In this presentation, several aspects about imaging, sentinel node and treatment of the N0 neck in head and neck cancer are discussed with emphasis on oral cancer. 2015

1. Imaging of the N0 Neck
Is it reliable enough to refrain from
elective treatment
Michiel van den Brekel
Netherlands Cancer Institute
Amsterdam
5th Annual Irish Head & Neck
Surgical Oncology Conference
2015 Dublin

4. www.hoofdhalskanker.info/skinsy
mposium
Guest of Honor: Jesus Medina

5. u Cervical node involvement is the most
significant prognostic factor in mucosal
SCC
u Management of the neck should be part
of a comprehensive treatment plan

6. Regional Metastasis

7. Options for the N0 Neck
u Observation
– Based on an estimated low risk of occult
metastases: T1 larynx
u Staging
– CT / MRI / PET
– Ultrasound (guided FNAC)
– Sentinel node biopsy
u Treatment
– Elective ND
– Elective Radiotherapy

8. The N0 Neck – Considerations
u Risk of occult disease
u Modality of treatment for primary
u Will the neck be entered?
u Prognostic impact of W&S policy
– Follow-Up reliability
u Morbidity of neck treatment
u Patient and doctor preferences

9. Risk of Occult Metastasis
u Site and size (stage) of primary tumor
u Depth infiltration (5 mm)
u Biological characteristics: gene expression
u Assessment technique
– palpation – imaging - SNB

10. US-FNAC
US-FNAC

11. Author N Stage Site Thickness Nodes Recurr. Surv.
Involved %
Yuen 72 T1, T2 N0 Tongue < 3 8 0 100
3-9 44 7 76
> 9 53 24 66
Jones 49 T1, T2 N0 Any oral  5
> 5  risk x 3
Spiro 105 T1-T3 N0 Tongue,  2 13 97
FOM 3-8 46 83
 9 65 65
Mohit- 84 T1, T2 N0 FOM  1.5 2
Tabatabai 1.6-3.5 33
 3.6 60
Urist 89 T1-T4 Buccal < 3 22 100
3-5.9 23 90
 6 54 40
Woolgar 45 T1-T4 Tongue, Mean 6-7mm for cases without metastases
FOM Mean 11.2mm for cases with metastases
Morton 26 T1, T2 <3cm Tongue Median 5 for cases without node involvement
Median 5.7 for cases with node involvement

12. Tumour thickness in oral cancer using an intra-oral ultrasound probe.
Lodder WL, Teertstra HJ, Tan IB, Pameijer FA, Smeele LE, van Velthuysen ML, van den
Brekel MW. Eur Radiol. 2011;21:98-106.

13. Predictors of neck metastasis
0
10
20
30
40
50
60
70
80
90
100
sensitivity specificity
vascular invasion
perineural invasion
cohesive front
bone invasion
tumour thickness>2mm
Ross et al Ann Surg Oncol 2004

15. Benefits of Elective ND
u Provides pathological information
u Facilitates microvascular surgery
u Early treatment
– Avoids delayed presentation
– may improve overall outcome ?
– Helps avoid radiotherapy
» In about 10% patient ?
u Limited morbidity if unilateral

16. Disadvantages Elective Neck Treatment
u Overtreatment for 50-70%
– costs, OR time
u morbidity
u Change in patterns of metastasis
– recurrences
– second primaries in 30%

17. Elective neck irradiation
u 45-50 Gy
u Neck control > 90%
u Fields should encompass at risk nodal groups
– Efficacy of selective RT / IMRT not studied
– Accuracy of staging per level never studied
u Appropriate if primary treated by radiotherapy ?
u No histopathology
– In case ENS, Chemo-radiation / boosting more appropriate ?
u “Once in a lifetime” treatment

18. Regional recurrence after (s)elective neck dissection
cN0 neck
Author Year Primary RTx Neck
recurrence
Percentage
failure
McGuirt 1995 FOM None 1/26 3.8%
Spiro 1996 Oral cavity None 6/152 5%
Hosal 2000 All None 6/127 4%
Chow 1989 Oral cavity None 5/63 8%
Carvalho 2000 Oral/Oropharynx 44% 7/154 4.5 %
Yuen 1997 Tongue Some 3/33 9%
BHNCSG 1998 Oral cavity Some 6/72 8%
D’Cruz 2008 Tongue 35% 9/159 5.7%

19. Brazilian Head and Neck
Cancer Study Group trial

20. Padegar NA, Gilbert RW. Selective Neck dissection: A
review of evidence, Oral Oncol 2008
Recommendation (Grade C).
Based on review of 13 peer reviewed articles
Patients with clinical N1 regional disease may
safely forego dissection of level V
Neck level IIB is more commonly involved with
regional metastasis and should be dissected in
patients with clinical disease.

