izindaba

Kule minyaka eyishumi edlule, ubuchwepheshe bokulandelana kwezakhi zofuzo buye basetshenziswa kabanzi ocwaningweni lomdlavuza nasezifundweni zomtholampilo, baba ithuluzi elibalulekile lokuveza izici zamangqamuzana omdlavuza. Intuthuko ekuxilongweni kwamangqamuzana nokwelashwa okuqondiwe kuye kwakhuthaza ukuthuthukiswa kwemiqondo yokwelapha ngokunemba kwesimila futhi kwaletha izinguquko ezinkulu kuwo wonke umkhakha wokuxilongwa nokwelashwa kwesimila. Ukuhlolwa kwezakhi zofuzo kungasetshenziswa ukuxwayisa ingozi yomdlavuza, ukuqondisa izinqumo zokwelashwa kanye nokuhlola ukubikezela, futhi kuyithuluzi elibalulekile lokuthuthukisa imiphumela yomtholampilo yesiguli. Lapha, sifingqa izindatshana zakamuva ezishicilelwe ku-CA Cancer J Clin, JCO, Ann Oncol namanye amajenali ukuze sibuyekeze ukusetshenziswa kokuhlolwa kofuzo ekuxilongweni nasekulapheni umdlavuza.

Ukuguqulwa kwe-Somatic kanye nokuguqulwa kwamagciwane. Ngokuvamile, umdlavuza ubangelwa ukuguqulwa kwe-DNA okungatholakala kubazali (ukuguqulwa kwegciwane) noma kutholwe ngeminyaka yobudala (ukuguqulwa kwe-somatic). Ukuguqulwa komugqa wamagciwane kukhona kusukela ekuzalweni, futhi i-mutor ngokuvamile ithwala ukuguqulwa ku-DNA yawo wonke amaseli emzimbeni futhi ingadluliselwa enzalweni. Ukuguqulwa kwe-Somatic kutholwa abantu ngabanye kumaseli angewona wegeyimu futhi ngokuvamile awadluliselwa enzalweni. Kokubili ukuguqulwa kwe-germline kanye ne-somatic kungabhubhisa umsebenzi ojwayelekile wokusebenza kwamaseli futhi kuholele ekuguqulweni okubi kwamaseli. Ukuguqulwa kwe-Somatic kungumshayeli oyinhloko we-malignancy kanye ne-biomarker ebikezela kakhulu ku-oncology; Nokho, cishe amaphesenti angu-10 kuya kwangu-20 eziguli zesimila athwala ukuguqulwa kwegciwane okwandisa kakhulu ingozi yomdlavuza, futhi ezinye zalezi zinguquko ziwukwelapha.
Ukushintshashintsha komshayeli kanye nokuguqulwa kwabagibeli. Akuzona zonke izinhlobo ze-DNA ezithinta ukusebenza kwamaseli; ngokwesilinganiso, kuthatha izenzakalo ezinhlanu kuya kweziyishumi ze-genomic, ezaziwa ngokuthi “ukuguqulwa komshayeli,” ukuze kuqalise ukonakala kwamaseli okuvamile. Ukuguqulwa komshayeli kuvame ukwenzeka ezakhini zofuzo ezihlobene eduze nemisebenzi yokuphila kwamangqamuzana, njengezakhi zofuzo ezihilelekile ekulawuleni ukukhula kwamangqamuzana, ukulungiswa kwe-DNA, ukulawulwa komjikelezo wamangqamuzana nezinye izinqubo zokuphila, futhi zinamandla okusetshenziswa njengezinhloso zokwelapha. Kodwa-ke, inani eliphelele lezinguquko kunoma yimuphi umdlavuza likhulu impela, lisuka ezinkulungwaneni ezimbalwa kweminye imidlavuza yebele kuya kweziyi-100,000 kweminye imidlavuza ye-colorectal ne-endometrial eguquguquka kakhulu. Ukuguqulwa okuningi akunakho noma okulinganiselwe ukubaluleka kwebhayoloji, noma ngabe ukuguqulwa kwenzeka endaweni yokubhala amakhodi, izehlakalo zokuguquka ezingabalulekile ezinjalo zibizwa ngokuthi “ukuguqulwa kwabagibeli”. Uma okuhlukile kofuzo ohlotsheni oluthile lwesimila kubikezela impendulo yaso noma ukumelana nokwelashwa, okuhlukile kuthathwa njengokusebenza ngokomtholampilo.
