Background
Classification/Grade | Mitotic Indexa | Ki-67 Indexb |
---|---|---|
Well-differentiated NEN | ||
NET G1 | < 2/10 | ≤ 2 |
NET G2 | 2–20 | 3–20 |
NET G3c | > 20 | > 20 |
Poorly differentiated NEN | ||
NEC G3 | > 20 | > 20 |
Small cell carcinoma | ||
Large cell carcinoma |
Methods
Results
Author [Ref] | Year | Study type | # of Cases | Incidence (%) | Early Stage/Advanced stage | Small cell/large cell/other | Immunohistochemical profile (n) | Molecular characteristics (n) |
---|---|---|---|---|---|---|---|---|
Baggar [135] | 2017 | CR | 1 | – | 1/0 | 1/0/0 | CHG (1), CD56 (1) | – |
Cho [34] | 2017 | CS | 16 | – | 12/4 | 16/0/0 | SYN (16), CHG (12), ERBB4 (16) | ATRX (4/5), ERBB4 (4/5) |
Damian [41] | 2017 | CR | 1 | – | 1/0 | 1/0/0 | – | – |
Kuji [67] | 2017 | CS | 37 | – | 30/7 | 29/8/0 | SYN (32), CHG (32) | – |
Paraghamian [149] | 2017 | CR | 1 | – | 1/0 | 1/0/0 | – | – |
Wu [128] | 2017 | CR | 1 | – | 1/0 | 1/0/0 | SYN (1), CHG (1) | – |
Xie [158] | 2017 | CS | 48 | – | 40/8 | 31/1/16 | SYN (45), NSE (25), CD56 (13) | – |
Cavalcanti [29] | 2016 | CR | 1 | – | – | 1/0/0 | – | p53 (1), MST1R (1), MYCN Ampl. (1), U2AF1 (1), GATA3 (1) |
Duan [45] | 2016 | CS | 26 | – | 22/4 | 25/0/1 | SYN (24), NSE (19), CD56 (13) | – |
Frumovitz [47] | 2016 | COS | 44 | – | 26/18 | 38/0/6 | – | p53 (5), PIK3CA (8), KRAS (6) |
Ganesan [48] | 2016 | CS | 31 | 31/2385 (1.30%) | – | 31/0/0 | – | – |
Lee [142] | 2016 | COS | 61 | – | 41/20 | 41/7/13 | SYN (33/43), CHG (30/43), CD56 (30/43) | – |
Margolis [145] | 2016 | COS | 1896 | 1896/127332 (1.49%) | 582/1157 | – | – | – |
Rajkumar [151] | 2016 | CR | 1 | – | 1/0 | 0/1/0 | SYN (1), CHG (1), CD56 (1), p16 (1) | – |
Robin [100] | 2016 | COS | 100 | – | – | – | – | – |
Stecklein [153] | 2016 | COS | 40 | – | 33/7 | 26/8/6 | SYN (36), CHG (26), CD56 (14) | – |
Majhi [79] | 2015 | CR | 1 | – | 1/0 | – | SYN (1), CHG (1), NSE (1) | – |
Nagao [86] | 2015 | CS | 23 | – | 18/5 | 11/12/0 | – | – |
Sheth [152] | 2015 | CR | 1 | – | 1/0 | 1/0/0 | SYN (1), CHG (1), CD56 (1) | – |
Singh [105] | 2015 | CR | 1 | – | 1/0 | 1/0/0 | SYN (1), CHG (1) | – |
Sodsanrat [109] | 2015 | CS | 44 | 44/2835 (1.55%) | – | – | – | – |
Wang [156] | 2015 | CR | 1 | – | 1/0 | 1/0/0 | SYN (1), CHG (1), CD56 (1) | – |
Wang [157] | 2015 | CS | 32 | – | 32/0 | 22/0/10 | – | – |
Yin [12] | 2015 | CS | 23 | – | 18/5 | 23/0/0 | – | – |
