Protokolle und Indikationen für die adjuvante Radio / Radiochemotherapie Prof. Dr. med. R. Fietkau...
-
Upload
maximilian-stubler -
Category
Documents
-
view
102 -
download
0
Transcript of Protokolle und Indikationen für die adjuvante Radio / Radiochemotherapie Prof. Dr. med. R. Fietkau...
Protokolle und Indikationen für die adjuvante Radio / Radiochemotherapie
Prof. Dr. med. R. FietkauStrahlenklinik Erlangen Hamburg, 03.02.2012
2
Head and Neck Tumors: Effect of Postoperative RT
regional control
S S + RT
Bartelink 1983* ~ 50 % ~ 80 % p = 0,036
Huang et al. 1992** 31 % 59 % p = 0,001
Nisi et al. 1998 68 % 87 % p = 0,04
* ECS ** ECS and or R+
3
Adjuvant radiotherapy and survival for patients with node-positive head and neck cancer: an analysis by primary site and nodal stage
Kao J, Lavaf A, Teng MS, Huang D, Genden EM. (Int J Radiat Oncol Biol Phys. 2008)
4
Adjuvant radiotherapy and survival for patients with node-positive head and neck cancer: an analysis by primary site and nodal stage
Kao J, Lavaf A, Teng MS, Huang D, Genden EM. (Int J Radiat Oncol Biol Phys. 2008)
5
Behandlung der Lymphabflussgebiete:Sofortige postoperative RT oder im Rezidiv
(Regine et al. 1999, Head and Neck)
Ergebnisse
Rezidive Primäre Therapie
(OP + RT) (OP + RT)(N = 31 ; 5 Jahre) (N = 143 ; 5 Jahre)
Lokoregionäre Kontrolle 46 % 69 % p = 0,03
NED – Überleben 32 % 54 % p = 0,04
6
Kopf – Hals – Tumoren: Indikation zur postoperativen Bestrahlung
Primärtumor : • pT3 / pT4
• R1 – Resektion
• Resektionsrand < 5 mm
7
Kopf – Hals – Tumoren: Indikation zur postoperativen Bestrahlung
Lymphabflussgebiete :
• N +
a b e r : - umstritten bei einem befallenen Lymphknoten
- unstrittig bei extrakapsulärem Wachstum oder 2 LK +
8
Einfluss der Dosis auf die regionäre Rezidivrate
(Peters et al. 1993)
• Randomisierte Studie zur postoperativen RT (R0 / R)• Stratifizierung nach Risikofaktoren : - Zahl der LK – Metastasen - Zahl der befallenen LK – Regionen - LK – Größe - Extrakapsuläres Wachstum - Invasion von Muskulatur, Gefäßen, Haut, Nerven, Schädelbasis
Low Risk High Risk
57,6 Gy 63 Gy 68,4 Gy
9
RT-Dosis postoperativ:Randomisierte Studie von Peters et al 1993; n = 240
Primärtumor:
Niedriges 54 Gy 63%
Risiko: 57,6 Gy 92%
63,0 Gy 89%
Hohes 63,0 Gy 89%
Risiko: 68,4 Gy 81%
2 year control actuarial control rates at the primary site
p = 0,02
10
57,6 Gy 52%
63,0 Gy 74%
68,4 Gy 72%
RT-Dosis postoperativ:Randomisierte Studie von Peters et al 1993; n = 240
„2 year control actuarial locoregional control rates“ ECS +
p = 0,003
11
Positive surgical margins in neck dissection specimens in patients with head and neck squamous cell carcinoma and the
effect of radiotherapySmeele LE, Leemans CR, Langendijk JA, Tiwari R, Slotman BJ, van Der Waal I, Snow GB. (Head Neck. 2000)
12
Postoperative therapy in head and neck cancer: state of the art, risk subset, prognosis and unsolved questions.
Denaro N, Russi EG, Adamo V, Colantonio I, Merlano MC. (Oncology 2011)
13
Postoperative therapy in head and neck cancer: state of the art, risk subset, prognosis and unsolved questions.
Denaro N, Russi EG, Adamo V, Colantonio I, Merlano MC. (Oncology 2011)
14
Postoperative RT/RCT bei Kopf-Hals-Tumoren:Einfluss Intervall OP RT
Intervall Lokoregionäre KontrolleAng 2001 - 31 Tage: 80% x 72% p=0,34 x
et al >31 Tage: 65% x 43% p=0,03 xx
Bastit 2001 0-30 Tage: 78% et al >30 Tage: 73% n.s.
