YIJOM-4266; No of Pages 7

Int. J. Oral Maxillofac. Surg. 2019; xxx: xxx–xxx

https://doi.org/10.1016/j.ijom.2019.03.967, available online at https://www.sciencedirect.com

Clinical Paper
Head and Neck Oncology

Clinical outcomes and Eun-Jae Chung1, Min-Woo Park2,

Kee-Hwan Kwon2, Young-Soo Rho2
1
Department of Otorhinolaryngology–Head

prognostic factor analysis after and Neck Surgery, Seoul National University
Hospital, Seoul National University College of
Medicine, Seoul, Republic of Korea;
2
Department of Otorhinolaryngology–Head

salvage surgery for recurrent and Neck Surgery, Ilsong Memorial Institute of
Head and Neck Cancer, Hallym University,
College of Medicine, Seoul, Republic of Korea

squamous cell carcinoma of the

oral cavity
Eun-Jae Chung, Min-Woo Park, Kee-Hwan Kwon, Young-Soo Rho: Clinical outcomes
and prognostic factor analysis after salvage surgery for recurrent squamous cell
carcinoma of the oral cavity. Int. J. Oral Maxillofac. Surg. 2019; xxx: xxx–xxx. ã
2019 Published by Elsevier Ltd on behalf of International Association of Oral and
Maxillofacial Surgeons.

Abstract. The purpose of this study was to analyze the oncological outcomes and
predictive factors for successful curative salvage surgery after recurrent oral cavity
squamous cell carcinoma. A retrospective study was conducted involving 73
patients who received surgery-based salvage treatment. The pattern of failure for
primary treatment was local failure in 29 patients, regional failure in 29 patients, and
loco-regional failure in 15 patients. The 5-year overall, loco-regional failure-free,
and disease-free survival rates were 54.8%, 58.9% and 49.3%, respectively. Patients
with an advanced initial N stage, previous treatment with combined modality
therapy, loco-regional recurrence, advanced recurrent T stage, a disease-free
survival of less than 8 months prior to salvage, and recurrence in a previously treated Key words: oral cavity cancer; recurrence;
field had a significantly worse prognosis. Given the potential surgical morbidity, surgery; prognosis; mortality.
salvage surgery should be undertaken after careful consultation with patients who
have factors for a poor prognosis. Accepted for publication

Recurrence of oral cavity squamous cell
carcinoma (OCSCC) occurs in up to 30%
of patients, with most failures being local
and/or regional recurrences1,2. Local and
regional recurrences remain the most fre-
quent recurrence types in patients with
OCSCC, and the incidence depends pri-
marily on the site of the tumour, clinical
stage, and pathological characteristics.
Despite advances in our ability to safely
treat patients with recurrent cancer of the
upper aerodigestive tract, prior studies
have demonstrated a poor prognosis for
patients with recurrent OCSCC3.
Many of these patients are offered sal-
vage surgery. Although there have been
advances in reconstructive techniques, sal-
vage treatment may result in significant
morbidity, including dysphagia, dysar-
thria, and disfigurement4,5. Considering
the potential morbidity of salvage surgery
and the poor prognosis, clinical factors
indicating which patients would have
more chance of success after salvage

0901-5027/000001+07 ã 2019 Published by Elsevier Ltd on behalf of International Association of Oral and Maxillofacial Surgeons.

Please cite this article in press as: Chung EJ, et al. Clinical outcomes and prognostic factor analysis after salvage surgery for recurrent
squamous cell carcinoma of the oral cavity, Int J Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.ijom.2019.03.967
YIJOM-4266; No of Pages 7

