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  • TME trialTMEradiotherapy5 x 5 GyTME alonerandomisationn = 1861resectablerectal carcinomaif CRM+: 50 GY

  • MRC CR 07: 5x5 Gy vs. postop CRT5x5 GySurgeryPathologyCRM -veCRM +veCRM -veCRM +veSurgeryPathologynothing45Gy + 5 FUchemotherapy as per local protocol

  • My belief in 2002:5x5 Gy for allNever heard of tailored treatmentMore insight:subgroup analysesMainly hypothesis generating

  • Local Recurrence TME studyp < 0.0015.6%10.9%TMERT+TME2.4%8.2%Peeters et al., Ann Surg 2007

  • Radiotherapy before TME:Is it beneficial?Local recurrence from 10.9% to 5.6%When you treat 100 patients:89.1 would never get recurrence: unnecessary5.6 still get recurrence: unnecessary5.3 recurrence prevented

    To save 1 patient a local recurrence, you treat 100 / 5.3= 19 unnecessary

  • And it gets even worse......0.4% vs 1.7% p = 0.09

    NNT 7710.6% vs 20.6% p < 0.001

    NNT 105.3% vs 7.2% p = 0.33

    NNT 53TNM ITNM IITNM III102030

  • But better in MRC CR 07!

    pre-op(n=674)postop(n=676)pNNT

    TNM I0%3%ns33TNM II2%8%sign16TNM III9%17%sign12

  • On basis of this:tailored treatment

    Stage I TMEStage IIshort-term RT + TMEStage III short-term RT + TMEFixed T4 long-term RT + TME

    Do we need it for all heights?

  • LAR vs APR LARAPRp
  • TME trial: Distance to anal verge24610202465 - 10 cm10 - 15 cm6.2% TME3.7% RT102013.7% TME3.7% RTp
  • Again other results in MRC CR 07: Selection because of Dutch results?

    pre-op(n=674)postop(n=676)pNNT

    0-5 cm6%10%sign255-10 cm5%10%sign2010-15 cm1%16%sign7

  • Abandon RT for high tumors? Too few LR in proximal tumours (> 10 cm)No significant effect of RT in proximal tumoursSide effects: incontinence and sexual function

  • Keep RT for high tumors ? Subgroup analyses are hazardous: use with cautionDiscrepancy with Swedish study for low tumorsDiscrepancy with German study for high tumorsVery effective in MRC CR 07 studyTumour distance from anal verge NOT standardized

  • On basis of this: tailored treatment

    Stage I TME, possible role TEMStage IIshort-term RT + TMEStage III short-term RT + TMEFixed T4 long term RT + TME

    RT for high tumors may be omitted in selected casesBut how to define a high tumor?

  • Stage I TMEStage IIshort-term RT + TMEStage III short-term RT + TMEFixed T4 long term RT + TME

    RT for high tumors may be omitted in selected casesAnd what about T3 tumors?On basis of this: tailored treatment

  • Few cells, still effective

    p = 0.0008RR=82%51015202466.1% TME1.1% RT+TMEYears since surgeryLocal recurrence rateupdate of Marijnen et al., IJROBP 2003CRM > 10 mm

  • Circumferential resection marginsMargin determined by tumor

  • CRM en prognosis Local Metastases Survival n Margin< 1 mm16.437.669.71201.1 - 2.0 mm14.921.084.8 532.1 - 5.0 mm10.317.287.01395.1 - 10 mm 6.0 8.291.2155> 10 mm 2.410.992.8189p-value 0.0007 < 0.0001 < 0.0001 Nagtegaal, Am. J. Surg. Pathol 2002

  • CRM > 1 mmn = 1089CRM < 1 mmn = 22724610203015.5% RT23.3% TME p = 0.16RR=33%246102030p = 0.001RR=59%9.1% TME 3.7% RTupdate Marijnen et al., IJROBP 20035x5 Gy does not compensate for positive margins!

  • MRC CR 07

    pre-op(n=674)postop(n=676)pCRM -ve3%10%signCRM +ve16%23%ns

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