Kaimen Rigor reviewed

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Medial retropharyngeal nodal region sparing radiotherapy in nasopharyngeal carcinoma: five year analysis of open label, non-inferiority, multicentre, randomised phase 3 trial.

Name: Kaimen Rigor review — Medial retropharyngeal nodal region sparing radiotherapy in nasopharyngeal carcinoma: five year analysis of open label, non-inferiority, multicentre, randomised phase 3 trial.
Item: Medial retropharyngeal nodal region sparing radiotherapy in nasopharyngeal carcinoma: five year analysis of open label, non-inferiority, multicentre, randomised phase 3 trial.
Rating: 88
Author: Alpha1

Wang SX, Tao YL, Gao TS, Zhang N, Zhou GQ, Xie FY, Zhang Y, Guo R, Yang Y, Li YJ, Liang SQ, Zeng YC, Lin L, Li WF, Liu X, Xu C, Chen YP, Lv JW, Liu LZ, Li HJ, Li JB, Wen HM, Sun Y, Tang LL, Liang XY, Ma J, Mao YP

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Kaimen Rigor review — 3.75★ (Adequate), 0 critical, 5 high issues for “Medial retropharyngeal nodal region sparing radiotherapy in nasopharyngeal carcinoma: five year analysis of open label, non-inferiority, multicentre, randomised phase 3 trial.”

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This rigor review was examined and confirmed by Alpha1 Editorial · August 10, 2026

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Medial retropharyngeal nodal region sparing radiotherapy in nasopharyngeal carcinoma: five year analysis of open label, non-inferiority, multicentre, randomised phase 3 trial.

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DOI

10.1136/bmj-2025-086050

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Kaimen Rigor reviewed

Rigor-Reviewed Manuscript

Medial retropharyngeal nodal region sparing radiotherapy in nasopharyngeal carcinoma: five year analysis of open label, non-inferiority, multicentre, randomised phase 3 trial.

Paper source

Medial retropharyngeal nodal region sparing radiotherapy in nasopharyngeal carcinoma: five year analysis of open label, non-inferiority, multicentre, randomised phase 3 trial.

Read full text (PMC)

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Alpha1 Editorial

This rigor review was examined and confirmed by Alpha1 Editorial · August 10, 2026

Kaimen Rigor review

Kaimen Rigor reviewed

3.75 / 5

Adequate — real issues to address

Interventional Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

IntegrityIntegrity concern ×2−1★
ReportingKey resources partially met−0.25★

Model-reported confidence: moderateReviewer agreement: moderateEngine: 7.29.0Source: full text

Findings by category

101ArithmeticNumerical inconsistencies 102OverreachOverstated conclusions 103AuthenticityData authenticity concerns 104DisclosureReporting gaps 05AvailabilityNone found 106CopyeditCopyediting

This Kaimen Rigor review uses Kaimen Rigor reviewers trained on a curated corpus of high-fidelity and retracted papers, with expert supervision and curation. It can still make mistakes; verify each finding against the source before relying on it.

This is a methodologically strong, pre-registered phase 3 non-inferiority RCT with a rigorous randomisation scheme, pre-specified power calculation, masked central assessors, transparent outcome reporting, and independently consistent recomputed statistics (13/14 consistent, no decision errors). The identified weaknesses are minor reporting gaps — analysis code only in a web appendix, some p-values reported as thresholds, no explicit CONSORT checklist reference, and a clear typographical error in Table 1 (Stage IVa '124 (448)') — none of which threatens the primary conclusions.

All three reviewers (independent runs of the same model) agreed on study type and on pass for scientific premise, study design, statistical analysis, and reporting transparency; they split 2-1 (majority pass) on biological variables, ethical approvals, and data code availability, and diverged three ways on key resources (adopted not applicable). The statistics component recomputed only a subset of tests (14 eligible; 13 consistent) — tests not recomputed are unverified, not confirmed. The citation check found 0 retracted and 0 undiscoverable references; the claim audit found 0 under-evidenced claims.

Numerical inconsistencies

1 finding · worst low

Values that contradict each other or are impossible for the stated sample: recomputed p-values and test statistics, GRIM/GRIMMER checks on summary numbers, percentages against their own counts, totals against their parts, and estimates against their own confidence intervals.

Internal contradictions in the reported numbersAssessed

Recomputed 13 tests: 13 consistent, 0 inconsistent; 1 recomputed directly from the reported test statistics, 12 via agent-written checks.

Overstated conclusions

1 finding · worst low

Conclusions that reach past what the paper's own results support — including a significance claim that no longer holds when the statistic is recomputed, and efficacy resting on an unvalidated surrogate endpoint.

Conclusions only partially backed by the presented evidenceAssessed

12 major claims checked against the paper's own evidence: all adequately supported.

Efficacy claim is anchored to an adequate endpoint and a meaningful effect.

Data authenticity concerns

1 finding · worst low

An adversarial read for patterns associated with data that may not be genuine: results that look too clean, implausibly large effects, duplicated data or images, and methods that do not match the results reported.

Data look implausibly cleanAssessed

2 integrity concerns flagged (0 high).

Reporting gaps

1 finding · worst medium

Required detail the manuscript never states — study design, biological variables, ethics approval and consent, key resources, statistical reporting, data and code availability, and overall transparency.

