1. LIP AND ORAL CAVITY SQUAMOUS CELL CARCINOMAS Guy ANDRY, M.D. Dept of Surgery Institut Jules Bordet, U.L.B. Statements 2008 on Head and Neck Cancer Frankfurt, 1 st & 2 nd February 2008

2. 5 Years Survival and Cause Specific Survival % LIP ORAL CAVITY ∆ SCSSSCSS St I 73836068  15 St II 64734653 St III 56623641  20 St IV 41472327 After SEER database

3. LIP CANCER The most common primary (~ 25 % of oral cavity cancer) The most common primary (~ 25 % of oral cavity cancer) ~ 12/100.000 habitants per year USA & Europe ~ 12/100.000 habitants per year USA & Europe Solar-radiation, tobacco smoking, HPV, immunosuppression Solar-radiation, tobacco smoking, HPV, immunosuppression

4. LIP CANCER SURGERY IS FIRST CHOICE < 2/3 invasion : < 2/3 invasion : –full-thickness pedicled flaps (Abbe or Estlander) > 2/3 invasion : > 2/3 invasion : –musculo mucosalflaps (Camille Bernard…) –free flaps –frontal flap → irradiation in debilitated PTS

9. LIP CANCER PROGNOSTIC FACTORS Maximum tumor thickness (cf. Martinez- Gimeno Scoring System) Maximum tumor thickness (cf. Martinez- Gimeno Scoring System) Site (upper & commissure more rapid growth and preauricular, submandibular lymph node metastases) Site (upper & commissure more rapid growth and preauricular, submandibular lymph node metastases)

10. LIP CANCER Scoring system → probability of lymph node invasion Tumor thicknessMartinez-Gimeno Scoring System T stage, Tumor thickness, microvascular, perineural invasion histologic grade of differentiation, presence of inflammatory infiltrate Group I : 0 %of lymph node invasion Group II :21 % Group III :50 % Group IV :67 %

11. LIP CANCER Mohs micrographic surgery has been successfully used Mohs micrographic surgery has been successfully used –No tumor related deaths or metastases at 5 yrs –All PTS with recurrent disease were successfully salvaged

12. LIP CANCER T 1 T 2 Surgeryif+ margins + lymph nodes  Adjuvant radiation Radiationif recurrence local regional External beam Brachytherapy  Salvage surgery or both  98 % local control 5 yrs

13. LIP CANCER There are no published randomized trials on There are no published randomized trials on the use of sequential surgery + radiationthe use of sequential surgery + radiation the use of chemotherapythe use of chemotherapy NB : one preliminary study on super selective intraarterial chemo (CDDP based) in six PTS with T 1, T 2 or local recurrence by Kishi & al, Radiology 213, 1999

14. FLOOR OF MOUTH CANCER High risk tumors (even in early stages) Proximity to the mandible Proximity to the mandible –Adhesion or invasion (by the alveolar ridge) –Risk of radiation induced bone necrosis No mechanical barrier in soft tissues No mechanical barrier in soft tissues –Blurred vision of margins, Even with high resolution MRI Early lymph node metastases Early lymph node metastases –20 % of occult invasion in T 1 –62 % of occult invasion in T 2 Will develop second primary tumors (~ 20 % in T 1 – T 2 ) “field cancerization” effect of carcinogens Will develop second primary tumors (~ 20 % in T 1 – T 2 ) “field cancerization” effect of carcinogens

15. FLOOR OF MOUTH CANCER Surgery is generally preferred for T 1 T 2 (primary & necks) Surgery is generally preferred for T 1 T 2 (primary & necks)  + radiationif margins are close or involved if lymph nodes are involved (CR) if mandible is invaded if perineural or/and vascular invasion (or chemo radiation) Role of sentinel node biopsy is under study Role of sentinel node biopsy is under study

18. FLOOR OF MOUTH CANCER Surgery S 5 yrs T1T1T1T1 95 % T2T2T2T2 86 % Control rate 90 % ← negative margins 62 % ← positive margins Primary ERT Control rate 90 % T1T1T1T1 77 % T2T2T2T2 Neck surgery when invasion depth ≥ 5 mm level I to IIIunilateral for lateral tumors bilateral for anterior/midline

19. ORAL TONGUE CANCER T 1 T 2 SURGERY Partial glossectomy (negative margins > 1 cm) Partial glossectomy (negative margins > 1 cm) → thickness, depth invasion, perineural spread, vascular invasion Elective neck node dissection Elective neck node dissection -T1T2 T3 T4 N0-T1T2 T3 T4 N0-T1T2 T3 T4 N0-T1T2 T3 T4 N0 N + 6 % 36 %50 %67 % Staging is crucial in defining the postsurgical treatment ERT + CHEMO After Hickx WL. & al, Am J Otolaryngol 1998

