Do all patients with T2-3 mid-high rectal adenocarcinomas require RT as part of their neoadjuvant therapy? - Yes - 
 Bruce Minsky

Colon vs. Rectal Cancer

Colon: Time to Recurrence Sargent et al JCO 2007

CAO/ARO/AIO 94 Roedel et al JCO 2012

Preoperative Staging TRUS or MRI: T stage: 90% N stage: 60-70% MRI + contrast*: T stage: 90% N stage: 70-80% (↑ appx 10%) *Gadofosveset (Lambregts, Ann Surg 2011) *Iron oxide (Will et al, Lancet Oncol 2006)

Risk of LN+ by Distance High tumors have equivalent risk of LN+ Guillem pooled analysis · 188 Pts with cT3N0 s/p preop CMT · 6 international centers Cm from AV # % ypN+ 0-5 103 23 5-12 85 20 High tumors have equivalent risk of LN+ Guillem et al JCO 2008

cT3N0 @ 10 cm: CMT vs. LAR PREOP CMT - improved local control - less toxicity - but over treat 20% (pT1-2N0) SURGERY - avoid RT - but if N+ (22% s/p preop CMT*) then need postop CMT - decreased local control - higher toxicity - poor function Guillem et al JCO 2008

Distance from the AV Caveats: · All are subset analysis · Include cT1-3 tumors · Variable methods to measure distance · 5 Gy x 5 · Dutch: flexible scope, < 15 cm, TME · German: rigid scope, < 16 cm, TME · SRCT: no details, variable surgery

Distance from the AV Surgery Preop RT Cm % 5-Yr LF % 5-Yr LF p Dutch High 10.1-15 6 4 - Mid 5.1-10 14 4 <0.001 Low < 5 12 11 - SRCT High > 11 12 8 - Mid 6-10 26 9 <0.001 Low < 5 27 10 0.003

Distance from the AV Location # %10-Yr LF < 6 cm 166 11 German Pre-op Location # %10-Yr LF < 6 cm 166 11 6- <12 cm 166 5 12-16 cm 37 10

Preop CMT – Selective RT ∙ 32 Pts, LAR eligible, uT2N1, uT3N0-1 FOXFOX/BEV x 4 FOLFOX x 2 Surgery ∙ If preop POD salvage preop RT ∙ If pT4, N2, or margin+ post RT ∙ R0: 30/30 ∙ pCR: 25% ∙ No preop RT, 2 postop RT ∙ 4 years: 0 LF, 84% DFS * Alliance N1048 – 1000 pt trial Schrag et al JCO 2014

Preop CMT – Selective RT • 28 pts, Multicenter phase II • MRI: T3 or > 2mm from mesorectal fascia (? LN) • Mid rectal (> 5 cm from AV) • 4 cycles Induction CAPOX-B • None required preop CMT • 15 % pCR, all R0 • 2 pts with pN2 needed postop CMT • 50% Gr 3+ toxicity Fernandez-Martos et al, ProcASCO 2012

….Yes · Local recurrences in rectal cancer occur late · LN+ is primary cause of LF · 22% ypN+ even after preop CMT for cT3N0 · LN + is independent of distance from AV ·CT alone data are investigational and may have higher toxicity