ONCOBIOLOGIE
PROF. DAAN DIERICKX
INHOUD
Hoofdstuk 1 – inleiding .......................................................................................................................................... 7
Definitie & kenmerken ............................................................................................................................................ 7
Types kanker ........................................................................................................................................................... 7
Vaste & vloeibare tumoren ................................................................................................................................ 8
Statistieken.............................................................................................................................................................. 8
Incidentie van kanker over de verschillende jaren: ............................................................................................ 8
5-jaars overleving ............................................................................................................................................... 8
Indeling.................................................................................................................................................................... 9
AYA’s ................................................................................................................................................................... 9
Familiaal .............................................................................................................................................................. 9
Sporadisch .......................................................................................................................................................... 9
De novo ............................................................................................................................................................... 9
Symptomatisch ................................................................................................................................................... 9
Klinisch gedrag .................................................................................................................................................... 9
Hoofdstuk 2 – oorzaken & preventie ................................................................................................................... 10
Oorzaken ............................................................................................................................................................... 10
Carcinogenen .................................................................................................................................................... 10
Medicatie .......................................................................................................................................................... 10
Biologische reagentia ........................................................................................................................................ 10
Beroepsblootstelling/omgevingsfactoren ........................................................................................................ 11
Straling .............................................................................................................................................................. 11
Voeding & middelen ..................................................................................................................................... 11
Alcohol .......................................................................................................................................................... 11
Roken............................................................................................................................................................ 11
Overgewicht ................................................................................................................................................. 11
Vlees ............................................................................................................................................................. 11
Zout .............................................................................................................................................................. 11
Primaire preventie ................................................................................................................................................ 12
Secundaire preventie ............................................................................................................................................ 12
Screening .......................................................................................................................................................... 12
Borstkanker....................................................................................................................................................... 13
1
, Screening ...................................................................................................................................................... 13
Baarmoederhalskanker ..................................................................................................................................... 14
Darmkanker (colorectale kanker) ................................................................................................................. 14
Screening: ..................................................................................................................................................... 14
Longkanker ....................................................................................................................................................... 15
Screening ...................................................................................................................................................... 15
Prostaatkanker.................................................................................................................................................. 15
Screening: ..................................................................................................................................................... 15
Huidkanker (melanoom) ................................................................................................................................... 16
Screening ...................................................................................................................................................... 16
Hoofdstuk 3 – diagnose ........................................................................................................................................ 17
Diagnostisch pad ................................................................................................................................................... 17
symptomen ........................................................................................................................................................... 17
Asymtomatisch ................................................................................................................................................. 17
Symptomen van kanker zijn…(5) ...................................................................................................................... 17
Soorten symptomen: ............................................................................................................................................ 18
Lokale effecten (primaire tumor of metastasen).............................................................................................. 18
Longkanker ................................................................................................................................................... 18
Borstkanker .................................................................................................................................................. 18
Darmkanker .................................................................................................................................................. 18
Huidkanker ................................................................................................................................................... 19
centrale zenuwstelseltumoren/hersentumoren .......................................................................................... 19
hematologische tumoren ............................................................................................................................. 19
Niet-specifieke symptomen .............................................................................................................................. 19
Metabole effecten ............................................................................................................................................ 20
Bv adhv bloedonderzoek: ............................................................................................................................. 20
Tumor lysis syndroom (TLS).......................................................................................................................... 20
- Afwijkingen .......................................................................................................................................... 20
- Labo vs. Klinisch TLS............................................................................................................................. 21
- Ricisostratificatie ................................................................................................................................. 21
- preventie en behandeling .................................................................................................................... 21
- Nierfunctie ........................................................................................................................................... 22
Paraneoplastische symptomen......................................................................................................................... 22
Alarmsymptomen ............................................................................................................................................. 22
Performantiestatus ............................................................................................................................................... 23
Diagnose................................................................................................................................................................ 23
