Sentimag® and OSNA® to support SLN concept in Head and Neck cancer

Florence Godey f.godey@rennes.unicancer.fr

Hamburg February 2017

Head and Neck Squamous Cell Carcinoma (HNSCC)

and Neck Lymph node (LN) dissection

• Carcinomatous cell diffusion in cervical lymph nodes is a major determinant of therapy and prognosis for patients with HNSCC as cure rates for patients with pathologically metastatic lymph nodes drop to one-half of those of patients without nodal involvement

• Until recently, a neck dissection was advocated routinely both to assess nodal involvement and to remove occult minimal residual cancer

• The morbidity of neck dissection is important

Neck dissection technique

Radical neck dissection (RND)Removal of levels I–V, accessory nerve, internal jugular vein and sternomastoid muscle

Modified radical neck dissection

Removal of levels I–V dissected; preservation of one or more of the accessory nerve, internal jugular vein or sternomastoid muscle (types I, II, III, respectively)

Selective neck dissection Preservation of one or more levels of lymph nodes

Extended radical neck dissection

Removal of one or more additional lymphatic and/or non-lymphatic structures(s) relative to a RND, e.g. level VII, retropharyngeal lymph nodes, hypoglossal nerve

Classification of neck dissection techniques

HNSCC and SLN concept• A more recent approach consists of limiting lymph node surgery to a

staging procedure by taking only the sentinel lymph nodes (SLN) which are representative of the whole neck node system

• Such a strategy aims to permit more thorough analysis of only a few lymph nodes to enhance the sensitivity and the specificity of the diagnosis of lymph node invasion

• The main goal of sentinel lymph node (SLN) detection in head and neck squamous cell carcinomas is to limit neck dissections to pN+ cases only.

• But SLN intraoperative + diagnosis cannot be routinely done using the current gold standard, serial step sectioning with immunohistochemistry.

Challenge for SLN in HNSCC

• Renewed interest in sentinel lymph node biopsy (SLNB) for HNSCC resulted from reassuring data with 95% negative predictive value (NPV) and also recent trials reinforcing the survival benefit of surgical neck staging.

• A significant drawback of SLNB is that, in the event of a positive lymph node, a costly (and more morbid) second surgical episode is necessitated. This delay, mandated by serial examination of SLN, delays the commencement of adjuvant therapy and creates additional patient distress.

• SLNB in HNSCC would be facilitated by intraoperative staging

SLN detection in head and neck cancer

• use of radioactive tracer, blue dye or indocyanine green

PLoS One. 2017; 12(1). Published online 2017 Jan 20. Diagnostic Efficacy of Sentinel Lymph Node Biopsy in Early Oral Squamous Cell Carcinoma: A Meta-Analysis of 66 Studies Muyuan Liu,#1 Steven J. Wang,#2 Xihong Yang,1 and Hanwei Peng1,*

Objectives The diagnostic efficacy of sentinel lymph node biopsy(SLNB) in early oral squamous cell carcinoma(OSCC) still remains controversial. This meta-analysis was conducted to assess the diagnostic value of SLNB in clinically neck-negative T1-2 OSCC.

Results 66 studies comprising 3566 patients with cT1-2N0 OSCC were included in this meta-analysis. The pooled SLN identification rate was 96.3%(95% CI: 95.3%-97.0%). The pooled sensitivity was 0.87 (95% CI: 0.85–0.89), pooled negative predictive value was 0.94 (95% CI: 0.93–0.95), and AUC was 0.98 (95% CI: 0.97–0.99). Subgroup analyses indicated that SLN assessment with immunohistochemistry(IHC) achieved a significantly higher sensitivity than without IHC.

Sentinel Lymph node indicationsin head and neck cancer

Pr Franck Jégoux Service ORL et Chirurgie Maxillo-Faciale

CHU Pontchaillou, Rennes

Head neck cancer

• Squamous cell carcinoma • T1T2N0 unpreviously treated • Oral cavity; oropharyngeal (injection under local

anaesthesia) • Supraglottic laryngeal but requires general

anaesthesia with a need of rapid response (ferromagnetic particules??)

• Melanoma: – N0 – T1b (Breslow>1mm or ulceration or mitotic

rate>1/mm2)

Management of neck metastases in head and neck cancer: United Kingdom National Multidisciplinary Guidelines.

Paleri V, Urbano TG, Mehanna H, Repanos C, Lancaster J, Roques T, Patel M, Sen M.J Laryngol Otol. 2016 May;130(S2):S161-S169

Eur Ann Otorhinolaryngol Head Neck Dis. 2016 Nov 11. pii: S1879-7296(16)30189-2. doi: 10.1016/j.anorl.2016.10.004. [Epub ahead of print] Review of sentinel node procedure in cN0 head and neck squamous cell carcinomas. Guidelines from the French evaluation cooperative subgroup of GETTEC. Garrel R1, Poissonnet G2, Temam S3, Dolivet G4, Fakhry N5, de Raucourt D6.

