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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.

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

DOI: 10.1136/bmj-2025-086050
Record issued: 2026-08-10
Engine: 7.29.0
Exported: 2026-09-20

Prepared by Alpha1. This document is confidential: it is intended for the recipient it was shared with and must not be redistributed. The live record at alpha1science.com/verify/6968e654-4337-4336-b155-95b108240e50 is authoritative.

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.

Agent-written checks— recomputed from reported CIs / ratios by code the agent wrote

CONSISTENTreported p = .900 · recomputed p = .912
Recomputed hazard ratio 1.03 (95% CI 0.61–1.74), reported p=0.90
“hazard ratio 1.03 (95% CI 0.61 to 1.74); P=0.90”
Find in source
Taken as given: 0.61–1.74 is a two-sided 95% confidence interval for the hazard ratio of 1.03, not a range, an IQR, or a different interval level; the hazard ratio is a RATIO measure, so the interval is symmetric on the log scale; p=0.90 is the p for THIS estimate, not for another comparison in the same sentence
Method: back the two-tailed p out of the log-scale CI width and compare it against the printed p
How we recomputed it: pCI(1.03, 0.61, 1.74, 1)
CONSISTENTreported p = .790 · recomputed p = .801Reviewer 1
Stratified hazard ratio for five-year overall survival (MRLN sparing vs standard) converted from HR and 95% CI.
“overall survival (89.2% (85% to 93%) versus 90.3% (87% to 94%); stratified hazard ratio 1.06 (0.68 to 1.68); P=0.79)”
Find in source
Taken as given: The HR of 1.06 is a ratio so log-transform applies (log=1); The 95% CI (0.68 to 1.68) is two-sided at the 95% level; The p-value is two-tailed from the normal approximation on the log scale
Method: p from a ratio estimate and its 95% CI using the normal approximation on the log scale.
How we recomputed it: pCI(1.06, 0.68, 1.68, 1)
CONSISTENTreported p = .230 · recomputed p = .232Reviewer 1
Stratified hazard ratio for five-year distant metastasis-free survival converted from HR and 95% CI.
“five year distant metastasis-free survival (84.8% (80% to 89)% versus 89.2% (85% to 93%); stratified hazard ratio 1.32 (0.84 to 2.09); P=0.23)”
Find in source
Taken as given: The HR of 1.32 is a ratio so log-transform applies (log=1); The 95% CI (0.84 to 2.09) is two-sided at the 95% level; The p-value is two-tailed from the normal approximation on the log scale
Method: p from a ratio estimate and its 95% CI using the normal approximation on the log scale.
How we recomputed it: pCI(1.32, 0.84, 2.09, 1)
CONSISTENTreported p = .010 · recomputed p = .015Reviewer 1
Grade ≥1 dysphagia comparison (45/206 vs 70/216) recomputed with Pearson chi-square on cell counts.
“the sparing group showed a lower rate of grade ≥1 dysphagia than the standard group (45 (22%) v 70 (32%); P=0.01)”
Find in source
Taken as given: The 45 and 70 are the event counts and the 206 and 216 are the group totals of the same arms; The test is a two-tailed Pearson chi-square (paper states 'Pearson's χ2 test or Fisher's exact test when appropriate'); df = 1 for a 2x2 table
Method: Two-tailed Pearson chi-square from the four cell counts.
How we recomputed it: pChi2x2(45, 161, 70, 146)
CONSISTENTreported p < .001 · recomputed p = <.001Reviewer 1
Vallecular residue prevalence (49/66 vs 62/62) recomputed with Fisher's exact test on cell counts.
“In comparison with the standard group, the sparing group had a lower prevalence of vallecular residue (49 (74%) v 62 (100%); P<0.001)”
Find in source
Taken as given: The 49 and 62 are event counts and the 66 and 62 are group totals of the same arms; The test is Fisher's exact (table footnote states 'P values were calculated using Fisher’s exact test'); The comparison is two-tailed
Method: Two-tailed Fisher's exact test from the 2x2 cell counts.
How we recomputed it: pFisher2x2(49, 17, 62, 0, 0)
CONSISTENTreported p = .010 · recomputed p = .007Reviewers 1, 2
Pyriform sinus residue prevalence (32/66 vs 45/62) recomputed with Fisher's exact test on cell counts.
“pyriform sinus residue (32 (48%) v 45 (73%); P=0.01)”
Find in source
Taken as given: The 32 and 45 are event counts and the 66 and 62 are group totals of the same arms; The test is two-tailed Fisher's exact (table footnote); df = 1 for a 2x2 table