Ama-oncogenes kanye nama-tumor suppressor genes. Izakhi zofuzo ezivame ukuguqulwa kumdlavuza zingahlukaniswa cishe izigaba ezimbili, i-oncogenes kanye ne-tumor suppressor gene. Kumaseli ajwayelekile, iphrotheni efakwe ama-oncogenes ikakhulukazi idlala indima yokukhuthaza ukwanda kwamaseli kanye nokuvimbela i-apoptosis yamaseli, kuyilapho iphrotheni efakwe ngekhodi izakhi zofuzo ze-oncosuppressor ikakhulukazi inesibopho sokulawula kabi ukuhlukaniswa kwamaseli ukuze kugcinwe ukusebenza kwamaseli okuvamile. Enqubweni yoguquko olubi, ukuguqulwa kwe-genomic kuholela ekuthuthukisweni komsebenzi we-oncogene kanye nokuncipha noma ukulahlekelwa komsebenzi we-oncosuppressor gene.
Ukuhluka okuncane nokuhlukahluka kwesakhiwo. Lezi yizinhlobo ezimbili eziyinhloko zoguquko ku-genome. Izinhlobonhlobo ezincane zishintsha i-DNA ngokushintsha, ukususa, noma ukwengeza inani elincane lezisekelo, okuhlanganisa ukufakwa kwesisekelo, ukususwa, uhlaka, ukulahlekelwa kokuqala kwekhodoni, ukumisa ukuguqulwa kokulahlekelwa kwe-codon, njll. Ukuhluka kwesakhiwo kuwukuhlelwa kabusha kwe-genome enkulu, okubandakanya amasegimenti ofuzo asuka kusayizi osuka ezinkulungwaneni ezimbalwa zezisekelo kuya kuningi le-chromosome ye-chromosome, okuhlanganisa izinguquko ze-chromosome, ukukopisha ukuguqulwa noma ukudluliselwa. Lokhu kuguqulwa kungase kubangele ukuncipha noma ukuthuthukiswa komsebenzi wamaprotheni. Ngaphezu kwezinguquko ezingeni lezakhi zofuzo zomuntu ngamunye, amasignesha e-genomic nawo ayingxenye yemibiko yokulandelana komtholampilo. Amasiginesha e-Genomic angabonwa njengamaphethini ayinkimbinkimbi wokuhluka okuncane kanye/noma kwesakhiwo, okuhlanganisa umthwalo wokuguqulwa kwesimila (TMB), ukungasebenzi kahle kwe-microsatellite (MSI), kanye nokukhubazeka kokuhlanganisa kabusha kwe-homologous.

Ukuguqulwa kwe-Clonal kanye nokuguqulwa kwe-subclonal. Ukuguqulwa kwe-clonal kukhona kuwo wonke amaseli e-tumor, akhona ekuxilongweni, futhi ahlala ekhona ngemva kokuthuthuka kokwelashwa. Ngakho-ke, ukuguqulwa kwe-clonal kunamandla okusetshenziswa njengezinhloso zokwelapha isimila. Ukuguqulwa kwe-subclonal kukhona kuphela ku-subset yamangqamuzana omdlavuza futhi kungase kutholakale ekuqaleni kokuxilongwa, kodwa zinyamalale ngokuphindaphinda okulandelayo noma zivele kuphela ngemva kokwelashwa. I-Cancer heterogeneity ibhekisela ekubeni khona kwezinguquko eziningi ze-subclonal kumdlavuza owodwa. Ngokuphawulekayo, iningi lezinguquko ezibalulekile emtholampilo kuzo zonke izinhlobo zomdlavuza ezivamile ukuguqulwa kwama-clonal futhi zihlala zizinzile phakathi nokuqhubeka komdlavuza. Ukumelana, okuvame ukulamula ama-subclones, kungase kungatholakali ngesikhathi sokuxilongwa kodwa kubonakala uma kuphinda kubuyela emuva ngemva kokwelashwa.

