I-Bisphosphonates kunye neDenosumab kwi-Bone Metastases kunye ne-Adjuvant Therapy
I-Cancer eyasasazeka kumathambo (i-boneast metastases) iqhelekileyo kwaye ingabangela enkulu intlungu kunye nokukhubazeka ezinxulumene neziqhekeza kunye nezinye iingxaki. Kwiminyaka yakutshanje imithi ebizwa ngokuba yi-agents-modifying agents iyanconywa ukuba ininzi i-cancer isebenzise ama-metastases ngokukhawuleza xa ifunyanwe. Kulo mqathango, ezi ziyobisi azinciphisi nje ingozi yokuphulwa komzimba kodwa ngezinye iimeko, kunokuphucula ukuphila.
Njengenzuzo yesibini, zombini iindidi zezilwanyana eziguqula amathambo zinempawu zokulwa nomhlaza. Yintoni oyifunayo ukuba uyazi malunga nezidakamizwa ezifana neZometa kunye ne-denosumab ukuba uhlala nomdlavuza we-metastatic?
I-Bone Metastases ne-Bone Cancer
Xa abantu beva ngomhlaza emathanjeni, kunokudideka kakhulu. Ininzi yexesha apho abantu bethetha "ngomhlaza wesifuba" bebhekisela kwiithambo zesifo; iisomhlaza ezaqala kwenye indawo yomzimba kwaye zazisasaza amathambo. Nangona abo bantu bangasebenzisa igama elithi "umhlaza wesifuba," iisomhlaza ezithatha amathambo aziqwalaselwa ngumhlaza wesifuba. Ngokomzekelo, umhlaza wesifuba oye wasasazeka kumathambo awuthiwa ngumhlaza wesifuba kodwa kunoko "umdlavuza webele wesifo emathambo" okanye umhlaza wesifuba ngamathambo. Umhlaza wesifuba weprayimari awuncinci kakhulu kunezifo zamathambo. Ngaphantsi kwe-microscope, umhlaza wesifuba wawuza kubonisa iiseli zesifo somhlaza. Ngokwahlukileyo, kunye neethambo zesithinteli iiseli zomhlaza kwisithambo zifana nezicubu ezifanayo njengomhlaza wesiqhelo; iiseli zesifuba somhlaza kwimeko yomhlaza wesifuba, amangqamuzana emiphunga yomhlaza emthanjeni (kunye nomhlaza wemiphunga) njalonjalo.
Ngomdlavuza wamathambo oyintloko, ngokuqhelekileyo kukho isisu esisinye kwelinye ithambo. Ngamathambo e-boneastases, kukho ubungqina bomhlaza kwiindawo ezahlukeneyo zethambo okanye ngamathambo amaninzi ahlukeneyo.
Amanqaku aKhansela ayenokuthi asasaze kwiThambo
Kukho ezininzi iintsholongwane ezingasasazeka kwiethambo eziqhelekileyo ngumhlaza wesifuba, umhlaza wamaphaphu, umdlavuza wesifo seprotate, kunye ne-myeloma yam.
Ezinye iidrakes ezingasasazeka kwithambo ziquka umhlaza wesifo, umdlavuza wesisu, umhlaza wesisu, umhlaza wesibeleko, umdlavuza we-thyroid kunye ne-cancer ye-colorectal.
I-Boneastas i-Bone isenzeka kuma-70 ekhulwini kwabasetyhini abanomdlavuza webele (amathambo yindawo eqhelekileyo ye-metastase), kunye ne- boneastases ye-boneastases evela kumhlaza wesifuba yimbangela ebalulekileyo yentlungu nokukhubazeka kwaba bafazi (kunye namadoda). Kwabaninzi bala bantu, i-boneastases ye-bone isisayine sokuqala ukuba umhlaza uye waphinda emva kweminyaka okanye kwamashumi eminyaka yokuxolelwa. Ezinye zezilwanyana zonyango ezisetyenziselwa umdlavuza webele (ezifana ne-aromatase inhibitors) zingakhokelela ekulahlekelweni kwethambo, ngokuqhubekayo kuhlanganiswe ingxaki. Amathambo aqhelekileyo apho umhlaza wesifuba usasazeka khona, umlenze, i-pelvis, namathambo emilenze ephezulu kunye neengalo.
