CLINICAL REVIEW David W.

Eisele, MD, Section Editor

INDICATIONS FOR RADIOTHERAPYAFTER NECK DISSECTION
Primoz Strojan, MD,
1
Alo Ferlito, MD, DLO, DPath, FRCSEd ad hominem,
FRCS (Eng, Glasg, Ir) ad eundem, FDSRCS ad eundem, FHKCORL, FRCPath, FASCP, IFCAP,
2
Johannes A. Langendijk, MD, PhD,
3
Carl E. Silver, MD
4
1
Department of Radiation Oncology, Institute of Oncology, Ljubljana, Slovenia
2
Department of Surgical Sciences, ENT Clinic, University of Udine, Udine, Italy. E-mail: a.ferlito@uniud.it
3
Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, The
Netherlands
4
Departments of Surgery and OtolaryngologyHead and Neck Surgery, Albert Einstein College of Medicine, Monteore
Medical Center, Bronx, New York
Accepted 29 July 2010
Published online 10 November 2010 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/hed.21599
Abstract: Up-front surgery and postoperative radiotherapy
constitute a well-recognized treatment concept for locally or
regionally advanced squamous cell carcinoma of the head and
neck. This treatment package is further intensied with the
concomitant application of chemotherapy during irradiation
when high-risk features (ie, microscopically involved resection
margins, extracapsular extension of the tumor from neck
nodes, the presence of soft tissue deposits) are found on his-
topathologic examination of a resected specimen. With regard
to neck disease, however, the demarcation line between low-
and higher-risk clinical situations, which would differ with
respect to the need for postoperative radiotherapy, is not
clear. In an attempt to dene the low-risk characteristics of
disease in the neck that do not require adjuvant irradiation, we
reviewed the available literature reports for any direct or indi-
rect evidence on the value of postoperative radiotherapy in
various clinical scenarios. The number of positive lymph nodes
found in a dissected tissue specimen that should be used as a
cut-off point for introduction of postoperative radiotherapy
was evaluated in the context of both primary tumor characteris-
tics and type of neck dissection. V VC 2010 Wiley Periodicals,
Inc. Head Neck 34: 113119, 2012
Keywords: neck dissection; postoperative radiotherapy; squamous
cell carcinoma; head and neck; regional control
Several retrospective studies have persuasively con-
rmed that the combination of initial surgery and
postoperative radiotherapy (PORT) yields signi-
cantly improved rates of locoregional tumor control as
well as an overall survival benet in squamous cell
carcinoma of the head and neck (SCCHN).
1
The con-
cept of a multimodal approach in the treatment of the
primary tumor and neck has gained wide acceptance
and has become a well-recognized pattern of practice
in head and neck oncology.
Considerable efforts have been invested in explor-
ing the indications for combined therapy. In 2 phase
III cooperative randomized trials conducted in Europe
and the United States,
2,3
extracapsular extension
(ECE) of nodal disease and the presence of tumor at
the surgical margins were identied as the most det-
rimental prognostic indicators for locoregional control
and disease-free survival, justifying intensication of
PORT with the addition of concomitantly applied
chemotherapy.
4
In practice, the same applies to the
soft tissue deposits in the neck other than those rec-
ognized as ECE. These deposits may represent clusters
of metastatic tumor cells from completely destructed
lymph node, without any residual lymphatic tissue visi-
ble at histopathologic examination or, alternatively,
they may represent tumor emboli within the vascular
system that became lodged in a lymphatic or vascular
space and continued to grow there.
5
Although supported by less evidence, adjuvant
chemoradiation protocols seem to yield a gain when
other disease characteristics, that put the patient at
increased risk for disease reappearance, are present.
These include stage III or stage IV disease, perineural
inltration, vascular embolisms, and involvement of
level IV or level V nodal basins in patients with oral
cavity or oropharynx primary tumors without ECE or
a positive margin. Conversely, the risk level in
patients with 2 positive lymph nodes without capsu-
lar penetration and with adequate surgical margins
seems to be only modest and does not present an indi-
cation for concomitant chemotherapy.
4
Other studies have provided data on risk-level
stratication, which are generally complementary to
the results of the aforementioned analyses,
613
although it was suggested that the prognostic impor-
tance of individual prognostic markers may vary
across different tumor sites in the head and neck.
