Comparing Local and Systemic Control between Partial- and Whole-Breast Radiotherapy in Low-Risk Breast Cancer—A Meta-Analysis of Randomized Trials
Abstract
:Simple Summary
Abstract
1. Introduction
2. Material and Methods
3. Results
3.1. Local Control
3.2. Other Endpoints
4. Discussion
4.1. Main Results
4.2. Techniques
4.3. Subgroups
4.4. Limitations of Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
3DCRT | 3D conventional radiation therapy |
BCS | breast-conserving surgery |
BID | twice daily |
BT | brachytherapy |
CTx | chemotherapy |
DCIS | ductal carcinoma in situ |
DMFI | distant metastasis-free interval |
e- | electrons |
EBRT | external beam radiotherapy |
EP | endpoint |
ER | estrogen receptor |
ET | endocrine therapy |
FU | follow-up |
IBC | invasive breast cancer |
IDC | invasive ductal cancer |
IBTR | in-breast tumor recurrence |
IMRT | intensity-modulated radiation therapy |
IORT | intraoperative radiotherapy |
ivhet | inverse variance heterogeneity mode |
HR+ | hormone receptor positive |
LR | local recurrence |
LREB | local recurrence elsewhere in the ipsilateral breast |
LRFS | local recurrence-free survival |
LRPS | local recurrence at the primary site |
Med. | median |
n | number |
N+ | nodal positive |
Noninf | non-inferiority |
n.r. | not reported |
PBI | partial-breast irradiation |
Pop | population |
QD | once daily |
RT | radiotherapy |
q.o.d. | every other day |
SIB | simultaneous integrated boost |
Stat. | statistical |
Strat. | stratification |
WBI | whole-breast irradiation |
X | photons |
y | years |
Appendix A
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Study | Synonym | Additional Publications | Years of Trial | FU | NTotal | Med. Age | Stat. Setting | Prim. EP | Population | Stratification Factors | PBI Technique | PBI Dose | WBI Dose | G3 | DCIS | N+ | HR+ | Her2+ | CTx | ET | Boost |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Vicini 2019 [48] | NSABP B-39 | Vicini et al. 2019 [52] White et al. 2019 [53] | 2005–2013 | 10.2 | 4216 | 54 | Equiv. | IBTR | IBC or DCIS; T < 3 cm, ≤N1; R0; >18 y | Stage, menopausal, ER, CTx | 3DCRT, single- and multicath. BT | 34/3.4; 38.5/3.85 10x in 5–8 d | 50/2; 50.4/1.8; opt. Boost | 26% | 24% | 10% | 81% | n.r. | 29% | n.r. | 80% |
Whelan 2019 [49] | RAPID | Olivotto et al. 2013 [54] Peterson et al. 2015 [55] Whelan et al. 2019 [56] | 02/2006–07/2011 | 8.6 | 2135 | 61 | noninf. | IBTR | IBC or DCIS; T < 3 cm; R0; N0; >40 y; unifocal | Age >< 50; histology, T >< 1.5 cm; ER, center | 3DCRT IMRT | 38.5/3.85 BID in 5–8 d | 50/2; 42.5/2.66+ opt. Boost | 16% | 18% | 0% | 84% | 6% | 13% | 55% | 21% |
