Otolaryngology beyond Laser and Scalpel W. Mann Almaty Dec 2012 Dept. of ORL-HNS, Mainz Medical School, Germany
Jan 23, 2016
Otolaryngology beyond Laser and
Scalpel
W. Mann
Almaty Dec 2012
Dept. of ORL-HNS,
Mainz Medical School, Germany
20 plus % of patients consulting a generalpractionner have ENT problems
Otolaryngology today
Infections and tumors of the ears, nose, throat and head and neck
Problems with hearing, speech, smell and deglutition
Neurootology for vestibulo-cochlear disorders
Endocrinology for thyroid disease
Facial reconstruction after trauma
Cosmetic surgery including skin tumors and vascular lesions
As a consequence otolaryngologist today must be:
Diagnostician including ultrasound, CT-scan and MRI Neurophysiologist Endoscopist Immunologist Microbiologist Oncologist Therapist Surgeon
HNSCC
approx. 600 000 new cases/year
WorlwideUSAEU
France
8161837
Yearly rate per 100 000inhabitants
Malignant Head and Neck Tumors
Mostly squamous cell carcinomas
Etiology: alcohol, tobacco,
HPV 16/18
B A
HNSCC incidence and mortality in Europe
Oropharynx Larynx
FrankreichSpanienBelgienItalien
PortugalLuxemburg
Europäische UnionGriechenland
DänemarkÖsterreich
Niederlande
DeutschlandGroßbritannien
SchwedenFinnland
25 20 15 10 5 5 10 15 20 250
Männer FrauenFrankreichLuxemburg
DeutschlandItalien
Europäische UnionSpanienPortugalBelgien
DänemarkÖsterreichSchweden
FinnlandIrland
GroßbritannienGriechenland
50 40 30 20 10 10 20 30 40 500
Männer Frauen
Inzidenz
Mortalität
Niederlande Irland
Therapy
Standard: surgery and/or radiotherapy
or: neoadjuvant chemotherapy
radiochemotherapy
antibodies
salvage surgery
Therapy
In breast, gastric and rectal tumors,
neoadjuvant chemotherapy is new goldstandard,
increasing R0-resection, progression free
survival and overall survival.
Hypopharyngeal carcinoma
before after 3 cycles TPF
Overall survival
Primary surgery VALSG OS (2J): 68% EORTC 24891 OS (3J): 43%, OS (5J): 32,6%
NeoadjuvantVALSG OS (2J): 68%EORTC 24891 OS (3J): 57%, OS (5J): 38%RTOG 91:11 OS (2J): 76%, OS (5J): 55%GORTEC 2000-01 OS (3J): 60%Mainz study OS (2J): 78%
Overall survivalMainz study
HPV infection
While HPV infection in females with
cervical carcinomas yields better
prognosis, this is still debated in head & neck tumors.
Role of histologic clear margins
pt
1 cm2 cm
CGH-analysis of primary tumors
2 3 4 5 6 7
8 9 10 14 15
16 17 18 19 20 2221
13
1
2 4 12 19
6 10 15 16
4 9 16 17 19 69 14 12 19
3 5 12 13 14 22
6 9 19 20
8 11 15 16 17
9 11 13
5 14 20 9 13 6 10 16 22
4 206 7 18
10 12 13 16 17
12
3 5 8 10 13 14 15 16 19 20 22
3 4 6 7 15 18 19
3 4 6 7 14 15 18 22
4 19
18
9 12 19 20
10 21
12 16 19
17 20
1 5 6 5 16 17 21 20 222
2 4 5 7 19 20 212211
18
2 9 16
7 19
13
7 156 10 21
19
7 9 121 4 16 19 20 22
10
1 5 8 10 13 15 16 18 21
17 3 4 19 20
11
The vast majority of gains and losses observed at 1 cm distance were also present in the
corresponding primary tumors.
2 3 4 5 6 7
8 9 10 11 14
16 17 19 20 2221
13
1
12 19
10
4 19 612
5 12
6
1112
3 5 15 20
3
3 16
4
12
10 21
12
4 7 9 19 20
4 7
7 196 10
12
10
5 10 13 15 21
4 19 20
15
18
Imbalances on 3q26 in 2cm
Yellow: gains not previously detected by CGH
D3S3689 D3S3575 D3S1268
D3S3886
D3S3712 D3S1614 D3S3715 D3S3565 D3S3609 D3S1580 D3S1601
3q25.31 3q25.32 3q26.1 3q26.1 3q26.2 3q26.32 3q26.33 3q27.2 3q28 3q28Primer
3q26.1
Locus
3q26.1
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
Imbalances are frequently observedImbalances are also seen at 2 cm distance by LOH-analysis, while no gains or losses were detected by CGH-analysis!
The increasing role of biomarkers in oncology
HER-2/new
K-RAS
BRAF
MAP-Kinase
EGFR
Alk
Erbitux
Iressa
Avastin
Cetuximab for the therapy of HNSCClocoregional control and overall survival
Bonner et al, New Engl J Med 2006
P< 0.05 P< 0.05
+ 20 months+ 9.5 months
Cetuximab
Cetuximab is relevant for head and neck
tumors independent of EGFR expression
when given together with
chemo- or radiotherapy
K-RAS
K-RAS mutation is of prognostic relevance only
in colo-rectal tumors while not in head and
neck cancer.
K-RAS
K-RAS negative, so called wild-type tumors
respond to Cetuximab with better prognosis.
BRAF
BRAF mutations in papillary thyroid carcinomas
are indicators of poor prognosis, while in
anaplastic thyroid carcinoma (70% BRAF
positive) BRAF inhibitors may be
beneficial.
BRAF
BRAF mutation in melanoma is predictive for
good response to Vemurafinib, however
because of fast development of resistance
it has to be combined with Kinase-inhibitors.
BRAF
Although BRAF mutations are „negative“
they offer further therapeutic options.
Laser and scalpel remain essential
surgical tools in otolaryngology,
however they have to be seen
in the framework of recently
developed therapeutic strategies.