Muriel 2001 0-50 Tage: 83%et al >50 Tage: 68% p=0,02
Langendijk 2005 6-8 Wochen: 73% n.s.et al >8 Wochen: 73%
Parsons 1997 0-50 Tage: 79% p=0,02et al >50 Tage: 54%
X: akzelerierte RT
XX: konventionelle RT
15
The relationship between waiting time for radiotherapy and clinical outcomes: a systematic review of the literature
Chen Z, King W, Pearcey R, Kerba M, Mackillop WJ. (Radiother Oncol. 2008)
16
Postoperative radiotherapy in squamous cell carcinoma of the oral cavity: the importance of the overall treatment time
Langendijk JA, de Jong MA, Leemans CR, de Bree R, Smeele LE, Doornaert P, Slotman BJ.(Int J Radiat Oncol Biol Phys. 2003)
17
Risk-group definition by recursive partitioning analysis of patients with squamous cell head and neck carcinoma treated with surgery and
postoperative radiotherapy.Langendijk JA, Slotman BJ, van der Waal I, Doornaert P, Berkof J, Leemans CR. (Cancer 2005)
18
Risk-group definition by recursive partitioning analysis of patients with squamous cell head and neck carcinoma treated with surgery and
postoperative radiotherapy.Langendijk JA, Slotman BJ, van der Waal I, Doornaert P, Berkof J, Leemans CR. (Cancer. 2005)
19
Risk-group definition by recursive partitioning analysis of patients with squamous cell head and neck carcinoma treated with surgery and
postoperative radiotherapy.Langendijk JA, Slotman BJ, van der Waal I, Doornaert P, Berkof J, Leemans CR. (Cancer 2005)
20
Risk-group definition by recursive partitioning analysis of patients with squamous cell head and neck carcinoma treated with surgery and
postoperative radiotherapy.Langendijk JA, Slotman BJ, van der Waal I, Doornaert P, Berkof J, Leemans CR. (Cancer. 2005)
21
Postoperative therapy in head and neck cancer: state of the art, risk subset, prognosis and unsolved questions.
Denaro N, Russi EG, Adamo V, Colantonio I, Merlano MC. (Oncology. 2011)
22
Postoperative therapy in head and neck cancer: state of the art, risk subset, prognosis and unsolved questions.
Denaro N, Russi EG, Adamo V, Colantonio I, Merlano MC. (Oncology. 2011)
23
Kopf-Hals-Tumore: Adjuvane RT versus RCTLaramore et al. 1992
3 x Cisplatin/5-FU RT
OP
RT
24
Kopf-Hals-Tumore: Adjuvane RT versus RCTLaramore et al. 1992
OP/RT OP/CT/RT4-Jahres-Überlebensrate 44 % 48 % n. s.4-Jahres NED-Rate 38 % 46 % n. s.Lokoregionäre Rezidive 29 % 26 % n. s.Fernmetastasen (erstes Ereignis) 10 % 5 % p=0,03
(insgesamt) 23 % 15 % p=0,03
25
Postoperative concomitant irradiation and chemotherapy with mitomycin C and bleomycin for advanced head-and-neck carcinoma
Smid L, Budihna M, Zakotnik B, Soba E, Strojan P, Fajdiga I, Zargi M, Oblak I, Dremelj M, LeSnicar H. (Int J Radiat Oncol Biol Phys. 2003)
26
Postoperative RT vs. RCT: Haffty et al 2003;Postoperative RCT mit Mitomycin C ± Dicumarol (n=182)
RT RCTLokale Kontrolle 67% 87% p=0,015(5 Jahre)
DFS 44% 67% p=0,03(5 Jahre)
Überleben 41% 56% n.s.(5 Jahre)
27
Kopf-Hals-Tumoren: postoperativ RT vs. RCT; Einschlußkriterien
Bachaud et al 1996 III , IV + extrakapsuläres Wachstum
EORTC 22931 pT3, pT4
pT1 pT2 pN2 – 3extrakapsuläres WachstumR1-Resektionperineurale Infiltrationvaskulärer Befall
RTOG 9501 > 2 LKs positivextrakapsuläres WachstumR1-Resektion
ARO-Studie > 3 LKs positivextrakapsuläres WachstumpT3 R1, pT4
28
HNO-Tumoren:Postoperative RCT versus RT
Studien : Chemotherapie
Bachaud et al 1996 : cis-Platin 50 mg / m² / Woche
EORTC 22931 : cis-Platin 100 mg / m² d 1, 22, 43
RTOG : cis-Platin 100 mg / m² d 1, 22, 43
ARO 95 – 6 : cis-Platin 20 mg / m² d 1 – 5 u. 29 – 33500 mg / m² 5-FU
29
Radiochemotherapie Kopf-Hals-TumorenAdjuvante RCT
Strahlentherapie
Cooper et al. 2004
RTOG 9501 Intergroup
PT + LAG 60Gy
Boost 6Gy
Bernier et al. 2004
EORTC Trial 22931
PT + LAG 54Gy
Boost 12Gy
Fietkau et al. 2006
ARO 96-3
PT: 64Gy
pN0: 50Gy
pN+: 56Gy
Extrakapsuläres Wachstum:
64Gy
30
Radiochemotherapie Kopf-Hals-TumorenAdjuvante RCT
Lokale Kontrolle [%]
Überlebensrate[%]
Fernmetastasen[%]
RT RCT RT RCT RT RCT
Cooper et al.°
70 81 p=0.01 47 56 p=0.19 23 20 n.s.
