 0.001 *
83.7
59.7
0.768 *
61.5
Performance status
0, 1
92.2
>2
81.4
0.005 *
96.0
0.367 *
93.8
80.3
0.154 *
69.7
62.0
0.178 *
42.9
Subsite
Tongue
95.8
Other
87.7
< 0.001 *
98.0
< 0.001 *
94.0
82.6
0.020 *
76.7
56.9
0.596 *
63.7
T classification
1, 2
94.8
3, 4a/b
85.4
< 0.001 *
98.2
0.001 *
91.3
86.2
< 0.001 *
74.2
64.4
0.003 *
57.7
Status of positive lymph metastasis
ENE -
ENE +
81.2
0.153 *
77.3
71.5
< 0.001 *
52.7
Number of pathological lymph node metastases
0, 1
82.7
0.104 *
70.8
< 0.001 *
More than 2
76.9
52.7
Surgical margins
Negative
93.8
Close or positive margins
80.1
< 0.001 *
96.8
< 0.001 *
91.0
83.4
< 0.001 *
63.4
63.1
0.055 *
51.6
Histological differentiation
Well or Moderately differentiated
92.1
Poorly differentiated
78.9
0.011 *
96.2
0.028 *
87.9
80.2
0.287 *
70.5
62.9
0.011 *
43.6
Lymphovascular space invasion
No
97.7
Yes
92.3
0.001 *
99.4
< 0.001 *
92.7
88.4
0.467 *
88.8
93.0
0.001 *
89.2
Neural Invasion
No
98.1
Yes
84.5
0.001 *
98.9
< 0.001 *
89.3
92.4
< 0.001 *
80.8
93.6
< 0.001 *
80.7
Postoperative adjuvant therapy
No
92.6
Yes
65.6
< 0.001 *
96.6
72.3
Abbreviations: LC, local control rates; DSS, disease-specific survival rates ENE, extranodal extension
< 0.001 *
76.7
83.5
0.024 *
61.7
0.409 *
59.3
*: Log-rank test.
Table 3. Results of multivariate Cox proportional hazards analysis of predictors of disease specific survival in pNpatients
95 % CI
Variable
P value
Hazards ratio
Lower
Upper
Higher T classification (T3 and 4)
< 0.001
4.33
2.14
8.79
Lymphovascular space invasion
< 0.001
3.53
1.89
6.61
Older age (> 70 years)
< 0.001
3.90
1.90
7.98
CI: Confidence interval
Table 4. Results of multivariate Cox proportional hazards analysis of predictors of disease specific survival in pN+
patients
95 % CI
Variable
P value
Hazards ratio
Lower
Upper
Extra nodal extension
< 0.001
2.24
1.57
3.19
Lymphovascular space invasion
0.004
1.72
1.19
2.48
Close or positive margins
0.013
1.66
1.11
2.47
Multiple lymph node metastases
0.028
1.50
1.04
2.15
CI: Confidence interval
...
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