40
Total Neoadjuvant Therapy for Rectal Cancer Mohamed Abdulla M.D. Prof. of Clinical Oncology Cairo University NEMROCK 21 Annual Meeting Cairo Marriott Hotel & Tower Thursday 17/03/2016
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Total Neoadjuvant Therapy for Rectal Cancer
Mohamed Abdulla MDProf of Clinical Oncology
Cairo University
NEMROCK 21 Annual MeetingCairo Marriott Hotel amp TowerThursday 17032016
Member of Advisory Board Consultant and Speaker forbull Amgen Astellas AstraZeneca Hoffman la Roche Janssen Cilag
Merck Serono Novartis Pfizer Mundipharmabull The content of this presentation does not relate to any product of a
commercial interest
Speaker Disclosures
Principles
Surgery is the cornerstone in management
However
Local Recurrence Following Surgery Alone
Clinical Colorectal Cancer Vol 4 No 4 233-240 2004
Adjuvant Radiation Therapy
Clinical Colorectal Cancer Vol 4 No 4 233-240 2004
Local Recurrence Better Insight
Circumferential Margins
Number Local Recurrence Rate
P
gt 2 mm 987 33 lt 00001
1 ndash 2 mm 100 85 002
lt 1 mm 227 131 008
Int J Radiation Oncology Biol Phys Vol 55 No 5 pp 1311ndash1320 2003
Adjuvant Chemoradiation in Stages II amp III Rectal Cancer
bull GITSGbull NCCTGbull NSABP R-01
N Engl J Med 1986 3151294FJ Natl Cancer Inst 1988 8021 N Engl J Med 1991 324709
Adjuvant Fluoroupyremidine
X 2 monthsCRT ndash 6 Weeks
Adjuvant Fluoroupyremidine
X 2 months
Adjuvant Therapy = 6 months
Neoadjuvant Therapy The German Study A Shifting Concept
N Engl J Med 20043511731-40
German CAOAROAIO-94 11 Years Update
Sauer R et al JCO 2012301926-33
Neoadjuvant Therapy TME Trial ldquoShort Courserdquo 10 Years FU
10 - Year RTh + S S P
LR 5 11 lt 00001
OAS 48 49 086
CCSD 17 22 004
Lancet Oncol 2011 12 575ndash82
CCSD Cumulative Incidence of Cancer Specific Death
Neoadjuvant Therapy TME Trial 10-Year Subset Analysis
Lancet Oncol 2011 12 575ndash82
OAS Benefit
Neoadjuvant TherapyShort versus Long Radiation Therapy Course
Polish Trial Trans-Tasman Radiation Oncology
Group
bull Local Recurrencebull DFSbull Distant Recurrencebull OASbull Severe Late Toxicity
EQUIVALENT
J Clin Oncol 2012 303827Br J Surg 2006 931215
Distal Tumors LC gt SC
LR = 0 12
Radiation + Chemotherapy are MANDATORY in Neoadjuvant Therapy
Gastrointest Cancer Res 149-56 copy2007 by International Society of Gastrointestinal Oncology
Neoadjuvant TherapyThe Use of Capecitabine
The Cancer Journal bull Volume 13 Number 3 MayJune 2007
EQUIVALENT
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
The PETACC-6 RCTltbr gt
Neoadjuvant TherapyAdding Oxaliplatin
ltbr gtPETACC-6 ltbr gtEarly analysis at 31 months shows no major differences between armsltbr gt
Neoadjuvant TherapyAdding Oxaliplatin
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Grade Regression Fibrosis
0 No All cells are viable
1 Minor lt 25 fibrosis
2 Moderate 26 ndash 50nFibrosis
3 Good gt50
4 Total No Viable Cells
Neoadjuvant TherapyTumor Regression Grade
Grade 10 ndash year DM
P 10 ndash Year DFS P
0 - 1 3960005
6300082 - 3 293 736
4 105 895
J Clin Oncol 321554-1562 copy 2014
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
The Cochrane Review Metanalysis Demonstrates DFS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on DFS
The Cochrane Review Metanalysis Demonstrates OS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on OAS
Postop Adjuvant 5FU or FOLFOX for Rectal Cancer The ADORE Trial Randomized Phase II ltbr gt
ltbr gtGerman CAOAROAIO-04 Studyltbr gtAdjuvant FOLFOX has better DFS not OS than 5FU after pre-op ChemoRT
bull Adjuvant Chemotherapy
bull Oxaliplatin ndash Based
Rectal Cancer
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
Total Neoadjuvant ParadigmBrown University Study (CONTRE)
FOLFOX X 8 Courses CRT + Cape TME
Pathologic Grade
Total Number Stage II Stage III
38 7 31
0 (Complete) 13 1 12
1 14 4 10
2 8 1 7
3 3 1 2
bull 35 Pts Completed Treatmentbull pCR = 33
Perez et al ASCO 2014 Abstract 3050
Slide 12
Near total neoadjuvant therapy
Questions Total Neoadjuvant YesNoAdjuvant Cth
YesNoLong versus Short
Course
PROSPECT N1048 is ongoingltbr gtSelective Use of Pelvic XRTltbr gt
Can we Omit Radiation From NAT
MSKCC 07-021 Phase II Trial of Selective Radiation for Rectal Cancer
Can we Omit Radiation From NAT
The Art for Today
bull Clinical Trial whenever possiblebull Careful assessmentbull Chemosensitization by 5-FU or Capecitabine is enoughbull Upfront chemotherapy is appealing Total amp Near
Total NAT should be encourgaed pCRbull TME IS THE STANDARD SURGICAL APPROACH (STAGES
II amp III)bull Postoperative chemotherapy should be discussed and
considered for high risk patients DFS
Thank You
Member of Advisory Board Consultant and Speaker forbull Amgen Astellas AstraZeneca Hoffman la Roche Janssen Cilag
Merck Serono Novartis Pfizer Mundipharmabull The content of this presentation does not relate to any product of a
commercial interest
Speaker Disclosures
Principles
Surgery is the cornerstone in management
However
Local Recurrence Following Surgery Alone
Clinical Colorectal Cancer Vol 4 No 4 233-240 2004
Adjuvant Radiation Therapy
Clinical Colorectal Cancer Vol 4 No 4 233-240 2004
Local Recurrence Better Insight
Circumferential Margins
Number Local Recurrence Rate
P
gt 2 mm 987 33 lt 00001
1 ndash 2 mm 100 85 002
lt 1 mm 227 131 008
Int J Radiation Oncology Biol Phys Vol 55 No 5 pp 1311ndash1320 2003
Adjuvant Chemoradiation in Stages II amp III Rectal Cancer
bull GITSGbull NCCTGbull NSABP R-01
N Engl J Med 1986 3151294FJ Natl Cancer Inst 1988 8021 N Engl J Med 1991 324709
Adjuvant Fluoroupyremidine
X 2 monthsCRT ndash 6 Weeks
Adjuvant Fluoroupyremidine
X 2 months
Adjuvant Therapy = 6 months
Neoadjuvant Therapy The German Study A Shifting Concept
N Engl J Med 20043511731-40
German CAOAROAIO-94 11 Years Update
Sauer R et al JCO 2012301926-33
Neoadjuvant Therapy TME Trial ldquoShort Courserdquo 10 Years FU
10 - Year RTh + S S P
LR 5 11 lt 00001
OAS 48 49 086
CCSD 17 22 004
Lancet Oncol 2011 12 575ndash82
CCSD Cumulative Incidence of Cancer Specific Death
Neoadjuvant Therapy TME Trial 10-Year Subset Analysis
Lancet Oncol 2011 12 575ndash82
OAS Benefit
Neoadjuvant TherapyShort versus Long Radiation Therapy Course
Polish Trial Trans-Tasman Radiation Oncology
Group
bull Local Recurrencebull DFSbull Distant Recurrencebull OASbull Severe Late Toxicity
EQUIVALENT
J Clin Oncol 2012 303827Br J Surg 2006 931215
Distal Tumors LC gt SC
LR = 0 12
Radiation + Chemotherapy are MANDATORY in Neoadjuvant Therapy
Gastrointest Cancer Res 149-56 copy2007 by International Society of Gastrointestinal Oncology
Neoadjuvant TherapyThe Use of Capecitabine
The Cancer Journal bull Volume 13 Number 3 MayJune 2007
EQUIVALENT
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
The PETACC-6 RCTltbr gt
Neoadjuvant TherapyAdding Oxaliplatin
ltbr gtPETACC-6 ltbr gtEarly analysis at 31 months shows no major differences between armsltbr gt
Neoadjuvant TherapyAdding Oxaliplatin
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Grade Regression Fibrosis
0 No All cells are viable
1 Minor lt 25 fibrosis
2 Moderate 26 ndash 50nFibrosis
3 Good gt50
4 Total No Viable Cells
Neoadjuvant TherapyTumor Regression Grade
Grade 10 ndash year DM
P 10 ndash Year DFS P
0 - 1 3960005
6300082 - 3 293 736
4 105 895
J Clin Oncol 321554-1562 copy 2014
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
The Cochrane Review Metanalysis Demonstrates DFS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on DFS
The Cochrane Review Metanalysis Demonstrates OS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on OAS
Postop Adjuvant 5FU or FOLFOX for Rectal Cancer The ADORE Trial Randomized Phase II ltbr gt
ltbr gtGerman CAOAROAIO-04 Studyltbr gtAdjuvant FOLFOX has better DFS not OS than 5FU after pre-op ChemoRT
bull Adjuvant Chemotherapy
bull Oxaliplatin ndash Based
Rectal Cancer
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
Total Neoadjuvant ParadigmBrown University Study (CONTRE)
FOLFOX X 8 Courses CRT + Cape TME
Pathologic Grade
Total Number Stage II Stage III
38 7 31
0 (Complete) 13 1 12
1 14 4 10
2 8 1 7
3 3 1 2
bull 35 Pts Completed Treatmentbull pCR = 33
Perez et al ASCO 2014 Abstract 3050
Slide 12
Near total neoadjuvant therapy
Questions Total Neoadjuvant YesNoAdjuvant Cth
YesNoLong versus Short
Course
PROSPECT N1048 is ongoingltbr gtSelective Use of Pelvic XRTltbr gt
Can we Omit Radiation From NAT
MSKCC 07-021 Phase II Trial of Selective Radiation for Rectal Cancer
Can we Omit Radiation From NAT
The Art for Today
bull Clinical Trial whenever possiblebull Careful assessmentbull Chemosensitization by 5-FU or Capecitabine is enoughbull Upfront chemotherapy is appealing Total amp Near
Total NAT should be encourgaed pCRbull TME IS THE STANDARD SURGICAL APPROACH (STAGES
II amp III)bull Postoperative chemotherapy should be discussed and
considered for high risk patients DFS
Thank You
Principles
Surgery is the cornerstone in management
However
Local Recurrence Following Surgery Alone
Clinical Colorectal Cancer Vol 4 No 4 233-240 2004
Adjuvant Radiation Therapy
Clinical Colorectal Cancer Vol 4 No 4 233-240 2004
Local Recurrence Better Insight
Circumferential Margins
Number Local Recurrence Rate
P
gt 2 mm 987 33 lt 00001
1 ndash 2 mm 100 85 002
lt 1 mm 227 131 008
Int J Radiation Oncology Biol Phys Vol 55 No 5 pp 1311ndash1320 2003
Adjuvant Chemoradiation in Stages II amp III Rectal Cancer
bull GITSGbull NCCTGbull NSABP R-01
N Engl J Med 1986 3151294FJ Natl Cancer Inst 1988 8021 N Engl J Med 1991 324709
Adjuvant Fluoroupyremidine
X 2 monthsCRT ndash 6 Weeks
Adjuvant Fluoroupyremidine
X 2 months
Adjuvant Therapy = 6 months
Neoadjuvant Therapy The German Study A Shifting Concept
N Engl J Med 20043511731-40
German CAOAROAIO-94 11 Years Update
Sauer R et al JCO 2012301926-33
Neoadjuvant Therapy TME Trial ldquoShort Courserdquo 10 Years FU
10 - Year RTh + S S P
LR 5 11 lt 00001
OAS 48 49 086
CCSD 17 22 004
Lancet Oncol 2011 12 575ndash82
CCSD Cumulative Incidence of Cancer Specific Death
Neoadjuvant Therapy TME Trial 10-Year Subset Analysis
Lancet Oncol 2011 12 575ndash82
OAS Benefit
Neoadjuvant TherapyShort versus Long Radiation Therapy Course
Polish Trial Trans-Tasman Radiation Oncology
Group
