Editing Cholangiocarcinoma (section)

==Treatment==
Cholangiocarcinoma is considered to be an incurable and rapidly lethal disease unless all the tumors can be fully [[Segmental resection|resected]] (cut out surgically). Since the operability of the tumor can only be assessed during surgery in most cases,<ref>{{cite journal | vauthors = Su CH, Tsay SH, Wu CC, Shyr YM, King KL, Lee CH, Lui WY, Liu TJ, P'eng FK | display-authors = 6 | title = Factors influencing postoperative morbidity, mortality, and survival after resection for hilar cholangiocarcinoma | journal = Annals of Surgery | volume = 223 | issue = 4 | pages = 384–94 | date = April 1996 | pmid = 8633917 | pmc = 1235134 | doi = 10.1097/00000658-199604000-00007 }}</ref> a majority of people undergo exploratory surgery unless there is already a clear indication that the tumor is inoperable.<ref name="feldman2"/> In 2008, the Mayo Clinic reported significant success treating early bile duct cancer with liver transplantation using a protocolized approach and strict selection criteria.<ref>{{cite journal | vauthors = Rosen CB, Heimbach JK, Gores GJ | title = Surgery for cholangiocarcinoma: the role of liver transplantation | journal = HPB | volume = 10 | issue = 3 | pages = 186–9 | year = 2008 | pmid = 18773052 | pmc = 2504373 | doi = 10.1080/13651820801992542 }}</ref>

Adjuvant therapy followed by [[liver transplantation]] may have a role in treatment of certain unresectable cases.<ref>{{cite journal | vauthors = Heimbach JK, Gores GJ, Haddock MG, Alberts SR, Pedersen R, Kremers W, Nyberg SL, Ishitani MB, Rosen CB | display-authors = 6 | title = Predictors of disease recurrence following neoadjuvant chemoradiotherapy and liver transplantation for unresectable perihilar cholangiocarcinoma | journal = Transplantation | volume = 82 | issue = 12 | pages = 1703–7 | date = December 2006 | pmid = 17198263 | doi = 10.1097/01.tp.0000253551.43583.d1 | s2cid = 25466829 }}</ref> Locoregional therapies including transarterial chemoembolization (TACE), transarterial radioembolization (TARE) and ablation therapies have a role in intrahepatic variants of cholangiocarcinoma to provide palliation or potential cure in people who are not surgical candidates.<ref>{{cite journal | vauthors = Kuhlmann JB, Blum HE | title = Locoregional therapy for cholangiocarcinoma | journal = Current Opinion in Gastroenterology | volume = 29 | issue = 3 | pages = 324–8 | date = May 2013 | pmid = 23337933 | doi = 10.1097/MOG.0b013e32835d9dea | s2cid = 37403999 }}</ref>

