DOI No.: 10.21176/ ojolhns.0974-5262.2016.10.

MANAGEMENT STRATEGY FOR RECURRENT HEAD AND NECK CANCER

FOLLOWING CHEMORADIATION AND CHALLENGES IN DECISION
MAKING FOR SURGICAL SALVAGE OF LOCO-REGIONAL DISEASE
*D R Nayak, **Suraj Nair, ***Balakrishnan R, ****Asheesh Dora, *****N Apoorva Reddy
Date of receipt of article -04-04-2016
Date of acceptance -2-5-2016
DOI-10.21176/ojolhns.2016.10.1.2
ABSTRACT
Background: Advanced head and neck cancers are often treated with Chemo-radiation (CT-RT) in an attempt
for organ preservation. Loco regional failure following CT-RT is a major challenge for surgical salvage especially
in the neck which constitutes bulk of the cases.
Aim: To determine the salvage strategy for the management of post CT-RT recurrent squamous cell carcinoma
of head and neck region with emphasis on the role of salvage neck dissection with its complications.
Methods: This is a retrospective analysis of 105 cases with post CT-RT recurrent cancer of head and neck from
2005 to 2014. Patients were divided into three groups based on the site of recurrence; primary only (I), primary
with neck (II) and only neck (III). Imaging was done in all cases . Surgical salvage was performed in all patients.
The specimens were assessed for any perineural, peri-vascular, dermal and muscle spread. 3 patients received reirradiation after 1 year.
Results: 36 cases in group I, 28 cases in group II and 41 cases in group III. 1 year disease specific survival rate was
calculated using Kaplan Meier and data analyzed with STATA 13. It was 83.84% for group-I, 56.25% for group
II and 60.8% for group III. Patients in group II and III performed poorly. Extra-capsular spread, muscle invasion,
peri-vascular involvement, peri-neural spread and dermal spread was assessed after salvage surgery.
Conclusions: Post CT-RT patients always have a poor prognosis and especially when associated with neck
recurrence.

INTRODUCTION
Head and neck cancers comprise a major bulk of
economical and social burden in our society1. Many of
these patients are treated with CT-RT as primary
modality owing to better and advanced modalities
available and social stigma of surgery and its
morbidity2,3. There is a dearth of strict guidelines and
protocols for management of these cases specially in
Indian scenario3.Concurrent CT-RT has emerged as a
preferred treatment option and has been shown to yield
tumor response rates that are higher than the other
combinations, while simultaneously achieving the goal
of organ preservation4.
Cases with recurrence at primary can be managed

surgically with conservative procedure like laser assisted

excision or partial surgeries like near total laryngectomy
or full-fledged procedures like total laryngectomy,
hemi-mandibulectomy depending on the extent of
primary disease. Management of neck in patients who
have received CT-RT as primary modality of treatment
with clinically positive neck remains an area of
controversy.
Affiliations:
*Professor,** Resident, Department of ENT-HNS, Kasturba Medical
College, Manipal University, Manipal, Karnataka, India.
Address of Correspondence:
Dipak Ranjan Nayak, M.S.
Professor & Chief of Unit-1, Kasturba Medical College, Manipal-576104
Karnataka, India. E mail: drnent@gmail.com, Mob.: +919880195957

Vol.-10, Issue-I, Jan-June - 2016

Keywords: chemo-radiation, salvage surgery, neck dissection.

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The neck is usually tackled in 3 ways:

1.

Observation and strict follow up in patients who

show a complete or near-complete response to
treatment and have a negative positron emission
tomography (PET) scan.

2.

Planned neck dissection within 6 weeks of CTRT

3.

Salvage neck dissection in all clinically and

radiologically positive neck cases5-10.

