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The Christie NHS Foundation Trust
Radiotherapy and radionuclides
Kate Garcez
Consultant Clinical Oncology
Christie NHS Foundation Trust
Manchester
9th Nov 2016
The Christie NHS Foundation Trust
How does radiotherapy work? • High energy photons produced by linear
accelerators cause ejection of electrons
from molecules
• Direct or indirect interaction with DNA
damages it
• Preferentially kills dividing cells
• No discrimination between cancerous or
normal……toxicity
• Aim is to exploit differences between normal
cells and cancer cells – normal cells better
able to repair damage
The Christie NHS Foundation Trust
The Challenge
Dose to cancer = cure rates
Dose to normal tissues = side effects
The Christie NHS Foundation Trust
• Relevance of acute vs late toxicity depends on prognosis
• All toxicity increases with total dose
• Fraction size affects late toxicity more than acute toxicity
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Aim of palliative EBRT for bone mets
• Treat bone pain
• Preserve function (eg MSCC)
• Consolidate surgical intervention
• 60-80% response rates
• Some (approx 25%) have complete pain response
• Can take 4-6 weeks to achieve result
The Christie NHS Foundation Trust
Case
• 84 yr old lady presented
with back pain
• PMH right hip replacement
• WHO PS 0
• Impending cord/cauda
equina compression at L2
and a large thyroid mass
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• Underwent spinal
decompression and
stabilisation
• Histology confirmed
follicular thyroid cancer
• Excellent post op recovery,
independently mobile, PS 1
• Referred for post-op RT
• 20Gy in 5# T12-L4
• Single post field
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Surgery/RT for MSCC
• Surgery + RT better than RT alone
• Scoring systems to evaluate prognosis/guide selection of patients • General condition, number of bone mets other than spinal mets, number of spinal mets, type
of primary lesion, presence of mets in other organs, state of paralysis
• Aim is to debulk and stabilise
• Does not obviate need for post op RT
• Little evidence re doses in post-op setting – aim is to eradicate
microscopic residual disease, often use longer fractionated
schedules
Patchell et al Lancet 2005; 26;366(9486):643-648
Tokuhashi et al Spine 2005;30:2186-2191
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Toxicity of EBRT
• Pain flare
• Lasts 1-2 days
• Treat with steroids
• Skin reaction
• Fatigue
• Location specific: nausea, diarrhoea, cystitis, hair loss
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Case cont’d
• Staging bone scan showed
known disease at L2,
patchy uptake elsewhere in
spine, and left upper femur
• X-ray
• Referred to orthopaedic
surgeons
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• Underwent prophylactic
nailing of left femur
• Well post-op
• Post-op RT
• 8Gy 1#
• Single ant/post field
• Cover metalwork
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Dose/fractionation
• Single vs fractionated treatment
• Equivalent rates of pain relief, time to pain relief (ASTRO guidelines)
• Convenience of single #
• Retreatment rates higher with single # (20% vs 8%)
• Acute toxicity greater/more prolonged with fractionated treatment
(except pain flare)
• Typical schedules - 8Gy/1#, 20Gy/5#, 30Gy/10#
• SCORAD III – single vs multifraction RT in MSCC
• Always important to consider prognosis/intended benefit
Lutz et al Int J Radiat Onc Biol Phys 2011; 15; 79(4):965-76
The Christie NHS Foundation Trust
Other examples
• 57 yr old man, locally advanced H&N cancer
• PS 3, severe lower back pain
• Wire to localise on planning scan, 8Gy 1#
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• 60 yr old lady
• Metastatic thyroid cancer
• 30Gy 10#
• Planned conformally (4
beams)
• Higher doses to disease,
less dose to surrounding
tissue
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• 69 yr old man incidental
finding of bone mets
• Biopsy confirmed metastatic
thyroid cancer
• Embolisation and
stabilisation of L1
• Post-op RT, 40Gy in 20#
• 6 beams
• OARs (organs at risk)
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SBRT (stereotactic body radiotherapy)
• Emerging for oligometastatic
disease (≤ 3 sites)
• Extremely conformal with steep
dose gradient
• Tight margins 2-3mm
• High total dose, few fractions
• 30-40Gy in 3# alt days
• 24-27Gy in 3# alt days spine
• Local control rates 90%
• May delay the need for systemic
therapy, possible improve PFS
Owen et al Pract Rad Oncol 2014; 4(2) e143-4149
The Christie NHS Foundation Trust
SBRT
• Immobilisation crucial – minimise intra-fraction motion
• Increased planning (dosimetry/verification/monitoring) time
• Increased treatment delivery time (ie time on the bed)
• Available in UK through Commissioning through Evaluation
programme for spine and bone mets
• CORE trial (Conventional care Or Radioablation in the treatment of
Extracranial metastases)
• Collect data (acute/late toxicity may be different)
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I131 – thyroid cancer • Differentiated thyroid cancer (papillary,
follicular)
• Iodine selectively taken up by thyroid
cells via sodium-iodide symporter
(NIS)
• β particles (path length 1-2mm)
• Excretion via urine 75%
• Half life 8 days
• Thyroid remnant ablation, first line
therapy for metastatic disease
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Case cont’d
• 84 yr old post spinal surgery, post op
RT, L femur nail, post op RT
• Total thyroidectomy
• Admitted for RAI therapy
• 5 day inpatient stay
• Post treatment scan
• Thyroid bed
• L2
• Left femur
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Case cont’d
• 1 year later
• Tg rising, more left hip pain
• Further admission for RAI
• Post treatment scan
• 3 months later pain
improved
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Toxicity and restrictions
• Acute: parotiditis, altered taste, nausea, possible tumour
‘flare’ – pain, swelling (caution with vertebral mets, consider
steroid cover)
• Late: xerostomia, sialadenitis, second malignancy
• Length of stay variable (5 days)
• Uptake scan before discharge
• Radiation protection precautions on discharge
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Radium 223 – prostate cancer
• Metastatic castration resistant
prostate cancer (bone)
• Bone seeking calcium mimetic,
accumulates in bone with increased
turnover eg osteoblastic or sclerotic
mets
• α emitter, very short path (< 100µm,
2-10 cell diameters) therefore highly
localised effect
• Half life 11.4 days
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Radium 223 therapy
• 6 treatments at monthly intervals
• IV administration
• Outpatient treatment
• Stop calcium supplements, check FBC
• Excretion via faeces – 75% in first week
• 5% in urine
• Minimal restrictions
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• 921 patients, phase 3, randomised, double blind
• 2:1 radium x 6 vs placebo x 6
• Primary: OS
• Secondary: time to first symptomatic skeletal event, various
biochemical endpoints
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Results • Eligibility:
• Progressive castration
resistant prostate cancer
• ≥ 2 symptomatic bone
mets, no visceral disease
• +/- previous docetaxel
• Baseline PSA ≥ 5ng/ml
• Median overall survival
extended by 3.6 months
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• 6 month delay to first
symptomatic skeletal event
• Well tolerated
• No clinically meaningful
differences in G3-4 adverse
events
• Improved QOL scores
• In practice:
• Consent for pain flare,
myelosuppression, nausea,
diarrhoea
• Most patients receive the planned
6 cycles
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Summary
• Radiation therapy remains an important treatment modality in
management of bone metastases
• Reduces symptoms and can improve overall survival
• Should be tailored to suit individual patients