Key resources under-identified (antibodies, cell lines, RRIDs)Assessed

Eight Dimensions7 pass · 1 warn

The introduction cites MRI-based studies showing MRLN metastasis rates below 0.6% and notes that traditional target delineation exposes pharyngeal constrictors to high doses, grounding the rationale. It acknowledges that prior guideline-based practice was anchored in two-dimensional era experience and that no other prospective study had explored this question, addressing gaps in prior work. The hypothesis follows logically: sparing the MRLN region should reduce dysphagia without compromising local control.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

The study clearly establishes its scientific foundation with extensive prior literature and a coherent mechanistic rationale.

Evidence

“Recently, several magnetic resonance imaging (MRI) based studies have shown that retropharyngeal lymph node involvement primarily occurs in the lateral group, with a metastasis rate of less than 0.6% in the medial group.”

Introduction ¶1Find in source

“So far, no other prospective studies have explored this question.”

Introduction ¶2Find in source

PASSReviewer 2· 90% conf

The paper establishes a clear scientific premise, citing prior research on retropharyngeal lymph node metastasis patterns and the rationale for MRLN sparing, and addresses limitations of prior work.

Evidence

Introduction ¶1Find in source

“So far, no other prospective studies have explored this question.”

Introduction ¶2Find in source

“Nevertheless, the long term effect of MRLN sparing radiotherapy on survival outcomes and swallowing function remained unknown”

Introduction ¶2Find in source

PASSReviewer 3· 90% conf

The paper clearly establishes its scientific foundation by citing prior research on MRLN involvement and the rationale for sparing, and it addresses limitations of prior work.

Evidence

Introduction ¶2Find in source

paraphrase[Introduction, paragraph 3]

“Consequently, we conducted the first non-inferiority randomised phase 3 trial to compare the efficacy and safety of MRLN sparing radiotherapy versus standard radiotherapy...”

“Nevertheless, the long term effect of MRLN sparing radiotherapy on survival outcomes and swallowing function remained unknown, and the rationale of decreasing dysphagia by using MRLN sparing radiotherapy needed to be explored.”

Introduction ¶4Find in source

Randomization used a computer-generated random list with block size of four, stratified by institution and treatment modality. The non-inferiority margin (8%) and power calculation (80% power, one-sided alpha 0.025, ~550 patients) are reported. Inclusion/exclusion criteria are specified. Blinding is described as open-label with masking of central radiologists and statistician. Outlier handling is not explicitly discussed, but the analysis population (ITT) and missing data approach (censoring) are defined.

Sub-criteria

controlsN/A

power analysisADEQUATE

blinding levelsADEQUATE

outlier handlingINADEQUATE

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 92% conf

The trial design is rigorous: central computer-generated block randomisation with stratification, a stated open-label design with masking of radiologists and statistician, a pre-specified power calculation, and defined eligibility criteria.

Evidence

“Patients were randomly assigned 1:1 to MRLN sparing radiotherapy or standard radiotherapy by use of a computer generated random list in a block size of four per stratum.”

MethodsFind in source

“To achieve 80% power at a one sided type I error of 0.025, approximately 550 patients (275 per group) were needed.”

Statistical analysisFind in source

“The study was open label and allocation was unmasked to physicians and patients, although the central responsible radiologists and the statistician were masked.”

MethodsFind in source

PASSReviewer 2· 95% conf

The trial design is rigorous: randomized, stratified, with a pre-specified non-inferiority margin, power calculation, and clear inclusion/exclusion criteria. Blinding is partially addressed (open-label with masked radiologists and statistician).

Evidence

“Patients were randomly assigned 1:1 to MRLN sparing radiotherapy or standard radiotherapy by use of a computer generated random list in a block size of four per stratum.”

MethodsFind in source

“To achieve 80% power at a one sided type I error of 0.025, approximately 550 patients (275 per group) were needed.”

Statistical analysisFind in source

“The study was open label and allocation was unmasked to physicians and patients, although the central responsible radiologists and the statistician were masked.”

MethodsFind in source

PASSReviewer 3· 95% conf

The study design is rigorous with adequate randomization, blinding of key assessors, a priori power analysis, and clear inclusion/exclusion criteria.

Evidence

“Patients were randomly assigned 1:1 to MRLN sparing radiotherapy or standard radiotherapy by use of a computer generated random list in a block size of four per stratum.”

MethodsFind in source

“The study was open label and allocation was unmasked to physicians and patients, although the central responsible radiologists and the statistician were masked.”

MethodsFind in source

“To achieve 80% power at a one sided type I error of 0.025, approximately 550 patients (275 per group) were needed.”

Statistical analysisFind in source

Sex, age, Karnofsky performance score, histology, tumour and nodal categories, and stage are reported in Table 1. Age is given as median (range). Health status is captured via Karnofsky score. Demographics include sex and age; race/ethnicity is not reported but is not typically required in this context. Species/strain and housing are not applicable.

Sub-criteria

demographicsADEQUATE

sex reportedADEQUATE

sex justifiedN/A

age weight healthADEQUATE

housing conditionsN/A

species strain sourceN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 80% conf

Sex, age, and health status (Karnofsky performance score) are reported in the baseline table; species/strain and housing conditions are not applicable to a human trial.

Evidence

“Male sex | 215 (75) | 209 (74) | | Median (range) age, years | 46 (19-64) | 49 (23-65)”

Table 1Find in source

paraphrase[Table 1 (Baseline characteristics)]

“Karnofsky performance score: | 70-80 | 9 (3) | 8 (3) | | 90-100 | 276 (97) | 275 (97)”

PASSReviewer 2· 90% conf

Key biological variables (sex, age, performance status, histology, stage) are reported in baseline characteristics; demographics are adequately covered for a human trial.

