Integrating modern imaging techniques

for optimization of treatment

Dr Andrew Scarsbrook

Consultant in Radiology and Nuclear Medicine

Pancreatic Cancer UK Study Day

Thackray Museum, Leeds, Thursday 26th March 2015

Learning Objectives

To learn about the potential role of PET-CT in

pancreatic cancer

To appreciate to use of imaging in planning

radiotherapy for pancreatic carcinoma

To understand emerging imaging applications in

guiding treatment of pancreatic carcinoma

PET-CT in Pancreatic Cancer

Sensitivity for detection of pancreatic adenocarcinoma similar to conventional imaging, but more specific

Particularly helpful in identifying unsuspected distant metastases and suspected recurrence when conventional imaging is inconclusive

FDG PET-CT may alter management in up to 43% of patients compared with CT alone

False positives occur in pancreatitis

False negatives in patients with elevated glucose levels and neuroendocrine tumours

May be useful for evaluating response to therapy and prognosis in the future

Primary staging

Primary staging

Prognostic information

• Quantification of tumour metabolic activity may be a prognostic indicator

• Metabolic tumour volume and total lesional glycolysis are PET derived

imaging biomarkers easily calculated using specialised software

Prognostic information

• Kaplan-Meier univariate analysis of overall survival of pancreatic cancer

patients stratified by pre-radiotherapy metabolic tumour volume and total

lesion glycolysis above and below median value predicts survival

Dholakia et al. Int J Radiation Oncol Biol Phys 2014;

89: 539-546

Occult peritoneal metastasis

Evaluation of suspected

recurrence

Diffuse peritoneal carcinomatosis

“One-stop” staging with PET-CT

Potential use of contrast-enhanced PET-CT for

pre-operative assessment of resectability in

pancreatic cancer

Relies upon a fixed-site scanner with appropriate

expertise

May allow “one-stop shop” assessment in the

future

Cost-effectiveness uncertain at present

PET-PANC Trial

The impact of combined modality

Positron Emission Tomography with

computerised tomography scanning

(PET-CT) in the diagnosis and

management of PANCreatic cancer

Study Design

Primary objective:

Determine incremental diagnostic accuracy and

impact of PET-CT in addition to standard diagnostic

workup in patients with suspected pancreatic cancer

Multi-centre prospective diagnostic accuracy study

PET-PANC Results

Sample size - 600 patients (disease prevalence

47%)

Interim analysis 200 patients: increased sensitivity

from 81% to 90% and specificity from 66% to 80%

Trial closed to recruitment in late 2013

Final results awaited in the near future

Cost-effectiveness data may inform commissioning

Tumour delineation: the weakest

link in the search for accuracy in

radiotherapy

Njeh C. J Med Phys 2008; 33: 136-140

Variability in clinical target volume

delineation between different Clinical

Oncologists

This can be reduced by:

Routine use of intravenous contrast-

enhanced CT for radiotherapy

planning

Multi-modality imaging co-registration

techniques

Collaborative multidisciplinary working

involving radiologists in the planning

process

Can PET-CT help ?

Steenbakkers IJROBP 2006; 64: 435

• FDG PET-CT dramatically reduces inter-observer variation

• Does increased consistency mean better ?

Contouring on CT versus PET-CT leads to differing treatment volumes

PET-CT in Target Definition

Comparative survival analyses between GTV lesser (GTVL) versus greater (GTVG)

A: Overall survival

B: Loco-regional progression-free survival

C: Progression-free survival

Parlak C et al. Radiation Oncol 2012; 7: 37

Impact of PET-CT on RTP

Only study that has looked at effect of PET-CT on

gross tumour volume (GTV) definition in pancreatic

cancer

CT-defined GTV compared to GTV delineated after

fusion of FDG PET with planning CT

PET-derived GTV 30% larger, due to extension of

primary tumour contours and additional nodes

No published data with histological correlation

Incorporating pancreatic tumour motion

Pancreatic tumours move with breathing,

leading to reduced tumour dose coverage or, if

margins are expanded, to increased normal

tissue toxicity

4-dimensional (respiratory-gated) CT reduces

the margin necessary for radiation therapy of

pancreatic tumours

Huguet F et al. IJROBP 2014; 91: 579-587

Respiratory-gated (4D) PET-CT

Radiotherapy

treatment planning

of tumours in the

diaphragmatic

region are hindered

by respiratory

motion

3D PET-CT

-PET takes significantly longer than CT to acquire

-CT is a ‘snapshot’ of tumour at certain point in

breathing cycle

-PET acquired over many breathing cycles, motion

smears out tumour, tumour boundaries blurred

4D PET-CT

-Respiratory gating eliminates breathing artefacts

-PET and CT datasets inherently registered

throughout breathing cycle

Why use 4D PET-CT ?