bull Local Recurrencebull DFSbull Distant Recurrencebull OASbull Severe Late Toxicity
EQUIVALENT
J Clin Oncol 2012 303827Br J Surg 2006 931215
Distal Tumors LC gt SC
LR = 0 12
Radiation + Chemotherapy are MANDATORY in Neoadjuvant Therapy
Gastrointest Cancer Res 149-56 copy2007 by International Society of Gastrointestinal Oncology
Neoadjuvant TherapyThe Use of Capecitabine
The Cancer Journal bull Volume 13 Number 3 MayJune 2007
EQUIVALENT
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
The PETACC-6 RCTltbr gt
Neoadjuvant TherapyAdding Oxaliplatin
ltbr gtPETACC-6 ltbr gtEarly analysis at 31 months shows no major differences between armsltbr gt
Neoadjuvant TherapyAdding Oxaliplatin
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Grade Regression Fibrosis
0 No All cells are viable
1 Minor lt 25 fibrosis
2 Moderate 26 ndash 50nFibrosis
3 Good gt50
4 Total No Viable Cells
Neoadjuvant TherapyTumor Regression Grade
Grade 10 ndash year DM
P 10 ndash Year DFS P
0 - 1 3960005
6300082 - 3 293 736
4 105 895
J Clin Oncol 321554-1562 copy 2014
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
The Cochrane Review Metanalysis Demonstrates DFS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on DFS
The Cochrane Review Metanalysis Demonstrates OS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on OAS
Postop Adjuvant 5FU or FOLFOX for Rectal Cancer The ADORE Trial Randomized Phase II ltbr gt
ltbr gtGerman CAOAROAIO-04 Studyltbr gtAdjuvant FOLFOX has better DFS not OS than 5FU after pre-op ChemoRT
bull Adjuvant Chemotherapy
bull Oxaliplatin ndash Based
Rectal Cancer
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
Total Neoadjuvant ParadigmBrown University Study (CONTRE)
FOLFOX X 8 Courses CRT + Cape TME
Pathologic Grade
Total Number Stage II Stage III
38 7 31
0 (Complete) 13 1 12
1 14 4 10
2 8 1 7
3 3 1 2
bull 35 Pts Completed Treatmentbull pCR = 33
Perez et al ASCO 2014 Abstract 3050
Slide 12
Near total neoadjuvant therapy
Questions Total Neoadjuvant YesNoAdjuvant Cth
YesNoLong versus Short
Course
PROSPECT N1048 is ongoingltbr gtSelective Use of Pelvic XRTltbr gt
Can we Omit Radiation From NAT
MSKCC 07-021 Phase II Trial of Selective Radiation for Rectal Cancer
Can we Omit Radiation From NAT
The Art for Today
bull Clinical Trial whenever possiblebull Careful assessmentbull Chemosensitization by 5-FU or Capecitabine is enoughbull Upfront chemotherapy is appealing Total amp Near
Total NAT should be encourgaed pCRbull TME IS THE STANDARD SURGICAL APPROACH (STAGES
II amp III)bull Postoperative chemotherapy should be discussed and
considered for high risk patients DFS
Thank You
Local Recurrence Following Surgery Alone
Clinical Colorectal Cancer Vol 4 No 4 233-240 2004
Adjuvant Radiation Therapy
Clinical Colorectal Cancer Vol 4 No 4 233-240 2004
Local Recurrence Better Insight
Circumferential Margins
Number Local Recurrence Rate
P
gt 2 mm 987 33 lt 00001
1 ndash 2 mm 100 85 002
lt 1 mm 227 131 008
Int J Radiation Oncology Biol Phys Vol 55 No 5 pp 1311ndash1320 2003
Adjuvant Chemoradiation in Stages II amp III Rectal Cancer
bull GITSGbull NCCTGbull NSABP R-01
N Engl J Med 1986 3151294FJ Natl Cancer Inst 1988 8021 N Engl J Med 1991 324709
Adjuvant Fluoroupyremidine
X 2 monthsCRT ndash 6 Weeks
Adjuvant Fluoroupyremidine
X 2 months
Adjuvant Therapy = 6 months
Neoadjuvant Therapy The German Study A Shifting Concept
N Engl J Med 20043511731-40
German CAOAROAIO-94 11 Years Update
Sauer R et al JCO 2012301926-33
Neoadjuvant Therapy TME Trial ldquoShort Courserdquo 10 Years FU
10 - Year RTh + S S P
LR 5 11 lt 00001
OAS 48 49 086
CCSD 17 22 004
Lancet Oncol 2011 12 575ndash82
CCSD Cumulative Incidence of Cancer Specific Death
Neoadjuvant Therapy TME Trial 10-Year Subset Analysis
Lancet Oncol 2011 12 575ndash82
OAS Benefit
Neoadjuvant TherapyShort versus Long Radiation Therapy Course
Polish Trial Trans-Tasman Radiation Oncology
Group
bull Local Recurrencebull DFSbull Distant Recurrencebull OASbull Severe Late Toxicity
EQUIVALENT
J Clin Oncol 2012 303827Br J Surg 2006 931215
Distal Tumors LC gt SC
LR = 0 12
Radiation + Chemotherapy are MANDATORY in Neoadjuvant Therapy
Gastrointest Cancer Res 149-56 copy2007 by International Society of Gastrointestinal Oncology
Neoadjuvant TherapyThe Use of Capecitabine
The Cancer Journal bull Volume 13 Number 3 MayJune 2007
EQUIVALENT
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
The PETACC-6 RCTltbr gt
Neoadjuvant TherapyAdding Oxaliplatin
ltbr gtPETACC-6 ltbr gtEarly analysis at 31 months shows no major differences between armsltbr gt
Neoadjuvant TherapyAdding Oxaliplatin
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Grade Regression Fibrosis
0 No All cells are viable
1 Minor lt 25 fibrosis
2 Moderate 26 ndash 50nFibrosis
3 Good gt50
4 Total No Viable Cells
Neoadjuvant TherapyTumor Regression Grade
Grade 10 ndash year DM
P 10 ndash Year DFS P
0 - 1 3960005
6300082 - 3 293 736
4 105 895
J Clin Oncol 321554-1562 copy 2014
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
The Cochrane Review Metanalysis Demonstrates DFS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on DFS
The Cochrane Review Metanalysis Demonstrates OS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on OAS
Postop Adjuvant 5FU or FOLFOX for Rectal Cancer The ADORE Trial Randomized Phase II ltbr gt
ltbr gtGerman CAOAROAIO-04 Studyltbr gtAdjuvant FOLFOX has better DFS not OS than 5FU after pre-op ChemoRT
bull Adjuvant Chemotherapy
bull Oxaliplatin ndash Based
Rectal Cancer
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
Total Neoadjuvant ParadigmBrown University Study (CONTRE)
FOLFOX X 8 Courses CRT + Cape TME
Pathologic Grade
Total Number Stage II Stage III
38 7 31
0 (Complete) 13 1 12
1 14 4 10
2 8 1 7
3 3 1 2
bull 35 Pts Completed Treatmentbull pCR = 33
Perez et al ASCO 2014 Abstract 3050
Slide 12
Near total neoadjuvant therapy
Questions Total Neoadjuvant YesNoAdjuvant Cth
YesNoLong versus Short
Course
PROSPECT N1048 is ongoingltbr gtSelective Use of Pelvic XRTltbr gt
Can we Omit Radiation From NAT
MSKCC 07-021 Phase II Trial of Selective Radiation for Rectal Cancer
Can we Omit Radiation From NAT
The Art for Today
bull Clinical Trial whenever possiblebull Careful assessmentbull Chemosensitization by 5-FU or Capecitabine is enoughbull Upfront chemotherapy is appealing Total amp Near
Total NAT should be encourgaed pCRbull TME IS THE STANDARD SURGICAL APPROACH (STAGES
II amp III)bull Postoperative chemotherapy should be discussed and
considered for high risk patients DFS
Thank You
Adjuvant Radiation Therapy
Clinical Colorectal Cancer Vol 4 No 4 233-240 2004
Local Recurrence Better Insight
Circumferential Margins
Number Local Recurrence Rate
P
gt 2 mm 987 33 lt 00001
1 ndash 2 mm 100 85 002
lt 1 mm 227 131 008
Int J Radiation Oncology Biol Phys Vol 55 No 5 pp 1311ndash1320 2003
Adjuvant Chemoradiation in Stages II amp III Rectal Cancer
bull GITSGbull NCCTGbull NSABP R-01
N Engl J Med 1986 3151294FJ Natl Cancer Inst 1988 8021 N Engl J Med 1991 324709
Adjuvant Fluoroupyremidine
X 2 monthsCRT ndash 6 Weeks
Adjuvant Fluoroupyremidine
X 2 months
Adjuvant Therapy = 6 months
Neoadjuvant Therapy The German Study A Shifting Concept
N Engl J Med 20043511731-40
German CAOAROAIO-94 11 Years Update
Sauer R et al JCO 2012301926-33
Neoadjuvant Therapy TME Trial ldquoShort Courserdquo 10 Years FU
10 - Year RTh + S S P
LR 5 11 lt 00001
OAS 48 49 086
CCSD 17 22 004
Lancet Oncol 2011 12 575ndash82
CCSD Cumulative Incidence of Cancer Specific Death
Neoadjuvant Therapy TME Trial 10-Year Subset Analysis
Lancet Oncol 2011 12 575ndash82
OAS Benefit
Neoadjuvant TherapyShort versus Long Radiation Therapy Course
Polish Trial Trans-Tasman Radiation Oncology
Group
bull Local Recurrencebull DFSbull Distant Recurrencebull OASbull Severe Late Toxicity
EQUIVALENT
J Clin Oncol 2012 303827Br J Surg 2006 931215
Distal Tumors LC gt SC
LR = 0 12
Radiation + Chemotherapy are MANDATORY in Neoadjuvant Therapy
Gastrointest Cancer Res 149-56 copy2007 by International Society of Gastrointestinal Oncology
Neoadjuvant TherapyThe Use of Capecitabine
The Cancer Journal bull Volume 13 Number 3 MayJune 2007
EQUIVALENT
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
The PETACC-6 RCTltbr gt
Neoadjuvant TherapyAdding Oxaliplatin
ltbr gtPETACC-6 ltbr gtEarly analysis at 31 months shows no major differences between armsltbr gt
Neoadjuvant TherapyAdding Oxaliplatin
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Grade Regression Fibrosis
0 No All cells are viable
1 Minor lt 25 fibrosis
2 Moderate 26 ndash 50nFibrosis
3 Good gt50
4 Total No Viable Cells
Neoadjuvant TherapyTumor Regression Grade
Grade 10 ndash year DM
P 10 ndash Year DFS P
0 - 1 3960005
6300082 - 3 293 736
4 105 895
J Clin Oncol 321554-1562 copy 2014
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
The Cochrane Review Metanalysis Demonstrates DFS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on DFS
The Cochrane Review Metanalysis Demonstrates OS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on OAS
Postop Adjuvant 5FU or FOLFOX for Rectal Cancer The ADORE Trial Randomized Phase II ltbr gt
ltbr gtGerman CAOAROAIO-04 Studyltbr gtAdjuvant FOLFOX has better DFS not OS than 5FU after pre-op ChemoRT
bull Adjuvant Chemotherapy
bull Oxaliplatin ndash Based
Rectal Cancer
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
Total Neoadjuvant ParadigmBrown University Study (CONTRE)
FOLFOX X 8 Courses CRT + Cape TME
Pathologic Grade
Total Number Stage II Stage III
38 7 31
0 (Complete) 13 1 12
1 14 4 10
2 8 1 7
3 3 1 2
bull 35 Pts Completed Treatmentbull pCR = 33
Perez et al ASCO 2014 Abstract 3050
Slide 12
Near total neoadjuvant therapy
Questions Total Neoadjuvant YesNoAdjuvant Cth
YesNoLong versus Short
Course
PROSPECT N1048 is ongoingltbr gtSelective Use of Pelvic XRTltbr gt
Can we Omit Radiation From NAT
MSKCC 07-021 Phase II Trial of Selective Radiation for Rectal Cancer
Can we Omit Radiation From NAT
The Art for Today
bull Clinical Trial whenever possiblebull Careful assessmentbull Chemosensitization by 5-FU or Capecitabine is enoughbull Upfront chemotherapy is appealing Total amp Near
Total NAT should be encourgaed pCRbull TME IS THE STANDARD SURGICAL APPROACH (STAGES
II amp III)bull Postoperative chemotherapy should be discussed and
