Introduction
Materials and methods
Literature search and data extraction
Data extraction and quality assessment
Statistical analyses
Results
Study characteristics
Author | Year | Design | Patients (n) | Inclusion | Neoadjuvant therapy regimen | Scanner | FDG dose (MBq) | Uptake time (min) | Median follow-up (months) |
---|---|---|---|---|---|---|---|---|---|
Akimoto [12] | 2018 | P | 130 | Not specified | Anthracycline + taxane-based | PET/CT | 3.7/kg | 60 | NR |
Champion [13] | 2015 | P | 23 | Inflammatory | Anthracycline ± taxane-based | PET/CT | 4–5/kg | 73 ± 21 | 76 ± 27 |
Chen [14] | 2017 | R | 86 | Stage II–III | Anthracycline ± taxane-based | PET/CT | 259–555 | 60 | 71 (8–118) |
Dunnwald [15] | 2011 | P | 75 | LABC | Anthracycline ± taxane-based | PET | 218–399 | 60 | DFS: 50 (1–156) OS: 60 (7–161) |
Emmering [16] | 2008 | P | 40 | LABC | Anthracycline-based | PET | 370 | 60–90 | 60 |
Garcia Vicente [17] | 2016 | P | 132 | Not specified | Anthracycline ± taxane-based | PET/CT | 370 | 60 | 35.5* (12–62) |
Groheux [18] | 2015 | P | 82 | ER+/HER2−, stage II–III | Anthracycline + taxane-based | PET/CT | 5/kg | 60 | 35 (10–71) |
Groheux [19] | 2016 | R | 78 | TN, stage II–III | Anthracycline + taxane-based; dose-intense anthracycline-based | PET/CT | 5/kg | 60 | 34 (3–85) |
Humbert [20] | 2014 | P | 42 | HR+/HER2−, stage II–IIIA | Anthracycline ± taxane-based | PET or PET/CT | PET: 2/kg; PET/CT: 5/kg | 60 | 64.2 (11.5–93.2) |
Humbert [21] | 2016 | P | 46 | TN, Stage II–III | Anthracycline ± taxane-based | PET/CT | 5/kg | 60 | 30 (6–73) |
Hyun [22] | 2015 | R | 167 | Stage II–III | Anthracycline ± taxane-based | PET/CT | 5.5/kg | 60 | 19 (3–85) |
Ishiba [23] | 2015 | R | 83 | Not specified | Anthracycline ± taxane-based | PET/CT | 3.7/kg | NR | 50 |
Jung [24] | 2010 | P | 66 | Stage II–III | Anthracycline ± taxane-based | PET | 370–555 | 60 | 61.5 (13.5–71.8) |
Kim [25] | 2016 | R | 139 | Stage II–III | Anthracycline + taxane-based | PET/CT | 5/kg | 60 | 26.2 ± 16.1* |
Kitajima [26] | 2018 | R | 56 | Not specified | Anthracycline ± taxane-based | PET/CT | 3–4/kg | 60 | No recurrence: 29.1 (12.3–96.4) Recurrence: 19.2 (11.4–37.4) |
Kiyoto [27] | 2016 | R | 32 | TN, stage II–III | Anthracycline ± taxane-based | PET/CT | 3/kg | 90 | 39.0 (5.8–91.2) |
Kolesnikov-Gauthier [28] | 2012 | P | 60 | Non-inflammatory, M0 | Anthracycline + taxane-based | PET | 370 | 60 | 43 (14–68) |