The site of the primary tumor and its extent is

also an important factor influencing therapeutic
decision-making, Metastatic nodal disease from tumors
of certain sites like the nasopharynx , tongue base, tonsil
are said to be exclusively sensitive to radiation therapy
with good locoregional control rates. A planned neck
dissection following complete response to CT-RT may
not be particularly beneficial in these patients with these
tumors. Hence, a salvage neck dissection in those with
recurrence is a better accepted approach7-11.The response
of the primary tumor to CT-RT also varies depending
on the site of involvement. Decision making for the
treatment of primary and neck plays a pivotal role in
the overall survival of patient, quality of life and early
rehabilitation and return to normal activities1, 2, 6-11.
MATERIALS AND METHODS:

Vol.-10, Issue-I, Jan-June - 2016

We have enrolled 105 patients with squamous cell

carcinoma of various sites of head and neck (Table-1)
for a retrospective observational study spanning over a
period of 9 years from January 2005 to December 2014.
All the patients had received concurrent CT-RT as the
primary modality of treatment. The patients were
divided into three groups based on the site of recurrence:
primary site only, primary site with neck recurrence
and cases with only neck recurrence during their follow

Table 2: Showing the primary sites.

up period. Average follow up period for each group

was about 22, 13 and 15 months respectively.
Amongst the 105 cases, 36 cases (34.20%) had
recurrence only at primary site, 28 cases (24.76%) were
with recurrence at primary site along with neck nodes
and 41 cases (39.04%) showed only neck disease. All
the patients were examined thoroughly with rigid/
flexible endoscopy and biopsy along with CT/MRI.
Ultrasound guided FNAC for suspected neck disease.
PET-CT was performed by only 17 cases (Fig-1) due
to financial constraints among the patients under study.
Distant metastasis was also evaluated pre operatively
and during their follow up. 13 patients showed
radiological evidence of distant spread during their post

Table-1: Showing year wise distribution of cases( N=105).

Figure 1: PET-CT showing a) left level IIA residual disease b) Pretreatment N3 disease (c) Post-treatment rN2 disease.

10

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maxillectomy (HAPMX), near-total laryngectomy

(NTL) total laryngectomy with partial pharyngectomy
(TL+ PP), total laryngo-pharyngo-esophagectomy
(TLPE) with gastric transposition (GT) and craniofacial
resection (CFR).(Fig-2)
Table-5: shows the number of cases in each group

Figur2: Showing N staging of pre-treatment neck.

A comprehensive neck dissection was performed

in all the patients depending on the primary site and
extent of neck recurrence with relation to pre-treatment
findings (Table-3). Modified/Radical neck dissection
was performed in all N positive cases. The management
of neck is illustrated in (Table-4).
Table 4: [MND: modified neck dissection, RND: radical neck
dissection, FND : functional neck dissection SOND: supra-omohyoid
neck dissection, C/L: contralateral, I/L: ipsilateral, B/L : bilateral]

Patients with Kornofsky score of >80 and

ECOG score >3 are said to better tolerate the
treatment modalities. 3 of our patients were having
Kornofsky grade of <80 while rest were in the above
80 group. 2 cases were above 70 years of age. 4 cases
were found to continue smoking and 3 with persistent
gutka chewing during their follow up. 3 patients with
suspicious positive margin received re-irradiation at 14
months, 16 months and 19 months post primary
radiation following the recent guidelines. Patients with
oncologically unresectable primary, pre operative
distant metastasis, those unfit or unwilling for surgery
were excluded from the study and treated with palliative
chemotherapy and supportive care. The cases are being
followed up in a regular manner to assess the quality
of life and re-recurrences.
RESULTS

The resected specimens were assessed meticulously

for any perineural, perivascular, dermal and myogenic
invasion which had a direct impact on the survival of
the patient. Primary sites of recurrence were surgically
resected with a healthy margin to provide R0 clearance.
It comprised of different approaches to surgical
resection which included Trans-oral laser assisted
resection (TOLR), hemi-mandibulectomy with partial

In our retrospective study, we analyzed 105

clinically and radiologically proven cases of post CTRT recurrent head and neck squamous cell carcinoma
and found 36 cases (34.20%) with recurrence only at
primary, 28 cases (24.76%) with recurrence at primary
site along with neck nodes and 41 cases (39.04%) with
only neck nodal disease. Average follow up period for
each group was about 22, 13 and 15 months respectively.
Surgical salvage was performed in all patients the extent
11

Vol.-10, Issue-I, Jan-June - 2016

treatment follow up period. Neck recurrences were

detected in all N stages and were managed
appropriately. Patients presented as unilateral (62.3%)
or bilateral (37.7%) neck disease in the following manner

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Figure 3 : Kaplan Meier analysis comparing 1 year disease specific

survival of 3 groups.