Meattini 2020 [46] | Florence | Livi et al. 2010 [57] Livi et al. 2015 [58] Meattini et al. 2017 [59] Meattini et al. 2020 [60] | 03/2005–06/2013 | 10.7 | 520 | n.r. | Equiv. | IBTR | IBC or DCIS; T < 2.5 cm; >40 y; BCS+ | None | IMRT | 30/6 q.o.d | 50/2+ opt. Boost 10/2 | 11.4% | 11% | 10% | 96% | 4% | 7% | 62% | n.r. |
Orecchia 2021 [61] | ELIOT | Veronesi et al. 2013 [62] | 11/2000–12/2007 | 12.4 | 1305 | n.r. | Equiv. | IBTR | IBC; T < 2.5 cm; cN0, R0; 48–75 y; unifocal | T < 1 cm, T 1–1.4 cm, T > 1.5 cm | IORT e- | 21/21 | 50/2+ opt. Boost 10/2 | 20.9% | 0% | 27% | 91% | 3% | 22% | 89% | n.r. |
Vaidya 2020 [41] | TARGIT-A prepathology | Vaidya et al. 2010 [51] Andersen et al. 2012 [63] Sperk et al. 2012 [64] Welzel et al. 2013 [65] Keshtgar et al. 2013 [66] Vaidya 2014 [39] Corica et al. 2016 [67] Corica et al. 2018 [68] | 03/2000–06/2012 | 8.6 | 2298 | Mean 63 | noninf. | LRFS | IDC; T < 2.5 cm; R0; >45 y; unifocal | Center, timing | IORT x | 20/20 | n.r. | 20% | 0% | ~21% | 90% | 15% | 21% | 81% | 38% |
Vaidya 2020 [38] | TARGIT-A postpathology | 03/2000–06/2012 | 9 | 1153 | Mean 63 | noninf. | LRFS | IDC; T < 2.5 cm; R0; >45 y; unifocal | Center, timing | IORT x | 20/20 | n.r. | 6% | 3% | 5% | 98% | 6% | 4% | 87% | n.r. | |
Strnad 2016 [69] | GEC Estro | Polgar et al. 2017 [70] Schäfer et al. 2018 [71] | 04/2004–07/2009 | 6.6 | 1328 | 62 | noninf. | IBTR | IBC or DCIS; T < 3 cm; R0; N0; >40 y; BCS+ | Center, menopausal, stage | multicath. BT | 32/4; 30.3/4.3 or PDR | 50/2; 50.4/1.8; Boost opt. | 8.3% | 5% | 6% | 95% | n.r. | 11% | 90% | 98% |
Coles 2017 [43] | Import low | Bhattacharya et al. 2019 [72] Bhattacharya et al. 2019 [73] Bhattacharya et al. 2019 [74] | 05/2007–10/2010 | 6 | 1343 | 62 | noninf. | IBTR | IDC; T < 3 cm; >50 y; pN0–1 | Centre | 3DCRT | 40/2.67 QD | 40/2.67 | 9.7% | 0% | 3% | 95% | 4% | 5% | 80% | n.r. |
Polgar 2020 [42] | Budapest | Polgar et al. 2004 [75] Polgar et al. 2007 [76] Lövey et al. 2007 [77] Polgar et al. 2013 [78] Polgar et al. 2014 [79] | 1998–2004 | 17 | 258 | Mean 59 | noninf. | LR | IBC; T < 2 cm; N0; R0; G1–2; unifocal | None | multicath. BT 3DCRT e- | BT: 36.4/5.2 BID; e-:50/2 QD | 50/2+ opt. 16/2 | 0.0% | 0% | 0% | 88% | n.r. | 3% | 99% | 0.8% |
Li 2021 [80] | Barcelona | Rodriguez et al. 2013 [50] | 2007–2013 | 10.3 | 102 | Mean 68 | noninf. | IBTR | IBC; T < 3 cm; R0; N0; >60 y; unifocal; G 1–2 | n.r. | 3DCRT | 37.5/3.75 BID | 48/2+ opt. Boost 10/2 or 20/2 | 0.0% | 0% | 0% | 98% | 1% | 3% | 99% | n.r. |
Offersen 2017 [44] | DBCG PBI | 2009–2016 | 3 | 882 | 66 | noninf. | Breast induration | IBC, T1, R0, >60 y, G1–2, HER2−, pN0 | Center, ET | 3DCRT | 40/2.67 QD | 40/2.67 | <1.0% | 0% | 0% | 100% | 0% | n.r. | 80% | n.r. | |