I-Boneastases yezifo zomdlavuza wamaphaphu ziqhelekileyo, zichaphazela malunga nama-30 ukuya kuma-40 ekhulwini abantu abanomdlavuza ophezulu wamaphaphu. Amathambo amaninzi achaphazelekayo ngumgudu, i-pelvis, kunye namathambo angaphezulu nasemlenzeni. Umdlavuza womlenze uyingqayizivele kwiimeko zokuthi i-metastases ingenzeka emathanjeni ezandleni nasezinyaweni. Phakathi kwabantu abaneethambo ezisuka kumdlavuza wamaphaphu, ama-22 ukuya kuma-59 ekhulwini aya kuba neengxaki "ezinxulumene nezifo" ezifana nokuqhekeka.
I-Boneastast i-Bone ibuye iqheleke kwimhlaza yomhlaza wesifo seprotate . Njengabafazi abanomdlavuza wesibele, unyango lwe-hormonal kunye ne-androgen yokunyanga ukunyanzelwa kwamathambo kunokunciphisa amathambo. Amadoda amane kwabangamahlanu anomdlavuza wesifo se-prostate aya kuba neentlobo zesifo. Isiza esiqhelekileyo seemastastases yizintlu, umlenze, kunye namathambo e-pelvic.
I-Boneastas ezivela kwi-myeloma ezininzi ziqhelekile. Ngama-x-ray, amathambo athabatha ukubonakala kwinyama. Xa i-myeloma eninzi ihlasela amathambo, iiseli zomhlaza zivimbela amathambo okwenza iiseli (i-osteoblasts) kwaye ivuselela iiseli zethambo eziphula i-bone (i-osteoclasts). I-myeloma yam amaninzi itholakala kumathambo amakhulu njengomthi womgudu, isikhala, i-pelvis, iimbambo kunye namathambo amakhulu emilenze.
Iintlobo ze-Bone Metastases
Kukho iintlobo ezimbini eziphambili zeethambo zesifo: i-osteolytic ne-osteoblastic. Nge-osteolytic metastases, i-tumor idala ukuchithwa (lysis) kwethambo. I-ostolytic metastases ibonakala nge-myeloma ezininzi kunye nezicubu ezinzima ezifana nomhlaza wesifuba. I-Osteoblastic metastases kubangele ukwanda kwemveliso yethambo kunye neyona nto ibonakala ibonwe ngumhlaza wesibeletho. Uninzi lweekliniki zineentlobo zombini zethambo zesifo kodwa ama-80 ukuya kuma-85 ekhulwini weemastastases kunye nesifo somhlaza wesifuba se-osteolytic. Iifractures zinokwenzeka ukuba zenzeke emathanjeni nge-osteolytic metastases kunama-astastas osteoblastic.
Iingxaki ezivela kwi-Bone Metastases
I-Boneastast i-Bone inokunciphisa kakhulu umgangatho wobomi kunye nomhlaza, kodwa unyango olutsha lwenza umehluko kubantu abaninzi. Akukhona nje ukuba amathambo e-metastases athetha ukuba umhlaza usasazeke kwaye awupheli, kodwa unokukhokelela kwiinkalo ezininzi.
Ubuhlungu obuvela kwi-boneastas ye-bone busenokuba nzima kakhulu kwaye kufuna ukuba unyango olunentlungu lugqithise kunye nemithi echasayo.
I-Boneastast i-Bone iyakwandisa amathuba okuphuka kwiindawo zethambo ezibuthathaka ngenxa yesikhumba. Xa ukuphuka kuvela emathanjeni ngomhlaza we-metastatic babizwa ngokuba yi- fracture pathologic. Iingcingo ze-pathologic zenzeke ngokulimala kakhulu. Ukongezelela kokudlulela kwintsimbi, i-boneastases yamathambo ingenza kube nzima ukuba amathambo aqhekekileyo aphilise.
Xa i-metastases ivela kumgca ongaphantsi, imeko yongxamiseko ebizwa ngokuba yi-spinal cord compression ingenzeka. I-Cancer kwi-vertebrae inokubangela ukuba bawile baze baxinzelele iintsholongwane ezihamba ukusuka kwintambo yomgogodla ukuya kwisiqingatha esingaphantsi komzimba. Iimpawu ziquka intlungu ebuyela emva emlenzeni, obuthathaka, kunye nokunyanzeliswa kwemilenze, kunye nokulahlekelwa kwezilwanyana kunye / okanye ukulawula i-bladder. Unyango olusisigxina nge-radiation okanye utyando luyakwazi ukuzinzisa umlenze ukuphepha ukukhubazeka okusisigxina.
