Ukuthola Ukujikeleza Amangqamuzana E-Tumor kanye ne-DNA Free Cell
* Ngo-June 1, 2016, i-FDA ivume ukuhlolwa kwe-biopsy yamanzi ukuthola ukuguqulwa kwe-EGFR kubantu abane-non-cell encane yomdlavuza wamaphaphu. Lona "ukuhlolwa kwegazi" lokuqala okuvunyelwe ukuhlola nokwelapha umdlavuza wamaphaphu.
Iyini i-biopsy yamanzi? I-oncologist yakho kungenzeka ukuthi ikhulume ngale ndlela entsha yokuhlola umdlavuza wamaphaphu noma kungenzeka ukuthi uzwile ngale nqubo ngenkathi ucwaninga ngomdlavuza wakho ku-intanethi.
Yiluphi uhlobo lwenqubo yilezi, lapho kungenziwa khona, yiziphi izinzuzo nezinkinga, futhi sihamba kuphi nalesi sici semithi ecacile yomdlavuza wamaphaphu?
Kuyini Ukuphikisa Kwemithi?
Ungase ujwayelane nama-biopsies avamile emdlavuza wamaphaphu. Ukuze kutholakale umdlavuza wamaphaphu , isampula se-tumor itholakala ngandlela-thile. Khona-ke, njengoba kutholakala ukwelashwa, okunye okudingeka kwenziwe ukuze kutholakale ukuthi i-tumor "iguqukile" -kuthi ngabe yenze ushintsho olusha olwenza lukwazi ukumelana nokwelashwa kwamanje.
Ngeke yini kube mnandi uma lezo zindabuko zendabuko (okungenani ezinye) zingashintshwa ngokuhlolwa kwegazi okulula? Ngomdlavuza wamaphaphu, okungenani ukuqapha abanye abantu abanephrofayili ethile yamangqamuzana, leso sifiso senziwa ngokoqobo.
Kukhona okuningi esingasazi uma kuziwa ekubambeni kwamakhemikhali amakhemikhali okuqapha umdlavuza wamaphaphu ukuxilongwa nokuphathwa, kodwa sizokwabelana ngalokho esikuziyo namuhla.
Njengamanje e-United States, zonke izinhlobo ze-biopsies zamanzi zibhekwa njengophenyo lokuxilongwa nokuphathwa komdlavuza wamaphaphu futhi akufanele zisetshenziswe yedwa ukuqondisa ukuxilongwa noma ukuqapha ukwelashwa kwalolu hlobo lomdlavuza.
Izinhlobo ze-Biopsies yamanzi
Igazi lingasisiza kanjani ukuqapha umdlavuza?
Amaseli afika kanjani lapho? Kuwusizo ukuqala ngokukhuluma ngokuqondile lokho odokotela abakufunayo kwisampula ye-biopsy (igazi) kusuka kumuntu onomdlavuza. Siyazi ukuthi amangqamuzana amathumba, futhi kaningi izingxenye zamangqamuzana amathumba, avame ukuphumula esiswini bese efaka igazi. Lokhu akusho ukuthi i-tumor i-metastatic futhi izingcezu zamangqamuzana omdlavuza zingabonakala egazini ngisho nasezigaba zokuqala zomdlavuza. Kucwaninga kuze kube manje, ososayensi bebelokhu befuna okukodwa kokulandelayo:
- Ukujikeleza amaseli we-tumor (CTCs) - Lokhu kubhekisela kumangqamuzana e-tumor angatholakala egazini labantu abathile abanomdlavuza. Kuze kube manje i-CTCs ibaluleke kakhulu emangqamuzaneni ngaphandle kwe- non-encane yomdlavuza wesifo samaphaphu futhi isetshenziselwa ngokuyinhloko ukucacisa ukuchazwa kwalawo mdlavuza. Kunobunye ubufakazi bokuthi i-CTCs ingasiza ngomdlavuza omncane wamangqamuzana wamaphaphu futhi, kwesinye isifundo, amaphesenti angu-85 weziguli ezine-cancer encane yamaphaphu amancane ane-CTCs. Ukuhlolwa kwala ma-CTC kumagciwane amancane omdlavuza wesifo samaphaphu kubonakala sengathi ukubikezela kokuphila konke.
