Ukujonga ukujikeleza kweeNtsholongwane zeTumor kunye neDNA yamahhala yeDNA
* Ngo-Juni 1, 2016, i-FDA ivume uvavanyo lwe-biopsy lwamanzi ukufumana utshintsho lwe-EGFR kubantu abanomdlavuza omncinci wamaselula. Lo ngowokuqala "ukuhlolwa kwegazi" kuvunyelwe ukuvavanya nokuphatha umhlaza wemiphunga.
Yintoni i-biopsy yamanzi? I-oncologist yakho inokuthi ichaze le ndlela entsha yokuvavanya umdlavuza wamaphaphu okanye mhlawumbi uyivile ngale ndlela ngelixa uphando ngomhlaza wakho kwi-intanethi.
Luhlobo luni lwenkqubo yile, xa kunokwenziwa ntoni, yintoni inzuzo kunye nokungahleleki, kwaye sihamba phi na le ngongoma yonyango echanekileyo yomhlaza wemiphunga?
Liyiphi i-Biopsy?
Unokuba nolwazi oluqhelekileyo lomhlaza womhlaza wamaphaphu. Ukuze uhlolisise umhlaza wemiphunga , isampula se-tumor ifunyanwa ngandlela-thile. Emva koko, njengengeniso yonyango, i-biopsies eyongezelelweyo ingadinga ukuba yenziwe ukuba ibone ukuba i-tumor "iguqukile" -kukuba ngaba ivelise utshintsho olutsha olwenza lukwazi ukunyango lwangoku.
Ngaba bekungeke kube mnandi ukuba loo mizobo yendabuko (ubuncinci abanye) ingatshintshwa ngokuhlolwa kwegazi? Umdlavuza wamaphaphu, ubuncinane ukubeka esweni abantu abathile ngeprofayile ethile, ukuba umnqweno uya kuba yinyani.
Kukho okuninzi esingayaziyo xa kufikeleleke kwizinto ezikhoyo zokwenza i-biopsies yamanzi ukujonga ukuxilongwa komhlaza wamaphaphu kunye nokunyangwa, kodwa siya kwabelana nabanye ngezinto esiziziyo namhlanje.
Njengamanje eUnited States, zonke ii-biopsies zamanzi zibhekwa uphando loxilongo kunye nokulawulwa komdlavuza wamaphaphu kwaye akufanele zisetyenziswe yodwa ukukhokela ukuxilongwa okanye unyango lwolu hlobo lomhlaza.
Iintlobo zeMihlaba yeMihlaba
Igazi lingafumana njani uncedo lokubeka umhlaza?
Iileli zifika njani? Kukunceda ukuqala ngokuthetha ngokuchanekileyo ngoko ogqirha abajonge kwi-biopsy (igazi) isampula kumntu onomdlavuza. Siyazi ukuba iiseli zesisu, kwaye ngokuphindaphindiweyo iinxalenye zeeseli zesisu, zivame ukuphuka kwisisu kwaye zifake igazi. Oku akuthethi ukuba i-tumor i-metastatic kwaye iinqununu zeseli zomhlaza zingabonakala egazini kwinqanaba langaphambili lomhlaza. Kuphando ngoku, izazinzulu ziye zafuna enye yezi zinto zilandelayo:
- Ukujikeleza iiseli zesisu (CTCs) - Oku kubhekisela kwiiseli zesisu ezinokufumaneka kwigazi labanye abantu abanomdlavuza. Okwangoku ii-CTCs zibaluleke kakhulu kwiidlers ngaphandle komncinci wesifo somhlaza wamaphaphu kwaye zisetyenziselwa ngokukhethekileyo ukucacisa ukuxela kwalawo maqhekeza. Kukho ubungqina bokuba i-CTC inokukunceda ngomdlavuza omncinci wamangqamuzana wesifo somhlaza kwaye, kwisifundo esinye, iipesenti ezingama-85 zezigulane ezinomdlavuza omncinci wamangqamuzana wesifo se-CTC. Ukuvavanya kwezi zi-CTC kwisigulane esincinci segciwane lesifo somdlavuza sibonakala sisigxina sokuphila.
