mrTRG as a predictor for DFS
mrTRG vs DFSypT vs DFS
Royal Marsden database n=208 irradiated patients
Hypothesis
Treatment stratification according to an MRI response biomarker improve survival and
enhance quality of life after chemoradiotherapy in patients with rectal cancer.
Patient Benefits• First trial to stratify patients into ‘good’ and ‘poor’
chemoradiotherapy responders.
• Good responders - ? Avoid surgery, or less radical surgery
• Poor responders – improve survival
Trial DesignMulticentre blinded randomised control trial
mrTRG based stratification in intervention armInclusion:
• Adenocarcinoma 0-15cm from anal verge (radiologically)• Deemed to required CRT by recruiting trial centre
Exclusion:• Metastatic disease• MRI or Chemoradiotherapy contraindications• Previous pelvic malignancy, breast feeding or pregnant• Secondary concomitant malignancy
1) Biopsy - adenocarcinoma
2) Baseline MRI3) Chemoradiotherapy†
4) Eligible & Consent
Intervention arm
Repeat MRI and REASSESS (mrTRGa)
Control arm
mrTRG III-VmrTRG I&II
Good Response Poor Response
Repeat MRI*
Rectal Cancer
Clinical assessmentand baseline MRI
1:2 Randomisation‡
FOLFOX††
24 weeks
Adjuvant Therapy
FOLFOX††
24 weeks
Adjuvant Therapy
Deferral of surgery** Surgery
Repeat MRI (mrTRGb)
FOLFOX 12 weeks
Surgery
FOLFOX 12 weeks
†Recommended CRT regimen – 45Gy/25# and Capecitabine††Recommended post-treatment regime – FOLFOX regimen‡Randomise following MRI assessment but before the MRI is report at the MDT.*MRI to assesses disease progression only** TME surgery if patient declines deferral of surgery mrTRGa - performed at 6 weeks post-CRT mrTRGb - performed 12 weeks into ‘up-front’ FOLFOX treatment
TRIGGER Trial
EndpointsPrimary Endpoint – 1 year and 3 year QALY•Feasibility
recruit 100 patients, reflecting adequate safety, accurate radiology assessment (Kappa 0.7), patient and clinician equipoise
•Secondary Outcomes: Overall Survival, DFS Stoma free survival pTRG – can ‘upfront’ pre-operative chemotherapy improve pathological
evidence of response health economic evaluation – we anticipate the intervention arm will be
cheaper because it is possible to avoid surgery altogether in at least ¼ of these patients.
Quality of Life Adverse event reporting - CTCAE for surgical and therapeutic TUMOUR BIOLOGY – mrTRG1&2 v mrTRG3-5
1) Biopsy - adenocarcinoma
2) Baseline MRI3) Chemoradiotherapy†
4) Eligible & Consent
Intervention arm
Repeat MRI and REASSESS (mrTRGa)
Control arm
mrTRG III-VmrTRG I&II
Good Response Poor Response
Repeat MRI*
Rectal Cancer
Clinical assessmentand baseline MRI
1:2 Randomisation‡
FOLFOX††
24 weeks
Adjuvant Therapy
FOLFOX††
24 weeks
Adjuvant Therapy
Deferral of surgery** Surgery
Repeat MRI (mrTRGb)
FOLFOX 12 weeks
Surgery
FOLFOX 12 weeks
†Recommended CRT regimen – 45Gy/25# and Capecitabine††Recommended post-treatment regime – FOLFOX regimen‡Randomise following MRI assessment but before the MRI is report at the MDT.*MRI to assesses disease progression only** TME surgery if patient declines deferral of surgery mrTRGa - performed at 6 weeks post-CRT mrTRGb - performed 12 weeks into ‘up-front’ FOLFOX treatment
TRIGGER Trial