In Chile we are making important improvements in BTC: We are developing knowledge We decreased mortality by almost 50%, We increased survival First positive trial, in the world, in Chemotx for GBC. 1
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In Chile we are making important improvements in BTC:
We are developing knowledge
We decreased mortality by almost 50%,
We increased survival
First positive trial, in the world, in Chemotx for GBC. 1
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ESMO SUMMIT LATIN AMERICA 2019
Biliary Tract Cancer
Jorge Gallardo MD
Medical Oncologist«SLAGO working group»Chilean Foundation for Development Oncology
Santiago de Chile.
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CONFLICT OF INTEREST DISCLOSURE
No conflicts of interest
3
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BILIARY TRACT CANCER (BTC)
1. Epidemiology of BTC 2. Diagnosis and pathology3. Risk assessment4. Radiological evaluation5. Management of local-regional disease6. Adjuvant treatment7. Management of metastatic disease
Agenda
4Reference:
Biliary Cancer: ESMO Clinical Practice Guidelines. Ann Oncol (2016)
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1.- INCIDENCE AND EPIDEMIOLOGY BILIARY TRACT CANCER (BTC)
• Comprise
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SUBCLASSIFICATION:
• intrahepatic cholangioca (iCCA), • Extrahepatic cholangioca (eCCA),
further subdivided in:– Perihilar cholangioca
(pCCA or Klatskin tumor)– Distal cholangioca (dCCA)
Frequency :10%–20% iCCA, 50% pCCA30%–40% eCCA.
6Ref: Biliary Cancer: ESMO Clinical Practice Guidelines. Ann Oncol (2016)
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INCIDENCE CHOLANGIOCARCINOMA (CCA)
In Europe, USA and Australasia: low (>3./100 000);Incidence and mortality rates have increased overall in most Western countries;
– Specifically, iCCA rates are rising and eCCA rates falling,
Parts where liver fluke infection iscommon (Thailand, China and Korea), rates are much higher.
– Annual incidence of 90/ 100 000, – accounting for >80% of all 1er liver cancers
CCA rates in Asia, overall, remains static.
7Ref: Biliary Cancer: ESMO Clinical Practice Guidelines. Ann Oncol (2016)
Ferida do fígado
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INCIDENCE OF GALLBLADDER CANCER (GBC)
• In western Europe and USA is low (1.6–2.0/100 000);• Significant health problem in Chile, India and
Central/Eastern Europe. • In the Valdivia region of Chile, GBC
incidence reaches 24.3/ 100 000 in females and 8.6/100 000 in males.
• Risk factors:– porcelain gallbladder,– gallbladder polyps, – primary sclerosing cholangitis, – chronic infection
Valdivia City, Chile
8Ref: Biliary Cancer: ESMO Clinical Practice Guidelines. Ann Oncol (2016)
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GBC estimated age-standardized mortality rates (World) in 2018,
Males, all age Females, all age
C h
i l
e
C h
i l
e
B r a s i l
Bolivia
Ref: GLOBOBCAN , International Agency for Research on Cancer; Sep 20189
Valdivia
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GBC Mortality in Latin-America, From 1995 to 2013
Female, all ages Males, all ages
Ref: GLOBOCAN, International Agency for Research on Cancer; Sep 2018Age-standarized rate (World) 10
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PATHOLOGY DIAGNOSIS
• Should be obtained before any non-surgical treatment modality
• Not essential in patients planned for curative surgery where radiological features are characteristic.
• ERCP- guided biopsies are preferred to biliary brush cytology
11Ref: Biliary Cancer: ESMO Clinical Practice Guidelines. Ann Oncol (2016)
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PATHOLOGY DIAGNOSIS
Cases of tumor seeding along the FNA track, – exact level of risk is uncertain, – it appears to be low.
12Ref: Biliary Cancer: ESMO Clinical Practice Guidelines. Ann Oncol (2016)
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3.- RADIOLOGIC ASSESMENT
1. MRI: Assessment of tumor, [T]-stage and bile duct involvement.
2. Thorax CT: metastases, (M)-stage.3. EUS: lymph node, (N)-stage. 4. ERCP or percutaneous transhepatic
cholangiography to improve assessment of T-stage,
13Ref: Biliary Cancer: ESMO Clinical Practice Guidelines. Ann Oncol (2016)
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5.- Contrast Abd CT: defines the relationship between the tumor and the vasculature (portal vein and hepatic artery).
6.- PET CT: Utility is controversial – It should only be used on a case-by-case basis.
T-stage is crucial for surgical decision-making.Staging according to the TNM system
– Specific for every subtype of BTC
RADIOLOGIC ASSESMENT 2
14Ref: Biliary Cancer: ESMO Clinical Practice Guidelines. Ann Oncol (2016)
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Cholelitiasis is the major risk for GBC
15
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Chilean National Policy against GBC: Prophylactic Cholecistectomy
Ref: IARC; Sep 2018
Mortality from Gallbladder CancerChile, 1993- 2013
y
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5.- MANAGEMENT OF LOCAL/LOCOREGIONAL DISEASE
Therapeutic strategy varies for each type of BTC depending on site of origin:
17Ref: Biliary Cancer: ESMO Clinical Practice Guidelines. Ann Oncol (2016)
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MANAGEMENT OF LOCAL/LOCOREGIONALINTRAHEPATIC CHOLANGIOCARCINOMA ICCA:
Usually arises within normal background liver parenchyma,
– Radiological appearance is of a mass-forming arterially enhancing tumor.
Radical surgical removal with clear margins is the only potentially curative therapy
18Ref: Biliary Cancer: ESMO Clinical Practice Guidelines. Ann Oncol (2016)
Adapted from Quino
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Prognostic parameters:• Presence of lymph node involvement routine
lymphadenectomy at the level of the hepato-duodenal ligament during surgery .
• Size,• number of tumors, • grade, • presence of satellite nodules, • vascular and/or perineural invasion
To guide decisions regarding adjuvant therapy
MANAGEMENT OF LOCAL/LOCOREGIONALINTRAHEPATIC CHOLANGIOCARCINOMA ICCA:
19Ref: Biliary Cancer: ESMO Clinical Practice Guidelines. Ann Oncol (2016)
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Gallbladder Cancer
3.Incidental diagnosis in the histological workup of simple cholecystectomies
– In Chile, a 1/3 of cases are diagnosed by microscopy, using a established protocol
21Ref: Biliary Cancer: ESMO Clinical Practice Guidelines. Ann Oncol (2016)
MANAGEMENT OF LOCAL/LOCOREGIONAL
GBC has three typical presentations: 1. Pre-OP Dg; right upper quadrant tumor. 2. Macroscopic tumor detected during Op.
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MANAGEMENT OF LOCAL/LOCOREGIONALGallbladder Cancer
Histopathological evaluations: T-stage, cystic duct margin, involvement of resected lymph nodes, grade, perineural and/or vascular invasion.
Every T-stage above T1a and positivity of any mentioned parameters reoperation: segment IVb/V resection
ligamentary lymphadenectomy.
Port sites should be resected If:– Gallbladder was not removed with a bag during laparoscopic resection – Gallbladder perforated
22
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Prognosis of GBC, if not diagnosed at a very early stage, is inferior to all other types of CCA.
23Ref: Biliary Cancer: ESMO Clinical Practice Guidelines. Ann Oncol (2016)
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6- ADJUVANT TREATMENT
High rates of local and distant recurrence following surgery justify the consideration of an adjuvant treatment
24Ref: Biliary Cancer: ESMO Clinical Practice Guidelines. Ann Oncol (2016)
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ADJUVANT TREATMENTA: Adjuvant chemoradiotherapy
• Lack of data from randomized trials. • Most studies are retrospective• Include small numbers of patients, • Mix of gallbladder and bile duct tumors. • Meta-analysis, adjuvant chemotherapy or
chemoradiotherapy give survival benefit in: – BTC with lymph node-positive disease – with microscopically involved margins .
25Ref: Biliary Cancer: ESMO Clinical Practice Guidelines. Ann Oncol (2016)
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ADJUVANT TREATMENTB: Adjuvant chemotherapy
26
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FIG 2. (A) Relapse-free survival and (B) overall survival Kaplan-Meier curves. GEMOX, gemcitabine and oxaliplatin.