14
Correspondence to: A. Ferlito
This article was written by members of the International Head and Neck
Scientic Group.
V VC
2010 Wiley Periodicals, Inc.
Indications for Radiotherapy After Neck Dissection HEAD & NECKDOI 10.1002/hed January 2012 113
At the other end of the risk spectrum, the
demarcation line between low-risk clinical scenarios
requiring only 1 treatment modality (ie, surgery or
radiotherapy) and those with higher risk, which should
be managed by a combined approach, is not clearly
dened. In the present report, we review the existing
evidence on the use of PORT against surgery alone in
the lower-risk setting, limiting the discussion and con-
clusions to neck disease. The number of positive lymph
nodes found in a dissected tissue specimen that should
be used as a decision-making criterion for the introduc-
tion of PORT is discussed and evaluated in the context
of both primary tumor characteristics and type of neck
dissection.
STATUS OF NODAL DISEASE
PORT for Multiple Positive Neck Nodes. The con-
cept of combined treatment in SCCHN evolved empiri-
cally, as did the indications for PORT. On the basis of
these developments, in 1992 Peters et al
15
at MD
Anderson Cancer Center reported on a scoring system
for assessment of risk for recurrence in the neck after
previous surgery (and a separate one for the primary
tumor). The criteria used for categorizing patients into
different risk groups in this system were based on the
authors best estimate of the relative importance of dif-
ferent clinicopathologic factors in disease control above
the clavicles, as documented in reports of surgical se-
ries. For the neck, they recognized 5 criteria: number
of involved nodes and nodal groups, size of the largest
positive node, ECE, and invasion of neighboring
structures. Analysis of prognostic factors predictive of
locoregional recurrence showed that the only variable
of independent signicance was extracapsular nodal
disease. However, clusters of 2 or more of the follow-
ing putative risk factors were associated with a pro-
gressively increased risk of recurrence: oral cavity
primary, mucosal margins close or positive, nerve
invasion, 2 positive lymph nodes, largest node >3
cm, treatment delay >6 weeks, and Zubrod perform-
ance status 2.
The results of a subsequent study on PORT from
the same institution were reported by Ang et al.
8
Of
the 213 patients with SCCHN included, they identi-
ed 31 who had no adverse pathologic factors with
regard to neck disease as characterized by Peters et
al,
15
ie, with only 1 positive node <3 cm in maximal
diameter and without ECE found in their dissected
tissue specimens. This group received no PORT and
at 5 years the actuarial locoregional control achieved
with surgery alone was comparable to that observed
in patients from the intermediate-risk group (patients
with 1 adverse feature other than ECE) who received
57.6 Gy PORT, and was signicantly superior com-
pared with the high-risk group (ECE or 2 other
adverse factors) treated with 63 Gy PORT: 90% ver-
sus 94% versus 68%, respectively (p .003).
There are several other reports supporting the cri-
teria developed in the studies from the MD Anderson
Cancer Center for identication of high-risk disease
that should be treated with a combined approach. In
1982, Snow et al
16
reported virtually no difference in
neck recurrence-free rates between pN0 (n 76) and
pN1 (n 81) patients with SCCHN with no ECE
treated solely with radical neck dissection. More than
90% of patients in both groups were free of neck recur-
rence at 5 years. These patients represented a subset
of 405 patients treated from 1960 to 1970. Similarly, in
1985 DeSanto et al
17
found no difference in recurrence
in the neck at 2 years between 33 irradiated (23%)
and 187 nonirradiated patients (20%) with pN1 disease
(ECE status not specied) who underwent modied
radical neck dissection between 1970 and 1980. In
1987, OBrien et al
18
described treatment results in a
group of 98 modied radical neck dissections per-
formed in 86 patients with SCCHN. Among 12
patients with 1 histologically positive lymph node, only
1 recurrence occurred in the ipsilateral neck; ECE was
also present in that patient. However, no difference in
ipsilateral neck failure rates was observed in OBriens
series between irradiated and nonirradiated patients
with positive nodes (4/22 vs 4/16), although patients in
the former group tended to have more aggressive dis-
ease. Moreover, in 10 pN1 and ECE-negative patients,
Medina and Byers
19
found only 1 recurrence within
the dissected side of the neck after supraomohyoid dis-
section compared with 0/8 in the postoperatively irra-
diated group. When multiple positive nodes or ECE
were recorded in the dissected specimen, adjuvant
radiotherapy reduced the neck recurrence rate from
24% of patients (5/21) to 15% of patients (6/41). Like-
wise, Traynor et al
20
reported no neck failure in 11
pN1 patients who underwent selective neck dissection;
however, no details on ECE or, subsequently, on the
use of PORT, which was implemented in such cases,
were provided for these patients.
