1. Dr Asha Arjunan, MD, DNB, DMRT
Additional Professor
Department of Radiation Oncology
Regional Cancer Centre, Trivandrum
12/NOV/2022

2. OUTLINE
 Adjuvant radiotherapy
Mastectomy
Breast Conservation Surgery
 Hypofractionated whole breast
radiotherapy(WBI)
 Accelerated partial breast irradiation(APBI)

3. • Important tool in treatment of breast cancer
• Postop RT: Decreases risk of loco regional recurrence
by treating residual microscopic disease
RADIOTHERAPY
• Increase local control & hence increase survival

4. • The analysis included 36 trials of post-mastectomy radiation with 16,177
women.
• Demonstrated a 5% absolute decrease in 15-year breast cancer mortality with
a 20% improvement in 5-year local control.
• Subset analysis in node-negative postmastectomy patients noted no survival
benefit in those who underwent mastectomy and radiotherapy with adjuvant
systemic therapy.

6. Effect of radiotherapy (RT) after breast-conserving surgery (BCS) on 10-year risk of any (locoregional or distant) first
recurrence and on 15-year risks of breast cancer death and death from any cause in 10 801 women (67% with
pathologically node-negative disease) in 17 trials
Early Breast Cancer Trialists' Collaborative Group (EBCTCG), Darby S, McGale P, Correa C, Taylor C, Arriagada R, Clarke M, Cutter D, Davies C,
Ewertz M, Godwin J, Gray R, Pierce L, Whelan T, Wang Y, Peto R. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-
year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet. 2011 Nov 12;378(9804):1707-16.

7. Effect of radiotherapy (RT) after breast-conserving surgery (BCS) on 10-year risk of any (locoregional or distant)
first recurrence and on 15-year risk of breast cancer death in women with pathologically verified nodal status
Early Breast Cancer Trialists' Collaborative Group (EBCTCG), Darby S, McGale P, Correa C, Taylor C, Arriagada R, Clarke M, Cutter D,
Davies C, Ewertz M, Godwin J, Gray R, Pierce L, Whelan T, Wang Y, Peto R. Effect of radiotherapy after breast-conserving surgery on 10-
year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet.
2011 Nov 12;378(9804):1707-16.

8. Early Breast Cancer Trialists' Collaborative Group (EBCTCG), Darby S, McGale P, Correa C, Taylor C, Arriagada R, Clarke M, Cutter D, Davies C, Ewertz
M, Godwin J, Gray R, Pierce L, Whelan T, Wang Y, Peto R. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast
cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet. 2011 Nov 12;378(9804):1707-16.

10. Effect of radiotherapy (RT) after mastectomy and axillary dissection (Mast+AD) on 10-year risks of
locoregional and overall recurrence and on 20-year risk of breast cancer mortality in 700 women with
pathologically node-negative (pN0) disease and in 3131 women with pathologically node-positive (pN+)
disease
Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual
patient data for 8135 women in 22 randomised trials EBCTCG (Early Breast Cancer Trialists' Collaborative Group) The Lancet Volume 383 Issue
9935 Pages 2127-2135 (June 2014)

11. Effect of radiotherapy (RT) after mastectomy and axillary dissection (Mast+AD) on 10-year risks of
locoregional and overall recurrence and on 20-year risk of breast cancer mortality in 1314 women with
one to three pathologically positive nodes (pN1–3) and in 1772 women with four or more pathologically
positive nodes (pN4+)
Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for
8135 women in 22 randomised trials EBCTCG (Early Breast Cancer Trialists' Collaborative Group) The Lancet Volume 383 Issue 9935 Pages 2127-2135 (June
2014)

12. Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer
mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials EBCTCG (Early Breast
Cancer Trialists' Collaborative Group) The Lancet Volume 383 Issue 9935 Pages 2127-2135 (June 2014)

