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Slide Prof. Aru Webinar CRC
Slide Prof. Aru Webinar CRC
Aru Sudoyo
Faculty of Medicine Universitas Indonesia (FKUI)
Indonesian Society of Hematology Oncology Internal Medicine
(PERHOMPEDIN)
Indonesian Society of Oncolgy (POI)
Global Cancer Statistics 2018 (GLOBOCAN)
• CYTOSTATICS
• BIOLOGICALS / TARGETED THERAPY
• IMMUNOTHERAPY
• OTHERS
Stage 2 and 3
STAGE 4
Advanced and Metastatic Disease
Algorithm of mCRC
A 10-15% B 75-90% C
Aim of treatment :
Aim of treatment : Curative Palliative
Algorithm of mCRC
A 10-15% B 75-90% C
Aim of treatment :
Aim of treatment : Curative Palliative
In mCRC
Cytotoxics Remain the Nucleus
• First Line:
– 5-FU/capecitabine +/- bevacizumab
– FOLFOX +/- bevacizumab
– FOLFIRI +/- bevacizumab
– FOLFIRINOX +/- bevacizumab
– ? Role for EGFR targeted therapy in first line: 80405
• Second Line
– Reciprocal of first line +/- EGFR monoclonal AB
• Third Line:
– KRAS wt: EGFR monoclonal +/- irinotecan
– KRAS mt: no standard therapy
Marshall, 2012
Stage 4 Colorectal Cancer is a
Continuum from curable
disease to incurable disease
Incurable
Curable High disease burden
with widespread
Low disease burden, metastatic cancer
generally with a single
solitary site of spread
1st line Palliative Chemotherapy
28
New Paradigm : Personalized Treatment
WHERE ARE WE NOW ?
WHERE ARE WE NOW ?
CHANGE IN PARADIGM
Let’s think of precision medicine !
Adenocarcinoma Adenocarcinoma
Adenocarcinoma Adenocarcinoma
Mutations in : Mutations in :
APC APC
KRAS BRAF
P53 PIK3CA
Mutations in : Mutations in :
APC APC
KRAS BRAF
P53 PIK3CA
• DISEASE PATIENT
Metabolism
Midgut Hindgut Almost inactive
Fermentation Biofilm Biofilm
metabolically
Proteolysis positive negative
Waste reservoir
Degradation
Processing
Epigenetic2,4,5 Genetic4,6
Methylation
MSI-High
BRAF mt See slide notes for references.
43
JNCCN, 2017
Sidedness matters in MCRC1–4
Figure from Salem ME, e t al. Oncotarget 2017;8:86356 –86368. 5 mCRC, metastatic colorectal cancer.
1. Kim SE, et al. World J Gastroenterol 2015;21:5167–5175; 2. Venook A, et al. ESMO 2016 (Oral Presentation); 3. Dan Aderka. ESMO 2017 (Merck Satellite Symposium); 4.
Venook A, et al. JAMA 2017;317:2392–2401; 5. Salem ME, et al. Oncotarget 2017;8:86356–86368.
Tumor location
A prognostic factor for overall survival
Stage IV
Unadj. HR 95% CI
Right vs. Left 1,32 1,30 – 1,35
Overall survival
— Right Colon
— Left Colon
— Rectum
n = 64770
Months
Primary CRC diagnosed 2000-2012 in a SEER region and followed for death through end of 2013,
N=64,770. R-sided 1° = cecum to transverse colon; L-sided 1° = splenic flexure to sigmoid
Schrag D, e t al. ASCO 2016 (Abstr. 3505) descending colon; 1° rectum = rectosigmoid and rectal
Hanahan, 2011
Cancer hallmarks in relation to colorectal cancer