21. ORAL TONGUE CANCER Role of elective neck dissection for T 1 N 0 ? No randomized Trial Retrospective studies remain controversial T 1-2 N 0 ELNTND Yii (RoyalMarsden) REC77 27 % 50 % (p.025) 1999 S 5yrs 75 % 65 % (NS) ELNTND Haddadin (Canniesburn) 1998 S 5yrs 137 81 % 45 % (p.001) But bias in the initial treatments (various types of surgery, RT or no RT to the primary and/or to the neck)

22. ELECTIVE VERSUS THERAPEUTIC NECK DISSECTION IN ORAL CAVITY CANCERS Randomized trial 39 ELND36 observations T 1-3 N 0 49 % N + 47 % N + : TND 13 % CR25 % CR DFS 5 yrs 57 % 60 % NS NB : 16 % of second primaries NB : 16 % of second primaries 45 % of deaths met caused by the original tumor After Vandenbrouck & al, Cancer 46 ; 1980

23. ELECTIVE VERSUS THERAPEUTIC NECK DISSECTION IN ORAL CAVITY CANCERS Randomized trial 30 hemiglossectomy + RND40 hemiglossectomy 10 N +20 N- 23 N+ ↓ 4 contralat + 47 % N+57 % N+ DFS63 %N.S52 % (T 1 : 70 % ; T 2 : 60 %)(T 1 : 64 % ; T 2 : 46 %) After Fakih & al, Am. J. Surg. 158; 1989

24. ELECTIVE VERSUS THERAPEUTIC NECK DISSECTION IN ORAL CAVITY CANCERS Randomized trial : effect of tumor depth in 51 PTS 21 Hemiglossectomy + ELN30 hemiglossectomy 9 (≥ 4 mm) 12 (< 4 mm) ↓↓ 6 N + (67 %)1 N + (8 %) S 43 % (p < 0.01) S 81 % After Fakih & al, Am. J. Surg. 158; 1989 21 (≥ 4 mm) 9 (< 4 mm) ↓↓↓↓↓↓↓↓ 15 N+ (76 %) 2 N+ (22 %)

25. LOWER ALVEOLAR RIDGE & RETROMOLAR TRIGONE T 1-2 cancers SURGERY Wide local excision with marginal mandibulectomy SURGERY Wide local excision with marginal mandibulectomy - close proximity to bone - infiltration into the masticator space - nodal involvement RADIATION Adjuvantfor close or positive margins RADIATION Adjuvantfor close or positive margins for lymph node invasion OR if used as first modality

26. UPPER ALVEOLAR RIDGE & HARD PALATE CANCERS SURGERY SURGERY Resection of part of the palatine process → maxillectomy followed by flap reconstruction or prosthetic rehabilitation -St I (9) St II (19) St III (14) St IV (20) * CSS75 % 46 %36 %11 % - neck dissection in Stage III RADIATION : alone or used for close margins, bulky & infiltrating tumors, nodal spread RADIATION : alone or used for close margins, bulky & infiltrating tumors, nodal spread After Evans & Shah, Am J Surg 1981

27. BUCCAL MUCOSA CANCERS SURGERY SURGERY transoral resection + check flaps + mandibular resection + maxillectomy - Neck : advocated for T 2 or invasion > 5 mm, muscle St I St II St IIISt IV * 78 % 66 %62 %50 % N 0 necks : 70 % → rec rate if no END or RT : 25 % vs 10 % (p<.05) N + necks : 49 % (no CR : 69 % vs +CR : 24 %) After Diaz & al, Head & Neck 2003 + free flaps S 5yrs

29. BUCCAL MUCOSA CANCERS (2) RADIATION : RADIATION : Used primarily for cure of T 1-2 → S3yrs : St I = 85 % ; St II = 63 % * Postop advocated for high risk - margins < 2 mm -perineural invasion -lymph node involvement After Nair & al, Cancer, 1988

30. CONCLUSIONS (1) Prognostic factors in oral cavity SCCA T size remains an «old timer» T size remains an «old timer» Depth of invasion is more informative Depth of invasion is more informative –as areperineural spread vascular invasion N involvement is a state of emergency from prompt an multidisciplinary aggressive treatment N involvement is a state of emergency from prompt an multidisciplinary aggressive treatment

31. CONCLUSIONS (2) No neck should not be a cause of debate on what is to be done in a randomized trial No neck should not be a cause of debate on what is to be done in a randomized trial Depth of invasion of the primary Depth of invasion of the primary Status of margins (close, involved, dysplasia,… molecular markers) Status of margins (close, involved, dysplasia,… molecular markers) Perineural spread Perineural spread Vascular invasion Vascular invasion –Shouldbe routinely reported and be the basis of planned treatment