20 plus % of patients consulting a general practionner have ENT problems

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.