Published in: Julien Edeline; Meher Benabdelghani; Aurélie Bertaut; Jérôme Watelet; Pascal Hammel, et al; Journal of Clinical Oncology Ahead of Print, DOI: 10.1200/JCO.18.00050; Copyright © 2019 American Society of Clinical Oncology
Gemcitabine and Oxaliplatin Chemotherapy or Surveillance in Resected Biliary Tract Cancer (PRODIGE 12-ACCORD 18-UNICANCER GI): A Randomized Phase III StudyJulien Edeline, M
http://ascopubs.org/author/Edeline,+Julien
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Chilean Adjuvant Trials in GBCAuthor Adjuvant Tx Pats N° Study 5 Y. OSB. Müller QT ( 5FU)-RT
(45–54 Gy)47 Retro 57%
M E. Gonzales
QT( 5FU)-RT (45–59.4 Gy)
67 Prosp 41%
Manterola QT ( 5FU Leucovorina)
40 Prosp 50%
Lendoire QT 24 Retro 53%
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BTC ESMO GUIDELINE
29Ref: Biliary Cancer: ESMO Clinical Practice Guidelines. Ann Oncol (2016)
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Carcinoma in situ at marginAdj with ChemoRtX ???(indicated only in R1 or LN+)Or Gemcit based Chtx?
30
Or Gemcit based Chtx ?(No benefit in adjuvant)
Must be considered forPalliative therapy
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7. MANAGEMENT OF ADVANCED DISEASEA: Radiation therapy
• Role radiation therapy remains unclear Chemoradiotherapy is a possible option
• non-randomised studies median survival rates between 9 and 14 months.
• Intensity-modulated radiotherapy (IMRT) was shown to allow safe dose escalation.
• Whether a dose escalation could improve the local control and survival remains unknown
31Ref: Biliary Cancer: ESMO Clinical Practice Guidelines. Ann Oncol (2016)
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MANAGEMENT OF ADVANCED DISEASERadiation therapy: Chemotx much better than ChemoRtx
French phase III trial compared chemoradiotherapy vs Chtx (Gem-Oxal) in this setting. . Trial was closed before the completion of planned inclusionsGemOx was better:
– Progression-free survival (median PFS, 11 vs 5.8 m) – Overall survival (20 versus 13.5 months).
32Ref: Biliary Cancer: ESMO Clinical Practice Guidelines. Ann Oncol (2016)
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MANAGEMENT OF ADVANCED DISEASE
B: Radiation-embolisation
• Experience is growing using 90Y-microspheres for Pts with iCCA.
• Prospective, randomised data are lacking; • Pooled analysis showed mOS of 15.5 months and RR
of 28% • 10% patients (7/73) in three selected studies were
converted to resectable disease,
33Ref: Biliary Cancer: ESMO Clinical Practice Guidelines. Ann Oncol (2016)
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MANAGEMENT OF ADVANCED DISEASEC: Systemic Chemotx
Chemotx extends survival in Pts with advanced BTC compared with best supportive care!
The phase III study has established the cisplatin/Gem combination as a standard of care
– Median survival 11.7 months (cisplatin/gem), vs 8.1 months for Gem alone.
34Ref: Biliary Cancer: ESMO Clinical Practice Guidelines. Ann Oncol (2016)
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MANAGEMENT OF ADVANCED DISEASE
Systemic Chemotx
– Pts benefit from the combination independent of:– age, gender,– primary tumour site (iCCC- vs, eCCC, vs GBC vs
ampullary), – stage of disease (locally advanced versus metastatic) – prior therapy (surgery or stenting)
– Pts with PS-2 may derive the least benefit from the combination.
– In Pts with PS-2, Gem monotherapy may be considered35Ref: Biliary Cancer: ESMO Clinical Practice Guidelines. Ann Oncol (2016)
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MANAGEMENT OF ADVANCED DISEASESystemic Chemotx, role of second line Chtx
There is no established second-line ChtxSystematic review was disappointing:
– median PFS 3.2 months;– media RR 7.7%; – Mean OS 7.2 months
No recommendation could be made about the most appropriate second-line regimenMagnitude of benefit to patients over best supportive care is not known.
36Ref: Biliary Cancer: ESMO Clinical Practice Guidelines. Ann Oncol (2016)
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Gem Clinical Cases 1998(cancer)
Abstract ASCO 2000
Gem in Advanced GBC Ph II StudyAnnals of Oncol 2001
Gem in advanced GBC and Cholangioc. ASCO 2001
“clinical benefit” of Gem GBC (ASCO Meeting 2002),
Gem-cisplat in advanced GBC ASCO GI Meeting 2003
Gem-cisplatin V/S Gem in GBC ASCO Meeting 2005
Gem-cisplat neoadyuvante + cirugía ASCO 2006
Phase I StudyGEMCITABINE + RADIOTHERAPYASCO MEETING, 2001UICC CONGRESS 2002:
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Chilean studies on GBC Chemotherapie
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0
25
50
75
100
1 7 13 19 25 31 37 43 49 55 61 67 73 79 85 91 97 103 109 115 121 127 133 139 145 151 157
%
weeks
surv ival comparation
gem protocol gem+cisp p roto pac fuera p rot
SURVIVALFirst Protocol: Gemcitabine monotherapySecond Protocol: Gemcitabine-cisplatin max 6 cyclesThird Serie: Gemcitabine +/- cisplatin (n: 29)
In third cohort 7 patients underwenta surgical resection
•Until progression•Two or more Chtx lines
Significant better survival
Hoja1
Pacientes fuera de protocolo
NombreApellidosgeneroedadfecha dg1° terafecha 1° teraresp 1° teraduración2° terapfecha 2° terresp 2° terduración3° terapfecha 3° terresp 3° terduraciónfecha de defuncsobrevida
1CarlosBustos YissiM2611/11/03G+C26/01/04EE5FU+C+A01/10/04PEN/AN/AN/A04/07/0571
2DorilaPinto RiverosF5920/04/05G+C09/02/06PE24/06/0619
3ErnaFuentes LagosF5927/04/06G+C30/05/06EE04/07/0757
4MariaFuentes VenegasF8024/09/04G02/12/04EE25/10/0699
5Maria CristVargas VillanuevaF6729/10/03G+C10/11/03PE25/12/036
6HectorVega VasquezMfolfox26/12/02PE5FU+Lv02/03/03G+C29/04/0323/09/0321
7GumercindoCastillo ArenasM53G23/08/01X+C07/05/02PE23/09/0257
8M MercedesHerrera AcuñaF6625/03/03G+C05/05/03RC20/02/0442
9JeanetteOsorio SorianoF4101/11/02Rtx+GG+C12/05/0305/03/0443
10AdrianaDiaz VargasF5606/09/04G+C20/05/0404/01/0685
11TrinidadHaisangF5313/01/03G+C16/01/0313/03/05112
12JoséOvalle VenegasM54G+C14/08/0324/02/0580
13CristinaYevenesF62Rtx+G15/06/0424/09/0566
14SoledadFlores CerdaF6604/08/03Rtx+G13/10/03G+C01/12/0326/10/06151
15MariaPino AbarcaF52G+C23/09/0206/09/05154
16PascualBiela YañezM56G+C28/08/0417/11/0412
17JuanAlvarezM5826/11/0409/10/07149
18OlgaNaviaF7027/07/0312/12/0319
19RamonSoto EspinozaM5811/04/0620/01/0740
20AlbertoGáticaM5904/08/0622/11/0616
21SergioOrellanaM6511/08/0408/08/0551
22GalvarinoSaldiaM6528/04/0428/05/0556
23InesAdasmeF6815/05/0502/12/0628
24ErikaSickertF7019/05/0628/12/0632
25MariaPereiraF5223/11/0609/10/0746
26SolangeLarroucauF6208/05/0330/06/05112
27NellyZuñigaF4403/04/0711/08/0718
28CristinaOyarceF5131/05/0704/10/0718
29
30
31
32
33
34
35
36
37
38
39
40
41
Gráfico1
100
100
100
100
100
96.4285714286
96.4285714286
96.4285714286
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71.4285714286
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53.3333333333
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11.4285714286
11.4285714286
11.4285714286
11.4285714286
5.7142857143
5.7142857143
5.7142857143
0
semanas
%
sobrevida pacientes fuera de protocolo
estudio1
C2C3C6C7C8C9C10
totalmuertosvivos(C2-(C6/2))(C3/C7)100100-C8C10prev xC9/100
26602623.076923076976.923076923176.9230769231
205020257557.6923076923
15401526.666666666773.333333333342.3076923077
11301127.272727272772.727272727330.7692307692
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100
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26002601001002
26002601001003
26002601001004
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240024010092.30769230776
240024010092.30769230777
240024010092.30769230778
24302412.587.580.76923076929
210021010080.769230769210
210021010080.769230769211
210021010080.769230769212
21302114.285714285785.714285714369.230769230813
180018010069.230769230814
180018010069.230769230815
180018010069.230769230816
180018010069.230769230817
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160016010061.538461538519
160016010061.538461538520
160016010061.538461538521
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140014010053.846153846223
140014010053.846153846224
140014010053.846153846225
14201414.285714285785.714285714346.153846153826
120012010046.153846153827
120012010046.153846153828
120012010046.153846153829
120012010046.153846153830
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100010010038.461538461532