Method: Two-tailed Fisher's exact test from the 2x2 cell counts.
How we recomputed it: pFisher2x2(32, 34, 45, 17, 0)
CONSISTENTreported p = .030 · recomputed p = .027Reviewers 1, 2
Aspiration prevalence (8/66 vs 18/62) recomputed with Fisher's exact test on cell counts.
“and aspiration (8 (12%) v 18 (29%); P=0.03)”
Find in source
Taken as given: The 8 and 18 are event counts and the 66 and 62 are group totals of the same arms; The test is two-tailed Fisher's exact (table footnote); df = 1 for a 2x2 table
Method: Two-tailed Fisher's exact test from the 2x2 cell counts.
How we recomputed it: pFisher2x2(8, 58, 18, 44, 0)
CONSISTENTreported p = .900 · recomputed p = .912Reviewer 2
Check p-value for local relapse-free survival hazard ratio using CI-based method.
“stratified hazard ratio 1.03 (95% CI 0.61 to 1.74); P=0.90”
Find in source
Taken as given: The hazard ratio is 1.03 with 95% CI 0.61 to 1.74.; The CI is two-sided at 95%.; The p-value is two-tailed.
Method: Recomputed p-value from hazard ratio and 95% CI using normal approximation.
How we recomputed it: pCI(1.03, 0.61, 1.74, 1)
CONSISTENTreported p = .790 · recomputed p = .801Reviewer 2
Check p-value for overall survival hazard ratio using CI-based method.
“stratified hazard ratio 1.06 (0.68 to 1.68); P=0.79”
Find in source
Taken as given: The hazard ratio is 1.06 with 95% CI 0.68 to 1.68.; The CI is two-sided at 95%.; The p-value is two-tailed.
Method: Recomputed p-value from hazard ratio and 95% CI using normal approximation.
How we recomputed it: pCI(1.06, 0.68, 1.68, 1)
CONSISTENTreported p = .230 · recomputed p = .232Reviewer 2
Check p-value for distant metastasis-free survival hazard ratio using CI-based method.
“stratified hazard ratio 1.32 (0.84 to 2.09); P=0.23”
Find in source
Taken as given: The hazard ratio is 1.32 with 95% CI 0.84 to 2.09.; The CI is two-sided at 95%.; The p-value is two-tailed.
Method: Recomputed p-value from hazard ratio and 95% CI using normal approximation.
How we recomputed it: pCI(1.32, 0.84, 2.09, 1)
CONSISTENTreported p = .250 · recomputed p = .257Reviewer 2
Check p-value for regional relapse-free survival hazard ratio using CI-based method.
“stratified hazard ratio 0.69 (0.36 to 1.30); P=0.25”
Find in source
Taken as given: The hazard ratio is 0.69 with 95% CI 0.36 to 1.30.; The CI is two-sided at 95%.; The p-value is two-tailed.
Method: Recomputed p-value from hazard ratio and 95% CI using normal approximation.
How we recomputed it: pCI(0.69, 0.36, 1.30, 1)
CONSISTENTreported p = .001 · recomputed p = <.001Reviewer 2
Check p-value for vallecular residue comparison using Fisher's exact test.
“vallecular residue (49 (74%) v 62 (100%); P<0.001)”
Find in source
Taken as given: The numbers 49 and 62 are the counts of patients with vallecular residue in the sparing and standard groups, respectively.; The group sizes are 66 and 62, so the non-event counts are 17 and 0.; The p-value is two-tailed from Fisher's exact test.
Method: Recomputed two-tailed Fisher's exact test from 2x2 table.
How we recomputed it: pFisher2x2(49, 17, 62, 0, 0)
UNCOMPUTABLEreported p = .010 · recomputed p = .022Reviewer 2
Check p-value for coating of pharyngeal wall comparison using Fisher's exact test.
“coating of pharyngeal wall (7 (11%) v 17 (27%); P=0.01)”
Find in source
Taken as given: The numbers 7 and 17 are the counts of patients with coating of pharyngeal wall in the sparing and standard groups, respectively.; The group sizes are 66 and 62, so the non-event counts are 59 and 45.; The p-value is two-tailed from Fisher's exact test.
Method: Recomputed two-tailed Fisher's exact test from 2x2 table.
How we recomputed it: pFisher2x2(7, 59, 17, 45, 0)
CONSISTENTreported p = .030 · recomputed p = .029Reviewer 2
Check p-value for pharyngeal transit time >1.0s comparison using Fisher's exact test.
“pharyngeal transit time >1.0 s (1 (2%) v 7 (11%); P=0.03)”
Find in source
Taken as given: The numbers 1 and 7 are the counts of patients with pharyngeal transit time >1.0s in the sparing and standard groups, respectively.; The group sizes are 66 and 62, so the non-event counts are 65 and 55.; The p-value is two-tailed from Fisher's exact test.
Method: Recomputed two-tailed Fisher's exact test from 2x2 table.
How we recomputed it: pFisher2x2(1, 65, 7, 55, 0)

