Multi modality imaging in cancer 2012

Multi-modality imaging and

Cancer

Parminder S. Basran, PhD, FCCPMSenior Medical PhysicistBCCA- Vancouver Island CentreAdjunct Associate ProfessorUniversity of Victoria- Dept. Physics & Astronomy

Outline

Introduction

Clinical Example: Lung cancer

Prostate

Conclusions / Future Directions

Introduction

Introduction

Multi-modality imaging is changing the way we treat cancer patients.

The information content of these images is vast and almost overwhelming.

Even at a qualitative level, multi-modality imaging is a powerful tool.

The challenge for the next decade will be on how we most efficiently deploy multi-modal imaging, and integrate it –quantitatively- with patient care.

Introduction

Cancer: what is it?

http://en.wikipedia.org/wiki/Cancer

“a class of diseases in which a group of cells display uncontrolled growth, invasion that intrudes upon and destroys adjacent tissues, and sometimes metastasis, or spreading to other locations in the body via lymph or blood.”

http://en.wikipedia.org/wiki/Cancer

Introduction

Cancer: how do you detect it?

Most cancers are initially recognized either because signs or symptoms appear or through screening (blood tests, X-rays, CT scans and endoscopy). Confirmation requires pathologic testing. People with suspected cancer are investigated with medical tests.

Introduction

Cancer: how do you detect it?

Multi-modality imaging is beginning to play a central role in detecting cancer.

Not only is imaging used to measure the extent of the disease, it is commonly used to screen patients (generally higher risk patients) to mitigate morbidity from cancer.

There is always a risk in an imaging procedure. A screening program requires a careful assessment of the risks.

Introduction

As our understanding of cancer increases, so does the recognition that each tumor is unique.

In the last decade, the focus in cancer research on the genetic make-up of cancer

Now it is clear that the tumor microenvironment, cellular and protein interactions affect disease progression, aggressiveness and response to treatment.

Introduction

Subsequently, imaging the •tumor micro-environment•host/stem cell interactions,•various proteins

can be used to assess •disease progression•aggressiveness •response to treatment.

Introduction: timelines

1875 1900 1925 1950 1975 2000 2025

MR-PET prototype

PET-CT

PET

Magnetic Resonance Imaging

X-ray CT

Ultrasound

Nuclear medicine

X-ray- Roentgen

Introduction

Multi-modality imaging (in cancer): what does that really mean?

Incorporation of two or more imaging modalities sometimes within the setting of a single examination in

• assessing disease progression / aggressiveness • delivering efficacious treatment• assessing response to treatment

Maybe with a single or several imaging devices obtained at (nearly) the same time points.

Example: Lung Cancer


•70 year old male•Smoker for 20 years, quit 2 years ago•Painter•History of cancer in family

•Father had prostate cancer•Uncle had lung cancer

Symptoms•Coughing starting about 3 years ago, persistent for 2 years but got worse over last year

•Dull chest pain over the last year•Wheezy/hoarsness in breathing •Weight loss over the last year


Tests that may be performed include:

* Chest x-ray * Sputum cytology test to look for cancer cells * Blood work

Chest x-ray


X-ray suggests a mass in the lower left lung, likely stage 1 or stage 2 disease.

Need to confirm the disease: biopsy. • Bronchoscopy combined with biopsy• Pleural biopsy (collect fluid)• CT-scan directed needle biopsy• Mediastinoscopy with biopsy• Open lung biopsy• Endoscopic esophageal ultrasound (EUS) with

biopsy


Endoscopic esophageal ultrasound biopsy confirms non-small cell lung carcinoma.

Stage of cancer determines course of treatment and likelihood of control/curing cancer

Stage 0 - the cancer has not spread beyond the inner lining of the lung Stage I - the cancer is small and hasn't spread to the lymph nodes

Stage II - the cancer has spread to some lymph nodes near the original tumor

Stage III - the cancer has spread to nearby tissue or spread to far away lymph nodes

Stage IV - the cancer has spread to other organs of the body such as the other

lung, brain, or liver


Stage

Survival rate after 5 years

Treatment

0 / 1 80% Surgery (segmentectomy/wedge resection), photodynamic therapy, cryotherapy, radiation therapy

2 40-50% Lobectomy; pneumonectomy; or segmental, wedge Radiation therapy, Adjuvant chemotherapy (cisplatin) after curative surgery.