bloedresultaten ................................................................................................................................................ 23
2
, Histologische classificatie ................................................................................................................................. 23
Enkel histologisch (weefsel-) onderzoek kan diagnose van kanker met zekerheid bevestigen ................... 23
Terminologie ................................................................................................................................................ 23
Doelen .......................................................................................................................................................... 24
Staging ................................................................................................................................................................... 24
Lymfomen ......................................................................................................................................................... 24
Solide tumoren ................................................................................................................................................. 24
Beeldvorming .................................................................................................................................................... 25
Hoofdstuk 4 – behandeling .................................................................................................................................. 26
Chemotherapie ..................................................................................................................................................... 26
Celcyclus ........................................................................................................................................................... 26
Ontwikkeling ..................................................................................................................................................... 26
Soorten ............................................................................................................................................................. 26
Alkylerende agentia ...................................................................................................................................... 26
Antimetabolieten ......................................................................................................................................... 27
Mitotische inhibitoren .................................................................................................................................. 27
Topoisomerase inhibitoren .......................................................................................................................... 27
Antitumorale antibiotica .............................................................................................................................. 27
Toediening ........................................................................................................................................................ 27
Dosis ................................................................................................................................................................. 28
Principes ........................................................................................................................................................... 28
Nevenwerkingen ............................................................................................................................................... 28
Hormonale therapie .............................................................................................................................................. 29
Indicaties ........................................................................................................................................................... 29
Neveneffecten .................................................................................................................................................. 29
Gerichte therapie .................................................................................................................................................. 29
Heelkunde ............................................................................................................................................................. 29
Profylactische heelkunde .................................................................................................................................. 30
Diagnose en staging .......................................................................................................................................... 30
Heelkunde met curatief opzet .......................................................................................................................... 30
Palliatieve heelkunde........................................................................................................................................ 30
Andere procedures ........................................................................................................................................... 31
Radiotherapie ........................................................................................................................................................ 31
Waarom radiotherapie doen? .......................................................................................................................... 32
Manieren van toediening ................................................................................................................................. 32
Nevenwerkingen ............................................................................................................................................... 32
Fractionering ..................................................................................................................................................... 33
3
, Radiosensitiviteit .............................................................................................................................................. 33
Repair ................................................................................................................................................................ 33
Repopulatie....................................................................................................................................................... 34
Redistributie ..................................................................................................................................................... 34
Reoxygenatie .................................................................................................................................................... 34
Hoofdstuk 5 - stamceltransplantatie ................................................................................................................... 35
Factoren die stamceltransplantatie beïnvloeden ................................................................................................. 35
Onderliggende ziekte ........................................................................................................................................ 35
Voorbeeld: acute leukemie .......................................................................................................................... 35
Patientkarakteristieken .................................................................................................................................... 35
Beschikbaarheid van stamcellen....................................................................................................................... 36
Stamcelmobilisatie en -collectie ........................................................................................................................... 36
Beenmergprelevatie ......................................................................................................................................... 36
Perifere stamcel collectie ................................................................................................................................. 37
- ‘poor mobilizers’ .................................................................................................................................. 37
- Complicaties ........................................................................................................................................ 38
- Soorten donoren ................................................................................................................................. 38
- Keuze stsmcelransplantie .................................................................................................................... 39
Conditionering ...................................................................................................................................................... 40
Autologe conditionering ................................................................................................................................... 40
Allo conditionering: .......................................................................................................................................... 40
Myeloablatieve = chemo die beenmerg kapot maakt. ................................................................................. 41
- Niet-Myeloablatieve= chemo die niet beenmerg kapot maakt........................................................... 41
Keuze stamceltransplantatie ........................................................................................................................ 41
Stamceltransplantatie ........................................................................................................................................... 41
Complicaties: .................................................................................................................................................... 41
Hospitalisatie na stamceltransplantatie ................................................................................................................ 41
Naar huis na stamceltransplantatie ...................................................................................................................... 42
HvGD vs GvHD .................................................................................................................................................. 42