2 Chung et al.

surgery are essential for guiding patients origin). Fifteen of the 23 patients (65.2%) A total of 62 patients (84.9%) under-
regarding salvage surgery. The purpose of who underwent surgery alone as the initial went neck dissection: unilateral in 32
this study was to analyze the oncological treatment were at stage I/II. patients and bilateral in 30. The extent
outcomes and predictive factors for suc- The mean disease-free time was 15.5 of the neck dissection depended on find-
cessful curative salvage surgery after re- months (range 2–98 months). The recur- ings regarding the extent of the disease at
current OCSCC. rent pathological T and N stages (rpT and the time of surgery (Supplementary Mate-
rpN) are summarized in Table 1. The rial, Table S2). Radical or modified radical
pattern of failure for primary treatment neck dissections were performed on 33
Materials and methods was local failure in 29 patients, regional sides of the neck, selective neck dissec-
failure in 29 patients, and loco-regional tions were performed on 32 sides of the
Patient population
failure in 15 patients. The following sur- neck, and extended radical neck dissec-
The study protocol was approved by the gical procedures were performed for the tions (ERND) were performed on 27 sides
Institutional Review Board of the Hallym resection of recurrent OCSCC: wide exci- of the neck. ERND refers to neck dissec-
University Kandong Sacred Heart Hospi- sion via transoral approach in 15 patients, tion with the removal of one or more
tal. The cases of 324 patients who under- pull-through or mandibular lingual release additional lymph node groups or the re-
went surgical treatment for recurrences at approach in 12, paramedian mandibulot- moval of non-lymphatic structures that are
the Ilsong Memorial Institute of Head and omy in 10, mandibulectomy in 10, lateral not ordinarily removed in conventional
Neck Cancer, Hallym University College pharyngotomy approach in three, and neck dissection. These structures should
of Medicine from 1993 through 2014 were maxillectomy in two. Tumour resection be removed for the resection of metastatic
reviewed retrospectively. Patients with was performed via the infratemporal fossa structures, not for the approach to the
head and neck tumours other than squa- approach in two patients. Conventional primary site. The hypoglossal nerve (n
mous cell carcinoma, who underwent pal- neck dissection was performed in 19 = 15) was the most common structure
liative surgery, who presented with a patients. (Supplementary Material, Table sacrificed during ERND. The external ca-
second primary or distant metastases, or S1). For reconstruction of the surgical rotid artery (n = 12) was the next most
who had stomal recurrences were exclud- defect, reconstruction with a free flap (lat- common, followed by lymph nodes (n
ed. Following these exclusions, a total of eral thigh free flap in 15, fibular osteocu- = 9), muscle (n = 9, excluding patients
196 patients remained who had undergone taneous free flap in 9, and radial forearm with resection for the approach), the vagus
salvage surgery for recurrent head and free flap in 7 patients), a pectoralis myo- nerve (n = 5), and skin (n = 5).
neck cancer. The primary tumour was cutaneous (PMMC) flap (n = 14), latissi- Postoperative adjuvant therapy (after
located in the oral cavity in 73 of the mus dorsi musculocutaneous flap (n = 4) salvage surgery) was decided upon at
196 patients (37.2%), in the larynx in 53 and temporalis muscle flap (n = 2) were the multidisciplinary tumour board meet-
(27.0%), hypopharynx in 27 (13.8%), oro- performed. Twenty-two patients under- ing. Surgical treatment was followed by
pharynx in 22 (11.2%), sinonasal tract in went ablation surgery only. postoperative radiation treatment in five
17 (8.7%), and nasopharynx in four
(2.1%). Consequently, 73 patients with
recurrent OCSCC were enrolled in this Table 1. Recurrent T and N stage of patients (n = 73).
study. rN0 rN1 rN2a rN2b rN2c rN3 Total
The original subsite of the primary tu-
rT0 0 3 8 11 2 5 29
mour was the mobile tongue in 48 patients rT1 7 1 0 0 0 0 8
(65.8%), the floor of the mouth in eight rT2 9 1 0 0 0 0 10
(11.0%), the buccal mucosa in six (8.2%), rT3 0 0 0 0 0 0 0
the retromolar trigone in six (8.2%), the rT4 13 3 1 3 6 0 26
gingiva or alveolar ridge in three (4.1%), Total 29 8 9 14 8 5 73
and the lip in two patients (2.7%). The
study group was composed of 49 male
patients and 24 female patients (mean
age 55 years, range 32–76 years). All Table 2. Determination of the optimal cut-off point for defining early versus late recurrence
patients were staged according to the before salvage surgery.
2010 American Joint Committee on Can- 5-year Disease-Free Survival 5-year Overall Survival
cer (AJCC) TNM staging system (seventh
Disease-free time, mo <(%)
(%) pvalue <(%)
(%) pvalue
edition). The tumours were classified ini-
tially as T1 in 16 patients (21.6%), T2 in 4 25.0% 50.7% 0.323 50.0% 58.0% 0.453
36 (50%), T3 in 10 (13.5%), and T4a in 11 5 18.2% 54.8% 0.028* 45.5% 59.7% 0.272
(6.9%). The initial N stages were as fol- 6 25.0% 58.5% 0.001* 50.0% 60.4% 0.077
7 26.9% 61.7% 0.001* 53.8% 59.6% 0.179
lows: 44 N0 (60.3%), nine N1 (12.3%),
8 28.1% 65.9% 0.001* 42.9% 71.1% 0.005*
one N2a (1.4%), 17 N2b (23.3%), two N2c 9 31.4% 65.8% 0.002* 42.9% 71.1% 0.005*
(2.7%). The initial previous treatment con- 10 35.7% 67.7% 0.003* 47.6% 71.0% 0.015*
sisted of surgery alone in 23 patients, 11 37.8% 67.9% 0.005* 46.7% 75.0% 0.008*
surgery and radiotherapy in 33 patients, 12 38.3% 69.2% 0.006* 46.8% 76.9% 0.008*
surgery and chemoradiotherapy in 15 13 38.3% 69.2% 0.006* 46.8% 76.9% 0.008*
patients, and chemoradiotherapy in two 14 40.8% 66.7% 0.016* 49.0% 75.0% 0.018*
patients (referred from another tertiary 15 41.2% 68.2% 0.007* 49.0% 77.3% 0.009*
centre; one with OCSCC in the floor of 16 40.4% 71.4% 0.004* 50.0% 76.2% 0.012*
the mouth and one with OCSCC of gingiva Significant P-values are indicated with an asterisk (*).

