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Austin Health Department of Molecular Imaging & Therapy

Dr. Aurora Poon

Nuclear Medicine Physician

PET in Rectal Cancer Management


1. What is PET – 18F-FDG vs 68Ga-DOTATATE

2. The incidentalomas

3. Staging TNM

4. Therapy monitoring

5. Restaging / Recurrence

6. Short falls

Overview

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1. What is PET – 18F-FDG


3. Staging TNM



6. Short falls

Overview


Positron Emission Tomography (PET)

- Imaging modality based on detecting radiation

emitted from positron emitters i.e. 15O, 11C, 13N,

18F, 68Ga & 124I

- Radionuclides -bound to biochemical tracers are

used to study diverse pathologic processes e.g.

blood flow and metabolism

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PET in Oncology- Malignant cells have enhanced aerobic glycolysis

(Warburg et al, 1930)

- Malignant cells develop significant alteration in

metabolism with:

Increased

• Glycolysis

• Amino acid use

• DNA synthesis

• Somatostatin receptor expression

• Prostatic specific membrane antigen

expression

These provide the biochemical basis of PET imaging


Glucose

transporter

protein

K3

K4

Hexokinase

Tumor Cell

Glucose-6-

phosphatase

18FDG-1-P

Glycogen

18F-fru-6-P

Glycolysis

18FDG-

6-

phosph

o-

glucon

o-

lactone

HMP

shunt

18FDG

Vascular

K1

K2

18FDG 18FDG-6P

18F-Fluorodeoxyglucose 18F-FDG

– glucose analogue, distributed in vivo & transported

into cells like glucose BUT not metabolised

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Mechanism of increased 18F-FDG uptake in cancer cells

- Increased expression of glucose transporter

molecules at the tumour surface

- Increased levels/activity of hexokinase

- Reduced level of glucose-6-phosphatase vs most

normal tissues

- Strong correlation b/n no. of viable cells and uptake

(higher 18F-FDG uptake in viable tumour than

necrotic tumour)


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18F +

-

p

c

c

Annihilation reaction

ring detector

Patient

PET/CT




3. Staging TNM



6. Short falls

Overview

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Incidental focal 18F-FDG uptake in large bowel

- Prevalence of incidental focal colorectal

uptake ~0.4-9.5%

- Prevalence of malignancy

~8-32%

- Prevalence of pre malignancy

21-83%

- 85/2916 patients (3%) in 2005-6 Austin Hospital

98% with endoscopic follow-up, 75% with either

colorectal cancer or adenoma

Hess 2014, Soltau 2017

Lee ST et al Mol Imaging Biol 2008 10(1):48-53


Low grade villous

adenoma

High grade villous

tubular adenomaCarcinoma

Ix for PMRStaging for urotheial ca staging for NSCLC

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- Dose uptake ratio

5% of 7318 pts had incidental colorectal uptake

242/404 foci with endoscopic follow up

- 10% adenocarcinoma

- 37% adenoma

- 53% other benign lesions

- SUV in malignancies higher than benign lesionsF. B. Hoeij et al EJNMMI 2015, 42(1) 66-71

Standardised Uptake Value (SUV)




3. Staging TNM



6. Short falls

Overview

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Staging T and N

T staging

- Conventional Imaging- Overall accuracy ~80%

- MRI 66-95%

- 18F-FDG PET/CT- Limited by spatial

resolution

- Inability to distinguish

layers of the wall

N staging

- Conventional Imaging- Overall Sn 55-65%

- MRI 63-95%

- 18F-FDG PET/CT- Limited by spatial

resolution

- Overall Sn/Sp ~

43%/88%

Chowdhury 2010, Lu 2012

review, meta-analysis

-18F-FDG PET does not replace conventional imaging


53 yo man with locally advanced rectal carcinoma

- Small right peri-rectal nodal metastasis

- Size matters, but tumour metabolism also important

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- Meta-analysis of 18 studies

in 1059 pts with colorectal

cancer and hepatic

metastases

- 18F-FDG PET is highly

accurate for detection of liver

metastases in per pt basis

- 18F-FDG PET is less

sensitive than MRI but more

specific

- 18F-FDG PET/CT changes

management in ~ 24% pt

Modality SensitivitySpecificity

per patient

CT 84-98% 70-95%

MRI 88-100% 70-93%

PET:

PET/CT 93-97% 81-97%

Per lesion

CT 69-80% 67%

MRI 80-89% 81%

PET:

PET/CT 60-81% 79-86%

Meffione et al EJNMMI 2015 42 (1) 152:163

M Staging


Comparison 18F-FDG PET/ multiphase CT and intraoperative ultrasound for detection

of hepatic metastases.- 131 pts selected for hepatic resection of

colorectal liver metastases:

- 363 liver metastases identified

- Sensitivity for detection:

- -63 lesions < 10 mm CT PET 16%

- 172 lesions 10-20 mm CT 72% PET 75%

- 128 lesions > 20 mm CT 97% PET 95%

- All CT 71% PET 72%

- Both CT and 18F-FDG PET missed ~ 30% smaller

lesions resulting in change in management in 7% of

patients Wiering B et al. Ann Surg Oncol 2007:14(2):818-26

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Impact of 18F-FDG PET in the management of pts with colorectal hepatic metastases

