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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
In Your practice how many patients are you aware of who have/had a diagnosis of
anal cancer?
1 or 2
2- 5
> 5
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
What is the standard treatment for Squamous anal cancer ?
Surgery Surgery Chemotherapy
Chemotherapy Chemoradiation
Chemotherapy Chemoradiation
What % of patients with squamous anal cancer have evidence of HPV infection ?
10 - 20%
20 - 40% 40 - 60% 60 - 80%
80 - 100%
In Rectal cancer what % of patients will achieve complete clinical response after
chemoradiation?
5 - 10%
15 - 25%
25 - 40%
40 - 50%
At what age does bowel screening start?
50
55
60
65
Malignancy Low Rectum/Anal Canal
• Sag MRI
Malignancy Low Rectum/Anal Canal
• CURED
• AVOID STOMA
Treatment Low Rectal/Anal Cancer
1980 APR/permanent Stoma
Anal Cancer Trials 1987-1994
Major Practice Change
CHEMORADIATION
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%
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
Lessons from ANAL CANCER
• Rare Cancer
• National/International collaboration
•Provide Practice Changing Evidence
• Enormous significance for patients
Radiosensitive
Wilms tumour
Ewings Sarcoma
Lymphoma
Multiple myeloma
Seminoma/
dysgerminoma
SCC
Radioresistant
Osteosarcoma
Fibrosarcoma/
Liposarcoma/
myosarcoma
Malignant melanoma
Gliomas
Adenocarcinomas
Radiocurable Disease - SCC
Head and Neck
Skin cancer
Anal Penis and Cervix Anal
Skin cancer Oesophageal
Rectum Preservation – locally advanced
2000 patients/yr - Pre-op Radiotherapy and Resection
Low Rectal Cancer Treatment Strategy
APR/permanent stoma
LR 30%
Pre-operative RT (25Gy in 5#)
LR 10%
IMAGING 1990s
SURGERY 1982
Evolutionary(Revolutionary)changes Rectal Cancer
Total Mesorectal Excision (TME)
MRI Staging
LR < 5% Selection/prognosis
Evolution of Rectal Cancer Management
1990s SURGERY
1990s + CHEMOTHERAPY
1990 + RADIOTHERAPY
POST OPERATIVE
PRE-OPERATIVE
Evolution of Rectal Cancer Management
SELECTION
EARLY
SURGERY
MRI
ADVANCED
NEOADJUVANT Chemoradiaton
Short course RT
Chemotherapy Short course RT
Where are the nodes?
EUS coverage MRI coverage
MRI coverage
EUS
Neo-adjuvant Strategies in Rectal Cancer
Do nothing
SCPRT
CRT
Systemic Treatment
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
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).
Week 1 Week 3
Bladder Filling
Pelvic Radiotherapy Supine Treatment Position
IMRT - Dose Distribution
Pre-treatment Post-treatment
Clinical Complete Response MR = black scar on T2 imaging
Smith JJ et al., BMC Cancer, 2015.
MR TRG
RT Responsiveness
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)
Timing after CRT? When is maximum response reached?
6 weeks
mrT3b
12 weeks
mrT2
Baseline
mrT4
Final Pathology: ypT2N0
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)
Headaches !!
• New concept Slow Accrual
• Suitability for surgery Poor PS patients
• Point of Entry Selection bias
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
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%)
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%
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
Malignancy Low Rectum/Anal Canal
• CURED
• AVOID STOMA
What is the standard treatment for Squamous anal cancer ?
Surgery Surgery Chemotherapy
Chemotherapy Chemoradiation
Chemotherapy Chemoradiation
What % of patients with squamous anal cancer have evidence of HPV infection ?
10 - 20%
20 - 40% 40 - 60% 60 - 80%
80 - 100%
In Rectal cancer what % of patients will achieve complete clinical response after
chemoradiation?
5 - 10%
15 - 25%
25 - 40%
40 - 50%
At what age does bowel screening start?
50
55
60
65
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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