Abstract The reliability of the sentinel lymph node (SN) technique has been established for more than ten years in T1-T2 oral cavity and oropharynx squamous cell carcinoma. Although most authors stress the necessity of rigorous implementation, there are no agreed guidelines. Moreover, other indications have been described, in other anatomical areas of the upper aerodigestive tract and in case of previous surgery or radiotherapy. SN expert teams, under the GETTEC head and neck tumor study group, conducted a review of the key points for implementation in head and neck cancers through guidelines and a review of classical and extended indications. Reliability depends on respecting key points of preoperative landmarking by lymphoscintigraphy, and intraoperative SN sampling and histological analysis. The SN technique is the best means of diagnosing occult lymph node involvement, whatever the primary tumor location, T stage or patient history.

SLN extended indicationsin HNSCC

Challenge for SLN analysis in HNSCC

Sensitive intraoperative detection and analysis of SLN

• The detection is limited for HNSCC accessible for tracer injection (oral cavity) under local anaesthesia, but could be extended to other localisations if possible intraoperatively ! Sentimag® probe and the Sienna+® magnetic tracer during surgery could be a ready to use solution with the possibility to extend SLN indications

• Classical Histopathogical examination intraoperatively is not enough sensitive for metastasis SLN detection ! OSNA during surgery could be a ready to use solution

HNSCC SLN analysis: OSNA / Histopathology validation studies

One-step nucleic acid amplification for detecting lymph node metastasis of head and neck cancer. Meeting: 2009 ASCO Annual Meeting Presenter: Hiroyuki Goda A total of 291 lymph nodes (59 patients) resected on SLN biopsy for cN0 SCCHN or neck dissection for cN1/2 SCCHN were diagnosed by one-step nucleic acid amplification (OSNA). An overall concordance rate between the OSNA assay and histopathology was 96.2%. Conclusions: The OSNA assay showing high sensitivity and specificity can be used as a novel genetic detection tool of lymph node metastasis in SCCHN patients.

! Oral Oncol. 2012 Oct;48(10):958-63.One-step nucleic acid amplification for detecting lymph node metastasis of head and neck squamous cell carcinoma.Goda H et al 61 of 312 lymph nodes (65 patients) were pathologically metastasis-positive. The overall concordance rate between the OSNA assay using breast cancer criteria and histopathology was 94.2%. The optimal cut-off for the copy number of CK19 mRNA in assessing lymph node metastasis of HNSCC was 300 copies/µl, which had the highest diagnostic accuracy (95.2%) .

! Ann Surg Oncol. 2012 Nov;19(12):3865-70. Intraoperative molecular assessment for lymph node metastasis in head and neck squamous cell carcinoma using one-step nucleic acid amplification (OSNA) assay. Matsuzuka T et al : 175 CLNs dissected from 56 patients .OSNA assay showed acceptable efficacy in the detection of pathological CLN metastasis (AUROC 0.918, 95 % confidence interval [CI] 0.852-0.984). Regarding the CK19mRNA cutoff value, the optimum cutoff point in HNSCC patients was 131 copies/µl (sensitivity: 82.4, 95 % CI 65.5-93.2; specificity: 99.3, 95 % CI 96.1-100.0; positive likelihood ratio 116.1; negative likelihood ratio 0.2].

SLN OSNA analysis in HNSCC what about CK19 expression

OSNA results showed CK19 expression in 80% of primary cases, so if used for diagnosis of lymph node metastasis would lead to a false-negative result in 20% of patients with cervical lymph node metastases.

HNSCC OSNA SLN analysis: Rennes collaboration

with Sysmex support

DEROULEMENT (Réalisation pratique)

-

STOPAnalyse définitive des autres lames (n=25 max)

1 3 2 4

OSNA

1 2 3 4

Congélation

OSNA

++

--

IHC (Résultat définitif)

Chirurgie avec curage => Isolement des ganglions par le chirurgien

Découpe des ganglions et répartition entre l’OSNA et la technique classique en salle

Les analyses OSNA seront regroupées donc mesure de la durée de préparation, du transport et du temps d’analyse.

Preliminary results• 26 patients HNSCC

• 158 nodes – 22 (13,9%) ! OSNA metastasis – 13 (8,23%) ! HES/ IHC metastasis

• 139 (87,9%) Concordant cases OSNA /HES : – 8 OSNA+/HES+ – 131 OSNA-/HES-

• 19 (12,1%) discordant cases OSNA /HES ! investigations in progress

Discordant cases • 19 (12,1%) discordant cases OSNA /HES !

investigations are necessary – 14 OSNA+ / HES- – 5 OSNA- / HES+

• Majority of micrometastasis (localion bias) • Only one patient suspected with CK19 low

expression • FINAL presentation IFOS 2017 paris

HNSCC Sentimag® SLN detection: Project Rennes collaboration

HNSCC Sentimag® probe and the Sienna+®

magnetic tracer.

• New challenge In 2017 • Adaptation of the breast protocol • HNSCC surgery with all SLN procedure during

the same anaesthesia

• ! possibility to extend SLN procedures to laryngeal HNSCC localisations

Thank you for your attention