UMIN-CTR Clinical Trial

Public title

Insulinoma-Associated Protein 1 (INSM1) for the Diagnosis of Small-Cell Lung Cancer and Large Cell Neuroendocrine Carcinoma: A Meta-Analysis of Diagnostic Test Accuracy

Acronym

Insulinoma-Associated Protein 1 (INSM1) for the Diagnosis of Small-Cell Lung Cancer and Large Cell Neuroendocrine Carcinoma: A Meta-Analysis of Diagnostic Test Accuracy

Scientific Title

Insulinoma-Associated Protein 1 (INSM1) for the Diagnosis of Small-Cell Lung Cancer and Large Cell Neuroendocrine Carcinoma: A Meta-Analysis of Diagnostic Test Accuracy

Scientific Title:Acronym

Insulinoma-Associated Protein 1 (INSM1) for the Diagnosis of Small-Cell Lung Cancer and Large Cell Neuroendocrine Carcinoma: A Meta-Analysis of Diagnostic Test Accuracy

Region

Japan

Condition

lung cancer

Classification by specialty

Pneumology

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

In the pathological diagnosis of pulmonary neuroendocrine tumors (carcinoid, small cell carcinoma, and large cell neuroendocrine carcinoma), the commonly used antibodies for confirming neuroendocrine differentiation of tumor cells are chromogranin A, synaptophysin, and CD56. While these antibodies are highly reliable, recent attention has been drawn to the utility of insulinoma-associated protein 1 (INSM1) as a novel neuroendocrine marker.

INSM1 has been utilized not only in the diagnosis of lung cancer but also as a marker for neuroendocrine tumors (NETs) such as carcinoid tumors and Merkel cell carcinoma. However, these tumors generally exhibit morphological differences from lung cancer, underscoring the importance of further validation of diagnostic utility of INSM1 specifically in lung cancer.

INSM1 is particularly valuable in the diagnosis of lung cancer when identifying large cell neuroendocrine carcinoma (LCNEC) among non-small cell lung cancers (NSCLC) or differentiating neuroendocrine tumors such as small cell lung cancer (SCLC) from LCNEC. LCNEC has traditionally been classified as a subtype of NSCLC, but its treatment strategies align more closely with those of SCLC. Therefore, it is essential to distinguish LCNEC from adenocarcinoma, squamous cell carcinoma, and conventional large cell carcinoma that is not LCNEC.

Recent studies have reported high diagnostic accuracy of INSM1 in determining these pathological subtypes of lung cancer. However, variations in sensitivity and specificity have been noted across studies, highlighting the need for a systematic review and meta-analysis (SR&MA) to integrate these data. This study aims to address this gap by conducting a meta-analysis to comprehensively evaluate the diagnostic performance of INSM1 in the pathological classification of lung cancer.

Basic objectives2

Others

Basic objectives -Others

Diagnostic test accuracy

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Two analytical models were employed:
1. The NSCLC model aimed to identify LCNEC, excluding SCLC.
2. The lung cancer model focused on identifying neuroendocrine-associated cancers, including both SCLC and LCNEC.
Sensitivity, specificity, the area under the curve (AUC), and the diagnostic odds ratio (DOR) were evaluated. If multiple cutoffs were used in an original article, all weakly, moderately, and strongly positive results were collectively considered positive.

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

Eligible studies included full-text articles, brief reports, and conference abstracts published in English that reported sensitivity and specificity data for the immunohistochemical marker INSM1 in diagnosing SCLC and LCNEC. Articles providing only sensitivity or specificity data were excluded, as bivariate analysis requires both.
Although one-gate patient recruitment is preferable for diagnostic accuracy assessments, two-gate studies, e.g., those that selected LCNEC patients and control groups (such as adenocarcinoma or squamous cell carcinoma) from separate datasets, were also included. All sample types, including surgical specimens, bronchoscopic specimens, and pleural effusion cell blocks, were eligible. Additionally, samples from non-pulmonary origins were accepted if they represented metastatic lung cancer in other organs or lymph nodes.
The reference standard for this analysis was a pathological diagnosis made by pathologists. Studies where INSM1 influenced the pathological diagnosis were not excluded but were scored with deductions in the QUADAS-2 evaluation.

Key exclusion criteria

studies focusing on neuroendocrine tumors (e.g., Merkel cell carcinoma) or other non-pulmonary neuroendocrine tumors that did not provide lung cancer-specific data were excluded, even if INSM1 data were available.

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

Address

3-9, Fukuura, 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, Fukuura, Kanazawa, Yokohama, Japan

TEL

045-787-2800

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

Yokohama City University Hospital

Address

3-9, Fukuura, Kanazawa, Yokohama, Japan

Tel

045-787-2800

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

2024

Year

12

Month

25

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

Preinitiation

Date of protocol fixation

2024

Year

12

Month

25

Day

Date of IRB

Anticipated trial start date

2024

Year

12

Month

25

Day

Last follow-up date

2026

Year

12

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

[Study Search] Three major online databases, PubMed, Web of Science, and Embase, were systematically searched on December 25, 2024. The PubMed search strategy was as follows: (insulinoma-associated protein 1 OR INSM1 OR INSM-1) AND (lung OR pulmonary OR respiratory OR thoracic OR bronchial OR bronchogenic OR tracheal OR alveolar).
[Statistical Analysis] A bivariate model was used to calculate pooled sensitivity and specificity and to construct a summary receiver operating characteristic curve (SROC) using Meta-DiSc ver 1.4 (Informer Technologies, Inc.)

Registered date

2024

Year

12

Month

25

Day

Last modified on

2024

Year

12

Month

25

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000064642