Please cite this article in press as: Chung EJ, et al. Clinical outcomes and prognostic factor analysis after salvage surgery for recurrent
squamous cell carcinoma of the oral cavity, Int J Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.ijom.2019.03.967
YIJOM-4266; No of Pages 7

Salvage treatment for recurrent oral cavity SCC 3

patients (6.8%) and chemoradiation treat-
ment in 18 patients (24.7%). Fifty patients
(68.5%) were treated with surgery alone.
Optimal cut-off point for the time to early
vs. late recurrence
The optimal cut-off point for defining
early and late recurrence was determined
on the basis of 5-year disease-free survival
(DFS) and overall survival (OS)6. The 5-
year DFS and OS rates were calculated
using Kaplan–Meier analysis after prima-
ry definitive treatment. The disease-free
time was defined as the period from the
last day of primary treatment up to the
time of confirmed recurrence. The salvage
time was defined as the interval between
the completion of salvage therapy and
recurrence or last follow-up.
Statistical analysis
Patient survival was based on a comparison
of Kaplan–Meier curves by log-rank test.
DFS was measured from the last day of
primary treatment up to the date of recur-
rence confirmed by imaging or pathology,
death, or the last follow-up date if censored.
OS was measured from the diagnosis date
until death from any cause or the last follow-
up date if censored. Cox proportional haz-
ard regression models were used for the
multivariate analysis of survival. A P-value
of less than 0.05 was considered significant.
IBM SPSS Statistics version 23.0 (IBM
Corp., Armonk, NY, USA) was used for
all analyses.
Results
Optimal cut-off point for early vs. late
recurrence
The 5-year DFS and OS rates across vari-
ous cut-off points for tumour recurrence
before the salvage treatment are summa-
rized in Table 2. The cut-off point that
yielded the most significant difference for
the DFS and OS rates was 8 months.
Oncological outcomes and prognostic
factor analysis
The overall success rate was 50.7% (37
out of 73 patients) after salvage surgery

Table 3. Clinicopathological factors influencing disease-free survival.