100010010038.461538461533
100010010038.461538461534
101010109034.615384615435
9009010034.615384615436
9009010034.615384615437
9009010034.615384615438
910911.111111111188.888888888930.769230769239
8008010030.769230769240
8008010030.769230769241
8008010030.769230769242
8008010030.769230769243
810812.587.526.923076923144
7007010026.923076923145
7007010026.923076923146
7007010026.923076923147
7007010026.923076923148
7007010026.923076923149
7007010026.923076923150
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7007010026.923076923152
730742.857142857157.142857142915.384615384653
4004010015.384615384654
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100101003.846153846299
100101003.8461538462100
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100101003.8461538462102
100101003.8461538462103
100101003.8461538462104
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100101003.8461538462116
100101003.8461538462117
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100101003.8461538462123
100101003.8461538462124
100101003.8461538462125
estudio2
C2C3C6C7C8C9C10
totalmuertosvivos(C2-(C6/2))(C3/C7)100100-C8C10prev xC9/100
100
14410442.272727272797.727272727397.7272727273
2430043010097.7272727273
3430043010097.7272727273
4430043010097.7272727273
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6420042010095.4545454545
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4014201414.285714285785.714285714327.2727272727
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42120012010027.2727272727
43120012010027.2727272727
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49110011010025
50110011010025
51110011010025
52110011010025
53110011010025
54110011010025
551110119.090909090990.909090909122.7272727273
56101010109020.4545454545
57910911.111111111188.888888888918.1818181818
588008010018.1818181818
598008010018.1818181818
60810812.587.515.9090909091
617007010015.9090909091
627007010015.9090909091
63710714.285714285785.714285714313.6363636364
646006010013.6363636364
65610616.666666666783.333333333311.3636363636
665005010011.3636363636
675005010011.3636363636
685005010011.3636363636
695005010011.3636363636
705005010011.3636363636
715005010011.3636363636
725005010011.3636363636
735005010011.3636363636
745005010011.3636363636
75510520809.0909090909
76410425756.8181818182
77300301006.8181818182
78300301006.8181818182
79300301006.8181818182
80300301006.8181818182
81300301006.8181818182
81300301006.8181818182
83300301006.8181818182
84300301006.8181818182
85300301006.8181818182
86300301006.8181818182
87300301006.8181818182
88300301006.8181818182
89300301006.8181818182
90300301006.8181818182
91300301006.8181818182
92300301006.8181818182
93300301006.8181818182
94300301006.8181818182
95300301006.8181818182
96300301006.8181818182
97300301006.8181818182
98300301006.8181818182
99310333.333333333366.66666666674.5454545455
100200201004.5454545455
101200201004.5454545455
102200201004.5454545455
103200201004.5454545455
104200201004.5454545455
105200201004.5454545455
106200201004.5454545455
107200201004.5454545455
108210250502.2727272727
109100101002.2727272727
110100101002.2727272727
111100101002.2727272727
112100101002.2727272727
113100101002.2727272727
114100101002.2727272727
115100101002.2727272727
116100101002.2727272727
117100101002.2727272727
118100101002.2727272727
119100101002.2727272727
120100101002.2727272727
121100101002.2727272727
122100101002.2727272727
123100101002.2727272727
124100101002.2727272727
125100101002.2727272727
126100101002.2727272727
127100101002.2727272727
128100101002.2727272727
129100101002.2727272727
130100101002.2727272727
131100101002.2727272727
132100101002.2727272727
133100101002.2727272727
134100101002.2727272727
135100101002.2727272727
136100101002.2727272727
137100101002.2727272727
138100101002.2727272727
139100101002.2727272727
140100101002.2727272727
141100101002.2727272727
142100101002.2727272727
143100101002.2727272727
144100101002.2727272727
145100101002.2727272727
146100101002.2727272727
147100101002.2727272727
148100101002.2727272727
149100101002.2727272727
150100101002.2727272727
151100101002.2727272727
152100101002.2727272727
153100101002.2727272727
154100101002.2727272727
155100101002.2727272727
156100101002.2727272727
157100101002.2727272727
estudio3
Pacientes fuera de protocolo
NombreApellidosgeneroedadsobrevida
5Maria CristVargas VillanuevaF676C2C3C6C7C8C9C10
16PascualBiela YañezM5612semanastotalmuertosvivos(C2-(C6/2))(C3/C7)100100-C8C10prev xC9/100
20AlbertoGáticaM5916
27NellyZuñigaF4418
28CristinaOyarceF5118totalmuertosvivos(C2-(C6/2))(C3/C7)100100-C8C10prev xC9/100
2DorilaPinto RiverosF5919100
18OlgaNaviaF701912800280100100
23InesAdasmeF682822800280100100
24ErikaSickertF703232800280100100
19RamonSoto EspinozaM584042800280100100
8M MercedesHerrera AcuñaF664252800280100100
9JeanetteOsorio SorianoF414362810283.571428571496.428571428696.4285714286
25MariaPereiraF52467270027010096.4285714286
21SergioOrellanaM65518270027010096.4285714286
22GalvarinoSaldiaM65569270027010096.4285714286
3ErnaFuentes LagosF595710270027010096.4285714286
7GumercindoCastillo ArenasM535711270027010096.4285714286
13CristinaYevenesF6266122710273.703703703796.296296296392.8571428571
1CarlosBustos YissiM267113260026010092.8571428571
12JoséOvalle VenegasM548014260026010092.8571428571
10AdrianaDiaz VargasF568515260026010092.8571428571
4MariaFuentes VenegasF8099162610263.846153846296.153846153889.2857142857
6EdithVillaF10017250025010089.2857142857
11TrinidadHaisangF531121825202589282.1428571429
26SolangeLarroucauF62112192320238.695652173991.304347826175
17JuanAlvarezM5814920210021010075
14SoledadFlores CerdaF6615121210021010075
15MariaPino AbarcaF5215422210021010075
23210021010075
24210021010075
25210021010075
26210021010075
27210021010075
282110214.761904761995.238095238171.4285714286
29200020010071.4285714286
30200020010071.4285714286
31200020010071.4285714286
3220102059567.8571428571
33190019010067.8571428571
34190019010067.8571428571
35190019010067.8571428571
36190019010067.8571428571
37190019010067.8571428571
38190019010067.8571428571
39190019010067.8571428571
401910195.263157894794.736842105364.2857142857
41180018010064.2857142857
421810185.555555555694.444444444460.7142857143
431710175.882352941294.117647058857.1428571429
44160016010057.1428571429
45160016010057.1428571429
46160115.5010057.1428571429
47150015010057.1428571429
48150015010057.1428571429
49150015010057.1428571429
50150015010057.1428571429
511510156.666666666793.333333333353.3333333333
52140014010053.3333333333
53140014010053.3333333333
54140014010053.3333333333
55140014010053.3333333333
561410147.142857142992.857142857149.5238095238
5713201315.384615384684.615384615441.9047619048
58110011010041.9047619048
59110011010041.9047619048
60110011010041.9047619048
61110011010041.9047619048
62110011010041.9047619048
63110011010041.9047619048
64110011010041.9047619048
65110011010041.9047619048
661110119.090909090990.909090909138.0952380952
67100010010038.0952380952
68100010010038.0952380952
69100010010038.0952380952
70100010010038.0952380952
71101010109034.2857142857
729009010034.2857142857
739009010034.2857142857
749009010034.2857142857
759009010034.2857142857
769009010034.2857142857
779009010034.2857142857
789009010034.2857142857
799009010034.2857142857
80910911.111111111188.888888888930.4761904762
818008010030.4761904762
828008010030.4761904762
838008010030.4761904762
848008010030.4761904762
85810812.587.526.6666666667
867007010026.6666666667
877007010026.6666666667
887007010026.6666666667
897007010026.6666666667
907007010026.6666666667
917007010026.6666666667
927007010026.6666666667
937007010026.6666666667
947007010026.6666666667
957007010026.6666666667
967007010026.6666666667
977007010026.6666666667
987007010026.6666666667
99720728.571428571471.428571428619.0476190476
1005005010019.0476190476
1015005010019.0476190476
1025005010019.0476190476
1035005010019.0476190476
1045005010019.0476190476
1055005010019.0476190476
1065005010019.0476190476
1075005010019.0476190476
1085005010019.0476190476
1095005010019.0476190476
1105005010019.0476190476
1115005010019.0476190476
1125205406011.4285714286
1133003010011.4285714286
1143003010011.4285714286
1153003010011.4285714286
1163003010011.4285714286
1173003010011.4285714286
1183003010011.4285714286
1193003010011.4285714286
1203003010011.4285714286