Evidence

“Male sex | 215 (75) | 209 (74) | | Median (range) age, years | 46 (19-64) | 49 (23-65)”

Table 1Find in source

paraphrase[Table 1]

“Karnofsky performance score: | 70-80 | 9 (3) | 8 (3) | | 90-100 | 276 (97) | 275 (97)”

WARNReviewer 3· 80% conf

Sex and age are reported, but weight, race/ethnicity, and comorbidities are not reported, making the assessment incomplete.

Evidence

paraphrase[Results, Table 1]

“Male sex: 215 (75) and 209 (74)”

paraphrase[Results, Table 1]

“Median (range) age, years: 46 (19-64) and 49 (23-65)”

absence[Results, Table 1]

Weight is not reported.

The paper states the study was approved by institutional ethics committees at each centre, with a protocol number (5010-2017-04-02). Written informed consent was obtained from all participants. Regulatory compliance with Declaration of Helsinki and ICH-GCP is explicitly stated.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

Ethics approval by named institutional committees with a protocol number, written informed consent, and explicit regulatory compliance are all reported.

Evidence

“This study was approved by the institutional review board or ethics committee at each site (5010-2017-04-02)”

EthicsFind in source

“All participants provided written informed consent.”

EthicsFind in source

PASSReviewer 2· 95% conf

Ethical approval from institutional ethics committees, written informed consent, and compliance with Declaration of Helsinki and ICH-GCP are reported.

Evidence

“This study was approved by the institutional review board or ethics committee at each site (5010-2017-04-02)”

EthicsFind in source

“All participants provided written informed consent.”

EthicsFind in source

“The study complied with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice Guideline.”

MethodsFind in source

WARNReviewer 3· 85% conf

Ethics approval is mentioned but the approving body is not named, and a protocol number is provided but insufficient by the strict criteria. Informed consent and regulatory compliance are adequate.

Evidence

“The study protocol (web appendix 1) was approved by institutional ethics committees in each centre, and all patients provided written informed consent for participation.”

MethodsFind in source

“all patients provided written informed consent for participation.”

MethodsFind in source

“The study complied with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice Guideline.”

MethodsFind in source

The study uses standard-of-care chemotherapy and radiotherapy, but the specific drugs, doses, and manufacturers are not named. The radiotherapy equipment is not described. Statistical software (SPSS 25.0, R 4.3.1) is well identified. The code is provided in web appendix, but not in a version-controlled repository, though this is not a key resource for this dimension.

Sub-criteria

mycoplasma testingN/A

reagents identifiedINADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedADEQUATE

Per reviewer (3) — the votes behind the verdict

N/AReviewer 1· 70% conf

The intervention is a radiotherapy technique (target-volume delineation) rather than an investigational drug, biologic, device, or bench reagent, so no key biological/chemical resource is scored; software used for analysis is identified.

Evidence

“We used SPSS software (version 25.0) and R (version 4.3.1) for all statistical analyses.”

Statistical analysisFind in source

PASSReviewer 2· 85% conf

The investigational product (radiotherapy technique) is described in detail, and statistical software is identified. No antibodies, cell lines, or wet-lab reagents are used.

Evidence

“All patients received intensity modulated radiation therapy, with target delineation following the guidelines detailed in web appendix 2 (pages 3-15).”

MethodsFind in source

“We used SPSS software (version 25.0) and R (version 4.3.1) for all statistical analyses.”

Statistical analysisFind in source

WARNReviewer 3· 80% conf

Statistical software is adequately identified, but the investigational products (chemotherapy drugs, radiotherapy equipment) are not specified, which is a reporting gap.

Evidence

“Standard-of-care chemotherapy (induction, concurrent, or both) was administered according to the extent of disease.”

MethodsFind in source

“We used SPSS software (version 25.0) and R (version 4.3.1) for all statistical analyses.”

Statistical analysisFind in source

absence[Methods, Procedures]

Radiotherapy equipment is not described.

Tests named include Kaplan-Meier, stratified Cox proportional hazards, Pearson's chi-square, Fisher's exact, Mann-Whitney U, and GEE. Effect sizes (hazard ratios, mean differences) with 95% CIs are reported. Exact p-values are given (e.g., P=0.90). Data presentation includes Kaplan-Meier curves and tables with per-group n. Assumptions are handled by design (Cox model, non-parametric tests). Mathematical plausibility checks were not possible for most continuous outcomes, but no obvious errors were found.

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedADEQUATE

mathematical plausibilityN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 85% conf

Statistical tests are named, exact p-values and effect estimates with confidence intervals are reported, software is identified, and the reported numbers are internally consistent.

Evidence

“stratified hazard ratio 1.03 (95% CI 0.61 to 1.74); P=0.90”

AbstractFind in source

“we compared differences by using Pearson’s χ 2 test or Fisher’s exact test when appropriate.”

Statistical analysisFind in source

PASSReviewer 2· 90% conf

Statistical tests are named, effect sizes with CIs are reported, software is identified, and data presentation follows clinical trial conventions. Exact p-values are reported for most comparisons.