Afstoting ........................................................................................................................................................... 42
Problemen na transplantatie ............................................................................................................................ 42
Secundaire maligniteiten .................................................................................................................................. 42
Hoofdstuk 6 – immuuntherapie ........................................................................................................................... 43
Herhaling immuunsysteem ................................................................................................................................... 43
Aangeboren immuunsysteem = aspecifieke immuunrespons .......................................................................... 43
Verworven immuunsysteem = specifieke immuunrespons .............................................................................. 43
Onco-immunotherapie ..................................................................................................................................... 44
4
,Monoklonale antistoffen....................................................................................................................................... 44
Ongeconjugeerde ............................................................................................................................................. 44
Ongeconjugeerd antibody ................................................................................................................................ 44
Radio-isotoop.................................................................................................................................................... 44
BiTE ................................................................................................................................................................... 44
Checkpoint inhibitoren.......................................................................................................................................... 44
Pseudoprogressie ............................................................................................................................................. 45
CAR-T cells = Chimeric Antigen Receptor T cells ................................................................................................... 45
Nevenwerkingen: .............................................................................................................................................. 45
Target antigen ................................................................................................................................................... 45
Hoofdstuk 7 - Klinisch voorbeeld infectie - geassocieerde kanker: PTLD ........................................................... 46
Introductie ............................................................................................................................................................ 46
Definitie ............................................................................................................................................................ 46
Kwaadaardigheid door transplantatie .......................................................................................................... 46
Incidentie ...................................................................................................................................................... 46
Risicofactoren ....................................................................................................................................................... 47
Orgaantype ....................................................................................................................................................... 47
EBV status ......................................................................................................................................................... 47
Immunosuppresieve therapie........................................................................................................................... 47
Pathogenese.......................................................................................................................................................... 47
Presentatie ............................................................................................................................................................ 48
Verschillen tussen EBV+ en EBV- PTLD ................................................................................................................... 48
Behandeling van EBV ............................................................................................................................................ 48
Restoring T-cell function ................................................................................................................................... 48
a) RIS: Reduction of immune suppression ............................................................................................... 48
b) Adoptive immunotherapy ................................................................................................................... 48
Tumor reduceren .............................................................................................................................................. 49
a) Lokale therapie (radiotherapie) ........................................................................................................... 49
b) Rituximab and/or chemotherapy ........................................................................................................ 49
c) RSST (Risk Stratified Sequential Treatment) ....................................................................................... 49
Targeting EBV.................................................................................................................................................... 49
‘new classical agents’ ........................................................................................................................................ 49
a) CARTs ................................................................................................................................................... 49
b) Re-transplantatie ................................................................................................................................. 49
c) Prevention/prophylaxis/preemptive ................................................................................................... 49
Conclusie schema .................................................................................................................................................. 50
Hoofdstuk 8 - Klinisch voorbeeld hallmarks: acute myeloïde leukemie (AML) ................................................. 50
5
,Epidemiologie........................................................................................................................................................ 50
Pathogenese.......................................................................................................................................................... 50
CHIP/ARCH ........................................................................................................................................................ 50
Risicofactoren ....................................................................................................................................................... 51
Symptomen ........................................................................................................................................................... 51
Diagnose................................................................................................................................................................ 51
Morfologie ........................................................................................................................................................ 52
Immuno fenotypering ....................................................................................................................................... 52
Cytogenetica ..................................................................................................................................................... 52
Moleculaire diagnostiek ................................................................................................................................... 52
Behandeling .......................................................................................................................................................... 52
risico stratificatie .............................................................................................................................................. 52
3 + 7 .................................................................................................................................................................. 53
Hypomethylating therapy (HMA): azacytidine, decitabine .............................................................................. 53
FLT3 inhibitors .................................................................................................................................................. 53
Gemtuzumab ozogamicin ................................................................................................................................. 53
Hedgehog inhibitors ......................................................................................................................................... 54
IDH1/2 inhibitors .............................................................................................................................................. 54
Venetoclax ........................................................................................................................................................ 54
Examen: 2 grote vragen, 3 kleine vragen behorend tot 1 vraag
• Bv bespreek primaire, secondaire preventie van borstkanker
• Alarmsymptomen van een kanker
• Bijvragen: bv wat oor allogene donoren zijn er
• Les van 25 april: noem 3 nieuwe therapieën van AML zijn er (Shh, hypomethylerend etc).
6
,HOOFDSTUK 1 – INLEIDING
DEFINITIE & KENMERKEN
Gekarakteriseerd door ongecontroleerde celdeling → groei van abnormaal weefsel (= tumor, neoplasie
Continue delend organen: huid, bloedcellen
Bedoeling van groei om homeostase te behouden.
Normaal:
- Ontwikkeling en groei
- gecontroleerd
- Volwassen weefsels
o Homeostase behouden
▪ Steady state
▪ Herstel /repair
o Adaptief inspelen op wijzigende situaties
▪ Hypertrofie = cellen worden groter.