- I-DNA (i-ctDNA) ye-cell (free circulation) ye-cell (free circulation) . Oku kunokuvela kwi-tumor yokuqala okanye i-tumast tumors. Lo mgca wafunyanwa kwisifundo esinye ukuba abekho kuma-82 ekhulwini lwezigulane zomhlaza ezineengxaki zeengxaki ezingekho ngengqondo. Kufunyenwe kwiimvumba zazo zonke izigaba kodwa kwakunokwenzeka ukuba kufumaneke nezigaba eziphezulu zomhlaza.
- I-RNA i-RNA kwiiplatelets - mhlawumbi uvile ngaphantsi nge-RNA ye-tumor kwiiplatelets kune-CTCs kunye ne-ctNA, kodwa le yindawo enye enomdla phantsi kwesihloko se-biopsies yamanzi. Iiplatelet ziyaziwa ngokuba zinako ukuthabatha i-RNA kwiimvumba kwaye zinokudlala indima ekusasazeni komhlaza.
Ngaloo ndlela, imvume ye-FDA inikwe kuphela ukusetyenziswa kwe-CTC njengomlinganiselo wokuqikelela ukuhlaziya (kwaye ngoku i-ctDNA ukubona iinguqu ze-EGFR) kodwa ukusetyenziswa kwe-ctDNA kunye ne-RNA ye-tumor kwiiplatelet kuya kunika uncedo olongezelelweyo ekujongeni umdlavuza njengoko ixesha lihamba .
I-Liopid Biopsy vs. I-Tissue Biopsy eqhelekileyo-Kutheni i-excit and What Would Look Like?
Usenokuzibuza ukuba kutheni unomdla kakhulu emoyeni ngenxa yokulandela ezinye iintsholongwane kunye ne-biopsies yamanzi.
Siza kubhala uluhlu lwezinto ezinokuba luncedo kunye neempembelelo ezingezantsi, kodwa masiqale siqhathanise umzekelo wendlela umhlaza wemiphunga unokwenziwa ngayo kwaye uphathwe ngayo ngaphandle kokusetyenziswa kwezi biopsi.
Ukuguqulwa Kwingqungquthela Yengqungquthela Yengcinezelo Yomdlavuza?
Khawucinge nje ukuba usandul 'ukuvavanywa ukuba unomdlavuza ongaselula. Ngokuqhelekileyo, ukuxilongwa kwenzelwa ukusetyenziswa kweengqungquthela zomhlaza zesifo somdlavuza kunye nezicubu ezithathwe ngu:
- Inaliti ye-biopsy
- I- endobronchial ultrasound kunye ne-biopsy (inaliti efakwe kwi-tumor nge-tube bronchial ngexesha le-bronchoscopy)
- I-biopsy evulekileyo yomphunga (mhlawumbi i-thoracoscopy, apho isixhobo esicacileyo sifakwe kwiimbobo ezincinci kwisifuba, okanye i-thoracotomy, ebandakanya ukuchithwa kwindonga yesifuba ukufikelela kwimiphunga)
Ezi ndlela zamanje ze-biopsy zonke zinomngcipheko wokusuleleka, ukuphuma kwamanzi, ukuwa kwempompo (pneumothorax), kunye nentlungu.
Emva kokuba izicubu zifunyenwe, zithunyelwa kwi-pathologist ukuba zijonge ngaphantsi kwe-microscope kunye neemvavanyo ezizodwa ezikhangela ukungaqhelekanga kofuzo kwiiseli zesisu. Lo mfuzo (okanye i-molecular) ukufayiliza kuthatha iiveki eziliqela (ngokuphindaphindiweyo ezintlanu ukuya ezintandathu) ngaphambi kokuba iziphumo zifumaneke. Ukuba ukungaqhelekanga kwemfuza (njenge-EGFR mutation) ifunyenwe, unyango lunokuqaliswa ngeziyobisi ezijoliswe kuyo, njenge-tyrosine kinase inhibitor iTarvava (erlotinib.)