21. Imaging and the Management of the N0 Neck
u Risk reduction might influence management
– Imaging should be very sensitive for N0 neck
u Metastases should be detected with minimal delay
– Strict follow-up should be ensured
– Imaging should be applicable for follow-up

22. MRI, US and CT
u Relies on morphological features
- Nodal size
- Central necrosis
- Indistinct nodal margins
- Peripheral contrast enhancement
- Gross extracapsular extension

23. Accuracy CT and MRI N0 neck
No Sensit Specif
u Stern CT 53 40 92
u Friedman CT 68 68 90
MRI 16 80 82
u Moreau CT 32 50 86
u Hillsamer CT 11 60 83
MRI 9 66 83
u Yucel MRI 20 57 93
u Vd Brekel CT 86 49 78
MRI 83 55 88
u Rhigi CT 25 60 100
u Okura CT 132 52 81
MRI 60 61 84
u Total CT 407 53 82
MRI 188 60 85

24. Elective neck dissection versus staging
procedure

25. Elective neck dissection versus staging
procedure

26. In 1994 Weiss et al. created a decision tree analysis and demonstrated that when the
probability of occult cervical metastasis is more than 20%, the neck should be electively
treated.
The treatment threshold (Rx) between elective neck dissection and observation was
estimated with three (a–c) probabilities of survival:
a = the curable probability with END and no neck recurrence,
b = the curable probability with observation and with late neck metastasis,
c = the curable probability with observation and no neck recurrence.
Rx = (c − 0.97a) ⁄ (0.00376 − 0.0776a − 0.94b + c) = 44.4%

27. CT misdiagnosis

28. Multiple nodes
Negative
Positive

30. u MRI
– New, more specific contast agents
» Paramagnetic iron particles
– Better contrast and higher resolution
» STIR
» Diffusion weighted MRI
Detection of Occult Metastases:
Possible Improvements

31. On the STIR image (D), the Node on the left has the same intensity as the
enlarged one on the right, both being a metastasis

32. BJ de Bondt: Diffusion
weighted MRI

33. PET in N0 cases

35. Motivation for US-FNAC
u T2N0 supraglottic
u Non-suspect LN at CT
u Tumor positive at US-
FNAC

37. Sensitivity US-FNAC N0 Neck
Author Tumor N0 Neck Sides Sens Spec
vdBrekel (1993) HNSCC 43 73 100
Righi (1997) HNSCC 33 50 100
Takes (1998) HNSCC 64 48 100
Nieuwenhuis
(2002)
Oral SCC (T3-4) 23 71 100
Nieuwenhuis
(2002)
Oral SCC (T1-2) 37 25 100
Hodder (2000) Oral SCC (T1-4) 33 58 100
Borgemeester
(2009)
Oral SCC (T1-2) 37 18 100
Borgemeester
(2009)
HNSCC (T3-4) 128 39 100

38. US-FNA pitfalls
Misses retropharyngeal, paratracheal nodes.
Operator dependent
Can only aspirate nodes > 3-4mm
- Majority of nondiagnostic samples are from nodes < 5mm
Location difficuly:
- Dificult locating exact nodal location for surgeon / RT
- Difficulty correlating with cross sectional imaging
- Difficulty correlating with followup US.

39. Sensitivity versus radiologist
Radiologist Neck sides examined HP positive Sensitivity (%)
1 39 11 9
2 29 14 29
3 31 11 45
4 43 17 53

40. US-FNAC vs conventional imaging
meta-analysis
De Bondt et al. Eur. J. Radiol. 2007

41. Sentinel node
Term described in 1961 in parotid carcinoma
(Gould et al.)
First described as a staging tool in penile
cancers (Cabanas 1977).
Popularized by Morton (Melanoma) and Krag
(breast cancer) in 1992 and 1993.

