UMIN-CTR Clinical Trial

Public title

Immunohistochemical markers to differentiate primary adenocarcinoma and squamous cell carcinoma of the lung: diagnostic test accuracy meta-analysis

Acronym

Immunohistochemical markers to differentiate primary adenocarcinoma and squamous cell carcinoma of the lung: diagnostic test accuracy meta-analysis

Scientific Title

Immunohistochemical markers to differentiate primary adenocarcinoma and squamous cell carcinoma of the lung: diagnostic test accuracy meta-analysis

Scientific Title:Acronym

Immunohistochemical markers to differentiate primary adenocarcinoma and squamous cell carcinoma of the lung: diagnostic test accuracy meta-analysis

Region

Japan

Condition

NSCLC

Classification by specialty

Pneumology

Chest surgery

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

Sensitivity and specificity are key metrics to understand the diagnostic test accuracy of immunohistochemical stain technique. Without knowing the sensitivity and specificity of each marker, pathologist cannot select appropriate immunohistochemical markers. In addition, these data are required to judge the pathological subtype of NSCLC when multiple markers indicate discrepant results. Numerous studies were conducted to reveal the diagnostic test accuracy of immunohistochemical markers. However, these articles reported highly diverse results. To our knowledge, a meta-analysis assessing diagnostic value of TTF--1 for metastases of pulmonary adenocarcinoma and a meta-analysis elucidating combined TTF-1 and Napsin A were published. However, no systematic review evaluated diagnostic test accuracy of each marker to distinguish adenocarcinoma and squamous cell carcinoma of lungs. Aim of the current systematic review and meta-analysis is to summarize data from the previous studies regarding diagnostic test accuracy of immunohistochemical markers that are used for distinguishing primary adenocarcinoma and squamous cell lung cancer of the lungs.

Basic objectives2

Others

Basic objectives -Others

Aim of the current systematic review and meta-analysis is to summarize data from the previous studies regarding diagnostic test accuracy of immunohistochemical markers that are used for distinguishing primary adenocarcinoma and squamous cell lung cancer of the lungs.

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Sensitivity, specificity, area under curve (AUC), and diagnostic odds ratio will be evaluated. If two or more of cutoffs are applied in an original article, all of weak, moderate, and strong positive will be collectively considered positive. To diagnose adenocarcinoma, both adenocarcinoma and adenosquamous carcinoma will be counted since adenosquamous carcinoma has adenocarcinoma component while large cell carcinoma and NSCLC not otherwise specified will not be counted as adenocarcinoma. Similar algorithm will be applied to diagnose squamous cell carcinoma.
If data for multiple clones, e.g. 8G7G3/1, SPT24, and SP141 clones of TTF-1, are available, the data of 8G7G3/1 will be selected for our analysis because 8G7G3/1 clone has been known to provide the best diagnostic odds ratio among the three clones. Subgroup analysis focusing on each clone will be also done.

Key secondary outcomes

Study type

Others,meta-analysis etc

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

Purpose of intervention

Type of intervention

Interventions/Control_1

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

Not applicable

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

We will include full article, brief report, and conference abstract published in any language that provide data for sensitivity and specificity by immunohistochemical markers to diagnose adenocarcinoma and squamous cell carcinoma of the lung. Case-control study design consisted of patients with adenocarcinoma and squamous cell carcinoma will be accepted though case-control design may be counted as risk of bias according to Quality Assessment of Diagnostic Accuracy Studies-2(QUADAS-2).
Target population will be patients with NSCLC. Commonly used pathological criteria will be accepted along with WHO 2015 criteria.
Patients with both surgical and biopsy specimens will be allowed. Specimen outside the lung such as lymph nodes and pleural effusion will be accepted. Immunocytochemical stein using pleural effusion cell block will be also accepted along with immunohistochemical stein.
Target immunohistochemical markers include P40, CK5/6, P63, and desmocollin-3 (DSC3) for squamous cell carcinoma and TTF-1, Napsin A, and cytokeratin 7 (CK7) for adenocarcinoma. Immunohistochemical technique using any commercially available antibodies and non-commercial antibodies will be accepted. Reference test should be pathological diagnosis by pathologists.