▪ Hyperplasie = Bv prostaat bij mannen, of endometrium bij de vrouwen. Of spiervergroting bij
trainging
Kanker:
- Groei zonder de wetten van het ecosysteem te respecteren
- Onaangepaste groei – ongecontroleerde groei
o Niet-adaptief: zonder uitlokkende fysiologische stimulus
o Niet flexibel of reversibel: zonder spontaan uitdoven
Differentiatie = de mate waarin het trekt uit het weefsel waaruit het
ontstaan is.
Mitotische activiteit ~ groeisnelheid
- Kan een goedaardige tumor levensbedreigend zijn? Meestal niet, maar zelden wel. Bijvoorbeeld in de
hersenen, omdat daar weinig plaats is.
- Links goedaardige tumor – rechts kwaadaardige tumor.
TYPES KANKER
afhankelijk van type cel waaruit ze ontstaan:
Melanocyten dienen voor bescherming tegen UV-schade. Die kunnen oiv UV kwaadaardig worden → melanoom.
Bindweefsel → bot- of ander = bindweefsel zijn sarcomen
Dus eigenlijk afhankelijk van de plaats & weefsel waaruit het ontstaat.
7
,VASTE & VLOEIBARE TUMOREN
Vloeibare = wat we vanuit de hematologie vinden. Wordt behandeld door hematoloog.
Carcinomen, sarcomen, melanomen, teratomen
lymfomen
vaste = worden behandelend door oncoloog
Leukemie
STATISTIEKEN
- Wereldwijd is borstkanker de meest voorkomende voor vrouwen.
- Voor mannen is dit prostaatkanker, voor de meesten is dit niet dodelijk.
- In Rusland longkanker.
Dit is puur om te kijken dat er REGIONALE VERSCHILLEN zijn.
Hoe ouder je wordt, hoe meer kans je hebt om kanker te ontwikkelen. Globaal ontwikkelen iets meer mannen
kanker tov vrouwen.
Als je kijkt naar DE TOP 3 VAN MANNEN & VROUWEN zie je ook verschillen:
Als je daarna kijkt naar
overlijdingskanker is dat voor
mannen en vrouwen longkanker.
Statistisch gezien, heb je weinig
kans om te overleven als je
pancreaskanker hebt. Als je
borstkanker hebt bv hebt je
statistisch gezien wel nog
redelijke kans om te overleven.
INCIDENTIE VAN KANKER OVER DE VERSCHILLENDE JAREN:
- Er was in de jaren 90 een piek van prognoses van prostaatkanker, omdat men toen heel intensief zijn gaan
screenen naar prostaatkanker. Screening is hiervoor eigenlijk niet zinvol.
- Bij vrouwen zie je dat de prognose voor borstkanker ook beetje stijgt, om dezelfde reden. Screening heel
zinvol.
5-JAARS OVERLEVING
= hoeveel procent is na 5 jaar nog in leven, met behandeling = 67,1% voor alle kankers samen.
- Prostaan 98%
- Melanoma 92%
- Borst 90%
- …
8
, - Slokdarm 20%
- Long 19%
- Lever 18%
- Pancreas 9%
Ook op jongere leeftijd is borstkanker voor vrouwen het meest dodelijk.
INDELING
AYA’S = jongvolwassenen & adolescenten. Die zijn interessant om te onderzoeken omdat ze toch een andere
biologie hebben, en moeten eerder met kinderschema’s behandeld worden, en niet de volwassen behandeling.
Een jongvolwassene moet er rekening mee houden dat zij nog verschillende fases van hun leven moeten
tegenmoet komen.
FAMILIAAL = genetische achtergrond die je gevoelig maakt voor kanker. Bv een gen die je gevoelig maar voor
borstkanker. 5-10%.
SPORADISCH = kanker die overkomt zonder dat iemand in je familie het heeft. de andere 90-95%.
DE NOVO = kanker krijgen zonder dat je kennelijk blootgesteld bent door iets.
SYMPTOMATISCH = prognose pas nadat je symptomen van de kanker merkt.
KLINISCH GEDRAG: agressief = zeer sterk groeiende. Indolent = alleen behandelen als mensen heel veel last
hebben – ze kunnen niet worden genezen maar wel dragelijker maken.
