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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
__________________________________________________________________________________________
Human papillomavirus-related (HPV+) oropharyngeal
cancer is a rapidly emerging disease in many countries
that differs from tobacco-related and alcohol-related
(HPV–) oropharyngeal cancer. HPV+ oropharyngeal
carcinoma is now established as a distinct biological
entity, being prognosis significantly superior than HPV
negative
tumor.
Some studies suggest that Trans Oral Radical Surgery
(TORS) achieves excellents outcomes with less toxicity.
Published clinical trials and published clinical data
comparing TORS and RT will be presented and discussed
as well as the most important ongoing trials.
Poster: Multidisciplinary management
PO-050 The interplay between all-trans-retinoic acid
and radiotherapy in inducing cancer stem cell arrest
L.G. Marcu
1
, D. Marcu
1
1
University of Oradea, Faculty of Science Department of
Physics, Oradea, Romania
Purpose or Objective
Head and neck cancer stem cells (CSC) display a number
of properties that lead to treatment failure. Conventional
treatment techniques are unsuccessful in long-term
tumour control due to radioresistance of CSCs and their
ability to regrow the tumour. Therefore, more targeted
therapies are needed. A CSC targeting agent is all-trans-
retinoic acid (ATRA) that was shown to induce CSC
differentiation, cell cycle arrest and apoptosis in head and
neck cancer cell lines. However, the limited data available
in the literature indicates that the effect of ATRA is cell
line dependent, as it can induce cell arrest in either G
1
or
G
2
phase. The aim of this work was to investigate the
interplay between ATRA and radiotherapy and to assess
the phase-specific treatment outcome.
Material and Methods
A hierarchical in silico head and neck cancer model has
been developed using Monte Carlo techniques. The tumour
contains cancer stem cells, differentiated cells and
quiescent cells with varying radioresistance. The pre-
treatment CSC population given by the model is 5.9%,
which changes during treatment. The tumour was treated
with hyperfractionated radiotherapy (1.2 Gy twice daily,
5 days a week, 7 weeks) given the higher locoregional
control obtained as compared to conventional
fractionation. Radiotherapy (RT) was simulated using the
Linear Quadratic model and the properties of ATRA were
implemented based on literature data.
Results
The model showed that with cell arrest in G
2
, the effect
of ATRA combined with radiotherapy leads to a dose
reduction of 28% for the same killing effect as
radiotherapy as a sole agent. However, with G
1
arrest
cellular response is substandard, requiring an increase in
dose of 11.7% as compared to radiation treatment. With
larger ATRA doses, when the dual effect of cell arrest and
apoptosis was simulated, both G
1
and G
2
arrests led to a
significant decrease of total dose required to control the
CSC population (see table 1).
Table 1. The cell cycle phase-dependent effect of ATRA +
RT
on
tumour
kill
Conclusion
CSC-targeting agents play a critical role in the future of
head and neck cancer treatment. While ATRA shows
promising early results, it needs more investigations in
determining the cell cycle phase-specific arrest for each
histopathological tumour type, as well as more
quantitative studies to establish the threshold values
required for its full potential. While both G
1
and G
2
phase
arrests can lead to improved results when combined with
radiotherapy, the model showed that the overall outcome
is phase-dependent.
PO-051 A 7-year overview on advanced nasopharynx’s
cancer: features influencing survival outcomes
A. Nogueira
1
, M. Teixeira
1
, L. Khouri
2
, F. Branquinho
1
, P.
Jacinto
1
1
Coimbra's Portuguese Institute of Oncology, Oncology,
Coimbra, Portugal
2
Coimbra's Portuguese Institute of Oncology,
Radiotherapy, Coimbra, Portugal
Purpose or Objective
Our aim was to assess population characteristics,
treatment safety and efficacy, PFS, OS and prognostic
value of population and treatment’s features.
Material and Methods
Retrospectively, we analyzed patients treated for
advanced nasopharynx’s cancer (stage III, IVA and IVB)
from January 2009 to December 2015, in one institute.
Clinical files enquiry were revised and SPSS analysis
(Kaplan Meier’s method) used for survival analysis.
Results
All 33 patients, 33.3% females and 66.7% males, had a
median diagnosis age of 47 years (15-74 years) and a good
performance status (ECOG 0 or 1). History of tobacco and
alcohol use was present in 51.5% and 36.4%, respectively,
and 39.4% had history of occupational exposure. Epstein
Barr DNA test was positive in 21% of them.
Histological study revealed undifferentiated carcinoma in
81.8% of cases. Tumors were classified as stage III (45.4%),
IVA (27.3%) and IVB (27.3%).
In this population, 84.8% underwent concomitant
chemoradiotherapy with cisplatin 100 mg/m
2
3/3 weeks.
Of those, 32.1% received the 3 planed cycles.
Radiotherapy dose was 70.2 Gy/33Fractions/6.5 weeks.
69.7% of patients underwent adjuvant chemotherapy with
5-FU and cisplatin with a median of 2 cycles, mostly with
dose reduction. Major acute toxicities were grade 3/4
neutropenia (26%), grade 3 mucositis (13%), nausea and
vomiting (8.7% and 4.3%, respectively) and anemia (8.7%).
There were major infectious complications in 33.3%.
We observed a complete response in 48.3% of patients,
partial response in 44.8%, stable diseases in 3.4% and
progression in 3.4%.
1 year and 5 year PFS was 72.2% and 46.4% respectively.
Infectious complications had a negative correlation with
PFS (p<0.0001) and adjuvant chemotherapy had a positive
correlation (p = 0.019).
1 year and 5 year OS was 84.3% and 42.6% respectively.
Infectious complications and weight loss had a negative
correlation with OS (p<0.0001 and p=0.004, respectively)