New potential treatment protocol for radiotherapy of glioblastoma
(2019) MSFT01 20191Medical Physics Programme
- Abstract
- Purpose: Improvements in mortality rate of glioblastoma patients have been limited
during the past decades, due to the tumor’s rapidly growing and infiltrative behavior
and resistance to current therapy. Recent findings show that higher brain mean dose
strongly correlates with inferior overall survival and that local recurrences mainly occur
centrally in previously irradiated regions. This project investigates the possibility
of a new radiotherapy protocol for glioblastoma patients, where treatment margins
are reduced in order to reduce brain dose while still cover the volume most prone to
relapse.
Method: Treatment plans from 45 patients who had been previously treated for glioblastoma,
with a prescribed dose of 60 Gy/30... (More) - Purpose: Improvements in mortality rate of glioblastoma patients have been limited
during the past decades, due to the tumor’s rapidly growing and infiltrative behavior
and resistance to current therapy. Recent findings show that higher brain mean dose
strongly correlates with inferior overall survival and that local recurrences mainly occur
centrally in previously irradiated regions. This project investigates the possibility
of a new radiotherapy protocol for glioblastoma patients, where treatment margins
are reduced in order to reduce brain dose while still cover the volume most prone to
relapse.
Method: Treatment plans from 45 patients who had been previously treated for glioblastoma,
with a prescribed dose of 60 Gy/30 fractions, were used. Recurrence volumes
(RV’s) were present for all patients. New treatment plans were produced, but with
1 cm clinical target volume (CTV) margins instead of 2 cm (current standard). Additional
plans were created for 20 patients, for which a simultaneous integrated boost
(SIB) of 75 Gy/30 fractions to the tumor volume was added to the reduced margins
tratment plans. The boost volume was defined as a 2 mm margin to a union of the
gross tumor volumes (GTVs) from MRI- and PET-scans. The 1 cm CTV was kept with
the previous ordinated dose of 60 Gy. Comparison of doses to target volumes, RV’s and OAR’s were performed using the Wilcoxon signed rank test in combination with identity plots. Spearman’s rank correlation coefficient was used to find whether there is a correlation between the reduction in PTV volume and reduction of brain mean dose as well as dose coverage of RV’s and GTV.
Results: Astatistically significant reduction in doses was found for whole brain (p<0.001),
left eye (p=0.003), right hippocampus (p=0.03) and remaining OAR’s (p<0.001). No
difference was found for RV’s (p=0.30) and PTV (p=0.22). Increased dose coverage
was found for GTV (p=0.03) due to some outliers. A statistically significant correlation
was found between reduction in brain mean dose and reduction in PTV volume
(r=0.4, p=0.006). Evaluating treatment plans with SIB, no significant difference in doses were found for the eyes and hippocampi. The remaining OAR’s experienced statistically significant
dose reductions (right optic nerve at p=0.005, the rest at p<0.001), while the target volumes
and RV’s received increased dose coverages (p<0.001).
Conclusion: Reducing the CTV margin from 2 cm to 1 cm may lead to better sparing
of OAR’s without sacrificing dose coverage of target and RV’s. However, clinical trials
would need to show whether this would change the recurrence patterns. These will
be necessary to find whether the increased local dose coverage following a SIB would
actually result in improved tumor control, since we have shown that OAR sparing
was not sacrificed. Nonetheless, reducing the irradiated volume without increased
treatment side effects would still be of benefit for the patient. (Less) - Popular Abstract (Swedish)
- Under de senaste decennierna har antalet diagnostiserade cancerfall stadigt ökat. För
patienter med den ödesdigra hjärntumören glioblastom har överlevnadsstatistiken
dock stått still. Forskare i Lund och Köpenhamn tros nu ha funnit pusselbiten som
kan komma att ändra på detta.
Cancern är en av de dödligaste sjukdomarna i Sverige och stod för 26 procent av alla
dödsfall år 2017. Däremot har man under de senaste 30–40 åren lyckats att nästan fördubbla
antalet patienter som är vid liv tio år efter sin cancerdiagnos. Bättre teknik och
förståelse för sjukdomarna har lett till att flera cancertyper, inklusive de två allra vanligaste,
idag har relativt god överlevnadsstatistik. En cancertyp vars prognos inte är
så god är hjärncancern... (More) - Under de senaste decennierna har antalet diagnostiserade cancerfall stadigt ökat. För
patienter med den ödesdigra hjärntumören glioblastom har överlevnadsstatistiken
dock stått still. Forskare i Lund och Köpenhamn tros nu ha funnit pusselbiten som
kan komma att ändra på detta.
Cancern är en av de dödligaste sjukdomarna i Sverige och stod för 26 procent av alla
dödsfall år 2017. Däremot har man under de senaste 30–40 åren lyckats att nästan fördubbla
antalet patienter som är vid liv tio år efter sin cancerdiagnos. Bättre teknik och
förståelse för sjukdomarna har lett till att flera cancertyper, inklusive de två allra vanligaste,
idag har relativt god överlevnadsstatistik. En cancertyp vars prognos inte är
så god är hjärncancern glioblastom. Lyckligtvis hör hjärntumörerna till de ovanligare
typerna av cancertumörer, eftersom de flesta glioblastompatienter avlider inom två
år. Utan behandling tar det endast någon månad. Anledningen är att cancercellerna
tycks vara resistenta mot dagens behandling, vilken består av att man först kirurgiskt
försöker avlägsna så mycket som möjligt av tumören, följt av chemo- och strålterapi.