===Adjuvant chemotherapy and radiation therapy===
If the tumor can be removed surgically, people may receive [[adjuvant therapy|adjuvant]] [[chemotherapy]] or [[radiation therapy]] after the operation to improve the chances of cure. If the tissue margins are negative (i.e. the tumor has been totally [[:wikt:excision|excised]]), adjuvant therapy is of uncertain benefit. Both positive<ref>{{cite journal | vauthors = Todoroki T, Ohara K, Kawamoto T, Koike N, Yoshida S, Kashiwagi H, Otsuka M, Fukao K | display-authors = 6 | title = Benefits of adjuvant radiotherapy after radical resection of locally advanced main hepatic duct carcinoma | journal = International Journal of Radiation Oncology, Biology, Physics | volume = 46 | issue = 3 | pages = 581–7 | date = February 2000 | pmid = 10701737 | doi = 10.1016/S0360-3016(99)00472-1 }}</ref><ref>{{cite journal | vauthors = Alden ME, Mohiuddin M | title = The impact of radiation dose in combined external beam and intraluminal Ir-192 brachytherapy for bile duct cancer | journal = International Journal of Radiation Oncology, Biology, Physics | volume = 28 | issue = 4 | pages = 945–51 | date = March 1994 | pmid = 8138448 | doi = 10.1016/0360-3016(94)90115-5 }}</ref> and negative<ref name="nakeeb"/><ref>{{cite journal | vauthors = González González D, Gouma DJ, Rauws EA, van Gulik TM, Bosma A, Koedooder C | title = Role of radiotherapy, in particular intraluminal brachytherapy, in the treatment of proximal bile duct carcinoma | journal = Annals of Oncology | volume = 10 | issue = Suppl 4 | pages = 215–20 | year = 1999 | pmid = 10436826 | doi = 10.1023/A:1008339709327 }}</ref><ref>{{cite journal | vauthors = Pitt HA, Nakeeb A, Abrams RA, Coleman J, Piantadosi S, Yeo CJ, Lillemore KD, Cameron JL | display-authors = 6 | title = Perihilar cholangiocarcinoma. Postoperative radiotherapy does not improve survival | journal = Annals of Surgery | volume = 221 | issue = 6 | pages = 788–97; discussion 797–8 | date = June 1995 | pmid = 7794082 | pmc = 1234714 | doi = 10.1097/00000658-199506000-00017 }}</ref> results have been reported with adjuvant radiation therapy in this setting, and no prospective [[randomized controlled trial]]s have been conducted as of March 2007. Adjuvant chemotherapy appears to be ineffective in people with completely resected tumors.<ref>{{cite journal |last1=Luvira |first1=V |last2=Satitkarnmanee |first2=E |last3=Pugkhem |first3=A |last4=Kietpeerakool |first4=C |last5=Lumbiganon |first5=P |last6=Pattanittum |first6=P |title=Postoperative adjuvant chemotherapy for resectable cholangiocarcinoma. |journal=The Cochrane Database of Systematic Reviews |date=13 September 2021 |volume=2021 |issue=9 |pages=CD012814 |doi=10.1002/14651858.CD012814.pub2 |pmid=34515993|pmc=8437098 }}</ref><ref>{{cite journal | vauthors = Takada T, Amano H, Yasuda H, Nimura Y, Matsushiro T, Kato H, Nagakawa T, Nakayama T | display-authors = 6 | title = Is postoperative adjuvant chemotherapy useful for gallbladder carcinoma? A phase III multicenter prospective randomized controlled trial in patients with resected pancreaticobiliary carcinoma | journal = Cancer | volume = 95 | issue = 8 | pages = 1685–95 | date = October 2002 | pmid = 12365016 | doi = 10.1002/cncr.10831 | doi-access = free }}</ref> The role of combined chemoradiotherapy in this setting is unclear. If the tumor tissue margins are positive, indicating the tumor was not completely removed via surgery, then adjuvant therapy with radiation and possibly chemotherapy is generally recommended based on the available data.<ref name="nccn">{{cite web|url= https://www.nccn.org/professionals/physician_gls/pdf/hepatobiliary.pdf |title=National Comprehensive Cancer Network (NCCN) guidelines on evaluation and treatment of hepatobiliary malignancies |access-date=13 March 2007|url-access=registration}}</ref>
<ref name="nccn2021">{{cite web |url=https://www.nccn.org/patients/guidelines/content/PDF/gallandbile-hp-patient.pdf  |title=NCCN Guidelines for Patients: Gallbladder and Bile Duct Cancers; Hepatobiliary Cancers |date=2021 |access-date=10 February 2021 |publisher=National Comprehensive Cancer Network }}</ref>

