Table 1 Characteristics of studies included in the meta-analysis
Study, Year | Country | Number of subjects | Stage | Treatment, n (%) | WHO subtypes, n (%) | Hodgkin-Reed-Sternberg EBV status, n (%) | Antibodies (clone) | Scoring | Threshold(s) | Follow-up median (range) & mean (range) (in years) | Outcome correlation |
|---|---|---|---|---|---|---|---|---|---|---|---|
Steidl et al., 2010 [10] | Canada | 166 | Limited/advanced | ABVD ± RT 165 (99), RT alone 1 (1) | NS 140 (84), MC 11 (7), Others 5 (3), NOS 10 (6) | Neg 137 (84), Pos 27 (16) | CD68 (KP1) | Visual estimation | 5 %, 25 % | 4.0 (0.5–20.8) | CD68, adverse (PFS, DSS) |
Tzankov et al., 2010 [11] | Switzerland | 105 | Limited/advanced | ABVD ± RT 30 (28), COPP ± RT 48 (46), RT alone 27 (26) | NS 60 (57), MC 32 (30), Others 5 (5), NOS 8 (8) | Neg 85 (81), Pos 20 (19) | CD68 (PGM1) | Visual, cell counting | 0.82 % | 11.8 (1.0–27.6) | CD68, adverse (OS) |
Kamper et al., 2011 [12] | Denmark | 288 | Limited/advanced | ABVD/COPP ± RT, ABVD ± RT, RT alone | NS 237 (82), MC 47 (16), NOS 4 (1) | Neg 193 (67), Pos 95 (33) | CD68 (KP1), CD163 (10D6) | Computer-assisted point counting | 7.8 % (CD68), 21.1 % (CD163) | 7.0 (0.2–18.6) | CD68, adverse (EFS, OS); CD163, adverse (EFS, OS) |
Hohaus et al., 2011 [13] | Italy | 93 | Limited/advanced | ABVD ± RT 55 (59), BEACOPP ± RT 32 (34), MOPP/Other ± RT 6 (7) | NS 64 (69), MC 4 (4), Other 6 (8), NOS 19 (20) | Neg 37 (69), Pos 17 (31) | CD68 (PGM1) | Visual estimation | 5 % | 1.1 (0.1–6.8) | CD68, adverse (PFS) |
Zaki et al., 2011 [23] | Japan | 82 | Limited/advanced | ABVD ± RT, RT alone | NS 20 (24), MC 52 (63), Other 10 (12) | NR | CD68 (PGM1), CD163 (10D6) | Visual, cell counting in 0.146 mm2 | Median (CD68), Median (CD163) | Mean: 4.0 (0.8–9.6) | CD68, NSS (OS); CD163, adverse (OS) |
Azambuja et al., 2012 [24] | USA | 265 | Limited/advanced | ABVD ± RT 265 (100) | NS 180 (68), MC 52 (20), Others 18 (6), NOS 15 (6) | Neg 122 (58), Pos 87 (42) | CD68 (KP1), CD163 (10D6) | Visual estimation | 5 %, 25 % (CD68), 5 %, 25 % (CD163) | 6 (1.5–11.7) | CD68, NSS (PFS, DSS); CD163, NSS (PFS, DSS) |
Yoon et al., 2012 [14] | South Korea | 144 | Limited/advanced | ABVD 113 (79), C-MOPP 10 (7), ABVD/C-MOPP hybrid 15 (10), BEACOPP 6 (4) | NS 90 (63), MC 34 (24), Others 11 (7), NOS 9(6) | Neg 66 (46), Pos 78 (54) | CD68 (KP1), CD163 (10D6) | Visual estimation | 20 % (CD68), 20 % (CD163) | 5.4 (0.7–19.0) | CD68, adverse (EFS, OS); CD163, adverse (EFS, OS) |
Tan et al., 2012 [15] | Canada | 287 | Advanced | ABVD ± RT 144 (50), Stanford V ± RT 143 (50) | NS 223 (78), MC 38 (13), Others 9 (3), NOS 17(6) | Neg 238 (83), Pos 49 (17) | CD68 (KP1), CD163 (10D6) | Computer-assisted image analysis | 12.7 % (CD68), 16.8 % (CD163) | 5.5 | CD63, adverse (FFS, OS); CD163, adverse (FFS, OS) |
Sanchez-Espiridion et al., 2012 [31] | USA | 103 | Advanced | NR | NS 74 (73), MC 22 (22), Others 6 (6) | NR | CD68 (KP1 and PGM1), CD163 (10D6) | Computer-assisted point counting | 5Â %, 25Â %, median (CD68), 5Â %, 25Â %, median (CD163) | NR | CD68, NSS (FFS, OS); CD163, NSS (FFS, OS) |
