1. Early Tongue Cancer Controversies in management of the neck Dr. Serena Wong Queen Elizabeth Hospital

2. Introduction Background Current debates in neck management ◦ Why is neck treatment so controversial? ◦ What are the options for neck treatment? ◦ What is the evidence on neck treatment?

3. Background

4. Background Incidence: 1.7 per 100000 108 new cases in 2011 0.7% of all new cancer cases 6 th leading cancer worldwide 32-40% of all head and neck cancers HK Cancer registry

5. How early is early? N0N1N2N3 T1I T2II T3III T4aIVa T4bIVb IVC: M1 AJCC Cancer Staging Manual. 7th ed, 2010

6. T staging Head and Neck Cancer Guide

7. N staging Head and Neck Cancer Guide

8. N staging Merritt et al. Arch Otolaryngol Head Neck Surg 1997; 123: 149-152 Giancarlo et al. Anticancer Res 1998; 18: 2805-9 Akoglu et al. J Otolaryngol 2005; 34: 384-94 Fan et al. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2014;49(1):39-43 SensitivitySpecificity Ultrasound72-80%59-96% CT78-83%80-96% MRI50%75% PET-CT67%85%

9. N staging Increased risk of occult metastasis Increased risk of occult metastasis ◦ Tumor thickness / depth of invasion (> 3 or 4mm) ◦ Higher T stage ◦ Perineural and angiolymphatic invasion ◦ Poor tumor differentiation Yuen et al. Am J Surg. 2000; 180: 139-143 Sparano et al. Otolarngol Head Neck Surg 2004; 131: 472-6

10. N staging Incidence of occult neck metastasis – T1: 16-38% – T2: 21-57% – T3: 77% Kaya et al. Am J Otolaryngol 2011;22:59-64 Presence of LN mets: most important prognostic factor – Woolgar JA: Oral Oncol 26. 42(3): 229-239

11. Current Debates in Neck Management

12. Debates in neck management Probability of neck metastasis Prognostic implications Complications of neck dissection

13. Options for neck management 1. Elective Neck Dissection (END) 2. Watchful waiting 3. Other options: ◦ Neck irradiation ◦ Sentinel LN biopsy

14. Which level? 95% metastatic nodes are in ipsilateral levels I-III Skip metastasis: 16% Liu et al. Oral Oncol 47 (2011) 136-141 Byers et al. Head Neck, 19 (1997) 14–19 Elective neck dissection

15. 1. Supraomohyoid neck dissection (I-III) 2. Modified radical neck dissection (I-V) Brazilian Head and Neck Cancer Study Group. Am J Surg. 1998 Nov;176(5):422-7 http://emedicine.medscape.com/article/1894829-overview Elective neck dissection No difference in survival and recurrence

16. Options for neck management 1. Prophylactic Elective Neck Dissection (END) 2. Watchful waiting 3. Other options: ◦ Neck irradiation ◦ Sentinel LN biopsy

17. Observation Compliance is crucial MRND for salvage of regional recurrences Many neck recurrences will be of advanced stage with poor prognostic factors such as extracapsular spread ◦ Andersen et al. Am J Surg 1996; 172:689-691

18. END vs Observation AuthorsDurationCountryStudy population T stageTumor location Survival Benefit Vandenbrouck et al (1980) 1966-1973France75T1-3Oral cavityNo Fakih et al (1989) 1985-1988India70T1-2TongueNo Kligerman et al (1994) 1987-1992Brazil67T1-2Oral cavityYes Yuen et al (2009) 1996-2004Hong Kong71T1-2TongueNo Vandenbrouck C et al. Cancer; 1980: 46: 386-90 Fakih AR et al. Am J Surg 1989; 158: 309-313 Kligerman J et al. Am J Surg 1994; 168: 391-4 Yuen AP et al. Head Neck 2009; 31: 765-72

19. Prospective randomized study of selective neck dissection versus observation for N0 neck of early tongue carcinoma Yuen PW, Ho CM, Chow TL, Tang LC, Wei W et al Outcomes: -Node related mortality: 0% -Salvage rate: 100% -5 year Disease specific survival: -END: 89% -Observation: 87% (Not statistically significant )

20. A meta-analysis of the RCTs on elective neck dissection versus therapeutic neck dissection in oral cavity cancers with clinically node-negative neck Fasunla AJ, Greene BH, Timmesfeld N et al.