Yuan [132] | 2015 | CS | 38 | – | 38/0 | 38/0/0 | – | – |
Bellefqih [136] | 2014 | CS | 6 | – | – | – | – | – |
Dongol [139] | 2014 | CS | 4 | – | 3/1 | 4/0/0 | SYN (4), NSE (4) | – |
Lyons [144] | 2014 | CR | 1 | – | 1/0 | 1/0/0 | – | KRAS (1) |
Omori [148] | 2014 | CR | 1 | – | 0/1 | 0/1/0 | SYN (1), CHG (1), CD56 (1), p16 (1), p53 (1) | – |
Yin [129] | 2014 | COS | 64 | 64/9474 (0.68%) | 47/17 | 64/0/0 | – | – |
Yousef [131] | 2014 | CR | 1 | – | 0/1 | 1/0/0 | SYN (1) | – |
Zaid [134] | 2014 | CS | 57 | – | 49/8 | 49/8/0 | – | – |
Intaraphet [59] | 2013 | COS | 130 | 130/2108 (6.17%) | 82/48 | 130/0/0 | – | – |
Kim [63] | 2013 | CR | 1 | – | 1/0 | 1/0/0 | CHG (1), NSE (1) | – |
Kuroda [69] | 2013 | CR | 1 | – | 1/0 | 0/1/0 | SYN (1), CD56 (1), p16 (1) | – |
Li [76] | 2013 | CS | 12 | 12/452 (2.65%) | 8/4 | 6/6/0 | SYN (11), CHG (10), CD56 (11), AE1/3 (12), p16 (11) | – |
McCann [146] | 2013 | COS | 26 | – | 14/12 | 21/2/2 | – | – |
Murakami [147] | 2013 | CR | 1 | – | 0/1 | 0/1/0 | SYN (1), CHG (1), NSE (1) | – |
Rekhi [96] | 2013 | COS | 50 | – | – | 26/14/10 | SYN (22/37), CHG (27/37), NSE (7/8), CD56 (8/8) | – |
Sitthinumsawan [108] | 2013 | COS | 14 | 14/389 (3.60%) | 9/5 | 8/3/3 | SYN (11), CHG (9), NSE (12), CD56 (11) | – |
Wang [125] | 2013 | CS | 13 | – | – | 13/0/0 | SYN (13), CHG (9) | – |
Hara [54] | 2012 | CR | 1 | – | 1/0 | 0/0/1 | SYN (1), CHG (1), CD56 (1) | – |
Lin [78] | 2012 | CS | 5 | – | 4/1 | – | – | – |
Peng [150] | 2012 | CS | 14 | 14/2074 (0.68%) | 11/3 | 9/0/5 | – | – |
Siriaunkgul [106] | 2012 | CS | 26 | – | 21/5 | 21/3/2 | – | – |
Sisti [107] | 2012 | CR | 1 | – | 1/0 | 1/0/0 | SYN (1), CHG (1), NSE (1) | – |
Tanimoto [154] | 2012 | CR | 1 | – | 0/1 | 0/1/0 | – | – |
Teefey [114] | 2012 | CR | 1 | – | 1/0 | 1/0/0 | SYN (1), CHG (1), CD56 (1), p16 (1) | – |
Hao [53] | 2011 | CR | 1 | – | 1/0 | 0/1/0 | CHG (1), CD56 (1), p16 (1) | – |
Komiyama [66] | 2011 | CR | 1 | – | 1/0 | 0/0/1 | SYN (1), CHG (1), NSE (1) | – |
Nasu [13] | 2011 | CR | 1 | – | 1/0 | 1/0/0 | – | – |
McCluggage [84] | 2010 | CS | 21 | – | – | 13/8/0 | SYN (19), CHG (11), CD56 (19), AE1/3 (17), p16 (21), PGP9.5 (9) | – |
Niwa [88] | 2010 | CR | 1 | – | 1/0 | 0/1/0 | – | – |
Rashed [95] | 2010 | CR | 1 | – | 1/0 | 1/0/0 | CHG (1) | – |
Bifulco [27] | 2009 | CR | 1 | – | 0/1 | 0/1/0 | SYN (1), NSE (1) | – |
Kajiwara [61] | 2009 | CS | 7 | – | 2/5 | 3/2/2 | SYN (7), CHG (6) | – |