42. Conventionele methode
Peritumorale injectie radiotracer
Lymfoscintigrafie
– Dynamische beelden
– Sequentiële statische opnamen
Markeren SN
Excisie SN
– Gamma detectie probe
– Patent blauw

43. Nadelen huidige beeldvorming
Hoofd/hals regio:
– Complexe anatomie
– Verstrengelde lymfebanen
– Onverwachte / variabele drainagepatronen
Lastige interpretatie:
– Geen anatomische informatie
SN bij injectiegebied worden gemist

44. SN procedure

45. SNB in HNSCC
The Evidence
60+ single institution prospective trials
2 multi-institutional prospective trials
2 international conference consensus
documents
1 Meta-analysis (Paleri HN 2011)
1 joint practice guidelines statement
No randomized trials

46. SND prospective studies
Oral cavity SCC
Author Year Necks Mean SN
(range)
Stage Sens. NPV
Keski 2008 52 2.1(1-5) T1-2 67% 91%
Hart 2005 20 1.5 (1-4) T1-4 100% 100%
Payoux 2005 36 1.8 (1-3) T1-4 86% 97%
Riqual 2005 22 1.95 (1-4) T2 83% 80%
Taylor 2001 11 1.6 (1-4) T1-2 100% 100%
Jeong 2006 20 2.55 (1-4) T1-2 100% 100%
Stoeckli 2007 28 1.2 (1-2) T1-2 100% 100%
Civanthos 2010 140 3 (median) T1-2 90% 96%

47. SND alone and long term follow up
Oral cavity SCC
Author Year N Stage FU (months) Sens. NPV Salvage
Frerich 2007 50 T1-3 28 (7.2-49.5) 80% 94% 50%
Stoeckli 2007 51 T1-2 19 (3-40) 91% 94% 100%
Alkureishi 2010 72 T1-2 > 65 90% 95% -
Pezier 2012 60 T1-2 22 (0.26-53) 94% 97% 100%

49. Methode
9 patiënten: 6 mondbodem, 3 tong
Peritumorale injectie radiotracer
Conventionele beeldvorming
Hybride SPECT-CT*
Intra-operatief:
» Gamma probe
» Mini gamma camera**
*SymbiaT, Siemens, Erlangen, Duitsland
** Sentinella, Gem Imaging, Valencia, Spanje

51. Fluorescence

52. Arguments against SNB procedure
Multiple sentinel nodes
Complicated process
- Organisation
- Learning curve
Limited applicability in HNSCC
- T1/T2 oral cavity
- T1 oropharyngeal
- T1 supraglottic larynx
- Free flap necessity
Nasty recurrences

53. Prognostic Impact Wait & See
Depends on salvage rate of neck metastases
– treatment delay
– metastatic rate of the lymph node metastases
Study: decrease treatment delay by regular
USFNAC follow-up after transoral excision

54. Wait & See and Prognosis
Kligerman 33 33% 27%
Ho 28 36% 30%
Fakih 40 57% 30%
Cunningham 43 42% 50%
McGuirt 103 36% 59%
Vandenbrouck 36 47% 82%
TOTAL 283 41% 50%
van den Brekel 77 18% 71%
Pts N+ salvaged
Nieuwenhuis 161 21% 79%

55. Elective neck dissection versus
observation
Fasunla el al Oral Oncology 2011

56. Survival NKI
5-year survival in W&S oral cavity (T1-2) is 79%.
5-year survival in END oral cavity(T2) is 75%.
years from diagnosis
SurvivalProbability
0 1 2 3 4 5 6 7
0.0
0.2
0.4
0.6
0.8
1.0
36 34 29 24 19 14 8 5 Mondholte W&S
40 31 23 15 14 10 7 4 Mondholte electief ND
Mondholte W&S
Mondholte electief ND
Survival
p = 0.48356 (logrank, two-sided)

57. Okura 2009
(http://cdn.intechopen.com/pdfs-wm/28960.pdf)

58. Conclusions
No difference in survival between W&S and END if follow-up is very strict
The incidence of occult LNM is very high in oral cancer, even T1
The sensitivity of imaging in these small tumors is quite low (18-25%)
Policy of US-FNAC to select for a W&S policy is disputable…..
SN biopsy might be more accurate than imaging but less than END, role
unclear