- Email: [email protected]
FRI-01 The four melanomas
S240
Abstracts of the 3rd ITLT Essen 2013 / Digestive and Liver Disease 45S (2013) S233–S260
patients’ performance status, tumor load, and tumor vascularization could be identified. Nevertheless, even if the current available data on TACE and RE in CC are quite encouraging substantial comparative studies are still missing defining the role of these techniques within the therapeutic concept for CC.
THU-16
Systemic therapies for cholangiocarcinoma: State of the art 2013 A.X. Zhu ∗ Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA Biliary tract cancers (BTC), which encompass intra- and extra-hepatic cholangiocarcinomas as well as gallbladder carcinomas, are a genetically diverse collection of cancers. Most patients with BTC will present with unresectable or metastatic disease. Although the standard systemic combination chemotherapy approaches are emerging, the prognosis remains poor with a median survival of less than one year. Development of molecularly targeted therapies in advanced BTC remains challenging. Recent early stage clinical trials with targeted therapies appear promising, though the relationships between subsets of patients with positive responses to therapy and tumor genetics remain unexplored. The author will discuss the relevant molecular pathogenesis, recent and ongoing clinical trials with targeted agents, and the key issues in clinical trial design in BTC.
THU-17
Endoscopic treatment options for cholangiocarcinomas K. Mönkemüller ∗ , J. Ramesh, C.M. Wilcox Basil Hirschowitz Center for Endoscopic Excellence, Division of Gastroenterology, Hepatology, University of Alabama at Birmingham, Alabama, USA Cholangiocellular carcinomas (CCC) account for approximately 2–3% of all cancer diagnoses with an incidence of about 2.1/100,000. About 60% of cases occur in patients over the age of 65 years, with a similar distribution between women and men. CCCs are heterogeneous groups of tumors of the bilary tract. In 1965 Gerald Klatskin described the distinct characteristics of hilar CCC arising at the hepatic bifurcation. Since then Klatksin tumor has been synonymous with CCC. However, there are several types of CCCs based on their anatomic location, and Klatskin tumors comprise only 10% of CCCs. The most common type is the peri-hilar variant (pCCC) (50%), followed by the distal type (dCCC) (40%) and intrahepatic (iCCC) (10%). Klatskin tumor is a type of pCCC. Because some CCCs arise from hepatic progenitor cells, some authors prefer to call these tumors cholangiocarcinoma (CCA). Therapy for CCC is based on the type, location and size of tumor. Whereas small dCCC and hCCC can and should be treated using radical surgical resection, mass tumors located inside the liver or large or metastatic extrahepatic tumors can only be treated with chemotherapy using a combination of gemcitabine and cisplatin. If the lesions are causing bilary luminal obstruction with resulting jaundice, endoscopic therapy using stents (plastic or metal) is a definite option. Plastic stents vary in caliber, length, material, and configuration depending on their design and intended application. The preferred plastic stents for biliary decompression in pCCC and dCCC are “large” diameter (i.e. 10 or 11.5 Fr) polyethylene or Teflon stents. The general rule is to apply the largest possible stent that can traverse the stricture and, if possible, place several stents. The major disadvantage of plastic stents is their high rate of occlusion (about 75% within 90 days of placement). Thus, if the patient is expected to survive longer than 3 months the use of self-expanding metal stents (SEMS) is indicated. The main advantage of SEMS is their larger diameter (6, 8 and 10 mm) and thus longer patency rate. Most SEMS for malignant biliary strictures are made of Nitinol, a superelastic nickel-titanium alloy with thermal shape memory, a property of reassuming a predetermined shape through heating. As these stents are placed through the endoscope fluoroscopy is always needed. Ideally, SEMS should be well visualized during fluoroscopic placement. Thus, the
radiopacity of some metal stents is enhanced by incorporating other metals into the body or the ends of the stent. Membrane-covered SEMS offer the potential advantage of preventing tissue ingrowth. Whereas the use of SEMS is clearly indicated for distal and hilar strictures, the use of double metal stenting into both intrahepatics is less well studied. Nonetheless, achieving drainage of both intrahepatic ducts is associated with less cholangitis, jaundice and morbidity. In recent years, intrabilary photodynamic therapy (PDT) delivered through the duodenscope has emerged as a good palliative measure in some pCCC and dCCC. Indeed, some data have studies that survival may be improved in patients undergoing PDT.
