1. Documentation of the Searches

DATA SUPPLEMENT

1. Documentation of the Searches

1.1 MEDLINE

Search date: May 24th, 2011
Databases: Ovid MEDLINE(R) Daily Update <May 20, 2011> AND Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R) <1948 to Present>

No. / Search Term / Results
1 / exp *Intestinal Neoplasms/ OR *Gastrointestinal Neoplasms/ / 124,524
2 / ((rectal OR rectum OR colon* OR colorect* OR colo-rect* or gastrointestinal OR gastro-intestinal OR intestinal OR solid) adj3 (cancer* OR carcinom* OR neoplas* OR tumo* OR metast*)).ti / 80,260
3 / 1 OR 2 / 139,084
4 / Neoplastic Cells, Circulating/ / 5,387
5 / (shedd* adj3 cell*).mp. / 994
6 / exp *Intestinal Neoplasms/bl OR *Gastrointestinal Neoplasms/bl / 1,501
7 / minimal residual disease.mp. / 3,594
8 / exp Intestinal Neoplasms/bl AND (tumo* cell* OR cancer* cell* OR neoplas* cell* OR cancer* cell* OR neoplas* cell* OR carcinoma cell*).mp. / 357
9 / ((hematogen* OR haematogen* OR blood OR bone marrow) adj3 (tumo* cell* OR cancer* cell* OR neoplas* cell* OR carcinoma cell*)).mp / 2,595
10 / ((dis?eminat* OR des?iminat* OR circulat*) adj3 (tumo* cell* OR cancer* cell* OR neoplas* cell* OR carcinoma cell*)).mp. / 7,704
11 / Neoplasm Recurrence, Local/bl / 1,308
12 / Bone marrow examination/ / 5,546
13 / Bone Marrow Neoplasms/sc / 721
14 / OR/4-13 / 22,321
15 / 3 AND 14 / 2,453
16 / exp Prognosis/ / 802,604
17 / exp risk/ / 661,166
18 / (prognos* OR risk* OR survival* OR recurren* OR relaps*).mp. / 2,339,753
19 / (predict* adj3 (factor* OR marker* OR biomarker* OR relevan* OR role*)).mp. / 42,221
20 / exp epidemiologic studies/ / 1,308,340
21 / OR/16-20 / 3,319,645
22 / 15 AND 21 / 1,405
23 / exp animals/ NOT humans/ / 3,585,410
24 / 22 NOT 23 / 1,373
25 / metast*.mp. / 311,090
26 / 24 AND 25 / 611

1.2 EMBASE

Search date: May 24th, 2011
Database: Embase Classic+Embase <1947 to 2011 May 20>

No. / Search Term / Results
1 / exp *Intestinal Neoplasms/ OR *Gastrointestinal Neoplasms/ / 149,638
2 / ((rectal OR rectum OR colon* OR colorect* OR colo-rect* or gastrointestinal OR gastro-intestinal OR intestinal OR solid) adj3 (cancer* OR carcinom* OR neoplas* OR tumo* OR metast*)).ti / 101,350
3 / 1 OR 2 / 169,627
4 / Neoplastic Cells, Circulating/ / 2,581
5 / (shedd* adj3 cell*).mp. / 1,201
6 / minimal residual disease.mp. / 9,479
7 / ((hematogen* OR haematogen* OR blood OR bone marrow) adj3 (tumo* cell* OR cancer* cell* OR neoplas* cell* OR carcinoma cell*)).mp / 7,466
8 / ((dis?eminat* OR des?iminat* OR circulat*) adj3 (tumo* cell* OR cancer* cell* OR neoplas* cell* OR carcinoma cell*)).mp. / 5,038
9 / Bone marrow examination/ / 5,846
10 / (blood AND (detect* adj3 (tumo* cell* OR cancer* cell* OR neoplas* cell* OR carcinoma cell*))).mp / 1,514
11 / (bone marrow AND (detect* adj3 (tumo* cell* OR cancer* cell* OR neoplas* cell* OR carcinoma cell*))).mp / 720
12 / (h#ematogen* AND (detect* adj3 (tumo* cell* OR cancer* cell* OR neoplas* cell* OR carcinoma cell*))).mp / 25
13 / (circulat* adj3 (tumo* cell* OR cancer* cell* OR neoplas* cell* OR carcinoma cell*)).mp / 2,853
14 / OR/4-13 / 29,729
15 / 3 AND 14 / 1,284
16 / exp disease course/ / 1,589,188
17 / exp risk/ / 1,032,594
18 / (prognos* OR risk* OR survival* OR recurren* OR relaps*).mp. / 2,961,776
19 / (predict* adj3 (factor* OR marker* OR biomarker* OR relevan* OR role*)).mp. / 55,362
20 / exp epidemiologic studies/ / 1,546,217
21 / OR/16-20 / 4,381,718
22 / 15 AND 21 / 840
23 / exp animals/ NOT humans/ / 1,265,875
24 / 22 NOT 23 / 831
25 / metast*.mp. / 437,334
26 / 24 AND 25 / 542

