radiotherapy and radionuclides - royal surrey county hospital · the christie nhs foundation trust...

The Christie NHS Foundation Trust

Radiotherapy and radionuclides

Kate Garcez

Consultant Clinical Oncology

Christie NHS Foundation Trust

Manchester

9th Nov 2016


Where does radiation fit in?


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 Challenge

Dose to cancer = cure rates

Dose to normal tissues = side effects


• Relevance of acute vs late toxicity depends on prognosis

• All toxicity increases with total dose

• Fraction size affects late toxicity more than acute toxicity


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


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


• 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


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


Treatment delivery


Toxicity of EBRT

• Pain flare

• Lasts 1-2 days

• Treat with steroids

• Skin reaction

• Fatigue

• Location specific: nausea, diarrhoea, cystitis, hair loss


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


• Underwent prophylactic

nailing of left femur

• Well post-op

• Post-op RT

• 8Gy 1#

• Single ant/post field

• Cover metalwork


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


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#


• 60 yr old lady

• Metastatic thyroid cancer

• 30Gy 10#

• Planned conformally (4

beams)

• Higher doses to disease,

less dose to surrounding

tissue


• 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)


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


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)


Radionuclides

Iodine 131

Radium 223


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


I 131 therapy

• Low iodine diet

• TSH stimulation

• Isolation


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


Case cont’d

• 1 year later

• Tg rising, more left hip pain

• Further admission for RAI

• Post treatment scan

• 3 months later pain

improved


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


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


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


• 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


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


• 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


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


Thank you

radiotherapy and radionuclides - royal surrey county hospital · the christie nhs foundation trust...

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