Hospital Alianca - Anatomia Patológica norteando conduta

8/9/2019 Hospital Alianca - Anatomia Patolgica norteando conduta

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Individualizando o tratamento:papel da anatomia patolgica nas

atuais decises da oncologia

Sesso Oncopatolgica do Hospital

Aliana

Gustavo Godoy

Salvador, 25 de maro de 2010


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Diagnstico

Origem de carcinoma no identificada clinicamente em

3%. Pavlidis et al, 2003; McCredie et al, 1991 ; Muir & Weiland, 1995 ; Parkin et al,

1997 ; Briasoulis & Pavlidis, 1997 ; Hainsworth & Greco, 1993

Apenas a minoria dos pacientes tero doenas com

potencial de cura ou para as quais exista benefcio

substancial de sobrevida.

O uso apropriado da patologia diagnstica especializadae exames radiogrficos selecionados identificaro esses

pacientes.


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Estratificao de risco: mama


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Mama: quimioterapia adjuvante

Metanlise EBCTCG (Early Breast Cancer Trialists'

Collaborative Group): Lancet 1998

14.000 mulheres Quando comparado a CMF, esquema baseado em antraciclina

reduz em 11% o risco anual de recidiva e 16% de mortalidade

(absoluto de 3% em 5 anos e 4% em 10 anos).

Maior benefcio antraciclina: hiperexpresso de HER2/neu

(associada recidiva e morte).

Thor et al, 1998; Paik et al, 1998;

Pritchard et al, 2006; Gennari et al, 2008.


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Mama: hormonioterapia adjuvante

IfER status is used to select adjuvant treatment, thestudy should be performed in a well-established, skilled

laboratory.

Harvey et al, 1999

Metanlise EBCTCG (Early Breast Cancer Trialists'

Collaborative Group): Lancet 2005

80.273 mulheres estgio I ou II

Benefcio de 5 anos de tamoxifeno restrito a ER-positivo ou

desconhecido

Reduo absoluta em 15 anos em recidiva e mortalidade 12% e

9%, respectivamente.


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Mama: biolgico paliativo

25% das pacientes hiperexpressam HER2/neu.

Pegram, Pauletti, Slamon, 1998

Pacientes tratados com quimioterapia e trastuzumabeapresentam sobrevida mais longa (25 vs. 20 meses,P=.05).

Seidman et al, 2002


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Mama: biolgico paliativo

Lapatinibe um inibidor de tirosina quinase deHER2/neu e EGFR (epidermal growth factor receptor)

Combinao capecitabina/lapatinibe (GSK-EGF100151)

324 pacientes que falharam a antraciclinas, taxanes e

trastuzumabe. SLP 8 meses vs. 4 meses (P


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Mama: biolgico adjuvante


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Estratificao de risco: mama

Risk stratification by hormonal receptor (ER, PgR) and

HER2 status in small (1cm) invasive breast cancer: Who

might be a possible candidate for adjuvant treatment? #564

Axillary lymph node involvement was much more common in HER-2

positive group (33% vs 11%, p < 0.0001) and triple negative (TN) group

(24% vs 11%, p = 0.002) than in hormone receptor positive group

HER-2 positivity and triple negativity were identified as independentprognostic factors to predict DFS (p = 0.026) and OS (p = 0.017) in

T1bN0 tumors. Limiting to T1aN0 tumors, statistical significance was

not maintained


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Estratificao de risco: mamaTumor phenotype and characteristics of metastatic brain

involvement in breast cancer patients: Potential clinical

consequences. #1026, #1064, #1069 (Ki67)


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Individualizao do tratamento: mama

Identification of a subpopulation of metastatic breast

cancer (MBC) patients with very high HER2 expression

levels and possible resistance to trastuzumab. #1059

MBC patients with very high levels of HER-2 could represent a sub-

group with de novo resistance to trastuzumab who may benefit from

combined therapy.

The HERmark assay was used to measure H2T in formalin-fixed,

paraffin-embedded (FFPE) primary breast tumor specimens.


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Cncer de mama

O que colhemos da A. Patolgica!

Tu

Axila Biologia ( imunohistoqumica)


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Microsatellite instability (MSI) in stage II and III colon

cancer treated with 5FU-LV or 5FU-LV and irinotecan

(PETACC 3-EORTC 40993-SAKK 60/00 trial). #4001, #4121

Microsatellite instability is a strong prognostic factor for RFS and OS when

considering Stage II, even in pts treated with 5FU (w/o IRI).

Estratificao de risco: clon


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Evaluation of CD133, VEGF, orEGFR as predictive

markers of distant recurrence after preoperative

chemoradiotherapy in rectal cancer. #4050

Elevated CD133 but not VEGF or EGFR on formalin-fixed paraffin-

embedded specimens may be a predictive marker of distant recurrence

and poor survival after preoperative CRT in rectal cancer.


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Immune infiltrates in liver metastases of colorectal cancer

and response to chemotherapy. #E15069

Positively stained tumor infiltrating lymphocytes in the invasive margin of

the liver metastasis allowed to predict response to chemotherapy.


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Individualizao de tratamento: clon

Crystal Study (+ #4068):

1,198 patients to FOLFIRI with or without cetuximab. Cetuximab was associated with an improved PFS (P=.048).

Improved OS confined to wild types of KRAS.

Van Cutsem et al, 2009


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Estratificao de risco: pulmo

A novel histopathological evaluation method for predicting

the outcome of non-small cell lung cancer treated by

neoadjuvant therapy. #e11574

Smaller area of residual tumor (400 mm2) and absence of pleural invasion

predict a better outcome of NSCLC in patients who receive neoadjuvant

therapy.


