1. 1789 patients, 1982 – 1989, premenopausal, node + or Tumor > 5cm, M0 Total mastectomy, level I + II (partly) + CMF +/- 50Gy/25fx (electrons + photons) Sx in 79 departments, RT in mainly 6 centres Overgaard et al. NEJM 1997 337:949 These Power Point presentations are free to download only for academic purposes, with due acknowledgements to authors and this website.

2. 318 patients, 1979 – 1986, premenopausal, node +, any T, M0 MRM + CMF +/- 37.5Gy/16fx RT (photons) Sx by ‘specialists’, CT & RT in one centre Ragaz et al. NEJM 1997 337:956 41% 56% 64% 54%

3. 1460 patients, 1982 – 1990, postmenopausal, node +, any T, M0 MRM + Tamoxifen +/- 50Gy/25fx RT (electrons + photons) Sx in 79 departments, RT in mainly 6 centres Overgaard et al. 1999, 353:1641

5. Vascular deaths: Proportional excess ratio=1.3, absolute rates 3 fold greater

6. What were the problems with the EBCT review?  Diverse surgical treatments (BCT, MRM, RM, simple mastectomy)  Systemic therapies (including trials with no systemic therapies)  Radiotherapy doses, areas treated, kind of radiation, doses to the heart

9. Any recurrence

10. Loco-regional recurrence

11. Survival

12.  Loco-regional failure (LRF) is  25% for >4 nodes; T >5 cm; < 6 nodes at axillary dissection; patient younger than 40  PMRT reduces this risk to 6 – 8% (absolute benefit of 17-19 women for each 100 treated)  In the subgroup of 1-3 nodes, LRF is 13%; PMRT reduces this to 3-4% (absolute benefit of 9-10 women for every 100 treated)  For a LRF reduction of 20%, cancer specific survival improves by 4-5%  A North-American trial on PMRT for 1-3 nodes was closed due to insufficient interest!!!

13. Objective: Information and recommendations on PMRT Outcomes: LRC, DFS, OS, toxicities Source of evidence: Review of meta analysis, consensus statements1966 – 2002 + RCTs between 1995 – 2002 (to supplement ASCO guidelines)

14. Recommendations -1  PMRT: Tumor > 5cm, invasion of skin, pectoral muscle or chest wall  PMRT: 4 or more positive nodes  PMRT ??: 1-3 positive nodes Danish 82b: T > 5cm: LR failure 12%(RT) vs 42% (no RT) Danish 82c: T > 5cm: LR Failure 10%(RT) vs 34% (no RT) Deep fascia: LR Failure 6%(RT) vs 45% (no RT) Skin: LR Failure 8%(RT) vs 34% (no RT)

15. LRF and OS by nodal status

16. Recommendations -2  PMRT not recommended in tumors less than 5 cm and negative axilla Risk of local recurrence is 9.2% without and 2.7% with PMRT (EBCTCG)

17. Recommendations -3  Age, grade, LVI, hormone receptor status, number of nodes removed, extracapsular spread may affect LRC but indications unclear

18. Recommendations -4  PMRT should encompass chest wall, supraclavicular, infraclavicular area and axillary apex  After complete dissection of the axilla (level I and II) avoid radiating the axilla  Definite recommendations to include IMC (Investigational in an EORTC trial)  Use modern techniques, avoid heart and lungs  Acute effects: skin reactions. Late effects-cardiac(relative hazard 3.2 times) /pulmonary (3%) /rib fractures/brachial plexopathy are rare

20. ISODOSE DISTRIBUTION Prescription Isodose (100%) 1cm off axis

21. Recommendations -5  Sequencing of PMRT and systemic therapy unclear. Do not administer concomitantly with anthracyclines or taxanes

22. Delay in RT (for giving CT before RT) reduces Local control Meta-Analysis of 1927 breast cancer patients (mostly BCT)

23. 154 patients (BCT – 107, MRM - 47) ref during 1996-99 RT 50Gy / 25# (BCT: 16Gy boost); Nodal RT in 71 patients Chemo if indicated; CMF or AC on Med Oncologist’s discretion RT alone (n=61)RT + CMF (n=51)RT + AC (n=42) Prospective detailed evaluation of acute Toxicities Before, During & After RT (up to 6 months) Univ. Med Centre, Utrecht, The Netherlands, Fiets et al

24. RT alone (n=61) RT + CMF (n=51) RT + AC (n=42 Incidence of SEVERE (Grade 2- 4) Acute Toxicities Moist Desquamation21%41%70% Dysphagia 5%18%36% Dyspnoea 17%43%43% R. Pneumonitis 2%4%5% (NS) Malaise 40%61%62% Anorexia2%20%41% Fever0%10%11%