Kahor bilowga maqaalka, aragtida koowaad ee sayniska.
Fahamka MSI-H, MSS, MSI-L
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MSS (xasilloonida MicroSatellite), xasilloonida microsatelite, marka la barbar dhigo MSI, ma jiro wax MSI oo muuqda.
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MSI-H (Xasillooni darrada MicroSatellite-Sare, xasillooni-darrada sare ee mikrosatelite-ka), taas oo ah, inta jeer ee xasillooni-darrada microsatellite-ka ay badan tahay, guud ahaanna ka sarreyso 30%;
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MSI-L (Xasillooni darrada MicroSatelite-Hoose, oo aan badnayn oo aan caadi ahayn oo microsatelite ah), taas oo ah, inta jeer ee xasillooni darrada microsatelite-ka ay yar tahay, guud ahaanna ka yar tahay 30%.
Saaxiibada ka walaacsan horumarkii ugu dambeeyay ee daawaynta kansarka waxay ogyihiin in dawooyinka ka hortagga kansarka ee ballaaran ee pembrolizumab iyo nivolumab loo oggolaaday daawaynta dhammaan bukaannada buro adag ee qaba MSI-H (xasillooni darro sare oo microsatellite ah). Gaar ahaan bukaanka mindhicirka, heerka ogaanshaha MSI-H waa mid aad u sarreeya, sidaa darteed bukaannada kansarka qaarkood waxay ka faa'iidaystaan daawaynta noocan ah si ay u sii dheereeyaan badbaadada.
Tilmaamaha daawaynta kansarka mindhicirka ee horumarsan ama metastatic ee NCCN, ikhtiyaarada immunotherapy ee safka hore ee bukaanada qaba MSI-H iyo dMMR waa nivolumab (nivolumab, Opdivo) ama pembrolizumab (pembrolizumab, Keytruda), ama nivolumab iyo ipilimumab (daawaynta isku dhafan Ciraaq ee Pitimab). , Yervoy).
Talooyinkani waa talooyinka qaybta 2B waxayna khuseeyaan bukaanada aan ku habboonayn isku darka daaweynta kemotherabi ee cytotoxic. Ikhtiyaaradan dawada difaaca jirka waxa ay sidoo kale ku taxan yihiin tilmaamaha sida talooyinka daawaynta safka labaad iyo saddexaad ee dMMR/MSI-H bukaanka.
Bukaannada qaba kansarka mindhicirka weyn ee deegaanka ee aan la-beddeli karin ee cudur ku dhacay ama ugu yaraan iska caabiya laba nidaam oo hore oo kiimiko ah, 95% ka mid ah ayaa ogaan kara MSS halkii laga heli lahaa MSI-H. Marka, sidee loo doortaa bukaanka kansarka mindhicirka ee MSS?
Dhowaan, tijaabada IMblaze370 waxaa loo daabacay sida wajiga III tijaabada sumadda furan, iyo 363 bukaan oo qaba kansarka mindhicirka ee metastatic kuwaas oo natiijooyinka baaritaanka hidda-wadaha MSS loo qoondeeyay si aan kala sooc lahayn atezolizumab (atezolizumab) oo ay weheliso cobimetinib (cobititib) at 2: 1: 1 Ni, MEK daroogada la beegsaday) kooxda, kooxda attuzumab monotherapy, regorafenib (regorafenib, kinase inhibitor-bartilmaameedka badan) kooxda. Bukaannada qaba kansarka mindhicirka ee MSS taariikh ahaan kama aysan jawaabin daaweynta tallaalka.
Natiijooyinka daraasaddan ayaa mar kale cadeynaya: Bukaannada MSS ee kansarka malawadka si wanaagsan ugama jawaabaan daweynta immunotherapy (PD-L1) atuzumab. Badbaadada guud ee guud ee aatzumab oo ay weheliso kooxda cobtinib waxay ahayd 8.87 bilood, marka loo barbardhigo 7.10 bilood ee kooxda atezumab oo keli ah iyo 8.51 bilood ee kooxda regofenib, iyadoon loo eegin in difaaca jirka keliya ama isku dhafan Ma jiro faa'iido badbaado oo muhiim ah.
Nolosha dhexdhexaad-la'aanta horumarka, saddexda kooxood ee daaweynta waxay ahaayeen bilooyin 1.91, bilo 1.94, iyo bilooyin 2.00, oo aan lahayn wax farqi ah. Heerka fasalka 3/4 dhacdooyinka xun wuxuu ahaa 61% kooxda daaweynta isku dhafan, 31% ee kooxda atuzumab monotherapy, iyo 58% ee kooxda regofenib.
"Natiijooyinkani waxay muujinayaan kala duwanaanshaha bayoolaji ee u dhexeeya MSS iyo MSI-H, waxayna xoogga saareysaa baahiyaha daaweynta ee kala duwan ee u dhexeeya labadan nooc ee cudur," ayay tiri Dr. Cathy Eng, oo ah cilmi-baare ka tirsan Jaamacadda Texas ee Xarunta Kansarka.
Taasi waa in la yiraahdo, bukaannada kansarka mindhicirka ee MSS lagu helo baaritaanka hidda-socodka kuma talinayaan doorashada tallaalka difaaca jirka, oo waxay isticmaalaan habab kale. Waqtigan xaadirka ah, bartilmaameedyada iyo daawooyinka la beegsanayo ee ay gaari karaan bukaanada qaba kansarka mindhicirka waa:
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VEGF: Bevacizumab, Apsip
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VEGFR: ramucirumab, rigofinib, fruquintinib
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EGFR: cetuximab, panitumumab
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PD-1 / PDL-1: pembrolizumab, nivolumab
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CTLA-4: Ipilimumab
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BRAF: Velofini
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NTRK: Larotinib
Haddii la ogaado isbeddellada bartilmaameedka kale ee u dhigma, daaweynta daroogada ee u dhiganta ayaa la dooran karaa.
Bukaannada kansarka mindhicirka mindhicirka, waxaad u dooran kartaa nooc caadi ah oo kiimiko ah-FOLFOXIRI (fluorouracil + leucovorin + oxaliplatin + irinotecan), oo ah isku-darka koox ka mid ah wakiillada kiimiko-daweynta cytotoxic, oo ku habboon dadka oo dhan.
Ka dib iska caabbinta daroogada, natiijada baaritaanka hidda-socodka maaha MSI-H. Waxa kale oo aad dooran kartaa kinase inhibitors badan oo bartilmaameed leh regorafenib (regorafenib, Stivarga) iyo TAS-102 (trifluridine / tipiracil; Lonsurf).
Cetuximab sidoo kale waa daroogo xiddig ah oo inta badan ay doortaan bukaanada mindhicirka, taas oo ah daawo inta badan ka muuqata qorshooyinka daawaynta shakhsi ahaaneed. Hababka qiimeynta waxaa ka mid ah: Buradu ma dhanka bidix mise midig? Ma ka kooban tahay isbeddellada KRAS/NRAS? Ka hor inta aan la dooran cetuximab ama panitumumab, beddelka hidda-wadaha RAS waa in la tixgeliyaa.
