Technological advances in Radiotherapy

Report
Technological advances in
Radiotherapy
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High-dose conformal radiotherapy
IMRT
IGRT
Protons
All: Spare the normal tissue, deliver as high a
dose as possible to cancer cells
External Radiotherapy Side Effects
• Short Term side effects
– Inconvenience / fatigue from travel daily for 7-8 weeks
– Starting weeks 2-4, irritation of bladder, rectum, tubing
– Means peeing more at night
• Alpha blocker pills, pyridium
• Patience – should get better a month after Radiotherapy
• Long term side effects
– Irritation of the front part of the rectum – bleeding in
stool (5-10%)
– Irritation of the urinary tubing and bladder
– Erectile dysfunction – in at least 50%
Intermediate-risk
prostate cancer
• Fair chance cancer is restricted to the prostate
gland
• Less than T3 and (PSA 10-20 or Gleason Score 7)
• Expect 60-80% chance of cure with treatment
• Best treatment is controversial
Surgery
Low tier
LDR brachy
vs. HDR +
EBRT
EBRT
ADT?
Int risk
Surgery
High tier
RTOG 0232 = LDR brachy ± EBRT
RTOG 0815 = RT (all forms) ± ADT
RTOG 0924 = any RT + hormones ± pelvic RT
HDR +
EBRT
EBRT +
ADT
? ADT
Intermediate-risk prostate cancer
<T3 and (PSA 10-20 or Gleason 7)
Seeds if low
intermediate
Radiotherapy
Intermediate
Risk
Surgery
High-dose
rate tubes
plus external
External plus
hormones
Patient flow for High Dose rate (tubes)
HDR brachy
Evaluation
Planning TRUS
• 15 Gy x 1
• CT simulation
EBRT
Followup
• 37.5 Gy in 15
Equipment
Stepper
Template and Catheters
Ultrasound and Planning System
Afterloader
Initial Image Acquisition
Needle Insertion
Catheter Reconstruction
Optimization
Optimisation
Optimization
Optimisation
Side effect from High Dose Rate
(tube) Brachytherapy
• Similar to side effects for seed implants
• Shorter duration of side effects (one month)
• Technology allows better sparing of normal
tissue
High-risk prostate cancer
• Cancer is LIKELY beyond the capsule of the prostate
gland and even in the blood stream
– Bone scan and CAT Scan normal
• T3 or PSA <20 or Gleason Score 8 (or higher)
• Expect 30% chance of cure with treatment
• Even if recurs life expectancy still greater than 10
years
• We need to test new therapies for this group
High-risk prostate cancer
T3 or PSA>20 or Gleason 8-10
Surgery
High risk
Post-op
Radiotherapy?
External RT plus
3 years hormones
High dose rate
+ External + HT
Hormone
duration?
Role of Surgery in high-risk Disease
• Aiming for cure!
• Most men will need radiotherapy after surgery
• Means side effects from both modalities
– Surgery causes possible incontinence
– Radiation causes possible rectal irritation
– Higher chance of erectile dysfunction with both
• Reasonable to consider in younger man to maximize
chance of cure
Treatment for cure: adding
hormone therapy to radiotherapy
• Hormones given as injections
• Six months up to 3 years
• Can increase the chance of cure by 5-10%
– Increasing effectiveness of radiotherapy
– And/or killing off cancer cells floating in blood stream
• This is the same type of hormone treatment that is
used if the cancer becomes incurable
Side effects of hormone therapy
• Loss of libido and erectile dysfunction from lack of
testosterone
• Hot flashes
• Bone loss and risk of osteoporosis / fractures
• Weight gain
• Decreased muscle strength
• Lowering of hemoglobin count by 8-15 g/L
• Mood changes – mild depression, irritability
• Slight decrease in some mental function
• Diabetes
• Increase in lipids / cholesterol
• Slight risk of heart attack –especially > 65 years old
Need for new agents
• Go on clinical trials – compares the standard
treatment with a newer treatment
Prostate cancer therapy milestones
Abiraterone Acetate
Cabazitaxel
Docetaxel
Mitoxantrone
1994
Denosumab
Zoledronic acid
2002
Current Treatments
MDV 3100
2004
2008
2011
Emerging Treatments
23
PSA after a prostate operation
• PSA should 0 if all normal prostate cells and
cancer cells have been removed
• An undetectable PSA does not mean there are
no prostate cancer cells left in the body
– It takes hundreds of cancer cells to produce
enough PSA for the blood test to detect it
• A rising PSA after an operation means that
there are cancer cells in the body
Radiotherapy after operation
• Called “Adjuvant” radiotherapy if PSA is
undetectable
• Called “Salvage” radiotherapy if the PSA is rising
• Radiation can target cells in the pelvis and where
the prostate was (bed)
