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

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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%

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

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

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

Any recurrence

Loco-regional recurrence

Survival

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!!!

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)

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)

LRF and OS by nodal status

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)

Recommendations -3

Age, grade, LVI, hormone receptor status, number of nodes removed,

extracapsular spread may affect LRC but indications unclear

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

ISODOSE DISTRIBUTIONISODOSE DISTRIBUTION

Prescription Isodose (100%) 1cm off axis

Recommendations -5

Sequencing of PMRT and systemic therapy unclear. Do not

administer concomitantly with anthracyclines or taxanes

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

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

RT alone (n=61) RT + CMF (n=51) RT + AC (n=42

Incidence of SEVERE (Grade 2- 4) Acute Toxicities

Moist Desquamation 21% 41% 70%

Dysphagia 5% 18% 36%

Dyspnoea 17% 43% 43%

R. Pneumonitis 2% 4% 5% (NS)

Malaise 40% 61% 62%

Anorexia 2% 20% 41%

Fever 0% 10% 11%