Lee [29] | 2016 | R | 87 | Stage II–III | Anthracycline-based | PET or PET/CT | 5.5/kg | 60 | 61 (10–107) |
Lian [30] | 2020 | R | 92 | Not specified | Anthracycline ± taxane ± platinum-based | PET/CT | 7.4/kg | 60 | No recurrence: 48.7 (20.6–84.1) Recurrence: 38.6 (11.4–82.7) |
Lim [31] | 2014 | P | 54 | Stage II–III | Anthracycline + taxane-based | PET/CT | 7.4/kg | 60 | 38 (25–45) |
Zucchini [32] | 2013 | R | 60 | Early, LABC, or oligometastatic | Anthracycline + taxane-based | PET/CT | 5.3/kg | 60–70 | 36.6 (8–79) |
Author | Mean age (range) | Initial stage (%) | Histology (ductal/lobular, %) | Grade (I/II/III, %) | Receptor phenotypes (ER+/PR+/HER2+, %) | Subtypes (luminal A/B/HER2/TN, %) | pCR (%) |
---|---|---|---|---|---|---|---|
Akimoto [12] | 53.9 | I/II/III: 8/73/19 | NR | 4/28/67 Unknown: 2 | 69/57/28 | ER+/HER2−: 53 HER2+: 28 TN: 19 | 23 |
Champion [13] | 51 ± 12.7 | all T4d, M0 | 95/0 | 9/30/61 | HR+:43 HER2+: 22 | HR+/HER2−: 48 HR−/HER2+: 22 TN: 30 | 22 |
Chen [14] | 51† | II/III: 14/86 | NR | NR | 56/37/28 | ER+/HER2−: 43 HER2+: 28 TN: 29 | 17 |
Dunnwald [15] | NR | T1/2/3/4: 3/21/57/19 N0/1/2/3: 19/61/17/3 | 92/8 | NR | 55/45/26 | NR | 28 |
Emmering [16] | 48† (29–63) | IIB: 15 IIIA/B/C: 43/30/13 | 70/13 | NR | NR | NR | 20 |
Garcia Vicente [17] | 52.6 ± 12.7 (25–80) | NR | 92/8 | NR | NR | 10/55/12/23 | NR |
Groheux [18]* | 50.4 ± 11.7 (30–82) | T1/2/3/4: 2/39/39/20 N0/1/2/3: 39/48/10/3 | 90/7 | 6/68/26 | 100/67/0 | ER+/HER2−: 100 | 5 |
Groheux [19] | 51† (27–78) | IIA/B: 27/23 IIA/B/C: 23/22/5 | 94/0 | 0/10/88 | 0/0/0 | TN: 100 | 37 |
Humbert [20] | NR | T1–2/3: 88/12 N0/1–2: 38/62 | 90/10 | 5/80/15 Unknown: 2 | 98/91/0 | HR+/HER2−: 100 Luminal A/B: 5/76 | 2 |
Humbert [21] | 46† (26–85) | IIA/B: 35/30 IIIA/B/C: 9/4/22 | 98/2 | 0/18/78 | 0/0/0 | TN: 100 | 43 |
Hyun [22] | 44 (22–68) | II/III: 32/68 | 95/2 | NR | HR+: 51 HER2+: 27 | HR+/HER2−: 40 HR−/HER2+: 16 TN: 33 | 17 |
Ishiba [23] | 54† (30–75) | II/III: 82/18 | 95/1 | 45/24/24 Unknown: 7 | NR | luminal A and B 65 luminal HER2 7 HER2: 12 TN 16 | 17 |
Jung [24] | 44† (21–64) | II/III: 56/44 | NR | NR | 56/36/41 | NR | T/N‡: 15/29 |
Kim [25] | 46.5 (27–72) | II/III: 80/20 | 100/0 | 21/44/35 | NR | HR+/HER2–55 HER2+: 27 TN: 18 | 16 |
Kitajima [26] | 53.6 ± 12.4 (29–77) | I/II/III: 7/48/45 | 96/0 | 12/11/32 Unknown: 45 | 50/38/45 | 14/39/20/27 | 34 |