Boutrus 2018 [45] | Cairo | n.r. | 2 | 91 | 50 | n.r. | IBTR | IBC; T < 3 cm; R0; N0; >40 y; unifocal; G1–3 | n.r. | 3DCRT | 38.5/3.85 QD 38.5/3.85 BID | 50/2+ opt: Boost | n.r. | 0% | 0% | 80% | n.r. | 19% | n.r. | n.r. | |
Franceschini 2020 [47] | HYPAB | 01/2015–01/2018 | 3 | 172 | 64 | Cosmesis | T1–2, postmeno, cN0, BCS, ER +, unicentric, R0 > 5 mm, | n.r. | VMAT | 30/6 q.o.d | 40.5/2.7 SIB to 48/3.2 | 3% | 0% | n.r. | 100% | n.r. | n.r. | 97% | 100% |
Five-Year in-Breast Tumor Recurrence | |||||||
---|---|---|---|---|---|---|---|
Study | Rate [%] PBI | Rate [%] WBI | OR | LCI 95% | HCI 95% | Weight (%) | p-Value |
NSABP B-39 | 2.68 | 2.26 | 1.19 | 0.80 | 1.77 | 42.5 | |
Budapest | 3.91 | 3.08 | 1.28 | 0.34 | 4.88 | 3.7 | |
IBTR 5y EBTR/BT | 2.76 | 2.32 | 1.20 | 0.82 | 1.75 | 46.2 | 0.349 |
RAPID | 2.35 | 1.67 | 1.42 | 0.75 | 2.70 | 15.9 | |
IMPORT LOW | 0.53 | 1.04 | 0.51 | 0.13 | 1.97 | 3.6 | |
Florence | 2.31 | 1.15 | 2.02 | 0.50 | 8.18 | 3.4 | |
IBTR 5y EBTR | 1.70 | 1.41 | 1.17 | 0.44 | 3.15 | 22.9 | 0.749 |
ELIOT | 4.26 | 0.52 | 8.53 | 2.56 | 28.50 | 4.6 | |
TARGIT prepath | 2.11 | 0.95 | 2.24 | 1.09 | 4.60 | 12.8 | |
TARGIT postpath | 3.96 | 1.05 | 3.89 | 1.57 | 9.62 | 8.1 | |
IBTR 5y IORT | 3.07 | 0.90 | 3.39 | 1.64 | 7.00 | 25.4 | 0.001 |
GEC ESTRO | 1.57 | 1.02 | 1.55 | 0.52 | 4.65 | 5.5 | |
IBTR 5y BT | 1.57 | 1.02 | 1.55 | 0.52 | 4.65 | 5.5 | 0.436 |
Total 5y IBTR | 2.47 | 1.46 | 1.61 | 0.97 | 2.66 | 100.0 | 0.066 |
I2 | 53.45 | 1.14 | 78.08 | ||||
Cochran’s Q | 17.19 | ||||||
Chi2, p | 0.028 |
Outcome (Median Follow-Up Range) | Anticipated Absolute Effects | Relative Effect (95% CI) | No. of Participants (Studies) | |||||
---|---|---|---|---|---|---|---|---|
Risk with WBI per 100 | Risk with PBI (95% CI) per 100 | |||||||
In-breast tumor recurrence (2–17 years) | 2.05 | 3.40 | 2.19 | 5.27 | 1.66 | 1.07 | 2.58 | 15,561 (13 RCTs) |
In-breast tumor recurrence at primary site (2–17 years) | 1.34 | 1.36 | 0.87 | 2.13 | 1.01 | 0.65 | 1.59 | 14,161 (10 RCTs) |
In-breast tumor recurrence at elsewhere site (2–17 years) | 0.53 | 1.17 | 0.81 | 1.69 | 2.21 | 1.53 | 3.20 | 14,161 (10 RCTs) |
Regional recurrence (3–17 years) | 0.33 | 0.58 | 0.35 | 0.95 | 1.75 | 1.07 | 2.88 | 15,485 (11 RCTs) |
Distant metastasis-free interval (3–17 years) | 2.60 | 2.80 | 2.31 | 3.39 | 1.08 | 0.89 | 1.30 | 15,222 (10 RCTs) |
Disease-free survival (3–17 years) | 11.71 | 13.60 | 12.34 | 15.00 | 1.16 | 1.05 | 1.28 | 14,778 (9 RCTs) |
Contralateral breast cancer (3–12.4 years) | 2.58 | 2.10 | 1.68 | 2.62 | 0.81 | 0.65 | 1.01 | 13,473 (9 RCTs) |
Second primary cancer (3–12.4 years) | 5.04 | 5.51 | 4.30 | 7.06 | 1.09 | 0.85 | 1.40 | 11,745 (8 RCTs) |