Ngendlela yokwenza i-biopsy yamanzi, endaweni yokwenza i-biopsy engavumelekanga njenge-needle biopsy ukufumana izicubu zeprofayili ye-gene (ukuhlolwa komzimba ngokuzenzekelayo ukutshintshwa kwezinto ezimbini uvavanyo oluya ku vavanywa ngoku), i-draw elula yegazi ingenziwa - vavanyo olungaphantsi. Kwaye endaweni yokulinda iiveki kwiziphumo, i-plasma ngokukhawuleza i-genotyping inganika iziphumo malunga neentsuku ezintathu. Ngoko ngexesha lokuxilongwa, izigulane ezinezinguquko ze- EGFR zingenakho ukuguqulwa kwezinto ezingafumananga nje kuphela ngokuvavanywa komncinci ongaphantsi kodwa kungaqaliswa kwonyango ukujongana nokuguqulwa kweentsuku ezimbalwa nje. (Asikabikho ne teknoloji "ukufumana" ezinye izinto ezingafaniyo zofuzo ezifana ne- ALK rearrangements kunye ne- ROS1 rearrangements .)
Unokujonga njani i-Cancer Lung Cancer Change?
Eyona nto inomdla kukuba mhlawumbi iyakwazi ukusebenzisa i-biopsies yamanzi ukubeka iliso abantu abasele baphathwe ngonyango ejolise kuguquko lwe-EGFR.
Ngeli xesha, xa umntu eqaliswa kwi-EGFR inhibitor efana neTarceva, isikolo sesifo sabo sigqitywa ngokwenza ii-CT izicwangciso zokujonga ukukhula kwe-tumor. Siyazi ukuba yonke i-tumor iya kuhlakulela ukunganyangeki kwezi ziyobisi ngexesha, kodwa ixesha lexesha lihluka kakhulu phakathi kwabantu abahlukeneyo. Ungazi njani ukuba ixesha lifikile? Ngokwesiko, sifunda ukuba kwi-tumor iye yaxhatshazwa xa ukukhangela (njenge-CT scan okanye iPET scan) kubonisa ukuba i-tumor isiqalile ukukhula kwakhona. Uninzi lwangethuba (ngaphandle kokuba iimpawu zibonisa ukuba umhlaza unzima kakhulu) izigulane zifunde ukuba iyeza zabo ziyeke ukusebenza xa zifumana iziphumo zokuskena ezibonisa ukuba i-tumor ikhula kwakhona.
Ngaloo xesha, amayeza anqatshelwe kwaye abantu baphinde baqalane nokwenza enye i-biopsy ukuvavanya i-tumor ukujonga utshintsho olwenza lukhuseleke. Njengoko kuphawuliwe ngasentla, ii-biopsies eziqhelekileyo zemiphunga zithatha ingozi yenkqubo enomngcipheko, kwaye kwakhona, kuthatha iiveki kungekho unyango ukwazi iziphumo kwaye uqonde ukuba uya kulandela.
Ngokwahlukileyo, kunye ne-biopsy yamanzi eyenziwe ngezikhathi ezithile, oogqirha babeza kuba nako ukuxelela ngokukhawuleza ukuba i-tumor iye yaxhatshazwa kumachiza. Kufunyenwe kwizifundo ezi zinguqulelo zibonakaliswe kwi-ctNA ngaphambi kokuba utshintsho olunxulumene nokuchasana luboniswe kwi-CT scan. Ngeli xesha lexesha - phakathi kwexesha xa uvavanyo lwegazi lubonisa ukuchasiseka kwaye lufumaneka kwi-CT scan - abantu babeya kusebenzisa iyeza elingahambi kakuhle kwaye lijongane nemiphumo emibi yesilwanyana esingenasidingo. Kwakhona ithetha ixesha elingaphambi kwexesha ngaphambi kokuba litshintshelwe kwiyeza elisebenzayo.