1213003010011.4285714286
1223003010011.4285714286
1233003010011.4285714286
1243003010011.4285714286
1253003010011.4285714286
1263003010011.4285714286
1273003010011.4285714286
1283003010011.4285714286
1293003010011.4285714286
1303003010011.4285714286
1313003010011.4285714286
1323003010011.4285714286
1333003010011.4285714286
1343003010011.4285714286
1353003010011.4285714286
1363003010011.4285714286
1373003010011.4285714286
1383003010011.4285714286
1393003010011.4285714286
1403003010011.4285714286
1413003010011.4285714286
1423003010011.4285714286
1433003010011.4285714286
1443003010011.4285714286
1453003010011.4285714286
1463003010011.4285714286
1473003010011.4285714286
1483003010011.4285714286
1493012.5010011.4285714286
1502002010011.4285714286
151210250505.7142857143
152100101005.7142857143
153100101005.7142857143
154110110000
0
estudio 4
sobrevidaC2C3C6C7C8C9C10
6Erika Sicker32totalmuertosvivos(C2-(C6/2))(C3/C7)100100-C8C10prev xC9/100
2Jeannette Osorio43100
7Eva Rojas60170070100100
1Jose Ovalle80270070100100
3Adriana Diaz85370070100100
4Trinidad Haisang112470070100100
5Juan Alvarez149570070100100
670070100100
770070100100
870070100100
970070100100
1070070100100
1170070100100
1270070100100
1370070100100
1470070100100
1570070100100
1670070100100
1770070100100
1870070100100
1970070100100
2070070100100
2170070100100
2270070100100
2370070100100
2470070100100
2570070100100
2670070100100
2770070100100
2870070100100
2970070100100
3070070100100
3170070100100
32710714.285714285785.714285714385.7142857143
336006010085.7142857143
346006010085.7142857143
356006010085.7142857143
366006010085.7142857143
376006010085.7142857143
386006010085.7142857143
396006010085.7142857143
406006010085.7142857143
416006010085.7142857143
426006010085.7142857143
43610616.666666666783.333333333371.4285714286
445005010071.4285714286
455005010071.4285714286
465005010071.4285714286
475005010071.4285714286
485005010071.4285714286
495005010071.4285714286
505005010071.4285714286
515005010071.4285714286
525005010071.4285714286
535005010071.4285714286
545005010071.4285714286
555005010071.4285714286
565005010071.4285714286
575005010071.4285714286
585005010071.4285714286
595005010071.4285714286
605105208057.1428571429
614004010057.1428571429
624004010057.1428571429
634004010057.1428571429
644004010057.1428571429
654004010057.1428571429
664004010057.1428571429
674004010057.1428571429
684004010057.1428571429
694004010057.1428571429
704004010057.1428571429
714004010057.1428571429
724004010057.1428571429
734004010057.1428571429
744004010057.1428571429
754004010057.1428571429
764004010057.1428571429
774004010057.1428571429
784004010057.1428571429
794004010057.1428571429
804104257542.8571428571
813003010042.8571428571
823003010042.8571428571
833003010042.8571428571
843003010042.8571428571
85310333.333333333366.666666666728.5714285714
862002010028.5714285714
872002010028.5714285714
882002010028.5714285714
892002010028.5714285714
902002010028.5714285714
912002010028.5714285714
922002010028.5714285714
932002010028.5714285714
942002010028.5714285714
952002010028.5714285714
962002010028.5714285714
972002010028.5714285714
982002010028.5714285714
992002010028.5714285714
1002002010028.5714285714
1012002010028.5714285714
1022002010028.5714285714
1032002010028.5714285714
1042002010028.5714285714
1052002010028.5714285714
1062002010028.5714285714
1072002010028.5714285714
1082002010028.5714285714
1092002010028.5714285714
1102002010028.5714285714
1112002010028.5714285714
1122102505014.2857142857
1131001010014.2857142857
1141001010014.2857142857
1151001010014.2857142857
1161001010014.2857142857
1171001010014.2857142857
1181001010014.2857142857
1191001010014.2857142857
1201001010014.2857142857
1211001010014.2857142857
1221001010014.2857142857
1231001010014.2857142857
1241001010014.2857142857
1251001010014.2857142857
1261001010014.2857142857
1271001010014.2857142857
1281001010014.2857142857
1291001010014.2857142857
1301001010014.2857142857
1311001010014.2857142857
1321001010014.2857142857
1331001010014.2857142857
1341001010014.2857142857
1351001010014.2857142857
1361001010014.2857142857
1371001010014.2857142857
1381001010014.2857142857
1391001010014.2857142857
1401001010014.2857142857
1411001010014.2857142857
1421001010014.2857142857
1431001010014.2857142857
1441001010014.2857142857
1451001010014.2857142857
1461001010014.2857142857
1471001010014.2857142857
1481001010014.2857142857
1491001010014.2857142857
150110110000
Gráfico3
100100100100
10097.7272727273100100
10097.7272727273100100
10097.7272727273100100
10097.7272727273100100
92.307692307795.4545454545100100
92.307692307795.454545454596.4285714286100
92.307692307795.454545454596.4285714286100
92.307692307793.181818181896.4285714286100
80.769230769293.181818181896.4285714286100
80.769230769290.909090909196.4285714286100
80.769230769290.909090909196.4285714286100
80.769230769288.636363636492.8571428571100
69.230769230884.090909090992.8571428571100
69.230769230884.090909090992.8571428571100
69.230769230879.545454545592.8571428571100
69.230769230879.545454545589.2857142857100
69.230769230879.545454545589.2857142857100
61.53846153857582.1428571429100
61.53846153857575100
61.538461538570.454545454575100
61.538461538570.454545454575100
53.846153846268.181818181875100
53.846153846268.181818181875100
53.846153846261.363636363675100
53.846153846261.363636363675100
46.153846153859.090909090975100
46.153846153859.090909090975100
46.153846153856.818181818271.4285714286100
46.15384615385071.4285714286100
46.153846153843.181818181871.4285714286100
38.461538461543.181818181871.4285714286100
38.461538461540.909090909167.857142857185.7142857143
38.461538461540.909090909167.857142857185.7142857143
38.461538461538.636363636467.857142857185.7142857143
34.615384615434.090909090967.857142857185.7142857143
34.615384615434.090909090967.857142857185.7142857143
34.615384615434.090909090967.857142857185.7142857143
34.615384615434.090909090967.857142857185.7142857143
30.769230769231.818181818267.857142857185.7142857143
30.769230769227.272727272764.285714285785.7142857143
30.769230769227.272727272764.285714285785.7142857143
30.769230769227.272727272760.714285714385.7142857143
30.769230769227.272727272757.142857142971.4285714286
26.92307692312557.142857142971.4285714286
26.92307692312557.142857142971.4285714286
26.92307692312557.142857142971.4285714286
26.92307692312557.142857142971.4285714286
26.92307692312557.142857142971.4285714286
26.92307692312557.142857142971.4285714286
26.92307692312557.142857142971.4285714286
26.92307692312553.333333333371.4285714286
26.92307692312553.333333333371.4285714286
15.38461538462553.333333333371.4285714286
15.38461538462553.333333333371.4285714286
15.384615384622.727272727353.333333333371.4285714286
15.384615384620.454545454549.523809523871.4285714286
7.692307692318.181818181841.904761904871.4285714286
7.692307692318.181818181841.904761904871.4285714286
7.692307692318.181818181841.904761904871.4285714286
3.846153846215.909090909141.904761904857.1428571429
3.846153846215.909090909141.904761904857.1428571429
3.846153846215.909090909141.904761904857.1428571429
3.846153846213.636363636441.904761904857.1428571429
3.846153846213.636363636441.904761904857.1428571429
3.846153846211.363636363641.904761904857.1428571429
3.846153846211.363636363638.095238095257.1428571429
3.846153846211.363636363638.095238095257.1428571429
3.846153846211.363636363638.095238095257.1428571429
3.846153846211.363636363638.095238095257.1428571429
3.846153846211.363636363638.095238095257.1428571429
3.846153846211.363636363634.285714285757.1428571429
3.846153846211.363636363634.285714285757.1428571429
3.846153846211.363636363634.285714285757.1428571429
3.846153846211.363636363634.285714285757.1428571429
3.84615384629.090909090934.285714285757.1428571429
3.84615384626.818181818234.285714285757.1428571429
3.84615384626.818181818234.285714285757.1428571429
3.84615384626.818181818234.285714285757.1428571429
3.84615384626.818181818234.285714285757.1428571429
3.84615384626.818181818230.476190476242.8571428571
3.84615384626.818181818230.476190476242.8571428571
3.84615384626.818181818230.476190476242.8571428571
3.84615384626.818181818230.476190476242.8571428571
3.84615384626.818181818230.476190476242.8571428571
3.84615384626.818181818226.666666666728.5714285714
3.84615384626.818181818226.666666666728.5714285714