3 10-23 % Chemo-radiation therapy for patients with stage IIIA-N2 disease.Radiation therapy alone for patients medically unfit

4 <10% Chemotherapy, Radiation for palliative/symptom relief


Prognosis:

- Likely stage 2 NSCLC- Pretty good chance of treating / controling the disease- Treatment options are optimistic

- Surgery: Lobectomy; pneumonectomy; or segmental, wedge resection

- Radiation therapy- Adjuvant chemotherapy (cisplatin) after curative surgery.


Treatment Strategy:

Radiation therapy• Deliver 60 Gray over 30 days (2 Gy/day)• Use high energy photons (6 MeV range)• Need to simulate the treatment virtually• Obtain a CT scan to define the tumor and normal tissues• Simulate the radiation beams in the CT dataset


Radiation Therapy• Obtain a CT scan of the patients tumor and surrounding

normal tissues in the treatment position• Special attention given to setting up the patient on the CT

couch in order to ensure accurate targeting over the 30 days of treatment delivery

Targeting the tumor• How do you know we are hitting the tumor?• In CT, some of the ‘blob’ could be water• Some tissue may not be cancerous


As our understanding of cancer increases, so does the recognition that each tumor is unique.

In the last decade, the focus in cancer research on the genetic make-up of cancer

Now it is clear that the tumor microenvironment, cellular and protein interactions affect disease progression, aggressiveness and response to treatment.

Introduction: 1 + 1 ≠ 2


Positron Emission Tomography (PET), is a non-invasive molecular imaging technique that uses various radio-labeled compounds and visualizes metabolic differences between tissues, thus depicting the functional status of a suspicious lesion.

Malignant cells have an increased glycolytic rate.

Radio labeled 18F-fluorodeoxyglucose (18F-FDG) is a glucose analogue that has the same cellular uptake as glucose but is metabolically trapped within the cell after enzymatic phosphorylation to FDG-6-phosphate.

Therefore, FDG can be used to quantify glucose metabolic rates.


What happens if you combine PET with the gold standard CT?

Does 1 + 1 = 2 ?

CT + PET = better targeting? Better planning?



Introduction: PET/CT

Introduction: PET/CT


Introduction: 1 + 1 ≠ 2

Non-small cell carcinoma of the lung

- Metastatic spread to the liver

- Upstaged the disease and therefore the management of the disease

- No longer a radical treatment: palliative treatment with emphasis on quality of life

- Huge implications for the patient, family, patient care, health care costs.

Example: Lung Cancer / Targeting


Clinically, the best example of multimodality imaging is seen in the rapid evolution of PET-CT and SPECT-CT scanner hybrids.

SPECT = Single Photon Emission Computed Tomography

Simpler version of PET scanning

Again, the main utility in SPECT-CT is the merging of functional with anatomical data (one of which is typically the gold standard).

Example: Lung Cancer SPECT/CT



What value might functional imaging have in such a case?

In radiation therapy, you can always eradicate the tumor… but you might suffer significant side effects.

In lung cancer RT, the most significant side-effect is the loss of lung function…

Obtain a SPECT image to assess healthy lung function.

SPECT-CT

Dual head gamma camera system

Single slice low dose CT imaging system

Example: Lung Cancer SPECT

Example: Lung Cancer CT


Both anatomical and functional information together is more insightful that each independently assessed.


In the absence of SPECT information, completely functioning parts of the lung would be needlessly irradiated.

High doses of radiation can destroy healthy lung tissue.

It might make sense to direct the beams through parts of the lung that are not functioning.



Has changed the practice of management.But challenges remain:-SUV?-Reconstruction algorithms?-Motion?