9
PROF. DAAN DIERICKX
INHOUD
Hoofdstuk 1 – inleiding .......................................................................................................................................... 7
Definitie & kenmerken ............................................................................................................................................ 7
Types kanker ........................................................................................................................................................... 7
Vaste & vloeibare tumoren ................................................................................................................................ 8
Statistieken.............................................................................................................................................................. 8
Incidentie van kanker over de verschillende jaren: ............................................................................................ 8
5-jaars overleving ............................................................................................................................................... 8
Indeling.................................................................................................................................................................... 9
AYA’s ................................................................................................................................................................... 9
Familiaal .............................................................................................................................................................. 9
Sporadisch .......................................................................................................................................................... 9
De novo ............................................................................................................................................................... 9
Symptomatisch ................................................................................................................................................... 9
Klinisch gedrag .................................................................................................................................................... 9
Hoofdstuk 2 – oorzaken & preventie ................................................................................................................... 10
Oorzaken ............................................................................................................................................................... 10
Carcinogenen .................................................................................................................................................... 10
Medicatie .......................................................................................................................................................... 10
Biologische reagentia ........................................................................................................................................ 10
Beroepsblootstelling/omgevingsfactoren ........................................................................................................ 11
Straling .............................................................................................................................................................. 11
Voeding & middelen ..................................................................................................................................... 11
Alcohol .......................................................................................................................................................... 11
Roken............................................................................................................................................................ 11
Overgewicht ................................................................................................................................................. 11
Vlees ............................................................................................................................................................. 11
Zout .............................................................................................................................................................. 11
Primaire preventie ................................................................................................................................................ 12
Secundaire preventie ............................................................................................................................................ 12
Screening .......................................................................................................................................................... 12
Borstkanker....................................................................................................................................................... 13
1
, Screening ...................................................................................................................................................... 13
Baarmoederhalskanker ..................................................................................................................................... 14
Darmkanker (colorectale kanker) ................................................................................................................. 14
Screening: ..................................................................................................................................................... 14
Longkanker ....................................................................................................................................................... 15
Screening ...................................................................................................................................................... 15
Prostaatkanker.................................................................................................................................................. 15
Screening: ..................................................................................................................................................... 15
Huidkanker (melanoom) ................................................................................................................................... 16
Screening ...................................................................................................................................................... 16
Hoofdstuk 3 – diagnose ........................................................................................................................................ 17
Diagnostisch pad ................................................................................................................................................... 17
symptomen ........................................................................................................................................................... 17
Asymtomatisch ................................................................................................................................................. 17
Symptomen van kanker zijn…(5) ...................................................................................................................... 17
Soorten symptomen: ............................................................................................................................................ 18
Lokale effecten (primaire tumor of metastasen).............................................................................................. 18
Longkanker ................................................................................................................................................... 18
Borstkanker .................................................................................................................................................. 18
Darmkanker .................................................................................................................................................. 18
Huidkanker ................................................................................................................................................... 19
centrale zenuwstelseltumoren/hersentumoren .......................................................................................... 19
hematologische tumoren ............................................................................................................................. 19
Niet-specifieke symptomen .............................................................................................................................. 19
Metabole effecten ............................................................................................................................................ 20
Bv adhv bloedonderzoek: ............................................................................................................................. 20
Tumor lysis syndroom (TLS).......................................................................................................................... 20
- Afwijkingen .......................................................................................................................................... 20
- Labo vs. Klinisch TLS............................................................................................................................. 21
- Ricisostratificatie ................................................................................................................................. 21
- preventie en behandeling .................................................................................................................... 21
- Nierfunctie ........................................................................................................................................... 22
Paraneoplastische symptomen......................................................................................................................... 22
Alarmsymptomen ............................................................................................................................................. 22
Performantiestatus ............................................................................................................................................... 23
Diagnose................................................................................................................................................................ 23
