Stefano Cascinu  Clinica di Oncologia Medica Ancona, Italy Rare  digestive cancers
Cancers by numbers (IARC) <ul><li>Lung 1.2 million </li></ul><ul><li>Breast 1  million </li></ul><ul><li>Colorectal   940....
Rare cancers <ul><li>Tumors with an incidence around or lower than 6/100.000/year </li></ul>Which digestive cancers can be...
GI Cancers Incidence rate/100.00/year N° of patients/year Oesophagus 7.49 60.723 Squamous 3.39 27.525 Adenocarcinoma 2.83 ...
Rare digestive cancers <ul><li>Uncommon histotypes in frequent tumors </li></ul><ul><ul><li>Squamous cell cancer stomach  ...
Rare digestive cancers <ul><ul><li>Small bowel carcinoma </li></ul></ul><ul><ul><li>Anal carcinoma </li></ul></ul><ul><ul>...
Small bowel adenocarcinoma <ul><li>Incidence: 0.73/100.000 </li></ul><ul><li>increasing </li></ul><ul><li>US 5640 </li></u...
Small bowel adenocarcinoma <ul><li>Risk factors: </li></ul><ul><li>Genetically predisposing conditions: </li></ul><ul><li>...
Small bowel adenocarcinoma <ul><li>Symptoms: </li></ul><ul><li>Epigastric pain </li></ul><ul><li>Gastric outlet obstructio...
Small bowel adenocarcinoma <ul><li>Lymphadenectomy </li></ul><ul><ul><li>Stage II </li></ul></ul><ul><li>N° exam. Lymph  5...
Small bowel adenocarcinoma <ul><li>Adjuvant treatment: </li></ul><ul><li>No randomized trials </li></ul><ul><li>2 large re...
Adjuvant therapy <ul><li>From 1981 --------------- to 2005 </li></ul><ul><li>increase from 8.1%  to  23.8% </li></ul><ul><...
Ampullary or periampullary adenocarcinoma: an intestinal or bilio-pancreatic tumor? <ul><li>Incidence:  0.3/100.000 2.100 ...
 
Palliative treatment <ul><li>No randomized trial comparing chemotherapy with BSC or 5FU  with combination chemotherapy </l...
Rare digestive cancers <ul><ul><li>Small bowell carcinoma </li></ul></ul><ul><ul><li>Anal carcinoma </li></ul></ul><ul><ul...
Anal cancer <ul><li>Incidence  1.1/100.000,  8.992, increasing </li></ul><ul><ul><li>Squamous cell 0.61/100.000  4.982 </l...
Diagnosis and staging <ul><li>Biopsy, anoscopy, pelvic CT scan, MRI (locoregional disease); </li></ul><ul><li>PET/CT scan ...
Surgery <ul><li>APR local failure 50% </li></ul><ul><li>  5yr survival 50% </li></ul><ul><li>Local excision for Tis or T1 ...
Surgery or RT or RT/CT? <ul><li>RT= surgery </li></ul><ul><ul><li>Salmon 1984; Papillon 1987 </li></ul></ul><ul><li>5FU/RT...
Surgery or RT or RT/CT? <ul><li>5FU-CDDP/RT=5FU-MitC/RT </li></ul><ul><ul><li>Ajani 2008; James 2009 </li></ul></ul><ul><l...
Anal cancer: treatment for >T2 or N+ in 2011 <ul><li>5FU-MitC/RT remains the standard </li></ul><ul><li>Surgery as salvage...
Response evaluation:  how should these patients be managed? <ul><li>Clinical response should be assessed at 6-8 weeks, by ...
Follow up: how should these patients be managed? <ul><li>Patients in complete remission after 8 weeks </li></ul><ul><li>Ev...
Rare digestive cancers <ul><ul><li>Small bowell carcinoma </li></ul></ul><ul><ul><li>Anal carcinoma </li></ul></ul><ul><ul...
Biliary tract cancers:  a spectrum disease <ul><li>2/3 of patients with irresectable disease at the time of diagnosis </li...
Gallblader and cholangiocarcinoma: two diseases
Biliary tract cancer: which problems? <ul><li>Adjuvant therapy </li></ul><ul><li>Neoadjuvant therapy </li></ul><ul><li>The...