lowinternal contradiction
In Table 1, the percentage for Stage IVa in the standard group is listed as 448%, which is impossible. This appears to be a typographical error.
“IVa | 117 (41) | 124 (448)”
Table 1Find in source

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.

partialReviewers 1, 2
MRLN sparing radiotherapy should be considered a standard of care for non-metastatic nasopharyngeal carcinoma.
The clinical benefits are well supported, but the 'standard of care' recommendation is partly a value/context judgement and the authors themselves note the endoscopic applicability caveats; the evidence supports it as a valid option rather than a firmly established standard.
Evidence: Non-inferior efficacy and improved swallowing outcomes at five years, with acknowledged limitations (open-label design, post-hoc exploratory VFSS, endemic-region population).
“supporting its use as a standard of care for non-metastatic nasopharyngeal carcinoma”
ConclusionFind in source
partialReviewer 3
MRLN sparing radiotherapy should be a standard of care for non-metastatic nasopharyngeal carcinoma.
The evidence supports efficacy and safety benefits, but the claim of 'standard of care' may be overstated given the study's limitations (open-label, post-hoc analyses, single-region population). However, the data strongly support its use as a valid option.
Evidence: The paper concludes that MRLN sparing radiotherapy is a valid option, but the conclusion is drawn from the presented data.
“Our robust data provide a strong rationale supporting MRLN sparing radiotherapy as a valid option to treat non-metastatic nasopharyngeal carcinoma.”
DiscussionFind in source
supportedReviewer 1
MRLN sparing radiotherapy maintained uncompromised efficacy (local control and survival) at five years.
The presented survival and local-control results directly support the efficacy claim within the pre-specified non-inferiority framework.
Evidence: Five-year local relapse-free survival 89.2% vs 90.6% (stratified HR 1.03, 95% CI 0.61-1.74; P=0.90) and overall survival 89.2% vs 90.3% (HR 1.06, 0.68-1.68; P=0.79), within the non-inferiority margin.
“MRLN sparing radiotherapy maintained uncompromised efficacy and better long term swallowing function by reducing radiation damage to pharyngeal contractors, supporting its use as a standard of care for non-metastatic nasopharyngeal carcinoma.”
ConclusionFind in source
supportedReviewer 1
MRLN sparing radiotherapy improved long-term swallowing function (observer-rated, patient-reported, and objective).
Multiple independent outcome measures (observer, patient-reported, and videofluoroscopic) consistently support the swallowing-function claim.
Evidence: Lower grade ≥1 dysphagia (45/206 vs 70/216; P=0.01), lower VFSS abnormalities (vallecular residue, pyriform sinus residue, aspiration; all P≤0.03), and improved swallowing-related QoL (mean difference -11.9; P<0.001).
“At five years, MRLN sparing radiotherapy significantly reduced observer rated, patient reported, and objectively assessed dysphagia, while maintaining uncompromised efficacy”
What this study addsFind in source
supportedReviewer 1
MRLN sparing reduced radiation damage to pharyngeal constrictors, mediating the swallowing benefits.
The MRI thickness and dosimetry correlation data provide direct evidence of reduced radiation damage, and the mechanism is consistent with the observed functional benefits.
Evidence: MRI-measured constrictor thickness showed less early oedema and less late atrophy in the sparing group (e.g., superior constrictor 1.80 vs 1.65 mm at 5 years; P=0.005), and dosimetry correlated with oedema/atrophy and dry mouth.
“MRLN sparing radiotherapy, through reducing early oedema and late atrophy of pharyngeal contractors, significantly decreased observer rated, patient reported, and objectively assessed dysphagia, without compromising efficacy.”
DiscussionFind in source
supportedReviewer 2
