Okufanele ukwenze mayelana nokumelana nezidakamizwa kwezidakamizwa eziqondiswe kumdlavuza wamaphaphu wamangqamuzana amancane, ufuna ukwazi lapha
Umdlavuza wamaphaphu ungumdlavuza onezifo eziphakeme nokufa kwabantu eChina. Babalelwa ezigidini ezingu-1.6 abantu ababulawa yilesi sifo unyaka ngamunye emhlabeni wonke, futhi cishe u-85% walezi zigameko umdlavuza wamaphaphu ongewona omncane (NSCLC). Njengamanje, imishanguzo eminingi eqondiswe kumdlavuza yenzelwe intuthuko umdlavuza wamaphaphu weselula ongewona omncane emhlabeni. Le mithi yokwelapha emisha iye yandisa isikhathi sokusinda esimaphakathi seziguli saba yizinyanga ezingama-35, ezingagcini nje ngokukhulisa kakhulu isikhathi sokuphila kwazo, kodwa futhi zazuza ukwelashwa komuntu siqu. Kodwa-ke, iziguli eziningi zizoba nokungazweli emishanguzweni kwesibili ezinyangeni eziyisi-8 kuya kweziyi-14 ngemva kokuthola i-EGFR-TKI (ukwelashwa okujwayelekile komugqa wokuqala ezigulini ezinokuguquka okuzwelayo kufuzo lwe-EGFR). Indlela yokuxazulula inkinga yokungazweli emithini isiphenduke isihloko esishisayo socwaningo. Izoqhubeka nokuphendula wonke umuntu.
1. Kungani ukwelashwa okubhekiswe kumdlavuza weseli wamaphaphu ongewona omncane?
Ukumelana nezidakamizwa okuhlosiwe kuvame ukuhlukaniswa kube ukumelana okuyinhloko nokumelana okwesibili.
1. Ukumelana nezidakamizwa okuyisisekelo: kubhekisa ekuguqulweni kwezinhloso ze-EGFR zesiguli, kepha ngenxa yobukhona bemvelo bokushintshwa kwezakhi zofuzo ze-KRAS, amaphilisi e-gefitinib kanye ne-erlotinib hydrochloride nezinye izidakamizwa ezihlosiwe azisebenzi, Ngemuva kwezinyanga ezintathu zokusetshenziswa, ukumelana nezidakamizwa kwenzeka.
2. Ukumelana nezidakamizwa kwesibili: Ngesikhathi sokwelashwa kwezidakamizwa ezihlosiwe, ngoba indlela yesignali eqondiwe iyaqhubeka nokuvinjelwa izidakamizwa, i isisu ikhiqiza okunye ukuguqulwa kwezakhi zofuzo ukuze kuphunyuke umuthi, ivimbele umphumela wokwelapha womuthi oqondiwe ekuqondisweni kwe-EGFR, ngaleyo ndlela Kuholele ekumelaneni nomuthi. Isikhathi esisebenzayo somuthi ngokuvamile singaphezu kwezinyanga ezi-3.
2. Indlela yokumelana nezidakamizwa yokwelashwa okuqondisiwe komdlavuza wamangqamuzana ongewona omncane
Njengamanje kunezinqubo ezintathu eziqondile zeseli elingelona elincane umdlavuza wamaphaphu ukumelana nezidakamizwa. Okokuqala, ukumelana nezidakamizwa kwenziwa ngokuguquguquka kofuzo. Cishe u-40% wezakhi zofuzo ezigulini ezinokuhlolwa kwezakhi zofuzo ezinhle zizokhiqiza izakhi zofuzo ezintsha ezakhini zofuzo zokuqala, okuzodala ukungazweli emithini yokuqala, okuholela ekungazweni nomuthi. Okwesibili, amangqamuzana omdlavuza anobuqili ngokuvamile "alungise indlela emnyama yomgwaqo wepulangwe" futhi aphambuke. Lesi simo sibanga cishe u-20% weziguli ezingazweli emishanguzweni. Ngaphezu kwalezi zindlela ezimbili ezingenhla zokungazweli emishanguzweni, indlela yokumelana nomuthi yama-30% asele eziguli ayikacaci kahle.
