1. The International Federation
of Head and Neck Oncologic Societies
Current Concepts in Head and Neck Surgery and Oncology 2012
Malignant Tumors
of the
Paranasal Sinuses and Skull Base
Dan
M
Fliss

2. Epidemiology
• Incidence 1:200,000 (USA)
• 3% of H&N malignancies
• Male predominance 1.8:1
• Age: 55-69 years
• Common histology: SCC (51%)
• Common site: Nasal cavity (44%),
2012
maxillary sinus (36%)
Turner et al. Head and Neck 2011

3. Risk Factors
• Environmental/Occupational
Aflatoxin, formaldehyde, chromium,
nickel, mustard gas, polycyclic
hydrocarbons, mesothorium
(Thorotrast), wood dust (AdenoCa)
• Smoking (SCC)
• Smoked food
2012 • HPV 6,11,18 (inverted papilloma)
Luce et al. Int J Cancer 1993 Katori et al. Eur J Surg Oncol 2005

4. Histology
• Epithelial (70-80%)
– SCC, verrucous ca, adenoCa, ACC, acinic cell ca,
mucoepidermoid ca, SNUC
• Neuroectodermal
– Melanoma, ENB, Ewing sarcoma/PNET
• Mesenchymal
– MFH, fibrosarcoma, RMS, osteosarcoma, chondrosarcoma,
angiosarcoma, hemangiopericytoma
2012
• Other
– Lymphoma, plasmacytoma, metastasis (RCC #1)

5. Clinical Presentation
• LATE
• Nasal (50%)
– Obstruction, bleeding, mass, sinusitis
• Oral (25-30%)
– Loose teeth, trismus, pain
• Ocular (25%)
– Proptosis, diplopia, epiphora
• Facial
– Distortion, anesthesia V2
2012
• Skull Base/Brain
– Headache, CN palsy -> anosmia

6. Clinical Examination
• Facial symmetry, sensation (V2)
• Eye
– Ocular motion, globe position, proptosis
• Ear
– Eustachian tube dysfunction, SOM
• Oral
– Trismus, ulcer/bulging, loose teeth
• Nose - FO endoscopy
2012
• Neck – LN enlargement

7. Preoperative Evaluation
• Endonasal endoscopy
• CT- Axial, coronal, contrast, 3D
• Bone erosion
• MR - Contrast, fat suppression
• Inflammatory vs. neoplastic
• Angiography, balloon occlusion
test, embolization
• Biopsy
2012

8. Preoperative Evaluation
PET-CT
• TNM Staging
• Residual disease
• Recurrence
• Second primary
2012 Gil and Fliss et al. Head and
Neck 2007

9. Preoperative Evaluation
PET-CT
• PET/CT offers accurate staging for skull base
neoplasms
• Accurate preoperative staging can change
treatment modality and prevents unnecessary
procedures in patients with distant metastases
• During follow-up PET/CT enables early detection
of tumor recurrence, guides biopsies and allows
selection of proper treatment
2012
Gil and Fliss et al. Head and Neck 2007

10. Staging
Ohngren s Line
2012

11. AJCC TNM Staging 2011
Maxillary Sinus
2012

12. AJCC TNM Staging 2011
Ethmoid Sinus and Nasal Cavity
2012

13. AJCC TNM Staging 2011
Neck and Distant Sites, Prognostic
Groups
2012

14. Treatment
• Surgery
• XRT
• Chemo
• Combinations
No
RCTs
available
2012

15. Levels of Evidence
2012

16. Factors Influencing Treatment
Choice
• Histology
• Stage
• Resectability
• Reconstruction
• Surgical expertise/
multidisciplinary team
• Comorbidity
2012

17. Management Radiation Tx
Technology:
• Stereotactic
• Proton/Neutron
• IMRT
– Intensity-modulated radiotherapy enables to create concave dose
distributions allowing better sparing of the optic structures without
compromising the dose in the target volume and local control
2012
Duthoy et al.
Cancer 2005