Indlela evamile ye-FISH noma i-karyotype yeseli isetshenziselwa ukuthola izinguquko ezingeni le-chromosomal. I-FISH ingasetshenziswa ukuze kutholwe ukuhlanganiswa kwezakhi zofuzo, ukususwa, nokukhulisa, futhi ibhekwa “njengezinga eligolide” lokuthola okuhlukile okunjalo, ngokunemba okuphezulu nokuzwela kodwa ukuphumela okulinganiselwe. Kwezinye izifo ze-hematological, ikakhulukazi i-acute leukemia, i-karyotyping isasetshenziswa ukuqondisa ukuxilongwa kanye nokubikezela, kodwa le ndlela kancane kancane ithathelwa indawo ukuhlolwa kwamangqamuzana okuhlosiwe okufana ne-FISH, WGS, ne-NGS.
Izinguquko kuzakhi zofuzo ezingazodwana zingatholwa yi-PCR, kokubili i-PCR yesikhathi sangempela kanye ne-digital drop PCR. Lawa masu azwela kakhulu, afaneleka ngokukhethekile ukutholwa nokuqapha izilonda ezincane ezinsalela, futhi angathola imiphumela ngesikhathi esifushane kakhulu, okubi ukuthi ububanzi bokubona bunomkhawulo (ngokuvamile kuthola kuphela ukuguqulwa kofuzo olulodwa noma ezimbalwa), kanye nekhono lokuhlola okuningi lilinganiselwe.
I-Immunohistochemistry (IHC) iyithuluzi lokuqapha elisekelwe kumaprotheni elivame ukusetshenziselwa ukuthola ukuvezwa kwama-biomarker afana ne-ERBB2 (HER2) nama-estrogen receptors. I-IHC ingase futhi isetshenziselwe ukuthola amaprotheni athile aguquliwe (njenge-BRAF V600E) kanye nokuhlanganiswa kwezakhi zofuzo ezithile (njengokuhlanganiswa kwe-ALK). Inzuzo ye-IHC yukuthi ingahlanganiswa kalula nenqubo yokuhlaziya izicubu, ngakho-ke ingahlanganiswa nezinye izivivinyo. Ngaphezu kwalokho, i-IHC ingahlinzeka ngolwazi mayelana nokwenza kwasendaweni kwamaprotheni angaphansi kwamaselula. Okubi ukuscalability okulinganiselwe kanye nezidingo eziphezulu zenhlangano.
Ukulandelana kwesizukulwane sesibili (NGS) I-NGS isebenzisa amasu okulandelana okuhamba phambili kwe-high-throughput ukuze kutholwe ukuhluka ku-DNA kanye/noma ileveli ye-RNA. Le nqubo ingasetshenziswa ukulandelana kokubili i-genome (WGS) kanye nezifunda zofuzo ezithakaselwayo. I-WGS ihlinzeka ngolwazi olubanzi kakhulu lokuguqulwa kwe-genomic, kodwa kunezithiyo eziningi ekusetshenzisweni kwayo emtholampilo, okuhlanganisa isidingo samasampula ezicubu zesimila esisha (i-WGS ayikakulungeli ukuhlaziya amasampula angasebenzi kahle) kanye nezindleko eziphezulu.