MRLN sparing radiotherapy maintained uncompromised efficacy at five years.
The five-year local relapse-free survival and overall survival are similar between groups, with hazard ratios close to 1 and non-significant p-values, supporting the claim of non-inferiority.
Evidence: Five-year local relapse-free survival 89.2% vs 90.6%, HR 1.03 (95% CI 0.61-1.74), P=0.90; overall survival 89.2% vs 90.3%, HR 1.06 (0.68-1.68), P=0.79.
“MRLN sparing and standard groups had similar five year local relapse-free survival (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)”
AbstractFind in source
supportedReviewer 2
MRLN sparing radiotherapy reduced dysphagia and improved swallowing function.
Multiple measures (observer-rated, patient-reported, videofluoroscopic, and MRI) consistently show lower dysphagia and better swallowing outcomes in the sparing group.
Evidence: Lower grade ≥1 dysphagia (22% vs 32%, P=0.01), better swallowing QoL (mean difference -11.9, P<0.001), lower prevalence of vallecular residue (74% vs 100%, P<0.001), and less atrophy of pharyngeal constrictors.
“Updated safety profiles of the MRLN sparing group showed a lower rate of grade ≥1 dysphagia (45/206 (22%) v 70/216 (32%); P=0.01)”
AbstractFind in source
supportedReviewer 2
MRLN sparing radiotherapy reduced radiation damage to pharyngeal constrictors.
MRI measurements show less oedema and atrophy in the superior and middle pharyngeal constrictors in the sparing group, supporting the mechanistic claim.
Evidence: Less oedema at 3 and 6 months and less atrophy at 3 and 5 years in superior and middle pharyngeal constrictors, with statistically significant differences.
“the sparing group had less severe atrophy at three and five years after radiotherapy in the superior pharyngeal constrictor (1.97 (0.50) v 1.87 (0.46) mm; P=0.02 and 1.80 (0.46) v 1.65 (0.39) mm; P=0.005)”
ResultsFind in source
supportedReviewer 3
MRLN sparing radiotherapy maintained uncompromised efficacy (local relapse-free survival, overall survival) at five years.
The paper presents five-year survival rates with hazard ratios and confidence intervals that show no significant difference between groups, supporting the claim of non-inferiority.
Evidence: Five-year local relapse-free survival: 89.2% vs 90.6%, HR 1.03 (95% CI 0.61-1.74), P=0.90. Overall survival: 89.2% vs 90.3%, HR 1.06 (0.68-1.68), P=0.79.
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
Resultsreviewer’s wording
supportedReviewer 3
MRLN sparing radiotherapy significantly reduced observer-rated dysphagia and dry mouth.
The paper reports lower rates of grade ≥1 dysphagia and grade ≥2 dry mouth in the sparing group with significant p-values, supporting the claim.
Evidence: Grade ≥1 dysphagia: 45/206 (22%) vs 70/216 (32%), P=0.01. Grade ≥2 dry mouth: 33/206 (16%) vs 55/216 (25%), P=0.02.
“the sparing group showed a lower rate of grade ≥1 dysphagia than the standard group (45 (22%) v 70 (32%); P=0.01)”
ResultsFind in source
supportedReviewer 3
MRLN sparing radiotherapy improved swallowing-related quality of life.
The paper reports a statistically and clinically significant improvement in the swallowing domain of the EORTC QLQ-H&N35, with a mean difference of -11.9 (P<0.001).
Evidence: Swallowing domain mean difference -11.9 (95% CI -15.3 to -8.5), P<0.001.
“swallowing (–11.9, –15.3 to –8.5; P<0.001)”
ResultsFind in source
supportedReviewer 3
Objective measures (videofluoroscopic swallowing study) show less dysphagia in the MRLN sparing group.
The paper provides detailed videofluoroscopic findings showing lower prevalence of vallecular residue, pyriform sinus residue, pharyngeal coating, prolonged transit time, and aspiration, all with significant p-values.
Evidence: Vallecular residue: 49/66 (74%) vs 62/62 (100%), P<0.001; aspiration: 8/66 (12%) vs 18/62 (29%), P=0.03.
“the sparing group had a lower prevalence of vallecular residue (49 (74%) v 62 (100%); P<0.001)”
ResultsFind in source