Evidence

“We calculated local relapse-free survival, overall survival, distant metastasis-free survival, and regional relapse-free survival by using the Kaplan-Meier method, with hazard ratios and 95% confidence intervals estimated using a stratified Cox proportional hazards model”

Statistical analysisFind in source

“stratified hazard ratio 1.03 (95% CI 0.61 to 1.74); P=0.90”

AbstractFind in source

“The estimated five year local relapse-free survival rates were 89.2% (95% confidence interval (CI) 85% to 92)% versus 90.6% (87% to 94%); stratified hazard ratio 1.03 (95% CI 0.61 to 1.74); P=0.90”

ResultsFind in source

PASSReviewer 3· 90% conf

Statistical tests are named, effect sizes with CIs are reported, software is identified, and data presentation is adequate. Assumptions are handled by design, and exact p-values are mostly given. No arithmetic inconsistencies found.

Evidence

paraphrase[Methods, Statistical analysis]

“We calculated local relapse-free survival... using the Kaplan-Meier method, with hazard ratios and 95% confidence intervals estimated using a stratified Cox proportional hazards model...”

paraphrase[Results, Efficacy outcomes]

“The estimated five year local relapse-free survival rates were 89.2% (95% confidence interval (CI) 85% to 92%) versus 90.6% (87% to 94%); stratified hazard ratio 1.03 (95% CI 0.61 to 1.74); P=0.90”

“We used SPSS software (version 25.0) and R (version 4.3.1) for all statistical analyses.”

Statistical analysisFind in source

The data availability statement names a public repository (Mendeley) with a URL and a data platform (RDDA2026205661). Code is available in web appendix 3. This meets the criteria for concrete access routes.

Sub-criteria

code sharingADEQUATE

accession numbersADEQUATE

repository depositADEQUATE

data availability statementADEQUATE

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 85% conf

Data availability is concrete (public Mendeley repository with DOI), but the analysis code is only supplied as a journal web appendix rather than in a version-controlled public repository with a permanent identifier.

Evidence

“The data underlying the findings in this paper are openly and publicly available and can be found at https://data.mendeley.com/datasets/vvnswtgdz8/1”

Data availabilityFind in source

“The code used to analyse the data can be found in web appendix 3.”

Data availabilityFind in source

PASSReviewer 2· 95% conf

Data availability statement provides a concrete public repository (Mendeley) and a data platform accession, and code is shared in web appendix.

Evidence

“The data underlying the findings in this paper are openly and publicly available and can be found at https://data.mendeley.com/datasets/vvnswtgdz8/1”

Data availabilityFind in source

“The code used to analyse the data can be found in web appendix 3.”

Data availabilityFind in source

PASSReviewer 3· 90% conf

Data are deposited in a public repository (Mendeley Data) with a URL and an additional platform accession. Code is provided in a web appendix, which is not a version-controlled repository, but the overall availability is adequate for a clinical trial.

Evidence

“The data underlying the findings in this paper are openly and publicly available and can be found at https://data.mendeley.com/datasets/vvnswtgdz8/1”

Data availabilityFind in source

“The code used to analyse the data can be found in web appendix 3.”

Data availabilityFind in source

“The raw data were also uploaded to the Research Data Deposit public platform (RDDA2026205661).”

Data availabilityFind in source

Trial registration number (NCT03346109) is provided. Funding sources and COI are declared. Limitations are discussed in detail. Conclusions are proportional to the evidence. Methods are detailed enough for replication. Reporting guideline (CONSORT) is not explicitly mentioned, but the paper follows clinical trial reporting standards.

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineINADEQUATE

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 85% conf

Methods are detailed, the trial is registered, outcomes are transparently reported, limitations are discussed, conclusions are measured, and funding/COI statements are provided.

Evidence

“Trial registration ClinicalTrials.gov NCT03346109”

AbstractFind in source

“Secondly, this was an open label study, and toxicity data were primarily obtained through clinical enquiries, introducing some unavoidable subjective bias.”

LimitationsFind in source

PASSReviewer 2· 90% conf

The paper is transparent: trial registration, funding, COI, limitations, and proportional conclusions are reported. Reporting guideline adherence is implied but not explicitly stated.

Evidence

“Trial registration ClinicalTrials.gov NCT03346109”

AbstractFind in source

“Our study has certain limitations. Firstly, as noted in our initial report, these findings were derived primarily from Epstein-Barr virus associated nasopharyngeal carcinoma in endemic regions”

LimitationsFind in source

“Funding: This study was supported by grants from the Noncommunicable Chronic Diseases-National Science and Technology Major Project (2024ZD0520701)”

FundingFind in source

PASSReviewer 3· 90% conf

Methods are detailed, trial is registered, all outcomes are reported, limitations are discussed, conclusions are proportional, and funding/COI are stated. The only gap is the lack of a referenced reporting checklist.

Evidence

paraphrase[Abstract]

“Trial registration ClinicalTrials.gov NCT03346109 (https://clinicaltrials.gov/ct2/show/NCT03346109).”

paraphrase[Discussion, Limitations of study]

“Our study has certain limitations. Firstly, as noted in our initial report, these findings were derived primarily from Epstein-Barr virus associated nasopharyngeal carcinoma in endemic regions...”

paraphrase[Funding and Competing interests]

“This study was supported by grants from ... The funders had no role in the design of the study... All authors have completed the ICMJE uniform disclosure form...”

Registered (1 ID: ClinicalTrials.gov). No reporting guideline cited.