- I-DNA (i-ctDNA) engenamakhalekhukhwini (ejikelezayo) - Ngokungafani namangqamuzana e-tumor amaningi angatholakali egazini, lawa masampuli angathola izingcezu zamangqamuzana omzimba aphukile emzimbeni futhi achithekele egazini. Lokhu kungase kwenzeke kusuka ku-tumor oyinhloko noma izicubu zemetastatic. Le i-ctDNA itholakala ocwaningweni owodwa ukuba ibe khona kumaphesenti angu-82 eziguli zomdlavuza ezinezinambuzane ezingezona ezingqondweni. Itholakale emathunjini azo zonke izigaba kepha cishe yayitholakala ngezigaba eziphakeme zomdlavuza.
- I-RNA ye-tumor emaplatelets - Kungenzeka ukuthi wezwa kancane nge-RNA ye-tumor emafletletheni kunama-CTCs ne-ctDNA, kodwa lena yindawo ejabulisayo ngaphansi kwesihloko samanzi we-liquid biopsies. Ama-platelets ayaziwa ngokukwazi kwabo ukuthatha i-RNA ezivela emathunjini futhi angadlala indima ekusabalaleni komdlavuza.
Kuze kube manje, ukugunyazwa kwe-FDA kunikwe kuphela ukusetshenziswa kwe-CTCs njengesilinganiso sokulinganisa ukubikezela (futhi manje i-ctDNA ukuthola ukuguqulwa kwe-EGFR) kodwa ukusetshenziswa kwe-ctDNA kanye ne-RNA ye-tumor kuma-platelet cishe kuyosiza kakhulu ekuqapheni umdlavuza njengoba isikhathi sihamba kuqhubeke.
Ukuphikisana Kwamafutha Nesisindo Esijwayelekile Sokwenyama - Kungani Isikhathi Sokuthakazelisa Nalokho Okubukeka Kanjani?
Ungase uzibuze ukuthi kungani kunezinjabulo eziningi emoyeni mayelana nethuba lokulandela ezinye ze-khansa ezinama-biopsies anemanzi.
Sizobhala ezinye izinzuzo nezinkinga ezingezansi, kodwa ake siqale siqhathanise nesibonelo sokuthi umdlavuza wamaphaphu ungabhekwa kanjani futhi uphathwe ngayo ngaphandle kokusetshenziswa kwala ma-biopsies.
Kungenzeka kanjani ukuthi ukuphathwa komdlavuza wamangqamuzana kungashintsha ekutholeni?
Ake ucabange ukuthi usanda kutholakala ukuthi unomdlavuza wamaphaphu ongewona omncane. Ngokujwayelekile, ukuxilongwa kwenziwa ngokusetshenziswa kwemvelo yomdlavuza wamaphaphu ngamashubhu athathwa ngu:
- I-biopsy yenaliti
- I- endobronchial ultrasound kanye ne-biopsy (inaliti efakwe emzimbeni ngokusebenzisa i-bronchial tube phakathi ne-bronchoscopy)
- I-pulp biopsy evulekile (mhlawumbe i-thoracoscopy, lapho insimbi ekhanyayo ifakwa emigodini emincane esifubeni, noma i-thoracotomy, ehilela ukufakwa ngaphakathi kwendonga yesifuba ukufinyelela emaphashini)
Lezi zinqubo zamanje ze-biopsy zonke zibeka ingozi yokutheleleka, ukuphuma kwegazi, ukuwa kwamaphaphu (pneumothorax), kanye nobuhlungu obukhulu.