I-hypercalcemia yesifo okanye i-calcium ephakamileyo kwigazi ingenzeka ngenxa yokukhululwa kwe-calcium ukusuka kwicandelo elithinteleyo lesithambo ukuya kwigazi. Kucinga ukuba i-10 ukuya kwe-15 ekhulwini labantu abanomdlavuza ophezulu baya kuba neengxaki (ezinokwenza ezinye izizathu kunye nokongeza kwimizimba ye-boneastases).
Ukulahleka kokuhamba ngenxa yokuphulwa kwempahla kungekhona nje ukunciphisa umgangatho wobomi kodwa kunokubeka ingozi kwezinye iingxaki. Umngcipheko weengcezu zegazi kubantu abanomhlaza sele usanda kwanda, kwaye ukungahambi kakuhle kuphakamisa umngcipheko wokuhlaselwa kweengxaki ze-vein or pulmonary emboli
Unyango lwe-Bone Metastases
Kukho iindawo ezininzi ezikhethiweyo zokufumana unyango lweethambo. Ezinye zezonyango eziqhelekileyo ezisetyenziselwa umhlaza wesifo se-metastatic zingaphinda zinciphise i-metastases yeethambo. Ezi zonyango zingabandakanya i- chemotherapy , iipilisi ezijoliswe kuzo, i- antiocidal monoclonal , kunye ne- immunotherapy drugs. Kukho nezokwelapha ezithatha i-boneastas eziphathekayo ngokuthe ngqo. Ezi ziquka:
- Ulwaphulo lwe-radiation: Ulwaphulo lwe- radiation yonyango lwengingqi kwaye lunokunciphisa kakhulu intlungu kunye kunye nokubonakala kwephuka.
- I-Radiopharmaceuticals: I- Radiopharmaceutics yiyobisi apho i-particle of radiation iqhotyoshelweyo kwenye ikhemikhali enokuthi ifakwe kwigazi. Imizekelo ibandakanya iStrontium-89 kunye neRadium-223. Ekubeni la ma particles of radiation athathwe ngegazi kwiiyo onke amathambo emzimbeni, inokuba yinkqubela ngokukhethekileyo kubantu abaninzi okanye abasasazekayo.
- Ugqirha: Kufuneka ukuba unyango luzinze ukuzinzisa ukuphuka okanye ukuzinzisa amathambo abonakalisiweyo ukukhusela ukuphuka.
- I-radiotherapy yomzimba ( Stereotactic body radiotherapy (SBRT) kunye nesipilisi sophotho lwe- proton : Kwimizimba eyodwa okanye embalwa kuphela (i-oligometastatic disease), ukupheliswa kweemastastasyathi zonyango ezifana nesifo se-radiotherapy okanye i-proton ye-stereotac. ngaqhelekanga.
- I-agents-modifying agents: Ezi ziya kuxutyushwa ngezantsi.
Imithi yeT Bone Metastases (i-Bone-Modifying Agents)
Kukho ezimbini iiprayimari eziphambili zezilwanyana ezisetyenziselwa ukuphatha i-metastases yamathambo. Ezi ziquka i-bisphosphates (njengeZometa) kunye ne-denosumab. I-agents-modification agents iyanconywa kunoma ubani onomdlavuza webele webele, kwaye ihlala isetyenziswa kunye nezinye izicubu ezinzima (ezifana nomhlaza wemiphunga). Ezinye iindlela zonyango (ezifana nokunyanga kwamayeza) zidla ngokufuneka kunye kunye nemithi yokulawula intlungu.
I-agents-modifying agents iyakunceda abantu abanomhlaza ngeendlela ezininzi.
- Baya kunceda amathambo achaphazelekayo ngama-metastases ukunciphisa iintlungu zombini kunye nomngcipheko weentlobo
- Uninzi lwezonyango ezisetyenziselwa umhlaza wesifuba kunye nomhlaza wesifo seprotate, unokwandisa umngcipheko we-osteoporosis, kunye kunye neethambo zesitastas zibeka abantu kwiintlobo. Oku kubaluleke ngakumbi kuba abantu bahlala ixesha elide kunye nomhlaza.