4D PET-CT imaging allows the motion path of

tumours to be visualized over the breathing cycle

Improved delineation confers a therapeutic

advantage by:

reduced toxicity due to reduction in dose to

organs at risk

Potential to escalate radiotherapy doses to

tumour volume

Leeds Cancer Centre Pilot Study

Evaluation of the impact of introducing 4D-

contrast-enhanced PET-CT guidance into the

radiotherapy planning process for patients with

Lung, Lower Oesophageal and Pancreatic

carcinomas

Collaboration between Radiology, Clinical

Oncology, Nuclear Medicine and Medical

Physics Departments

Primary objective

To evaluate the feasibility and potential benefit of utilising

4D PET-CT for improved Target Definition/Delineation in

Radiotherapy Planning

Secondary objectives

To assess if improved signal to noise with time of flight

PET in combination with 4D PET-CT allows more

accurate quantification of uptake within tumours

To evaluate if this improved spatial resolution and

precision of measurement of metabolic activity within

tumours is sufficient to allow dose boosting to these

areas

Study Design

Non-randomised prospective study

Peripheral stage I NSCLC planned to receive Lung

Stereotactic Body Radiotherapy

Locally advanced NSCLC, particularly central

tumours with distal collapse/consolidation who are

not fit for surgical resection

Pancreatic adenocarcinoma

Lower third oesophageal cancers

COMPLETED RECRUITMENT DECEMBER 2014

Potential clinical use

• Sequential chemo

and chemo-radiation

used for locally

advanced

unresectable

pancreatic cancer

Potential clinical use

• Improved delineation of target volume will reduce toxicity to organs at risk

• PET-CT outlining of pancreatic tumours has less inter-observer variability

Patient selection for 4D imaging

Main issue: Shallow

or erratic breathing

Uncontrolled Diabetes

Mellitus

Poor general

condition: limited

mobility, unable to

tolerate the study

Challenges

Analysis of the data is

complex and time

consuming

Data transfer

between different

systems is

challenging

Challenges

• FDG avidity may be substantially decreased if

chemotherapy is administered prior to 4D study

Multi-modality Imaging for RTP

Dalah E et al. IJROBP 2014; 89: 3

Various MRI, PET and CT techniques used to try to define

treatment targets for radiotherapy in pancreatic cancer

Significant differences in tumour volume defined by each

imaging modality and/or sequences

Further studies with radiological-pathological correlation

required to establish reliable imaging techniques for the

accurate delineation of tumour target

Crucial particularly in future dose escalation and/or dose

painting radiotherapy trials in pancreatic cancer

Multi-modality Imaging for RTP

Dalah E et al. IJROBP 2014; 89: 3

Treatment individualisation and

adaptation: a role of functional

imaging ?

Dose escalation to ‘radio-resistant’ areas

Selection of concurrent drug therapy

Alteration of treatment depending upon

early radiotherapy response

On treatment imaging FDG PET-CT scans in two patients before, during and after CRT for pancreatic cancer

Patient 1 failed to respond to CRT and progressed with liver metastases (not shown)

Patient 2 responded to treatment and had a curative resection performed

Bjerregaard JK et al. Acta Oncologica 2011; 50:

1250-1252

Conclusions

Emerging role for PET-CT in pancreatic cancer

Many challenges to the routine use of PET-CT for

radiotherapy planning of pancreatic tumours

Functional imaging (MRI and PET) may facilitate

individualised radiotherapy and treatment

adaptation in the future but require further validation

Multi-disciplinary collaboration is the key to success

Thank you

Any questions ?