Developments in Colorectal Cancer

gina.brown@rmh.nhs.uk

Developments in Colorectal Cancer

Professor Gina BrownDepartment of RadiologyRoyal Marsden Hospital

Imperial College

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Objectives of Clinical Research• Earlier diagnosis of patients with suspected

cancer• Accurate prediction of tumour extent to

maximise chances of surgical cure• Understanding high-risk disease and developing

tools to identify high and low risk• Better and earlier diagnosis of potential sites of

metastatic disease –increase cure rates • Improving surveillance of patients at high risk of

recurrence.

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Modern Objectives of assessing and treating Rectal Cancer

• Reduce perioperative and longterm postoperative morbidity – preserve quality of life

• Preservation of organ function• Minimise/eliminate risk of local recurrence:

selective radiotherapy and good surgery• Reduce risk of distant spread of tumour:

surveillance and modern chemotherapy

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Nodal status predicts recurrence when poor surgeryis performed

Patients undergoing non-TME / TME surgery with incomplete specimens –

nodal status strongly predicts local recurrence

18% incomplete rates- Dutch TME15% - CR07North American Trials – non TME surgery5% - MERCURY

Nodes left behind cause pelvic recurrence

The Royal MarsdenImprovements in Surgery and Training of Surgeons brought about a dramatic reduction in recurrence rates. Nodes were no longer a risk factor for pelvic recurrence. Improvements in surgery took almost 20 years to be accepted.

Investment in clinical surgical research could have brought about these changes sooner

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MRI assessment at diagnosis enables patients with good prognosis who would not benefit from additional radiotherapy to

be identified

Taylor et al, MERCURY

Annals of Surgery 2011

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Imaging Research by the MERCURY research group led to a change in the

national guidelines • Preoperative radiotherapy is not

indicated for MRI defined margin safe early T3 tumours

• Distinction between T2 and T3 no longer influences preoperative treatment choice

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Problems encountered when Mri is not used to plan the operatiob

‘WAIST’ at Puborectalis

Tumour is exposed leading to CRM involvement and likelihoodof recurrence

‘Standard’ APE

Tumour is exposed

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Slice 1 Slice 2

Slice 4Slice 3

Slice 5 Slice 6

Slice 1 Slice 2

Slice 3

Slice 6

Slice 4

Slice 5

The MRI scan enables the surgeon to plan the surgery more precisely and avoid tumour at the circumferential margins of resection

Mesorectal fasciaForms the surgical plane

vessels

Lymph nodes

Distance to CRM

Depth of spread/mm

Sigmoid Cancer is a problemthese are a large proportion of colorectal cancers and outcomes are not as good as rectal cancer

Dis Colon Rectum. 2010 Jan;53(1):57-64.

High risk features seen in a sigmoid cancer – MRI is not routinely performed but risks can be similar as

for rectal cancer

• Tumour involving non peritonealised fascial margin

• Tumour penetration of adjacent organs

• Extramural venous invasion• Depth of extramural spread

>5mm• Operation would result in a high

risk of pelvic recurrence

Eur J Surg Oncol. 2005 Oct;31(8):845-53.

Improved survival being seen in rectal cancer but

not so good for colon cancer

Why we should focus our attention on sigmoid cancer

assessment by MRI Sigmoid cancer has a high recurrence rate Sigmoid cancer has a worse outcome than rectal

cancer MRI is able to identify poor prognostic tumours

preoperatively Preoperative staging enhances optimal treatment

strategy including neoadjuvant treatment Sigmoid cancer with poor prognostic features

should be discussed for neoadjuvant treatment

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A Patient with a Low Rectal Cancer treated by PreoperativeChemoradiotherapy : on the post treatment scan the tumour has regressed so that no obvious tumour remainsPatients, will, in future be offered the opportunity to defer their Until such time that there is evidence that the tumour is viable and regrowing. For some patients this deferral may be permanent.

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2010

2007

Deferral of surgery trialPatients undergoing preop RT/CRT

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A CB

Tumour present at 6 wks No tumour at 16 wksBaseline pretreatment

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Current National Phase II/III

trial – TRIGGER - offering the possbility of

deferring surgery for patients with a good

response and intensifying treatment for those with a

poor response to radiotherapy

The Royal MarsdenCharacteristic features of blood vessel invasion as seen on MRI and histology

• Expansion of vessels by tumour

• tubular extension of tumour signal

MRI for detection of extramural vascular invasion in rectal cancer. AJR Am J Roentgenol 191(5): 1517-1522.

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Gross tubular extension along the course of lateral rectal vein

How tumour can spread within the pelvis

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0

20

40

60

80

100

0 1 2 3 4 5 6

Time since operation (Years)

% R

elap

se-f

ree

MRI-EMVI score= 0-2MRI-EMVI score= 3-4

p = 0.0015

Smith et al BJS 2008, 95(2): 229-236

Prognostic significance of magnetic resonance imaging-detected extramural vascular invasion in rectal cancer

Only 30% of patients with mrEMVI were free of tumour at 3 years compared withalmost 80% disease free if negative for EMVI

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Patient with vascular invasion detected on MRI, despite the success of surgery the patients developed irresectable liver metastases after 1 year.

The MRI identification of this risk factor before surgery could

1. Have helped to intensify preoperative treatment

2. Improved the monitoring and surveillance of the patient’s liver

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Odds ratio 4.6 (95% CI 1.3-

16.2)P=0.01

Odds Ratio 4.6(95% CI 2.9-

14.4)P=0.001

94 low risk 136 high risk

Whole group:33/230 (14.3%) distant

mets on PET/CT

230 patients with all imaging available

6 patients (2.5%) imaging unavailable for review236 patients enrolled

5/94 (5.3%) distant mets on PET/CT

28/136 (20.6%)distant mets on PET/CT

Same mets

PET/CT and CT

2/94(2.1%)

Same mets

PET/CT and CT10/136 (7.4%)

CT mets & more mets on PET/CT

2/94(2.1%)

CT Mets & more mets on PET/CT8/136 (5.9%)

Mets only on PET/CT

1/94(1.1%)

Mets only on PET/CT10/136 (7.4%)

Any mets on PET/CT not CT

3/94 (3.2%)

Any mets on PET/CT not CT

18/136 (13.2%)

T Vuong, A Garant, G Artho

R Lisbona

McGill University Health Centre

Patients with high risk features on MRI have a much higher rate of having spread elswhere (for example liver and lungs) but these can be successfully treated by surgery and chemotherapy if detected early. High risk patients should also benefit from more intensive surveillance

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A lot of funding has been invested into the investigation of tumour DNA and RNABut so far it has not been possible to demonstrate a common link that predicts how aggressively the tumour will behave or how it will respond

The Royal Marsden CANCER: 1948In 1948 most patients did not survive more than a few months with a diagnosis of advanced cancer

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Surgery – beyond TME – extended APE / extenteration

In 2016 the majority of patients with advanced cancerCan expect to survive complex surgery – however this requires referral and expertise in specialist centres

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Irresectable Tumour

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Pelvis

The Royal Marsden Before MDTs and imaging

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gina.brown@rmh.nhs.uk

Image-guidance capable radiation treatment machines

Jaffray, D. A. (2012) Image-guided radiotherapy: from current concept to future perspectivesNat. Rev. Clin. Oncol. doi:10.1038/nrclinonc.2012.194

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Dose painting tumour

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Putting it altogether

• Maximising information to surgeon• Enabling oncologists to seek out better

treatments for poor response to current treatment

• Giving patients the ability to avoid surgery altogether when non surgical treatment has had a good effect