- Ngenxa yemiphumo yazo kwi-microenvironment yamathambo, ama-agent-modifying agents anganciphisa umngcipheko weethambo zesifo esithintekayo kwindawo yokuqala (kunye nomhlaza wesifuba mhlawumbi nomhlaza wesifo se-prostate kude kube ngoku). Umngcipheko wesifo se-boneastases wehliswa yi-third to half, ngelixa isantya sokufa sehlile sithandathu.
- Kuphando olutshanje lujonge ama-agent aguqula amathambo ngomhlaza wamaphaphu, kubonakala ukuba ezi ziyobisi zingaphucula kokubili ukuqhubeka kokuhamba-mahhala kunye nokuphila ngokubanzi.
Bisphosphonates (Zometa)
I-Bisphosphonates yimishanguzo eyaqala ukuyisebenzisa ekunyangeni i-osteoporosis kwaye kamva yaqaphela ukukunceda ngeethambo zesifo. Xa zisetyenziselwa i-cancer, esasazeka kumathambo, ziyakwenza umsebenzi ombini. Akunako kuphela ukunciphisa ukulahleka kwethambo kodwa banemiphumo yokuchasa umdlavuza. Basebenza ngokunciphisa ukuphuka kwethambo ukuphucula uxinzelelo lweethambo.
Iibisphosphonates ezisetyenziswa kakhulu kwiithambo zesistim ziquka:
- I-Zometa (i-zoledronic acid): I- Zometa isilumkiso esisetyenzisiweyo esetyenziselwa i-boneastases yamathambo kwii-kanseri ezininzi ezahlukeneyo.
- Aredia (i-pamidronate) : U-Aredia uyinxalenye ye-bisphosphonate. Kuvunyiwe umhlaza wesifuba kunye ne-myeloma yam.
Iziphumo eziqhelekileyo ezichaphazelekayo zeZometa kunye ne-Aredia zizifo ezinjenge-flu-like syndrome kwiintsuku ezimbalwa zokuqala emva kokungeniswa. Ezinye iziphumo eziqhelekileyo eziqhelekileyo ze-bisphosphonates ezinikezwe kwangaphakathi zingabandakanya umonakalo wezintso, amanqanaba e-calcium aphantsi, ubuhlungu besisundu, odibeneyo kunye / okanye isifuba (esinokuvela naliphi na ixesha emva kokuba unyango), iintlobo ezingaqhelekanga ze-femur kunye ne-fibrillation ye-atrial. I-Bisphosphonates ayinakukhuthazwa kubantu abanesifo seengtso.
Isiganeko esingaqhelekanga kodwa esichukumisayo esinxulumene nokusetyenziswa kweZometa (kunye nezinye i-bisphosphonates) yi-osteonecrosis yomhlathi. Le meko ibonakaliswe ukuphazamiseka okuqhubekayo kwindawo yethambo kwi-mandible okanye i-maxilla kwaye ingaba ngumngeni kuLwazi lwaloo nto iyenzeka ngayo, kodwa umngcipheko we-2% watholakala kubasetyhini abaphathwa ngeZometa njenge-adjuvant therapy ekuqaleni komhlaza wesifuba. I-Osteonecrosis iyakwenzeka kunye naziphi na iziyobisi kwinqanaba le-bisphosphonates kodwa ama-94 ekhulwini amatyala afumaneka ngamachiza e-bisphosphonate angenangqumbo kwaye akunakwenzeka kakhulu ngezidakamizwa zomlomo.
I-Osteonecrosis yomhlathi iyakwenzeka ukuba abantu bafumana isifo segum, banokuhlambuluka kwamazinyo angamahlwempu, okanye bafumana iinkqubo zamazinyo ezinjengeziqhamo zinozinyo. Kukho ubungqina bokuba ukucwangcisa uviwo lwamazinyo rhoqo emva kweenyanga ezintathu kwaye usebenzisa i-antibiotics yokukhusela kwiinkqubo ezifana nokukhutshwa kwezinyo kunganciphisa umngcipheko. Izinyathelo zokwelapha ziquka ukudibanisa kovavanyo, iilinses, antibiotics, kunye neyeza ze-oksijeni zonyango.
I-bisphosphonates ivunyiwe kwakhona kubafazi be-postmenopausal kunye nomhlaza wesifuba. Kwizilingo zeklinikhi, i-Zometa ifumaneka ukunciphisa umngcipheko wokuphuhlisa i-boneastas yamathambo kwisithathu kunye nomngcipheko wokufa ngesithandathu.