Broken references and links

None found

References checked against Crossref, OpenAlex and Retraction Watch for retractions and resolvability, plus declared data and code links probed for whether they resolve to content matching the paper.

Checked — nothing surfaced.

Checked 37 references by DOI: 35 verified — 2 no DOI (shown, not verified).

2 data/code links checked; 2 live.

Copyediting

1 finding · worst low

Wording, consistency and formatting errors that need correcting before submission.

Wording or formatting errors that need correctingAssessed

10 copyedit issues flagged (1 major): mostly consistency, punctuation, other.

Kaimen Rigor Action ItemsFinal pass before journal submission

As published, the trial is robust: a well-designed, pre-registered phase 3 RCT with consistent recomputed statistics, live data links, no retracted or undiscoverable references, and no unsupported claims. An informed reader should weigh the minor reporting gaps — analysis code only in a web appendix rather than a version-controlled repository, a few p-values reported only as thresholds, and no explicit CONSORT checklist reference — and the Table 1 typo (Stage IVa '124 (448)'), which warrants a published correction. No validity threat to the primary findings was identified.

1.
HIGHcopyedit
Correct the Table 1 Stage IVa cell '124 (448)' to '124 (44)' in the Standard RT group via a published correction/erratum.
A percentage of 448% is impossible (124/283 = 43.8% ≈ 44%); this is the most consequential concrete error in the paper and is flagged by the copyedit, the integrity component, and Reviewer 1.
2.
HIGHdata code
Deposit the analysis code in a version-controlled public repository (e.g., GitHub with a Zenodo DOI) and link it in the Data availability statement, replacing the web-appendix-only code sharing.
Web-appendix-only code has no permanent identifier or version control, which undercuts reproducibility; this is the core reason Reviewer 1 rated data_code_availability a warn.
3.
HIGHreporting
Add an explicit CONSORT 2010 checklist reference and a statement of adherence in the Methods (and note the checklist is available as supplementary material).
A phase 3 RCT should reference its reporting guideline; all three reviewers flagged the absence of an explicit CONSORT statement.
4.
HIGHstatistics
Report exact p-values for comparisons currently given only as thresholds (e.g., 'P<0.05' in the correlation analyses, appendix 2 pages 46-48).
Threshold-only p-values cannot be independently verified and are a documented gap in the exact-p-value reporting.
5.
HIGHrigor
Add a sentence in the Statistical analysis section clarifying how outliers were handled for continuous outcomes (e.g., pharyngeal constrictor thickness) and, for the VFSS sub-study, the reasons for non-participation/missing data.
Reviewer 2 rated outlier_handling as inadequate; explicit handling of outliers and missing data in the exploratory swallowing substudy strengthens reproducibility.
6.
MEDIUMethics
Name the specific institutional ethics committee(s) (e.g., the IRB of Sun Yat-sen University Cancer Center) in the ethics statement.
Reviewer 3 flagged that the approving body is not named; naming it removes ambiguity about which body granted approval.
7.
MEDIUMrigor
Report baseline weight or BMI, and race/ethnicity and comorbidities if collected, in Table 1.
Reviewer 3 flagged these as missing from the baseline characteristics; adding them would fully address the biological-variables dissent.
8.
MEDIUMrigor
Specify the chemotherapy regimens and doses, and the radiotherapy delivery equipment (linear accelerator model and vendor), in the Methods/Procedures.
Reviewer 3 noted these are not specified; naming them aids replication even though the intervention is a procedural technique.
9.
MEDIUMcopyedit
Correct the recurring misspelling 'pharyngeal contractors' to 'pharyngeal constrictors' throughout (Abstract conclusions and Discussion).
This is a recurring terminology error that should be fixed in a correction for consistency.
10.
MEDIUMcopyedit
Fix the stray parentheses/punctuation in the CI formatting in Results/Efficacy outcomes (e.g., '92)% ' → '92%)', '89)% ' → '89%)').
The misplaced '%' and closing parenthesis obscure the confidence-interval formatting and were flagged multiple times by the copyedit pass.
11.
LOWcopyedit
Revise the awkward phrasing 'the number of deaths more than doubled since the primary analysis' to '...more than doubled compared with the primary analysis' in the Discussion.
The current preposition 'since' is grammatically awkward and unclear.
12.
LOWdata code
Clarify in the Data availability statement whether the Mendeley dataset is patient-level or aggregated, state the access conditions for the RDDA platform, and provide a DOI for the Mendeley dataset.
Clarifying the data granularity and access conditions, and adding a persistent DOI, strengthens the data-sharing statement.

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Medial retropharyngeal nodal region sparing radiotherapy in nasopharyngeal carcinoma: five year analysis of open label, non-inferiority, multicentre, randomised phase 3 trial.

Read full text (PMC)

DOI

10.1136/bmj-2025-086050

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Record fingerprint

263e7ab3dd9a056a112b89270bd8cf86fa87b6215a1af11dfd49765d3248dd16

Verify via API

Issued Aug 10, 2026Engine 7.29.0

Alpha1 assesses methodological rigor, not the importance of the findings. See how we calibrate →

Kaimen Rigor review

Kaimen Rigor reviewed

3.75 / 5

Adequate — real issues to address

Interventional Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

IntegrityIntegrity concern ×2−1★
ReportingKey resources partially met−0.25★

Model-reported confidence: moderateReviewer agreement: moderateEngine: 7.29.0Source: full text

Findings by category

101ArithmeticNumerical inconsistencies 102OverreachOverstated conclusions 103AuthenticityData authenticity concerns 104DisclosureReporting gaps 05AvailabilityNone found 106CopyeditCopyediting

Numerical inconsistencies

1 finding · worst low

Internal contradictions in the reported numbersAssessed

Recomputed 13 tests: 13 consistent, 0 inconsistent; 1 recomputed directly from the reported test statistics, 12 via agent-written checks.

