Radiotherapy continues to play an important role in palliating and treating metastatic breast cancer. It effectively relieves bone pain and treats spinal cord compression, pathological fractures, brain and other organ metastases. Single fraction radiotherapy is as effective as multiple fractions for pain relief and more cost-effective. Further research is still needed on stereotactic radiosurgery/radiotherapy techniques and optimal doses/fractionation for various metastatic sites. Radiotherapy must be part of good multidisciplinary care for metastatic breast cancer patients and consider the patient's quality of life as the primary goal.
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Role of Radiotherapy in Metastatic Breast Cancer
1. IS THERE STILL A ROLE FOR RADIOTHERAPY IN
METASTATIC BREAST CANCER?
ALAN RODGER
SPECIALTY EDITOR (RADIATION ONCOLOGY), THE BREAST.
RETIRED CLINICAL ONCOLOGIST.
ABC1, Lisbon, November 2011.
2. ALTERNATIVE QUESTIONS?
• HAVE BISPHOSPHONATES, CYTOTOXICS, TARGETED
THERAPIES AND AROMATASE INHIBITORS CURED
METASTATIC BREAST CANCER (MBC)?
• CAN THEY PALLIATE EVERY SYMPTOM AND PREVENT
EVERY COMPLICATION OF MBC?
3. SO IS THERE STILL A ROLE FOR
RADIOTHERAPY IN MBC?
UNDOUBTEDLY!
AND, WHAT’S MORE, THERE’S
EVIDENCE TO SUPPORT IT
4. • KEY MESSAGES.
RADIOTHERAPY HAS AN IMPORTANT ROLE IN MBC IN THE
PALLIATION AND TREATMENT OF:
• BONE PAIN
• SPINAL CORD COMPRESSION
• PATHOLOGICAL FRACTURES
• INTRACRANIAL METASTASES
• CRANIAL METASTASES – BASE OF SKULL AND ORBITAL
• SOFT TISSUE DISEASE
• SOLID VISCERAL METASTASES
5. PALLIATION OF BONE PAIN WITH RADIOTHERAPY
• COMPLETE PAIN RELIEF IN 25% @ 1 MONTH
(395/1580)
• > 50% PAIN RELIEF IN 41% AT SOME TIME (788/1933)
• WHEN COMPLETE PAIN RELIEF, 52% ACHIEVE THIS IN
4 WEEKS WITH MEDIAN DURATION 12 WEEKS
• LEVEL OF EVIDENCE I - Cochrane Review, McQuay et
al, 1999.
7. RADIATION FRACTIONATION for EBRT
• SINGLE FRACTION IS EQUIVALENT TO
MULTIPLE FRACTIONS
• LEVEL OF EVIDENCE I – Cochrane
Review, ASTRO 2011 Guidelines, other
guidelines, numerous RCTs.
8. SINGLE FRACTION EBRT for PAIN
RELIEF
• PAIN CONTROL EQUIVALENT
• TOXICITY SIMILAR (though poor assessment)
• RETREATMENT RATES HIGHER – 20% v. 8% (Kachnic
et al, 2011)
• MORE COST-EFFECTIVE – it costs less (ASTRO, 2011)
• BISPHOSPHONATES DO NOT ELIMINATE THE NEED
FOR RADIOTHERAPY
• LEVEL OF EVIDENCE I
9. NON-COMPRESSIVE SPINAL
METASTASES
• INTERVENTIONAL RADIOLOGY –
vertebroplasty, kyphoplasty (see Gerszten et al in
Neurosurg. Focus, 2005) with Stereotactic Body
Radiosurgery (SBRS)
• EXTERNAL BEAM RT
• STEREOTACTIC RADIOSURGERY (SBRS) – single
fraction
• STEREOTACTIC RADIOTHERAPY (SBRT) - multiple
fractions (often a few)
• LEVEL OF EVIDENCE III/IV
10. SPINAL SBRS/SBRT
• NO RCTs
• SMALL SERIES
• RETREATMENTS/SOLE TREATMENT/POST-
INTERVENTIONAL PROCEDURE – mixes in studies
• EQUIPMENT CAN BE EXPENSIVE – so cost per
treatment high
• COMPLEX, TIME CONSUMING RADIOTHERAPY
PLANNING
• NEED FOR MORE HIGH QUALITY STUDIES AND RCTs
• LEVEL OF EVIDENCE – need for more research (III/IV)
11. COMPRESSIVE SPINAL METASTASES
• SURGERY – decompression and stabilisation
• RADIOTHERAPY – sole treatment
• RADIOTHERAPY - postoperative
• RADIOTHERAPY - EBRT
• RADIOTHERAPY – SBRT/SBRS
• LEVEL OF EVIDENCE III/IV
12. COMPRESSIVE SPINAL CORD METASTASES
• EBRT and PROGNOSIS on MULTIVARIATE
ANALYSIS - Rades et al JCO 2006 (n = 1852) LoE
III
• BETTER LOCAL CONTROL – histology
(breast, prostate, lymphoma); no visceral mets;
no/few other bone mets; good ambulatory
status; longer interval from first diagnosis; slow