Kiyoto [27] | 54† (31–71) | IIA/B: 16/34 IIIA/B/C: 22/3/25 | 94/0 | 16/37/47 | 0/0/0 | TN:100 | 22 |
Kolesnikov-Gauthier [28] | 49 ± 9 (30–70) | T2/3: 60/37 N0/1/2: 58/37/3 | 97/3 | 5/42/27 Unknown: 27 | 53/37/20 | NR | 22 |
Lee [29] | 46.1 (26–73) | T1/2/3/4: 14/70/10/6 N1/2/3: 61/14/25 | NR | 11/33/22 Unknown: 33 | 41/33/48 | 25/20/31/24 | 20 |
Lian [30] | 48.1 (28–76) | II/III 74/26 | 100/0 | NR | 58/50/44 | 1/58/20/21 | 36 |
Lim [31] | 48† (26–68) | T1/2/3/4: 9/41/33/17 N0/1/2/3: 4/20/54/13 | 93/4 | NR | 54/74/35 | NR | NR |
Zucchini [32] | 49† (31–72) | II/III/IV: 50/38/12 | NR | NR | NR | ER+/HER2−: 52 HER2+: 23 TN: 25 | 22 |
Quality assessment
Qualitative synthesis
Author | PET timing | Parameter | DFS | OS |
---|---|---|---|---|
Akimoto [12] | After completion | %ΔSUVmax > 80 | N/S for TN or HER2+ | NR |
SUVmax ≤ 1.3 | P = 0.026 for TN or HER2+ | NR | ||
Champion [13] | After 3 cycles | %ΔSUVmax | N/S | N/S |
After completion | %ΔSUVmax > 72 | P = 0.05* Adjusted P = 0.01* | N/S | |
Chen [14] | During or after | Mid- or post-SUVmax† | HR = 1.13 (1.06–1.21) Adjusted HR = 1.09 (1.01–1.17) | HR = 1.16 (1.08–1.24) Adjusted HR = 1.14 (1.06–1.23) |
Mid- or post-SUVmax < 2.5 | HR = 0.28 (0.13–0.62) | HR = 0.25 (0.11–0.60) | ||
%ΔSUVmax† | N/S | N/S | ||
Dunnwald [15] | At mid-therapy | Log2(SUVpeak)† | N/S | HR = 1.96 (1.14–3.34) Adjusted HR = N/S |
Δ%SUVpeak† | N/S | HR = 0.72 (0.54–0.96) Adjusted HR = N/S | ||
Emmering [16] | After completion | CMR | HR = 0.24 (0.08–0.79) Adjusted HR = 0.28 (0.08–0.96) | N/S |
Garcia Vicente [17] | After 2 cycles | CMR-tumour | N/S | N/S |
%Δtumour-SUVmax ≥ 62 | N/S | N/S | ||
CMR-lymph node | N/S | N/S | ||
After completion | CMR-tumour | N/S | N/S | |
CMR-lymph node | P = 0.003 Adjusted P = N/S | P = 0.016 Adjusted P = N/S | ||
Tumour-SUVmax | < 1.05: HR = 0.06 (0.01–0.47) | < 1.15: N/S | ||
Lymph node-SUVmax | < 1.30: N/S | < 0.40: N/S | ||
%Δtumour-SUVmax | ≥ 74: N/S | ≥ 84: N/S | ||
Groheux [18] | After 2 cycles | SUVmax < 7.4 | P = 0.011 | NR |
%ΔSUVmax ≥ 12 | P = 0.033 | NR | ||
TLG < 30.5 | P = 0.017 | NR | ||
%ΔTLG ≥ 51 | P < 0.001 | NR | ||
Groheux [19] | After 2 cycles | %ΔSUVmax† | HR = 0.86 (0.78–0.94) Adjusted P = 0.004 | NR |
%ΔSUVmax | P = 0.021 and P = 0.028‡ | NR | ||
Humbert [20] | After 1 cycle | %ΔSUVmax ≥ 16 | HR = 0.19 (0.06–0.64) | HR = 0.09 (0.02–0.54) |
Humbert [21] | After 1 cycle | %ΔSUVmax ≥ 50% | N/S | N/S |