Overstated conclusions

1 finding · worst low

Conclusions only partially backed by the presented evidenceAssessed

12 major claims checked against the paper's own evidence: all adequately supported.

Efficacy claim is anchored to an adequate endpoint and a meaningful effect.

Data authenticity concerns

1 finding · worst low

Data look implausibly cleanAssessed

2 integrity concerns flagged (0 high).

Reporting gaps

1 finding · worst medium

Key resources under-identified (antibodies, cell lines, RRIDs)Assessed

Eight Dimensions7 pass · 1 warn

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

The study clearly establishes its scientific foundation with extensive prior literature and a coherent mechanistic rationale.

Evidence

Introduction ¶1Find in source

“So far, no other prospective studies have explored this question.”

Introduction ¶2Find in source

PASSReviewer 2· 90% conf

The paper establishes a clear scientific premise, citing prior research on retropharyngeal lymph node metastasis patterns and the rationale for MRLN sparing, and addresses limitations of prior work.

Evidence

Introduction ¶1Find in source

“So far, no other prospective studies have explored this question.”

Introduction ¶2Find in source

“Nevertheless, the long term effect of MRLN sparing radiotherapy on survival outcomes and swallowing function remained unknown”

Introduction ¶2Find in source

PASSReviewer 3· 90% conf

The paper clearly establishes its scientific foundation by citing prior research on MRLN involvement and the rationale for sparing, and it addresses limitations of prior work.

Evidence

Introduction ¶2Find in source

paraphrase[Introduction, paragraph 3]

“Consequently, we conducted the first non-inferiority randomised phase 3 trial to compare the efficacy and safety of MRLN sparing radiotherapy versus standard radiotherapy...”

Introduction ¶4Find in source

Sub-criteria

controlsN/A

power analysisADEQUATE

blinding levelsADEQUATE

outlier handlingINADEQUATE

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 92% conf

Evidence

“Patients were randomly assigned 1:1 to MRLN sparing radiotherapy or standard radiotherapy by use of a computer generated random list in a block size of four per stratum.”

MethodsFind in source

“To achieve 80% power at a one sided type I error of 0.025, approximately 550 patients (275 per group) were needed.”

Statistical analysisFind in source

“The study was open label and allocation was unmasked to physicians and patients, although the central responsible radiologists and the statistician were masked.”

MethodsFind in source

PASSReviewer 2· 95% conf

Evidence

“Patients were randomly assigned 1:1 to MRLN sparing radiotherapy or standard radiotherapy by use of a computer generated random list in a block size of four per stratum.”

MethodsFind in source

“To achieve 80% power at a one sided type I error of 0.025, approximately 550 patients (275 per group) were needed.”

Statistical analysisFind in source

“The study was open label and allocation was unmasked to physicians and patients, although the central responsible radiologists and the statistician were masked.”

MethodsFind in source

PASSReviewer 3· 95% conf

The study design is rigorous with adequate randomization, blinding of key assessors, a priori power analysis, and clear inclusion/exclusion criteria.

Evidence

“Patients were randomly assigned 1:1 to MRLN sparing radiotherapy or standard radiotherapy by use of a computer generated random list in a block size of four per stratum.”

MethodsFind in source

“The study was open label and allocation was unmasked to physicians and patients, although the central responsible radiologists and the statistician were masked.”

MethodsFind in source

“To achieve 80% power at a one sided type I error of 0.025, approximately 550 patients (275 per group) were needed.”

Statistical analysisFind in source

Sub-criteria

demographicsADEQUATE

sex reportedADEQUATE

sex justifiedN/A

age weight healthADEQUATE

housing conditionsN/A

species strain sourceN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 80% conf

Sex, age, and health status (Karnofsky performance score) are reported in the baseline table; species/strain and housing conditions are not applicable to a human trial.

Evidence

“Male sex | 215 (75) | 209 (74) | | Median (range) age, years | 46 (19-64) | 49 (23-65)”

Table 1Find in source

paraphrase[Table 1 (Baseline characteristics)]

“Karnofsky performance score: | 70-80 | 9 (3) | 8 (3) | | 90-100 | 276 (97) | 275 (97)”

PASSReviewer 2· 90% conf

Key biological variables (sex, age, performance status, histology, stage) are reported in baseline characteristics; demographics are adequately covered for a human trial.

Evidence

“Male sex | 215 (75) | 209 (74) | | Median (range) age, years | 46 (19-64) | 49 (23-65)”

Table 1Find in source

paraphrase[Table 1]

“Karnofsky performance score: | 70-80 | 9 (3) | 8 (3) | | 90-100 | 276 (97) | 275 (97)”

WARNReviewer 3· 80% conf

Sex and age are reported, but weight, race/ethnicity, and comorbidities are not reported, making the assessment incomplete.