loss of motor function
• RADIOTHERAPY COURSE – longer course (10, 15
or 20 fractions) better than shorter (1 or 5
fractions) – only a trend on univariate analysis
13. COMPRESSIVE SPINAL METASTASES
• EMERGENCY
• MRI – of not just area of neurological interest
but also adjacent areas superior and inferior
• MUTLIDISCIPLINARY OPINIONS – surgery and
radiation oncology
• CONSIDER FAST-TRACKING SYSTEM
• MORE RESEARCH REQUIRED – radiation
dose/fractionation; indications for SBRS/SBRT
14. IMPENDING LONG BONE FRACTURES
• PROPHYLACTIC SURGERY and POST-
OPERATIVE EBRT – when compared with
fracture followed by surgery and EBRT: more
likely to maintain or improve pre-diagnosis
level of mobility and self-care
Hardman et al Clin. Oncol.1992
LEVEL OF EVIDENCE IV
15. PATHOLOGICAL LONG BONE FRACTURES
• POST-OPERATIVE EBRT – more likely to regain
normal use of the extremity
• POST-OP EBRT – fewer re-operations
• MEDIAN SURVIVAL – 12-14 months after EBRT
v.3.3 months when no RT - ns ?? selection bias
• LEVEL OF EVIDENCE III – Townsend et al
JCO, 1994
16. CRANIAL METASTASES
BASE of SKULL
• BONE METASTASES
• COMPRESSIVE NEUROLOGICAL SYMPTOMS
and SIGNS
• RESPOND TO CONVENTIONAL PALLIATIVE
EBRT – five fractions/20 Gray
• RESPONSE MAY BE SEEN AFTER PROLONGED
SIGNS/SYMPTOMS (unlike cord compression)
• LEVEL OF EVIDENCE IV
17. CRANIAL METASTASES
ORBITAL
• SOFT TISSUE MASS MAY BE PRESENT
• COMPRESSIVE SYMPTOMS
• CHOROIDAL METASTASES – special case and
rare
• CONVENTIONAL PALLIATIVE EBRT
(dose/fractionation/technique) – can be
beneficial
• SBRS/SBRT may be considered
• LEVEL OF EVIDENCE III/IV
18. INTRACRANIAL (BRAIN) METASTASES
• PROGNOSIS – depends on age, PS and extent
of disease (LoE II – RTOG trials)
• PROGNOSIS in MBC – influenced also by ER
status, availability of therapy for extra-cranial
disease ( LoE III/IV)
• SINGLE/FEW BRAIN METS – generally respond
better. (LoE III/IV)
19. INTRACRANIAL (BRAIN) METASTASES
Treatment Options
• MULTIPLE METASTASES – EBRT 20 Gray/5
fractions as no other fractionation is superior
in terms of overall survival, symptom
control, neurological function, toxicity
• LEVEL OF EVIDENCE I – Cochrane Review 2007
20. SOLITARY OR FEW (1-3?) BRAIN
METASTASES
Treatment options
• SURGERY – with post-op whole brain EBRT
• SURGERY – alone
• EBRT – alone to whole brain
• EBRT (whole brain) – with SBRS/SBRT “boost”
• COMBINATION SBRS/SBRT and EBRT seems
‘equivalent’ to surgery and EBRT
• LEVEL OF EVIDENCE III/IV
21. BRAIN METASTASES
QUESTIONS FOR FURTHER RESEARCH
• SURGERY v. SBRS/SBRT
• PLACE of whole brain EBRT – in combination
or alone
• DOSE/FRACTIONATION of SBRT
22. SOFT TISSUE and SOLID VISCERAL
METASTASES
• LOCAL SYMPTOM CONTROL – from skin
lesions, nodal masses, uncontrolled local
recurrence
• RADIOTHERAPY
DOSE/FRACTIONATION/TECHNIQUE – will
depend on site, lesion, previous
EBRT, PS, symptoms
• LEVEL OF EVIDENCE IV
23. AREA for URGENT RESEARCH
SBRS and SBRT IN OLIGO-METASTATIC DISEASE
• NATURAL HISTORY of OLIGO-METASTATIC DISEASE in
MBC - what is it?
• The EFFICACY (RESPONSE and IMPACT ON SURVIVAL)
of IMRT and SBRS and SBRT against solid visceral
metastases
• OPTIMAL TECHNIQUES, DOSES and FRACTIONATION
– if any
• COST-EFFECTIVENESS
• TOXICITY
24. RADIOTHERAPY IN MBC
LET US NOT FORGET
• IT IS PALLIATIVE – reduce symptoms that are
there; cause no distress; do not treat the
asymptomatic (Ralston Patterson)
• TO BE EFFECTIVE IT MUST BE PART OF GOOD
MULTI-DISCIPLINARY CARE
• TODAY IT MUST BE COST-EFFECTIVE
• IT MUST CONSIDER THE PATIENT FOREMOST –
as sadly MBC is still incurable