nkhani

Pakafukufuku wa oncology, njira zapawiri, monga kupulumuka kwaulere (PFS) ndi kupulumuka kopanda matenda (DFS), zikulowa m'malo mwachikhalidwe cha kupulumuka kwapang'onopang'ono (OS) ndipo zakhala maziko oyeserera kuvomerezedwa ndi mankhwala ndi US Food and Drug Administration (FDA) ndi European Medicines Agency (EMA). Njirazi zimathandizira kuyeserera kwachipatala ndikuchepetsa ndalama pophatikiza zochitika zingapo (mwachitsanzo, kukula kwa chotupa, matenda atsopano, imfa, ndi zina zotero) kukhala gawo limodzi lomaliza, koma zimabweretsanso zovuta.

Kusintha kwa mapeto a mayesero a zachipatala a antitumor

M'zaka za m'ma 1970, a FDA adagwiritsa ntchito chiwongola dzanja (ORR) povomereza mankhwala a khansa. Sizinafike mpaka zaka za m'ma 1980 pomwe Komiti ya Oncology Drug Advisory Committee (ODAC) ndi FDA idazindikira kuti kusintha kwa moyo, moyo wabwino, magwiridwe antchito a thupi, ndi zotupa zokhudzana ndi chotupa sizinali zogwirizana ndi kulumikizana kwa ORR. M'mayesero azachipatala a oncology, OS ndiye mathero abwinoko azachipatala kuti athe kuyeza phindu lachipatala mwachindunji. Komabe, ORR imakhalabe njira ina yodziwika bwino yopezera chithandizo mukaganizira kuvomerezedwa kwamankhwala a khansa. M'mayesero a mkono umodzi mwa odwala omwe ali ndi zotupa zotupa, ORR imawonedwanso ngati gawo loyamba lachipatala.

Pakati pa 1990 ndi 1999, 30 peresenti ya mayesero a khansa omwe adavomerezedwa ndi FDA adagwiritsa ntchito OS monga mathero achipatala. Monga momwe njira zochiritsira zomwe zimapangidwira zasintha, mapeto oyambirira achipatala omwe amagwiritsidwa ntchito poyesa mankhwala oletsa khansa asinthanso. Pakati pa 2006 ndi 2011, chiwerengerochi chinatsika kufika pa 14.5 peresenti. Pamene chiwerengero cha mayesero a zachipatala ndi OS monga mapeto oyambirira achepa, kugwiritsa ntchito mapeto ophatikizika monga PFS ndi DFS kwakhala kawirikawiri. Ndalama ndi zovuta za nthawi zikuyendetsa kusinthaku, chifukwa OS imafuna mayesero aatali komanso odwala ambiri kuposa PFS ndi DFS. Pakati pa 2010 ndi 2020, 42% yamayesero oyendetsedwa mwachisawawa (RCTS) mu oncology ali ndi PFS ngati mathero awo oyamba. 67% ya mankhwala odana ndi chotupa omwe amavomerezedwa ndi FDA pakati pa 2008 ndi 2012 adachokera ku mapeto ena, 31% omwe adachokera ku PFS kapena DFS. A FDA tsopano akuzindikira ubwino wachipatala wa DFS ndi PFS ndipo amalola kuti agwiritsidwe ntchito ngati mapeto oyambirira pamayesero ofuna kuvomerezedwa ndi malamulo. A FDA adalengezanso kuti PFS ndi njira zina zomaliza zitha kugwiritsidwa ntchito kufulumizitsa kuvomereza kwamankhwala a matenda oopsa kapena owopsa.