3. Ungahlulela kanjani ukuthi iziguli ezinomdlavuza ongewona omncane wamangqamuzana wamaphaphu zinokumelana nemithi?
1. Ngokuvamile, lapho umuthi umelana, umuthi ohlosiwe awukwazi ukulawula ukukhula kwesimila, okuzobangela ukuba isimila sikhule noma simetastaze kude. Ngalesi sikhathi, isiguli sizoba nezimpawu ezithile, njengokuthi akukho ukukhwehlela ngaphambili, kodwa muva nje kuqale ukukhwehlela, noma ngemva kokumetastasis kobuchopho Isiguli sizoba nesiyezi, ikhanda elibuhlungu, ukuhlanza ngaphandle kwesizathu, futhi iziguli ezine-metastasis yamathambo zizozwa ubuhlungu, ukucindezelwa kwezinzwa kanye ezinye izimpawu. Ngalesi sikhathi, isiguli kudingeka siqaphe.
2. Ezigulini ezingakhula ukungazweli emthini, indlela engcono kakhulu yokuya esibhedlela ukuze ibuyekezwe njalo. Thola ukuthi ingabe umuthi ohlosiwe uyamelana nezimpawu zesimila nokuhlolwa kwe-imaging.
4. Ngemuva kokuthi isiguli siqale ukungazweli emthini, udokotela uvame ukuncoma ukuthi kwenziwe i-biopsy yesibili, kusho ukuthini
Ngokuvamile, zonke iziguli ezinomdlavuza wamaphaphu ezithatha imishanguzo ye-EGFR-TRI futhi zibe nokuqhubekela phambili kwezifo kufanele zenze i-biopsy yesibili.
1. Sula ukuxilongwa kwezifo futhi ukuze unqume ukuthi ngabe wumdlavuza omusha oyinhloko noma ukuphindeka komdlavuza yini.
2. Yenza ukuhlolwa kofuzo kwesibili ukuze uthole ukuthi ingabe kuwukumelana nomuthi okubangelwa ukuguqulwa kofuzo futhi, futhi uthole ukuthi ingabe lukhona yini uhlelo olusha lokwelapha oluhlosiwe.
I-biopsy yesibili ingakwazi ukubona ukukhula kwesifo ngokushesha, iveze izindlela zokumelana nemithi, futhi yakhe izinhlelo zokwelashwa ezifanele zokulandelela. I-biopsy yesibili ihlukaniswe ngokuyinhloko ibe i-tissue biopsy kanye ne-liquid biopsy. I-tissue biopsy ihlukaniswe ikakhulukazi i-thoracotomy biopsy, i-bronchoscopy biopsy kanye ne-percutaneous lung biopsy. Ezigulini ezingakwazi ukuthola izicubu zesimila, i-liquid biopsy esekelwe kubuchwepheshe bokulandelana kofuzo lwegazi lwe-NGS ingakhethwa ukuze kutholwe amanye amathuba okwelashwa.
5. Yini okufanele ngiyenze uma ukumelana nomuthi kuvela ngemuva kokwelashwa okuhlosiwe kwesizukulwane sokuqala kwe-TKI yomdlavuza ongewona omncane wamangqamuzana wamaphaphu?
Isizukulwane sokuqala se-EGFR-TKI sifaka i-gefitinib, i-erlotinib, ne-icotinib.
Ngokwemihlahlandlela ye-NCCN, ukuhlolwa kokuguqulwa kwezinguquko kwe-T790M kuqala kunconywa ngemuva kwesizukulwane sokuqala sokumelana ne-EGFR-TKI. Amasu ahlukene amukelwa ngokuya ngokuthi ngabe isiguli sinezimpawu yini, noma ngabe kukhona i-metastasis yobuchopho, noma ngabe ukuqhubekela phambili kwasendaweni noma ukuqhubekela phambili okuningi.