PET/CT & SPECT/CT: challenges

Example: Prostate Cancer


A variety of multi-modality applications in the management and treatment of prostate cancer.

MR imaging has become a powerful tool in imaging the prostate.

Even adding different types of imaging sequences within the MR poses some exciting possibilities.


.MR can provide exquisite detail of the prostate, gland, and foci.

T2 weighted image.


.

T2 weighted image T1 contrast enhanced image


.


MRI can provide exquisite detail of the prostate, gland, and foci.

Contrast enhanced imaging can provide details on the blood flow of the tumor’s micro-environment.

MRI can also be used as a spectrometer: permits the ability to detect proteins that resonate at specific frequencies.

Some of these proteins may be over/under expressed in tumors.

Ex: ratio to citrate to choline are higher in tumors.



.



… that the tumor microenvironment, cellular and protein interactions affect disease progression, aggressiveness and response to treatment.

Conclusions / Future Considerations


Certainly, these are not the only innovations on the horizon…


PET-MR



PET / MR

http://medicalphysicsweb.org/cws/article/research/43526


SPECT / MR




US / MR


. Barriers for wide-spread usage•What mixture is best?•What cases are the best?•Equipment Expense•Radiation/RF safety•Access to a cyclotron or radionuclides•Tools for quantitative analysis are in infancy


Barriers for wide-spread usage•What mixture is best?

It remains unclear what combination of modalities should be used.

PET/CT clearly shows benefits in lung, head and neck cancers.

MRI/PET could equally show such benefits in, example, prostate, but clinical cost-benefit has to be demonstrated.


Barriers for wide-spread usage•What cases are best?


Barriers for wide-spread usage•Expense

PET / SPECT detectors are the key source of costs in these systems.

Advances in material sciences and production efficiency will drive these costs lower.

For MRI, roughly costs ~ 1M / Tesla, and proportional to scan length

Most clinical MR scanners have settled in the 1-3 T range.

Operating costs remain high.

CT/US systems are very mature; slice-wars are over…costs are relatively stable.


Barriers for wide-spread usage•Radiation and RF Safety

Often one already has a ‘room’ and one would like to renovate the room to accommodate the multi-modality imager. Addressing safety issues will require re-assessment of RF/Radiation safety operations, equipment usage, licensing, and resource expertise.

Typically an x-ray or CT room.

MR: need to provide radiofrequency barrier, or cage, around the scanner.

PET/SPECT: room shielding requirements are minimal, but operational costs are high (radiation chemist, detectors, personnel dosimetry monitoring, etc. )


Barriers for wide-spread usage•Access to a cyclotron or radionuclides (PET/SPECT)

PET requires ready access to a cyclotron, F-18 ~ 110 minutesC-11 ~ 20 minutes0-15 ~ 2 minutes

SPECT requires access to radio-isotopes


Barriers for wide-spread usage•Tools for quantitative analysis are in infancySome additional challenges:

Radiology lingo ≠ Radiation Oncology lingoRadiology technology ≠ Radiation Oncology technology

Bridging these fields is not a bad idea


.EX: NCI:PAR-08-225: Quantitative Imaging for Evaluation of Responses to Cancer Therapies (U01)

NCI: Reference Image Database to Evaluate Response

- initiative seeking input from RSNA / AAPM / ACR /- started with 30 longitudinal CT studies, primarily from

MDACC- currently CT, PET CT, DCE MRI, DW MRI, for lung, breast,

neuro

Marks LB et al. “The utility of SPECT lung perfusion scans in minimizing and assessing the physiologic consequences of thoracic irradiation.” Int J Radiat Oncol Biol Phys. 1993 Jul 15;26(4):659-68.Boersma LJ “Lung function and radiotherapy: an analysis of local and overall radiation effects” 1995 Thesis



Bold Prediction

Multi-modality imaging will replace ‘gold standard’

• assessing disease progression / aggressiveness

• delivering efficacious treatment ?• assessing response to treatment …

Thank you…questions?

Health & Medicine

Multi modality imaging in cancer 2012