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%