Trials Flashcards
NSABP-B06
Trial type:
Trial arms:
Inclusion criteria:
Trial results:
- Randomized Prospective; 1976-1984
- 1) Total mastectomy vs
2) Lumpectomy + ALND vs
3) Lumpectomy + ALND + XRT (50 Gy no boost) - Stage I/II, <4 cm, N+/- allowed
@20 year f/u
First recurrences (mastectomy vs lumpectomy vs lumpectomy + RT):
- local failure: 10% vs. 9% vs. 3%;
- regional failure: 5% vs. 9% vs. 5%.
- Survival: No difference in DFS or OS (although there was before the 20 yr f/u)
- DFS 36% vs 35% vs 35% (NS).
- OS 47% vs 46% vs 46% (NS).
While there were no differences in overall survival the rates of ipsilateral recurrence were 39% in lumpectomy alone, 14% in those with lumpectomy + XRT.
EBCTCG (early breast cancer trial collective group)
Trial type:
Trial arms:
Inclusion criteria:
Trial results:
- Meta-analysis of 78 trials involving RT and surgery
- Lumpectomy vs Lumpectomy + XRT
- T1-T2 patients; N+/- allowed
- Addition of RT decreases ipsilateral BCA recurrence by approximately 2/3; effect is much more pronounced in N+ patients and younger women, but persists even in low risk small widely resected tumors.
- Overall LR: 26% vs. 7% (SS)
If LN- LR: 23% vs. 7% (SS)
If LN+ LR: 41% vs. 11% (SS) - 3.3% OS benefit at 15 years for all-comers
- Adjuvant XRT prevented 1 BCA death for every 4 local recurrences prevented, at 15 years
APT
Trial type:
Trial arms:
Inclusion criteria:
Trial results:
- Uncontrolled, single-group, multicenter study
- Adjuvant Paclitaxel and Trastuzumab
- Tumor <3 cm, N0, HER2 + breast cancer
@3-year rate of survival free from invasive disease was 98.7%
- Did see some grade 3 neuropathy, symptomatic congestive heart failure improved after discontinuation of trastuzumab.
- weekly treatment with paclitaxel (80 mg/m^2) and trastuzumab for 12 weeks (4 mg/kg loading, 2 mg/kg afterwards once weekly), followed by 9 months of trastuzumab monotherapy (6 mg/kg q3weeks)
HERA
Trial type:
Trial arms:
Inclusion criteria:
Trial results:
- International, multicenter, randomized trial
- 1 year trastuzumab vs. 2 yrs trastuzumab vs. obs
- Advanced breast cancer (no T4), HER2+ who completed local regional therapy
- Trastuzumab HR 0.54
- No difference in OS between trastuzumab vs obs
- 1-yr Herceptin gives 10% benefit in DFS
- 1 yr of trastuzumab improves long term DFS compared with observation. 2 years had no additional benefit.
- Severe cardiotoxicity in 0.5% of trastuzumab group
Mamounas, JCO 2012
Trial type:
Trial arms:
Inclusion criteria:
Trial results:
- Pooled analysis of NSABP B-27, NSABP B-18
- Outcomes w/ neoadjuvant chemotherapy (NC) w/ Mastectomy (had to have ALND) vs NC+ Lumpectomy + XRT
- T1c-3 N0M0 or T1-3 N1M0
- Contains NOMOGRAM for risk of LRR given cN status and ypN status
- Independent predictors of LRR in mastectomy patients: clinical tumor size >5 cm (before NC)
clinical nodal status (before NC)
pathologic nodal status/breast tumor response
-Independent predictors of LRR in lumpectomy patients: age <50 (worse)
clinical nodal status (before NC)
pathologic nodal status/breast tumor response
Z0011
Trial type:
Trial arms:
Inclusion criteria:
Trial results:
- Non-inferiority trial (1999-2004)
- Completion ALND vs no further dissection
- T1-T2, clinically N0, SNB+ (1-2 only)
- Lumpectomy w/ tangents RT, but no dedicated axillary RT. 81.1% received tangent-only treatment. Adjuvant systemic therapy 97%
-2011 update;
5-yr OS 91.8% (ALND) vs 92.5% (SLND)
5-yr DFS 82.2% vs 83.9%
- Among patients with limited SLN metastatic breast cancer treated with breast conservation and systemic therapy, the use of SLND alone compared with ALND did not result in inferior survival.
AMAROS
Trial type:
Trial arms:
Inclusion criteria:
Trial results:
- Randomized; In setting of positive sentinel LN then:
- Arm 1) completion ALND vs Arm 2) axillary/SCV RT 50/25.