Uma sekutholakala izicubu, ithunyelwa ukuba i-pathologist ibuke ngaphansi kwe-microscope kanye nokuhlolwa okukhethekile okubheke ukungafani okuyizo zofuzo emangqamuzaneni omzimba. Lokhu kufaka isakhi (noma ama-molecule) ngokuvamile kuthatha amasonto amaningana (ngokuvamile okuyisihlanu kuya kwesithupha) ngaphambi kokuthola imiphumela. Uma ukungajwayelekile kofuzo (njengokuguqulwa kwe-EGFR) kutholakala, ukwelashwa kungaqala ngomuthi ohlosiwe, njenge-tyrosine kinase inhibitor Tarceva (erlotinib.)
Ngendlela ye-biopsy ye-liquop, esikhundleni sokwenza i-biopsy engavamile njenge-biopsy yenaliti ukuze ithole izicubu zokuprofetha kwezakhi zofuzo (ukuhlolwa kokuguqula izakhi zemizimba emibili ukuhlolwa okungahlolwa manje), ukudweba kwegazi okulula kungenziwa - okuningi ukuhlolwa okuncane okungenasidingo. Futhi esikhundleni sokulinda amasonto ngemiphumela, ngokushesha i-plasma genotyping ingabangela imiphumela ezinsukwini ezintathu. Ngakho ngesikhathi sokuxilongwa, iziguli ezine- mutation e-EGFR zingahle zithole ukuguqulwa kwemvelo hhayi nje kuphela ngokuhlolwa okuncane kakhulu kodwa kungaqaliswa ukwelashwa ukuze kulungiswe lokho kuguqulwa ezinsukwini ezimbalwa nje. (Asisekho khona nobuchwepheshe ukuze 'sithole' ezinye izinto ezingezansi zofuzo ezifana ne- ALK rearrangements kanye nokulungiswa kabusha kwe-ROS1 .)
Kungenzeka kanjani Ukuqapha Ukuguqulwa Kwengculaza?
Okuthakazelisayo nakakhulu kungenzeka ukuthi kungenzeka ukusebenzisa ama-biopsies amakhemikhali ukuqapha abantu asebevele bephathwa ngemithi ehlose ukuguqulwa kwe-EGFR.
Ngalesi sikhathi, uma umuntu eqaliswa kwi-inhibitor ye-EGFR njenge-Tarceva, inkambo yesifo sabo ihlolwe ngokwenza ucwaningo lwe-CT ngezikhathi ezithile ukubuka ukukhula kwesisu. Siyazi ukuthi cishe zonke izicubu zizokhula ukuphikisana nalezi zidakamizwa ngokuhamba kwesikhathi, kodwa leso sikhathi sasihluka kakhulu phakathi kwabantu abahlukene. Ungazi kanjani ukuthi leso sikhathi sifikile? Ngokwesiko, sifunda ukuthi ku-tumor sekuye kwavela ukumelana lapho ukuskena (njenge-CT scan noma i-PET scan) kubonisa ukuthi lesi sifo siqalile ukukhula futhi. Esikhathini esiningi (ngaphandle uma izimpawu zisho ukuthi umdlavuza ukhula kakhulu) iziguli zizwa ukuthi imishanguzo yabo iyeke ukusebenza lapho bethola imiphumela yokuskena ebonisa ukuthi isisu sikhula futhi.
Ngaleso sikhathi, imithi ivaliwe futhi abantu baphinde babhekene nokwenza enye i-biopsy ukuze bahlole isisu ukuze bafune izinguquko ezenza kube nzima. Njengoba kuphawuliwe ngenhla, izidakamizwa ezivamile zamapayipi zithwala izinyathelo zendlela eyingozi kakhulu, kanti futhi kuthatha amasonto ngaphandle kokwelashwa ukwazi imiphumela futhi uqonde ukuthi uzohamba kuphi.