Resectability <ul><li>Gallbladder 35% </li></ul><ul><li>Biliary ducts 30% </li></ul><ul><li>Ampullomas 80% </li></ul>
Gallblader Adjuvant 5FU or GEM-based chemotherapy and radiation may be recommended as postoperative therapy except for pat...
Gallblader carcinoma:  adjuvant radiation therapy <ul><li>SEER 1992-2002: 3.187 cases  </li></ul><ul><li>Adjuvant radiatio...
 
Extrahepatic bile duct cancer <ul><li>Chemotherapy </li></ul><ul><ul><li>No advantage (Takada, 2002) </li></ul></ul><ul><l...
Adjuvant therapy: conclusions <ul><li>5FU or GEM-based chemotherapy and radiation are commonly used in US because of the h...
Biliary tract cancer <ul><li>Adjuvant therapy </li></ul><ul><li>Palliative treatment </li></ul>
Is it useful to perform a chemotherapy? Treatment patients mOS p   . BSC 19 2.5 mo 5FU-LV o ELF 18 6.5 mo ns Improvement o...
Advanced biliary tract cancer: old drugs not active   <ul><li>Drug patients OR </li></ul><ul><li>Metil-CCNU  17 6%  </li><...
Advanced biliary tract cancer:  new drugs, not active Agents patients RO TTP OS Capecitabine 63 14% 4 9 Docetaxel 83 14% N...
Combination chemotherapy:  Phase II studies <ul><li>Treatment pts OR mPFS mOS </li></ul><ul><li>GEM+platinum 156 17-55% 3-...
<ul><li>Treatment n° RR mPFS mOS 1yOS </li></ul><ul><li>CDDP+FUFA 29 19% 3.3 8 30% </li></ul><ul><li>HD-FU 29 7% 3.3 5 25%...
A  pooled analysis of clinical trials in advanced biliary tract cancers. <ul><li>104 trials (4 randomised!)  85% 2000-2006...
A  pooled analysis of clinical trials in biliary tract cancers. <ul><li>RR gallbladder>cholangiocarcinoma </li></ul><ul><l...
 
 
<ul><li>Treatment n° RR mPFS mOS </li></ul><ul><li>Sorafenib </li></ul><ul><li>El-Khoueiry, ASCO 07   36 6% 2.0 6.0 </li><...
Treatment n° RR mPFS mOS Cetuximab+GEMOX Gruenberger, ASCO 08   22 58% nd nd Bevacizumab+GEMOX Clark, ASCO 07   26 29% nd ...
<ul><li>What we should remember </li></ul><ul><li>Gallblader and cholangiocarcinoma are different </li></ul><ul><ul><li>Ad...
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Rare Solid Cancers: An Introduction - Slide 15 - S. Cascinu - Rare digestive cancers

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Rare Solid Cancers: An Introduction - Slide 15 - S. Cascinu - Rare digestive cancers

  1. 1. Stefano Cascinu Clinica di Oncologia Medica Ancona, Italy Rare digestive cancers
  2. 2. Cancers by numbers (IARC) <ul><li>Lung 1.2 million </li></ul><ul><li>Breast 1 million </li></ul><ul><li>Colorectal 940.000 </li></ul><ul><li>Stomach 870.000 </li></ul><ul><li>Liver 560.000 </li></ul><ul><li>Cervical 470.000 </li></ul><ul><li>Esophagus 410.000 </li></ul><ul><li>Pancreas 216.000 </li></ul>
  3. 3. Rare cancers <ul><li>Tumors with an incidence around or lower than 6/100.000/year </li></ul>Which digestive cancers can be defined rare?