Key exclusion criteria

An article that provide data of either sensitivity or specificity will be excluded since bivariate analysis is not applicable to such data.
Specificity evaluated among lung cancer cases will not be used for our analysis because analysis including both NSCLC and small-cell lung cancer will underestimate the specificity of markers. Studies focusing on non-pulmonary cancers and metastatic lung cancer of non-pulmonary origin will be excluded. Similarly, studies that compared NSCLC subtypes and mesothelioma will not be accepted.

Target sample size

Name of lead principal investigator

1st name	Nobuyuki
Middle name
Last name	Horita

Organization

Yokohama City University Hospital

Division name

Chemotherapy Center

Zip code

236-0004

Address

3-9, Fikuura, Kanazawa, Yokohama, Japan

TEL

045-787-2800

Email

horitano@yokohama-cu.ac.jp

Name of contact person

1st name	Nobuyuki
Middle name
Last name	Horita

Organization

Yokohama City University Hospital

Division name

Chemotherapy Center

Zip code

236-0004

Address

3-9, Fikuura, Kanazawa, Yokohama, Japan

TEL

0457872800

Homepage URL

Email

horitano@yokohama-cu.ac.jp

Institute

Yokohama City University Hospital

Institute

Department

Personal name

Organization

Yokohama City University Hospital

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

IRB not approved

Address

3-9, Fikuura, Kanazawa, Yokohama

Tel

0457872800

Email

horitano@yokohama-cu.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2020

Year

09

Month

03

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Main results already published

Date of protocol fixation

2020

Year

09

Month

03

Day

Date of IRB

2000

Year

09

Month

03

Day

Anticipated trial start date

2020

Year

09

Month

03

Day

Last follow-up date

2021

Year

09

Month

03

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Study overview
The protocol of this systematic review and meta-analysis of diagnostic test accuracy was composited following standard guidelines for systematic review of diagnostic test accuracy and PRISMA-DTA. Approval of Institutional Review Board was not required because of the nature of this study.

Study search
Four major electric databases, namely PubMed, Web of Science, Cochrane, and Embase will be searched on September 3, 2020. The following formula will be applied for PubMed: ((P40 OR deltaNp63 OR delta-NP63) OR (P63 OR DBR16.1) OR (ck5/6 OR Cytokeratin 5/6) OR (desmocollin 3 OR desmocollin-3 OR DSC3 OR DSC-3) OR (TTF1 OR TTF-1 OR Thyroid transcription factor-1 OR Thyroid transcription factor 1) OR (NapsinA OR Napsin A OR TA02 OR aspartic protease) OR (CK7 OR cytokeratin7 OR cytokeratin 7)) AND ((sensitivity AND specificity) OR (diagnostic test accuracy) OR (likelihood ratio) OR (sensitivity AND adenocarcinoma AND squamous)) AND (NSCLC OR lung OR pulmonary OR bronchial OR pleural OR respiratory OR bronchoscopy) AND (NSCLC OR adenocarcinoma OR squamous OR squamous-cell OR non-small OR non small).

Risk of bias
QUADAS2 was applied to assess the risk of bias in each study.

Statistics
Bivariate model will be used to obtain pooled sensitivity and specificity and to draw a summary receiver operating characteristic curves (SROC).
We will obtain DOR by DerSimonian-Laird random-model. Publication bias for DOR will be checked by visual inspection and by Begg-Kendall test after a funnel plot will be drawn uding RevMan ver. 5 (Cochrane, London, UK).
DOR will be calculated by "madauni" command ("netmeta" package of R project, Gerta Rucker, Denmark). Sensitivity and specificity will be pooled by "reitsma" command ("netmeta" package of R project, Gerta Rucker, Denmark). The statistical threshold for significance will set at 0.05.

Registered date

2020

Year

09

Month

03

Day

Last modified on

2022

Year

11

Month

18

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000047560