In 1996, Barzan and Talamini
21
reported on a se-
ries of 705 patients who underwent a total of 1097
neck dissections from 1976 to 1993. Briey, all but
those with clinically N0 neck and laryngeal or hypo-
pharyngeal primary tumors, who had selective dissec-
tions, underwent comprehensive neck dissection.
Only patients with >2 positive nodes without capsu-
lar rupture and those with ECE, irrespective of the
number of involved neck nodes, were also irradiated
postoperatively. Among 120 patients with pN1 and
ECE-negative disease, the regional recurrence rate
was only 6.7%. In multivariate analysis, an overall
number of positive nodes of >1 was predictive of a
higher nodal recurrence rate. The authors concluded
that a multidisciplinary approach might be suggested
for 2 node positive neck disease.
In a more homogeneous group with regard to the
primary tumor site and stage of the disease, Wolfens-
berger et al
22
found surgery alone an adequate treat-
ment for early-stage squamous cell carcinoma (SCC)
114 Indications for Radiotherapy After Neck Dissection HEAD & NECKDOI 10.1002/hed January 2012
of the oral cavity (pT12) with a maximum of 1
lymph node involved (pN01) and no capsular rup-
ture, provided that the resection margins were free of
tumor. Only 3 ipsilateral neck recurrences appeared
in 72 patients who had neck dissection, whereas in 11
patients with bilateral neck surgery, and in those 85
not treated contralaterally, the number of contralat-
eral neck failures was 0 and just 2, respectively.
In an unknown primary tumor setting, several
authors have emphasized that there is no need for
PORT when 1 neck node is inltrated with tumor
cells and there is no ECE present. Coster et al
23
reported a dissected neck recurrence rate of 15% of
patients (2/13, 4 cases with ECE) and 25% of patients
(1/4, 2 cases with ECE) for pN1 and pN2a disease,
respectively. In a series of 82 patients reviewed by
Iganej et al,
24
25 patients were diagnosed with pN1/
pN2a disease without ECE. Ultimate tumor control
above the clavicles was 81% in surgically treated
patients (13/16) and was 89% for patients (8/9)
treated by a combined approach. Furthermore, none
of the 5 patients with pN1 disease reported by Patel
et al
25
experienced neck recurrence, even though 4 of
those patients had undergone a single-modality
approach and only the one with ECE received PORT.
In 2008, more selective criteria for PORT were
used by Gourin et al.
26
In 337 patients with clinically
N0-staged SCCHN who underwent elective neck dis-
section, PORT was administered when 3 nodes were
found inltrated with tumor cells pathologically, as
well as to patients with involvement of multiple neck
levels, ECE, and adverse pathologic primary tumor
features (76% of patients overall). The use of PORT
was signicantly associated with improved disease-
free survival (p < .0001) and regional control at 5
years (p .0014) only when 3 nodes were involved,
but not in patients with <3 positive nodes. It should
be noted that a subgroup of patients without ECE, the
most powerful negative prognostic indicator, was not
analyzed separately.
In 2000, Hosal et al
27
reported regional recurrence
rates after 300 selective neck dissections in 210
patients, clinically classied N0, for pathologically node-
negative and node-positive necks without ECE of 3%
and 4%, respectively. However, the regional failure rate
was only 2% in 58 necks with up to 2 positive nodes,
whereas 2/4 necks containing >2 positive nodes failed
regionally. It is worth noting here that no distinction
was made between ECE-negative and -positive cases in
the later analysis. The authors concluded that ECE and
multiple nodal involvement should be considered
markers of the biological aggressiveness of the disease
and used to identify patients at high risk of recurrence,
requiring adjuvant therapy.