  4. 4. GI Cancers Incidence rate/100.00/year N° of patients/year Oesophagus 7.49 60.723 Squamous 3.39 27.525 Adenocarcinoma 2.83 22.986 Stomach 18.66 151.346 Adenocarcinoma 15.27 123.800 Squamous 0.13 1.049 Small bowel 0.73 5.882 Colon 42.78 346.910 Squamous 0.02 170 Anal 1.1 8.992 Pancreas 11.82 95.836 Adenocarcinoma 7.58 61.459 Squamous 0.03 211 Biliary tract Intrahepatic 0.83 6.761 Gallbladder and extrahepatic 2.64 21.403
  5. 5. Rare digestive cancers <ul><li>Uncommon histotypes in frequent tumors </li></ul><ul><ul><li>Squamous cell cancer stomach 1.049 </li></ul></ul><ul><ul><li>Squamous cell cancer colon 170 </li></ul></ul><ul><ul><li>Squamous cell cancer pancreas 211 </li></ul></ul><ul><li>Rare digestive cancers </li></ul><ul><ul><li>Small bowell adenocarcinoma 5.882 </li></ul></ul><ul><ul><li>Anal carcinoma 8.992 </li></ul></ul><ul><ul><li>Biliary tract carcinoma 28.164 </li></ul></ul>
  6. 6. Rare digestive cancers <ul><ul><li>Small bowel carcinoma </li></ul></ul><ul><ul><li>Anal carcinoma </li></ul></ul><ul><ul><li>Biliary tract carcinoma </li></ul></ul>
  7. 7. Small bowel adenocarcinoma <ul><li>Incidence: 0.73/100.000 </li></ul><ul><li>increasing </li></ul><ul><li>US 5640 </li></ul><ul><li>EU 5882 </li></ul><ul><li>44% neuroendocrine </li></ul><ul><li>33% adenocarcinoma </li></ul><ul><li>15% lymphoma </li></ul><ul><li>7% GIST </li></ul><ul><li>Adenocarcinoma </li></ul><ul><li>56% duodenum </li></ul><ul><li>31% jejunum </li></ul><ul><li>13% ileum </li></ul><ul><li>On presentation: </li></ul><ul><li>30% metastatic </li></ul><ul><li>25% locally advanced </li></ul>
  8. 8. Small bowel adenocarcinoma <ul><li>Risk factors: </li></ul><ul><li>Genetically predisposing conditions: </li></ul><ul><li>Peutz Jegher’s disease </li></ul><ul><li>Familial adenomatous polyposis </li></ul><ul><li>HNPCC </li></ul><ul><li>Inflammatory diseases: </li></ul><ul><li>Chron’s disease </li></ul><ul><li>Celiac sprue </li></ul><ul><li>Diet (high in red meat) </li></ul><ul><li>Alchohol, Tobacco usage </li></ul>Molecular alterations K-ras mutations MSI-H (20%) C-erb-B2
  9. 9. Small bowel adenocarcinoma <ul><li>Symptoms: </li></ul><ul><li>Epigastric pain </li></ul><ul><li>Gastric outlet obstruction </li></ul><ul><li>Duodenum: </li></ul><ul><li>Symptoms at an earlier stage </li></ul><ul><li>Jejunum/ileum: </li></ul><ul><li>At a later stage </li></ul><ul><li>Prognostic factors: </li></ul><ul><li>Stage </li></ul><ul><li>Grade </li></ul><ul><li>Surgical margins </li></ul><ul><li>Chron’s disease </li></ul><ul><li>5yr survival: 20-30% </li></ul><ul><li>Duodenum 50% </li></ul>
  10. 10. Small bowel adenocarcinoma <ul><li>Lymphadenectomy </li></ul><ul><ul><li>Stage II </li></ul></ul><ul><li>N° exam. Lymph 5yr surv </li></ul><ul><li>1-8 66% </li></ul><ul><li>9-12 80% </li></ul><ul><li>>12 88% </li></ul><ul><ul><li>Stage III </li></ul></ul><ul><li>Positive </li></ul><ul><li>lymph nodes 5yr survival </li></ul><ul><li>0-2 58% </li></ul><ul><li>>2 37% </li></ul><ul><li>Surgery </li></ul><ul><li>is the mainstay of treatment </li></ul>
  11. 11. Small bowel adenocarcinoma <ul><li>Adjuvant treatment: </li></ul><ul><li>No randomized trials </li></ul><ul><li>2 large retrospective studies </li></ul>
  12. 12. Adjuvant therapy <ul><li>From 1981 --------------- to 2005 </li></ul><ul><li>increase from 8.1% to 23.8% </li></ul><ul><li>Which therapy? </li></ul><ul><ul><li>5FU based therapy 90% </li></ul></ul><ul><ul><li>Folfox 10% </li></ul></ul>