Ngenxa yeziphumo ze-biopsy ezibonisa ukuxhatshazwa, isampuli ye-tumor (ukusuka kwi-biopsy yamanzi) ingahlolwa kwaye isigulane sinokutshintshwa kwiiyeza zenzalo ezilandelayo ezijolise ekutshintsheni kwemfuza okanye mhlawumbi olunye uhlobo lweyeza, ezifana ne- chemotherapy okanye i- immunotherapy .
I-Tumor Heterogenicity kunye ne-Liquid Biopsies
Enye inzuzo enokuthi i-biopsy yamanzi ayinokuba ngaphezu komdlavuza wesifo somdlavuza wempuphu ihambelana nokuxhamla kwe-tumor heterogenicity. Siyazi ukuba umdlavuza wamaphaphu uphezulu, oku kuthetha ukuba iindawo ezihlukileyo zesisu (kunye nezicathulo ezikhethekileyo ezifana nesifo sokuqala kunye ne-metastasis) zinokuthi zihluke kwiimpawu ze-molecular. Ngokomzekelo, ukuguqulwa okwenziwe kwintsholongwane yomhlaza kwisinye isinye se-tumor kungabi khona kwiiseli kwenye inxalenye yesifo. Ukuqonda oku, kunceda ukuqaphela ukuba iidlers zihlala zitshintsha, zivelise iimpawu ezintsha kunye nezinguquko.
I-biopsy yesiqhelo inqamlekile ukuba isampula enye indawo ethile yesikhumba. I-biopsy yamanzi, ngokuchaseneyo, inokuthi ikwazi ukubonakalisa iimpawu ze-tumor ngokubanzi. Oku sele kubonisiwe kwizifundo, apho ukuguqulwa komqhubi onokuthinteka kungafunyanwa ngophawu lwe-biopsy olungenakuphikwa kwi-biopsy yamathambo.
Iingenelelo zoTywala lweMixobo kwiNgqungquthela eNgqungquthelayo
Ukuyiqonda ngokwenene into evuyisayo, kodwa kunye nokukhawulelwa kwamanqaku okubhalwa kwe-biopsy yamanzi, kunokukunceda ukuba uludwele ezinye zeenzuzo kunye nokungahambi kakuhle kwenkqubo.
- Iziphumo ze-biopsy yamanzi zikufutshane "nexesha langempela." Ngamanye amazwi, banokuvumela ukuvavanya kwangaphambili kokusebenza kunye nokuchasana kwesikhumba ngexesha lotyando. Xa i-biopsy yezicubu zenziwe, iziphumo zeprofayili yamathambo (i-gene profiling) kwi-tumor idla iiveki eziliqela (ngokuphindaphindiweyo ukuya ezintlanu ukuya ezintandathu) kanti ukuhlolwa kwemizimba kwimoyi ye-biopsy yamanzi ithatha kuphela iintsuku ezintathu. Eli lixesha apho unyango oluthile lungasetyenziselwa khona okanye ngexesha apho isizukulwana esilandelayo singasetyenziselwa ukuba isiqhumane singasetyenziswa.
- Inkqubo ye-biopsy yamanzi ngokwayo ikhawuleza ngaphezu kwe-biopsy.
- I-biopsi ye-Liquid ayinakuncipha.
- Ezinye izicubu ziindawo ezilukhuni ukufikelela kuzo ukwenza i-biopsy yezicubu eziqhelekileyo.