No. of cases
with recurrence/total P value P value 95% CI for
Parameter cases (DFS) (univariate) (multivariate) HR HR
Age 0.333
<55 years 23/36 (36.1%)

55 years 14/37 (62.2%)
Primary tongue cancer 0.185
No 10/25 (60%)
Yes 27/48 (43.8%)
Initial T stage 0.163
T1-2 25/52 (51.9%)
T3-4 12/21 (42.9%)
Initial N stage 0.034* 0.682 1.179 0.536-2.595
N0-1 25/53 (52.8%)
N2-3 12/20 (40%)
Previous treatment 0.033* 0.4
Surgery alone 7/23 (69.6%) 1
Adjuvant (C)RT after primary surgery 29/48 (39.6%) 2.569 0.262-24.867
Primary CCRT 1/2 (50%) 1.803 0.744-4.371
Pattern of failure 0.018* 0.232
Local recurrence 12/29 (58.6%) 1
Regional recurrence 14/29 (51.7%) 1.673 0.678-4.126
Locoregional recurrence 11/15 (26.7%) 2.727 0.903-8.234
Time to recurrence 0.001* 0.025* 2.250 1.106-4.576
< 8 mo 23/32 (28.1%)

8 mo 14/41 (65.9%)
Recurrent T stage 0.019* 0.203 1.916 0.704-5.216
rT1-2 20/47 (57.4%)
rT3-4 17/26 (34.6%)
Recurrent N sate 0.151
rN0-1 17/37 (54.1%)
rN2-3 20/36 (44.4%)
Salvage treatment 0.609
Surgery + CCRT 8/16 (50%)
Others 29/57 (49.1%)
In-field recurrence 0.049* 0.08 2.744 0.885-8.512
No 5/13 (61.5%)
Yes 32/60 (46.7%)
Close margin 0.030*
(< 5 mm by histopathology)y
No 7/21 (66.7%)
Yes 5/ 8 (37.5%)
Abbreviations: DFS, disease-free survival; HR, hazard ratio; CI, confidence interval; CCRT, concurrent chemoradiotherapy.
*
Values are statistically significant.
y
Margin status included only patients with local failure (n = 29).

Please cite this article in press as: Chung EJ, et al. Clinical outcomes and prognostic factor analysis after salvage surgery for recurrent
squamous cell carcinoma of the oral cavity, Int J Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.ijom.2019.03.967
YIJOM-4266; No of Pages 7

4 Chung et al.

Fig. 1. Kaplan–Meier disease-free survival curves (A and C) and overall survival curves (B and D) according to early vs. late recurrence (A and B)
and in-field vs. out-of-field recurrence (C and D). Abbreviations: DFS = disease-free survival; OS = overall survival; ICT = induction chemo-
therapy; CRT = chemoradiotherapy; SRT = surgery-based therapy.

