Discussão de casos

HNSCC

ECIP 2018

Gilberto de Castro JuniorProfessor Colaborador Livre-Docente – Faculdade de Medicina

da USP

Serviço de Oncologia Clínica - Instituto do Câncer do Estado de

São Paulo

Centro de Oncologia - Hospital Sírio Libanês

Risco em CECCP

Tratamento adjuvante

Tratamento adjuvante

CECCP

Tratamento adjuvante CECCP

RTOG 95-01EORTC 22931

Tratamento adjuvante

do CECCP

Bernier et al. Head Neck 2005

Tratamento adjuvante

do CECCP

Bernier et al. Head Neck 2005

Pignon et al.,

2009

MACH-NC 2009

Pignon et al.,

2009

MACH-NC 2009

MACH-NC 2009

Pignon et al. Radiother Oncol

2009

Pignon et al.,

2009

MACH-NC 2009

Mucosite Dermatite

Candidíase

Toxicidade aguda

Graus 1 ou 2 Graus 3 ou 4

n (%) n (%)

Mucosite 14 (47) 12 (40)

Dermatite 19 (63) 7 (23)

Disfagia 9 (30) 14 (47)

Náuseas 14 (47) 4 (13)

Vômitos 17 (57) 3 (10)

Infecção 11 (37) 4 (13)

Anemia 15 (50) 7 (23)

Leucopenia 4 (13) 5 (16)

Linfopenia 12 (40) 7 (23)

Castro G Jr. et al. Eur Arch Otorhinolaryngol

2007;264:1475-82

Toxicidade aguda CCR

Bonner trial

R.R

.A.

9%

NNT = 11,1

SO

5 a

nos

36,4 x 45,6%

H.R

.

0,71

P = 0,018

Bonner trial

Bonner trial

RTOG 0522: Stage III-IV

Phase III Trial

Stage III and IVa SCC of:

– Oropharynx

– Hypopharynx

– Larynx

Stratify:

– Larynx vs. others

– N0~N1,2a,2b~N2c-3

– KPS

60–80 ~ 90–100

– 3-D vs IMRTb

1.Accelerated FXb +

CDDP: 100 mg/m2, q3W X 2

2.

Accelerated FXb +

CDDP: 100 mg/m2, q3W X 2

aExclude T1 any N and T2N1; b3-D: AFX-CB (72 Gy/42 F/6 W) IMRT: 70 Gy/35 F/6W (BID x 5d)

Cetuximab:

400 mg/m2, Week –1

250 mg/m2/w, Wks 2–8

R

A

N

D

O

M

I

Z

E

n=720

Qual o papel da

QT neoadj no

HNSCC ?• Avaliar resposta tumoral in vivo

• Tratamento precoce de doença

micrometastática

• Preditor de resposta à RT

• Alívio de sintomas relacionados

ao tumor, antes RT

• Preservação de órgão

• Estudo de biomarcadores

preditivos de resposta

Qual o papel da

QT neoadj no

HNSCC ?• Avaliar resposta tumoral in vivo

• Tratamento precoce de doença

micrometastática

• Preditor de resposta à RT

• Alívio de sintomas relacionados

ao tumor, antes RT

• Preservação de órgão

• Estudo de biomarcadores

preditivos de resposta

MACH – NC 2009

Pignon et al., 2009

PARADIGM trial

Overall Survival

P=

0.77

Progression Free

Survival

HR=1.07; 95%CI 0,59-

1,92

HR=1.09; 95%CI 0,59-

2,03

P=

0.82

Haddad et al. Lancet Oncol 2013

Desenho do estudo – Fase III

TPF* x 3Elegíveis

N= 421

• CEC

• Cavidade oral;

• orofaringe,

• hipofaringe

• EC III e IVA

• ECOG PS 0 e 1 Sem QT de indução

R

A

N

D

O

M

I

Z

A

D

O

S

RT 70Gy

PF

RT 70Gy

Cetuximabe(400 + 250mg/sem)

RT 70Gy

PF

RT 70Gy

Cetuximabe(400 + 250mg/sem)

Desfecho primário: Sobrevida global em 3 anos (indução vs não

indução)

* TPF: Docetaxel 75mg/m2 D1, CDDP 80mg/m2 D1 e 5FU 800mg/m2 D1-5/ PF: CDDP 20mg/m2 D1-4 , 5FU 800mg D1-5 sem 1 e

6.

n= 129

n= 79

n= 129

n= 78

Resultados

Sobrevida Global

201

4

Ghi MG. Abst # 6006

ESMO Guidelines

D´Souza G, et al. N Engl J Med. 2007;356(19):1944-1956

HPV Detection

Bishop JA, et al. Semin Diagn Pathol. 2015 Sep;32(5):344-51.

H&E P16 IHC

ISH for high risk HPV

DNA

ISH for E6/E7

mRNA

Optimal Testing Method for HPV?

Bishop JA, et al. Semin Diagn Pathol. 2015 Sep;32(5):344-51.

‘’It is now acknowledged that detecting transcriptionally active,

high-risk HPV is a necessity in routine clinical practice, but there is

considerable confusion among pathologists and clinicians alike

about the subsites and settings in which HPV testing should be

performed. Compounding this lack of clarity is the fact that there

are multiple HPV testing options available, but currently there is no

clear consensus on which test or combination of tests is optimal

for routine diagnostic use.’’

Ang KK, et al. N Engl J Med. 2010;363(1):24-35

RTOG 0129

HPV Survival Analyses

M. Gillison

HPV-Positivity:

Outcome Effects in RT

Ang KK, N Engl J Med. 2010;363:24-35; Rischin D, et al. J Clin Oncol. 2010;28(18):2989-2995; Beitler JJ, et al. Int J

Radiat Oncol Biol Phys. 2014;89(1):13-20; Posner MR, et al. Ann Oncol. 2011;22(5):1071-1077

TAX 324TPF vs PF Induction in

Locally Advanced HNSCC

Posner MR, et al. Ann Oncol. 2011;22(5):1071-1077

Vermorken JB, et al. Lancet Oncol.

2013;14(8):697-710

SPECTRUMCisplatin + Flurouracil ± Panitumumab

Oral HPV DNA Detection

Rettig E, et al. J Clin Oncol. 2015;33(Suppl): Abstract 6005

Time HPV16 prevalence,

N(%)

Other high-risk HPV

prevalance, N (%)

Diagnosis 67 (54%) 27 (22%)

Post-treatment 6 (5%) 17 (14%)

Persistent 5 (4%) 7 (6%)

Newly detected 1 (1%) 12 (10%)

% Cleared post-

treatment

93% 74%

Persistent Oral HPV16 DNA Detection

is Associated With Poor Survival

Rettig E, et al. J Clin Oncol. 2015;33(Suppl): Abstract 6005

5 participants with

persistent oral

HPV16

• All (5/5) recurred

• Most (3/5) died

of disease