Friday, 19 April 2013 FRI-01
The four melanomas U. Keilholz ∗ Charité Comprehensive Cancer Center, Berlin, Germany Until several years ago, metastatic melanoma has been a disease without a treatment option with proven impact on survival. DTIC was the reference treatment, based on moderate efficacy and low toxicity. Interleukin-2 and vaccines were immunologic treatment alternatives, and first-line experimental treatment was explicitely accepted. For metastatic mucosal and uveal melanoma, no reference treatment was defined. During the past three years, the situation has profoundly changed, based on molecular understanding of four different melanoma entities and development of novel therapies. Cutaneous melanoma has been devided into solar and non-solar melanoma. Solar melanoma predominantly arises on skin with intermittent UV exposure and frequently harbors activating braf or nras mutations. Non-solar cutaneous melanomas develop on skin areas rarely exposed to UV and typically show disruptive mutations of p53. In addition, a fraction of melanomas arising in areas of the skin with chronic UV exposure and from mucous membranes displays activating mutations of ckit, and, lastly, uveal melanomas are characterized by activating mutations of GNA11 and GNAQ. These discoveries have prompted rigorous development of targeted drugs and several compounds have proven to be highly active in inducing remissions and improving survival. These specifically include agents targeting mutated braf and also mek, and to a lesser extent ckit. Combination treatment studies are under way. For uveal melanomas, targeted agents still have to be tested. In addition to the molecularly targeted agents, immune checkpoint regulators, such as antibodies directed against CTLA4 and PD1/PDL1 have been developed and initiated a solid and efficient new era of immunotherapy of metastatic melanoma. These novel treatment modalities have now to be tested in combinations and in sequence in order to further improve quality of life and survival of metastatic melanoma patients. The indications of liver-directed therapies and all other locoregional treatment approaches, which remain effective and important, have to be reconsidered.
FRI-02
Liver metastases from melanoma R. Adam ∗ ,1 , L. Chiche 2 1 AP-HP Hopital Paul Brousse, and Université Paris-Sud, UMR-S 776, Villejuif, France; 2 Hopitaux Universitaires de Bordeaux, Service de Chirurgie Digestive, Maison du Haut Lévèque, Pessac, France
Liver metastases are a frequent mode of recurrence of choroid melanoma (60–90% of cases) and much less frequently of cutaneous melanoma (5–15% of cases). The outcome of metastatic melanoma is poor with median survival rates of 6–9 months and a 5-year survival inferior to 10%. The clinical presentation relies on the discovery of LM in the follow up of a known melanoma or of a multinodular hepatomegaly from an undiagnosed melanoma. Despite the improvements of imaging, there is frequently an underestimation of the lesions. The role of hepatic surgery is still questioned and the number of reported cases
Abstracts of the 3rd ITLT Essen 2013 / Digestive and Liver Disease 45S (2013) S233–S260
patients’ performance status, tumor load, and tumor vascularization could be identified. Nevertheless, even if the current available data on TACE and RE in CC are quite encouraging substantial comparative studies are still missing defining the role of these techniques within the therapeutic concept for CC.
THU-16
Systemic therapies for cholangiocarcinoma: State of the art 2013 A.X. Zhu ∗ Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA Biliary tract cancers (BTC), which encompass intra- and extra-hepatic cholangiocarcinomas as well as gallbladder carcinomas, are a genetically diverse collection of cancers. Most patients with BTC will present with unresectable or metastatic disease. Although the standard systemic combination chemotherapy approaches are emerging, the prognosis remains poor with a median survival of less than one year. Development of molecularly targeted therapies in advanced BTC remains challenging. Recent early stage clinical trials with targeted therapies appear promising, though the relationships between subsets of patients with positive responses to therapy and tumor genetics remain unexplored. The author will discuss the relevant molecular pathogenesis, recent and ongoing clinical trials with targeted agents, and the key issues in clinical trial design in BTC.
