ThefutureofradiotherapyforCNSmetastases:farewelltoWBRT?

AnthonyChalmersBrainMetastasesConference

Marseille6th October2017

Arapidlychangingfieldthatisdifficulttostudy:

• Highlyheterogenous groupofpatients:– Numberandvolumeofmets– Histology,extracranial disease,systemicandprimary

treatment– Performancestatus

• Difficultpatientgroupforclinicaltrials• Historicalnihilism• Rapidevolutionofradiotherapytechnology• EmergingmoleculartargetedagentswithBTBpenetration

Pre-radiation 18monthspost-radiation

WBRTcanbeatoxictreatment

Dothebenefitsjustifytherisks?

538patients,72centres

AddingWBRTtofocaltreatmentdoesnotimprovesurvival….

Soonetal,2014

…butimprovesintracranialdiseasecontrol

Noeffectof:- surgeryvSRS- singlevmultiple- scheduling- WBRTdose

Soonetal,2014

DobetterprognosispatientsbenefitfromWBRT?

Allpatients

Excludingpatientswithextracranial progression

before6months

NSCLCDS-GPA0.5– 1.5

NSCLCDS-GPA2.0– 4.0

Whataboutcognitionandqualityoflife?

Changetal,LancetOncology2009

Soffietti etal,JCO2013

Globalhealthstatus Physical

EmotionalCognitive

FarewelltoWBRT!Butwhatshouldwereplaceitwith?

IMRT– tomotherapy- VMAT- protons

Hippocampalsparingisdeliverableinmostcentres

• Primaryendpoint:HopkinsVerbalLearningTest–RevisedDelayedRecall(HVLT-RDR)at4months.

• 113patientsaccrued,42patientsanalyzableat4months.

• MeanrelativedeclineinHVLT-RDRfrombaselineto4months7.0%(4.7- 18.7%)

• Significantlylowerthan30%inhistoricalcontrols(p=.001).

Patientsaliveat6months Patientsdeadat6months

Randomised phase III trial of Memantine Hydrochloride and Whole-Brain Radiotherapywith or without Hippocampal Avoidance in Reducing Neurocognitive Decline in Patientswith Brain MetastasesBrown;NRGOncology

Determinewhethertheadditionofwhole-brainradiotherapywithhippocampalavoidance(HA-WBRT)increasestimetoneurocognitivefailureatmonths2,4,6,and12asmeasuredbyneurocognitivedecline(HVLT-R,COWA,TMT).

HIPPO: randomized phase II trial of Hippocampal Sparing versus Conventional Whole BrainRadiotherapy after surgical resection or radiosurgery in favourable prognosis patientswith 1-10 brain metastasesWhitfield;UKNCRI

PrimaryEndpoint:HVTL-Rat4months.

VMATSRSfor 3brainmetastases:25Gyin3minutes

Yamamotoetal,LancetOncology2014

PrescriptiondosesandSRStargetvolumeswere16Gy(for≤10cc),14Gy(for10·1–15cc),and12Gy(for>15cc).

Single isocentre, MLC based, non-coplanar VMAT solution for radiosurgery

SuzanneCurrie

PeterHouston

QFix Encompass and6Degrees ofFreedom Couch

NormalTissueObjectivesoftware

HyperArc software

18%dosewashinblue

Non-coplanarVMAT

HyperArc

4Gydosewashinblue

Improvedconformality andprecisionmayenabledoseescalationtolargervolumes

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• PanelofDNAdamageresponseinhibitorsenteringclinicaltrials

• ATMinhibitorsverypotentradiosensitisers

• AZD1390brainpenetrant

FarewelltoWBRTManynewoptionsemerging

Treatthepatient!