Ngokuphambene nalokho, nge-biopsy ye-liquide eyenziwe ngezikhathi ezithile, odokotela bazokwazi ukutshela ngokushesha uma isisu sesimelana nemithi. Kutholakala ezifundweni ukuthi lezi zinguquko zivela ku-ctDNA isikhathi eside ngaphambi kokuthi izinguquko ezihlobene nokumelana zivezwe ku-CT scan. Phakathi nale nkathi yesikhathi - phakathi kokuhlolwa kwegazi kubonisa ukumelana futhi kutholakala ku-CT scan - abantu bazobe besebenzisa imithi engasasebenzi futhi ihlangabezana nemiphumela emibi yomuthi ongadingeki. Kusho isikhathi eside kakhulu ngaphambi kokuba sitshintshwe ekwelapheni okuphumelelayo.
Ngomphumela we-biopsy wamanzi okhombisa ukuphikiswa, isampuli yesisu (kusuka ku-biopsy yamanzi) ingahlolwa futhi isiguli singaguqulwa sibe yimithi elandelayo yesizukulwane esibhekisela ekuguquleni kwezakhi zofuzo noma mhlawumbe olunye uhlobo lwezokwelapha, njenge- chemotherapy noma i- immunotherapy .
I-Tumor Heterogenicity ne-Biopsies ye-Liquid
Enye inzuzo okungenzeka ukuthi i-biopsy yamanzi ingaba ngaphezu komdlavuza we-lung wegazi wamapayipi ihlobene ne-tumor heterogenicity. Siyazi ukuthi i-cancer yamaphaphu i-heterogeneous, okusho ukuthi izingxenye ezihlukene zesisu (kanye nezicubu ezihlukahlukene ikakhulukazi njenge-tumor oyinhloko kanye nemetastasis) zingase zihluke kwezinye izici zazo zamangqamuzana. Isibonelo, ukuguqulwa okwenziwe emangqamuzaneni yomdlavuza engxenyeni eyodwa yesisu kungase kungabi khona emaseleni kwenye ingxenye ye-tumor. Ukuze uzwisise lokhu, kuyasiza ukuqaphela ukuthi i-khansela iqhubeka ishintsha, ithuthukisa izici ezintsha kanye nezinguquko.
I-biopsy evamile inomkhawulo ngoba ihlunga indawo eyodwa kuphela yesikhumba. I-biopsy ye-liquop, ngokuphambene, ingase ibe nemiphumela eminingi yokubonisa izici zesifo sofuba njengaso sonke. Lokhu sekuvele kuboniswe kwizifundo, lapho ukuguqulwa komshayeli onamandla okutholakala khona kungatholakala nge-biopsy yamanzi eyophuthelwa ngenye indlela kwi-biopsy yamathambo.
Izinzuzo Zokuqubuka Kwamanzi Nge-Biopsy Ejwayelekile
Ukuze uqonde ngempela injabulo, kodwa futhi nemingcele ye-liquid biopsy sampling, ingasiza ekubaleni ezinye izinzuzo nezinzuzo zenqubo.
- Imiphumela ye-biopsy yamanzi iseduze "nesikhathi sangempela." Ngamanye amazwi, bangavumela ukuhlolwa kwangaphambilini kokusebenza nokumelana nesifo ngesikhathi somuthi. Uma i-biopsy yezicubu seziqedile, imiphumela ye -profiling molecular (profiling gene) e-tumor ngokuvamile idinga amasonto amaningana (ngokuvamile amahlanu kuya kwayisithupha) kanti ukuhlolwa kwezakhi zofuzo embonini ye-biopsy yamanzi kuthatha cishe izinsuku ezintathu kuphela. Lesi yisikhathi lapho ukwelashwa okukhethekile okungasetshenziswa khona noma ngesikhathi esingasetshenziswa ngayo izidakamizwa ezihloselwe isizukulwane esilandelayo uma lesi sifo sitholakala singenamandla.
- Inqubo ye-biopsy yamanzi ngokwayo iyashesha kakhulu kune-biopsy evamile.
- Ama-biopsies e-liquid ayingxenye encane.
- Ezinye izicubu zisezindaweni ezinzima ukuzithola ukuze zenze i-biopsy yezicubu ezivamile.