Bernier et al.*
69 82 p=0.007 40 53 p=0.02 25 21 n.s.
Fietkau et al.*
62 83 p=0.006 49 58 p=0.11 32 31 n.s.
°2-Jahresdaten, *5-Jahresdaten
Cooper et al., NEJM 350;19, 05/2004Bernier et al., NEJM 350;19, 05/2004Fietkau et al., ASCO 2006
31
Radiochemotherapie Kopf-Hals-TumorenAdjuvante RCT
Akuttoxizität
Mukositis G3/G4 [%] Alle G3/G4 [%]
RT RCT RT RCT
Cooper et al. 2004
RTOG 9501 Intergroup
37 62 p=0.001 34 77 p<0.0001
Bernier et al. 2004
EORTC Trial 22931
21 44 p=0.004 21 41 p=0.001
Fietkau et al. 2006
ARO 96-3
13 21 p=0.04 --- --- ---
32
Radiochemotherapie Kopf-Hals-TumorenAdjuvante RCT
Spättoxizität
RT RCT
Bernier et al. 2004 41% 38% p=0.25
Cooper et al. 2004 17% 21% p=0.29
Bernier et al., NEJM 350;19, 05/2004
33
Adjuvante RCT bei Kopf-Hals-Tumoren
Durchführbarkeit der RT / CT
RT CT
EORTC 22931 90% 64%
RTOG 9501 80% 83%
ARO 96 – 3 96 % 73 %
34
Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501).Bernier J, Cooper JS, Pajak TF, van Glabbeke M, Bourhis J, Forastiere A, Ozsahin EM, Jacobs
JR, Jassem J, Ang KK, Lefèbvre JL. (Head Neck 2005)
35
Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501).Bernier J, Cooper JS, Pajak TF, van Glabbeke M, Bourhis J, Forastiere A, Ozsahin EM, Jacobs
JR, Jassem J, Ang KK, Lefèbvre JL. (Head Neck 2005)
36
Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients.
Pignon JP, le Maître A, Maillard E, Bourhis J; MACH-NC Collaborative Group.Radiother Oncol. 2009
37
Adjuvant chemotherapy prior to postoperative concurrent chemoradiotherapy for locoregionally advanced head and neck cancer.
Choe KS, Salama JK, Stenson KM, Blair EA, Witt ME, Cohen EE, Haraf DJ, Vokes EE. (Radiother Oncol. 2010)
38
Adjuvant chemotherapy prior to postoperative concurrent chemoradiotherapy for locoregionally advanced head and neck cancer.
Choe KS, Salama JK, Stenson KM, Blair EA, Witt ME, Cohen EE, Haraf DJ, Vokes EE. (Radiother Oncol. 2010)
39
Radiochemotherapie Kopf-Hals-TumorenAdjuvante RCT
Zusammenfassung: Postoperative RT Indiziert: pT3/4; R1; >/= 2 LK +; Bei 1 LK + (?; Dösak-Studie)
Postoperative RCT zeigt Vorteile im Überleben und lokoregionärer Kontrolle bei Hochrisikopatienten v.a. bei R1-/R2-Resektion und extrakapsulärem LK-Wachstum
Postoperative RT-Dosis: 56-66Gy (Risikoadaptiert)
Akuttoxizität erhöht bei RCT versus RT
Spättoxizität nicht erhöht
Keine Reduktion der Fernmetastasierung
Offene Fragen: Adjuvante Chemotherapie nach postoperativer Radiochemotherapie?
Andere Chemotherapeutika: Taxane?
Small Molecules/Antikörper?