I-Denosumab (i-Xgeva ne-Prolia)
I-Xgeva ne- Prolia (denosumab) yintsholongwane yomntu oyedwa (umntu owenziwe ngumntu) onokunciphisa uxinzelelo (njengeziqhekeza) ezinxulumene namathambo e-boneastases. Kukho imimiselo emibili yale nkunkuma enezibonakaliso ezahlukeneyo nomhlaza. Zinikezelwa ngejoza nganye kwiiveki ezine.
I-Denosumab isebenza ngokubopha kunye nokukhubaza i-receptor kwiprotheni (RANKL) elawula ukulungiswa kwethambo. Kukho iintlobo ezimbini ezibalulekileyo zeeseli kumathambo: i-osteoblasts ebangela ukukhula kwethambo, kunye ne-osteoclasts ephula ithambo. I-Denosumab inqanda i-osteoclasts kwaye ikhulisa ubuninzi beethambo.
Kuhlalutyo lwe-2016 lwezifundo, i-denosumab yavavanywa kwizilingo ezintathu ezihlukeneyo zeklinikhi ebhekise indima yayo kumdlavuza webele, umhlaza wesifo seprotate, kunye nesifundo sesithathu nabantu abane-multipleel myeloma okanye izilonda ezinamandla ngaphandle kwesifo somhlaza okanye isifo somhlaza. Ngomdlavuza wesifuba nomhlaza wesifo seprotate, i-denosumab yayiphezulu kwiZometa ekunciphiseni ingozi yeentlobo ezihlobene ne-boneastas. Ngama-myeloma amaninzi kunye nezinye izicubu eziqinileyo (ezinjalo i-denosumab yayilingana nokusebenza kwiZometa.
Ngomdlavuza wamaphaphu, uvavanyo luka-2015 lufumene ukuba xa kuthelekiswa neZometa, i-denosumab yanciphise ingozi yokuphuka okubangelwa ngama-17 ekhulwini. Kwakhona kubonakala kukulibazise ukuphuhliswa kweethambo zesitastas, ukunciphisa ukukhula kwe-tumor skeletal, kunye nokuphucula ixesha lokuphila ngephaya kwenyanga.
I-Denosumab nayo ifumaneka ukunciphisa umngcipheko we-ostoporosis echaphazeleka unyango kwi-cancer yombele kunye nomhlaza wesifo seprotate (ehlobene nokusetyenziswa kwe-aromatase inhibitors kumdlavuza webele kunye ne- androgen unyango lokunyanzelwa komdlavuza wesibeletho)
Imiphumo emibi ye-denosumab ifana ne-bisphosphonates kodwa ezi ziyobisi ziyakwazi ukuphumela kwizinga eliphantsi le-calcium ngokusetyenziswa kwexesha elide. Ngenxa yoko, ukuthatha isongezelelo se-calcium kunye ne-vitamin D kudla ngokucetyiswa. Ngokungafani ne-bisphosphonates, i-denosumab ingasetyenziselwa abantu abaneentsholongwane ezingasebenzi. Njengoko i-bisphosphonates, kukho umngcipheko omncinci we-osteonecrosis yomhlathi kunye nala mayeza.
Izikhokelo ze-Bone-Modifying Agents With Bone Metastases
Uphononongo olwenziwe ngamathambo aguqula amathambo lukhokelela kwizikhokelo ezisendaweni zezinye i-cancer.
Ngomdlavuza webele we-metastatic, nge-boneastases yamathambo, i-American Society ye-Clinical Oncology imihlahlandlela ukususela ngo-2017 uncetyisa abafazi ukuba baphathwe ngenye yezi ziyobisi ngokukhawuleza xa kuthe kwafunyanwa i-metastase ye-bone:
- Xgeva okanye Prolia 120 mg ngaphantsi kweeveki ezine
- Aredia 90 mg IV nganye kwiiveki ezi-3 ukuya kwezine
- I-Zometa 4 mg IV nganye kwiiveki ezili-12 okanye nganye kwiiveki ezi-3 ukuya kwezine
I-cancer yeprotate, izikhokelo zonyango lwe-2017 nazo zincoma ukuba ama-agent-modification agents aqalwe ngexesha lokuxilongwa kweethambo zesifo. Khetha ziquka:
- Xgeva / Prolia (denosumab) 120 mg ngaphantsi kweeveki ezine
- I-Zometa 4 mg IV nganye kwiiveki ezili-12 okanye nganye kwiiveki ezi-3 ukuya kwezine
Zonke ezinye izicubu ezinamandla kunye netastimase zethambo zingaphathwa ngenye yezi zinto zilandelayo:
- I-Zometa 4 mg IV rhoqo kwiiveki ezi-3 ukuya kwezine
- I-Denosumab 120 mg ngaphantsi kweeveki ezine
Ngaphambi kokuba uqale unyango
Ngaphambi kokuba uqale unyango kunye ne-denosumab okanye i-bisphosphonates, kunconywa ukuba abantu banokuhlolwa ngokusemgangathweni kwamazinyo bafuna ubungqina bentsholongwane yesifo kunye nokuba nawuphi na umsebenzi wamazinyo ofunekayo kufuneka uyenziwe ngaphambi kokuba uqalise la mayeza.