The patients underwent comprehensive neck

dissection for clearance of neck disease depending on
the N status. Careful histopathological examination
of the specimen by paraffin sectioning was done by
expert pathologists. The lymph nodes were assessed for
extra-capsular spread, perineural and perivascular
invasion. Dermal and muscular invasion was also
assessed. Table 4 shows the case-wise distribution of
the lesions. Most of the cases belong to N2A, N2B and
N3 stage.
Table 6: Histopathological analysis of resected specimens.
Figure-2: a) Trans oral laser resection for recurrent base tongue
cancer. b) Modified neck dissection in progress for a recurrent
supraglottic cancer c) Dermal metastasis following modified neck
dissection.

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of which depended on the post-treatment status of

primary and neck disease.
All the cases which were followed up for 1 year
were considered separately to calculate the 1 year disease
specific survival rate. It was found to be 83.84% for
isolated primary recurrence, 56.25% for primary and
neck recurrence and 60.8% for neck disease using Kaplan
Meier scale. Patients with neck nodal recurrence
performed poorly than those with only primary
recurrence with respect to survival and quality of life.
The mean survival time obtained for group I: 44.87
months, group II: 20 months, group III: 25 months.
Using the combined graph, there is difference in survival
functions between the 3 groups. Log rank test was
performed p= 0.0017(figure 3).
12

During follow up, careful clinical examination,

biochemical and radiologic investigations were
performed keeping the probable sites of metastasis in
mind. Distant metastasis to lungs (7cases), bone (3cases),
Skin (1 Case), spine and liver (2 cases each) were found
during the follow up period. Neck recurrences were

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DISCUSSION:
The management of post CT-RT recurrence
depends on the early detection by vigilant diagnostic
methods and keen methodical clinical judgment. There
is no universally accepted diagnostic technique which
has high sensitivity and specificity for detection of
persistent nodal disease after concurrent
chemoradiation4,5. Post-treatment changes obscure
accurate clinical judgment6. Anatomical diagnostic
imaging techniques such as CT, MRI, and
Ultrasonography, all fall short of consistently and
accurately demonstrating persistent or recurrent tumor
following chemotherapy and radiation4. One has to be
precise in taking biopsy specimens in a previously
treated area since large number of false negative cases
result due to sampling error owing to lack of a proper
demarcation between normal and tumor tissue7. The
benefit with less invasive biopsy techniques such as fineneedle aspiration may be even more doubtful since a
specimen interpreted as negative for malignancy may
still harbour viable tumor4. Previous studies by Wang
et al, Lavertu et al have demonstrated the inadequacy
in evaluation of tumor response by clinical examination
and other diagnostic techniques12-16. The discrepancy
existing between observed clinical response and
histological assessment of tumor persistence is mainly
due to our present inability to distinguish viable tumor
cells from tumor tissue by routine sectioning and
hematoxylin-and-eosin staining13, 14. Hence, a better way
of identifying patients with residual disease who would

