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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EThis article discusses the current state of pancreatic cancer (PC) research and treatment. Specific topics include hereditary subtypes, the treatment of locally advanced pancreatic cancer, treatment options for metastatic PC, as well as new treatment agents.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EGastrointestinal Cancers\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EGastrointestinal Cancers\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003ESeveral experts gathered to review the current state of pancreatic cancer (PC) research and treatment. Margaret Tempero, MD, University of California, San Francisco, San Francisco, California, USA, gave an overview of PC and hereditary subtypes. PC is a difficult disease to treat, because 80% of patients have advanced unresectable disease at diagnosis and 80% of patients who undergo surgical resection relapse. The cure rate is approximately 5% to 6%, and patients with metastases who are not treated live for a median of only 3 months. \u201cOf all the epithelial malignancies, this is probably the most aggressive,\u201d noted Dr. Tempero. Whereas deaths due to cancers such as lung, breast, and colorectal have been falling, deaths from PC are increasing. The aging population combined with inadequate treatments and a lack of early detection methods are expected to result in further increases in PC in the next 2 decades. Should current trends continue, PC could become the second leading cause of cancer death by 2030 [Rahib L et al. \u003Cem\u003EJ Can Res\u003C\/em\u003E 2014], exceeding breast and colorectal cancer.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003ERisk factors for developing PC include age, cigarette smoking, heavy alcohol consumption (\u0026gt; 9 drinks\/day), diabetes for \u0026gt; 10 years, higher body mass index and waist-to-hip ratios, and chronic pancreatitis. Five percent to 10% of PC cases are related to hereditary PC, of which there are 2 types. The first type is composed of families with recognized genetic syndromes with a germline mutation linked to an increased risk of PC (\u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E). The second type is familial pancreatic cancer, which is defined as families in which 2 or more members have had PC without a recognized mutation. Benign neoplasms are often detected in familial screening programs, and when cancer is diagnosed, it is not at an early stage. \u201cThis is very troubling right now for the entire community. Understanding which of these premalignant lesions are at highest risk is becoming a higher and higher priority,\u201d noted Dr. Tempero.\u003C\/p\u003E\u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/14855\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/14855\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/14855\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-4\u0022 class=\u0022first-child\u0022\u003ESyndromes Associated With Pancreatic Adenocarcinoma\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-6\u0022\u003EChristophe Louvet, MD, Institut Mutualiste Montsouris, Paris, France, gave an overview of the treatment of locally advanced pancreatic cancer (LAPC). The role of chemoradiation therapy (CRT) in the treatment of LAPC is currently debated because conflicting results have been obtained in clinical trials. CRT combined with chemotherapy remains a promising strategy, and its potential has been demonstrated in several studies. In the LAP-07 study [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00634725\u0026amp;atom=%2Fspmdc%2F14%2F22%2F19.atom\u0022\u003ENCT00634725\u003C\/a\u003E, Huguet F et al. \u003Cem\u003EASCO\u003C\/em\u003E 2014 (abstract 4001^)], the goal was to determine if CRT would increase overall survival (OS) in LAPC patients with tumors controlled after 4 months of chemotherapy. No difference in OS was seen by adding CRT. As a secondary end point, however, the local progression rate of 32% was significantly lower in the CRT group compared with the chemotherapy alone group (46%; p = .035). In addition, the time of treatment-free survival was longer with CRT (median, 6.1 months) compared with chemotherapy (median, 3.7 months; log-rank, p = .017).