Rectal Cancer: Advanced Technologies

1
Rectal Cancer Advanced Technologies

• Chris Willett, M.D.
• Department of Radiation Oncology
• Duke University Medical Center
• Durham, NC

2
Gastric Intergroup 0116 RT Considerations

• 35 of initially submitted RT plans Major
  deviations (2/3 undertreatment)
• 2 D Therapy AP/PA

3
Median Survival By Rx Arm And RT ComplianceAll
Patients
4
Stage II/III Rectal Ca 2006 Management

• Preoperative EBRT 5-FU Based ChT
• Surgery
• Adjuvant ChT

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Preoperative EBRT Rectal Ca

• CTV 45 Gy / 1.8 Gy Fx
• GTV 50.4 (T3) 54 Gy (T4) / 1.8 Gy Fx
• 3 Fields (PA and Laterals) or 4 Fields (AP/PA and
  Laterals)
• Minimize SB Tx Prone / False Table Top / Bladder
  Distention

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T4 Rectal Cancer 4 Fields
M. Mohiuddin 2006
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Ph III German Trial (CAO/ARO/AIO-94)

• 823 Pts. with cT3/T4 or N randomized to
• Preop 5-FU and Leucovorin / EBRT and TME Surgery
• TME Surgery and Postop 5-FU and Leucovorin / EBRT
  (Stage II/III)

NEJM 2004
8
CAO/ARO/AIO-94 Trial 5 Yr Results
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CAO/ARO/AIO-94 Trial Results
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CAO/ARO/AIO-94 Trial Conclusions

• Preop ChT EBRT vs Postop ChTEBRT
• Improved LC (93)
• Distal Lesions Enhanced Sphincter Preservation
• Less G3/4 Acute (12) / Chronic GI Toxicity (18)

11
PMH Phase 2 Trials Results
12
Fox Chase Phase I Rectal Ca
23 Pts 4 pCR (17)
13
Rectal Ca New Agents with EBRT

• Oral 5-FU Capecitabine (TS inhibition)
• Irinotecan (topo I inhibitor)
• Oxaliplatin (inter intra-strand DNA
  cross-links)
• Anti EGFR Cetuximab, Gefitinib, Erlotinib
• Anti-VEGF Bevacizumab

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RTOG 0012 CPT-11, 5-FU RT Preop

• Phase II, Pts with cT3-T4 Disease Randomized to
• CPT-11 5-FU RT 50.4-54 Gy/1.8 Gy qd
• 5-FU RT 55.2-60 Gy/1.2 Gy bid
• Opened February 2002
• Accrual 100
• Closed January 2003

R
JCO 2006
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RTOG 0012 Results
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CALGB 89901 Phase I/II Oxali, 5-FU RT Preop

5FU 200mg/m2/d RT 50.4Gy Oxali 3060mg/m2/d

• MTD 60 mg/m2, Gr 3 diarrhea
• 21/32 (66) completed 6 cycles
• 26/32 (81) completed 4 cycles

JCO 2006
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CALGB 89901 Results
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RTOG 0247 Cape, RT Oxali or CPT-11 Preop

• Phase II, Pts with cT3-T4 Disease Randomized to
• Oxali (50 d 1, 8, 15, 22 29), Cape (825 BID, 5
  d per w) RT 50.4 Gy/1.8 Gy qd
• CPT-11 (50 d1, 8, 22 29), Cape (600 BID, 5 d
  per w) RT 50.4 Gy/1.8 Gy qd
• Opened February 2004
• Amended March 2005
• Planned Accrual 141

R
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E5201 Preop INT Trial
S U R G
Preop CMT
FOLFOX

Bevacizumab
bolus 5FU LV, CI, or capecitabine
20
NSABP R-04 Preop
Capecitabine (825 mg BID) 50.4 Gy
CI 5-FU (225 mg/m2/d) 50.4 Gy
Oxaliplatin (60 mg/m2 qw)
Stratify T2 vs. T3 M vs. F SP vs. APR
Oxaliplatin (60 mg/m2 qw)
n1460
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Rectal Ca Preoperative Tx

• New Cytotoxic Agents 5-FU during EBRT
• Higher Rates of Acute GI Toxicity
• ? Rates of Late GI and other Toxicity

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Dose-Volume Relationship of Acute SB Toxicity

• 40 Rectal Ca Pts EBRT (50.4 Gy) 5-FU
• 3 D Tx Planning with SB excluding techniques
  bladder distention, prone position, false table
  top.
• Correlate Acute SB Toxicity (Diarrhea/Pain) to
  Volume of SB Irradiated

Baglan et al Int J Rad Onc Biol Phy 2002
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Dose-Volume Relationship of Acute SB Toxicity

• 40 Patients Overall Toxicity Rates
• Grade 0 7/40 (17.5)
• Grade 1 15/40 (37.5)
• Grade 2 8/40 (20)
• Grade 3 10/40 (25)
• No Grade 4/5

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Dose-Volume Relationship of Acute SB Toxicity
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Volume Effect Acute SB Toxicity
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Dose-Volume Relationship of Acute SB Toxicity

• 41 Rectal Ca Pts EBRT (45 Gy) 5-FU/Leucovorin
• All 3 D Tx Planning
• Correlate Acute SB Toxicity (Diarrhea) to Volume
  of SB Irradiated

Tho et al Int J Rad Onc Biol Phy 2006
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Dose-Volume Relationship of Acute SB Toxicity
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Rectal Ca 3-D
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Rectal Ca IMRT
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(No Transcript)
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IMRT in Rectal Ca Reduction in Bowel Dose

• Royal Marsden 5 Patients with Locally Advanced
  Rectal Ca
• Dosimetric Comparison of 3-D Conformal Radiation
  Therapy to IMRT
• No Clinical Data

Int J Rad Onc Biol Phy 2006
32
IMRT Reduction in V of Bowel Irradiated to High
Dose
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IMAT in Rectal Ca Reduction in Bowel Dose

• Ghent Hospital 7 Patients with Locally Advanced
  Rectal Ca (4 Pre and 3 Post)
• Dosimetric Comparison of 3 D Conformal Radiation
  Therapy to IMAT
• No Clinical Data

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IMAT Reduction in V of Bowel Irradiated to High
Dose
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IMRT in Rectal Ca Reduction in Bowel Dose

• 8 Patients (Glasgow) with Locally Advanced Rectal
  Ca
• Dosimetric Comparison of 3-D Conformal Radiation
  Therapy to IMRT
• No Clinical Data

Int J Rad Onc Biol Phy 2006
36
IMRT in Rectal Ca Reduction in Bowel Dose

• With the use of IMRT vs. 3 D CRT Statistically
  significant reduction in Median dose (5.08 Gy)
  and Mean dose (3.15 Gy) to Small Bowel

Int J Rad Onc Biol Phy 2006
37
Conclusions

• GI Toxicity (Acute and Late) Important
  Consideration
• Toxicity will increase with new agents with
  template of EBRT (50 Gy) 5-FU
• Dosimetric plans show reduction in Bowel
  irradiation with IMRT vs. 3 D CRT
• No Clinical Data
• Clear Need for Phase II Trials with IMRT