  13. 13. Ampullary or periampullary adenocarcinoma: an intestinal or bilio-pancreatic tumor? <ul><li>Incidence: 0.3/100.000 2.100 </li></ul><ul><li>Two tumors: </li></ul><ul><ul><li>5yr survival </li></ul></ul><ul><ul><li>Intestinal type 50% </li></ul></ul><ul><ul><li>Pancreatic cancer 20% </li></ul></ul>
  14. 15. Palliative treatment <ul><li>No randomized trial comparing chemotherapy with BSC or 5FU with combination chemotherapy </li></ul><ul><li>Only retrospective analyses: </li></ul><ul><ul><li>CDDP/5FU better response rate: 41% vs16% </li></ul></ul><ul><ul><li> larger PFS: 8.7 vs 3.9 months </li></ul></ul><ul><ul><li>trend to a better survival </li></ul></ul><ul><ul><li>CDDP/5FU is a reasonable choice for young patients with good PS; ampullary carcinoma less responsive to chemotherapy </li></ul></ul>
  15. 16. Rare digestive cancers <ul><ul><li>Small bowell carcinoma </li></ul></ul><ul><ul><li>Anal carcinoma </li></ul></ul><ul><ul><li>Biliary tract carcinoma </li></ul></ul>
  16. 17. Anal cancer <ul><li>Incidence 1.1/100.000, 8.992, increasing </li></ul><ul><ul><li>Squamous cell 0.61/100.000 4.982 </li></ul></ul><ul><ul><li>Adenocarcinoma 0.26/100.000 2.098 5-yr survival 62% (1980) </li></ul></ul><ul><ul><li>Etiology and risk factors: </li></ul></ul><ul><ul><li>HIV-positive </li></ul></ul><ul><ul><li>HPV-positive </li></ul></ul><ul><ul><li>Immunosoppressive post-organ transplant </li></ul></ul><ul><ul><li>No role for chronic inflammation (hemorroids, abscesses, fistula,..) </li></ul></ul>
  17. 18. Diagnosis and staging <ul><li>Biopsy, anoscopy, pelvic CT scan, MRI (locoregional disease); </li></ul><ul><li>PET/CT scan to detect lymphnodes </li></ul><ul><li>Survival: </li></ul><ul><ul><li>T1-2 50% </li></ul></ul><ul><ul><li>N+ 20% </li></ul></ul><ul><li>Size a relevant prognostic factor: </li></ul><ul><ul><li><5 cm </li></ul></ul><ul><ul><li>>5 cm relevant prognostic factor </li></ul></ul>
  18. 19. Surgery <ul><li>APR local failure 50% </li></ul><ul><li> 5yr survival 50% </li></ul><ul><li>Local excision for Tis or T1 N0 lesions of the anal margin in which the sphincter can be spared </li></ul>
  19. 20. Surgery or RT or RT/CT? <ul><li>RT= surgery </li></ul><ul><ul><li>Salmon 1984; Papillon 1987 </li></ul></ul><ul><li>5FU/RT>RT </li></ul><ul><ul><li>Cummings 1991; UK-group 1996; Bartelink 1997; </li></ul></ul><ul><li>5FU-MitC/RT>5FU/RT </li></ul><ul><ul><li>Flam 1996 </li></ul></ul>
  20. 21. Surgery or RT or RT/CT? <ul><li>5FU-CDDP/RT=5FU-MitC/RT </li></ul><ul><ul><li>Ajani 2008; James 2009 </li></ul></ul><ul><li>5FU/CDDP/RT+5FU/CDDP maintenance, no advantage </li></ul><ul><ul><li>James 2009 </li></ul></ul><ul><li>Induction chemotherapy, no advantage </li></ul><ul><ul><li>Conroy 2009 </li></ul></ul>
  21. 22. Anal cancer: treatment for >T2 or N+ in 2011 <ul><li>5FU-MitC/RT remains the standard </li></ul><ul><li>Surgery as salvage therapy </li></ul><ul><li>Doses radiation should be no lower than 45-50Gy; inguinal nodes should be included in the radiation field </li></ul><ul><li>Long overall treatment duration has a detrimental effect on local failure or colostomy rate (53days) </li></ul><ul><li>Smoking increases treatment related toxicities and may reduce efficacy </li></ul>
