Radioterapia em Cncer de Cabea e Pescoo

Michael Jenwei Chen Hospital Israelita Albert Einstein SP Hospital A. C. Camargo SP

IV Board Review Curso de Reviso em Oncologia Clnica 18 a 20 de junho de 2012

Objetivos de aprendizado
Conceitos bsicos em radioterapia em cncer de cabea e pescoo

Como maximizar o benefcio do tratamento irradiante

Uso de novas tecnologias e perspectivas futuras em Radioterapia

Conceitos bsicos

Radioterapia externa convencional (2D)

Conceitos bsicos

Radioterapia externa tri-dimensional (3D-CRT)

Conceitos bsicos

Radioterapia externa tri-dimensional (3D-CRT)

Conceitos bsicos

IMRT (Intensity Modulated Radiation Therapy)

3-campos RT 3-campos IMRT
Dose prescrita (distribuio tpica)
OR PTV OR PTV

Conceitos bsicos

Tratamento loco-regional em Cncer de Cabea e Pescoo

Tumores de lngua oral

Lindberg R. Cancer. 1972 Jun;29(6):1446-9.

Conceitos bsicos

Tratamento loco-regional em Cncer de Cabea e Pescoo

Tumores de base de lngua

Lindberg R. Cancer. 1972 Jun;29(6):1446-9.

Conceitos bsicos

Tratamento loco-regional em Cncer de Cabea e Pescoo

Tumores de trgono retromolar e pilar amigdaliano

Lindberg R. Cancer. 1972 Jun;29(6):1446-9.

Conceitos bsicos

Estratgias de tratamento

Corv R. Radiother Oncol. 2007 Oct;85(1):156-70.

Conceitos bsicos

Radioterapia adjuvante
Indicaes mais usuais:

margens de resseco positivas ou exguas estdio tumoral avanado (T3/T4) dois ou mais gnglios linfticos positivos (N2/N3) extenso extracapsular invaso perineural invaso do espao linfovascular

Conceitos bsicos

Radioterapia adjuvante
Cirurgia + Radioterapia vs. Cirurgia exclusiva:

Postoperative radiation as adjuvant treatment for carcinoma of the oral cavity, larynx, and pharynx: preliminary report of a prospective randomized trial. Kokal WA, et al.. J Surg Oncol. 1988;38(2):71. Post-operative radiotherapy in carcinoma of buccal mucosa, a prospective randomized trial. Mishra RC, et al.. Eur J Surg Oncol. 1996;22(5):502

Cirurgia + Radioterapia vs. Radioterapia exclusiva:

Early closure of a randomized trial: surgery and postoperative radiotherapy versus radiotherapy in the management of intra-oral tumours. Robertson AG, et al.. Clin Oncol (R Coll Radiol). 1998;10(3):155-60.

Conceitos bsicos

Radioterapia adjuvante

SEER

n = 8795 RT adjuvante para N+

SG: 43.2% para CIR + RT vs. 33.4% para CIR exclusiva

Lavaf A, et al.. Cancer. 2008 Feb 1;112(3):535-43.

Conceitos bsicos

Radioquimioterapia adjuvante

Cooper JS, et al.. N Engl J Med. 2004 May 6;350(19):1937-44. Bernier J, et al.. N Engl J Med. 2004 May 6;350(19):1945-52.

Conceitos bsicos

Radioquimioterapia concomitante
SG em 3 anos: Head & Neck Intergroup n = 295 CA de orofaringe, cavidade oral e hipofaringe, irressecveis
Adelstein DJ, et al.. J Clin Oncol. 2003 Jan 1;21(1):92-8.

RT: 23% RTQT: 37% RTQT (c/ split): 27%

Conceitos bsicos

Radioquimioterapia concomitante
Randomized trial of radiation therapy versus concomitant chemotherapy and radiation therapy for advanced-stage oropharynx carcinoma. Calais G, et al.. J Natl Cancer Inst. 1999 Dec 15;91(24):2081-6. Hyperfractionated irradiation with or without concurrent chemotherapy for locally advanced head and neck cancer. Brizel DM, et al.. N Engl J Med. 1998 Jun 18;338(25):1798-804. Chemoradiotherapy for locally advanced head and neck cancer: 10year follow-up of the UK Head and Neck (UKHAN1) trial. Tobias JS, et al.. Lancet Oncol. 2010 Jan;11(1):66-74. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. Bonner JA, et al.. N Engl J Med. 2006 Feb 9;354(6):567-78.

Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients.
Pignon JP, et al.. Radiother Oncol. 2009 Jul;92(1):4-14.

Conceitos bsicos

CA de laringe: preservao de rgos

CIR + RT vs. QT de induo + RT Veterans Affairs Larynx Trial n = 332 CA de laringe, EC III e IV

64% de taxa de preservao de laringe em 02 anos SG: ns QT + RT: maior falha local, menor taxa de metstases distncia
N Engl J Med. 1991 Jun 13;324(24):1685-90.