18. Radiation Tx Outcome
• Most patients get XRT (64%)
• Definitive XRT (single modality):
– 5y local control 43%
• Better as an adjuvant to surgery
– 5y local control 84%
– 5y overall survival 67%
2012
Mendenhall et al. Laryngoscope 2009 Hoppe et al. Radiat Oncol Biol Phys 2008

19. Radiation Tx
Who Benefits from
Adjuvant XRT ?
T1-2
T3-4/N1
T4/M1
2012
Turner et al. Head and Neck 2011

20. Radiation Tx
Side Effects
• Risk for acute toxicity •
Risk
for
blindness
• Other chronic toxicity
– Osteoradionecrosis
– Frontal lobe necrosis
– Panhypopituitarism
2012
Duthoy et al. Cancer 2005
Mendenhall et al. Laryngoscope 2009

21. Management
Chemotherapy
• Adjuvant chemotherapy
Chemotherapy employed after the primary tumor has
been removed by surgery
• Neoadjuvant chemotherapy
Initial use of chemotherapy in order to decrease the
tumor burden prior to treatment by other modalities
2012

22. Management
Chemotherapy
Meta-analysis of chemotherapy in head and neck cancer - 93 RCTs
and 17,346 patients
2012
Bourhis et al. Rad Oncol 2009

23. Chemotherapy in Sinonasal Ca
Adjuvant Systemic
• n=35, T4b unresectable tumors
• Cisplatin + XRT -> No surgery
• Poor outcome: 5y OS 15%
Hope et al. Radiat Oncol Biol Phys 2008
• n=15, T3-T4
• Induction cisplatin+5FU -> Surgery ->
5FU+hydroxyurea + XRT
• Good results: 10y DFS 65%
2012
Lee et al. Cancer J Sci Am 1999

24. Chemotherapy in Sinonasal Ca
Preoperative Intra-arterial (1)
• n=74, T2 T3 T4, maxillary sinus
• Multimodality: Preoperative XRT 50
grey + IA 5FU
• Then partial/total maxillectomy
• Good results: 5y OS 53%
5ys 53%
2012
Hayashi et al. Cancer 2001

25. Chemotherapy in Sinonasal Ca
Preoperative Intra-arterial (2)
• Concomitant preoperative XRT 50
grey + IA cisplatin
• Then CFR/ maxillectomy
• n=19, T3 T4
• Good results: 5y OS 53%
5ys 53%
2012
Samant et al. Archives 2004

26. Surgery Approaches
• Open
– Lateral rhinotomy/
Combinations
– Coronal
– Midfacial degloving
– Per-oral
– Facial translocation
– Subcranial /CFR
– Orbitozygomatic
• Endoscopic
• Combined
2012

27. Surgery Skin Incisions
1. Lateral Rhinotomy
2. Weber-Fergusson
3. WF + Lynch
4. WF + Subciliary
5. WF + Subciliary +
Supraciliary
2012

28. Surgery Type of Maxillectomy
1. Medial maxillectomy
2. Infrastructure
maxillectomy
3. Total maxillectomy
+- Orbit
4. Extended
maxillectomy
5. Bilateral
2012 maxillectomy
6. Subcranial / CFR

29. Surgery Reconstruction - Goals
Function
• Oral competency
• Clarity of speech
• Mastication
• Tactile sensation
• Globe support
Cosmesis
• Restoration of bony framework
• Soft tissue contour
2012

30. Surgery Reconstruction – Soft
Tissue
• Free flaps
– Rectus abdominis
– Lateral thigh
– Latissimus dorsi
– Radial Forearm
– Tensor fascia lata
– Osteocutaneus Fibula
• Temporalis muscle
system
• Fascia lata /
temporalis fascia
• Nasolabial flap
2012

31. Surgery Reconstruction – Bone
• Obturator
• Titanium mesh
• Bone grafts
– Calvarial
– Iliac
• Free flaps
– Fibula
– Scapula
– Iliac crest
• Septal
2012
cartilage

32. Maxillary
Defect
Type
1 Type
2 Type
3 Type
4
Prosthesis
So@
Assue
Free
flap
Prosthesis Orbital
floor
Prosthesis
Atanium
+-­‐
coated
2012
Brown et al. Lancet Oncology 2010

