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Tumor Discovery Expert consensus of NUT carcinoma

and creating summary tables of findings and decision (OS), and NUTM1 fusion partner (if known). The
tables for recommendations. methodological quality of the studies was assessed using
(iv) An external review group comprising 21 first-line the Agency for Healthcare Research and Quality (Table S3).
healthcare professionals was responsible for providing Two reviewers (LL and ZY) independently performed the
external review and feedback on the guideline. quality rating, and a third reviewer (JZ) was consulted if
disagreements occurred. Given that the most published
2.5. Ethical considerations studies on NUT carcinoma are observational, such as case
All steering committee and consensus panel members reports, case series, and small retrospective cohort studies,
completed a conflict-of-interest disclosure form before they carry a higher risk of bias.
participating in the guideline development process. No
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relevant financial conflicts of interest were identified. 2.7. Data analysis and survival analysis
Based on the data extracted from the literature, we
2.6. Systematic review and grading conducted a descriptive statistical analysis of NUT
To enhance an early and comprehensive understanding of carcinoma’s general characteristics, features, and current
NUT carcinoma and provide potentially effective treatment treatment strategies. In addition, we performed both
options for patients, we conducted a systematic review to univariate and multivariate analyses of OS. We ensured
collect detailed information on the key characteristics and that each subgroup in the survival analysis cohort
treatment scenarios associated with this malignancy. contained more than 10 individuals. Survival analyses

The protocol for this systematic review was registered were conducted for various factors, including patient
with PROSPERO (CRD42021277083) on November 10, gender, region of origin, age, site of metastasis, tumor-
2023. The review methodology followed the Preferred node-metastasis (TNM) classification stage, tumor
Reporting Items for Systematic Reviews and Meta-Analyses diameter, antigen Kile 67 (Ki-67) index, NUTM1 fusion
(PRISMA) guideline. Given the highly heterogeneous partner, treatment type, and chemotherapy regimen. It is
patient populations and differences in study designs, a important to note that due to the rarity of NUT carcinoma
meta-analysis was deemed inappropriate. and the lack of large-scale cohort data, the vast majority
of data in this study comes from case reports, making the
We searched for relevant studies in the following data non-continuous with significant heterogeneity. These
databases: PubMed, Web of Science, Embase, Cochrane data results are for clinical reference only, and the results
Library, and Ovid Medline, without language restrictions. of analyses and statistics based on these data should be
The search strategy was based on the following terms: “NUT interpreted and treated with caution.
Carcinoma,” “NUT midline carcinoma,” “nuclear protein
in testis carcinoma,” “NUTM1,” and “nuclear protein of the 2.8. Formulation of recommendations
testis midline carcinoma.” Further, details on the search After reviewing the literature and integrating clinical
terms are provided in Table S2. Each study was reviewed experience, we initially drafted a set of recommendations.
to confirm the presence of NUTM1 gene rearrangement The evidence levels and definitions of evidence-based
in the included patients, with diagnoses verified using medicine in this expert consensus are based on the Oxford
pathological tissues and techniques such as IHC, FISH, or Centre for Evidence-Based Medicine levels (Table S4). The
NGS. The final search was conducted on January 20, 2024. initial recommendations underwent expert consultation,
No restrictions were applied based on age, gender, country, with three voting options: “agree,” “uncertain,” or “disagree.”
or tumor stage. Some of the authors on our team were Experts were invited to provide suggestions for modification
trained in the purpose and methodology of the review. of each recommendation. After each round of consultation,
The selection process was conducted independently by the recommendations were revised or supplemented based
two reviewers (XL and ZMY), with disagreements resolved on expert feedback. The recommendations were categorized
through discussion or by consulting a third reviewer (JZ). as “strong recommendation,” “recommendation,” or “no
A PRISMA flow diagram illustrating the study selection consensus” based on expert votes. If the agreement rate
procedure is provided in Figure S2. (i.e., the proportion of experts selecting “agree”) was

Data extracted from each study included the following ≥ 70%, the recommendation was considered to have
variables: author, year of publication, country, sample reached a consensus. An agreement rate > 90% was
size, gender, region, age, smoking status, symptoms at classified as a “strong recommendation,” 70 – 90% as a
first diagnosis, tumor location, metastatic lesions, tumor “recommendation,” and anything less as “no consensus.”
staging, maximum tumor diameter, type of treatment The consensus draft was then submitted to the External
received, treatment sequence, IHC results, overall survival Review Group for additional external review.

Volume 3 Issue 4 (2024) 6 doi: 10.36922/td.4904