Study | HR | LCI 95% | HCI 95% | Weight (%) | p-Value | Study | HR | LCI 95% | HCI 95% | Weight (%) | p-Value |
---|---|---|---|---|---|---|---|---|---|---|---|
Age < 50 years | N0 | ||||||||||
Whelan 2019 [49] | 0.78 | 0.29 | 2.11 | 72.6 | Vicini 2019 [48] | 1.31 | 0.85 | 2.00 | 40.1 | ||
Livi 2015 [58] | 1.52 | 0.96 | 24.23 | 27.4 | Whelan 2019 [49] | 1.27 | 0.84 | 1.91 | 43.6 | ||
Total | 0.94 | 0.40 | 2.18 | 100.0 | 0.879 | Livi 2015 [58] | 1.08 | 0.15 | 7.70 | 1.9 | |
Age > 50 years | Orecchia 2021 [61] | 5.47 | 2.68 | 11.19 | 14.4 | ||||||
Whelan 2019 [49] | 1.44 | 0.91 | 2.11 | 84.2 | Total | 1.58 | 0.76 | 3.28 | 100 | 0.219 | |
Livi 2015 [58] | 1.07 | 0.07 | 17.08 | 2.0 | N1 | ||||||
Coles 2017 [43] | 0.65 | 0.23 | 1.84 | 13.8 | Vicini 2019 [48] | 1.91 | 0.57 | 6.34 | 32.9 | ||
Total | 1.28 | 0.87 | 1.89 | 100.0 | 0.206 | Orecchia 2021 [61] | 3.41 | 1.47 | 7.92 | 67.1 | |
Age > 70 years | Total | 2.82 | 1.41 | 5.62 | 100.0 | 0.003 | |||||
Livi 2015 [58] | 1.07 | 0.07 | 17.08 | 23.1 | Interaction N0/N1 | 0.260 | |||||
Orecchia 2021 [61] | 1.86 | 0.41 | 8.33 | 76.9 | Grade 1–2 | ||||||
Total | 1.64 | 0.44 | 6.13 | 100.0 | 0.464 | Whelan 2019 [49] | 1.10 | 0.60 | 2.01 | 54.2 | |
Interaction Age | 0.732 | Orecchia 2021 [61] | 4.50 | 2.33 | 8.68 | 45.8 | |||||
DCIS | Total | 2.10 | 0.53 | 8.37 | 100.0 | 0.294 | |||||
Vicini 2019 [48] | 1.01 | 0.61 | 1.68 | 69.7 | Grade 3 | ||||||
Whelan 2019 [49] | 1.81 | 0.84 | 3.91 | 30.3 | Whelan 2019 [49] | 1.06 | 0.44 | 2.55 | 42.4 | ||
Total | 1.21 | 0.69 | 2.11 | 100.0 | 0.513 | Livi 2015 [58] | 1.43 | 0.09 | 22.92 | 4.3 | |
Invasive Cancer | Orecchia 2021 [61] | 2.18 | 1.00 | 4.79 | 53.3 | ||||||
Vicini 2019 [48] | 1.37 | 0.91 | 2.05 | 24.3 | Total | 1.58 | 0.89 | 2.79 | 100.0 | 0.118 | |
Whelan 2019 [49] | 1.12 | 0.69 | 1.84 | 16.4 | Interaction G1–2/G3 | 0.709 | |||||
Orecchia 2021 [61] | 4.62 | 2.68 | 7.95 | 13.4 | Estrogen Receptor Positive | ||||||
Vaidya 2014 [39] | 2.13 | 1.01 | 4.49 | 7.1 | Vicini 2019 [48] | 1.32 | 0.91 | 1.92 | 50.5 | ||
Coles 2017 [43] | 0.65 | 0.23 | 1.84 | 3.7 | Whelan 2019 [49] | 1.19 | 0.69 | 2.07 | 23.3 | ||
Polgar 2013 [78] | 1.09 | 0.88 | 1.72 | 35.2 | Livi 2015 [58] | 1.79 | 0.80 | 10.69 | 4.2 | ||
Total | 1.44 | 0.85 | 2.44 | 100.0 | 0.171 | Orecchia 2021 [61] | 4.21 | 2.39 | 7.42 | 21.9 | |
Interaction DCIS/Invasive | 0.644 | Total | 1.68 | 0.84 | 3.35 | 100.0 | 0.139 | ||||
T1a/b | Estrogen Receptor Negative | ||||||||||
Vicini 2019 [48] | 0.58 | 0.27 | 1.22 | 68.2 | Vicini 2019 [48] | 0.98 | 0.54 | 1.77 | 72.6 | ||
Orecchia 2021 [61] | 4.01 | 1.33 | 12.1 | 31.8 | Whelan 2019 [49] | 1.01 | 0.34 | 3.04 | 21.3 | ||