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

ADEQUATESurrogate endpoint
Primary endpoint is local relapse-free survival, a hard clinical outcome (time to local recurrence or death). No surrogate needed.
“The primary outcome was local relapse-free survival.”
Find in source
ADEQUATEEffect size
Non-inferiority demonstrated with margin of 8% absolute difference; observed five-year local relapse-free survival 89.2% vs 90.6%, HR 1.03 (0.61-1.74). Swallowing improvements exceed minimal clinically important difference (mean difference –11.9).
“The estimated five year local relapse-free survival rates were 89.2% (95% (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) and improvement in the swallowing domain continued to be clinically significant (mean difference –11.9; P<0.001)”
Find in source

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).

lowdata too clean
The baseline characteristics are very well balanced between groups, which is expected in a randomized trial but the near-identical percentages (e.g., 75% vs 74% male) are plausible.
“Male sex | 215 (75) | 209 (74)”
Table 1Find in source

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.

ClinicalTrials.gov

NCT03346109

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).

NO DOI
Evaluation and Treatment of Swallowing Disorders.
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Feasibility analysis of non-prophylactic irradiation of retropharyngeal lymph nodes in medial group of nasopharyngeal carcinoma.
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).

2 data/code links checked; 2 live.

dataMendeley DataLIVEHTTP 200
https://data.mendeley.com/datasets/vvnswtgdz8/1
Resolves to Mendeley Data (data repository).
datahttps://clinicaltrials.gov/ct2/show/NCT03346109LIVEHTTP 200
Resolves, but the content could not be matched to the paper.

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.