Favorable experience with PORT used for similar
indications (ie, 3 positive nodes and ECE) was also
reported by Chepeha et al
28
in a group of 52 patients
with SCCHN who had 58 selective neck dissections
with at least 1 positive node of 3 cm found in a tis-
sue specimen. In addition, the use of PORT in a pN1
setting was not supported by the results presented by
Schmitz et al.
29
In a subset of 39 patients (of 163
patients with 281 selective neck dissection proce-
dures), regional control rates in patients who were
postoperatively irradiated (2/21) or treated solely with
surgery (1/18) were 9.5% and 5.5%, respectively,
although the data were not specied with regard to
ECE status.
The adverse impact of a high number of positive
nodes (4 against 13) on neck control was conrmed
with multivariate analysis by Olsen et al
30
in a large
retrospective review of 284 patients with pN12 neck
disease treated solely with surgery. ECE was recorded
in 120 of 144 patients for whom this characteristic
could be determined. However, because of the rather
poor neck recurrence-free survival in the pN1 group
(76% at 5 years), this study theoretically supports set-
ting the criterion for implementation of PORT all the
way down to a single positive node.
PORT for Pathologic N1 Neck. Several studies sug-
gested that the presence of a single positive node in a
neck dissection specimen already warrants PORT. In
this case, in particular, the presented evidence must
be considered along with the type of neck dissection
performed.
In 1990, Leemans et al
31
reported on the efcacy
of treatment of metastatic neck nodes relative to the
histopathologic ndings of 565 comprehensive neck
dissection specimens in a series of 495 patients with
SCCHN. They received PORT when 3 positive nodes
or ECE were found in the specimen. Because no dif-
ference in the neck recurrence-free survival was
observed between nonirradiated patients with 1 to 2
histologically positive nodes without ECE and other
patient groups that did receive adjuvant radiotherapy,
the authors were prompted to consider giving PORT
to every patient with histologically positive nodes,
irrespective of their number or ECE status.
In 1996, Spiro et al
32
reported on 287 patients
with predominantly oral cavity primaries (in 82%)
treated with supraomohyoid neck dissection. PORT
was administered to all patients who were found to
have metastases in cervical lymph nodes on patho-
logic examination; virtually the same incidence of
neck failure was recorded in pN0 necks (5%) and pN-
positive necks (7%). Likewise, analyzing a group of
363 patients with SCCHN who underwent 517 selec-
tive neck dissections, Byers et al
33
found the regional
recurrence rate in the dissected eld reduced roughly
by half when PORT was used, and advised the use of
PORT for all cases with even a single node found to
be invaded with cancer, irrespective of ECE status.
Specically in the pN1 setting with or without ECE,
neck recurrence rates for irradiated and nonirradiated
patients were 5.6% and 35.7% (12/36 vs 5/14, p .0137),
respectively.
Indications for Radiotherapy After Neck Dissection HEAD & NECKDOI 10.1002/hed January 2012 115
In the 1990s, the Brazilian Head and Neck Cancer
Study Group
34
conducted a prospective randomized
study of elective modied radical versus supraomo-
hyoid neck dissection in cT24N0 oral cavity SCCs.
In that study, PORT was implemented for pathologi-
cally classied N1 necks. The prevalence of ipsilat-
eral neck recurrences was 12% and was 5% in the
nondissected contralateral side, with no difference
between the 2 treatment groups. No details with
regard to the neck failure rates were provided for
pN0 and pN cases.
More indicative were the results reported by Kolli
et al,
35
who evaluated treatment outcomes in 69
patients with SCCHN, who underwent 84 supraomo-
hyoid neck dissections. Although there was no statis-
tically signicant difference in neck failure rates in a
subset of 15 patients with pN1 disease (but unspeci-
ed ECE status) when irradiated and nonirradiated
groups were compared (1/5 vs 4/10, p .35), a recur-
rence rate of 40% in the neck after surgery without
PORT made the authors hesitant to advocate surgery
alone in patients with pN1 disease. Yet, the favorable
effect of adjuvant radiotherapy on regional control in
20 patients with pN2 disease was highly signicant
(1/15 vs 4/5, p .005). A comparable conclusion was
presented by Schiff et al,
36
who reviewed a series of
220 patients with SCC of the oral tongue. In a cohort
of 50 patients with pN1 neck disease, 47 underwent
selective neck dissection; 40 patients did not have
ECE. In a comparison of patients who received PORT
with those only observed, 0/17 and 2/23 patients (p
.32), respectively, experienced ipsilateral regional recur-
rences. The authors concluded that patients with pN1
disease without ECE may also benet from PORT.