for recurrent OCSCC. Recurrent disease
developed in 37 patients, with local recur-
rence in five patients and regional recur-
rence in 11 patients. Eight patients had
both local and regional recurrence and 13
patients had distant metastasis. The 5-year
loco-regional failure-free survival
(LRFS), DFS, and OS rates were 58.9%,
49.3%, and 54.8%, respectively.
Various clinicopathological factors
were evaluated to identify significant
prognostic factors. DFS did not differ
significantly according to the location of
the primary tumour, initial T stage, recur-
rent N stage, or modality of salvage treat-
ment. The following patients showed a
significantly better 5-year DFS rate on
univariate analysis: those who presented
with an early initial N stage (52.8% for
N0–1 stage vs. 40% for N2–3 stage, P =
0.034), those who were treated initially
with a single modality of surgery (69.6%
for surgery alone, vs. 39.6% for adjuvant
radiation or chemoradiation therapy after
primary surgery vs. 50% for those treated
with primary chemoradiation therapy, P
= 0.033), those who developed isolated
local or regional recurrence after initial
treatment (58.6% for local recurrence, vs.
51.7% for regional recurrence vs. 26.7%
for loco-regional recurrence, P = 0.018),
those who had late recurrence (recurring at
an interval of more than 8 months after
initial curative treatment) (65.9% for
8
months vs. 28.1% for <8 months, P
= 0.001), those who had an early recurrent
T stage (57.4% for rT1–2 vs. 34.6% for
rT3–4, P = 0.019), and those who had out-
of-field recurrence (61.5% for recurrence
out of the previous treatment field vs.
46.7% for recurrence within the previous
treatment field, P = 0.049). Multivariate
analysis revealed that early recurrence
(hazard ratio (HR) 2.250, 95% confidence
interval (CI) 1.106–4.576; P = 0.025) was
independently associated with worse DFS
(Table 3 and Fig. 1). Margin status signif-
icantly influenced the DFS rate (66.7% for

5 mm vs. 37.5% for <5 mm by histo-
pathological margins, P = 0.03) in
patients who underwent salvage surgery
for local recurrence (n = 29, univariate
analysis) (Table 3).
Patients with an early initial N stage
(60.4% for N0–1 stage vs. 40% for N2–3
stage, P = 0.005), original treatment mo-
dality with surgery alone (73.9% for sur-
gery alone, vs. 45.8% for adjuvant
radiation or chemoradiation therapy after
primary surgery vs. 50% for those treated
with primary chemoradiation therapy, P
= 0.032), those who developed isolated
local or regional recurrence after initial
treatment (55.2% for local recurrence, vs.
65.5% for regional recurrence vs. 33.3%
for loco-regional recurrence, P = 0.004),
those with an early recurrent T stage
(63.8% for rT1–2 vs. 38.5% for rT3–4,
P = 0.006), and patients with out-of-field
recurrence (84.6% for recurrence out of
the previous treatment field vs. 48.3% for
recurrence within the previous treatment
field, P = 0.006) had a tendency towards a
higher OS rate on univariate analysis. On
multivariate analysis, the OS rate was
significantly worse in cases of in-field
recurrence (HR 5.209, 95% CI 1.109–
24.459; P = 0.037) (Table 4 and Fig. 1).
Postoperative complications
The overall rate of postoperative compli-
cations was 28.8% (21 out of 73 patients,
Table 5). Wound infection (n = 15),

Please cite this article in press as: Chung EJ, et al. Clinical outcomes and prognostic factor analysis after salvage surgery for recurrent
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YIJOM-4266; No of Pages 7

Salvage treatment for recurrent oral cavity SCC 5

Table 4. Clinicopathological factors influencing overall survival.

No. of cases
with recurrence/total P value P value 95% CI for
Parameter cases (DFS) (univariate) (multivariate) HR HR
Age 0.333
<55 years 23/36 (36.1%)

55 years 14/37 (62.2%)
Primary tongue cancer 0.185
No 10/25 (60%)
Yes 27/48 (43.8%)
Initial T stage 0.163
T1-2 25/52 (51.9%)
T3-4 12/21 (42.9%)
Initial N stage 0.034* 0.682 1.179 0.536-2.595
N0-1 25/53 (52.8%)
N2-3 12/20 (40%)
Previous treatment 0.033* 0.4
Surgery alone 7/23 (69.6%) 1
Adjuvant (C)RT after primary surgery 29/48 (39.6%) 2.569 0.262-24.867
Primary CCRT 1/2 (50%) 1.803 0.744-4.371
Pattern of failure 0.018* 0.232
Local recurrence 12/29 (58.6%) 1
Regional recurrence 14/29 (51.7%) 1.673 0.678-4.126
Locoregional recurrence 11/15 (26.7%) 2.727 0.903-8.234
Time to recurrence 0.001* 0.025* 2.250 1.106-4.576
< 8 mo 23/32 (28.1%)