considered for high risk patients DFS
Thank You
Local Recurrence Better Insight
Circumferential Margins
Number Local Recurrence Rate
P
gt 2 mm 987 33 lt 00001
1 ndash 2 mm 100 85 002
lt 1 mm 227 131 008
Int J Radiation Oncology Biol Phys Vol 55 No 5 pp 1311ndash1320 2003
Adjuvant Chemoradiation in Stages II amp III Rectal Cancer
bull GITSGbull NCCTGbull NSABP R-01
N Engl J Med 1986 3151294FJ Natl Cancer Inst 1988 8021 N Engl J Med 1991 324709
Adjuvant Fluoroupyremidine
X 2 monthsCRT ndash 6 Weeks
Adjuvant Fluoroupyremidine
X 2 months
Adjuvant Therapy = 6 months
Neoadjuvant Therapy The German Study A Shifting Concept
N Engl J Med 20043511731-40
German CAOAROAIO-94 11 Years Update
Sauer R et al JCO 2012301926-33
Neoadjuvant Therapy TME Trial ldquoShort Courserdquo 10 Years FU
10 - Year RTh + S S P
LR 5 11 lt 00001
OAS 48 49 086
CCSD 17 22 004
Lancet Oncol 2011 12 575ndash82
CCSD Cumulative Incidence of Cancer Specific Death
Neoadjuvant Therapy TME Trial 10-Year Subset Analysis
Lancet Oncol 2011 12 575ndash82
OAS Benefit
Neoadjuvant TherapyShort versus Long Radiation Therapy Course
Polish Trial Trans-Tasman Radiation Oncology
Group
bull Local Recurrencebull DFSbull Distant Recurrencebull OASbull Severe Late Toxicity
EQUIVALENT
J Clin Oncol 2012 303827Br J Surg 2006 931215
Distal Tumors LC gt SC
LR = 0 12
Radiation + Chemotherapy are MANDATORY in Neoadjuvant Therapy
Gastrointest Cancer Res 149-56 copy2007 by International Society of Gastrointestinal Oncology
Neoadjuvant TherapyThe Use of Capecitabine
The Cancer Journal bull Volume 13 Number 3 MayJune 2007
EQUIVALENT
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
The PETACC-6 RCTltbr gt
Neoadjuvant TherapyAdding Oxaliplatin
ltbr gtPETACC-6 ltbr gtEarly analysis at 31 months shows no major differences between armsltbr gt
Neoadjuvant TherapyAdding Oxaliplatin
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Grade Regression Fibrosis
0 No All cells are viable
1 Minor lt 25 fibrosis
2 Moderate 26 ndash 50nFibrosis
3 Good gt50
4 Total No Viable Cells
Neoadjuvant TherapyTumor Regression Grade
Grade 10 ndash year DM
P 10 ndash Year DFS P
0 - 1 3960005
6300082 - 3 293 736
4 105 895
J Clin Oncol 321554-1562 copy 2014
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
The Cochrane Review Metanalysis Demonstrates DFS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on DFS
The Cochrane Review Metanalysis Demonstrates OS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on OAS
Postop Adjuvant 5FU or FOLFOX for Rectal Cancer The ADORE Trial Randomized Phase II ltbr gt
ltbr gtGerman CAOAROAIO-04 Studyltbr gtAdjuvant FOLFOX has better DFS not OS than 5FU after pre-op ChemoRT
bull Adjuvant Chemotherapy
bull Oxaliplatin ndash Based
Rectal Cancer
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
Total Neoadjuvant ParadigmBrown University Study (CONTRE)
FOLFOX X 8 Courses CRT + Cape TME
Pathologic Grade
Total Number Stage II Stage III
38 7 31
0 (Complete) 13 1 12
1 14 4 10
2 8 1 7
3 3 1 2
bull 35 Pts Completed Treatmentbull pCR = 33
Perez et al ASCO 2014 Abstract 3050
Slide 12
Near total neoadjuvant therapy
Questions Total Neoadjuvant YesNoAdjuvant Cth
YesNoLong versus Short
Course
PROSPECT N1048 is ongoingltbr gtSelective Use of Pelvic XRTltbr gt
Can we Omit Radiation From NAT
MSKCC 07-021 Phase II Trial of Selective Radiation for Rectal Cancer
Can we Omit Radiation From NAT
The Art for Today
bull Clinical Trial whenever possiblebull Careful assessmentbull Chemosensitization by 5-FU or Capecitabine is enoughbull Upfront chemotherapy is appealing Total amp Near
Total NAT should be encourgaed pCRbull TME IS THE STANDARD SURGICAL APPROACH (STAGES
II amp III)bull Postoperative chemotherapy should be discussed and
considered for high risk patients DFS
Thank You
Adjuvant Chemoradiation in Stages II amp III Rectal Cancer
bull GITSGbull NCCTGbull NSABP R-01
N Engl J Med 1986 3151294FJ Natl Cancer Inst 1988 8021 N Engl J Med 1991 324709
Adjuvant Fluoroupyremidine
X 2 monthsCRT ndash 6 Weeks
Adjuvant Fluoroupyremidine
X 2 months
Adjuvant Therapy = 6 months
Neoadjuvant Therapy The German Study A Shifting Concept
N Engl J Med 20043511731-40
German CAOAROAIO-94 11 Years Update
Sauer R et al JCO 2012301926-33
Neoadjuvant Therapy TME Trial ldquoShort Courserdquo 10 Years FU
10 - Year RTh + S S P
LR 5 11 lt 00001
OAS 48 49 086
CCSD 17 22 004
Lancet Oncol 2011 12 575ndash82
CCSD Cumulative Incidence of Cancer Specific Death
Neoadjuvant Therapy TME Trial 10-Year Subset Analysis
Lancet Oncol 2011 12 575ndash82
OAS Benefit
Neoadjuvant TherapyShort versus Long Radiation Therapy Course
Polish Trial Trans-Tasman Radiation Oncology
Group
bull Local Recurrencebull DFSbull Distant Recurrencebull OASbull Severe Late Toxicity
EQUIVALENT
J Clin Oncol 2012 303827Br J Surg 2006 931215
Distal Tumors LC gt SC
LR = 0 12
Radiation + Chemotherapy are MANDATORY in Neoadjuvant Therapy
Gastrointest Cancer Res 149-56 copy2007 by International Society of Gastrointestinal Oncology
Neoadjuvant TherapyThe Use of Capecitabine
The Cancer Journal bull Volume 13 Number 3 MayJune 2007
EQUIVALENT
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
The PETACC-6 RCTltbr gt
Neoadjuvant TherapyAdding Oxaliplatin
ltbr gtPETACC-6 ltbr gtEarly analysis at 31 months shows no major differences between armsltbr gt
Neoadjuvant TherapyAdding Oxaliplatin
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Grade Regression Fibrosis
0 No All cells are viable
1 Minor lt 25 fibrosis
2 Moderate 26 ndash 50nFibrosis
3 Good gt50
4 Total No Viable Cells
Neoadjuvant TherapyTumor Regression Grade
Grade 10 ndash year DM
P 10 ndash Year DFS P
0 - 1 3960005
6300082 - 3 293 736
4 105 895
J Clin Oncol 321554-1562 copy 2014
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
The Cochrane Review Metanalysis Demonstrates DFS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on DFS
The Cochrane Review Metanalysis Demonstrates OS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on OAS
Postop Adjuvant 5FU or FOLFOX for Rectal Cancer The ADORE Trial Randomized Phase II ltbr gt
ltbr gtGerman CAOAROAIO-04 Studyltbr gtAdjuvant FOLFOX has better DFS not OS than 5FU after pre-op ChemoRT
bull Adjuvant Chemotherapy
bull Oxaliplatin ndash Based
Rectal Cancer
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
Total Neoadjuvant ParadigmBrown University Study (CONTRE)
FOLFOX X 8 Courses CRT + Cape TME
Pathologic Grade
Total Number Stage II Stage III
38 7 31
0 (Complete) 13 1 12
1 14 4 10
2 8 1 7
3 3 1 2
bull 35 Pts Completed Treatmentbull pCR = 33
Perez et al ASCO 2014 Abstract 3050
Slide 12
Near total neoadjuvant therapy
Questions Total Neoadjuvant YesNoAdjuvant Cth
YesNoLong versus Short
Course
PROSPECT N1048 is ongoingltbr gtSelective Use of Pelvic XRTltbr gt
Can we Omit Radiation From NAT
MSKCC 07-021 Phase II Trial of Selective Radiation for Rectal Cancer
Can we Omit Radiation From NAT
The Art for Today
bull Clinical Trial whenever possiblebull Careful assessmentbull Chemosensitization by 5-FU or Capecitabine is enoughbull Upfront chemotherapy is appealing Total amp Near
Total NAT should be encourgaed pCRbull TME IS THE STANDARD SURGICAL APPROACH (STAGES
II amp III)bull Postoperative chemotherapy should be discussed and
considered for high risk patients DFS
Thank You
Neoadjuvant Therapy The German Study A Shifting Concept
N Engl J Med 20043511731-40
German CAOAROAIO-94 11 Years Update
Sauer R et al JCO 2012301926-33
Neoadjuvant Therapy TME Trial ldquoShort Courserdquo 10 Years FU
10 - Year RTh + S S P
LR 5 11 lt 00001
OAS 48 49 086
CCSD 17 22 004
Lancet Oncol 2011 12 575ndash82
CCSD Cumulative Incidence of Cancer Specific Death
Neoadjuvant Therapy TME Trial 10-Year Subset Analysis
Lancet Oncol 2011 12 575ndash82
OAS Benefit
Neoadjuvant TherapyShort versus Long Radiation Therapy Course
Polish Trial Trans-Tasman Radiation Oncology
Group
bull Local Recurrencebull DFSbull Distant Recurrencebull OASbull Severe Late Toxicity
EQUIVALENT
J Clin Oncol 2012 303827Br J Surg 2006 931215
Distal Tumors LC gt SC
LR = 0 12
Radiation + Chemotherapy are MANDATORY in Neoadjuvant Therapy
Gastrointest Cancer Res 149-56 copy2007 by International Society of Gastrointestinal Oncology
Neoadjuvant TherapyThe Use of Capecitabine
The Cancer Journal bull Volume 13 Number 3 MayJune 2007
EQUIVALENT
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
The PETACC-6 RCTltbr gt
Neoadjuvant TherapyAdding Oxaliplatin
ltbr gtPETACC-6 ltbr gtEarly analysis at 31 months shows no major differences between armsltbr gt
Neoadjuvant TherapyAdding Oxaliplatin
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Grade Regression Fibrosis
0 No All cells are viable
1 Minor lt 25 fibrosis
2 Moderate 26 ndash 50nFibrosis
3 Good gt50
4 Total No Viable Cells
Neoadjuvant TherapyTumor Regression Grade
Grade 10 ndash year DM
P 10 ndash Year DFS P
0 - 1 3960005
6300082 - 3 293 736
4 105 895
J Clin Oncol 321554-1562 copy 2014
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
The Cochrane Review Metanalysis Demonstrates DFS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on DFS
The Cochrane Review Metanalysis Demonstrates OS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on OAS
Postop Adjuvant 5FU or FOLFOX for Rectal Cancer The ADORE Trial Randomized Phase II ltbr gt
ltbr gtGerman CAOAROAIO-04 Studyltbr gtAdjuvant FOLFOX has better DFS not OS than 5FU after pre-op ChemoRT
bull Adjuvant Chemotherapy
bull Oxaliplatin ndash Based
Rectal Cancer
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
Total Neoadjuvant ParadigmBrown University Study (CONTRE)
FOLFOX X 8 Courses CRT + Cape TME
Pathologic Grade
Total Number Stage II Stage III
38 7 31
0 (Complete) 13 1 12
1 14 4 10
2 8 1 7
3 3 1 2
bull 35 Pts Completed Treatmentbull pCR = 33
Perez et al ASCO 2014 Abstract 3050
Slide 12
Near total neoadjuvant therapy
Questions Total Neoadjuvant YesNoAdjuvant Cth
YesNoLong versus Short
Course
PROSPECT N1048 is ongoingltbr gtSelective Use of Pelvic XRTltbr gt
Can we Omit Radiation From NAT
MSKCC 07-021 Phase II Trial of Selective Radiation for Rectal Cancer
Can we Omit Radiation From NAT
The Art for Today
bull Clinical Trial whenever possiblebull Careful assessmentbull Chemosensitization by 5-FU or Capecitabine is enoughbull Upfront chemotherapy is appealing Total amp Near