bloedresultaten ................................................................................................................................................ 23
2
, Histologische classificatie ................................................................................................................................. 23
Enkel histologisch (weefsel-) onderzoek kan diagnose van kanker met zekerheid bevestigen ................... 23
Terminologie ................................................................................................................................................ 23
Doelen .......................................................................................................................................................... 24
Staging ................................................................................................................................................................... 24
Lymfomen ......................................................................................................................................................... 24
Solide tumoren ................................................................................................................................................. 24
Beeldvorming .................................................................................................................................................... 25
Hoofdstuk 4 – behandeling .................................................................................................................................. 26
Chemotherapie ..................................................................................................................................................... 26
Celcyclus ........................................................................................................................................................... 26
Ontwikkeling ..................................................................................................................................................... 26
Soorten ............................................................................................................................................................. 26
Alkylerende agentia ...................................................................................................................................... 26
Antimetabolieten ......................................................................................................................................... 27
Mitotische inhibitoren .................................................................................................................................. 27
Topoisomerase inhibitoren .......................................................................................................................... 27
Antitumorale antibiotica .............................................................................................................................. 27
Toediening ........................................................................................................................................................ 27
Dosis ................................................................................................................................................................. 28
Principes ........................................................................................................................................................... 28
Nevenwerkingen ............................................................................................................................................... 28
Hormonale therapie .............................................................................................................................................. 29
Indicaties ........................................................................................................................................................... 29
Neveneffecten .................................................................................................................................................. 29
Gerichte therapie .................................................................................................................................................. 29
Heelkunde ............................................................................................................................................................. 29
Profylactische heelkunde .................................................................................................................................. 30
Diagnose en staging .......................................................................................................................................... 30
Heelkunde met curatief opzet .......................................................................................................................... 30
Palliatieve heelkunde........................................................................................................................................ 30
Andere procedures ........................................................................................................................................... 31
Radiotherapie ........................................................................................................................................................ 31
Waarom radiotherapie doen? .......................................................................................................................... 32
Manieren van toediening ................................................................................................................................. 32
Nevenwerkingen ............................................................................................................................................... 32
Fractionering ..................................................................................................................................................... 33
3
, Radiosensitiviteit .............................................................................................................................................. 33
Repair ................................................................................................................................................................ 33
Repopulatie....................................................................................................................................................... 34
Redistributie ..................................................................................................................................................... 34
Reoxygenatie .................................................................................................................................................... 34
Hoofdstuk 5 - stamceltransplantatie ................................................................................................................... 35
Factoren die stamceltransplantatie beïnvloeden ................................................................................................. 35
Onderliggende ziekte ........................................................................................................................................ 35
Voorbeeld: acute leukemie .......................................................................................................................... 35
Patientkarakteristieken .................................................................................................................................... 35
Beschikbaarheid van stamcellen....................................................................................................................... 36
Stamcelmobilisatie en -collectie ........................................................................................................................... 36
Beenmergprelevatie ......................................................................................................................................... 36
Perifere stamcel collectie ................................................................................................................................. 37
- ‘poor mobilizers’ .................................................................................................................................. 37
- Complicaties ........................................................................................................................................ 38
- Soorten donoren ................................................................................................................................. 38
- Keuze stsmcelransplantie .................................................................................................................... 39
Conditionering ...................................................................................................................................................... 40
Autologe conditionering ................................................................................................................................... 40
Allo conditionering: .......................................................................................................................................... 40
Myeloablatieve = chemo die beenmerg kapot maakt. ................................................................................. 41
- Niet-Myeloablatieve= chemo die niet beenmerg kapot maakt........................................................... 41
Keuze stamceltransplantatie ........................................................................................................................ 41
Stamceltransplantatie ........................................................................................................................................... 41
Complicaties: .................................................................................................................................................... 41
Hospitalisatie na stamceltransplantatie ................................................................................................................ 41
Naar huis na stamceltransplantatie ...................................................................................................................... 42
HvGD vs GvHD .................................................................................................................................................. 42
Afstoting ........................................................................................................................................................... 42