1. Ezigulini ezine-T790M ezakhayo: the isincomo sokuqala ukwelashwa kwe-Osimertinib, qhubeka nokwelashwa kwe-TKI ezigulini ezihamba kancane, kanye nokwelashwa kwendawo ezigulini ezinokuqhubeka kwendawo, kuhlanganise ne-radiotherapy ye-metastasis yobuchopho, i-radiotherapy yendawo yesilonda esisodwa Ukuze uthathe i-chemotherapy ezigulini ezinenqubekelaphambili enkulu.
2. Ngeziguli ezingenayo i-T790M: kungenziwa ngamakhemikhali, noma immunotherapy ingase ikhethwe ngokusekelwe ekukhulumeni kwe-PD-L1 kwesiguli.
3. Ezigulini ezingenazimpawu ngemuva kokumelana nemithi: ukwelashwa kwendawo kungathathwa noma kuqhutshekiselwe ukwenziwa kokwelashwa kwe-TKI. Ezigulini ezine-metastases yobuchopho kuphela, ukwelashwa kwasendaweni kungacatshangelwa, futhi kuqhubeke nokusebenzisa isizukulwane sokuqala se-EGFR-TKI.
6. Kuyoze kube nini ngemuva kokuthatha i-osimertinib kuzoqala ukumelana nemithi?
I-Osimertinib yisidakamizwa esibhekiswe esizukulwaneni sesithathu se-EGFR-TKI esinesikhathi esimaphakathi sokumelana nezidakamizwa cishe izinyanga eziyi-11. Kodwa-ke, ekusetshenzisweni kwemitholampilo, iziguli eziningi ziphinde zithuthukise ukuguqulwa kokumelana ngemuva kweminyaka emibili noma emithathu ngemuva kokuthatha i-osimertinib, ngakho-ke Isimo esithile sesikhathi sokumelana ne-oxitinib siyahluka kuye ngomuntu.
7. Yini inqubo yokumelana nomuthi ka-osimertinib?
Indlela yokumelana nezidakamizwa ye-osimertinib inzima kakhulu, kufaka phakathi ukuguqulwa kwe-C797S, ukukhuliswa kwe-MET / ukuhlelwa kabusha kwe-RET / ukuhlelwa kabusha kwe-ROS-1, ukukhulisa kwe-HER-2, ukuguqulwa kwe-BRAF, ukuguqulwa kwe-RAS, ukuguqulwa kwe-FGFR1, ukuguqulwa kube ngumdlavuza omncane wamaphaphu, Azikho izakhi zofuzo ukuguquka kwezakhi zofuzo, njll., kanye nemithi yokwelashwa elandelayo yezindlela ezahlukahlukene zokumelana nezidakamizwa yehlukile.
1. Izinguquko zofuzo ze-EGFR futhi: Ukuguqulwa kwe-EGFR796 kanye no-797 kube ne-24.7%, ukuguqulwa kwe-EGFR 792 kube ngu-10.8%, u-EGFR 718 no-719 kuguqulwe izakhi zofuzo kube ne-9.7% -EGFR gene, ukuguqulwa kokuphikisana nezinye, kubalwa u-45% wazo zonke iziguli, cishe isigamu sezwe.
2. Okunye ukuguqulwa kwezakhi zofuzo: kufaka phakathi i-PIK3CA, i-BRAF, i-MET, i-RET, i-KRAS, njll. Izinhlobonhlobo zezakhi zofuzo zomshayeli wamaphaphu ezivamile futhi ezingavamile ziyabandakanyeka futhi zisakazeke kakhulu.
3. Siguqulwe saba umdlavuza omncane wamaphaphu weseli.
8. Yini okufanele uyenze ngemuva kokwelapha okubhekiswe ku-Oxitinib kokumelana nemithi?
Ngezakhi zofuzo ezahlukahlukene zokumelana, ikhambi lokuqala limi ngokulandelayo:
1. Mayelana nodaba lokuguquka kwezakhi eziphindwe kathathu (i-C797S / T790M / 19-del), umphumela wokukhetha i-bugatinib ungcono kune-osimertinib / gefitinib, futhi umphumela awuthinteki ngendawo yendawo ye-C797S ne-T790M. (1) I-Bugatinib ehlanganiswe nekilasi le-anti-EGFR (i-cetuximab / panitumumab) ingathuthukisa umphumela wokwelapha wezinguquko ezintathu, futhi inhlanganisela yezidakamizwa ezimbili ingadlala umthelela wokusebenzisana; (2) I-Bugatinib ihlangene neSelumetinib (Simetinib) ingakwazi ukunqoba ukumelana ne-osimertinib okudalwe ukuguquka kwe-C797S.