\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EDr. Louvet offered several different ideas for building on the results obtained in LAP-07. The first is to improve systemic chemotherapy by following up on positive results seen in studies with leucovorin calcium\u2014fluorouracil\u2014irinotecan hydrochloride\u2014oxaliplatin (FOLFIRINOX), nanoparticle albumin\u2014bound (nab)-paclitaxel plus gemcitabine, and nab-paclitaxel plus leucovorin calcium\u2014fluorouracil\u2014oxaliplatin (FOLFOX). The use of personalized medicine and further refining chemotherapy, surgery, and CRT protocols are also areas that may lead to improved outcomes. Two upcoming studies, RTOG 1201 [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01921751\u0026amp;atom=%2Fspmdc%2F14%2F22%2F19.atom\u0022\u003ENCT01921751\u003C\/a\u003E] and SCALOP 2 [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT02024009\u0026amp;atom=%2Fspmdc%2F14%2F22%2F19.atom\u0022\u003ENCT02024009\u003C\/a\u003E], will hopefully answer some of these questions.\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EEileen M. O\u0027Reilly MD, Memorial Sloan Kettering Cancer Center, New York, New York, USA gave an overview of treatment options for metastatic PC. In the PRODIGE 4\/ACCORD 11 study [Conroy T et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2011], FOLFIRINOX was superior to gemcitabine, with a median OS of 11.1 months vs 6.8 months for gemcitabine (HR, 0.57; 95% CI, 0.45 to 0.73; p \u0026lt; .001). Controlling the disease with FOLFIRINOX also preserves quality of life for a longer period of time [Gourgou-Bourgade S et al. \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E 2013]. \u201cThis is, I think, a key point that we need to remember when we are treating patients, as quality of life is such a critical component in any state of pancreas cancer, particularly in the advanced disease setting,\u201d Dr. O\u0027Reilly noted.\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EThe other frontline choice is nab-paclitaxel plus gemcitabine, which was superior to gemcitabine alone in the MPACT trial (8.5 vs 6.7 months; HR, 0.72; 95% CI, 0.62 to 0.83; p \u0026lt; .001) [Von Hoff DD et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2013]. Several modifications to FOLFIRINOX have been published, but no consensus currently exists regarding the best approach. \u201cOptions are good. Our challenge will be trying to select the right option for a given patient rather than saying that one is better than another,\u201d said Dr. O\u0027Reilly. A treatment algorithm based on patient age and performance status is presented in \u003Ca id=\u0022xref-table-wrap-2-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T2\u0022\u003ETable 2\u003C\/a\u003E.\u003C\/p\u003E\u003Cdiv id=\u0022T2\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/14856\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/14856\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/14856\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 2.\u003C\/span\u003E \n            \u003Cp id=\u0022p-10\u0022 class=\u0022first-child\u0022\u003ESystemic Treatment Options\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-14\u0022\u003EMany Phase 3 PC studies have yielded disappointing results, but Malcolm J. Moore, MD, Princess Margaret Cancer Center, University of Toronto, Toronto, Ontario, Canada, believes that new agents in development provide hope for the future of PC treatment. Agents that have been unsuccessful in the past include vascular endothelial growth factor inhibitors, metformin, epidermal growth factor receptor inhibitors, oxaliplatin in second-line therapy, insulin-like growth factor receptor targeting, stromal disruption, and human equilibrative nucleoside transporter 1 expression with gemcitabine. \u201cWe really should be going into Phase 3 only when we have very strong signals in Phase 2,\u201d emphasized Dr. Moore.\u003C\/p\u003E\u003Cp id=\u0022p-15\u0022\u003EPC is a genetically complex disease, with abnormalities occurring in a variety of different pathways that have become potential targets of pharmacological agents. New drugs in later phases of development focus on areas such as hypoxia (TH-302), DN repair inhibition (poly adenosine diphosphate ribose polymerase inhibitors), mitogen-activated protein kinase pathways (MEK 1\/2 inhibitors), and embryonic signaling pathways (gamma secretase inhibitors). Immunotherapeutic strategies are also being tested, including vaccines, T-cell activation via the CD40 pathway, targeting programmed cell death 1 and programmed death ligand 1, and targeting cytotoxic T-lymphocyte-associated protein 4. \u201cI think we have made some progress in the last few years, thankfully, but when you look at all these new approaches the best is yet to come,\u201d concluded Dr. Moore.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2014 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/14\/22\/19.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzl0v1\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_tables.js?nzl0v1\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}