  22. 23. Response evaluation: how should these patients be managed? <ul><li>Clinical response should be assessed at 6-8 weeks, by this time 60-85% of patients achieve CR </li></ul><ul><li>Good partial regression: close follow up; CR may occur after 3-6 months so that salvage surgery may be deferred </li></ul><ul><li>Before salvage surgery residual tumor must be confirmed histologically </li></ul>
  23. 24. Follow up: how should these patients be managed? <ul><li>Patients in complete remission after 8 weeks </li></ul><ul><li>Evaluation every 3-6 months for 2 years </li></ul><ul><li>Evaluation every 6-12 months until 5 years </li></ul><ul><li>Clinical examination (DRE, inguinal lymphnodes palpation) </li></ul><ul><li>CT scan is controversial </li></ul>
  24. 25. Rare digestive cancers <ul><ul><li>Small bowell carcinoma </li></ul></ul><ul><ul><li>Anal carcinoma </li></ul></ul><ul><ul><li>Biliary tract carcinoma </li></ul></ul>
  25. 26. Biliary tract cancers: a spectrum disease <ul><li>2/3 of patients with irresectable disease at the time of diagnosis </li></ul><ul><li>Five-year survival in radically resected patients </li></ul><ul><ul><li>Intrahepatic 30-40% </li></ul></ul><ul><ul><li>Distal cholangiocarcinoma 20-30% </li></ul></ul><ul><ul><li>Perihilar cholangiocarcinoma 9-18% </li></ul></ul><ul><ul><li>Gallbladder 14-18% </li></ul></ul>
  26. 27. Gallblader and cholangiocarcinoma: two diseases
  27. 28. Biliary tract cancer: which problems? <ul><li>Adjuvant therapy </li></ul><ul><li>Neoadjuvant therapy </li></ul><ul><li>The treatment of the advanced disease </li></ul>
  28. 29. Resectability <ul><li>Gallbladder 35% </li></ul><ul><li>Biliary ducts 30% </li></ul><ul><li>Ampullomas 80% </li></ul>
  29. 30. Gallblader Adjuvant 5FU or GEM-based chemotherapy and radiation may be recommended as postoperative therapy except for patients T1N0 (Kresl Int J Radiat Oncol Biol Phys 2002: 21 patients 5-y survival 64 vs 33%). Another small trial seemed to confirme these findings showing a 5-y survival of 26% vs 14%. (Takada Cancer 2002)
  30. 31. Gallblader carcinoma: adjuvant radiation therapy <ul><li>SEER 1992-2002: 3.187 cases </li></ul><ul><li>Adjuvant radiation 17% </li></ul><ul><li>Median survival: radiation vs not 14 vs 8 m </li></ul><ul><li>Advantage present only in patients with regional spread and tumors infiltrating the liver </li></ul><ul><li>Mojica, J Surg Oncol 2007 </li></ul>
  31. 33. Extrahepatic bile duct cancer <ul><li>Chemotherapy </li></ul><ul><ul><li>No advantage (Takada, 2002) </li></ul></ul><ul><li>Chemoradiotherapy </li></ul><ul><ul><li>Effects on R1 or N+ tumors (Borghero, 2008) </li></ul></ul><ul><li>Radiotherapy </li></ul><ul><ul><li>9.3% falls in risk of death ( SEER) </li></ul></ul>
  32. 34. Adjuvant therapy: conclusions <ul><li>5FU or GEM-based chemotherapy and radiation are commonly used in US because of the high incidence of local and distant relapses. </li></ul><ul><li>There are no randomised trials able to show any advantage for this approach. </li></ul>
  33. 35. Biliary tract cancer <ul><li>Adjuvant therapy </li></ul><ul><li>Palliative treatment </li></ul>
  34. 36. Is it useful to perform a chemotherapy? Treatment patients mOS p . BSC 19 2.5 mo 5FU-LV o ELF 18 6.5 mo ns Improvement of quality of life including pancreatic cancer Glimelius Ann Oncol 1996
  35. 37. Advanced biliary tract cancer: old drugs not active <ul><li>Drug patients OR </li></ul><ul><li>Metil-CCNU 17 6% </li></ul><ul><li>CISPLATIN 13 8% </li></ul><ul><li>AMSACRINE 23 9% </li></ul><ul><li>5-FU 70 14% </li></ul><ul><li>STREPTOZOTOCIN 14 17% </li></ul><ul><li>MITOMYCIN-C 49 20% </li></ul>