33. Surgery
Management of the Orbit
2012
Weizman, Fliss et al. Arch. Otol. (in press)

34. Surgery
Reconstruction of the Orbit – Partial Resection
2012
Weizman, Fliss et al. Arch. Otol. (in press)

35. Surgery
Reconstruction of the Orbit - Exenteration
2012
Weizman, Fliss et al. Arch. Otol. (in press)

36. Management of the Neck
• n=704, malignant tumors, maxillary and ethmoid,
T1-T4
• Low frequency of nodal involvement at diagnosis
Ethmoid tumors: 1.6% , Maxillary tumors: 8.3%
• Nodal status at baseline affects survival
s
• Risk for regional recurrence:
High Risk Low Risk
Site Maxillary (12.5%) Ethmoid (4.3%)
T-Stage T2 (18%)
Histology SCC (21%)
2012
ElecAve
ND
for
T2+
Maxillary
SCC
Cantu et al. Archives 2008

37. Management of the Neck
• Multicenter, n=146, oral (palate, alveolus) maxillary
SCC, T2-T4 N0
• Frequency of nodal involvement at diagnosis: 15%
• Overall rate of nodal involvement:
• N0 managed by observation only: 14.8% regional
2012 failure (only 53% were salvaged)
• N0 managed by neck dissection/XRT: n/a al. Head and Neck 2011
Montes et

38. Management of the Neck
• n=139, oral maxillary
SCC, T1-T4
• Frequency of nodal
involvement at
diagnosis: 8.6%
• Regional failure among
N0 patients: 29.5%
(34%) were salvaged
• Predictors of failure: T-
stage
2012
Morris et al. Head and Neck 2011

39. Management of the Neck
• A subgroup of high risk
patients:
Maxillary sinus, SCC/SNUC,
T2-T4
• High regional failure rate:
36%
• Reduced to 7% if ipsilateral
2012
neck is radiated
Bristol et al. Int J Radiat Oncol Biol Phys 2007
Hoppe et al. Int J Radiat Oncol Biol Phys 2008

40. Outcome Factors Influencing
Survival
• Site Nose > maxillary >
ethmoid
• T stage T1 > T4
• Histology AdenoCa > SCC > SNUC
• Subsite analysis – tumor extension associated
with reduced survival:
– Maxillary tumor: PPF
2012
– Ethmoid tumor: Cribriform, dura, brain, sphenoid
– Nasal tumor: Nasal floor
Dulguerov et al. Cancer 2001

41. Outcome Factors Influencing
Survival
Site
Histology
N+ / M+ Treatment
DSS
2012
Dulguerov et al. Cancer 2001
Turner et al. Head and Neck 2011

42. Skull Base Surgery Definition
• Skull base surgery is the interdisciplinary approach to
lesions afflicting those areas of the deep facial structures
that abut the undersurface of the cranium
• Requires a multidisciplinary approach:
– Head & Neck surgeon
– Neurosurgeon
– Plastic and Reconstructive surgeon
– Maxillofacial surgeon
– Neuroradiologist/interventional arteriographer
– Neuro-ophthalmologist
– Anesthetist
2012
– Pathologist

43. Multidisciplinary Team
2012

44. Skull Base Surgery Indications
• Tumors approaching or involving the skull base
• Intracranial tumors with extracranial extension
• Neurovascular tumors
2012

45. Evolution of SB Surgery
QOL
Adjuvant
therapy
Minimally
Invasive
Surgery
Evidence
based
medicine
Aggressive
approaches
Learning
of
surgical
skills
2012
1970
1980
1990
2000
2010

46. Evolution of SB Surgery The Future
MulA
center
clinical
trials
Broader
PopularizaAon
indicaAons
for
of
surgical
endoscopic
surgery
techniques
AdopAon
of
?
novel
targeted
Tx
from
other
Narrowing
New
tools
H&N
cancers
indicaAons
for
minimally
trials
for
open
surgery
RoboAc
surgery
invasive
surgery
?
?
2010 2020
2012