21. Do we have the answer yet? Elective Neck Dissection Observation Pros Less nodal recurrence Less surgical morbidity than radical or MRND Accurate N staging Avoid unnecessary neck dissection in truly N0 patients Cons Shoulder morbidities Strict compliance to FU Poor prognostic factors on recurrence

22. Options for neck management 1. Prophylactic Elective Neck Dissection (END) 2. Watchful waiting 3. Other options: ◦ Neck irradiation ◦ Sentinel LN biopsy

23. Irradiation Elective irradiation of the N0 neck produces results equivalent to that of neck dissection ◦ G.H. Fletcher. Cancer, 29 (1972), pp. 1450–1454 ◦ Bataini et al. Eur Arch Otorhinolaryngol, 250 (1993), 442–445 Disadvantages: ◦ No histopathological staging ◦ complications of radiation ◦ Secondary neoplasms

24. Sentinel LN biopsy Atula T et al. Eur Arch Otorhinolaryngol. 2008;265 Suppl 1:S19-23 Tschopp et al. Otolaryngol Head Neck Surg, 132 (2005), 99–102 Paleri et al. Head Neck, 27 (2005), 739–747 Kovacs AF. Surg Oncol Clin N Am 16 (2007), 81-100 s Sensitivity: 93% Negative predictive value: 94% Upstaging rate: 13-60%

25. Conclusion Management of the N0 neck in stage I and II tongue cancer is controversial ◦ Main options for management: Elective neck dissection vs observation Stringent follow up is crucial in detection of early nodal metastasis for successful salvage surgery Further developments: Sentinel LN biopsy

26. The End

27. References http://www.intechopen.com/books/melanoma-from-early-detection-to-treatment/sentinel-lymph-node-biopsy-for-melanoma-and-surgical-approach- to-lymph-node-metastasi (figure on slide 25) http://www.intechopen.com/books/melanoma-from-early-detection-to-treatment/sentinel-lymph-node-biopsy-for-melanoma-and-surgical-approach- to-lymph-node-metastasi Keski-Santti et al. Sentinel lymph node biopsy or elective neck dissection for patients with oral squamous cell carcinoma. Eur Arch Otorhinolaryngol 2008: 265 (suppl): S13-S17 Govers et al. Sentinel lymph node biopsy for SCC of the oral cavity: A diagnostic meta-analysis. Oral Oncol 2013: 49; 726-732 Fasunla AJ et al. A meta-analysis of the RCTs on elective neck dissection versus therapeutic neck dissection in oral cavity cancers with clinically node negative neck. Oral Oncol 2011: 47: 320-324 Kovacs AF. Head and neck squamous cell carcinoma: Sentinel node or selective neck dissection. Surg Oncol Clin N Am 2007; 16: 81- 100 Fan SF et al. Sentinel lymph node biopsy versus elective neck dissection in patients with cT1-2N0 oral tongue SCC. Oral Pathol Oral Radiol 2014; 117: 186-190 Melkane AE, et al. Sentinel Node biopsy in early oral squamous cell carcinomas: A 10 year experience. Laryngoscope 2012; 122: 1782- 1788 Amaral TMP et al. Predictive factors of occult metastasis and prognosis of clinical stages I and II squamous cell carcinoma of the tongue and floor of mouth. Oral Oncol 2004; 40: 780-786 Yuen APW et al. A comparison of the prognostic significance of tumor diameter, length, width, thickness, area, volume and clinicopathological features of oral tongue carcinoma. Am J Surg 2000; 180: 139-143 Sparano A et al. Multivariate predictors of occult neck metastasis in early oral tongue cancers. Otolaryngol Head Neck Surg 2004; 131: 472-6 Yuen APW et al. Prospective randomized study of selective neck dissection versus observation for N0 neck of early tongue carcinoma. Head Neck 2009; 31: 765-772 Kligerman et al. Supraomohyoid neck dissection in the treatment of T1/2 squamous cell carcinoma of oral cavity. Am J Surg 1994; 168: : 391-4

28. Prognostic implications ◦ Regional recurrence is the most common cause of treatment failure  Yuen et al. Head Neck 1997; 19:583-588 ◦ Recurrence rate: 23.7-42%  Brugere et al 1996; Khahf et al. 1991; Okamoto et al 2002 ◦ Poor salvage surgery outcomes ◦ Accurate N staging (diagnostic limitation)

29. Elective neck dissection Occult metastasis rate > 20% ◦ Weiss et al. Arch Otolaryncol Head Neck Surg 1994, 120(7): 699-702

30. Prognosis 5 year survival relative rate T1: 71% T2: 59% T3: 47% T4: 37% American Cancer Society

31. Elective Neck Dissection Which side? Contralateral LN metastasis: 4% ◦ Lim et al. Laryngoscope 2006; 116: 461-465 Higher risk of contralateral neck involvement: positive ipsilateral nodes advanced stage primary tumors tumors crossing midline Koo et al. Head Neck. 2006 Oct;28(0):896-901