MAJORotherTable 1 (Stage IVa row)
“IVa | 117 (41) | 124 (448)”
→ 124 (44)
The percentage for the Standard RT group is printed as '448' instead of '44'; 124/283 = 43.8% ≈ 44%, and the column otherwise sums to ~100%.
MINORconsistencyAbstract and Discussion
“pharyngeal contractors”
→ pharyngeal constrictors
'contractors' is a recurring misspelling of 'constrictors' (e.g., in Abstract conclusions and Discussion).
MINORpunctuationResults, Efficacy outcomes
“89.2% (95% confidence interval (CI) 85% to 92)% versus 90.6%”
→ 89.2% (95% confidence interval (CI) 85% to 92%) versus 90.6%
Stray '%' after the closing parenthesis.
MINORtypoAbstract, Results
“pharyngeal contractors”
→ pharyngeal constrictors
Typo: 'contractors' should be 'constrictors'.
MINORconsistencyTable 1, Stage row
“IVa | 117 (41) | 124 (448)”
→ 124 (44)
Percentage appears to be a typo: 124/283 = 43.8%, not 448%.
MINORconsistencyResults, Efficacy outcomes
“89.2% (95% confidence interval (CI) 85% to 92)%”
→ 89.2% (95% CI 85% to 92%)
Extra closing parenthesis after the percentage.
MINORgrammarDiscussion, Comparison with other studies
“the number of deaths more than doubled since the primary analysis”
→ the number of deaths more than doubled compared with the primary analysis
Preposition 'since' is awkward; 'compared with' is clearer.
MINORconsistencyTable 1, Stage IVa
“124 (448)”
→ 124 (44%) or 124 (44%)? The percentage appears incorrect; likely a typo.
The percentage for standard group stage IVa is shown as '124 (448)' which is likely a formatting error; should be 124 (44%).
MINORclarityResults, Efficacy outcomes
“89.2% (95% confidence interval (CI) 85% to 92)%”
→ Remove the extra closing parenthesis after 92%.
The text has a stray parenthesis: '92)%' should be '92%)'.
MINORpunctuationResults, Efficacy outcomes
“84.8% (80% to 89)%”
→ 84.8% (80% to 89%)
Extra parenthesis before the closing parenthesis.

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.

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

RigorReviewer 1

RigorReviewer 2

RigorReviewer 3

RigorPre-Submission Reviewer

CopyeditAgent Scribe

CitationsCitation Integrity

StatisticsStatistics Consistency

ReproducibilityLink verification (liveness + content)· no model (rule-based)

PreregistrationDeterministic check· no model (rule-based)

The star rating is the report’s one-glance summary. Every paper starts at 5★ and loses stars for the concrete problems the review finds — so a rating is never a vague average, it’s a running total you can read line by line under “How this rating was calculated.”

How stars are deducted

Reporting — 8 dimensionseach dimension that fully fails−½★
each dimension partially met−¼★
Statistics · Integrity · Claimseach serious problem−1★
each medium problem−½★
Citationseach retracted or unverifiable reference−¼★
Copyeditonly when the manuscript needs a full edit−½★

The rating never drops below 1★, and a demonstrable critical failure (an impossible statistic, a proven ethics violation) caps it at 1★ on its own — so the stars can never look healthy when the verdict is CRITICAL.

The rating draws on a panel of agents. Three independent Kaimen Rigor reviewers grade the eight dimensions below across several independent passes (the shown verdict is their majority vote — steadier than any single run), isolate the paper’s major claims and check its own evidence backs them, and flag integrity concerns. Alongside them, a citation agent resolves every reference against Crossref, OpenAlex, and Retraction Watch; a statistics agent recomputes reported tests; and rule-based checks verify that declared data/code links actually resolve. Full text is required — an abstract-only submission is not analyzed.

The eight reporting dimensions

Scientific PremisePrior work, rationale, and how it addresses gaps.

Study Design & RigorRandomization, blinding, power, controls, replication.

Biological VariablesSex, age, species/strain, housing, demographics.

Ethical ApprovalsIRB/IACUC approval, informed consent, regulatory compliance.

Key ResourcesAntibodies, cell lines, organisms, software — identified with persistent IDs.

Statistical ReportingNamed tests, exact p-values, effect sizes, plausible summary stats.

Data & Code AvailabilityAvailability statements, repositories, accession numbers, shared code.

Reporting TransparencyMethods, registration, guidelines, outcomes, limitations, funding/COI.

Graded against NIH, MDAR, ARRIVE 2.0, CONSORT, EQUATOR, and RRID guidelines. A dimension that doesn’t apply to the study type is skipped, never penalized.

This Kaimen Rigor review is model-assisted and is not a substitute for formal expert review. It complements human evaluation by surfacing potential methodological concerns — verify each finding against the source.

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

DOI

10.1136/bmj-2025-086050

Record issued

2026-08-10

Engine

7.29.0

Exported

2026-09-20