Total NAT should be encourgaed pCRbull TME IS THE STANDARD SURGICAL APPROACH (STAGES
II amp III)bull Postoperative chemotherapy should be discussed and
considered for high risk patients DFS
Thank You
German CAOAROAIO-94 11 Years Update
Sauer R et al JCO 2012301926-33
Neoadjuvant Therapy TME Trial ldquoShort Courserdquo 10 Years FU
10 - Year RTh + S S P
LR 5 11 lt 00001
OAS 48 49 086
CCSD 17 22 004
Lancet Oncol 2011 12 575ndash82
CCSD Cumulative Incidence of Cancer Specific Death
Neoadjuvant Therapy TME Trial 10-Year Subset Analysis
Lancet Oncol 2011 12 575ndash82
OAS Benefit
Neoadjuvant TherapyShort versus Long Radiation Therapy Course
Polish Trial Trans-Tasman Radiation Oncology
Group
bull Local Recurrencebull DFSbull Distant Recurrencebull OASbull Severe Late Toxicity
EQUIVALENT
J Clin Oncol 2012 303827Br J Surg 2006 931215
Distal Tumors LC gt SC
LR = 0 12
Radiation + Chemotherapy are MANDATORY in Neoadjuvant Therapy
Gastrointest Cancer Res 149-56 copy2007 by International Society of Gastrointestinal Oncology
Neoadjuvant TherapyThe Use of Capecitabine
The Cancer Journal bull Volume 13 Number 3 MayJune 2007
EQUIVALENT
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
The PETACC-6 RCTltbr gt
Neoadjuvant TherapyAdding Oxaliplatin
ltbr gtPETACC-6 ltbr gtEarly analysis at 31 months shows no major differences between armsltbr gt
Neoadjuvant TherapyAdding Oxaliplatin
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Grade Regression Fibrosis
0 No All cells are viable
1 Minor lt 25 fibrosis
2 Moderate 26 ndash 50nFibrosis
3 Good gt50
4 Total No Viable Cells
Neoadjuvant TherapyTumor Regression Grade
Grade 10 ndash year DM
P 10 ndash Year DFS P
0 - 1 3960005
6300082 - 3 293 736
4 105 895
J Clin Oncol 321554-1562 copy 2014
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
The Cochrane Review Metanalysis Demonstrates DFS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on DFS
The Cochrane Review Metanalysis Demonstrates OS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on OAS
Postop Adjuvant 5FU or FOLFOX for Rectal Cancer The ADORE Trial Randomized Phase II ltbr gt
ltbr gtGerman CAOAROAIO-04 Studyltbr gtAdjuvant FOLFOX has better DFS not OS than 5FU after pre-op ChemoRT
bull Adjuvant Chemotherapy
bull Oxaliplatin ndash Based
Rectal Cancer
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
Total Neoadjuvant ParadigmBrown University Study (CONTRE)
FOLFOX X 8 Courses CRT + Cape TME
Pathologic Grade
Total Number Stage II Stage III
38 7 31
0 (Complete) 13 1 12
1 14 4 10
2 8 1 7
3 3 1 2
bull 35 Pts Completed Treatmentbull pCR = 33
Perez et al ASCO 2014 Abstract 3050
Slide 12
Near total neoadjuvant therapy
Questions Total Neoadjuvant YesNoAdjuvant Cth
YesNoLong versus Short
Course
PROSPECT N1048 is ongoingltbr gtSelective Use of Pelvic XRTltbr gt
Can we Omit Radiation From NAT
MSKCC 07-021 Phase II Trial of Selective Radiation for Rectal Cancer
Can we Omit Radiation From NAT
The Art for Today
bull Clinical Trial whenever possiblebull Careful assessmentbull Chemosensitization by 5-FU or Capecitabine is enoughbull Upfront chemotherapy is appealing Total amp Near
Total NAT should be encourgaed pCRbull TME IS THE STANDARD SURGICAL APPROACH (STAGES
II amp III)bull Postoperative chemotherapy should be discussed and
considered for high risk patients DFS
Thank You
Neoadjuvant Therapy TME Trial ldquoShort Courserdquo 10 Years FU
10 - Year RTh + S S P
LR 5 11 lt 00001
OAS 48 49 086
CCSD 17 22 004
Lancet Oncol 2011 12 575ndash82
CCSD Cumulative Incidence of Cancer Specific Death
Neoadjuvant Therapy TME Trial 10-Year Subset Analysis
Lancet Oncol 2011 12 575ndash82
OAS Benefit
Neoadjuvant TherapyShort versus Long Radiation Therapy Course
Polish Trial Trans-Tasman Radiation Oncology
Group
bull Local Recurrencebull DFSbull Distant Recurrencebull OASbull Severe Late Toxicity
EQUIVALENT
J Clin Oncol 2012 303827Br J Surg 2006 931215
Distal Tumors LC gt SC
LR = 0 12
Radiation + Chemotherapy are MANDATORY in Neoadjuvant Therapy
Gastrointest Cancer Res 149-56 copy2007 by International Society of Gastrointestinal Oncology
Neoadjuvant TherapyThe Use of Capecitabine
The Cancer Journal bull Volume 13 Number 3 MayJune 2007
EQUIVALENT
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
The PETACC-6 RCTltbr gt
Neoadjuvant TherapyAdding Oxaliplatin
ltbr gtPETACC-6 ltbr gtEarly analysis at 31 months shows no major differences between armsltbr gt
Neoadjuvant TherapyAdding Oxaliplatin
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Grade Regression Fibrosis
0 No All cells are viable
1 Minor lt 25 fibrosis
2 Moderate 26 ndash 50nFibrosis
3 Good gt50
4 Total No Viable Cells
Neoadjuvant TherapyTumor Regression Grade
Grade 10 ndash year DM
P 10 ndash Year DFS P
0 - 1 3960005
6300082 - 3 293 736
4 105 895
J Clin Oncol 321554-1562 copy 2014
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
The Cochrane Review Metanalysis Demonstrates DFS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on DFS
The Cochrane Review Metanalysis Demonstrates OS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on OAS
Postop Adjuvant 5FU or FOLFOX for Rectal Cancer The ADORE Trial Randomized Phase II ltbr gt
ltbr gtGerman CAOAROAIO-04 Studyltbr gtAdjuvant FOLFOX has better DFS not OS than 5FU after pre-op ChemoRT
bull Adjuvant Chemotherapy
bull Oxaliplatin ndash Based
Rectal Cancer
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
Total Neoadjuvant ParadigmBrown University Study (CONTRE)
FOLFOX X 8 Courses CRT + Cape TME
Pathologic Grade
Total Number Stage II Stage III
38 7 31
0 (Complete) 13 1 12
1 14 4 10
2 8 1 7
3 3 1 2
bull 35 Pts Completed Treatmentbull pCR = 33
Perez et al ASCO 2014 Abstract 3050
Slide 12
Near total neoadjuvant therapy
Questions Total Neoadjuvant YesNoAdjuvant Cth
YesNoLong versus Short
Course
PROSPECT N1048 is ongoingltbr gtSelective Use of Pelvic XRTltbr gt
Can we Omit Radiation From NAT
MSKCC 07-021 Phase II Trial of Selective Radiation for Rectal Cancer
Can we Omit Radiation From NAT
The Art for Today
bull Clinical Trial whenever possiblebull Careful assessmentbull Chemosensitization by 5-FU or Capecitabine is enoughbull Upfront chemotherapy is appealing Total amp Near
Total NAT should be encourgaed pCRbull TME IS THE STANDARD SURGICAL APPROACH (STAGES
II amp III)bull Postoperative chemotherapy should be discussed and
considered for high risk patients DFS
Thank You
Neoadjuvant Therapy TME Trial 10-Year Subset Analysis
Lancet Oncol 2011 12 575ndash82
OAS Benefit
Neoadjuvant TherapyShort versus Long Radiation Therapy Course
Polish Trial Trans-Tasman Radiation Oncology
Group
bull Local Recurrencebull DFSbull Distant Recurrencebull OASbull Severe Late Toxicity
EQUIVALENT
J Clin Oncol 2012 303827Br J Surg 2006 931215
Distal Tumors LC gt SC
LR = 0 12
Radiation + Chemotherapy are MANDATORY in Neoadjuvant Therapy
Gastrointest Cancer Res 149-56 copy2007 by International Society of Gastrointestinal Oncology
Neoadjuvant TherapyThe Use of Capecitabine
The Cancer Journal bull Volume 13 Number 3 MayJune 2007
EQUIVALENT
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
The PETACC-6 RCTltbr gt
Neoadjuvant TherapyAdding Oxaliplatin
ltbr gtPETACC-6 ltbr gtEarly analysis at 31 months shows no major differences between armsltbr gt
Neoadjuvant TherapyAdding Oxaliplatin
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Grade Regression Fibrosis
0 No All cells are viable
1 Minor lt 25 fibrosis
2 Moderate 26 ndash 50nFibrosis
3 Good gt50
4 Total No Viable Cells
Neoadjuvant TherapyTumor Regression Grade
Grade 10 ndash year DM
P 10 ndash Year DFS P
0 - 1 3960005
6300082 - 3 293 736
4 105 895
J Clin Oncol 321554-1562 copy 2014
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
The Cochrane Review Metanalysis Demonstrates DFS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on DFS
The Cochrane Review Metanalysis Demonstrates OS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on OAS
Postop Adjuvant 5FU or FOLFOX for Rectal Cancer The ADORE Trial Randomized Phase II ltbr gt
ltbr gtGerman CAOAROAIO-04 Studyltbr gtAdjuvant FOLFOX has better DFS not OS than 5FU after pre-op ChemoRT
bull Adjuvant Chemotherapy
bull Oxaliplatin ndash Based
Rectal Cancer
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
Total Neoadjuvant ParadigmBrown University Study (CONTRE)
FOLFOX X 8 Courses CRT + Cape TME
Pathologic Grade
Total Number Stage II Stage III
38 7 31
0 (Complete) 13 1 12
1 14 4 10
2 8 1 7
3 3 1 2
bull 35 Pts Completed Treatmentbull pCR = 33
Perez et al ASCO 2014 Abstract 3050
Slide 12
Near total neoadjuvant therapy
Questions Total Neoadjuvant YesNoAdjuvant Cth
YesNoLong versus Short
Course
PROSPECT N1048 is ongoingltbr gtSelective Use of Pelvic XRTltbr gt
Can we Omit Radiation From NAT
MSKCC 07-021 Phase II Trial of Selective Radiation for Rectal Cancer
Can we Omit Radiation From NAT
The Art for Today
bull Clinical Trial whenever possiblebull Careful assessmentbull Chemosensitization by 5-FU or Capecitabine is enoughbull Upfront chemotherapy is appealing Total amp Near
Total NAT should be encourgaed pCRbull TME IS THE STANDARD SURGICAL APPROACH (STAGES
II amp III)bull Postoperative chemotherapy should be discussed and
considered for high risk patients DFS
Thank You
Neoadjuvant TherapyShort versus Long Radiation Therapy Course
Polish Trial Trans-Tasman Radiation Oncology
Group
bull Local Recurrencebull DFSbull Distant Recurrencebull OASbull Severe Late Toxicity
EQUIVALENT
J Clin Oncol 2012 303827Br J Surg 2006 931215
Distal Tumors LC gt SC
LR = 0 12
Radiation + Chemotherapy are MANDATORY in Neoadjuvant Therapy
Gastrointest Cancer Res 149-56 copy2007 by International Society of Gastrointestinal Oncology
Neoadjuvant TherapyThe Use of Capecitabine
The Cancer Journal bull Volume 13 Number 3 MayJune 2007
EQUIVALENT
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
The PETACC-6 RCTltbr gt
Neoadjuvant TherapyAdding Oxaliplatin
ltbr gtPETACC-6 ltbr gtEarly analysis at 31 months shows no major differences between armsltbr gt
Neoadjuvant TherapyAdding Oxaliplatin
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Grade Regression Fibrosis
0 No All cells are viable
1 Minor lt 25 fibrosis