47. SBS Techniques Craniofacial
Resection
2012
Ketcham et al. Am J Surg 1963

48. SBS Techniques The Subcranial
Approach
2012
Fliss et al. Laryngoscope 1999
Fliss et al. Operative Tech 2000

49. The Subcranial Approach
Combinations
• Subcranial with mid-facial degloving
2012
Fliss et al. J Oral Maxillofacial Surg. 2000
Fliss et al. Arch Otolaryngol Head Neck Surg 2007

50. The Subcranial Approach
Combinations
• Subcranial with pterional approach
2012
Fliss et al. Operative Tech 2000

51. The Subcranial Approach
Reconstruction
2012
Fliss et al. Neurosurg Focus 2002
Fliss et al. Skull Base 2007
Gil and Fliss et al. Skull Base 2007

52. Reconstruction NFO Segment
Wrapping
2012
Gil and Fliss. Plastics and Rec Surg 2005

53. Evidence Based Medicine in SBS
2012

54. Evidence Based Medicine in
SBS Large Single Center Series
Level
5
JC
Irish
et
al Head
&
Neck
1994 n
=
73
IP
Janecka
et
al Otolaryngology
Head
&Neck
Surgery
1994 n
=
183
JP
Shah
et
al Archives
1997 n=
115
V
Lund
et
al Head
&
Neck
1998 n
=
209
DM
Fliss
et
al Laryngoscope
1999 n=
55
G
Cantu
et
al Head
&
Neck
2011 n
=
366
2012

55. Evidence Based Medicine in SBS
Large Single Center Series
• Data obtained: Survival
JC
Irish
et
al OS
71%
at
4
years
IP
Janecka
et
al OS
67%
at
2.5
years
JP
Shah
et
al DSS
58%
at
5
years
V
Lund
et
al OS
44%
at
5
years
DM
Fliss
et
al OS
66%
at
2
years
G
Cantu
et
al OS
46%
at
5
years
2012

56. Evidence Based Medicine in SBS
Large Single Center Series
• Data
obtained:
PrognosAc
factors
Cantu et al. Head & Neck 2011 Lund et al. Head & Neck 1998
2012

57. Evidence Based Medicine in SBS
Large Single Center Series
• Data obtained: Safety
2012
Ganly et al. Head & Neck 2005

58. Evidence Based Medicine in SBS
Multi Center Collaborations
• The problem:
No single center treats enough patients to accumulate
significant numbers for meaningful analysis of patient related
and tumor related variables as predictors of surgical and
postoperative outcome
• The solution:
An international collaborative study group comprised of 17
institutions was set up to report their collective experience with
the objective of assessing the safety and efficacy of ASBS
2012

59. Evidence Based Medicine in SBS
Multi Center Collaborations
Level
5
• Retrospective cohort
• 17 institutions
• n = 1307 patient
• Follow-up
2012
– Median 25 months
– Range 1-940 months

60. Evidence Based Medicine in
SBS Multi-Center
Collaborations
• Survival
• Post operative
mortality – 4%
• Post operative
complications –
33%
2012

61. • Prognostic factors for OS
2012

62. Evidence Based Medicine in SBS
Multi-Center Collaborations
Conclusions
• CFR is safe and effective
• Histology, intracranial extent and
surgical margins are independent
determinants of outcome
2012

63. Evidence Based Medicine in SBS
Multi-Center Collaborations
• n= 334
• Prognostic factors for DSS:
Surgical Margins Orbital involvement
2012

64. Evidence Based Medicine in SBS
Multi-Center Collaborations
Intracranial involvement Histology
• Similar outcome and complication
rate
2012

65. SBS Techniques
Endoscopic Approach
Advantages
• Improved visualization
• No need for brain retraction
• No facial incisions/osteotomies
• Shorter hospitalization
Disadvantages
• Extension into the orbit or beyond
• Extensive dural resection (CSF leak)
• Piecemeal excision (?)
• Reconstructive issues
2012