Ukulandelana kwe-NGS okuhlosiwe kufaka phakathi ukulandelana okuphelele kwe-exon kanye nephaneli yofuzo eqondiwe. Lezi zivivinyo zinothisa izifunda ezithakaselwayo ngama-DNA probes noma i-PCR amplification, ngaleyo ndlela kunciphisa inani lokulandelana elidingekayo (yonke i-exome yenza amaphesenti angu-1 kuya kwangu-2 we-genome, ngisho namaphaneli amakhulu aqukethe izakhi zofuzo ezingu-500 akha amaphesenti angu-0.1 kuphela we-genome). Nakuba ukulandelana okuphelele kwe-exon kusebenza kahle ezicutshini ezilungisiwe ze-formalin, izindleko zayo zihlala ziphezulu. Izinhlanganisela zofuzo eziqondiwe ziyonga kakhulu futhi zivumela ukuguquguquka ekukhetheni izakhi zofuzo okufanele zihlolwe. Ngaphezu kwalokho, i-DNA yamahhala ejikelezayo (cfDNA) ivela njengendlela entsha yokuhlaziya i-genomic yeziguli ezinomdlavuza, eyaziwa ngokuthi i-liquid biopsies. Womabili amangqamuzana omdlavuza namaseli avamile angakhulula i-DNA egazini, futhi i-DNA echithwa kumangqamuzana omdlavuza ibizwa ngokuthi i-circulating tumor DNA (ctDNA), engahlaziywa ukuze kutholwe uguquko olungase lube khona kumaseli wesimila.
Ukukhethwa kokuhlolwa kuncike enkingeni ethile yomtholampilo okufanele kubhekwane nayo. Iningi lama-biomarker ahlobene nemithi yokwelapha egunyaziwe ingatholwa ngamasu e-FISH, IHC, kanye ne-PCR. Lezi zindlela zinengqondo ukuze kutholwe amanani amancane ama-biomarker, kodwa azithuthukisi ukusebenza kahle kokutholwa ngokukhuphuka komthamo, futhi uma kutholwa izimpawu ze-biomarker eziningi, kungase kungabi nezicubu ezanele zokutholwa. Kweminye imidlavuza ethile, njengomdlavuza wamaphaphu, lapho amasampula ezicubu okunzima ukuwathola futhi kunezimpawu eziningi ze-biomarker okufanele zihlolwe, ukusebenzisa i-NGS kuyisinqumo esingcono. Sengiphetha, ukukhetha kokuhlolwa kuncike enanini lama-biomarker okufanele ahlolwe isiguli ngasinye kanye nenani leziguli ezizohlolelwa i-biomarker. Kwezinye izimo, ukusetshenziswa kwe-IHC/FISH kwanele, ikakhulukazi lapho okuhlosiwe kukhonjwe, njengokutholwa kwama-estrogen receptors, ama-progesterone receptors, kanye ne-ERBB2 ezigulini zomdlavuza webele. Uma kudingeka ukuhlola okuphelele kokuguquguquka kwe-genomic kanye nosesho lwezinjongo zokwelapha ezingase zibe khona, i-NGS ihleleka kakhulu futhi iyonga kakhulu. Ngaphezu kwalokho, i-NGS ingacatshangelwa ezimeni lapho imiphumela ye-IHC/FISH ingaqondakali noma ingahlangani.

Iziqondiso ezahlukene zinikeza isiqondiso sokuthi yiziphi iziguli okufanele zifanelekele ukuhlolwa kofuzo. Ngo-2020, i-ESMO Precision Medicine Working Group yakhipha izincomo zokuqala zokuhlola i-NGS ezigulini ezinomdlavuza othuthukile, incoma ukuhlolwa kwe-NGS okujwayelekile komdlavuza wamaphaphu ongewona omncane we-squamous, umdlavuza we-prostate, umdlavuza we-colorectal, umdlavuza we-bile duct, namasampula omdlavuza we-ovarian, kwathi ngo-2024, i-ESMO yabuyekezwa ngalesi sisekelo somdlavuza webele, incoma umdlavuza webele. Okufana nezimila ze-stromal zamathumbu, ama-sarcomas, umdlavuza wegilo kanye nomdlavuza ongaziwa.