Lee [74] | 2009 | CR | 1 | – | 1/0 | 1/0/0 | NSE (1), CD56 (1) | – |
Li [77] | 2009 | CR | 1 | – | 0/1 | 0/1/0 | – | – |
Wang [123] | 2009 | CS | 7 | 7/8018 (0.09%) | 7/0 | 0/7/0 | – | – |
Zivanovic [159] | 2009 | COS | 17 | – | 11/6 | 17/0/0 | – | – |
Albores-Saavedra [21] | 2008 | CS | 2 | – | 2/0 | 0/2/0 | SYN (2), CHG (2), CD56 (2) | – |
Chung [36] | 2008 | CR | 1 | – | 1/0 | 1/0/0 | SYN (1), CHG (1), CD56 (1) | – |
Lee [71] | 2008 | CS | 68 | – | 68/0 | – | – | – |
Alphandery [22] | 2007 | CR | 1 | – | 0/1 | 1/0/0 | SYN (1), CHG (1), CD56 (1), c-Kit (1) | – |
Kasamatsu [62] | 2007 | CS | 10 | 10/2096 (0.48%) | 9/1 | – | – | – |
Ko [64] | 2007 | CR | 1 | – | 1/0 | 0/1/0 | SYN (1), CHG (1), NSE (1) | – |
Tangjitgamol [113] | 2007 | CR | 1 | – | 0/1 | 0/1/0 | – | – |
Cetiner [30] | 2006 | CR | 1 | – | 1/0 | 0/1/0 | CHG (1), NSE (1) | – |
Horn [56] | 2006 | CS | 9 | 9/677 (1.33%) | – | 9/0/0 | SYN (7), CHG (7), NSE (7), CD56 (8), p16 (9), p53 (2) | – |
Ohwada [89] | 2006 | CR | 1 | – | 1/0 | 0/1/0 | SYN (1), CHG (1), p16 (1) | – |
Wang [124] | 2006 | CS | 31 | – | – | 25/4/2 | – | – |
Baykal [26] | 2005 | CR | 1 | – | 1/0 | 0/0/1 | CHG (1), NSE (1) | – |
Chatterjee [32] | 2005 | CR | 1 | – | 1/0 | 1/0/0 | NSE (1) | – |
Tangjitgamol [112] | 2005 | CS | 24 | – | 16/8 | 18/6/0 | – | – |
Tsunoda [117] | 2005 | CS | 11 | 11/1370 (0.80%) | 7/4 | 11/0/0 | SYN (8), CHG (7), NSE (9), CD56 (6) | – |
Dikmen [43] | 2004 | CR | 1 | – | 1/0 | 0/1/0 | SYN (1), CHG (1), NSE (1) | – |
Ishida [60] | 2004 | CS | 10 | – | – | 5/5/0 | – | p53 (1) |
Trinh [116] | 2004 | CR | 1 | – | 1/0 | 1/0/0 | – | – |
Viswanathan [121] | 2004 | COS | 21 | – | 17/4 | 21/0/0 | SYN (19), CHG (16), CD56 (15) | – |
Wang [8] | 2004 | CS | 22 | – | 18/4 | 22/0/0 | SYN (16), CHG (16), NSE (15), p16 (20), Rb loss (18) | – |
Hoskins [14] | 2003 | CS | 34 | – | 17/17 | 34/0/0 | – | – |
Sato [101] | 2003 | CS | 6 | 6/972 (0.62%) | 6/0 | 0/6/0 | SYN (6), CHG (6) | – |
Conner [39] | 2002 | CS | 23 | – | – | 18/0/5 | SYN (13), CHG (10), p53 (10) | – |
Grayson [51] | 2002 | CS | 12 | – | – | 0/12/0 | SYN (11) | – |
Marshall [83] | 2002 | CR | 1 | – | 0/1 | – | SYN (1) | – |
Ribeiro-Silva [99] | 2002 | CR | 1 | – | 1/0 | 0/0/1 | CHG (1) | – |
Balega [25] | 2001 | CR | 1 | – | 1/0 | – | SYN (1), CHG (1) | – |
Bermúdez [15] | 2001 | COS | 20 | – | 14/6 | 12/6/2 | SYN (8/18), CHG (9/18), NSE (15/18) | – |