8 mo 14/41 (65.9%)
Recurrent T stage 0.019* 0.203 1.916 0.704-5.216
rT1-2 20/47 (57.4%)
rT3-4 17/26 (34.6%)
Recurrent N sate 0.151
rN0-1 17/37 (54.1%)
rN2-3 20/36 (44.4%)
Salvage treatment 0.609
Surgery + CCRT 8/16 (50%)
Others 29/57 (49.1%)
In-field recurrence 0.049* 0.08 2.744 0.885-8.512
No 5/13 (61.5%)
Yes 32/60 (46.7%)
Close margin 0.030*
(< 5 mm by histopathology)y
No 7/21 (66.7%)
Yes 5/ 8 (37.5%)
Abbreviations: OS, overall survival; HR, hazard ratio; CI, confidence interval; CCRT, concurrent chemoradiotherapy.
*
Values are statistically significant.
y
Margin status included only patients with local failure (n = 29).

pharyngocutaneous fistula (n = 6), sepsis
(n = 4), and postoperative bleeding (n = 1)
were the most common complications. A
carotid blowout developed in four patients
(5.5%). The rate of perioperative mortality
(defined as any death within 30 days after
surgery) was 6.8% (five out of the 73
patients died of sepsis or carotid blow out).
Discussion
OCSCC is notorious for a deeply infiltra-
tive nature, as well as significant potential
for occult neck metastasis. Recurrence
rates after initial treatment of OCSCC
are high because of these characteristics
of the tumour1,7. Most head and neck
oncologists agree that salvage surgery is
the primary therapeutic option to offer the
best curative opportunity. However, sal-
vage surgery is quite challenging because
of many factors for the surgeon, as well as
for the patients and their families. The
extensive surgery that is frequently re-
quired may be associated with various
surgical complications, permanent func-
tional losses, significant cosmetic defor-
mities, and even perioperative mortality8.
Approximately half of the patients who
had recurrences after treatment of OCSCC
were not considered adequate surgical
candidates for recurrent lesions, and un-
fortunately, the oncological results of
those patients who underwent salvage sur-
gery were usually poor. However, there
are no clear clinicopathological factors
that predict patient suitability for salvage
surgery in OCSCC. Therefore, it is essen-
tial to adequately identify those patients
who would most likely benefit from sal-
vage surgery.
In a large population data review of
4839 patients with recurrent head and
neck squamous cell carcinoma (HNSCC)
by Chang et al., advanced clinical stage
at first diagnosis, age
65 years, Charl-
son comorbidity index (CCI) score >6,
and a recurrence-free interval of less
than 1 year were significant independent
factors of a poor prognosis9. In a retro-
spective study of 83 patients with recur-
rent OCSCC, Borsetto et al.
demonstrated that the initial stage of
the primary tumour, the stage of recur-
rent disease, history of moderate alcohol
consumption, and close or positive mar-
gins at the initial surgery were four