Ma endpoints adzasintha osati kokha pamene mankhwala atsopano akupangidwa, komanso momwe kulingalira ndi njira zoyezera ma laboratories zikuyenda bwino. Izi zikuwonetseredwa ndi kusinthidwa kwa njira za World Health Organisation (WHO) ndi mfundo za RECIST za Kuwunika Kuchita Bwino mu Zotupa Zolimba (RECIST). Pamene madokotala amaphunzira zambiri za zotupa, odwala omwe amawaona ngati okhazikika amatha kupezeka kuti ali ndi micrometastases m'tsogolomu. M'tsogolomu, malekezero ena sangagwiritsidwenso ntchito, ndipo mathero atsopano angawonekere kuti afulumizitse kuvomereza mankhwala. Kuwonjezeka kwa immunotherapy, mwachitsanzo, kwachititsa kuti pakhale ndondomeko zatsopano zowunika monga irRECIST ndi iRECIST.

Composite pomaliza mwachidule

Mapeto ophatikizika amagwiritsidwa ntchito kwambiri m'maphunziro azachipatala, makamaka mu oncology ndi mtima. Mapeto ophatikizika amawongolera mphamvu zowerengera powonjezera kuchuluka kwa zochitika, kuchepetsa kukula kwachitsanzo chofunikira, nthawi yotsatila, ndi ndalama.
Mapeto omwe amagwiritsidwa ntchito kwambiri pazamtima ndizochitika zazikulu zoyipa zamtima (MACE). Mu oncology, PFS ndi DFS nthawi zambiri amagwiritsidwa ntchito ngati ma proxies for general Survival (OS). PFS imatanthauzidwa ngati nthawi yochokera ku randomisation kupita ku matenda kapena imfa. Kukula kwa chotupa cholimba kumatanthauzidwa motsatira malangizo a RECIST 1.1, kuphatikiza kukhalapo kwa zotupa zatsopano komanso kukulitsa zotupa zomwe mukufuna. Kupulumuka kopanda zochitika (EFS), DFS, ndi relapse-free survival (RFS) ndizonso zomaliza zophatikizika. EFS imagwiritsidwa ntchito m'mayesero a neoadjuvant therapy, ndipo DFS imagwiritsidwa ntchito m'maphunziro azachipatala a adjuvant therapy.

Zotsatira zosiyana muzochiritsira zosiyanasiyana pa mapeto apawiri

Kupereka lipoti zotsatira zophatikizika kungapangitsenso kuganiza kuti chithandizo chamankhwala chimagwira ntchito pagawo lililonse, zomwe sizowona kwenikweni. Lingaliro lofunika kwambiri pakugwiritsa ntchito mapeto ophatikizana ndilokuti mankhwalawa adzasintha zigawozo mofanana. Komabe, zotsatira za chithandizo cha antitumor pazosintha monga kukula kwa chotupa, metastasis, ndi kufa nthawi zina zimapita kwina. Mwachitsanzo, mankhwala oopsa kwambiri amatha kuchepetsa kufalikira kwa chotupa koma kumawonjezera kufa. Izi zinali choncho mu kuyesa kwa BELLINI kwa odwala omwe ali ndi myeloma yobwereranso / kukana, pomwe PFS idakula koma OS inali yotsika chifukwa cha kuchuluka kwa matenda okhudzana ndi chithandizo.

Kuphatikiza apo, pali zambiri zomwe zikuwonetsa kuti kugwiritsa ntchito chemotherapy kuti muchepetse chotupa choyambirira kumathandizira kufalikira kutali nthawi zina chifukwa chemotherapy imasankha ma cell omwe amatha kuyambitsa metastasis. Lingaliro lachilolezo silingathe kugwira pamene pali zochitika zambiri pamapeto ophatikizana, monga momwe zilili ndi matanthauzo ena a PFS, EFS, ndi DFS. Mwachitsanzo, mayesero a allogeneic hematopoietic stem cell transplantation therapy nthawi zambiri amagwiritsa ntchito mapeto omwe amaphatikizapo imfa, kubwereranso kwa khansa, ndi matenda a graft-versus-host (GVHD), omwe amadziwika kuti GVHD free RFS (GRFS). Mankhwala omwe amachepetsa kufala kwa GVHD angapangitse kuchuluka kwa khansa kuyambiranso, ndipo mosiyana. Pachifukwa ichi, GVHD ndi ziwopsezo zobwerera m'mbuyo ziyenera kufufuzidwa padera kuti ziyesedwe molondola chiŵerengero cha chiopsezo ndi phindu la chithandizo.