benefit from a neck dissection is the need of the hour

15, 16
.
PET-CT is a recent diagnostic modality with better
sensitivity for the detection of recurrence. It involves
assessment by functional imaging with 18Fluorodeoxyglucose (FDG) whose uptake is a
detrimental in differentiating tumor from viable tissue17.
It has been shown to correlate with clinical response to
concurrent CT-RT before, during, and after therapy.
Wong et al reviewed 143 patients with previously
treated head and neck squamous cell carcinoma who
underwent FDG-PET scan to detect recurrent disease
and found this to be a highly sensitive method with a
96% and 72% sensitivity and specificity, respectively17,18.
However, the specificity of PET-CT is low and number
of false positive cases would be more during the
immediate post-CT-RT period 18,19. Greven et al 19
evaluated 45 patients with head and neck cancer by
FDG-PET scan before radiotherapy and serially after
radiotherapy at 1, 4, 12, and 24 months after
radiotherapy and concluded that at 1 month postradiotherapy, the false-negative rate was 28%. The ideal
time to perform FDG-PET scans for the evaluation of
residual disease has yet to be determined, but seems to
be between 1 and 4 months19. Further prospective
studies are necessary prior to the adoption of PET
scanning as the gold standard evaluation of the neck
following CT-RT. Owing to financial constraints; PETCT was done for only 17 cases with the rest undergoing
CT or MRI scan in this study.
Biologic markers such as NEU, HSP27, p53, ki67, and GST may be useful in predicting nodal failure
after chemoradiation20. Given that anatomic imaging
techniques are inferior in identifying residual neck
disease, and that FDGPET is promising but lacks
specificity in the post-treatment setting, new molecular
diagnostic methods represent the future of optimal
patient assessment. Biologic markers such as NEU,
HSP27, p53, ki-67, and GST may be useful in predicting
nodal failure after radical radiotherapy or CT-RT19,20.
Fortin et al found that the presence of NEUoncoprotein and the absence of HSP27 expression were
associated with an increased rate of neck failure in
patients treated with radiotherapy20. These markers may
predict the subgroup of patients who require posttreatment neck dissection. The combination of
molecular markers with functional imaging would
13

Vol.-10, Issue-I, Jan-June - 2016

carefully evaluated and staged as per UICC 2010 guide

lines and were managed with comprehensive neck
dissection. The surgical complications include carotid
blow out(1 case) during the first week after surgery,
mucositis and dysphagia (12 cases), skin hyper
pigmentation (7cases), neck swelling/hematoma(4cases),
chyle leak (4cases) and 3 cases of pharyngo-cutaneous
fistula and 2 cases of osteoradionecrosis of mandible. 3
deaths were noted, one due to carotid blowout and 2
due to non-cancer causes and details were not available.
Viable tumor was higher in patients who had a lessthan-complete response to CT-RT compared with those
who had a complete response. Better survival rates were
observed in cases with negative neck disease. The cases
are being followed up and the survival rates and
prognosis of the patients are being further
contemplated.

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expand the horizons in view of early clinical detection

and thereby allowing significantly improved assessment
of the post treated neck20.
Neck dissection in a post-irradiated neck is
challenging and the ultimate aim is to maximize the
probability of achieving regional control. Patients with
low-volume (N1) neck disease have very high rates of
control in the neck. Risk of neck failure is steadily
associated with increasing neck node stage and tumor
burden. Parson et al reported better neck control rates
in patients with N2 and N3 disease treated with
radiotherapy followed by neck dissection than
radiotherapy alone21.With other studies as done by
Dubrey et al22, One can conclude that planned neck
dissection contributes to neck control in unselected N2
and N3 patients treated with radiation or
chemoradiation22. Recurrent (rN1) disease has better
prognostic outcome. Recurrent Neck staging (rN2-rN3
status) is an important prognostic indicator of poor
survival with propensity for distant metastasis.
Performance scale of patients is also detrimental to the
overall wellbeing of the patient. Patients with
Kornofsky score of >80 and ECOG score >3 are said
to better tolerate the treatment modality. 3 of our
patients were having Kornofsky grade of <80 while
rest were in the above 80 group.

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Table 7: Guidelines for selection of patients 23-25