  36. 38. Advanced biliary tract cancer: new drugs, not active Agents patients RO TTP OS Capecitabine 63 14% 4 9 Docetaxel 83 14% Na 8 CPT-11 61 8 Na 10 GEM 115 8-22% 3.5 10
  37. 39. Combination chemotherapy: Phase II studies <ul><li>Treatment pts OR mPFS mOS </li></ul><ul><li>GEM+platinum 156 17-55% 3-10 5-15 </li></ul><ul><li>GEM+FU/CAPE 160 10-36% 4-7 5-16 </li></ul><ul><li>CDDP+FU/CAPE 103 21-40% 4-7 9-12 </li></ul><ul><li>GEM+Docetaxel 43 9% 5 11 </li></ul><ul><li>ECF/ECX 67 10-40% 2-5 5-11 </li></ul><ul><li>FUFIRI 30 10% 4 7 </li></ul><ul><li>FOLFOX 16 19% 4 10 </li></ul><ul><li>PEFG 37 43% 7 12 </li></ul><ul><li>Pemetrexed+GEM 58 nd 3.8 6.3 </li></ul>
  38. 40. <ul><li>Treatment n° RR mPFS mOS 1yOS </li></ul><ul><li>CDDP+FUFA 29 19% 3.3 8 30% </li></ul><ul><li>HD-FU 29 7% 3.3 5 25% </li></ul><ul><li>Ducreux M, Eur J Cancer 2005 </li></ul><ul><li>GEM 44 15% 5.5 </li></ul><ul><li>CDDP+GEM 42 24% 8.0 </li></ul><ul><li>Valle JV, ASCO GI 2003 </li></ul><ul><li>S-1 16 12% nd 9.5 </li></ul><ul><li>S-1 + CDDP 10 40% nd 16 </li></ul><ul><li>Uchida K, ASCO 2005 </li></ul>Phase II randomised trials: platinum based regimens
  39. 41. A pooled analysis of clinical trials in advanced biliary tract cancers. <ul><li>104 trials (4 randomised!) 85% 2000-2006 </li></ul><ul><li>2810 patients (about 25-27 patients/trial) </li></ul><ul><li>OR (634/2810) 23% </li></ul><ul><li> mPFS 4.1 mo mOS 8.2 mo </li></ul><ul><li>Eckel F, Br J Cancer 2007 </li></ul>
  40. 42. A pooled analysis of clinical trials in biliary tract cancers. <ul><li>RR gallbladder>cholangiocarcinoma </li></ul><ul><li> (34 vs 20%) </li></ul><ul><li>OS gallbladder<cholangiocarcinoma </li></ul><ul><li> (7.2 vs 9.3) </li></ul><ul><li>2drugs>1 drug </li></ul><ul><li> (RR: 28 vs 15%; PFS: 4.4 vs 3.4 mo; OS: 9.3 vs 7.5 mo) </li></ul><ul><li>3drugs = 2drugs </li></ul><ul><li>CDDP+GEM > CDDP+FU (17 vs 9%); </li></ul><ul><li>Eckel F, Br J Cancer 2007 </li></ul>
  41. 45. <ul><li>Treatment n° RR mPFS mOS </li></ul><ul><li>Sorafenib </li></ul><ul><li>El-Khoueiry, ASCO 07 36 6% 2.0 6.0 </li></ul><ul><li>Dealis, ASCO 08 (2l) 46 4% 2.5 6.0 </li></ul><ul><li>Erlotinib </li></ul><ul><li>Philip, J Clin Oncol 06 42 8% 2.6 nd </li></ul><ul><li>Lapatinib </li></ul><ul><li>Ramanathan, ASCO 06 19 0% 1.8 nd </li></ul><ul><li>Erlotinib+Bevacizumab </li></ul><ul><li>Holen, ASCO 08 34 20% nd nd </li></ul>Biological agents
  42. 46. Treatment n° RR mPFS mOS Cetuximab+GEMOX Gruenberger, ASCO 08 22 58% nd nd Bevacizumab+GEMOX Clark, ASCO 07 26 29% nd nd Biological agents and chemotherapy
  43. 47. <ul><li>What we should remember </li></ul><ul><li>Gallblader and cholangiocarcinoma are different </li></ul><ul><ul><li>Adjuvant 5FU/radiation therapy may be considered for gallblader spread regionally and/or infiltrating the liver (level IV/V) </li></ul></ul><ul><ul><li>What we know </li></ul></ul><ul><li>GEM, 5FU, capecitabine, CDDP, oxaliplatin: the most active drugs </li></ul><ul><li>A 2-drug regimen improves outcome (CDPP and GEM) in the metastatic setting (level II) </li></ul><ul><li> What we can hope </li></ul><ul><li>New molecular targets (??) </li></ul><ul><li>Cooperative trials </li></ul>Biliary tract cancers:

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