Problemen na transplantatie ............................................................................................................................ 42
Secundaire maligniteiten .................................................................................................................................. 42
Hoofdstuk 6 – immuuntherapie ........................................................................................................................... 43
Herhaling immuunsysteem ................................................................................................................................... 43
Aangeboren immuunsysteem = aspecifieke immuunrespons .......................................................................... 43
Verworven immuunsysteem = specifieke immuunrespons .............................................................................. 43
Onco-immunotherapie ..................................................................................................................................... 44
4
,Monoklonale antistoffen....................................................................................................................................... 44
Ongeconjugeerde ............................................................................................................................................. 44
Ongeconjugeerd antibody ................................................................................................................................ 44
Radio-isotoop.................................................................................................................................................... 44
BiTE ................................................................................................................................................................... 44
Checkpoint inhibitoren.......................................................................................................................................... 44
Pseudoprogressie ............................................................................................................................................. 45
CAR-T cells = Chimeric Antigen Receptor T cells ................................................................................................... 45
Nevenwerkingen: .............................................................................................................................................. 45
Target antigen ................................................................................................................................................... 45
Hoofdstuk 7 - Klinisch voorbeeld infectie - geassocieerde kanker: PTLD ........................................................... 46
Introductie ............................................................................................................................................................ 46
Definitie ............................................................................................................................................................ 46
Kwaadaardigheid door transplantatie .......................................................................................................... 46
Incidentie ...................................................................................................................................................... 46
Risicofactoren ....................................................................................................................................................... 47
Orgaantype ....................................................................................................................................................... 47
EBV status ......................................................................................................................................................... 47
Immunosuppresieve therapie........................................................................................................................... 47
Pathogenese.......................................................................................................................................................... 47
Presentatie ............................................................................................................................................................ 48
Verschillen tussen EBV+ en EBV- PTLD ................................................................................................................... 48
Behandeling van EBV ............................................................................................................................................ 48
Restoring T-cell function ................................................................................................................................... 48
a) RIS: Reduction of immune suppression ............................................................................................... 48
b) Adoptive immunotherapy ................................................................................................................... 48
Tumor reduceren .............................................................................................................................................. 49
a) Lokale therapie (radiotherapie) ........................................................................................................... 49
b) Rituximab and/or chemotherapy ........................................................................................................ 49
c) RSST (Risk Stratified Sequential Treatment) ....................................................................................... 49
Targeting EBV.................................................................................................................................................... 49
‘new classical agents’ ........................................................................................................................................ 49
a) CARTs ................................................................................................................................................... 49
b) Re-transplantatie ................................................................................................................................. 49
c) Prevention/prophylaxis/preemptive ................................................................................................... 49
Conclusie schema .................................................................................................................................................. 50
Hoofdstuk 8 - Klinisch voorbeeld hallmarks: acute myeloïde leukemie (AML) ................................................. 50
5
,Epidemiologie........................................................................................................................................................ 50
Pathogenese.......................................................................................................................................................... 50
CHIP/ARCH ........................................................................................................................................................ 50
Risicofactoren ....................................................................................................................................................... 51
Symptomen ........................................................................................................................................................... 51
Diagnose................................................................................................................................................................ 51
Morfologie ........................................................................................................................................................ 52
Immuno fenotypering ....................................................................................................................................... 52
Cytogenetica ..................................................................................................................................................... 52
Moleculaire diagnostiek ................................................................................................................................... 52
Behandeling .......................................................................................................................................................... 52
risico stratificatie .............................................................................................................................................. 52
3 + 7 .................................................................................................................................................................. 53
Hypomethylating therapy (HMA): azacytidine, decitabine .............................................................................. 53
FLT3 inhibitors .................................................................................................................................................. 53
Gemtuzumab ozogamicin ................................................................................................................................. 53
Hedgehog inhibitors ......................................................................................................................................... 54
IDH1/2 inhibitors .............................................................................................................................................. 54
Venetoclax ........................................................................................................................................................ 54
Examen: 2 grote vragen, 3 kleine vragen behorend tot 1 vraag
• Bv bespreek primaire, secondaire preventie van borstkanker
• Alarmsymptomen van een kanker
• Bijvragen: bv wat oor allogene donoren zijn er
• Les van 25 april: noem 3 nieuwe therapieën van AML zijn er (Shh, hypomethylerend etc).
6
,HOOFDSTUK 1 – INLEIDING
DEFINITIE & KENMERKEN
Gekarakteriseerd door ongecontroleerde celdeling → groei van abnormaal weefsel (= tumor, neoplasie
Continue delend organen: huid, bloedcellen
Bedoeling van groei om homeostase te behouden.
Normaal:
- Ontwikkeling en groei
- gecontroleerd
- Volwassen weefsels
o Homeostase behouden
▪ Steady state
▪ Herstel /repair
o Adaptief inspelen op wijzigende situaties
▪ Hypertrofie = cellen worden groter.
