2. Hypofractionated RT
• SF – WBI : Standard fraction Whole Breast
Irradiation
= 50 Gy in 25 Fractions to whole breast ( axilla )
with or without boost.
Problems :
tissue toxicity : skin, muscles, ribs, lungs, upper
esophagus
Time consuming : 5- 7 weeks
3. Hypofractionated RT in Breast CA
Definition : delivery of adjuvant RT to whole
breast in short period of 3-4 weeks.
• Smaller no of fractions , but dose per fraction
is > 2 Gy.
• Early lab studies : Most tumors exhibit low
fractional sensitivity ( high alpha/beta values )
• Radiation induced late normal toxicity shows a
high fractional sensitivity ( low alpha/beta
values ).
4. Hypofractionated Trials
( > 5 yrs follow up)
• 4 RCTs of hypofractionated RT trials in Breast.
Canadian Trial – NEJM 2010, 362: 513
START Pilot (RMH/GOC )– Lancet Oncol, 2006; 7
START A- Lancet Oncol 2008; 331
START B – Lancet Oncol , 2008: 371
7. 2236 women, T1 –T3a, N0-1, M0 , margins >1mm --BCS. Mastectomy - 15 % women
Primary End point : Rate of local relapse
Three Arms : ( All given over 5 weeks )
Standard : 50 Gy in 25 fractions
Arm I : 41.6 Gy in 13 fractions
Arm II : 39 Gy in 13 fractions
Boost was given in 61 % women = 10 Gy as 5 fractions
Rate of local relapse at 10 yrs : Standard fraction = 6.7 %; Arm I = 5.6 %, Arm II = 8.5 %
OS and DFS ( not primary end points ) were same in all arms.
10. START A Trial
Radiobiological rationale
• The hypothesis was that breast cancer cells
are as sensitive to a fraction size of radiation
as the normal breast tissues and ribs.
• If confirmed then giving low fraction sizes of
2Gy or less --- no therapeutic benefit.
Hypothesis - Why not use lesser, higher fraction
sizes to a lower total dose ?
11. START A Trial
Conclusions
• Results consistent with hypothesis that Breast
Ca cells are as sensitive to a fraction of RT as
normal breast tissues.
• 41.6 Gy in 13 fractions was as effective as 50
Gy in 25 fractions in terms of local tissue
effects and local tumor control.
• ( START B Trial : 40 Gy in 15 fractions over 3
weeks was as effective as 50 Gy in 25 fractions
)
12. START A Trial
Conclusions
• Follow up period of 5 yrs is too short to assess
late effects on normal tissues like heart.
• RMH/GOC ( START Pilot ) with 10 yrs follow up
showed no difference in tissue effects at
different fraction doses.
• A 13-fraction schedule is not the lowest limit
of hypofractionation. ..The NCRN FAST trial is
testing 5 fractions of 5.7 and 6 Gy, with one
fraction per week .
13.
14. Hypofractionated RT in Breast CA
Results of 4 trials
• No difference in the ipsilateral recurrence rates
compared to SF dosing.
• Trend towards increased local recurrence rates
observed in START Pilot and START A trial arms giving
39 Gy in 13 fractions ( HR = 1.26 )
• In all other schedules, trend towards reduced local
recurrence was observed ( HR = 0.86 ).
• No difference in OS observed in Canadian, START A
and START Pilot trials
• START B – significant improvement in absolute OS rate
of 3.3 at 10 yrs ( ? Due to reduced distant mets in the
hypofractionated arm. )
15. Hypofractionated RT in Breast CA
Results of 4 Trials
• Effect on normal tissues:
Pronounced skin toxicity was significantly lower in pts on
hypofractionated RT:
(RR=0.21, CI=0.07-0.64, p=0.0067)
• 43.9 Gy in 13 fractions as in pilot trial had significant
effects of breast appearance and induaration.
• 40 Gy/15 fractions in START B trial had least toxicity in
terms of appearance, induratioin, breast edema,
telangiectasia at 10 yrs
16. Hypofractionated RT
Boost or no Boost ?
• A 10 Gy, 5 fraction boost was given in :
75 % pts in RMH/GOC trial
61 % pts in START A trial
43 % pts in START B trial
* Local tumor control and normal tissue effects
were similar irrespective of tumor boost.
17. Hypofractionated RT in Breast CA
Can it be given to regional nodes?
• Regional node irradiation given to :
21 % pts in RMH/GOC Trial
14% pts in START A trial
7 % in START B Trial
* No increased incidence of late effects like
shoulder stiffness, arm oedema, brachial
plexopathy or lung fibrosis.
18.
19. Hypofractionated RT in Breast CA
Results of 4 trials
• 42.9 Gy in 13 fractions – late toxicities
• All options are feasible :
- 40 Gy in 15 fractions
- 42.5 Gy in 16 fractions
- 41.6 Gy in 13 fractions
* The most favourable schedule was as per the
START B Trial : 40 Gy in 15 fractions each of
2.67 Gy in 3 weeks
21. Hypofractionated RT in Breast CA
Who are the pts to be offered ?
ASTRO Guidelines ( 2011 ) :
• Age > 50 yrs; pT1 or T2, No , BCS
• Pts < 40 yrs or after mastectomy should not be
offered HF- WBI.
• Not used after NACT ( no pt in 4 trials had
received NACT ) .
• Caveat : Radiobiology does not change in
younger pts or after mastectomy. !
Editor's Notes
Average age in all trials : > 50yrs
In the RMH/GOC and START A trials – conventional fractionated RT was compared to two arms of fractionated RT over 5 weeks in 1:1:1 randomisation.
In the Canadian and START B trials : standard fractionated RT was compared to 3 weeks hypofractionated regimen in a 1:1 design.
* Primary end point in all trials – ipsilateral tumor recurrence
KM curve showing low event rates in all radiation schedules.
The absolute difference in loco-regional relapse compared to the 50 Gy at 5 yrs was 0.2 % for the 41.6 Gy schedule and 0.9% for the 39 Gy schedule.
Changes is breast appearance and hardness were the most common side effects.
The rates of moderate or marked effects on the breast were similar in either of the grps receiving 41.6 Gy or 50 Gy.
But the rates of modetate or marked effects on the breast tended to be lower in the 39 Gy than in those receiving 50 Gy ( shift to left ) . These results generally favour the 39 Gy dose over the 50 Gy and both 41.6 Gy and 50 Gy being equal in terms of effects on breast tissue.