3.84615384626.818181818226.666666666728.5714285714
3.84615384626.818181818226.666666666728.5714285714
3.84615384626.818181818226.666666666728.5714285714
3.84615384626.818181818226.666666666728.5714285714
3.84615384626.818181818226.666666666728.5714285714
3.84615384626.818181818226.666666666728.5714285714
3.84615384626.818181818226.666666666728.5714285714
3.84615384626.818181818226.666666666728.5714285714
3.84615384626.818181818226.666666666728.5714285714
3.84615384626.818181818226.666666666728.5714285714
3.84615384626.818181818226.666666666728.5714285714
3.84615384626.818181818226.666666666728.5714285714
3.84615384624.545454545519.047619047628.5714285714
3.84615384624.545454545519.047619047628.5714285714
3.84615384624.545454545519.047619047628.5714285714
3.84615384624.545454545519.047619047628.5714285714
3.84615384624.545454545519.047619047628.5714285714
3.84615384624.545454545519.047619047628.5714285714
3.84615384624.545454545519.047619047628.5714285714
3.84615384624.545454545519.047619047628.5714285714
3.84615384624.545454545519.047619047628.5714285714
3.84615384622.272727272719.047619047628.5714285714
3.84615384622.272727272719.047619047628.5714285714
3.84615384622.272727272719.047619047628.5714285714
3.84615384622.272727272719.047619047628.5714285714
3.84615384622.272727272711.428571428614.2857142857
3.84615384622.272727272711.428571428614.2857142857
3.84615384622.272727272711.428571428614.2857142857
3.84615384622.272727272711.428571428614.2857142857
3.84615384622.272727272711.428571428614.2857142857
3.84615384622.272727272711.428571428614.2857142857
3.84615384622.272727272711.428571428614.2857142857
3.84615384622.272727272711.428571428614.2857142857
3.84615384622.272727272711.428571428614.2857142857
3.84615384622.272727272711.428571428614.2857142857
3.84615384622.272727272711.428571428614.2857142857
3.84615384622.272727272711.428571428614.2857142857
3.84615384622.272727272711.428571428614.2857142857
3.84615384622.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.42857142860
2.27272727275.7142857143
2.27272727275.7142857143
2.27272727275.7142857143
2.27272727270
2.27272727270
2.2727272727
2.2727272727
gem protocol
gem+cisp proto
pac fuera prot
pac cirug
weeks
survival comparation
Gráfico4
100100100100
10097.7272727273100100
10097.7272727273100100
10097.7272727273100100
10097.7272727273100100
92.307692307795.4545454545100100
92.307692307795.454545454596.4285714286100
92.307692307795.454545454596.4285714286100
92.307692307793.181818181896.4285714286100
80.769230769293.181818181896.4285714286100
80.769230769290.909090909196.4285714286100
80.769230769290.909090909196.4285714286100
80.769230769288.636363636492.8571428571100
69.230769230884.090909090992.8571428571100
69.230769230884.090909090992.8571428571100
69.230769230879.545454545592.8571428571100
69.230769230879.545454545589.2857142857100
69.230769230879.545454545589.2857142857100
61.53846153857582.1428571429100
61.53846153857575100
61.538461538570.454545454575100
61.538461538570.454545454575100
53.846153846268.181818181875100
53.846153846268.181818181875100
53.846153846261.363636363675100
53.846153846261.363636363675100
46.153846153859.090909090975100
46.153846153859.090909090975100
46.153846153856.818181818271.4285714286100
46.15384615385071.4285714286100
46.153846153843.181818181871.4285714286100
38.461538461543.181818181871.4285714286100
38.461538461540.909090909167.857142857185.7142857143
38.461538461540.909090909167.857142857185.7142857143
38.461538461538.636363636467.857142857185.7142857143
34.615384615434.090909090967.857142857185.7142857143
34.615384615434.090909090967.857142857185.7142857143
34.615384615434.090909090967.857142857185.7142857143
34.615384615434.090909090967.857142857185.7142857143
30.769230769231.818181818267.857142857185.7142857143
30.769230769227.272727272764.285714285785.7142857143
30.769230769227.272727272764.285714285785.7142857143
30.769230769227.272727272760.714285714385.7142857143
30.769230769227.272727272757.142857142971.4285714286
26.92307692312557.142857142971.4285714286
26.92307692312557.142857142971.4285714286
26.92307692312557.142857142971.4285714286
26.92307692312557.142857142971.4285714286
26.92307692312557.142857142971.4285714286
26.92307692312557.142857142971.4285714286
26.92307692312557.142857142971.4285714286
26.92307692312553.333333333371.4285714286
26.92307692312553.333333333371.4285714286
15.38461538462553.333333333371.4285714286
15.38461538462553.333333333371.4285714286
15.384615384622.727272727353.333333333371.4285714286
15.384615384620.454545454549.523809523871.4285714286
7.692307692318.181818181841.904761904871.4285714286
7.692307692318.181818181841.904761904871.4285714286
7.692307692318.181818181841.904761904871.4285714286
3.846153846215.909090909141.904761904857.1428571429
3.846153846215.909090909141.904761904857.1428571429
3.846153846215.909090909141.904761904857.1428571429
3.846153846213.636363636441.904761904857.1428571429
3.846153846213.636363636441.904761904857.1428571429
3.846153846211.363636363641.904761904857.1428571429
3.846153846211.363636363638.095238095257.1428571429
3.846153846211.363636363638.095238095257.1428571429
3.846153846211.363636363638.095238095257.1428571429
3.846153846211.363636363638.095238095257.1428571429
3.846153846211.363636363638.095238095257.1428571429
3.846153846211.363636363634.285714285757.1428571429
3.846153846211.363636363634.285714285757.1428571429
3.846153846211.363636363634.285714285757.1428571429
3.846153846211.363636363634.285714285757.1428571429
3.84615384629.090909090934.285714285757.1428571429
3.84615384626.818181818234.285714285757.1428571429
3.84615384626.818181818234.285714285757.1428571429
3.84615384626.818181818234.285714285757.1428571429
3.84615384626.818181818234.285714285757.1428571429
3.84615384626.818181818230.476190476242.8571428571
3.84615384626.818181818230.476190476242.8571428571
3.84615384626.818181818230.476190476242.8571428571
3.84615384626.818181818230.476190476242.8571428571
3.84615384626.818181818230.476190476242.8571428571
3.84615384626.818181818226.666666666728.5714285714
3.84615384626.818181818226.666666666728.5714285714
3.84615384626.818181818226.666666666728.5714285714
3.84615384626.818181818226.666666666728.5714285714
3.84615384626.818181818226.666666666728.5714285714
3.84615384626.818181818226.666666666728.5714285714
3.84615384626.818181818226.666666666728.5714285714
3.84615384626.818181818226.666666666728.5714285714
3.84615384626.818181818226.666666666728.5714285714
3.84615384626.818181818226.666666666728.5714285714
3.84615384626.818181818226.666666666728.5714285714
3.84615384626.818181818226.666666666728.5714285714
3.84615384626.818181818226.666666666728.5714285714
3.84615384626.818181818226.666666666728.5714285714
3.84615384624.545454545519.047619047628.5714285714
3.84615384624.545454545519.047619047628.5714285714
3.84615384624.545454545519.047619047628.5714285714
3.84615384624.545454545519.047619047628.5714285714
3.84615384624.545454545519.047619047628.5714285714
3.84615384624.545454545519.047619047628.5714285714
3.84615384624.545454545519.047619047628.5714285714
3.84615384624.545454545519.047619047628.5714285714
3.84615384624.545454545519.047619047628.5714285714
3.84615384622.272727272719.047619047628.5714285714
3.84615384622.272727272719.047619047628.5714285714
3.84615384622.272727272719.047619047628.5714285714
3.84615384622.272727272719.047619047628.5714285714
3.84615384622.272727272711.428571428614.2857142857
3.84615384622.272727272711.428571428614.2857142857
3.84615384622.272727272711.428571428614.2857142857
3.84615384622.272727272711.428571428614.2857142857
3.84615384622.272727272711.428571428614.2857142857
3.84615384622.272727272711.428571428614.2857142857
3.84615384622.272727272711.428571428614.2857142857
3.84615384622.272727272711.428571428614.2857142857
3.84615384622.272727272711.428571428614.2857142857
3.84615384622.272727272711.428571428614.2857142857
3.84615384622.272727272711.428571428614.2857142857
3.84615384622.272727272711.428571428614.2857142857
3.84615384622.272727272711.428571428614.2857142857
3.84615384622.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.428571428614.2857142857
2.272727272711.42857142860
2.27272727275.7142857143
2.27272727275.7142857143
2.27272727275.7142857143
2.27272727270
2.27272727270
2.2727272727
2.2727272727
gem protocol
gem+cisp proto