Ngo-2022, i-ASCO's Clinical Opinion ekuhlolweni kwe-somatic genome ezigulini ezinomdlavuza we-metastatic noma othuthukisiwe ithi uma ukwelashwa okuhlobene ne-biomarker kuvunywa ezigulini ezine-metastatic noma izimila eziqinile ezithuthukile, ukuhlolwa kofuzo kuyanconywa kulezi ziguli. Isibonelo, ukuhlolwa kwe-genomic kufanele kwenziwe ezigulini ezine-melanoma ye-metastatic ukuze kuhlolwe ukuguqulwa kokuguqulwa kwe-BRAF V600E, njengoba i-RAF ne-MEK inhibitor igunyazelwe lesi sibonakaliso. Ukwengeza, ukuhlolwa kofuzo kufanele futhi kwenziwe uma kunophawu olucacile lokungazweli ukuze umuthi unikezwe isiguli. I-Egfrmab, isibonelo, ayisebenzi kumdlavuza we-colorectal oguquguqukayo we-KRAS. Lapho kucutshungulwa ukufaneleka kwesiguli ukulandelana kwezakhi zofuzo, isimo somzimba wesiguli, ukuhlangana okuhambisanayo, kanye nesiteji sesimila kufanele kuhlanganiswe, ngoba uchungechunge lwezinyathelo ezidingekayo ngokulandelana kwe-genome, okuhlanganisa imvume yesiguli, ukucubungula elabhorethri, nokuhlaziywa kwemiphumela yokulandelana, kudinga isiguli ukuba sibe namandla anele omzimba neminyaka yokuphila.
Ngaphezu kokuguqulwa kwe-somatic, eminye imidlavuza kufanele futhi ihlolwe izakhi zofuzo zegciwane. Ukuhlolwa kokuguqulwa komugqa wamagciwane kungase kube nomthelela ezinqumweni zokwelashwa zomdlavuza ezifana nokuguqulwa kwe-BRCA1 kanye ne-BRCA2 kumabele, ama-ovarian, i-prostate, kanye nomdlavuza we-pancreatic. Ukuguqulwa kwe-germline kungase kube nomthelela ekuhlolweni komdlavuza esikhathini esizayo kanye nokuvinjelwa ezigulini. Iziguli okungenzeka zifanelekele ukuhlolelwa ukuguqulwa kwamagciwane zidinga ukuhlangabezana nezimo ezithile, ezibandakanya izici ezifana nomlando womndeni womdlavuza, iminyaka yokuxilongwa, kanye nohlobo lomdlavuza. Kodwa-ke, iziguli eziningi (ezifika ku-50%) eziphethe izinguquko ze-pathogenic emugqeni wegciwane azihlangabezani nenqubo evamile yokuhlola ukuguqulwa komugqa wamagciwane ngokusekelwe emlandweni womndeni. Ngakho-ke, ukuze kwandiswe ukuhlonza abathwali bokuguquguquka, i-National Comprehensive Cancer Network (NCCN) incoma ukuthi zonke noma iningi leziguli ezinomdlavuza webele, wesibeletho, i-endometrial, pancreatic, colorectal, noma i-prostate zihlolelwe ukuguqulwa komugqa wamagciwane.
Mayelana nesikhathi sokuhlolwa kwezakhi zofuzo, ngenxa yokuthi iningi lezinguquko ezibalulekile emtholampilo zingu-clonal futhi azinzile ngesikhathi sokuqhubeka komdlavuza, kunengqondo ukuhlola izakhi zofuzo ezigulini ngesikhathi sokutholakala komdlavuza osezingeni eliphezulu. Ekuhlolweni kofuzo okulandelayo, ikakhulukazi ngemva kokwelashwa okuqondiswe kumangqamuzana, ukuhlolwa kwe-ctDNA kunenzuzo kakhulu kune-DNA yezicubu zesimila, ngoba i-DNA yegazi ingaqukatha i-DNA evela kuzo zonke izilonda zesimila, esiza kakhulu ekutholeni ulwazi mayelana ne-tumor heterogeneity.