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YIJOM-4266; No of Pages 7
6 Chung et al.
Table 5. Postoperative complications after salvage surgery of oral cavity squamous cell carcinoma.
Postoperative complication
Wound infection/dehiscence
Pharyngocutaneous fistula
Sepsis
Carotid blow-out
Postoperative bleeding
Other medical problem
Total
independent predictors of overall surviv-
al10. Haque et al. evaluated 73 patients
with recurrent SCC of the oral cavity, aim-
ing to investigate whether the adverse path-
ological features (positive margins,
extracapsular extension of lymph nodes,
lymphovascular invasion, perineural inva-
sion, and multiple node metastases) influ-
enced the survival rate11. The authors found
that the patients with adverse pathological
features at the time of salvage surgery had a
worse prognosis.
In the present study, successful salvage
was significantly associated with factors
such as initial early N stage, initial treat-
ment with surgery alone, isolated local or
regional recurrence, early recurrent T
stage, late recurrence (DFS of
8
months), and recurrence in a previously
untreated field in the univariate analysis.
Regarding the multivariate prognostic fac-
tor analysis, the time interval to recurrence
(HR 2.250, 95% CI 1.106–4.576; P =
0.025) and in-field recurrence (HR
5.209, 95% CI 1.109–24.459; P =
0.037) were independently associated with
worse DFS and OS, respectively.
The timing of recurrence can be a
reliable prognostic factor to predict suc-
cessful surgical salvage for oral SCC.
Kowalski reported that patients who had
a recurrence at an interval of more than
6 months after initial curative treatment
were not usually candidates for curative
salvage surgery12. In contrast, Schwartz
et al. reported that patients who had
recurrence at an interval of more than
6 months had a significantly better sal-
vage success rate13. Koo et al. reported
that patients who had recurrence more
than 6 months after the initial treatment
showed a significantly improved surviv-
al time1. Stell reported that patients who
had recurrence at an interval of more
than 36 weeks after primary radiothera-
py had better survival14. In the present
study, the patients with OCSCC recur-
ring at an interval of more than 8 months
after initial treatment had a better 5-year
DFS rate than those with OCSCC recur-
ring at less than 8 months (65.9% vs.
28.1%).
Please cite this article in press as: Chung EJ, et al. Clinical outcomes and prognostic factor analysis after salvage surgery for recurrent
squamous cell carcinoma of the oral cavity, Int J Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.ijom.2019.03.967
No. of patients Perioperative mortality
15 Septic shock
6 Carotid blow-out
4
4
1
2
21/73 (28.8%)
The patients who had an in-field recur-
rence (recurrence in the treated area) had
worse DFS (64.3% vs. 46.7%; P = 0.029)
and OS (85.7% vs. 48.3%; P = 0.003)
rates in this study. Wong et al. showed
that recurrences in previously dissected
necks were significantly less likely to be
salvaged than were recurrences in undis-
sected necks3. Pearlman reported that
patients who had neck recurrence in pre-
viously untreated N0 necks had the best
chance of successful salvage7. Kowalski
reported that successful salvage was less
likely in patients with a previously treated
neck8. In the present study, patients who
had in-field recurrence experienced poor
DFS (64.3% vs. 46.7%; P = 0.029) and
OS (85.7% vs. 48.3%; P = 0.003).
Initial staging and restaging of recurrent
tumours are believed to be useful to pre-
dict the prognosis following salvage. Agra
et al. showed that restaging after recur-
rence was a significant predictor of im-
proved salvage15. Conversely, Schwartz
et al. reported that the stage of the recur-
rent tumour was not a significant predic-
tive factor9. In the present study, DFS did
not differ significantly by initial T stage
(52.8% vs. 42.9%; P = 0.139) or recurrent
pN stage (55.3% vs. 44.4%; P = 0.115). By
contrast, recurrent T stage (58.3% vs.
34.6%; P = 0.014) and initial pN stage
(53.7% vs. 40%; P = 0.028) were signifi-
cantly associated with poor DFS.
The modality of initial treatment for
the study patients was offered based on
the nature and initial presentation of the
tumour. Therefore, patients with poor
tumour biology (e.g., advanced T catego-
ry), advanced nodal disease, and adverse
pathological features would likely re-
ceive adjuvant radiotherapy or chemora-
diotherapy at the time of initial treatment.
Patients who underwent surgery alone as
the initial treatment had significantly im-
proved DFS (69.6% vs. 41.2%; P =
0.015) and OS (73.9% vs. 47.1%; P =
