1. Neck Cancer Head and STATEMENTS ON January 28, 2006 Frankfurt am Main, Germany Surgery Surgery in Multimodal Treatment

2. Jatin P. Shah, MD, FACS Hon. FRCS (Edin), Hon. FRACS, Hon. FDSRCS (Lond.) Professor of Surgery Elliot W. Strong Chair in Head and Neck Oncology Chief, Head and Neck Service Memorial Sloan-Kettering Cancer Center New York, New York

3. Development of Multimodal Therapy for Head & Neck Cancer Development of Multimodal Therapy for Head & Neck Cancer 1900 1950 1960 1980 2000 Surgery Radiotherapy Chemotherapy 1990 1970 Targeted Therapy 2005 Gene Therapy

5. Choice of Surgery vs. Radiotherapy Site Location Stage Histology Node Status and also Competence Convenience Cost Compliance Complications Site Location Stage Histology Node Status and also Competence Convenience Cost Compliance Complications Survival with single modality treatment Choice of Treatment depends upon:

6. Head and Neck Cancer Stage 115%90% Stage II20%70% Stage III25%55% Stage IV25%40% Inoperable15%5-10% Stage 115%90% Stage II20%70% Stage III25%55% Stage IV25%40% Inoperable15%5-10% Presentation 5 Yr Survival

7. Multimodal Treatment Combinations RT Surg Surg RT RT Surg RT Surg RT Chemo Chemo Surg RT (+ Chemo) Chemo RT (+ Chemo) Concurrent Chemo & RT Intraarterial Chemo Brachytherapy

8. Development of Multimodal Therapy for Head and Neck Cancer 20 th century 1960’s 1970’s 1980’s 2002 Single modality treatments Surgery – RT – Chemo Rx Pre-operative radiotherapy Post-operative radiotherapy Induction chemotherapy with surgery + RT Neoadjuvant chemo Rx Organ preservation strategies Concurrent chemo Rx & RT 1990’s

9. Levels of Evidence 1. Randomized controlled trial or Meta-analysis 2. Nonrandomized controlled clinical trial, subset analysis of RCT 3. Case series, population based, consecutive or not 4. Opinions of respected authorities based upon clinical experience or reports of expert committees

10. MEDLINE Over 9 million articles, dating to 1966 31,000 added each month –754,383 (8.4%) - human cancer –131,760 (1.5%) - clinical trials –68,301 (0.75%) - prospective randomized 5,811 (0.06%) human cancer prospective randomized clinical trials

11. Neurology Homunculus

12. U.S. Cancer Incidence The Onculus

13. U.S. Cancer Incidence U.S. Cancer Mortality

14. Cancer Level I Evidence U.S. Cancer Incidence U.S. Cancer Mortality

15. Surgery in Multimodal Treatment of Head & Neck Cancer Timeline 1960 - 1966Preop RT  Surgery Surgery  Postop RT – Induction Chemo  Surgery  RT or RT  Surgery – Planned Surgery or Salvage Surgery History Multimodal Treatment 1974 - 1978 1978 - 1982 1985 - 1991 – Organ Preservation with Chemo  RT  Salvage Surgery – Chemo  Surgery  RT 1992 - 2000 – Concurrent Chemo/RT vs Induction – Chemo and RT vs RT alone

16. Surgery in Multimodal Treatment of Head & Neck Cancer Timeline History Multimodal Treatment 1994 - 2000 Surgery  Adjuvant Chemo/RT Organ/Function Preservation Role of Conservation Surgery in Multimodal Treatment And Salvage Surgery Surgical? Non-Surgical? Salvage? e.g. Selective Neck Dissection Partial Laryngectomy

17. Preoperative Radiation and Radical Neck Dissection 1960 – 1966 348 Patients Surg Clin North Am. Apr 1969; 49(2):271-276. Strong EW.