Ngaphantsi kwe-Bone-Ukuguqula iMicrosoft for Bone Metastases ezivela kwiisondo eziqinileyo
I-boneast metastases inzima kubantu abaninzi abanomdlavuza we-metastatic kwaye banokunciphisa umgangatho wobomi kunye nokuphila. I-agents-modification agents (i-bone-modifying agents) iyindlela entsha kwaye ngoku iyanconywa ngokukhawuleza emva kokuxilongwa kweethambo zesifo samathambo amaninzi.
I-Bisphosphonates efana ne-Aredia kunye ne-Zometa inokunciphisa umngcipheko wezahlulo, kwaye ngenxa yoko ibangela intlungu kunye nokungahambi. I-Denusomab isebenza ngokuphumelelayo ekunciphiseni i-fractures ngokunjalo kwaye ingathi iphezulu kune-bisphosphonates yebele kunye ne-prostate cancer. Zomibini iiklasi zonyango zithwala ingozi enkulu ye-osteonecrosis yomhlathi, kwaye ukuhlolwa kwezilumko ngokucophelela kukhangelwe iimpawu zesifo segum kunokucetyiswa ngaphambi kokuba uqalise la mayeza.
Ukongezelela ekunciphiseni ingozi yokuphulwa komzimba, la mayeza angakunceda ukulungisa ukulahleka kwethambo ngenxa yamathambo e-hormone asetyenziselwa i-breast and prostate cancer. Bobabini i-bisphosphonates kunye ne-denosumab kubonakala sengathi banomsebenzi obangelwa ngumhlaza, okwandisa inzuzo kubantu abakhetha ukusetyenziswa kwezi ziyobisi. Enyanisweni, ukongeza kubantu abanomdlavuza webele we-metastatic, i-Zometa ngoku ikhuthazwa kwintsholongwane yokuqala yesifo somhlaza njenge-adjuvant therapy ukunciphisa ithuba lokuba umdlavuza webele usasazeka kumathambo kwindawo yokuqala.
> Imithombo:
> IBeti-Tasdogan, N., iMeya, B., u-Hussein, H., no-O. Zolk. Amanyathelo okuLawula i-Osteonecrosis ephathelene neMithi. I-Cochrane Database yeeNkqubo eziPhezulu . 2017. 10: CD012432.
> Coleman, R. Impact ye-Bone-Targeted Treatments kwi-Skeletal Morbidity and Survival kwi-Cancer Breast. I-Oncology (Williston Park) . 2016. 30 (8): 695-702.
> I-Dhesy-Intshumayelo, S., Fletcher, G., Blanchette, P. et al. Ukusetyenziswa kwee-Adjuvant Bisphosphonates kunye nezinye i-Bone-Modifying Agents kwiCanscer Breast: I-CancerCare yase-Ontario kunye neMelika yaseMelika ye-Clinical Oncology Clinical Practice Guideline. Umbhalo we-Clinical Oncology . 2017. 35 (18): 2062-2081.
> Gravalos, C., Rodriquez, C., Sabino, A. et al. I-SEOM Isikhokelo seKliniki yeT Bone Metastases ukusuka kwiMisongo eqinile (2016). I-Clinical and Translational Oncology . 2016. 18 (12): 1243-1253.
> Gul, G., Sendur, M., Aksoy, S., Sever, A., no K. Altundaq. Ukuhlaziywa ngokubanzi kweDenosumab kwi-Bone Metastasis kwizigulane ezinezondo eziqinileyo. Uphando lwezoPhando kunye neNgxelo . 2016. 32 (1): 133-45.