Boruta [137] | 2001 | CS | 11 | – | 11/0 | 9/1/1 | – | – |
Lenczewski [75] | 2001 | CS | 6 | 6/73 (8.22%) | – | 6/0/0 | – | – |
Rhemtula [97] | 2001 | CS | 5 | – | 2/3 | 0/5/0 | SYN (5), MNF116 (5) | – |
Straughn [110] | 2001 | CS | 16 | – | 15/1 | 15/0/0 | SYN (8/13), CHG (8), NSE (12) | p53 (8), c-myc (8/15), PCNA (5/15) |
Collinet [38] | 2000 | CS | 5 | – | 2/3 | 5/0/0 | – | – |
Delaloge [42] | 2000 | COS | 10 | – | 7/3 | 10/0/0 | – | – |
Herrington [55] | 1999 | CS | 25 | – | – | 25/0/0 | Rb (2) | – |
Koch [65] | 1999 | CR | 1 | – | 1/0 | 1/0/0 | SYN (1), CHG (1) | – |
McGarry [85] | 1999 | CR | 1 | – | 1/0 | 1/0/0 | SYN (1), CHG (1), NSE (1) | – |
Wistuba [127] | 1999 | CS | 15 | – | – | 2/8/5 | – | p53 (7), KRAS (0), LOH (7) |
Yun [133] | 1999 | CR | 1 | – | 1/0 | 0/1/0 | SYN (1), CHG (1) | – |
Mannion [80] | 1998 | CS | 38 | – | – | 25/5/8 | – | LOH (9) |
Wang [155] | 1998 | CS | 7 | – | 7/0 | 7/0/0 | CHG (4), NSE (7) | – |
Gilks [50] | 1997 | CS | 12 | – | 12/0 | 0/12/0 | SYN (6), CHG (12), NSE (4) | – |
Toki [115] | 1996 | CR | 1 | – | 1/0 | 1/0/0 | CHG (1), NSE (1), SER (1) | – |
Abulafia [19] | 1995 | CS | 3 | – | 3/0 | 3/0/0 | – | |
Abeler [18] | 1994 | COS | 26 | – | 16/10 | 26/0/0 | SYN (7), CHG (5), NSE (19) | – |
Chen [7] | 1994 | CS | 6 | – | – | 6/0/0 | NSE (6) | – |
Lewandowski [143] | 1993 | CS | 4 | – | 2/2 | 4/0/0 | CHG (1), NSE (2) | – |
Gersell [49] | 1988 | COS | 15 | – | 10/5 | 15/0/0 | SYN (10), CHG (11), NSE (11) | – |
Sheets [103] | 1988 | COS | 14 | 14/649 (2.16%) | 14/0 | 14/0/0 | – | – |
van Nagell [120] | 1988 | CS | 25 | 25/2201 (1.14%) | – | 25/0/0 | CHG (8), NSE (8) | – |
Walker [122] | 1988 | CS | 14 | 10/365 (2.74%) | 8/6 | 12/0/2 | – | – |
Turner [118] | 1986 | CR | 1 | – | 1/0 | 1/0/0 | – | – |
Pooled Analysis
|
–
|
–
|
3538
|
2303/163470 (1.41%)
|
1479 (50.7%)/ 1436 (49.3%)
|
1123 (80.0%)/ 176 (12.5%)/ 105 (7.5%)
|
SYN (424/538; 79%), CHG (323/486; 66%), NSE (196/285; 69%), CD56 (162/267; 61%), AE1/3 (29/33; 88%), c-Kit (1/1; 100%), ERBB4 (16/16; 100%), MNF116 (5/5; 100%), p16 (67/70; 96%), p53 (13/33; 39%), PGP9.5 (9/21; 43%), Rb (2/25; 8%), Rb loss (18/22; 82%), SER (1/1; 100%)
|
ATRX (4/5; 80%), ERBB4 (4/5; 80%), p53 (22/86; 26%), MST1R (1/1; 100%), MYCN Ampl. (1/1; 100%), U2AF1 (1/1; 100%), GATA3 (1/1; 100%), PIK3CA (8/44; 18%), KRAS (7/60; 12%), c-myc (8/15; 53%), PCNA (5/15; 33%), LOH (16/53; 30%)
|