0.021) than did patients who received
other treatment modalities. Tam et al.2
and Kernohan et al.16 reported that sur-
vival was poor in patients whose cancer
recurred when the initial treatment was
No. of patients
3
2
5/73 (6.8%)
surgery and adjuvant (chemo)radiothera-
py.
The presence of positive surgical mar-
gins at salvage surgery is known to be a
poor prognostic factor for OCSCC17. Re-
garding the 29 patients in this study who
underwent salvage surgery for local recur-
rence, margin status at salvage surgery
significantly influenced the DFS rate
(66.7% for
5 mm vs. 37.5% for
<5 mm by histopathological margins, P
= 0.03). Therefore, resection margin sta-
tus is important and is a potentially pre-
ventable, independent predictor for
salvage surgery.
The surgical salvage rate in this study
was 50.7% after salvage surgery for recur-
rent OCSCC. The 5-year OS, LRFS, and
DFS rates were 54.8%, 58.9% and 49.3%,
respectively. Matsuura et al. reported an
OS rate of 54.7% for 46 patients who
underwent salvage surgery, which was
comparable to those who were considered
disease-free after the first surgical treat-
ment followed by adjuvant treatment
when necessary17. Therefore, they recom-
mended salvage surgery whenever possi-
ble for patients with recurrent oral cavity
cancers, as survival rates were similar to
those of non-recurrent oral cavity cancer
patients, especially when there is no poor
prognostic factor. Tam et al. reported the
survival difference according to a risk
stratification2. The 5-year OS rate was
74% for the low risk patients (those who
received previous surgery alone, with a
mean age at diagnosis of <62 years), 39%
for the intermediate risk patients (those
who received previous surgery alone, with
a mean age at diagnosis of
62 years), and
10% for the high risk group (adjuvant
chemoradiotherapy or radiotherapy after
initial surgery). In the present study, the
DFS and OS rates were 62.5% and 68.8%
for the low risk group, 85.7% and 85.7%
for the intermediate risk group, and 40%
and 46% for the high risk group, respec-
tively (P = 0.026 for DFS and P = 0.045
for OS).
The oral cavity is the most common
subsite of HNSCC. As a result of the rising
incidence and increasing survival, more
YIJOM-4266; No of Pages 7
patients will be enrolled in routine follow-
up programmes. Follow-up in patients
treated for head and neck cancer (HNC)
is aimed at the early detection of recur-
rence, metastases, and second primary
tumours18. However, the evidence base
for follow-up after the curative treatment
of HNSCC in general and OCSCC in
particular is limited19. Therefore, future
research should focus on individually tai-
lored risk stratification and the active role
of the patient’s own follow-up regimen for
the survival benefits of asymptomatic de-
tection in OCSCC.
In conclusion, in this study of 73
patients surgically treated for OCSCC,
the surgical salvage rate was 50.7% (37
out of 73 patients) after salvage surgery
for recurrent OCSCC. Given the potential
surgical morbidity associated with sal-
vage surgery, it should be undertaken
after careful consultation with patients
who have poor prognostic factors, includ-
ing advanced initial N stage, previous
treatment with surgery and adjuvant (che-
mo)radiotherapy, loco-regional recur-
rence, advanced recurrent T stage,
recurrence less than 8 months after initial
treatment, and recurrence in a previously
treated field.
Patient consent
None.
Ethical approval
The study protocol was approved by the
Institutional Review Board of Hallym
University Kandong Sacred Heart Hospi-
tal (approval number KANGDONG 2019-
02-003).
Competing interests
None.
Funding
This research was supported by the Basic
Science Research Program through the
National Research Foundation of Korea
(NRF) funded by the Ministry of Educa-
tion (2017R1C1B2011132) and grant
Please cite this article in press as: Chung EJ, et al. Clinical outcomes and prognostic factor analysis after salvage surgery for recurrent
squamous cell carcinoma of the oral cavity, Int J Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.ijom.2019.03.967
Salvage treatment for recurrent oral cavity SCC
number 03-2017-0270 from the SNUH
Research Fund.
Appendix A. Supplementary data
Supplementary material related to this
article can be found, in the online version,
at doi:https://doi.org/10.1016/j.ijom.2019.
03.967.
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Address:
Young-Soo Rho
Ilsong Memorial Institute of Head and Neck
Cancer
Hallym University
College of Medicine
445 Gil-dong
Kangdong-gu
Seoul 134-701
Republic of Korea
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