Lipoti lachizoloŵezi la zochitika zosiyana siyana za zotsatira zovuta zimatsimikizira kuti zotsatira za chithandizo pa gawo lililonse zimakhala zofanana; "Kusiyanasiyana kwamtundu uliwonse" (mwachitsanzo, kusiyana kwa mayendedwe) kumabweretsa kusagwiritsa ntchito koyenera kwa mathero ophatikizika.

EMA imalimbikitsa "kusanthula kwaumwini kwa mitundu ya zochitika pawokha pogwiritsa ntchito matebulo ofotokozera mwachidule komanso, ngati kuli koyenera, kusanthula kwachiwopsezo champikisano kuti awone momwe chithandizo chimakhudzira chochitika chilichonse". Komabe, chifukwa cha mphamvu zosakwanira zowerengera za maphunziro ambiri, kusiyana kwakukulu kwa zochitika zamagulu muzotsatira zophatikizana sikunawonekere.

Kupanda kuwonekera pofotokoza zochitika zamagulu omaliza

M'mayesero amtima, ndizozoloŵera kupereka zochitika za gawo lililonse (monga sitiroko, myocardial infarction, kuchipatala, ndi imfa) pamodzi ndi mapeto a MACE. Komabe, kwa PFS ndi mathero ena ophatikizika pamayesero azachipatala a oncology, muyeso uwu sugwira ntchito. Kusanthula kwa kafukufuku waposachedwa wa 10 wofalitsidwa m'magazini asanu apamwamba a oncology omwe adagwiritsa ntchito PFS monga mapeto adapeza kuti atatu okha (6%) adanena za imfa ndi zochitika za kukula kwa matenda; Kafukufuku umodzi wokha womwe umasiyanitsa pakati pa kupita patsogolo kwapafupi ndi metastasis yakutali. Kuonjezera apo, kafukufuku wina adasiyanitsa pakati pa kupita patsogolo kwapafupi ndi kutali, koma sanapereke chiwerengero cha imfa matenda asanafike.

Zifukwa za kusiyana kwa malipoti azomwe zimapangidwira kumapeto kwa mtima ndi oncology sizikudziwika. Kuthekera kumodzi ndikuti mfundo zophatikizika monga PFS ndi DFS ndizozizindikiro zogwira ntchito. MACE idachokera ku zotsatira zachitetezo ndipo idagwiritsidwa ntchito koyamba pofufuza zovuta za percutaneous coronary intervention. Mabungwe olamulira ali ndi miyezo yapamwamba yofotokozera zotsatira zachitetezo, kotero pakufunika zolemba zatsatanetsatane za zochitika zoyipa pamayesero azachipatala. Pamene MACE idagwiritsidwa ntchito kwambiri ngati chomaliza chakuchita bwino, zitha kukhala zachizolowezi kupereka kuchuluka kwa chochitika chilichonse. Chifukwa china cha miyezo yosiyana ya malipoti ndi chakuti PFS imatengedwa ngati mndandanda wa zochitika zofanana, pamene MACE imatengedwa kuti ndi mndandanda wa zochitika zosiyana (mwachitsanzo, stroke vs. myocardial infarction). Komabe, kukula kwa chotupa choyambirira ndi ma metastases akutali amasiyana kwambiri, makamaka potengera momwe matenda amakhudzira. Malongosoledwe onsewa ndi ongopeka, koma mwachiwonekere palibe ndi limodzi mwa iwo amene amavomereza lipoti losakwanira. Kwa mayesero a oncology omwe amagwiritsa ntchito malekezero ophatikizika, makamaka pomwe mathero ophatikizika ndiwo mathero oyambira kapena amagwiritsidwa ntchito poyang'anira, ndipo pomwe gawo lophatikizika limakhala ngati chomaliza chachiwiri, malipoti azinthu zowonekera ayenera kukhala chizolowezi.