2 Moderate 26 ndash 50nFibrosis
3 Good gt50
4 Total No Viable Cells
Neoadjuvant TherapyTumor Regression Grade
Grade 10 ndash year DM
P 10 ndash Year DFS P
0 - 1 3960005
6300082 - 3 293 736
4 105 895
J Clin Oncol 321554-1562 copy 2014
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
The Cochrane Review Metanalysis Demonstrates DFS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on DFS
The Cochrane Review Metanalysis Demonstrates OS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on OAS
Postop Adjuvant 5FU or FOLFOX for Rectal Cancer The ADORE Trial Randomized Phase II ltbr gt
ltbr gtGerman CAOAROAIO-04 Studyltbr gtAdjuvant FOLFOX has better DFS not OS than 5FU after pre-op ChemoRT
bull Adjuvant Chemotherapy
bull Oxaliplatin ndash Based
Rectal Cancer
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
Total Neoadjuvant ParadigmBrown University Study (CONTRE)
FOLFOX X 8 Courses CRT + Cape TME
Pathologic Grade
Total Number Stage II Stage III
38 7 31
0 (Complete) 13 1 12
1 14 4 10
2 8 1 7
3 3 1 2
bull 35 Pts Completed Treatmentbull pCR = 33
Perez et al ASCO 2014 Abstract 3050
Slide 12
Near total neoadjuvant therapy
Questions Total Neoadjuvant YesNoAdjuvant Cth
YesNoLong versus Short
Course
PROSPECT N1048 is ongoingltbr gtSelective Use of Pelvic XRTltbr gt
Can we Omit Radiation From NAT
MSKCC 07-021 Phase II Trial of Selective Radiation for Rectal Cancer
Can we Omit Radiation From NAT
The Art for Today
bull Clinical Trial whenever possiblebull Careful assessmentbull Chemosensitization by 5-FU or Capecitabine is enoughbull Upfront chemotherapy is appealing Total amp Near
Total NAT should be encourgaed pCRbull TME IS THE STANDARD SURGICAL APPROACH (STAGES
II amp III)bull Postoperative chemotherapy should be discussed and
considered for high risk patients DFS
Thank You
Radiation + Chemotherapy are MANDATORY in Neoadjuvant Therapy
Gastrointest Cancer Res 149-56 copy2007 by International Society of Gastrointestinal Oncology
Neoadjuvant TherapyThe Use of Capecitabine
The Cancer Journal bull Volume 13 Number 3 MayJune 2007
EQUIVALENT
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
The PETACC-6 RCTltbr gt
Neoadjuvant TherapyAdding Oxaliplatin
ltbr gtPETACC-6 ltbr gtEarly analysis at 31 months shows no major differences between armsltbr gt
Neoadjuvant TherapyAdding Oxaliplatin
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Grade Regression Fibrosis
0 No All cells are viable
1 Minor lt 25 fibrosis
2 Moderate 26 ndash 50nFibrosis
3 Good gt50
4 Total No Viable Cells
Neoadjuvant TherapyTumor Regression Grade
Grade 10 ndash year DM
P 10 ndash Year DFS P
0 - 1 3960005
6300082 - 3 293 736
4 105 895
J Clin Oncol 321554-1562 copy 2014
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
The Cochrane Review Metanalysis Demonstrates DFS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on DFS
The Cochrane Review Metanalysis Demonstrates OS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on OAS
Postop Adjuvant 5FU or FOLFOX for Rectal Cancer The ADORE Trial Randomized Phase II ltbr gt
ltbr gtGerman CAOAROAIO-04 Studyltbr gtAdjuvant FOLFOX has better DFS not OS than 5FU after pre-op ChemoRT
bull Adjuvant Chemotherapy
bull Oxaliplatin ndash Based
Rectal Cancer
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
Total Neoadjuvant ParadigmBrown University Study (CONTRE)
FOLFOX X 8 Courses CRT + Cape TME
Pathologic Grade
Total Number Stage II Stage III
38 7 31
0 (Complete) 13 1 12
1 14 4 10
2 8 1 7
3 3 1 2
bull 35 Pts Completed Treatmentbull pCR = 33
Perez et al ASCO 2014 Abstract 3050
Slide 12
Near total neoadjuvant therapy
Questions Total Neoadjuvant YesNoAdjuvant Cth
YesNoLong versus Short
Course
PROSPECT N1048 is ongoingltbr gtSelective Use of Pelvic XRTltbr gt
Can we Omit Radiation From NAT
MSKCC 07-021 Phase II Trial of Selective Radiation for Rectal Cancer
Can we Omit Radiation From NAT
The Art for Today
bull Clinical Trial whenever possiblebull Careful assessmentbull Chemosensitization by 5-FU or Capecitabine is enoughbull Upfront chemotherapy is appealing Total amp Near
Total NAT should be encourgaed pCRbull TME IS THE STANDARD SURGICAL APPROACH (STAGES
II amp III)bull Postoperative chemotherapy should be discussed and
considered for high risk patients DFS
Thank You
Neoadjuvant TherapyThe Use of Capecitabine
The Cancer Journal bull Volume 13 Number 3 MayJune 2007
EQUIVALENT
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
The PETACC-6 RCTltbr gt
Neoadjuvant TherapyAdding Oxaliplatin
ltbr gtPETACC-6 ltbr gtEarly analysis at 31 months shows no major differences between armsltbr gt
Neoadjuvant TherapyAdding Oxaliplatin
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Grade Regression Fibrosis
0 No All cells are viable
1 Minor lt 25 fibrosis
2 Moderate 26 ndash 50nFibrosis
3 Good gt50
4 Total No Viable Cells
Neoadjuvant TherapyTumor Regression Grade
Grade 10 ndash year DM
P 10 ndash Year DFS P
0 - 1 3960005
6300082 - 3 293 736
4 105 895
J Clin Oncol 321554-1562 copy 2014
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
The Cochrane Review Metanalysis Demonstrates DFS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on DFS
The Cochrane Review Metanalysis Demonstrates OS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on OAS
Postop Adjuvant 5FU or FOLFOX for Rectal Cancer The ADORE Trial Randomized Phase II ltbr gt
ltbr gtGerman CAOAROAIO-04 Studyltbr gtAdjuvant FOLFOX has better DFS not OS than 5FU after pre-op ChemoRT
bull Adjuvant Chemotherapy
bull Oxaliplatin ndash Based
Rectal Cancer
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
Total Neoadjuvant ParadigmBrown University Study (CONTRE)
FOLFOX X 8 Courses CRT + Cape TME
Pathologic Grade
Total Number Stage II Stage III
38 7 31
0 (Complete) 13 1 12
1 14 4 10
2 8 1 7
3 3 1 2
bull 35 Pts Completed Treatmentbull pCR = 33
Perez et al ASCO 2014 Abstract 3050
Slide 12
Near total neoadjuvant therapy
Questions Total Neoadjuvant YesNoAdjuvant Cth
YesNoLong versus Short
Course
PROSPECT N1048 is ongoingltbr gtSelective Use of Pelvic XRTltbr gt
Can we Omit Radiation From NAT
MSKCC 07-021 Phase II Trial of Selective Radiation for Rectal Cancer
Can we Omit Radiation From NAT
The Art for Today
bull Clinical Trial whenever possiblebull Careful assessmentbull Chemosensitization by 5-FU or Capecitabine is enoughbull Upfront chemotherapy is appealing Total amp Near
Total NAT should be encourgaed pCRbull TME IS THE STANDARD SURGICAL APPROACH (STAGES
II amp III)bull Postoperative chemotherapy should be discussed and
considered for high risk patients DFS
Thank You
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
The PETACC-6 RCTltbr gt
Neoadjuvant TherapyAdding Oxaliplatin
ltbr gtPETACC-6 ltbr gtEarly analysis at 31 months shows no major differences between armsltbr gt
Neoadjuvant TherapyAdding Oxaliplatin
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Grade Regression Fibrosis
0 No All cells are viable
1 Minor lt 25 fibrosis
2 Moderate 26 ndash 50nFibrosis
3 Good gt50
4 Total No Viable Cells
Neoadjuvant TherapyTumor Regression Grade
Grade 10 ndash year DM
P 10 ndash Year DFS P
0 - 1 3960005
6300082 - 3 293 736
4 105 895
J Clin Oncol 321554-1562 copy 2014
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
The Cochrane Review Metanalysis Demonstrates DFS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on DFS
The Cochrane Review Metanalysis Demonstrates OS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on OAS
Postop Adjuvant 5FU or FOLFOX for Rectal Cancer The ADORE Trial Randomized Phase II ltbr gt
ltbr gtGerman CAOAROAIO-04 Studyltbr gtAdjuvant FOLFOX has better DFS not OS than 5FU after pre-op ChemoRT
bull Adjuvant Chemotherapy
bull Oxaliplatin ndash Based
Rectal Cancer
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
Total Neoadjuvant ParadigmBrown University Study (CONTRE)
FOLFOX X 8 Courses CRT + Cape TME
Pathologic Grade
Total Number Stage II Stage III
38 7 31
0 (Complete) 13 1 12
1 14 4 10
2 8 1 7
3 3 1 2
bull 35 Pts Completed Treatmentbull pCR = 33
Perez et al ASCO 2014 Abstract 3050
Slide 12
Near total neoadjuvant therapy
Questions Total Neoadjuvant YesNoAdjuvant Cth
YesNoLong versus Short
Course
PROSPECT N1048 is ongoingltbr gtSelective Use of Pelvic XRTltbr gt
Can we Omit Radiation From NAT
MSKCC 07-021 Phase II Trial of Selective Radiation for Rectal Cancer
Can we Omit Radiation From NAT
The Art for Today
bull Clinical Trial whenever possiblebull Careful assessmentbull Chemosensitization by 5-FU or Capecitabine is enoughbull Upfront chemotherapy is appealing Total amp Near
Total NAT should be encourgaed pCRbull TME IS THE STANDARD SURGICAL APPROACH (STAGES
II amp III)bull Postoperative chemotherapy should be discussed and
considered for high risk patients DFS
Thank You
The PETACC-6 RCTltbr gt
Neoadjuvant TherapyAdding Oxaliplatin
ltbr gtPETACC-6 ltbr gtEarly analysis at 31 months shows no major differences between armsltbr gt
Neoadjuvant TherapyAdding Oxaliplatin
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Grade Regression Fibrosis
0 No All cells are viable
1 Minor lt 25 fibrosis
2 Moderate 26 ndash 50nFibrosis
3 Good gt50
4 Total No Viable Cells
Neoadjuvant TherapyTumor Regression Grade
Grade 10 ndash year DM
P 10 ndash Year DFS P
0 - 1 3960005
6300082 - 3 293 736
4 105 895
J Clin Oncol 321554-1562 copy 2014
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
The Cochrane Review Metanalysis Demonstrates DFS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on DFS
The Cochrane Review Metanalysis Demonstrates OS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on OAS
Postop Adjuvant 5FU or FOLFOX for Rectal Cancer The ADORE Trial Randomized Phase II ltbr gt
ltbr gtGerman CAOAROAIO-04 Studyltbr gtAdjuvant FOLFOX has better DFS not OS than 5FU after pre-op ChemoRT
bull Adjuvant Chemotherapy
bull Oxaliplatin ndash Based
Rectal Cancer
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
Total Neoadjuvant ParadigmBrown University Study (CONTRE)
FOLFOX X 8 Courses CRT + Cape TME
Pathologic Grade
Total Number Stage II Stage III
38 7 31
0 (Complete) 13 1 12
1 14 4 10
2 8 1 7
3 3 1 2
bull 35 Pts Completed Treatmentbull pCR = 33
Perez et al ASCO 2014 Abstract 3050
Slide 12
Near total neoadjuvant therapy
Questions Total Neoadjuvant YesNoAdjuvant Cth