Author | Year | N | Treatment modalities (Initial) | Treatment modalities (Recurrence) | Chemotherapy regimens adjuvant/Neo-Adjuvant | Chemotherapy regimens recurrence/primary advanced | RXT (n)/Gray | Recurrence-free survival duration (m) | Overall survival duration (m) | 2- or 3-Year Overall survival rate (%) | 5-Year overall survival rate (%) |
---|---|---|---|---|---|---|---|---|---|---|---|
Paraghamian [149] | 2017 | 1 | S + CHXT | CHXT, RXT, NIV | EP | PACTOP | – | 1 | 7 | – | – |
Wu [128] | 2017 | 1 | NACT+S + CHXT | – | IfoEP | – | – | 78 | 78 | – | – |
Xie [158] | 2017 | 48 | NACT+S + CHXT, S + RXT, S + CHXT | – | EP, CPAC, BEP | – | – | – | 30 | 57 | 31 |
Lee [142] | 2016 | 61 | S + CHXT, RXCT, S + RXCT, CHXT | – | EP, CPAC, FUP | – | – | – | 64 | – | 36 |
Rajkumar [151] | 2016 | 1 | S + CHXT | – | EP | – | – | 18 | 18 | – | – |
Robin [100] | 2016 | 100 | RCXT, NACT+RCXT | – | – | – | – | – | 48 | ||
Stecklein [153] | 2016 | 40 | S, S + RXT, RXT + CHXT, RCXT | – | – | – | – | 9 | – | 30 | 27 |
Nagao [86] | 2015 | 23 | S + CHXT, S + RCXT, RXT | – | CPAC, IP | – | – | – | – | 64 | – |
Singh [105] | 2015 | 1 | S + CHXT | – | EP | – | – | 26 | 26 | – | – |
Wang [156] | 2015 | 1 | NACT+RXCT | – | EP, N | – | −/25 | 6 | 6 | – | – |
Yin [12] | 2015 | 23 | NACT+S + CHXT, NACT+S + RXT + CHXT | – | EP | – | – | – | 69 (3), 54 (20) | 55 | 39 |
Dongol [139] | 2014 | 4 | NACT+S + CHXT | – | EP, VPB | – | – | – | 10 | – | – |
Lyons [144] | 2014 | 1 | NACT+S + RXCT | MEK-Inh | EP | TRAM | 1/45 | 4 | 12 | – | – |
Omori [148] | 2014 | 1 | NACT+S + CHXT | – | IP | – | – | 21 | 21 | – | – |
Kim [63] | 2013 | 1 | S + RCXT | CHXT, S | – | CPAC, EP | 1/50 | 4 | 12 | – | – |
McCann [146] | 2013 | 26 | S, NACT+S, S + RXT | CHXT | EP | EPA | – | 34 | 49 | 71 | – |
Murakami [147] | 2013 | 1 | CHXT | – | IP | – | – | 3 | 5 | – | – |
Lin [78] | 2012 | 5 | RXT, RXCT, S + RXCT | CHXT | – | FUP, EPD | – | 6 | 22 | – | – |
Peng [150] | 2012 | 14 | S + RXT + CHXT, S + CHXT | – | EP, FUP, EP + CPAC | – | – | 6 | 32 | 40 | 25 |
Teefey [114] | 2012 | 1 | NACT+S | – | EP | – | – | 24 | 24 | – | – |
Komiyama [66] | 2011 | 1 | S + CHXT | CHXT, RXT | EPPAC | IP | – | 11 | 19 | – | – |
Nasu [13] | 2011 | 1 | NACT+S + CHXT | CHXT | IP | AMR, EP | – | 0 | 27 | – | – |
Bifulco [27] | 2009 | 1 | S + RXT + CHXT | – | CPAC | – | – | 12 | 12 | – | – |
Li [77] | 2009 | 1 | RXCT | – | EP | – | 1/63 | 21 | 21 | – | – |