1.3 Science Citation Index

Search date: May 24th, 2011
Database: Science Citation Index

No. / Search Term / Results
1 / TS=(shedd* same cell*) / 2,707
2 / TS="minimal residual disease" / 6,025
3 / TS=((hematogen* OR haematogen* OR blood OR bone marrow) same ("tumo* cell*" OR "cancer* cell*" OR "neoplas* cell*" OR "carcinoma cell*")) / 6,754
4 / TS=((disseminat* OR diseminat* OR dessiminat* OR desiminat* OR circulat*) same ("tumo* cell*" OR "cancer* cell*" OR "neoplas* cell*" OR "carcinoma cell*")) / 4,974
5 / TS=(("tumo* cell*" OR "cancer* cell*" OR "neoplas* cell*" OR "carcinoma cell*") same detect*) / 9,823
6 / #5 OR #4 OR #3 OR #2 OR #1 / 26,169
7 / TS=((rectal OR rectum OR colon* OR colorect* OR colo-rect* OR gastrointestinal OR gastro-intestinal OR intestinal OR solid) same (cancer* OR carcinom* OR neoplas* OR tumo*)) / >100,000
8 / #7 AND #6 / 4,388
9 / TS=(prognos* OR risk* OR survival* OR recurren* OR relaps*) / >100,000
10 / TS=(predict* same (factor* OR marker* OR biomarker* OR relevan* OR role*)) / >100,000
11 / #10 OR #9 / >100,000
12 / #11 AND #8 / 1,783
13 / TI=((rectal OR rectum OR colon* OR colorect* OR colo-rect* OR gastrointestinal OR gastro-intestinal OR intestinal OR solid) same (cancer* OR carcinom* OR neoplas* OR tumo*)) / 94,568
14 / #13 AND #12 / 576
15 / TS=(metast*) / >100,000
16 / #14 AND #15 / 365

