1 | [footer text here] UCSF Continuing Medical Education 24 April 2021 Dr David Thomson Consultant Clinical Oncologist The Christie NHS Foundation Trust, Manchester Proton beam therapy at The Christie, Manchester with a focus on head and neck cancers Disclosure Merck Sharp & Dohme Advisory Pecuniary, unrelated to talk International landscape and high level challenges Practical considerations and uncertainties NHS commissioned indications and avenues of clinical investigation Future translational, pre-clinical research Proton beam therapy at The Christie, Manchester with a focus on head and neck cancers
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UCSF Continuing Medical Education
24 April 2021
Dr David ThomsonConsultant Clinical Oncologist
The Christie NHS Foundation Trust, Manchester
Proton beam therapy at The Christie, Manchester with a focus on head and neck cancers
Disclosure
Merck Sharp & Dohme Advisory Pecuniary, unrelated to talk International landscape and high level challenges
Practical considerations and uncertainties
NHS commissioned indications and avenues of clinical investigation
Future translational, pre-clinical research
Proton beam therapy at The Christie, Manchester with a focus on head and neck cancers
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1019 15
2015
36 40
2020
27
Lack of level I evidence
Challenges
Cost - reimbursement/commissioning
Plan comparisons and models usually insufficient justification
Willingness to randomise
Practical considerations
Technology
Realising potential
IMPT more recently implemented
Robust optimisation
3D-verification imaging
Planning uncertainties
Proton range sensitivity
PBT barriers to routine implementation
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Practical Considerations and Uncertainties
Proton range uncertainties
Set-up and immobilisation
Weight loss and tumour regression
Dental amalgam and metal work
Data derived from: Hurley et al. (2012) Med. Phys. 39 (5)Courtesy: Dr Mat Lowe
Depth /mmCourtesy: Dr Mat Lowe
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5 beams, MFO with 5cm RS, split target, 3mm, 3.5%Avoid shoulder, amalgam, posterior and chinSpare central structures, SMG, parotid, OC
UK Proton Clinical Trials – Current, In Set-up, Future
A phase III trial of intensity-modulated proton beam therapy versus intensity-modulated radiotherapy for multi-toxicity reduction in oropharyngeal cancer
CRUK/18/010
CI: David Thomson
TOxicity Reduction using Proton bEam therapy for Oropharyngeal cancer
Observational Studies
Acute toxicities reduced (24% vs 47% required a feeding tube)
IMPT late toxicities - late grade 2 dryness 25% and 12-month gastrostomy dependence 2%
150 patients 1:2 IMPT:IMRT grade 3 weight loss or gastrostomy-tube dependence 12-months OR=0.23
Lower mandibular doses reduced rates of osteoradionecrosis (2% vs 8%)
Reduction in the ‘top 5’ MDASI symptoms scores up to 3 months
TOxicity Reduction using Proton bEam therapy for Oropharyngeal cancer
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Dose-volume parameters for organs-at-risk
Comparative planning of protons vs photons
Dutch composite model for different toxicities (xerostomia ≥grade 2, dysphagia ≥grade 2, tube feeding dependence) at 6 months
Method approved by the Netherlands whilst recognising the need for prospective biomarker validation and to inform selection thresholds
Hypothesise that for an enriched subgroup of patients (~50%) with a predicted difference in SUM-NTCP (IMRT vs IMPT) of 15% at 6 months, UW-QoL physical composite scale at 12 months would increase by ≥15 points
TOxicity Reduction using Proton bEam therapy for Oropharyngeal cancer
Validating a NTCP model to help identify who might benefit most from protons vs photons Translational Physics, Imaging, Biology
TOxicity Reduction using Proton bEam therapy for Oropharyngeal cancer
Pre-clinical, biological and physical science
Courtesy: Dr Mike Merchant
DNA damage and molecular and cellular responses, genomic markers RBE heterogeneityCombination with chemotherapy and immune response modifiersFLASH effect
Radiation OncologyDr Lip LeeDr Andrew McPartlinDr James PriceProf Mererid EvansProf Chris NuttingDr Anna ThompsonDr Dawn CarnellDr Matt BeasleyDr Olly DonnellyDr Bernie ForanDr Nachi PalaniappanDr Robin PrestwichDr Russell Banner
Translational ScienceProf Catharine WestProf Marcel Van HerkProf Karen KirkbyDr Mike MerchantDr Alan McWilliamProf Hans Langendijk
PhysicsProf Ran MackayDr Mat LoweDr Matt ClarkeDr Frances CharlwoodDr William BeasleyDr Callum Gilles
ENT SurgeryProf Terry JonesMr Jason FlemingProf Jarrod HomerMr Navin Mani
ICR CTSUProf Emma HallClare CruickshankNatasha Iles
Liverpool CTUCharlotte RawcliffeRichard Jackson
RTTQAElizabeth MilesDr Helen BainesDr Romaana Mir
NHS England Prof Adrian Crellin CBE
Patient Representatives Dr Helen BulbeckDr Tim HumphreyEmma Kinloch