- Ezinye iimvumi kunye ne-metastases azikho iisampula ezifanelekileyo zokwenza iprofayile yezofuzo-umzekelo, i-boneastases yamathambo
- I-biopsies yamanzi ivumela i-tumor heterogenicity. Njengoko kuphawuliwe ngasentla, amaninzi amathumba aphezulu. I-biopsy yamanzi iyakwazi ukunika iisampuli ithuba lokuba limelele i-tumor ngokubanzi ngokuphambene nesampula eqhelekileyo ye-biopsy eya kuba yimilo kuphela yamaseli kuloo nxalenye ethile ye-tumor.
- Kungenzeka ukuba izakhono ze-biopsy zamanzi ziza kuba zibizi ngaphantsi kunezinto eziqhelekileyo.
- Iimveliso zeengxube zamanzi zineengcipheko ezincinci zeengxaki kunokuba zindlela eziqhelekileyo ze-biopsy, ezifana nomngcipheko wokusuleleka, ukuphaphaka, kunye nokuwa kwempompo (pneumothorax.) Ezi ngxaki aziciphisi kuphela umgangatho wobomi kodwa zingabangela ukulibaziseka kwakhona (kunye nemiphumo yokulibaziseka kunokuthetha ukuqhubela phambili kwesisu.)
- Iimveliso zeengxube zetywala azibuhlungu kakhulu.
- Ukuba i-biopsy imele iphindwe ngokuphindaphindiweyo ngenxa yesikhumba esaneleyo, kulula kakhulu ukuphinda ukudweba kwegazi kunokubuyisela i-biopsy yesiqhelo.
- Ukuphucula isayensi yomhlaza. Ngokuqwalasela iziphumo ze-biopsies zamanzi ezidlulileyo ngokuphindaphindiweyo ngokukhawuleza, abaphandi banokufunda okungakumbi malunga nendlela iimvumi ziguqula ngayo i-genetically over time.
- I-biopsies yamanzi ingathatha ukutshintshwa kwezinto ezilahlekileyo kwiisampuli zenyama.
- Iimvelo ze-liquop - ukuba zibona ukuchaswa kungekudala-zinokukunceda ukukhusela unyango olungadingekile (kunye nayiphi na imiphumo echaphazelekayo ehamba naloo unyango) ngelixa ukhulula ixesha elithile umntu usebenzisa unyango olufanelekileyo.
- I-biopsies yamanzi ingakwazi ukunciphisa ngokwemali inani lemirhumo enikwe ngenxa yemfuno yangoku yokujonga rhoqo ukujonga inkqubela phambili.
Iintsilelo zeLiquid Biopsy
Ngeli xesha, kuninzi ukufunda malunga ne-biopsies yamanzi. Okwamanje banqamle ukujonga ukuguquka kwezinto ezifana nezo-EGFR (nangona bethetha ukuba baya kukwazi ukusetyenziswa ukutshintshwa kwezinto kunye nezinye iinguqulelo). iintlobo zesifo somhlaza wamaphaphu, ukusasazwa kweeseli zomhlaza okanye umhlaza wesibeleko i-DNA ibonakala kuphela kwinani elincinci lomdlavuza wamaphaphu kwaye ithonyelwe uhlobo kunye nesigaba somhlaza. Isiphumo esibi kwi-biopsy yamanzi ayithethi ukuba umhlaza awukho emzimbeni.
Isimo samanje se-Liquid Biopsies ye-Cancer Cancer
I-biopsies yamanzi isetyenziselwa ngokuyinhloko uphando e-United States, nangona ezinye i-oncologists zisetyenziselwa ukuba zibone okanye zijonge izigulane ngeenguqu ze-EGFR. Okokuthi, ukuhlolwa kwe-biopsy yamanzi - uvavanyo lokuqala lohlobo lomdlavuza wamaphaphu - luvunyiwe ngoJuni 1, 2016, ukuvavanya utshintsho lwe-EGFR kwizigulane ezinomdlavuza ongaselula.
