Validity of studies suggesting preoperative chemotherapy for resectable thoracic esophageal cancer: A critical appraisal of randomized trials

Table 1 Summary of the three analysed studies

Study (year)	Boonstra et al[16]	MRC Allum et al[17]	Ychou et al[15]
Number of included patients (intervention vs control)	85 vs 84	400 vs 402	113 vs 111
Inclusion criteria	100% squamous-cell cancer of thoracic oesophagus (upper, middle and lower third), T1-3, any N, M0 (M1a eligible if distal oesophageal cancer and suspected celiac nodes) < 80 yr of age, Karnofsky > 70	Squamous-cell cancer, adenocarcinoma, undifferentiated, upper, middle and lower thirds of oesophagus, as well as the gastric cardia	Resectable adenocarcinoma of the lower third of the oesophagus or gastro-oesophageal junction or stomach 18-75 years of age, WHO performance status 0 or 1, adequate renal (Cr < 120 mol/L) and hematologic functions
Intervention group	Preop. CTxa: Cisplatin, Etoposid iv. po. + surgery	Preop.CTx: Cisplatin, 5-FU + preop.radiotherapy + surgery	Preop.CTx: 5-FU, Cisplatin + surgery
Control group	Surgery	Preop. radiotherapy + surgery	Surgery
Outcome (intervention vs control)	Median overall survival 16 mo vs 12 mo, P = 0.03, by the log-rank test, HRb: 0.71; (95%CIc: 0.51-0.98)	Overall survival is significantly greater in CS group (HR: 0.84, 95%CI: 0.72-0.98, P = 0.03)	Overall survival significantly higher in CS group (HR for death 0.69, 95%CI: 0.50-0.95, P = 0.02) 5-year survival: 38% (95%CI: 29%-47%) in the CS group vs 24% (95%CI: 26%-44%) in the S group
Weight assigned in the Cochrane review (%)	24.1	20.5	24.5

^aCTx: chemotherapy,

^bHR: hazard ratio,

^cCI: Confidence interval. HR: Hazard ratio; CS: Chemotherapy + surgery; WHO: World Health Organization.

Table 2 Assessment of validity of the three analysed studies according to the CONSORT checklist (REF)

Section/Topic	Item number	Boonstra et al[16]	MRC Allum et al[17]	Ychou et al[15]
Title and Abstract	1a	Yes	Yes	No
	1b	Yes	Yes	Yes
Introduction
Background and objectives	2a	Yes	Yes	Yes
	2b	Yes	Yes	Yes
Methods
Trial design	3a	Yes	Yes	Yes
	3b	Not applicable	Not applicable	Yes
Participants	4a	Yes	Yes	Yes
	4b	Yes	No	No
Interventions	5	Yes	No	Yes
Outcomes	6a	Yes	Yes	Yes
	6b	Not applicable	Not applicable	Not applicable
Sample size	7a	Yes	No	Yes
	7b	Not applicable	Not applicable	Yes
Randomisation
-Sequence generation	8a	No	Yes	Yes
	8b	No	No	No
-Allocation concealment mechanism	9	No	No	No
- Implementation	10	No	No	No
Blinding	11a	No	Yes	No
	11b	Yes	No	No
Statistical methods	12a	Yes	Yes	Yes
	12b	Yes	Yes	Not applicable
Results
Participant flow	13a	Yes	Yes	Yes
	13b	Yes	Yes	Yes
Recruitment	14a	Yes	Yes	Yes
	14b	Not applicable	Not applicable	Nes
Baseline data	15	Yes	Yes	Yes
Numbers analysed	16	Yes	Yes	Yes
Outcomes and estimation	17a	Yes	Yes	Yes
	17b	Yes	Yes	Yes
Ancillary analysis	18	Yes	Yes	Not applicable
Harms	19	Yes	No	Yes
Discussion
Limitations	20	Yes	Yes	Yes
Generalisability	21	No	No	No
Interpretation	22	Yes	Yes	Yes
Other information
Registration	23	No	No	No
Protocol	24	No	No	No
Funding	25	Yes	Yes	No