13. Hypofractionated Whole
Breast radiotherapy
(HF-WBI)

14. Started as an empirical practice in government-run health care
systems of UK and Canada
Initially, a purely logistical exercise to reduce treatment duration &
create machine space

15. Analysis of available clinical data from multiple
institutions support that breast cancer has a
low ratio of α/β
Qi, X Sharon et al. “Is α/β for breast cancer really low?.” Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology vol. 100,2
(2011): 282-8

16. Ontario Clinical Oncology Group(OCOG)
Trial
 April 1993 and September 1996
 Invasive carcinoma of the breast with negative
axillary nodes foll. BCS & Axillary dissection
 Exclusion criteria: T >5 cm in dia., invasive disease
or DCIS involving the margins of excision & breast
width >25 cm
 Primary outcome: Local recurrence
 Secondary outcomes: Distant (including regional)
recurrence, second cancers(including contralateral
breast cancer; breast cosmesis; late toxic effects of
radiation; & death
50.0 Gy in 25 fractions
over a period of 35 days
42.5 Gy in 16 fractions over
a period of 22 days
Whelan T, Pignol J-P, Levine M, et al. Long-term results of hypofractionated radiation therapy for breast cancer. N Engl J Med
2010; 362: 513–20

17.  Panel A : Kaplan-Meier estimates for local
recurrence (P<0.001 for noninferiority)
 At 10 years, cumulative incidence of local
recurrence similar in two groups
 Panel B: Kaplan-Meier estimates for overall
survival[OS] (P=0.79)
 The probability of survival over time was
similar in the two groups
Whelan T, Pignol J-P, Levine M, et al. Long-term results of hypofractionated radiation therapy for breast cancer. N Engl J Med
2010; 362: 513–20
Outcomes in Patients with Breast Cancer Who Received
Hypofractionated Regimen of Radiation Therapy as Compared
with Patients Who Received the Standard Regimen
Ontario Clinical Oncology Group(OCOG) Trial

18. Ontario Clinical Oncology Group(OCOG) Trial
 Incidence of late toxic effects of radiation
increased over follow-up period
 No increase in toxic effects with
hypofractionated radiation therapy
compared to standard regimen
Whelan T, Pignol J-P, Levine M, et al. Long-term results of hypofractionated radiation therapy for breast cancer. N Engl J Med 2010; 362: 513–20
Late Toxic Effects of Radiation, Assessed
according to the RTOG-EORTC Late Radiation
Morbidity Scoring Scheme

20. UK Standardisation of Breast
Radiotherapy (START) trials
• 1999 to 2002
• Completely excised invasive breast
cancer (pT1–3a, pN0–1, M0)
• 35 UK radiotherapy centres
• Stratification: Centre, type of primary
surgery (BCS/MRM), and tumour
bed boost RT
• Primary endpoints: Local-regional
tumour relapse & Late normal tissue
effects
• Secondary endpoints: Local relapse,
distant relapse, DFS & OS
START A
START B

21. START Trials
START A
 Median Follow up: 9.3 years
 10-year rates of local-regional relapse did not
differ significantly between the 41·6 Gy and 50
Gy regimen groups or the 39 Gy and 50 Gy
regimen groups
START B
 Median Follow up: 9.9 years
 Proportion of patients with local-regional
relapse at 10 years did not differ significantly
between the 40 Gy group and the 50 Gy group
Cumulative risk of local-regional tumour relapse in
START-A (A) and START-B (B)

22. START Trials
START A
Distant relapses, DFS, & OS
not significantly different between
schedules
START B
 Fewer distant relapses in 40 Gy group
 Significantly higher rates of DFS & OS
in 40 Gy group compared with 50 Gy
group
Kaplan-Meier analysis of disease-free survival in
START-A (A) and START-B (B)

23. START Trials
 Estimated α/β value for local-regional relapse in START-A : 4 Gy
(95% CI 0·0–8·9)
 Meta-analysis of START-A and the START pilot trial (349 events,
3646 women): Adjusted α/β value for local-regional relapse of 3·5
Gy (95% CI 1·2–5·7)

24. START Trials
START A
 Moderate/marked breast induration, telangiectasia,
& breast oedema significantly less common normal
tissue effects in 39 Gy group than in 50 Gy group.
 Normal tissue effects did not differ significantly
between 41·6 Gy and 50 Gy groups.
START B
• Breast shrinkage, telangiectasia, & breast oedema
significantly less common normal tissue effects in
40 Gy group than in 50 Gy group.
Late normal tissue effects in START-A (A) and
START-B (B). Assessed as moderate or marked by
physicians.