Ukuhlaziywa kwe-ctDNA ngemva kokwelashwa kungase kukwazi ukubikezela impendulo yesimila ekwelapheni futhi kuhlonzwe ukuqhubeka kwesifo ngaphambi kwezindlela ezijwayelekile zokucabanga. Kodwa-ke, izivumelwano zokusebenzisa le datha ukuze ziqondise izinqumo zokwelashwa azikasungulwa, futhi ukuhlaziywa kwe-ctDNA akunconyiwe ngaphandle kwalapho ekuhlolweni komtholampilo. I-ctDNA ingase futhi isetshenziselwe ukuhlola izilonda ezincane ezinsalela ngemva kokuhlinzwa kwesimila esikhulu. Ukuhlolwa kwe-ctDNA ngemva kokuhlinzwa kuwukubikezela okunamandla kokuqhubeka kwesifo okulandelayo futhi kungasiza ekunqumeni ukuthi isiguli sizozuza yini ku-adjuvant chemotherapy, kodwa namanje akunconywa ukusebenzisa i-ctDNA ngaphandle kokuhlolwa komtholampilo ukuze kuqondiswe izinqumo ze-adjuvant chemotherapy.

Ukucubungula idatha Isinyathelo sokuqala sokulandelana kwe-genome ukukhipha i-DNA kumasampula esiguli, ukulungisa imitapo yolwazi, futhi kukhiqizwe idatha yokulandelana engahluziwe. Idatha eluhlaza idinga ukucutshungulwa okwengeziwe, okuhlanganisa ukuhlunga idatha yekhwalithi ephansi, ukuyiqhathanisa ne-reference genome, ukuhlonza izinhlobo ezahlukene zokuguqulwa ngokusebenzisa ama-algorithms ahlukene okuhlaziya, ukucacisa umthelela walokhu kuguqulwa ekuhumusheni amaprotheni, nokuhlunga ukuguqulwa komugqa wamagciwane.
Isichasiselo sofuzo lomshayeli siklanyelwe ukuhlukanisa ukuguqulwa komshayeli nabagibeli. Ukuguqulwa komshayeli kuholela ekulahlekelweni noma ekuthuthukisweni komsebenzi wofuzo wokucindezela isimila. Izinhlobonhlobo ezincane eziholela ekwenziweni kusebenze kwezakhi zofuzo ezicindezela isimila zifaka ukuguqulwa okungenangqondo, ukuguqulwa kwe-frameshift, nokuguqulwa kwesayithi lokuxhumanisa okubalulekile, kanye nokususwa kwekhodoni kokuqala okungajwayelekile, ukususwa kokumisa i-codon, kanye noguquko olubanzi lokufakwa/ukususwa kwe-intron. Ukwengeza, ukuguqulwa kwe-missense kanye nokuguqulwa kwe-intron encane / ukususwa kungaholela ekulahlekelweni komsebenzi wofuzo we-tumor suppressor uma kuthinta izizinda ezibalulekile zokusebenza. Izinhlobonhlobo zesakhiwo eziholela ekulahlekelweni komsebenzi wofuzo ocindezela isimila zihlanganisa ukususwa kofuzo okuyingxenye noma okuphelele nokunye okuhlukile kwe-genomic okuholela ekubhujisweni kohlaka lokufunda lofuzo. Okuhlukile okuncane okuholela ekusebenzeni okuthuthukisiwe kwama-oncogenes kufaka phakathi ukuguqulwa kwe-missense kanye nokufakwa/ukususwa kwe-intron ngezikhathi ezithile okuqondise ezizindeni ezisebenzayo zamaphrotheni. Ezimweni ezingavamile, ukuncishiswa kwamaprotheni noma ukuguqulwa kwesayithi okuhlanganisa kungaholela ekusebenziseni ama-oncogenes. Ukwehluka kwesakhiwo okuholela ekusebenzeni kwe-oncogene kufaka phakathi ukuhlanganiswa kwezakhi zofuzo, ukususwa kwezakhi zofuzo, nokuphindaphinda ufuzo.
