1. Postoperative Radiation for Oral Cavity Squamous Cell Carcinoma: The EP

2. The Difference? Album EP

3. Postoperative Radiation for Oral Cavity Squamous Cell Carcinoma Oral Cavity Cancer is a Surgical Disease Use Radiation Postoperatively for Appropriate Patients

4. RT can be used as primary therapy for small (T1, T2) tumors of the oral cavity. Oral tongue Floor of Mouth Lip Best results are with a combination of external beam radiation and brachytherapy

5. Difficult getting enough dose to primary with brachytherapy while still delivering adequate dose to the regional nodes IJROBP 1990; 18:1287-92. Brachytherapy complications: soft tissue necrosis, osteonecrosis

6. Postoperative Radiation for Oral Cavity Squamous Cell Cancer Who needs postop RT? Definite Indications: 1) Positive Margins 2) Multiple Nodes 3) Extracapsular Extension

7. Postoperative Radiation for Oral Cavity Squamous Cell Cancer Who needs postop RT? Less certain indications: 1) Lymphovascular space invasion 2) Perineural spread 3) Single encapsulated node + 4) Thick tumors ( Tumors 3-9 mm: 44% node+, 7% local recurrence; >9 mm: 53% subclinical node+, 24% local recurrence Head Neck 2002: 24:513-20 ) 5) Surgeon Vibe

8. Postoperative Radiation for Oral Cavity Squamous Cell Cancer Why give radiation after surgery? RTOG 73-03: locally advanced H&N cancers: supraglottic larynx, hypopharynx, oral cavity and oropharynx Preop (50 Gy) vs Postop (60 Gy) Oral Cavity/oropharynx also had definitive RT arm (65-70 Gy) followed by surgery if residual cancer Head Neck Surg 1987;10:19-30

9. Postoperative Radiation for Oral Cavity Squamous Cell Cancer RTOG 73-03 277 patients Ten year follow-up Improved locoregional control in postoperative RT arm (65%) vs. preop RT (48%, p=0.04) Trend toward improved survival: 38% vs 33%, p=0.10) Surgical and radiation therapy complications “similar”. IJROBP 1991;20:21-8.

10. Postoperative Radiation for Oral Cavity Cancer: Radiation Dose RTOG 7303 established 60 Gy as postop RT dose MD Anderson performed prospective randomized trial evaluating RT dose for 240 patients with resected stage III/IV cancers of oral cavity, oropharynx, hypopharynx, larynx 180 cGy fractions Dose ranged from 52.2 Gy to 68.4 Gy IJROBP 1993; 26:3-11.

11. Postoperative Radiation for Oral Cavity Cancer: Radiation Dose Patients receiving <54 Gy had significantly higher failure rate. No dose response beyond 57.6 Gy except for patients with extracapsular nodal spread. +ECE needed at least 63 Gy “Clusters” of two or more of the following also predicted increased risk of failure and need for 63 Gy: oral cavity primary, positive/close margins, nerve invasion, >2 positive nodes, largest node >3 cm, treatment delay >6weeks, Zubrod performance status>2 Moderate to severe complications seen in 7.1%; more if RT dose >63 Gy Dose escalation above 63 Gy “does not appear to improve the therapeutic ratio”.

12. Postoperative Radiation for Oral Cavity Cancer: RT + Chemotherapy Two large randomized trials evaluating RT with or without cisplatin chemotherapy in high-risk resected head and neck squamous cell cancers. EORTC RTOG NEJM 2004; 350:1945-1952 NEJM 2004: 350:1937-1944 High risk features: >2 + nodes, +ECE, + margins (EORTC also included perineural spread and vascular tumor embolism)

13. Postoperative Radiation for Oral Cavity Cancer: RT + Chemotherapy Radiation dose: 60 Gy RTOG; 66 Gy EORTC Cisplatin 100 mg/m2 days 1, 22, 43 both 334 EORTC + 459 RTOG patients (793 total) 26-27% oral cavity primaries In combined analysis, only patients with +ECE and/or + margins benefited from addition of cisplatin Head Neck 2005; 27: 843-850

14. Postoperative Radiation for Oral Cavity Cancer: RT + Chemotherapy

16. What’s Next? RTOG 0234 evaluated postop chemoRT (cisplatin or docetaxel) + EGFR inhibitor cetuximab (Erbitux) This phase II study completed but results are pending

17. Get to Work!! Three-Way Tie for Last