Adjuvant radiochemotherapy in head and neck tumors H. Christiansen and C. F. Hess Department of Radiotherapy Goettingen University

Local control Cause-specific survival Surgery + RT Surgery Lundahl et al. Int J Radiat Oncol Biol Phys 1998 Adjuvant RT pN+

Huang et al. Int J Radiat Oncol Biol Phys 1992

Risk factors for locoregional recurrence after radical surgery Tumor size (>T2) Lymph node involvement (N+) Positive margins after surgery

StudynAdjuvant therapyLocal control Survival Bachaud et al. (Int J Radiat Oncol Biol Phys 1996) RT (65-70 Gy) RT + cisplatin (50mg/m²/week) 55% 70% p=0.08 (5 years) 13% 36% p<0.01 (5 years) Cooper et al. (N Engl J Med 2004) RT (60-66 Gy) RT + cisplatin (100mg/m²/d 1, 22, 43) 72% 82% p=0.01 (2 years) n.s. Bernier et al. (N Engl J Med 2004) EORTC RT (66 Gy) RT + cisplatin (100mg/m²/d 1, 22, 43) 69% 82% p=0.007 (5 years) 40% 53% p=0.04 (5-years)

Progression-free survivalOverall survival Bernier et al. N Engl J Med 2004 Radio-chemotherapy Radiotherapy

EPO for correction of anaemia (locoregional progression free survival) Henke et. al. Lancet

Side effectRTRT + chemo Mucositis III°/IV°21% / 1%41% / 2% Severe nausea/vomittingnot given12% / 11% Severe leukopenianot given16% Severe xerostomia20%14% Bone complications1%2% Toxicity* *Bernier et al. N Engl J Med 2004

Application forms of concomitant cisplatin chemotherapy 100 mg/m² on days 1, 22, 43 (Cooper et al. 2004) weekly 50 mg/m² (Bachaud et al. 1996) → more intensive chemotherapy leads to increased toxicity

Prophylaxis of side effects Amifostine Patient Benefit Questionnaire (PBQ) locoregional control Brizel et. al. JCO 2000

Staar et al. Int J Radiat Oncol Biol Phys 2001 Local control Months G-CSF Patients receiving G-CSF showed reduced mucosal toxicities (p=0.066)

Nutrition support BNS = baseline nutrition support before treatment initiation TNS = nutrition support during treatment only no NS = no nutrition support Rabinovitch et. al. Head Neck 2006 (in press) Side effectBNSno BNSp-value Mucositis III°/IV° 34%40%0.057 Weight lossMedian 5% Median 7% <0.0001

Pilocarpine can maintain and protect unstimulated salivary flow however, there was no positive impact on the QOL outcome for patients taking pilocarpine Pilocarpin Fisher et. al. Int J Radiat Oncol Biol Phys 2003

Modern 3–D radiotherapy technique CTV = primary tumour region and cervical and supraclavicular lymph nodes Gregoire et. al. 2004

Adjuvant RT after laser surgery – the University of Goettingen experience (n=208; 40 stage III, 168 stage IV) Pradier, Christiansen et. al. Int J Radiat Oncol Biol Phys 2005

Preradiotherapeutic hemoglobin level – significant influence on prognosis (Stage III/IV) Pradier, Christiansen et. al. Int J Radiat Oncol Biol Phys 2005 Hb ≥ 13.5 g/dl Hb < 13.5 g/dl Survival

Preoperative hemoglobin level – no significant influence on prognosis (Stage III/IV) Christiansen, Pradier Unpublished data 2006 Hb ≥ 14.7 g/dl Hb < 14.7 g/dl median Hb-level 14.7 g/dl Survival

RT vs. RCT in the adjuvant situation after laser surgery (n=48) the University of Goettingen experience Christiansen, Pradier Unpublished data 2006

Summary Addition of chemo- to adjuvant radiotherapy -Increased local control (increased survival?) -Main agent: Cisplatinum (different modes of application) -Modestly increased toxicity (prophylaxis by Amifostine?) -Considerable impact of RT technique

-New agents e.g. EGFR blocking antibody (Cetuximab) -Patient selection via predictive factors -High precision RT-techniques -Potential impact of laser surgery on treatment efficacy (via better local perfusion) and better QOL Future aspects