gp educational day lower gi malignancy... · 2019-10-23 · anal cancer trials 1987-1994 major...
TRANSCRIPT
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The Royal Marsden
GP Educational Day Lower GI malignancy
The Royal Marsden Educational & Conference Centre
16th October 2019
Dr Diana Tait Consultant Clinical Oncologist The Royal Marsden Hospital
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In Your practice how many patients are you aware of who have/had a diagnosis of
anal cancer?
1 or 2
2- 5
> 5
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In your practice how many patients are you aware of who have/had a diagnosis of
rectal cancer?
1 or 2
2 - 5
5 - 10
> 10
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What is the standard treatment for Squamous anal cancer ?
Surgery Surgery Chemotherapy
Chemotherapy Chemoradiation
Chemotherapy Chemoradiation
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What % of patients with squamous anal cancer have evidence of HPV infection ?
10 - 20%
20 - 40% 40 - 60% 60 - 80%
80 - 100%
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In Rectal cancer what % of patients will achieve complete clinical response after
chemoradiation?
5 - 10%
15 - 25%
25 - 40%
40 - 50%
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At what age does bowel screening start?
50
55
60
65
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Malignancy Low Rectum/Anal Canal
• Sag MRI
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Malignancy Low Rectum/Anal Canal
• CURED
• AVOID STOMA
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Treatment Low Rectal/Anal Cancer
1980 APR/permanent Stoma
Anal Cancer Trials 1987-1994
Major Practice Change
CHEMORADIATION
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Anal Cancer – Pivotal Trials (1)
ACT 1 – UK RT +/- MMC +5FU EORTC – European
RT +/- MMC + 5FU similar reduction
RTOG – USA
RT + 5FU +/- MMC superior results MMC
LRF 36% v 59%
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Anal Cancer – Pivotal Trials (2)
RTOG – USA
CRT-MF V CRT cisplatin FU inferior outcomes
ACT 2 - UK
CRT-MF V CRT cisplatin F
+/- maintenance cisp FU No benefit
ACCORD
+/- Neoadjuvant cisplatin FU No benefit
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Lessons from ANAL CANCER
• Rare Cancer
• National/International collaboration
•Provide Practice Changing Evidence
• Enormous significance for patients
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Radiosensitive
Wilms tumour
Ewings Sarcoma
Lymphoma
Multiple myeloma
Seminoma/
dysgerminoma
SCC
Radioresistant
Osteosarcoma
Fibrosarcoma/
Liposarcoma/
myosarcoma
Malignant melanoma
Gliomas
Adenocarcinomas
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Radiocurable Disease - SCC
Head and Neck
Skin cancer
Anal Penis and Cervix Anal
Skin cancer Oesophageal
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Rectum Preservation – locally advanced
2000 patients/yr - Pre-op Radiotherapy and Resection
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Low Rectal Cancer Treatment Strategy
APR/permanent stoma
LR 30%
Pre-operative RT (25Gy in 5#)
LR 10%
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IMAGING 1990s
SURGERY 1982
Evolutionary(Revolutionary)changes Rectal Cancer
Total Mesorectal Excision (TME)
MRI Staging
LR < 5% Selection/prognosis
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Evolution of Rectal Cancer Management
1990s SURGERY
1990s + CHEMOTHERAPY
1990 + RADIOTHERAPY
POST OPERATIVE
PRE-OPERATIVE
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Evolution of Rectal Cancer Management
SELECTION
EARLY
SURGERY
MRI
ADVANCED
NEOADJUVANT Chemoradiaton
Short course RT
Chemotherapy Short course RT
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Where are the nodes?
EUS coverage MRI coverage
MRI coverage
EUS
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Neo-adjuvant Strategies in Rectal Cancer
Do nothing
SCPRT
CRT
Systemic Treatment
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Pre-Operative Radiotherapy Schedules
SCPRT V CRT
25Gy 5# 1w ≥ 45Gy 25# 5w
Min Acute Toxicity Mod Acute Toxicity
Long Term Morbidity ? Long-term Morbidity
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Organ motion - bladder status
Small Bowel
Small Bowel
Rectum
Rectum
Bladder
Bladder
Benefits of bladder distension demonstrated by
Brierely et al. (1994) and Nuyttens et al. (2001).
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Week 1 Week 3
Bladder Filling
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Pelvic Radiotherapy Supine Treatment Position
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IMRT - Dose Distribution
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Pre-treatment Post-treatment
Clinical Complete Response MR = black scar on T2 imaging
Smith JJ et al., BMC Cancer, 2015.
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MR TRG
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RT Responsiveness
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TRG 2
TRG 3
TRG 1
TRG 4/5
MRI Tumour Regression Grading
MRI After Treatment of Locally Advanced Rectal Cancer: How to report Tumor Response - The MERCURY Experience (AJR 199: 2012)
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Timing after CRT? When is maximum response reached?
6 weeks
mrT3b
12 weeks
mrT2
Baseline
mrT4
Final Pathology: ypT2N0
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Dose Response Relationship
Appelt et al, International Journal of Radiation Oncology*Biology*Physics Volume 85, Issue 1 2013 74 - 80
TRG1
(Solid line, filled squares)
TRG1-2
(Dashed line, open squares)
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Headaches !!
• New concept Slow Accrual
• Suitability for surgery Poor PS patients
• Point of Entry Selection bias
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Headaches !!
Entry point to trial –Non Standard
Introduced bias – selection of maintained responders
Per protocol (PP) At least one MRI
later than 8w post CRT
Late Entry (LE)
Consent ≤ 70d post CRT Consent ≥ 71d post CRT
60 40
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Primary Endpoints
• Time to Local disease regrowth (PP set) By 2 years - 29 events - 2 patients censored Kaplan-Meier probability of continued cCR at 2 years 50% (C1 37% - 62%)
• Time to Local Failure (PP set) By 2 years - 4 Local failures - 25 successful resection - 2 Censored – no regrowth Kaplan-Meier probability of local failure at 2 years 8% (C1 3.2% - 29%)
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SUMMARY
• Ground breaking study – lot of learning!
• Accrual and 2yr follow-up achieved (12yrs)
• Probability of continued CR at 2yrs 50%
• Probability LF at 2yrs 8%
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Functional Outcome
No LARS
Minor LARS
Major LARS
• 3yr colostomy free rate >90% • EORTC CR38 • Better in most domains • LARS
Netherland Cancer Institute Series
Major LARS
Minor LARS
Watch-and-Wait CRT/TME
No LARS
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Malignancy Low Rectum/Anal Canal
• CURED
• AVOID STOMA
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What is the standard treatment for Squamous anal cancer ?
Surgery Surgery Chemotherapy
Chemotherapy Chemoradiation
Chemotherapy Chemoradiation
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What % of patients with squamous anal cancer have evidence of HPV infection ?
10 - 20%
20 - 40% 40 - 60% 60 - 80%
80 - 100%
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In Rectal cancer what % of patients will achieve complete clinical response after
chemoradiation?
5 - 10%
15 - 25%
25 - 40%
40 - 50%
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At what age does bowel screening start?
50
55
60
65
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The Royal Marsden
GP Educational Day Lower GI malignancy
The Royal Marsden Educational & Conference Centre
16th October 2019
Dr Diana Tait Consultant Clinical Oncologist The Royal Marsden Hospital