66. Endoscopic Approaches
Level of Evidence
2012

67. Endoscopic Approaches
Evidence Based Medicine
• RetrospecAve
review
Level
5
• n=120,
15
years
2012

68. Endoscopic Approaches
Evidence Based Medicine
2012

69. Endoscopic Approaches
Evidence Based Medicine
2012

70. Endoscopic Approaches
Evidence Based Medicine
Level
5
• n=184, 10 years
• Mean follow-up 34 months (2-123)
2012

71. Endoscopic Approaches
Evidence Based Medicine
2012

72. Endoscopic Approaches
Evidence Based Medicine
EEA
CEA
• 5year
DSS:
91%
59%
(SelecAon
bias)
2012

73. Evidence Based Medicine in SBS
Endoscopic Surgery
Summary
• Evidence
quality
-­‐
low
• Long
term
follow-­‐up
-­‐
unavailable
• Staged
tumors
(ENB,
adenocarcinoma)
can
be
managed
with
results
equivalent
to
open
techniques
• Advanced
tumors
should
be
approached
by
minimally
invasive
open
techniques
or
by
a
combinaAon
of
open
and
endoscopic
approaches
2012
• PaAents
should
be
managed
by
trained
surgical
oncologists
and
nasal

74. Quality of Life in SBS
Problem
• ASBS has been established as safe and effective
• The physical and psychological consequences of ASBS on
a patient s QOL have not been clarified
Solution
• To develop a cancer-specific multidimensional instrument
to assess the impact of surgery on the QOL of patients
2012
with anterior cranial base tumors

75. Quality of Life in SBS
2012

76. Quality of Life in SBS
• Retrospective survey, n = 69
• Generation of questions: review of literature,
interview of patients and caregivers
• Assessment of reliability and validation of
the construct
• Domains:
– Performance - Pain
– Physical function - Influence on emotions
2012
– Vitality - Specific symptoms

77. Quality of Life in SBS
Overall QoL Social Activity
60 60
50 50
Patients (%)
Patients (%)
40 40
30 30
20 20
10 10
0 0
Worse Same Better Worse Same Better
60 Financial Status 60 Impact Upon emotions
50 50
Patients (%)
Patients (%)
40
40
30
30
20
20
10
0 10
Worse Same Better Worse Same Better
2012

78. Quality of Life in SBS
2012

79. Quality of Life in SBS
4.0
3.5
QOL Score
3.0 N=39
P<0.05
2.5
Preoperative 6 months 12 months
2012

80. Quality of Life in SBS
Conclusions
• The overall QOL in most patients after ASB surgery is good,
with significant improvement within 6 months
• The worst impact of surgery was on the patients financial
and emotional QOL domains.
• Negative prognostic factors for QOL:
– Old age
– Malignancy
– Comorbidity Gil and Fliss et al. Arch Otol H&N Surg 2003
2012
– Radiotherapy Gil and Fliss et al. Arch Otol H&N Surg 2004
Gil and Fliss et al. J Neurosurg 2004
– Wide surgery Abergel and Fliss et al. Harefua 2004
Gil and Fliss et al. Skull Base 2010

81. Trends in Survival and
Demographics of Patients
Undergoing SBS
Head
&
Neck
2011
• Study conducted in order to identify time-related changes
in the clinical characteristics and survival of patient
undergoing ASB surgery over the last four decades
• Pooled data from two cancer centers:
Memorial Sloan-Kettering Cancer Center 234
2012
Tel Aviv Sourasky Medical Center 48
Total n = 282

82. Trends in Survival and
Demographics of Patients
Undergoing SBS
• Demographics
and
clinical
characteristics
2012

83. Trends in Survival and
Demographics of Patients
Undergoing SBS
• Survival
2012

84. Trends in Survival and Demographics of
Patients Undergoing SBS
• Prognostic factors
for OS
2012

85. Trends in Survival and Demographics
of Patient Undergoing SBS
Conclusion
• Despite a higher risk for morbidity and
tumor recurrence, refinement of
surgical technique and the use of
adjuvant radiation therapy,
contributed to the current
improvement in survival of patients
2012
with anterior skull base malignancies