• May add hormone treatments if the gleason score
8+
Radiotherapy after operation
Radiation now
Cancer outside
prostate capsule or
margin involved
PSA=0 after
Operation
Cancer within
prostate gland +
margin good
Wait to see if PSA
rises
Adjuvant Radiotherapy after operation
• If PSA is undetectable
• Improves cure rates in selected cases
– Cancer cells penetrate beyond the capsule of prostate
– Cancer cells seen up against where surgeon cut (margin positive)
• Given as 33 treatments over 6 ½ weeks to prostate area +/pelvis +/- hormone treatment
• Typical short term side effects of prostate radiotherapy
– Fatigue, irritation of bladder and tubing (urethra), soreness of rectal
passage. All better within a month
• Long Term side effects:
– 10% mild bleeding from rectum,
– 5% scarring on urethra – usually needs reaming to open up
– High chance of erectile dysfunction
Radiation after operation for a Rising
PSA
• Called ‘Salvage’ Radiotherapy – +/- 25% success rate
• We can’t tell where the cancer cells are
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Localized to site of operation (prostate bed)
Spread to lymph nodes in pelvis
In the blood stream or into bone (even with normal bone scan)
Any combination of above
• Most likely to be localized to prostate bed
– Positive margin
– Slower growing cancer
• Operation in distant past
• PSA rising slowly
• Decision may be to not give radiotherapy
– PSA is rising too quickly and chance of cure too low
– Cancer is so slow in a man with a shorter life expectancy
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50%
dose
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Rising PSA after Radiotherapy
• Usually not a curable situation
• Only consider cure if
– Low risk disease at diagnosis
– Recurrent Cancer appears to be slow growing
– Biopsy of prostate confirms residual cancer
• Prostate surgery has 50% complication rate after
RT
• Options must spare normal tissue and kill cancer:
• Cryotherapy – is freezing tissue
Radiation for palliation
• Prostate Cancer spread to bone can cause
– Pain
– Fracture
– Spinal cord compression
• Call if you get numb feet or weakness of
legs!!!
• External radiation works very well 80-90% of
time
– 1-5 days of treatment – 10min per day
• Side Effects depend on part of body
Radiation by injection
• Strontium – radioactive substance that is picked
up by healing bones
• Best used when multiple sites of bony pain
• Need reasonable blood counts and kidney
function
• High chance of pain relief
Thank you!
ProstateCancer.ca
HealingandCancer.org
PSA after radiotherapy
• PSA rarely gets down to undetectable value after
RT because some normal prostate cells are still
alive
• PSA can bounce around a little because the
normal cells can get inflamed
• A rising PSA 2 points higher than the lowest PSA
value means the cancer has come back
• Rare to recommend surgery or cryotherapy if
cancer recurs
PSA after hormone treatment
• Hormone therapy starves both normal prostate cells
and cancer cells of testosterone
• Hormone therapy kills / disables over 99% of cancer
cells and should bring the PSA down to an undetectable
level
– Hormone therapy given as part of a curative plan increases
the chance of cure
• Once the effects of hormone therapy wear off,
testosterone will raise, and PSA levels will increase
according to whether normal prostate cells or cancer
•
Long survival times even
after
recurrence
2007: 70-year-old very well executive
– PSA rising up to 9.5
– Biopsy shows Gleason Score 9 (fast growing)
– Lump in prostate is confined
– Bone scan and cat scan show no obvious spread
• He goes on a clinical trial
– Hormones for 2.5 years, full dose radiotherapy,
and weekly chemotherapy during the
radiotherapy
• His PSA is undetectable for 4 years
Long survival times after
recurrence – Example case
• Ocotober 2011 PSA is 0.07 (testosterone is low
normal)
– His exam is normal
• April PSA is 0.15 (testosterone same)
– Doubling time is about 6 months
• Not defined as a recurrence until PSA >2 but likely
incurable cancer now
• PLAN: Wait for PSA > 10-15 - this will take 6
doubling times or 3 years
• Start on hormone therapy – will hold cancer in check
for 3-5 years
Long survival times after
recurrence – Example case
• He has many more years to live
• Don’t turn slow growing cancer cells into fast
growing cells
• He can do something about the side effects of
hormone therapy which can influence his quality of
life

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