Conceitos bsicos

CA de laringe: preservao de rgos

RTOG 91-11 Intergroup

n = 547 CA de laringe, EC III e IV SG: ns

Forastiere AA, et al.. N Engl J Med. 2003 Nov 27;349(22):2091-8.

Conceitos bsicos

Esvaziamento cervical psradio(quimio)terapia

Thariat J, et al.. Int J Radiat Oncol Biol Phys. 2012 Mar 1;82(3):e367-74.

Conceitos bsicos

Radioterapia exclusiva
CA de nasofaringe Sobrevida aps RT exclusiva (em 5 anos)
I
Cooper JS, et al. Cancer. 1998 Jul 15;83(2):213-9. Heng DM, et al.. Cancer. 1999 Nov 15;86(10):1912-20. Ma J, et al.. Int J Radiat Oncol Biol Phys. 2001 Aug 1;50(5):1181-9.

II 50% 74% 70%

III 56% 60% 53%

IV 30% 28 35% 37%

70% 88% 89%

Conceitos bsicos

Situaes especiais: CA de nasofaringe

INT 0099 (RTOG, ECOG, SWOG) n = 193 pacientes, EC III e IV (AJCC)

RxT (70Gy) + QT (CDDP) --> QT adjuvante (CDDP + 5-FU)

Fechamento precoce do estudo em funo do benefcio de RT + QT

RxT (70Gy)
Al-Sarraf M, et al.. J Clin Oncol. 1998 Apr;16(4):1310-7.

Conceitos bsicos

Situaes especiais: irradiao cervical unilateral possvel?

OSullivan B. Int J Radiat Oncol Biol Phys. 2001 Oct 1;51(2):332-43.

Recomendaes:

Invaso de palato mole ou base de lngua < 1 cm, estdio N0 ou N1

Expert Panel on Radiation Oncology. Head Neck. 2012 May;34(5):613-6.

Conceitos bsicos

Situaes especiais: CA de laringe inicial

CA de laringe gltica T1 T2 baixo risco de disseminao linfonodal

Campo de tratamento: ~ 5 x 5 cm

Conceitos bsicos

Situaes especiais: CA de laringe inicial

@2 Gy/dia
T1N0M0 SG: ns

@ 2,25 Gy/dia

Yamazaki H, et al.. Int J Radiat Oncol Biol Phys. 2006 Jan 1;64(1):77-82.

Maximizar o benefcio do tratamento irradiante

Tempo total de tratamento

Atraso no trmino do tratamento irradiante

TCP (tumor control probability)

Dimin. na probabil. de controle de doena de 1,4% /dia

Fowler JF et al. Int J Radiat Oncol Biol Phys. 1992;23(2):45767. Fowler JF. Acta Oncol. 2001;40(6):712-7

Bourhis JM. Lancet. 2006 Sep 2;368(9538):843-54.

Maximizar o benefcio do tratamento irradiante

Radioquimioterapia vs. radioterapia acelerada

RxT (70Gy @ 35fx, em 7 sem.) + QT (Carboplatina + 5-FU) RxT (70Gy @ 35fx, em 6 sem.) + QT (Carboplatina + 5-FU)

GORTEC 99-02 N = 840 pacientes

RxT (64,8Gy @ 36fx, b.i.d., em 3.5 sem.)

Bourhis J, et al.. Lancet Oncol. 2012 Feb;13(2):145-53.

Maximizar o benefcio do tratamento irradiante

Radioquimioterapia vs. radioterapia acelerada

Bourhis J, et al.. Lancet Oncol. 2012 Feb;13(2):145-53.

Bourhis J, et al.. Lancet Oncol. 2012 Feb;13(2):145-53.

Maximizar o benefcio do tratamento irradiante

IMRT: Onde est o benefcio?

Proteo de tecidos crticos

Melhor conformidade

Escalonamento de dose

Melhor homogeneidade de dose

Fracionamento alterado (S.M.A.R.T., S.I.B.)

Aplicaes clnicas de IMRT

S.M.A.R.T. / S.I.B.

70Gy

54Gy

45Gy

Reviso sistemtica da literatura:

Medline, Embase ~ 08/2007 Comparativos: IMRT vs. no-MRT excludos: no-IMRT, end-point mal-definido, menos de 10 pacientes, re-irradiao
Lancet Oncol. 2008 Apr;9(4):367-75.

Reviso sistemtica

IMRT em CA de nasofaringe
Velderman L, et al. Lancet Oncol. 2008 Apr;9(4):367-75.

Reviso sistemtica

IMRT em CA de seios da face

Velderman L, et al. Lancet Oncol. 2008 Apr;9(4):367-75.

Reviso sistemtica

IMRT em CA de orofaringe, hipofaringe, laringe e cavidade oral

Velderman L, et al. Lancet Oncol. 2008 Apr;9(4):367-75.