Evidence

paraphrase[Results, Table 1]

“Male sex: 215 (75) and 209 (74)”

paraphrase[Results, Table 1]

“Median (range) age, years: 46 (19-64) and 49 (23-65)”

absence[Results, Table 1]

Weight is not reported.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

Ethics approval by named institutional committees with a protocol number, written informed consent, and explicit regulatory compliance are all reported.

Evidence

“This study was approved by the institutional review board or ethics committee at each site (5010-2017-04-02)”

EthicsFind in source

“All participants provided written informed consent.”

EthicsFind in source

PASSReviewer 2· 95% conf

Ethical approval from institutional ethics committees, written informed consent, and compliance with Declaration of Helsinki and ICH-GCP are reported.

Evidence

“This study was approved by the institutional review board or ethics committee at each site (5010-2017-04-02)”

EthicsFind in source

“All participants provided written informed consent.”

EthicsFind in source

“The study complied with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice Guideline.”

MethodsFind in source

WARNReviewer 3· 85% conf

Ethics approval is mentioned but the approving body is not named, and a protocol number is provided but insufficient by the strict criteria. Informed consent and regulatory compliance are adequate.

Evidence

“The study protocol (web appendix 1) was approved by institutional ethics committees in each centre, and all patients provided written informed consent for participation.”

MethodsFind in source

“all patients provided written informed consent for participation.”

MethodsFind in source

“The study complied with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice Guideline.”

MethodsFind in source

Sub-criteria

mycoplasma testingN/A

reagents identifiedINADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedADEQUATE

Per reviewer (3) — the votes behind the verdict

N/AReviewer 1· 70% conf

Evidence

“We used SPSS software (version 25.0) and R (version 4.3.1) for all statistical analyses.”

Statistical analysisFind in source

PASSReviewer 2· 85% conf

The investigational product (radiotherapy technique) is described in detail, and statistical software is identified. No antibodies, cell lines, or wet-lab reagents are used.

Evidence

“All patients received intensity modulated radiation therapy, with target delineation following the guidelines detailed in web appendix 2 (pages 3-15).”

MethodsFind in source

“We used SPSS software (version 25.0) and R (version 4.3.1) for all statistical analyses.”

Statistical analysisFind in source

WARNReviewer 3· 80% conf

Statistical software is adequately identified, but the investigational products (chemotherapy drugs, radiotherapy equipment) are not specified, which is a reporting gap.

Evidence

“Standard-of-care chemotherapy (induction, concurrent, or both) was administered according to the extent of disease.”

MethodsFind in source

“We used SPSS software (version 25.0) and R (version 4.3.1) for all statistical analyses.”

Statistical analysisFind in source

absence[Methods, Procedures]

Radiotherapy equipment is not described.

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedADEQUATE

mathematical plausibilityN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 85% conf

Statistical tests are named, exact p-values and effect estimates with confidence intervals are reported, software is identified, and the reported numbers are internally consistent.

Evidence

“stratified hazard ratio 1.03 (95% CI 0.61 to 1.74); P=0.90”

AbstractFind in source

“we compared differences by using Pearson’s χ 2 test or Fisher’s exact test when appropriate.”

Statistical analysisFind in source

PASSReviewer 2· 90% conf

Statistical tests are named, effect sizes with CIs are reported, software is identified, and data presentation follows clinical trial conventions. Exact p-values are reported for most comparisons.

Evidence

Statistical analysisFind in source

“stratified hazard ratio 1.03 (95% CI 0.61 to 1.74); P=0.90”

AbstractFind in source

ResultsFind in source

PASSReviewer 3· 90% conf

Evidence

paraphrase[Methods, Statistical analysis]

“We calculated local relapse-free survival... using the Kaplan-Meier method, with hazard ratios and 95% confidence intervals estimated using a stratified Cox proportional hazards model...”

paraphrase[Results, Efficacy outcomes]

“We used SPSS software (version 25.0) and R (version 4.3.1) for all statistical analyses.”

Statistical analysisFind in source

Sub-criteria

code sharingADEQUATE

accession numbersADEQUATE

repository depositADEQUATE

data availability statementADEQUATE

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 85% conf

Evidence

“The data underlying the findings in this paper are openly and publicly available and can be found at https://data.mendeley.com/datasets/vvnswtgdz8/1”

Data availabilityFind in source

“The code used to analyse the data can be found in web appendix 3.”

Data availabilityFind in source

PASSReviewer 2· 95% conf

Data availability statement provides a concrete public repository (Mendeley) and a data platform accession, and code is shared in web appendix.

Evidence

“The data underlying the findings in this paper are openly and publicly available and can be found at https://data.mendeley.com/datasets/vvnswtgdz8/1”

Data availabilityFind in source

“The code used to analyse the data can be found in web appendix 3.”

Data availabilityFind in source

PASSReviewer 3· 90% conf

Evidence

“The data underlying the findings in this paper are openly and publicly available and can be found at https://data.mendeley.com/datasets/vvnswtgdz8/1”

Data availabilityFind in source

“The code used to analyse the data can be found in web appendix 3.”

Data availabilityFind in source

“The raw data were also uploaded to the Research Data Deposit public platform (RDDA2026205661).”

Data availabilityFind in source

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineINADEQUATE

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 85% conf

Methods are detailed, the trial is registered, outcomes are transparently reported, limitations are discussed, conclusions are measured, and funding/COI statements are provided.

Evidence

“Trial registration ClinicalTrials.gov NCT03346109”

AbstractFind in source

“Secondly, this was an open label study, and toxicity data were primarily obtained through clinical enquiries, introducing some unavoidable subjective bias.”