18. Elective Postoperative Radiation Therapy in Stages III and IV Epidermoid Carcinoma of the Head and Neck Vikram B, Strong EW, Shah J, Spiro RH. Am J Surg. Oct 1980; 140(4):580-584. 1974 – 1978 104 Patients

19. Adjuvant Chemotherapy for Advanced Head and Neck Squamous Carcinoma Final Report of the Head and Neck Contracts Program. Cancer. Aug 1 1987; 60(3):301-311. 1978 – 1982 462 Patients

20. Induction Chemotherapy Plus Radiation Compared with Surgery Plus Radiation in Patients with Advanced Laryngeal Cancer The Department of Veterans Affairs Laryngeal Cancer Study Group N Engl J Med. Jun 13 1991; 324(24):1685-1690. 1985 – 1991 332 Patients

21. Concurrent Chemotherapy and Radiotherapy for Organ Preservation in Advanced Laryngeal Cancer Forastiere AA, Goepfert H, Maor M, et al. N Engl J Med. Nov 27 2003; 349(22):2091-2098. 1992 – 2000 547 Patients

22. Postoperative Irradiation with or without Concomitant Chemotherapy for Locally Advanced Head and Neck Cancer Bernier J, Domenge C, Ozsahin M, et al. N Engl J Med. May 6 2004; 350(19):1945-1952. 1994 – 2000 334 Patients

23. Postoperative Concurrent Radiotherapy and Chemotherapy for High-Risk Squamous-Cell Carcinoma of the Head and Neck Cooper JS. Pajak TF, Forastiere AA, et al. N Engl J Med. May 6 2004; 350(19):1937-1944. 1995 – 2000 459 Patients

24. Limitations to Organ Preservation Approach Previous radiotherapy Cartilage invasion T4 primary Non laryngeal sites (BOT, hypopharynx) < C.R. Medical contraindications (renal, pulmonary, otologic)

25. 2. SCC of Nasal Cavity and Paranasal Sinuses Surgery Remains Initial Definitive Treatment for Most Sites in Head & Neck 3. Advanced Carcinomas (T 4 ) of the Larynx and Hypopharynx 1. SCC of Oral Cavity 4. Salivary Tumors 5. Thyroid Cancer 6. Sarcomas 7. Skin Cancer and Melanoma

26. Surgery Employed as Planned Intervention in Multimodal Treatment Programs N 2 – N 3 Disease Post Chemo/RT ?

27. Predictors of Long Term Regional Control in Pts treated with Chemo/RT 5 yr NRFS Survival5 yr NRFS Survival N0 – 87%C.R. – 92% N1 – 93%P.R. – 65% N2 – 69% (p<0.008)(p<0.0001) MSKCC – unpublished data. 58 pts

28. Planned Comprehensive Neck Dissection Planned Selective Neck Dissection Nidusectomy Observation Imaging – PET/CT/MRI Management of the Neck After Chemo/Radiotherapy

29. Surgery Employed as Salvage Treatment for Chemo/RT Failure/Recurrence 1. Ca of Oropharynx 2. Ca of Larynx/Hypopharynx 3. Ca of Nasopharynx (?) 4. Metastatic Ca to Neck Nodes

30. 139 pts – treated with RT 35 recurred in neck Salvage of Recurrent Neck Disease in Radiated Neck Salvage attempted in 9, but successful in 2 75 pts with OPH treated with RT Mendenhall W.M., et al (1984) Peters L.J., et al (1996) 62 had a CR 8 recurred in neck Salvage attempted in 7, but successful in 1

46. Jerry Goodwin

50. 2. Laryngeal edema/obstruction Surgery for Complications and Sequelae of Radiotherapy / Chemotherapy 3. Radionecrosis of larynx 1. Oro-nasopharyngeal stenosis 4. Pharyngoesophageal stricture 5. Osteoradionecrosis of mandible

51. 2. Bleeding Surgery Employed for Palliation 3. Airway Obstruction 1. Pain 4. Esophageal Obstruction 5. Fungating Tumor 6. Distant Metastases

57. Life History of a Patient with Head and Neck Cancer Life History of a Patient with Head and Neck Cancer Diagnosis Evaluation Definitive therapy Definitive therapy Rehabilitation Management of complications Management of complications Surveillance Salvage treatment Salvage treatment Palliation Prevention New primary S S S S S S S S SS R R R C C C C

59. Copyright restrictions may apply. Ganly, I. et al. Arch Otolaryngol Head Neck Surg 2006;132:59-66. Disease-specific survival (DSS) for T1 to T2 glottic laryngeal tumors that required salvage partial laryngectomy (SPL) or salvage total laryngectomy (STL) following failed radiation

60. Copyright restrictions may apply. Ganly, I. et al. Arch Otolaryngol Head Neck Surg 2006;132:59-66. Effect of T stage at recurrence on disease-specific survival (DSS) for patients with T1 to T2 glottic laryngeal tumors that required salvage laryngectomy following failed radiation