- Ezinye izicubu nama-metastases akuzona amasampula afanele okwenzela ukuprofetha kwezakhi zofuzo - isibonelo, ama-metastases amathambo
- Ama-biopsies e-liquid avumela ukubola kwe-tumor. Njengoba kuphawuliwe ngenhla, izicubu eziningi ziyingqimba. I-biopsy yamanzi ingakwazi ukunikeza amasampula amathuba amaningi okumela isisu ngokugcwele ngokuphambene nesampula esivamile ye-biopsy okungaba yiyo kuphela yamaseli akuleyo ngxenye ethile ye-tumor.
- Kungenzeka ukuthi amasu we-biopsy yamanzi azogcina engabizi kakhulu kunama-biopsies avamile.
- I-biopsies yamanzi ithwala ingozi ephansi yokucindezeleka kunelawo amasu ajwayelekile we-biopsy, njengengozi yokutheleleka, ukuphuma kwegazi, nokuwa kwamaphaphu (pneumothorax.) Lezi zinkinga azigcini nje kuphela ukunciphisa izinga lempilo kodwa zingabangela ukuphuza ukwelashwa kanye (futhi imiphumela yokulibaziseka kungasho ukuqhuma kwesisu.)
- Ama-biopsies we-liquid awabuhlungu kakhulu.
- Uma i-biopsy idinga ukuphindaphindiwe ngenxa yezicubu ezinganele, kulula kakhulu ukuphinda ukudweba kwegazi kunokuphindaphinda i-biopsy evamile.
- Ukuthuthukiswa kwesayensi yomdlavuza. Ngokubheka imiphumela ye-biopsies yamanzi ephindwe kaningi ngokuhamba kwesikhathi, abacwaningi bangafunda kabanzi mayelana nokuthi izicubu zishintsha kanjani izakhi zofuzo ngokuhamba kwesikhathi.
- Ama-biopsies e-liquid angase athathe ukuguqulwa okungahle kwenzeke ekutheni kufakwe isampula.
- I-biopsies yamanzi - uma ibona ukumelana ngokushesha - ingasiza ekugcineni ukwelashwa okungadingekile (nanoma yimiphi imiphumela emibi ehamba nalowo ukwelashwa) ngenkathi ukwandisa isikhathi esithile umuntu usebenzisa ukwelashwa okuphumelelayo.
- Ama-biopsies e-liquid angahle anciphise ngokweqile inani lemishanguzo enikeziwe ngenxa yesidingo samanje sokuhlola okuvamile ukuqapha inqubekela phambili.
Ukungahleleki kwe-Liquid Biopsy
Ngalesi sikhathi, kuningi okumele ufunde mayelana ne-biopsies yamanzi. Namanje futhi kunomkhawulo wokubona ukuguqulwa kwezakhi zofuzo ezifana ne-EGFR (nakuba kukhona ukukhuluma ukuthi maduzane bazokwazi ukusetshenziselwa ukubona ukuthunyelwa kweminye kanye nezinye izinguquko.) Kakhulu izinhlobo zomdlavuza wamaphaphu, ukusakazwa kwamangqamuzana omdlavuza noma umdlavuza I-DNA ibonakala kuphela engxenyeni encane yamagciwane ephaphu futhi ithonywe uhlobo kanye nesigaba somdlavuza. Umphumela omubi we-biopsy wamanzi akusho ukuthi umdlavuza awukho emzimbeni.
Isimo samanje se-Biopsies yamanzi we-Cancer Lung
Ama-biopsies e-liquid asetshenziselwa ukucwaninga e-United States, nakuba ezinye ze-oncologists zizisebenzisa ukuze zibone noma zibheke iziguli ezine-EGFR. Lokho kusho ukuthi ukuhlolwa kwe-biopsy yamanzi - ukuhlolwa kokuqala kohlobo lomdlavuza wamaphaphu - kuvunyelwe ngoJuni 1, 2016, ukuze kuhlolwe ukuguqulwa kwe-EGFR kuziguli ezine-non-small cell cancer umaphaphu.
