PMID- 36523938
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221222
IS  - 2304-3881 (Print)
IS  - 2304-389X (Electronic)
IS  - 2304-3881 (Linking)
VI  - 11
IP  - 6
DP  - 2022 Dec
TI  - Systemic review of the robustness of randomized controlled trials for the 
      treatment of cholangiocarcinoma in three domains: survival-inferred fragility 
      index, restricted mean survival time, and the spin effect.
PG  - 861-869
LID - 10.21037/hbsn-21-118 [doi]
AB  - BACKGROUND: The vast majority of patients with cholangiocarcinoma (CC) have 
      advanced disease at diagnosis and are candidates for palliative treatment only. 
      The robustness of the randomized controlled trials regarding the treatment of CC 
      are assessed. METHODS: A systematic review of all randomized control trials (RCT) 
      of treatments for both intra- and extrahepatic CC between 2010 and 2020 was 
      performed. The survival-inferred fragility index (SIFI; the minimum number of 
      reassignments of the best survivors between arms that would overturn the 
      statistical outcomes) was calculated. In addition, the gain, or loss, in survival 
      in RCTs was evaluated by the restricted mean survival time (RMST) difference. 
      Finally, the level of spin i.e., misrepresentation of study outcomes, was 
      measured in inconclusive studies to assess distorted reporting strategies. 
      RESULTS: Out of 6,167 studies retrieved, 11 could be retained for full text 
      revision (7 with both intra- and extrahepatic CC, 3 with peri-hilar CC, and 1 
      with peri-hilar or distal CC). Only 3 studies included resected patients (2 with 
      both intra- and extrahepatic CC and 1 with peri-hilar or distal CC). Nine studies 
      investigated systemic chemotherapy (including 3 after surgical resection), one 
      study evaluated photodynamic therapy, and another investigated the use of an 
      endoscopically inserted stent in the biliary tract. The median SIFI was -2 
      [interquartile range (IQR): -6.25, -0.25] across all studies. Overall, the median 
      RMST difference was 0.56 months (IQR: 0.10, 0.95). Finally, for inconclusive 
      studies, the level of spin was high, moderate, and low in respectively 12.5%, 
      25%, and 62.5% of the studies. CONCLUSIONS: RCTs of CC showed a low degree of 
      robustness with a frequent proportion of associated spin.
CI  - 2022 Hepatobiliary Surgery and Nutrition. All rights reserved.
FAU - Horesh, Nir
AU  - Horesh N
AD  - Unit of Hepatobiliary and Pancreatic Surgery and Transplantation, Sheba Medical 
      Center, Faculty of Medicine Tel Aviv University, Tel Aviv, Israel.
AD  - Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
FAU - Bomze, David
AU  - Bomze D
AD  - Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
FAU - Lim, Chetana
AU  - Lim C
AD  - Centre Hepato-Biliaire, Department of Hepatobiliary and Pancreatic Surgery and 
      Transplantation, Pitie Salpetriere Hospital, Assistance Publique-Hopitaux de 
      Paris, Paris, France.
FAU - Markel, Gal
AU  - Markel G
AD  - Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
AD  - Davidoff Cancer Center, Rabin Medical Center-Beilinson Hospital, Petah Tikva, 
      Israel.
FAU - Meirson, Tomer
AU  - Meirson T
AD  - Davidoff Cancer Center, Rabin Medical Center-Beilinson Hospital, Petah Tikva, 
      Israel.
AD  - Shamir Medical Center (Assaf Harofeh), Rishon Lezion, Israel.
AD  - The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel.
FAU - Azoulay, Daniel
AU  - Azoulay D
AD  - Unit of Hepatobiliary and Pancreatic Surgery and Transplantation, Sheba Medical 
      Center, Faculty of Medicine Tel Aviv University, Tel Aviv, Israel.
AD  - Centre Hepato-Biliaire, Department of Hepatobiliary and Pancreatic Surgery and 
      Transplantation, Paul Brousse Hospital, Assistance Publique-Hopitaux de Paris, 
      Universite Saclay, Villejuif, France.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - China (Republic : 1949- )
TA  - Hepatobiliary Surg Nutr
JT  - Hepatobiliary surgery and nutrition
JID - 101600750
PMC - PMC9745612
OTO - NOTNLM
OT  - Cholangiocarcinoma (CC)
OT  - randomized controlled trials
OT  - restricted mean survival time (RMST)
OT  - robustness of evidence
OT  - spin effect
OT  - survival-inferred fragility index (SIFI)
COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure 
      form (available at 
      https://hbsn.amegroups.com/article/view/10.21037/hbsn-21-118/coif). GM reported 
      receiving personal fees from MSD and Roche; grants and personal fees from BMS and 
      Novartis; personal fees and stock options from 4C Biomed; and stock options from 
      Nucleai, Biond Biologics, and Ella Therapeutics outside the submitted work. TM 
      reported receiving personal fees from TyrNovo outside the submitted work. The 
      other authors have no conflicts of interest to declare.
EDAT- 2022/12/17 06:00
MHDA- 2022/12/17 06:01
PMCR- 2022/12/01
CRDT- 2022/12/16 02:30
PHST- 2021/03/16 00:00 [received]
PHST- 2021/07/09 00:00 [accepted]
PHST- 2022/12/16 02:30 [entrez]
PHST- 2022/12/17 06:00 [pubmed]
PHST- 2022/12/17 06:01 [medline]
PHST- 2022/12/01 00:00 [pmc-release]
AID - hbsn-11-06-861 [pii]
AID - 10.21037/hbsn-21-118 [doi]
PST - ppublish
SO  - Hepatobiliary Surg Nutr. 2022 Dec;11(6):861-869. doi: 10.21037/hbsn-21-118.