pac fuera prot
pac cirug
weeks
%
survival comparation
Gráfico5
100100100
10097.7272727273100
10097.7272727273100
10097.7272727273100
10097.7272727273100
92.307692307795.4545454545100
92.307692307795.454545454596.4285714286
92.307692307795.454545454596.4285714286
92.307692307793.181818181896.4285714286
80.769230769293.181818181896.4285714286
80.769230769290.909090909196.4285714286
80.769230769290.909090909196.4285714286
80.769230769288.636363636492.8571428571
69.230769230884.090909090992.8571428571
69.230769230884.090909090992.8571428571
69.230769230879.545454545592.8571428571
69.230769230879.545454545589.2857142857
69.230769230879.545454545589.2857142857
61.53846153857582.1428571429
61.53846153857575
61.538461538570.454545454575
61.538461538570.454545454575
53.846153846268.181818181875
53.846153846268.181818181875
53.846153846261.363636363675
53.846153846261.363636363675
46.153846153859.090909090975
46.153846153859.090909090975
46.153846153856.818181818271.4285714286
46.15384615385071.4285714286
46.153846153843.181818181871.4285714286
38.461538461543.181818181871.4285714286
38.461538461540.909090909167.8571428571
38.461538461540.909090909167.8571428571
38.461538461538.636363636467.8571428571
34.615384615434.090909090967.8571428571
34.615384615434.090909090967.8571428571
34.615384615434.090909090967.8571428571
34.615384615434.090909090967.8571428571
30.769230769231.818181818267.8571428571
30.769230769227.272727272764.2857142857
30.769230769227.272727272764.2857142857
30.769230769227.272727272760.7142857143
30.769230769227.272727272757.1428571429
26.92307692312557.1428571429
26.92307692312557.1428571429
26.92307692312557.1428571429
26.92307692312557.1428571429
26.92307692312557.1428571429
26.92307692312557.1428571429
26.92307692312557.1428571429
26.92307692312553.3333333333
26.92307692312553.3333333333
15.38461538462553.3333333333
15.38461538462553.3333333333
15.384615384622.727272727353.3333333333
15.384615384620.454545454549.5238095238
7.692307692318.181818181841.9047619048
7.692307692318.181818181841.9047619048
7.692307692318.181818181841.9047619048
3.846153846215.909090909141.9047619048
3.846153846215.909090909141.9047619048
3.846153846215.909090909141.9047619048
3.846153846213.636363636441.9047619048
3.846153846213.636363636441.9047619048
3.846153846211.363636363641.9047619048
3.846153846211.363636363638.0952380952
3.846153846211.363636363638.0952380952
3.846153846211.363636363638.0952380952
3.846153846211.363636363638.0952380952
3.846153846211.363636363638.0952380952
3.846153846211.363636363634.2857142857
3.846153846211.363636363634.2857142857
3.846153846211.363636363634.2857142857
3.846153846211.363636363634.2857142857
3.84615384629.090909090934.2857142857
3.84615384626.818181818234.2857142857
3.84615384626.818181818234.2857142857
3.84615384626.818181818234.2857142857
3.84615384626.818181818234.2857142857
3.84615384626.818181818230.4761904762
3.84615384626.818181818230.4761904762
3.84615384626.818181818230.4761904762
3.84615384626.818181818230.4761904762
3.84615384626.818181818230.4761904762
3.84615384626.818181818226.6666666667
3.84615384626.818181818226.6666666667
3.84615384626.818181818226.6666666667
3.84615384626.818181818226.6666666667
3.84615384626.818181818226.6666666667
3.84615384626.818181818226.6666666667
3.84615384626.818181818226.6666666667
3.84615384626.818181818226.6666666667
3.84615384626.818181818226.6666666667
3.84615384626.818181818226.6666666667
3.84615384626.818181818226.6666666667
3.84615384626.818181818226.6666666667
3.84615384626.818181818226.6666666667
3.84615384626.818181818226.6666666667
3.84615384624.545454545519.0476190476
3.84615384624.545454545519.0476190476
3.84615384624.545454545519.0476190476
3.84615384624.545454545519.0476190476
3.84615384624.545454545519.0476190476
3.84615384624.545454545519.0476190476
3.84615384624.545454545519.0476190476
3.84615384624.545454545519.0476190476
3.84615384624.545454545519.0476190476
3.84615384622.272727272719.0476190476
3.84615384622.272727272719.0476190476
3.84615384622.272727272719.0476190476
3.84615384622.272727272719.0476190476
3.84615384622.272727272711.4285714286
3.84615384622.272727272711.4285714286
3.84615384622.272727272711.4285714286
3.84615384622.272727272711.4285714286
3.84615384622.272727272711.4285714286
3.84615384622.272727272711.4285714286
3.84615384622.272727272711.4285714286
3.84615384622.272727272711.4285714286
3.84615384622.272727272711.4285714286
3.84615384622.272727272711.4285714286
3.84615384622.272727272711.4285714286
3.84615384622.272727272711.4285714286
3.84615384622.272727272711.4285714286
3.84615384622.272727272711.4285714286
2.272727272711.4285714286
2.272727272711.4285714286
2.272727272711.4285714286
2.272727272711.4285714286
2.272727272711.4285714286
2.272727272711.4285714286
2.272727272711.4285714286
2.272727272711.4285714286
2.272727272711.4285714286
2.272727272711.4285714286
2.272727272711.4285714286
2.272727272711.4285714286
2.272727272711.4285714286
2.272727272711.4285714286
2.272727272711.4285714286
2.272727272711.4285714286
2.272727272711.4285714286
2.272727272711.4285714286
2.272727272711.4285714286
2.272727272711.4285714286
2.272727272711.4285714286
2.272727272711.4285714286
2.272727272711.4285714286
2.272727272711.4285714286
2.272727272711.4285714286
2.27272727275.7142857143
2.27272727275.7142857143
2.27272727275.7142857143
2.27272727270
2.27272727270
2.2727272727
2.2727272727
gem protocol
gem+cisp proto
pac fuera prot
weeks
%
survival comparation
Gráfico6
100100
10097.7272727273
10097.7272727273
10097.7272727273
10097.7272727273
92.307692307795.4545454545
92.307692307795.4545454545
92.307692307795.4545454545
92.307692307793.1818181818
80.769230769293.1818181818
80.769230769290.9090909091
80.769230769290.9090909091
80.769230769288.6363636364
69.230769230884.0909090909
69.230769230884.0909090909
69.230769230879.5454545455
69.230769230879.5454545455
69.230769230879.5454545455
61.538461538575
61.538461538575
61.538461538570.4545454545
61.538461538570.4545454545
53.846153846268.1818181818
53.846153846268.1818181818
53.846153846261.3636363636
53.846153846261.3636363636
46.153846153859.0909090909
46.153846153859.0909090909
46.153846153856.8181818182
46.153846153850
46.153846153843.1818181818
38.461538461543.1818181818
38.461538461540.9090909091
38.461538461540.9090909091
38.461538461538.6363636364
34.615384615434.0909090909
34.615384615434.0909090909
34.615384615434.0909090909
34.615384615434.0909090909
30.769230769231.8181818182
30.769230769227.2727272727
30.769230769227.2727272727
30.769230769227.2727272727
30.769230769227.2727272727
26.923076923125
26.923076923125
26.923076923125
26.923076923125
26.923076923125
26.923076923125
26.923076923125
26.923076923125
26.923076923125
15.384615384625
15.384615384625
15.384615384622.7272727273
15.384615384620.4545454545
7.692307692318.1818181818
7.692307692318.1818181818
7.692307692318.1818181818
3.846153846215.9090909091
3.846153846215.9090909091
3.846153846215.9090909091
3.846153846213.6363636364
3.846153846213.6363636364
3.846153846211.3636363636
3.846153846211.3636363636
3.846153846211.3636363636
3.846153846211.3636363636
3.846153846211.3636363636
3.846153846211.3636363636
3.846153846211.3636363636
3.846153846211.3636363636
3.846153846211.3636363636
3.846153846211.3636363636
3.84615384629.0909090909
3.84615384626.8181818182
3.84615384626.8181818182
3.84615384626.8181818182
3.84615384626.8181818182
3.84615384626.8181818182
3.84615384626.8181818182
3.84615384626.8181818182
3.84615384626.8181818182
3.84615384626.8181818182
3.84615384626.8181818182
3.84615384626.8181818182
3.84615384626.8181818182
3.84615384626.8181818182
3.84615384626.8181818182
3.84615384626.8181818182
3.84615384626.8181818182
3.84615384626.8181818182
3.84615384626.8181818182
3.84615384626.8181818182
3.84615384626.8181818182
3.84615384626.8181818182
3.84615384626.8181818182
3.84615384626.8181818182
3.84615384624.5454545455
3.84615384624.5454545455
3.84615384624.5454545455
3.84615384624.5454545455
3.84615384624.5454545455
3.84615384624.5454545455
3.84615384624.5454545455
3.84615384624.5454545455
3.84615384624.5454545455
3.84615384622.2727272727
3.84615384622.2727272727
3.84615384622.2727272727
3.84615384622.2727272727
3.84615384622.2727272727
3.84615384622.2727272727
3.84615384622.2727272727
3.84615384622.2727272727
3.84615384622.2727272727