Abdou et al., 2013 [16] | Egypt | 61 | Limited/advanced | Chemotherapy | NS 33 (54), MC 20 (33), Others 8 (13) | NR | CD68 (KP1) | Visual, cell counting | 40 % (CD68) | Mean: 1.2 ± 1.7 | CD68, adverse (OS) |
Greaves et al., 2013 [17] | United Kingdom | 122 | Limited/advanced | Anthracycline-based ± RT 56 (46), Alkalator-based ± RT 52 (43), RT alone 14 (11) | NS 93 (78), MC 25 (20), Others 2 (2) | Neg 84 (69), Pos 38 (31) | CD68 (KP1) | Computer-assisted image analysis | 5 %, 15 % | 16.5 (2–40) | CD68, adverse (FFTF, OS) across the 3 defined groups |
Deau et al., 2013 [25] | France | 59 | Limited/advanced | ABVD 47 (80), EBVP 8 (14), BEACOPP 3 (5) | NS 54 (92), Non-NS 5 (8) | NR | CD68 (KP1) | Visual estimation | 25Â % | NR | CD68, adverse (PFS); CD68, NSS (OS) |
Panico et al., 2015 [26] | Italy | 121 | Limited/advanced | ABVD ± RT 101 (83), ABVD-like ± RT 20 (17) | NS 73 (60), MC 40 (33), Others 8 (7) | NR | CD68 (KP1) | Visual, cell counting | 30 per 0.023 mm2 | Mean: 3.5 (0.1–9.3) | CD68, adverse (OS); CD68, NSS(PFS) |
Casulo et al., 2013 [18] | USA | 81 | Limited/advanced | ABVD 38 (47), Stanford V 11(13), ABVD/MOPP 16 (20), others 16 (20) | NR | NR | CD68 (KP1) | Computer-assisted image analysis | 30Â % | 8.8 | CD68, adverse (OS) |
Koh et al., 2014 [19] | South Korea | 116 | Limited/advanced | ABVD ± RT 116 (100) | NS 78 (67), MC 22 (19), Others 8 (7), NOS 8 (7) | Neg 73 (63), Pos 43 (37) | CD68 (KP1), CD163 (10D6) | Visual estimation | 20 % (CD68), 20 % (CD163) | 6.2 (3.8–10.3) | CD68, adverse (EFS, DSS, OS); CD163, adverse (EFS, DSS, OS) |
Ping et al., 2014 [27] | China | 72 | Limited/advanced | ABVD 49(68), BEACOPP 13(18), others 10 (14) | NS 41(57), MC 23 (32), Others 8 (11) | NR | CD68 (KP1) | Visual estimation | 250/HPF | 3.9 (0.7–15) | CD68, NSS (OS); |
Klein et al., 2014 [28] | USA | 88 | Limited/advanced | ABVD ± RT 88 (100) | NS 55 (63), MC 6 (7), Others 1 (1), NOS 19 (22) | NR | CD68 (KP1), CD163 (10D6) | Visual estimation | 5 %, 25 % (CD68), 5 %, 25 % (CD163) | NR | CD68, NSS (OS); CD163, adverse (OS) 25 % threshold |
Touati et al., 2014 [20] | France | 158 | Limited/advanced | ABVD 102(65), ABVD/MOPP 26 (17), BEACOPP 11 (7), ABVD-like 9 (5), others 10 (6) | NS 130 (82), MC 21 (13), Others 7 (5) | Neg 106 (67), Pos 40 (25), Not done 12 (8) | CD68 (PGM1) | Visual estimation | 25 % | 5.5 (0.2–16.2) | CD68, adverse (PFS, OS) |
Kayal et al., 2014 [30] | India | 100 | Limited/advanced | ABVD ± RT 88 (88), EVAP RT 11 (11), Other 1 (1) | NS 51 (51), MC 47 (47), Others 2 (2) | NR | CD68 (CD68/G2) | Visual, cell counting | 12.9 %, 18.2 %, 25 % (the quartiles) | 5.7 | CD68, NSS (PFS, DSS) |
Agur et al., 2015 [29] | Israel | 98 | Limited/advanced | ABVD 60(60), BEACOPP 29(29), others 9 (1) | NS 33 (34), MC 7 (7), Others 58 (59) | NR | CD68 (PGM1) | Visual, cell counting | 25 % | Mean: 3.8 (0.9–7.8) | CD68, NSS (PFS) |
Moreno et al., 2015 [21] | Spain | 249 | Advanced | NR | NS 162 (65), MC 68 (27), Others 19 (8) | NR | CD68 (PGM1), CD163 (10D6) | Computer-assisted point counting | 30Â % | NR | CD68, adverse (OS) |
Jakovic et al., 2016 [22] | Serbia | 101 | Advanced | ABVD ± RT 101 (100) | NS 80 (79), MC 13 (13), Others 8 (8) | NR | CD68 (PGM1) | Visual estimation | 25 % | 8.6 (0.2–16) | CD68, adverse (EFS, OS) |