ucsf continuing medical education the christie nhs

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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


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


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


5 beams, MFO with 5cm RS, split target, 3mm, 3.5%Avoid shoulder, amalgam, posterior and chinSpare central structures, SMG, parotid, OC

Parotids: 7Gy, 17.5Gy / OC: 19Gy / SMG: 23, 27Gy / Larynx: 25Gy

Ant: trt below chin, LAO: ipsilateral sideLlat, RPO: ipsilateral side to shoulders,

Post: L side to shoulder to help, spare parotid, OC

Weight gain / fluid from chemotherapyAffecting coverage

Weight loss Hot spot in lumen

Increased dose to spinal cordCTV2 under-coverage

Tumour responseCTV1 119% under uncertainty, spinal cord 2Gy over tolerance

Avoid where possible Beam arrangement

Discuss with dentists and surgeonsKnow what material is used

Some materials are preferred over otherse.g, PEEK / Carbon > Titanium > Cobalt Chrome

Adults

Base of skull tumours (radio-resistant).

Spinal and para-spinal tumours (radio-resistant).

Teenagers and Young Adults (TYA) - age 16–24

Adult indications.

Paediatric tumours – as per paediatric indications.

Paediatric

Tumours in adult indication list.

Most paediatric tumours, malignant and benign.

NHS Commissioned Indications

Curative intentWHO PS 0/1Where indicated, optimal surgery/clearance from dose limiting structure


1. Adult chordorma 73.8 Gy(RBE=1.1) in 41 fractions of 1.8 Gy(RBE=1.1)/fraction, SFO, 2 phases 4/2 fields

2. Paediatric grade I/II astrocytoma: 50.4 Gy(RBE=1.1) in 28 fractions of 1.8 Gy(RBE=1.1)/fraction, SFO 2 fields. VMAT plan also shown for comparison

Low cure ratehigh toxicities

High cure ratehigh late toxicities

High acute toxicities

CTCAE/PROMsInstrumental measurement

Biomarkers

Integral doseOAR dose-function

Dose-volume coverageIntegral dose

OAR dose-function

Oropharynx - TORPEdOBreast - PARABLECNS – APPROACH

Mediastinal lymphoma

SurvivalCTCAE, PROMs

Instrumental measurement

Oesophagus/Pancreas/LiverSinonasal

Lung, mesotheliomaRe-irradiation

Integral doseRT-drug delivery

Overall survival Patient factors

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



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


Validating a NTCP model to help identify who might benefit most from protons vs photons Translational Physics, Imaging, Biology


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

MCRCProf Rob BristowProf David Wedge

ucsf continuing medical education the christie nhs

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