Extensive evaluation of efcacy of selective node
dissection in elective and therapeutic treatment of the
neck in 503 patients with SCCHN undergoing 711 pro-
cedures was reported by Ambrosch et al.
37
A trend
was observed toward an improved 3-year neck recur-
rence rate in postoperatively irradiated patients with
pN1 necks (3% vs 6.3% for surgery only) and distinctly
improved regional control for pN2 disease (7% vs 24%).
As many as 82% of patients with ECE had PORT.
The value of PORT in patients with SCCHN with
pN1 disease without ECE was addressed by Ja ckel et
al
38
in 2008. The authors conducted a detailed analy-
sis of 167 neck dissections (165 were of selective type)
performed in 118 patients, of whom 46 patients (39%)
received PORT and 22/46 patients also received con-
current platinum-based chemotherapy. Altogether, 8
isolated nodal failures occurred: 1 of 46 patients from
the combined-therapy group and 7 of 72 patients who
had surgery alone. In the latter group, 4 of the re-
gional failures occurred in contralateral necks, of
which 3 were not previously dissected. The 3-year
neck recurrence rate for nonirradiated and irradiated
patients was 11.2% and 2.9% (p .0921), respectively.
PORT exerted no effect at all with regard to overall
survival. The same results were observed when
patients with pT1 and pT2 disease, to whom adjuvant
radiotherapy would normally not be recommended,
were analyzed.
In 2010, Chen et al
39
retrospectively reviewed a
homogeneous group of 59 patients with SCC of the
oral tongue with pathologic T12N1 disease. These
patients were treated with wide excision of the tongue
primary tumor and selective or modied neck dissec-
tion, in accordance with the clinical status of the
neck. In 28 patients, PORT was administered,
whereas the others were only observed. Neck recur-
rence was diagnosed in 7/31 patients (22.6%) and 2/28
patients (7.1%) observed and postoperatively irradi-
ated patients, respectively, and tended to occur later
in the group with PORT (18 vs 14 months). Further-
more, in the observed patients all 7 regional recur-
rences occurred in the ipsilateral neck, whereas in
the PORT group both regional failures appeared in
the contralateral neck. On multivariate analysis, only
PORT (hazard ratio [HR] 0.17, p .01) and ECE
(HR 7.56, p .03) were signicant predictors of
disease-free survival. To explore the effect of PORT in
pN1 disease in more details, patients with ECE, posi-
tive margins, and lymphovascular or perineural inva-
sion were excluded, leaving 20 patients who received
and 19 who did not receive PORT for comparison.
The 5-year disease-free survival rates in the 2 groups
were 95% and 54.7% (p .019), respectively, and
overall survival rates of 92.5% and 54.9% (p .015),
respectively. The authors concluded that the presence
of even a single lymph node metastasis may be indic-
ative of more aggressive tumor behavior, which
makes the tumor more difcult to control.
In 2008, extensive analysis of the SEER (Surveil-
lance, Epidemiology, and End Results) database has
conrmed the benecial effect of PORT of an approxi-
mately 10% absolute increase in 5-year cancer-specic
survival and overall survival for patients with lymph
node positive SCCHN compared with surgery alone.
40
More detailed analysis revealed that node-positive
patients benet from PORT, irrespective of the site of
the primary tumor (oropharynx, hypopharynx, larynx,
or oral cavity) or the nodal stage. At all nodal stages,
including pN1, PORT appeared superior to surgery
alone.
41
In 2010, in early SCC of the oral cavity, the
impact of PORT in the pN1 setting was questioned in
a recent study by Shrime et al.
42
In a group of 1539
patients with pT12N1 classications identied in
the SEER database, PORT was associated with statis-
tically signicant improved cause-specic and overall
survival in the T2 subset, most strongly in the oral
tongue and the oor of the mouth.