1.4 BIOSIS

Search date: May 24th, 2011
Database: BIOSIS Previews <1993 to 2011 Week 24>

No. / Search Term / Results
1 / (shedd* adj3 cell*).mp. / 758
2 / minimal residual disease.mp. / 4,270
3 / ((hematogen* OR haematogen* OR blood OR bone marrow) adj3 (tumo* cell* OR cancer* cell* OR neoplas* cell* OR carcinoma cell*)).mp / 11,281
4 / ((dis?eminat* OR des?iminat* OR circulat*) adj3 (tumo* cell* OR cancer* cell* OR neoplas* cell* OR carcinoma cell*)).mp. / 2,835
5 / ((rectal OR rectum OR colon* OR colorect* OR colo-rect* or gastrointestinal OR gastro-intestinal OR intestinal OR solid) adj3 (cancer* OR carcinom* OR neoplas* OR tumo* OR metast*)).tw / 123,393
6 / Digestive System/ / 632,566
7 / "14006".cc. / 576,201
8 / "24004".cc. / 910,551
9 / Neoplastic Disease/ / 831,502
10 / 6 OR 7 / 940,654
11 / 9 OR 8 / 1,009,704
12 / 10 AND 11 / 202,988
13 / 5 AND 12 / 71,417
14 / ((rectal OR rectum OR colon* OR colorect* OR colo-rect* or gastrointestinal OR gastro-intestinal OR intestinal OR solid) adj3 (cancer* OR carcinom* OR neoplas* OR tumo* OR metast*)).ti / 50,899
15 / 13 OR 14 / 84,747
16 / (prognos* OR risk* OR survival* OR recurren* OR relaps*).mp. / 1,111,611
17 / (predict* adj3 (factor* OR marker* OR biomarker* OR relevan* OR role*)).mp. / 26,980
18 / 17 OR 16 / 1,124,058
19 / 18 AND 15 / 26,208
20 / 4 OR 1 OR 3 OR 2 / 18,378
21 / 19 AND 20 / 258
22 / (animal* or mice or rat or rats).ti. / 631,548
23 / 21 NOT 22 / 247
24 / metast*.mp. / 135,770
25 / 23 AND 24 / 150

1.5 Cited Reference Search

Search date: July 10th, 2011
Database: Cited Reference Search, – Web of Science

First Author / Cited References
Wyld(1) / 105
Staritz(2) / 2
Cohen 2006(3) / 39
Hiraiwa(4) / 16
Cohen 2009(5) / 25
Yen(6) / 15
Gazzaniga(7) / 0
Königsberg(8) / 3
Tol(9) / 6
Matsusaka(10) / 0
Vlems(11) / 15
Koch(12) / 37
Schoppmeyer(13) / 6
Papavasiliou(14) / 0
Vogelaar(15) / 1
Rahbari(16) / 0

Total after deleting duplicates: 201 (69 duplicates)

1.6 Cochrane library

Search date: July 10th, 2011
Database: Cochrane library
Search query: Neoplastic cells, circulating (MeSH term)
Evaluated abstract of: 2 Cochrane Reviews, 6 other reviews, 287 clinical trials, 3 technology assessments, 1 economic evaluation
Relevant papers not found in Medline/Embase/Biosis/Science Citation Index searches: None

1.7 International Clinical Trials Registry Platform – WHO

Search date: July 10th, 2011
Database: International Clinical Trials Registry Platform – WHO
Search query: Circulating tumor cells
Evaluated abstracts: 33 clinical trials
Relevant papers not found in Medline/Embase/Biosis/Science Citation Index searches: None

2. Excluded studies

Exclusion criterium / Number of Studies
No survival data(17-49) / 33
No stage IV-specific survival data(50-88) / 39
No stage IV patients(89-106) / 18
<20 patients(107-110) / 4
no original data(111-113) / 3
Chinese(114-116) / 3
Excluded detection method(117,118) / 2
Redundant(119) / 1
Median follow-up <6 monts(120) / 1

3. Assessment of publication bias

Publication bias was assessed with funnel plots.

Funnel Plot Analysis on Overall Survival

Funnel Plot Analysis on Progression Free Survival

4. Additional study characteristics

First author / Synchronous metastases, % / Preoperative chemotherapy, % / Extrahepatic disease, % / Clinical risk score, mean / Disease free interval <12 months, % / Chemotherapy regimen
Vlems / 61 / 34 / 12 / - / - / -
Koch / 30 / 22 / 0 / 1.8 / 54 / -
Schoppmeyer / - / - / - / - / - / -
Papavasiliou / 70 / 85 / - / 1.3 / - / 75% FOLFOX/FOLFIRI
Vogelaar / - / 66 / 15 / 36% >2 / 59 / -
Rahbari / 42 / 34 / 0 / 40% >2 / - / 17% bevacizumab

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