Tråkigt nog tenderar tumören att komma tillbaka (det kallas då för recidiv) till området
som har behandlats, endast månader efter avslutad behandling.
Strålning förknippas i samhället idag som något otäckt, då trots att den inte syns eller
känns kan orsaka förödande konsekvenser. Om man däremot använder den rätt kan
den komma till oerhörd nytta. Hälften av alla cancerpatienter idag genomgår strålterapi.
Genom att fokusera strålningen mot tumören kan man ta kål på tumörcellerna.
Haken med strålbehandlingar är dock att stora delar frisk vävnad oundvikligen också
bestrålas, om än i lägre utsträckning.
Man har nyligen sett att det finns en stark korrelation mellan hög medelstråldos till
hela hjärnan och sämre överlevnad hos patienterna. Intuitivt vill man såklart genast
reducera mängden strålning som levereras till hjärnan. Däremot vet man även att
överlevnaden blir sämre om inte tillräckligt hög stråldos levereras till tumören. Inom
strålterapi behandlar man alltid med marginaler som ska ta hänsyn till osäkerheter
hos tumörens aktuella position och utbredning. Forskare har nu föreslagit en minskning
av dessa marginaler. Således skulle detta innebära att en mindre volym frisk
hjärnvävnad mottager den höga stråldos som är ämnad för tumören.
I detta examensarbete utfördes en simuleringsstudie med riktiga patientdata, där behandlingsmarginalerna
reducerades från 2 cm (nuvarande standard) till 1 cm. Information
om recidivens lägen fanns inkluderade för samtliga patienter. Genom att
genomföra denna minskning reducerades behandlingsvolymerna med ungefär 40 procent.
Intressant nog lyckades stråldosen till frisk omkringliggande hjärnvävnad sänkas
utan att behöva offra dos till tumör- och recidivområdena. Man fann även ett samband
mellan reducerad behandlingsvolym och reducerad medelstråldos till omkringliggande
hjärnvävnad.
Resultaten pekar mot ett potentiellt nytt protokoll för strålbehandling av glioblastom.
Säkerställning av dessa resultat samt ifall recidivlägena skulle komma att förändras
av att man ändrar på marginalerna återstår att se från framtida kliniska prövningar. (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/8995810
- author
- Pham, Victor
- supervisor
- organization
- course
- MSFT01 20191
- year
- 2019
- type
- H2 - Master's Degree (Two Years)
- subject
- language
- English
- id
- 8995810
- date added to LUP
- 2019-09-27 09:05:13
- date last changed
- 2019-09-27 09:05:13
@misc{8995810,
abstract = {{Purpose: Improvements in mortality rate of glioblastoma patients have been limited
during the past decades, due to the tumor’s rapidly growing and infiltrative behavior
and resistance to current therapy. Recent findings show that higher brain mean dose
strongly correlates with inferior overall survival and that local recurrences mainly occur
centrally in previously irradiated regions. This project investigates the possibility
of a new radiotherapy protocol for glioblastoma patients, where treatment margins
are reduced in order to reduce brain dose while still cover the volume most prone to
relapse.
Method: Treatment plans from 45 patients who had been previously treated for glioblastoma,
with a prescribed dose of 60 Gy/30 fractions, were used. Recurrence volumes
(RV’s) were present for all patients. New treatment plans were produced, but with
1 cm clinical target volume (CTV) margins instead of 2 cm (current standard). Additional
plans were created for 20 patients, for which a simultaneous integrated boost
(SIB) of 75 Gy/30 fractions to the tumor volume was added to the reduced margins
tratment plans. The boost volume was defined as a 2 mm margin to a union of the
gross tumor volumes (GTVs) from MRI- and PET-scans. The 1 cm CTV was kept with
the previous ordinated dose of 60 Gy. Comparison of doses to target volumes, RV’s and OAR’s were performed using the Wilcoxon signed rank test in combination with identity plots. Spearman’s rank correlation coefficient was used to find whether there is a correlation between the reduction in PTV volume and reduction of brain mean dose as well as dose coverage of RV’s and GTV.
Results: Astatistically significant reduction in doses was found for whole brain (p<0.001),
left eye (p=0.003), right hippocampus (p=0.03) and remaining OAR’s (p<0.001). No
difference was found for RV’s (p=0.30) and PTV (p=0.22). Increased dose coverage
was found for GTV (p=0.03) due to some outliers. A statistically significant correlation
was found between reduction in brain mean dose and reduction in PTV volume
(r=0.4, p=0.006). Evaluating treatment plans with SIB, no significant difference in doses were found for the eyes and hippocampi. The remaining OAR’s experienced statistically significant
dose reductions (right optic nerve at p=0.005, the rest at p<0.001), while the target volumes
and RV’s received increased dose coverages (p<0.001).
Conclusion: Reducing the CTV margin from 2 cm to 1 cm may lead to better sparing
of OAR’s without sacrificing dose coverage of target and RV’s. However, clinical trials
would need to show whether this would change the recurrence patterns. These will
be necessary to find whether the increased local dose coverage following a SIB would
actually result in improved tumor control, since we have shown that OAR sparing
was not sacrificed. Nonetheless, reducing the irradiated volume without increased
treatment side effects would still be of benefit for the patient.}},
author = {{Pham, Victor}},
language = {{eng}},
note = {{Student Paper}},
title = {{New potential treatment protocol for radiotherapy of glioblastoma}},
year = {{2019}},
}