Conclusions Regarding Indications for PORT in the
pN1 Neck. A perusal of the preceding 2 subsec-
tions indicates discrepancies in conclusions of individ-
ual studies regarding the indication for PORT,
particularly in patients with minimal cervical node
116 Indications for Radiotherapy After Neck Dissection HEAD & NECKDOI 10.1002/hed January 2012
involvement. In this respect, it is noteworthy that
multiple factors may differ among neck dissection
specimens classied as pN1. These include number of
dissected nodes, presence of ECE, and size of the posi-
tive node. Furthermore, the studies cited differ in the
criteria used for PORT in pN1 necks, as well as a va-
riety of other factors that may produce selection bias.
With regard to the latter issue, the level of evidence
produced by the particular study is based on its
design and is of paramount importance. Randomized
prospective studies would produce the highest quality
of evidence, but despite the length of time that PORT
after neck dissection has been in use, such studies
are lacking.
A meticulous review of the studies cited earlier
would lead, despite occasional discrepancies, to the
conclusion that 2 positive nodes and the presence of
ECE are adverse prognostic factors that are counter-
acted favorably by the addition of PORT to the treat-
ment regimen. However, it is not clear from these
studies whether ECE is an independent variable, or
whether it tends to occur mostly in association with
multiple node metastases. Metastases of 3 cm in
size are classied N2 or higher, where there is far
less dispute as to the indication for PORT.
Characteristics of the Primary Tumor. Well-recog-
nized indications for PORT related to the characteris-
tics of the primary tumor as determined at
histopathologic examination of a resected tissue speci-
men are positive (<1 mm) or close (<5 mm) surgical
margins, perineural tumor spread, vascular emboli,
and tumor size.
1,4
With the exception of the last,
these factors specically increase the risk for local tu-
mor reappearance and requests for adjuvant irradia-
tion of the primary tumor bed only. However, in an
attempt to adequately irradiate all tissue(s) at risk
for tumor cell residues around the resected primary
tumor, and taking into account all possible uncertain-
ties, including movements of different origin and the
physical characteristics of photon beams, irradiation
portals designed to target the primary tumor bed usu-
ally cover at least the adjacent lymph node region(s)
on the neck. However, the recent introduction of
highly conformational intensity-modulated radiation
therapy with image guidance to further improve pre-
cision of targeting of predened tissue volume might
substantially reduce this effect, although not com-
pletely. Because the pattern of lymphatic drainage in
the neck is rather predictable, lymph node groups
irradiated in conjunction with the primary tumor are,
as a rule, those with the highest probability for har-
boring occult metastases.
To the contrary, the size of the primary tumor per
se determines the frequency of neck node metastases,
with the distribution pattern in the neck character-
ized by its site of origin. It is generally accepted that
in clinical scenarios with an estimated risk of occult
lymph node metastases exceeding 20%, elective treat-
ment to the neck, whether up-front surgery or radio-
therapy, is indicated
43
; however, other authors have
suggested that this threshold be lowered to 15%.
44,45
Incidence gures based on the results of clinical rec-
ognition of the palpable cervical metastases reported
by Lindberg
46
and supplemented by data from a large
series of neck dissection specimens were summarized
by Medina.
47
Accordingly, because of the propensity
to metastasize to the lymph nodes of >20%, treatment
of a clinically negative neck is warranted for all but
T1 tumors of the oral cavity, whereas for glottic
tumors, the neck should be treated only in T4-classi-
ed lesions. However, all patients with primary tumors
arising in the oropharynx, hypopharyx, or supraglottic
larynx should have their necks treated electively. Both
surgery and irradiation are effective in this setting.
48,49
The decision as to which to use is usually driven by the
treatment of the primary lesion.
In this regard, there might be some exceptions.
First, in patients with well-lateralized tumors without
pathologically involved nodes, the target volume of
subsequent radiotherapy can be conned to the ipsi-
lateral neck. In the recent study by Vergeer et al,
50
the untreated contralateral neck control at 5 years af-
ter surgery (of the ipsilateral neck only in 83% of
patients) and unilateral PORT was 99% and 88% for
pN0 and pN12a cases, respectively, and was 73% for
N2b cases. To the opposite, the question as to whether
the PORT target volume can be conned to the pri-
mary site only remains to be answered, although it
could be suitable in well-selected cases, such as for
those with pathologically N0 ipsilateral necks.
