Table 5.

Intervention arm – ‘poor response’ to chemoradiotherapy

Intervention arm – poor responders		Registration period	Intervention phase								Annual follow-up			Disease statusg
Visit type	Prior to patient entry	Registration	Randomisation (baseline)	Post CRT	MDT	Chemo-therapy for 12 weeks	MDT	surgery	Surgical follow-up	Adjuvant chemotherapy for 12 weeks	12	24	36	60
Timelines		≤4 weeks prior to CRT	During CRT	4–6 weeks post CRT		≤12 weeks post CRT. Toxicity assessed at end of each cycle		6–12 weeks after pre-op chemo	6 weeks post surgery	Toxicity assessed at end of each cycle during chemotherapy	Months from end of CRT
Informed consenta		X	X
Check eligibility criteria		X	X
Diagnosis and clinical assessment		X
Randomisation			X
Quality of life		X									X		X
Chemoradiotherapy			X
Blood sampleb		X		X		X			X		X	X	X
Baseline MRI	X
Restaging MRIc				X		X i
Surgery								X
Surgical morbidityf									X		X
Pathologyd									X
Chemotherapyh						X end of each cycle				X end of each cycle
Toxicity assessment						X end of each cycle				X end of each cycle	X
Annual follow-upg											X	X	X	X
Adverse eventse				X		X end of each cycle				X end of each cycle
Concurrent medications		X	X	X		X end of each cycle		X	X	X end of each cycle	X

CRT preoperative chemoradiotherapy, MDT multidisciplinary team, MRI magnetic resonance imaging

The X also denotes that Clinical Report Forms (CRFs) need completing – tick or initial the boxes as the CRFs are completed

^aEligible subjects will be asked to provide written informed consent at registration and before randomisation

^bIf patient has consented to additional blood sample collection for research

^cThe post-CRT MRI should to be performed within 4–6 weeks (maximum of 10 weeks) from completion of CRT

^dResected specimen will be prepared and evaluated using a standardised protocol

^eAll adverse events will be recorded from the date the post-CRT MRI scan is performed until 30 days after the last dose of chemotherapy is administered during the intervention phase of the trial

^fBoth early (4–6 weeks) and late surgical complications (at 12 months) will be recorded

^gDisease status at 5 years (does not require clinic visit): alive without metastatic or recurrent disease, alive with metastatic and/or recurrent disease (date diagnosed), dead (date of death)

^hChemotherapy toxicity is assessed every 6 weeks during chemotherapy treatment. 12 weeks (6 cycles of FOLFOX or 4 cycles of CAPOX) are given pre-operatively and 12 weeks (6 cycles of FOLFOX or 4 cycles of CAPOX) are given post-operatively

ⁱFurther MRI scan should be performed within 4–6 weeks from completion of pre-operative chemotherapy and mrTRG reported