Ubuncinane esisinye isikhungo somhlaza somhlaza ngoku sinika uvavanyo kunye kunye ne-plasma ngokukhawuleza kwimizimba yazo zonke izigulane ezinomdlavuza ongasetyenzana wesifo samaphaphu ngexesha lokuxilongwa okanye emva kokuphindaphinda / ukuphindaphinda komdlavuza wamaphaphu .
EYurophu, ngoku kusetyenziselwa abantu abanomdlavuza ongasetyenzana wesifo somhlaza ukuze bahlalutye ukuguquguquka kwe-EGFR kwaye kubonwa njengimfuneko ukuba banqume ukuba ngaba ngabaviwa baphathwe ngonyango lwe-tyrosine kinase inhibitor.
Yintoni Esibambe Ngayo?
Kudideka xa ufunda malunga ne-biopsies yamanzi, ngesizathu sokuba le nkqubo ingenziwanga ngokubanzi. Into esingaziyo yindlela indlela i-biopsies yamanzi ezalisekisa ngayo imfuno ezimbini: ukuchaneka nokuthembeka. Kufuneka kuqinisekiswe ukuba i-biopsies yamanzi inganika ulwazi olufanayo (okanye bhetele) kunezinto ze-biopsies zenyama kunye kwaye ihlawule rhoqo loo ngcaciso.
Ngelixa elizayo
Kunzima ukwazi ngokuthe ngqo ukuba ubuchule be-biopsies yamanzi bubangakanani kweli nqanaba lophando kuba bebantsha. Ekugqibeleni, ithemba ukuba lobu buchule bungayi kunceda ekuqikeleleni ukugxekwa nokubeka iliso ekumanyeni kodwa njengesixhobo sokuhlola ukufumana umdlavuza - nangona kunjalo kusekho iindlela. Ngenye indlela, yinto enomdla wokwenza uphando lomhlaza ngexesha lokuchaneka kweyeza.
Imithombo:
Bettegowda, C., Sausen, M., Leary, R. et al. Ukufumanisa ukujikeleza kwe-DNA ye-tumor ekuqaleni kwexesha kunye nexesha elide lokuhlambalaza abantu. Inzululwazi yokuguqulela isayensi
Imamura, F., Uchida, J., Kukita, Y. et al. Ukubeka iliso kwiimpendulo zonyango kunye nokuveliswa kwee-cell tumors ngokujikeleza i-DNA ye-tumor ye-gene e-mutant EGFR enomdla kumdlavuza wamaphaphu. Cancer Lung . 2016. 94: 68-73.
Jiang, T., Ren, S., noC. Zhou. Inxaxheba yokuhlalutya kwe-DNA ukujikeleza kwe-DNA kwi-cell cell. Cancer Lung . 2015. 90 (2): 128-34.
Karachaliou, N., Mayo-de-las-Casas, C., Molina-Vila, M. et al. I-real-time liquid biopsies ibe yinyani ekwenzeni unyango lomhlaza. Iingxelo zeMicrosoft Medicine . 2015. 3 (3): 36.
Mahaswaran, S., Sequist, L., Nagrath, S. et al. Ukutholwa kweenguqu kwi-EGFR ekujikelezeni iiseli zomhlaza wamaphaphu. I-New England Journal of Medicine . 2008. 359 (4): 366-77.
Sacher, A., Paweletz, C., Dahlberg, S. et al. Ukuqinisekiswa okuqinisekileyo kwe-Rapid Plasma Genotyping yokuThola i-EGFR kunye ne-KRAS Intlashwano kwi-Cancer Advanced Lung Cancer. JAMA Oncology . Ishicilelwe ngo-Apreli 7, 2016.
Santarpia, M., Karachaliou, N., Gonzalez-Cao, M. et al. Ukufumaneka kwe-cell-free free circulation of tumor Testing DNA yomdlavuza wamaphaphu. Biomarkers kwiMida . 2016. 10 (4): 417-30.