3.84615384622.2727272727
3.84615384622.2727272727
3.84615384622.2727272727
3.84615384622.2727272727
3.84615384622.2727272727
3.84615384622.2727272727
3.84615384622.2727272727
3.84615384622.2727272727
3.84615384622.2727272727
2.2727272727
2.2727272727
2.2727272727
2.2727272727
2.2727272727
2.2727272727
2.2727272727
2.2727272727
2.2727272727
2.2727272727
2.2727272727
2.2727272727
2.2727272727
2.2727272727
2.2727272727
2.2727272727
2.2727272727
2.2727272727
2.2727272727
2.2727272727
2.2727272727
2.2727272727
2.2727272727
2.2727272727
2.2727272727
2.2727272727
2.2727272727
2.2727272727
2.2727272727
2.2727272727
2.2727272727
2.2727272727
gem protocol
gem+cisp proto
weeks
%
survival comparation
Gráfico7
100
100
100
100
100
92.3076923077
92.3076923077
92.3076923077
92.3076923077
80.7692307692
80.7692307692
80.7692307692
80.7692307692
69.2307692308
69.2307692308
69.2307692308
69.2307692308
69.2307692308
61.5384615385
61.5384615385
61.5384615385
61.5384615385
53.8461538462
53.8461538462
53.8461538462
53.8461538462
46.1538461538
46.1538461538
46.1538461538
46.1538461538
46.1538461538
38.4615384615
38.4615384615
38.4615384615
38.4615384615
34.6153846154
34.6153846154
34.6153846154
34.6153846154
30.7692307692
30.7692307692
30.7692307692
30.7692307692
30.7692307692
26.9230769231
26.9230769231
26.9230769231
26.9230769231
26.9230769231
26.9230769231
26.9230769231
26.9230769231
26.9230769231
15.3846153846
15.3846153846
15.3846153846
15.3846153846
7.6923076923
7.6923076923
7.6923076923
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
3.8461538462
gem protocol
weeks
%
4curvas
semgem protocolgem+cisp protopac fuera protpac cirug
100100100100
126002601001004410442.272727272797.727272727397.7272727273280028010010070070100100
22600260100100430043010097.7272727273280028010010070070100100
32600260100100430043010097.7272727273280028010010070070100100
42600260100100430043010097.7272727273280028010010070070100100
52620267.692307692392.307692307792.30769230774310432.325581395397.674418604795.4545454545280028010010070070100100
6240024010092.3076923077420042010095.45454545452810283.571428571496.428571428696.428571428670070100100
7240024010092.3076923077420042010095.4545454545270027010096.428571428670070100100
8240024010092.30769230774210422.38095238197.61904761993.1818181818270027010096.428571428670070100100
924302412.587.580.7692307692410041010093.1818181818270027010096.428571428670070100100
10210021010080.76923076924110412.439024390297.560975609890.9090909091270027010096.428571428670070100100
11210021010080.7692307692400040010090.9090909091270027010096.428571428670070100100
12210021010080.76923076924010402.597.588.63636363642710273.703703703796.296296296392.857142857170070100100
1321302114.285714285785.714285714369.23076923083920395.128205128294.871794871884.0909090909260026010092.857142857170070100100
14180018010069.2307692308370037010084.0909090909260026010092.857142857170070100100
15180018010069.23076923083720375.405405405494.594594594679.5454545455260026010092.857142857170070100100
16180018010069.2307692308350035010079.54545454552610263.846153846296.153846153889.285714285770070100100
17180018010069.2307692308350035010079.5454545455250025010089.285714285770070100100
1818201811.111111111188.888888888961.53846153853520355.714285714394.28571428577525202589282.142857142970070100100
19160016010061.53846153853300330100752320238.695652173991.30434782617570070100100
20160016010061.53846153853320336.060606060693.939393939470.454545454521002101007570070100100
21160016010061.5384615385310031010070.454545454521002101007570070100100
2216201612.587.553.84615384623110313.225806451696.774193548468.181818181821002101007570070100100
23140014010053.8461538462300030010068.181818181821002101007570070100100
24140014010053.8461538462303030109061.363636363621002101007570070100100
25140014010053.8461538462270027010061.363636363621002101007570070100100
2614201414.285714285785.714285714346.15384615382710273.703703703796.296296296359.090909090921002101007570070100100
27120012010046.1538461538260026010059.090909090921002101007570070100100
28120012010046.15384615382610263.846153846296.153846153856.81818181822110214.761904761995.238095238171.428571428670070100100
29120012010046.1538461538253025128850200020010071.428571428670070100100
30120012010046.153846153822302213.636363636486.363636363643.1818181818200020010071.428571428670070100100
3112201216.666666666783.333333333338.4615384615190019010043.1818181818200020010071.428571428670070100100
32100010010038.46153846151910195.263157894794.736842105340.909090909120102059567.8571428571710714.285714285785.714285714385.7142857143
33100010010038.4615384615180018010040.9090909091190019010067.85714285716006010085.7142857143
34100010010038.46153846151810185.555555555694.444444444438.6363636364190019010067.85714285716006010085.7142857143
35101010109034.615384615417201711.764705882488.235294117634.0909090909190019010067.85714285716006010085.7142857143
369009010034.6153846154150015010034.0909090909190019010067.85714285716006010085.7142857143
379009010034.6153846154150015010034.0909090909190019010067.85714285716006010085.7142857143
389009010034.6153846154150015010034.0909090909190019010067.85714285716006010085.7142857143
39910911.111111111188.888888888930.76923076921510156.666666666793.333333333331.8181818182190019010067.85714285716006010085.7142857143
408008010030.769230769214201414.285714285785.714285714327.27272727271910195.263157894794.736842105364.28571428576006010085.7142857143
418008010030.7692307692120012010027.2727272727180018010064.28571428576006010085.7142857143
428008010030.7692307692120012010027.27272727271810185.555555555694.444444444460.71428571436006010085.7142857143
438008010030.7692307692120012010027.27272727271710175.882352941294.117647058857.1428571429610616.666666666783.333333333371.4285714286
44810812.587.526.92307692311210128.333333333391.666666666725160016010057.14285714295005010071.4285714286
457007010026.9230769231110011010025160016010057.14285714295005010071.4285714286
467007010026.9230769231110011010025160115.5010057.14285714295005010071.4285714286
477007010026.9230769231110011010025150015010057.14285714295005010071.4285714286
487007010026.9230769231110011010025150015010057.14285714295005010071.4285714286
497007010026.9230769231110011010025150015010057.14285714295005010071.4285714286
507007010026.9230769231110011010025150015010057.14285714295005010071.4285714286
517007010026.92307692311100110100251510156.666666666793.333333333353.33333333335005010071.4285714286
527007010026.9230769231110011010025140014010053.33333333335005010071.4285714286
53730742.857142857157.142857142915.3846153846110011010025140014010053.33333333335005010071.4285714286
544004010015.3846153846110011010025140014010053.33333333335005010071.4285714286
554004010015.38461538461110119.090909090990.909090909122.7272727273140014010053.33333333335005010071.4285714286
564004010015.3846153846101010109020.45454545451410147.142857142992.857142857149.52380952385005010071.4285714286
57420450507.6923076923910911.111111111188.888888888918.181818181813201315.384615384684.615384615441.90476190485005010071.4285714286
58200201007.69230769238008010018.1818181818110011010041.90476190485005010071.4285714286
59200201007.69230769238008010018.1818181818110011010041.90476190485005010071.4285714286
60210250503.8461538462810812.587.515.9090909091110011010041.90476190485105208057.1428571429
61100101003.84615384627007010015.9090909091110011010041.90476190484004010057.1428571429
62100101003.84615384627007010015.9090909091110011010041.90476190484004010057.1428571429
63100101003.8461538462710714.285714285785.714285714313.6363636364110011010041.90476190484004010057.1428571429
64100101003.84615384626006010013.6363636364110011010041.90476190484004010057.1428571429
65100101003.8461538462610616.666666666783.333333333311.3636363636110011010041.90476190484004010057.1428571429
66100101003.84615384625005010011.36363636361110119.090909090990.909090909138.09523809524004010057.1428571429
67100101003.84615384625005010011.3636363636100010010038.09523809524004010057.1428571429
68100101003.84615384625005010011.3636363636100010010038.09523809524004010057.1428571429
69100101003.84615384625005010011.3636363636100010010038.09523809524004010057.1428571429
70100101003.84615384625005010011.3636363636100010010038.09523809524004010057.1428571429