26. UK FAST Trial
 Eligibility: Women ≥ 50 years with low-risk invasive
breast carcinoma pathologic tumour size < 3 cm,
axillary node negative, BCS with complete
microscopic resection, and whole-breast
radiotherapy
 Exclusion criteria: Mastectomy, lymphatic
radiotherapy, tumour bed boost, or cytotoxic
therapy
 Primary end point: Change in photographic breast
appearance
 Secondary end points: Physician assessments
of radiation-induced breast changes & ipsilateral
disease in the breast (relapse or new primary)
Brunt AM, Haviland JS, et al. Ten-Year Results of FAST: A Randomized Controlled Trial of 5-Fraction Whole-Breast Radiotherapy for Early Breast Cancer. J Clin
Oncol. 2020 Oct 1;38(28):3261-3272.
• October 2004 to March 2007
• 18 UK radiotherapy centers
• Median follow-up: 9.9 years

27. UK FAST Trial
Brunt AM, Haviland JS, et al. Ten-Year Results of FAST: A Randomized Controlled Trial of 5-Fraction Whole-Breast Radiotherapy for Early Breast Cancer. J Clin Oncol.
2020 Oct 1;38(28):3261-3272
Rates of mild/marked change in photographic breast appearance at 2 or 5 years significantly higher for
30 Gy compared with 50 Gy (P =.019) but not significantly different for 28.5 Gy and 50 Gy
Rates of mild/marked change in photographic breast appearance slightly higher for 30 Gy compared
with 28.5 Gy(P =.052)

28. UK FAST Trial
 Five- and 10-year cumulative incidence rates of
moderate/marked NTE in the breast : Higher for
30 Gy compared with 50 Gy, with statistically
significant differences for any NTE in the breast,
breast shrinkage, breast induration, and breast
edema
 Cumulative incidence rates of any moderate/marked
NTE in the breast and breast induration were
significantly higher for 28.5 Gy versus 50 Gy
 ORs for any moderate/marked physician-assessed
breast NTE (shrinkage, induration, telangiectasia,
edema): 2.12 (95% CI, 1.55 to 2.89; P < .001) for 30
Gy and 1.22 (95% CI, 0.87 to 1.72; P=.248) for 28.5
Gy versus 50 Gy
 Higher rates of breast shrinkage, telangiectasia, and
breast edema for 30 Gy compared with 28.5 Gy
Physician assessments of late normal tissue effects. (A) Breast shrinkage to 10
years; (B) time to first reported moderate/marked breast shrinkage; (C) breast
induration to 10 years; (D) time to first reported moderate/marked breast induration;
(E) breast edema to 10 years; (F) time to first reported moderate/marked breast
edema; (G) telangiectasia to 10 years; and (H) time to first reported
moderate/marked telangiectasia
Brunt AM, Haviland JS, et al. Ten-Year Results of FAST: A Randomized Controlled Trial of 5-Fraction Whole-Breast Radiotherapy for Early Breast Cancer. J Clin Oncol. 2020
Oct 1;38(28):3261-3272

29. UK FAST Trial
Change in photographic breast appearance gave an unadjusted α/ß
estimate of 2.7 Gy (95% CI, 1.5 to 3.9 Gy)
α/ß estimates for late adverse effects consistent with historical estimates