Wang [123] | 2009 | 7 | S, S + CHXT, S + RXT | – | EP, EPEpi, P, PE | – | – | – | 32 | – | 28 |
Zivanovic [159] | 2009 | 17 | S + CHXT, RXCT | – | EP | – | −/14 | – | 21 | 30 | – |
Lee [71] | 2008 | 68 | S, NACT+S + RXCT, NACT+S + RXT | – | EP, CPAC, VPB, IPPAC | – | – | – | 54 | 64.6 | 46.6 |
Kasamatsu [62] | 2007 | 10 | S, S + RXT, S + CHXT | – | EP, PDC | – | 2/45–50 | 8 | 29 | – | 43 |
Ko [64] | 2007 | 1 | S + RCXT+CHXT | – | P | – | 1/53 | 24 | 24 | – | – |
Tangjitgamol [113] | 2007 | 1 | S + CHXT | CHXT | CPAC | CPAC, EP | – | 19 | 27 | – | – |
Baykal [26] | 2005 | 1 | S + CHXT+RCXT | – | EP | – | 1/50 | 21 | 21 | – | – |
Tangjitgamol [112] | 2005 | 24 | S, S + CHXT, S + RXT, RCXT, RXT, CHXT | – | – | – | – | – | 21 | – | – |
Tsunoda [117] | 2005 | 11 | S + CHXT, S + RXT, RCXT | – | EP, PPep | – | 3/50; 2/80 | – | 27 | – | 27 |
Trinh [116] | 2004 | 1 | S + CHXT+RCXT | – | – | – | – | 52 | 52 | – | – |
Viswanathan [121] | 2004 | 21 | S, RXT, RCXT, S + CHXT, NACT+RXT | – | EP, EPD | – | – | – | 41 | – | 29 |
Hoskins [14] | 2003 | 34 | CHXT+RCXT | – | EP, CPAC | – | – | – | – | 60 | – |
Sato [101] | 2003 | 6 | S + RXT + CHXT | – | – | – | – | – | 36 | – | 33 |
Bermúdez [15] | 2001 | 20 | S + RXT, NACT+S, CHXT | – | VBP | – | −/50 | – | 39 | 60 | 39 |
Boruta [137] | 2001 | 11 | S + CHXT | – | VAC, EP | – | – | – | 24 | 38 | – |
Collinet [38] | 2000 | 5 | S + CHXT, S + RXT, RXT | EP, EDC | – | 3/55–105 | 15 | 17 | – | – | |
Delaloge [42] | 2000 | 3 | S + RXT, S + CHXT, S + RXCT | – | PVep | – | – | 16 | 33 | – | 20 |
McGarry [85] | 1999 | 1 | NACT+RXT | S | EP | – | −/83 | 0 | 18 | – | – |
Abulafia [19] | 1995 | 3 | S + CHXT, S + CHXT+RXT | RXT | EVP-16 | – | – | 30 | 36 | – | – |
Lewandowski [143] | 1993 | 4 | S + CHXT, CHXT+RXT, NACT+S + RXT, NACT+CHXT | – | EPD | – | 2/45 | – | 25 | – | – |
Gersell [49] | 1988 | 15 | S, RXT, S + RXT, RXT + CHXT | – | * | – | – | – | 18 | – | 33 |
Sheets [103] | 1988 | 14 | S, S + RXT | – | – | – | 8/45–60 | – | 19 | 15 | – |
Walker [122] | 1988 | 14 | RXT, S, CHXT, S + CHXT, RXT + CHXT | – | VDaCy | – | – | – | 14 | – | 14 |
Turner [118] | 1986 | 1 | S + CHXT+RXT | – | VACyMVP | – | 1/45 | 2 | 4 | – | – |
Pooled Analysis
| S + CHXT (21/48); NACT+S ± Other (12/48); RXT/RCXT or RXT + CHXT (15/43) | CHXT (7/10); RXT (3/10); S (2/10) | EP (24/40); EP + Other (6/40); CPAC (7/40); IP (4/40); FUP (3/40) | EP ± Other (5/8) | – | 16 Months | 40 Months | 50% | 34% |