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EGFR expresso em 40% a 80% dos casos

Inibidores da tirosina quinase de EGFR

(geftinibe/erlotinibe) demonstraram atividade

em pacientes previamente tratados.Fukuoka et al, 2003; Perez-Soler et al, 2003; Herbst

et al, 2004;

Giaccone et al, 2004; Herbst et al, 2004; Gatzemeier

et al, 2004;

Shepherd et al, 2005; Thatcher et al, 2005; Bezjak et

al, 2006.

Individualizao de tratamento: pulmo


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A resposta aos agentes envolvendo EGFR maior em:

Mulheres que nunca fumaram;

Adenocarcinoma e bronquioloalveolar;

Mutao na tirosina quinase de EGFR;

Hiperexpresso da protena de EGFR por IMH (?);

K-RAS tipo selvagem.

Tsao et al, 2005; Hirsch et al, 2006;Clark et al, 2006; Miller et al, 2004;

Paez et al, 2004; Lynch et al, 2004;

Pao et al, 2004; Pao et al, 2005.


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Estratificao de risco: pulmo

Molecular and clinical predictors of outcome for cetuximab in non-

small cell lung cancer (NSCLC): Data from the FLEX study. #8007

Not support the hypothesis that KRAS mutation status is predictive for cetuximab efficacy.

K-Ras mutation (mut), EGFR-related, and exploratory markers as

response predictors of cetuximab in first-line advanced NSCLC:Retrospective analyses of the BMS099 trial. #8021, #8022

There was no significant correlation between patient response to C and any

molecular marker evaluated to date (K-RASmut, EGFRmut, EGFR IHC, EGFR

FISH).

Prognostic and predictive impact ofEGFR and K-ras mutation, and EGFR genecopy number in patients with advanced non-small cell lung cancer (NSCLC)

who received first-line cytotoxic chemotherapy. #8096

EGFR mutations were good predictive marker and K-ras mutations were poor predictive marker

in first line cytotoxic chemotherapy.


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Biomarker analyses from the phase III placebo-controlled

SATURN study of maintenance erlotinib following first-

line chemotherapy for advanced NSCLC. #8020

Erlotinib significantly improving PFS in the EGFR IHC+ group


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MSH2 and adjuvant cisplatin-based chemotherapy in non-

small cell lung cancer. #CRA7502

HumanMutS homolog 2 (MSH2) protein and excision repair cross-complementing group 1 (ERCC1 ) are required to repair cisplatin-DNA

lesions.

Chemotherapy compared with observation prolonged survival in the

combined MSH2 negative/ERCC1 negative subgroup.


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Characteristics and outcomes of non-small cell lung

cancer (NSCLC) patients (pts) carrying epidermal growth

factor receptor (EGFR) mutations who progress after initial

erlotinib (E) response. #8064

Pts with EGFR mutations present a biologically different disease which

continued to be sensitive to other treatments after progressing to E.


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Estratificao de risco: SNC

Influence of expression ofEGFR and PTEN on outcome in patients with

primary glioblastoma treated with standard radiochemotherapy and

cetuximab: Interim analysis from the GERT-Protocol. #2050

Expression of EGFR, and coexpression of EGFR/PTEN is associated with significant increase

in PFS after RCHT with TMZ and CTX.


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Individualizao de tratamento: estmago

Efficacy results from the ToGA trial: A phase III study of

trastuzumab added to standard chemotherapy (CT) in first-

line human epidermal growth factor receptor 2 (HER2)-

positive advanced gastric cancer (GC). #LBA4509

H+CT is superior to CT alone. The OS benefit indicates that H

is a new, effective, and well-tolerated treatment for HER2-

positive GC.


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Estratificao de risco: melanoma

Long-term follow-up of patients with minimal sentinel node

tumor burden (< 0.1 mm) according to Rotterdam criteria:

A study of the EORTC Melanoma Group. #9005

Minimal SN tumor burden (< 0.1 mm) indicates relapse rates identical to SN

negative patients.


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Individualizao de tratamento: melanoma

Ulceration of primary melanoma and responsiveness to

adjuvant interferon therapy: Analysis of the adjuvant trials

EORTC18952 and EORTC18991 in 2,644 patients. #9007

Pts with an Ulcerated primary are far more sensitive to IFN than pts with N-

Ulcecated primaries. This hypothesis will now be tested in the EORTC18081

trial, which compares PEG-IFN-2b versus observation in pts with U1c

primaries > 1mm.


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Individualizao de tratamento: melanoma

Association of baseline and on-study tumor biopsy

markers with clinical activity in patients (pts) with

advanced melanoma treated with ipilimumab. #9008

Biomarkers [FOXP3 and indoleamine 2,3-dioxygenase (IDO)] in the tumor

microenvironment are associated with clinical activity in pts treated with

ipilimumab.


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Estratificao de risco: cabea e pescoo

Prognostic significance of HPV and p16 status in patients

with oropharyngeal cancer treated on a large international

phase III trial. #6003, #6004.

Tumor HPV and p16 status is strongly associated with higherOS/PFS.


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Individualizao de tratamento: endomtrio

Responses to hormones are correlated with the presence

and level of hormone receptors and the degree of tumor

differentiation.

Lentz, 1994


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Concluses e perspectivas

A anatomia patolgica norteia a conduta em oncologia e

pode ser utilizada de trs formas:

Ferramenta Diagnstica

Estratificao de risco Individualizao do tratamento

A biologia molecular est se envolvendo cada vez mais na patologia.

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Hospital Alianca - Anatomia Patológica norteando conduta