31. UK FAST Forward Trial
 Eligibility: Women or men aged ≥ 18 years with
invasive carcinoma of the breast (pT1–3, pN0–1,
M0) following complete microscopic excision of
the primary tumour by BCS or mastectomy
(reconstruction allowed)
 End Points:
Ipsilateral breast tumour relapse
Late normal tissue effects
• November 2011 to June 2014
• 97 UK centres
• Median follow-up: 71·5 months
Murray Brunt A, Haviland JS, Wheatley DA, et al; FAST-Forward Trial Management Group. Hypofractionated breast radiotherapy for 1 week versus 3 weeks (FAST-Forward):
5-year efficacy and late normal tissue effects results from a multicentre, non-inferiority, randomised, phase 3 trial. Lancet. 2020 May 23;395(10237):1613-1626

32. UK FAST Forward Trial
Ipsilateral breast tumour relapse:
Non inferiority for both five-fraction
schedules compared with 40 Gy in
15 fractions
Murray Brunt A, Haviland JS, Wheatley DA, et al; FAST-Forward Trial Management Group. Hypofractionated breast radiotherapy for 1 week versus 3 weeks
(FAST-Forward): 5-year efficacy and late normal tissue effects results from a multicentre, non-inferiority, randomised, phase 3 trial. Lancet. 2020 May
23;395(10237):1613-1626

33. UK FAST Forward Trial
Clinical assessment of normal tissue
effects: Significant difference between
40 Gy and 27 Gy (p=0·0003), but not
between 40 Gy and 26 Gy (p=0·17)
Murray Brunt A, Haviland JS, Wheatley DA, et al; FAST-Forward Trial Management Group. Hypofractionated breast radiotherapy for 1 week versus 3
weeks (FAST-Forward): 5-year efficacy and late normal tissue effects results from a multicentre, non-inferiority, randomised, phase 3 trial. Lancet. 2020
May 23;395(10237):1613-1626

34. Lancet 2020; 395: 1613–26

35.  Twenty-five controlled clinical trials
 3871 postmastectomy breast cancer patients
 No significant differences in OS, DFS, LRR, DM, acute skin toxicity, acute
lung toxicity, late skin toxicity, lymphedema, shoulder restriction or late
cardiac related toxicity between the two groups

37. Accelerated Partial Breast
Irradiation (APBI)
Accelerated partial breast irradiation (APBI) delivers therapeutic irradiation to the tumor bed
with a margin using a higher (than 2 Gy) dose per fraction
Rationale:
 Majority of local breast cancer recurrences occur at the site of the primary tumor * #
 Pathologic studies: Residual microscopic disease normally lies within 1.5 cm of the initial tumor in
> 90% of cases €
* Veronesi U, Marubini E, Mariani L, Galimberti V, Luini A, Veronesi P, Salvadori B, Zucali R. Radiotherapy after breast-conserving surgery in small breast
carcinoma: long-term results of a randomized trial. Ann Oncol. 2001;12(7):997–1003
# Gage I, Recht A, Gelman R, Nixon AJ, Silver B, Bornstein BA, Harris JR. Long-term outcome following breast-conserving surgery and radiation therapy. Int J
Radiat Oncol Biol Phys. 1995;33(2):245–251.
€ Vicini FA, Kestin LL, Goldstein NS. Defining the clinical target volume for patients with early-stage breast cancer treated with lumpectomy and accelerated
partial breast irradiation: a pathologic analysis. Int J Radiat Oncol Biol Phys. 2004;60(3):722–730.

38. APBI
Three major approaches:
 Interstitial Brachytherapy
 Intraoperative radiotherapy: Electron Beam / Low energy X rays
 External beam-based APBI

39. APBI
T Forster. Accelerated Partial Breast Irradiation: A New Standard of Care? Breast Care 2020;15:136–147

40. APBI
Goldberg M, Whelan TJ. Accelerated Partial Breast Irradiation (APBI): Where Are We Now? Curr Breast Cancer Rep. 2020;12(4):275-284.

41. APBI

43. THANK YOU