Extent of Neck Surgery. For successful treatment of
disease in the neck, 2 additional factors, besides its
pathohistologically determined characteristics, are of
importance: the extent of neck dissection and the
quality of the performed surgery. Whereas selective
neck dissection is considered an appropriate option in
a clinically negative neck when compared with a
more comprehensive surgical procedure,
33,48,51
in the
case of clinically positive node(s), the available evi-
dence on the adequacy of limited neck surgery does
not allow a clear answer.
49
Typically, in N0-classied oral cavity primaries,
metastases, when found pathologically, are located in
regions IIII, whereas those from oropharyngeal,
hypopharyngeal, and laryngeal SCCHN tend to
appear along the jugular chain, ie, in regions IIIV.
No difference in the distribution pattern of metasta-
ses in the neck was observed between patients who
underwent elective and therapeutic neck dissections;
however, spread of the disease into an extra level (or
levels) was noticed in patients with clinically positive
nodes.
52,53
Furthermore, whereas the phenomenon of
skip metastases, bypassing the orderly pattern of
progression in the neck, is not commonly observed in
SCCHN, in tumors originating in the oral cavity, the
Indications for Radiotherapy After Neck Dissection HEAD & NECKDOI 10.1002/hed January 2012 117
reported incidence of skip metastases reached
15.8%.
54,55
Thus, the high neck-control rates for sub-
clinical disease achieved after administration of elec-
tive radiotherapy in patients with clinically classied
N0 disease
48
intuitively leads clinicians to implement
PORT if they do not feel comfortable with the extent
of the performed surgical procedure, when either the
type of dissection or the thoroughness of the clear-
ance of individual neck compartments is in question.
In practice, this results in more frequent imple-
mentation of PORT in patients who have undergone
more limited regional dissection, even though the dis-
ease burden described at the histopathologic examina-
tion would be comparable to that found after
comprehensive neck dissection. However, the correc-
tive potential of PORT, which allows clinicians to
compensate for eventually insufcient surgery in a
low-risk setting when compared with adequate neck
dissection, was not evaluated in a prospective
manner.
CONCLUSIONS
What risk is low enough to allow for safe avoidance of
PORT to the neck? At the moment it is unclear where
to draw a decision line. The only well-characterized
indication for adjuvant irradiation of the dissected
neck is ECE, for which the PORT should be supple-
mented with concomitantly applied chemotherapy.
The number of nodes involved with cancer that
requires a combined approach has yet to be deter-
mined. In accord with the available evidence, the
most pressing questions for scientic evaluation
would be whether PORT is indicated in cases of mul-
tiple nodes or pN1 disease. Particularly in view of
more recent reports, specically questioning the value
of PORT in the pN1 setting and in the absence of
ECE,
38,39
PORT seems to be of benet for disease con-
trol in the neck when a single node of <3 cm with no
ECE has been found to be positive. Similarly, exten-
sive analyses of the SEER database have revealed
that implementation of PORT in the pN1 setting
could have a survival advantage.
4042
However,
because these studies suffer from all of the limitations
inherent in retrospective analyses, including diversity
in primary tumor types, disease stages, and treat-
ment procedures performed, prospective appraisal of
this question is essential.
According to Moergel et al,
56
who recently pre-
sented a design for a prospective multicenter random-
ized control clinical trial, this question will soon be
properly addressed. Under well-described guidelines
for surgical procedures and subsequent PORT,
patients with early-stage (pT12) oropharyngeal and
oor of mouth SCC with a singular ipsilateral lymph
node metastasis (pN1) without ECE will be randomized
after radical surgery to one of the 2 treatment arms (ie,
PORT/no PORT). The primary endpoint in this study
will be overall survival with a strong emphasis on qual-
ity-of-life issues evaluated in the context of secondary
study objectives. Because the aim of the authors is to
provide a basis for general treatment recommendations,
which are currently lacking in this subset of patients
with SCCHN, results are eagerly awaited.
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