YesNoLong versus Short
Course
PROSPECT N1048 is ongoingltbr gtSelective Use of Pelvic XRTltbr gt
Can we Omit Radiation From NAT
MSKCC 07-021 Phase II Trial of Selective Radiation for Rectal Cancer
Can we Omit Radiation From NAT
The Art for Today
bull Clinical Trial whenever possiblebull Careful assessmentbull Chemosensitization by 5-FU or Capecitabine is enoughbull Upfront chemotherapy is appealing Total amp Near
Total NAT should be encourgaed pCRbull TME IS THE STANDARD SURGICAL APPROACH (STAGES
II amp III)bull Postoperative chemotherapy should be discussed and
considered for high risk patients DFS
Thank You
ltbr gtPETACC-6 ltbr gtEarly analysis at 31 months shows no major differences between armsltbr gt
Neoadjuvant TherapyAdding Oxaliplatin
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Grade Regression Fibrosis
0 No All cells are viable
1 Minor lt 25 fibrosis
2 Moderate 26 ndash 50nFibrosis
3 Good gt50
4 Total No Viable Cells
Neoadjuvant TherapyTumor Regression Grade
Grade 10 ndash year DM
P 10 ndash Year DFS P
0 - 1 3960005
6300082 - 3 293 736
4 105 895
J Clin Oncol 321554-1562 copy 2014
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
The Cochrane Review Metanalysis Demonstrates DFS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on DFS
The Cochrane Review Metanalysis Demonstrates OS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on OAS
Postop Adjuvant 5FU or FOLFOX for Rectal Cancer The ADORE Trial Randomized Phase II ltbr gt
ltbr gtGerman CAOAROAIO-04 Studyltbr gtAdjuvant FOLFOX has better DFS not OS than 5FU after pre-op ChemoRT
bull Adjuvant Chemotherapy
bull Oxaliplatin ndash Based
Rectal Cancer
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
Total Neoadjuvant ParadigmBrown University Study (CONTRE)
FOLFOX X 8 Courses CRT + Cape TME
Pathologic Grade
Total Number Stage II Stage III
38 7 31
0 (Complete) 13 1 12
1 14 4 10
2 8 1 7
3 3 1 2
bull 35 Pts Completed Treatmentbull pCR = 33
Perez et al ASCO 2014 Abstract 3050
Slide 12
Near total neoadjuvant therapy
Questions Total Neoadjuvant YesNoAdjuvant Cth
YesNoLong versus Short
Course
PROSPECT N1048 is ongoingltbr gtSelective Use of Pelvic XRTltbr gt
Can we Omit Radiation From NAT
MSKCC 07-021 Phase II Trial of Selective Radiation for Rectal Cancer
Can we Omit Radiation From NAT
The Art for Today
bull Clinical Trial whenever possiblebull Careful assessmentbull Chemosensitization by 5-FU or Capecitabine is enoughbull Upfront chemotherapy is appealing Total amp Near
Total NAT should be encourgaed pCRbull TME IS THE STANDARD SURGICAL APPROACH (STAGES
II amp III)bull Postoperative chemotherapy should be discussed and
considered for high risk patients DFS
Thank You
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Grade Regression Fibrosis
0 No All cells are viable
1 Minor lt 25 fibrosis
2 Moderate 26 ndash 50nFibrosis
3 Good gt50
4 Total No Viable Cells
Neoadjuvant TherapyTumor Regression Grade
Grade 10 ndash year DM
P 10 ndash Year DFS P
0 - 1 3960005
6300082 - 3 293 736
4 105 895
J Clin Oncol 321554-1562 copy 2014
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
The Cochrane Review Metanalysis Demonstrates DFS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on DFS
The Cochrane Review Metanalysis Demonstrates OS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on OAS
Postop Adjuvant 5FU or FOLFOX for Rectal Cancer The ADORE Trial Randomized Phase II ltbr gt
ltbr gtGerman CAOAROAIO-04 Studyltbr gtAdjuvant FOLFOX has better DFS not OS than 5FU after pre-op ChemoRT
bull Adjuvant Chemotherapy
bull Oxaliplatin ndash Based
Rectal Cancer
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
Total Neoadjuvant ParadigmBrown University Study (CONTRE)
FOLFOX X 8 Courses CRT + Cape TME
Pathologic Grade
Total Number Stage II Stage III
38 7 31
0 (Complete) 13 1 12
1 14 4 10
2 8 1 7
3 3 1 2
bull 35 Pts Completed Treatmentbull pCR = 33
Perez et al ASCO 2014 Abstract 3050
Slide 12
Near total neoadjuvant therapy
Questions Total Neoadjuvant YesNoAdjuvant Cth
YesNoLong versus Short
Course
PROSPECT N1048 is ongoingltbr gtSelective Use of Pelvic XRTltbr gt
Can we Omit Radiation From NAT
MSKCC 07-021 Phase II Trial of Selective Radiation for Rectal Cancer
Can we Omit Radiation From NAT
The Art for Today
bull Clinical Trial whenever possiblebull Careful assessmentbull Chemosensitization by 5-FU or Capecitabine is enoughbull Upfront chemotherapy is appealing Total amp Near
Total NAT should be encourgaed pCRbull TME IS THE STANDARD SURGICAL APPROACH (STAGES
II amp III)bull Postoperative chemotherapy should be discussed and
considered for high risk patients DFS
Thank You
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Grade Regression Fibrosis
0 No All cells are viable
1 Minor lt 25 fibrosis
2 Moderate 26 ndash 50nFibrosis
3 Good gt50
4 Total No Viable Cells
Neoadjuvant TherapyTumor Regression Grade
Grade 10 ndash year DM
P 10 ndash Year DFS P
0 - 1 3960005
6300082 - 3 293 736
4 105 895
J Clin Oncol 321554-1562 copy 2014
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
The Cochrane Review Metanalysis Demonstrates DFS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on DFS
The Cochrane Review Metanalysis Demonstrates OS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on OAS
Postop Adjuvant 5FU or FOLFOX for Rectal Cancer The ADORE Trial Randomized Phase II ltbr gt
ltbr gtGerman CAOAROAIO-04 Studyltbr gtAdjuvant FOLFOX has better DFS not OS than 5FU after pre-op ChemoRT
bull Adjuvant Chemotherapy
bull Oxaliplatin ndash Based
Rectal Cancer
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
Total Neoadjuvant ParadigmBrown University Study (CONTRE)
FOLFOX X 8 Courses CRT + Cape TME
Pathologic Grade
Total Number Stage II Stage III
38 7 31
0 (Complete) 13 1 12
1 14 4 10
2 8 1 7
3 3 1 2
bull 35 Pts Completed Treatmentbull pCR = 33
Perez et al ASCO 2014 Abstract 3050
Slide 12
Near total neoadjuvant therapy
Questions Total Neoadjuvant YesNoAdjuvant Cth
YesNoLong versus Short
Course
PROSPECT N1048 is ongoingltbr gtSelective Use of Pelvic XRTltbr gt
Can we Omit Radiation From NAT
MSKCC 07-021 Phase II Trial of Selective Radiation for Rectal Cancer
Can we Omit Radiation From NAT
The Art for Today
bull Clinical Trial whenever possiblebull Careful assessmentbull Chemosensitization by 5-FU or Capecitabine is enoughbull Upfront chemotherapy is appealing Total amp Near
Total NAT should be encourgaed pCRbull TME IS THE STANDARD SURGICAL APPROACH (STAGES
II amp III)bull Postoperative chemotherapy should be discussed and
considered for high risk patients DFS
Thank You
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Grade Regression Fibrosis
0 No All cells are viable
1 Minor lt 25 fibrosis
2 Moderate 26 ndash 50nFibrosis
3 Good gt50
4 Total No Viable Cells
Neoadjuvant TherapyTumor Regression Grade
Grade 10 ndash year DM
P 10 ndash Year DFS P
0 - 1 3960005
6300082 - 3 293 736
4 105 895
J Clin Oncol 321554-1562 copy 2014
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
The Cochrane Review Metanalysis Demonstrates DFS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on DFS
The Cochrane Review Metanalysis Demonstrates OS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on OAS
Postop Adjuvant 5FU or FOLFOX for Rectal Cancer The ADORE Trial Randomized Phase II ltbr gt
ltbr gtGerman CAOAROAIO-04 Studyltbr gtAdjuvant FOLFOX has better DFS not OS than 5FU after pre-op ChemoRT
bull Adjuvant Chemotherapy
bull Oxaliplatin ndash Based
Rectal Cancer
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
Total Neoadjuvant ParadigmBrown University Study (CONTRE)
FOLFOX X 8 Courses CRT + Cape TME
Pathologic Grade
Total Number Stage II Stage III
38 7 31
0 (Complete) 13 1 12
1 14 4 10
2 8 1 7
3 3 1 2
bull 35 Pts Completed Treatmentbull pCR = 33
Perez et al ASCO 2014 Abstract 3050
Slide 12
Near total neoadjuvant therapy
Questions Total Neoadjuvant YesNoAdjuvant Cth
YesNoLong versus Short
Course
PROSPECT N1048 is ongoingltbr gtSelective Use of Pelvic XRTltbr gt
Can we Omit Radiation From NAT
MSKCC 07-021 Phase II Trial of Selective Radiation for Rectal Cancer
Can we Omit Radiation From NAT
The Art for Today
bull Clinical Trial whenever possiblebull Careful assessmentbull Chemosensitization by 5-FU or Capecitabine is enoughbull Upfront chemotherapy is appealing Total amp Near
Total NAT should be encourgaed pCRbull TME IS THE STANDARD SURGICAL APPROACH (STAGES
II amp III)bull Postoperative chemotherapy should be discussed and
considered for high risk patients DFS
Thank You
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Grade Regression Fibrosis
0 No All cells are viable
1 Minor lt 25 fibrosis
2 Moderate 26 ndash 50nFibrosis
3 Good gt50
4 Total No Viable Cells
Neoadjuvant TherapyTumor Regression Grade
Grade 10 ndash year DM
P 10 ndash Year DFS P
0 - 1 3960005
6300082 - 3 293 736
4 105 895
J Clin Oncol 321554-1562 copy 2014
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
The Cochrane Review Metanalysis Demonstrates DFS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on DFS
The Cochrane Review Metanalysis Demonstrates OS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on OAS
Postop Adjuvant 5FU or FOLFOX for Rectal Cancer The ADORE Trial Randomized Phase II ltbr gt
ltbr gtGerman CAOAROAIO-04 Studyltbr gtAdjuvant FOLFOX has better DFS not OS than 5FU after pre-op ChemoRT
bull Adjuvant Chemotherapy
bull Oxaliplatin ndash Based
Rectal Cancer
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
Total Neoadjuvant ParadigmBrown University Study (CONTRE)
FOLFOX X 8 Courses CRT + Cape TME
Pathologic Grade
Total Number Stage II Stage III
38 7 31
0 (Complete) 13 1 12
1 14 4 10
2 8 1 7
3 3 1 2
bull 35 Pts Completed Treatmentbull pCR = 33
Perez et al ASCO 2014 Abstract 3050
Slide 12
Near total neoadjuvant therapy
Questions Total Neoadjuvant YesNoAdjuvant Cth
YesNoLong versus Short
Course
PROSPECT N1048 is ongoingltbr gtSelective Use of Pelvic XRTltbr gt
Can we Omit Radiation From NAT
MSKCC 07-021 Phase II Trial of Selective Radiation for Rectal Cancer
Can we Omit Radiation From NAT
The Art for Today
bull Clinical Trial whenever possiblebull Careful assessmentbull Chemosensitization by 5-FU or Capecitabine is enoughbull Upfront chemotherapy is appealing Total amp Near
