Morris 1999.

Methods	2‐armed parallel, RCT conducted by the RTOG; study number RTOG 90‐01. Study duration: 1990–1997
Participants	388 women with FIGO stages IIB–IVA, squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the cervix or stage IB or IIA of 1 of these cancers with a tumour diameter ≥ 5 cm or biopsy‐confirmed metastasis to pelvic lymph nodes. Other inclusion criteria included Karnofsky performance score ≥ 60 and normal results of full blood counts and serum levels of urea, creatinine, and bilirubin. Exclusion criteria: disease outside the pelvic area or spread to para‐aortic lymph nodes; prior cancer other than cutaneous basal‐cell carcinoma; medical contraindications to chemotherapy; other rare histological subtypes; and prior hysterectomy or transperitoneal staging procedure for cervical cancer, pelvic RT, or systemic chemotherapy. Participants in each treatment group were stratified according to the tumour stage (IB, IIA, or IIB vs III or IVA) and the staging method used for para‐aortic lymph nodes (clinical vs surgical). 73.7% of participants underwent lymphangiography for para‐aortic lymph node evaluation. Approximately 40% of participants had cervical cancer stage III–IVA. Median tumour diameter in participants with stage IB and IIA was 6 cm. Allocations of participants were well balance between groups determined by equal distribution of characteristics of participants.
Interventions	Intervention arm: 45 Gy of EBRT given to the pelvis and para‐aortic lymph nodes. Control arm: 45 Gy of EBRT given to the pelvis alone plus 3 cycles of fluorouracil and cisplatin ( intravenous infusion of cisplatin 75 mg/m² of body‐surface area over a 4‐hour period followed by an intravenous infusion of fluorouracil 4000 mg/m² over a 96‐hour period; days 1–5; days 22–26 of RT; and during the time of the second intracavitary RT session). RT technique: either 2 fields or 4 fields (box technique) for field configuration during EBRT. Source of beam energy was a megavoltage machine. Brachytherapy using low‐dose‐rate intracavitary RT was performed within 2 weeks (preferably < 1 week) after the completion of pelvic radiation. For participants given RT plus systemic chemotherapy, the treatment field began from the space between L4 and L5 to the mid pubis or to a line 4 cm below the most distal vaginal or cervical lesion. Lateral fields were designed to encompass S3 posteriorly, with a margin of ≥ 3 cm from primary lesion. Shielding was designed to cover the areas of the pelvic lymph nodes, with a margin of ≥ 1–1.5 cm. For participants given RT alone, the pelvic and para‐aortic areas were treated as a continuous area, with a superior field border at the space between L1 and L2. The radiation dose was calculated at the midplane in the central ray of the field (for anteroposterior‐posteroanterior fields) or to the isocentre of the beams.
Outcomes	Primary endpoint: 5‐year and 8‐year overall survival Other study endpoints: 5‐year and 8‐year disease‐free survival rates of locoregional failure, para‐aortic failure, and distance metastasis, and grade 3–4 treatment‐related adverse effects within 60 days
Notes	The second round of interim analysis of this study, which was conducted when achieving the enrolment goal (July 1998), found the significant difference in terms of survival between groups that met the requirement for early reporting. The results presented in this study were updated using the results received by 11 November 1998. Median follow‐up time in Morris 1999 was 43 months. Eifel 2004 is an updated result of Morris 1999. The median follow‐up time of the participants in Eifel 2004 was 6.6 years.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	No statement regarding the method applied for random sequence generation provided in the published article. Kathryn Winter, Co‐Director, Division of Biostatistics and Science, NRG Oncology SDMC/RTOG and Senior Director of Statistics, American College of Radiology, confirmed that this study applied an algorithm that implemented a permuted block randomisation scheme (Winter 2017 [pers comm]).
Allocation concealment (selection bias)	Low risk	No statement regarding allocation concealment provided in the published article. Kathryn Winter, Co‐Director, Division of Biostatistics and Science, NRG Oncology SDMC/RTOG and Senior Director of Statistics, American College of Radiology, confirmed that central allocation was applied in this study (RTOG 9001) (Winter 2017 [pers comm]).
Blinding of participants and personnel (performance bias) All outcomes	Low risk	No statement regarding blinding of participants and personnel; however, outcomes of interest were unlikely to be affected by lack of blinding of outcome assessment.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	No statement regarding blinding of outcome assessor; however, outcomes of interest were unlikely to be affected by lack of blinding of outcome assessment. There was a well‐defined protocol for post‐treatment surveillance.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Only 15 (4%) participants were excluded after randomisation (6 in chemoradiation group and 9 in extended‐field RT group). Data used during the analyses of primary outcomes were obtained from approximately 96.5% of participants.
Selective reporting (reporting bias)	High risk	No data on quality of life and cost‐effectiveness reported.
Other bias	Low risk	Data analysed according to an intention‐to‐treat basis. The distributions of baseline characteristics of the participants which have had an impact on the treatment outcomes including age, performance status, histological subtypes, FIGO stage, and pelvic lymph node involvement were balanced between groups.