IMRT em Cncer de Cabea e Pescoo

Controle loco-regional
n
Dawson et al. IJROBP 2000 Lee et al. IJROBP 2003 Chao et al. IJROBP 2003 Eisbruch et al. IJROBP 2004 Bussels et al. Radiother Oncol 2004 Yao et al. IJROBP2005 Stueder et al. Strahlenther Onkol 2007

Falhas
16 10 17 21 20 11 77

Dentro do PTV
10 10 9 17 15 10 73

Marginal
2 0 3 4 5 1 1

Fora do campo
4 0 5 0 0 0 3

58 150 165 133 72 151 280

Total (%)

1009

172

144 (84)

16 (9)

12 (7)

IMRT em Cncer de Cabea e Pescoo

IMRT em estudos fase II

RTOG 0225

GORTEC 2004-03

Lee N, et al. J Clin Oncol. 2009 Aug 1;27(22):3684-90. Toledano I, et al.. Radiother Oncol. 2012 Apr;103(1):57-62.

IMRT em Cncer de Cabea e Pescoo

IMRT vs. 2D/3D-CRT

Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT)
Nutting CM, et al. Lancet Oncol. 2011 Feb;12(2):127-36.

IMRT em Cncer de Cabea e Pescoo

IMRT vs. 2D/3D-CRT

n = 94 pacientes SG e SLD: ns

Nutting CM, et al. Lancet Oncol. 2011 Feb;12(2):127-36.

A Randomized Trial Comparing Intensity Modulated Radiotherapy versus 2-Dimensional Radiotherapy for Stage II Nasopharyngeal Carcinoma
4 year local control was 90.5% with IMRT vs. 71.7% with 2DRT (p = 0.019). Neck control, distant metastasis, failure-free, and disease specific survival were not significantly different between the 2 arms. 25 patients in each arm underwent prospective salivary flow assessment. There was
gradual recovery of SWS and SPS among patients treated with IMRT while patient on 2DRT showed no improvement over time. The mean SWS and SPS flow at 12 months was 26% and 114% of baseline among patients treated with IMRT, compared with 5% and 0% among patients treated

()

was significant difference in SWS and SPS between patients treated with IMRT and 2DRT at 2, 6, and 12 months post-RT. ()
D. Kwong, et al. Int J Radiat Oncol Biol Phys. 2008 (Vol. 72, Issue 1, Page S98)

with 2DRT, respectively. There

Uso de novas tecnologias e perspectivas futuras em Radioterapia

Uso de imagens oncolgicas

Planejamento com fuso de imagens: PET-CT

In: Eisbruch A. IMRT for H&N Cancer: Some clinical considerations

In: Eisbruch A. IMRT for H&N Cancer: Some clinical considerations

PETPET -CT (falso positivo)

?
PETPET -CT (falso negativo)

PET-CT e predio de resposta ao tratamento

Porceddu SV, et al.. Head Neck. 2011 Dec;33(12):1675-82

IMRT em Cncer de Cabea e Pescoo

Preservao funcional

Dornfeld et al. Int J Radiat Oncol Biol Phys. 2007 Jul 1;68(3):750-7.

IMRT em Cncer de Cabea e Pescoo

Preservao funcional
Regio avaliada / dose mensurada (Gy) <10 Prega ari-epigltica D Prega ari-epigltica E Falsa corda vocal D Falsa corda vocal E 67.0 66.1 Perda de peso (kg) >10 78.1 75.7 p 0.05 0.06 76.4 76.6 61.5 60.0 0.03 0.04 Gastrostomia (em 1 ano) Sim No p

Dornfeld et al. Int J Radiat Oncol Biol Phys. 2007 Jul 1;68(3):750-7.

Novas tecnologias em Radioterapia

VMAT (Volumetric Modulated Arc Therapy)

Novas tecnologias em Radioterapia

IGRT (Image-Guided Radiation Therapy)

Sao Paulo, June 29, 2007 Target Delineation Symposium

5th Annual International IMRT Symposium

Elapsed Days Patient Immobilized with Acquaplast Mask CTs Aligned Using BBs on Mask

Dong/MDACC

Perspectivas futuras em Radioterapia

Tratamento de recidivas

Janot F, et al. J Clin Oncol. 2008 Dec 1;26(34):5518-23.

Perspectivas futuras em Radioterapia

Tumores HPV+
A randomized double-blind phase III study of (...). Results of the Danish Head and Neck Cancer Study (DAHANCA) Protocol 5-85.
Overgaard J, et al.. Radiother Oncol. 1998 Feb;46(2):135-46.

Lassen P, et al.. J Clin Oncol. 2009 Apr 20;27(12):1992-8.

Perspectivas futuras em Radioterapia

Tumores HPV+ e modulao de dose

RxT (54Gy) + QT (Cetuximab)

ECOG 1308 N = 90 pacientes

Paclitaxel + CDDP + Cetuximab

RC reavaliao RP, PD

RxT (70Gy) + QT (Cetuximab)

ASCO 2012. Marur S et al... J Clin Oncol 30, 2012 (suppl; abstr 5566)

Obrigado!