Total NAT should be encourgaed pCRbull TME IS THE STANDARD SURGICAL APPROACH (STAGES
II amp III)bull Postoperative chemotherapy should be discussed and
considered for high risk patients DFS
Thank You
Grade Regression Fibrosis
0 No All cells are viable
1 Minor lt 25 fibrosis
2 Moderate 26 ndash 50nFibrosis
3 Good gt50
4 Total No Viable Cells
Neoadjuvant TherapyTumor Regression Grade
Grade 10 ndash year DM
P 10 ndash Year DFS P
0 - 1 3960005
6300082 - 3 293 736
4 105 895
J Clin Oncol 321554-1562 copy 2014
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
The Cochrane Review Metanalysis Demonstrates DFS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on DFS
The Cochrane Review Metanalysis Demonstrates OS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on OAS
Postop Adjuvant 5FU or FOLFOX for Rectal Cancer The ADORE Trial Randomized Phase II ltbr gt
ltbr gtGerman CAOAROAIO-04 Studyltbr gtAdjuvant FOLFOX has better DFS not OS than 5FU after pre-op ChemoRT
bull Adjuvant Chemotherapy
bull Oxaliplatin ndash Based
Rectal Cancer
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
Total Neoadjuvant ParadigmBrown University Study (CONTRE)
FOLFOX X 8 Courses CRT + Cape TME
Pathologic Grade
Total Number Stage II Stage III
38 7 31
0 (Complete) 13 1 12
1 14 4 10
2 8 1 7
3 3 1 2
bull 35 Pts Completed Treatmentbull pCR = 33
Perez et al ASCO 2014 Abstract 3050
Slide 12
Near total neoadjuvant therapy
Questions Total Neoadjuvant YesNoAdjuvant Cth
YesNoLong versus Short
Course
PROSPECT N1048 is ongoingltbr gtSelective Use of Pelvic XRTltbr gt
Can we Omit Radiation From NAT
MSKCC 07-021 Phase II Trial of Selective Radiation for Rectal Cancer
Can we Omit Radiation From NAT
The Art for Today
bull Clinical Trial whenever possiblebull Careful assessmentbull Chemosensitization by 5-FU or Capecitabine is enoughbull Upfront chemotherapy is appealing Total amp Near
Total NAT should be encourgaed pCRbull TME IS THE STANDARD SURGICAL APPROACH (STAGES
II amp III)bull Postoperative chemotherapy should be discussed and
considered for high risk patients DFS
Thank You
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
The Cochrane Review Metanalysis Demonstrates DFS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on DFS
The Cochrane Review Metanalysis Demonstrates OS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on OAS
Postop Adjuvant 5FU or FOLFOX for Rectal Cancer The ADORE Trial Randomized Phase II ltbr gt
ltbr gtGerman CAOAROAIO-04 Studyltbr gtAdjuvant FOLFOX has better DFS not OS than 5FU after pre-op ChemoRT
bull Adjuvant Chemotherapy
bull Oxaliplatin ndash Based
Rectal Cancer
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
Total Neoadjuvant ParadigmBrown University Study (CONTRE)
FOLFOX X 8 Courses CRT + Cape TME
Pathologic Grade
Total Number Stage II Stage III
38 7 31
0 (Complete) 13 1 12
1 14 4 10
2 8 1 7
3 3 1 2
bull 35 Pts Completed Treatmentbull pCR = 33
Perez et al ASCO 2014 Abstract 3050
Slide 12
Near total neoadjuvant therapy
Questions Total Neoadjuvant YesNoAdjuvant Cth
YesNoLong versus Short
Course
PROSPECT N1048 is ongoingltbr gtSelective Use of Pelvic XRTltbr gt
Can we Omit Radiation From NAT
MSKCC 07-021 Phase II Trial of Selective Radiation for Rectal Cancer
Can we Omit Radiation From NAT
The Art for Today
bull Clinical Trial whenever possiblebull Careful assessmentbull Chemosensitization by 5-FU or Capecitabine is enoughbull Upfront chemotherapy is appealing Total amp Near
Total NAT should be encourgaed pCRbull TME IS THE STANDARD SURGICAL APPROACH (STAGES
II amp III)bull Postoperative chemotherapy should be discussed and
considered for high risk patients DFS
Thank You
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
The Cochrane Review Metanalysis Demonstrates DFS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on DFS
The Cochrane Review Metanalysis Demonstrates OS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on OAS
Postop Adjuvant 5FU or FOLFOX for Rectal Cancer The ADORE Trial Randomized Phase II ltbr gt
ltbr gtGerman CAOAROAIO-04 Studyltbr gtAdjuvant FOLFOX has better DFS not OS than 5FU after pre-op ChemoRT
bull Adjuvant Chemotherapy
bull Oxaliplatin ndash Based
Rectal Cancer
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
Total Neoadjuvant ParadigmBrown University Study (CONTRE)
FOLFOX X 8 Courses CRT + Cape TME
Pathologic Grade
Total Number Stage II Stage III
38 7 31
0 (Complete) 13 1 12
1 14 4 10
2 8 1 7
3 3 1 2
bull 35 Pts Completed Treatmentbull pCR = 33
Perez et al ASCO 2014 Abstract 3050
Slide 12
Near total neoadjuvant therapy
Questions Total Neoadjuvant YesNoAdjuvant Cth
YesNoLong versus Short
Course
PROSPECT N1048 is ongoingltbr gtSelective Use of Pelvic XRTltbr gt
Can we Omit Radiation From NAT
MSKCC 07-021 Phase II Trial of Selective Radiation for Rectal Cancer
Can we Omit Radiation From NAT
The Art for Today
bull Clinical Trial whenever possiblebull Careful assessmentbull Chemosensitization by 5-FU or Capecitabine is enoughbull Upfront chemotherapy is appealing Total amp Near
Total NAT should be encourgaed pCRbull TME IS THE STANDARD SURGICAL APPROACH (STAGES
II amp III)bull Postoperative chemotherapy should be discussed and
considered for high risk patients DFS
Thank You
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
The Cochrane Review Metanalysis Demonstrates DFS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on DFS
The Cochrane Review Metanalysis Demonstrates OS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on OAS
Postop Adjuvant 5FU or FOLFOX for Rectal Cancer The ADORE Trial Randomized Phase II ltbr gt
ltbr gtGerman CAOAROAIO-04 Studyltbr gtAdjuvant FOLFOX has better DFS not OS than 5FU after pre-op ChemoRT
bull Adjuvant Chemotherapy
bull Oxaliplatin ndash Based
Rectal Cancer
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
Total Neoadjuvant ParadigmBrown University Study (CONTRE)
FOLFOX X 8 Courses CRT + Cape TME
Pathologic Grade
Total Number Stage II Stage III
38 7 31
0 (Complete) 13 1 12
1 14 4 10
2 8 1 7
3 3 1 2
bull 35 Pts Completed Treatmentbull pCR = 33
Perez et al ASCO 2014 Abstract 3050
Slide 12
Near total neoadjuvant therapy
Questions Total Neoadjuvant YesNoAdjuvant Cth
YesNoLong versus Short
Course
PROSPECT N1048 is ongoingltbr gtSelective Use of Pelvic XRTltbr gt
Can we Omit Radiation From NAT
MSKCC 07-021 Phase II Trial of Selective Radiation for Rectal Cancer
Can we Omit Radiation From NAT
The Art for Today
bull Clinical Trial whenever possiblebull Careful assessmentbull Chemosensitization by 5-FU or Capecitabine is enoughbull Upfront chemotherapy is appealing Total amp Near
Total NAT should be encourgaed pCRbull TME IS THE STANDARD SURGICAL APPROACH (STAGES
II amp III)bull Postoperative chemotherapy should be discussed and
considered for high risk patients DFS
Thank You
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
The Cochrane Review Metanalysis Demonstrates DFS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on DFS
The Cochrane Review Metanalysis Demonstrates OS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on OAS
Postop Adjuvant 5FU or FOLFOX for Rectal Cancer The ADORE Trial Randomized Phase II ltbr gt
ltbr gtGerman CAOAROAIO-04 Studyltbr gtAdjuvant FOLFOX has better DFS not OS than 5FU after pre-op ChemoRT
bull Adjuvant Chemotherapy
bull Oxaliplatin ndash Based
Rectal Cancer
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
Total Neoadjuvant ParadigmBrown University Study (CONTRE)
FOLFOX X 8 Courses CRT + Cape TME
Pathologic Grade
Total Number Stage II Stage III
38 7 31
0 (Complete) 13 1 12
1 14 4 10
2 8 1 7
3 3 1 2
bull 35 Pts Completed Treatmentbull pCR = 33
Perez et al ASCO 2014 Abstract 3050
Slide 12
Near total neoadjuvant therapy
Questions Total Neoadjuvant YesNoAdjuvant Cth
YesNoLong versus Short
Course
PROSPECT N1048 is ongoingltbr gtSelective Use of Pelvic XRTltbr gt
Can we Omit Radiation From NAT
MSKCC 07-021 Phase II Trial of Selective Radiation for Rectal Cancer
Can we Omit Radiation From NAT
The Art for Today
bull Clinical Trial whenever possiblebull Careful assessmentbull Chemosensitization by 5-FU or Capecitabine is enoughbull Upfront chemotherapy is appealing Total amp Near
Total NAT should be encourgaed pCRbull TME IS THE STANDARD SURGICAL APPROACH (STAGES
II amp III)bull Postoperative chemotherapy should be discussed and
considered for high risk patients DFS
Thank You
The Cochrane Review Metanalysis Demonstrates DFS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on DFS
The Cochrane Review Metanalysis Demonstrates OS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on OAS
Postop Adjuvant 5FU or FOLFOX for Rectal Cancer The ADORE Trial Randomized Phase II ltbr gt
ltbr gtGerman CAOAROAIO-04 Studyltbr gtAdjuvant FOLFOX has better DFS not OS than 5FU after pre-op ChemoRT
bull Adjuvant Chemotherapy
bull Oxaliplatin ndash Based
Rectal Cancer
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
Total Neoadjuvant ParadigmBrown University Study (CONTRE)
FOLFOX X 8 Courses CRT + Cape TME
Pathologic Grade
Total Number Stage II Stage III
38 7 31
0 (Complete) 13 1 12
1 14 4 10
2 8 1 7
3 3 1 2
bull 35 Pts Completed Treatmentbull pCR = 33
Perez et al ASCO 2014 Abstract 3050
Slide 12
Near total neoadjuvant therapy
Questions Total Neoadjuvant YesNoAdjuvant Cth
YesNoLong versus Short
Course
PROSPECT N1048 is ongoingltbr gtSelective Use of Pelvic XRTltbr gt
Can we Omit Radiation From NAT
MSKCC 07-021 Phase II Trial of Selective Radiation for Rectal Cancer
Can we Omit Radiation From NAT
The Art for Today
bull Clinical Trial whenever possiblebull Careful assessmentbull Chemosensitization by 5-FU or Capecitabine is enoughbull Upfront chemotherapy is appealing Total amp Near
Total NAT should be encourgaed pCRbull TME IS THE STANDARD SURGICAL APPROACH (STAGES
II amp III)bull Postoperative chemotherapy should be discussed and
considered for high risk patients DFS
Thank You
The Cochrane Review Metanalysis Demonstrates OS Adjuvant Treatment Benefit
Impact of Adjuvant Therapy on OAS
Postop Adjuvant 5FU or FOLFOX for Rectal Cancer The ADORE Trial Randomized Phase II ltbr gt
ltbr gtGerman CAOAROAIO-04 Studyltbr gtAdjuvant FOLFOX has better DFS not OS than 5FU after pre-op ChemoRT
bull Adjuvant Chemotherapy
