Recent progress in the treatment for unresectable biliary tract cancer

Abstract

Approximately22 000casesofgallbladderandextrahepaticcholan-giocarcinomaarediagnosedeveryyearinJapan, 1 whichranks13th amongallcarcinomasandhasshownanincreasingtrendinrecent years.At17 773(2020),thenumberofdeathsissixth,andhasplateauedoverthepastfewyears.The5-yearrelativesurvivalrateis 24.5%,whichisthesecondworstafterpancreaticcancer.Surgical resection is considered the only potentially curative treatment for biliary tract cancer (BTC), but most patients with BTC (60%-70%) haveadvancedcancerthatisnotamenabletosurgicalresectionbecauseofdistantmetastasesorlocalprogressionatinitialpresentation.Patientswithmetastasesareconsideredtohaveaparticularly poor prognosis, as the median survival in such cases is less than 8 months. 2 Effortstoincreasethenumberoflong-termsurvivorsof BTC have been directed toward the establishment of safe surgical techniques, postoperative adjuvant chemotherapy, and resection afterpreoperativetreatmentforborderlineunresectable/unresectablepatients. 3-5 Iokaetal. 6 wroteanelaboratereviewofperioperativechemotherapyanddiscussedfutureprospects,whichwerevery informative. RecentchangesinthetreatmentofunresectableBTChavebeen remarkable. Primary treatment of unresectable BTC started with fluorouracil or gemcitabine (GEM) alone. Later, GEM plus cisplatin (GC) therapy was established as the current standard of care, but achievedonlyaslightmedianoverallsurvivalprolongation(11.7vs. 8.1 months)comparedwithGEMmonotherapy. 7 Subsequently,the FUGA-BTtrialwasconductedinJapan,comparingGCtherapywith thecombinationofGEMandS-1(anoralfluoropyrimidinecombinationconsistingoftegafur,gimeracil,andoteracil)(GS).Theresultsof thatstudyrevealedthatGStherapywasnon-inferiortoGCtherapy andwelltolerated. 8 Morerecently,triplecombinationtherapywith GCandS-1(GCS)wasusedasfirst-linetherapyforadvancedBTCin

PD-1 antibody–bound progenitor-exhausted CD8+ T cells in lymph nodes boost PD-1–blockade anti-tumor immunity in gastrointestinal cancer

“…The therapeutic applications of immune checkpoint inhibitors (ICIs) have expanded in several cancer types, including gastrointestinal cancers. However, their response rates are limited [1][2][3][4][5][6][7][8][9] . Given that preoperative ICI treatment is not currently recommended for gastrointestinal cancers, mechanistic analysis of the anti-tumor immune response with human samples after ICI treatment is of great importance, since elucidation of these mechanisms may improve therapeutic efficacy 10 .…”