Ukuhumusha ngokomtholampilo kokuhlukahluka kwe-genomic kuhlola ukubaluleka komtholampilo kokuguqulwa kwezakhi zofuzo ezikhonjiwe, okungukuthi inani lazo lokuxilonga, ukubikezela, noma ukwelashwa okungaba khona. Kunezinhlelo ezimbalwa zokugreda ezisekelwe ebufakazini ezingasetshenziswa ukuze ziqondise ukuchazwa komtholampilo kokuhlukahluka kwe-genomic.
I-Memorial Sloan-Kettering Cancer Center's Precision Medicine Oncology Database (OncoKB) ihlukanisa izakhi zofuzo zibe amazinga amane ngokusekelwe enanini lazo eliqagelayo lokusetshenziswa kwezidakamizwa: Izinga 1/2, ama-biomarker avunyelwe yi-FDA, noma ama-biomarker ajwayelekile emtholampilo abikezela impendulo yenkomba ethile emthini ogunyaziwe; Izinga lesi-3, ama-biomarker agunyazwe yi-FDA noma angagunyaziwe abikezela impendulo emishanguzweni eqondiswe inoveli ebonise isithembiso esivivinyweni somtholampilo, kanye ne-Level 4, ama-biomarker angavunyelwe yi-FDA abikezela impendulo emishanguzweni eqondiswe inoveli ebonise ubufakazi bebhayoloji obukholisayo ezivivinyweni zomtholampilo. Iqembu elincane lesihlanu elihlobene nokungazweli ekwelashweni lanezelwa.
I-American Society for Molecular Pathology (AMP)/American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) imihlahlandlela yokuchazwa kokuhlukahluka kwe-somatic ihlukanisa ukuhluka kwe-somatic ibe yizigaba ezine: IBanga I, elinokubaluleka okuqinile komtholampilo; IBanga lesi-II, elinokubaluleka komtholampilo okungenzeka; IBanga lesi-III, ukubaluleka komtholampilo akwaziwa; IBanga IV, elingaziwa njengelibalulekile emtholampilo. Okuhlukile kwebanga I kanye no-II kuphela okubalulekile ezinqumweni zokwelashwa.
I-ESMO's Molecular Target Clinical Operability Scale (ESCAT) ihlukanisa izakhi zofuzo zibe amazinga ayisithupha: Izinga I, okuhlosiwe okufanele ukusetshenziswa okujwayelekile; Isigaba II, okuhlosiwe okusacutshungulwa, kungenzeka sisetshenziselwe ukuhlola inani leziguli ezingazuza emthini oqondiwe, kodwa idatha eyengeziwe iyadingeka ukuze kusekelwe. Ibanga lesi-III, izakhi zofuzo ezihlosiwe eziye zabonisa inzuzo yomtholampilo kwezinye izinhlobo zomdlavuza; IBanga lesi-IV, izakhi zofuzo ezihlosiwe kuphela ezisekelwa ubufakazi bangaphambi komtholampilo; Ebangeni V, kunobufakazi obusekela ukubaluleka komtholampilo kokukhomba ukuguqulwa kwezakhi zofuzo, kodwa ukwelashwa komuthi owodwa ngokumelene nalokho okuhlosiwe akukweluleki ukusinda, noma isu lokwelapha elihlanganisiwe lingatholwa; IBanga X, ukuntuleka kwenani lomtholampilo.