- If ALND with 4+ lymph nodes, axillary RT allowed per institutional protocol
- RT: target all three levels of axilla and medial part of supraclavicular fossa to 50 Gy in 25 fractions
- T1-T2 (<3cm), SLN+
- 2014 Update; 5-year axillary recurrence ALND 0.43% vs RT 1.19%, underpowered to show non-inferiority
- 5-year DFS ALND 87% vs 83% RT (NS)
- 5-year OS ALND 93% vs RT 93% (NS)
-More lymphedema with ALND (5-year 23% vs 11%) (SS)
McGuire, IJROBP 2007
Trial type:
Trial arms:
Inclusion criteria:
Trial results:
- Single institution retrospective review
- Post-mastectomy Radiation in Locally Advanced Breast Cancer w/ Pathologic Complete Response to Neoadjuvant Chemotherapy
- Mostly stages 2-3B;
clinical stages at diagnosis were I in 2%, II in 31%, IIIA in 30%, IIIB in 25%, and IIIC in 11% - @ 10 years, LRR rates for Stage I or II disease was 0%
- @ 10 years, LRR rate for patients with Stage III disease was significantly improved with radiation therapy (7% vs. 33%)
Varadarajan, Oncology 2006
Trial type:
Trial arms:
Inclusion criteria:
Trial results:
- Roswell Park retrospective case study series
- Prognosis of occult breast carcinoma presenting as isolated axillary nodal metastasis
- Breast cancer with isolated axillary nodal metastasis and no primary tumor found
- 10 patients total
- The breast was managed with:
XRT alone in 8 patients
Lumpectomy + XRT in 1 patient
Mastectomy in 1 patient - No patient had a recurrence with a median 57 months of follow-up.
CALGB 9343
Trial type:
Trial arms:
Inclusion criteria:
Trial results:
- Elderly; Lumpectomy + 5 years Tamoxifen +/- XRT in Women Age 70 Years or Older With Early Breast Cancer
- 1994-1999; clinical stage I, ER-positive breast cancer, ≤ 2 cm cT1 N0; lumpectomy with clear margins, axillary node dissection was allowed but not encouraged
- RT tangential fields to whole breast + electron boost to the lumpectomy site.
- @10 years rates of ipsilateral breast tumor recurrence 2% in tamoxifen+RT group vs 9% in tamoxifen group.
- @10 years rates breast cancer–specific survival estimates were 97% tamoxifen-RT and 98% tamoxifen alone
PRIME II
Trial type:
Trial arms:
Inclusion criteria:
Trial results:
- Elderly; Breast-conserving surgery with or without irradiation in women aged 65 years or older with early breast cancer
- Randomized controlled trial
- Lumpectomy +/- whole-breast radiotherapy (40–50 Gy in 15–25 fractions)
- 2003-2009; Age> 65 years, early breast cancer, hormone receptor-positive, pN0, T1–T2 up to 3 cm, negative margins; grade 3 or LVI, but not both, were permitted
- @5 years, rates of ipsilateral breast tumor recurrence was 1.3% in lumpectomy with radiation vs 4.1% lumpectomy alone.
START A and B
Trial type:
Trial arms:
Inclusion criteria:
Trial results:
- Haviland et al 2013. UK Breast hypofractionation, 10 year follow up
- Prospective, randomized; 1999-2002
- Lumpectomy w/ adjuvant chemotherapy and endocrine therapy +/- adjuvant XRT
- START A: 50 Gy/25 fx vs. 39 Gy/13 fx vs. 41.6 Gy/13 fx - START B: 50 Gy/25 fx vs. 40 Gy/15 fx - 10 Gy lumpectomy boost given in 61% - Nodal and chest wall RT allowed
- @10 years LRR did not differ significantly between the 40 Gy group (4·3%) and the 50 Gy group (5·5%)
- In START-B, breast shrinkage, telangiectasia, and breast edema were significantly less common normal tissue effects in the 40 Gy group than in the 50 Gy group.
NSABP 32
Trial type:
Trial arms:
Inclusion criteria:
Trial results:
- Krag et al. Lancet 2010
- Randomized, prospective, multiinstitutional US/Canada trial; 1999-2004
- SLND -> ALND (Group 1) or to SLND alone with ALND only if sentinel nodes were positive (Group 2)
- Invasive breast cancer and clinically negative nodes
- Overall survival, disease-free survival, and regional control were statistically equivalent between groups
- @8 years, OS 91.8% in Group 1 and 90.3% in Group 2 (NS), DFS are 82.4% in Group 1 and 81.5% in Group 2 (NS)
ECOG (Hughes et al JCO 2009)
Trial type:
Trial arms:
Inclusion criteria:
Trial results:
- Local Excision Alone Without Irradiation for Ductal Carcinoma In Situ of the Breast
- Prospective trial; 2000
- Low or intermediate-grade DCIS ≤ 2.5 cm, or high-grade DCIS ≤ 1 cm w/ margin >= 3 mm and no residual calcifications on postoperative mammograms
- @5-year rate of ipsilateral breast events was 6.1% in low/intermediate grade, 15.3% in high grade DCIS
RTOG 9804
Trial type:
Trial arms:
Inclusion criteria:
Trial results:
- McCormick et al, JCO, 2015
- Prospective, randomized trial; 1998 to 2006
- BCS +/- adjuvant XRT
- Grade 1-2 DCIS, measuring ≤ 2.5 cm, margins ≥ 3 mm
- Arm 1: Observation W/WO tamoxifen 20 mg daily for 5 years
- Arm 2: WBI w/ or w/o tamoxifen tamoxifen 20 mg daily for 5 years
- Radiation given 50 Gy/ 25 fx, 50.4 Gy/ 28 fx, 42.5 Gy/ 16 fx with whole breast tangents
- 7 years rate of LR control 99.1% with RT versus 93.3% without. 62% used Tamoxifen