bull Oxaliplatin ndash Based
Rectal Cancer
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
Total Neoadjuvant ParadigmBrown University Study (CONTRE)
FOLFOX X 8 Courses CRT + Cape TME
Pathologic Grade
Total Number Stage II Stage III
38 7 31
0 (Complete) 13 1 12
1 14 4 10
2 8 1 7
3 3 1 2
bull 35 Pts Completed Treatmentbull pCR = 33
Perez et al ASCO 2014 Abstract 3050
Slide 12
Near total neoadjuvant therapy
Questions Total Neoadjuvant YesNoAdjuvant Cth
YesNoLong versus Short
Course
PROSPECT N1048 is ongoingltbr gtSelective Use of Pelvic XRTltbr gt
Can we Omit Radiation From NAT
MSKCC 07-021 Phase II Trial of Selective Radiation for Rectal Cancer
Can we Omit Radiation From NAT
The Art for Today
bull Clinical Trial whenever possiblebull Careful assessmentbull Chemosensitization by 5-FU or Capecitabine is enoughbull Upfront chemotherapy is appealing Total amp Near
Total NAT should be encourgaed pCRbull TME IS THE STANDARD SURGICAL APPROACH (STAGES
II amp III)bull Postoperative chemotherapy should be discussed and
considered for high risk patients DFS
Thank You
Postop Adjuvant 5FU or FOLFOX for Rectal Cancer The ADORE Trial Randomized Phase II ltbr gt
ltbr gtGerman CAOAROAIO-04 Studyltbr gtAdjuvant FOLFOX has better DFS not OS than 5FU after pre-op ChemoRT
bull Adjuvant Chemotherapy
bull Oxaliplatin ndash Based
Rectal Cancer
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
Total Neoadjuvant ParadigmBrown University Study (CONTRE)
FOLFOX X 8 Courses CRT + Cape TME
Pathologic Grade
Total Number Stage II Stage III
38 7 31
0 (Complete) 13 1 12
1 14 4 10
2 8 1 7
3 3 1 2
bull 35 Pts Completed Treatmentbull pCR = 33
Perez et al ASCO 2014 Abstract 3050
Slide 12
Near total neoadjuvant therapy
Questions Total Neoadjuvant YesNoAdjuvant Cth
YesNoLong versus Short
Course
PROSPECT N1048 is ongoingltbr gtSelective Use of Pelvic XRTltbr gt
Can we Omit Radiation From NAT
MSKCC 07-021 Phase II Trial of Selective Radiation for Rectal Cancer
Can we Omit Radiation From NAT
The Art for Today
bull Clinical Trial whenever possiblebull Careful assessmentbull Chemosensitization by 5-FU or Capecitabine is enoughbull Upfront chemotherapy is appealing Total amp Near
Total NAT should be encourgaed pCRbull TME IS THE STANDARD SURGICAL APPROACH (STAGES
II amp III)bull Postoperative chemotherapy should be discussed and
considered for high risk patients DFS
Thank You
ltbr gtGerman CAOAROAIO-04 Studyltbr gtAdjuvant FOLFOX has better DFS not OS than 5FU after pre-op ChemoRT
bull Adjuvant Chemotherapy
bull Oxaliplatin ndash Based
Rectal Cancer
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
Total Neoadjuvant ParadigmBrown University Study (CONTRE)
FOLFOX X 8 Courses CRT + Cape TME
Pathologic Grade
Total Number Stage II Stage III
38 7 31
0 (Complete) 13 1 12
1 14 4 10
2 8 1 7
3 3 1 2
bull 35 Pts Completed Treatmentbull pCR = 33
Perez et al ASCO 2014 Abstract 3050
Slide 12
Near total neoadjuvant therapy
Questions Total Neoadjuvant YesNoAdjuvant Cth
YesNoLong versus Short
Course
PROSPECT N1048 is ongoingltbr gtSelective Use of Pelvic XRTltbr gt
Can we Omit Radiation From NAT
MSKCC 07-021 Phase II Trial of Selective Radiation for Rectal Cancer
Can we Omit Radiation From NAT
The Art for Today
bull Clinical Trial whenever possiblebull Careful assessmentbull Chemosensitization by 5-FU or Capecitabine is enoughbull Upfront chemotherapy is appealing Total amp Near
Total NAT should be encourgaed pCRbull TME IS THE STANDARD SURGICAL APPROACH (STAGES
II amp III)bull Postoperative chemotherapy should be discussed and
considered for high risk patients DFS
Thank You
bull Adjuvant Chemotherapy
bull Oxaliplatin ndash Based
Rectal Cancer
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
Total Neoadjuvant ParadigmBrown University Study (CONTRE)
FOLFOX X 8 Courses CRT + Cape TME
Pathologic Grade
Total Number Stage II Stage III
38 7 31
0 (Complete) 13 1 12
1 14 4 10
2 8 1 7
3 3 1 2
bull 35 Pts Completed Treatmentbull pCR = 33
Perez et al ASCO 2014 Abstract 3050
Slide 12
Near total neoadjuvant therapy
Questions Total Neoadjuvant YesNoAdjuvant Cth
YesNoLong versus Short
Course
PROSPECT N1048 is ongoingltbr gtSelective Use of Pelvic XRTltbr gt
Can we Omit Radiation From NAT
MSKCC 07-021 Phase II Trial of Selective Radiation for Rectal Cancer
Can we Omit Radiation From NAT
The Art for Today
bull Clinical Trial whenever possiblebull Careful assessmentbull Chemosensitization by 5-FU or Capecitabine is enoughbull Upfront chemotherapy is appealing Total amp Near
Total NAT should be encourgaed pCRbull TME IS THE STANDARD SURGICAL APPROACH (STAGES
II amp III)bull Postoperative chemotherapy should be discussed and
considered for high risk patients DFS
Thank You
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
Total Neoadjuvant ParadigmBrown University Study (CONTRE)
FOLFOX X 8 Courses CRT + Cape TME
Pathologic Grade
Total Number Stage II Stage III
38 7 31
0 (Complete) 13 1 12
1 14 4 10
2 8 1 7
3 3 1 2
bull 35 Pts Completed Treatmentbull pCR = 33
Perez et al ASCO 2014 Abstract 3050
Slide 12
Near total neoadjuvant therapy
Questions Total Neoadjuvant YesNoAdjuvant Cth
YesNoLong versus Short
Course
PROSPECT N1048 is ongoingltbr gtSelective Use of Pelvic XRTltbr gt
Can we Omit Radiation From NAT
MSKCC 07-021 Phase II Trial of Selective Radiation for Rectal Cancer
Can we Omit Radiation From NAT
The Art for Today
bull Clinical Trial whenever possiblebull Careful assessmentbull Chemosensitization by 5-FU or Capecitabine is enoughbull Upfront chemotherapy is appealing Total amp Near
Total NAT should be encourgaed pCRbull TME IS THE STANDARD SURGICAL APPROACH (STAGES
II amp III)bull Postoperative chemotherapy should be discussed and
considered for high risk patients DFS
Thank You
Total Neoadjuvant ParadigmBrown University Study (CONTRE)
FOLFOX X 8 Courses CRT + Cape TME
Pathologic Grade
Total Number Stage II Stage III
38 7 31
0 (Complete) 13 1 12
1 14 4 10
2 8 1 7
3 3 1 2
bull 35 Pts Completed Treatmentbull pCR = 33
Perez et al ASCO 2014 Abstract 3050
Slide 12
Near total neoadjuvant therapy
Questions Total Neoadjuvant YesNoAdjuvant Cth
YesNoLong versus Short
Course
PROSPECT N1048 is ongoingltbr gtSelective Use of Pelvic XRTltbr gt
Can we Omit Radiation From NAT
MSKCC 07-021 Phase II Trial of Selective Radiation for Rectal Cancer
Can we Omit Radiation From NAT
The Art for Today
bull Clinical Trial whenever possiblebull Careful assessmentbull Chemosensitization by 5-FU or Capecitabine is enoughbull Upfront chemotherapy is appealing Total amp Near
Total NAT should be encourgaed pCRbull TME IS THE STANDARD SURGICAL APPROACH (STAGES
II amp III)bull Postoperative chemotherapy should be discussed and
considered for high risk patients DFS
Thank You
Slide 12
Near total neoadjuvant therapy
Questions Total Neoadjuvant YesNoAdjuvant Cth
YesNoLong versus Short
Course
PROSPECT N1048 is ongoingltbr gtSelective Use of Pelvic XRTltbr gt
Can we Omit Radiation From NAT
MSKCC 07-021 Phase II Trial of Selective Radiation for Rectal Cancer
Can we Omit Radiation From NAT
The Art for Today
bull Clinical Trial whenever possiblebull Careful assessmentbull Chemosensitization by 5-FU or Capecitabine is enoughbull Upfront chemotherapy is appealing Total amp Near
Total NAT should be encourgaed pCRbull TME IS THE STANDARD SURGICAL APPROACH (STAGES
II amp III)bull Postoperative chemotherapy should be discussed and
considered for high risk patients DFS
Thank You
Near total neoadjuvant therapy
Questions Total Neoadjuvant YesNoAdjuvant Cth
YesNoLong versus Short
Course
PROSPECT N1048 is ongoingltbr gtSelective Use of Pelvic XRTltbr gt
Can we Omit Radiation From NAT
MSKCC 07-021 Phase II Trial of Selective Radiation for Rectal Cancer
Can we Omit Radiation From NAT
The Art for Today
bull Clinical Trial whenever possiblebull Careful assessmentbull Chemosensitization by 5-FU or Capecitabine is enoughbull Upfront chemotherapy is appealing Total amp Near
Total NAT should be encourgaed pCRbull TME IS THE STANDARD SURGICAL APPROACH (STAGES
II amp III)bull Postoperative chemotherapy should be discussed and
considered for high risk patients DFS
Thank You
Questions Total Neoadjuvant YesNoAdjuvant Cth
YesNoLong versus Short
Course
PROSPECT N1048 is ongoingltbr gtSelective Use of Pelvic XRTltbr gt
Can we Omit Radiation From NAT
MSKCC 07-021 Phase II Trial of Selective Radiation for Rectal Cancer
Can we Omit Radiation From NAT
The Art for Today
bull Clinical Trial whenever possiblebull Careful assessmentbull Chemosensitization by 5-FU or Capecitabine is enoughbull Upfront chemotherapy is appealing Total amp Near
Total NAT should be encourgaed pCRbull TME IS THE STANDARD SURGICAL APPROACH (STAGES
II amp III)bull Postoperative chemotherapy should be discussed and
considered for high risk patients DFS
Thank You
PROSPECT N1048 is ongoingltbr gtSelective Use of Pelvic XRTltbr gt
Can we Omit Radiation From NAT
MSKCC 07-021 Phase II Trial of Selective Radiation for Rectal Cancer
Can we Omit Radiation From NAT
The Art for Today
bull Clinical Trial whenever possiblebull Careful assessmentbull Chemosensitization by 5-FU or Capecitabine is enoughbull Upfront chemotherapy is appealing Total amp Near
Total NAT should be encourgaed pCRbull TME IS THE STANDARD SURGICAL APPROACH (STAGES
II amp III)bull Postoperative chemotherapy should be discussed and
considered for high risk patients DFS
Thank You
MSKCC 07-021 Phase II Trial of Selective Radiation for Rectal Cancer
Can we Omit Radiation From NAT
The Art for Today
bull Clinical Trial whenever possiblebull Careful assessmentbull Chemosensitization by 5-FU or Capecitabine is enoughbull Upfront chemotherapy is appealing Total amp Near
Total NAT should be encourgaed pCRbull TME IS THE STANDARD SURGICAL APPROACH (STAGES
II amp III)bull Postoperative chemotherapy should be discussed and
considered for high risk patients DFS
Thank You
The Art for Today
bull Clinical Trial whenever possiblebull Careful assessmentbull Chemosensitization by 5-FU or Capecitabine is enoughbull Upfront chemotherapy is appealing Total amp Near
Total NAT should be encourgaed pCRbull TME IS THE STANDARD SURGICAL APPROACH (STAGES
II amp III)bull Postoperative chemotherapy should be discussed and
considered for high risk patients DFS
Thank You
Thank You
