Management of biliary Management of biliary tract cancer: a case tract cancer: a case

reportreport

Giovanni BrandiGiovanni Brandi

Institute of Hematology end Medical Oncology “L e A Seràgnoli”

Bologna University

JANUARY 2008

MAN, 74 YEARS OLD

20-01-08: abdominal pain, localized in the superior part of abdomen and involving the lumbar region

E.O, CHEST-X-RAY, ABDOMEN-X-RAY : normal

BLOOD TEST: Bil. Tot: 8,22; Bil. Dir: 6,27; AST: 63 UI/L; ALT: 100 UI/L; GGT: 253 UI/l; ALP: 525 UI/L; CA19.9: 928 U/ML

ABDOMINAL ULTRASOUND SCAN: gallstones and presence of a hypoecoic mass in the bottom of the gallbladder (4,5 x 3,0 cm)

ABDOMINAL CT WITH CONTRAST MEAN : lesion of gallbladder corpus with probably infiltration of hepatic parenchyma

FEBRUARY 2008

06/02/2008 SURGERY: resection of IV-V haepatic segments, including gallbladder

HISTOLOGICAL DIAGNOSIS: adenocarcinoma not well differentiated of the gallbladder infiltrating the surrounding fat and the liver.

Margins of liver resection not involved by neoplasm. Limph node metastasis

pT3N1M0, STAGE IIB

Biliary tract cancer treatment : results from the Biliary Tract Cancer Statistics Registry in Japan

Nagakawa et al. Journal of HBP Surgery, 2001

Gallbladder Cancer OS by staging and lymph node status

Staging Lymph node statusOS

Hilar-upper

papilla

lower

Killeen R P M et al, Abdom Imaging, 33(1):54-7,

2008

Is adjuvant therapy necessary in the gallbladder cancer?

Choose an alternative:

Only with N+ No

Always It’s not well defined

15 $1 MILLION14 $500.00013 $250.00012 $100.00011 $50.00010 $25.0009 $16.0009 $16.0008 $8.0007 $4.0006 $2.0005 $1.0004 $5003 $3002 $2001 $100

ADJUVANT THERAPY, TO DO OR NOT TO DO?

ADJUVANT THERAPY IS NOT EXECUTED

FOLLOW-UP

• In biliary tract cancer the percentage of curative resection is extremely low (37.7% GBC, 30.4% BDC)

• an effective adjuvant therapy could be useful in order to improve the overall survival

• standard adjuvant treatment is still not settled

• there are only few inadequate randomised trials

Randomised clinical trials of adjuvant chemotherapy for pancreatic and biliary tract cancer. Takada, 2002

Mitomycin C and 5FU therapy has not been established as the standard postoperative therapy in BTC, but this trial suggests the efficacy and the need of adjuvant treatments

Takada T at al. Cancer 2002; 95:1685-95

APRIL 2008

BLOOD TEST: CA19.9: 87 U/ML (N.V. <33)

PET: high FDG uptake (SUV max 10) at V-VI hepatic segments with involvement of hepatic capsule and adjacent peritoneum

CEUS: not homogeneous area at IV-V hepatic segments with fluid component (4.8 x 1.8 cm) near metallic clips

Follow-up was established at 2 months to clarify the clinical picture

APRIL 2008

SEPTEMBER 2008

BLOOD TEST: CA19.9: 220 U/ML (N.V. <33); AST: 34 U/L; ALT: 48 U/L; ALP: 281 U/L

PET: reduction of uptake at V-VI hepatic segments but find of a weak new area in the hilary region

CEUS: hypoechogenous hilary mass (2,9x2,1x2,0 cm), near main biliary duct

INTRAHEPATIC RECURRENCE OF CHOLANGIOCARCINOMA

SEPTEMBER 2008

OTTOBRE 2008CONCLUSIONS: unresectable patients.

Program: chemotherapy

Yonemoto et al. Jpn J Clin Oncol 2007Glimelius et al. Ann of Oncol 1996

Author, year Regimen Study N° pts

OS

Glimelius, 1996 Chemotherapy vs BSC

Randomised 90 6 mo vs 2,5 (P<0,01)

Yonemoto, 2007

Chemotherapy vs BSC

Retrospective

304 7.38 mo vs 3,12 (P<0,001)

CT

BSC

CT

BSC

Which is the best chemotherapy?