===Treatment of advanced disease===
The majority of cases of cholangiocarcinoma present as inoperable (unresectable) disease<ref name="ReferenceA">{{cite journal | vauthors = Vauthey JN, Blumgart LH | title = Recent advances in the management of cholangiocarcinomas | journal = Seminars in Liver Disease | volume = 14 | issue = 2 | pages = 109–14 | date = May 1994 | pmid = 8047893 | doi = 10.1055/s-2007-1007302 | s2cid = 37111064 }}</ref> in which case people are generally treated with [[palliation|palliative]] [[chemotherapy]], with or without [[radiotherapy]]. Chemotherapy has been shown in a [[randomized controlled trial]] to improve [[quality of life]] and extend survival in people with inoperable cholangiocarcinoma.<ref>{{cite journal | vauthors = Glimelius B, Hoffman K, Sjödén PO, Jacobsson G, Sellström H, Enander LK, Linné T, Svensson C | display-authors = 6 | title = Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cancer | journal = Annals of Oncology | volume = 7 | issue = 6 | pages = 593–600 | date = August 1996 | pmid = 8879373 | doi = 10.1093/oxfordjournals.annonc.a010676 | doi-access = free }}</ref> There is no single chemotherapy regimen which is universally used, and enrollment in [[clinical trial]]s is often recommended when possible.<ref name="nccn2021"/> Chemotherapy agents used to treat cholangiocarcinoma include [[5-fluorouracil]] with [[leucovorin]],<ref>{{cite journal | vauthors = Choi CW, Choi IK, Seo JH, Kim BS, Kim JS, Kim CD, Um SH, Kim JS, Kim YH | display-authors = 6 | title = Effects of 5-fluorouracil and leucovorin in the treatment of pancreatic-biliary tract adenocarcinomas | journal = American Journal of Clinical Oncology | volume = 23 | issue = 4 | pages = 425–8 | date = August 2000 | pmid = 10955877 | doi = 10.1097/00000421-200008000-00023 }}</ref> [[gemcitabine]] as a single agent,<ref>{{cite journal | vauthors = Park JS, Oh SY, Kim SH, Kwon HC, Kim JS, Jin-Kim H, Kim YH | display-authors = 6 | title = Single-agent gemcitabine in the treatment of advanced biliary tract cancers: a phase II study | journal = Japanese Journal of Clinical Oncology | volume = 35 | issue = 2 | pages = 68–73 | date = February 2005 | pmid = 15709089 | doi = 10.1093/jjco/hyi021 | doi-access = free }}</ref> or gemcitabine plus [[cisplatin]],<ref>{{cite journal | vauthors = Giuliani F, Gebbia V, Maiello E, Borsellino N, Bajardi E, Colucci G | title = Gemcitabine and cisplatin for inoperable and/or metastatic biliary tree carcinomas: a multicenter phase II study of the Gruppo Oncologico dell'Italia Meridionale (GOIM) | journal = Annals of Oncology | volume = 17 | issue = Suppl 7 | pages = vii73–7 | date = June 2006 | pmid = 16760299 | doi = 10.1093/annonc/mdl956 | doi-access = free }}</ref> [[irinotecan]],<ref>{{cite journal | vauthors = Bhargava P, Jani CR, Savarese DM, O'Donnell JL, Stuart KE, Rocha Lima CM | title = Gemcitabine and irinotecan in locally advanced or metastatic biliary cancer: preliminary report | journal = Oncology | volume = 17 | issue = 9 Suppl 8 | pages = 23–6 | date = September 2003 | pmid = 14569844 }}</ref> or [[capecitabine]].<ref>{{cite journal | vauthors = Knox JJ, Hedley D, Oza A, Feld R, Siu LL, Chen E, Nematollahi M, Pond GR, Zhang J, Moore MJ | display-authors = 6 | title = Combining gemcitabine and capecitabine in patients with advanced biliary cancer: a phase II trial | journal = Journal of Clinical Oncology | volume = 23 | issue = 10 | pages = 2332–8 | date = April 2005 | pmid = 15800324 | doi = 10.1200/JCO.2005.51.008 }}</ref> A small pilot study suggested possible benefit from the [[tyrosine kinase]] inhibitor [[erlotinib]] in people with advanced cholangiocarcinoma.<ref>{{cite journal | vauthors = Philip PA, Mahoney MR, Allmer C, Thomas J, Pitot HC, Kim G, Donehower RC, Fitch T, Picus J, Erlichman C | display-authors = 6 | title = Phase II study of erlotinib in patients with advanced biliary cancer | journal = Journal of Clinical Oncology | volume = 24 | issue = 19 | pages = 3069–74 | date = July 2006 | pmid = 16809731 | doi = 10.1200/JCO.2005.05.3579 }}</ref>
Radiation therapy appears to prolong survival in people with resected extrahepatic cholangiocarcinoma,<ref>{{cite journal|vauthors=Bonet Beltrán M, Allal AS, Gich I, et al. |title=Is adjuvant radiotherapy needed after curative resection of extrahepatic biliary tract cancers? A systematic review with a meta-analysis of observational studies |journal=Cancer Treat Rev.|year=2012|volume=38|issue=2 |pages=111–119|doi= 10.1016/j.ctrv.2011.05.003|pmid=21652148}}</ref> and the few reports of its use in unresectable cholangiocarcinoma appear to show improved survival, but numbers are small.<ref name=Brid2016 />

