1) Imaging modalities like CT, MRI, PET, and ultrasound with FNAC can detect occult metastases in the clinically node-negative neck in 50-60% of cases, according to literature, but their reported sensitivities are likely overestimated since histopathology is used as the gold standard. 2) Ultrasound with FNAC has the highest reported accuracy for detecting occult metastases in the N0 neck when performed by well-trained clinicians, with a sensitivity of 56% and specificity of 100% according to meta-analyses. 3) However, even the most accurate imaging may fail to detect at least 25-30% of occult metastases that are smaller than 5mm, suggesting imaging has fundamental limits in

1. Imaging and Management of the N0 Neck
Jatin Shah
Michiel van den Brekel
Snehal Patel
Baris Karakullukcu
Ian Ganly
Abrahim Al-Mamgani
Symposium 2015 IAOO
Sao Paulo
MSKCC – NKI AVL

3. 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

4. Imaging of the N0 Neck
u Modalities and developments
u Sensitivity, Specificity and impact on the risk of
occult metastases
u What is the maximum accuracy

5. Imaging of the N0 Neck
u Risk reduction might influence management
– Imaging should be very sensitive for N0 neck
u What risk is acceptable ??

6. In 1994 Weiss et al. created a decision analysis and demonstrated that when the
probability of occult cervical metastasis is more than 20%, the neck should be
electively treated.
This risk cut-of (Rx) was calculated with three variables:
a = the cure rate with END and no neck recurrence
b = the cure rate with observation and late neck metastasis
c = the cure rate with observation and no neck metastasis
Rx = (c − 0.97a) ⁄ (0.00376 − 0.0776a − 0.94b + c) = 44.4%

7. MRI, US and CT
u Rely on morphological features
- Nodal size
- Central necrosis / irregular enhancement
- Signal intensities / enhancement
- Indistinct nodal margins
- Gross extracapsular extension

8. Easy Cases
Negative
Positive

10. 1
3
PET-CT: very promising

11. BJ de Bondt: Diffusion
weighted MRI (2009)

12. CT misdiagnosis

13. False Positive PT-CT

15. 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

16. PET (CT) in cN0 cases
Author Necks N+ Sensitivity Specificity NPV
Myers 1998 14 30% 79% 100%
Civantes 2001 18 61% 30% 100% 45%
Hyde 2003 18 22% 0% 87% 77%
Brouwer 2003 15 67% 92%
Wensing 2006 30 30% 33% 76% 73%
Schroder 2006 36 25% 67% 85% 88%
Krabbe 2008 38 21% 50% 97% 88%
Ozer 2012 112 57% 82% 59%
Sohn 2015 49 51% 55%

17. Sensitivity US-FNAC N0 Neck
Author Tumor Neck Sides Sensitivity Specificity
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
Wensing (2010) Oral (T1-2) 224 78 100

18. 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

19. US-FNAC vs CT, MRI, US: meta-analysis
De Bondt et al. Eur. J. Radiol. 2007

20. Computed tomography versus magnetic resonance imaging for diagnosing cervical
lymph node metastasis of head and neck cancer: a systematic review and meta-
analysis. Sun J, Li B, Li CJ, Li Y, Su F, Gao QH, Wu FL, Yu T, Wu L, Li LJ.
Onco Targets Ther. 2015;8:1291-313

22. Analysis of sentinel node biopsy combined with other diagnostic
tools in staging cN0 head and neck cancer: A diagnostic meta-
analysis. Liao LJ, Hsu WL, Wang CT, Lo WC, Lai MS. Head Neck
2015

23. Hypothetic 100 cN0 patients, 40 pN+
Sensitivity 56%, Specificity 100% (USgFNAC)
– Neck treatment in 22 (4-9% recur !!)
– Wait & See policy in 78
» Undertreatment in 18 (30-70% salvaged)
Sensitivity 56%, Specificity 79% (MRI)
– Neck Treatment in 35
» Overtreatment in 13
– Wait and See in 65
» Undertreatment in 18 (30-70% salvaged)

24. Maximum Sensitivity of Imaging
Depends on imaging criteria, spatial
resolution, contrast, uptake of tracers
BUT ALSO ON THE SIZE OF THE
METASTASIS
The challenge is to detect metastases
smaller than 3-4-5 mm

25. MICROMETASTASES IN 96 cN0 ND SPECIMENS
van den Brekel et al. Laryngoscope 1996
In 25% of pN+, cN0
necks only metastases
smaller than 25% are
present

26. Conclusions
Imaging can detect 50-60% of occult
metastases according to literature
As all studies used HP as gold standard, the
reported sensitivities are overestimated
So far USgFNAC has the highest accuracy in
well trained and motivated doctors
At least 25-30% of occult metastases cannot
be detected with imaging