Choose an alternative:

Gem-based regimen

5-FU-based regimen

Not defined Taxanes

15 $1 MILLION14 $500.00013 $250.00012 $100.00012 $100.00011 $50.00010 $25.0009 $16.0008 $8.0007 $4.0006 $2.0005 $1.0004 $5003 $3002 $2001 $100

70

20

0

10

50

40

30

60

5-FUPOLI

GEM GEM+5-FU

GEMOX

GEM POLI

CAPE TAXAN

other HAI

Chemotherapy in advanced BTC

653 321 155 437331 55 121161234N°

PTS

Resp

onse

%

RangeRO

CPT11

81

Guidelines EBM 2008SINGLE AGENT

AGENT N° STUDY STUDY DESIGN RR(RANGE)

EVIDENCE LEVEL

5-fu/ analogues

12 1 Randomised11 Cohort study

05-34%

Level IILevel III

Gem 7 7 Cohort study 0-36% Level III

Taxanes 3 3 Cohort study 0-20% Level III

Others 4 4 Cohort study 8-10% Level III

COMBINATION THERAPY

AGENT N° STUDY STUDY DESIGN RR(RANGE)

EVIDENCE LEVEL

5-fu-BASED 4 4 Cohort study 0-29% Level III

Gem-BASED 11 11 Cohort study 9-38% Level III

Platinum-BASED

10 10 Cohort study 19-40% Level III

J Furuse. J Hepatobiliary Pancreat Surg 2008

HOSPITALIZATION: obstructive jaundice. Bil. Tot.: 16,56 mg/dl

NOVEMBER 2008

MANAGEMENT OF UNRESECTABLE BILIARY TUMOR

UNRESECTABLE TUMOR

JAUNDICE NO JAUNDICE

DECOMPRESSION OF BILIARY TRACT (stent/drainage)

CHEMOTHERAPY ± RADIOTHERAPY

ILBT ± EBRT

JAUNDICE RESOLUTION (bil ~ 3-4)

CHEMOTHERAPY

BSC

NOVEMBER 2008

PTC: double internal-external trans-stenotic biliary drainage

COMMON BILE DUCT STENT HILAR STENT

BRACHITHERAPY: two 7 Gy fractions (total dose 14 Gy)

DICEMBRE 2008

Approachable lesion well defined small size

BRACHYTHERAPY

JANUARY 2009

PET: patological uptake at VI hepatic segment (SUV max: 8.8). Another metastasis next to anterior margin of left hepativ lobe.

SEPTEMBER 2008

JANUARY 2009

PET COMPARISON

TERAPIA IN CORSOEXTERNAL BEAM RADIOTHERAPY + METRONOMIC CAPECITABINE + LMWH

RT+ CT

Author, year Treatment N° pts OS

Brunner et al, 2004

EBRT (50 Gy) + 5-FU or GEM-based chemotherapy 98 OS: 11.8 mo (all pts)OSstent: 9.3 mo

OSCT+RT: 16.5

Deodato et alIJROBP, 2005

EBRT + 5-FU i.c ± boost of ILBR (12 pts) 22 22 mo without ILBT13 mo with ILBT

Golfieri et al In Vivo 2006

A: drainage + ILBT +EBRT + CTA1: drainage + ILBT

B: surgical palliationC: percutaneous decompression alone

A: 9A1: 7

B: 5C: 5

A: 10 m.oA1: 6 m.o

B: 10 m.oC: 2.75 m.o

Brunner et al, Strahlenther Onkol 2004

This studies confirmed the role of concurrent chemoradiation in advanced BTC; the role of ILBT boost remains to be further analysed

CHEMORADIATION

STENT ALONE

A BA: OS from diagnosis

B: OS from start of chemoradiation

TRIAL YEAR N° PTS DRUGS MEDIAN OS(months)

p

FAMOUS 2004 374 Dalteparin Placebo

10.8 9.14

p=0,19

CLOT 2005 602 DalteparinOral anticoagulants

62%61%

p=0,62

SCLC 2004 79 Dalteparin Placebo

13.08.0

p=0.01

MALT 2005 302 NadroparinPlacebo

8.06.6

p=0.021

LMWH AND CANCER TREATMENT

November2005 March2009

A CASE OF STABLE DISEASE AFTER LMWH TREATMENT

TTP : 7,2 m

OS: 13,2 m

GEM-CAPE Multicentre Phase II trial

Koeberle et al , JCO August 2008

N° pts 44 (36 BTC, 8 gallbladder)

Treatment

Gem 1000 (1,8/21)+ Cape 650 bid (1-14)

Pr( Recist)

25%

SD(≥8w) 55%

TTP 7,2 m

OS 13,2 m

QoL↔ ORR

Positive