[[Infigratinib]] (Truseltiq) is a [[tyrosine kinase inhibitor]] of [[fibroblast growth factor receptor]] (FGFR) that was approved for medical use in the United States in May 2021.<ref name="BridgeBio Pharma PR">{{cite press release | title=BridgeBio Pharma's Affiliate QED Therapeutics and Partner Helsinn Group Announce FDA Approval of Truseltiq (infigratinib) for Patients with Cholangiocarcinoma | publisher=BridgeBio Pharma | via=GlobeNewswire | date=28 May 2021 | url=https://www.globenewswire.com/news-release/2021/05/28/2238443/0/en/BridgeBio-Pharma-s-Affiliate-QED-Therapeutics-and-Partner-Helsinn-Group-Announce-FDA-Approval-of-TRUSELTIQ-infigratinib-for-Patients-with-Cholangiocarcinoma.html | access-date=28 May 2021}}</ref> It is [[Indication (medicine)|indicated]] for the treatment of people with previously treated locally advanced or metastatic cholangiocarcinoma harboring an FGFR2 fusion or rearrangement.<ref name="BridgeBio Pharma PR" />

[[Pemigatinib]] (Pemazyre) is a kinase inhibitor of [[fibroblast growth factor receptor 2]] (FGFR2) that was approved for medical use in the United States in April 2020.<ref>{{Cite web |date=2020 |title=Pemazyre Prescribing Information |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213736s000lbl.pdf |url-status=dead |access-date=5 March 2022 |website=Food and Drug Administration|archive-url=https://web.archive.org/web/20200720125745/https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213736s000lbl.pdf |archive-date=20 July 2020 }}</ref> It is indicated for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test.

[[Ivosidenib|Ivodesinib]] (Tibsovo) is a small molecule inhibitor of [[IDH1|isocitrate dehydrogenase 1]]. The FDA approved ivosidenib in August 2021 for adults with previously treated, locally advanced or metastatic cholangiocarcinoma with an isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test.<ref>{{Cite journal |last=Research |first=Center for Drug Evaluation and |date=2022-02-01 |title=FDA approves ivosidenib for advanced or metastatic cholangiocarcinoma |url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-ivosidenib-advanced-or-metastatic-cholangiocarcinoma |journal=FDA |language=en}}</ref>

[[Durvalumab]], (Imfinzi) is an immune checkpoint inhibitor that blocks the PD-L1 protein on the surface of immune cells, thereby allowing the immune system to recognize and attack tumor cells. In Phase III clinical trials, durvalumab, in combination with standard-of-care chemotherapy, demonstrated a statistically significant and clinically meaningful improvement in [[Survival rate|overall survival]] and [[progression-free survival]] versus chemotherapy alone as a 1st-line treatment for patients with advanced biliary tract cancer.<ref>{{Cite web |title=Imfinzi plus chemotherapy reduced risk of death by 20% in 1st-line advanced biliary tract cancer |url=https://www.astrazeneca.com/media-centre/press-releases/2022/imfinzi-plus-chemotherapy-reduced-risk-of-death-by-20-in-1st-line-advanced-biliary-tract-cancer.html |access-date=2022-03-05 |website=www.astrazeneca.com |date=18 January 2022 |language=en}}</ref>

[[Futibatinib]] (Lytgobi) was approved for medical use in the United States in September 2022.<ref>{{cite press release | title=FDA Approves Taiho's Lytgobi (futibatinib) Tablets for Previously Treated, Unresectable, Locally Advanced or Metastatic Intrahepatic Cholangiocarcinoma | publisher=Taiho Oncology | via=PR Newswire | date=30 September 2022 | url=https://www.prnewswire.com/news-releases/fda-approves-taihos-lytgobi-futibatinib-tablets-for-previously-treated-unresectable-locally-advanced-or-metastatic-intrahepatic-cholangiocarcinoma-301638254.html | access-date=4 October 2022}}</ref>