Hyun [22] | After completion | Log2(SUVmax)† | HR = 1.86 (1.38–2.51) Adjusted HR = 1.51 (1.04–2.19) | NR |
%ΔSUVmax† | HR = 0.98 (0.97–0.99) Adjusted HR = 0.99 (0.98–1.00) | NR | ||
Log2(MTV)† | HR = 1.26 (1.15–1.38) Adjusted HR = 1.14 (1.01–1.27) | NR | ||
%ΔMTV† | HR = 0.99 (0.99–1.00) Adjusted HR = 1.00 (0.99–1.00) | NR | ||
Ishiba [23] | After completion | SUVmax ≤ 1.7 | P = 0.004 Adjusted P = 0.014 | P = 0.01 Adjusted P = 0.029 |
Jung [24] | After completion | Δ%SUVpeak ≥ 84.8 | P = 0.04 Adjusted P = N/S | NR |
Kim [25] | After completion | SUVmax† | HR = 1.20 (1.12–1.28) | NR |
MTV† | HR = 1.02 (1.01–1.03) | NR | ||
TLG† | HR = 1.00 (0.99–1.00) | NR | ||
%ΔSUVmax† | HR = 0.99 (0.98–0.99) | NR | ||
%ΔMTV† | HR = 1.00 (0.99–1.00) Adjusted HR = 0.99 (0.98–1.00) | NR | ||
%ΔMTV > 90.7 | HR = 0.39 (0.19–0.79) | NR | ||
%ΔTLG† | HR = 0.99 (0.99–1.00) | NR | ||
Kitajima [26] | After completion | CMR | HR = 0.15 (0.02–0.70) Adjusted HR = N/S | NR |
Kiyoto [27] | After completion | %ΔSUVmax > 15.9 | HR = 0.18 (0.05–0.88) | NR |
Kolesnikov-Gauthier [28] | After 1 cycle | %ΔSUVmax > 15 | 4-year DFS: 85% vs. 44%, P = 0.008 | N/S |
Lee [29] | After 3 cycles | %ΔSUVmax > 66.4 | P < 0.001 | P = 0.009 |
%ΔSUVmax† | HR = 0.97 (0.95–0.98) Adjusted HR = 0.97 (0.95–0.99) | HR = 0.98 (0.96–0.99) Adjusted HR = 0.97 (0.95–0.99) | ||
Lian [30] | After 2 cycles | CMR | HR = 0.17 (0.04–0.73) Adjusted HR = 0.04 (0.00–0.42) | NR |
Lim [31] | After 1 cycle | %ΔSUVmax > 41 | P < 0.001 Adjusted HR = 0.13 (0.03–0.49) | NR |
Zucchini [32] | After 2 cycles | %ΔSUVmax > 50 | N/S for all P = 0.049 for ER+/HER2− | NR |
Quantitative synthesis
Outcomes | PET timing | PET parameter | Studies (n) | Pooled hazard ratios | 95% confidence interval | I2 (%) | P for subgroup difference |
---|---|---|---|---|---|---|---|
Disease-free survival | Interim | %ΔSUVmax | 9 | 0.20 | 0.13–0.31 | 0 | 0.8539 |
SUVmax | 1 | 0.24 | 0.07–0.82 | NA | |||
CMR | 2 | 0.31 | 0.07–1.37 | 32 | |||
Post-treatment | %ΔSUVmax | 2 | 0.16 | 0.05–0.48 | 0 | 0.5821 | |
%ΔSUVpeak | 1 | 0.16 | 0.02–1.28 | NA | |||
%ΔMTV | 1 | 0.39 | 0.19–0.79 | NA | |||
ΔSUVmax | 2 | 0.38 | 0.19–0.78 | 0 | |||
CMR | 3 | 0.25 | 0.12–0.50 | 0 | |||
Overall survival | Interim | %ΔSUVmax | 3 | 0.20 | 0.09–0.44 | 0 | 0.7303 |
CMR | 1 | 0.34 | 0.02–6.64 | NA | |||
Post-treatment | SUVmax | 1 | 0.30 | 0.11–0.81 | NA | 0.7373 | |
CMR | 2 | 0.24 | 0.10–0.59 | 0 |