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5-year Results ( med f/u 6.9 yrs). social community. patient. treatment. cancer control. organ preservation. function preservation (swallow,speak,breathe). costs. quality of life. unemployment. rehabilitation. adverse events (therapeutical, compliance).
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social community patient treatment cancer control organ preservation function preservation (swallow,speak,breathe) costs quality of life unemployment rehabilitation adverse events (therapeutical, compliance) Why larynx preservation at all ?
Vocal cord T2 / T3 N0 / N1 / N2a/b/c / N3 Surgery CCS TLS SCPL neck dissection comprehensive / selective Radiation (3-D CRT/IMRT) standard hyperfractionated/accelerated(protocol?) Chemotherapy neoadjuvant (protocol?) concurrent (protocol?) Other therapy Larynx preservation / function tumor control adverse events (CTCAE v3.0) survival
Vocal cord T4a N1 / N2a/b/c / N3 Surgery CCS TLS SCPL neck dissection comprehensive / selective Radiation (3-D CRT/IMRT) standard hyperfractionated/accelerated(protocol?) Chemotherapy neoadjuvant (protocol?) concurrent (protocol?) Other therapy Larynx preservation / function tumor control adverse events (CTCAE v3.0) survival
Vocal cord/subglottis T3 / T4a N1 / N2a/b/c / N3 Surgery CCS TLS SCPL neck dissection comprehensive / selective Radiation (3-D CRT/IMRT) standard hyperfractionated/accelerated(protocol?) Chemotherapy neoadjuvant (protocol?) concurrent (protocol?) Other therapy Larynx preservation / function tumor control adverse events (CTCAE v3.0) survival
Supraglottis (central epiglottis) T2 / T3 / T4a N1 / N2a/b/c / N3 Surgery CCS TLS SCPL neck dissection comprehensive / (selective) Radiation (3-D CRT/IMRT) standard hyperfractionated/accelerated(protocol?) Chemotherapy neoadjuvant (protocol?) concurrent (protocol?) Other therapy Larynx preservation / function tumor control adverse events (CTCAE v3.0) survival
Supraglottis (carcinoma of the angle) T2 / T3 / T4a N1 / N2a/b/c / N3 Surgery CCS TLS SCPL neck dissection comprehensive / selective Radiation (3-D CRT/IMRT) standard hyperfractionated/accelerated(protocol?) Chemotherapy neoadjuvant (protocol?) concurrent (protocol?) Other therapy Larynx preservation / function tumor control adverse events (CTCAE v3.0) survival
Supraglottis / hypopharynx (carcinoma of the margin) T1 / T2 / T3 / T4a N1 / N2a/b/c / N3 Surgery CCS TLS SCPL neck dissection comprehensive / selective Radiation (3-D CRT/IMRT) standard hyperfractionated/accelerated(protocol?) Chemotherapy neoadjuvant (protocol?) concurrent (protocol?) Other therapy Larynx preservation / function tumor control adverse events (CTCAE v3.0) survival
standard evaluation of adverse events (CTCAE v.3.0?) and quality of life (EORTC QLQ • C30 / HN 35 ?) under and after therapy • standard evaluation of costs • realistic standard endpoints for studies observation period cancer control adverse events costs 2 years 5 years larynx preservation rate local control regional control distant control Second primary LFS DFS OS CTEAE v. 3.0 organ function compliance treatment rehabilitation unemployment Which questions have to be answered in the future ?
1 separation (larynx a functional but not a cancerlogic entity) larynx hypopharynx glottis supraglottis postcricoid sinus piriformis posterior wall Vocal cord commisura anterior central epiglottis carcinoma of the angle medial posterolateral 2 radiation / chemotherapy • conformal radiotherapy 3-DCRT, IMRT as standards • concurrent radiochemotherapy with standard or altered fractionation (hyperfractionation, • acceleration). • altered fractionation without chemotherapy • chemotherapy with new protocols / application (TPF, TIC, Gemcitabine, Vinorelbine, Irinotecan, • ..../ intraarterial chemotherapy). - Studies
epidermal growth factor/tyrosine kinase inhibitors C 225 OSI 774 ZD 1839 • angiogenesis Thalidomide SU 5416 Bevacizumab • RAS: Farnesyl Transferase inhibitors BMS 24662 R 115777 SCH 6636 Onyx 015 • tumor hypoxia misonidazole nimorazole tirapazamine 3 targeted therapy (combined modality) 4 interventional therapy LIT
1. standard radiation (standard 2Gy/d, 5 days /week, 70Gy/7weeks) larynx hypopharynx glottis (med./lat.) supraglottis (med./lat.) angle sinus piriformis (med./lat.) postcricoid posterior wall 2. hyperfract. radiation RTOG 9003 (2x1,2Gy/d, 5 days/week, 81,6 Gy/7weeks) 3. accelerated fract. radiation with boost RTOG 9003 (1,8Gy/d - 1,8 Gy+1,5Gy/d, 5 days/week, 72 Gy/6weeks) 4. concurrent radiochemo RTOG 91-11 (standard radiation+Cisplatin 100mg/m2/d1-22-43) 5. concurrent radiochemo with hyperfract: radiation (Budach, Brizel, Wendt) 6. newer Inductionschemo + (TPF/TIC/....) 7. TLS / CCS+ 8. chemotherapy exclusive (protocol?) Building up models for future studies
RTOG 91-11(n=547 foll. Up median 3,8 years) Veterans Affair (n=332 foll. Up median 2,75 years) locoregional control % larynx preservarion % local control % distant metastasis % larynx cancer III/IV (2/3 supraglottis 60% T3) laryngectomy free survival % disease free survival % overall survival % 76 55 68 50 induction chemo radiation (ICR) 2y 5y 75 70 66 64 88 61 59 80 9 15 17 59 43 88 52* 38* 65 50 66 concurrent radiochemo (RC) 2y 5y 88* 85* 66 80 66 78* 73 66 8* 12 66 66* 45* 66 61* 36* 66 74 54 66 radiation (R) 2y 5y 70 65 66 58 66 56 50 66 16 22 66 53 38 66 44 27 66 75 56 68 65 radical surgery + radiation (S) 2y 5y 70 65 66 70 65 66 70 65 93 70 65 11 70 65 11 70 65 73 65 70 65 * p<0,05 Steiner TLS ± rad. (n=141,foll.up med. 3years, all supraglottis, III/IV=50%) 5y 84 (all) 74 (all) 74 (all) 74 (all) 66 (all) 74 (all) 45 (all) 66 (all) 74 (all) 45 (all) Laccourreye chemo (platin) chemo+CCS/SCPL (n=231,foll.up >3years, glottis, T1-3 N0M0 5y 5y 65 65 62 0 0 0 89 68
hypopharynx cancer (II) III/IV (80% piriformis sinus 75% T3) larynx preservarion % disease free survival % overal survival % distant metastasis % local control % locoregional control % induction chemo radiation (ICR) 3y 5y 64 58 43 25 57 30 27* 35* 59 k 59 k radical surgery radiation 3y 5y m 31 27 43 35 40 45 59 k 59 k EORTC Lefebvre (n=202 foll. up median 4.25 years) * P <0,05 5y 71 (I/II) 47 (III/IV) Steiner TLS ± rad. II/ III/ IV piriformis sinus 60% T2 25% T3/4 (n=129,foll.up med. 3,75 years 95 (I / II) 69 (III / IV) Laccourreye III / IV chemo n=31 5y 5y 55 64 5y 5y 10 38 96 90 5y 64 55 10 38 CCS 5y 96 90 (pharyngolarynx foll. up > 3 years)