Okungenani isikhungo esisodwa somdlavuza omkhulu manje sihlinzeka ngokuhlolwa kanye ne-plasma ngokushesha ye-genotyping yazo zonke iziguli ezine-non-cell encane yomdlavuza wamaphaphu ngesikhathi sokuxilongwa noma emva kokuphindaphindiwe / ukuphindaphindiwe komdlavuza wamaphaphu .
EYurophu, asetshenziselwa abantu abanomdlavuza we-cell wamaphaphu okungewona omncane ukuze bahlolisise ukuguqulwa kwe-EGFR futhi kubhekwa njengadingekile ukucacisa ukuthi ngabe abantu bayakhonjwa ukwelashwa nge-tyrosine kinase inhibitor.
Yini Okusibuyisela Emuva?
Kungaba ukudideka uma ufunda mayelana ne-biopsies yamanzi, ukuthi kungani le nqubo ingakenziwa kabanzi. Lokho esingakasazi khona ukuthi ama-biopsies ahlanzekile ayogcwalisa izidingo ezimbili: ukunemba nokuthembeka. Kumele kunqunywe ukuthi ama-biopsies anamanzi anganikeza ulwazi olufanayo (noma kangcono) kunama-biopsies wezincubu futhi ahlinzeke ngaleyo ndlela njalo.
Ikusasa
Kunzima ukwazi kahle ukuthi yini engaba khona ye-biopsies yamanzi kulesi sigaba socwaningo njengoba isanda kangaka. Ekugcineni, sithemba ukuthi le nqubo ngeke isebenzise kuphela ukulinganisela ukubikezelwa nokuqapha kokumelana kodwa njengethuluzi lokuhlola ukutholakala komdlavuza - nakuba lokho kuseyizinyathelo. Ngenye indlela, kuyisici esithakazelisayo sokucwaninga komdlavuza ngesikhathi sokunakekelwa kwemithi.
Imithombo:
UBettegowda, C., Sausen, M., Leary, R. et al. Ukutholakala kokudlulisa i-DNA ye-tumor ekuqaleni kwezikhathi zesibindi kanye nezokugcina. I-Science Translational Medicine
Imamura, F., Uchida, J., Kukita, Y. et al. Ukuqapha izimpendulo zokwelapha nokuziphendukela kwemvelo kwamangqamuzana amathumba ngokusakaza i-DNA ye-tumor yezinhlobo ze-EGFR ezingenangqamuzana e-EGFR emdlalweni wamaphaphu. I-Cancer Lung . 2016. 94: 68-73.
Jiang, T., Ren, S., noC. Zhou. Indima yokuhlaziya i-DNA ye-tumor emdlalweni wesifo samangqamuzana ongasona omncane. I-Cancer Lung . 2015. 90 (2): 128-34.
Karachaliou, N., Mayo-de-las-Casas, C., Molina-Vila, M. et al. Ama-biopsies wamanzi wangempela-sikhathi ayenzeka empilweni yokwelashwa. Ama-Annal of Medicational Medicine . 2015. 3 (3): 36.
Mahaswaran, S., Sequist, L., Nagrath, S. et al. Ukutholwa kwezinguquko ku-EGFR ekusakazeni amangqamuzana omdlavuza wamaphaphu. I-New England Journal of Medicine . 2008. 359 (4): 366-77.
Sacher, A., Paweletz, C., Dahlberg, S. et al. Ukuqinisekiswa okubonakalayo kwe-Rapid Plasma Genotyping yokuthola i-EGFR ne-KRAS Izinguquko ku-Cancer Advanced Lung Cancer. I-JAMA Oncology . Ishicilelwe ku-intanethi ngo-Ephreli 7, 2016
Santarpia, M., Karachaliou, N., Gonzalez-Cao, M. et al. Ukutholakala kwe-cell free circulation of DNA ukuhlolwa kwe-DNA yomdlavuza wamaphaphu. Ama-Biomarkers ku-Medicine . 2016. 10 (4): 417-30.