Total | 1.07 | 0.15 | 7.82 | 100.0 | 0.945 | Orecchia 2021 [61] | 9.25 | 1.19 | 71.70 | 6.1 | |
T1c | Total | 1.13 | 0.40 | 3.16 | 100.0 | 0.815 | |||||
Vicini 2019 [48] | 2.66 | 1.24 | 5.68 | 48.2 | Interaction ER + /ER- | 0.529 | |||||
Livi 2015 [58] | 1.32 | 0.08 | 21.23 | 3.6 | Her2 Negative | ||||||
Orecchia 2021 [61] | 4.91 | 2.30 | 10.51 | 48.3 | Orecchia 2021 [61] | 4.35 | 2.47 | 7.64 | 92.3 | ||
Total | 2.53 | 1.22 | 5.28 | 100.0 | 0.013 | Livi 2015 [58] | 1.13 | 0.16 | 8.02 | 7.7 | |
T2 | Total | 3.92 | 1.15 | 13.40 | 100.0 | 0.029 | |||||
Vicini 2019 [48] | 1.34 | 0.52 | 3.46 | 57.9 | ASTRO Risk Group Criteria—Suitable | ||||||
Orecchia 2021 [61] | 4.80 | 1.58 | 14.58 | 42.1 | Vicini 2019 [48] | 1.12 | 0.46 | 2.76 | 32.0 | ||
Total | 2.29 | 0.65 | 8.05 | 100.0 | 0.195 | Whelan 2019 [49] | 1.06 | 0.57 | 1.95 | 68.0 | |
Interaction T1ab/T1c/T2 | 0.729 | Total | 1.08 | 0.65 | 1.79 | 100.0 | 0.769 | ||||
T < 1.5 cm | ASTRO Risk Group Criteria—Not Suitable | ||||||||||
Whelan 2019 [49] | 1.02 | 0.59 | 1.75 | 63.7 | Vicini 2019 [48] | 1.26 | 0.77 | 2.08 | 56.6 | ||
Orecchia 2021 [61] | 4.92 | 2.39 | 10.12 | 36.3 | Whelan 2019 [49] | 1.46 | 0.83 | 2.58 | 43.4 | ||
Total | 1.80 | 0.37 | 8.85 | 100.0 | 0.467 | Total | 1.34 | 0.92 | 1.95 | 100.0 | 0.122 |
T > 1.5 cm | Interaction ASTRO Risk Group | 0.495 | |||||||||
Whelan 2019 [49] | 2.01 | 1.03 | 3.93 | 60.8 | |||||||
Orecchia 2021 [61] | 4.31 | 1.87 | 9.92 | 39.2 | |||||||
Total | 2.71 | 1.28 | 5.72 | 100.0 | 0.009 | ||||||
Interaction T-size 1.5 cm | 0.650 |
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Haussmann, J.; Budach, W.; Strnad, V.; Corradini, S.; Krug, D.; Schmidt, L.; Tamaskovics, B.; Bölke, E.; Simiantonakis, I.; Kammers, K.; et al. Comparing Local and Systemic Control between Partial- and Whole-Breast Radiotherapy in Low-Risk Breast Cancer—A Meta-Analysis of Randomized Trials. Cancers 2021, 13, 2967. https://doi.org/10.3390/cancers13122967
Haussmann J, Budach W, Strnad V, Corradini S, Krug D, Schmidt L, Tamaskovics B, Bölke E, Simiantonakis I, Kammers K, et al. Comparing Local and Systemic Control between Partial- and Whole-Breast Radiotherapy in Low-Risk Breast Cancer—A Meta-Analysis of Randomized Trials. Cancers. 2021; 13(12):2967. https://doi.org/10.3390/cancers13122967
Chicago/Turabian StyleHaussmann, Jan, Wilfried Budach, Vratislav Strnad, Stefanie Corradini, David Krug, Livia Schmidt, Balint Tamaskovics, Edwin Bölke, Ioannis Simiantonakis, Kai Kammers, and et al. 2021. "Comparing Local and Systemic Control between Partial- and Whole-Breast Radiotherapy in Low-Risk Breast Cancer—A Meta-Analysis of Randomized Trials" Cancers 13, no. 12: 2967. https://doi.org/10.3390/cancers13122967