▪ Hyperplasie = Bv prostaat bij mannen, of endometrium bij de vrouwen. Of spiervergroting bij
trainging
Kanker:
- Groei zonder de wetten van het ecosysteem te respecteren
- Onaangepaste groei – ongecontroleerde groei
o Niet-adaptief: zonder uitlokkende fysiologische stimulus
o Niet flexibel of reversibel: zonder spontaan uitdoven
Differentiatie = de mate waarin het trekt uit het weefsel waaruit het
ontstaan is.
Mitotische activiteit ~ groeisnelheid
- Kan een goedaardige tumor levensbedreigend zijn? Meestal niet, maar zelden wel. Bijvoorbeeld in de
hersenen, omdat daar weinig plaats is.
- Links goedaardige tumor – rechts kwaadaardige tumor.
TYPES KANKER
afhankelijk van type cel waaruit ze ontstaan:
Melanocyten dienen voor bescherming tegen UV-schade. Die kunnen oiv UV kwaadaardig worden → melanoom.
Bindweefsel → bot- of ander = bindweefsel zijn sarcomen
Dus eigenlijk afhankelijk van de plaats & weefsel waaruit het ontstaat.
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,VASTE & VLOEIBARE TUMOREN
Vloeibare = wat we vanuit de hematologie vinden. Wordt behandeld door hematoloog.
Carcinomen, sarcomen, melanomen, teratomen
lymfomen
vaste = worden behandelend door oncoloog
Leukemie
STATISTIEKEN
- Wereldwijd is borstkanker de meest voorkomende voor vrouwen.
- Voor mannen is dit prostaatkanker, voor de meesten is dit niet dodelijk.
- In Rusland longkanker.
Dit is puur om te kijken dat er REGIONALE VERSCHILLEN zijn.
Hoe ouder je wordt, hoe meer kans je hebt om kanker te ontwikkelen. Globaal ontwikkelen iets meer mannen
kanker tov vrouwen.
Als je kijkt naar DE TOP 3 VAN MANNEN & VROUWEN zie je ook verschillen:
Als je daarna kijkt naar
overlijdingskanker is dat voor
mannen en vrouwen longkanker.
Statistisch gezien, heb je weinig
kans om te overleven als je
pancreaskanker hebt. Als je
borstkanker hebt bv hebt je
statistisch gezien wel nog
redelijke kans om te overleven.
INCIDENTIE VAN KANKER OVER DE VERSCHILLENDE JAREN:
- Er was in de jaren 90 een piek van prognoses van prostaatkanker, omdat men toen heel intensief zijn gaan
screenen naar prostaatkanker. Screening is hiervoor eigenlijk niet zinvol.
- Bij vrouwen zie je dat de prognose voor borstkanker ook beetje stijgt, om dezelfde reden. Screening heel
zinvol.
5-JAARS OVERLEVING
= hoeveel procent is na 5 jaar nog in leven, met behandeling = 67,1% voor alle kankers samen.
- Prostaan 98%
- Melanoma 92%
- Borst 90%
- …
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, - Slokdarm 20%
- Long 19%
- Lever 18%
- Pancreas 9%
Ook op jongere leeftijd is borstkanker voor vrouwen het meest dodelijk.
INDELING
AYA’S = jongvolwassenen & adolescenten. Die zijn interessant om te onderzoeken omdat ze toch een andere
biologie hebben, en moeten eerder met kinderschema’s behandeld worden, en niet de volwassen behandeling.
Een jongvolwassene moet er rekening mee houden dat zij nog verschillende fases van hun leven moeten
tegenmoet komen.
FAMILIAAL = genetische achtergrond die je gevoelig maakt voor kanker. Bv een gen die je gevoelig maar voor
borstkanker. 5-10%.
SPORADISCH = kanker die overkomt zonder dat iemand in je familie het heeft. de andere 90-95%.
DE NOVO = kanker krijgen zonder dat je kennelijk blootgesteld bent door iets.
SYMPTOMATISCH = prognose pas nadat je symptomen van de kanker merkt.
KLINISCH GEDRAG: agressief = zeer sterk groeiende. Indolent = alleen behandelen als mensen heel veel last
hebben – ze kunnen niet worden genezen maar wel dragelijker maken.
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