Several studies like the one by McHamm et al 26

have shown that patients with a complete response to
CT-RT clinically and radiologically may have
microscopic residual disease in the neck which makes
planned neck dissection a viable option. Similarly,
Stenson et al27 analyzed 69 patients with advanced-stage
head and neck cancer that underwent a neck dissection
within 5 to 17 weeks of primary concurrent CT-RT of
which 35% had microscopic residual disease that was
not correlated with clinical or radiological response.
Only one patient had recurrent disease in the neck after
neck dissection, emphasizing the importance of neck
dissection after CT-RT to remove residual viable
tumor. Wanebo et al28 reported a series of 43 patients
treated with concurrent CT-RT for advanced stage head
and neck squamous cell carcinoma. A planned neck
dissection was performed 3 to 4 weeks after the
completion of CT-RT among patients with clinically
N1-3 nodes prior to therapy, 9 (31%) of 29 had residual
node involvement at neck dissection and none of these
patients had failure in the neck. These studies suggested
that neck dissection plays a vital role in optimizing
tumor control in such group of cases. The presence of
clinically positive nodal disease in neck dissection
specimens after concurrent CT-RT has been found to
correlate with neck recurrence and survival probability.
Lavertu et al12 evaluated 53 patients with N2/3necks
who had planned neck dissections after concurrent CTRT. He concluded that pathologically positive neck
disease was associated with a worse survival in most of
the studies. Some studies like Strasser et al15suggested
that many of the pathologically positive necks did not
contain viable cancer cells and that continued cell kill
occurs for several weeks or months after CT-RT. These
findings reiterated the importance of timing of neck
dissection and the interval between chemo-radiation and
neck dissection because cell death continues to occur
for many weeks following completion of treatment.
Recurrence at the primary site needs separate
mention in management since the role of conservative
laser assisted surgery is still controversial and is much
dependent on the surgical expertise and accurate
assessment of the extent of lesion. Radical procedures
like hemi-mandibulectomy with partial maxillectomy,
total laryngectomy with partial pharyngectomy, near
total laryngectomy, total-laryngo-pharyngo-

14

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Patients treated with CT-RT are at high risk of

developing complications after neck dissection owing
to poor local tissue healing capacity in irradiated neck,
poor vascularity, prior positive node with extracapsular spread, adhesions to surrounding tissues,
difficulty in detecting viable tissue from tumor tissue,
pre-treatment micro-metastasis, CT-RT resistant
clones26,27. Common complication encountered after
neck dissection in these patients are wound infection
and dehiscence with fistula formation, bleeding and
hematoma, chyle leak, sialadenitis, injury to major
vessels and Spinal accessory nerve, Greater auricular
nerve, Vagus nerve and cervical and brachial plexus with
comorbidities 27. Early recognition with adequate
conservative management techniques before surgical
intervention should be routinely followed.
Re-irradiation as an additional modality of
treatment is gaining grounds in recent times. We had 3
cases with positive margin on resection which were reirradiated with 50 Gray (5 fractions per week) for 4-6
weeks at 14 weeks, 16 weeks and 19 weeks post-primary
radiation respectively in accordance to the principle of
not re-irradiating within 1 year of primary
radiotherapy. The dosage of radiation depends on the
tumor volume, type and amount of primary radiation
exposure29. The performance status of the host and comorbidities along with tumor factors play an important
role in overall survival and response to treatment. It is
generally advised to undertake re-irradiation at the
center where initial radiation therapy was undertaken30.
IMRT has enabled use of higher targeted dosages while
reducing the complications at the same time31. Mucositis,
hyper-pigmentation of skin and dysphagia are noted
in 2 cases. No major complication noted in any of the
3 patients after re-irradiation.

surgical challenge and requires adequate training and

experience. Treatment of recurrent primary site lesion
remains controversial, especially with high-volume
nodal metastases. The role of imaging techniques such
as FDG-PET scan, biomarkers and stringent follow up
with a curious eye is mandatory in this setting32. It is
noted that cases with nodal recurrence with or without
primary involvement have poorer survival rates and
response to treatment than those with only primary
recurrence. Re-irradiation +/- chemotherapy following
salvage resection may improve disease free survival and
locoregional control but not the overall survival.
Considerable progress needs to be made in developing
more reliable means of detecting recurrent disease in
the treated neck and more reliable biologic markers of
response to CT-RT are under research. Until our
ability to predict and detect recurrence in the treated
neck improves, it seems prudent to recommend a
planned neck dissection for all patients treated with
CT-RT for high-volume neck disease33,34. Surgical
resection of the recurrent primary site and neck disease
needs expertise and vigilant post-operative care to
identify the potential complications as early
management can prevent a catastrophe.
Acknowledgement : We are thankful to Professor
Ashok Shenoy for his kind informative advise related
to the article and Melissa Glenda for statistical analysis.
DISCLOSURES
(a)
(b)
(c)
(d)

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Competing interests/Interests of Conflict- None

Sponsorships - None ,
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