LimitationsFind in source

PASSReviewer 2· 90% conf

The paper is transparent: trial registration, funding, COI, limitations, and proportional conclusions are reported. Reporting guideline adherence is implied but not explicitly stated.

Evidence

“Trial registration ClinicalTrials.gov NCT03346109”

AbstractFind in source

“Our study has certain limitations. Firstly, as noted in our initial report, these findings were derived primarily from Epstein-Barr virus associated nasopharyngeal carcinoma in endemic regions”

LimitationsFind in source

“Funding: This study was supported by grants from the Noncommunicable Chronic Diseases-National Science and Technology Major Project (2024ZD0520701)”

FundingFind in source

PASSReviewer 3· 90% conf

Evidence

paraphrase[Abstract]

“Trial registration ClinicalTrials.gov NCT03346109 (https://clinicaltrials.gov/ct2/show/NCT03346109).”

paraphrase[Discussion, Limitations of study]

paraphrase[Funding and Competing interests]

“This study was supported by grants from ... The funders had no role in the design of the study... All authors have completed the ICMJE uniform disclosure form...”

Registered (1 ID: ClinicalTrials.gov). No reporting guideline cited.

Broken references and links

None found

References checked against Crossref, OpenAlex and Retraction Watch for retractions and resolvability, plus declared data and code links probed for whether they resolve to content matching the paper.

Checked — nothing surfaced.

Checked 37 references by DOI: 35 verified — 2 no DOI (shown, not verified).

2 data/code links checked; 2 live.

Copyediting

1 finding · worst low

Wording, consistency and formatting errors that need correcting before submission.

Wording or formatting errors that need correctingAssessed

10 copyedit issues flagged (1 major): mostly consistency, punctuation, other.

Kaimen Rigor Action ItemsFinal pass before journal submission

1.
HIGHcopyedit
Correct the Table 1 Stage IVa cell '124 (448)' to '124 (44)' in the Standard RT group via a published correction/erratum.
A percentage of 448% is impossible (124/283 = 43.8% ≈ 44%); this is the most consequential concrete error in the paper and is flagged by the copyedit, the integrity component, and Reviewer 1.
2.
HIGHdata code
Deposit the analysis code in a version-controlled public repository (e.g., GitHub with a Zenodo DOI) and link it in the Data availability statement, replacing the web-appendix-only code sharing.
Web-appendix-only code has no permanent identifier or version control, which undercuts reproducibility; this is the core reason Reviewer 1 rated data_code_availability a warn.
3.
HIGHreporting
Add an explicit CONSORT 2010 checklist reference and a statement of adherence in the Methods (and note the checklist is available as supplementary material).
A phase 3 RCT should reference its reporting guideline; all three reviewers flagged the absence of an explicit CONSORT statement.
4.
HIGHstatistics
Report exact p-values for comparisons currently given only as thresholds (e.g., 'P<0.05' in the correlation analyses, appendix 2 pages 46-48).
Threshold-only p-values cannot be independently verified and are a documented gap in the exact-p-value reporting.
5.
HIGHrigor
Add a sentence in the Statistical analysis section clarifying how outliers were handled for continuous outcomes (e.g., pharyngeal constrictor thickness) and, for the VFSS sub-study, the reasons for non-participation/missing data.
Reviewer 2 rated outlier_handling as inadequate; explicit handling of outliers and missing data in the exploratory swallowing substudy strengthens reproducibility.
6.
MEDIUMethics
Name the specific institutional ethics committee(s) (e.g., the IRB of Sun Yat-sen University Cancer Center) in the ethics statement.
Reviewer 3 flagged that the approving body is not named; naming it removes ambiguity about which body granted approval.
7.
MEDIUMrigor
Report baseline weight or BMI, and race/ethnicity and comorbidities if collected, in Table 1.
Reviewer 3 flagged these as missing from the baseline characteristics; adding them would fully address the biological-variables dissent.
8.
MEDIUMrigor
Specify the chemotherapy regimens and doses, and the radiotherapy delivery equipment (linear accelerator model and vendor), in the Methods/Procedures.
Reviewer 3 noted these are not specified; naming them aids replication even though the intervention is a procedural technique.
9.
MEDIUMcopyedit
Correct the recurring misspelling 'pharyngeal contractors' to 'pharyngeal constrictors' throughout (Abstract conclusions and Discussion).
This is a recurring terminology error that should be fixed in a correction for consistency.
10.
MEDIUMcopyedit
Fix the stray parentheses/punctuation in the CI formatting in Results/Efficacy outcomes (e.g., '92)% ' → '92%)', '89)% ' → '89%)').
The misplaced '%' and closing parenthesis obscure the confidence-interval formatting and were flagged multiple times by the copyedit pass.
11.
LOWcopyedit
Revise the awkward phrasing 'the number of deaths more than doubled since the primary analysis' to '...more than doubled compared with the primary analysis' in the Discussion.
The current preposition 'since' is grammatically awkward and unclear.
12.
LOWdata code
Clarify in the Data availability statement whether the Mendeley dataset is patient-level or aggregated, state the access conditions for the RDDA platform, and provide a DOI for the Mendeley dataset.
Clarifying the data granularity and access conditions, and adding a persistent DOI, strengthens the data-sharing statement.

Full text (46,059 chars)Analyzed: Aug 10, 2026