Hypofractionation

Question 1

OCOG 93-010 (Canadian, Whelan)

Reason for Trial?

Answer 1

Radiobiological models suggest that hypo-fractionation may be just as effective as 50 Gy in 25 fxs

More convenient

Improve compliance

Question 2

OCOG 93-010 (Canadian, Whelan)

How many yrs of data is available?

Answer 2

5 and 10 yr

Question 3

OCOG 93-010 (Canadian, Whelan)

Inclusion Criteria?

Answer 3

Invasive carcinoma w/ -ve LNs

tx’ed with lumpectomy and ALND

Question 4

OCOG 93-010 (Canadian, Whelan)

Exclusion Criteria?

Answer 4

IDC or DCIS with +ve margins
Tumors > 5 cm
Breast width > 25 cm

Question 5

OCOG 93-010 (Canadian, Whelan)

Why was the breast width chosen as such?

Answer 5

Larger breasts can cause dose heterogeneity

Question 6

OCOG 93-010 (Canadian, Whelan)

RT Regimen?

Answer 6

50/25 vs. 42.5/16. No boost
Delivered via 2 opposed tangential beams (2D planning)
No RT to the LNs( (Supraclav, IM, or axillary)

Question 7

OCOG 93-010 (Canadian, Whelan)

Patient stratification?

Answer 7

Age (<50 yrs or >50 yrs)
Tumor Size (<2cm or >2cm)

Question 8

OCOG 93-010 (Canadian, Whelan)

Primary outcomes?

Answer 8

Local recurrence

Question 9

OCOG 93-010 (Canadian, Whelan)

Secondary outcomes?

Answer 9

distant recurrence
contralateral breast recurrence
second cancers
breast cosmesis
late toxic effects of RT
Death

Question 10

OCOG 93-010 (Canadian, Whelan)

How was RT toxicity assessed?

Answer 10

Using Late Radiation Morbidity Scoring Scheme

Question 11

OCOG 93-010 (Canadian, Whelan)

How was breast cosmesis asessed?

Answer 11

Using EORTC Cosmetic rating system

Question 12

OCOG 93-010 (Canadian, Whelan)

Type of Trial?

Answer 12

Non-inferiority trial

Question 13

OCOG 93-010 (Canadian, Whelan)

How many pts?

Answer 13

1234. LOL

Question 14

OCOG 93-010 (Canadian, Whelan)

Pt characteristics?

Answer 14

25% < 50 yrs
33% T2
26% ER-
11% Chemo (5 FU, Cyclophosphamide, MTX)
41% tamoxifen

Question 15

OCOG 93-010 (Canadian, Whelan)

Results: Local Recurrence of invasive disease?

Answer 15

10 yr LR

hypo: 6.2%
conv: 6.7%

Question 16

OCOG 93-010 (Canadian, Whelan)

Results: Cosmesis?

Answer 16

10 yr Cosmesis

Excellent or good cosmetic outcome

hypo: 70%
conv: 71%

Older age and larger tumors were associated with worse outcomes

Question 17

OCOG 93-010 (Canadian, Whelan)

Results: Skin G3 TOX?

Answer 17

10 yr TOX

hypo: 2.5%
conv: 2.7%

Question 18

OCOG 93-010 (Canadian, Whelan)

Results: DSS?

Answer 18

10 yr DSS

hypo: 87%
conv: 87%

Question 19

OCOG 93-010 (Canadian, Whelan)

Results: OS?

Answer 19

10 yr OS

hypo: 84%
conv: 84%

Question 20

OCOG 93-010 (Canadian, Whelan)

Conclusion?

Answer 20

Hypo WB RT okay for -ve margin, -ve LN, and breast separation < 25 cm

Question 21

OCOG 93-010 (Canadian, Whelan)

Was there any subanalysis?

Answer 21

Yes, subanalysis for high grade tumors (19% of tumors)
RT less effective for high-grade tumors

10 yr LR for HG

hypo: 15%
conv: 5%

Question 22

OCOG 93-010(Canadian, Whelan)

Limitations of the trial

Answer 22

No patients with DCIS alone!

Question 23

START A&B

How many trials?

Answer 23

2 PRT

Question 24

START A&B

When was the study run?

Answer 24

1999-2002

Question 25

START A&B What does START stand for?

Answer 25

Standardization of Breast Radiotherapy

Question 26

START A&B What RT doses were assessed?

Answer 26

START A: 50/25 vs. 41.6/13 or 39/13 QOD START B: 50/25 vs. 40/15 Both permit a 10 Gy boost

Question 27

START A&B Tumor characteristics?

Answer 27

pT 1-3a pN 0-1 M0

Question 28

START A&B What does the N mean?

Answer 28

N1 mi: >0.2 mm and/or >200cells, but < 2mm a: 1-3 axillary LNs b: IM LN +ve pathologically but -ve clinically c: pN1a + pN1b

Question 29

START A&B Primary end-points?

Answer 29

1. Loco-regional relapse (relapse within the breast, chest wall, ip axilla, supraclav fossa, or within an irradiated volume 2. Late normal tissue side-effects

Question 30

START A&B Secondary end-points?

Answer 30

1. Distant relapse 2. DFS 3. OS

Question 31

START A&B of pt's recrutied?

Answer 31

START A: 2236 | START B: 2215

Question 32

START A&B How many LN +ve pts?

Answer 32

START A: 29% | START B: 23%

Question 33

START A&B How many % lumpectomy?

Answer 33

START A: 85% | START B: 92%

Question 34

START A&B START A: Important pt characteristics?

Answer 34

START A: 1. Age 57 (25-85) 2. Adjuvant Chemo 35% 3. Tamoxifen 79% 4. Lumpectomy 85% 5. RT Boost 61% 6. LN RT 14%

Question 35

START A&B How many yrs of data do we have?

Answer 35

5 and 10 yrs

Question 36

START A&B Results of START A?

Answer 36

START A: No sig difference 10yr LRR: 6.3% (41.6 Gy) vs. 8.8% (39 Gy) vs. 7.4 (50 Gy)

Question 37

START A&B START B: Important pt characteristics?

Answer 37

START B: Age 57 (23-86) 1. Age 57 (23-86) 2. Adjuvant Chemo 22% 3. Tamoxifen 87% 4. Lumpectomy 92% 5. RT Boost 23% 6. LN RT 7%

Question 38

START A&B Results of START B?

Answer 38

START B 1. 10yr LRR: 4.3% (40 Gy) vs. 5.5% (50 Gy). No sig. 2. 10yr distant relapse: 12.3% (40) vs. 16% (50). Sig 3. 10 yr all-cause mortality: 7.9& (40) vs. 10.9% (50). Sig 4. Local side effects were significantly less common with 40 than 50. 2 and 3 were not observed START A.

Question 39

START A&B Conclusions?

Answer 39

Hypo-fractionated WBI is safe and effective for early breast cancer. 40/15 is SOC in the UK.