• The National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG) MA.20 trial:
  • Randomized 1,832 high-risk women:
    • Who were treated with breast-conserving surgery and sentinel node biopsy (SLNB) or axillary lymph node dissection (ALND):
      • To either WBI alone or WBI plus regional nodal irradiation (RNI)
  • Axillary lymph node dissection:
    • Was required for any patients with a positive SLN
  • RNI included:
    • The internal mammary, supraclavicular, and high axillary nodes
  • The trial enrolled patients with:
    • Node-positive or high-risk node-negative disease:
      • 85% of patients had 1 to 3 positive nodes
      • 5% had more than 4 positive nodes
      • 10% were node negative
  • Node-negative patients with tumors greater than or equal to 2 cm who had fewer than 10 axillary nodes removed were considered high risk if they had at least one of the following:
    • ER negative
    • Lymphovascular invasion
    • Nuclear grade 3
  • All patients had systemic therapy
• With a median follow-up of 10 years:
  • The addition of RNI improved:
    • Locoregional DFS from:
      • 92.2% to 95.2% (P=0.009)
    • Distant DFS from:
      • 82.4% to 86.3% (P=0.03)
  • There was no difference in OS from:
    • 81.8% to 82.8% (P=0.38)
  • The addition of RNI to WBI was associated with:
    • An increase in:
      • Grade 2 or greater pneumonitis from:
        • 0.2% to 1.2% (P=0.01)
      • Lymphedema from:
        • 4.5% to 8.4% (P=0.001)
• Similarly, European Organisation for Research and Treatment of Cancer (EORTC) 22922:
  • Randomized 4004 women undergoing breast-conserving surgery or mastectomy and ALND for histological stage I, II, or III breast cancer to:
    • RNI (supraclavicular and internal mammary nodal irradiation) or no regional nodal irradiation
  • At a median follow-up of 10.9 years:
    • The addition of regional nodal irradiation improved:
      • DFS from:
        • 69.1% to 72.1% (P=0.04)
      • Again, there was a non-significant trend toward improvement in OS from:
        • 80.7% to 82.3% (P=0.06 among the RNI group
• The results of NCIC CTG MA.20 have led many to conclude that:
  • All patients with axillary nodal metastases, regardless of tumor size or extent of nodal involvement:
    • Should receive comprehensive nodal radiation therapy (RT)
• A major conundrum in current practice is resolving the apparently contradictory findings of American College of Surgeons Oncology Group (ACOSOG) Z0011 and After Mapping of the Axilla, Radiation or Surgery? (AMAROS) with those of NCIC CTG MA.20:
  • The modest benefit in DFS with nodal RT in NCIC CTG MA.20:
    • May reflect differences in patient populations between the studies:
      • Patients with clinically positive nodes were excluded from ACOSOG Z0011 and AMAROS (and not MA.20)
      • In addition, fewer than 10 nodes were removed in one-third of patients in the NCIC CTG MA.20 study and the median node count was 12:
        • Compared to a median of 17 in the ALND arms of Z0011 and AMAROS:
          • The benefit of nodal RT therefore may be limited to higher risk patients with more extensive nodal disease and perhaps more limited axillary surgery

References

1. Poortmans PM, Collette S, Kirkove C, Limbergen EV, Budach V, Struikmans H, et al. Internal mammary and medial supraclavicular irradiation in breast cancer. N Engl J Med. 2015;37(4)3:317-327.

2. Pepels MJ, de Boer M, Bult P, van Dijck A, van Deurzen CH, Menke-Pluymers MB, et al. Regional recurrence in breast cancer patients with sentinel node micrometastases and isolated tumor cells. Ann Surg. 2012;255(1):116-121.

3. Whelan TJ, Olivotto IA, Parulekar WR, Ackerman I, Chua BH, Nabid A, et al; MA.20 Study Investigators. Regional nodal irradiation in early-stage breast cancer. N Engl J Med. 2015;373(4):307-316.