2. Ngokuhlelelwa kokushintshaniswa kwe-EGFR C797S, cabanga ngezidakamizwa eziqondisiwe zesizukulwane sokuqala zihlangene nezidakamizwa eziqondisiwe zesizukulwane sesithathu, njenge-osimertinib ehlanganiswe ne-gefitinib / erlotinib. Ngokuqondaniswa kwe-cis, ungakwazi
khetha izidakamizwa ezibhekiswe ku-Bugatinib + VEGF.
3. Uma kukhona kuphela ukuguqulwa kwe-C79CS, ungasebenzisa isizukulwane sokuqala se-EGFR inhibitor, njenge gefitinib, erlotinib, icotinib.
4. Ukukhuliswa kwe-MET kuphakamisa ukuthi i-osimertinib ihlanganiswe nama-MET inhibitors (i-camatinib, i-crizotinib, i-Savolitinib, njll.). Izinguquko ze-BRAF ziphakamisa ukuthi i-osimertinib ihlanganiswe ne-BRAF inhibitors (dalafinib + trametinib). Ukuguqulwa kwe-RET kuphakamise ukuthi i-Osimertinib ihlanganiswe neKotinib, futhi-ke okungcono ukuthi i-Osimertinib ihlanganiswe neBLU-667.
Kunconywa ukuthi ngemuva kokumelana ne-oxetinib, kungcono ukwenza ukuhlolwa kofuzo futhi, bese ukhetha umuthi ofanele ohlosiwe ngokuya ngenhloso yokuguqula ukuze usize kangcono ukwelashwa. Kungcono ukubonisana nodokotela oqeqeshiwe ukuthola inhlanganisela yokwelashwa kwezidakamizwa ezihlosiwe.
9. Imiphumela engemihle yemithi eqondiswe emdlavuza wamangqamuzana ongeyona emincane
Umgomo wezidakamizwa ezihlosiwe ngamangqamuzana ucacile, kepha akusho ukuthi akukho miphumela emibi emitholampilo ezokwenzeka. Impendulo emibi yezidakamizwa ezihlosiwe ezifana nohudo, i-proteinuria, umfutho wegazi ophakeme, ukuqubuka okufana nezinduna nesifo senhliziyo kuyaziwa. Yize izidakamizwa eziqondisiwe ziphansi kunezidakamizwa zendabuko ezinobuthi, kusamele zingabukelwa phansi. Okunye ukusabela okuphikisayo okungavamile ngokuvamile kunzima ukukuthola ngenxa yokuxilongwa komtholampilo, okuvame ukuholela emiphumeleni emibi.
Isibonelo, ukwelashwa kwe-erlotinib kungadala ukuphakama kwesibindi se-transaminase, futhi ukuphuma kwegazi emathunjini akuvamile ukubikwa, kanti i-gefitinib iyindlela yokwelashwa ebhekiswe ku-molecule encane elwa ne-EGFR, yize imetabolism yayo ikakhulu isibindi Cishe i-4% isuswa izinso ngendlela yama-prototypes nama-metabolites, futhi athambekele ekuhlulekeni kwezinso okunamandla, okuthuthuka ngemuva kokuhoxa kwezidakamizwa. Ekwelashweni kwezidakamizwa okuhlosiwe, ukusabela okubi kakhulu futhi okubulalayo kufanele kugwenywe ngangokunokwenzeka. Ukusabela okungathandeki kuzothinta ukuzethemba kwesiguli ekwelashweni. Ukusabela okubi kakhulu kungaphazamisa inqubo yokwelashwa.