THU-17
Endoscopic treatment options for cholangiocarcinomas K. Mönkemüller ∗ , J. Ramesh, C.M. Wilcox Basil Hirschowitz Center for Endoscopic Excellence, Division of Gastroenterology, Hepatology, University of Alabama at Birmingham, Alabama, USA Cholangiocellular carcinomas (CCC) account for approximately 2–3% of all cancer diagnoses with an incidence of about 2.1/100,000. About 60% of cases occur in patients over the age of 65 years, with a similar distribution between women and men. CCCs are heterogeneous groups of tumors of the bilary tract. In 1965 Gerald Klatskin described the distinct characteristics of hilar CCC arising at the hepatic bifurcation. Since then Klatksin tumor has been synonymous with CCC. However, there are several types of CCCs based on their anatomic location, and Klatskin tumors comprise only 10% of CCCs. The most common type is the peri-hilar variant (pCCC) (50%), followed by the distal type (dCCC) (40%) and intrahepatic (iCCC) (10%). Klatskin tumor is a type of pCCC. Because some CCCs arise from hepatic progenitor cells, some authors prefer to call these tumors cholangiocarcinoma (CCA). Therapy for CCC is based on the type, location and size of tumor. Whereas small dCCC and hCCC can and should be treated using radical surgical resection, mass tumors located inside the liver or large or metastatic extrahepatic tumors can only be treated with chemotherapy using a combination of gemcitabine and cisplatin. If the lesions are causing bilary luminal obstruction with resulting jaundice, endoscopic therapy using stents (plastic or metal) is a definite option. Plastic stents vary in caliber, length, material, and configuration depending on their design and intended application. The preferred plastic stents for biliary decompression in pCCC and dCCC are “large” diameter (i.e. 10 or 11.5 Fr) polyethylene or Teflon stents. The general rule is to apply the largest possible stent that can traverse the stricture and, if possible, place several stents. The major disadvantage of plastic stents is their high rate of occlusion (about 75% within 90 days of placement). Thus, if the patient is expected to survive longer than 3 months the use of self-expanding metal stents (SEMS) is indicated. The main advantage of SEMS is their larger diameter (6, 8 and 10 mm) and thus longer patency rate. Most SEMS for malignant biliary strictures are made of Nitinol, a superelastic nickel-titanium alloy with thermal shape memory, a property of reassuming a predetermined shape through heating. As these stents are placed through the endoscope fluoroscopy is always needed. Ideally, SEMS should be well visualized during fluoroscopic placement. Thus, the
radiopacity of some metal stents is enhanced by incorporating other metals into the body or the ends of the stent. Membrane-covered SEMS offer the potential advantage of preventing tissue ingrowth. Whereas the use of SEMS is clearly indicated for distal and hilar strictures, the use of double metal stenting into both intrahepatics is less well studied. Nonetheless, achieving drainage of both intrahepatic ducts is associated with less cholangitis, jaundice and morbidity. In recent years, intrabilary photodynamic therapy (PDT) delivered through the duodenscope has emerged as a good palliative measure in some pCCC and dCCC. Indeed, some data have studies that survival may be improved in patients undergoing PDT.
Friday, 19 April 2013 FRI-01
The four melanomas U. Keilholz ∗ Charité Comprehensive Cancer Center, Berlin, Germany Until several years ago, metastatic melanoma has been a disease without a treatment option with proven impact on survival. DTIC was the reference treatment, based on moderate efficacy and low toxicity. Interleukin-2 and vaccines were immunologic treatment alternatives, and first-line experimental treatment was explicitely accepted. For metastatic mucosal and uveal melanoma, no reference treatment was defined. During the past three years, the situation has profoundly changed, based on molecular understanding of four different melanoma entities and development of novel therapies. Cutaneous melanoma has been devided into solar and non-solar melanoma. Solar melanoma predominantly arises on skin with intermittent UV exposure and frequently harbors activating braf or nras mutations. Non-solar cutaneous melanomas develop on skin areas rarely exposed to UV and typically show disruptive mutations of p53. In addition, a fraction of melanomas arising in areas of the skin with chronic UV exposure and from mucous membranes displays activating mutations of ckit, and, lastly, uveal melanomas are characterized by activating mutations of GNA11 and GNAQ. These discoveries have prompted rigorous development of targeted drugs and several compounds have proven to be highly active in inducing remissions and improving survival. These specifically include agents targeting mutated braf and also mek, and to a lesser extent ckit. Combination treatment studies are under way. For uveal melanomas, targeted agents still have to be tested. In addition to the molecularly targeted agents, immune checkpoint regulators, such as antibodies directed against CTLA4 and PD1/PDL1 have been developed and initiated a solid and efficient new era of immunotherapy of metastatic melanoma. These novel treatment modalities have now to be tested in combinations and in sequence in order to further improve quality of life and survival of metastatic melanoma patients. The indications of liver-directed therapies and all other locoregional treatment approaches, which remain effective and important, have to be reconsidered.
FRI-02
Liver metastases from melanoma R. Adam ∗ ,1 , L. Chiche 2 1 AP-HP Hopital Paul Brousse, and Université Paris-Sud, UMR-S 776, Villejuif, France; 2 Hopitaux Universitaires de Bordeaux, Service de Chirurgie Digestive, Maison du Haut Lévèque, Pessac, France
Liver metastases are a frequent mode of recurrence of choroid melanoma (60–90% of cases) and much less frequently of cutaneous melanoma (5–15% of cases). The outcome of metastatic melanoma is poor with median survival rates of 6–9 months and a 5-year survival inferior to 10%. The clinical presentation relies on the discovery of LM in the follow up of a known melanoma or of a multinodular hepatomegaly from an undiagnosed melanoma. Despite the improvements of imaging, there is frequently an underestimation of the lesions. The role of hepatic surgery is still questioned and the number of reported cases