Meta-analysisPooled sensitivity and specificity of 18F-FDG PET

and CT from studies in patients evaluated for hepatic resection:

Hepatic metastases:

Sensitivity : PET 88% CT 82%

Specificity: PET 96% CT 84%

Extra-hepatic metastases:

Sensitivity: PET 91% CT 61%

Specificity: PET 95% CT 91%

Change in management : ~31% ( 20-58%)

Wiering B et al. Cancer 2005; 104:2658-2670


Metastatic Rectal Cancer

- Good overview of disease burden

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63 yo woman with metastatic multifocal colorectal cancer

Extensive retroperitoneal, mediastinal and

supraclavicular nodal metastases, hepatic metastases

and likely lymphangitis




3. Staging TNM



6. Short falls

Overview

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Therapeutic Monitoring

- FDG PET/CT is standard of care in patient

receiving radiotherapy +/- concurrent

chemotherapy for rectal cancer

- Useful in high risk patients and patients with

metastatic disease


81 yo man with synchronous sigmoid and rectal cancer post Hartmann's for obstructive symptoms.

Pre CR therapy Post CR therapy

Pre CR therapyPost CR therapy

Complete metabolic response of primary rectal cancer but

progressive hepatic metastases

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57 yo man with poorly differentiated rectal cancer with nodal disease on baseline staging, treated with neoadjuvant chemoradiotherapy followed by ULAR

Restaging 18F-FDG PET – resolution of nodal disease, residual primary

rectal ca - pT3N0

Pre CRT Post CRT


55 yo woman with low rectal gastrointestinal stromal tumour (GIST)

Pre Glivec therapy Post 12 weeks Glivec therapy

18F-FDG PET imaging post Imatinib

(Glivec) therapy in GIST

- metabolic changes precede by weeks or

months before significant decrease in

tumour size on CT

- metabolic responses seen on 18F-FDG

PET have been shown to correlate with

progress free survival

(Fuster D et al. 2011, Quart JNMMI )

Pre Glivec

4/52 post Glivec

Van den Abbeele The Oncologist 2008

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3. Staging TNM



6. Short falls

Overview


Recurrence

Studies number Sn Sp PPV NPV

Overall ( suspected rectal recurrence on CT)

Votrubova 2006(PET/CT)

Fiocchi 2010 (PET/CT)

60-84 89-93% 69-92% 50% 97%

CEA-based regimen (elevated CEA and normal/equivocal CT)

Chowdhury 2010 (PET)

Gade 2015 (PET/CT)

22-103 67-86% 82-95% 89-94% 95-100%

Presacral mass ( suspected pelvic recurrence)

Even-Sapir 2004 (PET/CT) 62 100% 96% 88% 100%

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53 yo man with recurrent rectal cancer-anterior resection in1999 followed by chemotherapy- recurrence 2015 – redo anterior resection- 2017 with rising CEA

Pre XRT 2012

Local recurrence

2015

Presacral rec 17

Biopsy confirmed

new colonic ca

arising from TVA

and presacral rec




3. Staging TNM



6. Short falls

Overview

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Shortfall of 18F-FDG PET

- Physiological bowel uptake may be intense,

especially in diabetic patients on metformin and at

anorectal junction

- Benign tubulovillous adenoma can have similar

FDG uptake to malignant lesions

- Infection/inflammation can be associated with

increased FDG uptake

- Some mucinous adenocarcinoma are not FDG

avid

- Poor spatial resolution for T and N staging.


Chronic pre sacral collection

Nov 2014

July 2016

Feb 2017

July 2017

Physiological large bowel 18F-FDG uptake

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68Ga DOTATATE PET

- Somatostatin analogue conjugated to a

positron emitting isotope 68Ga

- Reflects somatostatin receptor density

(highest affinity for SSTR-2)

- Higher resolution and better target to

background ratio when compared to 111Indium labelled octreotide

SPECT/CT

- More accessible than 111In octreotide in

Australia


65 year old man with poorly differentiated large cell neuroendocrine tumour of the rectum

- Primary rectal

tumour uptake is low

(poorly differentiated)

- Extensive nodal

and bone

metastases

- Useful when

combined with 18F-

FDG PET

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PET MRI – is that the future?

- Attenuation correction with MRI still requires

optimisation

- Many patients may not tolerate long

procedure

- No medicare funding – more research/data

collection required.


Thank you

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PET tracers in tumour imaging

Increased aerobic and anaerobic glycolysis c.f.

most normal tissue 18F-FDG

Increased rate of growth 11C-thymidine

Increased rate of protein synthesis 11C-

methionine

Physiological alterations in tumour & PET tracers :


Detection of Extra Hepatic Metastases

- 155 patients analysed by sites of lesions:

- Sensitivity of PET > CT for all locations

except for the lungs where the two

modalities are equivalent

- FDG PET particularly helpful for abdomen,

pelvis and retroperitoneum

- Specificity: FDG PET > CT at all sites except

for retroperitoneum.

Valk PE et al. Arch Surg 1999:134:503-511

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