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6th ICHNO
6
th
ICHNO Conference
International Conference on innovative approaches in Head and Neck Oncology
16 – 18 March 2017
Barcelona, Spain
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propensity for infiltrating adjacent tissues, mostly by
perineural invasion. Combined with frequent origin in
anatomical sites with difficult access, the surgeon is
frequently disappointed following the attempted clear
margin resection. A University of Michigan study reported
80% of skull base AdCC resection specimens with positive
surgical margins, despite the preoperative impression that
resection with clear margins would be possible
(Naficy,1999). The latest trend is thus against super-
radical surgery that still frequently fails to achieve
negative margins. In this line, for parotid AdCC, there is
consensus to preserve a normally functioning facial nerve,
relying on RT to deal with residual microscopic disease
(Vander Poorten,2012).Historically, a low prevalence of
occult nodal metastasis in AdCC is assumed. Neck
dissection is classically only performed for cN+ disease,
which is infrequently encountered. For specific MiSG
subsites (oral cavity-oropharynx), recent scrutinized
literature appraisal of “elective neck dissection (END)
specimens” suggests a higher rate of occult metastasis,
ranging from 15 to 44%, (Suarez, 2016) and especially in
AdCC with high-grade transformation, lymph node
metastasis may occur in 43–57% of patients
(Hellquist,2016), suggesting to reconsider the role of END
in these patients. It remains unclear, however, whether
regional control, let alone survival, is improved by
performing END as compared to primary RT to the neck
nodes.
Salvage surgery
Local salvage surgery is rarely feasible and indicated(Spiro
2013). When local recurrence occurs, frequently distant
metastasis (DM) is imminent. In the MSKCC database of 191
patients with recurrent SGC only 2 of 22 patients with
locally resectable disease were effectively salvaged.
Generous radical surgery should be considered and almost
invariably patients will need flap reconstruction (free
flaps, but frequently pedicled flaps like the MPM are a
sound option in extensively operated and radiated necks).
There are retrospective data that re-resection followed by
chemo-reirradiation gives better DFS in those selected for
surgical
salvage(Pederson,2010;
Erovic,2010).
Prognostic
factors
In general, prognosis of AdCC is poor and the experience
of many authors is that ‘‘cure is never achieved’’ in
this‘‘clinically high grade’’ neoplasm. Disease-related
deaths occur for as long as patients are followed. One
series reports an overall survival of 24.5% and a
recurrence-free survival of 22.6% at 15 years.
(Huang,1997). In the posttreatment setting, the
appearance of DM determines long term prognosis. In one
study, on average, death occurred at 32 months following
the occurrence of lung metastases and at 21 months
following metastases elsewhere (van der Wal,2002).
The most important clinical factor is TNM stage at
presentation, which is closely linked to the site of origin
(Spiro and Huvos,1992;Vander Poorten,2000). Remarkably
early stage disease can do well, with T1N0 tumors being
reported with 10, 15 and 20 years DSS of 94%, 81% and 73%
respectively, and T2N0 already doing significantly worse
(DSS 50%, 40% and 33% at 10, 15 and 20 years,
respectively). As stated above, nodal metastases can be
histopathologically detected when the primary tumor is
surgically removed together with a neck dissection.
Metastases are often small, which may explain why clinical
examination or imaging may fail to detect them.
Histological prognostic factors are tumor grade and
perineural/intraneural invasion. Tumors showing a
predominantly “solid” growth pattern have been
repeatedly associated with worse prognosis, advanced
stage and development of DM. PerineuraI invasion has
been inconsistently associated with DM and adverse final
outcome. In this respect, recently, a prognostically
relevant distinction has been made between perineural
(P2: no impact on survival) and intraneural invasion (P1:
independent
predictor of
poor
prognosis).(Teymoortasch,2014;Amit,2015)
Among molecular biological factors with prognostic
relevance are (1) cell cycle-based proliferation markers
(high Ki-67, PCNA, MCM and AgNOR expression), and
specific genetic and epigenetic changes in (2) growth
factor receptor proteins and ligands(c-KIT, VEGF-
C/VEGFR-3, Eph2a, EGFR, NGF), (3) cell cycle oncogenes
(cyclin D1, SOX-4, SOX-10, NFκB, PI3K, STAT3 and mTOR),
(4) DNA damage repair proteins (p53), (5) cell adhesion
proteins (loss of E-cadherin expression, ICAM-A, increased
expression of Ezrin and ILK), (6) estrogen receptors, (7)
lymphangiogenesis markers (podoplanin) and (8)
transcription factors. Most notably the reciprocal
translocation t(6;9) (6q22–23; 9p23–24), fusing the MYB
gene on chromosome 6q22–q23 and the transcription
factor NFIB on chromosome 9p23–p24, has recently been
associated with prognosis in AdCC.
SP-040 Radiotherapy in adenoid cystic carcinoma (ACC)
of the head and neck
A. Jensen
1
1
University of Munich, Radiation Oncology, Munich,
Germany
Abstract text
Adenoid cystic carcinoma (ACCs) is a rare disease with an
incidence of 1.3/100,000 per year. Many patients are
diagnosed with advanced tumours, especially when these
are located in the paranasal sinus, hence both surgical and
radiotherapy treatments remain a challenge. Standard
treatment consists of complete resection followed by
adjuvant radiotherapy in the presence of risk factors. Due
to their aggressive local growth patterns, high radiation
doses are needed to achieve long-term local control. In
standard photon radiotherapy though, this can be difficult
to achieve faced with close proximity of critical structures
at the base of skull. Neutron radiotherapy for salivary
gland malignancies was explored in the early 1980s due to
its increased biological effectiveness and did indeed
demonstrate superior local control rates. Long-term
toxicities however, were substantial. Due to their physical
properties, charged particle beams can achieve highly
conformal dose distributions through sharp dose gradients
thereby leading to improved normal tissue sparing
especially at complex anatomical sites. In consequence,
the use of particle therapy and especially carbon ion
therapy (C12) for adenoid cystic carcinoma has been
intensively investigated by both Japanese and European
groups. Recent analyses showed significantly improved
control and survival rates in patients treated with a
combination regimen of C12 plus IMRT. Results were
confirmed by the prospective COSMIC trial and validated
in a larger patient cohort. Moreover, control rates did not
differ according to resection status in patients with T4
tumours treated C12. Therefore, debulking surgery with
sometimes substantial morbidity may have to be
reconsidered. Management of local recurrence following
full course radiotherapy also presents a problem in ACC.
When surgery is not feasible, the most active
chemotherapeutic regimen can achieve response rates of
between 40-50%. Due to the physical beam properties, re-
irradiation with charged particles and comparatively high
re-irradiation doses can be feasible and achieves response
rates of >50% with moderate toxicity. However, further
dose escalation needs to be considered carefully as the
risk of higher-grade late toxicity increases. Particle
therapy is also a good option to treat patients with locally
recurrent disease, when surgery may not be feasible.
In summary, particle therapy is a good treatment option