71100101003.84615384625005010011.3636363636101010109034.28571428574004010057.1428571429
72100101003.84615384625005010011.36363636369009010034.28571428574004010057.1428571429
73100101003.84615384625005010011.36363636369009010034.28571428574004010057.1428571429
74100101003.84615384625005010011.36363636369009010034.28571428574004010057.1428571429
75100101003.8461538462510520809.09090909099009010034.28571428574004010057.1428571429
76100101003.8461538462410425756.81818181829009010034.28571428574004010057.1428571429
77100101003.8461538462300301006.81818181829009010034.28571428574004010057.1428571429
78100101003.8461538462300301006.81818181829009010034.28571428574004010057.1428571429
79100101003.8461538462300301006.81818181829009010034.28571428574004010057.1428571429
80100101003.8461538462300301006.8181818182910911.111111111188.888888888930.47619047624104257542.8571428571
81100101003.8461538462300301006.81818181828008010030.47619047623003010042.8571428571
82100101003.8461538462300301006.81818181828008010030.47619047623003010042.8571428571
83100101003.8461538462300301006.81818181828008010030.47619047623003010042.8571428571
84100101003.8461538462300301006.81818181828008010030.47619047623003010042.8571428571
85100101003.8461538462300301006.8181818182810812.587.526.6666666667310333.333333333366.666666666728.5714285714
86100101003.8461538462300301006.81818181827007010026.66666666672002010028.5714285714
87100101003.8461538462300301006.81818181827007010026.66666666672002010028.5714285714
88100101003.8461538462300301006.81818181827007010026.66666666672002010028.5714285714
89100101003.8461538462300301006.81818181827007010026.66666666672002010028.5714285714
90100101003.8461538462300301006.81818181827007010026.66666666672002010028.5714285714
91100101003.8461538462300301006.81818181827007010026.66666666672002010028.5714285714
92100101003.8461538462300301006.81818181827007010026.66666666672002010028.5714285714
93100101003.8461538462300301006.81818181827007010026.66666666672002010028.5714285714
94100101003.8461538462300301006.81818181827007010026.66666666672002010028.5714285714
95100101003.8461538462300301006.81818181827007010026.66666666672002010028.5714285714
96100101003.8461538462300301006.81818181827007010026.66666666672002010028.5714285714
97100101003.8461538462300301006.81818181827007010026.66666666672002010028.5714285714
98100101003.8461538462300301006.81818181827007010026.66666666672002010028.5714285714
99100101003.8461538462310333.333333333366.66666666674.5454545455720728.571428571471.428571428619.04761904762002010028.5714285714
100100101003.8461538462200201004.54545454555005010019.04761904762002010028.5714285714
101100101003.8461538462200201004.54545454555005010019.04761904762002010028.5714285714
102100101003.8461538462200201004.54545454555005010019.04761904762002010028.5714285714
103100101003.8461538462200201004.54545454555005010019.04761904762002010028.5714285714
104100101003.8461538462200201004.54545454555005010019.04761904762002010028.5714285714
105100101003.8461538462200201004.54545454555005010019.04761904762002010028.5714285714
106100101003.8461538462200201004.54545454555005010019.04761904762002010028.5714285714
107100101003.8461538462200201004.54545454555005010019.04761904762002010028.5714285714
108100101003.8461538462210250502.27272727275005010019.04761904762002010028.5714285714
109100101003.8461538462100101002.27272727275005010019.04761904762002010028.5714285714
110100101003.8461538462100101002.27272727275005010019.04761904762002010028.5714285714
111100101003.8461538462100101002.27272727275005010019.04761904762002010028.5714285714
112100101003.8461538462100101002.27272727275205406011.42857142862102505014.2857142857
113100101003.8461538462100101002.27272727273003010011.42857142861001010014.2857142857
114100101003.8461538462100101002.27272727273003010011.42857142861001010014.2857142857
115100101003.8461538462100101002.27272727273003010011.42857142861001010014.2857142857
116100101003.8461538462100101002.27272727273003010011.42857142861001010014.2857142857
117100101003.8461538462100101002.27272727273003010011.42857142861001010014.2857142857
118100101003.8461538462100101002.27272727273003010011.42857142861001010014.2857142857
119100101003.8461538462100101002.27272727273003010011.42857142861001010014.2857142857
120100101003.8461538462100101002.27272727273003010011.42857142861001010014.2857142857
121100101003.8461538462100101002.27272727273003010011.42857142861001010014.2857142857
122100101003.8461538462100101002.27272727273003010011.42857142861001010014.2857142857
123100101003.8461538462100101002.27272727273003010011.42857142861001010014.2857142857
124100101003.8461538462100101002.27272727273003010011.42857142861001010014.2857142857
125100101003.8461538462100101002.27272727273003010011.42857142861001010014.2857142857
126100101002.27272727273003010011.42857142861001010014.2857142857
127100101002.27272727273003010011.42857142861001010014.2857142857
128100101002.27272727273003010011.42857142861001010014.2857142857
129100101002.27272727273003010011.42857142861001010014.2857142857
130100101002.27272727273003010011.42857142861001010014.2857142857
131100101002.27272727273003010011.42857142861001010014.2857142857
132100101002.27272727273003010011.42857142861001010014.2857142857
133100101002.27272727273003010011.42857142861001010014.2857142857
134100101002.27272727273003010011.42857142861001010014.2857142857
135100101002.27272727273003010011.42857142861001010014.2857142857
136100101002.27272727273003010011.42857142861001010014.2857142857
137100101002.27272727273003010011.42857142861001010014.2857142857
138100101002.27272727273003010011.42857142861001010014.2857142857
139100101002.27272727273003010011.42857142861001010014.2857142857
140100101002.27272727273003010011.42857142861001010014.2857142857
141100101002.27272727273003010011.42857142861001010014.2857142857
142100101002.27272727273003010011.42857142861001010014.2857142857
143100101002.27272727273003010011.42857142861001010014.2857142857
144100101002.27272727273003010011.42857142861001010014.2857142857
145100101002.27272727273003010011.42857142861001010014.2857142857
146100101002.27272727273003010011.42857142861001010014.2857142857
147100101002.27272727273003010011.42857142861001010014.2857142857
148100101002.27272727273003010011.42857142861001010014.2857142857
149100101002.27272727273012.5010011.42857142861001010014.2857142857
150100101002.27272727272002010011.4285714286110110000
151100101002.2727272727210250505.7142857143
152100101002.2727272727100101005.7142857143
153100101002.2727272727100101005.7142857143
154100101002.2727272727110110000
155100101002.27272727270
156100101002.2727272727
157100101002.2727272727
158
4curvas
gem protocol
gem+cisp proto
pac fuera prot
pac cirug
weeks
%
survival comparation
-
41
BTC ESMO GUIDELINE
Ref: Biliary Cancer: ESMO Clinical Practice Guidelines. Ann Oncol (2016)
-
2019
42
-
Thanks for the invitation and your attention
We invite you to join us in SLAGO Meetingswww.slago.com
43Dr. R. ReichelmannCo-organizer 2019
Slide Number 1ESMO Summit �LATIN AMERICA 2019Conflict of interest disclosureBiliary Tract Cancer (BTC)1.- Incidence and Epidemiology �Biliary Tract Cancer (BTC)Subclassification:Incidence cholangiocarcinoma (CCA) Incidence of gallbladder cancer (GBC)GBC estimated age-standardized mortality rates (World) in 2018, GBC Mortality in Latin-America, From 1995 to 2013Pathology diagnosis Pathology diagnosis 3.- Radiologic Assesment Radiologic Assesment 2Cholelitiasis is the major risk for GBCChilean National Policy against GBC: Prophylactic Cholecistectomy5.- Management of local/locoregional diseaseManagement of local/locoregional�Intrahepatic cholangiocarcinoma iCCA:Management of local/locoregional�Intrahepatic cholangiocarcinoma iCCA:Management of local/locoregional Management of local/locoregionalSlide Number 236- Adjuvant treatmentAdjuvant treatmentAdjuvant treatmentSlide Number 27Chilean Adjuvant Trials in GBCBTC ESMO GuidelineSlide Number 307. Management of advanced diseaseManagement of advanced diseaseManagement of advanced diseaseManagement of advanced diseaseManagement of advanced diseaseManagement of advanced diseaseSlide Number 37Chilean studies on GBC Chemotherapie Slide Number 40BTC ESMO GuidelineSlide Number 42Slide Number 43
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